Abstract 29: Post-stroke Neovascularization and Functional Outcomes Differ in Type 2 Diabetes Depending on the Severity of Ischemia Reperfusion Injury and Sex Potential Link to Hemorrhagic Transformation

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It is a clinically well-established fact that patients with diabetes have very poor stroke outcomes. Yet, the underlying mechanisms are largely unknown. Previously we have shown that male diabetic animals show greater hemorrhagic transformation (HT), profound loss of cerebral vasculature in the recovery period and poor outcomes after ischemic stroke induced by a 90-min or embolic middle cerebral artery occlusion (MCAO). Given that young females have a 3.5-fold higher risk of stroke with the onset of diabetes and women account for the majority of stroke mortality, the current study postulated that diabetes causes greater vascular injury/repair and worsens sensorimotor and cognitive recovery after stroke even in young females. After 8 weeks of type 2 diabetes induced by a combination of high fat diet and low dose streptozotocin (30mg/kg;IP), Wistar rats were subjected to 60-min MCAO and followed for 3 or 14 days for evaluation of neurovascular injury (infarct size, HT, edema) and repair (vascularization patterns and functional outcomes), respectively. Vascular indices measured included branch density, tortuosity, vascular volume and surface area in cortex and striatum using confocal imaging of FITC-filled vasculature. Males had comparable infarct size and edema regardless of disease while diabetic females had greater infarction/edema compared to control. In contrast to our previous studies, there was no difference in HT or vascularization patterns between control and diabetic animals. All groups recovered from functional deficits to the same degree. These results 1) provide evidence that diabetes negates neuroprotection typically seen in female animals, 2) strongly suggest that HT impacts recovery responses and 3) post-stroke vascularization pattern is influenced by the degree of acute vascular injury and correlates with functional recovery in both sexes. Treatment of bleeding that occurs as a result of HT may provide a novel therapeutic strategy in diabetes.

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