Chronic constriction injury of the sciatic nerve in rats causes different activation modes of microglia between the anterior and posterior horns of the spinal cord
Chronic constriction injury of the sciatic nerve in rats causes different activation modes of microglia between the anterior and posterior horns of the spinal cord
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DOI：
10.1016/j.neuint.2020.104672
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发表时间：
2020-03-01
影响因子：
4.2
通讯作者：
Yorozuya, Toshihiro
中科院分区：
文献类型：
--
作者：
Nishihara, Tasuku;Tanaka, Junya;Yorozuya, Toshihiro
坐骨神经的慢性压迫损伤通常被认为是慢性神经性疼痛的原因。关于这种疼痛，已经明确后角（PH）中小胶质细胞的显着激活。然而，在此过程中，前角（AH）中的小胶质细胞也被强烈诱导。因此，在本研究中，我们比较了Wistar大鼠左侧坐骨神经慢性压迫损伤后7天腰脊髓AH和PH中小胶质细胞的差异激活模式。同侧 AH 和 PH 中的小胶质细胞均表现出小胶质细胞标记物 Iba1 和 CD11b 的免疫反应性增加。此外，在细胞质中观察到丰富的CD68(+)吞噬体。 AH 中的小胶质细胞显示出细长的体细胞，紧密包围着运动神经元，而 PH 中的细胞则显示出类似阿米巴的形态，并且附着在髓鞘上而不是神经元上。 AH 中的小胶质细胞强烈表达 NG2 硫酸软骨素蛋白多糖。尽管与 AH 中的神经元紧密附着，但突触蛋白的减少并不明显，这表明激活的小胶质细胞参与了突触剥离。在 PH 中激活的小胶质细胞的吞噬体中观察到髓磷脂碱性蛋白免疫反应性，表明髓磷脂被吞噬细胞清除。 CCI 引起运动缺陷和痛觉过敏，分别通过应用 BBB 运动评定量表和 von Frey 检验进行评估。运动缺陷在术后第一天最明显，此后变得不那么明显。相比之下，痛觉过敏在第 1 天并不严重，但至少在第 7 天变得更严重。总的来说，AH 和 PH 之间的小胶质细胞激活模式不同，这可能与运动和感觉症状过程的差异有关。
Chronic constriction injury of the sciatic nerve is frequently considered as a cause of chronic neuropathic pain. Marked activation of microglia in the posterior horn (PH) has been well established with regard to this pain. However, microglial activation in the anterior horn (AH) is also strongly induced in this process. Therefore, in this study, we compared the differential activation modes of microglia in the AH and PH of the lumbar cord 7 days after chronic constriction injury of the left sciatic nerve in Wistar rats. Microglia in both the ipsilateral AH and PH demonstrated increased immunoreactivity of the microglial markers Iba1 and CD11b. Moreover, abundant CD68(+) phagosomes were observed in the cytoplasm. Microglia in the AH displayed elongated somata with tightly surrounding motoneurons, whereas cells in the PH displayed a rather ameboid morphology and were attached to myelin sheaths rather than to neurons. Microglia in the AH strongly expressed NG2 chondroitin sulfate proteoglycan. Despite the tight attachment to neurons in the AH, a reduction in synaptic proteins was not evident, suggesting engagement of the activated microglia in synaptic stripping. Myelin basic protein immunoreactivity was observed in the phagosomes of activated microglia in the PH, suggesting the phagocytic removal of myelin. CCI caused both motor deficit and hyperalgesia that were evaluated by applying BBB locomotor rating scale and von Frey test, respectively. Motor defict was the most evident at postoperative day1, and that became less significant thereafter. By contrast, hyperalgesia was not severe at day 1 but it became worse at least by day 7. Collectively, the activation modes of microglia were different between the AH and PH, which may be associated with the difference in the course of motor and sensory symptoms.