Can gender differences be evaluated in a rhesus macaque (Macaca mulatta) model of focal cerebral ischemia?
Can gender differences be evaluated in a rhesus macaque (Macaca mulatta) model of focal cerebral ischemia?
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发表时间：
2008-12
影响因子：
0.8
通讯作者：
S. Murphy;J. Kirsch;Wenri H Zhang;M. Grafe;G. A. West;G. D. del Zoppo;R. Traystman;P. D. Hum
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文献类型：
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作者：
S. Murphy;J. Kirsch;Wenri H Zhang;M. Grafe;G. A. West;G. D. del Zoppo;R. Traystman;P. D. Hum
性别差异、性类固醇效应和性别特异性候选治疗方法在缺血性卒中中的研究已在啮齿类动物中进行，但未在非人类灵长类动物中进行。在这项可行性研究中（每组n = 3），我们在成年雄性和雌性恒河猴中建立了一种暂时性局灶性脑缺血模型，其中包括白质损伤。这些动物还被用来确定在未来更大规模的临床前试验中，是否可以在该模型中评估组织病理学结果的性别相关差异。在大脑中动脉（MCA）可逆闭塞90分钟后第4天进行脑组织病理组织学评估。通过经眶入路和临时放置动脉瘤夹完成MCA闭塞。研究对象为7至11岁的雄性和雌性恒河猴。各组间基线和缺血血糖、收缩压、心率、血氧饱和度、潮末CO2和直肠温度无差异。损伤体积的可变性与人类局灶性脑血管缺血和其他非人灵长类动物近端MCA闭塞模型中观察到的结果相当。在这个小样本中，损伤体积在男性和女性受试者之间没有差异，但在女性尾状核、壳核和半球中观察到的变异性更高。该报告首次比较了雌性和雄性恒河猴的脑缺血结果。雌性恒河猴缺血性脑卒中模型可以在啮齿类动物研究后使用，为女性临床试验提供临床前数据。
Gender differences, sex steroid effects, and sex-specific candidate therapeutics in ischemic stroke have been studied in rodents but not in nonhuman primates. In this feasibility study (n = 3 per group), we developed a model of transient focal cerebral ischemia in adult male and female rhesus macaques that consistently includes white matter injury. The animals also were used to determine whether gender-linked differences in histopathologic outcomes could be evaluated in this model in future, larger preclinical trials. Histologic brain pathology was evaluated at 4 d after 90 min of reversible occlusion of the middle cerebral artery (MCA). MCA occlusion was accomplished by using a transorbital approach and temporary placement of an aneurysm clip. Male and female rhesus macaques 7 to 11 y of age were studied. Baseline and intraischemic blood glucose, systolic blood pressure, heart rate, oxygen saturation, end-tidal CO2, and rectal temperatures were not different among groups. The variability in injury volume was comparable to that observed in human focal cerebrovascular ischemia and in other nonhuman primate models using proximal MCA occlusion. In this small sample, the volume of injury was not different between male and female subjects, but observed variability was higher in female caudate nucleus, putamen, and hemisphere. This report is the first to compare cerebral ischemic outcomes in female and male rhesus macaques. The female rhesus macaque ischemic stroke model could be used after rodent studies to provide preclinical data for clinical trials in women.