Capillary Remodeling and Collateral Growth Without Angiogenesis After Unilateral Common Carotid Artery Occlusion in Mice

Abstract

To clarify the mechanisms of blood flow restoration after major artery occlusion, we presented first dynamic changes in cortical vessel morphology observed through a cranial window in mice after unilateral common carotid artery (CCA) occlusion. The density and diameter of capillaries, as well as diameters of pial arteries, were measured by confocal laser-scanning microscopy and fluorescent microscopy, respectively. Possible angiogenesis was evaluated by detecting any outgrowth of endothelial cells from pre-existing vessels or intussusception in Tie2-GFP mice. Immediately after unilateral CCA occlusion, cerebral blood flow (CBF) index, the reciprocal of mean transit time, reduced significantly and returned to the previous level after 14 days. Repeated observation of the cortical vessels did not reveal any angiogenesis, whereas the cortical capillary diameter increased by 74% after 14 days. The anterior cerebral artery (ACA) and collateral vessels connecting ACA and middle cerebral artery also dilated significantly. The capillary dilatation to the size of arteriole in the settings of collateral growth and CBF restoration suggested capillary remodeling. Our results indicate that capillary remodeling, pial artery dilatation and collateral growth without angiogenesis are sufficient mechanisms to restore normal cerebral blood flow after unilateral CCA occlusion.