Nurse S, Corbett D
Division of Basic Medical Sciences, Faculty of Medicine, Health Sciences Centre, Memorial University of Newfoundland, St. John's, Canada.
J Cereb Blood Flow Metab. 1996 May;16(3):474-80. doi: 10.1097/00004647-199605000-00014.
Stroke trials are initiated after demonstrated pharmacological protection in animal models. NBQX protects CA1 neurons against global ischemia; however, this glutamate antagonist induces a period of subnormal temperature (e.g., a decrease of only 1.0-1.5 degrees C) lasting several days. In this study, NBQX (3 x 30 mg/kg, i.p.) was administered starting 60 min after reperfusion, and brain temperature had declined significantly below vehicle-treated animals by 2 h after reperfusion. When the postischemic brain temperature of NBQX-treated gerbils was regulated, no neuronal protection was found. Mimicking an NBQX-induced temperature profile for 28 h postischemia yielded histological protection 4 days later comparable to that of NBQX. However, both the NBQX and temperature simulation groups showed decreased protection after 10-day survival. Our data suggest that a protracted period of subnormal temperature during postischemic period can obscure the interpretation of preclinical drug studies.
在动物模型中证实有药理学保护作用后才开展中风试验。NBQX可保护CA1神经元免受全脑缺血损伤；然而，这种谷氨酸拮抗剂会引发一段持续数天的体温低于正常水平的时期（例如，仅降低1.0 - 1.5摄氏度）。在本研究中，于再灌注60分钟后开始腹腔注射NBQX（3×30毫克/千克），再灌注2小时后，脑温显著低于给予赋形剂处理的动物。当对经NBQX处理的沙鼠缺血后脑温进行调节时，未发现神经元保护作用。在缺血后模拟NBQX诱导的体温曲线28小时，4天后产生的组织学保护作用与NBQX相当。然而，在存活10天后，NBQX组和体温模拟组的保护作用均减弱。我们的数据表明，缺血后长时间体温低于正常水平会掩盖临床前药物研究的结果解读。
