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Cerebral Biomarkers and Blood-Brain Barrier Integrity in Preeclampsia
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.ORCID iD: 0000-0001-6431-3303
Univ Bio Bio, Fac Sci, Dept Basic Sci, Vasc Physiol Lab, Chillan 3810178, Chile.;Grp Res & Innovat Vasc Hlth GRIVAS Hlth, Chillan 3810178, Chile..
Univ Bio Bio, Fac Sci, Dept Basic Sci, Vasc Physiol Lab, Chillan 3810178, Chile.;Grp Res & Innovat Vasc Hlth GRIVAS Hlth, Chillan 3810178, Chile.;Univ Santo Tomas, Fac Salud, Escuela Enfermeria, Los Angeles 4441171, Chile..
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2022 (English)In: Cells, E-ISSN 2073-4409, Vol. 11, no 5, article id 789Article in journal (Refereed) Published
Abstract [en]

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 mu g/L, p < 0.001 and 0.08 vs. 0.05 mu g/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.

Place, publisher, year, edition, pages
MDPI AG MDPI, 2022. Vol. 11, no 5, article id 789
Keywords [en]
blood-brain barrier, preeclampsia, pregnancy, in vitro studies, cerebral biomarkers, NfL, tau, NSE, S100B
National Category
Gynaecology, Obstetrics and Reproductive Medicine Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-471012DOI: 10.3390/cells11050789ISI: 000768983100001PubMedID: 35269411OAI: oai:DiVA.org:uu-471012DiVA, id: diva2:1648871
Note

De två sista författarna delar sistaförfattarskapet.

Available from: 2022-04-01 Created: 2022-04-01 Last updated: 2025-03-08Bibliographically approved
In thesis
1. Preeclampsia and the brain: The blood-brain barrier and neurological consequences
Open this publication in new window or tab >>Preeclampsia and the brain: The blood-brain barrier and neurological consequences
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cerebral complications of preeclampsia are among the leading causes of maternal mortality. Women with previous preeclampsia and eclampsia have increased long-term risks of cognitive impairment, stroke, and vascular dementia. They report a lower quality of life, concentration issues, and tiredness after childbirth. The pathophysiology of cerebral complications remains unclear, however, is suggested to involve blood-brain barrier (BBB) impairment, loss of cerebral autoregulation, microinfarctions, and edema.

This translational thesis aimed to explore pathophysiological mechanisms of BBB impairment in preeclampsia and to investigate whether preeclampsia and eclampsia increase the risk of neurological disorders and sick leave in the years following childbirth. This was explored through two preclinical laboratory studies and two register-based cohort studies.

The BBB was explored using an in vitro model. Results were correlated to plasma concentrations of cerebral biomarkers. Correlations were estimated with non-parametric tests. Plasma from women with preeclampsia affected the in vitro model of the human BBB by increasing permeability to FITC-Dextran and decreasing transendothelial electrical resistance (TEER) at the cellular level. All cerebral biomarkers were increased in plasma from women with preeclampsia, compared with normotensive pregnancy. Increased plasma concentrations of NfL were correlated to a decrease in TEER over the BBB. Plasma concentrations of tau, NSE and S100B were not associated with TEER.

Associations between gestational hypertension, preeclampsia and eclampsia, and a composite of neurological disorders (migraine, headache, epilepsy, sleep disorders and neurasthenia) were estimated with multivariate Cox regression models. All exposure groups were associated with an increased risk of a composite of neurological disorders, compared with normotensive pregnant women. Gestational hypertension and preeclampsia were associated with increased migraine risk. The strongest association was found between eclampsia and epilepsy.

Associations between preeclampsia and sick leave rates in the second year postpartum were assessed with augmented inverse probability weighting. Women with preeclampsia took more sick leave compared with women without preeclampsia.

In conclusion, plasma from women with preeclampsia impairs BBB function in vitro, and BBB leakage is indicated by correlation between decreased TEER and increased plasma NfL. Women with preeclampsia, particularly eclampsia, face a higher risk of developing neurological disorders postpartum, which may reflect the increased sick leave observed in this group.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2025. p. 90
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2130
Keywords
Preeclampsia, Eclampsia, Blood-Brain Barrier, Cerebral Biomarkers, Neurological Disorders, Sick Leave
National Category
Gynaecology, Obstetrics and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-552137 (URN)978-91-513-2411-1 (ISBN)
Public defence
2025-04-25, Humanistiska Teatern, Engelska Parken, Thunbergsvägen 3C, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2025-04-02 Created: 2025-03-08 Last updated: 2025-04-02Bibliographically approved

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Friis, ThereseWikström, Anna-KarinNelander, MariaÅkerud, HelenaKaihola, HelenaBergman, Lina

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Friis, ThereseWikström, Anna-KarinNelander, MariaÅkerud, HelenaKaihola, HelenaCluver, CatherineBergman, Lina
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Clinical ObstetricsExperimental and Clinical OncologyDepartment of Immunology, Genetics and Pathology
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