目的:探讨脑源性神经生长因子是否能促进脑梗死后小鼠内源性神经干细胞的活跃,能否刺激其分化成神经元。方法:实验于2004-07/2005-02在墨尔本大学完成。选取10周龄纯种C57BL/6J小鼠24只,分为盐水对照组、脑源性神经生长因子治疗组,每组雌雄各6只。①两组均采用结扎左侧大脑中动脉远心端法建立脑梗死模型,同时采用Matsushita描述的方法监测大脑中动脉供血区的血流量,血流量降低至少75%为有效。②脑源性神经生长因子治疗组于梗死后24h给予脑起源神经营养因子治疗,用药方式采用ALZET锇药物泵缓慢释放。将500μg/kg脑起源神经营养因子溶解于生理盐水中,加入到ALZET泵中,可在28d内持续缓慢释放药物。盐水对照组于梗死后24h给予等量生理盐水。③造模前后对两组小鼠运动功能进行Rotarod测试,记录小鼠在Rotarod上的停留时间。采用双重免疫荧光组化及共焦计数系统检测方法,对两组小鼠内源性神经干细胞的数量、密度及其分化方向进行评估。结果:①运动功能测试结果:与梗死前比较,两组小鼠在梗死后第1周均表现出明显的运动功能下降。但梗死后第2,3,4周,脑起源神经营养因子治疗组小鼠在Rotarod上的停留时间延长,运动功能的恢复明显优于盐水对照组,差异有显著性意义(P<0.01)。②组织切片双重免疫荧光染色结果:两组小鼠脑内均出现免疫荧光阳性表达的内源性神经干细胞,主要分布在病灶周围,在损伤侧的对侧也出现表达。脑起源神经营养因子治疗组的表达数量明显高于盐水对照组。③内源性神经干细胞的激活情况:梗死4周后,两组小鼠脑内都出现内源性神经干细胞的再表达,脑起源神经营养因子治疗组内源性神经干细胞数较盐水对照组明显增加,约4.2倍。同时脑起源神经营养因子治疗组分化为神经元的比例明显高于盐水对照组(36%,15%),分化为星形胶质细胞的比例低于盐水对照组(54%,77%),分化为少突胶质细胞的比例二者基本相似(10%,8%)。结论:脑起源神经营养因子可能是基于内源性神经干细胞治疗脑卒中的一种有效的方法.通过调控内源性神经干细胞的增殖分化来治疗神经系统疾病在未来将是一种新的干细胞治疗方法. Objective: To investigate whether BDNF can promote the activity of endogenous neural stem cells in mice after cerebral infarction, and whether it can stimulate the differentiation into neurons. Methods: The experiment was completed at Melbourne University from July 2004 to February 2005. 24 purebred C57BL / 6J mice of 10 weeks old were selected and divided into saline control group and brain-derived nerve growth factor treatment group, 6 in each group. (1) The cerebral infarction model was established by ligation of the left middle cerebral artery by the telecentric approach, and the blood flow of the middle cerebral artery was monitored by the Matsushita method. The blood flow decreased by at least 75% was effective. ② Brain-derived neurotrophic factor treatment group was given neurotrophic factor of brain origin 24h after infarction, and the drug was slowly released by ALZET osmium drug pump. 500μg / kg brain-derived neurotrophic factor was dissolved in saline and added to the ALZET pump to release sustained and sustained release of the drug within 28 days. Saline control group at 24 h after infarction given an equal amount of saline. ③ Before and after modeling, the motor function of two groups of mice was tested by Rotarod, and the retention time of mice on Rotarod was recorded. Double immunofluorescence staining and confocal counting system were used to evaluate the number, density and differentiation of endogenous neural stem cells in both groups. Results: ① Motor function test results: Compared with the pre-infarction, both groups showed obvious decrease of motor function in the first week after infarction. However, on the 2nd, 3rd and 4th weeks after infarction, the mice in the brain-derived neurotrophic factor therapy group had longer residence time on Rotarod and better recovery of motor function than saline control group (P <0.01). ② The results of double immunofluorescence staining of tissue sections: The endogenous neural stem cells with positive immunofluorescence appeared in the brain of both groups, mainly distributed around the lesion and also expressed on the opposite side of the lesioned side. The number of brain-derived neurotrophic factor-treated groups was significantly higher than that of the saline control group. ③ Activation of endogenous neural stem cells: After 4 weeks of infarction, re-expression of endogenous neural stem cells appeared in the brains of both groups, and the number of endogenous neural stem cells in brain-derived neurotrophic factor group was significantly higher than that in saline control group Increase about 4.2 times. At the same time, the proportion of neurotrophic factor-treated neurons was significantly higher in NSCLC group than that in saline control group (36%, 15%). The percentage of differentiated astrocytes was lower than saline control group (54%, 77% The rates of differentiation into oligodendrocytes were similar (10%, 8%). Conclusion: Brain derived neurotrophic factor may be an effective method based on endogenous neural stem cells for the treatment of stroke. The treatment of nervous system diseases by regulating the proliferation and differentiation of endogenous neural stem cells will be a new stem cell therapy in the future method.