Cross-species comparisons between pigs and mice reveal conserved sex-specific intraspinal inflammatory responses after spinal cord injury
Abstract Objective Therapeutic translation is challenging in spinal cord injury (SCI) and large animal models with high clinical relevance may accelerate therapeutic development. Pigs have important anatomical and physiological similarities to humans. Intraspinal inflammation mediates SCI pathophysi...
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2025-01-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-025-03338-1 |
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| author | Reena Kumari Gabrielle V. Hammers Robert H. Hammons Andrew N. Stewart Steven M. MacLean Tracy Niedzielko Lonnie E. Schneider Candace L. Floyd John C. Gensel |
| author_facet | Reena Kumari Gabrielle V. Hammers Robert H. Hammons Andrew N. Stewart Steven M. MacLean Tracy Niedzielko Lonnie E. Schneider Candace L. Floyd John C. Gensel |
| author_sort | Reena Kumari |
| collection | DOAJ |
| description | Abstract Objective Therapeutic translation is challenging in spinal cord injury (SCI) and large animal models with high clinical relevance may accelerate therapeutic development. Pigs have important anatomical and physiological similarities to humans. Intraspinal inflammation mediates SCI pathophysiology. The purpose of this study was to evaluate the effect of sex on inflammation and outcomes in a pig thoracic contusion/compression SCI model. Methods Adult (gonad-intact) male and female Yucatan miniature swine were subjected to either SCI or sham (laminectomy-only) injury. Results SCI caused locomotor dysfunction (measured with the Porcine Thoracic Injury Behavior Score) with some recovery over 6 weeks and limited tissue sparing at 6 weeks with no difference between sexes. Immunohistological evaluations of spinal cord tissue at 2 days and 6 weeks post-injury revealed intraspinal microglia/macrophage (IBA-1, CD68) and lymphocyte responses (T-cells (CD3) and B-cells (CD79a)) consistent with observations in rodents and humans. Astrocyte (GFAP) immunoreactivity was observed within the lesion core at 6 weeks in contrast to observations in rodents. No differences were seen for astrocytes, microglia, macrophages, B-cells, and neutrophil infiltration between males and females. Intraspinal CD3 + T-cell counts and T-cell microclusters were significantly higher in females compared to males 6 weeks post-injury. Interestingly, we observed a similar significant increase in intraspinal CD3 + T-cell accumulation in female vs. male mice at 6 weeks post-thoracic contusion SCI. Interpretation Our observations indicate that sex is a potential biological variable for T-cell infiltration and may contribute to sex-based differences in SCI pathophysiology and recovery outcomes. |
| format | Article |
| id | doaj-art-f031e94fe7c9428b84648246f523c4b5 |
| institution | Kabale University |
| issn | 1742-2094 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj-art-f031e94fe7c9428b84648246f523c4b52025-01-26T12:45:18ZengBMCJournal of Neuroinflammation1742-20942025-01-0122111610.1186/s12974-025-03338-1Cross-species comparisons between pigs and mice reveal conserved sex-specific intraspinal inflammatory responses after spinal cord injuryReena Kumari0Gabrielle V. Hammers1Robert H. Hammons2Andrew N. Stewart3Steven M. MacLean4Tracy Niedzielko5Lonnie E. Schneider6Candace L. Floyd7John C. Gensel8Spinal Cord and Brain Injury Research Center, Department of Physiology, College of Medicine, University of KentuckySpinal Cord and Brain Injury Research Center, Department of Physiology, College of Medicine, University of KentuckySpinal Cord and Brain Injury Research Center, Department of Physiology, College of Medicine, University of KentuckySpinal Cord and Brain Injury Research Center, Department of Neuroscience, College of Medicine, University of KentuckySpinal Cord and Brain Injury Research Center, Department of Physiology, College of Medicine, University of KentuckyDepartment of Emergency Medicine, School of Medicine, Emory UniversityDepartment of Emergency Medicine, School of Medicine, Emory UniversityDepartment of Emergency Medicine, School of Medicine, Emory UniversitySpinal Cord and Brain Injury Research Center, Department of Physiology, College of Medicine, University of KentuckyAbstract Objective Therapeutic translation is challenging in spinal cord injury (SCI) and large animal models with high clinical relevance may accelerate therapeutic development. Pigs have important anatomical and physiological similarities to humans. Intraspinal inflammation mediates SCI pathophysiology. The purpose of this study was to evaluate the effect of sex on inflammation and outcomes in a pig thoracic contusion/compression SCI model. Methods Adult (gonad-intact) male and female Yucatan miniature swine were subjected to either SCI or sham (laminectomy-only) injury. Results SCI caused locomotor dysfunction (measured with the Porcine Thoracic Injury Behavior Score) with some recovery over 6 weeks and limited tissue sparing at 6 weeks with no difference between sexes. Immunohistological evaluations of spinal cord tissue at 2 days and 6 weeks post-injury revealed intraspinal microglia/macrophage (IBA-1, CD68) and lymphocyte responses (T-cells (CD3) and B-cells (CD79a)) consistent with observations in rodents and humans. Astrocyte (GFAP) immunoreactivity was observed within the lesion core at 6 weeks in contrast to observations in rodents. No differences were seen for astrocytes, microglia, macrophages, B-cells, and neutrophil infiltration between males and females. Intraspinal CD3 + T-cell counts and T-cell microclusters were significantly higher in females compared to males 6 weeks post-injury. Interestingly, we observed a similar significant increase in intraspinal CD3 + T-cell accumulation in female vs. male mice at 6 weeks post-thoracic contusion SCI. Interpretation Our observations indicate that sex is a potential biological variable for T-cell infiltration and may contribute to sex-based differences in SCI pathophysiology and recovery outcomes.https://doi.org/10.1186/s12974-025-03338-1GenderImmuneNeurotraumaAdaptiveInnateNeuron |
| spellingShingle | Reena Kumari Gabrielle V. Hammers Robert H. Hammons Andrew N. Stewart Steven M. MacLean Tracy Niedzielko Lonnie E. Schneider Candace L. Floyd John C. Gensel Cross-species comparisons between pigs and mice reveal conserved sex-specific intraspinal inflammatory responses after spinal cord injury Journal of Neuroinflammation Gender Immune Neurotrauma Adaptive Innate Neuron |
| title | Cross-species comparisons between pigs and mice reveal conserved sex-specific intraspinal inflammatory responses after spinal cord injury |
| title_full | Cross-species comparisons between pigs and mice reveal conserved sex-specific intraspinal inflammatory responses after spinal cord injury |
| title_fullStr | Cross-species comparisons between pigs and mice reveal conserved sex-specific intraspinal inflammatory responses after spinal cord injury |
| title_full_unstemmed | Cross-species comparisons between pigs and mice reveal conserved sex-specific intraspinal inflammatory responses after spinal cord injury |
| title_short | Cross-species comparisons between pigs and mice reveal conserved sex-specific intraspinal inflammatory responses after spinal cord injury |
| title_sort | cross species comparisons between pigs and mice reveal conserved sex specific intraspinal inflammatory responses after spinal cord injury |
| topic | Gender Immune Neurotrauma Adaptive Innate Neuron |
| url | https://doi.org/10.1186/s12974-025-03338-1 |
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