YM872是一种高度水溶性的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂，可保留血流动力学半暗带并减轻大鼠永久性局灶性缺血后的脑损伤。

YM872, a highly water-soluble AMPA receptor antagonist, preserves the hemodynamic penumbra and reduces brain injury after permanent focal ischemia in rats.

作者信息

Shimizu-Sasamata M, Kano T, Rogowska J, Wolf G L, Moskowitz M A, Lo E H

机构信息

Departments of Neurosurgery and Neurology, Stroke and Neurovascular Regulation Laboratory, Harvard Medical School, Charlestown, MA.

出版信息

Stroke. 1998 Oct;29(10):2141-8. doi: 10.1161/01.str.29.10.2141.

DOI:10.1161/01.str.29.10.2141

PMID:9756596

Abstract

BACKGROUND AND PURPOSE

We recently described an image analysis technique based on the temporal correlation mapping (TCM) of injected contrast agents that can be used to distinguish the hemodynamic core and hemodynamic penumbra after focal ischemia. In this study we used this technique for the first time to investigate the effects of the water-soluble AMPA receptor antagonist YM872 in permanent focal ischemia.

METHODS

Fischer 344 rats were subjected to permanent occlusion of the middle cerebral artery. Approximately 30 minutes after ischemia, functional CT images were collected with the use of a dynamic scanning protocol with bolus injections of nonionic contrast agent iohexol (1 mL/kg). TCM analysis defined the distributions of hemodynamic core and hemodynamic penumbra. Cerebral perfusion indices were calculated on the basis of the area under the first-pass transit curves. One hour after ischemia, animals were randomly treated with YM872 (n=8, 20 mg/kg per hour over 4 hours) or normal saline (n=10). Twenty-four hours later, neurological deficits were evaluated, and conventional CT and triphenyltetrazolium chloride staining were used to define volumes of ischemic damage.

RESULTS

At 24 hours after ischemia, hypodense lesions were visible on conventional CT scans that were highly correlated with triphenyltetrazolium chloride lesion volumes. YM872 improved neurological deficits and reduced volumes of ischemic damage in cortex (90+/-14 versus 170+/-16 mm3 in controls) but not striatum (57+/-14 versus 79+/-6 mm3 in controls). Comparison of early TCM images with conventional CT scans of ischemic injury showed that the hemodynamic core was always damaged in all rats. In controls, 54% of the tissue within the hemodynamic penumbra evolved into ischemic damage compared with 24% in YM872-treated rats. Furthermore, the perfusion index corresponding to the ischemic damage threshold was significantly reduced by YM872 (28+/-2% versus 37+/-2% in controls).

CONCLUSIONS

These results indicate that YM872 is a neuroprotective compound that ameliorates the deterioration of the hemodynamic penumbra after focal ischemia.

摘要

背景与目的

我们最近描述了一种基于注射造影剂的时间相关性映射（TCM）的图像分析技术，该技术可用于区分局灶性缺血后的血流动力学核心区和血流动力学半暗带。在本研究中，我们首次使用该技术来研究水溶性AMPA受体拮抗剂YM872在永久性局灶性缺血中的作用。

方法

将Fischer 344大鼠进行大脑中动脉永久性闭塞。缺血后约30分钟，采用动态扫描方案并团注非离子型造影剂碘海醇（1 mL/kg）收集功能CT图像。TCM分析确定血流动力学核心区和血流动力学半暗带的分布。根据首过通过曲线下的面积计算脑灌注指数。缺血1小时后，动物随机接受YM872治疗（n = 8，4小时内每小时20 mg/kg）或生理盐水治疗（n = 10）。24小时后，评估神经功能缺损，并使用传统CT和氯化三苯基四氮唑染色来确定缺血损伤体积。

结果

缺血2小时后，传统CT扫描可见低密度病变，其与氯化三苯基四氮唑病变体积高度相关。YM872改善了神经功能缺损，并减少了皮质的缺血损伤体积（对照组为170±16 mm³，YM872治疗组为90±14 mm³），但对纹状体无影响（对照组为79±6 mm³，YM872治疗组为57±14 mm³））。早期TCM图像与缺血损伤的传统CT扫描比较显示，所有大鼠的血流动力学核心区均受损。在对照组中，血流动力学半暗带内有54%的组织演变为缺血损伤，而在YM872治疗组中这一比例为24%。此外，YM872使对应于缺血损伤阈值的灌注指数显著降低（对照组为37±2%，YM872治疗组为28±2%）。