INHIBITION OF NKCC1 PROMOTES AXONAL GROWTH AND MOTOR RECOVERY IN ISCHEMIC RATS
INHIBITION OF NKCC1 PROMOTES AXONAL GROWTH AND MOTOR RECOVERY IN ISCHEMIC RATS
复制标题
抑制 NKCC1 可促进缺血大鼠的轴突生长和运动恢复
DOI：
10.1016/j.neuroscience.2017.09.036
复制
发表时间：
2017-12-04
期刊：
影响因子：
3.3
通讯作者：
Zhao, C. S.
中科院分区：
文献类型：
--
作者：
Mu, X. P.;Wang, H. B.;Zhao, C. S.
布美他尼是Na+-K+-Cl-协同转运蛋白1（NKCC 1）的选择性抑制剂。我们研究了布美他尼是否能影响中风大鼠的轴突生长和行为结果。成年雄性Wistar大鼠随机分为4组：假手术组大鼠（用溶媒或布美他尼处理）和缺血组大鼠（用溶媒或布美他尼处理）。内皮素-1诱导局灶性脑缺血。布美他尼给药（i. c. v.）术后第7天开始，持续3周。术后第14天在右侧运动皮质注射生物素化葡聚糖胺（BDA），追踪皮质脊髓束（CST）纤维在失神经支配颈髓内的出芽情况。采用免疫组化和/或Western blot法检测损伤周围皮质Nogo-A、NKCC 1、KCC 2和BDNF的表达，以及失神经脊髓中BDA、PSD-95和vGlut 1的表达。大鼠的行为结果进行了评估的横梁行走和缸测试。脑卒中后，CST纤维出芽进入失神经颈髓的总长度显著增加，布美他尼进一步增加了这种出芽。布美他尼治疗还降低了脑缺血后NKCC 1和Nogo-A的表达，增加了KCC 2和BDNF的表达，增强了失神经颈髓突触可塑性。布美他尼能显著改善缺血大鼠的行为学表现。总之，布美他尼促进卒中后轴突发芽，同时改善行为结果，这可能是通过恢复和维持神经元氯稳态，并通过克服大鼠脑缺血后遇到的轴突生长抑制来创造促进恢复的微环境。(C)2017年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Bumetanide is a selective inhibitor of the Na+-K+-Cl--co-transporter 1(NKCC1). We studied whether bumetanide could affect axonal growth and behavioral outcome In stroke rats. Adult male Wistar rats were randomly assigned to four groups: sham-operated rats treated with vehicle or bumetanide, and ischemic rats treated with vehicle or bumetanide. Endothelin-1 was used to induce focal cerebral ischemia. Bumetanide administration (i.c.v.) started on postoperative day 7 and continued for 3 weeks. Biotinylated dextran amine (BDA) was Injected into the right imotor cortex on postoperative day 14 to trace corticospinal tract (CST) fibers sprouting into the denervated cervical spinal cord. Nogo-A, NKCC1, KCC2 and BDNF in the perilesional cortex and BDA, PSD-95 and vGlut1 in the denervated spinal cord were measured by immunohistochemistry and/or Western blot. Behavioral outcome of rats was assessed by the beam walking and cylinder tests. The total length of CST fibers sprouting into the denervated cervical spinal cord significantly increased after stroke and bumetanide further increased this sprouting. Bumetanide treatment also decreased the expressions of NKCC1 and Nogo-A, increased the expressions of KCC2 and BDNF in the perilesional cortex and enhanced the synaptic plasticity in the denervated cervical spinal cord after cerebral ischemia. The behavioral performance of ischemic rats was significantly improved by bumetanide. In conclusion, bumetanide promoted post-stroke axonal sprouting together accompanied by an improved behavioral outcome possibly through restoring and maintaining neuronal chloride homeostasis and creating a recovery-promoting microenvironment by overcoming the axonal growth inhibition encountered after cerebral ischemia in rats. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.