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BACKGROUND Cerebral complications in preeclampsia are leading causes of maternal mortality worldwide but pathophysiology is largely unknown and a challenge to study. Using an in vitro model of the human blood–brain barrier (BBB), we explored the role of vascular endothelial growth factor receptor 2 (VEGFR2) in preeclampsia. METHODS The human brain endothelial cell line (hCMEC/D3) cultured on Tranwells insert was exposed (12 hours) to plasma from women with preeclampsia (n = 28), normal pregnancy (n = 28), and nonpregnant (n = 16) controls. Transendothelial electrical resistance (TEER) and permeability to 70 kDa fluorescein isothiocyanate (FITC)-dextran were measured for the assessment of BBB integrity. We explored possible underlying mechanisms, with a focus on the expression of tight junction proteins and phosphorylation of 2 tyrosine residues of VEGFR2, associated with vascular permeability and migration (pY951) and cell proliferation (pY1175). Plasma concentrations of soluble FMS-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were also measured. RESULTS hCMEC/D3 exposed to plasma from women with preeclampsia exhibited reduced TEER and increased permeability to 70 kDa FITC-dextran. These cells upregulated the messenger ribonucleic acid (mRNA) levels of VEGFR2, and pY951-VEGFR2, but reduced pY1175-VEGFR2 (P < 0.05 in all cases). No difference in mRNA expression of tight junction protein was observed between groups. There was no correlation between angiogenic biomarkers and BBB permeability. CONCLUSIONS We present a promising in vitro model of the BBB in preeclampsia. Selective tyrosine phosphorylation of VEGFR2 may participate in the increased BBB permeability in preeclampsia irrespective of plasma concentrations of angiogenic biomarkers. [ABSTRACT FROM AUTHOR]

Introduction: Cerebral complications are the main reasons for morbidity and mortality in preeclampsia and eclampsia. As yet, we do not know whether the pathophysiology entails hypo- or hyperperfusion of the brain, or how and when edema emerges, due to the difficulty of examining the cerebral circulation.Material and Methods: We have used a non-invasive diffusion weighted-magnetic resonance imaging technique, intravoxel incoherent motion, to study cerebral perfusion on the capillary level and cerebral edema in women with preeclampsia (n = 30), normal pregnancy (n = 32), and non-pregnant women (n = 16). Estimates of cerebral blood volume, blood flow, and edema were measured in 5 different regions. These points were chosen to represent blood supply areas of both the carotid and vertebrobasilar arteries, and to include both white and gray matter.Results: Except for the caudate nucleus, we did not detect any differences in cerebral perfusion measures on a group level. In the caudate nucleus, we found lower cerebral blood volume and lower blood flow in preeclampsia than in either normal pregnancy (P = .01 and P = .03, respectively) or non-pregnant women (both P = .02). No differences in edema were detected between study groups.Conclusion: The cerebral perfusion measures were comparable between the study groups, except for a portion of the basal ganglia where hypoperfusion was detected in preeclampsia but not in normal pregnancy or non-pregnant women. [ABSTRACT FROM AUTHOR]

BACKGROUND Cerebral complications contribute substantially to mortality in preeclampsia. Pregnancy calls for extensive maternal adaptations, some associated with increased propensity for seizures, but the pathophysiology behind the eclamptic seizures is not fully understood. Plasma osmolality and sodium levels are lowered in pregnancy. This could result in extrusion of cerebral organic osmolytes, including the excitatory neurotransmitter glutamate, but this remains to be determined. The hypothesis of this study was that cerebral levels of organic osmolytes are decreased during pregnancy, and that this decrease is even more pronounced in women with preeclampsia. METHODS We used proton magnetic resonance spectroscopy to compare levels of cerebral organic osmolytes, in women with preeclampsia (n = 30), normal pregnancy (n = 32), and nonpregnant controls (n = 16). Cerebral levels of organic osmolytes were further correlated to plasma osmolality and plasma levels of glutamate and sodium. RESULTS Compared to nonpregnant women, women with normal pregnancy and preeclampsia had lower levels of the cerebral osmolytes, myo-inositol, choline and creatine (P = 0.001 or less), and all these metabolites correlated with each other (P < 0.05). Women with normal pregnancies and preeclampsia had similar levels of osmolytes, except for glutamate, which was significantly lower in preeclampsia. Cerebral and plasma glutamate levels were negatively correlated with each other (P < 0.008), and myo-inositol, choline and creatine levels were all positively correlated with both plasma osmolality and sodium levels (P < 0.05). CONCLUSIONS Our results indicate that pregnancy is associated with extrusion of cerebral organic osmolytes. This includes the excitatory neurotransmitter glutamate, which may be involved in the pathophysiology of seizures in preeclampsia. [ABSTRACT FROM AUTHOR]

BACKGROUND Magnesium sulfate (MgSO4) is used as a prophylaxis for eclamptic seizures. The exact mechanism of action is not fully established. We used phosphorus magnetic resonance spectroscopy (31P-MRS) to investigate if cerebral magnesium (Mg2+) levels differ between women with preeclampsia, normal pregnant, and nonpregnant women. METHODS This cross-sectional study comprised 28 women with preeclampsia, 30 women with normal pregnancies in corresponding gestational week (range: 23-41 weeks) and 11 nonpregnant healthy controls. All women underwent 31P-MRS from the parieto-occipital region of the brain and were interviewed about cerebral symptoms. Differences between groups were assessed by analysis of variance and Tukey's post-hoc test. Correlations between Mg2+ levels and specific neurological symptoms were estimated with Spearman's rank test. RESULTS Mean maternal cerebral Mg2+ levels were lower in women with preeclampsia (0.12 mM ± 0.02) compared to normal pregnant controls (0.14 mM ± 0.03) (P = 0.04). Nonpregnant and normal pregnant women did not differ in Mg2+ levels. Among women with preeclampsia, lower Mg2+ levels correlated with presence of visual disturbances (P = 0.04). Plasma levels of Mg2+ did not differ between preeclampsia and normal pregnancy. CONCLUSIONS Women with preeclampsia have reduced cerebral Mg2+ levels, which could explain the potent antiseizure prophylactic properties of MgSO4. Within the preeclampsia group, women with visual disturbances have lower levels of Mg2+ than those without such symptoms. [ABSTRACT FROM AUTHOR]

BACKGROUND S100B is supposed to be a peripheral biomarker of central nervous system (CNS) injury. The purpose of this study was to compare levels of S100B in women with preeclampsia with levels in healthy pregnant control subjects and furthermore to analyze levels of S100B in relation to possible CNS effects. METHODS A cross-sectional case–control study in antenatal care centers in Uppsala, Sweden, was performed. Fifty-three women with preeclampsia and 58 healthy pregnant women were recruited at similar gestational length; women with preeclampsia were recruited at time of diagnosis, and control subjects were recruited during their routine visit to an antenatal clinic. Plasma samples were collected, and levels of S100B were analyzed with an enzyme-linked immunosorbent assay. Information about demographic and clinical characteristics, including symptoms related to CNS affection, was collected from the medical records. The main outcome measures were plasma levels of S100B and possible CNS effects. RESULTS Levels of S100B were significantly higher among women with preeclampsia than among control subjects (0.12 µg/L vs. 0.07 µg/L; P < 0.001). In preeclampsia, there was a significant association between high levels of S100B and visual disturbances (P < 0.05). CONCLUSIONS S100B is increased among women with preeclampsia, and high levels of S100B associate with visual disturbances, which might reflect CNS affection in women with preeclampsia. [ABSTRACT FROM AUTHOR]

Abstract: Objective: S100B is suggested to be a peripheral biomarker of central nervous system injury with increased blood–brain barrier permeability. The aim of this study was to investigate if there is a difference in plasma levels of S100B throughout pregnancy between women developing pre-eclampsia and those who did not. Study design: A nested case-control study within a longitudinal study cohort was performed. Healthy pregnant women were enrolled and plasma samples were collected at gestational weeks 10, 25, 28, 33 and 37. Levels of S100B throughout pregnancy were analyzed with an ELISA assay. Results: The levels of S100B did not change between gestational weeks 10 and 37 (0.047 vs. 0.052; p =0.71) in the healthy controls, but the S100B levels increased between corresponding weeks in women who developed pre-eclampsia (0.052 vs. 0.075; p <0.05). In gestational weeks 33 and 37 women who developed pre-eclampsia had higher levels of S100B than the controls (p =0.047 and p =0.010, respectively). Conclusion: S100B levels increase during pregnancy in women who develop pre-eclampsia and there is an increased S100B level in women who develop pre-eclampsia compared with healthy pregnancies several weeks before clinical symptoms of the disease. The increased amount of plasma S100B in women developing pre-eclampsia might be secondary to cerebral vascular damage and S100B is a potential peripheral biomarker reflecting cerebral involvement in pre-eclampsia. [Copyright &y& Elsevier]

Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. The burden of disease lies mainly in low-middle income countries. The aim of this project is to establish a pre-eclampsia biobank in South Africa to facilitate research in the field of pre-eclampsia with a focus on phenotyping severe disease.The approach of our biobank is to collect biological specimens, detailed clinical data, tests, and biophysical examinations, including magnetic resonance imaging (MRI) of the brain, MRI of the heart, transcranial Doppler, echocardiography, and cognitive function tests.Women diagnosed with pre-eclampsia and normotensive controls are enrolled in the biobank at admission to Tygerberg University Hospital (Cape Town, South Africa). Biological samples and clinical data are collected at inclusion/delivery and during the hospital stay. Special investigations as per above are performed in a subset of women. After two months, women are followed up by telephonic interviews. This project aims to establish a biobank and database for severe organ complications of pre-eclampsia in a low-middle income country where the incidence of pre-eclampsia with organ complications is high. The study integrates different methods to investigate pre-eclampsia, focusing on improved understanding of pathophysiology, prediction of organ complications, and potentially future drug evaluation and discovery. [ABSTRACT FROM AUTHOR]