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72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

06.06. - 09.06.2021

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The administration of Interleukin-4 ameliorates secondary brain damage after experimental traumatic brain injury in mice

Die Applikation von Interleukin-4 reduziert den sekundären Hirnschaden nach experimentellem Schädel-Hirn-Trauma im Mausmodell

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  • presenting/speaker Johannes Walter - Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
  • Samuel Hutagalung - Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
  • Jannis Mende - Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
  • Christa Maurer - Ruprecht-Karls-Universität Heidelberg, Institut für Anatomie und Zellbiologie, Heidelberg, Deutschland
  • Joachim Kirsch - Ruprecht-Karls-Universität Heidelberg, Institut für Anatomie und Zellbiologie, Heidelberg, Deutschland
  • Thomas Skutella - Ruprecht-Karls-Universität Heidelberg, Institut für Anatomie und Zellbiologie, Heidelberg, Deutschland
  • Alexander Younsi - Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
  • Andreas W. Unterberg - Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
  • Klaus Zweckberger - Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie. sine loco [digital], 06.-09.06.2021. Düsseldorf: German Medical Science GMS Publishing House; 2021. DocV031

doi: 10.3205/21dgnc033, urn:nbn:de:0183-21dgnc0332

Published: June 4, 2021

© 2021 Walter 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: Recent focus of experimental research in traumatic brain injury (TBI) has been directed towards the role of inflammatory processes. It has been shown that activation of the Interleukin-4 (IL-4) pathway ameliorates secondary brain injury; therefore, we assessed the effect of therapeutic application of IL-4 on secondary brain damage after experimental TBI in mice.

Methods: C57/Bl6 wildtype mice were subjected to controlled cortical impact (CCI) injury (tip diameter 2mm, impact depth 1mm, velocity 8m/s, contact time 150ms). IL-4 was administered subcutaneously at a dose of 5mg/kg 15 minutes after trauma induction. Neurological function was assessed using hole board, video open field and CatWalk XT gait analysis tests 24 hours as well as three, seven, 14 and 28 days after CCI. In addition, contusion volume was determined by Nissl staining. Finally, inflammatory response (quantification of macrophages and microglia as well as astrogliosis, M1/M2 microglia differentiation) and proliferation (quantification of oligodendroglial differentiation and myelinization) was assessed in the pericontusional area as well as in the hippocampus by immunofluorescent staining.

Results: IL-4 treatment resulted in reduced contusion volumes throughout days one to 28 (e.g. 7.82 vs. 10.03 mm³ on day seven), improved gait and motor function as well as reduced inflammatory response. Macrophages tended to differentiate into the anti-inflammatory M2-type more often and proliferation processes were observed more frequently after IL-4 application.

Conclusion: As application of Interleukin-4 plays leads to reduced structural damage and improves neurological function after experimental TBI, it poses an interesting treatment option. The current results provide the basis for a potential translation into clinical research that might be possible in the near future.