Magnesium sulfate provides neuroprotection in lipopolysaccharide-activated primary microglia by inhibiting NF-κB pathway

• Published in: The Journal of surgical research Vol. 184; no. 2; pp. 944 - 950
• Main Authors: Gao, Feng, MD, Ding, Baozhong, MD, Zhou, Longan, MD, Gao, Xueshan, MD, Guo, Huiguang, MD, Xu, Hong, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2013
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Animals; Calcium Channel Agonists - pharmacology; Calcium Channels, L-Type - drug effects; Calcium Channels, L-Type - physiology; Cells, Cultured; Dinoprostone - metabolism; Dose-Response Relationship, Drug; Inflammation; Inflammation - chemically induced; Inflammation - physiopathology; Inflammation - prevention & control; Interleukin-1beta - metabolism; L-type calcium channels; Lipopolysaccharides; Lipopolysaccharides - adverse effects; Lipopolysaccharides - pharmacology; Magnesium sulfate; Magnesium Sulfate - pharmacology; Magnesium Sulfate - therapeutic use; Microglia; Microglia - cytology; Microglia - drug effects; Microglia - physiology; Models, Animal; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; NF-kappa B; NF-kappa B - antagonists & inhibitors; NF-kappa B - drug effects; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects; Signal Transduction - physiology; Surgery; Tumor Necrosis Factor-alpha - metabolism; Magnesium sulfate; Inflammation; NF-kappa B; L-type calcium channels; Microglia; Lipopolysaccharides
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2013.03.034

Abstract Background Magnesium sulfate has been used as an anticonvulsant in severe preeclamptic or eclamptic women prior to surgical trauma, but its effects on neuroinflammation is not well defined. In the present study, we investigated the neuroprotective effects of magnesium sulfate in lipopolysaccharide (LPS)-induced microglia and explored the underlying mechanism. Materials and methods Microglia was incubated with LPS in the presence or absence of various concentrations of magnesium sulfate, or L-type calcium channel activator BAY-K8644. The levels of inflammatory mediators, such as nitric oxide, prostaglandin E2 , interleukin 1β, and tumor necrosis factor α, were measured using enzyme-linked immunosorbent assay. The expression of inducible nitric oxide synthase mRNA was detected by reverse-transcription polymerase chain reaction. Nuclear factor κB (NF-κB) activity in the nuclear extract of microglia was detected by NF-κB p50/p65 transcription factor assay kit. Results Magnesium sulfate at 5 and 10 mmol/L significantly inhibited the release of nitric oxide, prostaglandin E2 , interleukin 1β, and tumor necrosis factor α, and the expression of inducible nitric oxide synthase mRNA in LPS-activated microglia. Furthermore, magnesium sulfate inhibited the translocation of NF-κB from the cytoplasm to the nucleus in a dose-dependent manner. Notably, these effects were significantly reversed by L-type calcium channel activator BAY-K8644. Conclusions Magnesium sulfate protects microglia against LPS-induced release of inflammatory mediators, and these effects may be mediated by inhibiting L-type calcium channels and NF-κB signaling.