Analysis of the spatiotemporal dynamics of vascular injury and regeneration following experimental Spinal Cord Injury

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

Brain and Spine (Jan 2025)

Analysis of the spatiotemporal dynamics of vascular injury and regeneration following experimental Spinal Cord Injury

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

Affiliations

Christian J. Entenmann: Department of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
Emily J. von Bronewski: Department of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
Lilly Waldmann: Department of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
Lea Meyer: Department of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
Katharina Kersting: Department of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
Laurens T. Roolfs: Department of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
Lasse M. Schleker: Department of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
Melina Nieminen-Kelhä: Department of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
Irina Kremenetskaia: Department of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
Frank L. Heppner: Department 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, Germany
Michael G. Fehlings: Division of Neurosurgery and Krembil Neuroscience Center, Toronto Western Hospital, University Health Network and University of Toronto, Toronto, Canada
Peter Vajkoczy: Department of Neurosurgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
Vanessa Hubertus: Department 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.

Journal volume & issue: Vol. 5
p. 104191

Abstract

Read online

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.

Published in Brain and Spine

ISSN: 2772-5294 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: https://www.journals.elsevier.com/brain-and-spine

About the journal

Abstract

Keywords