Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Brain Res Bull. 2024 Feb;207:110864. doi: 10.1016/j.brainresbull.2023.110864. Epub 2023 Dec 28.
Ischemic stroke induced inflammatory responses contribute significantly to neuronal damage and stroke outcomes. CD200 ligand and its receptor, CD200R, constitute an endogenous inhibitory signaling that is being increasingly recognized in studies of neuroinflammation in various central nervous system disorders. CD200 is a type 1 membrane glycoprotein that is broadly expressed by endothelia and neurons in the brain. In the present study, we have examined the role of endothelial CD200 signaling in acute ischemic stroke. Endothelial CD200 conditional knock out (CKO) mice were generated by breeding CD200 gene floxed mice with Cdh5 mice. The mice were subjected to a 60-min transient middle cerebral artery occlusion (MCAO). Flow cytometry, Immunohistochemical staining, and Western blotting were performed to assess the post-stroke inflammation; stroke outcomes (infarct volume and neurobehavioral deficits) were evaluated at 72 h after MCAO. We found CD200R was near-null expressed on microglia at 24 h after stoke. Endothelial CKO of CD200 had no impact on peripheral immune cell development. Immunohistochemical staining confirmed CD200 was expressed on CD200 floxed but not on CD200 CKO endothelia. CD200 CKO mice exhibited larger infarct size, worse neurological deficit scores (NDS), and more deficits in the adhesive removal when compared with control mice, 72 h after MCAO. Western blot results showed that endothelial CKO of CD200 did not change BBB protein expression. Together it suggests that endothelial CD200 signaling protects brains against ischemic injury through a mechanism not directly related to microglial activation.
缺血性脑卒中引起的炎症反应对神经元损伤和脑卒中结局有重要贡献。CD200 配体及其受体 CD200R 构成了内源性抑制信号，在各种中枢神经系统疾病的神经炎症研究中越来越受到重视。CD200 是一种 I 型膜糖蛋白，在大脑内皮细胞和神经元中广泛表达。在本研究中，我们研究了内皮细胞 CD200 信号在急性缺血性脑卒中中的作用。通过将 CD200 基因 floxed 小鼠与 Cdh5 小鼠杂交，生成内皮细胞 CD200 条件敲除（CKO）小鼠。将小鼠进行 60 分钟短暂性大脑中动脉闭塞（MCAO）。通过流式细胞术、免疫组织化学染色和 Western blot 检测评估卒中后炎症；在 MCAO 后 72 小时评估卒中结局（梗死体积和神经行为缺陷）。我们发现，在卒中后 24 小时，小胶质细胞上 CD200R 几乎呈阴性表达。内皮细胞 CD200 的 CKO 对周围免疫细胞的发育没有影响。免疫组织化学染色证实 CD200 表达在 CD200 floxed 内皮细胞上，但不在 CD200 CKO 内皮细胞上。与对照组小鼠相比，CD200 CKO 小鼠在 MCAO 后 72 小时表现出更大的梗死体积、更严重的神经功能缺损评分（NDS）和更严重的粘连去除缺陷。Western blot 结果表明，内皮细胞 CD200 的 CKO 不改变 BBB 蛋白表达。综上所述，内皮细胞 CD200 信号通过一种与小胶质细胞激活无关的机制保护大脑免受缺血性损伤。
