The Neuroprotective Actions of a Calcium Channel Antagonist, Flunarizine, in the Infant Rat

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Abstract
One postulated final common pathway leading to neuronal death after hypoxic-ischemic insults is increase in intracellular calcium concentrations. We examined the effect of pretreatment with flunarizine, a calcium channel antagonist known to pass the blood brain barrier, on the behavioral and histologic changes after hypoxic-ischemic insult in the infant rat. The 21-d-old were subjected to unilateral carotid ligation, then to 2 hypoxia. They were pretreated with either flunarizine mg/kg, intraperitoneally) or with an equal volume diluent. After 5 days of observation they were killed histology. Acute behavioral abnormalities were observed in more controls than treatment animals, 52 vs 11% (p 0.002). Cerebral injury was almost entirely confined to ligated side and was significantly worse in the control rats. Full thickness cortical infarction was noted in 56% controls (n=27) vs 4% of flunarizine-treated rats (n=24), (pp<0.005). These observations confirm that flunarizine, when given prophylactically, a neuroprotective effect against hypoxic-ischemic injury the developing brain.