Faculty: O. Carter Snead III, MD
Professor of Pediatrics and Medicine (Neurology)
Head of Neurology,
Director of the Centre for Brain & Behavior
Hospital for Sick Children
General Research Area: Neuropharmacology
Basic Mechanisms of Epileptogenesis
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.
- Joshi K, Shen L, Michaeli A, Salter M, Thibault-Messier G, Hashmi S, Eubanks JH, Cortez MA, SNEAD OC. Infantile spasms in Down syndrome: Rescue by knockdown of the GIRK2 channel. Ann Neurol 2016;80:511-21.
- Pang EW, SNEAD OC. From structures to circuits: The contribution of MEG connectivity studies to functional neurosurgery. Front Neuroanat 2016 Jun 21;10:67
- Zhang L, Wither RG, Lang M, Wu C, Sidorva-Darmos E, Netchev H, Matolcsy CB, SNEAD OC, Eubanks JH. A role for diminished GABA transporter activity in the cortical discharge phenotype of MeCP2 deficient mice. Neuropsychopharmacology. 2016 May;41(6):1467-76.
- Cortez MA, Kostopoulos GK, SNEAD OC. Acute and chronic pharmacological models of generalized absence seizures. J Neurosci Methods 2015;42:360-71.
- Jones K, Go C, Boyd J, Ochi A, McCoy B, Puka K, SNEAD OC. Vigabatrin as first-line treatment for infantile spasms not related to tuberous sclerosis comples. Pediatr Neurol 2015;53:141-5.
- Blichowski M, Shephard A, Armstrong J, Shen L, Cortez MA, Eubanks JH, SNEAD OC. The GIRK2 subunit is involved in infantile spasms like seizures induced by GABAB receptor agonists. Epilepsia. 2015;56;1081-7.
- Ibrahim GM, Morgan BR, Doesburg SM, Taylor MJ, Pang EW, Donner E, Go CY, Rutka JT, SNEAD OC. Atypical language laterality is associated with large scale disruption of network integration in children with intractable focal epilepsy. Cortex 2015;65:83-8
- Mercimek-Mahmutoglu S, Patel J, Cordeiro D, Hewson S, Callen D, Donner EJ, Hahn CD, Kannu P, Kobayashi J, Minassian BA, Moharir M, Siriwardena K, Weiss SK, Weksberg R, SNEAD OC. Diagnostic yield of genetic testing in epileptic encephalopathy in childhood. Epilepsia 2015; 56(5):707-16.
- Ibrahim GM, Rutka JT, SNEAD OC, Network analysis reveals patterns of antiepileptic drug use in children with medically refractory epilepsy. Epilepsy Behav 2013;28:22-5
- Elliott I, Smith, Ambanibe J, Angwafor SA, Smith ML, Takougang T, Noh J, Tsang V, Wilkins P, Cockburn L, Keystone J, Njamnshi AK, SNEAD OC. Epilepsy and cysticercosis in North-West Cameroon: A serological study. Seizure 2013;283-6
- Onat FY, van Luijtelaar G, Nehlig A, SNEAD OC. The involvement of limbic structures in typical and atypical absence epilepsy. Epilepsy Res 2013;103:111-23
Bowen JM, SNEAD OC (C), Chandra K, Blackhouse G, Goeree R. Epilepsy care in Ontario: an economic analysis of increasing access to epilepsy surgery. Ont Health Technol Assess Ser 2012;12:1-41
Hospital For Sick Children
Division of Neurology
Hospital for Sick Children
555 University Avenue