Suppressor of Cytokine Signaling-2 (SOCS2) Regulates the Microglial Response and Improves Functional Outcome after Traumatic Brain Injury in Mice.
Suppressor of Cytokine Signaling-2 (SOCS2) Regulates the Microglial Response and Improves Functional Outcome after Traumatic Brain Injury in Mice.
复制标题
细胞因子信号2（SOCS2）的抑制剂调节小胶质细胞反应并改善小鼠创伤性脑损伤后的功能结果。
DOI：
10.1371/journal.pone.0153418
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Turnley AM
中科院分区：
文献类型：
--
作者：
Basrai HS;Christie KJ;Turbic A;Bye N;Turnley AM
创伤性脑损伤 (TBI) 的常见特征是神经元、轴突和髓磷脂损失、反应性神经胶质增生和神经炎症，通常与功能缺陷相关。内源性修复机制包括从前体细胞产生新神经元，但通常新神经元无法整合并存活超过几周。这部分是由受损大脑中存在的有毒和炎症环境介导的，该环境激活前体细胞增殖和分化，但限制了新生后代的存活。因此，了解调节新生神经元产生和存活的机制以及脑损伤后的神经炎症反应可能会导致改善结果的治疗选择。细胞因子信号传导抑制因子 2 (SOCS2) 促进海马神经发生和成人大脑中新生神经元的存活，并调节外周的抗炎反应，表明它可能是改善 TBI 结局的有用候选者。在这项研究中，将轻度或中度严重 TBI 后 SOCS2 过表达转基因 (SOCS2Tg) 小鼠与野生型同窝小鼠的功能和细胞反应进行了比较。与野生型对照不同，SOCS2Tg 小鼠在阶梯测试中显示出功能改善，在轻度损伤范例中，损伤后 7 天损伤体积较小，并且损伤后 35 天增殖性 CD11b+ 小胶质细胞/巨噬细胞数量增加。中度严重损伤后 7 天，表达抗炎 M2 表型标记物 (CD206+) 的细胞覆盖的面积有所增加，但表达促炎 M1 表型标记物 (CD16/32+) 的细胞没有差异。即使存在神经保护剂促红细胞生成素 (EPO)，也未观察到 SOCS2 过表达对新生神经元的产生或存活有影响。因此，SOCS2可能通过调节神经炎症反应的各个方面、促进更具抗炎性的环境来改善小鼠TBI的结果，尽管这不足以提高新生皮质神经元的存活率。
Traumatic brain injury (TBI) is frequently characterized by neuronal, axonal and myelin loss, reactive gliosis and neuroinflammation, often associated with functional deficits. Endogenous repair mechanisms include production of new neurons from precursor cells, but usually the new neurons fail to integrate and survive more than a few weeks. This is in part mediated by the toxic and inflammatory environment present in the injured brain which activates precursor cells to proliferate and differentiate but limits survival of the newborn progeny. Therefore, an understanding of mechanisms that regulate production and survival of newborn neurons and the neuroinflammatory response after brain injury may lead to therapeutic options to improve outcomes. Suppressor of Cytokine Signaling 2 (SOCS2) promotes hippocampal neurogenesis and survival of newborn neurons in the adult brain and regulates anti-inflammatory responses in the periphery, suggesting it may be a useful candidate to improve outcomes of TBI. In this study the functional and cellular responses of SOCS2 over-expressing transgenic (SOCS2Tg) mice were compared to wildtype littermates following mild or moderately severe TBI. Unlike wildtype controls, SOCS2Tg mice showed functional improvement on a ladder test, with a smaller lesion volume at 7d post injury and increased numbers of proliferative CD11b+ microglia/macrophages at 35d post-injury in the mild injury paradigm. At 7d post-moderately severe injury there was an increase in the area covered by cells expressing an anti-inflammatory M2 phenotype marker (CD206+) but no difference in cells with a pro-inflammatory M1 phenotype marker (CD16/32+). No effect of SOCS2 overexpression was observed in production or survival of newborn neurons, even in the presence of the neuroprotective agent erythropoietin (EPO). Therefore, SOCS2 may improve outcome of TBI in mice by regulating aspects of the neuroinflammatory response, promoting a more anti-inflammatory environment, although this was not sufficient to enhance survival of newborn cortical neurons.