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

Hypertension. 2018 Oct;72(4):946-954. doi: 10.1161/HYPERTENSIONAHA.118.11770.

Abstract

Hypertension and inflammation during pregnancy are suggested to contribute to the development of postpartum depression and anxiety. Using a rat model of severe preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome, which displays both hypertension and inflammation during pregnancy, we evaluated whether rats were prone to develop depression or anxiety in the postpartum period. On gestational day 12, miniosmotic pumps infusing sFlt-1 (soluble fms-like tyrosine kinase-1) and sEng (soluble endoglin) were placed into rats, a subset of these rats was infused with 2 mg/kg of Orencia (abatacept) the following day to determine whether immune suppression via T-cell depletion prevented any changes in maternal depression or anxiety-like behavior. All rats, including normal pregnant (NP) controls, delivered between gestational days 21 and 22. Postpartum severe preeclamptic rats buried significantly more marbles compared with NP 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 with NP rats ( P=0.009) and Orencia-treated rats ( P=0.05). Severe preeclamptic rats were hypertensive compared with NP ( P=0.03) and Orencia-treated rats ( P=0.01). Finally, severe preeclamptic rats had increased blood-brain barrier permeability compared with NP rats ( P=0.03), which was reversed in Orencia-treated rats ( P=0.008). These results suggest that severe preeclampsia/hemolysis, elevated liver enzymes, and low platelet count syndrome during pregnancy contributes to an increase in anxiety-like behavior, blood-brain barrier permeability, and hypertension in the postpartum. The current results suggest that T-cell suppression during pregnancy can also help prevent chronic hypertension and increased anxiety in the postpartum period.

Keywords: HELLP syndrome; anxiety; hypertension; inflammation; preeclampsia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept / pharmacology*
  • Animals
  • Anxiety* / diagnosis
  • Anxiety* / immunology
  • Anxiety* / prevention & control
  • Behavior, Animal / physiology
  • Blood-Brain Barrier / physiopathology
  • Capillary Permeability / immunology
  • Depression* / diagnosis
  • Depression* / immunology
  • Depression* / prevention & control
  • Disease Models, Animal
  • Female
  • HELLP Syndrome* / diagnosis
  • HELLP Syndrome* / physiopathology
  • HELLP Syndrome* / psychology
  • HELLP Syndrome* / therapy
  • Hypertension* / diagnosis
  • Hypertension* / etiology
  • Hypertension* / prevention & control
  • Immunosuppressive Agents / pharmacology
  • Pre-Eclampsia* / diagnosis
  • Pre-Eclampsia* / psychology
  • Pregnancy
  • Pregnancy Complications / diagnosis
  • Pregnancy Complications / physiopathology
  • Pregnancy Complications / psychology
  • Pregnancy Complications / therapy
  • Prognosis
  • Puerperal Disorders* / diagnosis
  • Puerperal Disorders* / immunology
  • Puerperal Disorders* / prevention & control
  • Rats
  • T-Lymphocytes / immunology*

Substances

  • Immunosuppressive Agents
  • Abatacept