Post-partum Anxiety and Hypertension, but not Chronic Neuroinflammation Occur in Response to Hypertensive Pregnancies

During pregnancy hypertensive related disorders, such as preeclampsia and HELLP syndrome, are associated with systemic inflammation and changes in the central nervous system. Previous clinical and experimental studies have shown that circulating inflammatory factors in the blood can contribute to blood brain barrier (BBB) damage in some women with these conditions, which could serve as one possible explanation for the alterations in post‐partum behavior. Using two animal models of hypertensive pregnancy (preeclampsia vs HELLP) we tested the hypothesis that T cell activation during a hypertensive pregnancy is associated with post‐partum anxiety and chronic neuroinflammation. On gestational day (GD) 12 mini‐osmotic pumps infusing sFlt‐1 (4ug) and sEng (7ug) were placed into rats to induce HELLP or with sFlt‐1 alone to increase blood pressure. A subset of rats had 2mg/kg of Orencia infused on GD13 to decrease T cell activation. All rats delivered on GD21 and beginning postpartum week (PPW) 6 animals completed open field and zero maze testing. Blood pressure was measured via tail cuff and animals were euthanized. At euthanization brains were collected, sectioned into frontal and posterior cortices, brainstem and cerebellum. T cells and microglia were isolated from the posterior cortex and brainstem through enzymatic and microbead isolations. Cell populations were cultured overnight and assayed for inflammatory markers via ELISA. Data was analyzed via ANOVA with Tukeys multiple comparison test for post‐hoc analysis using Graphpad Prism. All rats spent significantly less time in the open field compared to NP control rats (p<0.0001). Orencia treatment did not significantly increase the time spent in the open field compared to untreated rats (p=0.18). Both HELLP (p=0.005) and NP+sFlt‐1 (p=0.0005) rats spent significantly less time in the open sections of the zero maze compared to NP rats. However, this behavior was reversed with Orencia treatment (p=0.223). MAP was significantly increased in HELLP rats (p<0.01) and hypertensive rats (p=0.02) compared to NP rats. Orencia prevented hypertension in HELLP (p=0.01) and hypertensive rats (p=0.004) compared to the untreated rats. There were not any significant differences in IL‐17 (p=0.25 brainstem, p=0.89 posterior cortex) or TNF‐alpha (p=0.45 brainstem, p=0.11 posterior cortex) secretion between any of the brain regions or groups when analyzed via ELISA. The results from the current study suggest that hypertension and T cell activation during pregnancy contributes to changes in post‐partum anxiety and post‐partum hypertension but not chronic neuroinflammation. Future studies will examine cognition and look at additional inflammatory pathways. Support or Funding Information 1R01MH116027‐01A1