Delayed treatment with Rho-kinase inhibitor does not enhance axonal regeneration or functional recovery after spinal cord injury in rats
Delayed treatment with Rho-kinase inhibitor does not enhance axonal regeneration or functional recovery after spinal cord injury in rats
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DOI：
10.1016/j.expneurol.2006.02.123
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发表时间：
2006-08-01
影响因子：
5.3
通讯作者：
Yamashita, Toshihide
中科院分区：
文献类型：
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作者：
Nishio, Yutaka;Koda, Masao;Yamashita, Toshihide
中枢神经系统中的轴突再生被许多不同的生长抑制因子所阻断。其中一些抑制物通过激活RhoA和RhoA的效应器Rho-Kinase作用于神经元。一些研究表明，脊髓损伤后立即抑制Rho-Kinase可促进轴突萌发和功能恢复。在这项研究中，我们询问延迟使用Rho-Kinase抑制剂治疗在促进再生和功能恢复方面是否有效。我们在大鼠胸段脊髓挫伤后4周或立即在损伤部位局部应用Rho-Kinase抑制剂法舒地尔。虽然即刻治疗明显促进了轴突的萌发和后肢功能的恢复，但术后4周开始的治疗对神经纤维的萌发和运动功能的恢复没有影响。我们的发现表明，在中枢神经系统损伤的慢性阶段，RhoA/Rho-Kinase本身可能不能解释轴突生长的不可逆转停滞。(C)2006 Elsevier Inc.保留所有权利。
Axonal regeneration in the central nervous system is blocked by many different growth inhibitory factors. Some of these inhibitors act on neurons by activating RhoA and Rho-kinase, an effector of RhoA. Several studies have shown that Rho-kinase inhibition immediately after spinal cord injury enhances axonal sprouting and functional recovery. In this study, we ask whether delayed treatment with Rho-kinase inhibitor is effective in promoting regeneration and functional recovery. We administered Fasudil, a Rho-kinase inhibitor, locally to the injury site 4 weeks or immediately after contusion of the thoracic spinal cord in rats. Although the immediate treatment significantly stimulated axonal sprouting and recovery of hindlimb function, treatment started 4 weeks after surgery had no effect on fiber sprouting or locomotor recovery. Our findings suggest RhoA/Rho-kinase alone may not account for the irreversible arrest of axon outgrowth in the chronic stage of injury in the central nervous system. (c) 2006 Elsevier Inc. All rights reserved.