Magnesium sulfate attenuates brain edema by lowering AQP4 expression and inhibits glia-mediated neuroinflammation in a rodent model of eclampsia

Eclampsia is characterized by high morbidity and mortality wordwide. Magnesium sulfate (MgSO4) is used frequently as a prophylaxis for eclamptic seizure in clinical settings. However, the underlying mechanism is less studied, we have previously demonstrated that MgSO4 pretreatment decreases eclampsia-like seizure threshold. Here, we further evaluated the hypothesis that MgSO4 exert neuroprotective actions in eclampsia-like rats model by ameliorating neuroinflammation and brain edema. In this study, the eclampsia-like model was established by administering lipopolysaccharide plus pentylenetetrazol in pregnant Sprague-Dawley rats. Rats were given MgSO4 from gestation day14–19. Then, Iba-1 (a marker for microglia) and S100-B (a marker for astrocytes) expression levels in the hippocampus CA3 region were detected by Enzyme-linked immunosorbent assay. Cerebrospinal fluid (CSF) levels of inflammatory cytokines were measured by Luminex assays. Aquaporin-4 (a transmembrane water channel protein) expression levels in cortex were analyzed using immunohistochemistry. Astrocyte and microglia expressions were detected by immunofluorescence, neuronal damage were evaluated by Nissl staining, and changes in neuronal number in the hippocampal CA3 region (CA3) among different groups were detected by neuronal nuclei staining. Our results demonstrated that MgSO4 effectively attenuated astrocyte and microglia activation and promoted the neuronal survival in the CA3. Additionally, MgSO4 significantly reduced inflammatory cytokines response in the CSF, and decreased the expression of AQP-4 protein in the cortex. Collectively, the findings of this study indicated that MgSO4 has a neuroprotective role in eclampsia-like seizure rats through its anti-neuroninflammatory and brain edema-attenuating properties.