抗LINGO-1抗体可促进小鼠脊髓损伤后运动纤维再生及抑制感觉纤维萎缩

目的:观察抗LINGO-1抗体对小鼠脊髓损伤后下行运动与上行感觉纤维的保护作用?方法:采用LISA脊髓损伤造模仪制作小鼠第9胸髓背侧切割伤模型(深度1.1 mm),术后腹腔注射抗LINGO-1抗体,运用免疫组化与免疫荧光观察在脊髓损伤后,生物素化葡聚糖胺(BDA)标记的下行皮质脊髓束(CST)轴突和霍乱毒素B亚单位(CTB)标记的上行感觉纤维的变化?结果:抗LINGO-1抗体注射组动物,可见少量BDA阳性纤维长入或越过损伤部位,且在尾侧白质内前行,最远可达损伤部位尾侧端1.5 mm;同时,在切口尾侧缘可见较对照组更多的CTB阳性纤维,但未见CTB阳性纤维长入或越过损伤切口?接受IgG注射的对照组动物,未发现任何BDA或CTB阳性纤维长入或越过损伤部位?结论:系统注射抗LINGO-1抗体可促进小鼠脊髓损伤后CST轴突再生,同时能抑制CTB标记的上行感觉纤维萎缩?提示抗LINGO-1抗体可作为一种新的药物用于脊髓损伤后促进轴突再生的治疗学研究?

Anti-LINGO-1 antibody promotes motor axonal regeneration and inhibits sensory axonal dying back after spinal cord injury in mice

Objective:To observe the protective effect of anti-LINGO-1 antibody on the motor and sensory axons after mice spinal cord injury (SCI). Methods:Anti-LINGO-1 antibody was administrated by intraperitoneal injection to the mice after a precise 1.1 mm depth dorsal laceration on the 9th thoracic spinal segment was generated by LISA (Louisville injury systems apparatus). Immunohistochemistry or immunofluorescence was used to detect the changes of biotin dextran amine(BDA) labeled descending axons and cholera toxin B subunit(CTB) labeled ascending axons. Results:In anti-LINGO-1 antibody treated mice,a few BDA positive fibers grew into or beyond the lesion gap,and then,extended to the caudal white matter. The longest one reached the site of 1.5 mm caudal to the lesion epicenter. At the same time,more CTB positive sensory fibers were found at the edge of lesion gap than the control group,but no CTB positive fibers extended into or beyond the lesion gap. In IgG treated control mice,neither BDA nor CTB positive fibers extended into or beyond the lesion gap. Conclusion:Systemic injection of the anti-LINGO-1 antibody promotes CST axonal regeneration and limits the dying back of CTB labeled sensory axons. The results indicate that severed CST axons have more robust response to anti-LINGO-1 antibody treatment than CTB labeled sensory axons and suggest that anti-LINGO-1 antibody may serve as a new potential drug for the therapeutic study of SCI.