Protection with flunarizine against hypoxic-ischaemic damage of the rat cerebral cortex. A quantitative morphologic...

The protective effect of flunarizine against cerebral cortical damage was evaluated in the "Levine preparation" after 24 hr of a combined hypoxic-ischaemic insult. Ligation of the right carotid artery, followed by intermittent exposure of the rats to pure nitrogen resulted in two major types of cellular damage in the ipsilateral hemisphere: coagulative necrosis of neurones (ischaemic cell change) and extreme cellular swelling (severe cell change). Quantification of the degree of damage was obtained by calculating the number of both types of cell change per mm3 of cortex. Flunarizine given orally at doses of 20 mg/kg and 10 mg/kg 5 hr before mild hypoxia and at doses of 40 mg/kg and 10 mg/kg 5 hr before severe hypoxia, led to a significant reduction of ischaemic and severe cell change. The calcium entry blocking properties of flunarizine are held responsible for these beneficial effects.