Modeling immunity and inflammation in stroke: differences between rodents and humans?

Abstract

A recent article “Genomic responses in mouse models poorly mimic human inflammatory diseases” showed that among genes that changed significantly in humans, the murine orthologs were close to random in matching their human counterparts.1 Although this study focused on sepsis, it also raises questions about how well the rodent inflammatory response corresponds to the human inflammatory response after ischemic stroke. In this essay we argue that the peripheral inflammatory response in rodent ischemic stroke models is different than in human stroke. Given the important role of the immune system in stroke, this could be a major handicap in translating results in rodent stroke models to clinical trials in patients with stroke. Leukocyte composition in blood differs considerably in humans compared with rodents. In humans ≈50% to ≈60% of leukocytes are neutrophils and 15% to 30% are lymphocytes. In contrast, rats and mice have only 15% to 20% neutrophils and ≈60% lymphocytes. The impact of such a difference in stroke is uncertain, although certainly noteworthy. Functional differences in the immune systems of rodents and humans also exist. For example, rodents are much more resistant to infections compared with humans after surgical …