ASTROGLIOSIS AND EPILEPTOGENESIS

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Although glial scarring has long been associated with focal epilepsy, studies to date have failed to establish a pathophysiologic linkage. There is increasing evidence however that central nervous system astrocytes play an essential role in regulating extracellular ion homeostasis and extracellular space (ECS) size in response to neuronal activity. Preliminary results have shown that altering different glial mechanisms that regulate the extracellular environment can either result in an increase of decrease of neuronal synchronization. In normal hippocampal slices, blocking potassium uptake into glia results in epileptiform activity. In contrast, preventing ECS shrinkage antagonizes epileptiform activity in both in vitro and acute animal models of epilepsy. We propose to study astrocytic regulation of the extracellular environment in the kainate rat model of chronic temporal lobe epilepsy and in human specimens from temporal lobed epilepsy resections. We will test the hypothesis that there is altered regulation of potassium and/or ECS size by the astrocyte syncytium in gliotic hippocampus from kainate treated rats and human surgical specimens from temporal lobe epilepsy resections.