Reversing brain injury in newborns and adults

April 16, 2018, Oregon Health & Science University
Credit: CC0 Public Domain

Children and adults diagnosed with brain conditions such as cerebral palsy, multiple sclerosis and dementia may be one step closer to obtaining new treatments that could help to restore normal function.

Researchers at OHSU in Portland, Oregon, have identified a new molecule within the brain's white matter that blocks the organ's ability to repair itself following injury.

"By preventing the production of this molecule, we can create an effective pathway to allow the brain to continue its regenerative process. This may help to limit long-term physical and mental disability associated with devastating neurological conditions," said Stephen Back, M.D., Ph.D., Clyde and Elda Munson Professor of Pediatric Research and Pediatrics, OHSU School of Medicine, OHSU Doernbecher Children's Hospital.

The results of the study published today in the Journal of Clinical Investigation.

Discovering the 'bad actor'

Hyaluronic acid, one of the largest molecules in the human body, fills spaces between cells, lubricates joints and accumulates in lesions—or abnormalities—within the brain's white matter. This build-up is known to halt the brain's repair process, also called myelination, causing dramatic disruption to overall brain function.

To better understand the repair roadblocks created by , Back and colleagues showed that while brain lesions break down these large into a broad range of sizes, only one specific-sized fragment will selectively block the development of brain cells needed to promote repair.

By tracing the molecular pathway that prevented brain repair, the researchers discovered that the specialized fragment also activated a protein called FoxO3, which blocked key genes that turn on the . Remarkably, this road block did not allow other strong repair signals to detour around it.

"We've identified a molecule that plays the role of the 'bad actor.' In essence, it hijacked the molecular machinery of the immune system and repurposed it to shut down brain repair after injury," said Back. "And, while this new molecule may not be easily detected in the brain, FoxO3 may serve as a viable biomarker for identifying its detrimental effects in the white matter, creating an opportunity for further research and targeted therapies to fully reverse the impacts of brain injury for people of all ages."

What's next?

"For many years, researchers and clinicians alike have struggled to understand and effectively treat the significant physical disabilities associated with white matter injury," said study co-author Larry Sherman, Ph.D., professor, Division of Neuroscience, Oregon National Primate Research Center; and professor of cell, developmental and cancer biology, OHSU School of Medicine. "This discovery means that we now have the potential to start looking at multiple ways of intervening to promote that weren't available to use before."

One promising direction is the development of new pharmaceuticals that can prevent the generation of hyaluronic acid fragments. Additionally, says Back, new understanding of the 's pathway to may provide with new insights that will positively impact therapies such as stem cell transplantation.

Explore further: Researchers discover potential way to repair brain damage in multiple sclerosis

More information: A TLR/AKT/FoxO3 immune tolerance–like pathway disrupts the repair capacity of oligodendrocyte progenitors, J Clin Invest. doi.org/10.1172/JCI94158 , www.jci.org/articles/view/94158

Related Stories

Researchers discover potential way to repair brain damage in multiple sclerosis

October 31, 2012
Researchers at Oregon Health & Science University have discovered that blocking a certain enzyme in the brain can help repair the brain damage associated with multiple sclerosis and a range of other neurological disorders.

Scientists watch the brain's lining heal after a head injury

April 16, 2018
Following head injury, the protective lining that surrounds the brain may get a little help from its friends: immune cells that spring into action to assist with repairs. In a new study, scientists from the National Institutes ...

Lack of oxygen, not blood flow, delays brain maturation in preterm infants

November 3, 2017
Premature infants are at risk for a broad spectrum of life-long cognitive and learning disabilities. Historically, these conditions were believed to be the result of lack of blood flow to the brain. However, a new study published ...

Blood-clotting protein prevents repair in the brain

November 2, 2017
Picture a bare wire, without its regular plastic coating. It's exposed to the elements and risks being degraded. And, without insulation, it may not conduct electricity as well as a coated wire. Now, imagine this wire is ...

Study identifies protein to repair damaged brain tissue in MS

February 7, 2014
Vittorio Gallo, PhD, Director of the Center for Neuroscience Research at Children's National Health System, and other researchers have found a "potentially novel therapeutic target" to reduce the rate of deterioration and ...

Recommended for you

Neural inflammation plays critical role in stress-induced depression

July 19, 2018
A group of Japanese researchers has discovered that neural inflammation caused by the innate immune system plays an unexpectedly important role in stress-induced depression. This insight could potentially lead to the development ...

Paralyzed mice with spinal cord injury made to walk again

July 19, 2018
Most people with spinal cord injury are paralyzed from the injury site down, even when the cord isn't completely severed. Why don't the spared portions of the spinal cord keep working? Researchers at Boston Children's Hospital ...

Understanding the neuroscience of binge drinking

July 19, 2018
A new study from researchers at Columbia University Irving Medical Center found that binge drinking impairs working memory in the adolescent brain. The study, in mice, explains why teenagers who binge drink are 15 times more ...

Scientists uncover the role of a protein in production and survival of myelin-forming cells

July 19, 2018
The nervous system is a complex organ that relies on a variety of biological players to ensure daily function of the human body. Myelin—a membrane produced by specialized glial cells—plays a critical role in protecting ...

Neurons can carry more than one signal at a time

July 18, 2018
Back in the early days of telecommunications, engineers devised a clever way to send multiple telephone calls through a single wire at the same time. Called time-division multiplexing, this technique rapidly switches between ...

Researchers solve mystery of how ALL enters the central nervous system

July 18, 2018
A deadly feature of acute lymphoblastic leukemia (ALL) is its invasion of the central nervous system.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.