Macrophage Activation in the Dorsal Root Ganglion in Rats Developing Autotomy after Peripheral Nerve Injury.

Macrophage Activation in the Dorsal Root Ganglion in Rats Developing Autotomy after Peripheral Nerve Injury.
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DOI:
10.3390/ijms222312801
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发表时间:
2021-11-26
影响因子:
5.6
通讯作者:
Jia X
Jia X
中科院分区:
生物学2区
文献类型:
--
作者:
Xu X;Zhou X;Du J;Liu X;Qing L;Johnson BN;Jia X

文献摘要

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动物周围神经损伤(PNI)后,自体切断术,即无神经支配肢体的自残,很常见,也是人类神经性疼痛的可靠替代方法。了解自体切开术的发生和治疗仍然具有挑战性。本研究的目的是研究裸鼠和Wistar大鼠自体切开术的发生,并评估巨噬细胞激活和纤维致敏的差异,从而有助于理解自体切开术行为。在坐骨神经修复术后6周和12周对裸鼠和Wistar大鼠进行自切观察和评价。采用免疫荧光法比较两组大鼠巨噬细胞数量及背根神经节(DRG)神经元类型。同时对DRG中的T细胞进行免疫染色。裸大鼠自残频率低于Wistar大鼠。裸鼠的自体切开术症状也相对较轻。免疫荧光研究显示Wistar大鼠DRG中巨噬细胞积聚和活化增加。Wistar大鼠在6周和12周时NF200+神经元的百分比高于裸大鼠,但CGRP+神经元的百分比在两组之间没有差异。此外,巨噬细胞集中在nf200标记的A纤维周围。在PNI后6周和12周,两组患者DRG中均未发现CD4+ T细胞。巨噬细胞在DRG的积累和激活可能是Wistar大鼠自体切开术频率和严重程度增加的原因。我们的研究结果还表明,DRG中的A纤维神经元在自切中起重要作用。
Autotomy, self-mutilation of a denervated limb, is common in animals after peripheral nerve injury (PNI) and is a reliable proxy for neuropathic pain in humans. Understanding the occurrence and treatment of autotomy remains challenging. The objective of this study was to investigate the occurrence of autotomy in nude and Wistar rats and evaluate the differences in macrophage activation and fiber sensitization contributing to the understanding of autotomy behavior. Autotomy in nude and Wistar rats was observed and evaluated 6 and 12 weeks after sciatic nerve repair surgery. The numbers of macrophages and the types of neurons in the dorsal root ganglion (DRG) between the two groups were compared by immunofluorescence studies. Immunostaining of T cells in the DRG was also assessed. Nude rats engaged in autotomy with less frequency than Wistar rats. Autotomy symptoms were also relatively less severe in nude rats. Immunofluorescence studies revealed increased macrophage accumulation and activation in the DRG of Wistar rats. The percentage of NF200+ neurons was higher at 6 and 12 weeks in Wistar rats compared to nude rats, but the percentage of CGRP+ neurons did not differ between two groups. Additionally, macrophages were concentrated around NF200-labeled A fibers. At 6 and 12 weeks following PNI, CD4+ T cells were not found in the DRG of the two groups. The accumulation and activation of macrophages in the DRG may account for the increased frequency and severity of autotomy in Wistar rats. Our results also suggest that A fiber neurons in the DRG play an important role in autotomy.