Grant: Project Grant

A growing number of Canadians have some form of diabetes which costs the Canadian healthcare system 15.6 billion dollars a year. Although diabetes related disease is well appreciated in the heart, kidney and eye, the brain appears to be particularly sensitive given that diabetics are at significantly greater risk for developing cognitive impairment and suffer more severe disability after stroke. Unfortunately no cure exists as insulin therapy cannot completely prevent these problems. Making matters worse, current stroke therapies such as clot busting drugs are not recommended for some diabetics. One common explanation for the diverse array of brain disturbances is that diabetes perturbs brain circulation in the smallest blood vessels (micro-circulation). Here, our working hypothesis is that blood flow in the microcirculatory networks of the diabetic brain are prone to stalling. These microcirculatory traffic jams can accumulate over time, which in tandem with capillary pruning (a common outcome of stalling), lead to progressive deterioration of vascular, neuronal and cognitive function. Since diabetes is a major risk factor for stroke and poor outcome, we suspect that diabetes worsens capillary stalling after stroke, thereby limiting the return of blood flow in vulnerable, but salvageable brain regions. The goal of our research will be to determine how diabetes affects brain micro-circulation. Since we have preliminary data showing there are problems, we will then explore ways to improve brain microcirculation by targeting a specific protein (called IL-10) that modulates inflammation. And finally, by altering IL-10 signaling after stroke, we believe we can better protect brain tissue from stroke damage and improve recovery in an experimental model of diabetes. Ultimately, this project will shed new light on the effects of diabetes on brain circulation and function, which will stimulate new treatment options for those Canadians suffering from diabetes.