Existing drug aids stroke recovery by rewiring undamaged neurons

 

An existing drug could help patients regain motor control after a stroke by rewiring the undamaged side of the brain

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Most treatments for strokes aim to help reduce or repair damage to affected neurons. But a new study in mice has shown that a drug already in use to treat certain neurological disorders could help patients recover from strokes by getting undamaged neurons to pick up the slack.

An ischemic stroke occurs when a blood vessel blockage interrupts blood flow to the brain, causing neurons to die off. Survivors can suffer impaired fine motor control and speech, and other disabilities, for which long-term rehabilitation is often required.

Logically, many treatment options in development focus on minimizing or reversing damage to neurons, using things like stem cells, anti-inflammatory drugs, injectable hydrogels, or molecules that convert neighboring cells into neurons.

But in a new study, researchers at Ohio State University found a promising alternative – a drug known as gabapentin that essentially rewires the undamaged part of the brain to repair broken connections between neurons and restore motor functions.

To test the drug, the team administered gabapentin daily for six weeks to mice following a stroke. Treated mice recovered fine motor function of their forelimbs to a much greater degree than control mice, and this improvement persisted two weeks after treatment ended. This, the team says, indicates that the changes have been solidified in the nervous system.

The drug works by blocking the expression of a receptor protein called alpha2delta2, which can become “hyperexcited” after an injury like a stroke and prevent axon growth that could patch up the damage. When gabaprentin blocks this protein, neurons on the undamaged side of the brain were seen to sprout new axons and restore signals, allowing the animals to regain some motor function.

“Imagine this protein is the brake pedal and recovery is the gas pedal,” said Andrea tedeschi, lead author of the study. “You can push on the gas pedal but can’t accelerate as long as you’re also pushing on the brake pedal. If you start lifting the brake pedal and continuously press on the gas, you can really speed up recovery. We think that is gabapentin’s effect on neurons, and there is a contribution of non-neuronal cells that tap into this process and make it even more effective.”

As always, there’s no guarantee that results from animal studies will carry across into humans, but there is at least one good sign in this case. Gabapentin is already in use in humans for other neurological disorders, such as nerve pain and seizures, so its safety record and side effects are already known.

The research was published in the journal Brain.

Source: Ohio State University