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Every year, nearly 800,000 people in the U.S. suffer a stroke. It’s the country’s third-leading cause of death, and a primary cause of severe, long-term disability—the damage it does to the brain is largely irreparable. But a study published online yesterday in the journal Nature describes how a drug helped repair the brains of mice to a degree that was previously impossible. This breakthrough happened because of the discovery of a neural signaling system in the brain that plays a role in recovering from a stroke.

A stroke is usually caused by a clot that blocks blood flow to an area of the brain. Tissue in that part of the brain dies from lack of oxygen unless the clot is detected immediately and is either dissolved or removed. The dead tissue cannot be revived, but often the brain can be trained to redirect nerve impulses via still-living nearby neurons. But such training is difficult, can require months to years of arduous rehab, and is often not sufficient to overcome complex disability.

The new research, by neurologist S. Thomas Carmichael and his colleagues at the University of California at Los Angeles, shows that neurons in the areas of the brain closest to the site of a stroke are impaired after it occurs. The reason for that is a buildup of an inhibitory signaling molecule called GABA that prevents the neurons from firing. When those nerves are inhibited, it’s harder for the brain to recruit them into its rerouted circuits.

In studies in mice, the researchers discovered that blocking a particular piece of the GABA signaling system with an existing drug allowed the nerves to reactivate, reversing the repressed excitability, allowing them to more easily respond to other neurons, and encouraging and enhancing early recovery after a stroke by as much as 50 percent. “At face value, it’s a new pharmacological target for repair and recovery in stroke,” Carmichael says.

That’s no small feat. Currently, the only drug that’s known to help with post-stroke recovery is tissue plasminogen activator, or tPA, which breaks up clots and can be very effective at restoring blood flow to the brain when administered within the first few hours after a stroke. But tPA can only be used in a small subset of patients (because it dissolves all blood clots, which can lead to harmful side effects), and can’t help restore lost brain function—it only helps prevent tissue from dying in the first place. Despite decades of research, there are no known drugs that can encourage brain repair after a stroke, and the only proven techniques for recovering lost function involve frequent and intense physical therapy.

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Credit: S. Thomas Carmichael, University of California at Los Angeles

Tagged: Biomedicine, drugs, stroke

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