Seizure-induced neurogenesis: are more new neurons good for an adult brain?
The idea that neural stem cells may play a role in the pathophysiology or potential treatment of specific epilepsy syndromes is relatively new. This notion relates directly to advances in the field of stem cell biology over the past decade, which have confirmed prior theories that both neural stem cells and neurogenesis, the birth of new neurons, persist in specific regions of the adult mammalian brain. The physiological role of persistent neurogenesis is not known, although recent work implicates this process in specific learning and memory tasks. Knowledge of the normal neurogenic pathways in the mature brain has led to recent studies of neurogenesis in rodent models of acute seizures or epileptogenesis. Most of these studies have examined neurogenesis in the adult rodent dentate gyrus, and current evidence indicates that single brief or prolonged seizures, as well as repeated kindled seizures, increase dentate granule cell (DGC) neurogenesis. The models studied to date include pilocarpine and kainic acid models of temporal lobe epilepsy, limbic kindling, and intermittent perforant path stimulation. Recent work also suggests that pilocarpine-induced status epilepticus increases rostral forebrain subventricular zone (SVZ) neurogenesis and caudal SVZ gliogenesis. Several lines of evidence implicate newly generated neurons in structural and functional network abnormalities in the epileptic hippocampal formation of adult rodents. These abnormalities include aberrant mossy fiber reorganization, persistence of immature DGC structure (e.g. basal dendrites), and the abnormal migration of newborn neurons to ectopic sites in the dentate gyrus. Taken together, these findings suggest a pro-epileptogenic role of seizure- or injury-induced neurogenesis in the epileptic hippocampal formation. However, the induction of forebrain SVZ neurogenesis and directed migration to injury after seizures and other brain insults underscores the potential therapeutic use of neural stem cells as a source for neuronal replacement after injury.