Hypertension, Anxiety, and Blood-Brain Barrier Permeability Are Increased in Postpartum Severe Preeclampsia/Hemolysis, Elevated Liver Enzymes, and Low Platelet Count Syndrome Rats

Abstract

Hypertension and inflammation during pregnancy are suggested to contribute to the development of post-partum depression and anxiety. Using a rat model of severe preeclampsia and Hemolysis Elevated Liver enzymes Low Platelet syndrome which displays both hypertension and inflammation during pregnancy we evaluated whether rats were prone to develop depression or anxiety in the post-partum period. On gestational day 12, mini-osmotic pumps infusing sFlt-1 and sEng were placed into rats, a subset of these rats were infused with 2mg/kg of Orencia (Abatacept) the following day to determine if immune suppression via T cell depletion prevented any changes in maternal depression and/or anxiety-like behavior. All rats including normal pregnant controls delivered between gestational days 21–22. Post-partum severe preeclamptic rats buried significantly more marbles compared to normal pregnant rats (p=0.002) and Orencia treated rats (p=0.05). Severe preeclamptic rats spent significantly more time in closed arms of the elevated plus maze compared to normal pregnant rats (p=0.009) and Orencia treated rats (p=0.05). Severe preeclamptic rats were hypertensive compared to normal pregnant (p=0.03) and Orencia treated rats (p=0.01). Finally, severe preeclamptic rats had increased blood brain barrier permeability compared to normal pregnant rats (p=0.03), which was reversed in Orencia treated rats (p=0.008). These results suggest that severe preeclampsia/Hemolysis Elevated Liver enzymes Low Platelet syndrome during pregnancy contributes to an increase in anxiety-like behavior, blood brain barrier permeability and hypertension in the post-partum. The current results suggest that T cell suppression during pregnancy can also help prevent chronic hypertension and increased anxiety in the post-partum period.

Prenatal intake of omega‐3 promotes Wnt/β‐catenin signaling pathway, and preserves integrity of the blood–brain barrier in preeclamptic rats

“…Increased circulating sFlt1 in preeclampsia is implicated in development of vasculopathy that underline proteinuria, disruption of the BBB and cerebral edema (Miller., 2019). Moreover, sFlt1 infusion to pregnant rats induces preeclampsia-like syndrome (Wallace et al, 2018). The results of the present work showed increased sFlt1 and TNF-α in the PE group compared to control pregnant group.…”

Preeclampsia and Cerebrovascular Disease

“…49 Pregnant rats infused with sFlt-1 and sEng developed a PE-like syndrome and increased BBB permeability in the postpartum period. 50 Exposing rat cerebral vessels to serum from women with PE resulted in an 18-fold increase in BBB permeability; surprisingly, this effect was prevented by VEGF inhibition. 44 Placental-ischemic rats had evidence of cerebral edema and neuroinflammation 2 months postpartum, suggesting that the deleterious effects of PE on the NVU persist after delivery.…”

Edema associated with low plasma protein level and any gestational hypertension as warning signs of HELLP syndrome

“…Hecht et al [14] recently identified from 317 autopsies of women who died of eclampsia not only "brain perivascular edema" (68.4%), which was unsurprising, but also liver lesions characterized by "periportal hemorrhage and dilation of the sinusoids" (72.2% in this series) as the predominant problems. The presence of HELLP syndrome is also characterized by impaired capillary perfusion [15] and increased permeability to plasma proteins, and it may be linked to cerebral edema [15][16][17][18].…”