Nerve decompression surgery suppresses TNF-ɑ expression and T cell infiltration in a rat sciatic nerve chronic constriction injury model

神经减压手术抑制大鼠坐骨神经慢性压迫性损伤模型中的 TNF-ɑ 表达和 T 细胞浸润

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作者:Michiaki Mukai, Kentaro Uchida, Gen Inoue, Masashi Satoh, Masayuki Miyagi, Yuji Yokozeki, Naoya Hirosawa, Yusuke Matsuura, Seiji Ohtori, Masashi Takaso

Abstract

Decompression surgery (DS) is a standard treatment for chronic nerve compression injuries; however, the mechanisms underlying its effects remain unclear. Here, we investigated the effects of DS on messenger RNA (mRNA) expression of tumor necrosis factor-α (TNF-α) and T cell recruitment in a rat sciatic nerve (SN) chronic constriction injury (CCI) model. Male Wistar rats were subjected to CCI to establish a model of SN injury (CCI group). DS, in which all ligatures were removed, was performed 3 days after CCI surgery (CCI + dec group). Mechanical sensitivity was assessed using the von Frey test 3, 7, and 14 days after the CCI surgery. Gene expression of Tnfa, Cd3, Cxcl10, and immunolocalization of TNF-α and the pan T cell marker, CD3, was evaluated using quantitative polymerase chain reaction (qPCR) and immunohistochemistry, respectively. In addition, the effects of TNF-α on Cxcl10 expression and CXCL10 protein production were evaluated using qPCR and enzyme-linked immunosorbent assay in SN cell culture. Rats that received DS had significantly higher withdrawal threshold levels than those in the CCI group. In addition, Tnfa, Cd3, and Cxcl10 mRNA expression increased following CCI. DS suppressed this elevated expression, with the CCI + dec group showing significantly reduced expression levels compared to the CCI group. Furthermore, TNF-α induced Cxcl10 expression and CXCL10 protein production in SN cell culture. Therefore, DS reduced TNF-α expression and T cell recruitment in the rat SN CCI model. These observations may partly explain the mechanism underlying the therapeutic effects of DS.

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