Astrocytes Key to Spinal Cord Repair & Potential MS, Stroke Treatments | Cedars-Sinai Study

Scientists at Cedars-Sinai Medical Center have discovered a previously unknown repair mechanism in the spinal cord that offers potential new avenues for treating paralysis, stroke, and neurological diseases including multiple sclerosis. The findings, published in the journal Nature, center on the role of specialized support cells called astrocytes.

“Astrocytes are critical responders to disease and disorders of the central nervous system – the brain and spinal cord,” explained Joshua Burda, PhD, assistant professor of Biomedical Sciences and Neurology at Cedars-Sinai, and the study’s senior author. “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.”

The research team designated these responsive astrocytes as “lesion-remote astrocytes,” or LRAs. They identified distinct subtypes within the LRA population, with one subtype playing a particularly crucial role in initiating the repair process. This subtype produces a protein called CCN1, which acts as a signal to immune cells known as microglia.

Microglia function as the central nervous system’s primary “garbage collectors,” clearing away damaged nerve tissue debris after injury. However, this debris is rich in fats, which can overwhelm the microglia’s digestive capabilities. Burda’s team found that the CCN1 signal from LRAs alters the microglia’s metabolism, enabling them to more efficiently break down and remove the fatty debris.

“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,” Burda said. “Our experiments showed that astrocyte CCN1 signals the microglia to change their metabolism so they can better digest all that fat.”

Experiments conducted on mice with spinal cord injuries demonstrated the importance of this LRA-microglia interaction. Researchers observed similar activity in spinal cord tissue samples obtained from human patients. Blocking the CCN1 signal significantly hindered the healing process. Without CCN1, microglia were able to engulf the debris but unable to properly digest it, leading to a buildup of inflammatory material and impaired tissue repair.

“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 explained. “Considerable 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.”

The team’s investigation extended to spinal cord samples from individuals with multiple sclerosis, revealing the presence of the same CCN1-mediated repair process. This suggests that the underlying biological principles governing central nervous system repair may be broadly applicable to a range of neurological conditions.

David Underhill, PhD, chair of the Department of Biomedical Sciences at Cedars-Sinai, emphasized the significance of the findings. “The role of astrocytes in central nervous system healing is remarkably understudied,” he said. “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.”

Burda and his team are now focused on developing therapeutic strategies to leverage the CCN1 pathway to enhance spinal cord healing. They are also investigating the potential influence of astrocyte CCN1 on inflammatory neurodegenerative diseases and the aging process.