Groundbreaking research from the University of Kentucky has earned a spot on the cover of the prestigious Journal of Neuroscience, highlighting a major challenge in spinal cord injury recovery.
Andrew Stewart, Ph.D., assistant professor at the Spinal Cord and Brain Injury Research Center (SCoBIRC) in the Department of Neuroscience in the UK College of Medicine, is investigating why treatments that could help repair and regenerate the damaged spinal cord stop working shortly after the injury has occurred. So far, scientists have a limited understanding of why these treatments fail in chronic cases.
"The initial injury is only one part of the problem. It's the inflammation and scaring, that peaks a week or two after injury, that disrupts healing," said Stewart. "Inflammation in the spinal cord behaves a lot like inflammation in the skin - except the skin heals, while the spinal cord doesn't. Inflammation can cause more damage over time. Unlike in the skin, these inflammatory cells don't go away. They stick around for life, making recovery even harder."
Stewart began this work in 2020 as a postdoctoral student in John Gensel's UK lab. Alongside Gensel and fellow researchers Chris Bosse-Joseph, Reena Kumari, William M. Bailey, Kennedy A. Park and Victoria K. Slone, he investigated long-term inflammation in spinal cord injuries and tested whether PLX-5622 (PLX), a drug designed to target specific immune cells, could reverse it.
"In animal models, the treatment worked exactly as we hoped - it dramatically reduced the number of inflammatory cells at the injury site," said Stewart. "The real surprise came when we stopped the treatment. The inflammatory cells quickly returned to the exact same high levels as before. That suggests the body isn't just passively holding onto these cells - something is actively keeping inflammation high."
This unexpected finding led to another important discovery. Stewart and his team set out to determine whether reducing inflammation would help nerve fibers, or axons, regenerate.
"It did but only for one specific type of sensory nerve fiber. The nerve cells we were actually trying to regenerate didn't respond the way we expected," said Stewart. "That led us to a new question: why did these sensory nerves grow back, but not the others? If we can figure that out, we might be able to apply the same principle to other nerve cells and improve treatments for spinal cord injuries."
Stewart says these findings featured in this publication have reshaped how researchers think about chronic inflammation in spinal cord injuries.
"Our discoveries have opened up exciting new research directions. We now have a better understanding of how chronic inflammation influences recovery, and we're exploring new ways to promote healing in the spinal cord."
The project, titled "Nonresolving Neuroinflammation Regulates Axon Regeneration in Chronic Spinal Cord Injury," was featured in the Journal of Neuroscience (Jan. 2025) and funded by the Wings for Life Foundation and the Craig H. Neilsen Foundation, with additional support from the Neuroscience Research Priority Area, the Spinal Cord and Brain Injury Research Center Endowed Chair #5, the University of Kentucky's Light Microscopy Core and the Genomics Core Laboratory.
Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Numbers R01NS116068 and F32NS111241. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
