ArticlePloS one2014
Magnesium sulfate treatment reverses seizure susceptibility and decreases neuroinflammation in a rat model of severe preeclampsia.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.
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Who cites it
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 108 citations in OpenAlex.
- Analysis of the evolution of placental oxidative stress research from a bibliometric perspective.Frontiers in pharmacology · 2024Pooled it
- Hypertension, seizures, and epilepsy: a review on pathophysiology and management.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2019Pooled it
- Evaluation of intravenous infusion of labetalol versus magnesium sulfate on cerebral hemodynamics of preeclampsia patients with severe features using transcranial doppler.Journal of clinical monitoring and computing · 2023Trial
- Trial
- Chronic hypertension and social isolation disrupt the blood-brain barrier and memory in a sex-dependent manner.Neurobiology of disease · 2026Article
- Assessing the efficacy of the ESC 2025 guidelines for the management of cardiovascular disease and pregnancy.Clinics (Sao Paulo, Brazil) · 2026Article
- Mouse offspring exposed to preeclampsia/eclampsia-like symptoms exhibit cerebral hypoperfusion and mild cognitive impairment at 2 mo of age.American journal of physiology. Heart and circulatory physiology · 2026Article
- Aberrant Uteroplacental and Vascular Signaling and Remodeling by Matrix Metalloproteinases in Pregnancy-Related Hypertension and Preeclampsia.Biomolecules · 2026Review
- Context-dependent NMDA receptor dysfunction predicts seizure treatment in mice with human GluN1 variant.iScience · 2026Article
- Considering Litter Effects in Preclinical Research: Evidence from E17.5 Acid-Sensing Ion Channel 2a Knockout Mice Exposed to Acute Seizures.Brain sciences · 2025Article
- Characteristics of eclampsia not preceded by hypertensive disorders of pregnancy: a case control study.BMC pregnancy and childbirth · 2025Article
- Pharmacological Efficacy of Intravenous Magnesium in Attenuating Remifentanil-Induced Postoperative Hyperalgesia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Placental ischemia-upregulated angiotensin II type 1 receptor in hypothalamic paraventricular nucleus contributes to hypertension in rat.Pflugers Archiv : European journal of physiology · 2024Article
- The Role of Gut Microbiota, Nutrition, and Physical Activity in Depression and Obesity-Interdependent Mechanisms/Co-Occurrence.Nutrients · 2024Review
- Edaravone Confers Neuroprotective, Anti-inflammatory, and Antioxidant Effects on the Fetal Brain of a Placental-ischemia Mouse Model.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- Worsened Stroke Outcome in a Model of Preeclampsia is Associated With Poor Collateral Flow and Oxidative Stress.Stroke · 2023Article
- A theoretical model of dietary lipid variance as the origin of primary ciliary dysfunction in preeclampsia.Frontiers in molecular biosciences · 2023Article
- Blood-brain barrier leakage years after pre-eclampsia: dynamic contrast-enhanced 7-Tesla MRI study.Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology · 2022Observational
- Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Eclampsia, defined as unexplained seizure in a woman with preeclampsia, is a life-threatening complication of pregnancy with unclear etiology. Magnesium sulfate (MgSO4) is the leading eclamptic seizure prophylactic, yet its mechanism of action remains unclear. Here, we hypothesized severe preeclampsia is a state of increased seizure susceptibility due to blood-brain barrier (BBB) disruption and neuroinflammation that lowers seizure threshold. Further, MgSO4 decreases seizure susceptibility by protecting the BBB and preventing neuroinflammation. To model severe preeclampsia, placental ischemia (reduced uteroplacental perfusion pressure; RUPP) was combined with a high cholesterol diet (HC) to cause maternal endothelial dysfunction. RUPP+HC rats developed symptoms associated with severe preeclampsia, including hypertension, oxidative stress, endothelial dysfunction and fetal and placental growth restriction. Seizure threshold was determined by quantifying the amount of pentylenetetrazole (PTZ; mg/kg) required to elicit seizure in RUPP + HC ± MgSO4 and compared to normal pregnant controls (n = 6/group; gestational day 20). RUPP+HC rats were more sensitive to PTZ with seizure threshold being ∼ 65% lower vs. control (12.4 ± 1.7 vs. 36.7 ± 3.9 mg/kg PTZ; p<0.05) that was reversed by MgSO4 (45.7 ± 8.7 mg/kg PTZ; p<0.05 vs. RUPP+HC). BBB permeability to sodium fluorescein, measured in-vivo (n = 5-7/group), was increased in RUPP+HC vs. control rats, with more tracer passing into the brain (15.9 ± 1.0 vs. 12.2 ± 0.3 counts/gram ×1000; p<0.05) and was unaffected by MgSO4 (15.6 ± 1.0 counts/gram ×1000; p<0.05 vs. controls). In addition, RUPP+HC rats were in a state of neuroinflammation, indicated by 35 ± 2% of microglia being active compared to 9 ± 2% in normal pregnancy (p<0.01; n = 3-8/group). MgSO4 treatment reversed neuroinflammation, reducing microglial activation to 6 ± 2% (p<0.01 vs. RUPP+HC). Overall, RUPP+HC rats were in a state of augmented seizure susceptibility potentially due to increased BBB permeability and neuroinflammation. MgSO4 treatment reversed this, increasing seizure threshold and decreasing neuroinflammation, without affecting BBB permeability. Thus, reducing neuroinflammation may be one mechanism by which MgSO4 prevents eclampsia during severe preeclampsia.
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