Proliferating Immature Schwann Cells Contribute to Nerve Regeneration After Ischemic Peripheral Nerve Injury
Proliferating Immature Schwann Cells Contribute to Nerve Regeneration After Ischemic Peripheral Nerve Injury
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DOI：
10.1097/nen.0b013e318257fe7b
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发表时间：
2012-06-01
影响因子：
3.2
通讯作者：
Mizusawa, Hidehiro
中科院分区：
文献类型：
--
作者：
Kobayashi, Masaki;Ishibashi, Satoru;Mizusawa, Hidehiro
成人周围神经机械损伤后，雪旺细胞表现出高度的可塑性；因此，它们与促进神经再生有关。然而，雪旺细胞在缺血性损伤后的行为尚不清楚。为了确定雪旺细胞的可塑性如何有助于缺血性神经病变的恢复，我们使用了一个大鼠模型，该模型通过阻断供应动脉5小时诱导胫骨神经缺血。通过p75神经营养因子受体和增殖细胞核抗原的双重免疫染色评估损伤神经中出现的未成熟雪旺细胞的增殖情况。增殖细胞核抗原/p75神经营养因子受体双阳性细胞数量在缺血后1 ~ 2周显著增加，4周后减少。在此期间，有丝分裂后的雪旺细胞分化为成熟细胞，如溴脱氧尿苷掺入，促进轴突引导和随后的轴突再髓鞘形成。这些结果表明，未成熟雪旺细胞的出现和增殖有助于缺血性损伤后神经再生。操纵这群增殖的未成熟雪旺细胞可能是治疗缺血性周围神经病变的有用策略。
Schwann cells exhibit a high degree of plasticity in adult peripheral nerves after mechanical injury; they have, therefore, been implicated in promoting nerve regeneration. However, Schwann cell behavior after ischemic injury has not yet been elucidated. To determine how Schwann cell plasticity may contribute to recovery from ischemic neuropathy, we used a rat model in which ischemia was induced in the tibial nerve by a 5-hour occlusion of the supplying arteries. Proliferation of immature Schwann cells that emerged in the injured nerve was evaluated by double immunostaining for the p75 neurotrophin receptor and proliferating cell nuclear antigen. The number of proliferating cell nuclear antigen/p75 neurotrophin receptor double-positive cells increased significantly in 1 to 2 weeks after ischemia and subsequently decreased by 4 weeks. During this time, the postmitotic Schwann cells differentiated into mature cells, as demonstrated with bromodeoxyuridine incorporation, which facilitated axon guidance and subsequent axon remyelination. These results suggest the emergence and proliferation of immature Schwann cells that contribute to nerve regeneration after ischemic injury. The manipulation of this population of proliferating immature Schwann cells may be a useful strategy for treating ischemic peripheral neuropathy.