Abstract
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.