大鼠脑梗死后内源性神经干细胞的增殖及迁移

背景传统观点认为中枢神经组织在发育成熟和损伤后不能再生,但近年来研究证实,人及成年动物神经系统中均存在神经干细胞,只是大部分神经干细胞在体内处于静止状态.神经干细胞对脑梗死损伤的治疗作用,已成为研究的焦点问题.目的观察脑梗死后内源性神经干细胞的反应过程,探讨内源性神经干细胞在中枢神经系统损伤修复中的作用,为脑梗死损伤后机体自我修复提供理论依据.设计以实验动物为研究对象,随机、对照的实验研究.单位北京协和医院神经外科.材料实验于2003-03/10在中国医学科学院中国协和医科大学北京协和医院神经外科实验室完成.选择健康雄性Wistar大鼠82只,体质量250～300 g.方法用线栓法制作大鼠脑梗死模型,将其分成梗死后1,3,7,14,28 d组,每组14只,对照组为假手术组(12只).免疫组织化学方法动态检测大鼠脑内5-溴脱氧尿苷嘧啶(BrdU)、巢蛋白(Nestin)的表达.主要观察指标大鼠脑梗死后BrdU,Nestin阳性细胞数的变化.结果对照组中,海马齿状回及SVZ区存在少量BrdU和Nestin阳性细胞,脑梗死后1 d,海马和SVZ区BrdU阳性细胞较对照组显著增加(P＜0.05);7 d达到高峰(P＜0.05);14 d后开始下降,但仍高于正常水平(P＜0.05);28 d后接近正常.并且,梗死侧BrdU和Nestin阳性细胞数明显多于对侧(P＜0.05),并且通过胼胝体向对侧迁移.结论脑梗死可激活内源性神经干细胞原位增殖及迁移.

Proliferation and migration of endogenous neural stem cells in rats after cerebral infarct

BACKGROUND: Conventional opinions believe tissues of central nervous system(CNS) cannot regenerate after injury when they have been developed and maturated. However, recent researches have validated that neural stem cells exist in human and adult animal nervous system, and most of them are in static status in vivo. The therapeutic effects of neural stem cells in cerebral infarct have been a key point in the researches.OBJECTIVE: To observe the reactive process of endogenous neural stem cells after cerebral infarct to explore the effects of endogenous neural stem cell in CNS traumatic rehabilitation, which provides theoretical gist for the self-restoration after cerebral infarct.DESIGN: A randomized controlled trial by using experimental animals as subjects.SETTING: Department of Neurosurgery of Peking Union Hospital.MATERIALS: The study was conducted in the Laboratory of Neurosurgery Department of Peking Union Hospital from March to October in 2003. Totally 82 healthy male Wistar rats with a body mass between 250 g and 300 g were selected.METHODS: Cerebral infarct model was established in rats by thread-ligation method. Rats were divided into post-infarct 1 day, 3 days, 7 days, 14 days and 28 days groups with 14 rats each. Control group was sham-operation group( n= 12). The expressions of bromodeoxyuridine (BrdU) and Nestin in the brain of the rats were dynamically detected by immunohistochemical method.MAIN OUTCOME MEASURES: The changes of BrdU and Nestin positive cell numbers after cerebral infarct in rats.RESULTS: Only very few BrdU and Nestin positive cells had survived in hippocampal dentate gyrus and subventricular zone(SVZ) area in control group. BrdU positive cell significantly increased compared with control group in hippocampus and SVZ area after 1 day of cerebral infarct( P ＜ 0.05),which reached its peak on the 7th day( P ＜ 0.05), started to reduce after 14 days but still in the level significantly higher than normal( P ＜ 0.05), and closed to normal level after 28 days. And moreover, BrdU and Nestin positive cells were significantly more in infarct side than the opposite side ( P＜ 0.05), which migrated towards the opposite side through callus.CONCLUSION: Cerebral infarct can activate the proliferation in situ and migration of endogenous neural stem cell.