Department of Neurology, Wannan Medical College, Yijishan Hospital, Wuhu, China.
Department of Neurology, Zhu Madian Central Hospital, Zhumadian, China.
Brain Behav. 2020 Dec;10(12):e01882. doi: 10.1002/brb3.1882. Epub 2020 Oct 17.
To study how the CD200-CD200R1 signaling pathway modulates poststroke inflammation and advances our knowledge of immune responses to ischemia insults in stroke.
Focal middle cerebral artery occlusion (MCAO) was induced in mice for 90 min, and mice were sacrificed at 1, 3, and 7 days of reperfusion. CD200, CD200R1, iNOS, and Arg-1 expression in ischemic brains was assessed by Western blotting (WB), and immunohistochemical (IHC) staining was performed to examine the expression of CD200 on neurons and CD200R1 on infiltrating lymphocytes. The severity of neurobehavioral deficits was evaluated by neurological deficit scores (NDS) and infarction volume estimated by TTC staining. To study the relationship between CD200/CD200R1 expression and the diversity of the neuroinflammatory response in stroke, CD200Fc (CD200R1 agonist) was subcutaneously injected at onset, at 1 day and 2 days after MCAO operation, and the brains were collected for detection at 3 days after MCAO/R (reperfusion).
CD200 expression on neurons increased at 1 day and then decreased at 3 days after MCAO/R, and the expression of CD200R1 on lymphocytes showed an opposite temporal pattern as tested by IHC. The WB results showed that CD200/CD200R1 variance exhibited a similar pattern of IHC results, and the level of iNOS peaked at 1 day and then decreased gradually, but Arg-1 increased with time after MCAO/R in ischemic brains. After CD200Fc injection, CD200R1 expression significantly increased, and CD200Fc promoted Arg-1 but inhibited iNOS expression. The infarct volume and NDS of the group treated with CD200Fc were significantly smaller than those of the IgG2a-treated group.
The CD200-CD200R1 signaling pathway regulates neuroinflammation after stroke. Stimulation of CD200R1 by CD200Fc promotes the anti-inflammatory response and alleviates ischemic injury.
研究 CD200-CD200R1 信号通路如何调节卒中后的炎症反应，增进我们对卒中后缺血损伤免疫反应的认识。
利用大脑中动脉闭塞（MCAO）模型诱导小鼠 90 分钟脑缺血，再灌注 1、3、7 天后处死小鼠。通过 Western blot（WB）检测缺血脑组织中 CD200、CD200R1、诱导型一氧化氮合酶（iNOS）和精氨酸酶-1（Arg-1）的表达，免疫组织化学（IHC）染色检测神经元上的 CD200 和浸润淋巴细胞上的 CD200R1 表达。通过神经功能缺损评分（NDS）和 TTC 染色估计梗死体积评估神经行为缺损的严重程度。为了研究 CD200/CD200R1 表达与卒中后神经炎症反应多样性之间的关系，在 MCAO 术后即刻、第 1 天和第 2 天皮下注射 CD200Fc（CD200R1 激动剂），MCAO/R（再灌注）后 3 天收集大脑进行检测。
MCAO/R 后 1 天神经元上的 CD200 表达增加，然后在第 3 天减少，通过 IHC 检测到淋巴细胞上的 CD200R1 表达呈现相反的时间模式。WB 结果显示 CD200/CD200R1 变化呈现出与 IHC 结果相似的模式，iNOS 水平在第 1 天达到峰值，然后逐渐下降，但 Arg-1 在 MCAO/R 后随时间增加。注射 CD200Fc 后，CD200R1 表达显著增加，CD200Fc 促进 Arg-1 但抑制 iNOS 表达。CD200Fc 治疗组的梗死体积和 NDS 明显小于 IgG2a 治疗组。
CD200-CD200R1 信号通路调节卒中后的神经炎症。CD200Fc 刺激 CD200R1 促进抗炎反应，减轻缺血性损伤。
