Stroke pediatric research and clinical trials

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Otx2

Researchers have long sought a factor that can switch on the brain's ability to learn. Now, research led by Takao Hensch, PhD, of Boston Children's Hospital's FM Kirby Neurobiology Center and the Department of Neurology, has identified such a trigger. Called Otx2, it signals certain cells in the cortex (parvalbumin cells) to mature and initiate a critical period—a time window when the brain can readily rewire itself.

Surprisingly, the signal actually comes from the eye—but only after the eye has matured enough to provide good vision. Hensch speculates that other sensory organs may send similar signals to the brain as they mature, triggering critical periods for hearing, smell, etc.

Controlling the onset of plasticity could help in developmental disorders like autism, in which critical periods are thought to be mis-timed. "If the timing is off, the brain won't set up its circuits properly," says Hensch. Launching a critical period might also help people recover from stroke or brain injury, or learn languages or musical instruments as easily as young children, adds Hensch, who last fall won the highly competitive National Institutes of Health Director's Pioneer Award. He also speculates that Otx2 could be harnessed to carry drugs from the eye to the brain, envisioning eye drops for disorders like amblyopia (lazy eye). Sayaka Sugiyama, PhD, postdoctoral research fellow, was first author of the study, published in Cell on August 8.

mTOR

Because injured neurons in the brain or spinal cord can't grow back, damage from spinal cord injury, stroke or other forms of brain injury can't be repaired. But researchers led by Zhigang He, PhD, a neurologist at Boston Children's Hospital, have found a way to overcome natural inhibitory mechanisms that suppress regeneration, causing nerve fibers to re-grow vigorously.

Previous studies, including some from He's lab, tried to spur re-growth by removing inhibitory molecules from the neurons' environment. But this approach had only modest effects. He's team, collaborating with Children's neurologist Mustafa Sahin, MD, PhD, now shows that re-growth is primarily regulated from inside the cells. Using genetic techniques, the researchers deleted two of these internal regulators in mice with injured optic nerves. This allowed a growth pathway called mTOR—normally silenced in mature neurons—to become active again. As a result, up to 50 percent of injured neurons survived, versus about 20 percent in mice without the genetic deletions. Up to 10 percent of the mice showed significant, long-distance re-growth of nerve fibers.

He believes it may be possible to accomplish the same re-growth with drugs. But the next step is to determine whether the regenerating fibers can actually restore function.Kevin Park, PhD, Kai Liu, PhD, Yang Hu, PhD, and Patrice Smith, PhD, all of Neurobiology, were coauthors on the paper, published in Science on November 7.

Mst3b

Researchers at Children's have discovered an enzyme (known as Mst3b) that's essential for regenerating damaged nerves and may hold promise as a possible treatment for brain and spinal cord injury.

Inosine for spinal cord injury or stroke

Neuroscientist Dr Larry Benowitz has found that inosine, a naturally occurring cellular compound improves motor function after spinal cord injury or stroke and is pursuing potential treatments. 

MoyaMoya Disease

Neurosurgeon-in-chief, Michael Scott, MD, has pioneered an operation that improves oxygenation of the brain and arrests Moyamoya disease.  He hopes his research will lead to ways of predicting strokes and stimulating blood vessel growth so patients can recover more quickly or avoid stroke altogether.

Sickle Cell Anemia Risk

Researchers at Children's have developed a novel approach to predicting the risk of stroke in sickle cell anemia patients by looking at genetic variations.

STROKE AND MOTOR FUNCTION

Larry Benowitz, PhD, of the Boston Children's Department of Neurosurgery lead a study using molecular therapies to promote the growth of new circuits in nerves in rats. This study could lead to molecular treatment for strokes in humans. Learn more about this exciting research in the Boston Children’s newsroom.

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- Sandra L. Fenwick, President and CEO

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