Grant: Operating Grant

Control of blood flow to the brain relies on appropriate contraction and relaxation of muscle cells within the walls of blood vessels. Inappropriate contraction of these muscle cells is observed in serious disease conditions, such as hypertension, stroke and diabetes. This abnormal behaviour can result in low blood flow to the brain and/or death or disability by causing stroke. The molecular mechanisms that underlie the abnormal contraction of blood vessels in the brain in these conditions are not known. Accumulating evidence indicates that the regulation of the contractile apparatus and cellular skeleton of the muscle cells are altered. These changes cause too much contraction in the vessels leading to increased vessel narrowing and low blood flow. The proposed experiments will investigate this possibility using rat models of hypertension, stroke and diabetes. Small blood vessels of 0.2 mm in width will be removed from the brain of normal and disease rats and studied by pressurizing the inside of the vessels as occurs in the body. The muscle cells contract in response to pressure, but the contraction is too large in the disease models. We will prepare these vessels to detect the changes in contractile apparatus and cytoskeleton proteins associated with the abnormal contraction in hypertension, stroke and diabetes. These experiments will provide novel, important information about how brain blood vessel contraction is regulated in health and disease. The long-term goal is to identify the changes so that we may find ways to restore normal contraction and regulation of brain blood flow.