Blood–Brain Barrier Dysfunction in Hypertensive Disorders of Pregnancy

Kaur, Simranjit; Ewing, Hadley T; Warrington, Junie P.

doi:10.1007/s11906-023-01288-8

Cited by 4 publications

(1 citation statement)

References 38 publications

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“…Even so, there are several limitations in this study that warrant further analyses. For instance, we did not assess the impact of reproductive experience on blood-brain barrier permeability, which may contribute to vulnerability of brain-specific regions to oxidative stressors during physiological and pathophysiological pregnancies (62). Additionally, the reduced locomotive activity in pregnant rats during late gestation warrants the modification of memory and anxiety-like behavior tasks to accommodate reductions in overall movement.…”

Section: Limitations Perspectives and Significancementioning

confidence: 99%

Pregnancy-associated oxidative stress and inflammation are not associated with impaired maternal neuronal activity or memory function

Bradshaw,

Wilson,

Gardner

et al. 2024

Preprint

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Pregnancy is associated with neural and behavioral plasticity, systemic inflammation, and oxidative stress. Yet, the impact of systemic inflammation and oxidative stress on maternal neural and behavioral plasticity during pregnancy are unclear. We hypothesized that the maternal hippocampal CA1, a brain region associated with cognition, would be protected from pregnancy-associated systemic elevations in inflammation and oxidative stress, mediating stable peripartum cognitive performance. Cognitive performance was tested using novel object recognition (recollective memory), Morris water maze (spatial memory), and open field (anxiety-like) behavior tasks in female Sprague-Dawley rats of varying reproductive states [non-pregnant (nulliparous), pregnant (near term), and two months post-pregnancy (primiparous); n = 7-8/group]. Plasma and CA1 proinflammatory cytokines were measured using a MILLIPLEX magnetic bead assay. Plasma oxidative stress was measured via advanced oxidation protein products (AOPP) assay. CA1 markers of oxidative stress, neuronal activity, and apoptosis were quantified via western blotting. Our results demonstrate CA1 oxidative stress-associated markers were elevated in pregnant compared to nulliparous rats (p ≤ 0.017) but were equivalent levels in pregnant and primiparous rats. In contrast, reproductive state did not impact CA1 inflammatory cytokines, neuronal activity, or apoptosis. Likewise, there was no effect of reproductive state on recollective or spatial memory. Even so, spatial learning was impaired (p ≤ 0.007) while anxiety-like behavior (p ≤ 0.034) was reduced in primiparous rats. Overall, our data suggest maternal hippocampal CA1 is protected from systemic inflammation but vulnerable to peripartum oxidative stress. Thus, peripartum oxidative stress elevations, such as in pregnancy complications, may contribute to peripartum neural and behavioral plasticity.

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Section: Limitations Perspectives and Significancementioning

confidence: 99%

Pregnancy-associated oxidative stress and inflammation are not associated with impaired maternal neuronal activity or memory function

Bradshaw,

Wilson,

Gardner

et al. 2024

Preprint

View full text Add to dashboard Cite

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Gestational Hypertension, Preeclampsia, and Eclampsia and Future Neurological Disorders

Friis,

Bergman,

Hesselman

et al. 2024

JAMA Neurol

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ImportanceGestational hypertension, preeclampsia, and eclampsia are established risk factors for stroke and dementia later in life. Whether these pregnancy complications are associated with an increased risk of new-onset neurological disorders within months to years after giving birth is not known.ObjectiveTo explore whether gestational hypertension, preeclampsia, and eclampsia are associated with new-onset migraine, headache, epilepsy, sleep disorder, or mental fatigue within months to years after giving birth.Design, Setting, and ParticipantsIn this register-based cohort study, exposures were identified in the Swedish Medical Birth Register from 2005 to 2018. Follow-up was conducted using the National Patient Register, containing diagnoses from specialized inpatient and outpatient care. Follow-up started 42 days after delivery and continued until the first event, death, emigration, or the end of the follow-up period (2019). The risk was calculated with Cox regression analysis and expressed as adjusted hazard ratio (aHR) with a 95% CI. Through the Swedish Medical Birth Register, 659 188 primiparous women with singleton pregnancies between 2005 and 2018 were identified. Women with a diagnosis of chronic hypertension (n = 4271) or a prepregnancy neurological disorder (n = 6532) were excluded. The final study population included 648 385 women. Data analyses were conducted in 2023.ExposuresGestational hypertension, preeclampsia, and eclampsia.Main outcomeThe primary outcome was a composite neurological outcome of migraine, headache, epilepsy, sleep disorder, or mental fatigue.ResultsThe study included 648 385 women with a mean age of 28.5 (SD, 5.0) years at the time of their first pregnancy. Women with gestational hypertension (n = 11 133), preeclampsia (n = 26 797), and eclampsia (n = 625) all had an association with increased risk for a new-onset neurological disorder compared with women with normotensive pregnancies. The aHR for gestational hypertension was 1.27 (95% CI, 1.12-1.45), 1.32 (95% CI, 1.22-1.42) for preeclampsia, and 1.70 (95% CI, 1.16-2.50) for eclampsia. When exploring individual outcomes, women with eclampsia were associated with more than a 5 times increased risk of epilepsy (aHR, 5.31; 95% CI, 2.85-9.89).Conclusion and RelevanceIn this study, gestational hypertension, preeclampsia, and eclampsia were associated with an increased risk of new-onset migraine, headache, epilepsy, sleep disorder, or mental fatigue within months to years after giving birth. Guidelines recommend follow-up after delivery for women with gestational hypertension and preeclampsia for their increased risk of cardiovascular disease. At these visits, caregivers should also pay attention to persisting or new-onset of neurological symptoms, since this group of women appears to be vulnerable to developing or experiencing neurological disorders.

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Idiopathic Intracranial Hypertension Is Associated With an Increased Risk of Hypertensive Pregnancy Disorders

Shaia,

Trinh,

Alam

et al. 2024

Journal of Neuro-Ophthalmology

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Background: Idiopathic intracranial hypertension (IIH) mainly occurs in women of a reproductive age who are overweight or obese. As pregnancy occurs in this age group, it is important to understand whether there are associations between IIH and pregnancy. The purpose of this study was to determine the incidence of IIH development during a pregnancy and whether IIH is associated with hypertensive disorders of pregnancy (HDP). Methods: In this retrospective cohort analysis, electronic health records from a tertiary care center were used to identify patients with IIH. Patients who had a diagnostic code for IIH or papilledema and were seen between June 1, 2012, and September 1, 2023, were included. After meeting the revised Dandy diagnostic criteria, patients were evaluated for a history of pregnancy before, during, or after their IIH diagnosis and hypertensive disorders including preeclampsia/eclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome, and hypertension. Incidence and risk ratios (RR) were calculated comparing patients with IIH with controls without IIH. To corroborate these results while controlling for obesity and migraine, the TriNetX platform housing more than 100 million patients was used to design a case–control analysis evaluating the odds of an IIH patient having an HDP. Results: Two hundred ninety-two IIH patients with a prior pregnancy were identified of which 7% developed new onset IIH during pregnancy. Patients had increased risks of all HDP including eclampsia (RR: 12.92, 95% CI: 5.35, 31.22), preeclampsia (2.39, CI 1.84, 3.10), and HELLP syndrome (6.72, CI 2.16, 20.90) compared with controls. Patients with IIH also had higher risks of ectopic pregnancies and miscarriages (P < 0.05). When controlling for obesity and migraine, patients continued to have increased odds of all HDP and eclampsia (P < 0.05). Conclusions: Patients with IIH had an increased risk of having an HDP, especially eclampsia and HELLP syndrome highlighting a need for increased clinical monitoring of these patients during pregnancy.

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Blood–Brain Barrier Dysfunction in Hypertensive Disorders of Pregnancy

Cited by 4 publications

References 38 publications

Pregnancy-associated oxidative stress and inflammation are not associated with impaired maternal neuronal activity or memory function

Pregnancy-associated oxidative stress and inflammation are not associated with impaired maternal neuronal activity or memory function

Gestational Hypertension, Preeclampsia, and Eclampsia and Future Neurological Disorders

Idiopathic Intracranial Hypertension Is Associated With an Increased Risk of Hypertensive Pregnancy Disorders

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