Cerebral collateral arteriogenesis and cerebrovascular reserve in aged and diet-induced obese mice after unilateral common carotid occlusion

Aging and metabolic syndrome, common risk factors for ischemic stroke, are associated with collateral rarefaction. We investigated the effects of aging and diet-induced obesity on cerebral collateral arteriogenesis and the restoration of cerebrovascular reserve following proximal arterial occlusion, using a right common carotid artery occlusion (RCCAO) model. Male and female C57BL/6J mice from three age groups (young: 4-6, aging: 16-20, aged: 24-28 months) and a high-fat diet group underwent either RCCAO or sham surgery. The diameters of the circle of Willis (COW) arteries and pial collaterals were measured 4 weeks after RCCAO. Resting cerebral blood flow (CBF) and CBF reserve during induced hypotension were assessed by laser speckle flowmetry at 3 hours and 4 weeks after RCCAO. In young mice, RCCAO induced a significant increase in the diameters of the COW and pial collaterals, leading to complete recovery of baseline CBF at 4 weeks. In contrast, aging progressively diminished arteriogenesis, resulting in partial (aging) and absent (aged) CBF recovery. Cerebrovascular reserve was diminished with advancing age. Diet-induced obesity had milder effects on arteriogenesis. Our study revealed that cerebral collateral arteriogenesis is a strong determinant of impaired cerebrovascular reserve following proximal arterial occlusion and progressively diminishes with aging.