Molecular pathology of acute spinal cord injury in middle-aged mice
Abstract The median age at which spinal cord injuries occur has steadily increased from 29 to 43 over the last several decades. Although more pre-clinical studies in aged rodents are being done to address this shift in demographics, comprehensive transcriptomic studies investigating SCI pathobiology...
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| Format: | Article |
| Language: | English |
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BMC
2025-07-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-025-03494-4 |
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| author | Corey Fehlberg Danny John Brian Kang James S. Choi Susana Cerqueira Alexis Brake Jae K. Lee |
| author_facet | Corey Fehlberg Danny John Brian Kang James S. Choi Susana Cerqueira Alexis Brake Jae K. Lee |
| author_sort | Corey Fehlberg |
| collection | DOAJ |
| description | Abstract The median age at which spinal cord injuries occur has steadily increased from 29 to 43 over the last several decades. Although more pre-clinical studies in aged rodents are being done to address this shift in demographics, comprehensive transcriptomic studies investigating SCI pathobiology in middle-aged mice are lacking. To address this gap in knowledge, we compared behavioral, histopathological, and transcriptional outcomes in young (2–4 months old) and middle-aged (10–12 months old) mice. In contrast to most previous studies, open field tests showed no differences in locomotor recovery between the young and middle-aged mice over a one-month period. The injury site also demonstrated similar histopathology in terms of lesion size, and numbers of macrophages and fibroblasts. Acutely after injury, proliferation of macrophages, fibroblasts, and astrocytes were also similar between the two age groups. In addition, spatial transcriptomics showed similar, transcriptionally defined regions around the injury site at 3 days post-injury. However, single cell RNA-sequencing of the cells at the injury site and surrounding spared tissue showed differences in select cell subpopulations. Taken together, our results indicate that although young and middle-aged mice display similar locomotor recovery and histopathology after SCI, changes in cell subpopulations may underlie a decline in repair mechanisms that manifest after middle age. |
| format | Article |
| id | doaj-art-84a8a0066b8b43dd918162b55fc0ea66 |
| institution | DOAJ |
| issn | 1742-2094 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj-art-84a8a0066b8b43dd918162b55fc0ea662025-08-20T03:05:16ZengBMCJournal of Neuroinflammation1742-20942025-07-0122112110.1186/s12974-025-03494-4Molecular pathology of acute spinal cord injury in middle-aged miceCorey Fehlberg0Danny John1Brian Kang2James S. Choi3Susana Cerqueira4Alexis Brake5Jae K. Lee6Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of MedicineMiami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of MedicineMiami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of MedicineMiami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of MedicineMiami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of MedicineMiami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of MedicineMiami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of MedicineAbstract The median age at which spinal cord injuries occur has steadily increased from 29 to 43 over the last several decades. Although more pre-clinical studies in aged rodents are being done to address this shift in demographics, comprehensive transcriptomic studies investigating SCI pathobiology in middle-aged mice are lacking. To address this gap in knowledge, we compared behavioral, histopathological, and transcriptional outcomes in young (2–4 months old) and middle-aged (10–12 months old) mice. In contrast to most previous studies, open field tests showed no differences in locomotor recovery between the young and middle-aged mice over a one-month period. The injury site also demonstrated similar histopathology in terms of lesion size, and numbers of macrophages and fibroblasts. Acutely after injury, proliferation of macrophages, fibroblasts, and astrocytes were also similar between the two age groups. In addition, spatial transcriptomics showed similar, transcriptionally defined regions around the injury site at 3 days post-injury. However, single cell RNA-sequencing of the cells at the injury site and surrounding spared tissue showed differences in select cell subpopulations. Taken together, our results indicate that although young and middle-aged mice display similar locomotor recovery and histopathology after SCI, changes in cell subpopulations may underlie a decline in repair mechanisms that manifest after middle age.https://doi.org/10.1186/s12974-025-03494-4Spinal cord injuryMiddle-ageAgingAge as a biological variableSingle-cell RNA sequencingSpatial transcriptomics |
| spellingShingle | Corey Fehlberg Danny John Brian Kang James S. Choi Susana Cerqueira Alexis Brake Jae K. Lee Molecular pathology of acute spinal cord injury in middle-aged mice Journal of Neuroinflammation Spinal cord injury Middle-age Aging Age as a biological variable Single-cell RNA sequencing Spatial transcriptomics |
| title | Molecular pathology of acute spinal cord injury in middle-aged mice |
| title_full | Molecular pathology of acute spinal cord injury in middle-aged mice |
| title_fullStr | Molecular pathology of acute spinal cord injury in middle-aged mice |
| title_full_unstemmed | Molecular pathology of acute spinal cord injury in middle-aged mice |
| title_short | Molecular pathology of acute spinal cord injury in middle-aged mice |
| title_sort | molecular pathology of acute spinal cord injury in middle aged mice |
| topic | Spinal cord injury Middle-age Aging Age as a biological variable Single-cell RNA sequencing Spatial transcriptomics |
| url | https://doi.org/10.1186/s12974-025-03494-4 |
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