脑缺血再灌流诱导内源性神经干细胞的增殖、分化  

Cerebral ischemia-reperfusion in rats induces proliferation,differentiation of intrinsic neural stem/progenitor cells

作　　者：高小青[1] 李雷激[2] 陈波[1] 邓莉[1] 杨朝鲜[1] 袁琼兰[3] 

机构地区：[1]泸州医学院神经生物学实验室,四川泸州600644 [2]泸州医学院附属医院耳鼻咽喉头颈外科,四川泸州646000 [3]同济大学医学院解剖与神经生物学教研室,上海200029

出　　处：《中风与神经疾病杂志》2009年第5期541-544,共4页Journal of Apoplexy and Nervous Diseases

摘　　要：目的观察脑缺血再灌注后内源性神经干细胞的分布、增殖和分化。方法阻塞大鼠大脑中动脉2h不同时间的再灌流制成局灶性脑缺血模型,免疫组化单标、双标观察神经干细胞的增殖、分布、分化。结果正常组和假手术组,多数脑室室管膜细胞Brdu免疫反应阳性,脑实质内有零星散在Brdu阳性细胞。再灌流1d,室管膜及室管膜下层的Brdu阳性细胞显著增多;再灌流3～10d,视前区梗死区周边区、缺血纹状体和额顶皮质的Brdu阳性细胞显著增加。再灌流3d,Brdu阳性细胞出现于海马齿状回的颗粒下层,并随再灌流时间延长,阳性细胞数量增多。免疫组化双标显示再灌流3d视前区有很少量的Brdu/GFAP双阳性细胞,随后增多。再灌流10d内,未检查到Brdu/NF双标阳性细胞。结论成年哺乳动物的室管膜、脑实质有少量神经干细胞,脑缺血后室管膜、齿状回颗粒下层出现大量的神经干细胞增殖,这些增殖神经干细胞向缺血区迁移、分化,试图补偿丢失的细胞,重塑受损的神经组织。Objective To investigate the distribution, proliferation, and differentiation of intrinsic neural stem/progenitor cells after focal cerebral ischemia in adult rats. Methods Brains from rats subjected to 2h of transient middle cerebral artery occlusion（MCAO） and reperfusion with different time were processed by labeled immunohistochemistry to observe the proliferation and distribution of the intrinsic neural stem/progenitor using Brdu antibody. The double-labeled immunohistochemical staining was employed to identify the cell type of proliferative cells by antibodies against glial fibrillary a- cidic protein（ GFAP） and neural filament（NF）. Results Brdu immunoreactivity was present in most ependymal cells of ventricle zones（YZ） , and sparsely positive cells in the parenchyma in normal and sham group. At ld of reperfusion and on- ward, Brdu-labeled ceils in VZ and subventricular zone （SVZ）significantly increased, compared to control groups. At 12h of reperfusion and onward, Brdu-positive cells appeared in some choroid plexus cells of bilateral lateral VZ. From 3d to 10d of reperfusion, Brdu-labeled cells significantly increased in boundary of infarct in preoptic area, striatum and deep layer of frontoparietal cortex. Brdu-labeled cells were first detected in subgranular zone （SGZ）of dentate gyms （DG）3d after reperfusion,and increased with time. A very few of double-positive cell expressed with Brdu and GFAP were first detected in boundary of infracted in preoptic area at 3d and onward. No double Brdu and NF positive cell was detected within 10 days of reperfusion. Conclusion A few neural stem cells reside in ependyma and parenchyma in adult mammalian brain, and ischemia induces potential neural stem cells in subependymal, choroids plexus cells as well as cells in SGZ of DG to prolif- erate and migrate toward ischemic areas and try to compensate for lost ceils to restore damaged nervous tissue.

关 键 词：神经干细胞 增殖 分化 脑缺血再灌注 大鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学]