Abstract

Introduction: In the pathophysiology of ischemic stroke, Leptomeningeal collateral circulation plays a key role on the severity of infarction. Balb/C mice have impaired leptomeningeal collateral due to variants of Rabep2 on chromosome 7 ( Candq1 ), causing sever stroke compared to C57BL/6 mice with rich collateral anastomosis. However, it still remains unclear whether and how poor collateral circulation specifically affects hemodynamic adaptation of microvessels during cerebral ischemia. Method: Male C57BL/6 and Balb/C mice were subjected to distal middle cerebral artery occlusion (dMCAO) combined with 90 minutes-occlusion of the ipsilateral common carotid artery. A 4x4 mm 2 cranial window was created on the parietal cortex 2 mm lateral and 1 mm posterior from the bregma 3 weeks prior to imaging. Spatial and temporal changes of the total flow and axial velocity of the penetrating arterioles (PA), as well as mean transit time (MTT) and capillary transit time heterogeneity (CTTH) in the capillaries bordering the distal MCA and ACA branches were determined by optical coherent tomography-based microangiography and capillary velocimetry at baseline, during dMCAO, 1 hour, 1 day and 7 days after reperfusion in each strain. Results: Stroke-induced increase in CTTH in the region of middle cerebral artery was significantly greater in Balb/C compared to C57BL/6 mice, leading to significantly increased microvascular resistance and reduced oxygen extraction during MCAO and 1 hour after reperfusion in the former (P<0.05). The total blood flow in PA reduced immediately after dMCAO in both strains of mice but it remained reduced in Balb/C mice after reperfusion in contrast to a sustainable recovery at 50% of prestroke level 7 days after stroke. Conclusion: Poor collateral anastomosis and impaired flow of penetrating arterioles is an additional risk factor for hemodynamic compromise during cerebral ischemia caused by reduced oxygen extraction, which may increase the severity of stroke.

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