The neuroprotective actions of a calcium channel antagonist, flunarizine, in the infant rat

Abstract

One postulated final common pathway leading to neuronal death after hypoxic-ischemic insults is an 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 an hypoxic-ischemic insult in the infant rat. The 21-d-old rats were subjected to unilateral carotid ligation, then to 2 h of hypoxia. They were pretreated with either flunarizine (30 mg/kg, intraperitoneally) or with an equal volume of diluent. After 5 days of observation they were killed for 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 the ligated side and was significantly worse in the control rats. Full thickness cortical infarction was noted in 56% of controls (n = 27) vs 4% of flunarizine-treated rats (n = 24), (p < 0.001). Mean and maximum damage scores for all areas assessed including cortex, corpus striatum, thalamus, amygdala, and hippocampus were improved markedly in treatment rats (p < 0.005). These observations confirm that flunarizine, when given prophylactically, has a neuroprotective effect against hypoxic-ischemic injury in the developing brain. © 1989 International Pediatric Research Foundation, Inc.