Depletion of microglia mitigates cerebrovascular dysfunction in diet-induced obesity mice.

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.