Inhibiting effect of minocycline on the regeneration of peripheral nerves
Inhibiting effect of minocycline on the regeneration of peripheral nerves
复制标题
DOI：
10.1002/dneu.20384
复制
发表时间：
2007-09-01
影响因子：
3
通讯作者：
Fansa, Hisham
中科院分区：
文献类型：
--
作者：
Keilhoff, Gerburg;Langnaese, Kristina;Fansa, Hisham
在急性坐骨神经损伤大鼠模型中研究了米诺环素对神经再生的影响，其中损伤是由右侧坐骨神经切除和再植入引起的。使用免疫组织化学和分子生物学方法，以及形态测量和电子显微镜技术。与未损伤和 PBS 处理的损伤神经相比，米诺环素治疗的损伤神经表现出：（i）巨噬细胞募集和活化减少，可能是由于通过减少 MMP2 和 MMP9 诱导来抑制血脑屏障破坏，通过进一步减少 VEGF 诱导来抑制血运重建，以及抑制诱导型 NO 合酶 (iNOS) 诱导； (ii) 吞噬雪旺细胞的活化减少，可能是通过抑制 MOS、MMP2 和 MMP9 表达来实现的； (iii) 减缓华勒变性；随后，(iv) 神经再生减少。巨噬细胞，特别是其清除细胞碎片和形成有利于神经再生的微环境的功能，与神经损伤后的建设性事件密切相关。因此，我们建议在进行进一步的临床试验之前，需要进一步研究优化米诺环素干预治疗神经退行性疾病。 (C) 2007 年 Wiley 期刊公司。
The effect of minocycline on nerve regeneration was studied in a rat model of acute sciatic nerve injury, in which the injury was caused by resection and reimplantation of the right sciatic nerve. Immunohistochemical and molecular biological methods, as well as morphometric and electron microscopic techniques, were used. Compared with uninjured and PBS-treated injured nerves, the minocycline-treated injured nerve showed: (i) a decrease in macrophage recruitment and activation, probably resulting from inhibition of blood-brain-barrier break-down via reduced MMP2 and MMP9 induction, inhibition of revascularization via additional reduction of VEGF induction, and inhibition of inducible NO synthase (iNOS) induction; (ii) reduced activation of phagocytic Schwann cells, probably by inhibition of MOS, MMP2 and MMP9 expression; (iii) a slowed Wallerian degeneration; and subsequently, (iv) a diminished nerve regeneration. Macrophages, especially their function in the removal of cellular debris and formation of a microenvironment beneficial for nerve regeneration, are strongly implicated in constructive events after nerve injuries. Therefore, we suggest that additional research into optimizing minocycline intervention for treatment of neurodegenerative diseases is needed before further clinical trials are performed. (C) 2007 Wiley Periodicals, Inc.