Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation.
Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation.
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DOI：
10.1038/srep08269
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发表时间：
2015-02-05
影响因子：
4.6
通讯作者：
Ohshima T
中科院分区：
文献类型：
--
作者：
Nagai J;Kitamura Y;Owada K;Yamashita N;Takei K;Goshima Y;Ohshima T
轴突生长抑制剂和瘢痕形成是中枢神经系统（CNS）修复的两个主要障碍。没有靶分子调节轴突生长和瘢痕形成已被确定。在这里，我们确定了脊髓损伤（SCI）后轴突生长抑制和瘢痕形成的一个关键因素，是一种常见的神经损伤后抑制信号的介导蛋白4（CRMP 4）。我们发现在受损的脊髓中CRMP 4的抑制和毒性形式增加。值得注意的是，CRMP 4表达在脊髓横断后的炎性细胞以及神经元中明显。Crmp 4 −/−小鼠表现出对SCI的神经保护作用，并减少炎症反应和瘢痕形成。由于CRMP 4缺失而导致的轴突生长的宽松环境在愈合的异常早期阶段恢复了运动活动。这些结果表明，CRMP 4的缺失是一种独特的治疗策略，可以克服SCI后CNS修复的两个障碍。
Axonal outgrowth inhibitors and scar formation are two major obstacles to central nervous system (CNS) repair. No target molecule that regulates both axonal growth and scarring has been identified. Here we identified collapsin response mediator protein 4 (CRMP4), a common mediator of inhibitory signals after neural injury, as a crucial factor that contributes to both axonal growth inhibition and scarring after spinal cord injury (SCI). We found increases in the inhibitory and toxic forms of CRMP4 in injured spinal cord. Notably, CRMP4 expression was evident in inflammatory cells as well as in neurons after spinal cord transection. Crmp4−/− mice displayed neuroprotection against SCI and reductions in inflammatory response and scar formation. This permissive environment for axonal growth due to CRMP4 deletion restored locomotor activity at an unusually early phase of healing. These results suggest that deletion of CRMP4 is a unique therapeutic strategy that overcomes two obstacles to CNS repair after SCI.
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影响因子：
5.3
作者：
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