Ixodes ricinus‐Contact Phase Inhibitor Promotes Functional Recovery and Attenuates Neutrophil Associated Neuroinflammation After Experimental Intracerebral Hemorrhage
- 1Bioxodes SA Gosselies Belgium
- 2ETAP‐Lab Caen France
- 3Department of Clinical Research Caen University Hospital Caen France
Abstract
Aims: Neutrophil‐associated inflammation contributes to secondary brain injury after intracerebral hemorrhage (ICH). We evaluated whether Ixodes ricinus ‐Contact Phase Inhibitor (Ir‐CPI), a selective factor XIa/XIIa inhibitor with reported thromboinflammatory modulatory properties, improves outcome after experimental ICH without worsening bleeding.
Methods: In a collagenase‐induced mouse ICH model, Ir‐CPI was administered as an intravenous bolus followed by a 3‐day infusion. Vehicle animals served as controls and enoxaparin as an anticoagulant comparator. Cohorts evaluated hemorrhage and lesion volumes, endothelial activation, neutrophil‐associated inflammation, and longitudinal functional recovery. Ir‐CPI association with human neutrophils was evaluated in vitro.
Results: Ir‐CPI did not increase hemorrhage or lesion volumes versus PBS through Day 14, whereas enoxaparin showed a higher Day 1 hemorrhage volume than Ir‐CPI. Flow cytometry showed Ir‐CPI association with human neutrophils. In the mouse model, Ir‐CPI produced region‐specific reductions in neutrophil infiltration and NET formation and reduced neuronal degeneration at the injection site and caudal level, without affecting VCAM‐1‐associated endothelial activation. Ir‐CPI accelerated functional recovery, improving neurological scores and sensorimotor asymmetry by Day 5, with restoration of baseline corner test performance by Day 14.
Conclusion: Ir‐CPI improves recovery after experimental ICH without exacerbating bleeding and is associated with reduced neutrophil‐associated secondary brain injury. These findings support its translational potential as a therapeutic strategy for ICH.
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BibTeX
@article{demoulin2026ixodes,
title = {{Ixodes ricinus‐Contact Phase Inhibitor Promotes Functional Recovery and Attenuates Neutrophil Associated Neuroinflammation After Experimental Intracerebral Hemorrhage}},
author = {Stéphanie Demoulin and Annelise Letourneur and Florent Lebrun and Nicolas Violle and Denis Vivien and Valérie Pireaux},
journal = {CNS neuroscience \& therapeutics},
year = {2026},
month = oct,
doi = {10.1002/cns.71227},
url = {https://europepmc.org/article/PMC/PMC13722891},
note = {CC BY},
}
RIS
TY - JOUR
TI - Ixodes ricinus‐Contact Phase Inhibitor Promotes Functional Recovery and Attenuates Neutrophil Associated Neuroinflammation After Experimental Intracerebral Hemorrhage
AU - Stéphanie Demoulin
AU - Annelise Letourneur
AU - Florent Lebrun
AU - Nicolas Violle
AU - Denis Vivien
AU - Valérie Pireaux
PY - 2026
DA - 2026/10/30
JO - CNS neuroscience & therapeutics
DO - 10.1002/cns.71227
UR - https://europepmc.org/article/PMC/PMC13722891
AB - Aims: Neutrophil‐associated inflammation contributes to secondary brain injury after intracerebral hemorrhage (ICH). We evaluated whether Ixodes ricinus ‐Contact Phase Inhibitor (Ir‐CPI), a selective factor XIa/XIIa inhibitor with reported thromboinflammatory modulatory properties, improves outcome after experimental ICH without worsening bleeding. Methods: In a collagenase‐induced mouse ICH model, Ir‐CPI was administered as an intravenous bolus followed by a 3‐day infusion. Vehicle animals served as controls and enoxaparin as an anticoagulant comparator. Cohorts evaluated hemorrhage and lesion volumes, endothelial activation, neutrophil‐associated inflammation, and longitudinal functional recovery. Ir‐CPI association with human neutrophils was evaluated in vitro. Results: Ir‐CPI did not increase hemorrhage or lesion volumes versus PBS through Day 14, whereas enoxaparin showed a higher Day 1 hemorrhage volume than Ir‐CPI. Flow cytometry showed Ir‐CPI association with human neutrophils. In the mouse model, Ir‐CPI produced region‐specific reductions in neutrophil infiltration and NET formation and reduced neuronal degeneration at the injection site and caudal level, without affecting VCAM‐1‐associated endothelial activation. Ir‐CPI accelerated functional recovery, improving neurological scores and sensorimotor asymmetry by Day 5, with restoration of baseline corner test performance by Day 14. Conclusion: Ir‐CPI improves recovery after experimental ICH without exacerbating bleeding and is associated with reduced neutrophil‐associated secondary brain injury. These findings support its translational potential as a therapeutic strategy for ICH.
SN - 1755-5930
SN - 1755-5949
ER -