Perioperative neurocognitive disorder (PND) is the mild cognitive impairment associated with surgery and anesthesia. It is a common surgical complication in the elderly. An important mechanism of PND is the surgically induced neuroinflammation. The interaction between the neuronal surface protein CD200 and its receptor in microglia, CD200R1, is an important regulatory pathway to control neuroinflammation. However, the potential role of the CD200-CD200R1 pathway in the acute period of PND has not been fully investigated. In this study, in a PND mouse model, we first measured the protein expression level of CD200, CD200R1, and the related pro- and anti-inflammatory cytokines in the hippocampus. Then, we investigated cognitive function, neuroinflammation and postsynaptic density protein 95 (PSD-95) expression after the injection of CD200-Fc (agonist), CD200R1-Fc (antagonist) or IgG1-Fc (vehicle) into lateral ventricle in PND models. Compared with the control group, the expression of CD200 was up-regulated at day 1 after surgery in PND models. The injection of the CD200-Fc into the lateral ventricle could mitigate primed neuroinflammation and cognitive decline, increase the expression of PSD-95 at day 1 after surgery in PND models. In conclusion, we have demonstrated that CD200-CD200R1 signaling was involved in the acute inflammatory process of PND, and activating CD200R1 can inhibit neuroinflammation and attenuate PND. Thus, the CD200-CD200R1 axis is a potential novel target for PND prevention and treatment.

围手术期神经认知障碍（PND）是与手术和麻醉相关的轻度认知障碍。是老年人常见的手术并发症。PND的一个重要机制是手术诱导的神经炎症。神经元表面蛋白 CD200 与其在小胶质细胞中的受体 CD200R1 之间的相互作用是控制神经炎症的重要调节途径。然而，CD200-CD200R1 通路在 PND 急性期的潜在作用尚未得到充分研究。在这项研究中，在 PND 小鼠模型中，我们首先测量了海马中 CD200、CD200R1 以及相关的促炎和抗炎细胞因子的蛋白质表达水平。然后，我们研究了注射 CD200-Fc（激动剂）后的认知功能、神经炎症和突触后密度蛋白 95（PSD-95）的表达，CD200R1-Fc（拮抗剂）或 IgG1-Fc（载体）进入 PND 模型中的侧脑室。与对照组相比，PND模型术后第1天CD200表达上调。在 PND 模型中，将 CD200-Fc 注射到侧脑室可以减轻引发的神经炎症和认知能力下降，增加术后第 1 天 PSD-95 的表达。总之，我们已经证明CD200-CD200R1信号参与了PND的急性炎症过程，激活CD200R1可以抑制神经炎症并减轻PND。因此，CD200-CD200R1 轴是 PND 预防和治疗的潜在新靶点。在 PND 模型中，CD200 的表达在术后第 1 天上调。在 PND 模型中，将 CD200-Fc 注射到侧脑室可以减轻引发的神经炎症和认知能力下降，增加术后第 1 天 PSD-95 的表达。总之，我们已经证明CD200-CD200R1信号参与了PND的急性炎症过程，激活CD200R1可以抑制神经炎症并减轻PND。因此，CD200-CD200R1 轴是 PND 预防和治疗的潜在新靶点。在 PND 模型中，CD200 的表达在术后第 1 天上调。在 PND 模型中，将 CD200-Fc 注射到侧脑室可以减轻引发的神经炎症和认知能力下降，增加术后第 1 天 PSD-95 的表达。总之，我们已经证明CD200-CD200R1信号参与了PND的急性炎症过程，激活CD200R1可以抑制神经炎症并减轻PND。因此，CD200-CD200R1 轴是 PND 预防和治疗的潜在新靶点。我们已经证明CD200-CD200R1信号参与PND的急性炎症过程，激活CD200R1可以抑制神经炎症并减轻PND。因此，CD200-CD200R1 轴是 PND 预防和治疗的潜在新靶点。我们已经证明CD200-CD200R1信号参与PND的急性炎症过程，激活CD200R1可以抑制神经炎症并减轻PND。因此，CD200-CD200R1 轴是 PND 预防和治疗的潜在新靶点。