(Stroke. 1999;30:1464-1471.)
© 1999 American Heart Association, Inc.
Original Contributions |
Effects of Citicoline Combined With Thrombolytic Therapy in a Rat Embolic Stroke Model
From the Neurovascular Research Laboratory, Rigshospitalet (M.A.), and Department of Neurology, Bispebjerg Hospital (K.O., P.M., G.B.), Copenhagen University (Denmark).
Correspondence to Karsten Overgaard, MD, Department of Neurology, Copenhagen University Hospital, Bispebjerg Hospital, DK-2400 Copenhagen NV, Denmark. E-mail karsten overgaard{at}dadlnet.dkovergaard@dadlnet.dk
Background and Purpose—We sought to evaluate the effects of the combination of cytidine-5'-diphosphocholine (citicoline) and thrombolysis on infarct size, clinical outcome, and mortality in a rat embolic stroke model.
Methods—Eighty-three Sprague-Dawley rats were embolized in the carotid territory with a single fibrin embolus and randomly assigned to the following treatment groups: (1) control (saline), (2) citicoline 250 mg/kg, (3) citicoline 500 mg/kg, (4) recombinant tissue plasminogen activator (rtPA) 5 mg/kg, (5) rtPA 5 mg/kg plus citicoline 250 mg/kg, and (6) rtPA 5 mg/kg plus citicoline 500 mg/kg. rtPA was administered as a continuous intravenous infusion over 45 minutes starting 45 minutes after embolization; citicoline was given intraperitoneally 30 minutes and 24, 48, and 72 hours after embolization. At 96 hours, the brains were fixed and stained by hematoxylin-eosin, and infarct volumes were measured. Neurological scores were determined daily.
Results—The median infarct size, measured as percentage of the affected hemisphere, in the control group was 37% (interquartile range, 26% to 69%) compared with 22% (5% to 52%; P=NS) in group 2, 11% (5% to 34%; P=NS) in group 3, 24% (12% to 31%; P=NS) in group 4, 11% (3% to 22%; P=0.02) in the combined group 5, and 19% (9% to 51%; P=NS) in group 6. The infarct size was significantly reduced in the combined citicoline+rtPA–treated groups to a median of 13% (5% to 30%; P<0.01). Citicoline 500 mg/kg and citicoline combined with rtPA also promoted functional recovery.
Conclusions—These results demonstrate that the combination of low-dose citicoline and rtPA significantly reduced infarct size in this focal ischemia model.
Editorial Comment
Department of Biostatistics, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia
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