Frontline Science: Blood-circulating leukocytes fail to infiltrate the spinal cord parenchyma after spared nerve injury
Frontline Science: Blood-circulating leukocytes fail to infiltrate the spinal cord parenchyma after spared nerve injury
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DOI：
10.1002/jlb.hi1118-458r
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发表时间：
2019-09-01
影响因子：
5.5
通讯作者：
Cunha, Thiago M.
中科院分区：
文献类型：
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作者：
Guimaraesi, Rafaela M.;Davoli-Ferreira, Marcela;Cunha, Thiago M.
周围神经损伤后神经性疼痛的发展涉及脊髓中神经免疫-胶质细胞的相互作用。然而，神经病理性疼痛的发展是否依赖于外周免疫细胞（如单核细胞）在外周神经损伤后向脊髓实质的浸润仍不清楚。在这里，我们使用了不同的技术，如转基因报告小鼠（Cx 3cr 1（GFP/+）和Ccr 2（RFP/+）小鼠），骨髓嵌合小鼠，和共生的组合，以调查这个问题在备用神经损伤（SNI）模型。在本文中，我们提供了强有力的证据，尽管小胶质细胞在SNI后在脊髓背角被激活/增殖，但外周造血细胞（包括单核细胞）不能浸润到脊髓实质中。此外，没有证据表明脊髓内在细胞中有CCR 2表达。然而，在Ccr 2缺陷小鼠中，SNI后脊髓中的小胶质细胞活化/增殖和机械异常性疼痛减少。这些结果表明，血液循环中的白细胞细胞不能渗透到远端周围神经损伤后的脊髓实质。然而，他们表明，CCR 2表达细胞可能间接调节SNI后脊髓中小胶质细胞的活化/增殖。总之，我们的研究支持CCR 2抑制可以探索作为一种干预方法，以减少周围神经损伤后小胶质细胞活化，从而减少神经病理性疼痛的发展。
The development of neuropathic pain after peripheral nerve injury involves neuroimmune-glial interactions in the spinal cord. However, whether the development of neuropathic pain depends on the infiltration of peripheral immune cells, such as monocytes, into the spinal cord parenchyma after peripheral nerve damage remains unclear. Here, we used a combination of different techniques such as transgenic reporter mouse (Cx3cr1(GFP/+) and Ccr2(RFP/+) mice), bone marrow chimeric mice, and parabiosis to investigate this issue in spared nerve injury (SNI) model. Herein, we provided robust evidence that, although microglial cells are activated/proliferate at the dorsal horn of the spinal cord after SNI, peripheral hematopoietic cells (including monocytes) are not able to infiltrate into the spinal cord parenchyma. Furthermore, there was no evidence of CCR2 expression in intrinsic cells of the spinal cord. However, microglial cells activation/proliferation in the spinal cord and mechanical allodynia after SNI were reduced in Ccr2-deficient mice. These results suggest that blood-circulating leukocytes cells are not able to infiltrate the spinal cord parenchyma after distal peripheral nerve injury. Nevertheless, they indicate that CCR2-expressing cells might be indirectly regulating microglia activation/proliferation in the spinal cord after SNI. In conclusion, our study supports that CCR2 inhibition could be explored as an interventional approach to reduce microglia activation and consequently neuropathic pain development after peripheral nerve injury.