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

• Published in: International journal of developmental neuroscience 2012-10, Vol.30 (6), p.465-469
• Main Authors: Lecht, Shimon, Rotfeld, Elena, Arien-Zakay, Hadar, Tabakman, Rinat, Matzner, Henry, Yaka, Rami, Lelkes, Peter I., Lazarovici, Philip
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Calcium - metabolism; Caspase 3 - metabolism; Catecholamines - metabolism; Cell Differentiation - drug effects; Cell Hypoxia - drug effects; Glucose - deficiency; Hippocampus - drug effects; Hypocampal slices; In Vitro Techniques; Indexing in process; L-Lactate Dehydrogenase - metabolism; Nerve Growth Factor - metabolism; Nerve Growth Factor - pharmacology; Neuroprotection; Neuroprotective Agents - pharmacology; Nifedipine; Nifedipine - pharmacology; Nimodipine; Nimodipine - pharmacology; Oxygen and glucose deprivation; PC12; PC12 Cells - drug effects; Rats
• ISSN: 0736-5748; 1873-474X
• DOI: 10.1016/j.ijdevneu.2012.05.007

► 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 5h 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. 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 (1–100μM) 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 5h but not at longer OGD exposures. Nifedipine (1–100μM), 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 100μM 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.