tretinoin and Seizures

Caloric restriction (CR) possesses different cellular mechanisms. Though there are still gaps in the literature regarding its plausible beneficial effects, the suggestion that this alternative therapy can improve the inflammatory and antioxidant response to control epileptic seizures is explored throughout this study. Epilepsy is the second most prevalent neurodegenerative disease in the world. However, the appropriate mechanisms for it to be fully controlled are still unknown. Neuroinflammation and oxidative stress promote epileptic seizures' appearance and might even aggravate them. There is growing evidence that caloric restriction has extensive anti-inflammatory and antioxidant properties. For instance, nuclear factor erythroid 2-related factor 2 (Nrf2) and all-trans retinoic acid (ATRA) have been proposed to induce antioxidant processes and ulteriorly improve the disease progression. Caloric restriction can be an option for those patients with refractory epilepsy since it allows for anti-inflammatory and antioxidant properties to evolve within the brain areas involved.

Topics: Anti-Inflammatory Agents; Antioxidants; Caloric Restriction; Epilepsy; Humans; Neurodegenerative Diseases; NF-E2-Related Factor 2; Oxidative Stress; Seizures; Tretinoin

Hyperexcitability of brain circuits is a common feature of autism spectrum disorders (ASDs). Genetic deletion of a chromatin-binding protein,

Topics: Animals; Chromatin; Disease Models, Animal; Hippocampus; Mice; Phenotype; Seizures; Smith-Magenis Syndrome; Trans-Activators; Tretinoin

Neonatal stroke presents with seizures and results in neurologic morbidity, including epilepsy, hemiparesis, and cognitive deficits. Stem cell-based therapy offers a possible therapeutic strategy for neonatal stroke. We developed an immature mouse model of stroke with acute seizures and ischemic brain injury. Postnatal day 12 CD1 mice received right-sided carotid ligation. Two or 7 days after ligation, mice received an intrastriatal injection of B5 embryonic stem cell-derived neural stem cells. Four weeks after ligation, hemispheric brain atrophy was measured. Pups receiving stem cells 2 days after ligation had less severe hemispheric brain atrophy compared with either noninjected or vehicle-injected ligated controls. Transplanted cells survived, but 3 out of 10 pups injected with stem cells developed local tumors. No difference in hemispheric brain atrophy was seen in mice injected with stem cells 7 days after ligation. Neural stem cells have the potential to ameliorate ischemic injury in the immature brain, although tumor development is a serious concern.

Topics: Animals; Atrophy; Brain Ischemia; Brain Neoplasms; Carotid Arteries; Cell Survival; Ligation; Mice; Neurons; Seizures; Stem Cell Transplantation; Stem Cells; Stereotaxic Techniques; Stroke; Teratoma; Tretinoin

Amygdala plays an important role in induction and control of limbic seizures. There is a network of gap junctional communications in basolateral amygdala (BLA) as well. We compared the effect of intra-BLA infusion of the typical gap junction (GJ) blocker carbenoxolone (CBX), with the effect of putative GJ blocker all-trans retinoic acid (ATRA), on the afterdischarge (AD) recorded from BLA in amygdala-kindled rats. Both CBX and ATRA showed a rapid anti-seizure effect. Conversely, intra-BLA infusion of the known GJ opener, trimethylamine (TMA), enhanced seizure susceptibility by prolonging the duration of AD and generalized behavioral seizures. ATRA administered intra-BLA prevented the proconvulsant effect of TMA. The reduction of gap junctional conductance might be involved in the observed anticonvulsant effect of ATRA.

Topics: Amygdala; Animals; Carbenoxolone; Dose-Response Relationship, Drug; Electric Stimulation; Gap Junctions; Kindling, Neurologic; Male; Methylamines; Microinjections; Rats; Rats, Wistar; Seizures; Stereotaxic Techniques; Tretinoin

The major antiepileptic drugs used for the control of seizures can induce developmental toxicity when administered during pregnancy. Vitamin A and retinoids are thought to control many processes of embryonic development including growth, differentiation and morphogenesis. We have therefore studied if the teratogenic action of antiepileptic agents could be mediated via alteration of the endogenous vitamin A--retinoid metabolism. Retinol and its oxidative metabolites all-trans-, 13-cis- and 13-cis-4-oxo-retinoic acid were measured in the plasma of 75 infants and children treated with various antiepileptic drugs for the control of seizures, and in 29 untreated controls of comparable age. Retinol levels increased with age, while the concentrations of retinoic acid compounds did not exhibit age-dependency. Valproic acid monotherapy increased retinol levels in the young age group and a trend toward increased retinol concentrations was also observed in all other patient groups. The plasma levels of the oxidative metabolites 13-cis- and 13-cis-4-oxo-retinoic acids were strongly decreased in all patient groups treated with phenytoin, phenobarbital, carbamazepine and ethosuximide, in combination with valproic acid, to levels which were below 1/3rd and 1/10th of corresponding control values, respectively. Little changes were observed with all-trans-retinoic acid except in one patient group treated with valproic acid/ethosuximide cotherapy where increased levels of this retinoid were found. Our study indicates that therapy with antiepileptic agents can have a profound effect on the endogenous retinoid metabolism. Because of the importance of retinoids for the signaling of crucial biological events during embryonic development, such altered retinoid metabolism may be highly significant in regard to antiepileptic drug teratogenesis.

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Isotretinoin; Male; Oxidation-Reduction; Retinoids; Seizures; Tretinoin; Vitamin A