In the minutes and days after a person experiences a spinal cord injury, quick and early intervention is key to reducing a secondary injury — damage like inflammation and swelling, decreased blood flow and even cell death. While limiting secondary injury could improve a patient’s outcome, treatment is often difficult in real-world emergencies.
Researchers at the Indiana University School of Medicine have discovered that a Food and Drug Administration-approved drug, dexmedetomidine, which is widely used as a sedative in hospitals, can be repurposed as an early neuroprotective therapy after spinal cord injury.
"When given shortly after injury, dexmedetomidine rapidly induces a controlled and sustained lowering of body temperature — called pharmacological hypothermia," said Lingxiao Deng, MD, PhD, assistant professor of neurological surgery. "It not only enables faster and more reliable cooling, but it has its own intrinsic neuroprotective and anti‑inflammatory effects."
The study, published recently in The Journal of Neuroscience, found that a single dose of dexmedetomidine administered in spinal cord injury animal models rapidly lowered body temperature, preserved spinal cord tissue, reduced inflammation and significantly improved both walking and bladder function — outperforming standard physical cooling methods. Deng led the study along with Xiang Gao, PhD, assistant professor of neurological surgery. Aytak Khabbaz, MD, postdoctoral fellow in the Deng lab, and Lilesh Kumar Pradhan, PhD, postdoctoral fellow in the Gao lab, were the two co-first authors of the paper.
"This study represents a conceptual shift in how we think about treating acute injuries to the brain and spinal cord," Deng said. "By combining drug‑induced hypothermia with direct cellular protection, we introduce a dual‑action, immediately translatable strategy that could be applied not only to spinal cord injury but potentially other forms of neurotrauma, such as traumatic brain injury and stroke — conditions where early intervention is critical and treatment options remain limited."
Therapeutic hypothermia has for decades been known to provide neuroprotection in neurotrauma conditions, like traumatic brain injury and stroke, Deng said. Its efficacy in spinal cord injury, however, has remained challenging, and neither clinical nor preclinical studies have previously demonstrated a benefit for autonomic outcomes such as bladder function.
"This is the first study to show that therapeutic hypothermia can significantly improve bladder function after spinal cord injury," Deng said. "This novel strategy enables extraordinarily early intervention with multidimensional neuroprotective effects during the "golden window," when secondary injury is actively unfolding — something traditional hypothermia approaches have struggled to achieve."
Building upon these findings, the research team is working toward developing a clinical trial through the Department of Neurological Surgery to test dexmedetomidine-based early hypothermia and neuroprotection in patients with acute spinal cord injury.
Deng and Gao are both members of the Indiana Spinal Cord and Brain Injury Research Group at Stark Neurosciences Research Institute. Deng’s lab focuses on spinal cord injury research while Gao’s lab investigates traumatic brain injuries.
Gao’s team previously found that dexmedetomidine has intrinsic neuroprotective effects in traumatic brain injury models, a discovery that led Deng and Gao to the start their collaborative investigation into whether combining the drug with hypothermia could help overcome the longstanding clinical barrier to apply cooling strategies in spinal cord injuries.
"By combining Dr. Gao’s strength in molecular and histopathological analysis with my lab's expertise in spinal cord injury modeling and functional outcome evaluation, we were able to rigorously test a concept that bridges basic mechanisms with translational relevance — ultimately leading to this study," Deng said.
In addition to initiating a clinical trial, Deng said the team is refining dosing strategies, evaluating safety windows and extending their studies to clinically relevant injury severities. Their goal is to develop a treatment protocol that can be safely and effectively integrated into current trauma‑care systems.
