Grant: Master's Award: Canada Graduate Scholarships

Approximately 7% of Canadians are living with some form of diabetes. When poorly controlled (which is often the case), this disease is associated with cerebrovascular pathology, increased risk of dementia and poor cognitive function. Diabetes related impairments in vascular and cognitive function are likely a consequence of neuroinflammation caused by increased oxidative stress and protein glycation of cells that comprise the blood brain barrier(BBB). Microglia, the resident immune cells of the central nervous system, constantly survey the environment for neuronal and vascular damage and remove cells by phagocytosis. A hallmark of brain pathology is activation of microglia; however the question remains whether microglial cells have detrimental or beneficial functions in neuropathology. Chronic activation of microglia may exacerbate neuronal damage caused by vascular insults through release of cytotoxic molecules. Chronic neuroinflammation has been reported in disorders such as diabetes. Very early changes in microglia activation states have been observed to precede major vascular pathology in the retina of diabetic patients and animal models5. Thus, microglia likely play a key role in the development of vascular impairment in the retina. In the cerebral cortex, diabetes is commonly associated with microvascular pathology such as microhemorrhages6. Even small microhemorrhages in the brain drive an inflammatory cascade, leading to microglia response and invasion of neutrophils and macrophages, which can exacerbate injury. Suppression of microglia-mediated inflammation has been considered an important strategy in therapy, but its effect in the diabetic brain is unknown.