Blockade of EphB2 enhances neurogenesis in the subventricular zone and improves neurological function after cerebral cortical infarction in hypertensive rats
Blockade of EphB2 enhances neurogenesis in the subventricular zone and improves neurological function after cerebral cortical infarction in hypertensive rats
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阻断EphB2可增强高血压大鼠脑皮质梗死后室下区的神经发生并改善神经功能
DOI：
10.1016/j.brainres.2008.06.097
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发表时间：
2008-09
期刊：
影响因子：
--
通讯作者：
Pei Z
中科院分区：
文献类型：
--
作者：
He Y;Ling L;Hou Q;Zeng J;Yu J;Xing S;Pei Z
EphB 2/ephrinBs最近已被证明调节神经源性脑室下区（SVZ）中的细胞增殖。然而，EphB 2在脑梗死后成人神经发生中的作用知之甚少。在本研究中，我们研究了EphB 2在SVZ内前体细胞增殖和分化中的作用，以及高血压大鼠永久性大脑中动脉闭塞（MCAO）后神经功能恢复。从MCAO后24 h开始每天2次给予溴脱氧尿苷（BrdU），连续6天。重组EphB 2-Fc或IgG-Fc通过与抗人Fcγ孵育预聚簇，然后在MCAO后24小时心室内施用。分别于术前、术后7、14、21天进行神经功能评定。分别于MCAO后7、14、21天测定脑梗死面积及BrdU、Nestin、DCX、GFAP、NeuN免疫反应。用EphB 2-Fc治疗显著改善MCAO后3周内的神经功能恢复。平行地，EphB 2-Fc显著增加BrdU标记的细胞的数量，并分别导致MCAO后2周同侧SVZ内BrdU+/DCX+和BrdU+/Nestin+细胞的显著增加（所有p < 0.05）。在MCAO后3周内EphB 2-Fc输注后，梗死周围区域和邻近同侧纹状体中的BrdU+/NeuN+细胞显著增加（所有p < 0.05）。我们的数据表明，在24小时给予外源性成簇EphB 2-Fc可以增强内源性神经发生，并伴随改善脑梗死后的神经恢复。
EphB2/ephrinBs has been recently demonstrated to regulate cell proliferation in the neurogenic subventricular zone (SVZ). However, little is known about the role of EphB2 in adult neurogenesis following cerebral infarction. In the present study, we investigated the role of EphB2 in proliferation and differentiation of precursor cells within the SVZ, as well as the neurological function recovery after permanent middle cerebral artery occlusion (MCAO) in hypertensive rats. Bromodeoxyuridine (BrdU) was given twice per day starting from 24h after MCAO for 6-consecutive days. Recombinant EphB2-Fc or IgG-Fc was preclustered by incubation with anti-human Fcγ and then intraventricularly administrated at 24h after MCAO. The neurological function was evaluated before operation and at 7, 14 and 21 days after MCAO respectively. The infarct size and immunoreactivities of BrdU, Nestin, DCX, GFAP and NeuN were measured at 7, 14 and 21 days after MCAO respectively. Treatment with EphB2-Fc markedly improved the neurological function recovery within 3 weeks after MCAO. In parallel, EphB2-Fc significantly increased the number of BrdU-labeled cells and led to marked increases in BrdU+/DCX+and BrdU+/Nestin+cells within the ipsilateral SVZ for 2 weeks after MCAO respectively (all p < 0.05). The BrdU+/NeuN+cells in the peri-infarct area and neighboring ipsilateral striatum were significantly increased following EphB2-Fc infusion within 3 weeks after MCAO (all p < 0.05). Our data suggest that administration of exogenous clustered EphB2-Fc at 24h can enhance the endogenous neurogenesis and concomitantly improve neurological recovery after cerebral infarction.
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影响因子：
--
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
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
影响因子：
8.3
作者：
Zeng, JS;Zhang, YQ;Huang, RX
通讯作者：
Huang, RX
影响因子：
2.9
作者：
MILLER, MW;NOWAKOWSKI, RS
通讯作者：
NOWAKOWSKI, RS
影响因子：
3.5
作者：
Ricard, J;Salinas, J;Liebl, DJ
通讯作者：
Liebl, DJ
影响因子：
11.2
作者：
Raber, J;Fan, Y;Liu, JL
通讯作者：
Liu, JL