Inflammatory gene expression in focal cortical brain ischemia: differences between rats and mice.
The impact of species-specific factors on postischemic brain inflammation is largely unknown. In this study, we used quantitative real-time polymerase chain reaction in a highly standardized model of focal cortical brain ischemia for the comparison of cytokine and inducible nitric oxide synthase (iNOS) gene expression in rats and mice. In rats, we found rapid and strong induction of tumor necrosis factor-alpha (TNF-alpha) mRNA reaching its peak at 4 h after ischemia, followed by a slightly delayed peak of interleukin-1beta (IL-1beta) and iNOS mRNA at 16 h. Inflammatory gene induction in mice was overall weaker and considerably more protracted. Both TNF-alpha and IL-1beta transcripts reached their peak around 24 h. In addition, iNOS mRNA exhibited a rather variable, delayed increase between days 3 and 14. Accordingly, immunocytochemistry revealed strong iNOS immunoreactivity in the infarct borderzone at days 1 and 3 in rats whereas only a few iNOS-positive cells were detectable in mice. Taken together, our study demonstrates considerable species differences in inflammatory gene induction after focal brain ischemia.