Study of the protective effect of calcium channel blockers against neuronal damage induced by glutamate in cultured hippocampal neurons.
Journal Title: Pharmacological Reports - Year 2013, Vol 65, Issue 3
Abstract
Background: The aim of this study was to examine the putative protective effect of calcium channel blockers on hippocampal neurons in the experimental model of excitotoxic damage. Methods: Seven-day old primary dissociated cultures of rat hippocampal neural cells containing one of the following calcium channel blockers: cinnarizine, flunarizine or nimodipine were exposed to glutamate-induced injury. Quantitative assessments of neuronal injury were accomplished by measuring lactate dehydrogenase (LDH) activity in the media 24 h after exposure to glutamate and by counting and establishing the apoptotic and necrotic cells in flow cytometry with Annexin V-FITC/PI staining. Results: In our experiment, glutamate induced a 339% elevation of apoptotic cells and a 289% increase of necrotic cells in hippocampal neurons as compared to control cultures without drugs. In cultures containing flunarizine, glutamate-induced cell apoptosis was suppressed by 62% while necrosis showed no significant alternation. Cinnarizine exerted no anti-apoptotic effects on glutamate-injured cultured hippocampal neurons, while nimodipine intensified the apoptotic pathway of cell death and promoted an increase in the number of apoptotic neurons by 26%. When cinnarizine or nimodipine were used, the percentage of necrotic cells was significantly lower when compared with glutamate-injured cultures and it amounted to 44% and 24% for cinnarizine and nimodipine, respectively. Conclusions: The obtained results suggest the beneficial anti-apoptotic potential of flunarizine and the anti-necrotic potential of cinnarizine against glutamate-induced death of cultured hippocampal neurons. Nimodipine can protect neurons against necrosis, but has an intensified adverse pro-apoptotic effect on cultured neurons in the experimental model of excitotoxic injury.
Authors and Affiliations
Krzysztof Sendrowski, Małgorzata Rusak, Piotr Sobaniec, Elżbieta Iłendo, Milena Dąbrowska, Leszek Boćkowski, Alicja Koput, Wojciech Sobaniec
Keywords
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