Department of Neurosurgery, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany.
Department of Anaesthesiology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany.
Int J Mol Sci. 2020 Nov 24;21(23):8921. doi: 10.3390/ijms21238921.
Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs-nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)-might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage ( = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.
有效的药物神经保护是现代医学最理想的目标之一。我们假设两种临床使用的药物——尼莫地平（L 型电压门控钙通道阻滞剂）和阿米洛利（酸感应离子通道抑制剂）——可能在缺血的实验模型中协同作用，针对细胞内钙的升高作为神经元细胞死亡的途径。我们使用了来自幼鼠的器官型海马切片和已建立的氧葡萄糖剥夺（OGD）方案来评估可能的神经保护作用。尼莫地平（10 或 20 μM）单独或与阿米洛利（100 μM）联合使用均未显示出任何改善作用。以 2.0 体积%二甲亚砜（DMSO）溶解，两种成分的组合甚至增加了细胞损伤（=0.0001），而单独使用阿米洛利则没有观察到这种作用。我们的结论是，在体外缺血模型中，阿米洛利和尼莫地平都不能提供神经保护。在技术层面上，由于 DMSO 可能改变细胞损伤，因此在神经保护实验中应谨慎评估其使用。
