新生鼠缺氧缺血性脑损伤后内源性神经干细胞的增殖及迁移

The proliferation and migration of endogenous neural stem cells in cerebral tissue of newborn rat with hypoxic-ischemic brain damage

目的观察新生鼠缺氧缺血损伤后内源性神经干细胞的增殖及迁移。方法制成新生鼠缺氧缺血脑损伤模型,采用单、双标免疫组织化学方法检测5溴脱氧尿苷(BrdU)和巢蛋白(Nestin)的表达。BrdU标记增殖的新生细胞,Nestin标记神经干细胞。结果正常新生鼠生后保持较短一段时间的增殖活跃,生后3d达高峰,7d后逐渐减弱,生后21d后形成与成年动物相似的发生模式。缺氧缺血损伤后,细胞增殖恢复活跃,BrdU阳性细胞数于伤后4d达高峰,皮层、纹状体、海马可见散在阳性细胞,大多数BrdU阳性细胞集中位于室管膜下区的背外侧角及外侧壁处,伤后7d后逐渐减少,21d更多的BrdU阳性细胞迁移至损伤区;损伤后Nestin阳性细胞数增加,同时一定数量的Nestin阳性细胞由G0期进入增殖周期。结论缺氧缺血脑损伤可刺激新生鼠内源性神经干细胞的增殖及迁移。

Objective To investigate the proliferation and migration of endogenous neural stem cells after hypoxic-ischemic brain injury (HIBD) in newborn rats. Methods The HIBD model was induced in 30 newborn rats by ligation of left common carotid artery followed by 8% O 2 2.5 hours. Bromodeoxyuridine (BrdU, 50 μg/g, tid for 3 days) were intraperitoneally administered to the newborn rats in injured group and control group. Rats were sacrificed at different given time points and brains were then harvested. The dynamic expressions of BrdU and Nestin were visualized by immunocytochemical staining. Results In the normal newborn rats, the BrdU positive cells in the brains reached a maximum at postnatal 3 days, and then decreased gradually. After HIBD, the BrdU positive cells in the brains were significantly increased. The positive cells mainly located at subventricular zone, even though some solitary positive cells could be noted in cortex, striatum and hippocampus. Twenty-one days later, the maximum amount of positive cells were noted in the injured areas. The patterns of staining for Nestin were similar to those for BrdU staining. Conclusion Our results indicate that HIBD stimulates the proliferation and migration of endogenous neural stem cells in the brains of newborn rats.