control of brain blood flow
Precise control of blood flow is essential for ensuring brain cells have enough energy (extracted from the sugar, glucose, and oxygen) to fulfill their functions. Early in the development of Alzheimer’s disease and related dementias—which together affect almost 50 million people worldwide—brain blood flow control is disrupted, but it is unclear how this happens. We are exploring novel signaling mechanisms that brain pericytes use to adjust blood flow to protect brain metabolism. These mechanisms appear to be disrupted in Alzheimer’s disease, leading to loss of blood flow control. Therefore, our work may lead to the identification of novel targets on pericytes for therapies aimed at protecting or restoring blood flow in Alzheimer’s patients.
Pericytes are a truly fascinating cell type that reside on capillaries (the smallest of brain blood vessels), extending extremely delicate processes which cover the entirety of the capillary bed of the brain. They were first identified over a century ago, but we still lack even a basic understanding of their functions, largely due to the experimental challenges their fine processes and intimate association with the vasculature and other cells of the brain pose. Thus, we are developing new tools and approaches to study the functions of pericytes, with the aim of elucidating their role in the control of brain blood flow.
To this end, we recently demonstrated that single capillary pericytes are capable of exerting robust control over local blood flow. To do this, they monitor local glucose and subtle decreases in its availability activate an 'energy switch' that engages KATP channel activity, leading to electrical signaling through the capillaries to cause dilation of upstream arterioles and an increase in blood flow.
You can learn more about this area and the types of experiments we do by clicking the images below.
This aspect of our work is funded by the NIH National Institute on Aging.
If you are interested in learning more about our research and potentially joining us, please get in touch!