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- Bergman, Lina, 1982-
(författare)
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Cerebral biomarkers in women with preeclampsia
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Preeclampsia and eclampsia are among the most common causes of maternal and fetal mortality and morbidity worldwide. There are no reliable means to predict eclampsia or cerebral edema in women with preeclampsia and knowledge of the brain involvement in preeclampsia is still limited. S100B and neuron specific enolase (NSE) are two cerebral biomarkers of glial- and neuronal origin respectively. They are used as predictors for neurological outcome after traumatic brain injuries and cardiac arrest but have not yet been investigated in preeclampsia.This thesis is based on one longitudinal cohort study of pregnant women (n=469, Paper I and III), one cross sectional study of women with preeclampsia and women with normal pregnancies (n=53 and 58 respectively, Paper II and IV) and one experimental animal study of eclampsia (Paper V).In Paper I and III, plasma concentrations of S100B and NSE were investigated throughout pregnancy in women developing preeclampsia (n=16) and in women with normal pregnancies (n=36) in a nested case control study. Plasma concentrations were increased in women developing preeclampsia in gestational week 33 and 37 for S100B and in gestational week 37 for NSE compared to women with normal pregnancies.In Paper II and IV, increased plasma concentrations of S100B and NSE were confirmed among women with preeclampsia compared to women with normal pregnancies. Furthermore, increased plasma concentrations of S100B correlated to visual disturbances among women with preeclampsia (Paper II) and plasma concentrations of S100B and NSE remained increased among women with preeclampsia one year after delivery (Paper IV).In Paper V, an experimental rat model of preeclampsia and eclampsia demonstrated increased serum concentrations of S100B after seizures in normal pregnancy (n=5) and a tendency towards increased plasma concentrations of S100B in preeclampsia (n=5) compared to normal pregnancy (n=5) without seizures. Furthermore, after seizures, animals with magnesium sulphate treatment demonstrated increased serum concentrations of S100B and NSE compared to no treatment.In conclusion; plasma concentrations of S100B and NSE are increased in preeclampsia during late pregnancy and postpartum and S100B correlates to visual disturbances in women with preeclampsia. The findings are partly confirmed in an animal model of eclampsia.
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- Bergman, Lina, et al.
(författare)
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Investigating Maternal Brain Alterations in Preeclampsia : the Need for a Multidisciplinary Effort
- 2019
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Ingår i: Current Hypertension Reports. - : Springer Science and Business Media LLC. - 1522-6417 .- 1534-3111. ; 21:9
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: To provide insight into the mechanisms underlying cerebral pathophysiology and to highlight possible methods for evaluation, screening, and surveillance of cerebral complications in preeclampsia.RECENT FINDINGS: The pathophysiology of eclampsia remains enigmatic. Animal studies show that the cerebral circulation in pregnancy and preeclampsia might be affected with increased permeability over the blood-brain barrier and altered cerebral blood flow due to impaired cerebral autoregulation. The increased blood pressure cannot be the only underlying cause of eclampsia and cerebral edema, since some cases of eclampsia arise without simultaneous hypertension. Findings from animal studies need to be confirmed in human tissues. Evaluation of brain alterations in preeclampsia and eclampsia is challenging and demands a multidisciplinary collaboration, since no single method can accurately and fully describe how preeclampsia affects the brain. Cerebral complications of preeclampsia are significant factors in maternal morbidity and mortality worldwide. No single method can accurately describe the full picture of how preeclampsia affects the brain vasculature and parenchyma. We recommend an international and multidisciplinary effort not only to overcome the issue of limited sample availability but also to optimize the quality of research.
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- Bergman, Lina, et al.
(författare)
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Plasma Levels of S100B in Preeclampsia and Association With Possible Central Nervous System Effects
- 2014
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Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 27:8, s. 1105-1111
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Bergman, Lina, et al.
(författare)
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Preeclampsia and Increased Permeability Over the Blood–Brain Barrier : A Role of Vascular Endothelial Growth Receptor 2
- 2021
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Ingår i: American Journal of Hypertension. - : Oxford University Press. - 0895-7061 .- 1941-7225. ; 34:1, s. 73-81
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cerebral complications in preeclampsia are leading causes of maternal mortality worldwide but the underlying 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 were exposed (12 h) to plasma from women with preeclampsia (n=28), normal pregnancy (n=28) and non-pregnant (n=16) controls. Transendothelial electrical resistance (TEER) and permeability to 70 kDa FITC-dextran were measured for assessment of BBB integrity. We explored possible underlying mechanisms, with focus on expression of tight junction proteins and phosphorylation of two 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 measured in order to establish correlations with in vitro results.RESULTS: hCMEC/D3 exposed to plasma from women with preeclampsia exhibited reduced TEER and increased permeability to 70 kDa FITC-dextran. Further, these cells up-regulated the mRNA levels of VEGFR2, as well as pY951-VEGFR2; but reduced pY1175-VEGFR2 (p&0.05 in all cases). No difference in mRNA expression of tight junction protein was observed between gruops. There was no correlation between angiogenic biomarkers and BBB permeability.CONCLUSION: 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.
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- Casar Borota, Olivera, et al.
(författare)
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Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas : Markers in the Differential Diagnosis of Neuroendocrine Tumors of the Sellar Region.
- 2017
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Ingår i: American Journal of Surgical Pathology. - 0147-5185 .- 1532-0979. ; 41:9, s. 1238-1246
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Tidskriftsartikel (refereegranskat)abstract
- Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors that remain localized to the sellar and perisellar region. A lack of ATRX or DAXX in a sellar NET suggests a nonpituitary NET, probably of pancreatic origin. One of the 2 examined corticotroph carcinomas, however, demonstrated negative ATRX immunolabeling due to an ATRX gene mutation. Further studies on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs.
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- Correia de Verdier, Maria, 1983-, et al.
(författare)
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Effect of MRI acquisition parameters on accuracy and precision of phase-contrast measurements in a small-lumen vessel phantom
- 2024
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Ingår i: European radiology experimental. - : Springer. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPhase-contrast magnetic resonance imaging (PC-MRI) quantifies blood flow and velocity noninvasively. Challenges arise in neurovascular disorders due to small vessels. We evaluated the impact of voxel size, number of signal averages (NSA), and velocity encoding (VENC) on PC-MRI measurement accuracy and precision in a small-lumen vessel phantom.MethodsWe constructed an in vitro model with a constant flow rate using a 2.2-mm inner diameter plastic tube. A reservoir with a weight scale and timer was used as standard reference. Gradient-echo T1 weighted PC-MRI sequence was performed on a 3-T scanner with varying voxel size (2.5, 5.0, 7.5 mm3), NSA (1, 2, 3), and VENC (200, 300, 400 cm/s). We repeated measurements nine times per setting, calculating mean flow rate, maximum velocity, and least detectable difference (LDD).ResultsPC-MRI flow measurements were higher than standard reference values (mean ranging from 7.3 to 9.5 mL/s compared with 6.6 mL/s). Decreased voxel size improved accuracy, reducing flow rate measurements from 9.5 to 7.3 mL/s. The LDD for flow rate and velocity varied between 1 and 5%. The LDD for flow rate decreased with increased voxel size and NSA (p = 0.033 and 0.042). The LDD for velocity decreased with increased voxel size (p < 10-16). No change was observed when VENC varied.ConclusionsPC-MRI overestimated flow. However, it has high precision in a small-vessel phantom with constant flow rate. Improved accuracy was obtained with increasing spatial resolution (smaller voxels). Improved precision was obtained with increasing signal-to-noise ratio (larger voxels and/or higher NSA).
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- Correia de Verdier, Maria, 1983-
(författare)
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Evaluation of Intracranial Arteriovenous Malformations with Magnetic Resonance Imaging
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Intracranial arteriovenous malformations (AVMs) are characterized by feeding arteries, a tangle of abnormal vessels (nidus) and draining veins. Radiological evaluation methods are used in diagnosing AVMs, treatment planning, post-treatment evaluation and monitoring stability. The general aim of our studies reviewed in this thesis was to develop and evaluate magnetic resonance imaging (MRI) techniques for the evaluation of AVMs. MethodsPaper I – In 30 patients treated with proton radiation therapy, radiation-induced MRI changes (vasogenic edema, contrast enhancement and cavitation) and their association with development of neurological symptoms and nidus obliteration were assessed. Paper II – We evaluated the effect of acquisition parameters (voxel size, number of signal averages and velocity encoding) on the accuracy and precision of phase-contrast MRI (PC-MRI)-measured flow and velocity in a small-lumen vessel phantom with constant flow. Paper III – Normal ranges and test-retest reproducibility of flow and velocity in the anterior, middle and posterior cerebral arteries were measured with PC-MRI in 30 healthy volunteers.Paper IV – We studied PC-MRI-measured flow and velocity in feeding arteries in 10 patients with AVMs and compared the values obtained with the results from paper III. We also assessed post-treatment changes in flow and velocity in three patients. Results Paper I – Radiation-induced MRI changes were found in 87% of patients after proton radiation treatment of AVMs. MRI changes were associated with neurological symptoms but not with nidus obliteration. Paper II – PC-MRI overestimated flow in a small-lumen vessel phantom. Accuracy for flow measurements improved by decreasing voxel size. Precision for both flow and velocity measurements improved by increasing voxel size. Precision for flow measurements improved by increasing the number of signal averages.Paper III – We reported normal ranges and test-retest reproducibility for PC-MRI-measured flow and velocity in the main intracranial arteries. Reproducibility was overall quite low, but higher for the middle cerebral arteries than for the anterior and posterior cerebral arteries.Paper IV – Patients with a large nidus have increased velocity measured with PC-MRI in feeding arteries compared to intracranial arteries in healthy individuals. There is a reduction in PC-MRI-measured flow and velocity after treatment. ConclusionRadiation-induced MRI changes are common after proton radiation treatment of AVMs. The accuracy and precision of PC-MRI measurements in a phantom depend on acquisition parameter settings. In patients with AVMs with a large nidus, increased velocity is observed in feeding arteries, and a decrease in flow and velocity is observed after treatment. PC-MRI can potentially be used as a clinical tool to aid treatment planning and post-treatment evaluation.
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