Paul Chantler, an associate professor in the WVU School of Medicine, is performing NIH-funded research into stroke recovery among obese patients. In the future, his findings may contribute to new treatments that can improve how obese patients bounce back from strokes.
Obesity doesn’t just make strokes more likely. It also makes them more damaging—and more lethal.
Paul Chantler, an associate professor in the West Virginia University School of Medicine, is researching why obese stroke patients have more trouble recovering than their lean counterparts. His work, funded by the National Institutes of Health, hints at a medical treatment that may narrow this gap.
“When you have a stroke, it’s not just localized to the brain,” he said. Not only does a stroke deprive the brain of oxygen, but it also floods the bloodstream with inflammatory markers that travel to distant organs and tissues—including the heart—and damage them. “There’s evidence to suggest that if you’ve had a stroke, you can have a heart attack soon after.” Likewise, the cardiovascular dysfunctions that often accompany obesity make it harder for the brain to heal.
Chantler and his team induced strokes in obese and lean preclinical models. They discovered that after the stroke, the blood vessels of obese models couldn’t open and close as well. Particularly, the middle cerebral artery—which Chantler calls a “major feeder artery in the brain”—was damaged more severely in obese models than in lean ones. Fifteen days later, the middle cerebral artery in lean models had recovered, but in obese models, it remained seriously compromised.
The researchers then repeated the experiment, but this time, they injected some of the models with a peptide that reduces a certain inflammatory marker—called NOX2—in the bloodstream. The rest of the models received a placebo. “We saw substantial improvements, especially in the obese model,” said Chantler. “Many of them didn’t die. In the past, we had a 40 percent mortality rate. Now, pretty much all of the models survived.” In addition, the functioning of the middle cerebral artery was better preserved.
Of course, as Chantler points out, “you don’t know when you’re going to have a stroke.” So, to better emulate the treatment that a stroke patient would receive upon arriving at an emergency room, he and his team tried giving the injection three and then six hours after the stroke. In each case, the injection had the same effect.
In the future, blood transfusions might prove to be a powerful way to ameliorate a stroke’s effects in an obese patient. “If you’re obese and you have these systemic inflammatory markers just swimming around, and then you have a stroke, this pro-inflammatory stroke is going to drive a worse stroke response. So, can you give them a transfusion of blood with a healthier profile after a stroke?”
The prospect is especially relevant to West Virginia. According to the Centers for Disease Control and Prevention, the state ranks first in adult obesity. “We live in a state that’s heavily obese, with diabetic complications and metabolic issues, and a lot of the stroke patients that you see tend to have preexisting cardiovascular complications,” Chantler said.
“Dr. Chantler’s research is novel and points to an innovative treatment to protect the brain from the damaging effects of stroke, particularly in obese patients,” said James Simpkins, who directs the WVU Center for Basic and Translational Stroke Research and leads the WVU Stroke Center of Biomedical Research Excellence. “As such, it is important that his research be translated into clinical trials.”
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number 5P20GM109098 and the West Virginia Clinical and Translational Science Institute under Award Number U54GM104942. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the West Virginia Clinical and Translational Science Institute.
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see/10/30/18
CONTACT: Cassie Thomas, WVU School of Medicine
304.293.3412, cassie.thomas@hsc.wvu.edu
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