Cerebral Biomarkers and Blood-Brain Barrier Integrity in Preeclampsia.

Catherine Cluver,Jesenia Acurio,Anna-Karin Wikström,Helena Åkerud,Felipe Troncoso,José León,Helena Kaihola,Maria Nelander,Kaj Blennow,Henrik Zetterberg,Carlos Escudero,Therese Friis,Lina Bergman,Pablo Torres-Vergara

doi:10.3390/cells11050789

Abstract

Cerebral complications in preeclampsia contribute substantially to maternal mortality and morbidity. There is a lack of reliable and accessible predictors for preeclampsia-related cerebral complications. In this study, plasma from women with preeclampsia (n = 28), women with normal pregnancies (n = 28) and non-pregnant women (n = 16) was analyzed for concentrations of the cerebral biomarkers neurofilament light (NfL), tau, neuron-specific enolase (NSE) and S100B. Then, an in vitro blood–brain barrier (BBB) model, based on the human cerebral microvascular endothelial cell line (hCMEC/D3), was employed to assess the effect of plasma from the three study groups. Transendothelial electrical resistance (TEER) was used as an estimation of BBB integrity. NfL and tau are proteins expressed in axons, NSE in neurons and S100B in glial cells and are used as biomarkers for neurological injury in other diseases such as dementia, traumatic brain injury and hypoxic brain injury. Plasma concentrations of NfL, tau, NSE and S100B were all higher in women with preeclampsia compared with women with normal pregnancies (8.85 vs. 5.25 ng/L, p < 0.001; 2.90 vs. 2.40 ng/L, p < 0.05; 3.50 vs. 2.37 µg/L, p < 0.001 and 0.08 vs. 0.05 µg/L, p < 0.01, respectively). Plasma concentrations of NfL were also higher in women with preeclampsia compared with non-pregnant women (p < 0.001). Higher plasma concentrations of the cerebral biomarker NfL were associated with decreased TEER (p = 0.002) in an in vitro model of the BBB, a finding which indicates that NfL could be a promising biomarker for BBB alterations in preeclampsia.

Highlights

Preeclampsia affects 3–5% of all pregnancies and is one of the most common causes of maternal and perinatal morbidity and mortality [1]
Women with preeclampsia had a higher early-pregnancy body mass index (BMI) and were more often nulliparous compared with women with normal pregnancies and non-pregnant women
We demonstrated a reduction of Transendothelial electrical resistance (TEER), and increased permeability to 70 kDa FITC-dextran over the blood–brain barrier (BBB), when a monolayer of cells was exposed to plasma from women with preeclampsia and compared with plasma from women with normal pregnancies and non-pregnant controls [30]

Summary

Introduction

Preeclampsia affects 3–5% of all pregnancies and is one of the most common causes of maternal and perinatal morbidity and mortality [1]. Preeclampsia is defined as de novo hypertension after 20 weeks of gestation accompanied by signs of maternal organ dysfunction, such as renal insufficiency, liver dysfunction, neurological features, hematological complications or fetal growth restriction as a sign of uteroplacental dysfunction [2,3]. More than 70,000 maternal deaths are associated with hypertensive disorders of pregnancy, where cerebral complications due to preeclampsia, such as eclampsia, cerebral edema and cerebral hemorrhage are leading causes of maternal death [3–5]. There is a lack of objective biomarkers for cerebral complications to preeclampsia and the underlying pathophysiology remains partly unknown. The cerebral biomarkers neurofilament light (NfL), tau, neuron-specific enolase (NSE)

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