Modeling Immunity and Inflammation in Stroke Can Mice Be Trusted?

Sounds like a researcher problem to solve.
http://stroke.ahajournals.org/content/45/9/e177.extract?etoc

1. Ulrich Dirnagl, MD

+ Author Affiliations

1. From the Departments of Neurology and Experimental Neurology Charité, Center for Stroke Research Berlin, Charité, ExcellenceCluster NeuroCure–Universitätsmedizin Berlin, Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE), Partner Site, Berlin, Germany; and German Center for Cardiovascular Diseases (DZHK), Partner Site, Berlin, Germany.

1. Correspondence to Ulrich Dirnagl, MD, Center for Stroke Research Berlin, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. E-mail ulrich.dirnagl@charite.de

Key Words:

• immune system
• inflammation
• models, animal
• stroke

Introduction

Sixty-five million years have passed since mouse and man shared a common ancestor. The principles of evolution, as well as the scientific literature, suggest that there are many similarities between both mammal species but also significant differences. Humans are definitely no 75 kg mice,¹ but is it true that “the mouse model has been totally misleading for at least three major killers—sepsis, burns, and trauma,” as the New York Times concluded after the publication of a study by Seok et al?² By looking at transcriptional responses of blood cells, this study found “that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another.”

The results of the Seok et al² study are by no means surprising or new,³ but they nevertheless carry an important message for experimental stroke research. The authors used male mice of the C57 BL/6J strain, which is exquisitely resistant to sepsis: more than one million-fold doses of endotoxin are required to cause shock in this mouse strain. The mice are inbred and raised under specific pathogen-free conditions, so at the time of the study, the 8-week-old mice had a naive and immature immune system.

In contrast, rodents are as sensitive to focal cerebral ischemia as humans. The evolution of the infarct and surrounding penumbra has similar temporal and histopathologic dynamics, and the time windows for thrombolysis after embolic stroke are practically …

[Full Text of this Article]