Abstract WP410: Reduced Recovery of Penetrating Arteriole Flow and Increased Capillary Transit Time Heterogeneity After Stroke in Type 2 Diabetic Mice

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Introduction: Capillary transit time heterogeneity (CTTH) is altered during functional activation and in pathological conditions, affecting the extraction efficiency of oxygen from blood. Diabetes deteriorates ischemic brain damage, although the impact of diabetes in microvascular environment remains insufficiently characterized. Cerebral microvascular blood flow is considered to be regulated by pericytes, which are reportedly less in the retina of diabetic patients. However, it still remains unclear whether type 2 diabetes (T2DM) specifically affects hemodynamic adaptation of microvessels during cerebral ischemia. Hypothesis: MTT and CTTH are increased after ischemic stroke and exacerbated by T2DM, which is associated with a greater hemodynamic compromise. Methods: A 4x4 mm 2 cranial window was created on the parietal cortex 2 mm lateral and 1 mm posterior from the bregma three weeks prior to imaging. Experimental stroke was induced by permanent distal middle cerebral artery occlusion (dMCAO) combined with 90 minutes-occlusion of the ipsilateral common carotid artery. Spatial and temporal changes of the total flow and axial velocity of the penetrating arterioles (PA), as well as mean transit time (MTT) and 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, 1hr and 24 hrs after reperfusion in db/+ and db/db mice, a mouse model of obesity and T2DM. Results: Stroke-induced increase in MTT and CTTH was greater in the db/db compared to db/+ mice, leading to increased microvascular resistance and reduced oxygen extraction after stroke in the former. The total blood flow in PA reduced immediately after dMCAO in both strains of mice by nearly 80%, but it remained reduced in the db/db mice after reperfusion in contrast to a sustainable recovery at 50% of prestroke level. Conclusions: T2DM is an additional risk factor for hemodynamic compromise during cerebral ischemia, which may increase the severity of stroke. The mechanisms underlying T2DM exacerbated CTTH and reduced recovery of PA flow are under investigation.