Ixodes ricinus ‐Contact Phase Inhibitor Promotes Functional Recovery and Attenuates Neutrophil Associated Neuroinflammation After Experimental Intracerebral Hemorrhage
Stéphanie Demoulin, Annelise Letourneur, Florent Lebrun, Nicolas Violle, Denis Vivien, Valérie PireauxABSTRACT
Aims
Neutrophil‐associated inflammation contributes to secondary brain injury after intracerebral hemorrhage (ICH). We evaluated whether
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.