TISSUE-TYPE PLASMINOGEN-ACTIVATOR IMPROVES NEUROLOGICAL FUNCTIONS IN A RAT MODEL OF THROMBOEMBOLIC STROKE

Background and Purpose The capacity of an intravenous infusion of doub le-stranded tissue-type plasminogen activator to salvage neurological functions in a rat model of thromboembolic stroke was studied. Methods The model of thromboembolic stroke was induced by the intracarotid in jection of 2-hour-old homologous blood clots to rats. Neurological fun ctions were scored on a 5-point scale 48 hours after the injection of the clots. Infarction size was determined by triphenyltetrazolium chlo ride staining, and cerebral hemorrhage was examined macroscopically. R esults Intravenous infusion of tissue-type plasminogen activator (1 or 5x10(5) IU/kg) within 3 hours after embolization significantly improv ed neurological functions (P<.01) and reduced infarction size (P<.05). Tissue-type plasminogen activator treatment 6 hours after embolizatio n failed to attenuate the neurological status score. Treatment with ti ssue-type plasminogen activator did not increase the incidence of intr acerebral hemorrhage and was not associated with a systemic fibrinolyt ic state. In comparison with tissue-type plasminogen activator treatme nt, although urokinase treatment (5x10(5) IU/kg) improved neurological functions, it was associated with a systemic fibrinolytic state and a tendency to increase the incidence of intracerebral hemorrhage. Concl usions These findings in this model suggest that tissue-type plasminog en activator should be given early after the onset of ischemic symptom s to effectively prevent or limit pathological infarction and improve neurological functions without an increase in the incidence of cerebra l hemorrhage.