Neuroscience

Blood Vessels in Your Brain Don’t All Act the Same

by Kim Krieger


Certain blood vessels in the brainstem constrict when blood vessels elsewhere in the body would dilate. And that contrary behavior is what keeps us breathing, according to a new paper by UConn researchers published in the journal eLife.

Neuroscientists studying the brainstem have historically focused on neurons, which are brain cells that send signals to one another and all over the body. Recently, neuroscientists have come to understand that astrocytes, cells once thought to simply provide structure to the brain, also release signaling molecules, which regulate neuron function. But until now, no one even considered the possibility that blood vessels may be similarly specialized.

For more than a century, doctors and scientists have known that blood vessels dilate when cellular waste products like carbon dioxide build up. Widening the vessels allows fresh blood to flush through, carrying in oxygen and washing away the acidic carbon dioxide. This has been shown to be true throughout the body, and is standard dogma in undergraduate physiology classes.

Neuroscientists have come to understand that astrocytes release signaling molecules that regulate neuron function. Until now, no one even considered the possibility that blood vessels may be similarly specialized.

UConn physiologist Dan Mulkey was teaching exactly that to undergraduates one day when he realized that it couldn’t possibly be true in the part of the brainstem he studies. The retrotrapezoid nucleus (RTN), a small region in the brainstem, controls breathing. Mulkey has shown in the past that RTN neurons respond to rising levels of carbon dioxide in brain tissue by stimulating the lungs to breathe. But if the blood vessels in the RTN dilated in response to rising carbon dioxide the same way blood vessels do everywhere else, it would wash out that all-important signal, preventing cells in the RTN from doing their job of driving us to breathe.

Mulkey’s team, primarily comprising UConn undergraduates, studied thin slices of brainstem and found that RTN blood vessels constricted when carbon dioxide levels rose. But blood vessels from slices of cortex (the wrinkled top part of the brain) dilated in response to high carbon dioxide, just like the rest of the body.

Mulkey guessed that astrocytes had something to do with the change in blood vessel behavior, and his hypothesis was proved right in the lab. The astrocytes in the RTN were behaving differently than astrocytes anywhere else in the body. When these brainstem astrocytes detected high levels of carbon dioxide, they released adenosine triphosphate signaling to the neurons and blood vessels that they should constrict.

“This is a big change in how we think about breathing,” Mulkey says.

New Epilepsy Drug May Be Safer, More Effective

A PET scan of human brain

A PET (positron emission tomography) scan shows blood flow and metabolic activity, used to diagnose the cause of epilepsy and for surgical planning.


A new drug that selectively affects potassium channels in the brain may offer effective treatment for epilepsy and prevent tinnitus, UConn neurophysiologist Anastasios Tzingounis and colleagues reported in a recent issue of The Journal of Neuroscience.

The existing drugs to treat epilepsy don’t always work, and can have serious side effects. One of the more effective, called retigabine, helps open KCNQ potassium channels, which shut down the signaling of overly excited nerves. Unfortunately, retigabine has significant adverse side effects, including sleepiness, dizziness, problems with urination and hearing, and an unnerving tendency to turn people’s skin and eyes blue. Because of this, it’s usually only given to adults who don’t get relief from other epilepsy drugs.

This drug gives me a better tool to dissect the function of these channels. We need to find solutions for kids – and adults – with [epilepsy].

There are five different kinds of KCNQ potassium channels in the body, but only two are important in epilepsy and tinnitus: KCNQ2 and KCNQ3. The problem with retigabine is that it acts on other KCNQ potassium channels as well, and that’s why it has so many unwanted side effects.

Tzingounis’ research has found that a new drug – SF0034, which is chemically identical to retigabine, except with an extra fluorine atom – seems to open only KCNQ2 and KCNQ3 potassium channels, not affecting KCNQ4 or 5. It was more effective than retigabine at preventing seizures in animals, and it was also less toxic.

The drug company that developed SF0034, SciFluor, now plans to start FDA trials to see whether the drug is safe and effective in people. Treating epilepsy is the primary goal, but tinnitus can be similarly debilitating, and sufferers would welcome a decent treatment.

“This drug gives me another tool, and a better tool, to dissect the function of these channels,” Tzingounis says. “We need to find solutions for kids – and adults – with this problem.”