AMPA受体拮抗剂YM90K可保护大鼠免受永久性和短暂性大脑中动脉闭塞所引起的缺血性损伤。

YM90K, an AMPA receptor antagonist, protects against ischemic damage caused by permanent and transient middle cerebral artery occlusion in rats.

作者信息

Kawasaki-Yatsugi S, Ichiki C, Yatsugi S, Shimizu-Sasamata M, Yamaguchi T

机构信息

Neuroscience Research, Pharmacological Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1998 Nov;358(5):586-91. doi: 10.1007/pl00005297.

DOI:10.1007/pl00005297

PMID:9840429

Abstract

The neuroprotective effect of YM90K, a potent AMPA receptor antagonist, was examined in rats with permanent and transient occlusion of middle cerebral artery (MCA) using intraluminal suture occlusion method. In rats with permanent MCA occlusions, two types of occluders were used to compare the efficacy of YM90K. When a 4-0 (diameter: 0.19 mm) suture was used, YM90K (20 mg kg(-1) h(-1) i.v. infusion for 4 h) significantly reduced infarct volume (P<0.05) and neurologic deficits (P<0.05) 24 h after MCA occlusion. Infarct volume was also reduced by YM90K at the same dose (P<0.01) when severe ischemia was induced by a 3-0 (diameter: 0.23 mm) suture. In rats with transient (3 h) MCA occlusions, a 10-mg kg(-1) h(-1) dose of YM90K that did not show significant protection in rats with permanent MCA occlusion offered neuroprotective effects. These data demonstrate that YM90K provides cerebral neuroprotection against a wide range of ischemic insults.

摘要

使用管腔内缝合闭塞法，在大脑中动脉（MCA）永久性和短暂性闭塞的大鼠中检测了强效AMPA受体拮抗剂YM90K的神经保护作用。在永久性MCA闭塞的大鼠中，使用两种类型的闭塞器来比较YM90K的疗效。当使用4-0（直径：0.19毫米）缝线时，YM90K（20毫克·千克⁻¹·小时⁻¹静脉输注4小时）在MCA闭塞后24小时显著减少梗死体积（P<0.05）和神经功能缺损（P<0.05）。当用3-0（直径：0.23毫米）缝线诱导严重缺血时，相同剂量的YM90K也能减少梗死体积（P<0.01）。在短暂性（3小时）MCA闭塞的大鼠中，10毫克·千克⁻¹·小时⁻¹剂量的YM90K在永久性MCA闭塞的大鼠中未显示出显著保护作用，但却具有神经保护作用。这些数据表明，YM90K对广泛的缺血性损伤具有脑保护作用。