Obesity is frequently associated with cerebrovascular dysfunction, however, the underlying mechanism remains less well understood. In this study, by using pharmacological approaches, we show that neuroinflammation involving microglia plays an important role in obesity-related cerebrovascular dysfunction. PLX3397 treatment, which leads to depletion of microglia, reduced the wall thickness and collagen deposition in the basilar artery of diet-induced obesity (DIO) mice. Besides, the phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177 was enhanced, suggesting improved endothelial function of the basilar artery. The wire myography data show that acetylcholine-elicited relaxation of basilar artery isolated from DIO mice was improved after the treatment with PLX3397. Moreover, our data demonstrate that brain administration of IL-18 impaired cerebrovascular function in mice with normal body weight. Together, these data suggest that neuroinflammation involving microglia is important in obesity-related vascular dysfunction in the brain.

中文翻译：

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小胶质细胞的消耗减轻了饮食诱导的肥胖小鼠的脑血管功能障碍

肥胖常常与脑血管功能障碍有关，然而，其潜在机制仍不太清楚。在这项研究中，通过使用药理学方法，我们表明涉及小胶质细胞的神经炎症在肥胖相关的脑血管功能障碍中起着重要作用。PLX3397 治疗导致小胶质细胞耗竭，减少了饮食诱导肥胖 (DIO) 小鼠基底动脉的壁厚和胶原沉积。此外，内皮一氧化氮合酶 (eNOS) 在 Ser1177 处的磷酸化增强，表明基底动脉的内皮功能得到改善。线肌造影数据显示，在用 PLX3397 治疗后，从 DIO 小鼠分离的基底动脉的乙酰胆碱引起的舒张得到改善。而且，我们的数据表明，大脑给予 IL-18 会损害体重正常小鼠的脑血管功能。总之，这些数据表明涉及小胶质细胞的神经炎症在大脑中与肥胖相关的血管功能障碍中很重要。