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

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 c...

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Hauptverfasser: Walter, Johannes (VerfasserIn) , Mende, Jannis (VerfasserIn) , Hutagalung, Samuel (VerfasserIn) , Alhalabi, Obada (VerfasserIn) , Grutza, Martin (VerfasserIn) , Zheng, Guoli (VerfasserIn) , Skutella, Thomas (VerfasserIn) , Unterberg, Andreas (VerfasserIn) , Zweckberger, Klaus (VerfasserIn) , Younsi, Alexander (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2023
In: International journal of molecular sciences
Year: 2023, Jahrgang: 24, Heft: 16, Pages: 1-17
ISSN:1422-0067
DOI:10.3390/ijms241612756
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms241612756
Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/24/16/12756
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Verfasserangaben:Johannes Walter, Jannis Mende, Samuel Hutagalung, Obada T. Alhalabi, Martin Grutza, Guoli Zheng, Thomas Skutella, Andreas Unterberg, Klaus Zweckberger and Alexander Younsi

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520 |a 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. 
650 4 |a behavioral test 
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650 4 |a interleukin-4 
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