Fig. 5

Systemic administration of Ago2 restores endothelial barrier function and normalizes glial activation in the cortex. Mice injected intraperitoneally with lipopolysaccharide (LPS, 2 mg/kg) showed the activation of p38 signaling pathway, i.e., increased p38 phosphorylation (Pp38) (b) and produced higher levels of eNOS (c), iNOS (d), NOX2 (e), Iba-1 (g), GFAP (h) and S100B (i), and lower levels of VE-cadherin (a) and p47phox (f). LPS-injected mice treated with Ago2 (0.4 nmol/l) had marker levels similar to sham controls (animals injected with phosphate-buffered saline, CTR), with the exception of the Pp38 and iNOS markers. The same pattern of reduction below control levels was obtained with Ago2 injection in sham controls. Ago2 cortical levels did not change significantly in any of the experimental conditions (j). The levels of NRP1 were only raised in LPS-injected mice treated with Ago2 (k). The table summarizes data from these experiments (l). Schematic representation of the experimental setup used herein (and in this figure) (m). Data are expressed as the mean ± SEM of the indicated number of repeats and as a percentage relative to sham controls (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 compared to sham controls; ^#p < 0.05, ^##p < 0.01, ^####p < 0.0001 compared to LPS-injected animals; one-way ANOVA; in a, c and f, Student’s t test was used for the comparison between CTR and LPS). Ago2 argonaute-2, eNOS endothelial nitric oxide synthase, GFAP glial fibrillary acidic protein, Iba-1 ionized calcium-binding adaptor molecule-1, iNOS inducible nitric oxide synthase, LPS lipopolysaccharide, NG2 oligodendrocyte precursor cells, NO nitric oxide, NOX2 NADPH oxidase 2, NRP1 neuroplilin-1, p47phox neutrophil cytosol factor 1, Pp38 phosphorylated p38 mitogen-activated protein kinases signaling pathway, S100B S100 calcium-binding protein B, VE-cadherin vascular endothelial-cadherin