ABSTRACT NUMBER: ESOC2026A756 ACUTE SEPSIS INCREASES HEMORRHAGIC TRANSFORMATION AND WORSENS OUTCOME AFTER EXPERIMENTAL ISCHEMIC STROKE IN MICE

Abstract Background and aims Systemic infections are independently associated with poor outcome after ischemic stroke. Hemorrhagic transformation (HT) represents a major cause of neurological worsening. Although sepsis is known to exacerbate stroke severity, its role in promoting HT and the contribution of innate immune mechanisms remain insufficiently characterized. We hypothesized that sepsis induced at arterial occlusion potentiates ischemic brain injury by the amplifying thrombo-inflammation. Methods Adult C57Bl6/J mice underwent transient middle cerebral artery occlusion (tMCAO). five minutes after ischemia onset, animal received an intraperitoneal injection of LPS (10 mg/kg) or saline. In a subset, neutrophils were depleted using an anti-Ly6G antibody. Neurological deficit was assessed at 24 hours. HT incidence and infarct volume were quantified. Brain protein extracts were analyzed for markers of inflammation, blood brain barrier (BBB) disruption and neuroinflammation. Results Sepsis induction significantly increased HT incidence (LPS+tMCAO: 4/14 vs tMCAO: 0/11) and worsened neurological deficits (12±1 vs 7±1, p<0.05), despite no difference in infarct volume. LPS+tMCAO mice developed marked inflammation and thrombocytopenia. Cerebral analyses revealed increased myeloperoxidase and YKL-40 levels and enhanced IgG extravasation in ipsilateral hemispheres. Neutrophil depletion showed a non-significant reduction in HT in septic stroke mice (33% vs 25%). Conclusions Acute sepsis at ischemic stroke onset markedly increases HT incidence and worsens functional outcome independently of infarct size likely through BBB disruption and enhanced neuroinflammation. Neutrophil depletion suggests a contributory role for neutrophils in sepsis-associated HT after stroke. These findings support further investigations to reduce hemorrhagic risk in infected stroke patients. Conflict of interest Nothing to disclose