Sex Differences in the Effects of High Fat Diet on Neuroinflammation in a Mouse Model of VCID

Neuroinflammation plays a central role in the progression of vascular contributions to cognitive impairment and dementia (VCID). Unfortunately, anti‐inflammatory therapeutics have proven insufficient so far at ameliorating the progression of VCID. This may be because broadly suppressing inflammation prohibits its beneficial functions. Instead, supporting endogenous inflammation resolving programs may prove more effective. Mid‐life metabolic disease is a major risk factor for VCID, particularly in women. Therefore, we examined neuroinflammation at middle‐age in both males and females with VCID. We modeled metabolic disease via long‐term administration of a high fat (HF) diet, and VCID via unilateral carotid artery occlusion surgery which results in chronic cerebral hypoperfusion. We hypothesized that metabolic disease would lead to more adverse cognitive and neuroinflammatory effects in middle‐aged females compared to males in a mouse model of VCID.