Endogenous glucocorticoids improve myelination via Schwann cells after peripheral nerve injury: An in vivo study using a crush injury model
Endogenous glucocorticoids improve myelination via Schwann cells after peripheral nerve injury: An in vivo study using a crush injury model
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DOI：
10.1002/glia.20977
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发表时间：
2010-06
期刊：
影响因子：
6.2
通讯作者：
Shinsuke Morisaki;M. Nishi;H. Fujiwara;R. Oda;M. Kawata;T. Kubo
中科院分区：
文献类型：
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作者：
Shinsuke Morisaki;M. Nishi;H. Fujiwara;R. Oda;M. Kawata;T. Kubo
糖皮质激素可改善周围神经紊乱的症状，如腕管综合征和周围神经病变。糖皮质激素的作用主要是抗炎，但其对周围神经疾病的作用机制尚不清楚。外周神经雪旺细胞表达糖皮质激素受体（GR），糖皮质激素可提高髓磷脂的体外形成率。因此，糖皮质激素对周围神经疾病的临床改善可能是由于，至少部分是由于髓鞘形成的调节。在这项研究中，进行肾上腺切除术（ADX），然后每天注射低剂量（1mg /kg）或高剂量（10mg /kg）皮质酮（CORT）。然后我们模拟了坐骨神经的挤压损伤。进行假ADX手术，随后进行模拟挤压伤，作为对照。免疫组化结果显示，体内雪旺细胞细胞核表达GR，糖皮质激素影响雪旺细胞的GR免疫反应性。与假手术组相比，ADX与载药组髓鞘碱性蛋白mRNA和蛋白表达明显降低。然而，在低剂量CORT替代组中，表达恢复。形态学分析显示，与低剂量CORT替代组和假手术组相比，ADX与载药组的髓鞘厚度明显降低。这些结果表明，体内周围神经损伤后，内源性糖皮质激素通过GR在雪旺细胞髓鞘形成中起重要作用。©2010 Wiley‐Liss, Inc。
Glucocorticoids improve the symptoms of peripheral nerve disorders, such as carpal tunnel syndrome and peripheral neuropathy. The effects of glucocorticoids are mainly anti‐inflammatory, but the mechanisms of their effects in peripheral nerve disorders remain unclear. Schwann cells of the peripheral nerves express glucocorticoid receptors (GR), and glucocorticoids enhance the rate of myelin formation in vitro. Therefore, it is possible that the clinical improvement of peripheral nerve disorders by glucocorticoids is due, at least in part, to the modulation of myelination. In this study, an adrenalectomy (ADX) was performed, and followed by a daily injection of either low dose (1 mg/kg) or high dose (10 mg/kg) corticosterone (CORT). We then simulated a crush injury of the sciatic nerves. A sham ADX operation, followed by a simulated crush injury, was conducted as a control. Immunohistochemistry showed that the nuclei of in vivo Schwann cells expressed GR and that glucocorticoids impacted the GR immunoreactivity of the Schwann cells. The mRNA and protein expression of myelin basic protein was significantly lower in the animals given ADX with vehicle than in the sham operation group. However, the expression was restored in the low‐dose CORT replacement group. Morphological analyses showed that the ADX with vehicle group had a significantly lower myelin thickness than did the low‐dose CORT replacement group and the sham operation group. These results suggest that endogenous glucocorticoids have an important role in myelination through the GR in Schwann cells after an in vivo peripheral nerve injury. © 2010 Wiley‐Liss, Inc.