Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Department of Obstetrics, Guangzhou Women and Children's Medical Center, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei, China.
Department of Obstetrics, Guangzhou Women and Children's Medical Center, China.
Behav Brain Res. 2019 May 17;364:403-412. doi: 10.1016/j.bbr.2017.12.031. Epub 2017 Dec 27.
Eclampsia is characterized by high morbidity and mortality wordwide. Magnesium sulfate (MgSO) is used frequently as a prophylaxis for eclamptic seizure in clinical settings. However, the underlying mechanism is less studied, we have previously demonstrated that MgSO pretreatment decreases eclampsia-like seizure threshold. Here, we further evaluated the hypothesis that MgSO 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 MgSO 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 MgSO effectively attenuated astrocyte and microglia activation and promoted the neuronal survival in the CA3. Additionally, MgSO 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 MgSO has a neuroprotective role in eclampsia-like seizure rats through its anti-neuroninflammatory and brain edema-attenuating properties.
子痫是一种全球性高发病率和高死亡率的疾病。在临床环境中，硫酸镁（MgSO）常用于预防子痫发作。然而，其潜在机制研究较少，我们之前的研究表明，MgSO 预处理可降低子痫样发作阈值。在这里，我们通过改善神经炎症和脑水肿进一步评估了 MgSO 在子痫样大鼠模型中发挥神经保护作用的假设。在这项研究中，通过给予脂多糖加戊四氮在妊娠 Sprague-Dawley 大鼠中建立子痫样模型。大鼠从妊娠第 14 天至 19 天给予 MgSO。然后，通过酶联免疫吸附试验检测海马 CA3 区小胶质细胞（Iba-1）和星形胶质细胞（S100-B）标志物的表达水平。通过 Luminex 分析测定脑脊液（CSF）中炎症细胞因子的水平。使用免疫组织化学分析皮质中水通道蛋白-4（一种跨膜水通道蛋白）的表达水平。通过免疫荧光检测星形胶质细胞和小胶质细胞的表达，通过尼氏染色评估神经元损伤，并用神经元核染色检测不同组间海马 CA3 区（CA3）神经元数量的变化。我们的结果表明，MgSO 可有效减轻星形胶质细胞和小胶质细胞的激活，并促进 CA3 中的神经元存活。此外，MgSO 显著降低 CSF 中的炎症细胞因子反应，并降低皮质中 AQP-4 蛋白的表达。总之，这项研究的结果表明，MgSO 通过其抗神经元炎症和减轻脑水肿的特性在子痫样发作大鼠中发挥神经保护作用。
