New Research Highlights Unexpected Role of Astrocytes in Spinal Cord Repair
Researchers at Cedars-Sinai have identified a biological repair process involving astrocytes – a major support cell in the central nervous system – that holds promise for new treatments for spinal cord injuries, stroke, and neurological diseases such as multiple sclerosis. The findings, published in in Nature, reveal that astrocytes located far from the site of injury play a critical role in promoting healing.
“Astrocytes are critical responders to disease and disorders of the central nervous system – the brain and spinal cord,” said neuroscientist Joshua Burda, PhD, assistant professor of Biomedical Sciences and Neurology at Cedars-Sinai and senior author of the study. “We discovered that astrocytes far from the site of an injury actually help drive spinal cord repair. Our research also uncovered a mechanism used by these unique astrocytes to signal the immune system to clean up debris resulting from the injury, which is a critical step in the tissue-healing process.”
Understanding the Spinal Cord’s Response to Injury
The spinal cord, a long bundle of nerve tissue extending from the brain down the back, is composed of gray matter – containing nerve cell bodies and astrocytes – and white matter, which consists of astrocytes and long nerve fibers that transmit signals. Astrocytes are essential for maintaining a stable environment for these signals to travel efficiently.
When the spinal cord is injured, nerve fibers are torn, potentially leading to paralysis and sensory disruption. This damage results in debris that triggers inflammation. Unlike in most tissues where inflammation remains localized, the spinal cord’s long nerve fibers allow damage and inflammation to spread beyond the initial injury site.
Lesion-Remote Astrocytes and the Immune System
The research team identified a specific type of astrocyte, termed “lesion-remote astrocytes” (LRAs), which play a key role in promoting repair. These LRAs were also found to exhibit the same process in spinal cord tissue from human patients. The study details how one subtype of LRA detects damage from a distance and initiates a response that supports recovery.
Specifically, one LRA subtype produces a protein called CCN1. This protein sends signals to immune cells known as microglia, which function as the central nervous system’s “garbage collectors.”
“One function of microglia is to serve as chief garbage collectors in the central nervous system,” Burda explained. “After tissue damage, they eat up pieces of nerve fiber debris – which are very fatty and can cause them to get a kind of indigestion. Our experiments showed that astrocyte CCN1 signals the microglia to change their metabolism so they can better digest all that fat.”
This improved debris removal may explain why some patients experience partial, spontaneous recovery after spinal cord injury. Researchers found that eliminating astrocyte-derived CCN1 significantly reduced healing. “If we remove astrocyte CCN1, the microglia eat, but they don’t digest. They call in more microglia, which also eat but don’t digest,” Burda said. “Big clusters of debris-filled microglia form, heightening inflammation up and down the spinal cord. And when that happens, the tissue doesn’t repair as well.”
Implications for Multiple Sclerosis and Beyond
Interestingly, scientists observed the same CCN1-related repair process in spinal cord samples from individuals with multiple sclerosis. This suggests that the fundamental repair principles identified in this study may be broadly applicable to injuries affecting both the brain and spinal cord.
“The role of astrocytes in central nervous system healing is remarkably understudied,” said David Underhill, PhD, chair of the Department of Biomedical Sciences. “This work strongly suggests that lesion-remote astrocytes offer a viable path for limiting chronic inflammation, enhancing functionally meaningful regeneration, and promoting neurological recovery after brain and spinal cord injury and in disease.”
Future Directions
Burda is now focused on developing strategies to harness the CCN1 pathway to enhance spinal cord healing. His team is also investigating how astrocyte CCN1 may influence inflammatory neurodegenerative diseases and the aging process. The research was supported by grants from the US National Institutes of Health (NIH), the Paralyzed Veterans Research Foundation of America, Wings for Life, and other organizations.
