Abstract TP277: Diabetes Amplifies Vascular Injury and Worsens Ischemic Stroke Outcome in Young Female Rats

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Abstract

Women are protected from stroke until they reach menopause in part due to neuroprotection conferred by sex hormones. We and others have shown that that diabetes increases neurovascular injury and worsens stroke outcomes in males. Given the clinical evidence that diabetes increases stroke risk especially in younger individuals and females, we hypothesized that diabetes worsens stroke outcome even in young females. We further postulated that moderate hyperglycemia worsens hemorrhagic transformation (HT) and outcomes independent of changes in infarct size. High fat diet plus low dose streptozotocin model of diabetes was used. Control and diabetic weight-matched male and female rats (10-12 weeks old, n=5-7) were subjected to embolic stroke with a fibrin-rich humanized clot. Neurological deficits (Bederson score, adhesive removal test -ART and grip strength), infarct size, HT index, and edema ratio were assessed 3 days after surgery (Table). As expected in the control group, females rats had smaller infarct size, less edema, and better functional outcomes as compared to male rats. In the diabetic group, however, HT score was greater and this was more profound in females. Diabetes worsened the functional outcome to a much greater extent in females. While there was partial improvement of neurological deficits by Day 3 in control animals, diabetic animals did not improve but worsened. Additional studies will explore the long-term effects and the underlying mechanisms contributing to worse outcome in young and old diabetic females.

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