Distribution and polarization of microglia and macrophages at injured sites and the lumbar enlargement after spinal cord injury
Distribution and polarization of microglia and macrophages at injured sites and the lumbar enlargement after spinal cord injury
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DOI：
10.1016/j.neulet.2020.135152
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发表时间：
2020-10-15
影响因子：
2.5
通讯作者：
Matsumine, Akihiko
中科院分区：
文献类型：
--
作者：
Nakajima, Hideaki;Honjoh, Kazuya;Matsumine, Akihiko
脊髓损伤（SCI）导致运动功能丧失和慢性神经性疼痛（NeP）。造血巨噬细胞和活化的小胶质细胞是对脊髓损伤反应的关键单核细胞系细胞类型，它们都有m1和m2表型。为了了解这些细胞在脊髓损伤后神经元再生和慢性NeP中的作用，我们在损伤部位和作为偏远区域的腰椎肿大处检测了脊髓损伤后活化的小胶质细胞和浸润的巨噬细胞的分布和表型差异。嵌合小鼠用于分化活化的小胶质细胞和造血巨噬细胞。在脊髓损伤后第14天，疼痛超敏反应最严重的时候，激活的小胶质细胞和浸润性巨噬细胞的患病率增加，损伤部位主要是m1型血源性巨噬细胞，腰椎肿大部位主要是m2型活化的小胶质细胞。tnf - α（一种m1诱导的细胞因子）的峰值表达出现在脊髓损伤后第4天，但直到第14天腰椎增大时才出现。IL-4（一种m2诱导的细胞因子）的表达在脊髓损伤后4天达到峰值。这些结果表明，激活的小胶质细胞和巨噬细胞（包括每种细胞的两种表型）在脊髓损伤后的神经元再生和慢性NeP和腰椎增大中发挥了不同的作用。损伤部位直到脊髓损伤后亚急性期M1大于M2表型的流行可能是脊髓损伤后缺乏功能恢复和慢性NeP的部分原因。来自损伤部位的炎症细胞因子激活腰椎肿大的m2型小胶质细胞可能在慢性低水平疼痛中起重要作用。这些发现有助于建立一个治疗靶点，以预防脊髓损伤时间依赖性反应中的运动恶化和NeP。
Spinal cord injury (SCI) causes loss of locomotor function and chronic neuropathic pain (NeP). Hematogenous macrophages and activated microglia are key monocytic lineage cell types in the response to SCI, and each has M1and M2-phenotypes. To understand the roles of these cells in neuronal regeneration and chronic NeP after SCI, differences in distribution and phenotypes of activated microglia and infiltrated macrophages after SCI were examined at the injured site and the lumbar enlargement, as a remote region. Chimeric mice were used for differentiating activated microglia from hematogenous macrophages. The prevalences of activated microglia and infiltrating macrophages increased at day 14 after SCI, at the time of most severe pain hypersensitivity, with mainly M1-type hematogenous macrophages at the injured site and M2-type activated microglia at the lumbar enlargement. Peak expression of TNF-alpha, an M1-induced cytokine, occurred on day 4 post-SCI at the injured site, but not until day 14 at the lumbar enlargement. Expression of IL-4, a M2-induced cytokine, peaked at 4 days after SCI at both sites. These results suggest different roles of activated microglia and hematogenous macro-phages, including both phenotypes of each cell, in neuronal regeneration and chronic NeP after SCI at the injured site and lumbar enlargement. The prevalence of the M1 over the M2 phenotype at the injured site until the subacute phase after SCI may be partially responsible for the lack of functional recovery and chronic NeP after SCI. Activation of M2-type microglia at the lumbar enlargement in response to inflammatory cytokines from the injured site might be important in chronic below-level pain. These findings are useful for establishment of a therapeutic target for prevention of motor deterioration and NeP in the time-dependent response to SCI.