Parent Jack M
Department of Neurology, University of Michigan Medical Center, Ann Arbor 48109-0585, USA.
Neuroscientist. 2003 Aug;9(4):261-72. doi: 10.1177/1073858403252680.
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.
成年哺乳动物前脑神经发生的持续性表明，内源性前体细胞可能是损伤或神经退行性变后神经元替代的潜在来源。然而，关于成年期神经发生的正常功能及其因脑损伤而发生的改变，人们了解有限。神经前体细胞在哺乳动物前脑的脑室下区（SVZ）-嗅球通路和海马齿状回中终生产生神经元。越来越多的证据表明，各种脑损伤会增加这些持续生发区的神经发生。特别是成年啮齿动物的实验性癫痫和中风这两种脑损伤模型，为损伤诱导的神经发生的后果提供了重要见解。对成年啮齿动物癫痫模型中齿状回神经发生的研究表明，癫痫发作诱导的神经发生涉及异常的神经母细胞迁移和整合，这可能导致海马持续的兴奋性过高。相比之下，中风诱导的成年大鼠前脑SVZ神经发生可能具有修复作用。SVZ神经前体细胞迁移到局灶性或全脑缺血损伤区域，似乎形成了合适的神经元亚型来替代受损神经元。这些发现强调了更好地理解成年期损伤诱导的神经发生的必要性，并表明对内源性神经前体细胞的操控是脑修复治疗的一种潜在策略。
