Adachi N, Chen J, Liu K, Nagaro T, Arai T
Department of Anesthesiology and Resuscitology, Ehime University School of Medicine, Onsen-gun, Japan.
Eur J Pharmacol. 1999 Jun 4;373(2-3):147-52. doi: 10.1016/s0014-2999(99)00294-0.
Transient forebrain ischemia was induced in gerbils, and the effect of a pre-ischemic treatment with metyrapone (100 mg/kg) on delayed neuronal death in hippocampal CA1 neurons was evaluated. The effect of metyrapone on the ischemic release of amino acids in the CA1 region was also examined by microdialysis. Hippocampal slices were used for the evaluation of the hypoxia-induced intracellular Ca2+ increase by microfluorometry. The metyrapone treatment morphologically improved the damage provoked by 3 min of ischemia, although it did not alleviate the damage by 5 min. Ischemia for 3 min produced a 306% increase in the glutamate concentration in perfusates, and metyrapone suppressed the peak value to 42% of that in the control group. The extent of the increase in fluorescence intensity by intracellular Ca2+ was lower by 16% in slices from metyrapone-treated animals than in controls 600 s after induction of hypoxia. The removal of Ca2+ from the perfusion medium suppressed the hypoxic Ca2+ increase, and the increase was further reduced in slices pretreated with metyrapone. The increase in the level of endogenous glucocorticoids, which occurs in cerebral ischemia, may aggravate ischemic neuronal damage.
在沙鼠中诱导短暂性前脑缺血，评估用甲吡酮（100mg/kg）进行缺血前处理对海马CA1神经元延迟性神经元死亡的影响。还通过微透析检查了甲吡酮对CA1区缺血性氨基酸释放的影响。使用海马切片通过微荧光测定法评估缺氧诱导的细胞内Ca2+增加。甲吡酮治疗在形态上改善了3分钟缺血引起的损伤，尽管它没有减轻5分钟缺血造成的损伤。3分钟缺血使灌注液中谷氨酸浓度增加306%，甲吡酮将峰值抑制至对照组的42%。在缺氧诱导600秒后，甲吡酮处理动物的切片中细胞内Ca2+引起的荧光强度增加程度比对照组低16%。从灌注培养基中去除Ca2+可抑制缺氧性Ca2+增加，在用甲吡酮预处理的切片中增加进一步减少。脑缺血时内源性糖皮质激素水平的升高可能会加重缺血性神经元损伤。
