Researchers at Washington University School of Medicine in St. Louis believe they have reopened the debate over potential stroke treatments decades after they were abandoned.
Analyzing more than 5,000 genomes from ischemic stroke patients, the team found two genetic markers that were associated with patient outcomes in the 24 hours after stroke. Both genes were related to how a neurotransmitter called glutamate (yes, in MSG) works in the brain.
The presence of too much glutamate can “stimulate” cells to death, a condition known as “excitotoxicity”, which was thought to affect stroke patients until decades ago after several unsuccessful clinical trials. The tests caused scientists to move on from the idea.
The Washoo team believes their work warrants re-evaluation of glutamate — and inhibiting excitotoxicity — as a potential treatment.
The team found two genetic markers associated with outcomes 24 hours after the stroke. Both genes were related to how a neurotransmitter called glutamate (yes, in MSG) works in the brain.
“The question remains about whether excitotoxicity really matters for stroke recovery in people,” Jin-Moo Lee, head of the Department of Neurology and co-senior author, said in a statement.
Preventing excitotoxicity can cure stroke in rats, but every human trial of glutamate inhibitors in humans failed — “we couldn’t move the needle,” Lee said. But two of the genes in the army analyzed suggest that there may be something to treat excitotoxicity and stroke recovery.
“It’s pretty remarkable,” Lee said. “This is the first genetic evidence showing excitotoxicity cases in people, not just rats.”
What is Glutamate? The chemical is most well-known or infamous, depending on your diet theory as an ingredient in the food additive MSG. While undoubtedly delicious, it “does not cause enormous scientific interest in glutamate,” researchers from the University of Oslo explain in the Journal of Neural Transmission. review on excitotoxicity.
Instead, glutamate is interesting because it is the most common free amino acid — not bound to a protein — in the brain. So the scientists were surprised to learn that glutamate has the ability to increase the ability of neurons to fire, which is known as a “stimulatory effect.”
When that effect goes into overdrive, cells can die.
The presence of too much glutamate can “stimulate” cells to death, which is referred to as “excitotoxicity”.
Excitotoxicity and stroke: In the 1990s, Dennis Choi, then chief of neurology at the University of Washington, pioneered the association between excitotoxicity and stroke.
His lab was able to prove that stroke can cause neurons to release massive amounts of glutamate, but this glutamate glut to treat stroke was never successful outside of rats, eventually abandoning the technique. Went.
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However, Lee, who worked with Choi, remained interested. Recently, Lee and colleagues studied the genomes of 5,876 patients with ischemic stroke in Europe, Asia and North America.
Using the National Institutes of Health (NIH) Stroke Scale, they characterized each patient’s recovery over the first 24 hours, then began scanning the genome for any genes that were related to recovery.
“We did not initiate any hypotheses about the mechanism of neuronal injury,” said genetics researcher and co-senior author Carlos Cruchaga. “We started with the assumption that certain genetic variants are associated with stroke recovery, but which ones they are, we did not speculate.”
Two genes stood out from the rest. One, called ADAM32, makes it easier to transfer brain signals from one neuron to another. The second, GluR1, is a glutamate receptor.
The researchers believe their work warrants re-evaluation of glutamate — and inhibiting excitotoxicity — as a potential stroke treatment.
In the years since anti-excitotoxicity drugs have been abandoned, drugs that break down blood clots have become the standard therapy for ischemic stroke. These drugs help restore blood flow to the brain which not only prevents further damage, but also means that drugs that aid in recovery may now have a better chance of getting to the brain and working. Is.
“We’ve learned a lot about stroke over the past few decades,” Lee said. “I think it’s exam time again.”
This article was originally published on Freethink, our sister site.
