کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3056609 | 1186571 | 2008 | 12 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Minocycline protects Schwann cells from ischemia-like injury and promotes axonal outgrowth in bioartificial nerve grafts lacking Wallerian degeneration Minocycline protects Schwann cells from ischemia-like injury and promotes axonal outgrowth in bioartificial nerve grafts lacking Wallerian degeneration](/preview/png/3056609.png)
Minocycline, a broad-spectrum antimicrobial tetracycline, acts neuroprotectively in ischemia. Recently, however, minocycline has been revealed to have ambiguous effects on nerve regeneration. Thus its effects in a rat sciatic nerve transplantation model and on cultivated Schwann cells stressed by oxygen glucose deprivation (OGD) were studied. The negative effect of minocycline on Wallerian degeneration, the essential initial phase of degeneration/regeneration after nerve injury, that was recently demonstrated, was excluded by using predegenerated nerve and Schwann cell-enriched muscle grafts, both free of Wallerian degeneration. They were compared with common nerve grafts. The principle findings were that in vitro minocycline provided protective effects against OGD-induced death of Schwann cells by preventing permeability of the mitochondrial membrane. It suppressed the OGD-mediated induction of HIF-1α and BAX, and stabilized/induced BCL-2. Cytochrome c release and cleavage of procaspase-3 were diminished; release and translocation of AIF and cytotoxic cleavage of actin into fractin were stopped. In common nerve grafts, minocycline, besides its direct anti-ischemic effect, hampered revascularization by down-regulation of MMP9 and VEGF prolonging ischemia and impeding macrophage recruitment. In bioartificial nerve grafts that were free of Wallerian degeneration and revealed lower immunogenicity, minocycline aided the regeneration process. Here, the direct anti-ischemic effect of minocycline on Schwann cells, which are mandatory for successful peripheral nerve regeneration, dominated the systemic anti-angiogenic/pro-ischemic effects. In common nerve grafts, however, where Wallerian degeneration is a prerequisite, the anti-angiogenic and macrophage-depressing effect is an obstacle for regeneration.
Journal: Experimental Neurology - Volume 212, Issue 1, July 2008, Pages 189–200