Lecht Shimon, Rotfeld Elena, Arien-Zakay Hadar, Tabakman Rinat, Matzner Henry, Yaka Rami, Lelkes Peter I, Lazarovici Philip
Integrated Cellular Tissue Engineering & Regenerative Medicine Laboratory, School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19102, USA.
Int J Dev Neurosci. 2012 Oct;30(6):465-9. doi: 10.1016/j.ijdevneu.2012.05.007. Epub 2012 Jun 5.
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.
本研究的目的是比较L型Ca²⁺通道阻滞剂尼莫地平和硝苯地平的神经保护特性，使用经神经生长因子（NGF）分化的PC12神经元培养物，使其暴露于氧-葡萄糖剥夺（OGD）和营养物质撤除诱导的细胞死亡环境中。尼莫地平（1 - 100 μM）在暴露于OGD时可提供65±13%的神经保护作用，对于通过乳酸脱氢酶和半胱天冬酶3活性测定的不同营养物质撤除诱导的细胞死亡，可提供35±6%的神经保护作用。尼莫地平发挥神经保护作用的时间窗在最初5小时内被检测到，但在更长时间的OGD暴露时未检测到。硝苯地平（1 - 100 μM），其效力低于尼莫地平，在PC12细胞中对OGD可提供30 - 55±8%的神经保护作用，在大鼠海马切片中为29±5%，在100 μM时对营养物质撤除诱导的PC12细胞死亡可提供10±3%的神经保护作用。能够证明尼莫地平在狭窄的治疗时间窗内发挥神经保护作用，表明OGD PC12模型模拟了体内模型，因此适用于神经保护药物的发现和开发。
