限制诱导运动疗法克服了脑卒中大鼠内在的轴突生长抑制信号。

Constraint-induced movement therapy overcomes the intrinsic axonal growth-inhibitory signals in stroke rats.

机构信息

Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning, PR China.

出版信息

Stroke. 2013 Jun;44(6):1698-705. doi: 10.1161/STROKEAHA.111.000361. Epub 2013 Apr 30.

DOI:10.1161/STROKEAHA.111.000361

PMID:23632976

Abstract

BACKGROUND AND PURPOSE

Constraint-induced movement therapy (CIMT) improves functional outcome in patients with stroke possibly through structural plasticity. We hypothesized that CIMT could enhance axonal growth by overcoming the intrinsic growth-inhibitory signals, leading eventually to improved behavioral performance in stroke rats.

METHODS

Focal cerebral ischemia was induced by intracerebral injection of endothelin-1. Adult Wistar rats were divided into a sham-operated group, an ischemic group, and an ischemic group treated with CIMT. CIMT started at postoperative day 7 and continued for 3 weeks. Biotinylated dextran amine was injected into the contralateral sensorimotor cortex at postoperative day 14 to trace crossing axons at the cervical spinal cord. The expressions of Nogo-A, Nogo receptor, RhoA, and Rho-associated kinase in the peri-infarct cortex, and the expressions of biotinylated dextran amine, growth associated protein-43, synaptophysin, vGlut1, and postsynaptic density-95 in the denervated spinal cord were measured by immunohistochemistry and Western blots. Behavioral recovery was analyzed at postoperative days 29 to 32.

RESULTS

Infarct volumes were not different between groups after stroke. CIMT significantly increased the length and the number of midline crossings of contralateral corticospinal axons to the denervated cervical spinal cord. CIMT significantly decreased the expressions of Nogo-A/Nogo receptor and RhoA/Rho-associated kinase in the peri-infarct cortex, and increased the expressions of growth associated protein-43, synaptophysin, vGlut1, and postsynaptic density-95 in the denervated cervical spinal cord. Behavioral performances assessed by the beam-walking test and the water maze test were improved significantly by CIMT.

CONCLUSIONS

CIMT promoted poststroke synaptic plasticity and axonal growth at least partially by overcoming the intrinsic growth-inhibitory signaling, leading to improved behavioral outcome.

摘要

背景与目的

约束诱导运动疗法（CIMT）可通过结构可塑性改善脑卒中患者的功能预后。我们假设 CIMT 可以通过克服内在的生长抑制信号来增强轴突生长，最终改善脑卒中大鼠的行为表现。

方法

通过脑内注射内皮素-1诱导局灶性脑缺血。成年 Wistar 大鼠分为假手术组、缺血组和 CIMT 治疗组。CIMT 于术后第 7 天开始，持续 3 周。术后第 14 天，将生物素化葡聚糖胺注入对侧感觉运动皮层，以追踪颈脊髓中的交叉轴突。免疫组化和 Western blot 检测梗死周围皮质中 Nogo-A、Nogo 受体、RhoA 和 Rho 相关激酶的表达，以及去神经脊髓中的生物素化葡聚糖胺、生长相关蛋白-43、突触素、vGlut1 和突触后密度-95 的表达。术后第 29 至 32 天分析行为恢复情况。

结果

脑卒中后各组梗死体积无差异。CIMT 明显增加了对侧皮质脊髓轴突到去神经颈脊髓的中线交叉的长度和数量。CIMT 明显降低了梗死周围皮质中 Nogo-A/Nogo 受体和 RhoA/Rho 相关激酶的表达，增加了去神经颈脊髓中生长相关蛋白-43、突触素、vGlut1 和突触后密度-95 的表达。CIMT 显著改善了平衡木行走试验和水迷宫试验评估的行为表现。