Grant: Project Grant

Healthy brain requires that active regions receive more blood than those that are inactive. This is called brain hyperemia and is normally taken care of naturally. Stroke, hypertension, diabetes, Alzheimer's Disease and repeated concussion can all lead to cognitive decline. Impaired brain hyperemia is common to all of these conditions and is a likely common underlying cause of regional brain starvation and associated dementia. Brain hyperemia results from active brain cells communicating messages to small arteries in the brain, signaling them to open and allow more blood to flow. We recently identified a new mechanism responsible for this signaling. Our proposal is to develop this observation to fully understand how brain hyperemia works and how this new mechanism and others fail in hypertension. We will use sophisticated live rodent models to visualize cellular signaling in brain hyperemia. Animals will be awake and allowed to move on a mobile platform while their heads are fixed in place for imaging with a specialized microscope that detects cell signaling processes below the brain surface. Experimental brain hyperemia will be monitored in both normal and hypertensive animals to look for differences. Genetic tools will be used to determine important proteins involved. Discoveries resulting from our proposal will help us understand the reasons why brain hyperemia fails in neurodegenerative disorders. This knowledge will help us to identify new therapeutic approaches that could limit or prevent dementia across a wide range of diseases, including stroke, hypertension, diabetes and Alzheimer's Disease. The impact of this would be improved quality of life for patients with a broad spectrum of diseases affecting cognitive function.