Attenuation of extravasation of tissue plasminogen activator by the free radical scavenger, edaravone: evaluation in a rat thromboembolic stroke model.
OBJECTIVE
Deleterious effects of tissue plasminogen activator (tPA) have been described recently in experimental studies. For example, tPA can aggravate ischemic neuronal damage through its proteolytic activity. The present study was undertaken to examine whether or not the free radical scavenger, edaravone, could prevent the extravasation of tPA administered for the purpose of fibrinolysis in a rat model of thromboembolic stroke.


RESULTS
Significant amounts of tPA were extravasated through the cerebral vessels even when early recanalization was induced by administering tPA at 30 minutes after the onset of schema. Edaravone significantly attenuated such extravasation of tPA.


CONCLUSIONS
In acute ischemic stroke patients, combination therapy using tPA with edaravone appears to be a reasonable strategy for diminishing the negative effects of tPA.
Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan. tuneok@med.nihon-u.ac.jp
Tsuneo
T
Kano
Tadashi
T
Harada
Yoichi
Y
Katayama
D000704:Analysis of Variance; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004347:Drug Interactions; D000077553:Edaravone; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D016166:Free Radical Scavengers; D010959:Tissue Plasminogen Activator; D000077553:Edaravone; D000983:Antipyrine