Artikel
Investigation of the neuroprotective impact of nimodipine on Neuro2a cells by the means of a surgery-like stress model
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Veröffentlicht: | 13. Mai 2014 |
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Objective: The application of nimodipine reduces the risk of DIND and low functional outcomes following aSAB. Animal experiments and clinical trials showed beneficial impacts of nimodipine treatment concerning functional preservation of facial and cochlear nerves after surgery of vestibularis schwannoma, laryngeal and maxillofacial surgery. A prospective, monocentric and open, randomized study showed that nimodipine medication initiated prior to surgery was predominant compared to operatively initiated medication or no treatment. The mechanism underlying this neuroprotective effect remains unknown. The neuroprotective effect of nimodipine ought to be analysed using Neuro2a cells treated with different stressors, which typically occur during surgery.
Method: Neuro2a cells in certain amounts were pre-treatd with defined nimodipine concentrations (1, 10, or 20 µM). Afterwards cells were stressed by different concentrations of ethanol, NaCl as well as by heat and mechnical manipulation. Cytotoxicity was measured by analysing the release of lactate dehydrogenase into culture medium 24 h post stress. Cell death was calculated relatively to 100% cell death (positive control) and compared to negative controls (without nimodipine treatment).
Results: Nimodipine pre-treatmen led to a reduction of cell death at 1.8% EtOH (p<0.05), which was found to induce approx. 50% cell death. Nimodipine pre-treated cells were incubated at 42°C for 2, 4, or 6 h to induce heat stress. Subsequently cells were incubated at 37°C. After incubation at 42°C for 4 or 6 h, respectively, a slight reduction of cell death was observed at 10 or 20 µM (p<0.05), but not at 1 µM nimodipine. For induction of mechanical stress, cells were shaken with two 2 mm steel beads for 30 sec at 500 rpm. Pre-treatment of cells with either tested concentration of nimodipine led to a reduced LDH release up to 15% (p<0.05). Cell death induced by osmotic stress was not influenced by nimodipine in our hands.
Conclusions: Our findings indicate nimodipine as a potent drug for protection of Neuro2a cells from ethanol, heat and mechanical induced cell death to different extents in a dosage dependent manner. This model seems suitable for investigation of molecular mechanisms involved in the neuroprotective signal pathways influenced by nimodipine.