Injury-Induced Neurogenesis in the Adult Mammalian Brain

Abstract

The persistence of neurogenesis in the adult mammalian forebrain suggests that endogenous precursors may be a potential source for neuronal replacement after injury or neurodegeneration. Limited knowledge exists, however, regarding the normal function of neurogenesis in the adult and its alteration by brain injury. Neural precursors generate neurons throughout life in the mammalian forebrain subventricular zone (SVZ)-olfactory bulb pathway and hippocampal dentate gyrus. Accumulating evidence indicates that various brain insults increase neurogenesis in these persistent germinative zones. Two brain injury models in particular, experimental epilepsy and stroke in the adult rodent, have provided significant insight into the consequences of injury-induced neurogenesis. Studies of dentate gyrus neurogenesis in adult rodent epilepsy models suggest that seizure-induced neurogenesis involves aberrant neuroblast migration and integration that may contribute to persistent hippocampal hyperexcitability. In contrast, adult rat forebrain SVZ neurogenesis induced by stroke may have reparative effects. SVZ neural precursors migrate to regions of focal or global ischemic injury and appear to form appropriate neuronal subtypes to replace damaged neurons. These findings underscore the need for a better understanding of injury-induced neurogenesis in the adult and suggest that the manipulation of endogenous neural precursors is a potential strategy for brain reparative therapies.