Discovery could lead to drug to enhance recovery from stroke

neurons-with-new-connections
These brain cells grew new connections after exposure to GDF10. Image credit: UCLA

A study led by researchers from the University of California-Los Angeles (UCLA) and published in Nature Neurologyidentifies a molecule called growth differentiation factor 10 (GDF10) that signals brain tissue to form new connections following a stroke.

The senior author of the study is neurologist and neuroscientist S. Thomas Carmichael, professor and vice chair for research and programs in UCLA’s department of neurology. He and his colleagues hope their findings will lead to new treatments to help patients recover brain function following a stroke.

Prof. Carmichael says their study is the first to identify that GDF10 has a function in the adult brain. He explains the importance of the finding:

“The brain has a limited capacity for recovery after stroke. 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, then it might be possible to enhance brain repair after stroke.”

The researchers started by searching for molecules that are prevalent in the brain following a stroke and listing all the genes that are switched on or off (they had already identified them in earlier work).

This was how GDF10 emerged as a possible trigger for brain repair, so the team investigated it more closely by looking at how it behaves in brain cells in the Petri dish and in animals.

GDF10 encourages brain cells to make new connections

The researchers found that GDF10 appears to encourage brain cells to make new connections. Prof. Carmichael comments:

“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.”

After identifying the signaling systems that control the process of making new connections, the team then pinpointed the molecules that GDF10 switches on and off in brain cells after a stroke.

They compared what happens to the RNA in these cells to what happens to the RNA in similar cells during brain development and learning, and to the RNA in brain cells of people with other types of disease.

RNA (ribonucleic acid) is an essential molecule that helps to pass the genetic information held in DNA onto proteins. It is also important for protein synthesis and gene regulation.

The researchers found that GDF10 controls a unique group of molecules that help brain tissue recover following a stroke.

They suggest this process of brain tissue repair following a stroke is unique and not simply a reactivation of molecules involved in brain development.

The researchers then explored the effect of GDF10 on brain areas linked to limb control. They mapped brain connections in this area in animals (rats and mice) that were given GDF10 following a stroke, in animals that suffered stroke but did not receive GDF10, in healthy animals and in animals that were given less GDF10 following a stroke.

Prof. Carmichael describes what they found:

“The results indicated that GDF10 normally is responsible for the very limited process of the formation of new connections after stroke. 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.”

He and his colleagues are now looking for a small molecule that could trigger GDF10 signaling and possibly lead to a drug to improve recovery after stroke.

Meanwhile, Medical News Today recently learned of new research that shows high-stress jobs can lead to stroke, especially in women. Reporting in the journal Neurology, researchers from Southern Medical University in Guangzhou, China, defined high-stress jobs as being occupations where demands are high and control is low – such as that experienced by waitresses and nursing aides.

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Source: Medical News Today

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