Abstract

Magnesium sulfate (MgSO4) is the most widely used therapy in the clinic to prevent the progression of preeclampsia, a hypertensive disorder of pregnancy, to eclampsia. Eclampsia, manifested as unexplained seizures and/or coma during pregnancy or postpartum, accounts for ~13% of maternal deaths worldwide. While MgSO4 continues to be used in the clinic, the mechanisms by which it exerts its protective actions are not well understood. In this study, we tested the hypothesis that MgSO4 protects against placental ischemia-induced increases in brain water content and cerebrospinal fluid cytokines. To test this hypothesis, MgSO4 was administered via mini-osmotic pump (60 mg/day, i.p.) to pregnant and placental ischemic rats, induced by mechanical reduction of uterine perfusion pressure, from gestational day 14–19. This treatment regimen of MgSO4 led to therapeutic level of 2.8 ± 0.6 mmol/L Mg in plasma. MgSO4 had no effect on improving placental ischemia-induced changes in mean arterial pressure, number of live fetuses, or fetal and placental weight. Placental ischemia increased, while MgSO4 prevented the increase in water content in the anterior cerebrum. Cytokine and chemokine levels were measured in the cerebrospinal fluid using a multi-plex assay. Results demonstrate that cerebrospinal fluid, obtained via the cisterna magna, had reduced protein, albumin, interleukin (IL)-17A, IL-18, IL-2, eotaxin, fractalkine, interferon gamma, vascular endothelial growth factor (VEGF), and macrophage inflammatory protein (MIP)-2 following MgSO4 treatment. These data support the hypothesis that MgSO4 offers neuroprotection by preventing placental ischemia-induced cerebral edema and reducing levels of cytokines/chemokines in the cerebrospinal fluid.

Highlights

  • Magnesium sulfate (MgSO4) is the main course of treatment for preeclampsia patients with severe symptoms and is often used to prevent the progression of the disorder from preeclampsia to eclampsia

  • We found that while MgSO4 had no effect on improving blood pressure or fetal outcomes following placental ischemia, it reduced Cerebrospinal fluid (CSF) protein and albumin concentration as well as the level of cytokines in placental ischemic rats and prevented placental ischemia-induced increases in brain water content

  • The current study showed no change in placental weight following placental ischemia but a significant reduction in placental weight following placental ischemia and MgSO4 treatment

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Summary

Introduction

Magnesium sulfate (MgSO4) is the main course of treatment for preeclampsia patients with severe symptoms and is often used to prevent the progression of the disorder from preeclampsia to eclampsia. Preeclampsia is characterized by new-onset hypertension with proteinuria or in the absence of proteinuria, Magnesium Sulfate and Cerebrospinal Fluid low platelet count, renal insufficiency, impaired liver function, pulmonary edema, or cerebral or visual symptoms manifesting after the 20th week of gestation (American College of Obstetricians & Gynecologists and Task Force on Hypertension in Pregnancy, 2013). Additional evidence that the cerebral vasculature is affected in preeclampsia is provided by the common manifestations of neurological symptoms ranging from headaches to seizures (in the case of eclampsia) (Chakravarty and Chakrabarti, 2002) in patients. Novel therapies for the treatment of preeclampsia are needed, and the mechanisms by which MgSO4 exerts its beneficial effects need to be elucidated

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