Fig. 2

AT1R levels progressively increase in both the brains (a) and spinal cords (b) of mice with NSV encephalomyelitis; receptor expression remains restricted to microglia (c) and infiltrating monocytes (d) in infected mice and receptor deletion confers significant protection against lethal disease (e). Normalized AT1R expression in whole tissue extracts (n = 5 samples per time point) was determined by Western blot. One-way ANOVA confirmed that AT1R levels changed significantly in both CNS compartments over time (p < 0.0001 for both brain and spinal cord). Using transgenic mice selectively expressing GFP in CX3CR1+ cells, AT1R expression was found on a subset of microglia from the hippocampal formations of uninfected animals (c). AT1R staining was not detected on any CX3CR1− cells. Bar = 20 μm. At peak inflammation (day 6), CD45^low/CD11b + microglia and CD45^high/CD11b + infiltrating monocytes expressed equivalent levels of agtr1a mRNA (n = 5 samples per group) (d). Finally, global AT1R KO mice survived NSV infection more readily than WT controls (n = 7 mice per group, p = 0.0148 using a log-rank (Mantel-Cox) test) (e)