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Discovery of Molecular Signals Could Lead to Improved Stroke Recovery

  Molecular Signals Could Lead to Improved Stroke Recovery  
 

Neurons (in green) are producing growth differentiation factor 10 (red), a molecule discovered by UCLA scientists that previously had no known role in the adult brain.
Image: Courtesy of Dr. S. Thomas Carmichael

UCLA researchers have identified a molecule that signals brain tissue to form new connections to compensate for damage after a stroke and initiate repairs to the brain. The finding could lead to new treatments to promote brain repair and functional recovery in people who have suffered a stroke. The five-year study, performed in an animal model, was the first to identify growth differentiation factor 10, or GDF10, a molecule that previously had no known role in the adult brain, says S. Thomas Carmichael, MD (FEL ’01), PhD, Carol and James Collins Chair in the UCLA Department of Neurology.

“The brain has a limited capacity for recovery after stroke,” Dr. Carmichael says. “Most stroke patients get better after their initial stroke, but few fully recover. If the signals that lead to this limited recovery after stroke can be identified and turned into a treatment, it might be possible to enhance brain repair after stroke.

The study also showed that GDF10 is released after a stroke in humans and in many different animals. During a previous study, Dr. Carmichael and his team determined which molecules become more prevalent in the brain during the recovery period after a stroke and listed all of the genes that are up- or- down-regulated. Heading into the new study, researchers believed that one of the molecules on the list could be a signal telling the brain to repair itself after a stroke, and they screened for the molecules that saw the biggest increase in the brain after stroke.

The scientists found that GDF10 promotes the ability of brain cells to form new connections, and they identified the signaling systems that control the process. “We found that GDF10 induces new connections to form in the brain after stroke and that this mediates the recovery of the ability to control bodily movement,” Dr. Carmichael says.

Finally, the team identified all of the molecules that are turned on or off by GDF10 in brain cells after a stroke and compared the cells’ RNA to RNA in comparable cells during brain development and normal learning and to RNA in the brain cells of people with other diseases.

They found that GDF10 regulates a unique collection of molecules that improves recovery after stroke. The discovery indicates that brain-tissue regenerating after a stroke is a unique process rather than just a reactivation of the molecules that are active in brain development.

The team also administered GDF10 to the animals that had experienced strokes and then mapped the connections in the brain that are tied to body movement. They compared those to the connections in animals that had experienced a stroke but were not given GDF10, in animals with healthy brains and in animals that had experienced a stroke and had a reduced level of GDF10. “The results indicated that GDF10 normally is responsible for the very limited process of the formation of new connections after stroke,” Dr. Carmichael says. “Delivering more GDF10 markedly enhances the formation of new connections and does so mostly in a specific brain circuit. The formation of connections in this circuit with GDF10 administration significantly enhanced recovery of limb control after stroke.”

“GDF10 Is a Signal for Axonal Sprouting and Functional Recovery after Stroke,” Nature Neuroscience, October 26, 2015

 





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