oxytocin and Seizures

Nitric oxide (NO), a molecule with multidimensional effects has generated exponential amount of research since its identification as a biological messenger almost two decades back. The recent trend in NO research is to explore newer dimensions in the cellular and molecular mechanisms of actions and interactions of NO with various biomolecules and their implications in various pathophysiological states. Advances in our knowledge of the mechanisms by which this pleiotropic molecule regulates the expression of eukaryotic genes has generated considerable excitement and is paving the way for development of novel NO based therapeutic strategies. However, it is still a challenge to understand fully the paradox of beneficial and damaging effects of this exciting molecule. This review will discuss the current trends of research in this area especially highlighting the new insights gained from recent experimental and clinical studies. New approaches to reduce or augment the availability of NO to benefit a wide range of clinical conditions and avenues for future research are also briefly discussed.

Topics: Animals; Biomedical Research; Cell Adhesion Molecules; Cytokines; Estrogens; Gene Expression; Heat-Shock Proteins; Humans; Melatonin; Mitochondria; Natriuretic Peptides; Neoplasms; Neuroimmunomodulation; Neuronal Plasticity; Neuropeptide Y; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Opioid Peptides; Oxytocin; Seizures; Steroids; Stress, Physiological

Traumatic brain injury (TBI) is a major risk factor to develop epilepsy and cognitive impairments. Neuropeptide oxytocin has been previously evidenced to produce antiepileptic effects. However, the involvement of central oxytocin in TBI-induced epileptic status and cognitive dysfunctions is not fully elucidated. In this study, we aim to investigate the role of oxytocin on a TBI model followed by seizure induction to clarify whether the epilepsy and cognitive deficits could be mitigated by oxytocin. TBI was established by weight drop and epileptic behaviors were induced by pentylenetetrazole (PTZ) injection in mice. Moreover, oxytocin was microinjected into the medial prefrontal cortex (mPFC) to observe the effects on the epilepsy and cognition. The blood-brain barrier (BBB) function and the neuroinflammation were measured by Evans Blue staining and enzyme-linked immunosorbent assays, respectively. Mice exposed to TBI demonstrate increased vulnerability to PTZ-mediated seizures and cognitive disturbances with a decrease in peripheral and brain oxytocin levels. Additionally, TBI reduces oxytocin, disrupts the BBB permeability and triggers neuroinflammation in mPFC in PTZ-treated mice. Intra-mPFC oxytocin simultaneously mitigates epilepsy and cognitive impairments. Finally, oxytocin restores BBB integrity and reduces mPFC inflammation in PTZ-treated TBI mice. These findings showed that intra-mPFC oxytocin suppressed the seizure vulnerability and cognitive deficits in TBI mice. The normalization of BBB integrity and inhibition of neuroinflammation may be involved in the antiepileptic and cognition-improved effects of oxytocin, suggesting that targeting inflammatory procedure in mPFC may decrease the risk to develop epilepsy and cognitive impairments in individuals previously experienced TBI.

Topics: Animals; Anticonvulsants; Brain Injuries, Traumatic; Cognitive Dysfunction; Disease Models, Animal; Epilepsy; Mice; Neuroinflammatory Diseases; Oxytocin; Pentylenetetrazole; Prefrontal Cortex; Seizures

Pentylenetetrazole (PTZ)-induced kindling is an animal model for studying human temporal lobe epilepsy (TLE), which is characterized by alterations of hippocampal neurons and memory. Although the intranasal (IN) administration of oxytocin (OT) has limited efficiency, nanoparticles (NPs) are a promising candidate to deliver OT to the brain. However, there are very limited data on epilepsy research about oxytocin-loaded nanoparticles (NP-OTs). The aim of this study is to investigate the effects of IN administration of chronic NP-OTs on the hippocampus of PTZ-induced male epileptic rats in terms of seizure severity, memory, neurogenesis, and neuronal damage. Saline/OT/NP-OTs were administrated to both control (Ctrl) and PTZ groups intranasally. Consequently, saline and PTZ were injected, respectively, 25 times every 48 h. Then, seizure severity (score and latency) was calculated for the PTZ groups. A spatial working memory evaluation test (SWMET) was performed after the last injection. Hippocampus histopathology, neurogenesis, and apoptosis were demonstrated. Serum total antioxidant status (TAS) and total oxidant status (TOS) levels and the oxidative stress index (OSI) were measured. We showed that OTs and NP-OTs prevented the kindling development and had positive effects on seizure severity. SWMET-related behaviors were also recovered in the PTZ + NP-OT group. A significant increase of neurogenesis and decrease of apoptosis in the hippocampus of the PTZ + NP-OT group were observed, while OTs and NP-OTs had protective effects against PTZ-induced damage to hippocampal neurons. Our results indicate that the chronic administration of NP-OTs may have positive effects on hippocampal damage via increasing neurogenesis and decreasing apoptosis and seizure severity.

Topics: Animals; Disease Models, Animal; Epilepsy; Hippocampus; Male; Nanoparticles; Neurogenesis; Neurons; Oxytocin; Pentylenetetrazole; Rats; Seizures

Oxytocin (OT) has broad effects in the brain and plays an important role in cognitive, social, and neuroendocrine function. OT has also been identified as potentially therapeutic in neuropsychiatric disorders such as autism and depression, which are often comorbid with epilepsy, raising the possibility that it might confer protection against the behavioral and seizure phenotypes in epilepsy. Dravet syndrome (DS) is an early-life encephalopathy associated with prolonged and recurrent early-life febrile seizures (FSs), treatment-resistant afebrile epilepsy, and cognitive and behavioral deficits. De novo loss-of-function mutations in the voltage-gated sodium channel SCN1A are the main cause of DS, while genetic epilepsy with febrile seizures plus (GEFS+), also characterized by early-life FSs and afebrile epilepsy, is typically caused by inherited mutations that alter the biophysical properties of SCN1A. Despite the wide range of available antiepileptic drugs, many patients with SCN1A mutations do not achieve adequate seizure control or the amelioration of associated behavioral comorbidities. In the current study, we demonstrate that nanoparticle encapsulation of OT conferred robust and sustained protection against induced seizures and restored more normal social behavior in a mouse model of Scn1a-derived epilepsy. These results demonstrate the ability of a nanotechnology formulation to significantly enhance the efficacy of OT. This approach will provide a general strategy to enhance the therapeutic potential of additional neuropeptides in epilepsy and other neurological disorders.

Topics: Animals; Behavior, Animal; Epilepsies, Myoclonic; Male; Mice; Nanoparticles; NAV1.1 Voltage-Gated Sodium Channel; Oxytocin; Seizures; Social Behavior

The Wistar audiogenic rat (WAR) strain is used as an animal model of epilepsy, which when submitted to acute acoustic stimulus presents tonic-clonic seizures, mainly dependent on brainstem (mesencephalic) structures. However, when WARs are exposed to chronic acoustic stimuli (audiogenic kindling-AK), they usually present tonic-clonic seizures, followed by limbic seizures, after recruitment of forebrain structures such as the cortex, hippocampus and amygdala. Although some studies have reported that hypothalamic-hypophysis function is also altered in WAR through modulating vasopressin (AVP) and oxytocin (OXT) secretion, the role of these neuropeptides in epilepsy still is controversial. We analyzed the impact of AK and consequent activation of mesencephalic neurocircuits and the recruitment of forebrain limbic (LiR) sites on the hypothalamic-neurohypophysial system and expression of Avpr1a and Oxtr in these structures. At the end of the AK protocol, nine out of 18 WARs presented LiR. Increases in both plasma vasopressin and oxytocin levels were observed in WAR when compared to Wistar rats. These results were correlated with an increase in the expressions of heteronuclear (hn) and messenger (m) RNA for Oxt in the paraventricular nucleus (PVN) in WARs submitted to AK that presented LiR. In the paraventricular nucleus, the hnAvp and mAvp expressions increased in WARs with and without LiR, respectively. There were no significant differences in Avp and Oxt expression in supraoptic nuclei (SON). Also, there was a reduction in the Avpr1a expression in the central nucleus of the amygdala and frontal lobe in the WAR strain. In the inferior colliculus, Avpr1a expression was lower in WARs after AK, especially those without LiR. Our results indicate that both AK and LiR in WARs lead to changes in the hypothalamic-neurohypophysial system and its receptors, providing a new molecular basis to better understaind epilepsy.

Topics: Acoustic Stimulation; Animals; Disease Models, Animal; Epilepsy, Reflex; Gene Expression Regulation; Hippocampus; Hypothalamus; Kindling, Neurologic; Male; Neurosecretory Systems; Oxytocin; Pituitary Gland, Posterior; Rats; Rats, Wistar; Seizures; Vasopressins

Sildenafil is a phosphodiesterase type 5 inhibitor used to treat male erectile dysfunction and pulmonary hypertension. A potential side effect of sildenafil is a noticeable decrease in seizure threshold. Oxytocin (OXT) secretion and the subsequent cAMP-responsive element-binding (CREB) phosphorylation are involved in proconvulsant effects of sildenafil in experimental models. The aim of the present study was to investigate the potential role of OXT receptors and their downstream calcineurin (CN)/inducible nitric oxide synthase (iNOS) pathways in proconvulsant effects of sildenafil. The pentylenetetrazole (PTZ)-induced seizure was used as a standard convulsion model in this study. Cortical CN activity, hippocampal nitrite levels, and proinflammatory cytokine content were measured. Our results indicated that following PTZ administration, sildenafil significantly increased CN activity at 40 mg/kg, respectively, in the control group. The combination of sildenafil and OXT receptor antagonist, atosiban (10 μg/kg, i.c.v) 30 min before sildenafil administration significantly reduced the CN activity. Also, the subeffective dose of CN inhibitor cyclosporine (5 mg/kg) 30 min before the administration of effective dose of sildenafil (40 mg/kg) reversed proconvulsant actions of sildenafil. This effect was iNOS-dependent because pretreatment of a low dose of aminoguanidine (20 mg/kg) 15 min before the administration of a low dose of cyclosporine (1 mg/kg) reversed the proconvulsant action of sildenafil (40 mg/kg). Finally, sildenafil induced the elevation of tumor necrosis factor alpha (TNF-α) and the nitrite level was blocked by the administration of cyclosporine in PTZ-treated mice. Collectively, our data provide insights into the role of OXT receptor/CN/iNOS pathway in the proconvulsant aspect of sildenafil.

Topics: Animals; Calcineurin; Convulsants; Dose-Response Relationship, Drug; Hippocampus; Male; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Oxytocin; Phosphodiesterase 5 Inhibitors; Receptors, Oxytocin; Seizures; Signal Transduction; Sildenafil Citrate

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by changes in social interactions, impaired language and communication, fear responses and presence of repetitive behaviours. Although the genetic bases of ASD are well documented, the recent increase in clinical cases of idiopathic ASD indicates that several environmental risk factors could play a role in ASD aetiology. Among these, maternal exposure to psychosocial stressors during pregnancy has been hypothesized to affect the risk for ASD in offspring. Here, we tested the hypothesis that preconceptional stressful experiences might also represent crucial elements in the aetiology of ASD. We previously showed that social isolation stress during adolescence results in a marked decrease in the brain and plasma concentrations of progesterone and in the quality of maternal care that these female rats later provide to their young. Here we report that male offspring of socially isolated parents showed decreased agonistic behaviour and social transmission of flavour preference, impairment in reversal learning, increased seizure susceptibility, reduced plasma oxytocin levels, and increased plasma and brain levels of BDNF, all features resembling an ASD-like phenotype. These alterations came with no change in spatial learning, aggression, anxiety and testosterone plasma levels, and were sex-dependent. Altogether, the results suggest that preconceptional stressful experiences should be considered as crucial elements for the aetiology of ASD, and indicate that male offspring of socially isolated parents may be a useful animal model to further study the neurobiological bases of ASD, avoiding the adaptations that may occur in other genetic or pharmacologic experimental models of these disorders.

Topics: Animals; Autism Spectrum Disorder; Behavior, Animal; Brain-Derived Neurotrophic Factor; Disease Models, Animal; Female; Hippocampus; Isoniazid; Male; Maternal Exposure; Oxytocin; Paternal Exposure; Phenotype; Prefrontal Cortex; Pregnancy; Rats; Seizures; Social Behavior; Social Isolation; Stress, Psychological; Testosterone

Psychogenic non-epileptic seizures (PNES) is a conversion disorder that reflects underlying psychological distress. Female patients with PNES often present with a history of prolonged stressors, especially sexual abuse. In the current study, we studied the relationship between neuropeptide Y (NPY) and PNES symptoms in women with a history of sexual abuse. NPY has been associated with resilience to stress and we hypothesized that low levels would increase the extent and severity of PNES symptoms in this patient population. Serum levels of NPY, and related hormones were measured in fifteen female PNES patients and sixty female controls. PNES patients reported more severe abuse histories, feeling of abandonment, and decreased perception of quality of life than controls. Importantly, they also had lower NPY levels. Our analysis indicates that low levels of NPY in PNES may confer greater vulnerability to exhibit seizure-like symptoms and lower quality of life.

Topics: Adrenocorticotropic Hormone; Adult; Case-Control Studies; Conversion Disorder; Disease Susceptibility; Electroencephalography; Estradiol; Female; Humans; Hydrocortisone; Neuropeptide Y; Oxytocin; Progesterone; Prolactin; Quality of Life; Resilience, Psychological; Seizures; Sex Offenses; Stress, Psychological; Testosterone; Young Adult

Sildenafil is a phosphodiesterase type 5 inhibitor mainly used for male erectile dysfunction. One of rare yet serious adverse effects of Sildenafil is its potential to decrease seizure threshold. Ample evidence suggests that Sildenafil exerts central effects through induction of Oxytocin (OT) secretion and CREB phosphorylation. The aim of the present study is to evaluate potential roles of OT and CREB in the proconvulsant effects of Sildenafil. The Pentylenetetrazole-induced seizure was used as a standard convulsion model in this study. OT release and pCREB expression were evaluated in the hippocampus of mice using ELISA and western blot assays, respectively. Our results showed that Sildenafil at the dose of 10mgkg(-1) or higher, significantly decreased seizure threshold. Pretreatment with a non-effective dose of OT, potentiated while OT receptor antagonist, Atosiban, reversed fully the proconvulsant effects of Sildenafil (5mgkg(-1)). At biochemical inspection, Sildenafil markedly increased CREB which was attenuated by coadministration of Atosiban. The present study shows for the first time that OT release and the subsequent CREB phosphorylation are involved in the proconvulsant effects of acute Sildenafil treatment in an experimental model of seizure.

Topics: Animals; CREB-Binding Protein; Disease Models, Animal; Dose-Response Relationship, Drug; Hippocampus; Hormone Antagonists; Male; Mice; Oxytocin; Pentylenetetrazole; Phosphodiesterase 5 Inhibitors; Phosphorylation; Receptors, Oxytocin; Seizures; Signal Transduction; Sildenafil Citrate; Time Factors; Vasotocin

To determine the incidence of moderate to severe neonatal encephalopathy (NE) and neonatal seizures without encephalopathy, and the association with metabolic acidemia. Secondly, to investigate the occurrence of suboptimal intrapartum care and its impact on neonatal outcome.. Clinical audit.. Two university hospitals in Sweden.. Neonates ≥34 weeks with moderate or severe NE and neonatal seizures alone, i.e. without encephalopathy, from a population of 71 189 births, where umbilical blood gases were routinely analyzed.. Neonates were categorized depending on the presence of metabolic acidemia at birth by umbilical artery pH < 7.00, base deficit ≥12 mmol/L. Records were audited for suboptimal care and a decision was made on whether management was assessed to have impacted neonatal outcome.. Encephalopathy and seizures alone.. We identified 80 neonates with NE and 30 with seizures alone, of which 48 (60%) and none, respectively, had metabolic acidemia. Suboptimal care could be assessed in 77 and occurred in 28 (36%) NE cases and in one neonate with seizures alone (p < 0.001). In 47 NE cases with metabolic acidemia, suboptimal care occurred in 22 (47%) vs. 6/30 (20%) without metabolic acidemia (p = 0.02). Suboptimal care had an impact on outcome in 18/77 (23%) NE cases but in no cases with seizures alone.. Suboptimal care was commonly seen with NE, particularly in neonates with metabolic acidemia, and also affected neonatal outcome. No such associations were found in neonates with seizures alone.

Topics: Acidosis; Blood Gas Analysis; Cardiotocography; Cerebral Palsy; Child Behavior Disorders; Child, Preschool; Clinical Audit; Cognition Disorders; Fetal Blood; Humans; Incidence; Infant, Newborn; Intellectual Disability; Mental Disorders; Oxytocics; Oxytocin; Perinatal Care; Quality of Health Care; Retrospective Studies; Seizures; Speech Disorders; Sweden; Vacuum Extraction, Obstetrical

We aimed to reveal the anti-convulsant effects of oxytocin (OT) in pentylenetetrazol (PTZ)-induced seizures in rats. Thirty rats were randomly divided into 5 equal groups. Using stereotaxy, we implanted electroencephologram (EEG) electrodes in the left nucleus of the posterior thalamus. After 2 days, the first and second groups were used as the control and PTZ (35 mg/kg) groups, respectively. We administered 40, 80 and 160 nmol/kg OT+35 mg/kg PTZ to the rats, constituting the third, fourth, and fifth groups, respectively, for 5 days. At the end of 5 days, we recorded EEGs via bipolar EEG electrodes. After 12h, all groups except the first received 70 mg/kg PTZ and we determined the dose-response ratio. Racine's Convulsion Scale was used to evaluate seizures. The spike-wave complex percentage in the EEG was determined as 0% for the first group, 38.6%±7.2 for the second group, 36.4%±5.6 for the third group, 4.3%±1.8 for the fifth group and 4.1%±1.1 for the fifth group. The fourth and fifth groups had significantly decreased spike-wave complex percentages compared to the second group (p<0.0001). OT may prevent PTZ-induced epilepsy on an EEG. OT may also be considered for use in the treatment of epilepsy in the future.

Topics: Animals; Disease Models, Animal; Electrodes, Implanted; Electroencephalography; Epilepsy; Male; Oxytocin; Pentylenetetrazole; Rats; Seizures

The possible involvement of oxytocin (OT) in the generation of seizures has not received a lot of attention in the past, although generalized epileptic convulsions were observed in humans following intravenous OT infusion. We here aimed to investigate the effect of exogenous OT administration on seizure susceptibility in C57Bl/6 mice subjected to the pentylenetetrazol (PTZ) model. In addition, we studied via which receptor possible effects on seizure thresholds could be mediated since OT binds to both the OT receptor (OTR) and the vasopressin 1a receptor (V1aR). We showed that C57Bl/6 mice treated with 0.5 mg/kg OT had decreased PTZ thresholds for ear twitch, myoclonic twitch, tail twitch, forelimb clonus and falling. This pronconvulsive effect was reversed by the OTR antagonist L-368.899, however, it was not mimicked by the OTR agonist carbetocin (CBT). Nevertheless, CBT had antidepressant-like effects in the forced swim test that could be reversed by L-368.899. These experiments shed some doubt on the involvement of OTR in the observed effect of OT on seizure thresholds. Therefore, we investigated the role of the V1aR as a possible mediator of the proconvulsive effects of OT. We found that the proconvulsive effects of both arginine vasopressin and OT were reversed by the V1aR antagonist SR49059. In summary, OT has proconvulsive effects in our mouse model of generalized seizures that could not be mimicked by CBT. Our results suggest that the binding of OT to V1aRs is the most plausible explanation for the proconvulsive effects of OT.

Topics: Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Mice; Mice, Inbred C57BL; Oxytocin; Pentylenetetrazole; Receptors, Vasopressin; Seizures

The authors sought to determine whether subjects with pathophysiological conditions that are characterized by increased concentrations of aldosterone have increased susceptibility to the side effects of neonatal anesthesia with sevoflurane.. Postnatal day 4-20 (P4-P20) rats were exposed to sevoflurane, 6% and 2.1%, for 3 min and 60-360 min, respectively. Exogenous aldosterone was administered to imitate pathophysiological conditions with increased concentrations of aldosterone.. Six hours of anesthesia with sevoflurane on P4-P5 rats resulted in a more than 30-fold increase in serum concentrations of aldosterone (7.02 ± 1.61 ng/dl vs. 263.75 ± 22.31 ng/dl, mean ± SE, n = 5-6) and reduced prepulse inhibition of the acoustic startle response (F(2,37) = 5.66, P < 0.001). Administration of exogenous aldosterone during anesthesia with sevoflurane enhanced seizure-like electroencephalogram patterns in neonatal rats (48.25 ± 15.91 s vs. 222.00 ± 53.87 s, mean ± SE, n = 4) but did not affect electroencephalographic activity in older rats. Exogenous aldosterone increased activation of caspase-3 (F(3,28) = 11.02, P < 0.001) and disruption of prepulse inhibition of startle (F(3,46) = 6.36; P = 0.001) caused by sevoflurane. Intracerebral administration of oxytocin receptor agonists resulted in depressed seizure-like electroencephalogram patterns (F(2,17) = 6.37, P = 0.009), reduced activation of caspase-3 (t(11) = 2.83, P = 0.016), and disruption of prepulse inhibition of startle (t(7) = -2.9; P = 0.023) caused by sevoflurane.. These results suggest that adverse developmental effects of neonatal anesthesia with sevoflurane may involve both central and peripheral actions of the anesthetic. Subjects with increased concentrations of aldosterone may be more vulnerable, whereas intracerebral oxytocin receptor agonists may be neuroprotective.

Topics: Aldosterone; Anesthesia, Inhalation; Anesthetics, Inhalation; Animals; Animals, Newborn; Blotting, Western; Caspase 3; Electroencephalography; Female; Male; Methyl Ethers; Oxytocin; Rats; Rats, Sprague-Dawley; Reflex, Startle; Seizures; Sensory Gating; Sevoflurane

Oxytocin (OT) has been suggested as a treatment to improve social behavior in autistic patients. Accordingly, the OT (Oxt(-/-)) and the OT receptor null mice (Oxtr(-/-)) display autistic-like deficits in social behavior, increased aggression, and reduced ultrasonic vocalization.. Oxtr(-/-) mice were characterized for general health, sociability, social novelty, cognitive flexibility, aggression, and seizure susceptibility. Because vasopressin (AVP) and OT cooperate in controlling social behavior, learning, and aggression, they were tested for possible rescue of the impaired behaviors. Primary hyppocampal cultures from Oxtr(+/+) and Oxtr(-/-) mouse embryos were established to investigate the balance between gamma-aminobutyric acid (GABA) and glutamate synapses and the expression levels of OT and AVP (V1a) receptors were determined by autoradiography.. Oxtr(-/-) mice display two additional, highly relevant, phenotypic characteristics: 1) a resistance to change in a learned pattern of behavior, comparable to restricted interests and repetitive behavior in autism, and 2) an increased susceptibility to seizures, a frequent and clinically relevant symptom of autism. We also show that intracerebral administration of both OT and AVP lowers aggression and fully reverts social and learning defects by acting on V1a receptors and that seizure susceptibility is antagonized by peripherally administered OT. Finally, we detect a decreased ratio of GABA-ergic versus total presynapses in hippocampal neurons of Oxtr(-/-) mice.. Autistic-like symptoms are rescued on administration of AVP and OT to young Oxtr(-/-) adult animals. The Oxtr(-/-) mouse is thus instrumental to investigate the neurochemical and synaptic abnormalities underlying autistic-like disturbances and to test new strategies of pharmacologic intervention.

Topics: Aggression; Analysis of Variance; Animals; Arginine Vasopressin; Autistic Disorder; Autoradiography; Cells, Cultured; Cognition; Disease Models, Animal; Hippocampus; Immunohistochemistry; Male; Mice; Mice, Knockout; Neurons; Oxytocin; Receptors, Oxytocin; Seizures; Social Behavior

Hyponatremia is not uncommon, serious cases can cause dangerous complications as seizures, brain damage and even death. We present a case of a young mother with post partum hemorrhage and some of the serious complications.

Topics: Adult; Coma; Diuretics; Female; Humans; Hyponatremia; Infusions, Intravenous; Mannitol; Oxytocin; Postpartum Hemorrhage; Pregnancy; Saline Solution, Hypertonic; Seizures; Sodium

Topics: Adult; Female; Humans; Hyponatremia; Hypotonic Solutions; Iatrogenic Disease; Labor, Obstetric; Oxytocin; Pregnancy; Seizures; Tocolytic Agents; Water Intoxication

Our purposes were to determine the effect of preeclampsia, magnesium sulfate prophylaxis, and maternal weight on labor induction in women with preeclampsia and identify risk factors associated with its failure.. Fifty-five preeclamptic women and 176 non-preeclamptic women requiring labor induction over an 18-month period were studied retrospectively. Prostaglandin E(2) (dinoprostone) and oxytocin were used for labor induction. Women with rupture of the membranes, spontaneous contraction resulting in cervical change, or an initial cervical examination showing more than 2 cm dilatation and 50% effacement were excluded. Statistics were analyzed with chi(2) test, Fisher's exact test, Student t test, Mann-Whitney U test, and multiple logistic regression.. The women with preeclampsia had a significantly higher rate of failed induction than did those without preeclampsia (p = 0.01). However, the women with preeclampsia had a higher mean maternal weight and an increased use of magnesium sulfate, and labor was induced at earlier gestational age than in those without preeclampsia (p < 0.05 for each). Multiple logistic regression showed that the use of magnesium sulfate, higher maternal weight, and unfavorable cervix, but not preeclampsia, were significantly associated with an increased risk of failed induction after correction for known confounding variables.. Although the risk of failed induction is increased in preeclamptic women, preeclampsia is not an independent risk factor for failed induction. The use of magnesium sulfate, higher maternal weight, and unfavorable cervix are independent risk factors for failed induction.

Topics: Adult; Anticonvulsants; Body Weight; Case-Control Studies; Chi-Square Distribution; Dinoprostone; Female; Humans; Labor, Induced; Magnesium Sulfate; Oxytocin; Pre-Eclampsia; Pregnancy; Retrospective Studies; Seizures

Our goals were to compare duration of labor at term for (1) women with preeclampsia versus normotensive nulliparous women and (2) nulliparous women with preeclampsia who received magnesium for seizure prophylaxis versus those who did not.. We performed a retrospective cohort study of all nulliparous, term vaginal deliveries from 1989 through 1995 at University of California, San Francisco. The perinatal database and medical records were reviewed for information on duration of labor, maternal and labor characteristics, and neonatal outcomes. The chi2 odds ratio, and Student t tests were used to compare categoric and continuous variables between women with preeclampsia and control women and between women with preeclampsia who did and those who did not receive magnesium. Logistic regression was used to evaluate variables predictive of labor duration.. Our study subjects were 4083 normotensive nulliparous women and 154 women with preeclampsia. A sample size calculation revealed that 1764 normotensive control subjects were needed to show a 10% difference in labor duration with 80% power and alpha of 0.05. Among women with preeclampsia, 93 (60%) were treated with magnesium and 61 (40%) were not. More women with preeclampsia than normotensive women had induction of labor and received epidural anesthesia, prostaglandin gel, and oxytocin (P <.003). Total labor duration did not differ between women with preeclampsia and normotensive women (P =.15) or between women with preeclampsia who received magnesium and those who did not (P =.09). In comparison with normotensive women, those with preeclampsia had a higher rate of postpartum hemorrhage (31% vs 22%, P =.005), and the rate was even higher among preeclamptic women treated with magnesium versus those who received no magnesium (34% vs 26%, P =.002). Logistic regression, with prolonged first stage of labor (>12 hours) used as the outcome variable, indicated that epidural anesthesia (odds ratio 2.3, 95% confidence interval 1.9-2. 6), oxytocin (odds ratio 1.8, 95% confidence interval 1.6-2.2), and persistent occipitoposterior presentation (odds ratio 1.6, 95% confidence interval 1.1-2.4) were associated with prolonged labor, whereas preeclampsia (odds ratio 0.9, 95% confidence interval 0.7-1. 1) and treatment with magnesium were not (odds ratio 1.1, 95% confidence interval 0.9-1.4). Induction (odds ratio 0.5, 95% confidence interval 0.4-0.6) and birth weight <2500 g (odds ratio 0. 5, 95% confidence interval 0.4-0.8) were associated with faster labor.. In term nulliparous women, neither preeclampsia nor magnesium prophylaxis affected labor duration.

Topics: Adult; Anesthesia, Epidural; Cohort Studies; Female; Humans; Labor, Induced; Labor, Obstetric; Magnesium; Obstetric Labor Complications; Oxytocin; Postpartum Hemorrhage; Pre-Eclampsia; Pregnancy; Retrospective Studies; Seizures; Time Factors

Intractable temporal lobe epilepsy is a disabling disorder with far reaching effects on brain function, behavior and neuroendocrine function. Previous work in the kindled-seizure model for temporal lobe epilepsy has shown that these seizures cause vasopressin (VP) release, an increase in resting VP and lasting increases in VP mRNA in the supraoptic nucleus (SON) of the hypothalamus. In this study we used in situ hybridization to examine the effects of kindled seizures on the expression of two other functionally-related, neuroendocrine genes, oxytocin (OT) and corticotrophin releasing factor (CRF). Comparisons in kindled and sham-stimulated controls revealed an increase in VP mRNA but not OT mRNA in magnocellular neurons and an increase in CRF mRNA in parvocellular neurons of the paraventricular nucleus (PVN) of the hypothalamus 1 month after the last seizure. We conclude that kindled seizures induce selective changes in neuroendocrine gene expression in neuroendocrine systems, VP and CRF but not OT.

Topics: Animals; Corticotropin-Releasing Hormone; In Situ Hybridization; Kindling, Neurologic; Male; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred Strains; Reference Values; RNA, Messenger; Seizures; Supraoptic Nucleus; Vasopressins

Subcutaneously (s.c.) administered [Arg8]vasopressin (AVP) potentiated seizures induced by intracerebroventricular (i.c.v.) injection of 1.95 mg pilocarpine (a muscarinic cholinergic agonist). A bell-shaped relation between dose and effect was found. I.c.v. pretreatment with a V1, V2 or oxytocin receptor antagonist was performed to determine whether and what type of receptor is involved in this proconvulsive effect of vasopressin. For these experiments a higher dose of pilocarpine (2.4 mg i.c.v.) was injected. This caused seizures in a slightly but not significantly higher percentage of the rats. A dose-dependent protective action of the V2 receptor antagonist d(CH2),[D-Ile2,Ile4]AVP (effective doses were 25 and 125 ng) on seizures was found. A reduction was observed in the number of animals that developed tonic-clonic convulsions. Neither the V1 receptor antagonist d(CH2)5[Tyr(Me)2]AVP nor the oxytocin receptor antagonist desGly(NH2)9d(CH2)5[Tyr(Me)2Thr4]OVT possessed anti-convulsive activity. Subsequently the type of receptor was studied in detail with fragments of AVP with either V1 or V2 activity. AVP (with V1 and V2 affinity) (1 and 3 microg s.c.) potentiated pilocarpine (1.95 mg) induced seizures. Vasotocin and oxytocin were without effect. Interestingly neither s.c. nor i.c.v. administration of the selective kidney type vasopressin receptor (V2) agonist dDAVP potentiated pilocarpine induced seizures. Several selective antidiuretic agonists (V2), such as d[Val4]AVP, d[Phe2,Val4,D-Arg8]vasopressin (3 microg), [Val4,D-Arg8]vasopressin (3 microg) and d[Val4,D-Arg8]vasopressin (3 microg) were active. Other selective antidiuretic compounds, such as [Val4]AVP, dAVP, d[Tyr(Me)2]AVP and HO[D-Arg8]vasopressin (3 microg) did not influence seizures. These results demonstrate that a combination of substitution of aminoacid 4 (Gln) by Val and to a lesser extent deamination and the D-arginine form yield an active molecule, which can potentiate pilocarpine induced seizures and suggest the existence of a V2 receptor subtype in the brain.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Brain; Deamino Arginine Vasopressin; Drug Synergism; Injections, Intraventricular; Male; Muscarinic Agonists; Oxytocin; Peptide Fragments; Pilocarpine; Rats; Rats, Wistar; Receptors, Oxytocin; Receptors, Vasopressin; Seizures; Vasotocin

Due to the complex nature of generalized limbic seizures, marked disturbances in physiological homeostasis occur. Accompanying the motor manifestations which characteristically are associated with generalized limbic seizures, alterations in neuroendocrine, behavioral, and autonomic functions may be observed. The paraventricular nucleus (PVN) of the hypothalamus is known to play a significant role in such neuronal responses to stressful stimuli; however, the effect of seizures on hypothalamic neurons is unknown. We have used the immunocytochemical detection of the Fos protein to anatomically identify neurons in the PVN which are activated following generalized limbic seizures. To induce seizures, rats received intraperitoneal injections of kainic acid or were kindled from the entorhinal cortex. We have demonstrated that elicitation of generalized limbic seizures induces a dramatic number of neurons in the PVN to express the Fos protein. Numerous Fos-immunolabeled neurons were identified in both the parvicellular and magnocellular component of the PVN. In the latter, this study clearly reveals a preferential and selective activation of oxytocin-containing neurons, and it extends and supports the hypothesis that oxytocin plays a role in the body's response to specific stress paradigms. Data suggest that an activation of the oxytocin neuronal system may be part of the adaptive mechanism that enables the hypothalamus to modulate and maintain an adequate response to stressors (e.g., generalized seizures) to regain homeostasis.

Topics: Animals; Immunohistochemistry; In Situ Hybridization; Male; Nerve Tissue Proteins; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Seizures

In this study, the regulation of hypothalamic oxytocin and vasopressin messenger RNA expression following the induction of seizures was investigated by in situ hybridization. Following kainic acid-induced seizures, a significant increase in oxytocin messenger RNA in the paraventricular nucleus was demonstrated at 1.5 h, one and two weeks; its level decreased at three weeks and was significantly increased again at four weeks; at eight weeks the messenger RNA level still remained higher than that of controls. Vasopressin messenger RNA in the paraventricular nucleus was increased significantly only at 1.5 h following induction of seizures. The oxytocin messenger RNA level in the supraoptic nucleus was also increased early at 1.5 h and later at four weeks following seizures; however, these increases did not last as long as those in the paraventricular nucleus. Vasopressin messenger RNA in the supraoptic nucleus was also increased after the initial seizures; however, its messenger RNA level vacillated up and down throughout the post-seizure times studied. The earliest significant increase of vasopressin messenger RNA was at one week after seizures, and there was a late significant increase of vasopressin messenger RNA at three weeks after seizures. The present study demonstrates that following kainic acid-induced seizures both, the oxytocin and vasopressin messenger RNA expressions, were up-regulated and these up-regulations were long-term events. The increase of oxytocin messenger RNA in the paraventricular nucleus was more persistent than the others. The pattern of messenger RNA up-regulation was different for oxytocin and vasopressin, and different in the paraventricular nucleus and supraoptic nucleus. These different patterns of messenger RNA elevations suggest that the different components of the rat hypothalamus were regulated differentially by kainic acid-induced seizures.

Topics: Animals; Gene Expression; Hypothalamus; Image Processing, Computer-Assisted; In Situ Hybridization; Kainic Acid; Male; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; RNA, Messenger; Seizures; Supraoptic Nucleus; Up-Regulation; Vasopressins

Following our recent demonstration of metrazole-induced immediate-early gene expression in the hypothalamic supraoptic nucleus (SON), we have now performed a mRNA and transcription analysis to determine the consequences of metrazole treatment for neurohypophyseal peptide gene expression in male rats. Levels of hypothalamic vasopressin (VP) and oxytocin (OT) mRNA were significantly reduced at 2 and 4 h after metrazole (50 mg/kg, i.p.), whereas pro-dynorphin mRNA was significantly elevated at 2 h. No changes in mRNA levels were found at 8, 24 or 48 h after treatment. Another convulsant (kainic acid, 8 mg/kg, i.p.) elicited similar effects on VP and OT mRNAs at 2 h. Specific analysis of the SON, following metrazole, revealed an equivalent effect on VP and OT mRNA levels but a nuclear run-on assay did not detect any change in SON VP gene transcription at 0.5, 1 and 2 h after treatment. The results provide evidence of a novel mechanism which may provide an additional level of control in the regulation of neuropeptide gene expression.

Topics: Animals; Blotting, Northern; Cell Nucleus; Enkephalins; Gene Expression; Hypothalamus; Male; Oxytocin; Pentylenetetrazole; Pituitary Gland, Posterior; Protein Precursors; Rats; Rats, Sprague-Dawley; RNA, Messenger; Seizures; Supraoptic Nucleus; Transcription, Genetic; Vasopressins

Experiments were undertaken to test whether oxytocin (OT) may modulate the antipyretic action of arginine vasopressin (AVP) and to determine whether the action of endogenously released OT and/or AVP evoked by fever may modulate the motor actions of exogenous AVP. Intracerebroventricular (icv) injection of interleukin-1 alpha (IL-1 alpha, 40 ng) elicited a significantly attenuated rise in body temperature during the 2nd h of the febrile responses in OT-pretreated (0.1-10 pmol icv, 24 h earlier) rats. At the end of the 2nd h, administration of AVP (1 pmol icv), but not OT (10 pmol icv), significantly suppressed the febrile response in OT-pretreated but not in saline-pretreated rats. In nonfebrile OT-pretreated rats, 10 but not 1 pmol of AVP (icv) caused a significant decrease in body temperature. In rats pretreated with IL-1 alpha (40 ng icv) injection of AVP (100 pmol icv) induced enhanced motor responses. In summary, the ability of OT pretreatment to alter the febrile response to IL-1 alpha and the antipyretic action of AVP suggests a role for this peptide in fever. Furthermore, the observation that fever pretreatment can lower the threshold for convulsive-like behavior evoked by subsequent exposure to AVP raises the possibility that central OT and/or AVP released during fever could play a role in the genesis of febrile convulsions.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arginine Vasopressin; Body Temperature Regulation; Brain; Interleukin-1; Male; Motor Activity; Oxytocin; Rats; Rats, Sprague-Dawley; Seizures

The intracerebroventricular (ICV) injection of oxytocin at doses between 5 and 100 ng induced repeated episodes of penile erection and yawning, while at doses between 100 ng and 10 micrograms it induced motor disturbances often culminating in barrel rotation in rats. The intensity of motor disturbances was inversely correlated to the number of yawning and penile erection episodes. Pretreatment with the dopaminergic agonist apomorphine (80 and 240 micrograms/kg SC) failed to modify the incidence of motor disturbance induced by high doses of oxytocin, but markedly reduced the intensity of the symptomatology in a dose-dependent manner. The present results suggest that high doses of oxytocin induce motor disturbances which mask penile erection and yawning, and that brain dopaminergic systems have a protective role against this symptomatology.

Topics: Animals; Dose-Response Relationship, Drug; Injections, Intraventricular; Male; Movement Disorders; Oxytocin; Penile Erection; Rats; Rats, Inbred Strains; Seizures; Yawning

Topics: Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Labor, Obstetric; Oxytocin; Pregnancy; Seizures

The effect of oxytocin (OXT) and vasopressin (VP) on alcohol withdrawal was investigated. CFLP mice were treated with alternating daily injections of tert-butanol and ethanol for four days, which resulted in physical dependence on ethanol. The severity of withdrawal symptoms was assessed by picrotoxin. The lowest dose (0.02 IU) of each of the peptides precipitated tonic convulsions, while higher doses resulted in different tendencies. OXT-treated mice displayed milder withdrawal symptoms in response to increasing doses of peptide (0.2-2.0 IU). VP showed a U-shaped dose-response effect. The lowest (0.02 IU) and the highest (2.0 IU) doses increased the occurrence of withdrawal convulsions and the frequency of deaths.

Topics: Alcohol Withdrawal Delirium; Alcoholism; Animals; Lypressin; Male; Mice; Oxytocin; Picrotoxin; Psychoses, Alcoholic; Seizures

Topics: Female; Humans; Infant, Newborn, Diseases; Oxytocin; Pregnancy; Seizures

Histamine administered intraperitoneally increased, in a dose-dependent manner, AVP, OXT and PRL levels in plasma of rats, whereas alpha-MSH levels were not affected. Levels of AVP in plasma after histamine 20.0 mg/kg treatment were approximately 100-fold higher than those of controls, while OXT and PRL levels were approximately 7-fold higher after this treatment. CSF content of AVP, OXT, PRL and alpha-MSH was not influenced by histamine, indicating that a stimulated release of hormones from the pituitary into the blood is not accompanied by a concomitant increase of secretion of these hormones into the CSF. Convulsions induced by pentylenetetrazol were accompanied by a temporary increase in AVP levels and by strongly and consistently elevated OXT levels in plasma. PRL and alpha-MSH plasma levels were affected in a biphasic manner. A convulsion type 1 induced elevated PRL levels and diminished alpha-MSH levels, while a convulsion type 2 had no effect on plasma PRL concentration, but increased the concentration of alpha-MSH. Only the level of OXT in CSF was increased after a pentylenetetrazol-induced convulsion type 1. The present data suggest that histamine affects the release of AVP, while pentylenetetrazol might act more specifically on the OXT-releasing system. Furthermore, a possible relationship between the pentylenetetrazol-induced increase of OXT levels in the CSF and amnesia is suggested.

Topics: Animals; Arginine Vasopressin; Histamine; Kinetics; Male; Melanocyte-Stimulating Hormones; Oxytocin; Pentylenetetrazole; Pituitary Gland; Pituitary Hormones; Prolactin; Rats; Rats, Inbred Strains; Seizures

Topics: Abortion, Induced; Adult; Brain Edema; Female; Humans; Hyponatremia; Oxytocin; Pregnancy; Pregnancy Trimester, Second; Seizures; Water Intoxication

The clinical course is described of an infant who accidentally received an adult dose of Syntometrine (synthetic oxytocin + ergometrine) at delivery. The infant soon became ill with convulsions and ventilatory failure, and later with water intoxication. Similar reported cases are reviewed and recommendations are given for the management of future cases.

Topics: Accidents; Drug Combinations; Ergonovine; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Oxytocin; Respiratory Insufficiency; Seizures; Water Intoxication

When vasopressin is administered into the lateral ventricles of rats it produces severe convulsive activity characterized by a rapid barrel rotation. Electrical recordings from the dorsal hippocampus indicate marked elevations in the amplitude and frequency at doses of 5 microliter of 2 x 10(-5) M vasopressin. No significant behavioral effects were noted with oxytocin, somatostatin, beta-melanophore-stimulating hormone, adrenocorticotropin, or leu-enkephalin. Pretreatment of the rats with intraventricularly administered oxytocin, beta-MSH, or systemically administered Dilantin prevented the vasopressin-induced seizures. With the use of chemical and enzymic modification procedures, the essential fragment and amino acids of vasopressin needed for the activity were determined. It was concluded that although the peptide could be acting by vasoconstricting blood arterioles and capillaries in the brain, it may also be exerting a direct excitatory action on neurons.

Topics: Animals; Dose-Response Relationship, Drug; Hippocampus; Injections, Intraventricular; Myoclonus; Oxytocin; Peptides; Rats; Seizures; Vasopressins

A case of severe water intoxication with convulsion and prolonged coma, following the use of a high dose Syntocinon infusion is described. The pathogenesis and treatment of the condition are discussed.

Topics: Adult; Coma; Diuresis; Female; Humans; Oxytocin; Pregnancy; Seizures; Water Intoxication

A patient who had a generalized epileptiform convulsion after intra-amniotic prostaglandin F2 alpha administration with intravenous oxytocin infusion is described. The convulsion was possibly due to either or both of these drugs. The aetiological associations are reviewed. Intra-amniotic prostaglandins and intravenous oxytocin are frequently used to induce mid-trimester abortions, and the case described serves as a reminder of some of the dangers associated with this procedure.

Topics: Abortion, Therapeutic; Adult; Female; Humans; Oxytocin; Pregnancy; Pregnancy Trimester, Second; Prostaglandins F; Seizures

Topics: Abortion, Induced; Amnion; Electroencephalography; Female; Humans; Injections, Intravenous; Oxytocin; Pregnancy; Prostaglandins; Seizures

Topics: Action Potentials; Animals; Biometry; Drug Interactions; Electrodes, Implanted; Electroencephalography; Female; Glutamates; Hypothalamus; Injections, Spinal; Oxytocin; Rabbits; Seizures

Topics: Abortion, Induced; Adolescent; Adult; Brain Edema; Edema; Female; Humans; Hypotonic Solutions; Oxytocin; Seizures; Sodium Chloride; Water Intoxication

Topics: Animals; Brain Diseases; Central Nervous System Diseases; Humans; Meningitis; Multiple Sclerosis; Oxytocin; Rats; Sciatica; Seizures

Topics: Abortion, Missed; Adult; Electroencephalography; Female; Humans; Oxytocin; Pregnancy; Prognosis; Seizures; Water Intoxication

Topics: Abortion, Induced; Adult; Female; Humans; Oxytocin; Pentobarbital; Potassium; Pregnancy; Seizures; Sodium; Water Intoxication

Topics: Abortion, Spontaneous; Adult; Brain Edema; Electroencephalography; Female; Humans; Injections, Intravenous; Oxytocin; Pregnancy; Seizures; Water Intoxication; Water-Electrolyte Balance

Topics: Abortion, Induced; Diuresis; Female; Humans; Injections, Intravenous; Oxytocin; Pharmacology; Pregnancy; Seizures; Toxicology; Urine; Vasopressins; Water Intoxication; Water-Electrolyte Balance

Topics: Anesthesia, Epidural; Anesthesia, Obstetrical; Anesthesia, Spinal; Antihypertensive Agents; Anuria; Coma; Eclampsia; Female; Hibernation; Humans; Hypertension; Hypothermia, Induced; Labor, Induced; Labor, Obstetric; Oxytocin; Pre-Eclampsia; Pregnancy; Seizures

Topics: Animals; Breast Feeding; Citrates; Female; Humans; Hypocalcemia; Lactation; Mammary Glands, Animal; Oxytocin; Parathyroid Glands; Pharmacology; Pregnancy; Rats; Research; Seizures; Sodium Citrate

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Ascorbic Acid; Calcium; Cortisone; Epinephrine; Fasting; Glucagon; Growth Hormone; Hydrocortisone; Hypocalcemia; Insulin; Luteinizing Hormone; Norepinephrine; Oxytocin; Parathyroid Hormone; Rabbits; Research; Seizures; Tetany; Thyrotropin; Vasopressins