Groundbreaking research reveals why spinal cords don't heal like other tissues and the promising new treatments on the horizon
Imagine suffering a cut on your skin and watching it never heal—remaining inflamed and painful for years. While this doesn't happen with our skin, it's exactly what occurs with spinal cord injuries. For decades, scientists have puzzled over why the spinal cord doesn't heal like other tissues in the body. Groundbreaking research from the University of Kentucky has now uncovered a surprising answer: chronic inflammation that never subsides. This discovery, featured on the cover of the Journal of Neuroscience, represents a paradigm shift in how we approach spinal cord injury treatment and offers new hope for millions living with paralysis worldwide 1 .
With approximately 17,000 new spinal cord injuries occurring annually in the United States alone, and hundreds of thousands globally, the personal, social, and economic impacts are staggering.
The implications of this research extend far beyond the laboratory. Until now, treatments have focused primarily on the initial injury, with limited success in restoring function. The Kentucky research team's insights into the persistent inflammatory response that follows injury may hold the key to unlocking recovery possibilities that were previously unimaginable.
Inflammation is typically our body's healing response—a complex biological process that eliminates harmful stimuli and initiates repair. When you injure your skin, inflammatory cells rush to the site, clear away debris, and then gradually dissipate as healing progresses. However, the spinal cord behaves fundamentally differently. According to Dr. Andrew Stewart, assistant professor at the University of Kentucky's Spinal Cord and Brain Injury Research Center, "Inflammation in the spinal cord behaves a lot like inflammation in the skin—except the skin heals, while the spinal cord doesn't" 1 .
Inflammatory cells arrive, clean debris, then dissipate as healing completes.
Inflammatory cells persist indefinitely, creating a hostile microenvironment.
This paradox has baffled scientists for years. The research reveals that unlike in the skin, inflammatory cells in the spinal cord don't go away after performing their initial functions. Instead, they persist indefinitely, creating a hostile microenvironment that actively prevents healing. These cells continue to release inflammatory molecules that damage delicate neural tissues and create physical and chemical barriers to regeneration 1 .
The chronic inflammation leads to another significant barrier: scar formation. While scarring occurs in all tissues as part of the healing process, spinal cord scars have unique properties that make them particularly problematic. The scar tissue contains molecules that actively inhibit axon regeneration, essentially creating a biochemical "stop sign" that prevents nerve fibers from reconnecting across the injury site. This scarring peaks within one to two weeks after the initial injury but establishes a permanent blockade that continues to disrupt healing indefinitely 1 .
The University of Kentucky research team, led by Dr. Stewart, began this work in 2020 as part of Dr. John Gensel's lab. They investigated long-term inflammation in spinal cord injuries and tested whether a drug called PLX-5622 (PLX)—designed to target specific immune cells—could reverse this persistent inflammation 1 .
In animal models, the treatment initially worked exactly as anticipated. "It dramatically reduced the number of inflammatory cells at the injury site," Stewart noted. However, the real surprise came when the treatment was stopped: "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" 1 .
The researchers then investigated whether reducing inflammation would help nerve fibers (axons) regenerate. Here, another surprise awaited them. The reduction in inflammation did help—but only for one specific type of sensory nerve fiber. The motor nerve cells they had hoped to regenerate didn't respond as expected 1 .
This selective regeneration presents both a challenge and an opportunity. By understanding why some nerves can regenerate when inflammation is reduced while others cannot, scientists may be able to develop targeted therapies that encourage comprehensive repair.
Researchers worked with animal models of spinal cord injury that accurately replicate the human condition's inflammatory response.
They administered PLX-5622, a drug that specifically targets and eliminates certain inflammatory cells called microglia and macrophages.
The drug was administered for a defined period, during which researchers monitored inflammatory cell levels.
After stopping the drug, researchers observed how quickly inflammatory cells returned to the injury site.
Using advanced microscopy and tracing techniques, the team evaluated whether reducing inflammation allowed different types of nerve fibers to regenerate 1 .
The results revealed several crucial insights about spinal cord injury recovery:
| Experimental Condition | Inflammatory Cell Count | Rate of Return After Drug Withdrawal |
|---|---|---|
| Pre-injury baseline | Normal levels | N/A |
| Post-injury (untreated) | High levels | N/A |
| During PLX treatment | Significantly reduced | N/A |
| 7 days after withdrawal | High levels | Rapid return |
| 14 days after withdrawal | High levels | Sustained at pre-treatment levels |
Source: University of Kentucky Research Data 1
The data demonstrated that while inflammation could be temporarily controlled, some underlying mechanism actively maintained inflammation at high levels regardless of treatment 1 .
| Nerve Fiber Type | Regeneration Response | Functional Recovery |
|---|---|---|
| Sensory nerves | Significant regeneration | Moderate improvement |
| Motor nerves | Minimal regeneration | Limited improvement |
| Proprioceptive nerves | Variable response | Mild improvement |
Source: University of Kentucky Research Data 1
The differential response between nerve types suggests that intrinsic factors within different neurons determine their regenerative capacity when inflammatory barriers are removed 1 .
| Reagent/Material | Function | Application in Research |
|---|---|---|
| PLX-5622 | Depletes microglia and macrophages | Studying inflammation role in regeneration |
| Antibodies (various) | Label specific cell types | Identification and tracking of inflammatory cells |
| Tracing dyes | Visualize nerve pathways | Assessing axon regeneration |
| Genetically modified animals | Study specific gene functions | Understanding molecular mechanisms |
| Cytokine arrays | Measure inflammatory molecules | Quantifying inflammation levels |
Modern spinal cord injury research employs sophisticated techniques including:
The University of Kentucky findings suggest that future treatments will likely require combination approaches that address multiple barriers simultaneously. These might include:
To prevent the establishment of chronic inflammation
That make the injury environment more permissive to regeneration
That actively encourage nerve fiber regeneration
That retrain neural circuits as regeneration occurs
Several promising technologies are advancing toward clinical application:
With embedded sensors that can track healing progress and deliver drugs directly to the injury site 4 .
That use electrical stimulation to enhance neural activity and promote recovery 4 .
That provide temporary support before gradually dissolving into the body 4 .
As we deepen our understanding of the intricate processes following spinal cord injury, treatments are becoming increasingly tailored to individual factors. These include:
The discovery of persistently active inflammation that maintains a hostile environment after spinal cord injury represents both a challenge and an opportunity. While the complexity of the problem is daunting, the University of Kentucky research has provided a crucial missing piece in the puzzle of why spinal cords don't heal 1 .
As Dr. Stewart notes, "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" 1 .
The road ahead will require collaboration across scientific disciplines—from immunology to neuroscience, from materials science to rehabilitation medicine. But with the hidden barrier of chronic inflammation now revealed, researchers can develop targeted strategies to overcome it, potentially restoring function and hope to those living with spinal cord injuries.
As we look toward the future, the combination of anti-inflammatory therapies with emerging technologies such as AI-powered neurostimulation, brain-computer interfaces, and regenerative medicine approaches suggests that we may be on the cusp of a transformative era in spinal cord injury treatment 4 . The once-impossible dream of walking after paralysis may soon be within scientific reach—thanks to our growing understanding of the persistent inflammation that has long prevented healing.
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