Unlike the rest of the body, the brain does not have adequate space for stored energy. Instead, the brain depends on the hundreds of miles of blood arteries that run through it to provide new energy.
However, until recently, it was unclear how the brain signals a demand for extra energy during greater activity and subsequently directs blood flow to particular hot spots.
Researchers from the University of Maryland School of Medicine and the University of Vermont have now shown how the brain interacts with blood arteries when it requires energy, and how blood vessels react by relaxing or contracting to guide blood flow to particular brain areas.
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The researchers say in their new paper, published on July 21 in Science Advances, that understanding how the brain directs energy to itself in intricate detail can help determine what goes wrong in conditions like Alzheimer’s disease and dementia, where faulty blood flow is a predictor of cognitive impairment.
If the brain does not receive the blood it needs when it needs it, the neurons get stressed and degrade over time, eventually leading to cognitive decline and memory difficulties.
arge arteries nourish medium-sized channels known as arterioles, which in turn nourish even tinier capillaries—so tiny that only one blood cell may travel through at a time.
The researchers demonstrated in a 2017 Nature Neuroscience article that electrical pulses flowing through the capillaries control blood flow from medium-sized arterioles feeding vast areas of the brain.
For this latest study, the team wanted to study the fine-tuning of blood as it flows through the capillaries to precisely regulate energy supply to tiny regions in the brain.
According to Dr. Thomas Longden of the University of Maryland School of Medicine:
There seem to be two mechanisms working in tandem to ensure that energy in the form of blood makes it to specific regions of the brain: one broad and the other precise.
The first electrical mechanism is like a sledgehammer approach to get more blood to the general vicinity of the increased brain activity by controlling the medium-sized arterioles, and then capillary calcium signals ensure exquisite fine-tuning to make sure the blood gets to exactly the right place at the right time through the tiny capillaries.
Dr Longden and his team employed a protein that glows green when calcium levels rise in the cell. Michael Kotlikoff’s team at Cornell University was able to activate this technique in mouse blood vessel cells. Following that, the researchers looked into the function of calcium in regulating blood flow in capillaries in the brains of mice. When calcium flooded the blood vessel cells, they became green.
Capillaries in the small area of the brain visible via the window produced 5,000 calcium signals per second, equating to approximately 1,000,000 calcium responses per second in the whole brain’s blood artery system.
Until we deployed this new technology, there was this wholly unseen world of calcium signaling in the brain hidden from view, and now we can see a ton of activity within the brains blood vessels – they are constantly firing
says Dr. Longden.
Dr. Longden and his colleagues next examined the complex biological process underlying calcium’s involvement in brain blood flow. They discovered that as neurons fire electrical impulses, the calcium in blood vessel cells rises. In response, enzymes instruct cells to produce nitric oxide. Nitric oxide is a hormone (and a gas) that relaxes muscle cells surrounding blood arteries, enabling more blood to flow in.
Mark T. Nelson, PhD, Distinguished Professor and Chair of Pharmacology at the University of Vermont, is a co-senior author, explains:
Capillaries were traditionally thought as simple conduits for red blood cells, and the barrier between the blood and brain.
Here, we revealed an unknown universe of calcium signaling in capillaries, and much like traffic lights, these calcium signals direct vital nutrients to nearby active neurons.
“The first step towards figuring out what goes wrong in diseases is to determine how the system works as it normally should,” E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs at UM Baltimore and John Z. and Akiko K. Bowers Distinguished Professor and Dean at the University of Maryland School of Medicine, agrees.
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Now that the researchers have a handle on how this process works, they can begin to investigate how the blood flow is disrupted in Alzheimer’s disease and dementia in order to figure out ways to fix it.
Image Credit: Getty