Differential Regional Vulnerability of the Brain to Mild Neuroinflammation Induced by Systemic LPS Treatment in Mice

Background: Peripheral inflammation-triggered mild neuroinflammation impacts the brain and behavior through microglial activation. In this study, we performed an unbiased analysis of the vulnerability of different brain areas to neuroinflammation induced by systemic inflammation. Methods: We injected mice with a single low dose of LPS to induce mild inflammation and then analyzed microglial activation in 34 brain regions by immunohistochemical methods and whole-brain imaging using multi-slide scanning microscopy. We also conducted quantitative RT-PCR to measure the levels of inflammatory cytokines in selected brain regions of interest. Results: We found that microglia in different brain regions are differentially activated by mild, LPS-induced inflammation relative to the increase in microglia numbers or increased CD68 expression. The increased number of microglia induced by mild inflammation was not attributable to infiltration of peripheral immune cells. In addition, microglia residing in brain regions, in which a single lowdose injection of LPS produced microglial changes, preferentially generated pro-inflammatory cytokines. Conclusion: Our results suggest that mild neuroinflammation induces regionally different microglia activation, producing proinflammatory cytokines. Our observations provide insight into induction of possible region-specific neuroinflammation-associated brain pathologies through microglial activation.