Grant: Fellowship: Bisby (Prize)

The brain is intrinsically capable of controlling its own cerebral blood flow (CBF) for the appropriate delivery of nutrients to the cells. This process is compromised after stroke, in vascular dementia and in other brain pathologies. It is imperative to discover how the brain regulates CBF under normal circumstances before we can attempt effective treatments for people suffering from abnormalities in CBF. The most convincing model from the scientific literature important for normal CBF control, relies on astrocytes (a specific type of brain cell) to sense the neurotransmitter glutamate and then translate this signal in a calcium-dependent manner into vasoconstriction or vasodilation, thereby regulating CBF. However, the proposed project will show that this is may not be the primary method through which astrocytes control CBF. Here we will examine a previously unknown molecular pathway in astrocytes in the control of CBF which is by contrast calcium independent and requires the sensing of potassium levels rather than glutamate. This pathway involves a very recently discovered enzyme that our lab has localized to the astrocyte over other brain cells, which is exquisitely sensitive to potassium. Uncovering all the details associated with this novel mechanism will be critical for understanding how the brain controls CBF and how to effectively treat people with abnormalities to CBF.