新生鼠脑缺氧缺血损伤后神经细胞再生增加(英文)

Enhanced neurogenesis in neonatal rats after hypoxic-ischemic brain damage

摘要:

目的：许多研究已证实成年鼠脑缺血后神经细胞再生增加,但新生鼠脑缺氧缺血后神经细胞再生如何尚不太清楚。本文旨在调查新生鼠脑缺氧缺血后神经再生情况。方法：24只7日龄新生鼠分为对照组(n= 8)和缺氧缺血组(n=16),缺氧缺血组于缺氧后24h行MR扫描以证实脑梗塞灶产生。术后或缺氧后第2～6天每日腹腔注射1次BrdU标记新生的细胞,应用免疫荧光法检查缺血缺氧后1周和4周时神经再生情况。结果：缺氧缺血后1周或4周时缺血侧脑室管膜下区(SVZ)明显增宽。缺血侧SVZ的BrdU阳性细胞数在缺氧缺血后1周时显著高于对照组和非缺血侧(P<0.05),缺氧缺血后4周时较1周时下降,但仍显著高于对照组(P<0.05)。缺血侧海马齿状回颗粒细胞层下区(SGZ)的BrdU阳性细胞数在缺氧缺血后1周增高,明显高于对照组(P<0.05), 缺氧缺血后4周时较1周时减少,但仍显著高于对照组(P<0.05)。缺氧缺血后1周或4周时在皮质和纹状体梗塞坏死灶周围可见散在分布的BrdU阳性细胞。结论：新生鼠与成鼠类似,脑缺氧缺血后神经再生增强,提示不成熟脑具有一定自身修复能力。

Abstract:

OBJECTIVE: Many studies have demonstrated that neurogenesis is enhanced after cerebral ischemia in the adult rats. However, little is known about neurogenesis in the brain of neonatal rats after hypoxia-ischemia (HI). This study investigated neurogenesis in neonatal rats 1 and 4 weeks after HI. METHODS: Twenty-four seven-day-old Wistar rats were randomly assigned into Control group (n=8) and Experimental group (n=16). HI was induced by ligating the right common carotid artery combined with hypoxia exposure (8% oxygen in nitrogen) in the Experimental group. In the Control group, the right common carotid artery was isolated but not ligated and there was no exposure to hypoxia. MR imaging was performed 24 hrs after HI to confirm the formation of infarct. Bromodeoxyuridine (BrdU) was injected intraperitonally daily between 2-6 days after operation or HI to label newly generated cells in both groups. Neurogenesis was examined by immunofluorescence assay 1 and 4 weeks after HI. RESULTS: Subventricular zone (SVZ) was obviously enlarged in the ischemic hemisphere but not in the contralateral hemisphere in the Experimental group 1 or 4 weeks after HI. The number of BrdU positive cells in the SVZ of the ischemic hemisphere in the Experimental group increased significantly compared with that in the Control group or that in the contralateral hemisphere 1 week after HI (both P< 0.05). After 4 weeks of HI the number of BrdU positive cells in the ischemic hemisphere decreased compared with that 1 week after HI, but still remained significantly higher than that in the Control group (P<0.05). The number of BrdU positive cells in the subgranular zone (SGZ) of the ischemic hemisphere increased 1 week after HI, being significantly higher than that in the Control group (P<0.05). After 4 weeks of HI the number of BrdU positive cells in the SGZ of the ischemic hemisphere decreased compared with that 1 week after HI, but still was significantly higher than that in the Control group (P<0.05). Some scattered BrdU positive cells were observed in the striatum or cortex of the ischemic hemisphere, particularly in peri-infarct 1 or 4 weeks after HI. CONCLUSIONS: Similar to the brain of adult rats, neurogenesis is enhanced in the brain of neonatal rats following HI. This result suggests that immature brain may have the capacity for self-repair.