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Effects of Acute Probenecid Administration on Histopathological and Functional Outcomes after Spinal Cord Injury in
Toru Asari1,2, Sunao Tanaka1,2, Damien D Pearse1
1Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, USA.
Neurotrauma Reports
|July 23, 2025
Summary
Probenecid, an inhibitor of pannexin-1, reduces secondary injury and improves functional recovery after spinal cord injury (SCI) in rats. This treatment preserves tissue and enhances coordination, suggesting therapeutic potential for SCI outcomes.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Spinal cord injury (SCI) initiates an inflammatory response involving the inflammasome and pro-inflammatory cytokines.
- Pannexin-1 plays a role in inflammasome activation, and probenecid inhibits this caspase-1-mediated process.
Purpose of the Study:
- To investigate the therapeutic potential of acute probenecid administration on histopathological and functional outcomes in an in vivo model of contusive spinal cord injury.
Main Methods:
- Adult female Fischer rats underwent moderate thoracic SCI and were treated with PBS or varying doses of probenecid (1, 10, 100 mg/kg) subcutaneously at 15 min and 12 h post-injury.
- Histopathological analysis (Luxol Fast Blue/hematoxylin and eosin) and CatWalk gait analysis were performed to assess outcomes.
Main Results:
- Probenecid at 100 mg/kg significantly reduced penumbra volume compared to the PBS group.
- Gait analysis at 7 weeks post-SCI revealed significant differences in coordination between the probenecid 100 mg/kg and PBS groups.
Conclusions:
- Acute probenecid administration after SCI preserves penumbra formation and improves coordination function in a thoracic SCI rat model.
- Probenecid, as a pannexin-1 inhibitor, shows potential in preventing secondary injury and improving outcomes following spinal cord injury.
