Department of Neurology with Institute of Translational Neurology, University of Münster, Albert-Schweitzer-Campus 1, Gebäude A1, 48149, Münster, Germany.
Institute of Epidemiology and Social Medicine, University of Münster, Albert-Schweitzer-Campus 1, Münster, Germany.
Transl Stroke Res. 2021 Dec;12(6):976-990. doi: 10.1007/s12975-021-00887-4. Epub 2021 Jan 26.
Although several studies have suggested that anti-inflammatory strategies reduce secondary infarct growth in animal stroke models, clinical studies have not yet demonstrated a clear benefit of immune modulation in patients. Potential reasons include systematic differences of post-ischemic neuroinflammation between humans and rodents. We here performed a systematic review and meta-analysis to summarize and compare the spatial and temporal distribution of immune cell infiltration in human and rodent stroke. Data on spatiotemporal distribution of immune cells (T cells, macrophages, and neutrophils) and infarct volume were extracted. Data from all rodent studies were pooled by means of a random-effect meta-analysis. Overall, 20 human and 188 rodent stroke studies were included in our analyses. In both patients and rodents, the infiltration of macrophages and neutrophils preceded the lymphocytic influx. Macrophages and neutrophils were the predominant immune cells within 72 h after infarction. Although highly heterogeneously across studies, the temporal profile of the poststroke immune response was comparable between patients and rodents. In rodent stroke, the extent of the immune cell infiltration depended on the duration and location of vessel occlusion and on the species. The density of infiltrating immune cells correlated with the infarct volume. In summary, we provide the first systematic analysis and comparison of human and rodent post-ischemic neuroinflammation. Our data suggest that the inflammatory response in rodent stroke models is comparable to that in patients with stroke. However, the overall heterogeneity of the post-ischemic immune response might contribute to the translational failure in stroke research.
尽管有几项研究表明抗炎策略可减少动物中风模型中的继发性梗塞生长，但临床研究尚未证明免疫调节对中风患者有明确的益处。潜在的原因包括人类和啮齿动物中风后神经炎症的系统差异。我们在此进行了系统评价和荟萃分析，以总结和比较人类和啮齿动物中风中免疫细胞浸润的时空分布。提取了免疫细胞（T 细胞、巨噬细胞和中性粒细胞）和梗塞体积的时空分布数据。通过随机效应荟萃分析汇总了所有啮齿动物研究的数据。总体而言，我们的分析纳入了 20 项人类和 188 项啮齿动物中风研究。在患者和啮齿动物中，巨噬细胞和中性粒细胞的浸润先于淋巴细胞的涌入。巨噬细胞和中性粒细胞是梗塞后 72 小时内的主要免疫细胞。尽管研究之间存在高度异质性，但患者和啮齿动物之间的中风后免疫反应的时间进程是可比的。在啮齿动物中风中，免疫细胞浸润的程度取决于血管闭塞的持续时间和位置，以及物种。浸润免疫细胞的密度与梗塞体积相关。总之，我们提供了人类和啮齿动物缺血后神经炎症的首次系统分析和比较。我们的数据表明，啮齿动物中风模型中的炎症反应与中风患者的炎症反应相当。然而，缺血后免疫反应的总体异质性可能导致中风研究的转化失败。
