Mitigation of cerebrovascular dysfunction in dietary obesity mice via suppression neuroinflammation involving microgliosis and IL-18 2267797

Abstract

Abstract Introduction Obesity is commonly associated with cerebrovascular dysfunction, but the mechanisms linking excess adiposity to impaired cerebral vascular homeostasis are not fully understood. We tested the hypothesis that brainstem neuroinflammation–specifically microglial activation and IL-18 signaling–contributes to obesity-related cerebrovascular pathology. Methods Using diet-induced obese (DIO) mice and pharmacological approaches to deplete microglia, we assessed structural and functional changes in the basilar artery. Outcomes included vessel wall thickness, collagen deposition, endothelial nitric oxide synthase (eNOS) phosphorylation (Ser1177), and endothelium-dependent relaxation measured by wire myography. To probe causality, lean mice received intracerebroventricular (i.c.v.) injections of interleukin-18 (IL-18). Results Pharmacological depletion of microglia in DIO mice reduced basilar artery wall thickness and collagen accumulation and increased eNOS Ser1177 phosphorylation, consistent with improved endothelial function. Endothelium-dependent relaxation to acetylcholine was markedly improved after microglial depletion. Conversely, i.c.v. administration of IL-18 in lean mice impaired cerebrovascular function. Conclusion These findings indicate that neuroinflammation–mediated by microglia and IL-18–plays a critical role in obesity-associated cerebrovascular dysfunction. Targeting central inflammatory pathways may therefore represent a therapeutic strategy to preserve cerebrovascular health in obesity. Funding Source n/a Topic Categories Neuroimmunology (NEUR)