Magnesium Sulfate Provides Neuroprotection in Eclampsia-Like Seizure Model by Ameliorating Neuroinflammation and Brain Edema

Abstract

Eclampsia is a hypertensive disorder of pregnancy that is defined by the new onset of grand mal seizures on the basis of preeclampsia and a leading cause of maternal and fetal mortality worldwide. Presently, magnesium sulfate (MgSO) is the most effective treatment, but the mechanism by which MgSO prevents eclampsia has yet to be fully elucidated. We previously showed that systemic inflammation decreases the seizure threshold in a rat eclampsia-like model, and MgSO treatment can decrease systemic inflammation. Here, we hypothesized that MgSO plays a neuroprotective role in eclampsia by reducing neuroinflammation and brain edema. Pregnant Sprague-Dawley rats were given an intraperitoneal injection of pentylenetetrazol following a tail vein injection of lipopolysaccharide to establish the eclampsia-like seizure model. Seizure activity was assessed by behavioral testing. Neuronal loss in the hippocampal CA1 region (CA1) was detected by Nissl staining. Cerebrospinal fluid levels of S100-B and ferritin, indicators of neuroinflammation, were detected by enzyme-linked immunosorbent assay, and ionized calcium binder adapter molecule 1 (Iba-1, a marker for microglia) and glial fibrillary acid protein (GFAP, a marker for astrocytes) expression in the CA1 area was determined by immunofluorescence staining. Brain edema was measured. Our results revealed that MgSO effectively attenuated seizure severity and CA1 neuronal loss. In addition, MgSO significantly reduced cerebrospinal fluid levels of S100-B and ferritin, Iba-1 and GFAP activation in the CA1 area, and brain edema. Our results indicate that MgSO plays a neuroprotective role against eclampsia-like seizure by reducing neuroinflammation and brain edema.

Changes in the Expression of AQP4 and AQP9 in the Hippocampus Following Eclampsia-Like Seizure

“…On the basis of methods reported in the study of Fass et al [ 21 ] following the infusion of lipopolysaccharide (LPS), in our previous study intraperitoneal injection of PTZ was used to induce seizures [ 5 , 22 ]. In addition, we detected the biometric parameters of the two models; changes in blood pressure, and urinary albumin data were similar to the present study, and these two variables in the previous studies had the same time course.…”

“…Based on the classical PE models (LPS infusion) established by Fass et al [ 21 ], we used intraperitoneal injection of PTZ (40 mg/kg body weight) to induce seizures to set an eclampsia-like model to be used in the subsequent studies in order to fully investigate the mechanisms underlying PE and E, and we would try to apply other models. By using PTZ-induced rat models, our previous studies suggested that excessive systemic inflammation and increased brain inflammation in pre-eclampsia decreased the eclampsia-like seizure threshold [ 22 , 39 ], and seizures further increased brain inflammation [ 5 ]. We also found that the number of activated microglia cells and astrocytes in the CA1 area was higher in the pre-eclampsia group than in the normal pregnancy group; this number continued to increase in the eclampsia group [ 5 ].…”

“…Clinical evidence showed that approximately 90% of women with eclampsia have cerebral edema formation [ 4 ]. Our recent studies also showed that the brain water content significantly increased following eclampsia-like seizures compared to pre-eclampsia and normal pregnancy [ 5 ]. These studies suggested that cerebral edema is closely related to the occurrence and development of eclampsia-like seizures.…”

Tetrahydrocurcumin Provides Neuroprotection in Experimental Traumatic Brain Injury and the Nrf2 Signaling Pathway as a Potential Mechanism

“…For the Nissl staining, paraffin-embedded sections of brain tissue (5-μm-thick) were stained with cresyl violet, as previously described [17]. Normal neurons had large bodies, round nuclei located in the central soma, and abundant cytoplasm.…”

Magnesium supplementation during pregnancy

“…Также доказано, что назначение сульфата магния при преждевременных родах значитель-но снижает риск развития кровоизлияния в мозг у недо-ношенного новорожденного [14]. Кроме того, изучено и показано нейропротекторное действие сульфата маг-ния с целью профилактики и лечения эклампсии у бере-менных женщин за счет предупреждения процессов нейровоспаления и отека головного мозга [15].…”