The single-dose application of interleukin-4 ameliorates secondary brain damage in the early phase after moderate experimental traumatic brain injury in mice

• Verfasst von: Walter, Johannes [VerfasserIn]
• Verfasst von: Mende, Jannis [VerfasserIn]
• Verfasst von: Hutagalung, Samuel [VerfasserIn]
• Verfasst von: Alhalabi, Obada [VerfasserIn]
• Verfasst von: Grutza, Martin [VerfasserIn]
• Verfasst von: Zheng, Guoli [VerfasserIn]
• Verfasst von: Skutella, Thomas [VerfasserIn]
• Verfasst von: Unterberg, Andreas [VerfasserIn]
• Verfasst von: Zweckberger, Klaus [VerfasserIn]
• Verfasst von: Younsi, Alexander [VerfasserIn]
• Titel: The single-dose application of interleukin-4 ameliorates secondary brain damage in the early phase after moderate experimental traumatic brain injury in mice
• Verf.angabe: Johannes Walter, Jannis Mende, Samuel Hutagalung, Obada T. Alhalabi, Martin Grutza, Guoli Zheng, Thomas Skutella, Andreas Unterberg, Klaus Zweckberger and Alexander Younsi
• Jahr: 2023
• Umfang: 17 S.
• Illustrationen: Illustrationen
• Fussnoten: Veröffentlicht: 14. August 2023 ; Gesehen am 16.10.2023
• Titel Quelle: Enthalten in: International journal of molecular sciences
• Ort Quelle: Basel : Molecular Diversity Preservation International, 2000
• Jahr Quelle: 2023
• Band/Heft Quelle: 24(2023), 16, Artikel-ID 12756, Seite 1-17
• ISSN Quelle: 1422-0067
• ISSN Quelle: 1661-6596
• DOI: doi:10.3390/ijms241612756
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: behavioral test
• Sach-SW: CCI
• Sach-SW: controlled cortical impact
• Sach-SW: IL-4
• Sach-SW: immunomodulation
• Sach-SW: inflammation
• Sach-SW: interleukin-4
• Sach-SW: secondary brain damage
• Sach-SW: TBI
• Sach-SW: traumatic brain injury
• K10plus-PPN: 1865734195

Abstract

Activation of the interleukin-4 (IL-4) pathway ameliorates secondary injury mechanisms after experimental traumatic brain injury (TBI); therefore, we assessed the effect of a therapeutic IL-4 administration on secondary brain damage after experimental TBI. We subjected 100 C57/Bl6 wildtype mice to controlled cortical impact (CCI) and administered IL-4 or a placebo control subcutaneously 15 min thereafter. Contusion volume (Nissl staining), neurological function (hole board, video open field, and CatWalkXT®), and the immune response (immunofluorescent staining) were analyzed up to 28 days post injury (dpi). Contusion volumes were significantly reduced after IL-4 treatment up to 14 dpi (e.g., 6.47 ± 0.41 mm3 vs. 3.80 ± 0.85 mm3, p = 0.011 3 dpi). Macrophage invasion and microglial response were significantly attenuated in the IL-4 group in the acute phase after CCI (e.g., 1.79 ± 0.15 Iba-1+/CD86+ cells/sROI vs. 1.06 ± 0.21 Iba-1/CD86+ cells/sROI, p = 0.030 in the penumbra 3 dpi), whereas we observed an increased neuroinflammation thereafter (e.g., mean GFAP intensity of 3296.04 ± 354.21 U vs. 6408.65 ± 999.54 U, p = 0.026 in the ipsilateral hippocampus 7 dpi). In terms of functional outcome, several gait parameters were improved in the acute phase following IL-4 treatment (e.g., a difference in max intensity of −7.58 ± 2.00 U vs. −2.71 ± 2.44 U, p = 0.041 3 dpi). In conclusion, the early single-dose administration of IL-4 significantly reduces secondary brain damage in the acute phase after experimental TBI in mice, which seems to be mediated by attenuation of macrophage and microglial invasion.