valproic acid and Disease Models, Animal studies

Valproic Acid: A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS.
valproic acid : A branched-chain saturated fatty acid that comprises of a propyl substituent on a pentanoic acid stem.

Disease Models, Animal: Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.

Research Excerpts

Excerpt	Relevance	Reference
"Valproic acid (VPA) induced rodent model of autism is a widely accepted and extensively used rodent model to investigate the pharmacotherapy against autism."	9.22	Critical Evaluation of Valproic Acid-Induced Rodent Models of Autism: Current and Future Perspectives. ( Chopra, M; Mehra, S; Seth, E; Ul Ahsan, A, 2022)
" Previously, we have established a mouse model of ASD based on clinical research, which shows that exposure to valproic acid, an antiepileptic drug, during pregnancy causes an increase in the risk of developing ASD in children."	9.01	[Chronic Activation of the Dopaminergic Neuronal Pathway Improves Behavioral Abnormalities in the Prenatal Valproic Acid Exposure Mouse Model of Autism Spectrum Disorder]. ( Hara, Y, 2019)
"The mood stabilizers lithium, valproate and lamotrigine are traditionally used to treat bipolar disorder."	8.87	Beneficial effects of mood stabilizers lithium, valproate and lamotrigine in experimental stroke models. ( Chuang, DM; Fessler, EB; Wang, ZF, 2011)
"Administration of the antiepileptic drug valproic acid (VPA) during early pregnancy can result in a 1-2% incidence of spina bifida aperta, a closure defect of the posterior neural tube in the human."	8.78	Valproic acid-induced neural tube defects in mouse and human: aspects of chirality, alternative drug development, pharmacokinetics and possible mechanisms. ( Ehlers, K; Hauck, RS; Nau, H, 1991)
"In this study, based on the excitatory/inhibitory imbalance theory of autism, the time window of GABA switch, the role of K-Cl co-transporter 2 (KCC2) in adjustment GABA switch, and brain permeability to erythropoietin (EPO), the effects of postnatal -EPO and- nano- erythropoietin (NEPO) have been evaluated in the valproic acid (VPA) rat model of autism."	8.31	The effects of postnatal erythropoietin and nano-erythropoietin on behavioral alterations by mediating K-Cl co-transporter 2 in the valproic acid-induced rat model of autism. ( Basiri, M; Darvishzadeh-Mahani, F; Haratizadeh, S; Nozari, M; Ranjbar, M, 2023)
"Risperidone is the first antipsychotic to be approved by Food and Drug Administration (FDA) for treating autism spectrum disorder (ASD)."	8.31	The comparative effectiveness of metformin and risperidone in a rat model of valproic acid-induced autism, Potential role for enhanced autophagy. ( Ashour, RH; Atia, AA; Rahman, KM; Ramadan, NM; Zaki, MM, 2023)
" VPA-exposed male pups were administered with two doses of ibudilast (5 and10 mg/kg) and all the groups were evaluated for behavioral parameters like social interaction, spatial memory/learning, anxiety, locomotor activity, and nociceptive threshold."	8.31	Phosphodiesterase inhibitor, ibudilast alleviates core behavioral and biochemical deficits in the prenatal valproic acid exposure model of autism spectrum disorder. ( Gautam, V; Kumar, A; Rawat, K; Saha, L; Sandhu, A; Sharma, A, 2023)
"N-acetylcysteine (NAC) has been reported to improve social interaction behavior, irritability, self-injury, and anxiety-like behavior in autism."	8.31	N-acetylcysteine improves autism-like behavior by recovering autophagic deficiency and decreasing Notch-1/Hes-1 pathway activity. ( Deng, YN; He, XL; Li, YF; Wang, LJ; Wang, T; Zhang, YH, 2023)
" Valproic acid (VPA) exposure during pregnancy causes autistic-like traits in offspring."	8.31	The antipsychotic olanzapine reduces memory deficits and neuronal abnormalities in a male rat model of Autism. ( Aguilar-Hernandez, L; Bringas, ME; Flores, G; Garcés-Ramírez, L; Lima-Castañeda, LÁ; Morales-Medina, JC, 2023)
"Prenatal exposure to valproic acid (VPA) may enhance the risk of autism spectrum disorder (ASD) in children."	8.31	Prangos ferulacea (L.) ameliorates behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid. ( Aldaghi, MR; Raise-Abdullahi, P; Saadat, M; Sameni, HR; Taherian, AA; Vafaei, AA, 2023)
"This study aims to understand the relationship between fecal metabolites and gut microbiota in an adolescent valproic acid-induced rat autism model (VPA-exposed offspring)."	8.12	Correlation among gut microbiota, fecal metabolites and autism-like behavior in an adolescent valproic acid-induced rat autism model. ( Gu, Y; Han, Y; Qin, J; Ren, S; Wang, X; Zhang, B; Zhang, S; Zhao, Y, 2022)
" Therefore, in this study, we focused on the rapid and persistent neuroprotective function of DLX following valproic acid (VPA)-triggered hyperactivity, anxiety-like behavior and social deficits in zebrafish."	8.12	Duloxetine ameliorates valproic acid-induced hyperactivity, anxiety-like behavior, and social interaction deficits in zebrafish. ( Chen, H; Joseph, TP; Lin, SL; Sai, LY; Schachner, M; Zhou, F, 2022)
" The anxiety induced by pilocarpine was also significantly (P < 0."	8.12	Anticonvulsant effects of Cymbopogon giganteus extracts with possible effects on fully kindled seizures and anxiety in experimental rodent model of mesio-temporal epilepsy induced by pilocarpine. ( Bum, EN; Kouemou Emegam, N; Neteydji, S; Pale, S; Taiwe, GS, 2022)
"Valproic acid (VPA) exposure as an environmental factor that confers risk of autism spectrum disorder (ASD), its functional mechanisms in the human brain remain unclear since relevant studies are currently restricted to two-dimensional cell cultures and animal models."	8.12	Human forebrain organoids reveal connections between valproic acid exposure and autism risk. ( Chen, C; Jiao, C; Liu, C; Meng, Q; Tang, B; Wang, X; Xu, S; Zhang, W, 2022)
" Here we examine the effects of valproic acid (VA) plus 4-phenylbutyric acid (4-PBA) on abnormal electrical brain activity, ER stress and apoptosis in acute seizures induced by pentylenetetrazole (PTZ)."	8.12	4-Phenylbutyric Acid Plus Valproic Acid Exhibits the Therapeutic and Neuroprotective Effects in Acute Seizures Induced by Pentylenetetrazole. ( Amanvermez, R; Arslan, G; Gün, S; Rzayev, E; Tiryaki, ES, 2022)
"We previously demonstrated that prenatal exposure to valproic acid (VPA), an environmental model of autism spectrum disorder (ASD), leads to a hyperexcitable phenotype associated with downregulation of inward-rectifying potassium currents in nucleus accumbens (NAc) medium spiny neurons (MSNs) of adolescent rats."	8.12	Acute rapamycin rescues the hyperexcitable phenotype of accumbal medium spiny neurons in the valproic acid rat model of autism spectrum disorder. ( Costa, A; Curti, L; D'Ambrosio, M; Gerace, E; Iezzi, D; Ilari, A; La Rocca, A; Luceri, C; Mannaioni, G; Masi, A; Ranieri, G; Scardigli, M; Silvestri, L, 2022)
"Prenatal exposure to valproic acid (VPA) has been implicated in the manifestation of autism spectrum disorder (ASD)-like behavioral and functional changes both in human and rodents including mice and rats."	8.12	Metabolomics profiling of valproic acid-induced symptoms resembling autism spectrum disorders using 1H NMR spectral analysis in rat model. ( Kim, HY; Kim, JW; Kim, KB; Kim, S; Kim, SJ; Ko, MJ; Lee, JD; Lee, YJ; Shin, CY, 2022)
"The cilostazol regimen, attenuated prenatal VPA exposure associated hyperlocomotion, social interaction deficits, repetitive behavior, and anxiety."	8.02	Cilostazol attenuated prenatal valproic acid-induced behavioural and biochemical deficits in a rat model of autism spectrum disorder. ( Kulkarni, GT; Luhach, K; Sharma, B; Singh, VP, 2021)
" The present work aimed to detect changes in the AVP numbers and level in a valproic acid (VPA)-induced rat model of autism and the underlying mechanism of its pathogenesis."	8.02	Postnatal AVP treatments prevent social deficit in adolescence of valproic acid-induced rat autism model. ( Bai, SZ; Dai, YC; Han, JS; Han, SP; Hu, Y; Lan, XY; Wu, J; Zhang, HF; Zhang, R, 2021)
" In the pharmacodynamic interaction study, seizures were induced using pentylenetetrazole (PTZ) (60 mg/kg, i."	8.02	Pharmacodynamic and pharmacokinetic interactions of hydroalcoholic leaf extract of Centella asiatica with valproate and phenytoin in experimental models of epilepsy in rats. ( Agarwal, A; Arora, R; Ganeshan N, S; Gupta, YK; Kaleekal, T; Kumar, R; Sarangi, SC, 2021)
"It has been reported that valproic acid (VPA) combined with therapeutic hypothermia can improve survival and neurologic outcomes in a rat asphyxial cardiac arrest model."	8.02	HSP70-mediated neuroprotection by combined treatment of valproic acid with hypothermia in a rat asphyxial cardiac arrest model. ( Choi, KH; Choi, S; Jeong, HH; Kim, K; Oh, JS; Oh, YM; Park, J, 2021)
"The goal of our study was to examine the long-term effect of vigabatrin (VGB), a γ-aminobutyric acid aminotransferase (GABA-AT) inhibitor on clonazepam (CLO), ethosuximide (ETX) and valproate (VPA) anticonvulsive activity against pentylenetetrazole (PTZ)-induced seizures in mice."	7.96	Long-term vigabatrin treatment modifies pentylenetetrazole-induced seizures in mice: focused on GABA brain concentration. ( Czuczwar, SJ; Krzyżanowski, M; Świąder, K; Świąder, MJ; Wróbel, A; Zakrocka, I; Łuszczki, JJ, 2020)
" This study examined the effect of metformin on VPA-induced autism spectrum disorders in rats."	7.96	Novel potential of metformin on valproic acid-induced autism spectrum disorder in rats: involvement of antioxidant defence system. ( Adeyemi, OO; Balogun, AO; Ishola, IO, 2020)
"This study was performed to evaluate the effects of prenatal exposure to pregabalin (PGB) on behavioral changes of rat offspring in an animal model of valproic acid (VPA)-induced autism-like symptoms."	7.96	Prenatal pregabalin is associated with sex-dependent alterations in some behavioral parameters in valproic acid-induced autism in rat offspring. ( Bashiri, H; Moslemizadeh, A; Sepehri, G; Shamsi Meymandi, M; Vakili Shahrbabaki, S, 2020)
"In previous studies we produced autism like behavioral changes in mice by Valproic acid (VPA) with significant differences between genders."	7.91	Gender Related Changes in Gene Expression Induced by Valproic Acid in A Mouse Model of Autism and the Correction by S-adenosyl Methionine. Does It Explain the Gender Differences in Autistic Like Behavior? ( Ergaz, Z; Ornoy, A; Szyf, M; Turgeman, G; Weinstein-Fudim, L; Yanai, J, 2019)
" Here, we aim to determine whether Valproic acid (VPA), a FDA approved inhibitor of histone deacetylation for bipolar disease, could protect heart against myocardial infarction (MI) injury and elucidate key molecular pathways."	7.91	HDAC inhibitor valproic acid protects heart function through Foxm1 pathway after acute myocardial infarction. ( Alam, HB; Creech, J; Eugene Chen, Y; Gao, W; Guo, Y; Herron, TJ; Lei, I; Li, Y; Liu, L; Ma, PX; Tian, S; Wang, Z; Xian, S, 2019)
" Valproic acid (VPA) is an anticonvulsant drug in both human and rodents with teratogenic effects during pregnancy."	7.91	Benefits of Fenofibrate in prenatal valproic acid-induced autism spectrum disorder related phenotype in rats. ( Mirza, R; Sharma, B, 2019)
"To establish an improved mouse model of valproic acid (VPA)-induced autism that better mimics human autism."	7.91	[Improvement of a mouse model of valproic acid-induced autism]. ( Chen, D; Hu, Y; Li, Y; Wang, S; Zheng, W, 2019)
"We utilized a valproic acid (VPA) -induced rat model of autism to evaluate the levels of S1P and the expression of sphingosine kinase (SphK), a key enzyme for S1P production, in serum and hippocampal tissue."	7.88	Modulation of sphingosine 1-phosphate (S1P) attenuates spatial learning and memory impairments in the valproic acid rat model of autism. ( Cao, Y; Gao, J; Hao, Y; Sun, C; Wang, J; Wu, H; Wu, L; Xia, W; Zhang, Q, 2018)
" There have been no studies that have explained if HDAC inhibition by valproic acid (VPA) affects the NF-κB pathway via acetylation of STAT1 dependent of HDAC activity in the microglia-mediated central inflammation following SCI."	7.88	Valproic acid attenuates traumatic spinal cord injury-induced inflammation via STAT1 and NF-κB pathway dependent of HDAC3. ( Chen, S; Chen, X; Fu, H; Li, S; Li, Y; Lin, W; Shi, J; Wu, W; Ye, J, 2018)
"Histone deacetylase inhibitors such as valproic acid (VPA) improve survival in lethal models of hemorrhagic shock and polytrauma."	7.88	Rapid valproic acid-induced modulation of the traumatic proteome in a porcine model of traumatic brain injury and hemorrhagic shock. ( Alam, HB; Dennahy, IS; Georgoff, PE; Ghandour, MH; Higgins, GA; Nikolian, VC; Remmer, H; Weykamp, M, 2018)
"Considering the potential role of lymphocytes in the pathophysiology of autism spectrum disorder (ASD), we aimed to evaluate possible alterations of T cell pools in the lymphoid organs of an animal model of autism induced by valproic acid (VPA)."	7.88	Reduced CD4 T Lymphocytes in Lymph Nodes of the Mouse Model of Autism Induced by Valproic Acid. ( Bambini-Junior, V; Baronio, D; Bauer-Negrini, G; Castro, K; Della-Flora Nunes, G; Gottfried, C; Mendes-da-Cruz, DA; Riesgo, R; Savino, W, 2018)
") on sociability, social novelty, anxiety, and aggressive/repetitive behavior in male Tuck-Ordinary (TO) mice with ASD-like behaviors induced by prenatal exposure to valproic acid (VPA, 500 mg/kg, i."	7.88	The histamine H3R antagonist DL77 attenuates autistic behaviors in a prenatal valproic acid-induced mouse model of autism. ( Al-Houqani, M; Azimullah, S; Eissa, N; Jalal, FY; Jayaprakash, P; Kieć-Kononowicz, K; Ojha, SK; Sadek, B; Łażewska, D, 2018)
"We have investigated the species richness and microbial composition in a valproic acid (VPA)-induced rat model autism."	7.88	The valproic acid rat model of autism presents with gut bacterial dysbiosis similar to that in human autism. ( Horton-Sparks, K; Hull, V; Li, RW; Liu, F; Martínez-Cerdeño, V, 2018)
"The aim was to identify the effects of early vitamin D supplementation on autism-like behaviors (ASD) induced by valproic acid (VPA, an anti-convulsant and a mood stabilizer) in rats."	7.85	Behavioral improvements in a valproic acid rat model of autism following vitamin D supplementation. ( Du, L; Duan, Z; Li, F; Zhao, G, 2017)
"The study was performed using a rodent model of autism by exposing rat fetuses to valproic acid (VPA) on the 12."	7.85	Postnatal treatment using curcumin supplements to amend the damage in VPA-induced rodent models of autism. ( Al-Askar, M; Al-Ayadhi, L; Bhat, RS; El-Ansary, A; Selim, M, 2017)
" Here, we investigate the impact on the corticostriosomal pathway in the valproic acid (VPA)-induced autism spectrum disorder mouse model."	7.85	Valproic acid induces aberrant development of striatal compartments and corticostriatal pathways in a mouse model of autism spectrum disorder. ( Kuo, HY; Liu, FC, 2017)
"VPA prevented HFD-induced hypertension by downregulating angiotensin II and its receptor via inhibition of HDAC1, offering a novel therapeutic option for HFD-induced hypertension."	7.85	Role of the histone deacetylase inhibitor valproic acid in high-fat diet-induced hypertension via inhibition of HDAC1/angiotensin II axis. ( Choi, J; Kim, JI; Kwon, TK; Park, KM; Park, S; Sohn, SI, 2017)
"Recent studies have reported that oxytocin ameliorates behavioral abnormalities in both animal models and individuals with autism spectrum disorders (ASD)."	7.85	Oxytocin attenuates deficits in social interaction but not recognition memory in a prenatal valproic acid-induced mouse model of autism. ( Ago, Y; Hara, Y; Hasebe, S; Hashimoto, H; Higuchi, M; Matsuda, T; Nakazawa, T; Takuma, K, 2017)
"Prenatal exposure to the antiepileptic, mood-stabilizing drug, valproic acid (VPA), increases the incidence of autism spectrum disorders (ASDs); in utero administration of VPA to pregnant rodents induces ASD-like behaviors such as repetitive, stereotyped activity, and decreased socialization."	7.85	Sexually Dimorphic Epigenetic Regulation of Brain-Derived Neurotrophic Factor in Fetal Brain in the Valproic Acid Model of Autism Spectrum Disorder. ( Densmore, AL; Konopko, MA; Krueger, BK, 2017)
"The present study was undertaken to elucidate the effect of alpha-linolenic acid (ALA, 18:3, ω-3) and gamma-linolenic acid (GLA, 18:3, ω-6) on experimental autism features induced by early prenatal exposure to valproic acid (VPA) in albino wistar pups."	7.85	Comparative efficacy of alpha-linolenic acid and gamma-linolenic acid to attenuate valproic acid-induced autism-like features. ( Ansari, MN; Devi, U; Gautam, S; Kaithwas, G; Prakash, A; Rawat, JK; Roy, S; Saeedan, AS; Saraf, SA; Singh, M; Tiwari, V; Yadav, RK; Yadav, S, 2017)
"Prenatal exposure to valproic acid (VPA) in rat offspring is capable of inducing experimental autism with neurobehavioral aberrations."	7.83	Neuroprotective effects of docosahexaenoic acid on hippocampal cell death and learning and memory impairments in a valproic acid-induced rat autism model. ( Cao, Y; Gao, J; Liang, S; Sun, H; Wang, H; Wang, X; Wang, Y; Wu, L; Yang, F; Zhang, F, 2016)
"Rodents exposed prenatally to valproic acid (VPA) show autism-related behavioral abnormalities."	7.83	Improvement by methylphenidate and atomoxetine of social interaction deficits and recognition memory impairment in a mouse model of valproic acid-induced autism. ( Ago, Y; Hara, Y; Hasebe, S; Hashimoto, H; Katashiba, K; Matsuda, T; Onaka, Y; Takano, E; Takuma, K; Taruta, A, 2016)
"Exposure to valproic acid (VPA) during pregnancy has been linked with increased incidence of autism, and has repeatedly been demonstrated as a useful autism mouse model."	7.83	Early Behavioral Abnormalities and Perinatal Alterations of PTEN/AKT Pathway in Valproic Acid Autism Model Mice. ( Ahn, S; Kim, HS; Lee, K; Mahmood, U; Yang, EJ, 2016)
" Here, we suggest that triggering limbic seizures with low doses of PTZ in pilocarpine-treated marmosets might provide a more effective basis for the development of AED."	7.83	Seizures triggered by pentylenetetrazol in marmosets made chronically epileptic with pilocarpine show greater refractoriness to treatment. ( Blanco, MM; Cinini, SM; Lima, TZ; Mello, LE; Pontes, JC; Queiroz, CM, 2016)
"Components of the mTOR pathway were assayed by Western blotting in postmortem fusiform gyrus samples from 11 subjects with idiopathic autism and 13 controls and in valproic acid versus saline-exposed rat neocortex."	7.81	Decreased mTOR signaling pathway in human idiopathic autism and in rats exposed to valproic acid. ( Ahn, Y; Fahnestock, M; Michalski, B; Nicolini, C; Rho, JM, 2015)
"Male Sprague-Dawley rats were injected with a single, subcutaneous dose of monocrotaline (60 mg/kg), and were exposed to chronic hypoxia to induce severe PH."	7.81	Therapeutic efficacy of valproic acid in a combined monocrotaline and chronic hypoxia rat model of severe pulmonary hypertension. ( Furutani, Y; Hayama, E; Kawaguchi, N; Lan, B; Nakanishi, T, 2015)
"We report that the oxytocin-mediated neuroprotective γ-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery is abolished in the valproate and fragile X rodent models of autism."	7.80	Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring. ( Ben-Ari, Y; Brouchoud, C; Burnashev, N; Chazal, G; Eftekhari, S; Ferrari, DC; Khalilov, I; Lemonnier, E; Lozovaya, N; Nardou, R; Shahrokhi, A; Tsintsadze, T; Tsintsadze, V; Tyzio, R, 2014)
"The aims of this study were to characterize a lamotrigine-resistant kindled model of epilepsy in mice, to study the anticonvulsant effect of carbamazepine (CBZ) and valproic acid (VPA), and to probe into the mechanism for resistance."	7.80	Characterization of a lamotrigine-resistant kindled model of epilepsy in mice: evaluation of drug resistance mechanisms. ( Mehndiratta, M; Pillai, KK; Singh, E, 2014)
"We have previously shown that resuscitation with fresh frozen plasma (FFP) in a large animal model of traumatic brain injury (TBI) and hemorrhagic shock (HS) decreases the size of the brain lesion, and that addition of a histone deacetylase inhibitor, valproic acid (VPA), provides synergistic benefits."	7.80	Treatment with a histone deacetylase inhibitor, valproic acid, is associated with increased platelet activation in a large animal model of traumatic brain injury and hemorrhagic shock. ( Alam, HB; Andjelkovic, AV; Bambakidis, T; Boer, C; Dekker, SE; Halaweish, I; Jin, G; Johansson, PI; Linzel, D; Liu, B; Sillesen, M, 2014)
"Post natal exposure to VPA (valproic acid) in mice induces behavioral deficits, abnormal sensitivity to sensory stimuli and self-injurious behavior, observed in autism."	7.80	Ameliorating effect of piperine on behavioral abnormalities and oxidative markers in sodium valproate induced autism in BALB/C mice. ( Kameshwari, JS; Pragnya, B; Veeresh, B, 2014)
"We recently showed that prenatal exposure to valproic acid (VPA) in mice causes autism-like behavioral abnormalities, including social interaction deficits, anxiety-like behavior and spatial learning disability, in male offspring."	7.80	Chronic treatment with valproic acid or sodium butyrate attenuates novel object recognition deficits and hippocampal dendritic spine loss in a mouse model of autism. ( Ago, Y; Hara, Y; Hashimoto, H; Hayata-Takano, A; Kataoka, S; Kawanai, T; Maeda, Y; Matsuda, T; Takano, E; Takuma, K; Watanabe, R, 2014)
"Levetiracetam has been reported to be well tolerated and effective in status epilepticus (SE) refractory to benzodiazepine."	7.79	The effect of levetiracetam on status epilepticus-induced neuronal death in the rat hippocampus. ( Choi, HC; Kang, TC; Kim, JE; Kim, YI; Lee, DS; Ryu, HJ; Song, HK, 2013)
" (MQ) in maximal electroshock (MES) and pentylenetetrazole (PTZ) induced rat models of epilepsy."	7.79	Evaluation of anti-epileptic property of Marsilea quadrifolia Linn. in maximal electroshock and pentylenetetrazole-induced rat models of epilepsy. ( Avinash, H; Chandrashekar, BR; Mukunda, N; Naduvil Narayanan, S; Nayak, BS; Raghavendra Rao, K; Sadhana, N; Satish Kumar, MC; Snehunsu, A; Vijay Kapgal, K, 2013)
" Using the prenatal valproic acid (VPA)-injection model of autism spectrum disorder (ASD) in rats, which produces social impairrment and altered seizure susceptibility as in human ASD patients as well as mild neural tube defects like crooked tail phenotype, we examined whether chronic administration of red ginseng extract may rescue the social impairment and crooked tail phenotype in prenatally VPA-exposed rat offspring."	7.79	Effects of Korean red ginseng extracts on neural tube defects and impairment of social interaction induced by prenatal exposure to valproic acid. ( Han, SH; Kim, HJ; Kim, HY; Kim, KC; Kim, P; Kwon, KJ; Lee, JM; Park, JH; Shin, CY, 2013)
" This study was designed to evaluate the effect of valproic acid (VPA) and progesterone (P4) in a rat model of endometriosis on serum tumor necrosis factor-α (TNF-α) levels, hot plate and tail-flick latencies, lesion size, and body weight."	7.78	Valproic acid and progestin inhibit lesion growth and reduce hyperalgesia in experimentally induced endometriosis in rats. ( Guo, SW; Liu, M; Liu, X; Zhang, Y, 2012)
" Both valproic acid, a class I HDAC inhibitor, and suberoylanilide hydroxamic acid (vorinostat), an inhibitor of class I, II, and IV HDACs, mitigated the development of and reduced established hypoxia-induced pulmonary hypertension in the rat."	7.78	Histone deacetylation inhibition in pulmonary hypertension: therapeutic potential of valproic acid and suberoylanilide hydroxamic acid. ( Chen, CN; Cotroneo, E; Hajji, N; Li, M; McKinsey, TA; Oliver, E; Stenmark, KR; Wang, D; Wharton, J; Wilkins, MR; Zhao, L, 2012)
" We studied the potential anticonvulsant effect of thalidomide: Different doses of thalidomide were tested against seizures induced by 50 mg/kg or 70 mg/kg of pentylenetetrazole (PTZ); the anticonvulsant effect of thalidomide was also compared with that of valproic acid."	7.74	Thalidomide inhibits pentylenetetrazole-induced seizures. ( Calderon, A; Palencia, G; Sotelo, J, 2007)
" The combination of AGLD (5 mg/kg) with phenobarbital (PB, applied at its subeffective dose of 15 mg/kg) significantly shortened motor seizure and afterdischarge duration in amygdala-kindled seizures."	7.73	Aminoglutethimide but not spironolactone enhances the anticonvulsant effect of some antiepileptics against amygdala-kindled seizures in rats. ( Borowicz, KK; Czuczwar, SJ, 2005)
") continuous valproic acid (VPA) infusion, as compared with acute injections in the kindling epilepsy model."	7.73	Effect of intracerebroventricular continuous infusion of valproic acid versus single i.p. and i.c.v. injections in the amygdala kindling epilepsy model. ( Alós, M; Barcia, JA; Durán, C; Hernández, ME; Ortiz, P; Serralta, A, 2006)
" In this study, we investigated whether valproic acid (VPA), a known mood stabilizer and anticonvulsant with HDAC-inhibiting activity, improves survival following otherwise lethal hemorrhage in rats."	7.73	Valproic acid prevents hemorrhage-associated lethality and affects the acetylation pattern of cardiac histones. ( Alam, HB; Britten-Webb, J; Burris, D; Chen, H; Gonzales, E; Koustova, E; Mehrani, T; Munuve, R; Nadel, A; Wherry, D, 2006)
" Pentylenetetrazole (PTZ)-induced seizures were used to evaluate the anticonvulsant effect of drugs."	7.73	Modulation of pentylenetetrazole-induced seizures and oxidative stress parameters by sodium valproate in the absence and presence of N-acetylcysteine. ( Pillai, KK; Uma Devi, P; Vohora, D, 2006)
" Maternal treatment with valproic acid (VPA) during pregnancy induces NTD in susceptible fetuses."	7.73	Effect of maternal exposure to homocystine on sodium valproate-induced neural tube defects in the mouse embryos. ( Benedict, S; Nagelkerke, N; Padmanabhan, R; Shafiullah, M, 2006)
"To develop novel orthotopic xenograft models of medulloblastoma in severe combined immunodeficient mice and to evaluate the in vivo antitumor efficacy of valproic acid."	7.73	Valproic Acid prolongs survival time of severe combined immunodeficient mice bearing intracerebellar orthotopic medulloblastoma xenografts. ( Adesina, A; Antalffy, B; Blaney, SM; Lau, CC; Li, XN; Ou, CN; Pietsch, T; Shu, Q; Su, JM, 2006)
" Periconceptional folic acid supplementation is reported to protect embryos from developing neural tube defects (NTD)."	7.72	Amelioration of sodium valproate-induced neural tube defects in mouse fetuses by maternal folic acid supplementation during gestation. ( Padmanabhan, R; Shafiullah, MM, 2003)
"Valproic acid (VPA) treatment in female patients is suggested to be associated with the occurrence of a variety of endocrine side effects that include many characteristic symptoms of polycystic ovary syndrome (PCOS)."	7.72	Valproic acid fails to induce polycystic ovary syndrome in female rats. ( Lagace, DC; Nachtigal, MW, 2003)
" Anticonvulsant effects were evaluated against seizures induced by 14 mg kg(-1) of 4-aminopyridine (4-AP) and by 110 mg kg(-1) of pentylenetetrazole (PTZ), and neurotoxicity by the rotarod test."	7.72	Is the interaction between felbamate and valproate against seizures induced by 4-aminopyridine and pentylenetetrazole in mice beneficial? ( Amat, G; Armijo, JA; Cuadrado, A, 2003)
"We investigated the effects of valproate (VPA) on an in vivo model of status epilepticus (SE) induced by intrahippocampal application of 4-aminopyridine (4-AP)."	7.72	Valproate suppresses status epilepticus induced by 4-aminopyridine in CA1 hippocampus region. ( Martín, ED; Pozo, MA, 2003)
" The aim of this study was to evaluate the profile of interactions between FBM and four conventional antiepileptic drugs (AEDs): clonazepam (CZP), ethosuximide (ESM), phenobarbital (PB), and valproate (VPA), in pentylenetetrazole (PTZ)-induced convulsions in mice, a model of myoclonic seizures in humans."	7.72	Isobolographic and subthreshold analysis of interactions among felbamate and four conventional antiepileptic drugs in pentylenetetrazole-induced seizures in mice. ( Borowicz, KK; Czuczwar, SJ; Luszczki, JJ, 2004)
"A potential model for bipolar disorder, quinpirole-induced biphasic locomotion, was used for a preliminary evaluation of behavioral effects of oral anticonvulsant treatment."	7.71	Preliminary evaluation of oral anticonvulsant treatment in the quinpirole model of bipolar disorder. ( Belmaker, RH; Einat, H; Shaldubina, A; Shimon, H; Szechtman, H, 2002)
"The efficacy of Flunarizine (FLU), a calcium channel blocker, in combination with conventional antiepileptic drugs, phenytoin (PHT), carbamazepine (CBZ), sodium valproate (VPA), and ethosuximide (ESM), at ED50 doses, were examined for protective effects against maximal electroshock seizures (MES) and pentylenetetrazol (PTZ) induced seizures in mice."	7.70	Additive anticonvulsant effect of flunarizine and sodium valproate on electroshock and chemoshock induced seizures in mice. ( David, J; Joseph, S; Joseph, T, 1998)
"Perimenstrual catamenial epilepsy, the exacerbation of seizures in association with menstruation, may in part be due to withdrawal of the progesterone metabolite allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), an endogenous anticonvulsant neurosteroid that is a positive allosteric modulator of gamma-aminobutyric acid(A) receptors."	7.70	Enhanced anticonvulsant activity of ganaxolone after neurosteroid withdrawal in a rat model of catamenial epilepsy. ( Reddy, DS; Rogawski, MA, 2000)
"Valproic acid-treated animals had significantly less neurologic impairment on days 2 (16."	7.30	Prolonging the therapeutic window for valproic acid treatment in a swine model of traumatic brain injury and hemorrhagic shock. ( Alam, HB; Chtraklin, K; Dimonte, D; Ho, JW; Jin, G; Joaquin, TA; Keeney-Bonthrone, TP; Latif, Z; Ober, RA; Pai, MP; Vercruysse, C; Wen, B, 2023)
"Valproic acid (VPA) is an anticonvulsant and mood stabilizer that, when used during the gestational period, increases the risk of ASD in the offspring."	6.58	Neuroimmune Alterations in Autism: A Translational Analysis Focusing on the Animal Model of Autism Induced by Prenatal Exposure to Valproic Acid. ( Bambini-Junior, V; Deckmann, I; Fontes-Dutra, M; Gottfried, C; Schwingel, GB, 2018)
"Valproic acid (VPA) is a known human teratogen."	6.45	Valproic acid in pregnancy: how much are we endangering the embryo and fetus? ( Ornoy, A, 2009)
"Valproic acid (VPA) is an effective drug, which is preferred for the treatments of epilepsy and various kinds of seizures."	6.44	The effects of valproic acid neurotoxicity on aggressive behavior in zebrafish autism model. ( Feng, T; Li, X; Lu, W, 2024)
"Thymol is a bioactive monoterpene isolated from Thymus vulgaris that has anti-inflammatory properties and is helpful in neurodevelopmental disorders."	5.91	Thymol improves autism-like behaviour in VPA-induced ASD rats through the Pin1/p38 MAPK pathway. ( Chen, J; Li, Y; Lv, M; Tang, B; Wang, F; Xiong, Y; Zhang, H, 2023)
" The repetitive behaviors were ameliorated relatively in VPA groups with NEPO2000 treatment, and astrogliosis was reduced even when VPA rats were treated with a lower dosage of NEPO."	5.91	Astrocyte responses to postnatal erythropoietin and nano-erythropoietin treatments in a valproic acid-induced animal model of autism. ( Basiri, M; Haratizadeh, S; Nozari, M; Ranjbar, M, 2023)
"Many studies show that the number of cognitive impairmentscan be reduced by antagonists of the histamine H3 receptor (H3R)."	5.91	Amelioration of cognition impairments in the valproic acid-induced animal model of autism by ciproxifan, a histamine H3-receptor antagonist. ( Esmaeilpour, K; Sepehri, G; Sheibani, V; Shekari, MA; Taheri, F, 2023)
"Valproic acid (VPA) is a well-known anti-epileptic drug, but its prenatal exposure to animals causes social impairment, neurotransmitters imbalance, and neuroinflammation with ASD-like phenotypes."	5.91	Syringic acid alleviates valproic acid induced autism via activation of p38 mitogen-activated protein kinase: Possible molecular approach. ( Mallan, S; Singh, S, 2023)
"The mouse model of autism induced by prenatal exposure to valproic acid (VPA) was used to assess the therapeutic potential of STX209 on autism‑like behaviour in the present study."	5.72	The GABAB receptor agonist STX209 reverses the autism‑like behaviour in an animal model of autism induced by prenatal exposure to valproic acid. ( Chang, H; Ding, J; Gao, C; He, M; Jiang, S; Li, W; Sun, T; Sun, Y; Wang, F; Wang, Y; Xiao, L; Zhu, C, 2022)
" Pregnant C57BL/6 J mice were intraperitoneally injected with a dosage of 500 mg/kg valproic acid (VPA) on embryonic day 10."	5.72	Size anomaly and alteration of GABAergic enzymes expressions in cerebellum of a valproic acid mouse model of autism. ( Kwan, KM; Ma, SY, 2022)
"Valproic acid (VPA) has been extensively used for treatment of anxiety and seizure."	5.72	Valproic acid during hypotensive resuscitation in pigs with trauma and hemorrhagic shock does not improve survival. ( Bynum, J; Cap, AP; Martini, WZ; Ryan, KL; Xia, H, 2022)
"Autism spectrum disorder is a neurodevelopmental disorder characterized by sensory abnormalities, social skills impairment and cognitive deficits."	5.72	Alterations in the intrinsic discharge activity of CA1 pyramidal neurons associated with possible changes in the NADPH diaphorase activity in a rat model of autism induced by prenatal exposure to valproic acid. ( Behzadi, G; Borjkhani, M; Davoudi, S; Hajisoltani, R; Hosseinmardi, N; Janahmadi, M; Karimi, SA; Khatibi, VA; Rahdar, M, 2022)
"Previous studies have indicated that autism-like behavioral phenotypes detected in F1 VPA mice transgenetically appear in F2 and F3 generations."	5.72	Early-onset of social communication and locomotion activity in F2 pups of a valproic acid-induced mouse model of autism. ( Fu, P; Furuhara, K; Higashida, H; Minami, K; Mizutani, R; Tsuji, C; Tsuji, T; Yokoyama, S; Zhong, J, 2022)
"Melatonin is an endogenous hormone and can restore gut microbial dysbiosis under various disease conditions."	5.72	Rescue of social deficits by early-life melatonin supplementation through modulation of gut microbiota in a murine model of autism. ( Cui, Y; Li, XG; Liu, W; Liu, X; Qiu, B; Wang, X; Xiang, G; Yu, M; Zhang, D; Zhang, Y, 2022)
"Valproic acid-treated animals demonstrated significantly less neurologic impairment on PID 1 and returned to baseline faster (PID 1 mean neurologic severity score, control = 22 ± 3 vs."	5.62	Administration of valproic acid in clinically approved dose improves neurologic recovery and decreases brain lesion size in swine subjected to hemorrhagic shock and traumatic brain injury. ( Alam, HB; Bhatti, UF; Biesterveld, BE; Chtraklin, K; Kemp, MT; O'Connell, RL; Pai, MP; Siddiqui, AZ; Srinivasan, A; Vercruysse, CA; Wakam, GK; Williams, AM, 2021)
"Despite the increasing prevalence of autism spectrum disorder (ASD), there is still a deficiency in understanding its exact pathophysiology and treatment, therefore validation of translational ASD animal model is warranted."	5.62	Validation of prenatal versus postnatal valproic acid rat models of autism: A behavioral and neurobiological study. ( Abdelraouf, SM; Aboul-Fotouh, S; Abuelezz, SA; Ahmed, AI; Bahaa, N; Elnahas, EM; Hassan, GA; Ibrahim, EA; Mohamad, MI; Nabil, MM, 2021)
"Like valproic acid, treatment with primidone reduced free-C levels in LE/LY in NPC1-null/mutant cells."	5.62	Beneficial effects of primidone in Niemann-Pick disease type C (NPC)-model cells and mice: Reduction of unesterified cholesterol levels in cells and extension of lifespan in mice. ( Ashikawa, H; Honda, T; Mogi, H; Murayama, T; Nakamura, H, 2021)
"Epilepsy is one of the most frequent neurological disorders characterized by an enduring predisposition to generate epileptic seizures."	5.62	Histopathological and Biochemical Assessment of Neuroprotective Effects of Sodium Valproate and Lutein on the Pilocarpine Albino Rat Model of Epilepsy. ( Al-Rafiah, AR; Mehdar, KM, 2021)
"Suramin treatment did not affect VPA-induced upregulation of P2X4 and P2Y2 receptor expression in the hippocampus, and P2X4 receptor expression in the medial prefrontal cortex, but normalized an increased level of interleukin 6 (IL-6)."	5.56	Effects of single-dose antipurinergic therapy on behavioral and molecular alterations in the valproic acid-induced animal model of autism. ( Bambini-Junior, V; Bauer-Negrini, G; Brum Schwingel, G; Carello-Collar, G; Castillo, ARG; Corrêa-Velloso, J; Deckmann, I; Fontes-Dutra, M; Gonçalves, MCB; Gottfried, C; Hirsch, MM; Körbes-Rockenbach, M; Naaldijk, Y; Rabelo, B; Santos-Terra, J; Schneider, T; Staevie, GZ; Ulrich, H, 2020)
"Corticosterone plasma level was increased in the CUMS compared to the non-stressed group (p < 0."	5.56	Valproic acid administration exerts protective effects against stress-related anhedonia in rats. ( Barati, M; Eslami, M; Goudarzi, M; Mehrabi, S; Nahavandi, A; Shahbazi, A, 2020)
"The manifestations of autism spectrum disorder (ASD) are highly heterogeneous."	5.56	Vitamin A deficiency exacerbates autism-like behaviors and abnormalities of the enteric nervous system in a valproic acid-induced rat model of autism. ( Chen, J; Cheng, B; Li, T; Liu, H; Wang, S; Wu, Q; Yang, T; Zhang, X; Zhu, J, 2020)
"The social motivational theory of autism spectrum disorder (ASD) focuses on social anhedonia as key causal feature of the impaired peer relationships that characterize ASD patients."	5.56	Targeting PPARα in the rat valproic acid model of autism: focus on social motivational impairment and sex-related differences. ( Braccagni, G; De Montis, MG; Gambarana, C; Guzzi, F; Parenti, M; Scheggi, S, 2020)
"A structural, electrical and metabolic atrial remodeling is central in the development of atrial fibrillation (AF) contributing to its initiation and perpetuation."	5.51	HDAC (Histone Deacetylase) Inhibitor Valproic Acid Attenuates Atrial Remodeling and Delays the Onset of Atrial Fibrillation in Mice. ( Hamer, S; Hammer, E; Himmler, K; Müller, FU; Pluteanu, F; Scholz, B; Schulte, JS; Seidl, MD; Stein, J; Völker, U; Wardelmann, E, 2019)
"Sepsis is a leading cause of death and disability worldwide."	5.51	Valproic acid attenuates sepsis-induced myocardial dysfunction in rats by accelerating autophagy through the PTEN/AKT/mTOR pathway. ( Liu, Y; Shi, X; Xiao, D; Zhang, D, 2019)
"Combined traumatic brain injury and hemorrhagic shock are highly lethal."	5.48	Improvement of Blood-Brain Barrier Integrity in Traumatic Brain Injury and Hemorrhagic Shock Following Treatment With Valproic Acid and Fresh Frozen Plasma. ( Alam, HB; Andjelkovic, AV; Bambakidis, T; Dekker, SE; Dennahy, IS; Georgoff, PE; Higgins, GA; Nikolian, VC; Williams, AM, 2018)
"Valproic acid (VPA) is a histone deacetylase inhibitor that improves outcomes in large animal models of trauma."	5.48	Valproic acid induces prosurvival transcriptomic changes in swine subjected to traumatic injury and hemorrhagic shock. ( Alam, HB; Athey, B; Chtraklin, K; Eidy, H; Georgoff, PE; Ghandour, MH; Higgins, G; Nikolian, VC; Williams, A, 2018)
"Curcumin is a phytochemical with promising effects on epilepsy treatment."	5.48	Micronization potentiates curcumin's anti-seizure effect and brings an important advance in epilepsy treatment. ( Aguiar, GPS; Bertoncello, KT; Oliveira, JV; Siebel, AM, 2018)
"Autism is characterized by numerous behavioral impairments, such as in communication, socialization and cognition."	5.48	Zinc as a therapy in a rat model of autism prenatally induced by valproic acid. ( Bernardi, MM; Cezar, LC; da Fonseca, CCN; de Lima, APN; Felicio, LF; Kirsten, TB, 2018)
"Rats of the VPA model of autism showed reduced total reciprocal social interaction, prevented by prenatal treatment with resveratrol (RSV)."	5.48	Behavioral alterations in autism model induced by valproic acid and translational analysis of circulating microRNA. ( Bambini-Junior, V; Bauer-Negrini, G; Deckmann, I; Della-Flora Nunes, G; Fontes-Dutra, M; Gottfried, C; Hirsch, MM; Margis, R; Nunes, W; Rabelo, B; Riesgo, R, 2018)
"The etiology of autism remains unknown and its molecular basis is not yet well understood."	5.48	Social behavior, neuroimmune markers and glutamic acid decarboxylase levels in a rat model of valproic acid-induced autism. ( Imai, M; Lwin, TT; Mar, O; Nway, NC; Watanabe, H; Win-Shwe, TT, 2018)
" The aim of the study was to conduct an in vivo evaluation of the relationship between treatments with synthetic cannabinoid arachidonyl-2'-chloroethylamide (ACEA) alone or in combination with valproic acid (VPA) and hippocampal neurogenesis in a mouse pilocarpine model of epilepsy."	5.46	A Long-Term Treatment with Arachidonyl-2'-Chloroethylamide Combined with Valproate Increases Neurogenesis in a Mouse Pilocarpine Model of Epilepsy. ( Andres-Mach, M; Dudra-Jastrzębska, M; Haratym, J; Haratym-Maj, A; Maj, M; Rola, R; Zagaja, M; Łuszczki, JJ, 2017)
"Valproic acid-treated animals demonstrated significantly less neurologic impairment between PID 1 to 5 and smaller brain lesions on PID 3 (mean lesion size ± SEM, mm: ISCS = 4,956 ± 1,511 versus ISCS + VPA = 828 ± 279; p = 0."	5.46	Valproic acid decreases brain lesion size and improves neurologic recovery in swine subjected to traumatic brain injury, hemorrhagic shock, and polytrauma. ( Alam, HB; Chtraklin, K; Dennahy, IS; Eidy, H; Georgoff, PE; Ghandour, MH; Han, Y; Li, Y; Nikolian, VC; Pai, MP; Srinivasan, A, 2017)
"The novel therapeutic strategy against autism is essential due to the limited therapeutic efficacy."	5.46	Laser Acupuncture at HT7 Improves the Cerebellar Disorders in Valproic Acid-Rat Model of Autism. ( Khongrum, J; Wattanathorn, J, 2017)
"Valproic acid (VPA) is a short-chain branched fatty acid with anti-epileptic, neuro-protective and anti-inflammatory effects."	5.46	Valproic acid attenuates inflammation of optic nerve and apoptosis of retinal ganglion cells in a rat model of optic neuritis. ( Li, H; Liu, Q; Niu, X; Wang, Z; Yang, J; Zhao, C; Zhao, L, 2017)
"Chronic pain is a multifactorial disease comprised of both inflammatory and neuropathic components that affect ∼20% of the world's population."	5.46	sec-Butylpropylacetamide (SPD), a new amide derivative of valproic acid for the treatment of neuropathic and inflammatory pain. ( Bialer, M; Brennan, KC; Devor, M; Kaufmann, D; Smith, MD; West, PJ; White, HS; Yagen, B, 2017)
"Renal fibrosis is a common pathological feature of the progression of chronic kidney disease."	5.46	Valproic acid attenuates renal fibrosis through the induction of autophagy. ( Doi, S; Doi, T; Kawaoka, K; Masaki, T; Nakashima, A; Ueno, T; Yamada, K, 2017)
"Valproic acid (VA) has been shown to be neuroprotective in several experimental brain diseases."	5.43	Valproic Acid Pretreatment Reduces Brain Edema in a Rat Model of Surgical Brain Injury. ( Applegate, RL; Huang, L; Khatibi, NH; Krafft, P; Martin, RD; Rolland, W; Sherchan, P; Woo, W; Zhang, J, 2016)
"Traumatic brain injury and hemorrhagic shock (TBI+HS) elicit a complex inflammatory response that contributes to secondary brain injury."	5.43	Resuscitation with Valproic Acid Alters Inflammatory Genes in a Porcine Model of Combined Traumatic Brain Injury and Hemorrhagic Shock. ( Alam, HB; Bambakidis, T; de Vries, HE; Dekker, SE; Jin, G; Johnson, CN; Li, Y; Liu, B; Sillesen, M, 2016)
"Recently, the use of acute seizure tests in epileptic rats or mice has been proposed as a novel strategy for evaluating novel AEDs for increased antiseizure efficacy."	5.43	Evaluation of the pentylenetetrazole seizure threshold test in epileptic mice as surrogate model for drug testing against pharmacoresistant seizures. ( Löscher, W; Töllner, K; Twele, F, 2016)
"Valproic acid treated animals were treated from 5 days preceding behavioral testing in the Morris water maze at a clinically relevant concentration."	5.42	Standard dose valproic acid does not cause additional cognitive impact in a rodent model of intractable epilepsy. ( Jellett, AP; Jenks, K; Lucas, M; Scott, RC, 2015)
"Valproic acid (600 mg/kg) was administered intraperitoneally to the pregnant mice on gestational day 12."	5.42	Astaxanthin improves behavioral disorder and oxidative stress in prenatal valproic acid-induced mice model of autism. ( Al-Amin, MM; Khan, FR; Mahmud Reza, H; Rahman, MM; Zaman, F, 2015)
"Valproic acid (VPA) was described as a histone deacetylase inhibitor that had anti-inflammatory effects and reduced the production of proinflammatory cytokines in experimental autoimmune disease models."	5.42	Valproic Acid Ameliorates Graft-versus-Host Disease by Downregulating Th1 and Th17 Cells. ( Chang, L; Chen, Z; Dou, HB; Fang, WY; Gao, WH; Hu, J; Huang, MM; Long, J; Shan, JH; Shen, Y; Wang, Y; Wang, YY; Wu, YN; Zhu, J, 2015)
"The therapeutic strategy against autism, a severe neurological development disorder, is one of the challenges of this decade."	5.42	Laser Acupuncture Improves Behavioral Disorders and Brain Oxidative Stress Status in the Valproic Acid Rat Model of Autism. ( Khongrum, J; Wattanathorn, J, 2015)
"Valproic acid (VPA) has been reported to have survival and neuroprotective effects in a cardiac arrest rat model."	5.42	Effect of valproic acid combined with therapeutic hypothermia on neurologic outcome in asphyxial cardiac arrest model of rats. ( Hwang, JE; Jo, YH; Kim, K; Kim, MA; Lee, JH; Lee, MJ, 2015)
"Valproic acid (VPA) treatment protected hippocampal neurons from radiation-induced damage in both cell culture and animal models."	5.42	Valproic acid enhances the efficacy of radiation therapy by protecting normal hippocampal neurons and sensitizing malignant glioblastoma cells. ( DeWees, TA; Engelbach, JA; Garbow, JR; Hallahan, AN; Hallahan, DE; Karvas, RM; Laszlo, A; Thotala, D, 2015)
" In spite of limited results, the use of another dosage of VPA or of VPA in a combined therapy with molecules targeting other pathways, cannot be excluded as potential strategies for MJD therapeutics."	5.42	Limited Effect of Chronic Valproic Acid Treatment in a Mouse Model of Machado-Joseph Disease. ( Duarte-Silva, S; Esteves, S; Maciel, P; Naia, L; Neves-Carvalho, A; Rego, AC; Silva-Fernandes, A; Teixeira-Castro, A, 2015)
"Previously, autism spectrum disorder (ASD) has been identified mainly by social communication deficits and behavioral symptoms."	5.42	Alteration of spontaneous spectral powers and coherences of local field potential in prenatal valproic acid mouse model of autism. ( Cheaha, D; Kumarnsit, E, 2015)
"Valproic acid (VPA) has been known to reduce neuronal injury, has anti-inflammatory and anti-apoptotic effects as a histone deacetylase (HDAC) inhibitor."	5.39	Effect of valproic acid on survival and neurologic outcomes in an asphyxial cardiac arrest model of rats. ( Jo, YH; Kang, C; Kim, J; Kim, K; Kim, MA; Lee, JH; Lee, MJ; Lee, SH; Park, CJ; Rhee, JE, 2013)
"Autism is characterized by behavioral impairments in three main domains: social interaction; language, communication and imaginative play; and the range of interests and activities."	5.39	Increased hippocampal cell density and enhanced spatial memory in the valproic acid rat model of autism. ( Edalatmanesh, MA; Moghadas, M; Nikfarjam, H; Vafaee, F, 2013)
" This study describes synthesis and stereospecific comparative pharmacodynamics (PD, anticonvulsant activity and teratogenicity) and pharmacokinetic (PK) analysis of four individual SPD stereoisomers."	5.39	Stereoselective pharmacodynamic and pharmacokinetic analysis of sec-Butylpropylacetamide (SPD), a new CNS-active derivative of valproic acid with unique activity against status epilepticus. ( Bialer, M; Finnell, RH; Hen, N; McDonough, JH; Shekh-Ahmad, T; Wlodarczyk, B; Yagen, B, 2013)
"Vagus nerve stimulation prevents seizures by continuously activating noradrenergic projections from the brainstem to the cortex."	5.39	Closed-loop neural stimulation for pentylenetetrazole-induced seizures in zebrafish. ( Beattie, CE; Hall, CW; Pineda, R, 2013)
"Valproic acid (VPA) is a short-chain branched fatty acid with anti-inflammatory, neuro-protective and axon remodeling effects."	5.38	Valproic acid ameliorates inflammation in experimental autoimmune encephalomyelitis rats. ( Schluesener, HJ; Wu, Y; Zhang, Z; Zhang, ZY, 2012)
"One primary goal of medical treatment of endometriosis is to alleviate pain and there is a pressing need for new therapeutics for endometriosis with better efficacy and side-effect profiles."	5.37	Levo-tetrahydropalmatine retards the growth of ectopic endometrial implants and alleviates generalized hyperalgesia in experimentally induced endometriosis in rats. ( Guo, SW; Liu, X; Zhao, T; Zhen, X, 2011)
"In order to establish the etiology of autism with facial palsy, research into developmental abnormalities of the peripheral facial nerves is necessary."	5.37	Morphological abnormalities of embryonic cranial nerves after in utero exposure to valproic acid: implications for the pathogenesis of autism with multiple developmental anomalies. ( Imura, Y; Narita, M; Narita, N; Oyabu, A; Tashiro, Y; Uchida, A, 2011)
"Curcumin was co-administered with sub-therapeutic dose of valproate 60min before PTZ injection."	5.37	Pharmacokinetic and pharmacodynamic interactions of valproate, phenytoin, phenobarbitone and carbamazepine with curcumin in experimental models of epilepsy in rats. ( Gupta, YK; Mehla, J; Pahuja, M; Reeta, KH, 2011)
"Valproic acid treatment did not affect inflammation parameters; however, valproic acid treatment resulted in reduced epithelial thickness as compared to vehicle treated mice (p < 0."	5.37	Protective effects of valproic acid against airway hyperresponsiveness and airway remodeling in a mouse model of allergic airways disease. ( Dang, W; De Sampayo, N; El-Osta, A; Karagiannis, TC; Royce, SG; Tang, ML; Ververis, K, 2011)
"Autism is a behaviorally characterized disorder with impairments in social interactions, as well as stereotyped, repetitive patterns of behaviors and interests."	5.36	Nonexploratory movement and behavioral alterations in a thalidomide or valproic acid-induced autism model rat. ( Imura, Y; Kamada, N; Narita, M; Narita, N; Oyabu, A; Tano, K; Uchida, A; Yokoyama, T, 2010)
"Clonic seizures were rare in NMDA-treated P25 rats, but valproate pretreatment increased their incidence significantly."	5.36	Vigabatrin but not valproate prevents development of age-specific flexion seizures induced by N-methyl-D-aspartate (NMDA) in immature rats. ( Kubová, H; Mares, P, 2010)
" We report here that, while dietary supplementation with high VPA dosage slows down motor neuron death, as assessed by measurement of a specific marker for cholinergic neurons in the spinal cord, it has no significant effect on lifespan."	5.35	Long-term dietary administration of valproic acid does not affect, while retinoic acid decreases, the lifespan of G93A mice, a model for amyotrophic lateral sclerosis. ( Bonamassa, B; Canistro, D; Contestabile, A; Crochemore, C; Paolini, M; Pena-Altamira, E; Virgili, M, 2009)
"Autism is a severe behavioral disorder characterized by pervasive impairments in social interactions, deficits in verbal and non-verbal communication, and stereotyped behaviors, with a four times higher incidence in boys than in girls."	5.35	Gender-specific behavioral and immunological alterations in an animal model of autism induced by prenatal exposure to valproic acid. ( Basta-Kaim, A; Budziszewska, B; Kubera, M; Przewłocki, R; Roman, A; Schneider, K; Schneider, T, 2008)
"Using an amygdala-kindled seizure paradigm, we evaluated the acute and chronic anticonvulsant effects of lamotrigine (LTG)."	5.31	Tolerance to the anticonvulsant effects of lamotrigine on amygdala kindled seizures: cross-tolerance to carbamazepine but not valproate or diazepam. ( Heynen, T; Krupp, E; Li, XL; Post, RM; Weiss, SR, 2000)
"QUIN seizures showed particular sensitivity to carbamazepine (5 mg/kg) but were resistant to diphenylhydantoin unless a relatively high dose was used (100 mg/kg)."	5.27	Anticonvulsant drugs effective against human temporal lobe epilepsy prevent seizures but not neurotoxicity induced in rats by quinolinic acid: electroencephalographic, behavioral and histological assessments. ( Samanin, R; Tullii, M; Vezzani, A; Wu, HQ, 1986)
"Valproic acid (VPA) induced rodent model of autism is a widely accepted and extensively used rodent model to investigate the pharmacotherapy against autism."	5.22	Critical Evaluation of Valproic Acid-Induced Rodent Models of Autism: Current and Future Perspectives. ( Chopra, M; Mehra, S; Seth, E; Ul Ahsan, A, 2022)
" Previously, we have established a mouse model of ASD based on clinical research, which shows that exposure to valproic acid, an antiepileptic drug, during pregnancy causes an increase in the risk of developing ASD in children."	5.01	[Chronic Activation of the Dopaminergic Neuronal Pathway Improves Behavioral Abnormalities in the Prenatal Valproic Acid Exposure Mouse Model of Autism Spectrum Disorder]. ( Hara, Y, 2019)
" In particular, exposure to valproic acid (VPA) during pregnancy has been demonstrated to increase the risk of autism in children."	4.98	The valproic acid-induced rodent model of autism. ( Fahnestock, M; Nicolini, C, 2018)
"The mood stabilizers lithium, valproate and lamotrigine are traditionally used to treat bipolar disorder."	4.87	Beneficial effects of mood stabilizers lithium, valproate and lamotrigine in experimental stroke models. ( Chuang, DM; Fessler, EB; Wang, ZF, 2011)
"Administration of the antiepileptic drug valproic acid (VPA) during early pregnancy can result in a 1-2% incidence of spina bifida aperta, a closure defect of the posterior neural tube in the human."	4.78	Valproic acid-induced neural tube defects in mouse and human: aspects of chirality, alternative drug development, pharmacokinetics and possible mechanisms. ( Ehlers, K; Hauck, RS; Nau, H, 1991)
"In this study, based on the excitatory/inhibitory imbalance theory of autism, the time window of GABA switch, the role of K-Cl co-transporter 2 (KCC2) in adjustment GABA switch, and brain permeability to erythropoietin (EPO), the effects of postnatal -EPO and- nano- erythropoietin (NEPO) have been evaluated in the valproic acid (VPA) rat model of autism."	4.31	The effects of postnatal erythropoietin and nano-erythropoietin on behavioral alterations by mediating K-Cl co-transporter 2 in the valproic acid-induced rat model of autism. ( Basiri, M; Darvishzadeh-Mahani, F; Haratizadeh, S; Nozari, M; Ranjbar, M, 2023)
" The aim of this study was to determine the anticonvulsant profiles of scoparone (a simple coumarin) and borneol (a bicyclic monoterpenoid) when administered separately and in combination, as well as their impact on the antiseizure effects of four classic ASMs (carbamazepine, phenytoin, phenobarbital and valproate) in the mouse model of maximal electroshock-induced (MES) tonic-clonic seizures."	4.31	Antiseizure Effects of Scoparone, Borneol and Their Impact on the Anticonvulsant Potency of Four Classic Antiseizure Medications in the Mouse MES Model-An Isobolographic Transformation. ( Bojar, H; Góralczyk, A; Skalicka-Woźniak, K; Łuszczki, JJ, 2023)
"The prenatal valproic acid (VPA) model was used to induce autism-like behaviors in offspring rats."	4.31	Inhalation of Cananga odorata essential oil relieves anxiety behaviors in autism-like rats via regulation of serotonin and dopamine metabolism. ( Wang, ST; Yao, L; Zhang, N, 2023)
"Microglial dysfunction has been reported in the valproic acid (VPA)-induced autism spectrum disorder (ASD) rat models."	4.31	Prenatally VPA exposure is likely to cause autistic-like behavior in the rats offspring via TREM2 down-regulation to affect the microglial activation and synapse alterations. ( Chen, J; Hu, C; Li, T; Luo, L; Wei, H; Wu, Q; Yang, T; Yuan, B, 2023)
"Risperidone is the first antipsychotic to be approved by Food and Drug Administration (FDA) for treating autism spectrum disorder (ASD)."	4.31	The comparative effectiveness of metformin and risperidone in a rat model of valproic acid-induced autism, Potential role for enhanced autophagy. ( Ashour, RH; Atia, AA; Rahman, KM; Ramadan, NM; Zaki, MM, 2023)
" Valproic acid (VPA) is an anticonvulsant drug that, when administered during pregnancy, causes various birth defects."	4.31	Social deficits in mice prenatally exposed to valproic acid are intergenerationally inherited and rescued by social enrichment. ( Barrios, CD; Depino, AM; Zappala, C, 2023)
" VPA-exposed male pups were administered with two doses of ibudilast (5 and10 mg/kg) and all the groups were evaluated for behavioral parameters like social interaction, spatial memory/learning, anxiety, locomotor activity, and nociceptive threshold."	4.31	Phosphodiesterase inhibitor, ibudilast alleviates core behavioral and biochemical deficits in the prenatal valproic acid exposure model of autism spectrum disorder. ( Gautam, V; Kumar, A; Rawat, K; Saha, L; Sandhu, A; Sharma, A, 2023)
"Valproic acid (VPA) treatment during pregnancy is a risk factor for developing autism spectrum disorder, cognitive deficits, and stress-related disorders in children."	4.31	Adolescent swimming exercise following maternal valproic acid treatment improves cognition and reduces stress-related symptoms in offspring mice: Role of sex and brain cytokines. ( Amouzad Mahdirejei, H; Barzegari, A; Esmaeili, MH; Hanani, M; Salari, AA, 2023)
"N-acetylcysteine (NAC) has been reported to improve social interaction behavior, irritability, self-injury, and anxiety-like behavior in autism."	4.31	N-acetylcysteine improves autism-like behavior by recovering autophagic deficiency and decreasing Notch-1/Hes-1 pathway activity. ( Deng, YN; He, XL; Li, YF; Wang, LJ; Wang, T; Zhang, YH, 2023)
" Valproic acid (VPA) exposure during pregnancy causes autistic-like traits in offspring."	4.31	The antipsychotic olanzapine reduces memory deficits and neuronal abnormalities in a male rat model of Autism. ( Aguilar-Hernandez, L; Bringas, ME; Flores, G; Garcés-Ramírez, L; Lima-Castañeda, LÁ; Morales-Medina, JC, 2023)
"Prenatal exposure to valproic acid (VPA) may enhance the risk of autism spectrum disorder (ASD) in children."	4.31	Prangos ferulacea (L.) ameliorates behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid. ( Aldaghi, MR; Raise-Abdullahi, P; Saadat, M; Sameni, HR; Taherian, AA; Vafaei, AA, 2023)
"This study aims to understand the relationship between fecal metabolites and gut microbiota in an adolescent valproic acid-induced rat autism model (VPA-exposed offspring)."	4.12	Correlation among gut microbiota, fecal metabolites and autism-like behavior in an adolescent valproic acid-induced rat autism model. ( Gu, Y; Han, Y; Qin, J; Ren, S; Wang, X; Zhang, B; Zhang, S; Zhao, Y, 2022)
"Autism spectrum disorder (ASD) is a developmental disorder associated with in utero exposure to the antiepileptic valproic acid (VPA) in humans, and similar exposure serves as a validated animal model."	4.12	Brainstem motor neuron dysmorphology and excitatory/inhibitory imbalance in an animal model of autism. ( Alhelo, H; Kulesza, RJ, 2022)
" Therefore, in this study, we focused on the rapid and persistent neuroprotective function of DLX following valproic acid (VPA)-triggered hyperactivity, anxiety-like behavior and social deficits in zebrafish."	4.12	Duloxetine ameliorates valproic acid-induced hyperactivity, anxiety-like behavior, and social interaction deficits in zebrafish. ( Chen, H; Joseph, TP; Lin, SL; Sai, LY; Schachner, M; Zhou, F, 2022)
" The anxiety induced by pilocarpine was also significantly (P < 0."	4.12	Anticonvulsant effects of Cymbopogon giganteus extracts with possible effects on fully kindled seizures and anxiety in experimental rodent model of mesio-temporal epilepsy induced by pilocarpine. ( Bum, EN; Kouemou Emegam, N; Neteydji, S; Pale, S; Taiwe, GS, 2022)
" Valproic acid (VPA) injection during pregnancy elicits autism-like behavior in the offspring, making it a classic animal model of ASD."	4.12	iTRAQ-Based Proteomics Analysis of Rat Cerebral Cortex Exposed to Valproic Acid before Delivery. ( Cao, X; Chen, M; Lin, J; Liu, X; Shen, L; Tang, X; Ullah Khan, N; Zhang, H; Zhang, K; Zhao, Y, 2022)
"Valproic acid (VPA) exposure as an environmental factor that confers risk of autism spectrum disorder (ASD), its functional mechanisms in the human brain remain unclear since relevant studies are currently restricted to two-dimensional cell cultures and animal models."	4.12	Human forebrain organoids reveal connections between valproic acid exposure and autism risk. ( Chen, C; Jiao, C; Liu, C; Meng, Q; Tang, B; Wang, X; Xu, S; Zhang, W, 2022)
"Maternal exposure to anti-epileptic drug Valproic acid (VPA) during pregnancy increases the risk for the development of autism spectrum disorders (ASD)."	4.12	Prenatal exposure to valproic acid alters Reelin, NGF expressing neuron architecture and impairs social interaction in their autistic-like phenotype male offspring. ( Rajan, KE; Sivasangari, K, 2022)
" Here we examine the effects of valproic acid (VA) plus 4-phenylbutyric acid (4-PBA) on abnormal electrical brain activity, ER stress and apoptosis in acute seizures induced by pentylenetetrazole (PTZ)."	4.12	4-Phenylbutyric Acid Plus Valproic Acid Exhibits the Therapeutic and Neuroprotective Effects in Acute Seizures Induced by Pentylenetetrazole. ( Amanvermez, R; Arslan, G; Gün, S; Rzayev, E; Tiryaki, ES, 2022)
"Valproic acid (VPA) is a clinically used antiepileptic drug, but it is associated with a significant risk of a low verbal intelligence quotient (IQ) score, attention-deficit hyperactivity disorder and autism spectrum disorder in children when it is administered during pregnancy."	4.12	A CCR5 antagonist, maraviroc, alleviates neural circuit dysfunction and behavioral disorders induced by prenatal valproate exposure. ( Honda, T; Ishihara, N; Ishihara, Y; Itoh, K; Namba, K; Taketoshi, M; Tominaga, T; Tominaga, Y; Tsuji, M; Vogel, CFA; Yamazaki, T, 2022)
"We previously demonstrated that prenatal exposure to valproic acid (VPA), an environmental model of autism spectrum disorder (ASD), leads to a hyperexcitable phenotype associated with downregulation of inward-rectifying potassium currents in nucleus accumbens (NAc) medium spiny neurons (MSNs) of adolescent rats."	4.12	Acute rapamycin rescues the hyperexcitable phenotype of accumbal medium spiny neurons in the valproic acid rat model of autism spectrum disorder. ( Costa, A; Curti, L; D'Ambrosio, M; Gerace, E; Iezzi, D; Ilari, A; La Rocca, A; Luceri, C; Mannaioni, G; Masi, A; Ranieri, G; Scardigli, M; Silvestri, L, 2022)
"This study aimed to explore the effect of concomitant use of Furosemide (FRS) and Valproic acid (VPA), demonstrating anti-inflammation efficacy, on epilepsy, and its underlying mechanism."	4.12	The effect of valproic acid and furosemide on the regulation of the inflammasome complex (NLRP1 and NLRP3 mRNA) in the brain of epileptic animal model. ( Abdolmaleki, Z; Faedmaleki, F; Samadianzakaria, A, 2022)
"Prenatal exposure to valproic acid (VPA) has been implicated in the manifestation of autism spectrum disorder (ASD)-like behavioral and functional changes both in human and rodents including mice and rats."	4.12	Metabolomics profiling of valproic acid-induced symptoms resembling autism spectrum disorders using 1H NMR spectral analysis in rat model. ( Kim, HY; Kim, JW; Kim, KB; Kim, S; Kim, SJ; Ko, MJ; Lee, JD; Lee, YJ; Shin, CY, 2022)
"The cilostazol regimen, attenuated prenatal VPA exposure associated hyperlocomotion, social interaction deficits, repetitive behavior, and anxiety."	4.02	Cilostazol attenuated prenatal valproic acid-induced behavioural and biochemical deficits in a rat model of autism spectrum disorder. ( Kulkarni, GT; Luhach, K; Sharma, B; Singh, VP, 2021)
"We previously showed that the addition of valproic acid (VPA), a histone deacetylase inhibitor, to fresh frozen plasma (FFP) resuscitation attenuates brain lesion size and swelling following traumatic brain injury (TBI) and hemorrhagic shock (HS)."	4.02	Modulation of Brain Transcriptome by Combined Histone Deacetylase Inhibition and Plasma Treatment Following Traumatic Brain Injury and Hemorrhagic Shock. ( Alam, HB; Bambakidis, T; Biesterveld, BE; Dekker, SE; Johnson, CN; Li, Y; Liu, B; Sillesen, M; Tagett, R; Williams, AM, 2021)
" We exploited 2 different animal models of autism, the methyl CpG binding protein 2-null (Mecp2y/-) mouse model of Rett syndrome and mice prenatally exposed to valproic acid, and found increased ATM levels."	4.02	The DNA repair protein ATM as a target in autism spectrum disorder. ( Antonucci, F; Bifari, F; Cambria, C; Desiato, G; Ferrara, S; Focchi, E; Landsberger, N; Matteoli, M; Menna, E; Murru, L; Passafaro, M; Pizzamiglio, L; Ponzoni, L; Sala, M, 2021)
" The present work aimed to detect changes in the AVP numbers and level in a valproic acid (VPA)-induced rat model of autism and the underlying mechanism of its pathogenesis."	4.02	Postnatal AVP treatments prevent social deficit in adolescence of valproic acid-induced rat autism model. ( Bai, SZ; Dai, YC; Han, JS; Han, SP; Hu, Y; Lan, XY; Wu, J; Zhang, HF; Zhang, R, 2021)
" In the pharmacodynamic interaction study, seizures were induced using pentylenetetrazole (PTZ) (60 mg/kg, i."	4.02	Pharmacodynamic and pharmacokinetic interactions of hydroalcoholic leaf extract of Centella asiatica with valproate and phenytoin in experimental models of epilepsy in rats. ( Agarwal, A; Arora, R; Ganeshan N, S; Gupta, YK; Kaleekal, T; Kumar, R; Sarangi, SC, 2021)
" In this study, we examined the effect of both acute and chronic treatment with moclobemide on seizures and the action of first-generation antiepileptic drugs: valproate, carbamazepine, phenobarbital and phenytoin."	4.02	Acute and chronic treatment with moclobemide, a reversible MAO-inhibitor, potentiates the antielectroshock activity of conventional antiepileptic drugs in mice. ( Banach, M; Borowicz-Reutt, KK, 2021)
" For the first time, we assessed the synthesis of 5-hydroxytryptamine (5HT) and the metabolic capacity of the 5HT system in the peripheral and central nervous systems (PNS and CNS, respectively) based on tryptophan metabolism based on VPA-induced autism model."	4.02	Daily intake of Lactobacillus alleviates autistic-like behaviors by ameliorating the 5-hydroxytryptamine metabolic disorder in VPA-treated rats during weaning and sexual maturation. ( Chen, W; Kong, Q; Li, X; Tian, P; Wang, B; Wang, G; Zhang, H; Zhao, J, 2021)
"The development of refractory status epilepticus (SE) induced by sarin intoxication presents a therapeutic challenge."	4.02	Neuroprotection by delayed triple therapy following sarin nerve agent insult in the rat. ( Baranes, S; Chapman, S; David, T; Dekel Jaoui, H; Efrati, R; Egoz, I; Gez, R; Gore, A; Grauer, E; Lazar, S; Neufeld-Cohen, A; Yampolsky, M, 2021)
" The present work detected the effects of pregnancy supplementation with folic acid (FA) at different doses on rat models of ASD induced by prenatal exposure to valproic acid (VPA), an anti-epileptic increasing the risk of ASD when administered during pregnancy."	4.02	Maternal folic acid supplementation prevents autistic behaviors in a rat model induced by prenatal exposure to valproic acid. ( Cheng, Q; Di, Y; Fan, J; Kang, M; Lan, J; Li, J; Li, Z; Ren, W; Tian, Y; Wei, C; Zhai, C; Zheng, Q, 2021)
"It has been reported that valproic acid (VPA) combined with therapeutic hypothermia can improve survival and neurologic outcomes in a rat asphyxial cardiac arrest model."	4.02	HSP70-mediated neuroprotection by combined treatment of valproic acid with hypothermia in a rat asphyxial cardiac arrest model. ( Choi, KH; Choi, S; Jeong, HH; Kim, K; Oh, JS; Oh, YM; Park, J, 2021)
" Exposure to the antiepileptic drug valproic acid (VPA) during pregnancy significantly increases the risk of ASD in humans, and consequently is utilized as a validated animal model of ASD in rodents; however, the precise molecular and cellular mechanisms remain ill-defined."	4.02	Abnormal spatiotemporal expression pattern of progranulin and neurodevelopment impairment in VPA-induced ASD rat model. ( Chen, D; Hu, Y; Lan, J; Li, Y; Liao, A; Wang, S; Wang, X; Wang, Y; Yang, F; Zheng, W, 2021)
"Prenatal exposure to the antiepileptic valproic acid (VPA) is associated with an increased risk of autism spectrum disorder (ASD) in humans."	3.96	In utero exposure to valproic acid disrupts ascending projections to the central nucleus of the inferior colliculus from the auditory brainstem. ( Fech, T; Kulesza, RJ; Mansour, Y; Smith, A; Zimmerman, R, 2020)
"The goal of our study was to examine the long-term effect of vigabatrin (VGB), a γ-aminobutyric acid aminotransferase (GABA-AT) inhibitor on clonazepam (CLO), ethosuximide (ETX) and valproate (VPA) anticonvulsive activity against pentylenetetrazole (PTZ)-induced seizures in mice."	3.96	Long-term vigabatrin treatment modifies pentylenetetrazole-induced seizures in mice: focused on GABA brain concentration. ( Czuczwar, SJ; Krzyżanowski, M; Świąder, K; Świąder, MJ; Wróbel, A; Zakrocka, I; Łuszczki, JJ, 2020)
"Valproic acid (VPA) administered to mice during the early postnatal period causes social, cognitive, and motor deficits similar to those observed in humans with autism spectrum disorder (ASD)."	3.96	Long-lasting Behavioral and Neuroanatomical Effects of Postnatal Valproic Acid Treatment. ( Derbaly, A; Gifford, JJ; Kusnecov, AW; Norton, SA; Pawlak, AP; Sherman, SL; Wagner, GC; Zhang, H, 2020)
" This study examined the effect of metformin on VPA-induced autism spectrum disorders in rats."	3.96	Novel potential of metformin on valproic acid-induced autism spectrum disorder in rats: involvement of antioxidant defence system. ( Adeyemi, OO; Balogun, AO; Ishola, IO, 2020)
"This study was performed to evaluate the effects of prenatal exposure to pregabalin (PGB) on behavioral changes of rat offspring in an animal model of valproic acid (VPA)-induced autism-like symptoms."	3.96	Prenatal pregabalin is associated with sex-dependent alterations in some behavioral parameters in valproic acid-induced autism in rat offspring. ( Bashiri, H; Moslemizadeh, A; Sepehri, G; Shamsi Meymandi, M; Vakili Shahrbabaki, S, 2020)
"The ovalbumin-induced (OVA) chronic allergic airways murine model is a well-established model for investigating pre-clinical therapies for chronic allergic airways diseases, such as asthma."	3.96	Investigation of molecular mechanisms of experimental compounds in murine models of chronic allergic airways disease using synchrotron Fourier-transform infrared microspectroscopy. ( Bambery, KR; Karagiannis, TC; Licciardi, PV; Mazarakis, N; Royce, SG; Samuel, CS; Snibson, KJ; Tobin, MJ; Ververis, K; Vongsvivut, J, 2020)
" The histone deacetylase inhibitor, high-dose valproic acid (VPA) has been shown to have cytoprotective potential in models of combined TBI and hemorrhagic shock, but it has not been tested in an isolated TBI model."	3.96	Valproic acid treatment rescues injured tissues after traumatic brain injury. ( Alam, HB; Biesterveld, BE; Iancu, A; Kemp, MT; O'Connell, RL; Pai, MP; Pumiglia, L; Remmer, HA; Shamshad, AA; Siddiqui, AZ; Wakam, GK; Williams, AM, 2020)
" The agents tested were: alpha-lactoalbumin (ALAC), a whey protein rich in tryptophan, effective in some animal models of epilepsy and on colon/intestine inflammation, valproic acid (VPA), an effective antiepileptic drug in this seizure model, mesalazine (MSZ) an effective aminosalicylate anti-inflammatory treatment against ulcerative colitis and sodium butyrate (NaB), a short chain fatty acid (SCFA) normally produced in the intestine by gut microbiota, important in maintaining gut health and reducing gut inflammation and oxidative stress."	3.91	Intestinal inflammation increases convulsant activity and reduces antiepileptic drug efficacy in a mouse model of epilepsy. ( Avagliano, C; Calignano, A; Citraro, R; Constanti, A; De Caro, C; De Sarro, G; di Cesare Mannelli, L; Ghelardini, C; Leo, A; Mainardi, P; Nesci, V; Russo, E; Striano, P, 2019)
" Maternal exposure to valproic acid (VPA), a commonly prescribed antiepileptic drug during pregnancy in human, has long been considered a risk factor to contribute to ASD susceptibility in offspring from epidemiological studies in humans."	3.91	Maternal valproic acid exposure leads to neurogenesis defects and autism-like behaviors in non-human primates. ( Guo, X; Jiang, YH; Li, XJ; Tu, Z; Wang, Q; Xu, HJ; Yan, T; Yu, HP; Zhang, Y; Zhang, YQ; Zhao, H; Zhou, H, 2019)
"In previous studies we produced autism like behavioral changes in mice by Valproic acid (VPA) with significant differences between genders."	3.91	Gender Related Changes in Gene Expression Induced by Valproic Acid in A Mouse Model of Autism and the Correction by S-adenosyl Methionine. Does It Explain the Gender Differences in Autistic Like Behavior? ( Ergaz, Z; Ornoy, A; Szyf, M; Turgeman, G; Weinstein-Fudim, L; Yanai, J, 2019)
" This study evaluated the efficacy of sodium valproate encapsulated in nanoparticles in pentylenetetrazole (PTZ) induced acute and kindling models of seizures in male Wistar rats."	3.91	Evaluation of sodium valproate loaded nanoparticles in acute and chronic pentylenetetrazole induced seizure models. ( Dinda, AK; Gupta, YK; Kottarath, SK; Meenu, M; Reeta, KH, 2019)
" Here, we aim to determine whether Valproic acid (VPA), a FDA approved inhibitor of histone deacetylation for bipolar disease, could protect heart against myocardial infarction (MI) injury and elucidate key molecular pathways."	3.91	HDAC inhibitor valproic acid protects heart function through Foxm1 pathway after acute myocardial infarction. ( Alam, HB; Creech, J; Eugene Chen, Y; Gao, W; Guo, Y; Herron, TJ; Lei, I; Li, Y; Liu, L; Ma, PX; Tian, S; Wang, Z; Xian, S, 2019)
" Valproic acid (VPA) is an anticonvulsant drug in both human and rodents with teratogenic effects during pregnancy."	3.91	Benefits of Fenofibrate in prenatal valproic acid-induced autism spectrum disorder related phenotype in rats. ( Mirza, R; Sharma, B, 2019)
"Abnormally high levels of homocysteine (Hcy) are associated with autism spectrum disorder."	3.91	Betaine ameliorates prenatal valproic-acid-induced autism-like behavioral abnormalities in mice by promoting homocysteine metabolism. ( Chen, X; Chen, Z; Cui, C; Huang, F; Jiang, X; Niu, J; Sun, J, 2019)
" Pentylenetetrazole- (PTZ) and pilocarpine-induced seizures are well-established models of human epilepsy."	3.91	The effect of co-administration of pentylenetetrazole with pilocarpine: New modified PTZ models of kindling and seizure. ( Jand, A; Mousavi-Hasanzadeh, M; Palizvan, MR; Rezaeian-Varmaziar, H; Shafaat, O, 2019)
"To establish an improved mouse model of valproic acid (VPA)-induced autism that better mimics human autism."	3.91	[Improvement of a mouse model of valproic acid-induced autism]. ( Chen, D; Hu, Y; Li, Y; Wang, S; Zheng, W, 2019)
" Pregabalin, valproic acid and levetiracetam all terminate seizures in the rat SE model and attenuate cholinergic and metabolic changes within two hours."	3.91	Effects of Three Anti-Seizure Drugs on Cholinergic and Metabolic Activity in Experimental Status Epilepticus. ( Imran, I; Klein, J; Koch, K; Lau, H; Schöfer, H, 2019)
"Postnatal exposure to valproic acid (VPA) in rodents induces autism-like neurobehavioral defects which are comparable to the motor and cognitive deficits observed in humans with autism spectrum disorder (ASD)."	3.91	The dual-active histamine H3 receptor antagonist and acetylcholine esterase inhibitor E100 ameliorates stereotyped repetitive behavior and neuroinflammmation in sodium valproate induced autism in mice. ( Azimullah, S; Beiram, R; Eissa, N; Jayaprakash, P; Jayaraj, RL; Kieć-Kononowicz, K; Ojha, SK; Reiner, D; Sadek, B; Stark, H; Łażewska, D, 2019)
" In this study, we examined how exposure to valproic acid (VPA) during pregnancy is associated with an increased incidence of ASD."	3.88	Dendritic spine anomalies and PTEN alterations in a mouse model of VPA-induced autism spectrum disorder. ( Ahn, S; Cho, K; Choi, M; Kim, H; Kim, HS; Mahmood, U; Regan, P; Yang, EJ, 2018)
"Prenatal exposure to the antiepileptic and mood stabilizer valproic acid (VPA) is an environmental risk factor for autism spectrum disorders (ASD), although recent epidemiological studies show that the public awareness of this association is still limited."	3.88	Impaired repair of DNA damage is associated with autistic-like traits in rats prenatally exposed to valproic acid. ( Ascenzi, P; Campolongo, P; di Masi, A; Leboffe, L; Manduca, A; Melancia, F; Palmery, M; Schiavi, S; Servadio, M; Trezza, V, 2018)
"We utilized a valproic acid (VPA) -induced rat model of autism to evaluate the levels of S1P and the expression of sphingosine kinase (SphK), a key enzyme for S1P production, in serum and hippocampal tissue."	3.88	Modulation of sphingosine 1-phosphate (S1P) attenuates spatial learning and memory impairments in the valproic acid rat model of autism. ( Cao, Y; Gao, J; Hao, Y; Sun, C; Wang, J; Wu, H; Wu, L; Xia, W; Zhang, Q, 2018)
" Nonselective histone deacetylase inhibitors (HDACIs), such as valproic acid (VPA), have been shown to improve outcomes in hemorrhagic shock (HS)."	3.88	Histone deacetylase inhibitors: Isoform selectivity improves survival in a hemorrhagic shock model. ( Alam, HB; Bhatti, UF; Chang, P; Dennahy, IS; Li, Y; Liu, B; Nikolian, VC; Weykamp, M; Williams, AM, 2018)
"Here, we aimed at determining whether a well-acknowledged animal model of autism spectrum disorders, the valproic acid model, displays motor impairments and whether they may correlate with social deficits and neuronal loss within motor brain areas."	3.88	Motor Impairments Correlate with Social Deficits and Restricted Neuronal Loss in an Environmental Model of Autism. ( Al Sagheer, T; Balbous, A; Fernagut, PO; Francheteau, M; Haida, O; Jaber, M; Matas, E, 2018)
" There have been no studies that have explained if HDAC inhibition by valproic acid (VPA) affects the NF-κB pathway via acetylation of STAT1 dependent of HDAC activity in the microglia-mediated central inflammation following SCI."	3.88	Valproic acid attenuates traumatic spinal cord injury-induced inflammation via STAT1 and NF-κB pathway dependent of HDAC3. ( Chen, S; Chen, X; Fu, H; Li, S; Li, Y; Lin, W; Shi, J; Wu, W; Ye, J, 2018)
"Histone deacetylase inhibitors such as valproic acid (VPA) improve survival in lethal models of hemorrhagic shock and polytrauma."	3.88	Rapid valproic acid-induced modulation of the traumatic proteome in a porcine model of traumatic brain injury and hemorrhagic shock. ( Alam, HB; Dennahy, IS; Georgoff, PE; Ghandour, MH; Higgins, GA; Nikolian, VC; Remmer, H; Weykamp, M, 2018)
"We previously showed that nicotine evoked kinetic tremor by activating the inferior olive, which is implicated in the pathogenesis of essential tremor, via α7 nicotinic acetylcholine receptors."	3.88	Pharmacological characterization of nicotine-induced tremor: Responses to anti-tremor and anti-epileptic agents. ( Abe, K; Hashimura, M; Iha, HA; Iwai, C; Kato, M; Kawaji, S; Kawakita, K; Kunisawa, N; Ogawa, M; Ohno, Y; Shimizu, S, 2018)
"Elevated circulating uric acid has been postulated to play an important pathophysiological role in estrogen-progestin combined oral contraceptive (COC)-induced hypertension and endothelial dysfunction."	3.88	Inhibition of adenosine deaminase and xanthine oxidase by valproic acid abates hepatic triglyceride accumulation independent of corticosteroids in female rats treated with estrogen-progestin. ( Areola, ED; Badmus, OO; Kim, I; Michael, OS; Olatunji, LA; Omolekulo, TE, 2018)
"Considering the potential role of lymphocytes in the pathophysiology of autism spectrum disorder (ASD), we aimed to evaluate possible alterations of T cell pools in the lymphoid organs of an animal model of autism induced by valproic acid (VPA)."	3.88	Reduced CD4 T Lymphocytes in Lymph Nodes of the Mouse Model of Autism Induced by Valproic Acid. ( Bambini-Junior, V; Baronio, D; Bauer-Negrini, G; Castro, K; Della-Flora Nunes, G; Gottfried, C; Mendes-da-Cruz, DA; Riesgo, R; Savino, W, 2018)
") on sociability, social novelty, anxiety, and aggressive/repetitive behavior in male Tuck-Ordinary (TO) mice with ASD-like behaviors induced by prenatal exposure to valproic acid (VPA, 500 mg/kg, i."	3.88	The histamine H3R antagonist DL77 attenuates autistic behaviors in a prenatal valproic acid-induced mouse model of autism. ( Al-Houqani, M; Azimullah, S; Eissa, N; Jalal, FY; Jayaprakash, P; Kieć-Kononowicz, K; Ojha, SK; Sadek, B; Łażewska, D, 2018)
"We have investigated the species richness and microbial composition in a valproic acid (VPA)-induced rat model autism."	3.88	The valproic acid rat model of autism presents with gut bacterial dysbiosis similar to that in human autism. ( Horton-Sparks, K; Hull, V; Li, RW; Liu, F; Martínez-Cerdeño, V, 2018)
"The aim was to identify the effects of early vitamin D supplementation on autism-like behaviors (ASD) induced by valproic acid (VPA, an anti-convulsant and a mood stabilizer) in rats."	3.85	Behavioral improvements in a valproic acid rat model of autism following vitamin D supplementation. ( Du, L; Duan, Z; Li, F; Zhao, G, 2017)
"The study was performed using a rodent model of autism by exposing rat fetuses to valproic acid (VPA) on the 12."	3.85	Postnatal treatment using curcumin supplements to amend the damage in VPA-induced rodent models of autism. ( Al-Askar, M; Al-Ayadhi, L; Bhat, RS; El-Ansary, A; Selim, M, 2017)
" Here, we investigate the impact on the corticostriosomal pathway in the valproic acid (VPA)-induced autism spectrum disorder mouse model."	3.85	Valproic acid induces aberrant development of striatal compartments and corticostriatal pathways in a mouse model of autism spectrum disorder. ( Kuo, HY; Liu, FC, 2017)
"VPA prevented HFD-induced hypertension by downregulating angiotensin II and its receptor via inhibition of HDAC1, offering a novel therapeutic option for HFD-induced hypertension."	3.85	Role of the histone deacetylase inhibitor valproic acid in high-fat diet-induced hypertension via inhibition of HDAC1/angiotensin II axis. ( Choi, J; Kim, JI; Kwon, TK; Park, KM; Park, S; Sohn, SI, 2017)
"Rodents exposed prenatally to valproic acid (VPA) exhibit autism spectrum disorder (ASD)-like behavioral abnormalities."	3.85	Risperidone and aripiprazole alleviate prenatal valproic acid-induced abnormalities in behaviors and dendritic spine density in mice. ( Ago, Y; Hara, Y; Hasebe, S; Hashimoto, H; Kawase, H; Matsuda, T; Nakazawa, T; Takuma, K; Tanabe, W; Taruta, A; Tsukada, S, 2017)
"Recent studies have reported that oxytocin ameliorates behavioral abnormalities in both animal models and individuals with autism spectrum disorders (ASD)."	3.85	Oxytocin attenuates deficits in social interaction but not recognition memory in a prenatal valproic acid-induced mouse model of autism. ( Ago, Y; Hara, Y; Hasebe, S; Hashimoto, H; Higuchi, M; Matsuda, T; Nakazawa, T; Takuma, K, 2017)
"Prenatal exposure to the antiepileptic, mood-stabilizing drug, valproic acid (VPA), increases the incidence of autism spectrum disorders (ASDs); in utero administration of VPA to pregnant rodents induces ASD-like behaviors such as repetitive, stereotyped activity, and decreased socialization."	3.85	Sexually Dimorphic Epigenetic Regulation of Brain-Derived Neurotrophic Factor in Fetal Brain in the Valproic Acid Model of Autism Spectrum Disorder. ( Densmore, AL; Konopko, MA; Krueger, BK, 2017)
"Sotalol as a drug blocking β-receptors and potassium KCNH2 channels may interact with different substances that affect seizures."	3.85	Sotalol enhances the anticonvulsant action of valproate and diphenylhydantoin in the mouse maximal electroshock model. ( Banach, M; Borowicz-Reutt, KK; Popławska, M, 2017)
" Its etiology is still unknown, but different environmental factors during pregnancy, such as exposure to valproic acid (VPA), are associated with high incidence of ASD in children."	3.85	The effect of ketogenic diet in an animal model of autism induced by prenatal exposure to valproic acid. ( Baronio, D; Castro, K; Gottfried, C; Perry, IS; Riesgo, RDS, 2017)
"The present study was undertaken to elucidate the effect of alpha-linolenic acid (ALA, 18:3, ω-3) and gamma-linolenic acid (GLA, 18:3, ω-6) on experimental autism features induced by early prenatal exposure to valproic acid (VPA) in albino wistar pups."	3.85	Comparative efficacy of alpha-linolenic acid and gamma-linolenic acid to attenuate valproic acid-induced autism-like features. ( Ansari, MN; Devi, U; Gautam, S; Kaithwas, G; Prakash, A; Rawat, JK; Roy, S; Saeedan, AS; Saraf, SA; Singh, M; Tiwari, V; Yadav, RK; Yadav, S, 2017)
"Prenatal exposure to valproic acid (VPA) enhances the risk for later development of autism spectrum disorders (ASD)."	3.85	Increased GABAA receptor binding in amygdala after prenatal administration of valproic acid to rats. ( Bertelsen, F; Drasbek, KR; Folloni, D; Landau, AM; Møller, A; Scheel-Krüger, J, 2017)
" The initial anticonvulsant screening was performed in mice (ip) using the 'classical' maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests as well as in the six-Hertz (6Hz) model of pharmacoresistant limbic seizures."	3.83	New hybrid molecules with anticonvulsant and antinociceptive activity derived from 3-methyl- or 3,3-dimethyl-1-[1-oxo-1-(4-phenylpiperazin-1-yl)propan-2-yl]pyrrolidine-2,5-diones. ( Abram, M; Andres-Mach, M; Kamiński, K; Obniska, J; Rapacz, A; Zagaja, M; Łuszczki, JJ, 2016)
"We isolated deep layer prefrontal circuits in brain slices then used single-photon GCaMP imaging to record activity from many (50 to 100) neurons simultaneously to study patterns of spontaneous activity generated by these circuits under normal conditions and in two etiologically distinct models of autism: mice exposed to valproic acid in utero and Fmr1 knockout mice."	3.83	Putative Microcircuit-Level Substrates for Attention Are Disrupted in Mouse Models of Autism. ( Horn, ME; Luongo, FJ; Sohal, VS, 2016)
"Prenatal exposure to valproic acid (VPA) in rat offspring is capable of inducing experimental autism with neurobehavioral aberrations."	3.83	Neuroprotective effects of docosahexaenoic acid on hippocampal cell death and learning and memory impairments in a valproic acid-induced rat autism model. ( Cao, Y; Gao, J; Liang, S; Sun, H; Wang, H; Wang, X; Wang, Y; Wu, L; Yang, F; Zhang, F, 2016)
"Rodents exposed prenatally to valproic acid (VPA) show autism-related behavioral abnormalities."	3.83	Improvement by methylphenidate and atomoxetine of social interaction deficits and recognition memory impairment in a mouse model of valproic acid-induced autism. ( Ago, Y; Hara, Y; Hasebe, S; Hashimoto, H; Katashiba, K; Matsuda, T; Onaka, Y; Takano, E; Takuma, K; Taruta, A, 2016)
"Exposure to valproic acid (VPA) during pregnancy has been linked with increased incidence of autism, and has repeatedly been demonstrated as a useful autism mouse model."	3.83	Early Behavioral Abnormalities and Perinatal Alterations of PTEN/AKT Pathway in Valproic Acid Autism Model Mice. ( Ahn, S; Kim, HS; Lee, K; Mahmood, U; Yang, EJ, 2016)
"Exposure to alcohol and valproic acid (VPA) during pregnancy can lead to fetal alcohol spectrum disorders and fetal valproate syndrome, respectively."	3.83	Effects of developmental alcohol and valproic acid exposure on play behavior of ferrets. ( Filgueiras, CC; Krahe, TE; Medina, AE, 2016)
" Here, we suggest that triggering limbic seizures with low doses of PTZ in pilocarpine-treated marmosets might provide a more effective basis for the development of AED."	3.83	Seizures triggered by pentylenetetrazol in marmosets made chronically epileptic with pilocarpine show greater refractoriness to treatment. ( Blanco, MM; Cinini, SM; Lima, TZ; Mello, LE; Pontes, JC; Queiroz, CM, 2016)
"The present study aimed to develop a neurochemistry-based single or adjuvant therapy approach for comprehensive management of epilepsy and associated depression employing pentylenetetrazole-kindled animals."	3.83	Evidence in support of using a neurochemistry approach to identify therapy for both epilepsy and associated depression. ( Goel, RK; Singh, T, 2016)
"Rodents exposed to valproic acid (VPA) in prenatal life exhibit post-natal characteristics analogous to autism spectrum disorder (ASD)."	3.83	A single low dose of valproic acid in late prenatal life alters postnatal behavior and glutamic acid decarboxylase levels in the mouse. ( Cheung, C; Chua, SE; Lam, S; Leung, J; Li, Q; McAlonan, GM; Sham, PC; Wei, R; Zhang, X, 2016)
"The role of zinc in seizure models and with antiepileptic drugs sodium valproate (SV) and phenytoin (PHT) was studied using experimental models of seizures in rats."	3.81	Low dose zinc supplementation beneficially affects seizure development in experimental seizure models in rats. ( Gupta, YK; Katyal, J; Kumar, H, 2015)
"Components of the mTOR pathway were assayed by Western blotting in postmortem fusiform gyrus samples from 11 subjects with idiopathic autism and 13 controls and in valproic acid versus saline-exposed rat neocortex."	3.81	Decreased mTOR signaling pathway in human idiopathic autism and in rats exposed to valproic acid. ( Ahn, Y; Fahnestock, M; Michalski, B; Nicolini, C; Rho, JM, 2015)
"Male Sprague-Dawley rats were injected with a single, subcutaneous dose of monocrotaline (60 mg/kg), and were exposed to chronic hypoxia to induce severe PH."	3.81	Therapeutic efficacy of valproic acid in a combined monocrotaline and chronic hypoxia rat model of severe pulmonary hypertension. ( Furutani, Y; Hayama, E; Kawaguchi, N; Lan, B; Nakanishi, T, 2015)
"A single treatment of valproate and olanzapine did not ameliorate the hyperactivity or abnormal anxiety level of DGKβ KO mice."	3.81	The effects of valproate and olanzapine on the abnormal behavior of diacylglycerol kinase β knockout mice. ( Hara, H; Ishisaka, M; Mizoguchi, T; Shimazawa, M; Tsujii, S; Tsuruma, K, 2015)
"To investigate whether the decreased level of serum polyunsaturated fatty acids (PUFAs) in patients with autism is associated with the expression of related liver metabolic enzymes, we selected rats that were exposed to valproic acid (VPA) on embryonic day 12."	3.81	Study of the serum levels of polyunsaturated fatty acids and the expression of related liver metabolic enzymes in a rat valproate-induced autism model. ( Cao, Y; Gao, J; Hao, Y; Li, X; Liang, S; Sun, C; Wang, X; Wu, L; Xia, W; Zhao, G, 2015)
" We evaluated influence of DHA on anticonvulsant activity of AEDs phenytoin, valproate, and lamotrigine in maximal electroshock (MES), pentylenetetrazole (PTZ), and kindling models of epilepsy."	3.81	Synergistic effect of docosahexaenoic acid on anticonvulsant activity of valproic acid and lamotrigine in animal seizure models. ( Babapour, V; Gavzan, H; Sardari, S; Sayyah, M, 2015)
"To investigate the consequences of histone deacetylase inhibition by histone deacetylase inhibitor valproic acid and IκB kinase/nuclear factor-κB signaling blockade by IκB kinase inhibitor BAY11-7082 on (microvascular) endothelial cell behavior in vitro as well as in mice subjected to hemorrhagic shock/resuscitation in vivo."	3.81	Histone Deacetylase Inhibition and IκB Kinase/Nuclear Factor-κB Blockade Ameliorate Microvascular Proinflammatory Responses Associated With Hemorrhagic Shock/Resuscitation in Mice. ( Aslan, A; Jongman, RM; Li, R; Molema, G; Moorlag, HE; Moser, J; van Meurs, M; Yan, R; Zijlstra, JG; Zwiers, PJ, 2015)
" Epileptic rats that developed spontaneous recurrent seizures after a pilocarpine-induced status epilepticus were treated with a KD or control diet (CD)."	3.81	Ketogenic diet prevents epileptogenesis and disease progression in adult mice and rats. ( Akula, KK; Boison, D; Coffman, SQ; Lusardi, TA; Masino, SA; Ruskin, DN, 2015)
"The natural compounds carvacrol and thymol completely prevented seizures in the 6 Hz, 32 mA partial seizure model."	3.80	Seizure prevention by the naturally occurring phenols, carvacrol and thymol in a partial seizure-psychomotor model. ( Baker, MT; Mishra, RK, 2014)
"We report that the oxytocin-mediated neuroprotective γ-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery is abolished in the valproate and fragile X rodent models of autism."	3.80	Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring. ( Ben-Ari, Y; Brouchoud, C; Burnashev, N; Chazal, G; Eftekhari, S; Ferrari, DC; Khalilov, I; Lemonnier, E; Lozovaya, N; Nardou, R; Shahrokhi, A; Tsintsadze, T; Tsintsadze, V; Tyzio, R, 2014)
"The aims of this study were to characterize a lamotrigine-resistant kindled model of epilepsy in mice, to study the anticonvulsant effect of carbamazepine (CBZ) and valproic acid (VPA), and to probe into the mechanism for resistance."	3.80	Characterization of a lamotrigine-resistant kindled model of epilepsy in mice: evaluation of drug resistance mechanisms. ( Mehndiratta, M; Pillai, KK; Singh, E, 2014)
"We have previously shown that resuscitation with fresh frozen plasma (FFP) in a large animal model of traumatic brain injury (TBI) and hemorrhagic shock (HS) decreases the size of the brain lesion, and that addition of a histone deacetylase inhibitor, valproic acid (VPA), provides synergistic benefits."	3.80	Treatment with a histone deacetylase inhibitor, valproic acid, is associated with increased platelet activation in a large animal model of traumatic brain injury and hemorrhagic shock. ( Alam, HB; Andjelkovic, AV; Bambakidis, T; Boer, C; Dekker, SE; Halaweish, I; Jin, G; Johansson, PI; Linzel, D; Liu, B; Sillesen, M, 2014)
"Post natal exposure to VPA (valproic acid) in mice induces behavioral deficits, abnormal sensitivity to sensory stimuli and self-injurious behavior, observed in autism."	3.80	Ameliorating effect of piperine on behavioral abnormalities and oxidative markers in sodium valproate induced autism in BALB/C mice. ( Kameshwari, JS; Pragnya, B; Veeresh, B, 2014)
"We have previously shown that addition of valproic acid (VPA; a histone deacetylase inhibitor) to hetastarch (Hextend [HEX]) resuscitation significantly decreases lesion size in a swine model of traumatic brain injury (TBI) and hemorrhagic shock (HS)."	3.80	Effect of pharmacologic resuscitation on the brain gene expression profiles in a swine model of traumatic brain injury and hemorrhage. ( Alam, HB; Bambakidis, T; Dekker, SE; Jin, G; Johnson, CN; Li, Y; Liu, B; Sillesen, M, 2014)
"We recently showed that prenatal exposure to valproic acid (VPA) in mice causes autism-like behavioral abnormalities, including social interaction deficits, anxiety-like behavior and spatial learning disability, in male offspring."	3.80	Chronic treatment with valproic acid or sodium butyrate attenuates novel object recognition deficits and hippocampal dendritic spine loss in a mouse model of autism. ( Ago, Y; Hara, Y; Hashimoto, H; Hayata-Takano, A; Kataoka, S; Kawanai, T; Maeda, Y; Matsuda, T; Takano, E; Takuma, K; Watanabe, R, 2014)
" Initial anticonvulsant screening was performed in mice (ip) using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizures tests."	3.79	Design, synthesis and anticonvulsant properties of new N-Mannich bases derived from 3-phenylpyrrolidine-2,5-diones. ( Chlebek, I; Kamiński, K; Obniska, J; Rzepka, S; Wiklik, B, 2013)
"Levetiracetam has been reported to be well tolerated and effective in status epilepticus (SE) refractory to benzodiazepine."	3.79	The effect of levetiracetam on status epilepticus-induced neuronal death in the rat hippocampus. ( Choi, HC; Kang, TC; Kim, JE; Kim, YI; Lee, DS; Ryu, HJ; Song, HK, 2013)
"Valproic acid (VPA) is a blocker of histone deacetylase widely used to treat epilepsy, bipolar disorders, and migraine; its administration during pregnancy increases the risk of autism spectrum disorder (ASD) in the child."	3.79	Rearrangement of the dendritic morphology in limbic regions and altered exploratory behavior in a rat model of autism spectrum disorder. ( Atzori, M; Bringas, ME; Carvajal-Flores, FN; Flores, G; López-Ramírez, TA, 2013)
" We investigated for the first time whether class I histone deacetylase inhibitor valproic acid (VPA) can reverse cognitive deficits in a mouse model of sepsis-associated encephalopathy (SAE)."	3.79	Class I histone deacetylase inhibitor valproic acid reverses cognitive deficits in a mouse model of septic encephalopathy. ( Dong, L; Ji, M; Jia, M; Qiu, L; Wu, J; Yang, J; Zhang, G; Zhang, M, 2013)
" We describe the effects of focally applied valproate (VPA) in a newly emerging rat model of neocortical epilepsy induced by tetanus toxin (TeT) plus cobalt chloride (CoCl₂)."	3.79	Locally applied valproate enhances survival in rats after neocortical treatment with tetanus toxin and cobalt chloride. ( Altenmüller, DM; Feuerstein, TJ; Freiman, TM; Hebel, JM; Rassner, MP; Volz, S; Zentner, J, 2013)
" (MQ) in maximal electroshock (MES) and pentylenetetrazole (PTZ) induced rat models of epilepsy."	3.79	Evaluation of anti-epileptic property of Marsilea quadrifolia Linn. in maximal electroshock and pentylenetetrazole-induced rat models of epilepsy. ( Avinash, H; Chandrashekar, BR; Mukunda, N; Naduvil Narayanan, S; Nayak, BS; Raghavendra Rao, K; Sadhana, N; Satish Kumar, MC; Snehunsu, A; Vijay Kapgal, K, 2013)
" Using the prenatal valproic acid (VPA)-injection model of autism spectrum disorder (ASD) in rats, which produces social impairrment and altered seizure susceptibility as in human ASD patients as well as mild neural tube defects like crooked tail phenotype, we examined whether chronic administration of red ginseng extract may rescue the social impairment and crooked tail phenotype in prenatally VPA-exposed rat offspring."	3.79	Effects of Korean red ginseng extracts on neural tube defects and impairment of social interaction induced by prenatal exposure to valproic acid. ( Han, SH; Kim, HJ; Kim, HY; Kim, KC; Kim, P; Kwon, KJ; Lee, JM; Park, JH; Shin, CY, 2013)
" Our data have demonstrated that pentylenetetrazole (PTZ)-induced seizures did not alter ATP, ADP, and AMP hydrolysis in brain membrane fractions."	3.79	Antiepileptic drugs prevent changes in adenosine deamination during acute seizure episodes in adult zebrafish. ( Bogo, MR; Bonan, CD; Nery, LR; Piato, AL; Schaefer, IC; Siebel, AM, 2013)
"Valproic acid (VPA) is the most widely prescribed epilepsy treatment worldwide, but its mechanism of action remains unclear."	3.78	The antiepileptic drug valproic acid and other medium-chain fatty acids acutely reduce phosphoinositide levels independently of inositol in Dictyostelium. ( Bialer, M; Chang, P; Deranieh, RM; Dham, M; Greenberg, ML; Hoeller, O; Orabi, B; Shimshoni, JA; Walker, MC; Williams, RS; Yagen, B, 2012)
" As we have recently shown, inhibitors of histone deacetylases, in particular, valproic acid (VA), were capable of up-regulating NEP expression and activity in human neuroblastoma SH-SY5Y cell lines characterised by very low levels of NEP."	3.78	Effect of sodium valproate administration on brain neprilysin expression and memory in rats. ( Bagrova, DI; Belyaev, ND; Dubrovskaya, NM; Lewis, DI; Makova, NZ; Nalivaeva, NN; Pickles, AR; Plesneva, SA; Turner, AJ; Zhuravin, IA, 2012)
" This study was designed to evaluate the effect of valproic acid (VPA) and progesterone (P4) in a rat model of endometriosis on serum tumor necrosis factor-α (TNF-α) levels, hot plate and tail-flick latencies, lesion size, and body weight."	3.78	Valproic acid and progestin inhibit lesion growth and reduce hyperalgesia in experimentally induced endometriosis in rats. ( Guo, SW; Liu, M; Liu, X; Zhang, Y, 2012)
" Both valproic acid, a class I HDAC inhibitor, and suberoylanilide hydroxamic acid (vorinostat), an inhibitor of class I, II, and IV HDACs, mitigated the development of and reduced established hypoxia-induced pulmonary hypertension in the rat."	3.78	Histone deacetylation inhibition in pulmonary hypertension: therapeutic potential of valproic acid and suberoylanilide hydroxamic acid. ( Chen, CN; Cotroneo, E; Hajji, N; Li, M; McKinsey, TA; Oliver, E; Stenmark, KR; Wang, D; Wharton, J; Wilkins, MR; Zhao, L, 2012)
"We have previously demonstrated that valproic acid (VPA), a histone deacetylase inhibitor, can improve survival after hemorrhagic shock (HS), protect neurons from hypoxia-induced apoptosis, and attenuate the inflammatory response."	3.78	Pharmacologic resuscitation for hemorrhagic shock combined with traumatic brain injury. ( Alam, HB; Demoya, MA; Duggan, M; Hwabejire, J; Imam, A; Jepsen, CH; Jin, G; Liu, B; Lu, J; Mejaddam, AY; Sillesen, M; Smith, WM; Socrate, S; Velmahos, GC, 2012)
"Hyperammonemia is a frequent side-effect of valproic acid (VPA) therapy, which points to an imbalance between ammoniagenesis and ammonia disposal via the urea cycle."	3.77	New insights on the mechanisms of valproate-induced hyperammonemia: inhibition of hepatic N-acetylglutamate synthase activity by valproyl-CoA. ( Aires, CC; de Almeida, IT; Duran, M; Ijlst, L; Silva, MF; van Cruchten, A; Wanders, RJ, 2011)
"Prenatal exposure to valproic acid (VPA) induces neural tube defects and impairment in social behaviors related to autistic spectrum disorder in newborns, which make it a useful animal model of autism."	3.77	The critical period of valproate exposure to induce autistic symptoms in Sprague-Dawley rats. ( Cheong, JH; Choi, CS; Go, HS; Kim, KC; Kim, P; Ko, KH; Shin, CY; Yang, SI, 2011)
"The anticonvulsant activity of BmK AS, a sodium channel site 4-selective modulator purified from scorpion venom (Buthus martensi Karsch), was investigated in unanesthetized rats with acute pentylenetetrazole (PTZ)- and pilocarpine-induced seizures."	3.77	Anticonvulsant activity of BmK AS, a sodium channel site 4-specific modulator. ( Chen, L; Feng, Q; Ji, YH; Wang, Y; Weng, CC; Zhang, XY; Zhao, R; Zhu, HY, 2011)
"Valproic acid (VPA), widely used as mood stablizer, has been shown therapeutic effects in controlling both episodes of mania and depression."	3.77	Microinjection of valproic acid into the ventrolateral orbital cortex exerts an antidepressant-like effect in the rat forced swim test. ( Chen, T; Dang, Y; Huang, J; Luo, Q; Xing, B; Zhang, H; Zhao, Y, 2011)
" We previously showed that tolerance to levetiracetam (LEV) developed within 4 days after the start of the treatment in a rat model for spontaneous seizures after electrically induced status epilepticus."	3.76	Improved seizure control by alternating therapy of levetiracetam and valproate in epileptic rats. ( Edelbroek, PM; Gorter, JA; van Vliet, EA, 2010)
" Antiepileptics (carbamazepine, sodium valproate, zonisamide, clobazam, and topiramate), which are used for complex partial epilepsy or secondary generalized epilepsy in clinical practice, were orally administrated to kindled rats."	3.76	The usefulness of olfactory bulb kindling as a model for evaluation of antiepileptics. ( Akagi, M; Fujiwara, A; Ishikawa, T; Kaida, Y; Kamei, C; Takechi, K; Watanabe, Y, 2010)
"Valproic acid (VPA) is widely used clinically in epilepsy, bipolar disorder, and migraine."	3.76	Inhibition of long-term potentiation by valproic acid through modulation of cyclic AMP. ( Chandler, KE; Chang, P; Walker, MC; Williams, RS, 2010)
" The aim of the current study was to evaluate the effects of losartan (2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'(1H-tetrazol-5-yl)-biphenil-4-yl)methyl]imidazole) and telmisartan (49-[(1,49-dimethyl-29-propyl[2,69-bi-1H-benzimidazo]-19-yl)methyl]-[1,19-biphenyl]-2-carboxylic acid), the angiotensin AT1 receptor antagonists which are widely used in clinical practice, on the protective action of conventional antiepileptic drugs (carbamazepine, phenytoin, valproate and phenobarbital) against maximal electroshock-induced seizures in mice."	3.76	Angiotensin AT1 receptor antagonists enhance the anticonvulsant action of valproate in the mouse model of maximal electroshock. ( Czuczwar, SJ; Jakubus, T; Janowska, A; Tochman-Gawda, A; Łukawski, K, 2010)
"For the acute study, in the maximal electroshock seizure model, the administration of 1 mg/kg of amlodipine resulted in the complete abolition of seizures in 33 percent of the mice, and this was increased to 67 percent with the administration of 4 mg/kg."	3.76	An experimental study of the anticonvulsant effect of amlodipine in mice. ( Sathyanarayana Rao, KN; Subbalakshmi, NK, 2010)
" Valproic acid (VPA) was found to enhance alpha7 integrin levels, induce muscle hypertrophy, and inhibit apoptosis in myotubes by activating the Akt/mTOR/p70S6K pathway."	3.75	Valproic acid activates the PI3K/Akt/mTOR pathway in muscle and ameliorates pathology in a mouse model of Duchenne muscular dystrophy. ( Burkin, DJ; Gurpur, PB; Kaufman, SJ; Liu, J, 2009)
" Here we examine the temporal relation between the onset of hyperglycemia, glucosamine accumulation in the vessel wall, ER stress, and the development of atherosclerosis."	3.75	Evidence supporting a role for endoplasmic reticulum stress in the development of atherosclerosis in a hyperglycaemic mouse model. ( Bowes, AJ; Khan, MI; Pichna, BA; Shi, Y; Werstuck, GH, 2009)
"This study was designed so as to characterize the interactions between levetiracetam (LEV) and the conventional antiepileptic drugs (AEDs) clonazepam (CZP), ethosuximide (ETS), phenobarbital (PB), and valproate (VPA) in suppressing pentylenetetrazole (PTZ)-induced clonic seizures in mice by use of type II isobolographic analysis."	3.75	Isobolographic characterization of the anticonvulsant interaction profiles of levetiracetam in combination with clonazepam, ethosuximide, phenobarbital and valproate in the mouse pentylenetetrazole-induced seizure model. ( Andres-Mach, MM; Czuczwar, SJ; Dudra-Jastrzebska, M; Luszczki, JJ; Patsalos, PN; Ratnaraj, N, 2009)
"We have demonstrated that valproic acid (VPA), a histone deacetylase inhibitor (HDACI), can improve animal survival after hemorrhagic shock, and protect neurons from hypoxia-induced apoptosis."	3.75	Pharmacologic resuscitation: cell protective mechanisms of histone deacetylase inhibition in lethal hemorrhagic shock. ( Alam, HB; Butt, MU; DeMoya, M; King, DR; Li, Y; Liu, B; Sailhamer, EA; Shuja, F; Velmahos, GC, 2009)
" Using rats exposed prenatally to valproic acid (VPA) as an animal model of autism, we examined locomotor activity and feeding under a reversed 12-h light/dark cycle, and found disturbance of the circadian rhythm characterized by frequent arousal during the light/sleep phase."	3.74	Abnormality of circadian rhythm accompanied by an increase in frontal cortex serotonin in animal model of autism. ( Arita, H; Nakamura, M; Nakasato, A; Nakatani, Y; Seki, Y; Sugawara, M; Tsujino, N, 2007)
" We studied the potential anticonvulsant effect of thalidomide: Different doses of thalidomide were tested against seizures induced by 50 mg/kg or 70 mg/kg of pentylenetetrazole (PTZ); the anticonvulsant effect of thalidomide was also compared with that of valproic acid."	3.74	Thalidomide inhibits pentylenetetrazole-induced seizures. ( Calderon, A; Palencia, G; Sotelo, J, 2007)
" In the present study, we compared the effects of riluzole and valproate (VPA) in the pilocarpine-induced limbic seizure model and in the gamma-hydroxybutyrate lactone (GBL)-induced absence seizure model."	3.74	Anti-glutamatergic effect of riluzole: comparison with valproic acid. ( Choi, HC; Choi, SY; Kang, TC; Kim, DS; Kim, JE; Kim, YI; Kwak, SE; Kwon, OS; Song, HK, 2007)
" In sight of the scarcity of studies with other neurotrophins, and the possible relevance of multiple neurotrophic signaling systems in bipolar disorder we investigated the effects of Li and VPT on NT-3 levels in rat serum and hippocampus, using an animal model of mania induced by amphetamine (AMPH)."	3.74	Effects of lithium and valproate on serum and hippocampal neurotrophin-3 levels in an animal model of mania. ( Andreazza, AC; Cacilhas, AA; Ceresér, KM; Frey, BN; Kapczinski, F; Quevedo, J; Valvassori, SS; Walz, JC, 2008)
"Using the mouse maximal electroshock-induced seizure model, indicative of tonic-clonic seizures in humans, the present study was aimed at characterizing the interaction between remacemide and valproate, carbamazepine, phenytoin, and phenobarbital."	3.74	Isobolographic analysis of interactions between remacemide and conventional antiepileptic drugs in the mouse model of maximal electroshock. ( Borowicz, KK; Czuczwar, SJ; Luszczki, JJ; Malek, R; Patsalos, PN; Ratnaraj, N, 2007)
"Exposure to valproic acid (VPA) during embryogenesis can cause several teratogenic effects, including developmental delays and in particular autism in humans if exposure occurs during the third week of gestation."	3.74	Hyperconnectivity of local neocortical microcircuitry induced by prenatal exposure to valproic acid. ( Markram, H; Rinaldi, T; Silberberg, G, 2008)
" The anticonvulsant activity of F1,6BP was determined in rat models of acute seizures induced by pilocarpine, kainic acid, or pentylenetetrazole."	3.74	Fructose-1,6-bisphosphate has anticonvulsant activity in models of acute seizures in adult rats. ( Khan, FA; Lian, XY; Stringer, JL, 2007)
"Oral rufinamide suppressed pentylenetetrazol-induced seizures in mice (ED(50) 45."	3.74	The anticonvulsant profile of rufinamide (CGP 33101) in rodent seizure models. ( Franklin, MR; Kupferberg, HJ; Schmutz, M; Stables, JP; White, HS; Wolf, HH, 2008)
" The combination of AGLD (5 mg/kg) with phenobarbital (PB, applied at its subeffective dose of 15 mg/kg) significantly shortened motor seizure and afterdischarge duration in amygdala-kindled seizures."	3.73	Aminoglutethimide but not spironolactone enhances the anticonvulsant effect of some antiepileptics against amygdala-kindled seizures in rats. ( Borowicz, KK; Czuczwar, SJ, 2005)
" Lower doses of valproate and carbamazepine were required to prevent hyperactivity compared to doses required to block tonic-clonic seizures induced by pentylenetetrazole."	3.73	Evaluation of the effects of lamotrigine, valproate and carbamazepine in a rodent model of mania. ( Arban, R; Brackenborough, K; Gerrard, P; Large, C; Maraia, G; Wilson, A; Winyard, L, 2005)
"Structure-activity relationship studies of valproic acid (VPA) derivatives have revealed a quantitative correlation between histone deacetylase (HDAC) inhibition and induction of neural tube defects (NTDs) in the NMRI-exencephaly-mouse model, but this correlation has been, so far, limited to congeners with a carboxylic acid function."	3.73	S-2-pentyl-4-pentynoic hydroxamic acid and its metabolite s-2-pentyl-4-pentynoic acid in the NMRI-exencephaly-mouse model: pharmacokinetic profiles, teratogenic effects, and histone deacetylase inhibition abilities of further valproic acid hydroxamates an ( Eikel, D; Hoffmann, K; Lampen, A; Nau, H; Zoll, K, 2006)
" The present study aims to investigate the effects of the mood stabilizers lithium (Li) and valproate (VPT) in an animal model of bipolar disorder."	3.73	Effects of mood stabilizers on hippocampus BDNF levels in an animal model of mania. ( Andreazza, AC; Ceresér, KM; Frey, BN; Kapczinski, F; Martins, MR; Quevedo, J; Réus, GZ; Valvassori, SS, 2006)
" Valproic acid (VPA) and suberyolanilide hydroxamic acid (SAHA) were chosen for further studies in dextran sulfate sodium- and trinitrobenzene sulfonic acid-induced colitis in mice."	3.73	Histone hyperacetylation is associated with amelioration of experimental colitis in mice. ( Batra, A; Dinarello, CA; Fantuzzi, G; Fedke, I; Glauben, R; Lehr, HA; Leoni, F; Mascagni, P; Siegmund, B; Zeitz, M, 2006)
") continuous valproic acid (VPA) infusion, as compared with acute injections in the kindling epilepsy model."	3.73	Effect of intracerebroventricular continuous infusion of valproic acid versus single i.p. and i.c.v. injections in the amygdala kindling epilepsy model. ( Alós, M; Barcia, JA; Durán, C; Hernández, ME; Ortiz, P; Serralta, A, 2006)
" In this study, we investigated whether valproic acid (VPA), a known mood stabilizer and anticonvulsant with HDAC-inhibiting activity, improves survival following otherwise lethal hemorrhage in rats."	3.73	Valproic acid prevents hemorrhage-associated lethality and affects the acetylation pattern of cardiac histones. ( Alam, HB; Britten-Webb, J; Burris, D; Chen, H; Gonzales, E; Koustova, E; Mehrani, T; Munuve, R; Nadel, A; Wherry, D, 2006)
" Pentylenetetrazole (PTZ)-induced seizures were used to evaluate the anticonvulsant effect of drugs."	3.73	Modulation of pentylenetetrazole-induced seizures and oxidative stress parameters by sodium valproate in the absence and presence of N-acetylcysteine. ( Pillai, KK; Uma Devi, P; Vohora, D, 2006)
" Maternal treatment with valproic acid (VPA) during pregnancy induces NTD in susceptible fetuses."	3.73	Effect of maternal exposure to homocystine on sodium valproate-induced neural tube defects in the mouse embryos. ( Benedict, S; Nagelkerke, N; Padmanabhan, R; Shafiullah, M, 2006)
"To develop novel orthotopic xenograft models of medulloblastoma in severe combined immunodeficient mice and to evaluate the in vivo antitumor efficacy of valproic acid."	3.73	Valproic Acid prolongs survival time of severe combined immunodeficient mice bearing intracerebellar orthotopic medulloblastoma xenografts. ( Adesina, A; Antalffy, B; Blaney, SM; Lau, CC; Li, XN; Ou, CN; Pietsch, T; Shu, Q; Su, JM, 2006)
"Isobolographic analysis was used to characterize the interactions between stiripentol (STP) and clonazepam (CZP), ethosuximide (ETS), phenobarbital (PB), and valproate (VPA) in suppressing pentylenetetrazole (PTZ)-induced clonic seizures in mice."	3.73	Characterization of the anticonvulsant, behavioral and pharmacokinetic interaction profiles of stiripentol in combination with clonazepam, ethosuximide, phenobarbital, and valproate using isobolographic analysis. ( Czuczwar, SJ; Luszczki, JJ; Patsalos, PN; Ratnaraj, N, 2006)
" Periconceptional folic acid supplementation is reported to protect embryos from developing neural tube defects (NTD)."	3.72	Amelioration of sodium valproate-induced neural tube defects in mouse fetuses by maternal folic acid supplementation during gestation. ( Padmanabhan, R; Shafiullah, MM, 2003)
"Valproic acid (VPA) treatment in female patients is suggested to be associated with the occurrence of a variety of endocrine side effects that include many characteristic symptoms of polycystic ovary syndrome (PCOS)."	3.72	Valproic acid fails to induce polycystic ovary syndrome in female rats. ( Lagace, DC; Nachtigal, MW, 2003)
" Anticonvulsant effects were evaluated against seizures induced by 14 mg kg(-1) of 4-aminopyridine (4-AP) and by 110 mg kg(-1) of pentylenetetrazole (PTZ), and neurotoxicity by the rotarod test."	3.72	Is the interaction between felbamate and valproate against seizures induced by 4-aminopyridine and pentylenetetrazole in mice beneficial? ( Amat, G; Armijo, JA; Cuadrado, A, 2003)
"We investigated the effects of valproate (VPA) on an in vivo model of status epilepticus (SE) induced by intrahippocampal application of 4-aminopyridine (4-AP)."	3.72	Valproate suppresses status epilepticus induced by 4-aminopyridine in CA1 hippocampus region. ( Martín, ED; Pozo, MA, 2003)
"In the current study, we wanted to extend our findings and test the hypothesis that Folbp2(-/-) mice are more susceptible to the teratogenic effects of valproic acid (VPA), a commonly used antiepileptic drug that is known to induce neural tube defects (NTDs) in both humans and laboratory animals."	3.72	Valproate-induced neural tube defects in folate-binding protein-2 (Folbp2) knockout mice. ( Finnell, RH; Merriweather, MY; Spiegelstein, O; Wicker, NJ, 2003)
"The nootropic drug piracetam was investigated in various experimental models of epilepsy."	3.72	Effects of piracetam alone and in combination with antiepileptic drugs in rodent seizure models. ( De Sarro, G; Fischer, W; Kittner, H; Regenthal, R; Russo, E, 2004)
" The aim of this study was to evaluate the profile of interactions between FBM and four conventional antiepileptic drugs (AEDs): clonazepam (CZP), ethosuximide (ESM), phenobarbital (PB), and valproate (VPA), in pentylenetetrazole (PTZ)-induced convulsions in mice, a model of myoclonic seizures in humans."	3.72	Isobolographic and subthreshold analysis of interactions among felbamate and four conventional antiepileptic drugs in pentylenetetrazole-induced seizures in mice. ( Borowicz, KK; Czuczwar, SJ; Luszczki, JJ, 2004)
"Perimenstrual catamenial epilepsy may in part be due to withdrawal of the endogenous progesterone-derived neurosteroid allopregnanolone that potentiates gamma-aminobutyric acidA (GABA(A)) receptor-mediated inhibition."	3.71	Enhanced anticonvulsant activity of neuroactive steroids in a rat model of catamenial epilepsy. ( Reddy, DS; Rogawski, MA, 2001)
"A potential model for bipolar disorder, quinpirole-induced biphasic locomotion, was used for a preliminary evaluation of behavioral effects of oral anticonvulsant treatment."	3.71	Preliminary evaluation of oral anticonvulsant treatment in the quinpirole model of bipolar disorder. ( Belmaker, RH; Einat, H; Shaldubina, A; Shimon, H; Szechtman, H, 2002)
"The efficacy of Flunarizine (FLU), a calcium channel blocker, in combination with conventional antiepileptic drugs, phenytoin (PHT), carbamazepine (CBZ), sodium valproate (VPA), and ethosuximide (ESM), at ED50 doses, were examined for protective effects against maximal electroshock seizures (MES) and pentylenetetrazol (PTZ) induced seizures in mice."	3.70	Additive anticonvulsant effect of flunarizine and sodium valproate on electroshock and chemoshock induced seizures in mice. ( David, J; Joseph, S; Joseph, T, 1998)
" The effects of systemic pretreatment with hydrocortisone (5-25 mg/kg), pyridoxine (20-250 mg/kg), and sodium valproate (VPA; 200 and 400 mg/kg) against the NMDA-induced automatisms, emprosthotonic (hyperflexion), and clonic-tonic seizures were determined."	3.70	Age-specific N-methyl-D-aspartate-induced seizures: perspectives for the West syndrome model. ( Kábová, R; Liptáková, S; Pometlová, M; Slamberová, R; Velísek, L, 1999)
"Perimenstrual catamenial epilepsy, the exacerbation of seizures in association with menstruation, may in part be due to withdrawal of the progesterone metabolite allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), an endogenous anticonvulsant neurosteroid that is a positive allosteric modulator of gamma-aminobutyric acid(A) receptors."	3.70	Enhanced anticonvulsant activity of ganaxolone after neurosteroid withdrawal in a rat model of catamenial epilepsy. ( Reddy, DS; Rogawski, MA, 2000)
" In a search for protection against neural tube defects, we investigated the effect of methionine on the incidence of VPA-induced spina bifida in the mouse."	3.69	Methionine reduces the valproic acid-induced spina bifida rate in mice without altering valproic acid kinetics. ( Ehlers, K; Elmazar, MM; Nau, H, 1996)
"We report the effects of two new dihydropyridine derivatives, isradipine (4-(4'-benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedic arboxylic acid methylisopropylester) and niguldipine (1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinecarboxylic acid 3-(4,4-diphenyl-1-piperidinyl)-propyl methyl ester hydrochloride), and of dantrolene (1-[(5-[p-nitrophenyl]furfurylidene)-amino]hydantoin sodium, an inhibitor of Ca2+ release from intracellular stores) on the protective efficacy of antiepileptic drugs against maximal electroshock-induced seizures."	3.69	Influence of isradipine, niguldipine and dantrolene on the anticonvulsive action of conventional antiepileptics in mice. ( Borowicz, KK; Czuczwar, SJ; Gasior, M; Kleinrok, Z, 1997)
"Prenatal exposure to the antiepileptic drug valproic acid (VPA) has been associated with the formation of spina bifida aperta, meningocele, and meningomyelocele in the human."	3.68	Valproic acid-induced spina bifida: a mouse model. ( Ehlers, K; Merker, HJ; Nau, H; Stürje, H, 1992)
"The anticonvulsant effect of either phenobarbital or dilantin was potentiated by exogenous glycine in DBA/2 audiogenic seizure mice and in 3-mercaptopropionic acid-induced seizures."	3.67	Glycine potentiates the action of some anticonvulsant drugs in some seizure models. ( Lajtha, A; Toth, E, 1984)
"Seven GABAmimetic drugs, namely cetyl gamma-aminobutyric acid (cetyl GABA), 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridine-3-ol, progabide, aminooxyacetic acid, alpha-acetylenic GABA, (-)-nipecotic acid ethyl ester and (+/-)-cis-4-hydroxynipecotic acid methyl ester, were tested for their potency to block "major" (generalized clonic-tonic) seizures in gerbils, induced by blowing at the animals with compressed air."	3.66	High anticonvulsant potency of gamma-aminobutyric acid (GABA)mimetic drugs in gerbils with genetically determined epilepsy. ( Frey, HH; Löscher, W; Reiche, R; Schultz, D, 1983)
"Valproic acid-treated animals had significantly less neurologic impairment on days 2 (16."	3.30	Prolonging the therapeutic window for valproic acid treatment in a swine model of traumatic brain injury and hemorrhagic shock. ( Alam, HB; Chtraklin, K; Dimonte, D; Ho, JW; Jin, G; Joaquin, TA; Keeney-Bonthrone, TP; Latif, Z; Ober, RA; Pai, MP; Vercruysse, C; Wen, B, 2023)
"The term of autism spectrum disorders (ASD) is used to account for the diversity of symptoms that characterize this pathology."	2.61	[The valproate model of autism]. ( Bossu, JL; Roux, S, 2019)
"Valproic acid (VPA) is an anticonvulsant and mood stabilizer that, when used during the gestational period, increases the risk of ASD in the offspring."	2.58	Neuroimmune Alterations in Autism: A Translational Analysis Focusing on the Animal Model of Autism Induced by Prenatal Exposure to Valproic Acid. ( Bambini-Junior, V; Deckmann, I; Fontes-Dutra, M; Gottfried, C; Schwingel, GB, 2018)
"Drug-induced steatohepatitis is a rare form of liver injury known to be caused by only a handful of compounds."	2.52	Mechanistic review of drug-induced steatohepatitis. ( Guo, GL; Schumacher, JD, 2015)
"Valproic acid (VPA) is a known human teratogen."	2.45	Valproic acid in pregnancy: how much are we endangering the embryo and fetus? ( Ornoy, A, 2009)
"Valproic acid (VPA) is an effective drug, which is preferred for the treatments of epilepsy and various kinds of seizures."	2.44	The effects of valproic acid neurotoxicity on aggressive behavior in zebrafish autism model. ( Feng, T; Li, X; Lu, W, 2024)
"A major challenge in the treatment of bipolar depression is the tendency for antidepressant medications, particularly tricyclic antidepressants, to precipitate episodes of mania, or to increase cycle frequency or symptom intensity."	2.44	The role of mood stabilisers in the treatment of the depressive facet of bipolar disorders. ( Bourin, M; Prica, C, 2007)
"Nocturnal epilepsy is a neurological disease that has a significant effect on sleep."	1.91	Effect of valproate on sleep patterns disturbed by epilepsy. ( Ayala-Guerrero, F; Castro-Domínguez, D; Gutiérrez-Chávez, CA; Mateos-Salgado, EL; Mexicano-Medina, G, 2023)
"In order to develop better treatments for autism spectrum disorder (ASD) it is critical to understand the developmental trajectory of the disorder and the accompanying brain changes."	1.91	Adolescent female valproic acid rats have impaired extra-dimensional shifts of attention and enlarged anterior cingulate cortices. ( Bossmann, SH; Challans, B; Davison, T; King, C; Mali, I; Maze, TR; Payne, M; Plakke, B, 2023)
"Thymol is a bioactive monoterpene isolated from Thymus vulgaris that has anti-inflammatory properties and is helpful in neurodevelopmental disorders."	1.91	Thymol improves autism-like behaviour in VPA-induced ASD rats through the Pin1/p38 MAPK pathway. ( Chen, J; Li, Y; Lv, M; Tang, B; Wang, F; Xiong, Y; Zhang, H, 2023)
"Aripiprazole (APZ) is an atypical antipsychotic that can safeguard mice against autism-like behavior induced by valproic acid (VPA)."	1.91	Maternal treatment with aripiprazole prevents the development of a valproic acid-induced autism-like phenotype in juvenile male mice. ( de Andrade, GM; de Barros Viana, GS; de Oliveira Ferreira, E; Lima, FAV; Neves, KRT; Pessoa Gomes, JM, 2023)
" The repetitive behaviors were ameliorated relatively in VPA groups with NEPO2000 treatment, and astrogliosis was reduced even when VPA rats were treated with a lower dosage of NEPO."	1.91	Astrocyte responses to postnatal erythropoietin and nano-erythropoietin treatments in a valproic acid-induced animal model of autism. ( Basiri, M; Haratizadeh, S; Nozari, M; Ranjbar, M, 2023)
"Here we developed a novel mania mice model by combining a series of chronic unpredictable rhythm disturbances (CURD), which include disruption of circadian rhythm, sleep deprivation, exposure to cone light, with subsequent interference of followed spotlight, stroboscopic illumination, high-temperature stress, noise disturbance and foot shock."	1.91	A novel murine model of mania. ( Chen, B; Cui, L; Feng, Y; Gong, W; Ji, M; Li, B; Li, X; Verkhratsky, A; Wang, S; Wu, X; Xia, M; Zhang, D, 2023)
"Valproic acid (VPA) is a known drug for treating epilepsy and mood disorders; however, it is not recommended for pregnant women because of its possible teratogenicity."	1.91	Neonatal Exposure to Valproate Induces Long-Term Alterations in Steroid Hormone Levels in the Brain Cortex of Prepubertal Rats. ( Cho, SH; Jang, EH; Kim, SA; Lee, J, 2023)
"Many studies show that the number of cognitive impairmentscan be reduced by antagonists of the histamine H3 receptor (H3R)."	1.91	Amelioration of cognition impairments in the valproic acid-induced animal model of autism by ciproxifan, a histamine H3-receptor antagonist. ( Esmaeilpour, K; Sepehri, G; Sheibani, V; Shekari, MA; Taheri, F, 2023)
"Autism is a neurodevelopmental condition, and it's associated pathophysiology, viz."	1.91	Neuroprotective Efficacy of Fisetin Against VPA-Induced Autistic Neurobehavioral Alterations by Targeting Dysregulated Redox Homeostasis. ( Ahsan, AU; Budhwar, M; Chopra, M; Mehra, S; Sharma, M, 2023)
"Autism has a strong genetic and heritable component; however, environmental factors including toxins, pesticides, infection and in utero exposure to drugs such as VPA have also been implicated in ASD."	1.91	Striatal synaptic changes and behavior in adult mouse upon prenatal exposure to valproic acid. ( Delgado-González, E; Durairaj, RV; Espinosa, F; Hernandez, A; Martínez-Torres, A; Reyes-Haro, D, 2023)
"Valproic acid (VPA) is a well-known anti-epileptic drug, but its prenatal exposure to animals causes social impairment, neurotransmitters imbalance, and neuroinflammation with ASD-like phenotypes."	1.91	Syringic acid alleviates valproic acid induced autism via activation of p38 mitogen-activated protein kinase: Possible molecular approach. ( Mallan, S; Singh, S, 2023)
"Skeletal muscles in animal models of Duchenne muscular dystrophy (DMD) are more susceptible to contraction-induced functional loss, which is not related to fatigue."	1.91	Valproic acid reduces muscle susceptibility to contraction-induced functional loss but increases weakness in two murine models of Duchenne muscular dystrophy. ( Agbulut, O; Delacroix, C; Ferry, A; Furling, D; Lemaitre, M; Moutachi, D, 2023)
"Autism is a neurobehavioral disease that induces cognitive and behavioral alterations, usually accompanied by oxidative stress in the brain."	1.91	Saffron and crocin ameliorate prenatal valproic acid-induced autistic-like behaviors and brain oxidative stress in the male offspring rats. ( Abbarin, D; Raise-Abdullahi, P; Rashidy-Pour, A; Sedaghat, K; Seyedinia, SA; Tarahomi, P; Vafaei, AA; Yaribeygi, H, 2023)
"The mouse model of autism induced by prenatal exposure to valproic acid (VPA) was used to assess the therapeutic potential of STX209 on autism‑like behaviour in the present study."	1.72	The GABAB receptor agonist STX209 reverses the autism‑like behaviour in an animal model of autism induced by prenatal exposure to valproic acid. ( Chang, H; Ding, J; Gao, C; He, M; Jiang, S; Li, W; Sun, T; Sun, Y; Wang, F; Wang, Y; Xiao, L; Zhu, C, 2022)
" Pregnant C57BL/6 J mice were intraperitoneally injected with a dosage of 500 mg/kg valproic acid (VPA) on embryonic day 10."	1.72	Size anomaly and alteration of GABAergic enzymes expressions in cerebellum of a valproic acid mouse model of autism. ( Kwan, KM; Ma, SY, 2022)
"Valproic acid (VPA) has been extensively used for treatment of anxiety and seizure."	1.72	Valproic acid during hypotensive resuscitation in pigs with trauma and hemorrhagic shock does not improve survival. ( Bynum, J; Cap, AP; Martini, WZ; Ryan, KL; Xia, H, 2022)
"Autism spectrum disorder is a developmental disorder that can affect social interactions and sensory-motor behaviors."	1.72	Sex difference in cognitive behavioral alterations and barrel cortex neuronal responses in rats exposed prenatally to valproic acid under continuous environmental enrichment. ( Afarinesh, MR; Joushy, S; Mafi, F; Mollashahi, M; Sabzalizadeh, M; Sheibani, V, 2022)
"Autism spectrum disorder is a neurodevelopmental disorder characterized by sensory abnormalities, social skills impairment and cognitive deficits."	1.72	Alterations in the intrinsic discharge activity of CA1 pyramidal neurons associated with possible changes in the NADPH diaphorase activity in a rat model of autism induced by prenatal exposure to valproic acid. ( Behzadi, G; Borjkhani, M; Davoudi, S; Hajisoltani, R; Hosseinmardi, N; Janahmadi, M; Karimi, SA; Khatibi, VA; Rahdar, M, 2022)
"X-linked myotubular myopathy (XLMTM) is a fatal neuromuscular disorder caused by loss of function mutations in MTM1."	1.72	X-linked myotubular myopathy is associated with epigenetic alterations and is ameliorated by HDAC inhibition. ( Alvi, SA; Beggs, AH; Bonnemann, CG; Celik, A; Chater-Diehl, E; Chicanne, G; Combes-Soia, L; Dowling, JJ; Froment, C; Genetti, CA; Ghahramani-Seno, MM; Goodman, SJ; Maani, N; Mansat, M; Monis, S; Muntoni, F; Pannia, E; Payrastre, B; Sabha, N; Sarikaya, E; Uusküla-Reimand, L; Viaud, J; Volpatti, JR; Weksberg, R; Wilson, MD; Yuki, KE, 2022)
"Previous studies have indicated that autism-like behavioral phenotypes detected in F1 VPA mice transgenetically appear in F2 and F3 generations."	1.72	Early-onset of social communication and locomotion activity in F2 pups of a valproic acid-induced mouse model of autism. ( Fu, P; Furuhara, K; Higashida, H; Minami, K; Mizutani, R; Tsuji, C; Tsuji, T; Yokoyama, S; Zhong, J, 2022)
"Melatonin is an endogenous hormone and can restore gut microbial dysbiosis under various disease conditions."	1.72	Rescue of social deficits by early-life melatonin supplementation through modulation of gut microbiota in a murine model of autism. ( Cui, Y; Li, XG; Liu, W; Liu, X; Qiu, B; Wang, X; Xiang, G; Yu, M; Zhang, D; Zhang, Y, 2022)
"Valproic acid-treated animals demonstrated significantly better neuroseverity scores on postinjury 1 (control, 9."	1.62	A single dose of valproic acid improves neurologic recovery and decreases brain lesion size in swine subjected to an isolated traumatic brain injury. ( Alam, HB; Biesterveld, BE; Chtraklin, K; Kemp, MT; O'Connell, RL; Pai, MP; Rajanayake, KK; Vercruysse, CA; Wakam, GK, 2021)
"Valproic acid (VPA) is an antiepileptic drug with a pronounced teratogenic effect associated with a high risk of ASD, and its administration to rats during the gestation is used for autism modeling."	1.62	Assessment of behavioral, morphological and electrophysiological changes in prenatal and postnatal valproate induced rat models of autism spectrum disorder. ( Chavushyan, V; Danielyan, M; Fereshetyan, K; Yenkoyan, K, 2021)
"Valproic acid (VPA) has been shown to attenuate brain lesion size and swelling within the first few hours following TBI."	1.62	Pharmacologic modulation of brain metabolism by valproic acid can induce a neuroprotective environment. ( Alam, HB; Bhatti, UF; Biesterveld, BE; Dennahy, IS; Kachman, M; Karnovsky, A; Li, Y; Liu, B; Nikolian, VC; O'Connell, RL; Siddiqui, A; Williams, AM, 2021)
"Valproic acid-treated animals demonstrated significantly less neurologic impairment on PID 1 and returned to baseline faster (PID 1 mean neurologic severity score, control = 22 ± 3 vs."	1.62	Administration of valproic acid in clinically approved dose improves neurologic recovery and decreases brain lesion size in swine subjected to hemorrhagic shock and traumatic brain injury. ( Alam, HB; Bhatti, UF; Biesterveld, BE; Chtraklin, K; Kemp, MT; O'Connell, RL; Pai, MP; Siddiqui, AZ; Srinivasan, A; Vercruysse, CA; Wakam, GK; Williams, AM, 2021)
"Despite the increasing prevalence of autism spectrum disorder (ASD), there is still a deficiency in understanding its exact pathophysiology and treatment, therefore validation of translational ASD animal model is warranted."	1.62	Validation of prenatal versus postnatal valproic acid rat models of autism: A behavioral and neurobiological study. ( Abdelraouf, SM; Aboul-Fotouh, S; Abuelezz, SA; Ahmed, AI; Bahaa, N; Elnahas, EM; Hassan, GA; Ibrahim, EA; Mohamad, MI; Nabil, MM, 2021)
"Spinal inflammation is a pathophysiological state of neuropathic pain (NP)."	1.62	Valproic acid mitigates spinal nerve ligation-induced neuropathic pain in rats by modulating microglial function and inhibiting neuroinflammatory response. ( Chen, C; Feng, X; Guo, A; Ke, J; Li, J; Lu, Q; Luo, L, 2021)
"Like valproic acid, treatment with primidone reduced free-C levels in LE/LY in NPC1-null/mutant cells."	1.62	Beneficial effects of primidone in Niemann-Pick disease type C (NPC)-model cells and mice: Reduction of unesterified cholesterol levels in cells and extension of lifespan in mice. ( Ashikawa, H; Honda, T; Mogi, H; Murayama, T; Nakamura, H, 2021)
"Epilepsy is one of the most frequent neurological disorders characterized by an enduring predisposition to generate epileptic seizures."	1.62	Histopathological and Biochemical Assessment of Neuroprotective Effects of Sodium Valproate and Lutein on the Pilocarpine Albino Rat Model of Epilepsy. ( Al-Rafiah, AR; Mehdar, KM, 2021)
"Muscular dystrophies are debilitating neuromuscular disorders for which no cure exists."	1.62	Valproic acid stimulates myogenesis in pluripotent stem cell-derived mesodermal progenitors in a NOTCH-dependent manner. ( Breuls, N; Carai, P; Deroose, C; Garrido, GM; Giarratana, N; Heymans, S; Ranga, A; Sampaolesi, M; Yedigaryan, L, 2021)
"Machado-Joseph disease (MJD, also known as spinocerebellar ataxia type 3) is a fatal neurodegenerative disease that impairs control and coordination of movement."	1.62	Sodium valproate increases activity of the sirtuin pathway resulting in beneficial effects for spinocerebellar ataxia-3 in vivo. ( Chung, RS; Cole, NJ; De Luca, A; Guillemin, GJ; Laird, AS; Lee, A; Luu, L; Nicholson, GA; Robinson, KJ; Suddull, HJ; Tym, MC; Watchon, M; Yuan, KC, 2021)
" In conclusion, MDC-1112 should be further explored as a potential agent to be used in combination with GEM for treating PC."	1.56	Phospho-valproic acid (MDC-1112) reduces pancreatic cancer growth in patient-derived tumor xenografts and KPC mice: enhanced efficacy when combined with gemcitabine. ( Digiovanni, MG; Lacomb, JF; Luo, D; Mackenzie, GG; Rigas, B; Wei, R; Williams, JL, 2020)
"Suramin treatment did not affect VPA-induced upregulation of P2X4 and P2Y2 receptor expression in the hippocampus, and P2X4 receptor expression in the medial prefrontal cortex, but normalized an increased level of interleukin 6 (IL-6)."	1.56	Effects of single-dose antipurinergic therapy on behavioral and molecular alterations in the valproic acid-induced animal model of autism. ( Bambini-Junior, V; Bauer-Negrini, G; Brum Schwingel, G; Carello-Collar, G; Castillo, ARG; Corrêa-Velloso, J; Deckmann, I; Fontes-Dutra, M; Gonçalves, MCB; Gottfried, C; Hirsch, MM; Körbes-Rockenbach, M; Naaldijk, Y; Rabelo, B; Santos-Terra, J; Schneider, T; Staevie, GZ; Ulrich, H, 2020)
"Corticosterone plasma level was increased in the CUMS compared to the non-stressed group (p < 0."	1.56	Valproic acid administration exerts protective effects against stress-related anhedonia in rats. ( Barati, M; Eslami, M; Goudarzi, M; Mehrabi, S; Nahavandi, A; Shahbazi, A, 2020)
" Treatment with VPA induced Ncs-1 gene expression in cell line while chronic administration of this drug to mice increased both Ncs-1 protein and mRNA levels in the mouse frontal cortex."	1.56	Contribution of neuronal calcium sensor 1 (Ncs-1) to anxiolytic-like and social behavior mediated by valproate and Gsk3 inhibition. ( Beaulieu, JM; Collodetti, M; Del'Guidice, T; Khlghatyan, J; Magno, LAV; Nicolau, ES; Romano-Silva, MA; Tenza-Ferrer, H, 2020)
"Five groups of each of 12 female rats were orally dosed daily for 8 weeks with either carbamazepine (CBZ) (60 mg/kg), eslicarbazepine (ESL) (80 mg/kg), valproic acid (VPA) (300 mg/kg), levetiracetam (LEV) (50 mg/kg) or saline (control (CTL))."	1.56	Effects of carbamazepine, eslicarbazepine, valproic acid and levetiracetam on bone microarchitecture in rats. ( Andersen, NB; Diemar, SS; Ding, M; Eiken, P; Ellegaard, M; Jørgensen, NR; Sejling, AS, 2020)
"The manifestations of autism spectrum disorder (ASD) are highly heterogeneous."	1.56	Vitamin A deficiency exacerbates autism-like behaviors and abnormalities of the enteric nervous system in a valproic acid-induced rat model of autism. ( Chen, J; Cheng, B; Li, T; Liu, H; Wang, S; Wu, Q; Yang, T; Zhang, X; Zhu, J, 2020)
"The social motivational theory of autism spectrum disorder (ASD) focuses on social anhedonia as key causal feature of the impaired peer relationships that characterize ASD patients."	1.56	Targeting PPARα in the rat valproic acid model of autism: focus on social motivational impairment and sex-related differences. ( Braccagni, G; De Montis, MG; Gambarana, C; Guzzi, F; Parenti, M; Scheggi, S, 2020)
"Valproic acid (VPA) is a drug commonly used for epileptic seizure control."	1.56	Valproic acid inhibits interferon-γ production by NK cells and increases susceptibility to Listeria monocytogenes infection. ( Chacón-Salinas, R; Chávez-Blanco, AD; Estrada-García, I; Estrada-Parra, S; Flores-Borja, F; Flores-Mejía, R; García-Pérez, BE; Serafín-López, J; Soria-Castro, R; Wong-Baeza, I, 2020)
"After intracerebral hemorrhage (ICH), mechanical compression by hematoma, neuroinflammation, oxidative stress, and cytotoxicity of hematoma lysates caused the destruction of the blood brain barrier (BBB)."	1.56	Valproate Sodium Protects Blood Brain Barrier Integrity in Intracerebral Hemorrhage Mice. ( Guo, Z; Hou, Y; Jiang, J; Song, Y; Zhao, L; Zhao, W, 2020)
"In order to produce this demyelination model, LPC (1%, 2 μL) was injected into the rat optic chiasm."	1.51	Fingolimod (FTY720) improves the functional recovery and myelin preservation of the optic pathway in focal demyelination model of rat optic chiasm. ( Ghasemi-Kasman, M; Hashemian, M; Parsian, H; Sadeghi, F, 2019)
"Exencephaly/anencephaly is one of the leading causes of neonatal mortality and the most extreme open neural tube defect with no current treatments and limited mechanistic understanding."	1.51	Cell necrosis, intrinsic apoptosis and senescence contribute to the progression of exencephaly to anencephaly in a mice model of congenital chranioschisis. ( Duru, S; Fernandez-Alonso, I; Fernandez-Martin, A; Figueira, RL; Marotta, M; Oria, M; Peiro, JL; Sbragia, L; Scorletti, F; Shaaban, AF; Turner, LE, 2019)
"Autism is far more prevalent in males than females, and sex-specific properties of PCs have been reported recently."	1.51	Regional and sex-dependent alterations in Purkinje cell density in the valproate mouse model of autism. ( Bailly, Y; Bossu, JL; Roux, S, 2019)
"The 6-Hz psychomotor seizure induced ultra-structural changes in both cortex and hippocampus in mice treated with PCPA."	1.51	Serotonergic mechanisms in the 6-Hz psychomotor seizures in mice. ( Jahan, K; Pillai, KK; Vohora, D, 2019)
" Additionally, we established the relationship between treatment with ACEA in combination with LEV and hippocampal neurogenesis in mouse brain."	1.51	Levetiracetam combined with ACEA, highly selective cannabinoid CB1 receptor agonist changes neurogenesis in mouse brain. ( Andres-Mach, M; Haratym-Maj, A; Maj, M; Rola, R; Szewczyk, A; Zagaja, M; Łuszczki, JJ, 2019)
"Electrically-induced tonic-clonic seizures were experimentally evoked in adult male albino Swiss mice."	1.51	New derivative of 1,2,4-triazole-3-thione (TP427) potentiates the anticonvulsant action of valproate, but not that of carbamazepine, phenytoin or phenobarbital in the mouse tonic-clonic seizure model. ( Gut-Lepiech, A; Karwan, S; Kondrat-Wróbel, MW; Marzeda, P; Plech, T; Wróblewska-Łuczka, P; Łuszczki, JJ, 2019)
"A structural, electrical and metabolic atrial remodeling is central in the development of atrial fibrillation (AF) contributing to its initiation and perpetuation."	1.51	HDAC (Histone Deacetylase) Inhibitor Valproic Acid Attenuates Atrial Remodeling and Delays the Onset of Atrial Fibrillation in Mice. ( Hamer, S; Hammer, E; Himmler, K; Müller, FU; Pluteanu, F; Scholz, B; Schulte, JS; Seidl, MD; Stein, J; Völker, U; Wardelmann, E, 2019)
"Valproic acid treatment marginally enhanced global DNA methylation in the frontal cortex."	1.51	Brain derived neurotrophic factor expression and DNA methylation in response to subchronic valproic acid and/or aldosterone treatment. ( Balagova, L; Buzgoova, K; Graban, J; Hlavacova, N; Jezova, D, 2019)
"Valproic acid (VPA) has been shown to have beneficial properties in lethal hemorrhage/trauma models."	1.51	Valproic acid improves survival and decreases resuscitation requirements in a swine model of prolonged damage control resuscitation. ( Alam, HB; Bhatti, UF; Biesterveld, BE; Chtraklin, K; Dennahy, IS; Graham, NJ; Kathawate, RG; Li, Y; Russo, RM; Vercruysse, CA; Williams, AM; Zhou, J, 2019)
"Sepsis is a leading cause of death and disability worldwide."	1.51	Valproic acid attenuates sepsis-induced myocardial dysfunction in rats by accelerating autophagy through the PTEN/AKT/mTOR pathway. ( Liu, Y; Shi, X; Xiao, D; Zhang, D, 2019)
"Gentamicin (GM) is an aminoglycoside antibiotic used to treat several types of bacterial infections."	1.48	Anticonvulsant effect of gentamicin on the seizures induced by kainic acid. ( Ji, Y; Jiang, N; Kuang, P; Lao, W; Lin, W; Wang, Z; Yin, T; Zhao, Y; Zhu, H, 2018)
"Combined traumatic brain injury and hemorrhagic shock are highly lethal."	1.48	Improvement of Blood-Brain Barrier Integrity in Traumatic Brain Injury and Hemorrhagic Shock Following Treatment With Valproic Acid and Fresh Frozen Plasma. ( Alam, HB; Andjelkovic, AV; Bambakidis, T; Dekker, SE; Dennahy, IS; Georgoff, PE; Higgins, GA; Nikolian, VC; Williams, AM, 2018)
"Valproic acid (VPA) is a histone deacetylase inhibitor that improves outcomes in large animal models of trauma."	1.48	Valproic acid induces prosurvival transcriptomic changes in swine subjected to traumatic injury and hemorrhagic shock. ( Alam, HB; Athey, B; Chtraklin, K; Eidy, H; Georgoff, PE; Ghandour, MH; Higgins, G; Nikolian, VC; Williams, A, 2018)
"Curcumin is a phytochemical with promising effects on epilepsy treatment."	1.48	Micronization potentiates curcumin's anti-seizure effect and brings an important advance in epilepsy treatment. ( Aguiar, GPS; Bertoncello, KT; Oliveira, JV; Siebel, AM, 2018)
"Autism is characterized by numerous behavioral impairments, such as in communication, socialization and cognition."	1.48	Zinc as a therapy in a rat model of autism prenatally induced by valproic acid. ( Bernardi, MM; Cezar, LC; da Fonseca, CCN; de Lima, APN; Felicio, LF; Kirsten, TB, 2018)
"Rats of the VPA model of autism showed reduced total reciprocal social interaction, prevented by prenatal treatment with resveratrol (RSV)."	1.48	Behavioral alterations in autism model induced by valproic acid and translational analysis of circulating microRNA. ( Bambini-Junior, V; Bauer-Negrini, G; Deckmann, I; Della-Flora Nunes, G; Fontes-Dutra, M; Gottfried, C; Hirsch, MM; Margis, R; Nunes, W; Rabelo, B; Riesgo, R, 2018)
"The etiology of autism remains unknown and its molecular basis is not yet well understood."	1.48	Social behavior, neuroimmune markers and glutamic acid decarboxylase levels in a rat model of valproic acid-induced autism. ( Imai, M; Lwin, TT; Mar, O; Nway, NC; Watanabe, H; Win-Shwe, TT, 2018)
"Valproic acid-treated animals developed biochemical evidence of FS as judged by elevated serum gamma-glutamyl transferase (γ-GT), alkaline phosphatase (ALP), creatinine (Cr), and blood urea nitrogen (BUN) along with hypokalaemia, hypophosphataemia, and a decrease in serum uric acid."	1.48	Mechanism of valproic acid-induced Fanconi syndrome involves mitochondrial dysfunction and oxidative stress in rat kidney. ( Heidari, R; Jafari, F; Khodaei, F; Niknahad, H; Shirazi Yeganeh, B, 2018)
" The aim of the study was to conduct an in vivo evaluation of the relationship between treatments with synthetic cannabinoid arachidonyl-2'-chloroethylamide (ACEA) alone or in combination with valproic acid (VPA) and hippocampal neurogenesis in a mouse pilocarpine model of epilepsy."	1.46	A Long-Term Treatment with Arachidonyl-2'-Chloroethylamide Combined with Valproate Increases Neurogenesis in a Mouse Pilocarpine Model of Epilepsy. ( Andres-Mach, M; Dudra-Jastrzębska, M; Haratym, J; Haratym-Maj, A; Maj, M; Rola, R; Zagaja, M; Łuszczki, JJ, 2017)
"Using pentylenetetrazole (PTZ)-induced seizures model in mice, the effect of DATS on the anticonvulsant activity of VP was found to be positive, meaning that combination of DATS with VP can confer protection against VP-induced hepatic injurious effects through its antioxidant, antiinflammatory, and antiapoptotic properties without affecting VP antiepileptic activity."	1.46	Cytoprotective effects of diallyl trisulfide against valproate-induced hepatotoxicity: new anticonvulsant strategy. ( El-Agamy, DS; Shaaban, AA, 2017)
"Valproic acid-treated animals demonstrated significantly less neurologic impairment between PID 1 to 5 and smaller brain lesions on PID 3 (mean lesion size ± SEM, mm: ISCS = 4,956 ± 1,511 versus ISCS + VPA = 828 ± 279; p = 0."	1.46	Valproic acid decreases brain lesion size and improves neurologic recovery in swine subjected to traumatic brain injury, hemorrhagic shock, and polytrauma. ( Alam, HB; Chtraklin, K; Dennahy, IS; Eidy, H; Georgoff, PE; Ghandour, MH; Han, Y; Li, Y; Nikolian, VC; Pai, MP; Srinivasan, A, 2017)
"Nocturnal frontal lobe epilepsy (NFLE) is an idiopathic partial epilepsy with a family history in about 25% of cases, with autosomal dominant inheritance (autosomal dominant NFLE [ADNFLE])."	1.46	Rationale for an adjunctive therapy with fenofibrate in pharmacoresistant nocturnal frontal lobe epilepsy. ( Aroni, S; Marrosu, F; Melis, M; Milioli, G; Muntoni, AL; Parrino, L; Pillolla, G; Pistis, M; Puligheddu, M; Sagheddu, C; Terzano, GM, 2017)
"Valproic acid (VPA) was combined with gemcitabine (GCb) to stimulate EBV reactivation, followed by antiviral treatment with ganciclovir (GCV)."	1.46	Cytolytic virus activation therapy and treatment monitoring for Epstein-Barr virus associated nasopharyngeal carcinoma in a mouse tumor model. ( de Greeuw, I; Eersels, JLH; Greijer, AE; Middeldorp, JM; Molthoff, CFM; Novalić, Z; Verkuijlen, SAWM; Verlaan, M, 2017)
" Serum levels of valproate were estimated using HPLC for pharmacokinetic study."	1.46	Pharmacokinetic and pharmacodynamic interaction of hydroalcoholic extract of Ocimum sanctum with valproate. ( Gupta, YK; Joshi, D; Kaleekal, T; Kumar, R; Sarangi, SC, 2017)
"The novel therapeutic strategy against autism is essential due to the limited therapeutic efficacy."	1.46	Laser Acupuncture at HT7 Improves the Cerebellar Disorders in Valproic Acid-Rat Model of Autism. ( Khongrum, J; Wattanathorn, J, 2017)
"Valproic acid (VPA) is a short-chain branched fatty acid with anti-epileptic, neuro-protective and anti-inflammatory effects."	1.46	Valproic acid attenuates inflammation of optic nerve and apoptosis of retinal ganglion cells in a rat model of optic neuritis. ( Li, H; Liu, Q; Niu, X; Wang, Z; Yang, J; Zhao, C; Zhao, L, 2017)
"The median seizure stage, latency onset of first stage 4/5 seizures, and incidence of convulsing animals were recorded."	1.46	Octreotide ameliorates inflammation and apoptosis in acute and kindled murine PTZ paradigms. ( Al-Shorbagy, MY; Nassar, NN, 2017)
"Chronic pain is a multifactorial disease comprised of both inflammatory and neuropathic components that affect ∼20% of the world's population."	1.46	sec-Butylpropylacetamide (SPD), a new amide derivative of valproic acid for the treatment of neuropathic and inflammatory pain. ( Bialer, M; Brennan, KC; Devor, M; Kaufmann, D; Smith, MD; West, PJ; White, HS; Yagen, B, 2017)
"Renal fibrosis is a common pathological feature of the progression of chronic kidney disease."	1.46	Valproic acid attenuates renal fibrosis through the induction of autophagy. ( Doi, S; Doi, T; Kawaoka, K; Masaki, T; Nakashima, A; Ueno, T; Yamada, K, 2017)
" The maximal in vivo VPA dosage that showed no significant cytotoxicity compared with control was 10 mg/kg/day."	1.46	Synergistic effect of cytokine-induced killer cell with valproate inhibits growth of hepatocellular carcinoma cell in a mouse model. ( Chang, Y; Cho, E; Cho, H; Cho, YY; Kang, SH; Kim, YJ; Lee, DH; Lee, JH; Nam, JY; Yoon, JH; Yu, SJ, 2017)
"Sulforaphane (SFN) is a thiol compound found in wide abundance in cruciferous plants that has numerous reported therapeutic efficacies."	1.46	Sulforaphane protects against sodium valproate-induced acute liver injury. ( Atef, H; El-Khouly, OA; Nazmy, EA; Said, E, 2017)
"The regulatory paradigm in cardiac hypertrophy involves alterations in gene expression that is mediated by chromatin remodeling."	1.46	Selective inhibition of HDAC2 by magnesium valproate attenuates cardiac hypertrophy. ( Goyal, RK; Patel, BM; Raghunathan, S, 2017)
"Sporadic Alzheimer's disease (SAD) is a slowly progressive neurological disorder that is the most common form of dementia."	1.46	Protective effect of valproic acid in streptozotocin-induced sporadic Alzheimer's disease mouse model: possible involvement of the cholinergic system. ( El Sayed, NSED; Sorial, ME, 2017)
" Pharmacokinetic parameters were estimated using non-compartmental analysis."	1.46	Plasma and cerebrospinal fluid pharmacokinetics of select chemotherapeutic agents following intranasal delivery in a non-human primate model. ( Cruz, R; Figg, WD; League-Pascual, JC; Lester-McCully, CM; Peer, CJ; Rodgers, L; Ronner, L; Shandilya, S; Warren, KE, 2017)
"The 6-Hz-induced seizures were accompanied by reduced brain 5-HT, DA, NE, histamine, GABA, and enhanced glutamate levels."	1.46	Parachlorophenylalanine-induced 5-HT depletion alters behavioral and brain neurotransmitters levels in 6-Hz psychomotor seizure model in mice. ( Jahan, K; Pillai, KK; Vohora, D, 2017)
"Adequate control of seizures remains an unmet need in epilepsy."	1.43	Anticonvulsant activity, crystal structures, and preliminary safety evaluation of N-trans-cinnamoyl derivatives of selected (un)modified aminoalkanols. ( Gunia-Krzyżak, A; Koczurkiewicz, P; Marona, H; Nitek, W; Pękala, E; Szkaradek, N; Słoczyńska, K; Waszkielewicz, AM; Żelaszczyk, D; Żesławska, E, 2016)
"Epilepsy is a kind of neurogenic diseases with high prevalence and characterized by seizure, brain paradoxical discharge and convulsion in spontaneous, transient, recurrent and uncontrolled manner."	1.43	[Establish and use of an epilepsy model in larval zebrafish]. ( Song, DQ; Tang, S; Zhang, JP; Zheng, YM, 2016)
"Males are predominantly affected by autism spectrum disorders (ASD) with a prevalence ratio of 5:1."	1.43	MeCP2 Modulates Sex Differences in the Postsynaptic Development of the Valproate Animal Model of Autism. ( Cheong, JH; Choi, CS; Han, SH; Kim, JW; Kim, KC; Ryu, JH; Shin, CY, 2016)
"Valproic acid (VA) has been shown to be neuroprotective in several experimental brain diseases."	1.43	Valproic Acid Pretreatment Reduces Brain Edema in a Rat Model of Surgical Brain Injury. ( Applegate, RL; Huang, L; Khatibi, NH; Krafft, P; Martin, RD; Rolland, W; Sherchan, P; Woo, W; Zhang, J, 2016)
"Autism is a neurodevelopment disorder."	1.43	Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats. ( Kumar, H; Sharma, B, 2016)
"Background The development of novel migraine therapies has been slow, in part because of the small number of clinically relevant animal models."	1.43	The effects of acute and preventive migraine therapies in a mouse model of chronic migraine. ( Charles, A; McGuire, B; Pradhan, AA; Tarash, I; Tipton, AF, 2016)
"Hemorrhage is a major cause of morbidity and mortality among trauma patients."	1.43	Valproic acid-mediated myocardial protection of acute hemorrhagic rat via the BCL-2 pathway. ( He, M; He, Y; Kuai, Q; Li, W; Qiao, Z; Ren, S; Wang, C; Wang, X; Wang, Y; Yu, Q, 2016)
"Traumatic brain injury and hemorrhagic shock (TBI+HS) elicit a complex inflammatory response that contributes to secondary brain injury."	1.43	Resuscitation with Valproic Acid Alters Inflammatory Genes in a Porcine Model of Combined Traumatic Brain Injury and Hemorrhagic Shock. ( Alam, HB; Bambakidis, T; de Vries, HE; Dekker, SE; Jin, G; Johnson, CN; Li, Y; Liu, B; Sillesen, M, 2016)
"Recently, the use of acute seizure tests in epileptic rats or mice has been proposed as a novel strategy for evaluating novel AEDs for increased antiseizure efficacy."	1.43	Evaluation of the pentylenetetrazole seizure threshold test in epileptic mice as surrogate model for drug testing against pharmacoresistant seizures. ( Löscher, W; Töllner, K; Twele, F, 2016)
"Treatment with memantine has significantly attenuated prenatal valproic acid-induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity."	1.43	Memantine ameliorates autistic behavior, biochemistry & blood brain barrier impairments in rats. ( Kumar, H; Sharma, B, 2016)
"Nitroglycerin (NTG) was employed to induce a migraine model in rats and the migraine animals were exposed to treatment of VPA of different doses."	1.43	Valproate ameliorates nitroglycerin-induced migraine in trigeminal nucleus caudalis in rats through inhibition of NF-кB. ( Li, Q; Li, Y; Qi, D; Yi, L; Zhang, L; Zhang, Q; Zhang, Z, 2016)
"Spinal muscular atrophy is a devastating disease that is characterized by degeneration and death of a specific subclass of motor neurons in the anterior horn of the spinal cord."	1.43	Neuron-specific knock-down of SMN1 causes neuron degeneration and death through an apoptotic mechanism. ( Battaglia, GS; Bazzicalupo, P; Castro, S; Chaplin, JC; Di Schiavi, E; Donato, A; Esposito, A; Gallotta, I; Hilliard, MA; Mazzarella, N; Zampi, G, 2016)
"The treatment with methylphenidate (10mg/kg, ip) increased locomotion in the open field test."	1.43	Lithium and valproate prevent methylphenidate-induced mania-like behaviors in the hole board test. ( Asth, L; Gavioli, EC; Lobão-Soares, B; Medeiros, IU; Santos, WB; Silva, EF; Soares-Rachetti, VP; Souza, LS, 2016)
"McArdle disease is due to an absence of the enzyme muscle glycogen phosphorylase and results in significant physical impairment in humans."	1.42	Investigating sodium valproate as a treatment for McArdle disease in sheep. ( Creed, KE; Dunton, E; Howell, JM; Quinlivan, R; Sewry, C, 2015)
"In a first step, we examined anti-seizure effects of 6 AEDs on spontaneous recurrent focal electrographic seizures and secondarily generalized convulsive seizures in epileptic mice, showing that the focal nonconvulsive seizures were resistant to carbamazepine and phenytoin, whereas valproate and levetiracetam exerted moderate and phenobarbital and diazepam marked anti-seizure effects."	1.42	Inter-individual variation in the effect of antiepileptic drugs in the intrahippocampal kainate model of mesial temporal lobe epilepsy in mice. ( Bankstahl, M; Klein, S; Löscher, W, 2015)
"Eslicarbazepine acetate is a recently approved antiepileptic drug that is rapidly metabolized to (S)-licarbazepine."	1.42	Oxcarbazepine and its active metabolite, (S)-licarbazepine, exacerbate seizures in a mouse model of genetic generalized epilepsy. ( Kim, TH; Petrou, S; Reid, CA, 2015)
"A relationship between sleep and seizures is well-described in both humans and rodent animal models; however, the mechanism underlying this relationship is unknown."	1.42	A new model to study sleep deprivation-induced seizure. ( Leahy, A; Lucey, BP; Rosas, R; Shaw, PJ, 2015)
"Autism is a severe neurodevelopmental disorder with a population prevalence of 1 in 68, and dramatically increasing."	1.42	Tactile stimulation improves neuroanatomical pathology but not behavior in rats prenatally exposed to valproic acid. ( Gibb, R; Harker, A; Kolb, B; Raza, S; Richards, S, 2015)
" The treatment was started on the 5th day after STZ injection with the same dose as in group II and it was considered as 1st day of treatment with gold nanoparticles for 7 days to each rat of (group IV) treated autistic diabetic group(TAD) at a dosage of 2."	1.42	Pancreatic response to gold nanoparticles includes decrease of oxidative stress and inflammation in autistic diabetic model. ( Abd-Elhakim, YM; Al-Ayadhi, LY; Selim, ME, 2015)
"Valproic acid treated animals were treated from 5 days preceding behavioral testing in the Morris water maze at a clinically relevant concentration."	1.42	Standard dose valproic acid does not cause additional cognitive impact in a rodent model of intractable epilepsy. ( Jellett, AP; Jenks, K; Lucas, M; Scott, RC, 2015)
"Valproic acid (600 mg/kg) was administered intraperitoneally to the pregnant mice on gestational day 12."	1.42	Astaxanthin improves behavioral disorder and oxidative stress in prenatal valproic acid-induced mice model of autism. ( Al-Amin, MM; Khan, FR; Mahmud Reza, H; Rahman, MM; Zaman, F, 2015)
"Treatment-resistant seizures affect about a third of patients suffering from epilepsy."	1.42	Cross-species pharmacological characterization of the allylglycine seizure model in mice and larval zebrafish. ( Afrikanova, T; Buenafe, OE; Crawford, AD; De Prins, A; de Witte, PA; Esguerra, CV; Kaminski, RM; Langlois, M; Leclercq, K; Rospo, CC; Smolders, I; Van Eeckhaut, A, 2015)
"Patients with Alzheimer's disease are at increased risk for unprovoked seizures and epilepsy compared with age-matched controls."	1.42	Reduction of epileptiform activity by valproic acid in a mouse model of Alzheimer's disease is not long-lasting after treatment discontinuation. ( Hiltunen, M; Pitkänen, A; Tanila, H; Viswanathan, J; Ziyatdinova, S, 2015)
" Chronic administration of lithium chloride or valproic acid, two clinically effective mood stabilizers, reverses the majority of these behavioral abnormalities."	1.42	Mice heterozygous for cathepsin D deficiency exhibit mania-related behavior and stress-induced depression. ( Duan, S; Han, Y; Li, X; Lou, H; Lu, Y; Zhen, X; Zhou, R; Zhu, L, 2015)
"Although animal models of autism have demonstrated that model animals engage less in social interaction or attend less to conspecifics than control animals, no animal model has yet replicated the deficit in recognition of complex social interaction as is seen in humans with autism."	1.42	Indifference of marmosets with prenatal valproate exposure to third-party non-reciprocal interactions with otherwise avoided non-reciprocal individuals. ( Banno, T; Ichinohe, N; Kawai, N; Nakagaki, K; Nakagami, A; Yasue, M, 2015)
"Valproic acid (VPA) was described as a histone deacetylase inhibitor that had anti-inflammatory effects and reduced the production of proinflammatory cytokines in experimental autoimmune disease models."	1.42	Valproic Acid Ameliorates Graft-versus-Host Disease by Downregulating Th1 and Th17 Cells. ( Chang, L; Chen, Z; Dou, HB; Fang, WY; Gao, WH; Hu, J; Huang, MM; Long, J; Shan, JH; Shen, Y; Wang, Y; Wang, YY; Wu, YN; Zhu, J, 2015)
"Despite former publications no clear seizures could be reproduced but it was possible to establish focal EPs, which proved to be a reliable marker for epileptic activity."	1.42	Reduction of epileptiform activity through local valproate-implants in a rat neocortical epilepsy model. ( Altenmüller, DM; Feuerstein, TJ; Freiman, TM; Hebel, JM; Herrmann, LS; Rassner, MP; Volz, S, 2015)
"A major focus of animal models of autism has been to mimic the social deficits of the disorder."	1.42	Effects of prenatal exposure to valproic acid on the development of juvenile-typical social play in rats. ( Gibb, R; Harker, A; Himmler, BT; Himmler, SM; Kolb, B; Pellis, SM; Raza, S, 2015)
"The therapeutic strategy against autism, a severe neurological development disorder, is one of the challenges of this decade."	1.42	Laser Acupuncture Improves Behavioral Disorders and Brain Oxidative Stress Status in the Valproic Acid Rat Model of Autism. ( Khongrum, J; Wattanathorn, J, 2015)
"Valproic acid (VPA) has been reported to have survival and neuroprotective effects in a cardiac arrest rat model."	1.42	Effect of valproic acid combined with therapeutic hypothermia on neurologic outcome in asphyxial cardiac arrest model of rats. ( Hwang, JE; Jo, YH; Kim, K; Kim, MA; Lee, JH; Lee, MJ, 2015)
"Valproic acid (VPA) treatment protected hippocampal neurons from radiation-induced damage in both cell culture and animal models."	1.42	Valproic acid enhances the efficacy of radiation therapy by protecting normal hippocampal neurons and sensitizing malignant glioblastoma cells. ( DeWees, TA; Engelbach, JA; Garbow, JR; Hallahan, AN; Hallahan, DE; Karvas, RM; Laszlo, A; Thotala, D, 2015)
" In spite of limited results, the use of another dosage of VPA or of VPA in a combined therapy with molecules targeting other pathways, cannot be excluded as potential strategies for MJD therapeutics."	1.42	Limited Effect of Chronic Valproic Acid Treatment in a Mouse Model of Machado-Joseph Disease. ( Duarte-Silva, S; Esteves, S; Maciel, P; Naia, L; Neves-Carvalho, A; Rego, AC; Silva-Fernandes, A; Teixeira-Castro, A, 2015)
"Previously, autism spectrum disorder (ASD) has been identified mainly by social communication deficits and behavioral symptoms."	1.42	Alteration of spontaneous spectral powers and coherences of local field potential in prenatal valproic acid mouse model of autism. ( Cheaha, D; Kumarnsit, E, 2015)
" In order to prove through face, construct, and predictive validities, we evaluated behavioral parameters (locomotor activity, stereotypy activity, and fecal boli amount) and brain energy metabolism (enzymes citrate synthase; malate dehydrogenase; succinate dehydrogenase; complexes I, II, II-III, and IV of the mitochondrial respiratory chain; and creatine kinase) in rats submitted to acute and chronic administration of fenproporex, treated with lithium (Li) and valproate (VPA)."	1.40	Fenproporex increases locomotor activity and alters energy metabolism, and mood stabilizers reverse these changes: a proposal for a new animal model of mania. ( Cardoso, MR; Ferreira, GK; Furlanetto, CB; Gonçalves, CL; Jeremias, IC; Quevedo, J; Resende, WR; Rezin, GT; Scaini, G; Streck, EL; Valvassori, SS; Varela, RB, 2014)
" Our previous studies have demonstrated the social cognition deficits observed in this model, a major core symptom of ASD, to be ameliorated following chronic administration of histone deacetylase (HDAC) inhibitors."	1.40	Pentyl-4-yn-VPA, a histone deacetylase inhibitor, ameliorates deficits in social behavior and cognition in a rodent model of autism spectrum disorders. ( Cassidy, AW; Foley, AG; Regan, CM, 2014)
"Treatment with rosiglitazone (5, 10 mg/kg) and VPA (100, 200 mg/kg) for 21 days significantly attenuated these behavioral, biochemical, and cellular alterations as compared to control (QA 200 nmol) group."	1.40	Rosiglitazone synergizes the neuroprotective effects of valproic acid against quinolinic acid-induced neurotoxicity in rats: targeting PPARγ and HDAC pathways. ( Chaudhary, T; Kumar, A; Mishra, J, 2014)
"A novel intrastriatal rotenone model of Parkinson's disease was used to examine the neuroprotective effects of valproic acid (VPA), which is known to upregulate neurotrophic factors and other protective proteins in the brain."	1.40	Neuroprotection by valproic acid in an intrastriatal rotenone model of Parkinson's disease. ( Carriere, CH; Kang, NH; Niles, LP, 2014)
"Valproic acid (VPA) is an anticonvulsant that is a known risk factor for autism in prenatally exposed children."	1.40	Degraded auditory processing in a rat model of autism limits the speech representation in non-primary auditory cortex. ( Borland, MS; Carraway, RS; Centanni, TM; Engineer, CT; Im, KW; Kilgard, MP; Moreno, NA; Wilson, LG, 2014)
" This type of protocol can be used to further evaluate AEDs and test effects of chronic administration of AEDs."	1.40	Effects of conventional anticonvulsant drugs on generalized tonic-clonic seizures in Noda epileptic rats. ( Inoue, M; Kaneko, Y; Naito, H; Noda, A; Yamamoto, A, 2014)
"Valproic acid (VPA) has been used widely to treat mood disorder, epilepsy, and a growing number of other disorders."	1.40	VPA alleviates neurological deficits and restores gene expression in a mouse model of Rett syndrome. ( Guo, W; Igarashi, K; Irie, K; Nakashima, K; Otsuka I, M; Tsujimura, K; Zhao, X, 2014)
"In vehicle-treated animals, ocular hypertension resulted in a 29."	1.40	Acetylation preserves retinal ganglion cell structure and function in a chronic model of ocular hypertension. ( Alsarraf, O; Chou, CJ; Crosson, CE; Dahrouj, M; Fan, J; Yates, PW, 2014)
"Valproic acid (VPA) has been known to reduce neuronal injury, has anti-inflammatory and anti-apoptotic effects as a histone deacetylase (HDAC) inhibitor."	1.39	Effect of valproic acid on survival and neurologic outcomes in an asphyxial cardiac arrest model of rats. ( Jo, YH; Kang, C; Kim, J; Kim, K; Kim, MA; Lee, JH; Lee, MJ; Lee, SH; Park, CJ; Rhee, JE, 2013)
"Valproic acid (VPA) is a histone deacetylase inhibitor that may decrease cellular metabolic needs following traumatic injury."	1.39	Beneficial effects of histone deacetylase inhibition with severe hemorrhage and ischemia-reperfusion injury. ( Alam, H; Causey, MW; Hempel, J; Hoffer, Z; Jin, G; Martin, M; Miller, S; Stallings, JD, 2013)
"Autism is characterized by behavioral impairments in three main domains: social interaction; language, communication and imaginative play; and the range of interests and activities."	1.39	Increased hippocampal cell density and enhanced spatial memory in the valproic acid rat model of autism. ( Edalatmanesh, MA; Moghadas, M; Nikfarjam, H; Vafaee, F, 2013)
" This study describes synthesis and stereospecific comparative pharmacodynamics (PD, anticonvulsant activity and teratogenicity) and pharmacokinetic (PK) analysis of four individual SPD stereoisomers."	1.39	Stereoselective pharmacodynamic and pharmacokinetic analysis of sec-Butylpropylacetamide (SPD), a new CNS-active derivative of valproic acid with unique activity against status epilepticus. ( Bialer, M; Finnell, RH; Hen, N; McDonough, JH; Shekh-Ahmad, T; Wlodarczyk, B; Yagen, B, 2013)
" This VPA dosage regimen has been in the past related to a specific pathogenic pathway cascade: (1) VPA in utero exposure, (2) H4 histone hyperacetylation (hAC) at the level of somites, (3) expression of pro-apoptotic factors in somite tissues, (4) apoptosis of somite cells, and (5) axial defects in embryos (abnormal or fused somites) and fetuses (fusions, duplications, respecifications of vertebrae, and/or ribs)."	1.39	Methionine pretreatment enhances the effects of valproate on axial development in a CD1 mouse model. ( Di Renzo, F; Giavini, E; Menegola, E, 2013)
"Hypoesthesia is a clinical feature of neuropathic pain."	1.39	HDAC inhibitors restore C-fibre sensitivity in experimental neuropathic pain model. ( Araki, K; Matsushita, Y; Mukae, T; Omotuyi, Oi; Ueda, H, 2013)
"Mutations in SHANK3 and large duplications of the region spanning SHANK3 both cause a spectrum of neuropsychiatric disorders, indicating that proper SHANK3 dosage is critical for normal brain function."	1.39	SHANK3 overexpression causes manic-like behaviour with unique pharmacogenetic properties. ( Breman, AM; Chen, H; Cheung, SW; Han, K; Hao, S; Holder, JL; Kang, H; Lu, H; Lu, HC; Patel, A; Schaaf, CP; Sun, H; Tang, J; Wu, Z; Yu, P; Zoghbi, HY, 2013)
"Vagus nerve stimulation prevents seizures by continuously activating noradrenergic projections from the brainstem to the cortex."	1.39	Closed-loop neural stimulation for pentylenetetrazole-induced seizures in zebrafish. ( Beattie, CE; Hall, CW; Pineda, R, 2013)
"Valproic acid (VPA) is a widely used mood stabilizer and antiepileptic drug."	1.39	Valproic acid attenuates neuronal loss in the brain of APP/PS1 double transgenic Alzheimer's disease mice model. ( Chu, Y; He, G; Long, Z; Song, C; Song, W; Xie, P; Zhao, L; Zheng, M, 2013)
"The biological mechanisms of autism spectrum disorders (ASDs) are largely unknown in spite of extensive research."	1.39	Impairment of cortical GABAergic synaptic transmission in an environmental rat model of autism. ( Atzori, M; Banerjee, A; Galindo, LC; García-Oscos, F; Hall, S; Kilgard, MP; Roychowdhury, S, 2013)
" Oral dosing of mice results in absorption of intact prodrug with slow systemic hydrolysis yielding higher plasma levels of LY2334737 than gemcitabine and prolonged gemcitabine exposure."	1.39	Efficacy of low-dose oral metronomic dosing of the prodrug of gemcitabine, LY2334737, in human tumor xenografts. ( Dantzig, AH; Donoho, GP; Durland-Busbice, S; Perkins, EJ; Pratt, SE; Shepard, RL; Starling, JJ; Wickremsinhe, ER, 2013)
" Additionally, the effects of acute and chronic administration of both statins on the adverse effect potential of three antiepileptic drugs were assessed in the chimney test (motor performance) and passive avoidance task (long-term memory)."	1.38	The interactions of atorvastatin and fluvastatin with carbamazepine, phenytoin and valproate in the mouse maximal electroshock seizure model. ( Czuczwar, SJ; Luszczki, JJ; Stepien, KM; Tomaszewski, M, 2012)
"Valproic acid (VPA) is a major antiepileptic drug (AED) that is less potent than other AEDs."	1.38	Synthesis and anticonvulsant evaluation of dimethylethanolamine analogues of valproic acid and its tetramethylcyclopropyl analogue. ( Bialer, M; Shekh-Ahmad, T; Yavin, E, 2012)
"Hyperglycinemia was induced in healthy vervet monkeys when treated with a single oral dose of 50 mg/kg valproate."	1.38	Paracetamol prevents hyperglycinemia in vervet monkeys treated with valproate. ( Bergh, JJ; Kotze, HF; Mienie, LJ; Terre'Blanche, G; Viljoen, J, 2012)
"Although autism is diagnosed according to three core features of social deficits, communication impairments, and repetitive or stereotyped behaviors, other behavioral features such as sensory and motor impairments are present in more than 70% of individuals with autism spectrum disorders (ASD)."	1.38	Sensory and motor characterization in the postnatal valproate rat model of autism. ( Devine, DP; Millette, A; Reynolds, S, 2012)
"Valproic acid (VPA) is a short-chain branched fatty acid with anti-inflammatory, neuro-protective and axon remodeling effects."	1.38	Valproic acid ameliorates inflammation in experimental autoimmune encephalomyelitis rats. ( Schluesener, HJ; Wu, Y; Zhang, Z; Zhang, ZY, 2012)
"Currently, no transplantable gastric cancer syngeneic animal models exist; therefore, we set out to establish a mouse gastric carcinoma cell line, which was named mouse gastric carcinoma cell line 3I (MGCC3I), from forestomach carcinoma developed in benzo[a]pyrene-treated ICR mice."	1.37	Establishment of an orthotopic transplantable gastric cancer animal model for studying the immunological effects of new cancer therapeutic modules. ( Chen, YL; Fang, JH; Hsu, HP; Lai, MD; Lin, CY; Lin, PW; Shan, YS; Yen, MC, 2011)
"One primary goal of medical treatment of endometriosis is to alleviate pain and there is a pressing need for new therapeutics for endometriosis with better efficacy and side-effect profiles."	1.37	Levo-tetrahydropalmatine retards the growth of ectopic endometrial implants and alleviates generalized hyperalgesia in experimentally induced endometriosis in rats. ( Guo, SW; Liu, X; Zhao, T; Zhen, X, 2011)
"In order to establish the etiology of autism with facial palsy, research into developmental abnormalities of the peripheral facial nerves is necessary."	1.37	Morphological abnormalities of embryonic cranial nerves after in utero exposure to valproic acid: implications for the pathogenesis of autism with multiple developmental anomalies. ( Imura, Y; Narita, M; Narita, N; Oyabu, A; Tashiro, Y; Uchida, A, 2011)
"In a clinically relevant lethal polytrauma model, administration of SDP significantly improves survival without any long-term organ dysfunction or complications."	1.37	Hemostatic and pharmacologic resuscitation: results of a long-term survival study in a swine polytrauma model. ( Alam, HB; Bramos, A; Chong, W; Duggan, M; Fikry, K; Fukudome, EY; Hamwi, KB; Kim, K; Lu, J; Velmahos, G, 2011)
"Despite the prevalence of autism, the neurobiology of this disorder is poorly understood."	1.37	Malformation of the superior olivary complex in an animal model of autism. ( Kulesza, RJ; Lukose, R; Murawski, NJ; Schmidt, E; Wolski, TP, 2011)
"Curcumin was co-administered with sub-therapeutic dose of valproate 60min before PTZ injection."	1.37	Pharmacokinetic and pharmacodynamic interactions of valproate, phenytoin, phenobarbitone and carbamazepine with curcumin in experimental models of epilepsy in rats. ( Gupta, YK; Mehla, J; Pahuja, M; Reeta, KH, 2011)
"Autism is characterized by behavioral impairments in three main domains: social interaction; language, communication and imaginative play; and range of interests and activities."	1.37	Animal model of autism induced by prenatal exposure to valproate: behavioral changes and liver parameters. ( Bambini-Junior, V; Behr, GA; Gottfried, C; Moreira, JC; Riesgo, R; Rodrigues, L, 2011)
"The less VPA was able to raise seizure threshold, the lower was the VPA-induced reduction of SNr firing rate and the VPA-induced regularity of SNr firing."	1.37	The anticonvulsant response to valproate in kindled rats is correlated with its effect on neuronal firing in the substantia nigra pars reticulata: a new mechanism of pharmacoresistance. ( Gernert, M; Löscher, W; Töllner, K; Wolf, S, 2011)
"Valproic acid treatment did not affect inflammation parameters; however, valproic acid treatment resulted in reduced epithelial thickness as compared to vehicle treated mice (p < 0."	1.37	Protective effects of valproic acid against airway hyperresponsiveness and airway remodeling in a mouse model of allergic airways disease. ( Dang, W; De Sampayo, N; El-Osta, A; Karagiannis, TC; Royce, SG; Tang, ML; Ververis, K, 2011)
" VCU was mainly eliminated by metabolism with a half-life of 2 h."	1.36	Evaluation of stereoselective anticonvulsant, teratogenic, and pharmacokinetic profile of valnoctylurea (capuride): a chiral stereoisomer of valproic acid urea derivative. ( Bialer, M; Finnell, RH; Schurig, V; Shimshoni, JA; Wlodarczyk, B; Yagen, B, 2010)
"Autism is a behaviorally characterized disorder with impairments in social interactions, as well as stereotyped, repetitive patterns of behaviors and interests."	1.36	Nonexploratory movement and behavioral alterations in a thalidomide or valproic acid-induced autism model rat. ( Imura, Y; Kamada, N; Narita, M; Narita, N; Oyabu, A; Tano, K; Uchida, A; Yokoyama, T, 2010)
"Clonic seizures were rare in NMDA-treated P25 rats, but valproate pretreatment increased their incidence significantly."	1.36	Vigabatrin but not valproate prevents development of age-specific flexion seizures induced by N-methyl-D-aspartate (NMDA) in immature rats. ( Kubová, H; Mares, P, 2010)
"Levetiracetam (LEV) is a unique antiepileptic drug that preferentially interacts with synaptic vesicle protein 2A (SV2A)."	1.36	Antiepileptogenic and anticonvulsive actions of levetiracetam in a pentylenetetrazole kindling model. ( Ishihara, S; Ohno, Y; Sasa, M; Serikawa, T; Terada, R, 2010)
"Approximately 30% of individuals with autism have normal development up to the age of about 30 months after which they experience behavioral regression and lose previously acquired motor, cognitive and social skills."	1.36	Animal model of autism using GSTM1 knockout mice and early post-natal sodium valproate treatment. ( Bhattacharya, P; Mirochnitchenko, O; Patti, L; Wagner, GC; Yochum, CL, 2010)
"Although right ventricular hypertrophy (RVH) is an adaptive process to stresses such as outflow tract obstruction, uncorrected persistent RVH often results in failure of the right ventricle or even the left ventricle."	1.36	Sodium valproate, a histone deacetylase inhibitor, but not captopril, prevents right ventricular hypertrophy in rats. ( Cho, YK; Choi, WY; Eom, GH; Kee, HJ; Kim, HS; Kook, H; Ma, JS; Nam, KI, 2010)
"PTZ provoked clonic convulsions, reduced GABA content, deranged brain redox status, and elevated nitric oxide (NO)."	1.36	Magnesium supplementation enhances the anticonvulsant potential of valproate in pentylenetetrazol-treated rats. ( Abdallah, DM; Abdel-Aziz, MT; Arafa, NM; Safar, MM, 2010)
" Dose-response studies revealed that systemic administration of 400 mg/kg (i."	1.36	Valproate administered after traumatic brain injury provides neuroprotection and improves cognitive function in rats. ( Dash, PK; Grill, RJ; Moore, AN; Orsi, SA; Pati, S; Zhang, M; Zhao, J, 2010)
" Comparative pharmacokinetic analysis showed that α-Cl-TMCD is less susceptible to liver first-pass effect than α-F-TMCD because of lower total (metabolic) clearance and liver extraction ratio."	1.36	Comparative pharmacodynamic and pharmacokinetic analysis of two anticonvulsant halo derivatives of 2,2,3,3-tetramethylcyclopropanecarboxamide, an amide of a cyclic analog of valproic acid. ( Bialer, M; Finnell, RH; Hen, N; Kaufmann, D; Pessah, N; Wlodarczyk, B; Yagen, B, 2010)
"Valproic acid (VPA) is a major antiepileptic drug (AED) with efficacy against multiple seizure types."	1.35	Increase in antiepileptic efficacy during prolonged treatment with valproic acid: role of inhibition of histone deacetylases? ( Czapp, M; Hoffmann, K; Löscher, W, 2008)
"Nicotine pretreatment reversed the anti-lipid peroxidative action of sodium valproate in the PTZ-induced seizure model in mice."	1.35	Dose-finding study with nicotine as a proconvulsant agent in PTZ-induced seizure model in mice. ( Chakrabarti, A; Medhi, B; Sahai, AK; Sood, N, 2008)
"(2007) Seizure suppression by top1 mutations in Drosophila."	1.35	DNA topoisomerase I inhibitors ameliorate seizure-like behaviors and paralysis in a Drosophila model of epilepsy. ( Hormozi, L; Parker, L; Song, J; Tanouye, MA, 2008)
" The isobolographic analysis for parallel and nonparallel dose-response effects was used in the mouse maximal electroshock seizure (MES) model for evaluation of pharmacodynamic interaction."	1.35	Isobolographic characterization of interactions of retigabine with carbamazepine, lamotrigine, and valproate in the mouse maximal electroshock-induced seizure model. ( Czuczwar, SJ; Luszczki, JJ; Raszewski, G; Wu, JZ, 2009)
"Children with Down syndrome are highly susceptible to infantile spasms."	1.35	Infantile spasms and Down syndrome: a new animal model. ( Aleem, IS; Ashraf, A; Cortez, MA; Kanawaty, A; Liu, CC; Sadeghnia, HR; Shen, L; Snead, OC; Stewart, L; Trepanier, CH; Wu, Y, 2009)
" We report here that, while dietary supplementation with high VPA dosage slows down motor neuron death, as assessed by measurement of a specific marker for cholinergic neurons in the spinal cord, it has no significant effect on lifespan."	1.35	Long-term dietary administration of valproic acid does not affect, while retinoic acid decreases, the lifespan of G93A mice, a model for amyotrophic lateral sclerosis. ( Bonamassa, B; Canistro, D; Contestabile, A; Crochemore, C; Paolini, M; Pena-Altamira, E; Virgili, M, 2009)
"Valproic acid (VPA) has been used for many years as a drug of choice for epilepsy and mood disorders."	1.35	Chronic dietary administration of valproic acid protects neurons of the rat nucleus basalis magnocellularis from ibotenic acid neurotoxicity. ( Brignani, S; Contestabile, A; Eleuteri, S; Monti, B, 2009)
"Treatment with valproic acid decreases muscle myostatin levels and enhances both follistatin expression and the inactivating phosphorylation of GSK-3beta, while these parameters are not affected by trichostatin-A."	1.35	Deacetylase inhibitors modulate the myostatin/follistatin axis without improving cachexia in tumor-bearing mice. ( Baccino, FM; Bonelli, G; Bonetto, A; Costelli, P; Minero, VG; Penna, F; Reffo, P, 2009)
" Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3s stimulus duration) delivered via ocular electrodes and isobolographic analysis for parallel and non-parallel dose-response effects was used to characterize the consequent anticonvulsant interactions between the various drug combinations."	1.35	Isobolographic characterization of interactions of levetiracetam with the various antiepileptic drugs in the mouse 6 Hz psychomotor seizure model. ( Luszczki, JJ; Patsalos, PN; Wlaz, A; Wojda, E, 2009)
"A core feature of autism spectrum disorders is the impairment in social interactions."	1.35	Abnormal fear conditioning and amygdala processing in an animal model of autism. ( La Mendola, D; Markram, H; Markram, K; Rinaldi, T; Sandi, C, 2008)
" We found that chronic administration of the antimanic agents lithium and valproate (VPA) reduced synaptic AMPA receptor GluR1/2 in hippocampal neurons in vitro and in vivo."	1.35	The role of hippocampal GluR1 and GluR2 receptors in manic-like behavior. ( Blumenthal, R; Chen, G; Creson, TK; Du, J; Falke, C; Gray, NA; Machado-Vieira, R; Manji, HK; Ren, M; Wang, Y; Wei, Y; Wu, LJ; Yuan, P; Zhuo, M, 2008)
"Autism is a severe behavioral disorder characterized by pervasive impairments in social interactions, deficits in verbal and non-verbal communication, and stereotyped behaviors, with a four times higher incidence in boys than in girls."	1.35	Gender-specific behavioral and immunological alterations in an animal model of autism induced by prenatal exposure to valproic acid. ( Basta-Kaim, A; Budziszewska, B; Kubera, M; Przewłocki, R; Roman, A; Schneider, K; Schneider, T, 2008)
"Epilepsy is a major public health problem affecting nearly 50 million people world wide."	1.35	Fish liver oil and propolis as protective natural products against the effect of the anti-epileptic drug valproate on immunological markers of bone formation in rats. ( El Elshamy, KA; Elwakkad, AS; Sibaii, H, 2008)
"In amphetamine-pretreated animals, valproate administration reversed citrate synthase activity inhibition induced by amphetamine."	1.34	Effects of lithium and valproate on hippocampus citrate synthase activity in an animal model of mania. ( Amboni, G; Assis, LC; Corrêa, C; Kapczinski, F; Martins, MR; Quevedo, J; Streck, EL, 2007)
"Given that there is no effective treatment for stroke, HDAC inhibitors, such as VPA, SB, and TSA, should be evaluated for their potential use for clinical trials in stroke patients."	1.34	Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke: multiple mechanisms of action. ( Chen, PS; Chuang, DM; Hong, JS; Kim, HJ; Ren, M; Rowe, M, 2007)
"Valproic acid (VPA) is a widely used treatment for both epilepsy and bipolar disorders, although its therapeutic mechanism of action is not fully understood."	1.33	Reduced anticonvulsant efficacy of valproic acid in dopamine beta-hydroxylase knockout mice. ( Liles, LC; Schank, JR; Weinshenker, D, 2005)
" No tolerance was evident in the intravenous pentylenetetrazol test after twice-daily dosing of ABT-769 (0."	1.33	Preclinical profiling and safety studies of ABT-769: a compound with potential for broad-spectrum antiepileptic activity. ( Bennani, Y; Bitner, RS; Chemburkar, SR; Chen, J; Curzon, P; Dart, MJ; Decker, MW; Durmuller, N; Fox, GB; Giardina, WJ; Grayson, GK; Harris, RR; Hui, JY; Jolly, R; Komater, VA; Ku, Y; Lockwood, M; Marsh, KC; Miner, HM; Nikkel, AL; Pan, JB; Pu, YM; Radek, RJ; Roux, S; Sullivan, JP; Wang, L; Waring, JF, 2005)
"Pretreatment with clofibrate results in partial reversal of changes produced by valproate."	1.33	Oxidative stress in experimental liver microvesicular steatosis: role of mitochondria and peroxisomes. ( Balasubramanian, KA; Eapen, CE; Natarajan, SK; Pullimood, AB, 2006)
"Using cells and prostate cancer xenograft mouse models, we demonstrate in this study that a combination treatment using the PPARgamma agonist pioglitazone and the histone deacetylase inhibitor valproic acid is more efficient at inhibiting prostate tumor growth than each individual therapy."	1.33	Peroxisome proliferator-activated receptor gamma regulates E-cadherin expression and inhibits growth and invasion of prostate cancer. ( Abella, A; Annicotte, JS; Berthe, ML; Culine, S; Dubus, P; Fajas, L; Fritz, V; Iankova, I; Iborra, F; Maudelonde, T; Miard, S; Noël, D; Pillon, A; Sarruf, D, 2006)
"Identifying genes for bipolar mood disorders through classic genetics has proven difficult."	1.32	Candidate genes, pathways and mechanisms for bipolar (manic-depressive) and related disorders: an expanded convergent functional genomics approach. ( Geyer, MA; Kuczenski, R; Lohr, JB; Niculescu, AB; Ogden, CA; Paulus, MP; Rich, ME; Schork, NJ, 2004)
"Valproic acid (VPA) has long been used as an antiepileptic drug and recently as a mood stabilizer, and evidence is increasing that VPA exerts neuroprotective effects through changes in a variety of intracellular signalling pathways including upregulation of Bcl-2 protein with an antiapoptotic property and inhibiting glycogen synthase kinase 3-beta, which is considered to promote cell survival."	1.32	Benefit of valproic acid in suppressing disease progression of ALS model mice. ( Goto, M; Hamasaki, T; Miyaguchi, K; Sakoda, S; Sugai, F; Sumi, H; Yamamoto, Y; Zhou, Z, 2004)
"Despite the frequency of seizure disorders in the human population, the genetic basis for these defects remains largely unclear."	1.31	Anticonvulsant valproate reduces seizure-susceptibility in mutant Drosophila. ( Kuebler, D; Tanouye, M, 2002)
"Using an amygdala-kindled seizure paradigm, we evaluated the acute and chronic anticonvulsant effects of lamotrigine (LTG)."	1.31	Tolerance to the anticonvulsant effects of lamotrigine on amygdala kindled seizures: cross-tolerance to carbamazepine but not valproate or diazepam. ( Heynen, T; Krupp, E; Li, XL; Post, RM; Weiss, SR, 2000)
" In this study, we examined the anticonvulsant and adverse effects of the three clinically established AEDs carbamazepine (CBZ), phenobarbital (PB), and valproate (VPA) once per month in the same two groups of amygdala-kindled rats over a period of 9 (group 1) or 6 (group 2) consecutive months."	1.31	Repeated acute testing of anticonvulsant drugs in amygdala kindled rats: increase in anticonvulsant but decrease in adverse effect potential. ( Fiedler, M; Löscher, W, 2000)
"Haloperidol-induced TD was also attenuated by the antioxidant, vitamin E (400 and 800 mg/kg, p."	1.31	Effect of Withania somnifera glycowithanolides on a rat model of tardive dyskinesia. ( Bhattacharya, D; Bhattacharya, SK; Ghosal, S; Sairam, K, 2002)
" The purpose of our study was to evaluate the effects of chronic administration of valproate (VPA), phenytoin (PHT), and MK-801 on the change in seizure phenotype observed in our model system."	1.30	Effects of valproate, phenytoin, and MK-801 in a novel model of epileptogenesis. ( Applegate, CD; Ozduman, K; Samoriski, GM, 1997)
" AWD 140-190 thus presents an orally active and safe anticonvulsant agent, which is structurally unrelated to anticonvulsants currently used."	1.30	AWD 140-190: a new anticonvulsant with a very good margin of safety. ( Bartsch, R; Engel, J; Rostock, A; Rundfeldt, C; Tober, C; Unverferth, K; White, HS; Wolf, HH, 1997)
" For comparison of drug potencies, doses increasing seizure thresholds by 20 or 50% were calculated from dose-response curves."	1.30	Anticonvulsant drug effects in the direct cortical ramp-stimulation model in rats: comparison with conventional seizure models. ( Krupp, E; Löscher, W, 1998)
" PHT pharmacokinetics was described by a pharmacokinetic model with Michaelis-Menten elimination."	1.30	Modelling of the pharmacodynamic interaction between phenytoin and sodium valproate. ( Danhof, M; Della Paschoa, OE; Voskuyl, RA, 1998)
"This report characterizes seizures in a novel genetic model of developmental epilepsy, the Flathead (FH) rat."	1.30	Characterization of seizures in the flathead rat: a new genetic model of epilepsy in early postnatal development. ( D'Mello, SR; LoTurco, JJ; Rattan, S; Sarkisian, MR, 1999)
"In this model, the threshold for seizures in rats is determined at short time intervals by applying ramp-shaped electrical pulse-trains directly to the cerebral cortex, allowing one to determine the time course of anti- or proconvulsant drug effects in individual rats."	1.29	Dose-dependent anticonvulsant and proconvulsant effects of nitric oxide synthase inhibitors on seizure threshold in a cortical stimulation model in rats. ( Gerecke, U; Koch, R; Löscher, W; Mevissen, M; Richter, A; Rundfeldt, C, 1995)
"To evaluate an animal model of multiple-dose activated charcoal (MDAC) therapy and correlate the pharmacokinetic properties of four drugs with the efficacy of MDAC."	1.29	Correlation of drug pharmacokinetics and effectiveness of multiple-dose activated charcoal therapy. ( Chyka, PA; Holley, JE; Mandrell, TD; Sugathan, P, 1995)
"The data suggest that this rat cardiac arrest model may be a valuable tool for investigating the pathophysiologic mechanisms of posthypoxic myoclonus and for developing new therapeutic strategies for treating the disorder."	1.29	Novel rat cardiac arrest model of posthypoxic myoclonus. ( Hussong, MJ; Matsumoto, RR; Schwartz, PH; Truong, DD; Wasterlain, CG, 1994)
"Treatment of phenytoin responders and nonresponders with other primary antiepileptic drugs showed that valproate and phenobarbital induced much smaller increases in focal seizure threshold in phenytoin nonresponders than in responders, whereas carbamazepine induced about the same threshold increase in both groups."	1.29	Pharmacological characterization of phenytoin-resistant amygdala-kindled rats, a new model of drug-resistant partial epilepsy. ( Hönack, D; Löscher, W; Rundfeldt, C, 1993)
"ACTH4-7 pro-gly-pro decreased seizure threshold in the audiogenic epilepsy test, but did not prevent the motor convulsions."	1.28	[Anticonvulsive properties of peptide ACTH4-7 pro-gly-pro detected in amygdaloid kindling and audiogenic epilepsy in rats]. ( Artiukhova, MV; Chepurnov, SA; Chepurnova, NE; Kuznetsova, EIu; Nezavibat'ko, VN, 1989)
"QUIN seizures showed particular sensitivity to carbamazepine (5 mg/kg) but were resistant to diphenylhydantoin unless a relatively high dose was used (100 mg/kg)."	1.27	Anticonvulsant drugs effective against human temporal lobe epilepsy prevent seizures but not neurotoxicity induced in rats by quinolinic acid: electroencephalographic, behavioral and histological assessments. ( Samanin, R; Tullii, M; Vezzani, A; Wu, HQ, 1986)
" It was found that both the dosage and timing of VPA administration were crucial in the development of lesions which are similar to human spina bifida aperta."	1.27	New animal model for the study of neural tube defects. ( McCollough, D; Michejda, M, 1987)
"VPA-induced exencephaly in mice may provide an animal model to further investigate biochemical markers for prenatal diagnosis of neural tube defects."	1.27	Amniotic fluid cholinesterase of valproate-induced exencephaly in the mouse: an animal model for prenatal diagnosis of neural tube defects. ( Elmazar, MM; Spielmann, H; Vogel, R, 1988)
" The PTZ infusion model was tested in a preliminary dose-response study of the anticonvulsant valproic acid (VPA)."	1.27	A timed intravenous pentylenetetrazol infusion seizure model for quantitating the anticonvulsant effect of valproic acid in the rat. ( Pollack, GM; Shen, DD, 1985)
"Carbamazepine and phenytoin were ineffective or aggravated the seizures."	1.27	Antiepileptic drug evaluation in a new animal model: spontaneous petit mal epilepsy in the rat. ( Depaulis, A; Marescaux, C; Micheletti, G; Reis, J; Rumbach, L; Vergnes, M; Warter, JM, 1985)
"According to our convulsion intensity scoring system, these animals have an audiogenic response score (ARS) of 3 and the colony is designated the GEPR-3 colony."	1.27	Anticonvulsant drugs and the genetically epilepsy-prone rat. ( Dailey, JW; Jobe, PC, 1985)
" The dose-response curve for naloxone against seizure activity induced by leucine enkephalin was the same as that in gamma-hydroxybutyrate-induced petit mal."	1.26	Anticonvulsants specific for petit mal antagonize epileptogenic effect of leucine enkephalin. ( Bearden, LJ; Snead, OC, 1980)

Research

Studies (866)

Authors

Clinical Trials (14)

Trial Overview

Trial Outcomes

Behavioral Performance as Assessed in the Functional Magnetic Resonance Imaging (fMRI) Memory Task

Timeframe	Studies, this research(%)	All Research%
pre-1990	34 (3.93)	18.7374
1990's	36 (4.16)	18.2507
2000's	140 (16.17)	29.6817
2010's	453 (52.31)	24.3611
2020's	203 (23.44)	2.80

Authors	Studies
Xie, ZF	1
Chai, KY	1
Piao, HR	1
Kwak, KC	1
Quan, ZS	1
Kamiński, K	8
Obniska, J	7
Chlebek, I	1
Wiklik, B	1
Rzepka, S	1
Mishra, RK	1
Baker, MT	1
Rapacz, A	8
Łuszczki, JJ	10
Latacz, G	2
Kieć-Kononowicz, K	4
Filipek, B	4
Zagaja, M	6
Andres-Mach, M	7
Rybka, S	4
Powroźnik, B	1
Pękala, E	3
Żmudzki, P	2
Edayadulla, N	1
Ramesh, P	1
Gunia-Krzyżak, A	2
Żesławska, E	2
Słoczyńska, K	2
Koczurkiewicz, P	1
Nitek, W	2
Żelaszczyk, D	2
Szkaradek, N	1
Waszkielewicz, AM	2
Marona, H	2
Abram, M	2
Góra, M	2
Sałat, K	2
Pańczyk, K	1
Abrams, RPM	1
Yasgar, A	1
Teramoto, T	1
Lee, MH	1
Dorjsuren, D	1
Eastman, RT	1
Malik, N	1
Zakharov, AV	1
Li, W	4
Bachani, M	1
Brimacombe, K	1
Steiner, JP	1
Hall, MD	1
Balasubramanian, A	1
Jadhav, A	1
Padmanabhan, R	3
Simeonov, A	1
Nath, A	1
Luhach, K	2
Kulkarni, GT	2
Singh, VP	2
Sharma, B	5
Watanabe, S	1
Kurotani, T	1
Oga, T	2
Noguchi, J	1
Isoda, R	1
Nakagami, A	3
Sakai, K	1
Nakagaki, K	4
Sumida, K	2
Hoshino, K	2
Saito, K	2
Miyawaki, I	2
Sekiguchi, M	1
Wada, K	1
Minamimoto, T	2
Ichinohe, N	4
Gu, Y	1
Han, Y	3
Ren, S	3
Zhang, B	1
Zhao, Y	8
Wang, X	13
Zhang, S	2
Qin, J	1
Alhelo, H	1
Kulesza, RJ	7
Joseph, TP	1
Zhou, F	1
Sai, LY	1
Chen, H	4
Lin, SL	1
Schachner, M	1
Wakam, GK	4
Biesterveld, BE	9
Pai, MP	6
Kemp, MT	4
O'Connell, RL	5
Rajanayake, KK	1
Chtraklin, K	9
Vercruysse, CA	3
Alam, HB	31
Lotufo Denucci, B	1
Silva de Lima, L	1
Ferreira Lima Mota, I	1
Rocha Madureira Azevedo, J	1
Germino Veras, L	1
Montenegro Luzardo Bicca, JV	1
de Miranda Santana, B	1
Beserra Pinheiro, G	1
Gonçalves Coelho, G	1
Mortari, MR	1
Punapart, M	1
Seppa, K	1
Jagomäe, T	1
Liiv, M	1
Reimets, R	1
Kirillov, S	1
Kaasik, A	1
Moons, L	1
De Groef, L	1
Terasmaa, A	1
Vasar, E	1
Plaas, M	1
Pale, S	1
Neteydji, S	1
Taiwe, GS	1
Kouemou Emegam, N	1
Bum, EN	1
Fereshetyan, K	1
Chavushyan, V	1
Danielyan, M	1
Yenkoyan, K	1
Battistoni, M	1
Bacchetta, R	1
Di Renzo, F	2
Metruccio, F	1
Moretto, A	1
Menegola, E	2
Tao, ZS	2
Li, TL	1
Xu, HG	2
Yang, M	2
Gyawali, A	1
Latif, S	1
Choi, SH	1
Hyeon, SJ	1
Ryu, H	1
Kang, YS	1
Elnahas, EM	3
Abuelezz, SA	2
Mohamad, MI	3
Nabil, MM	2
Abdelraouf, SM	2
Bahaa, N	2
Hassan, GAM	2
Aboul-Fotouh, S	4
Lin, J	1
Zhang, K	2
Cao, X	1
Ullah Khan, N	1
Liu, X	6
Tang, X	2
Chen, M	3
Zhang, H	6
Shen, L	2
Vakili Shahrbabaki, SS	1
Jonaidi, H	1
Sheibani, V	5
Bashiri, H	3
Bankole, O	1
Scambi, I	1
Parrella, E	2
Muccilli, M	1
Bonafede, R	1
Turano, E	1
Pizzi, M	2
Mariotti, R	1
Cheng, Y	1
Tang, B	3
Zhang, G	3
An, P	1
Sun, Y	3
Gao, M	1
Zhang, Y	13
Shan, Y	1
Zhang, J	5
Liu, Q	4
Lai, CSW	1
de Villers-Sidani, É	1
Wang, Y	15
Zhou, X	1
Bódi, V	1
Májer, T	1
Kelemen, V	1
Világi, I	1
Szűcs, A	1
Varró, P	1
Jiang, S	1
Xiao, L	1
He, M	3
Gao, C	1
Zhu, C	1
Chang, H	1
Ding, J	1
Sun, T	1
Wang, F	2
Santrač, A	1
Bijelić, D	1
Stevanović, V	1
Banićević, M	1
Aranđelović, J	1
Batinić, B	1
Sharmin, D	1
Cook, JM	1
Savić, MM	1
Can Kantarci, B	1
Sanli, A	1
Gavas, S	1
Toplu, A	1
Nur Turgan Asik, Z	1
Tugce Cilingir-Kaya, O	1
Gulcebi Idrizoglu, M	1
Ercan, F	1
Onat, F	1
Abhishek, M	1
Rubal, S	1
Rohit, K	1
Rupa, J	1
Phulen, S	1
Gurjeet, K	1
Raj, SA	1
Manisha, P	1
Alka, B	1
Ramprasad, P	1
Bikash, M	1
Meng, Q	1
Zhang, W	3
Jiao, C	1
Xu, S	1
Liu, C	1
Chen, C	2
Imam, B	1
Rahmatinia, M	1
Shahsavani, A	1
Khodagholi, F	1
Hopke, PK	1
Bazazzpour, S	1
Hadei, M	1
Yarahmadi, M	1
Abdollahifar, MA	1
Torkmahalleh, MA	1
Kermani, M	1
Ilkhani, S	1
MirBehbahani, SH	1
Santos, DS	1
Rocha, MA	1
Mello, MLS	1
Ma, SY	1
Kwan, KM	1
Elesawy, RO	1
El-Deeb, OS	1
Eltokhy, AK	1
Arakeep, HM	1
Ali, DA	1
Elkholy, SS	1
Kabel, AM	1
Santos-Terra, J	6
Deckmann, I	7
Carello-Collar, G	2
Nunes, GD	2
Bauer-Negrini, G	5
Schwingel, GB	3
Fontes-Dutra, M	8
Riesgo, R	7
Gottfried, C	13
Galizio, A	1
Odum, AL	1
Seiffe, A	2
Ramírez, MF	1
Sempé, L	1
Depino, AM	4
Taheri, F	3
Esmaeilpour, K	3
Sepehri, G	4
Ur Rehman, N	1
Maneshian, M	1
Martini, WZ	1
Xia, H	1
Ryan, KL	1
Bynum, J	1
Cap, AP	1
Liu, Z	5
Wang, J	6
Xu, Q	1
Wu, Z	2
You, L	1
Hong, Q	1
Zhu, J	3
Chi, X	1
Mehra, S	2
Ul Ahsan, A	1
Seth, E	1
Chopra, M	2
Dufour, A	2
Dumon, C	2
Gouty-Colomer, LA	2
Eftekhari, S	3
Ferrari, DC	3
Ben-Ari, Y	3
Sivasangari, K	1
Rajan, KE	1
Jian, J	2
Li, LG	2
Zhao, PJ	2
Zheng, RJ	2
Dong, XW	2
Zhao, YH	2
Yin, BQ	3
Cheng, H	3
Li, HL	2
Li, EY	2
Sabzalizadeh, M	1
Mollashahi, M	1
Afarinesh, MR	1
Mafi, F	1
Joushy, S	1
Rzayev, E	1
Amanvermez, R	1
Gün, S	1
Tiryaki, ES	1
Arslan, G	1
Avolio, E	2
Olivito, I	2
Rosina, E	1
Romano, L	1
Angelone, T	1
De Bartolo, A	1
Scimeca, M	1
Bellizzi, D	1
D'Aquila, P	1
Passarino, G	1
Alò, R	2
Facciolo, RM	2
Bagni, C	1
De Lorenzo, A	1
Canonaco, M	2
Chu, MC	2
Wu, HF	3
Lee, CW	3
Chung, YJ	1
Chi, H	1
Chen, PS	6
Lin, HC	5
Alpay, M	1
Yucel, F	1
Rahdar, M	4
Hajisoltani, R	3
Davoudi, S	4
Karimi, SA	2
Borjkhani, M	2
Khatibi, VA	1
Hosseinmardi, N	4
Behzadi, G	4
Janahmadi, M	4
Volpatti, JR	1
Ghahramani-Seno, MM	1
Mansat, M	1
Sabha, N	1
Sarikaya, E	1
Goodman, SJ	1
Chater-Diehl, E	1
Celik, A	1
Pannia, E	1
Froment, C	1
Combes-Soia, L	1
Maani, N	1
Yuki, KE	1
Chicanne, G	1
Uusküla-Reimand, L	1
Monis, S	1
Alvi, SA	1
Genetti, CA	1
Payrastre, B	1
Beggs, AH	1
Bonnemann, CG	1
Muntoni, F	1
Wilson, MD	1
Weksberg, R	1
Viaud, J	1
Dowling, JJ	1
Ishihara, Y	1
Honda, T	2
Ishihara, N	1
Namba, K	1
Taketoshi, M	1
Tominaga, Y	1
Tsuji, M	1
Vogel, CFA	1
Yamazaki, T	1
Itoh, K	1
Tominaga, T	1
Takayama, K	1
Tobori, S	1
Andoh, C	1
Kakae, M	1
Hagiwara, M	1
Nagayasu, K	1
Shirakawa, H	1
Ago, Y	9
Kaneko, S	1
Tsuji, C	3
Furuhara, K	2
Mizutani, R	2
Minami, K	2
Fu, P	1
Zhong, J	1
Higashida, H	1
Yokoyama, S	1
Tsuji, T	3
Kim, H	2
Woo, RS	1
Yang, EJ	3
Kim, HB	1
Jo, EH	1
Lee, S	1
Im, H	1
Kim, S	5
Kim, HS	4
Anshu, K	2
Nair, AK	2
Srinath, S	2
Laxmi, TR	2
Mansour, Y	2
Burchell, A	1
Kulesza, R	2
Iezzi, D	1
Curti, L	1
Ranieri, G	1
Gerace, E	1
Costa, A	1
Ilari, A	1
La Rocca, A	1
Luceri, C	1
D'Ambrosio, M	1
Silvestri, L	1
Scardigli, M	1
Mannaioni, G	1
Masi, A	1
Serra, D	1
Henriques, JF	1
Sousa, FJ	1
Laranjo, M	1
Resende, R	1
Ferreira-Marques, M	1
de Freitas, V	1
Silva, G	1
Peça, J	1
Dinis, TCP	1
Almeida, LM	1
Imado, E	1
Sun, S	2
Abawa, AR	1
Tahara, T	1
Kochi, T	1
Huynh, TNB	1
Asano, S	1
Hasebe, S	6
Nakamura, Y	1
Hisaoka-Nakashima, K	1
Kotake, Y	1
Irifune, M	1
Tsuga, K	1
Takuma, K	8
Morioka, N	1
Kiguchi, N	1
Zhuo, C	1
Zhou, C	1
Tian, H	1
Li, Q	5
Chen, J	8
Yang, L	4
Zhang, Q	4
Li, R	3
Ma, X	1
Cai, Z	2
Chen, G	3
Xu, Y	3
Song, X	1
Jeon, SJ	3
Kwon, H	1
Bae, HJ	1
Gonzales, EL	4
Kim, J	2
Chung, HJ	1
Kim, DH	1
Ryu, JH	3
Shin, CY	11
Singla, R	4
Mishra, A	4
Joshi, R	2

Trial	Phase	Enrollment	Study Type	Start Date	Status
Efficacy of Lactobacillus Reuteri in Managing Social Deficits in Children With Autistic Spectrum Disorder: a Randomized Clinical Trial With Evaluation of Gut Microbiota and Metabolomics Profiles[NCT04293783]		43 participants (Actual)	Interventional	2020-04-01	Completed
The Infant MiND Study: An Examination of Infants' Microbiome, Nutrition, and Development Study.[NCT03229863]		102 participants (Actual)	Interventional	2017-04-18	Active, not recruiting
A 12-weeks, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety and Related Mechanism of Sulforaphane in Treatment of Autism Spectrum Disorder[NCT02879110]		110 participants (Actual)	Interventional	2016-08-31	Completed
Evaluation of Valproic Acid (VPA) as Adjunctive Therapy for Liver Transplant Patients With Moderate to Severe Hemorrhage at Risk of Ischemia Reperfusion (I/R) Injury[NCT04531592]	Phase 2	0 participants (Actual)	Interventional	2022-01-31	Withdrawn (stopped due to Study terminated by the Sponsor)
Evaluation of Valproic Acid (VPA) as Adjunctive Therapy for Trauma Patients With Moderate to Severe Hemorrhage at Risk of Ischemia Reperfusion (I/R) Injury[NCT04531579]	Phase 2	0 participants (Actual)	Interventional	2022-01-31	Withdrawn (stopped due to Study terminated by the Sponsor.)
A Phase II Pilot Study to Explore Treatment With Sodium Valproate in Adults With McArdle Disease (Glycogen Storage Disorder Type V, GSDV)[NCT03112889]	Phase 2	8 participants (Anticipated)	Interventional	2015-01-31	Completed
Efficacy of Combined Ketamine and Midazolam for Treatment of Generalized Convulsive Status Epilepticus in Children .[NCT05779657]	Phase 2/Phase 3	144 participants (Anticipated)	Interventional	2023-03-21	Recruiting
A Randomized Clinical Trial, Double Blind, Placebo-controlled of Lithium and Valproate in Amyotrophic Lateral Sclerosis.[NCT03204500]	Phase 2	43 participants (Actual)	Interventional	2016-05-31	Completed
Bridging Cognitive Aging in Rodents to Man Using fMRI in Amnestic MCI[NCT01044758]	Phase 2	96 participants (Actual)	Interventional	2009-12-31	Completed
Network-Level Mechanisms for Preclinical Alzheimer's Disease Development[NCT03461861]	Phase 2	26 participants (Actual)	Interventional	2019-04-11	Completed
Rett Syndrome, MECP2 Duplication, and Rett-Related Disorders Consortium, Rare Disease Clinical Research Network: Neurophysiologic Correlates[NCT03077308]		185 participants (Actual)	Observational	2017-01-02	Completed
A Phase II Multiple Site, Randomized, Placebo-Controlled Trial of Oral Valproic Acid for Autosomal Dominant Retinitis Pigmentosa[NCT01233609]	Phase 2	90 participants (Actual)	Interventional	2010-11-30	Completed
Regional Anesthesia and Valproate Sodium for the Prevention of Chronic Post-Amputation Pain[NCT01928849]	Phase 2	128 participants (Actual)	Interventional	2013-12-31	Completed
Effect of the Treatment of Vitamin D Deficiency in Drug-resistant Epilepsy[NCT03475225]	Phase 3	400 participants (Anticipated)	Interventional	2018-04-30	Not yet recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Mnemonic similarity task which assesses long term memory function. Scale ranges from 0-100 with higher scores indicating better memory performance. (NCT01044758)
Timeframe: 2 weeks

Brain Activity in the Dentate Gyrus / CA3 Subregion of the Hippocampus Measured With Blood Oxygenation Level Dependent (BOLD) Functional MRI

Intervention	percent correct recalled (Mean)
aMCI_62.5	38
aMCI_62.5 Placebo	33
aMCI_125	33
aMCI_125 Placebo	28
aMCI_250	34
aMCI_250 Placebo	31
Age Matched Control	44

Measurement of average brain activity in the dentate gyrus / CA3 subregion of the hippocampus measured with BOLD functional MRI in patients with mild cognitive impairment on placebo and on drug compared to average brain activity in this brain area in control subjects. (NCT01044758)
Timeframe: 2 weeks

Functional Connectivity Strengths of Neural Networks

Intervention	mean beta coefficient (Mean)
aMCI_62.5	-0.1203
aMCI_62.5 Placebo	0.4353
aMCI_125	-0.2238
aMCI_125 Placebo	0.8814
aMCI_250	0.3928
aMCI_250 Placebo	0.4825
Age Matched Control	-.02507

The seed-based functional connectivity strengths of the hippocampus network and the default mode network will be employed to measure the changes between AGB101 and Placebo perturbation. The functional connectivity strengths will be measured with the median of the Pearson cross-correlation coefficients over entire brain regions. (NCT03461861)
Timeframe: 2 weeks after treatment between AGB101 and Placebo

Rey Auditory Verbal Learning Test (AVLT), Delayed Recall Scaled Integer. The Higher is the Better

Intervention	Pearson coefficient (Median)
AGB101 220 mg	0.233
Placebo	0.318

Rey Auditory Verbal Learning Test (AVLT), delayed recall Scaled integer will be employed to measure the episodic memory changes before and after AGB101 treatment. The AVLT score will be recorded as a standard score. The theoretical range: min 50, max 155, the higher the better. The higher the number is, the better the memory. It is an integer number. (NCT03461861)
Timeframe: Placebo vs AGB101 2 weeks after treatment paired t-test

Mean Change From Baseline in Best Corrected Visual Acuity

Intervention	score on a scale (Mean)
AGB101 220 mg	108
Placebo	105

Mean change in best corrected visual acuity as assessed by ETDRS (Early Treatment Diabetic Retinopathy Study) method from baseline to week 52 (NCT01233609)
Timeframe: baseline to week 52

Mean Change in Visual Field Area From Baseline to 52 Weeks--I4e Isopter

Intervention	letters read correctly (Mean)
Valproic Acid -- Right Eye	-1.4
Valproic Acid--Left Eye	0.0
Placebo --Right Eye	0.2
Placebo --Left Eye	1.3

Mean change in visual field area from baseline to 52 weeks. Visual field area is measured with semi-automated kinetic perimetry (SKP) using the Octopus 900 (Haag-Streit) with the I4e target size for each eye and done at least twice to ensure reliable sessions; the visual field area measurements are averaged over the two sessions. Analysis performed with linear mixed model (NCT01233609)
Timeframe: baseline to week 52

Mean Change in Visual Field Area From Baseline to 52 Weeks--III4e Isopter

Intervention	Visual field area (degrees squared) (Mean)
Placebo--Right Eye	80.9
Placebo--Left Eye	115.7
Valproic Acid--Right Eye	5.3
Valproic Acid--Left Eye	19.5

Mean change in visual field area from baseline to 52 weeks. Visual field area is measured with semi-automated kinetic perimetry (SKP) using the Octopus 900 (Haag-Streit) with the III4e target size for each eye and done at least twice to ensure reliable sessions; the visual field area measurements are averaged over the two sessions. Analysis performed with linear mixed model (NCT01233609)
Timeframe: baseline to week 52

Static Perimetry by Treatment Arm--Full Field Hill of Vision

Intervention	Visual field area (degrees squared) (Mean)
Placebo--Right Eye	-122.9
Placebo--Left Eye	-112.0
Valproic Acid--Right Eye	-293.7
Valproic Acid--Left Eye	-237.1

Mean change from baseline at week 52 for Full field Hill of Vision (Static perimetry) (NCT01233609)
Timeframe: baseline to week 52

Static Perimetry Volume--30 Degree Hill of Vision

Intervention	db-steridians (Mean)
Placebo--Right Eye	-0.3
Placebo--Left Eye	-1.4
Valproic Acid--Right Eye	-0.2
Valproic Acid--Left Eye	-0.6

Mean Change from baseline to week 52 for Static Perimetry Volume --30 Degree Hill of Vision. Full field static perimetry protocol was followed using the Octopus 900 (Haag-Streit) for a single session for each eye. (NCT01233609)
Timeframe: baseline to week 52

Change in Self-Reported Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (S-LANSS)

Intervention	db-steridans (Mean)
Placebo--Right Eye	-0.3
Placebo--Left Eye	-0.3
Valproic Acid--Right Eye	-0.2
Valproic Acid--Left Eye	-0.2

The S-LANSS is a self-reported version of the Leeds Assessment of Neuropathic Symptoms and Signs pain scale. It aims to differentiate neuropathic pain from somatic or nociceptive pain. We will analyze the change in numeric average pain score during the past week (range from 0-10) from baseline. Higher scores indicate greater pain. (NCT01928849)
Timeframe: Assessments at enrollment and 3 months or time of final adjudication assessment (up to 6 months)

Number of Patients With Chronic Post-amputation Pain

Intervention	score on a scale (Median)
Cherry Syrup	-2
Valproic Acid	-2

The primary endpoint is the incidence of chronic pain after surgery. The study team will use the average pain score over the past week as noted on the Self-Reported Leeds Assessment of Neuropathic Symptoms and Signs pain scale (S-LANSS) for the assessment of pain, and define chronic pain as a score greater than or equal to 3. (NCT01928849)
Timeframe: 3 months or time of final adjudication assessment, up to 6 months

Brief Pain Inventory (BPI) Short Form Score

Intervention	Participants (Count of Participants)
Cherry Syrup	37
Valproic Acid	36

The BPI short form is a multidimensional patient-completed measure that assesses the sensory component of pain intensity. We will analyze the change in average pain score question (ranges 0-10) and the sum of the 7 interference questions (total range 0-70) from baseline. Higher score indicates greater pain and interference. (NCT01928849)
Timeframe: Assessments at enrollment and 3 months or time of final adjudication assessment (up to 6 months)

Defense and Veterans Pain Rating Scale (DVPRS) Score

Intervention	score on a scale (Median)
	BPI Average Pain Score	BPI interference question sum
Cherry Syrup	-2	-15
Valproic Acid	-1	-7

The DVPRS is a pain assessment tool developed by the military in an effort to improve reliability and interpretability of pain assessment in the military population. It has been found to be an effective and valid tool in this population. We will analyze the change in numeric pain response (range 0-10) and the sum of the four supplemental questions (range 0-40) from baseline. Higher scores indicate greater pain and functional limitations. (NCT01928849)
Timeframe: Assessments at enrollment and 3 months or time of final adjudication assessment (up to 6 months)

Effect on Analgesic Requirement

Intervention	score on a scale (Median)
	DVPRS numeric pain	DVPRS Supplemental Question Sum
Cherry Syrup	-2	-9
Valproic Acid	0	-4.5

The effect of study drug on perioperative analgesic consumption and corresponding analysis of pain/sedation scales. Outcome defined as total opioid consumption (mg) during each 24-hour periods following surgery. (NCT01928849)
Timeframe: Assessments during hospitalization (0-24 hours and 24-48 hours post-surgery)

Incidence of Pain Sub-types

Intervention	morphine milligram equivalents (Median)
	Postoperative hours 0-24	Postoperative hours 24-48
Cherry Syrup	59	49
Valproic Acid	33	45

The incidence of neuropathic limb or post-amputation pain sub-types as defined by adjudication classification at each assessment time point. (NCT01928849)
Timeframe: Assessments at enrollment and 3 months or time of final adjudication assessment (up to 6 months)

Richmond Agitation-Sedation Scale (RASS)

Intervention	Participants (Count of Participants)
	Residual limb pain	Phantom limb
Cherry Syrup	29	22
Valproic Acid	31	26

The RASS is a commonly used, valid and reliable assessment tool for use in hospitalized patients. Validity testing reveals good inter-rater reliability among medical, surgical, and intensive care units. We will analyze the numeric score at each assessment (range -5 (unarousable) to 4 (combative)). (NCT01928849)
Timeframe: during hospitalization (0-24 hours and 24-48 hours post-surgery)

Article	Year
Current knowledge, challenges, new perspectives of the study, and treatments of Autism Spectrum Disorder. Reproductive toxicology (Elmsford, N.Y.), 2021, Volume: 106 Topics: Animals; Antipsychotic Agents; Autism Spectrum Disorder; Disease Models, Animal; Humans; Mice; Oxyto	2021
Epigenetic studies in insects and the valproic acid perspective. Brazilian journal of biology = Revista brasleira de biologia, 2022, Volume: 84 Topics: Acetylation; Animals; Disease Models, Animal; Epigenesis, Genetic; Histones; Insecta; Valproic Acid	2022
Critical Evaluation of Valproic Acid-Induced Rodent Models of Autism: Current and Future Perspectives. Journal of molecular neuroscience : MN, 2022, Volume: 72, Issue:6 Topics: Animals; Autism Spectrum Disorder; Autistic Disorder; Behavior, Animal; Disease Models, Animal; Fema	2022
Sex-Related Changes in the Clinical, Genetic, Electrophysiological, Connectivity, and Molecular Presentations of ASD: A Comparison between Human and Animal Models of ASD with Reference to Our Data. International journal of molecular sciences, 2023, Feb-07, Volume: 24, Issue:4 Topics: Animals; Autism Spectrum Disorder; Brain; Disease Models, Animal; Female; Humans; Male; Mice; S-Aden	2023
[Chronic Activation of the Dopaminergic Neuronal Pathway Improves Behavioral Abnormalities in the Prenatal Valproic Acid Exposure Mouse Model of Autism Spectrum Disorder]. Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 2019, Volume: 139, Issue:11 Topics: Animals; Anticonvulsants; Antipsychotic Agents; Autism Spectrum Disorder; Behavior; Disease Models,	2019
A Systematic Review of the Valproic-Acid-Induced Rodent Model of Autism. Developmental neuroscience, 2020, Volume: 42, Issue:1 Topics: Animals; Anticonvulsants; Autistic Disorder; Behavior, Animal; Disease Models, Animal; Humans; Roden	2020
Valproic Acid and Propionic Acid Modulated Mechanical Pathways Associated with Autism Spectrum Disorder at Prenatal and Neonatal Exposure. CNS & neurological disorders drug targets, 2022, Volume: 21, Issue:5 Topics: Animals; Autism Spectrum Disorder; Behavior, Animal; Disease Models, Animal; Female; Food Preservati	2022
The valproic acid-induced rodent model of autism. Experimental neurology, 2018, Volume: 299, Issue:Pt A Topics: Adult; Animals; Autism Spectrum Disorder; Behavior, Animal; Disease Models, Animal; Female; Humans;	2018
Dopamine transporter knockdown mice in the behavioral pattern monitor: A robust, reproducible model for mania-relevant behaviors. Pharmacology, biochemistry, and behavior, 2019, Volume: 178 Topics: alpha-Methyltyrosine; Animals; Antimanic Agents; Behavior, Animal; Bipolar Disorder; Cohort Studies;	2019
Neuroimmune Alterations in Autism: A Translational Analysis Focusing on the Animal Model of Autism Induced by Prenatal Exposure to Valproic Acid. Neuroimmunomodulation, 2018, Volume: 25, Issue:5-6 Topics: Animals; Autistic Disorder; Disease Models, Animal; Enzyme Inhibitors; Female; Humans; Mice; Neuroim	2018
Prevention or Amelioration of Autism-Like Symptoms in Animal Models: Will it Bring Us Closer to Treating Human ASD? International journal of molecular sciences, 2019, Mar-01, Volume: 20, Issue:5 Topics: Animals; Autism Spectrum Disorder; Disease Models, Animal; Fatty Acids, Omega-3; Humans; S-Adenosylm	2019
[The valproate model of autism]. Medecine sciences : M/S, 2019, Volume: 35, Issue:3 Topics: Animals; Autism Spectrum Disorder; Autistic Disorder; Disease Models, Animal; Female; Humans; Mice;	2019
Improving basic and translational science by accounting for litter-to-litter variation in animal models. BMC neuroscience, 2013, Mar-22, Volume: 14 Topics: Animals; Animals, Newborn; Antimanic Agents; Databases, Factual; Disease Models, Animal; Female; Mic	2013
Current advances in drug development in spinal muscular atrophy. Current opinion in pediatrics, 2013, Volume: 25, Issue:6 Topics: Animals; Child; Child, Preschool; Disease Models, Animal; Drug Design; Female; Genetic Therapy; Huma	2013
Modulation of antioxidant enzymatic activities by certain antiepileptic drugs (valproic acid, oxcarbazepine, and topiramate): evidence in humans and experimental models. Oxidative medicine and cellular longevity, 2013, Volume: 2013 Topics: Animals; Anticonvulsants; Antioxidants; Carbamazepine; Disease Models, Animal; Enzymes; Fructose; Hu	2013
Coagulation changes following traumatic brain injury and shock. Danish medical journal, 2014, Volume: 61, Issue:12 Topics: Animals; Blood Coagulation; Brain Injuries; Disease Models, Animal; Humans; Platelet Activation; Sho	2014
Is the Modulation of Autophagy the Future in the Treatment of Neurodegenerative Diseases? Current topics in medicinal chemistry, 2015, Volume: 15, Issue:21 Topics: Animals; Autophagy; Disease Models, Animal; Food; Humans; Isothiocyanates; Lithium; Neurodegenerativ	2015
Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research. Progress in lipid research, 2015, Volume: 59 Topics: Animals; Biomarkers; Diet, High-Fat; Disease Models, Animal; Fatty Acids; Humans; Lipid Metabolism;	2015
Mechanistic review of drug-induced steatohepatitis. Toxicology and applied pharmacology, 2015, Nov-15, Volume: 289, Issue:1 Topics: Amiodarone; Animals; Camptothecin; Chemical and Drug Induced Liver Injury; Disease Models, Animal; F	2015
The plausibility of maternal toxicant exposure and nutritional status as contributing factors to the risk of autism spectrum disorders. Nutritional neuroscience, 2017, Volume: 20, Issue:4 Topics: Animals; Autism Spectrum Disorder; Benzhydryl Compounds; Brain; Diethylhexyl Phthalate; Disease Mode	2017
Genetic and non-genetic animal models for autism spectrum disorders (ASD). Reproductive toxicology (Elmsford, N.Y.), 2016, Volume: 64 Topics: Animals; Autism Spectrum Disorder; Behavior, Animal; Disease Models, Animal; Epigenesis, Genetic; Fe	2016
A review of the preclinical and clinical evidence for protein kinase C as a target for drug development for bipolar disorder. Current psychiatry reports, 2008, Volume: 10, Issue:6 Topics: Adult; Animals; Antimanic Agents; Bipolar Disorder; Brain; Controlled Clinical Trials as Topic; Dise	2008
Valproic acid in pregnancy: how much are we endangering the embryo and fetus? Reproductive toxicology (Elmsford, N.Y.), 2009, Volume: 28, Issue:1 Topics: Abnormalities, Drug-Induced; Adolescent; Animals; Anticonvulsants; Autistic Disorder; Child; Child D	2009
[Rational combinations of antiepileptic drugs for refractory epilepsy]. Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology, 2011, Volume: 31, Issue:2 Topics: Animals; Anticonvulsants; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carbamazepine; Cl	2011
Beneficial effects of mood stabilizers lithium, valproate and lamotrigine in experimental stroke models. Acta pharmacologica Sinica, 2011, Volume: 32, Issue:12 Topics: Animals; Antipsychotic Agents; Bipolar Disorder; Disease Models, Animal; Humans; Lamotrigine; Lithiu	2011
Basic pharmacology of valproate: a review after 35 years of clinical use for the treatment of epilepsy. CNS drugs, 2002, Volume: 16, Issue:10 Topics: Animals; Anticonvulsants; Disease Models, Animal; Dopamine; Epilepsy; Excitatory Amino Acids; gamma-	2002
Carnitine transport: pathophysiology and metabolism of known molecular defects. Journal of inherited metabolic disease, 2003, Volume: 26, Issue:2-3 Topics: Animals; Biological Transport; Carnitine; Carrier Proteins; Chemical and Drug Induced Liver Injury;	2003
Prevention of epilepsy after head trauma: do we need new drugs or a new approach? Epilepsia, 2003, Volume: 44, Issue:s10 Topics: Animals; Anticonvulsants; Cerebral Cortex; Disease Models, Animal; Drug Administration Schedule; Epi	2003
Glycogen synthase kinase-3: a putative molecular target for lithium mimetic drugs. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2005, Volume: 30, Issue:7 Topics: Animals; Antidepressive Agents; Antipsychotic Agents; Circadian Rhythm; Disease Models, Animal; Elec	2005
Cellular plasticity cascades: genes-to-behavior pathways in animal models of bipolar disorder. Biological psychiatry, 2006, Jun-15, Volume: 59, Issue:12 Topics: Animals; Antimanic Agents; Behavior, Animal; Bipolar Disorder; Disease Models, Animal; Extracellular	2006
The role of mood stabilisers in the treatment of the depressive facet of bipolar disorders. Neuroscience and biobehavioral reviews, 2007, Volume: 31, Issue:6 Topics: Affective Symptoms; Animals; Antimanic Agents; Bipolar Disorder; Carbamazepine; Depressive Disorder;	2007
GSK-3 is a viable potential target for therapeutic intervention in bipolar disorder. Neuroscience and biobehavioral reviews, 2007, Volume: 31, Issue:6 Topics: Affective Symptoms; Animals; Bipolar Disorder; Disease Models, Animal; Enzyme Inhibitors; Female; Gl	2007
[Current progress in research and treatment of epilepsy]. Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica, 1984, Volume: 86, Issue:12 Topics: Animals; Brain; Clonazepam; Disease Models, Animal; Electroencephalography; Epilepsy; Humans; Kindli	1984
Sodium valproate. Advances in neurology, 1980, Volume: 27 Topics: Animals; Anticonvulsants; Disease Models, Animal; Humans; Kinetics; Phenobarbital; Seizures; Structu	1980
Ziskind-Somerfeld Research Award. Protein kinase C signaling in the brain: molecular transduction of mood stabilization in the treatment of manic-depressive illness. Biological psychiatry, 1999, Nov-15, Volume: 46, Issue:10 Topics: Animals; Antimanic Agents; Awards and Prizes; Binding, Competitive; Bipolar Disorder; Blotting, West	1999
The nature of bipolar disorder. The Journal of clinical psychiatry, 2000, Volume: 61 Supp 13 Topics: Bipolar Disorder; Cell Death; Circadian Rhythm; Corticotropin-Releasing Hormone; Disease Models, Ani	2000
Regulation of ER stress proteins by valproate: therapeutic implications. Bipolar disorders, 2002, Volume: 4, Issue:2 Topics: Animals; Antidepressive Agents; Bipolar Disorder; Brain; Disease Models, Animal; Endoplasmic Reticul	2002
Pharmacological and biochemical studies in epileptic fowl. Federation proceedings, 1979, Volume: 38, Issue:10 Topics: Animals; Anticonvulsants; Benzodiazepinones; Brain; Chickens; Disease Models, Animal; Ethosuximide;	1979
Pharmacological prophylaxis in the kindling model of epilepsy. Archives of neurology, 1977, Volume: 34, Issue:7 Topics: Amygdala; Anesthetics, Local; Animals; Antidepressive Agents, Tricyclic; Atropine; Aziridines; Carba	1977
Valproic acid-induced neural tube defects in mouse and human: aspects of chirality, alternative drug development, pharmacokinetics and possible mechanisms. Pharmacology & toxicology, 1991, Volume: 69, Issue:5 Topics: Abnormalities, Drug-Induced; Animals; Disease Models, Animal; Female; Humans; Maternal-Fetal Exchang	1991
Valproate and myoclonus. Advances in neurology, 1986, Volume: 43 Topics: 5-Hydroxytryptophan; Amino Acids; Animals; Aspartic Acid; Clonazepam; DDT; Disease Models, Animal; F	1986
Effects of different classes of antiepileptic drugs on brain-stem pathways. Federation proceedings, 1985, Volume: 44, Issue:8 Topics: Animals; Anticonvulsants; Baclofen; Brain Stem; Carbamazepine; Disease Models, Animal; Electroshock;	1985

Article	Year
Effects of in utero exposure to valproate or levetiracetam on the seizures and newborn histopathology of genetic absence epilepsy rats. Neuroscience letters, 2022, 04-17, Volume: 776 Topics: Animals; Anticonvulsants; Disease Models, Animal; Electroencephalography; Epilepsy, Absence; Female;	2022
Prolonging the therapeutic window for valproic acid treatment in a swine model of traumatic brain injury and hemorrhagic shock. The journal of trauma and acute care surgery, 2023, 11-01, Volume: 95, Issue:5 Topics: Animals; Brain Injuries, Traumatic; Disease Models, Animal; Resuscitation; Saline Solution; Shock, H	2023
Effects of fluoxetine on the anticonvulsant action of valproate and ethosuximide in mouse model of myoclonic convulsions. Annals of agricultural and environmental medicine : AAEM, 2012, Volume: 19, Issue:3 Topics: Animals; Anticonvulsants; Antidepressive Agents, Second-Generation; Avoidance Learning; Convulsants;	2012

valproic acid and Disease Models, Animal