Abstract DP316: BB-031 inhibition of VWF in AIS: does it cast a large NETs?

Introduction: Acute ischemic stroke (AIS) is the leading cause of long-term disability. rtPA/TNK treatment results in intracranial hemorrhage (ICH) in ~7% of patients with ~40% mortality. Increased Neutrophil Extracellular Traps (NETs) correlate with ICH, and blood brain barrier (BBB) disruption. Von Willebrand Factor (VWF) induces thrombosis and inflammation in AIS. BB-031 aptamer targets VWF resulting in thrombolysis and BB-025 reverses BB-031. We hypothesize BB-031 will reduce NETs in canine thromboembolic middle cerebral artery occlusion (eMCAO), improving infarct volumes. Methods: Six hours after autologous canine eMCAO, animals received vehicle, 0.5, 1.0, or 5.0 mg/kg BB-031, or 0.5 mg/kg BB-031+0.5 mg/kg BB-025. Circulating neutrophil elastase (NE), citrullinated histone (CitH3), myeloperoxidase (MPO), VWF and modulator, ADAMTS13 levels were analyzed 3 hours after treatment at time of sacrifice. Results: Inflammatory markers at time of sacrifice VWF levels with 0.5 mg/kg (4.55 ± 1.38 ng/ml, n=8, p=.0068), 1.0 mg/kg 3.18 ± 1.33 ng/ml, n=4, p