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

作者：Lecht Shimon^*; Rotfeld Elena; Arien Zakay Hadar; Tabakman Rinat; Matzner Henry; Yaka Rami; Lelkes Peter I; Lazarovici Philip

来源：International Journal of Developmental Neuroscience, 2012, 30(6): 465-469.

DOI：10.1016/j.ijdevneu.2012.05.007

• Nifedipine
• Nimodipine
• Oxygen and glucose deprivation
• PC12
• Hypocampal slices
• Neuroprotection

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 mu M) 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 mu M), 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 mu M 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.

• 出版日期2012-10