S. Thomas Carmichael, MD, PhD
Stroke research from a team of faculty in the David Geffen School of Medicine at UCLA has identified a protein called growth differentiation factor 10 (GDF10), which signals brain tissue to form new neural connections following a stroke.
S. Thomas Carmichael, MD, PhD, senior author of "GDF10 is a signal for axonal sprouting and functional recovery after stroke," published in Nature Neuroscience, is a professor and vice chair for research and programs in UCLA's Department of Neurology. His five-year study — performed on brain tissue from mice, monkeys and humans — is the first to identify the function of GDF10 in the adult brain.
How it benefits axon activity
The team initially determined which molecules are present in the brain following a stroke, drawing upon their previously published research that identified all the genes that had been up- and down-regulated. This process identified GDF10 as a possible trigger for stroke-damaged brain cells to make new connections.
The scientists examined animal models of stroke and human autopsy tissue and determined that GDF10 is activated very early after a stroke. They then studied rodent and human neurons in vitro, concluding that GDF10 both stimulated axonal growth and increased axon length.
Turning discovery into medicine
To explore how GDF10 can affect functional recovery, the team treated mouse models of stroke with the protein, then had the animals perform motor tasks to test their recovery. Performance dropped when GDF10 was blocked.
If the signals that limit recovery can be identified and turned into a treatment, that discovery could be used to increase brain repair after a stroke. Specifically, Dr. Carmichael and his colleagues are focusing on identifying the trigger for GDF10 signaling.
The need for new stroke therapies is enormous. The Centers for Disease Control and Prevention (CDC) considers stroke the fifth-leading cause of death for Americans and the top cause of adult-onset disability. Although the brain is known for its regenerative abilities, its ability to recover following stroke appears to be limited. Most patients improve after their initial stroke, but few fully recover.
Axonal sprouting
About 87 percent of all strokes are ischemic, according to American Stroke Association. This means the brain's blood flow has been blocked, depriving it of oxygen and nutrients. That's when repair mechanisms like axonal sprouting become active in an attempt to overcome damage in the brain.
In axonal sprouting, healthy neurons send out new projections known as "sprouts," which reestablish connections affected by the stroke or form new ones. Before this study, the mechanism that triggers axonal sprouting was unknown.
For stroke patients, recovery involves the re-mapping of sensory and motor functions around the damaged cortical areas. Against this backdrop, Dr. Carmichael's team conducted analyses to compare the effects of GDF10 on genes related to stroke repair with those involved in development, learning and memory. Their tests revealed that GDF10 affected entirely different genes after the stroke, challenging the widely held belief that similar mechanisms affect both normal brain development and repair following injury.
It's unclear just what these findings mean for the future of stroke recovery, but they certainly present an intriguing avenue for future research into the condition. Of course, more stroke research is necessary to determine whether GDF10 may be a potential treatment.
By Darcy Lewis
