Nishio Yutaka, Koda Masao, Kitajo Keiko, Seto Minoru, Hata Katsuhiko, Taniguchi Junko, Moriya Hideshige, Fujitani Masashi, Kubo Takekazu, Yamashita Toshihide
Department of Neurobiology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba 260-8670, Japan.
Exp Neurol. 2006 Aug;200(2):392-7. doi: 10.1016/j.expneurol.2006.02.123. Epub 2006 Apr 19.
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 that 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.
中枢神经系统中的轴突再生受到许多不同生长抑制因子的阻碍。其中一些抑制剂通过激活RhoA和RhoA的效应器Rho激酶作用于神经元。多项研究表明，脊髓损伤后立即抑制Rho激酶可增强轴突发芽和功能恢复。在本研究中，我们探究延迟使用Rho激酶抑制剂治疗是否能有效促进再生和功能恢复。我们将Rho激酶抑制剂法舒地尔局部应用于大鼠胸段脊髓挫伤后4周或立即应用于损伤部位。尽管立即治疗显著刺激了轴突发芽和后肢功能恢复，但术后4周开始的治疗对纤维发芽或运动恢复没有影响。我们的研究结果表明，仅RhoA/Rho激酶可能无法解释中枢神经系统损伤慢性期轴突生长的不可逆停滞。
