Effects of Acute Probenecid Administration on Histopathological and Functional Outcomes after Spinal Cord Injury in Rats
Spinal cord injury (SCI) triggers an inflammatory response that is partially mediated by the inflammasome and the production of pro-inflammatory cytokines. We have previously shown that pannexin-1 is involved in the activation of the inflammasome, and that probenecid inhibits this caspase-1-mediated...
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Mary Ann Liebert
2025-01-01
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| Series: | Neurotrauma Reports |
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| Online Access: | https://www.liebertpub.com/doi/10.1089/neur.2025.0044 |
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| author | Toru Asari Sunao Tanaka Damien D. Pearse Juan Pablo de Rivero Vaccari Toshitada Sawada Yasuyuki Ishibashi Robert W. Keane W. Dalton Dietrich |
| author_facet | Toru Asari Sunao Tanaka Damien D. Pearse Juan Pablo de Rivero Vaccari Toshitada Sawada Yasuyuki Ishibashi Robert W. Keane W. Dalton Dietrich |
| author_sort | Toru Asari |
| collection | DOAJ |
| description | Spinal cord injury (SCI) triggers an inflammatory response that is partially mediated by the inflammasome and the production of pro-inflammatory cytokines. We have previously shown that pannexin-1 is involved in the activation of the inflammasome, and that probenecid inhibits this caspase-1-mediated inflammatory process. In this study, we employed an in vivo model of contusive SCI to investigate the therapeutic effect of acute probenecid administration on histopathological and functional outcomes following SCI. Adult female Fischer rats (n = 46) underwent moderate thoracic SCI produced by dropping a 10 g weight from a height of 12.5 mm onto the exposed cord at T9, assigned three different groups, PBS administration group, and 1, 10, 100 mg/kg probenecid group, those were injected subcutaneously 15 min and 12 h after SCI. The sham group (n = 11) was the group that only had a laminectomy and did not have SCI. Histopathological analysis by Luxol Fast Blue/hematoxylin and eosin staining revealed that the penumbra volume was significantly reduced in the probenecid 100 mg/kg group compared with the PBS group. CatWalk gait analysis was performed at 7 weeks after SCI, which showed significant differences in coordination between the PBS and the probenecid 100 mg/kg-treated groups. Acute administration of probenecid after SCI resulted in the preservation of penumbra formation and coordination function in a thoracic SCI rat model. This report suggests that probenecid, an inhibitor of pannexin-1, has the potential to prevent secondary injury after SCI and improve outcomes following SCI. |
| format | Article |
| id | doaj-art-16a0dcaa3f634a8f91a15b0bbf0c6ca7 |
| institution | DOAJ |
| issn | 2689-288X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Mary Ann Liebert |
| record_format | Article |
| series | Neurotrauma Reports |
| spelling | doaj-art-16a0dcaa3f634a8f91a15b0bbf0c6ca72025-08-20T03:12:20ZengMary Ann LiebertNeurotrauma Reports2689-288X2025-01-016142543410.1089/neur.2025.0044Effects of Acute Probenecid Administration on Histopathological and Functional Outcomes after Spinal Cord Injury in RatsToru Asari0Sunao Tanaka1Damien D. Pearse2Juan Pablo de Rivero Vaccari3Toshitada Sawada4Yasuyuki Ishibashi5Robert W. Keane6W. Dalton Dietrich7Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, USA.Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, USA.Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, USA.Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, USA.Department of Orthopaedic Surgery, Takaoka Seishikai Hospital, Takaoka, Japan.Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, USA.Spinal cord injury (SCI) triggers an inflammatory response that is partially mediated by the inflammasome and the production of pro-inflammatory cytokines. We have previously shown that pannexin-1 is involved in the activation of the inflammasome, and that probenecid inhibits this caspase-1-mediated inflammatory process. In this study, we employed an in vivo model of contusive SCI to investigate the therapeutic effect of acute probenecid administration on histopathological and functional outcomes following SCI. Adult female Fischer rats (n = 46) underwent moderate thoracic SCI produced by dropping a 10 g weight from a height of 12.5 mm onto the exposed cord at T9, assigned three different groups, PBS administration group, and 1, 10, 100 mg/kg probenecid group, those were injected subcutaneously 15 min and 12 h after SCI. The sham group (n = 11) was the group that only had a laminectomy and did not have SCI. Histopathological analysis by Luxol Fast Blue/hematoxylin and eosin staining revealed that the penumbra volume was significantly reduced in the probenecid 100 mg/kg group compared with the PBS group. CatWalk gait analysis was performed at 7 weeks after SCI, which showed significant differences in coordination between the PBS and the probenecid 100 mg/kg-treated groups. Acute administration of probenecid after SCI resulted in the preservation of penumbra formation and coordination function in a thoracic SCI rat model. This report suggests that probenecid, an inhibitor of pannexin-1, has the potential to prevent secondary injury after SCI and improve outcomes following SCI.https://www.liebertpub.com/doi/10.1089/neur.2025.0044inflammasomeprobenecidPannexin-1spinal cord injury |
| spellingShingle | Toru Asari Sunao Tanaka Damien D. Pearse Juan Pablo de Rivero Vaccari Toshitada Sawada Yasuyuki Ishibashi Robert W. Keane W. Dalton Dietrich Effects of Acute Probenecid Administration on Histopathological and Functional Outcomes after Spinal Cord Injury in Rats Neurotrauma Reports inflammasome probenecid Pannexin-1 spinal cord injury |
| title | Effects of Acute Probenecid Administration on Histopathological and Functional Outcomes after Spinal Cord Injury in Rats |
| title_full | Effects of Acute Probenecid Administration on Histopathological and Functional Outcomes after Spinal Cord Injury in Rats |
| title_fullStr | Effects of Acute Probenecid Administration on Histopathological and Functional Outcomes after Spinal Cord Injury in Rats |
| title_full_unstemmed | Effects of Acute Probenecid Administration on Histopathological and Functional Outcomes after Spinal Cord Injury in Rats |
| title_short | Effects of Acute Probenecid Administration on Histopathological and Functional Outcomes after Spinal Cord Injury in Rats |
| title_sort | effects of acute probenecid administration on histopathological and functional outcomes after spinal cord injury in rats |
| topic | inflammasome probenecid Pannexin-1 spinal cord injury |
| url | https://www.liebertpub.com/doi/10.1089/neur.2025.0044 |
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