Iron-Induced Cerebellar Purkinje Cell Loss Is Ameliorated by Flunarizine

Abstract

Aim: In this study, we investigated the effect of intracerebroventricular-injected iron neurotoxicity on the total number of cerebellar Purkiinje cells in rats and the possible neuroprotective effect of flunarizine, a piperazine-derived calcium channel blocker. Materials and Methods: Rats were divided into four groups: control, flunarizine. iron, and iron + flunarizine groups. Rats in the iron and iron + flunarizine groups received intracerebro-ventricular iron (FeCl(36)H(2)O. 200 mM, 2.5 mu l), while those in flunarizine and iron + flunarizine groups were intraperitoneally injected with flunarizine (10 mg/kg/day) once a day after the operation for 10 days. After 10 days, all rats were perfused intracardially and then sacrificed. Brain tissues were removed and standard histological techniques were performed. The total numbers of Purkinje cells were estimated using unbiased stereological techniques. Results: Means of the total numbers of Purkinje cells in the cerebellum were estimated as 310441 +/- 6558, 298658 +/- 9636, 200201 +/- 6822 and 282658 +/- 6327 in the control, flunarizine, iron, and iron + flunarizine groups. respectively. Comparison between iron and iron + flunarizine groups revealed that flunarizine significantly attenuates the iron-induced neuron loss from 35.5% to 8.9% (P < 0.05). Conclusions: Findings of the present study suggest that flunarizine has a neuroprotective effect on iron-induced Purkinje cell loss in the rat cerebellum via blocking influx of calcium ions into neurons.