Activated neural stem cells contribute to stroke-induced neurogenesis and neuroblast migration toward the infarct boundary in adult rats
Activated neural stem cells contribute to stroke-induced neurogenesis and neuroblast migration toward the infarct boundary in adult rats
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DOI：
10.1097/00004647-200404000-00009
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发表时间：
2004-04-01
影响因子：
6.3
通讯作者：
Chopp, M
中科院分区：
文献类型：
--
作者：
Zhang, RL;Zhang, ZG;Chopp, M
中风增加神经发生。作者研究了大鼠成年室下区（SVZ）的神经干细胞或祖细胞是否有助于中风诱导的神经发生增加。诱导大鼠中风后，同侧SVZ和纹状体中对双皮质素（未成熟神经元的标记物）免疫反应的细胞数量增加。向同侧皮质注入抗有丝分裂剂（胞嘧啶- β - d -阿拉比氟脲苷，Ara-C），消除了SVZ中98%以上的活跃增殖细胞和同侧纹状体中双皮质素阳性细胞。然而，双皮质素阳性细胞在抗有丝分裂剂耗尽后迅速补充。在体内消耗活跃增殖细胞的数量对体外形成的神经球数量没有影响，但脑卒中大鼠神经球数量显著增加（P < 0.05）。脑卒中大鼠神经球自我更新分化为神经元和神经胶质。此外，SVZ中产生的双皮质素阳性细胞以链状结构向缺血纹状体迁移。这些发现表明，在成年中风脑中，神经干细胞募集的增加有助于中风诱导的神经发生，并且新生成的神经元从SVZ迁移到缺血纹状体。
Stroke increases neurogenesis. The authors investigated whether neural stem cells or progenitor cells in the adult subventricular zone (SVZ) of rats contribute to stroke-induced increase in neurogenesis. After induction of stroke in rats, the numbers of cells immunoreactive to doublecortin, a marker for immature neurons, increased in the ipsilateral SVZ and striatum. Infusion of an antimitotic agent (cytosine-beta-D-arabiofuranoside, Ara-C) onto the ipsilateral cortex eliminated more than 98% of actively proliferating cells in the SVZ and doublecortin-positive cells in the ipsilateral striatum. However, doublecortin-positive cells rapidly replenished after antimitotic agent depletion of actively proliferating, cells. Depleting the numbers of actively proliferating cells in vivo had no effect oil the numbers of neurospheres formed in vitro, yet the numbers of neurospheres derived from stroke rats significantly (P < 0.05) increased. Neurospheres derived from stroke rats self-renewed and differentiated into neurons and glia. In addition, doublecortin-positive cells generated in the SVZ migrated in a chainlike structure toward ischemic striatum. These findings indicate that in the adult stroke brain, increases in recruitment of neural stem cells contribute to stroke-induced neurogenesis, and that newly generated neurons migrate from the SVZ to the ischemic striatum.