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Neuroprotective effects of nimodipine and nifedipine in the NGF‐differentiated PC12 cells exposed to oxygen‐glucose deprivation or trophic withdrawal
Author(s) -
Lecht Shimon,
Rotfeld Elena,
ArienZakay Hadar,
Tabakman Rinat,
Matzner Henry,
Yaka Rami,
Lelkes Peter I.,
Lazarovici Philip
Publication year - 2012
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2012.05.007
Subject(s) - neuroprotection , nimodipine , pharmacology , nifedipine , nerve growth factor , chemistry , medicine , receptor , calcium
The goal of this study was to compare the neuroprotective properties of the l ‐type Ca 2+ 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.