Nav: Home

New role identified for scars at the site of injured spinal cord

April 07, 2016

For decades, it was thought that scar-forming cells called astrocytes were responsible for blocking neuronal regrowth across the level of spinal cord injury, but recent findings challenge this idea. According to a new mouse study, astrocyte scars may actually be required for repair and regrowth following spinal cord injury. The research was funded by the National Institutes of Health, and published in Nature.

"At first, we were completely surprised when our early studies revealed that blocking scar formation after injury resulted in worse outcomes. Once we began looking specifically at regrowth, though, we became convinced that scars may actually be beneficial," said Michael V. Sofroniew, M.D., Ph.D., professor of neurobiology at the University of California, Los Angeles, and senior author of the study. "Our results suggest that scars may be a bridge and not a barrier towards developing better treatments for paralyzing spinal cord injuries."

Neurons communicate with one another by sending messages down long extensions called axons. When axons in the brain or spinal cord are severed, they do not grow back automatically. For example, damaged axons in the spinal cord can result in paralysis. When an injury occurs, astrocytes become activated and go to the injury site, along with cells from the immune system and form a scar. Scars have immediate benefits by decreasing inflammation at the injury site and preventing spread of tissue damage. However, long-term effects of the scars were thought to interfere with axon regrowth.

Using three different mouse models to examine the effect of astrocyte scars on axonal regrowth, Dr. Sofroniew's team was able to remove the scars or prevent them from forming after a spinal cord injury. The results revealed that without astrocyte scars, there was no regrowth.

In another experiment of spinal cord injury in mice, Dr. Sofroniew's team shuttled growth factors, specific molecules that stimulate axons to grow, to the injury site and discovered that there was robust regrowth through astrocyte scars. However, if the researchers prevented scar formation, the regrowth was significantly reduced.

Genetic analyses revealed that astrocytes as well as non-astrocyte cells released a variety of chemicals involved in regrowth at the injury site. In this mix, Dr. Sofroniew and his colleagues found molecules that block regrowth along with molecules that support it.

"This important research provides further evidence about the complexity of the brain and spinal cord's injury response. It shows that scar forming astrocytes support axon growth and suggests that therapeutics directed only at blocking these cells may not enhance regeneration of the injured spinal cord," said Lyn Jakeman, Ph.D., program director at the NIH's National Institute of Neurological Disorders and Stroke (NINDS), which provided funding for the study.

Trauma leads to spinal cord injury in about 12,500 people in the U.S. each year. It is estimated that 276,000 individuals in the country suffer from long-term effects of spinal cord injury. The ultimate goal of spinal cord injury research is to enable connections to develop that cross the level of injury and rewire the normal cord below.

Dr. Sofroniew and his colleagues are planning to investigate the exact mechanisms by which astrocytic scars support growth and ways to increase that response. "These preliminary findings established that axonal growth can occur in the presence of scars in mice. Eventually, we would like to see the regenerating axons grow far enough into healthy tissue to establish functional connections," said Dr. Sofroniew.
-end-
This work was supported by the NIH (NS057624, NS084030, NS060677, MH099559A, MH104069), the Dr. Miriam and Sheldon G. Adelson Medical Foundation and Wings for Life.

References:

Anderson MA et al. Astrocyte scar formation aids CNS axon regeneration. Nature. March 30, 2016. DOI: 10.1038/nature17623The NINDS is the nation's leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIH/National Institute of Neurological Disorders and Stroke

Related Spinal Cord Injury Articles:

Spinal cord injury patients face many serious health problems besides paralysis
Spinal cord patients are at higher risk for cardiovascular disease; pneumonia; life-threatening blood clots; bladder, bowel and sexual dysfunction; constipation and other gastrointestinal problems; pressure ulcers; and chronic pain, according to a report published in the journal Current Neurology and Neuroscience Reports.
A review on the therapeutic antibodies for spinal cord injury
Spinal cord injury (SCI) causes long-lasting damage in the spinal cord that leads to paraparesis, paraplegia, quadriplegia and other lifetime disabilities.
Health behaviors and management critical for spinal cord injury patients
U-M researcher is the co-editor of a two-part series of Topics in Spinal Cord Injury Rehabilitation focused on recent research studies about health behaviors and health management in individuals with spinal cord injury.
First clinical guidelines in Canada for pain following spinal cord injury
Researchers at Lawson Health Research Institute are the first in Canada to develop clinical practice guidelines for managing neuropathic pain with patients who have experienced a spinal cord injury.
Improving cell transplantation after spinal cord injury: When, where and how?
Spinal cord injuries are mostly caused by trauma, often incurred in road traffic or sporting incidents, often with devastating and irreversible consequences.
Discovery in roundworms may one day help humans with spinal cord injury and paralysis
A newly discovered pathway leading to the regeneration of central nervous system (CNS) brain cells (neurons) in a type of roundworm (C. elegans) sheds light on the adult human nervous system's ability to regenerate.
Protective effect of genetically modified cord blood on spinal cord injury in rats
Researchers of Kazan Federal University genetically modified cord blood which managed to increase tissue sparing and numbers of regenerated axons, reduce glial scar formation and promote behavioral recovery when transplanted immediately after a rat contusion spinal cord injury.
Aging diminishes spinal cord regeneration after injury
Researchers at University of California, San Diego School of Medicine and University of British Columbia (UBC) have determined that, in mice, age diminishes ability to regenerate axons, the brain's communication wires in the spinal cord.
Neuroscientific evidence that motivation promotes recovery after spinal cord injury
The research team led by Associate Professor Yukio Nishimura, National Institute for Physiological Sciences, Natural Institutes of Natural Sciences, found that the nucleus accumbens, that control motivation in the brain, activates the activity of the motor cortex of the brain, and then promotes recovery of motor function during the early stage of recovery after spinal cord injury.
New approach to spinal cord and brain injury research
Many an injury will heal, but the damaged spinal cord is notoriously recalcitrant.

Related Spinal Cord Injury Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...