Auer R N, Anderson L G
Department of Pathology, University of Calgary, Alberta, Canada.
Diabetologia. 1996 Feb;39(2):129-34. doi: 10.1007/BF00403954.
Hypoglycaemic brain damage consists of selective necrosis of cerebral neurons related to the extracellular release of excitatory amino acids. Neuronal excitatory amino acid receptors are activated and calcium channels are opened. The present investigation was designed to test the effectiveness of dihydropyridine blockade of voltage-sensitive calcium channels in hypoglycaemic brain damage. Sixty-four rats were given either high-dose nimodipine, consisting of an initial bolus of 300 micrograms/kg nimodipine administered at the stage of EEG slowing (blood glucose levels of 1.0-1.5 mmol/l), followed by continuous intravenous nimodipine infusion at 1.5 micrograms.kg-1.min-1, low-dose nimodipine, consisting of an initial bolus of 30 micrograms/kg at the time of EEG slowing, followed by 0.15 microgram.kg-1.min-1, an equal volume of vehicle solution, or 154 mmol/l NaCl. Animals receiving either low- or high-dose nimodipine had higher mortality, and increased brain damage compared with controls. Examination of the perfusion-fixed brains 1 week after recovery with glucose revealed that quantitated neuronal necrosis was worsened by nimodipine in the hippocampus, caudate nucleus and cerebral cortex. The present results in profound hypoglycaemia (accompanied by a flat EEG) contrast with the beneficial effect of nimodipine in brain ischaemia.
低血糖性脑损伤包括与兴奋性氨基酸细胞外释放相关的脑神经元选择性坏死。神经元兴奋性氨基酸受体被激活，钙通道开放。本研究旨在测试二氢吡啶对电压敏感性钙通道的阻断在低血糖性脑损伤中的有效性。64只大鼠分别给予高剂量尼莫地平，即在脑电图减慢阶段（血糖水平为1.0 - 1.5 mmol/L）静脉推注300微克/千克尼莫地平，随后以1.5微克·千克⁻¹·分钟⁻¹的速度持续静脉输注尼莫地平；低剂量尼莫地平，即在脑电图减慢时静脉推注30微克/千克，随后以0.15微克·千克⁻¹·分钟⁻¹的速度输注；等体积的赋形剂溶液，或154 mmol/L氯化钠。与对照组相比，接受低剂量或高剂量尼莫地平的动物死亡率更高，脑损伤增加。在恢复血糖1周后对灌注固定的大脑进行检查发现，尼莫地平使海马体、尾状核和大脑皮层的定量神经元坏死恶化。本研究在严重低血糖（伴有脑电图平坦）中的结果与尼莫地平在脑缺血中的有益作用形成对比。
