1814-P: Type 2 Diabetes Increases Stroke Severity through Sustained Hyperperfusion of Cerebral Vasculature following Ischemic Stroke in Rats

Stroke is a leading cause of death and permanent disability. Type 2 diabetes (T2D) increases the incidence of stroke by four-fold and is a strong predictor of worse outcome following stroke with greater disability and mortality than in nondiabetics. While the reasons for increased stroke severity in T2D are unclear, we hypothesized that T2D alters the cerebral vascular response to ischemic stroke leading to reduced vascular reperfusion and hence greater infarct following restoration of blood flow post-stroke. To address this hypothesis, 15-week-old male Sprague Dawley rats were given a high fat diet and treated with osmotic-mini pump infused STZ (110mg/kg over 14 days) to develop a mild T2D phenotype, characterized by obesity and glucose of 8-10mM. Normal chow-fed aged matched rats were used as controls. Four weeks after induction of T2D, we quantified cerebral perfusion in real-time using contrast enhanced ultrasound (CEU) before, during and immediately after middle cerebral artery occlusion, the gold standard model of ischemic stroke. Following this, rats were allowed to recover and a battery of behavioral tests was used to assess stroke severity over 14 days. A final CEU measure was obtained 14 days post-stroke to track vascular changes over time. Cerebral perfusion tended to be increased in T2D rats at baseline but was similarly reduced during middle cerebral artery occlusion. Strikingly, T2D rats had a 3-fold increase in cerebral perfusion immediately post-stroke and this hyperperfusion was sustained 14 days post-stroke. Importantly, although there was no difference in behavior at baseline or immediately following stroke, by day 6, T2D rats developed a greater level of disability compared with control rats that was sustained until day 14.

In conclusion, we demonstrate that T2D alters the cerebral vascular response to ischemic stroke, leading to severe vascular hyperperfusion and that this is associated with a greater level of disability in rats.