[EphB2-Fc promotes activation of endogenous neural stem cells after cerebral cortex infarction: experimental with hypertensive rats].

[EphB2-Fc promotes activation of endogenous neural stem cells after cerebral cortex infarction: experimental with hypertensive rats].
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DOI:
10.3760/j:issn:0376-2491.2005.34.006
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发表时间:
2005-09
影响因子:
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通讯作者:
Yang-dong He;Jin-sheng Zeng;Jian Yu;M. He;Chun-mei Cui;Zhan Zhao;Li Xiong;Hua Hong;Wen-li Sheng;Yan-nan Fang;Ru-xun Huang
Yang-dong He;Jin-sheng Zeng;Jian Yu;M. He;Chun-mei Cui;Zhan Zhao;Li Xiong;Hua Hong;Wen-li Sheng;Yan-nan Fang;Ru-xun Huang
中科院分区:
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文献类型:
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作者:
Yang-dong He;Jin-sheng Zeng;Jian Yu;M. He;Chun-mei Cui;Zhan Zhao;Li Xiong;Hua Hong;Wen-li Sheng;Yan-nan Fang;Ru-xun Huang

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目的探讨脑室注射EphB2-Fc对脑梗塞后固有神经干细胞活化的影响。方法96只SD大鼠采用双肾双夹法建立卒中易发肾血管性高血压模型。96只易卒中肾血管性高血压大鼠中72只建立大脑中动脉闭塞(MCAO)模型,其余24只为假手术组。然后将72只大鼠随机分为3组:脑梗死组在MCAO后不作任何处理,MCAO+EphB2-Fc组在右侧大脑中动脉远端结扎后4d侧脑室立体定向注射EphB2-Fc,剂量为20mlx 200微克/ml,MCAO+Ig-Fc组在右侧大脑中动脉远端结扎后4d,在侧脑室立体定向注射Ig G-Fc,剂量为20mlx200微克/毫升。分别于MCAO后1、4周末处死每组大鼠12只,取脑进行原位杂交、免疫组织化学和Western blotting分析,检测EphB2蛋白和mRNA、巢蛋白和多唾液酸-神经细胞黏附分子(PSA-NCAM)的表达。结果右侧大脑中动脉远端结扎1周后,脑梗死组同侧皮质和室下区EphB2蛋白和mRNA表达水平均低于假手术组(P<0.05),脑梗死组与MCAO+Ig G-Fc组比较差异无统计学意义(P>0.05);脑梗死组同侧SVZ内Nestin和PSA-NCAM表达水平均高于假手术组(均P<0.05),各组同侧SVZ内Nestin和PSA-NCAM表达水平均降低,各组间Nestin表达差异无统计学意义,但脑梗死组同侧SVZ内PSA-NCAM表达仍高于假手术组。结论EphB2信号的破坏促进了内源性神经干细胞在大脑皮质梗塞后SVZ的增殖和迁移。
OBJECTIVE To explore the effects of intraventricular injection of EphB2-Fc on activation of inherent neural stem cells after cerebral cortex infarction. METHODS Stroke-prone renovascular hypertension model was established in 96 SD rats by two-kidney, two-clip method. Middle cerebral artery occlusion (MCAO) model was established in 72 of these 96 stroke-prone renovascular hypertensive rats and the other 24 rats were used as sham operation group. Then the 72 rats were randomly divided into 3 equal groups: cerebral infarction group without any treatment after the MCAO, MCAO + EphB2-Fc group undergoing stereotaxical infusion of EphB2-Fc at the dose of 20 microl x 200 microg/ml into the lateral ventricle 4 days after the distal ligation of right middle cerebral artery, and MCAO + IgG-Fc group undergoing stereotaxical infusion of IgG-Fc at the dose of 20 microl x 200 microg/ml into the lateral ventricle 4 days after the distal ligation of right middle cerebral artery. By the ends of the first and fourth weeks after the MCAO procedure 12 rats from each group were killed and their brains were taken out to undergo in situ hybridization, immunohistochemistry and Western blotting analysis in order to determine the expression of EphB2 protein and mRNA, nestin and polysialic acid-neural cell adhesion molecule (PSA-NCAM). RESULTS One week after the distal ligation of right middle cerebral artery, the EphB2 protein and mRNA expression levels in the ipsilateral cortex and subventricular zone (SVZ) of the cerebral infraction group were both lower than those of the sham operation group (P 0.05), and there were no differences in such levels between the cerebral infarction group and MCAO + IgG-Fc group (both P > 0.05); the nestin and PSA-NCAM expression levels in the ipsilateral SVZ of the cerebral infraction group were both higher than those of the sham operation group (both P 0.05), the nestin and PSA-NCAM expression levels in the ipsilateral SVZ decreased in all groups, there were no significant differences in the expression of nestin among all groups, but the PSA-NCAM expression in the ipsilateral SVZ of the cerebral infraction group was still higher than that of the sham operation group. CONCLUSION Disruption of EphB2 signal promotes the proliferation and migration of endogenous neural stem cells in the SVZ after cerebral cortex infarction.