Neuroprotection in acute stroke has not been successfully translated from animals to humans. Animal research on promising agents continues largely in rats and mice which are commonly available to researchers. However, controversies continue on the most suitable species to model the human situation. Generally, putative agents seem less effective in mice as compared with rats. We hypothesized that this may be due to inter-species differences in stroke response and that this might be manifest at a genetic level. Here we used whole-genome microarrays to examine the differential gene regulation in the ischemic penumbra of mice and rats at 2 and 6 h after permanent middle cerebral artery occlusion (pMCAO; Raw microarray CEL data files are available in the GEO database with an accession number GSE163654). Differentially expressed genes (adj. p ≤ 0.05) were organized by hierarchical clustering, correlation plots, Venn diagrams and pathway analyses in each species and at each time-point. Emphasis was placed on genes already known to be associated with stroke, including validation by RT-PCR. Gene expression patterns in the ischemic penumbra differed strikingly between the species at both 2 h and 6 h. Nearly 90% of significantly regulated genes and most pathways modulated by ischemia differed between mice and rats. These differences were evident globally, among stroke-associated genes, immediate early genes, genes implicated in stress response, inflammation, neuroprotection, ion channels, and signal transduction. The findings of this study may have significant implications for the choice of species for screening putative stroke therapies.

急性中风的神经保护尚未成功地从动物转化为人类。关于有前途的药物的动物研究主要在研究人员通常可用的大鼠和小鼠中继续进行。然而，关于最适合模拟人类状况的物种的争议仍在继续。一般来说，与大鼠相比，假定的药物在小鼠中的效果似乎较差。我们假设这可能是由于中风反应的物种间差异，这可能在遗传水平上表现出来。在这里，我们使用全基因组微阵列检查永久性大脑中动脉闭塞后 2 和 6 小时小鼠和大鼠缺血半影中的差异基因调控（pMCAO；原始微阵列 CEL 数据文件可在 GEO 数据库中获得，登录号为GSE163654）。差异表达基因（adj.p  ≤ 0.05) 由每个物种和每个时间点的层次聚类、相关图、维恩图和通路分析组织。重点放在已知与中风相关的基因上，包括通过 RT-PCR 验证。缺血半影区的基因表达模式在 2 小时和 6 小时的物种之间存在显着差异。近 90% 的显着调节基因和大多数受缺血调节的通路在小鼠和大鼠之间存在差异。这些差异在全球范围内都很明显，包括中风相关基因、早期基因、与压力反应、炎症、神经保护、离子通道和信号转导有关的基因。这项研究的结果可能对筛选推定的中风疗法的物种选择具有重要意义。