Flunarizine reduces cerebral infarct size after photochemically induced thrombosis in spontaneously hypertensive rats.
The cerebroprotective effect of flunarizine was studied in a minimally invasive model of photochemically induced cerebral infarction in spontaneously hypertensive rats. Intravenous administration of the photosensitizing dye rose bengal and intense focal illumination of the brain produced a deep cortical infarction that resulted from singlet oxygen-induced peroxidative injury to the endothelial membrane, subsequent platelet adhesion, and eventual thrombus formation. The infarct size was calculated from area measurements on consecutive histologic sections prepared from the brain cortex 4 hours after the onset of the insult. Oral treatment with 40 mg/kg flunarizine 3 hours before photoexcitation resulted in a significant reduction of the median infarct size from 11.75 mm3 in the untreated group to 6.40 mm3 in the treated group (n = 13, p less than 0.001). At this dose, flunarizine had no effect on systemic blood pressure. In a separate experiment the area of thrombotic obstruction was quantified 30 minutes after the onset of light exposure. Flunarizine did not significantly reduce early thrombus formation (2.28 mm3 in the untreated and 1.78 mm3 in the treated group) (n = 12, p = 0.2). The infarcted area at 4 hours was considerably larger than the initial thrombotic area. Protection with flunarizine against development of cortical infarction has been unequivocally shown. Although some effect may already be present at the early stage of lesion formation, the major protective action admittedly occurred in the later postinsult period when the lesion was expanding.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Life Sciences, Janssen Pharmaceutica, Beerse, Belgium.
J
J
Van Reempts
B
B
Van Deuren
M
M
Van de Ven
F
F
Cornelissen
M
M
Borgers
D000818:Animals; D002540:Cerebral Cortex / Q000473:pathology; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D005444:Flunarizine / Q000627:therapeutic use*; D002542:Intracranial Embolism and Thrombosis / Q000209:etiology; D008027:Light; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D012395:Rose Bengal
D012395:Rose Bengal; D005444:Flunarizine