O. Carter Snead III
Professor
Hospital for Sick Children
University of Toronto;Department of Medicine, Temerty Faculty of Medicine, University of Toronto;Department of Pharmacology and Toxicology, Temerty Faculty of Medicine, University of Toronto;Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto
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The goal of my laboratory is to develop animal models of epilepsy syndromes that are unique to children, and to investigate mechanisms of epileptogenesis in these models. We defined and standardized the g-hydroxybutyrate (GHB) rat model of generalized absence seizures which is now utilized world wide to screen for anti absence activity of putative antiepileptic compounds and to investigate basic mechanisms of absence seizures. We have shown that GABAB receptor (GABABR) agonists exacerbate, that both GHB and GABABR antagonists block, experimental absence seizures. More recently, we have developed, characterized, and standardized an animal model of atypical absence epilepsy in rat and mouse. This model is created by inhibiting cholesterol synthesis in the brain by AY 9944 (AY) during postnatal brain development. Atypical absence seizures in children are a component of epilepsy syndromes in children which are hard to treat and which have a very poor neurodevelopmental outcome. The AY model of atypical absence epilepsy in rat is clinically relevant because it reliably and accurately mirrors the EEG, behavioural, pharmacological, and developmental characteristics of the human condition. Recently we have created mutant mice that over-express the GABA(B) receptor R1 subunit and shown that these animals show a phenotype consistent with atypical absence seizures. We are currently investigating GABA(B) receptor-mediated mechanisms within thalamohippocampal circuitary in this genetic animal model of atypical absence seizures.
Research Interests
Papers共 408 篇Author StatisticsCo-AuthorSimilar Experts
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Epilepsiano. 8 (2023): 2162-2171
Epilepsiano. 12 (2023): 3342-3353
JAMA NETWORK OPENno. 3 (2023): e234858-e234858
EPILEPSIA (2023): 524-524
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