Shibata S, Kagami-Ishi Y, Tominaga K, Kodama K, Ueki S, Watanabe S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Eur J Pharmacol. 1992 Dec 8;229(1):21-9. doi: 10.1016/0014-2999(92)90281-8.
Various in vitro models have been developed to study ischemia and/or hypoxia. In the present experiment, we examined whether hypoxia/hypoglycemia (ischemia) in rat hippocampal slices reduced the 2-deoxyglucose (2-DG) uptake and CA1 field potentials evoked by stimulation of Schaffer collaterals. Autoradiograms revealed that ischemia for 15 or 20 min reduced 2-DG uptake in the stratum radiatum of the CA1 and the dentate gyrus. Similarly, the CA1 field potentials of slices exposed to ischemia for 15 and 20 min decreased by about 70 and 90% after a 6-h washout. In the second experiment, we evaluated the neuroprotective effect of the 5-HT1A receptor agonists 8-OH-DPAT and buspirone, and the 5-HT2 receptor antagonists cyproheptadine, mianserin and ketanserin on deficits of 2-DG uptake and Schaffer-CA1 field potentials induced by ischemia. The 5-HT1A receptor agonists and 5-HT2 receptor antagonists exhibited significant neuroprotective actions against ischemia-induced deficits. Therefore, impairments of 2-DG uptake and CA1 field potentials induced by ischemia may be good markers of ischemia-induced functional deficits. The attenuating action of 5-HT1A receptor agonists and 5-HT2 receptor antagonists were assessed using this model of ischemia.
已经开发了各种体外模型来研究缺血和/或缺氧。在本实验中，我们研究了大鼠海马切片中的缺氧/低血糖（缺血）是否会降低由刺激Schaffer侧支诱发的2-脱氧葡萄糖（2-DG）摄取和CA1场电位。放射自显影片显示，缺血15或20分钟会降低CA1辐射层和齿状回中的2-DG摄取。同样，暴露于缺血15和20分钟的切片的CA1场电位在6小时洗脱后分别降低约70%和90%。在第二个实验中，我们评估了5-HT1A受体激动剂8-OH-DPAT和丁螺环酮，以及5-HT2受体拮抗剂赛庚啶、米安色林和酮色林对缺血诱导的2-DG摄取和Schaffer-CA1场电位缺陷的神经保护作用。5-HT1A受体激动剂和5-HT2受体拮抗剂对缺血诱导的缺陷表现出显著的神经保护作用。因此，缺血诱导的2-DG摄取和CA1场电位损伤可能是缺血诱导的功能缺陷的良好标志物。使用这种缺血模型评估了5-HT1A受体激动剂和5-HT2受体拮抗剂的衰减作用。
