Blocking Brain Protein Helps Ease Brain Injury After Stroke

Madison, Wisconsin - Experiments on small mammals show that blocking a protein helped ease the damage caused when an ischemic stroke temporarily cuts off blood and oxygen to the brain.

Interestingly, this same protein, α-Synuclein (α-Syn), is known to cause Parkinson’s disease when it builds up in the neurons resulting in death of neurons in the brain and peripheral nervous system.

“While the damage α-Syn causes in Parkinson’s disease happens over years, it plays a role much more rapidly in ischemic brain cell death,” says Dr. Suresh Mehta, a scientist in the Raghu Vemuganti laboratory in the department of neurosurgery of the University of Wisconsin School of Medicine and Public Health.

The study was published this week in the Journal of Neuroscience.

Lead author TaeHee Kim, a doctoral candidate, looked at the role that the protein, α-Syn, plays after the blood supply is temporarily cut off to part of the brain, a condition known as an ischemic stroke. The neuroscientists found that following a stroke, and the re-perfusion of the brain when the blood supply is restored, the brain cells produce more α-Syn and that it plays a role in oxidative stress, cell death and cell destruction.

They showed that “knockout mice” bred so that they can’t produce α-Syn not only recovered better after a stroke and suffered less brain injury but also survived longer after a stroke.

In other experiments, they looked to see if blocking α-Syn in normal rats would help them recover more quickly from a stroke. They injected the rats with small interfering RNA (siRNA) that was designed to block the production of α-Syn. Rats treated with siRNA not only produced less α-Syn in their brains following the stroke, they did better on behavioral measures such as walking and their ability to remove an adhesive sticker from their paws.

“We injected them both pre- and post-stroke, and found that treating them even 30 minutes after an ischemic stroke offered significant protections,” Kim says.

This indicates that α-Syn could be a potent treatment target for stroke, because people suffering a stroke could be treated with a substance that blocks α-Syn after they arrive at the hospital for treatment.

Ongoing work in the lab is looking at better understanding how α-Syn causes cell death, and finding the least toxic means to block α-Syn. The scientists are also trying the method in different species, in females, and in aging animals, since stroke is mostly a disorder affecting the elderly.

“Already, our results are encouraging,” says Kim. The work was supported in part by grants from the U.S. Department of Veterans’ Affairs and the American Heart Association.

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Blocking Brain Protein Helps Ease Brain Injury After Stroke