Nogo-66 receptor antagonist peptide (NEP1-40) administration promotes functional recovery and axonal growth after lateral funiculus injury in the adult rat
Nogo-66 receptor antagonist peptide (NEP1-40) administration promotes functional recovery and axonal growth after lateral funiculus injury in the adult rat
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DOI：
10.1177/1545968307308550
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发表时间：
2008-05-01
影响因子：
4.2
通讯作者：
Murray, M.
中科院分区：
文献类型：
--
作者：
Cao, Y.;Shumsky, J. S.;Murray, M.
客观的。髓磷脂蛋白 Nogo 通过与其轴突上的受体 (NgR) 结合来抑制轴突再生。鞘内递送 NgR 拮抗剂 (NEP1-40) 可促进受损皮质脊髓轴突的生长和背侧半切后运动功能的恢复。作者使用类似的设计来检查中断红核脊髓束 (RST) 的病变后的恢复和修复。方法。大鼠在 C4 处接受侧索切开术，并将 NEP1-40 或载体递送至颈髓，持续 4 周。结果测量包括运动和感觉测试以及免疫组织化学。结果。步态分析显示，与手术对照组相比，NEP1-40 治疗组有所恢复，前肢使用测试也显示出有益的效果。在 NEP1-40 组中，病灶头侧外侧索的同侧以及灰质和白质的对侧，标记的 RST 轴突密度增加。因此，红核脊髓轴突表现出减少的枯死和/或生长至病变部位。在 NEP1-40 组中，这伴随着邻近和进入病变/基质位点的 5HT 和降钙素基因相关肽轴突的密度更大。结论。 RST 损伤后的 NgR 阻断与轴突生长和/或切断的 RST 轴突枯死减少相关，直至但不进入或超出病变/基质部位，以及邻近和进入病变/基质部位的血清素能和背根轴突的生长。 NgR 封锁也支持部分功能恢复。作者的结果表明，切断的红核脊髓轴突对 NEP1-40 治疗有反应，但不如皮质脊髓、中缝脊髓或背根轴突强烈。
Objective. The myelin protein Nogo inhibits axon regeneration by binding to its receptor (NgR) on axons. Intrathecal delivery of an NgR antagonist (NEP1-40) promotes growth of injured corticospinal axons and recovery of motor function following a dorsal hemisection. The authors used a similar design to examine recovery and repair after a lesion that interrupts the rubrospinal tract (RST). Methods. Rats received a lateral funiculotomy at C4 and NEP1-40 or vehicle was delivered to the cervical spinal cord for 4 weeks. Outcome measures included motor and sensory tests and immunohistochemistry. Results. Gait analysis showed recovery in the NEP1-40-treated group compared to operated controls, and a test of forelimb usage also showed a beneficial effect. The density of labeled RST axons increased ipsilaterally in the NEP1-40 group in the lateral funiculus rostral to the lesion and contralaterally in both gray and white matter. Thus, rubrospinal axons exhibited diminished dieback and/or growth up to the lesion site. This was accompanied by greater density of 5HT and calcitonin gene-related peptide axons adjacent to and into the lesion/matrix site in the NEP1-40 group. Conclusions. NgR blockade after RST injury is associated with axonal growth and/or diminished dieback of severed RST axons up to but not into or beyond the lesion/matrix site, and growth of serotonergic and dorsal root axons adjacent to and into the lesion/matrix site. NgR blockade also supported partial recovery of function. The authors' results indicate that severed rubrospinal axons respond to NEP1-40 treatment but less robustly than corticospinal, raphe-spinal, or dorsal root axons.