Postdoc The University of Hong Kong Hong Kong, Hong Kong
Introduction/Rationale: 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.
