Groundbreaking research from the University of Kentucky has earned a spot on the cover of the prestigious , highlighting a major challenge in spinal cord injury recovery.
Andrew Stewart, PhD, assistant professor at the Spinal Cord and Brain Injury Research Center (SCoBIRC) in the Department of Neuroscience in the 好色先生 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.
鈥淭he initial injury is only one part of the problem. It鈥檚 the inflammation and scaring, that peaks a week or two after injury, that disrupts healing,鈥 said Stewart. 鈥淚nflammation in the spinal cord behaves a lot like inflammation in the skin 鈥 except the skin heals, while the spinal cord doesn鈥檛. Inflammation can cause more damage over time. Unlike in the skin, these inflammatory cells don鈥檛 go away. They stick around for life, making recovery even harder.鈥
Stewart began this work in 2020 as a postdoctoral student in John Gensel鈥檚 好色先生 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.
鈥淚n animal models, the treatment worked exactly as we hoped 鈥 it dramatically reduced the number of inflammatory cells at the injury site,鈥 said Stewart. 鈥淭he 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鈥檛 just passively holding onto these cells 鈥 something is actively keeping inflammation high.鈥
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.
鈥淚t did but only for one specific type of sensory nerve fiber. The nerve cells we were actually trying to regenerate didn鈥檛 respond the way we expected,鈥 said Stewart. 鈥淭hat 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.鈥
Stewart says these findings featured in this publication have reshaped how researchers think about chronic inflammation in spinal cord injuries.
鈥淥ur discoveries have opened up exciting new research directions. We now have a better understanding of how chronic inflammation influences recovery, and we鈥檙e exploring new ways to promote healing in the spinal cord.鈥
The project, titled 鈥淣onresolving Neuroinflammation Regulates Axon Regeneration in Chronic Spinal Cord Injury,鈥 was featured in the 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鈥檚 Light Microscopy Core and the Genomics Core Laboratory.