Endothelial-endothelial signaling as a mechanism for neurovascular coupling

Abstract

The brain is an energetically expensive organ, consuming 20% of the body’s cardiac output at rest while only accounting for 2% of its mass. Unable to store long-term energy reserves, the brain rapidly redistributes blood flow to active regions in order to meet moment-to-moment changes in metabolic demand. This dynamic process, known as neurovascular coupling, is the basis of most non-invasive human imaging and plays a crucial role in maintaining brain health. However, despite its broad-ranging importance, the cellular mechanisms that underlie neurovascular coupling remain elusive. During neurovascular coupling, activity-evoked signals drive smooth muscle relaxation, resulting in arterial dilation and a robust increase in downstream capillary blood flow. These dilation events occur quickly – on the order of milliseconds – and spread rapidly through the arterial network to effectively recruit perfusion. Electrical signals propagated along the cerebrovascular endothelium are increasingly speculated to underpin this phenomenon, but this idea remains fundamentally untested. Here, we leverage a combination of mouse genetics, molecular biology techniques, and in vivo imaging in awake mice to evaluate the role of propagated electrical signals in the neurovascular coupling response. Our preliminary results indicate that brain endothelial cells are capable of electrical communication and establish a foundation to test the physiological significance of the signals they relay. R01 HL153261/HL/NHLBI NIH HHS/United States; HHMI/Howard Hughes Medical Institute/United States This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.