The main objective of the Epilepsy Research Center (ERC) at the Medical College of Virginia is to establish an integrated and focused research program to improve health care for individuals with epilepsy and to investigate clinical and basic biological mechanisms regulating neuronal excitability and the pathogenesis of seizure disorders. The ERC has developed a consortium of five Jacob Javits Scholars and 28 experienced scientists from diverse disciplines to develop a collaborative program to study the clinical and experimental aspects of epilepsy. A major effort of this integrated research program is directed at studying the pathophysiology of status epilepticus. A unique and rigorously validated status epilepticus data base has been established in the Greater Richmond Metropolitan Area and serves as sa valuable resource for studying mortality, outcome predictors, and serves as a valuable resource for studying mortality, outcome predictors and clinical parameters of this major neurological conditions. Both animal and human studies will investigate the role of microvascular changes and superoxide formation in the pathogenesis of prolonged convulsions. Studies will also probe the role of calcium and a specific anticonvulsant binding protein in the regulation of neuronal excitability and modulation of sustained neuronal discharge. Genetic studies will investigate the genetic basis of some forms of seizures by utilizing one of the largest twin registries in the world. The research projects in the Epilepsy Research Center will test specific hypotheses developed to investigate basic mechanisms and clinical aspects of epilepsy. The component projects will investigate: 1) demographics and epidemiology of status epilepticus; 2) mortality of status epilepticus; 3) microvascular changes and superoxide formation in the pathogenesis of prolonged convulsions; 4) the role of a specific anticonvulsant binding protein in regulating neuronal excitability; 5) calcium modulation of neuronal excitability and seizure discharge; and 6) genetic basis of seizures in twins. The ERC has a clear focus of integrated research projects to understand the clinical and fundamental basis of altered neuronal excitability and seizure discharge and ultimately to develop strategies to improve the diagnosis and treatment of epilepsy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS025630-10
Application #
2714468
Study Section
Neurological Disorders Program Project Review A Committee (NSPA)
Program Officer
Jacobs, Margaret
Project Start
1989-01-01
Project End
1999-12-31
Budget Start
1998-06-01
Budget End
1999-12-31
Support Year
10
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Neurology
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
Deshpande, Laxmikant S; Sombati, Sompong; Blair, Robert E et al. (2007) Cannabinoid CB1 receptor antagonists cause status epilepticus-like activity in the hippocampal neuronal culture model of acquired epilepsy. Neurosci Lett 411:11-6
Deshpande, Laxmikant S; Blair, Robert E; Nagarkatti, Nisha et al. (2007) Development of pharmacoresistance to benzodiazepines but not cannabinoids in the hippocampal neuronal culture model of status epilepticus. Exp Neurol 204:705-13
Falenski, K W; Blair, R E; Sim-Selley, L J et al. (2007) Status epilepticus causes a long-lasting redistribution of hippocampal cannabinoid type 1 receptor expression and function in the rat pilocarpine model of acquired epilepsy. Neuroscience 146:1232-44
Deshpande, Laxmikant S; Blair, Robert E; Ziobro, Julie M et al. (2007) Endocannabinoids block status epilepticus in cultured hippocampal neurons. Eur J Pharmacol 558:52-9
Carter, Dawn S; Haider, S Naqeeb; Blair, Robert E et al. (2006) Altered calcium/calmodulin kinase II activity changes calcium homeostasis that underlies epileptiform activity in hippocampal neurons in culture. J Pharmacol Exp Ther 319:1021-31
Blair, Robert E; Deshpande, Laxmikant S; Sombati, Sompong et al. (2006) Activation of the cannabinoid type-1 receptor mediates the anticonvulsant properties of cannabinoids in the hippocampal neuronal culture models of acquired epilepsy and status epilepticus. J Pharmacol Exp Ther 317:1072-8
DeLorenzo, Robert J; Sun, David A; Deshpande, Laxmikant S (2006) Erratum to ""Cellular mechanisms underlying acquired epilepsy: the calcium hypothesis of the induction and maintenance of epilepsy."" [Pharmacol. Ther. 105(3) (2005) 229-266] Pharmacol Ther 111:288-325
DeLorenzo, Robert J (2006) Epidemiology and clinical presentation of status epilepticus. Adv Neurol 97:199-215
Delorenzo, Robert J; Sun, David A; Deshpande, Laxmikant S (2005) Cellular mechanisms underlying acquired epilepsy: the calcium hypothesis of the induction and maintainance of epilepsy. Pharmacol Ther 105:229-66
Singleton, Michael W; Holbert 2nd, William H; Ryan, Matthew L et al. (2005) Age dependence of pilocarpine-induced status epilepticus and inhibition of CaM kinase II activity in the rat. Brain Res Dev Brain Res 156:67-77

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