Hippocampal neurogenesis and neural stem cells in temporal lobe epilepsy

Virtually all mammals, including humans, exhibit neurogenesis throughout life in the hippocampus, a learning and memory center in the brain. Numerous studies in animal models imply that hippocampal neurogenesis is important for functions such as learning, memory, and mood. Interestingly, hippocampal neurogenesis is very sensitive to physiological and pathological stimuli. Certain pathological stimuli such as seizures alter both the amount and the pattern of neurogenesis, though the overall effect depends on the type of seizures. Acute seizures are classically associated with augmentation of neurogenesis and migration of newly born neurons into ectopic regions such as the hilus and the molecular layer of the dentate gyrus. Additional studies suggest that abnormally migrated newly born neurons play a role in the occurrence of epileptogenic hippocampal circuitry characteristically seen after acute seizures, status epilepticus, or head injury. Recurrent spontaneous seizures such as those typically observed in chronic temporal lobe epilepsy are associated with substantially reduced neurogenesis, which, interestingly, coexists with learning and memory impairments and depression. In this review, we discuss both the extent and the potential implications of abnormal hippocampal neurogenesis induced by acute seizures as well as recurrent spontaneous seizures. We also discuss the consequences of chronic spontaneous seizures on differentiation of neural stem cell progeny in the hippocampus and strategies that are potentially useful for normalizing neurogenesis in chronic temporal lobe epilepsy.