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(Stroke. 2004;35:2402.)
© 2004 American Heart Association, Inc.

Original Contributions

Microplasmin Reduces Ischemic Brain Damage and Improves Neurological Function in a Rat Stroke Model Monitored With MRI

Yasuhiro Suzuki, PhD; Feng Chen, MD; Yicheng Ni, MD PhD; Guy Marchal, MD PhD; Desire Collen, MD PhD Nobuo Nagai, PhD

From the Center for Molecular and Vascular Biology (Y.S., D.C., N.N.), University of Leuven, Belgium; the Department of Radiology (F.C., Y.N., G.M.), University Hospitals, Leuven, Belgium; and the Department of Radiology (F.C.), Zhong Da Hospital, Southeast University, Nanjing, China.

Correspondence to Dr Nobuo Nagai, Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, O & N, Herestraat 49, B-3000 Leuven, Belgium. E-mail nobuo.nagai{at}med.kuleuven.ac.be

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 rangeP<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.

Key Words: brain infarction • magnetic resonance imaging • models, animal

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				F. Chen, Y. Suzuki, N. Nagai, X. Sun, H. Wang, J. Yu, G. Marchal, and Y. Ni Microplasmin and Tissue Plasminogen Activator: Comparison of Therapeutic Effects in Rat Stroke Model at Multiparametric MR Imaging Radiology, August 1, 2007; 244(2): 429 - 438. [Abstract] [Full Text] [PDF]