The objective of this proposal is to identify the mechanism involved in the suppression of seizures as a function of age. Ongoing studies have demonstrated that the increased seizure susceptibility of the immature brain may be due to an alteration of the functional activity of the GABA sensitive neurons in the substantia nigra (SN) and their efferent connections.
The aims of the proposal are to determine: 1) the age-related differences in the development of GABA receptor substypes in the SN; 2) the role of specific GABA receptor subtypes in the SN-mediated modification of seizures in adults and rat pups; 3) the efferent pathways from the SN that mediate the different GABAergic effects on seizures in adults and rat pups. The methods include in vivo studies to determine the seizure susceptibility of adult rats and 16-day old rat pups after GABAergic pre-treatment using chronically implanted cannulae, intracranial microinfusions and the flurothyl model of epilepsy; in vitro quantitative light microscopy receptor autoradiography; and deoxyglucose autoradiographic studies to map the SN efferent pathways. The goal is to develop a better understanding of the endogenous processes involved in the modification of seizures with maturation. These studies may lead to the development of new therapeutic approaches that will compensate for the maturational state of the CNS.

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National Institute of Neurological Disorders and Stroke (NINDS)
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Neurology A Study Section (NEUA)
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Albert Einstein College of Medicine
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Galanopoulou, Aristea S; Mowrey, Wenzhu B; Liu, Wei et al. (2017) Preclinical Screening for Treatments for Infantile Spasms in the Multiple Hit Rat Model of Infantile Spasms: An Update. Neurochem Res 42:1949-1961
Shandra, Oleksii; Moshé, Solomon L; Galanopoulou, Aristea S (2017) Inflammation in Epileptic Encephalopathies. Adv Protein Chem Struct Biol 108:59-84
Nariai, Hiroki; Beal, Jules; Galanopoulou, Aristea S et al. (2017) Scalp EEG Ictal gamma and beta activity during infantile spasms: Evidence of focality. Epilepsia 58:882-892
Galanopoulou, Aristea S; Moshé, Solomon L (2015) Neonatal and Infantile Epilepsy: Acquired and Genetic Models. Cold Spring Harb Perspect Med 6:a022707
Sánchez Fernández, Iván; Loddenkemper, Tobias; Galanopoulou, Aristea S et al. (2015) Should epileptiform discharges be treated? Epilepsia 56:1492-504
Akman, Ozlem; Moshé, Solomon L; Galanopoulou, Aristea S (2015) Early life status epilepticus and stress have distinct and sex-specific effects on learning, subsequent seizure outcomes, including anticonvulsant response to phenobarbital. CNS Neurosci Ther 21:181-92
Akman, Ozlem; Gulcebi, Medine I; Carcak, Nihan et al. (2015) The role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsy. Epilepsia 56:1793-802
Shinnar, Shlomo; Cnaan, Avital; Hu, Fengming et al. (2015) Long-term outcomes of generalized tonic-clonic seizures in a childhood absence epilepsy trial. Neurology 85:1108-14
Galanopoulou, Aristea S; Moshé, Solomon L (2015) Pathogenesis and new candidate treatments for infantile spasms and early life epileptic encephalopathies: A view from preclinical studies. Neurobiol Dis 79:135-49
Jette, Nathalie; Beghi, Ettore; Hesdorffer, Dale et al. (2015) ICD coding for epilepsy: past, present, and future--a report by the International League Against Epilepsy Task Force on ICD codes in epilepsy. Epilepsia 56:348-55

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