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183: Interleukin 1 beta is increased in the hippocampus and posterior cortex of rats with hypertension and systemic inflammation during pregnancy

      Objective

      HELLP syndrome is a severe form of preeclampsia. We have previously shown that both women and animals with HELLP have an increase in T cells, inflammatory cytokines and blood brain barrier (BBB) permeability. Our objective was to determine if rats with HELLP have evidence of BBB permeability and increase in inflammatory cytokines within the brain.

      Study Design

      On gestational day (GD) 12 we infused sEndoglin and sFlt-1 (7 and 4.7ug/kg/day respectively) via a mini-osmotic pump into timed-pregnant rats. Rats not infused served as normal pregnant (NP) controls. On GD19, MAP was measured via carotid arterial catheters placed on GD18, tissues collected, animals euthanized. The brain was weighed, dissected and frozen until assay prep. The cerebellum, hippocampus, frontal and posterior cortex were defrosted on ice. Tissue was homogenized on ice in ice-cold Tris buffer (pH7.4) with protease inhibitor cocktail. Homogenates were centrifuged and supernatants aliquoted. Samples were run using a Milliplex Kit (EMD Millipore) assaying for these cytokines: IL-4, IL-1β, IL-6, IL-10, IL-17A, and VEGFA. All samples were normalized to total protein using the bicinchoninic acid assay. Data was analyzed with a repeated measures two way ANOVA with a Bonferroni post-hoc analysis if applicable. P<0.05.

      Results

      MAP was significantly increased in HELLP rats compared to NP rats (p=0.04; n=4-5/group) on GD19. Infusion of Texas Red dextran on GD19 led to higher dye leakage in the posterior cortex and brainstem of HELLP rats compared to NP rats when viewed by in vivo imaging (IVIS Lumina), indicative of BBB permeability. IL-1β was significantly increased in the posterior cortex (p=0.03) and hippocampus (p=0.01) of HELLP rats compared to NP rats. There were no significant differences in the frontal cortex (p=0.996) between the groups. In the cerebellum IL-1β was significantly decreased (p=0.002) compared to NP rats as was IL-6 (p=0.03). There were no significant differences between HELLP and NP rats in any other cytokines measured.

      Conclusion

      These findings suggest that levels of inflammation in the posterior and hippocampal regions of HELLP rats may indicate increased anxiety or cognitive disorders such as changes in learning and memory or reflective of the posterior reversible encephalopathy syndrome.