CXCR4 antagonist AMD3100 reverses the neurogenesis and behavioral recovery promoted by forced limb-use in stroke rats
CXCR4 antagonist AMD3100 reverses the neurogenesis and behavioral recovery promoted by forced limb-use in stroke rats
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CXCR4 拮抗剂 AMD3100 逆转中风大鼠强迫肢体使用促进的神经发生和行为恢复
DOI：
10.3233/rnn-150515
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发表时间：
2015
影响因子：
2.8
通讯作者：
Chuansheng Zhao
中科院分区：
文献类型：
--
作者：
Shanshan Zhao;Huiling Qu;Yi Zhao;Ting Xiao;Mei Zhao;Yong Li;Jukka Jolkkonen;Yunpeng Cao;Chuansheng Zhao
目的：强迫肢体活动能促进神经发生和行为恢复，提高间质水平。细胞衍生因子-1 （SDF-1）在脑卒中大鼠中的作用。我们研究了SDF-1/CXCR4通路是否参与了这种增强的。方法：采用CXCR4拮抗剂AMD3100阻断缺血大鼠SDF-1/CXCR4通路。大脑。内皮素-1诱导缺血。缺血1周后，将未损伤的大鼠前肢固定3周，观察dcx阳性细胞在脑室下区（SVZ）的增殖、迁移和存活，以及树突复杂性。分析齿状回（DG） dcx阳性细胞及梗死纹状体炎症反应的变化。通过免疫组织化学。结果：强迫肢体活动增强新生神经元的增殖、迁移、树突复杂性和存活。此外，强迫肢体活动抑制了中风后的炎症反应，改善了运动和认知功能。AMD3100显著消除了强迫肢体使用引起的神经发生和行为恢复的增强。结论：SDF-1/CXCR4通路似乎参与了神经发生和行为恢复诱导的增强。中风后被迫使用肢体。
Purpose: Forced limb-use can enhance neurogenesis and behavioral recovery as well as increasing the level of stromal.cell-derived factor-1 (SDF-1) in stroke rats. We examined whether the SDF-1/CXCR4 pathway is involved in the enhanced.neurogenesis and promoted behavioral recovery induced by forced limb-use in the chronic phase of stroke..Methods: The CXCR4 antagonist, AMD3100, was used to block the SDF-1/CXCR4 pathway in the ischemic rats. Brain.ischemia was induced by endothelin-1. One week after ischemia, the unimpaired forelimb of rats was immobilized for 3 weeks..The proliferation, migration, and survival of DCX-positive cells in the subventricular zone (SVZ), and the dendritic complexity.of DCX-positive cells in the dentate gyrus (DG), as well as the inflammatory response in the infarcted striatum were analyzed.by immunohistochemistry. Functional recovery was assessed in beam-walking and water maze tests..Results: Forced limb-use enhanced the proliferation, migration, dendritic complexity and the survival of newborn neurons..Furthermore, forced limb-use suppressed the inflammatory response and improved both motor and cognitive functions after.stroke. AMD3100 significantly abrogated the enhanced neurogenesis and behavioral recovery induced by forced limb-use.without influencing the inflammatory response..Conclusions: SDF-1/CXCR4 pathway seems to be involved in the enhancement of neurogenesis and behavioral recovery induced.by post-stroke forced limb-use.