Neuroprotective effects of nimodipine and nifedipine in the NGF-differentiated PC12 cells exposed to oxygen-glucose deprivation or trophic withdrawal

The goal of this study was to compare the neuroprotective properties of the l-type Ca2+ channel blockers, nimodipine and nifedipine, using nerve growth factor (NGF)-differentiated PC12 neuronal cultures exposed to oxygen-glucose deprivation (OGD) and trophic withdrawal-induced cell death. Nimodipine (1–100 μM) conferred 65 ± 13% neuroprotection upon exposure to OGD and 35 ± 6% neuroprotection towards different trophic withdrawal-induced cell death measured by lactate dehydrogenase and caspase 3 activities. The time window of nimodipine conferred neuroprotection was detected during the first 5 h but not at longer OGD exposures. Nifedipine (1–100 μM), to a lower potency than nimodipine, conferred 30–55 ± 8% neuroprotection towards OGD in PC12 cells and 29 ± 5% in rat hypocampal slices, and 10 ± 3% neuroprotection at 100 μM towards trophic withdrawal-induced PC12 cell death. The ability to demonstrate that nimodipine conferred neuroprotection in a narrow therapeutic time-window indicates that the OGD PC12 model mimics the in vivo models and therefore suitable for neuroprotective drug discovery and development.

► We studied Ca2+ channel blockers-mediated neuroprotection using in vitro PC12 model. ► Nimodipine/nifedipine induced neuroprotection against OGD and trophic withdrawal. ► Time window of nimodipine-induced neuroprotection was during first 5 h of OGD. ► Nifedipine conferred neuroprotection towards OGD insult in rat hypocampal slices. ► OGD PC12 model mimics in vivo results, thus useful for neuroprotective drug discovery.