Restoring Spinal Cord Connections

Health Editor’s Note:  A neuron is a nerve cell which transmits, processes, and receives information through chemical and electrical signals which cross between synapses or gaps between the neurons. Neurons make up the central nervous system (spinal cord and brain) and the peripheral nervous system which is made up of the somatic nervous system (voluntary control of body movements through muscles) and autonomic nervous system (influences the function of internal organs.)

Neurons are futher specialized into sensory neurons which react to touch, light, sound, and other stimuli, and motor neurons which control muscle contractions and output of the glands and receive their signals from the brain and spinal cord. There are also interneurons which connect neurons within the same region of the spinal cord or brain.

Mostly neurons are made by special types of stem cells during the development of the brain and also during childhood.  Adult brain neurons do not usually undergo cell division (making more neurons) thus, damage to neurons is viewed as being permanent and not repairable by the body.  There is some evidence that neurons may generate in the hippocampus and olfactory bulb, but not in the spinal cord or other areas of the brain.

Damage of neurons in the spinal cord, depending upon the severity of the damage, can paralyze a person below the body area that the spinal cord controls.  Damage to the upper portions of the spinal cord will even create a paralyzing of the breathing mechanism. A person would have to live on a respirator for the remainder of his or her life. If the key can be found to successfully cause neurons to regenerate, those who have had damage to the spinal cord, would be able to continue to move about on their two legs, instead of in a wheel chair. 

Causing the damaged neuron to be able to reset/repair itself is the key and would change countless lives. If spinal cord injuries can be repaired people who suffer blows to the spinal cord during car accidents, falls, bombings, etc. would be able to repair themselves and lead normal lives. Since the brain also is made of neurons, if the key can be found for turning on the “make new neurons action” neurons in the brain that are damaged by strokes, head injuries, etc. would also be able to repair themselves. In my opinion, this is some research that should move forward as quickly as possible..Carol

Study provides an early recipe for rewiring spinal cords

NIH-funded preclinical results suggest returning nerve cells to a younger state could aid in repair.

For many years, researchers have thought that the scar that forms after a spinal cord injury actively prevents damaged neurons from regrowing. In a study of rodents, scientists supported by the National Institutes of Health showed they could overcome this barrier and reconnect severed spinal cord nerves by turning back the neurons’ clocks to put them into an early growth state. Once this occurs, neurons could be induced to regrow across the scarred tissue. The research was supported by the National Institute of Neurological Disorders and Stroke (NINDS), part of NIH.

“For decades researchers have been trying to make severed neurons regrow across a spinal cord injury and reconnect with neurons on the other side. This study suggests that may require manipulating three key growth processes,” said Lyn Jakeman, Ph.D., program director, NINDS. “These insights are important for understanding the mechanisms of injury and regeneration that may one day be applied to develop potential treatments for spinal cord injury.”

Neurons send signals to each other through long projections called axons. When the spinal cord is injured, many of these axons are severed, leading to a loss of sensation and/or paralysis below the injury site. In response, a scar forms within the damaged tissue, and while the axons may briefly attempt to regrow, this process is unsuccessful. Because these connections between neurons are made initially as the body is developing, researchers have sought to restore those developmental conditions to potentially help the damaged cord heal.

“There are several growth patterns in the spinal cord that shut down after development,” said Michael V. Sofroniew, M.D., Ph.D., professor at the Brain Research Institute at UCLA and senior author of the study published in Nature. “We wanted to see if we could reactivate those patterns following injury and whether that would lead to regrowth of the axons.”

Using both mouse and rat spinal cord injury models, the researchers from UCLA and their collaborators at Harvard Medical School, Boston, and the Swiss Federal Institute of Technology, Lausanne, Switzerland, looked at three components of the regrowth process.

First, they tried to genetically turn back the neurons’ clock by reactivating the growth program that produced the original connections, specifically neurons that look like they are trying to regrow. While not active in adults, the neurons still carry the program used during early growth. By injecting viruses containing genes related to this program, the researchers were able to revert spinal cord neurons back to a state where axon growth could occur.

Second, the new axons needed to travel through the damaged tissue. Normally, growing axons move along highways paved with molecules that are not found in the scar tissue. After injecting the injury site with a gel containing a combination of growth-promoting proteins, the scientists saw an increase in axon-supportive molecules, effectively providing a “road” across the injury.

Finally, the growing axons needed to exit the injury site and find targets. During development, neurons release proteins called chemoattractants that axons home in on. To mimic this, the researchers injected chemoattractant proteins in a trail beyond the injury site and saw that these “chemical breadcrumbs” successfully led axons to grow completely through the injury site.

When any of the three treatments — viral activation of the growth program, formation of the path for axon travel, and the addition of chemoattractants — were not provided, minimal, if any regrowth was seen.  In contrast, when all three were used in the order described, the neurons grew robustly. Tens or hundreds of axons traveled across the scar and reconnected with neurons on the other side.

Although their results suggest that the new connections could conduct electrical signals across the injury, the rodents could not move any better. However, Dr. Sofroniew emphasized that this was not unexpected.

“We would expect that these regrown axons would behave very much like the new axons we see in development,” he explained. “Much like a newborn must learn to walk, these newly formed circuits will probably require training before functional recovery can be seen.”

Spinal cord trauma affects roughly 12,500 people in the United States each year, and an estimated 276,000 individuals in the U.S. currently live with the long-term effects of spinal cord injury. The goal of research into spinal cord injury is to restore connections severed by the injury to provide functional recovery.

Dr. Sofroniew and his colleagues are now looking to continue to refine their understanding of the mechanisms involved in axon regeneration and to determine how newly wired circuits can best be retrained to restore movement.

This work was supported by NIH grants (NS084030, NS096858, NS096294, NS062691), the Dr. Miriam and Sheldon G. Adelson Medical Foundation, the International Foundation for Research in Paraplegia, Craig H. Neilsen Foundation, European Research Council, Swiss National Science Foundation, and Wings for Life.

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

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 www.nih.gov.

Reference

Anderson MA et al. Required growth facilitators propel axon regeneration across complete spinal cord injury. Nature. August 29, 2018. DOI: 10.1038/s41586-018-0467-6

Study provides an early recipe for rewiring spinal cords

NIH-funded preclinical results suggest returning nerve cells to a younger state could aid in repair.

For many years, researchers have thought that the scar that forms after a spinal cord injury actively prevents damaged neurons from regrowing. In a study of rodents, scientists supported by the National Institutes of Health showed they could overcome this barrier and reconnect severed spinal cord nerves by turning back the neurons’ clocks to put them into an early growth state. Once this occurs, neurons could be induced to regrow across the scarred tissue. The research was supported by the National Institute of Neurological Disorders and Stroke (NINDS), part of NIH.

“For decades researchers have been trying to make severed neurons regrow across a spinal cord injury and reconnect with neurons on the other side. This study suggests that may require manipulating three key growth processes,” said Lyn Jakeman, Ph.D., program director, NINDS. “These insights are important for understanding the mechanisms of injury and regeneration that may one day be applied to develop potential treatments for spinal cord injury.”

Neurons send signals to each other through long projections called axons. When the spinal cord is injured, many of these axons are severed, leading to a loss of sensation and/or paralysis below the injury site. In response, a scar forms within the damaged tissue, and while the axons may briefly attempt to regrow, this process is unsuccessful. Because these connections between neurons are made initially as the body is developing, researchers have sought to restore those developmental conditions to potentially help the damaged cord heal.

“There are several growth patterns in the spinal cord that shut down after development,” said Michael V. Sofroniew, M.D., Ph.D., professor at the Brain Research Institute at UCLA and senior author of the study published in Nature. “We wanted to see if we could reactivate those patterns following injury and whether that would lead to regrowth of the axons.”

Using both mouse and rat spinal cord injury models, the researchers from UCLA and their collaborators at Harvard Medical School, Boston, and the Swiss Federal Institute of Technology, Lausanne, Switzerland, looked at three components of the regrowth process.

First, they tried to genetically turn back the neurons’ clock by reactivating the growth program that produced the original connections, specifically neurons that look like they are trying to regrow. While not active in adults, the neurons still carry the program used during early growth. By injecting viruses containing genes related to this program, the researchers were able to revert spinal cord neurons back to a state where axon growth could occur.

Second, the new axons needed to travel through the damaged tissue. Normally, growing axons move along highways paved with molecules that are not found in the scar tissue. After injecting the injury site with a gel containing a combination of growth-promoting proteins, the scientists saw an increase in axon-supportive molecules, effectively providing a “road” across the injury.

Finally, the growing axons needed to exit the injury site and find targets. During development, neurons release proteins called chemoattractants that axons home in on. To mimic this, the researchers injected chemoattractant proteins in a trail beyond the injury site and saw that these “chemical breadcrumbs” successfully led axons to grow completely through the injury site.

When any of the three treatments — viral activation of the growth program, formation of the path for axon travel, and the addition of chemoattractants — were not provided, minimal, if any regrowth was seen.  In contrast, when all three were used in the order described, the neurons grew robustly. Tens or hundreds of axons traveled across the scar and reconnected with neurons on the other side.

Although their results suggest that the new connections could conduct electrical signals across the injury, the rodents could not move any better. However, Dr. Sofroniew emphasized that this was not unexpected.

“We would expect that these regrown axons would behave very much like the new axons we see in development,” he explained. “Much like a newborn must learn to walk, these newly formed circuits will probably require training before functional recovery can be seen.”

Spinal cord trauma affects roughly 12,500 people in the United States each year, and an estimated 276,000 individuals in the U.S. currently live with the long-term effects of spinal cord injury. The goal of research into spinal cord injury is to restore connections severed by the injury to provide functional recovery.

Dr. Sofroniew and his colleagues are now looking to continue to refine their understanding of the mechanisms involved in axon regeneration and to determine how newly wired circuits can best be retrained to restore movement.

This work was supported by NIH grants (NS084030, NS096858, NS096294, NS062691), the Dr. Miriam and Sheldon G. Adelson Medical Foundation, the International Foundation for Research in Paraplegia, Craig H. Neilsen Foundation, European Research Council, Swiss National Science Foundation, and Wings for Life.

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

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 www.nih.gov.

Reference

Anderson MA et al. Required growth facilitators propel axon regeneration across complete spinal cord injury. Nature. August 29, 2018. DOI: 10.1038/s41586-018-0467-6

Carol Duff, MSN, BA, RN

Carol graduated from Riverside White Cross School of Nursing in Columbus, Ohio and received her diploma as a registered nurse. She attended Bowling Green State University where she received a Bachelor of Arts Degree in History and Literature. She attended the University of Toledo, College of Nursing, and received a Master’s of Nursing Science Degree as an Educator.

She has traveled extensively, is a photographer, and writes on medical issues. Carol has three children RJ, Katherine, and Stephen – one daughter-in-law; Katie – two granddaughters; Isabella Marianna and Zoe Olivia – and one grandson, Alexander Paul. She also shares her life with her husband Gordon Duff, many cats, and two rescues.

• Carol’s Archives 2009-2013