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Brain Disorders Might Arise from Starving Neurons

blood to the brainThe complete article appeared in Scientific American Mind Volume 25, Issue 4 and was authored by Elizabeth M. C. Hillman,who is an associate professor of biomedical engineering and radiology at Columbia University. Her laboratory develops and uses advanced optical imaging and microscopy techniques to study blood flow regulation in the living brain.

Those of you who read this newsletter know that I am a huge advocate of expanding our blood flow to neurons through exercise. The assumption is adequate amounts of glucose and oxygen to our brain cells results is healthy brains. However determining how brain cells coordinate with our blood vessels to increase/decrease blood flow to our neurons poses many interesting research questions. Professor Hillman explains:Your brain is an energy hog. It weighs less than 2 percent of your total weight yet consumes one fifth of your body’s energy. The brain draws its fuel—oxygen and glucose—from blood delivered by a whopping 400 miles of blood vessels. Lined up end to end, all that vasculature would extend from New York City to Montreal.

These blood vessels are astonishingly dynamic. They tune the flow of blood to respond to the brain’s needs from moment to moment. When certain brain areas work hard at something, more blood flows to those regions to help them refuel. Vessels do this by dilating near the spots that need a supply boost. This widening coaxes blood to reroute, much as customers in a busy store redistribute themselves whenever a new checkout line opens.

Fuel for neurons is limited, so your blood vessels must carefully choreograph every instant to sustain your brain. Yet what if the brain’s blood vessels fall out of sync with their neurons? If the vasculature fails to deliver more blood when neurons need it, those cells might starve. In the short term, cognition could suffer. Longer term, entire networks of brain cells could wither away.

Historically, neuroscientists have seen blood vessels in the brain as mundane roadways, irrelevant to the neurons they support. Yet a city needs its roads. More than a simple conduit for noisy cars, transport infrastructure profoundly alters how we function. When Hurricane Sandy hit New York, for example, the rising water levels and power outages disrupted distribution networks for people, food and supplies, bringing the city to a standstill.

Blood flow is equally vital to brain function, and there are compelling reasons to think that dysfunction in one could impair the other. Brain scans have shown us that the brains of healthy individuals behave differently from those of people with Alzheimer’s disease, attention-deficit/hyperactivity disorder, schizophrenia, depression, autism or multiple sclerosis, to name just a few conditions. The standard interpretation is that neuronal activity has deviated from a typical state.

There is a catch, though. Functional magnetic resonance imaging (fMRI), the technique most widely used for imaging brain activity, measures changes in blood flow as a proxy for neuronal activity. If the relation between blood flow and neurons has gone off the rails, fMRI scans will still deviate from the norm no matter what the neurons are up to. Scientists are left in the dark as to which brain disorders might solely affect neurons and which might also disturb cerebral blood flow.

To get to the bottom of this, my laboratory has embarked on a mission to uncover how and when blood vessels and neurons might fall into discord. The evidence we have found suggests that this relation can indeed go awry and that it could contribute to—or even cause—neurological or psychiatric disorders. Fortunately, we might already possess the tools we need to correct the patterns of blood flow in the brain.A critical next step is to nail down how it is that neurons and blood vessels communicate. We have a lot to learn. For example, it is tempting to think that hungry neurons use up local oxygen supplies, triggering an increase in blood flow, but the reality is not quite that simple. Even when a rodent is inside a hyperbaric oxygen chamber, which saturates the brain with oxygen, the animal will still exhibit a surge of blood to an area where neurons are hard at work. The same thing happens when very high levels of glucose are available.

So the call for more blood involves something more than a simple “low fuel” alarm. Fortunately, we already have an exceptional tool for studying blood flow in the human brain: fMRI. We can use fMRI to hunt for signs of neurovascular dysfunction by looking for deviations from the normal patterns of responses in different disease states. If we find reliable signatures, fMRI could become a valuable clinical tool for diagnosing and monitoring neurovascular disorders and could help guide us to new treatments.

Our work suggests that we can no longer ignore the brain’s vasculature as if it were mundane infrastructure. It is a critical partner in normal brain function. Scrutinizing the brain’s vasculature, learning its language, and understanding how it develops, ages and responds to injury could finally bring us closer to untangling the mysteries of the human brain. Professor Hillman’s research is both fascinating and I believe on target. Our better understanding of blood flow and brain cells will indeed lead to progressive treatments for devastating brain diseases.