Clear Thinking

Patrick Drew can’t see inside your brain. But he has found a way to see inside a mouse’s—and by doing so, he is gaining new insights into how the human brain may function.

“I’m interested in the ‘infrastructure’ of the brain—the network of blood vessels that supply oxygen and nutrients and help regulate temperature,” says Drew, assistant professor of engineering science and mechanics at Penn State. One reason for that interest is health-related: “If something goes wrong between your ears—stroke, trauma, dementia—it’s usually the blood vessels.”

Another is that localized changes in blood flow and volume are good indicators of brain activity—in fact, that’s the basis for fMRI, an imaging technique now widely used to pinpoint brain functions and even to analyze emotions and behavior.

But what exactly is happening in the brain when blood flow changes? What is the precise relationship to neuronal signals? Which vessels change when a brain region is activated: arteries or veins?

“People thought veins,” Drew says. “The idea was that the vein blows up like a balloon, filling with blood. But nobody really knew—they couldn’t actually see it.” Not until Drew and his colleagues devised a way to observe the brain’s blood vessels directly.

Previously, he explains, to watch a brain at work you had to perform a craniotomy, i.e., remove the top of the skull. But “the brain is really well-protected, sealed away,” he says. Removing the skull results in inflammation—and that means changes in vascular development.

Patrick Drew
Laura Stocker Waldhier

Patrick Drew

Instead, Drew and colleagues devised a way to see through a mouse’s skull. Rather than removing bone, they grind it down—thin enough to see through—then polish it and cover it with protective glass. Through this window, using a fluorescence imaging technique known as two-photon microscopy, they can watch individual blood vessels at work in mouse brains that are fully awake and functioning normally.

As a postdoc at the University of California at San Diego, before coming to Penn State, Drew used this method to show that the brain’s arteries—not the veins—dilate in response to sensory stimuli. “Instead of a balloon, it’s more like a bagpipe,” he explains. “This means the changes in blood flow and volume are not as sloppy or passive as previously thought. The changes are largely under the active control of the muscles that line the artery walls, which in turn are controlled by neural activity.”

Now Drew is using the same approach to address other questions, like how exercise affects the brain. “We know that exercise is important in protecting brain health, that it causes neurogenesis,” he explains. “But we have a very poor idea of the changes in blood flow during physical activity. It’s hard to measure in humans. With this system, we can put a mouse on an exercise ball and look at brain activity.”

Drew is also studying how the brain’s vasculature develops. “When you’re born, you have a lot more blood vessels on the surface,” he notes. “Ever been to Boston? It’s like the road system there: It works, but it’s extremely convoluted. As you age the network becomes refined, like a good freeway system. How does this happen?”

In mice, he reports, “We see a lot of remodeling in the first two weeks of life.” During this process, “Pathways can close off. So this work is applicable to understanding stroke and other problems. After all, aging is a sort of development. Blood vessels disappear, and you lose a lot of the brain’s built-in redundancy. When you’re young, if one way is blocked, blood finds another way. As we age, there tend to be bottlenecks.

“Maybe early life experiences can prevent some of this loss,” Drew suggests. “We know that sensory deprivation decreases metabolic activity in the brain. We also know that the more active parts of the brain tend to have more blood vessels.

“Maybe a highly stimulating childhood, by building up vascular redundancy, can be protective in later life.”

Last Updated May 02, 2012