Neural Stem Cells in Experimental Mesial Temporal Lobe Epilepsy

Neurogenesis persists in the adult mammalian hippocampal dentate gyrus and is influenced by epileptogenic insults. Studies of rodent mesial temporal lobe epilepsy (mTLE) models indicate that status epilepticus acutely increases dentate granule cell (DGC) neurogenesis, but in chronic stages neurogenesis may decrease. The functional implications of altered neurogenesis in either stage of mTLE are poorly understood. Accumulating evidence suggests, however, that altered neurogenesis contributes to several well-characterized cellular abnormalities seen in human and experimental mTLE. These abnormalities include mossy fiber sprouting, DGC layer dispersion, aberrant migration of DGC progenitors, and the appearance of DGCs in ectopic locations or with hilar basal dendrites. The mechanisms underlying these structural abnormalities are beginning to be characterized, and ongoing work aims to define their role in epileptogenesis or associated cognitive dysfunction. Other research on neural stem or progenitor cells suggest that cell grafts may offer a strategy to repair epileptogenic damage or to deliver anticonvulsant treatments. Thus, both manipulating endogenous neural progenitors and neural stem cell transplantation offer potential therapeutic strategies for mTLE. This chapter describes ongoing investigations of experimental mTLE aimed at elucidating the roles of endogenous neural stem cells in acquired epileptogenesis, as well as the potential use of neural stem cell grafts to treat epilepsy.