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
Related Articles
- EP ID EP125726
- DOI -
- Views 84
- Downloads 0
Prevention of 1,2-dimethylhydrazine-induced circulatory oxidative stress by bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione during colon carcinogenesis.
We have performed this study to investigate the modulatory effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione, a bisdemethoxy curcumin analog (BDMCA) on circulatory lipid peroxidation (LPO) and antioxidant sta...
Association studies of 5-HT(2A) and 5-HT(2C) serotonin receptor gene polymorphisms with prophylactic lithium response in bipolar patients.
Lithium is one of the most commonly used drugs in the prophylaxis and treatment of bipolar disorder. The mechanisms of mood stabilization by lithium incorporate its effect on serotonergic neurotransmission. This paper in...
Effect of aniracetam on phosphatidylinositol transfer protein alpha in cytosolic and plasma membrane fractions of astrocytes subjected to simulated ischemia in vitro.
Brain ischemia affects phosphoinositide metabolism and the level of lipid-derived second messengers. Phosphatidylinositol transfer proteins (PI-PTs) are responsible for the transport of phosphatidylinositol (PI) and othe...
Influence of the antagonist of the glycine site of NMDA receptors, MRZ 2/576, on the anticonvulsant activity of conventional antiepileptic drugs in mice.
The purpose of this study was to evaluate the influence of the glycine site antagonist of the NMDA receptor, MRZ 2/576 (8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinolin-5-oxide choline salt), on the anticonv...
New neostigmine-based behavioral mouse model of abdominal pain.
Background: Animal models of visceral pain have gained much attention as an important tool to elucidate the possible mechanisms underlying functional gastrointestinal (GI) disorders. Here we report the development of a n...