Post‐partum hypertension and anxiety in an animal model of HELLP/Severe Preeclampsia
Authors: Spencer Shauna‐Kay , Bowles Teylor , Bean Cindy , Owens Michelle Y , Wallace Kedra 
Published: November 2023

Background

Hemolysis Elevated Liver enzyme Low Platelet (HELLP) syndrome and severe preeclampsia (sPreE) is associated with hypertension and inflammation during pregnancy. Women with both conditions are reported to be at an increased risk of developing postpartum depression or post‐traumatic stress disorder (PTSD) therefore we set out to determine if we could detect PTSD and anhedonia in an animal model of HELLP/sPreE. Additionally, we wanted to determine if hypertension persisted into the post‐partum period in this animal model, similar to what is seen in some patients.

Methods

On gestational day (GD) 12, mini‐osmotic pumps infusing sFlt‐1 and sEng (4.7 and 12ug/kg respectively) are placed into timed‐pregnant rats to induce HELLP syndrome and were not removed until 12–24hrs post‐delivery. All pups were permanently removed at the time of pump removal. Sickness behavior was assessed at post‐partum days (PPD) 2–4 and 7–9 by assessing rats home cage behavior. Anxiety‐like behavior was assessed by the marble burying behavioral paradigm and anhedonia measured via two‐bottle sucrose preference test. One week after behavioral testing of rats were complete, mean arterial pressure was measured via an indwelling carotid catheter and blood was collected to assess hemolysis, liver enzyme and platelet levels.

Results

Sickness behavior was assessed at different post‐partum days to determine if systemic inflammation during pregnancy resulted in cytokine induced sickness behavior in the post‐partum period. Rats in the HELLP group displayed a significant reduction in investigatory behavior at PPD2 (p=0.05), but all behaviors normalized by PPD3. Rats were tested between PPD10–12 and PPD21–23 for anxiety‐like behavior. At both periods, rats in the HELLP group buried significantly more marbles (56±4.3%, p=0.006) compared to NP (30.2±6.3%) rats and (61.1±11%, p=0.03) compared to NP rats (30.2±7.38%) respectively. When rats were tested in for anhedonia at either 3 weeks post‐partum or 1 month post‐partum there was no significant difference between rats in the HELLP group and NP group. Mean arterial pressure was assessed between PPD30–35 and rats in the HELLP group were found to be significantly hypertensive (129.2±3.6 vs. 114.6±5.2 p=0.02) compared to NP rats. However while there were no significant differences in hemolysis (p=0.856) or in platelet levels (p=0.287), liver enzymes were significantly increased in rats with a history of HELLP (184.7±16.19 vs. 141.4±10.57 IU/L; p=0.03) compared to NP rats. In addition Texas red dextran infusion at PPD30 revealed a trend towards an increase in blood brain barrier permeability in HELLP rats compared to NP rats (n=3/group).

Conclusions

These results suggest that hypertension and systemic inflammation during pregnancy contributes to an increase in anxiety‐like behavior in the postpartum period, similar to the PTSD that is experienced by women with a history of HELLP syndrome and sPreE. Underlying endothelial damage might serve as one potential mechanism to explain the continued hypertension, liver damage and possible BBB damage in the post‐partum period, thereby serving as a possible therapeutic target.

Support or Funding Information

This work was funded by an Institutional Development Award (IDeA) from the NIGMS under grant number P30GM103328.