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73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

29.05. - 01.06.2022, Köln

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Functional recovery in relation to the posttraumatic restitution of the Blood-Spinal-Cord-Barrier after experimental spinal cord injury in the mouse

Funktionelle Erholung und die posttraumatische Restitution der Blut-Rückenmarks-Schranke nach experimenteller traumatischer Rückenmarksschädigung in der Maus

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  • Lea Meyer - Charité – Universitätsmedizin Berlin, Neurochirurgie und experimentelle Neurochirurgie, Berlin, Deutschland
  • Lilly Waldmann - Charité – Universitätsmedizin Berlin, Neurochirurgie und experimentelle Neurochirurgie, Berlin, Deutschland
  • Nima Taheri - Charité – Universitätsmedizin Berlin, Neurochirurgie und experimentelle Neurochirurgie, Berlin, Deutschland
  • Laurens Roolfs - Charité – Universitätsmedizin Berlin, Neurochirurgie und experimentelle Neurochirurgie, Berlin, Deutschland
  • Katharina Kersting - Charité – Universitätsmedizin Berlin, Neurochirurgie und experimentelle Neurochirurgie, Berlin, Deutschland
  • Melina Nieminen-Kelhä - Charité – Universitätsmedizin Berlin, Neurochirurgie und experimentelle Neurochirurgie, Berlin, Deutschland
  • Irina Kremenetskaia - Charité – Universitätsmedizin Berlin, Neurochirurgie und experimentelle Neurochirurgie, Berlin, Deutschland
  • Adnan Ghori - Charité – Universitätsmedizin Berlin, Neurochirurgie und experimentelle Neurochirurgie, Berlin, Deutschland
  • Andre Rex - Charité – Universitätsmedizin Berlin, Experimentelle Neurologie, Berlin, Deutschland
  • Michael Fehlings - Toronto Western Hospital, University Health Network, Neurosurgery, Toronto, Kanada
  • Peter Vajkoczy - Charité – Universitätsmedizin Berlin, Neurochirurgie und experimentelle Neurochirurgie, Berlin, Deutschland
  • presenting/speaker Vanessa Hubertus - Charité – Universitätsmedizin Berlin, Neurochirurgie und experimentelle Neurochirurgie, Berlin, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie. Köln, 29.05.-01.06.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. DocV020

doi: 10.3205/22dgnc021, urn:nbn:de:0183-22dgnc0219

Published: May 25, 2022

© 2022 Meyer et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: Spinal Cord Injury (SCI) is a devastating condition that presents a major socioeconomic burden for healthcare systems. The posttraumatic disruption of the Blood-Spinal-Cord-Barrier (BSCB) is a leading pathophysiology in SCI and its restitution plays a crucial role in structural spinal cord regeneration. A deeper understanding of the pathophysiology and its timeframe will enhance the search for restorative therapies facilitating functional regeneration. With this study we characterize the posttraumatic BSCB disruption and restitution in relation to functional recovery in a mouse model up to 28 days post SCI.

Methods: Adult C57BL/6J mice (m/f, n=55) underwent mid-thoracic (Th6/7) clip-compression SCI using a modified aneurysm clip (5g, 60s) or sham injury (two-level-laminectomy). Perioperative antibiotic therapy with amoxicillin and postoperative pain medication with buprenorphine was applied. Longitudinal neurobehavioral analysis was performed (n=23) using Catwalk® automated gait analysis and Basso Mouse Scale with Tally sub-score at days 1, 3, 7, 14 and 28 post SCI. Additionally, in vivo imaging with 7T MRI was performed for tissue morphology analysis. Individual specimens were sacrificed at each time point for qualitative histological analysis (Luxol-Fast-Blue + H&E, CD31+Evans-Blue, n=5). BSCB disruption was quantified by measuring Evans-Blue(EVB)-extravasation via fluorescence microplate reader (n=50).

Results: As the posttraumatic disruption of the BSCB is most severe up to 7d post SCI, histological analysis up to this point showed vast structural damage and edema to the spinal cord with considerable EVB-leakage, supported by MRI findings, with an increasing restitution in the chronic phase (14d, 28d). Quantitative assessment of EVB-extravasation displayed a significant disruption of the BSCB up to 14 days post SCI (14d: p=0.001), with restitution after 28 days (p=0.096). Neurological recovery started between days 7 and 14 post SCI, with most specimens having regained hindlimb function by day 28 (p=0.552).

Conclusion: Functional recovery following SCI is associated with the restitution of the BSCB, which remains significantly disrupted up to 14d post SCI, revealing a potential time frame for therapy application. Further detailed examinations of the regenerative capacities and the molecular players involved in BSCB regeneration are necessary for the development of restorative therapies targeting the neurovascular unit.