Microbiome dataset supporting paper "A preclinical randomized controlled multicenter trial of anti-IL-17A treatment for acute ischemic stroke"
This folder contains the raw microbiome data from the study "A preclinical randomized controlled multicenter trial of anti-IL-17A treatment for acute ischemic stroke".
See related materials in Collection at: https://doi.org/10.25452/figshare.plus.c.6371439
Multiple consensus statements have called for preclinical randomized controlled trials (pRCT) to improve translation in stroke research. We investigated the efficacy of an IL-17A neutralizing antibody in a multicenter pRCT using a murine ischemia reperfusion stroke model. Twelve week old, male C57BL/6 mice were subjected to 45 minutes of transient middle cerebral artery occlusion (tMCAO) in four centers. Mice were randomly assigned (1:1) to receive either an anti-IL-17A (500 µg) or isotype antibody (500 µg) intravenously one hour after reperfusion. The primary endpoint was infarct volume measured by MRI three days after tMCAO. Secondary analysis included mortality, neurological score, neutrophil infiltration and the impact of the gut microbiome on treatment effects. Out of 136 mice, 109 mice were included in the analysis of the primary endpoint. Mixed model analysis revealed that IL-17A neutralization significantly reduced infarct sizes (anti-IL-17A: 61.77 ± 31.04 mm3; IgG control: 75.66 ± 34.79 mm3; p=0.01). Secondary outcome measures showed a decrease in mortality (Hazard Ratio=3.43, 95% CI=1.157-10.18; p=0.04) and neutrophil invasion into ischemic cortices (anti-IL-17A: 7222 ± 6108 cells; IgG control: 28153 ± 23206 cells; p<0.01). There was no difference in Bederson score. The analysis of the gut microbiome showed significant heterogeneity between centers (R=0.78, p<0.001, n=40). Taken together, neutralization of IL-17A in a therapeutic time window resulted in a significant reduction of infarct sizes and mortality compared to isotype control. It suggests IL-17A neutralization as a potential therapeutic target in stroke.
This work was supported by grants from Deutsche Forschungsgemeinschaft (KFO Immunostroke 2879: Project A1 (T.M. 4248778651), Project B3 (M.G. 428778375)), the Schilling foundation (T.M.) and the core unit PIX of the Interdisciplinary Center for Clinical Research Münster.
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