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 5h 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.
Integrated Cellular Tissue Engineering & Regenerative Medicine Laboratory, School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19102, USA. shimon.lecht@drexel.edu
Shimon
S
Lecht
Elena
E
Rotfeld
Hadar
H
Arien-Zakay
Rinat
R
Tabakman
Henry
H
Matzner
Rami
R
Yaka
Peter I
PI
Lelkes
Philip
P
Lazarovici
D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D015687:Cell Hypoxia / Q000187:drug effects; D005947:Glucose / Q000172:deficiency*; D006624:Hippocampus / Q000187:drug effects; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology*; D016716:PC12 Cells / Q000187:drug effects; D051381:Rats
D002395:Catecholamines; D018696:Neuroprotective Agents; D009553:Nimodipine; D020932:Nerve Growth Factor; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; D009543:Nifedipine; D005947:Glucose; D002118:Calcium