Study Finds Calcium Precisely Directs Blood Flow In The Brain

Unlike the rest of the body, there is not enough space in the brain for stored energy. Instead, the brain relies on the hundreds of miles of blood vessels it contains to deliver fresh energy through the blood. Yet how the brain expresses a need for more energy during increased activity and then directs its blood supply to specific hot spots has, until now, been poorly understood.

Today, researchers at the University of Maryland School of Medicine and the University of Vermont have shown how the brain communicates with blood vessels when it needs energy, and how those blood vessels respond to it. relaxing or contracting to direct blood flow to specific areas of the brain.

In their new article, published on July 21 in Scientists progress, researchers say that understanding how the brain directs energy to itself in fine detail can help determine what is wrong with conditions like Alzheimer’s disease and dementia, where poor blood flow is a predictor of cognitive impairment. If the brain is not getting blood where it needs it when it needs it, neurons become stressed and over time deteriorate, ultimately leading to cognitive decline and memory problems.

Large arteries supply medium-sized vessels called arterioles which then supply even smaller capillaries, so small that only one blood cell can pass through them at a time. In a 2017 Neuroscience of nature article, the researchers showed that electrical impulses passing through capillaries direct blood flow to medium-sized arterioles supplying large areas of the brain. For this latest paper, the team wanted to study the fine-tuning of blood as it circulates through capillaries in order to precisely regulate the energy supply to tiny regions of the brain.

“There appear to be two mechanisms working in tandem to ensure that energy in the form of blood reaches specific regions of the brain: one large and the other precise,” explains Thomas Longden, Ph.D., assistant professor of physiology at the University of Maryland School of Medicine. “The first electrical mechanism is like a rough hammer approach to bring more blood into general proximity to increased brain activity by controlling medium-sized arterioles, then capillary calcium signals provide exquisite fine-tuning to ensure that the blood gets to exactly the right place at the right time through the tiny capillaries. “

Dr. Longden and his colleagues used a protein that emits a green light when calcium increases in the cell. Thanks to the efforts of Michael Kotlikoff’s team at Cornell University, they were able to activate this tool in cells lining the blood vessels of mice. The researchers then looked through small windows in the brains of these mice to study the role of calcium in controlling blood flow in the brain’s capillaries. When the cells lining the blood vessels received an influx of calcium, they turned green. They detected 5,000 calcium signals per second in capillaries in the tiny section of the brain visible through the window, which they say represents about 1,000,000 of these responses every second throughout the brain’s vasculature. .

“Until we deployed this new technology, there was this totally invisible world of calcium signaling in the brain hidden from view, and now we can see a ton of activity in the blood vessels of the brain – they are. constantly on, ”says Dr. Longden.

Dr. Longden and the research team then dissected the complex cellular mechanism behind calcium’s role in directing blood branch-by-branch through the brain’s tiny vessels. They found that when neurons emit electrical signals, they cause an increase in calcium in the cells lining the blood vessels. Then the enzymes detect this calcium and direct the cells to make nitric oxide. Nitric oxide is a hormone (and a gas) that causes muscle cells around the blood vessels to relax, which then widens the vessels allowing more blood to flow.

“Capillaries have traditionally been viewed as simple conduits for red blood cells and the blood-brain barrier,” says co-lead author Mark T. Nelson, Ph.D., Professor Emeritus and Chair of Pharmacology at the University of Vermont. “Here, we have revealed an unknown universe of calcium signaling in capillaries, and just like traffic lights, these calcium signals direct vital nutrients to nearby active neurons.”

“The first step in determining what is wrong with diseases is to determine how the system is functioning as it should normally,” says E. Albert Reece, MD, Ph.D., MBA, executive vice president of medical affairs , UM Baltimore, and Distinguished Professor and Dean John Z. and Akiko K. Bowers of the University of Maryland School of Medicine. “Now that researchers understand how this process works, they can begin to study how blood flow is disrupted in Alzheimer’s disease and dementia to find ways to fix it.”