Tissue-type plasminogen activator improves neurological functions in a rat model of thromboembolic stroke.
OBJECTIVE
The capacity of an intravenous infusion of double-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 injection of 2-hour-old homologous blood clots to rats. Neurological functions were scored on a 5-point scale 48 hours after the injection of the clots. Infarction size was determined by triphenyltetrazolium chloride staining, and cerebral hemorrhage was examined macroscopically.


RESULTS
Intravenous infusion of tissue-type plasminogen activator (1 or 5 x 10(5) IU/kg) within 3 hours after embolization significantly improved neurological functions (P < .01) and reduced infarction size (P < .05). Tissue-type plasminogen activator treatment 6 hours after embolization failed to attenuate the neurological status score. Treatment with tissue-type plasminogen activator did not increase the incidence of intracerebral hemorrhage and was not associated with a systemic fibrinolytic state. In comparison with tissue-type plasminogen activator treatment, although urokinase treatment (5 x 10(5) IU/kg) improved neurological functions, it was associated with a systemic fibrinolytic state and a tendency to increase the incidence of intracerebral hemorrhage.


CONCLUSIONS
These findings in this model suggest that tissue-type plasminogen activator should be given early after the onset of ischemic symptoms to effectively prevent or limit pathological infarction and improve neurological functions without an increase in the incidence of cerebral hemorrhage.
Sakurama
T
T
Research Laboratories, Sumitomo Pharmaceuticals Co, Ltd, Osaka, Japan.
Kitamura
R
R
Kaneko
M
M
D000818:Animals; D001921:Brain / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000473:pathology / Q000517:prevention & control; D002544:Cerebral Infarction / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D003128:Coma; D003643:Death; D004195:Disease Models, Animal; D006801:Humans; D007262:Infusions, Intravenous; D002542:Intracranial Embolism and Thrombosis / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012640:Seizures; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*
D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator