Datasets supporting paper "A preclinical randomized controlled multicenter trial of anti-IL-17A treatment for acute ischemic stroke"

Posted on 2023-01-12 - 02:13 authored by Simon Koch

This collection contains the MRI, microbiome, histology and FACS data used in the paper "A preclinical randomized controlled multicenter trial of anti-IL-17A treatment for acute ischemic stroke".


Manuscript abstract

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.  

CITE THIS COLLECTION

Koch, Simon; Gelderblom, Mathias; Strecker, Jan-Kolja; Jørgensen, Carina; Garcia-Bonilla, Lidia; Ludewig, Peter; et al. (2023): Datasets supporting paper "A preclinical randomized controlled multicenter trial of anti-IL-17A treatment for acute ischemic stroke". Figshare+. Collection. https://doi.org/10.25452/figshare.plus.c.6371439.v1
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FUNDING

FOR 2879:  ImmunoStroke: From immune cells to stroke recovery

Deutsche Forschungsgemeinschaft

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.

Research Institution(s)

Department of Neurology, University Medical Center Hamburg-Eppendorf; Hamburg, Germany

Contact email

mgelderblom@uke.de

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AUTHORS (20)

Mathias Gelderblom
Jan-Kolja Strecker
Carina Jørgensen
Lidia Garcia-Bonilla
Peter Ludewig
Ines S. Schädlich
Marius Piepke
Karoline Degenhardt
Christian Bernreuther
Hans Pinnschmidt
Thiruma Valavan Arumugam
Götz Thomalla
Cornelius Faber
Jan Sedlacik
Christian Gerloff
Jens Minnerup
Bettina Hjelm Clausen
Josef Anrather
Tim Magnus
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