Nishio Takeshi, Fujiwara Hiroshi, Kanno Isaku
Department of Integrative Brain Science, Kyoto University Graduate School of Medicine, Yoshida-Konoe, Sakyo, Kyoto 606-8501, Japan.
Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Sciences, Takara-Machi 13-1, Kanazawa 920-8641, Japan.
Neurosci Res. 2018 Jun;131:19-29. doi: 10.1016/j.neures.2017.10.011. Epub 2017 Nov 10.
In general, axonal regeneration is very limited after transection of adult rat spinal cord. We previously demonstrated that regenerative axons reached the lesion site within 6h of sharp transection with a thin scalpel. However, they failed to grow across the lesion site, where injured axon fragments (axon-glial complex, AGC) were accumulated. Considering a possible role of these axon fragments as physicochemical barriers, we examined the effects of prompt elimination of the barriers on axonal growth beyond the lesion site. In this study, we made additional oblique section immediately after the primary transection and surgically eliminated the AGC (debridement). Under this treatment, regenerative axons successfully traversed the lesion site within 4h of surgery. To exclude axonal sparing, we further inserted a pored sheet into the debrided lesion and observed the presence of fascicles of unmyelinated axons traversing the sheet through the pores by electron microscopy, indicating bona fide regeneration. These results suggest that the sequential trial of reduction and early elimination of the physicochemical barriers is one of the effective approaches to induce spontaneous and rapid regeneration beyond the lesion site.
一般来说,成年大鼠脊髓横断后轴突再生非常有限。我们之前证明,用薄手术刀锐性横断后,再生轴突在6小时内到达损伤部位。然而,它们未能穿过损伤部位,损伤的轴突碎片(轴突-胶质复合体,AGC)在该部位聚集。考虑到这些轴突碎片可能作为物理化学屏障发挥作用,我们研究了迅速清除这些屏障对损伤部位以外轴突生长的影响。在本研究中,我们在初次横断后立即进行额外的斜切,并通过手术清除AGC(清创)。在这种治疗下,再生轴突在手术4小时内成功穿过损伤部位。为了排除轴突保留,我们进一步将有孔薄片插入清创后的损伤部位,并通过电子显微镜观察到无髓轴突束通过孔隙穿过薄片,表明是真正的再生。这些结果表明,依次尝试减少和早期清除物理化学屏障是诱导损伤部位以外自发快速再生的有效方法之一。