Abstract W P203: Clot Injection Speed Differentially Affects Infarct Volume and Neurological Outcome in Vehicle Versus tPA Treated Rats

Abstract

Introduction: Embolic stroke models closely mimic the pathophysiology of human stroke. Numerous models have been developed in an attempt to reduce lesion variability. However, while close attention has been paid to clot properties and site of injection, no study has considered the potential impact of the injection technique. We sought to investigate the relation between clot injection (CI) speed and neurological outcome following vehicle or recombinant tissue plasminogen activator (tPA) infusions. Methods: Male Wistar Kyoto rats operated by a single experienced surgeon were randomly assigned to one of four groups: Slow CI-vehicle (n=49); slow CI-tPA (n=30); fast CI-vehicle (n=50); fast CI-tPA (n=37). Real-time flow during CI was measured in a subset of animals (fast n=11, slow n=11). Saline or tPA (10 mg/kg body weight) was given 60 min post CI for a duration of 60 min. Clot properties as well as animal setup and surgery were identical in all experiments. At 24 h edema corrected infarct volume and neurologic outcomes were assessed. Results: Volume flow curves during CI were similar within respective slow and fast CI experiments indicating reproducible injection speed (Figure1A, data are mean±S.D.). Slow CI resulted in significantly smaller infarct volumes (p=0.024, Figure 1B, data are mean±S.E.M.) and better neurological outcomes (p=0.01, Figure 1C) compared to fast CI at 24 h. Unexpectedly, rtPA treatment attenuated infarct size in fast (p<0.001) but not slow CI experiments (p=0.382, Figure 1C). Conclusion: Investigators should assess their CI technique because it can critically determine infarct extent and response to thrombolysis after rat embolic stroke. Further investigations into cerebral blood flow changes as well as severity of edema formation and hemorrhagic conversion are ongoing to elucidate potential mechanisms underlying our observation.