Effect of acute calcium influx after mechanical stretch injury in vitro on the viability of hippocampal neurons
Effect of acute calcium influx after mechanical stretch injury in vitro on the viability of hippocampal neurons
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DOI：
10.1089/089771504772695959
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发表时间：
2004-01-01
影响因子：
4.2
通讯作者：
Meaney, DF
中科院分区：
文献类型：
--
作者：
Lusardi, TA;Wolf, JA;Meaney, DF
我们使用一种新的体外模型来研究机械变形对神经元的影响。我们研究了细胞内钙浓度（[Ca2+](i)）的急性变化，这是由培养海马神经元的快速拉伸引起的，使用机械负荷条件来模拟创伤期间的大脑变形。我们发现神经元的拉伸损伤诱导了[Ca2+]的应变依赖性增加(i)。值得注意的是，这种钙反应的程度超过了NMDA （100 mM）或谷氨酸（5 mM）暴露的化学毒性所引发的水平。拉伸后24小时碘化丙啶标记显示，仅在最严重的机械损伤水平发生神经元死亡。尽管nmda诱导的毒性可以在无钙培养基或MK-801处理中被抑制，但拉伸诱导的神经元死亡在两种处理中都没有类似地减少。出乎意料的是，使用无钙介质或MK-801减少急性拉伸诱导的钙瞬态导致较低拉伸水平下神经元死亡的增加。这些数据表明，机械拉伸可以启动海马神经元的钙内流，但从细胞外空间或通过NMDA通道实质性地调节早期钙通量并不是改善神经元存活的有效手段。
We use a new in vitro model to examine the effect of mechanical deformation on neurons. We examined acute changes in cytosolic calcium concentrations ([Ca2+](i)) caused by a rapid stretch of cultured hippocampal neurons, using mechanical loading conditions that mimic brain deformations during trauma. We found that stretch-injury of neurons induces a strain-dependent increase in [Ca2+](i). Remarkably, the extent of this calcium response exceeded the levels initiated by chemical toxicity with NMDA (100 muM) or glutamate (5 mM) exposure. Propidium iodide labeling at 24 h following stretch showed neuronal death occurred only at the most severe level of mechanical injury. Although NMDA-induced toxicity could be inhibited in calcium free media or by treatment with MK-801, stretch-induced neuronal death was not similarly reduced with either treatment. Unexpectedly, reduction of the acute stretch-induced calcium transient with calcium-free media or MK-801 resulted in an increase in neuronal death at lower stretch levels. These data suggest that mechanical stretch can initiate calcium influx in hippocampal neurons, but substantially modulating the early calcium flux from the extracellular space or through the NMDA channel does not provide an effective means for improving neuronal survival.