Angiographic evaluation of middle cerebral artery reperfusion caused by platelet glycoprotein IIb/IIIa receptor complex antagonist murine 7E3 F(ab')2 in a model of focal cerebral ischemia in rats.
OBJECTIVE
Antagonists of the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor complex are currently used for the treatment of acute coronary syndromes. The platelet GPIIb/IIIa mediates platelet aggregation, and blocking this receptor complex can reduce or prevent arterial thrombosis. To study the recanalization efficacy of a GPIIb/IIIa antagonist in treating cerebral ischemia, we investigated the therapeutic effects of murine 7E3 F(ab'), in a focal embolic cerebral ischemia model in rats.


METHODS
Focal cerebral ischemia was produced by introducing an autologous thrombus into the right side of the middle cerebral artery (MCA). Thirty male Wistar rats were randomly divided into three groups of 10 rats each: control, 7E3 F(ab')2 administered 1 hour postischemia, and 7E3 F(ab')2 administered 3 hours postischemia. Animals in the therapeutic groups received intravenous infusion of 6 mg/kg 7E3 F(ab')2 at 1 or 3 hours following cerebral embolization. Brain infarct volume, neurobehavioral scores, duration of bleeding, and findings on angiograms of the MCA (before and after infusion) were assessed in all animals. Angiographic evaluation revealed full MCA recanalization in three of 10 animals in each 7E3 F(ab')2 treatment group. Animals in these groups exhibited a significant reduction in infarct volume when compared with animals in the control group: 1) infarct volume 1 hour postischemia, 22 +/- 13.9% (p = 0.005); 2) infarct volume 3 hours postischemia, 22.1 +/- 14.8% (p = 0.008); and 3) infarct volume in control animals, 42.4 +/- 16%. Postischemia treatment with 7E3 F(ab')2 also improved the animal's neurobehavioral performance. The duration of bleeding significantly increased by more than two times, but there was no associated increase in intracerebral hemorrhage in any group.


CONCLUSIONS
On the basis of their findings, the authors conclude that murine 7E3 F(ab'), is a potent and safe antiplatelet agent in this experimental focal embolic cerebral ischemia model. Neuronal lesions were significantly reduced when the treatment was delayed up to 3 hours.
Yang
Y
Y
Division of Neurology, University of Alberta Hospital, Edmonton, Canada.
Li
Q
Q
Nakada
M T
MT
Yang
T
T
Shuaib
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D001760:Bleeding Time; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D002533:Cerebral Angiography; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D002544:Cerebral Infarction / Q000473:pathology; D015994:Incidence; D008297:Male; D020768:Middle Cerebral Artery / Q000503:physiopathology*; D009422:Nervous System Diseases / Q000209:etiology / Q000503:physiopathology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D013623:Tail / Q000098:blood supply
D000911:Antibodies, Monoclonal; D019039:Platelet Glycoprotein GPIIb-IIIa Complex