Background and Purpose--Microplasmin (µPli), a derivative of plasmin lacking the 5 "kringle" domains, was studied in a rat thrombotic stroke model with MRI monitoring.

Methods--Brain ischemia was induced by middle cerebral artery (MCA) occlusion with photochemically induced thrombosis. Brain tissue damage was assessed at 1 hour and 24 hours after MCA occlusion by MRI and 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Neurological symptoms were scored at 24 hours. Animals with insufficient evidence of significant jeopardized brain tissue on perfusion-weighted imaging (PWI) at 1 hour were excluded before randomization. Included animals were randomized (blinded) to controls (solvent), 7.5 or 10 mg/kg µPli, administered as an intravenous bolus 90 minutes after MCA occlusion (n=8 per dose group).

Results--µPli treatment reduced cerebral damage measured by TTC staining at 24 hours, from 250±69 mm³ (mean±SD) in controls to 150±30 and 170±62 mm³ with 7.5 and 10 mg/kg µPli, respectively; it reduced the expansion of the PWI positive area between 1 and 24 hours, and it reduced neurological deficits from a Bederson score of 7 (6 to 9) in controls to 4.5 (3 to 8) and 4 (3 to 6), with 7.5 and 10 mg/kg µPli, respectively (median and range P<0.05 for each dose versus controls for all parameters).

Conclusions--Bolus intravenous µPli given 90 minutes after thrombotic MCA occlusion in rats reduces cerebral ischemic damage and improves neurological dysfunction, suggesting that µPli could be beneficial in ischemic stroke patients.