Special Vascular Cells Adjust Blood Flow in Brain Capillaries Based on Local Energy Needs

When we smell hot dogs, it may trigger memories of backyard barbeques or attending baseball games during childhood. During this process, the areas of the brain that control smell and long-term memory are rapidly firing off impulses. To fuel these signals from neurons, the active brain regions need oxygen and energy in the form of blood sugar glucose, which is quickly delivered through blood vessels.

Now, University of Maryland School of Medicine’s researchers have discovered that a certain type of cell that sits on top of the brain’s smallest blood vessels senses when their brain region needs energy. When glucose levels are low, these cells signal blood vessels to dilate, increasing the blood flow regionally and allowing more energy to fuel that part of the brain.

These findings from experiments in mice were published on Dec. 27, 2022, in Cell Reports.

“These fluctuations in blood flow help direct the brain’s energy resources to support everyday functions,” said study leader Thomas Longden, PhD, Assistant Professor of Physiology at UMSOM. “As I am speaking now, the blood flow in my brain will be diverted to the language areas and the motor (or movement) areas that control my vocal cords to fuel these processes.”

In 2022, Dr. Longden’s laboratory showed that signals in the form of calcium—shaped by electrical impulses through the blood vessels—cause certain brain capillaries to relax controlling blood flow, through a paper published in Science Advances. In their newest study, his team demonstrated that a specific type of cell located along the outside of the capillaries, known as pericytes, direct these electrical pulses based on their perception of local energy needs.

The researchers directly observed this process playing out in mouse brains using advanced microscopy, and then dissected out the capillaries with their attached pericytes. They then measured electrical signals given off by the pericytes when glucose levels were adjusted. They found that the pericytes rapidly generated electrical signals when the sugar levels were low, but not when the levels were high.

“If adequate energy is not supplied by the brain blood vessels to the neurons in a timely manner, there can be a mismatch of energy supply and demand. This causes the brain’s neurons to undergo stress, which can lead to impaired protein metabolism, changes in how the neurons fire, and even eventually cell death,” said study co-author Ashwini Hariharan, PhD, Postdoctoral Fellow in Physiology at UMSOM. 

“This energetic failure in blood vessel function of the brain has been shown to occur during the aging process, in certain neurodegenerative diseases, like Alzheimer’s, and in stroke,” said Dean of UMSOM Mark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor.

Dr. Longden added, “By studying how this process functions normally, researchers may be able to gain further insight into what happens in aging or in neurodegenerative diseases, so they can develop better therapies.”

This study was funded by the National Institutes of Health's National Institute on Aging and National Institute of Neurological Disorders and Stroke (1R01AG066645, 5R01NS115401, and 1DP2NS121347-01), the American Heart Association, and the D.C. Women’s Board.

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world — with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.3 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic, and clinically based care for nearly 2 million patients each year. The School of Medicine has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System (“University of Maryland Medicine”) has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2021, the UM School of Medicine is ranked #9 among the 92 public medical schools in the U.S., and in the top 15 percent (#27) of all 192 public and private U.S. medical schools. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu