Establishment of minimal positive-control conditions to ensure brain safety during rapid development of emergency vaccines

Baek, Hyekyung; Kim, Kwang Ho; Park, Min Young; Kim, Kyeongryun; Ko, Bokyeong; Seo, Hyung Seok; Kim, Byoung Soo; Hahn, Tae-Wook; Yi, Sun Shin

The study design's time schedule in the present study did not allow determination of the exact times when the mRNA and protein expressions were up-or downregulated; however, we speculate on some important clues in which some diverse cytokine actions, closely related with ZO-1 and occludin activity in cytoplasm, might be achieved by mouse strain-specific differences in signal transduction following LPS treatment. It appears that diverse cytokines produced in cytoplasm after LPS injection can break down the intracellular linkage between occludin and ZO-1. Damaged occludin and ZO-1 proteins are degraded by proteasomes and a recovery pathway is needed. In endothelial cells of the BBB in ICR mice, the impairment and recovery routes for occludin and ZO-1 might be time-consuming. As mentioned, the TJ molecular structure or the inflammatory and recovery pathways of BBB in B6 mice might be different from those in ICR mice. Considering the EB assay results demonstrating the disruption of TJs in BBB, we suggest two possibilities for the differences between B6 and ICR mice. First, impairment of ZO-1 and occludin protein of B6 mice might be less caused than those of ICR mice by an inflammatory activity suppressed by an unknown factor. Second, the structure and function of ZO-1 and occludin in B6 mice are recovered after 24 h PI. However, the hypothesis that there might be unknown factors in B6 mice which protects TJs from being destroyed by LPS or it requires time longer than 24 h to be destroyed and/or recovered should be investigated through further study.