Rodent stroke recovery raises hopes for humans

Larry Benowitz, PhD, and colleagues are hopeful that future clinical trials of inosine will enhance brain function in stroke-impaired humans. Related link: Inosine induces axonal rewiring and improves behavioral outcome after stroke (PNAS)

How did researchers at Children's, investigating brain function after a stroke, discover that a naturally-occurring substance promotes a "rewiring" of the brain?

By putting rats into rehab.

Stroke-impaired rodents were treated with inosine, a chemical produced in the brain, and observed completing tasks such as reaching for food, placing their paws on a tabletop as they approached it and controlling the movement of their paws while swimming. The investigators found that inosine dramatically improved the rats' performance.

Why? When inosine was introduced into the rats' brains, nerve cells increased their growth of axons, the part of the neuron that conveys electrical signals. Typically after a stroke, brain cells die, severing connections between undamaged cells in adjacent regions of the brain.

But stimulated by inosine, those cells can potentially establish new connections, and this "rewiring" can result in a limited amount of spontaneous recovery after a stroke. Although inosine occurs naturally in the brain, its natural quantities are insufficient to stimulate significant recovery.

"This rewiring is apparently sufficient to promote substantial functional recovery," says Larry Benowitz, PhD, director of the Laboratories for Neuroscience Research and the principal investigator of the study, which was published June 25 in the Proceedings of the National Academy of Sciences. "In terms of clinical implications, inosine - which has had no apparent side effects in animals thus far - has potential as a novel nerve regeneration approach to treatment of stroke and other types of brain injuries."

Stroke occurs when the brain is deprived of its blood supply, either by a blood clot blocking a blood vessel (ischemic stroke) or a blood vessel rupturing in the brain, leaking blood and damaging tissue (hemorrhagic stroke). It is estimated that 750,000 people suffer first or recurrent strokes every year in the United States, and strokes claim the lives of 160,000 Americans each year.

In humans, strokes similar to the ones in the study cause long-lasting or permanent losses in movement and sensation. Current treatments are limited to methods of restoring blood flow and preventing the damage from spreading. As yet, there are no clinically approved methods to enhance brain rewiring. Benowitz and his fellow investigators are hopeful that inosine may prove to be one such method. Clinical trials are expected to begin within a few months. —CM

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