Artikel
Neuroprotective effects of nimodipine treatment on astrocytes, neurons and Schwann cells
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Autoren
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Sandra Leisz
- Martin-Luther-Universität Halle-Wittenberg, Klinik für Neurochirurgie, Medizinische Fakultät, Halle, Deutschland
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Eva Herzfeld
- Martin-Luther-Universität Halle-Wittenberg, Klinik für Neurochirurgie, Medizinische Fakultät, Halle, Deutschland
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Christian Strauss
- Martin-Luther-Universität Halle-Wittenberg, Klinik für Neurochirurgie, Medizinische Fakultät, Halle, Deutschland
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Christian Scheller
- Martin-Luther-Universität Halle-Wittenberg, Klinik für Neurochirurgie, Medizinische Fakultät, Halle, Deutschland
| Veröffentlicht: | 18. Juni 2018 |
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Gliederung
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Objective: Nimodipine is a dihydropyridine calcium channel blocker, which is well characterized for the management of aneurysmal subarachnoid hemorrhage and has been shown to promote a better outcome. Furthermore, clinical studies showed a neuroprotective impact of nimodipine after vestibular schwannoma surgeries, but there is only little information about the mode of action and molecular mechanisms of nimodipine treatment. Therefore, the aim of this study was to investigate the influence of nimodipine treatment on the in-vitro neurotoxicity and the associated mechanisms via different surgery-like stress models.
Methods: To analyze the neuroprotective influence of nimodipine, immortalized cell lines from neurons (RN33B), astrocytes (C8-D1A) and Schwann cells (SW10) as well as primary astrocytes and neuronal cells were used. Cells were incubated under stress conditions like heat, osmotic and oxidative stress during different nimodipine concentrations. The cell toxicity was measured via lactate dehydrogenase (LDH) activity of the cell culture supernatant and normalized to total cell lysate LDH activity.
The nimodipine-dependent regulation of anti-apoptotic and endoplasmic reticulum (ER) stress-related genes or proteins was determined via quantitative PCR and Western Blot analysis. For the measurement of intracellular calcium levels a colorimetric assay (Abcam) was used.
Results: The nimodipine treated cell lines (neurons, astrocytes, Schwann cells) and primary cells showed up to 32% significantly lower cytotoxicity during nimodipine treatment after six hour incubation at 42°C. The LDH activity of the Schwann cells during oxidative and osmotic stress was reduced to approximately 75% by treatment of 10 µM nimodipine in comparison to untreated cells. An induction of anti-apoptotic genes and proteins was detected under nimodipine treatment and stress induction, which was accompanied by a reduced intracellular calcium level.
Conclusion: These results indicate that nimodipine is a drug to protect astrocytes, neurons and Schwann cells from stress induced cell death during surgery through the reduction of calcium-dependent apoptosis.
