An experimental model has been developed to study the functional and structural consequences of seizure activity and to elucidate the normal structure and function of the hippocampus. Seizure activity in the hippocampus, which occurs in human temporal lobe epilepsy, the most common form of epilepsy, and in status epilepticus, a condition of continuous seizure discharge, is often associated with a characteristic pattern of hippocampal damage. This pattern of damage can be replicated in normal animals by electrical stimulation of the perforant path, the main afferent pathway to the hippocampus. Animals stimulated and allowed to recover for various periods can be used to determine the changes in function and structure that occur as a result of seizure activity. These animals therefore constitute a model of one aspect of the epileptic state, ie, the effects of repetitive seizures. Experiments have been designed to determine the relationship between selective neuron loss and the observed changes in both the excitability and inhibitory control of remaining neurons. Degeneration methods are used first to determine precisely which neurons are irreversibly damaged by seizure activity. The cells most sensitive will be identified as will the location of their efferent projections. Then, immunocytochemical methods are used to identify the neuroactive substances that may be depleted by the seizure-induced loss of susceptible neurons and interneurons. Since a long-lasting decrease in inhibition has been found to result from stimulation-induced seizures, the cells possibly responsible for this functional deficit will be identified. They will then be removed by means not involving seizures in order to determine which interneurons, when irreversibly damaged, might be responsible for the changes that occur after seizures. The long- term goals of this research are to describe the detrimental effects of seizure activity per se and to determine the mechanism by which seizures cause irreversible damage. This will allow the development of strategies to prevent epileptic brain damage and to retard the possibly progressive nature of the disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS018201-08
Application #
3398251
Study Section
Neurology A Study Section (NEUA)
Project Start
1984-12-01
Project End
1992-11-30
Budget Start
1991-12-01
Budget End
1992-11-30
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Helen Hayes Hospital
Department
Type
DUNS #
157119244
City
Menands
State
NY
Country
United States
Zip Code
12204
Sloviter, Robert S; Bumanglag, Argyle V (2013) Defining ""epileptogenesis"" and identifying ""antiepileptogenic targets"" in animal models of acquired temporal lobe epilepsy is not as simple as it might seem. Neuropharmacology 69:3-15
Norwood, Braxton A; Bumanglag, Argyle V; Osculati, Francesco et al. (2010) Classic hippocampal sclerosis and hippocampal-onset epilepsy produced by a single ""cryptic"" episode of focal hippocampal excitation in awake rats. J Comp Neurol 518:3381-407
Kienzler, Friederike; Norwood, Braxton A; Sloviter, Robert S (2009) Hippocampal injury, atrophy, synaptic reorganization, and epileptogenesis after perforant pathway stimulation-induced status epilepticus in the mouse. J Comp Neurol 515:181-96
Bumanglag, Argyle V; Sloviter, Robert S (2008) Minimal latency to hippocampal epileptogenesis and clinical epilepsy after perforant pathway stimulation-induced status epilepticus in awake rats. J Comp Neurol 510:561-80
Sloviter, Robert S (2008) Hippocampal epileptogenesis in animal models of mesial temporal lobe epilepsy with hippocampal sclerosis: the importance of the ""latent period"" and other concepts. Epilepsia 49 Suppl 9:85-92
Sloviter, Robert S; Zappone, Colin A; Bumanglag, Argyle V et al. (2007) On the relevance of prolonged convulsive status epilepticus in animals to the etiology and neurobiology of human temporal lobe epilepsy. Epilepsia 48 Suppl 8:6-10
Sloviter, Robert S; Zappone, Colin A; Harvey, Brian D et al. (2006) Kainic acid-induced recurrent mossy fiber innervation of dentate gyrus inhibitory interneurons: possible anatomical substrate of granule cell hyper-inhibition in chronically epileptic rats. J Comp Neurol 494:944-60
Schwarzacher, Stephan W; Vuksic, Mario; Haas, Carola A et al. (2006) Neuronal hyperactivity induces astrocytic expression of neurocan in the adult rat hippocampus. Glia 53:704-14
Frotscher, Michael; Jonas, Peter; Sloviter, Robert S (2006) Synapses formed by normal and abnormal hippocampal mossy fibers. Cell Tissue Res 326:361-7
Harvey, Brian D; Sloviter, Robert S (2005) Hippocampal granule cell activity and c-Fos expression during spontaneous seizures in awake, chronically epileptic, pilocarpine-treated rats: implications for hippocampal epileptogenesis. J Comp Neurol 488:442-63

Showing the most recent 10 out of 45 publications