Analysis of the spatiotemporal dynamics of vascular injury and regeneration following experimental Spinal Cord Injury
Introduction: The loss of vasculature in Spinal Cord Injury (SCI) contributes to secondary injury, expanding the injury to unharmed spinal cord (SC) regions. Understanding these mechanisms is crucial for developing therapeutic interventions. Research question: Comprehensive analysis of the temporosp...
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Elsevier
2025-01-01
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| Series: | Brain and Spine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772529425000104 |
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| author | Christian J. Entenmann Emily J. von Bronewski Lilly Waldmann Lea Meyer Katharina Kersting Laurens T. Roolfs Lasse M. Schleker Melina Nieminen-Kelhä Irina Kremenetskaia Frank L. Heppner Michael G. Fehlings Peter Vajkoczy Vanessa Hubertus |
| author_facet | Christian J. Entenmann Emily J. von Bronewski Lilly Waldmann Lea Meyer Katharina Kersting Laurens T. Roolfs Lasse M. Schleker Melina Nieminen-Kelhä Irina Kremenetskaia Frank L. Heppner Michael G. Fehlings Peter Vajkoczy Vanessa Hubertus |
| author_sort | Christian J. Entenmann |
| collection | DOAJ |
| description | Introduction: The loss of vasculature in Spinal Cord Injury (SCI) contributes to secondary injury, expanding the injury to unharmed spinal cord (SC) regions. Understanding these mechanisms is crucial for developing therapeutic interventions. Research question: Comprehensive analysis of the temporospatial dynamics of vascular injury and regeneration following SCI. Materials and methods: Adult C57BL/6J mice were subjected to clip-compression SCI (Th 6/7, 5g, 60s, n = 20) or sham injury (laminectomy, n = 4), and sacrificed at 1, 3, 7, 14, and 28 days (d) post-injury following intracardial fluorescein isothiocyanate (FITC)-Lectin perfusion. Histological analysis (CD31, FITC-Lectin, Ki-67, IgG, TER-119) assessed vascular changes, permeability, and proliferation within the injury epicenter (region 0 (R0), ± 0,5 mm) and two adjacent SC regions (R1: ± 1 mm, R2: ± 2.5 mm). Results: Perfusion loss (FITC-Lectin+/CD31+), was most severe in R0 and R1 at d3 (p < 0.01). Significant vascular loss in R2 started at d3 (p = 0.043). Perfusion was restored at d28 in R0 and R1, and at d7 in R2. Vessel density (CD31+) returned to baseline quicker (R0: d3, R1 and R2: d14). Vascular proliferation (CD31+/Ki-67+) manifested across all regions at d3 (p < 0.01), and most notably in R2 (p < 0.01). Vascular permeability for IgG remained disrupted until d3 in R0 and R1 and until d14 in R2. Discussion and conclusion: Vascular injury is most severe initially and spreads to the surrounding SC regions. Gradual vascular regeneration occurs early and up to a considerable distance from the injury epicenter, highlighting the potential of early therapeutic interventions targeted at vascular repair and regeneration. |
| format | Article |
| id | doaj-art-0bf3ae4d76094fd29d44ece5b7366f72 |
| institution | Kabale University |
| issn | 2772-5294 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Brain and Spine |
| spelling | doaj-art-0bf3ae4d76094fd29d44ece5b7366f722025-01-29T05:02:46ZengElsevierBrain and Spine2772-52942025-01-015104191Analysis of the spatiotemporal dynamics of vascular injury and regeneration following experimental Spinal Cord InjuryChristian J. Entenmann0Emily J. von Bronewski1Lilly Waldmann2Lea Meyer3Katharina Kersting4Laurens T. Roolfs5Lasse M. Schleker6Melina Nieminen-Kelhä7Irina Kremenetskaia8Frank L. Heppner9Michael G. Fehlings10Peter Vajkoczy11Vanessa Hubertus12Department of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, GermanyDepartment of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, GermanyDepartment of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, GermanyDepartment of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, GermanyDepartment of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, GermanyDepartment of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, GermanyDepartment of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, GermanyDepartment of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, GermanyDepartment of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, GermanyDepartment of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany; Cluster of Excellence, NeuroCure, Berlin, GermanyDivision of Neurosurgery and Krembil Neuroscience Center, Toronto Western Hospital, University Health Network and University of Toronto, Toronto, CanadaDepartment of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, GermanyDepartment of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany; Berlin Institute of Health (BIH) – Charité Clinician Scientist Program, Berlin, Germany; Corresponding author. Charité – Universitätsmedizin Berlin, Department of Neurosurgery, Charitéplatz 1, 10117, Berlin, Germany.Introduction: The loss of vasculature in Spinal Cord Injury (SCI) contributes to secondary injury, expanding the injury to unharmed spinal cord (SC) regions. Understanding these mechanisms is crucial for developing therapeutic interventions. Research question: Comprehensive analysis of the temporospatial dynamics of vascular injury and regeneration following SCI. Materials and methods: Adult C57BL/6J mice were subjected to clip-compression SCI (Th 6/7, 5g, 60s, n = 20) or sham injury (laminectomy, n = 4), and sacrificed at 1, 3, 7, 14, and 28 days (d) post-injury following intracardial fluorescein isothiocyanate (FITC)-Lectin perfusion. Histological analysis (CD31, FITC-Lectin, Ki-67, IgG, TER-119) assessed vascular changes, permeability, and proliferation within the injury epicenter (region 0 (R0), ± 0,5 mm) and two adjacent SC regions (R1: ± 1 mm, R2: ± 2.5 mm). Results: Perfusion loss (FITC-Lectin+/CD31+), was most severe in R0 and R1 at d3 (p < 0.01). Significant vascular loss in R2 started at d3 (p = 0.043). Perfusion was restored at d28 in R0 and R1, and at d7 in R2. Vessel density (CD31+) returned to baseline quicker (R0: d3, R1 and R2: d14). Vascular proliferation (CD31+/Ki-67+) manifested across all regions at d3 (p < 0.01), and most notably in R2 (p < 0.01). Vascular permeability for IgG remained disrupted until d3 in R0 and R1 and until d14 in R2. Discussion and conclusion: Vascular injury is most severe initially and spreads to the surrounding SC regions. Gradual vascular regeneration occurs early and up to a considerable distance from the injury epicenter, highlighting the potential of early therapeutic interventions targeted at vascular repair and regeneration.http://www.sciencedirect.com/science/article/pii/S2772529425000104Spinal cord injuryVascular injuryVascular proliferationBlood spinal cord barrierRevascularizationAngiogenesis |
| spellingShingle | Christian J. Entenmann Emily J. von Bronewski Lilly Waldmann Lea Meyer Katharina Kersting Laurens T. Roolfs Lasse M. Schleker Melina Nieminen-Kelhä Irina Kremenetskaia Frank L. Heppner Michael G. Fehlings Peter Vajkoczy Vanessa Hubertus Analysis of the spatiotemporal dynamics of vascular injury and regeneration following experimental Spinal Cord Injury Brain and Spine Spinal cord injury Vascular injury Vascular proliferation Blood spinal cord barrier Revascularization Angiogenesis |
| title | Analysis of the spatiotemporal dynamics of vascular injury and regeneration following experimental Spinal Cord Injury |
| title_full | Analysis of the spatiotemporal dynamics of vascular injury and regeneration following experimental Spinal Cord Injury |
| title_fullStr | Analysis of the spatiotemporal dynamics of vascular injury and regeneration following experimental Spinal Cord Injury |
| title_full_unstemmed | Analysis of the spatiotemporal dynamics of vascular injury and regeneration following experimental Spinal Cord Injury |
| title_short | Analysis of the spatiotemporal dynamics of vascular injury and regeneration following experimental Spinal Cord Injury |
| title_sort | analysis of the spatiotemporal dynamics of vascular injury and regeneration following experimental spinal cord injury |
| topic | Spinal cord injury Vascular injury Vascular proliferation Blood spinal cord barrier Revascularization Angiogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S2772529425000104 |
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