The Journal of surgical research
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High mobility group box 1 (HMGB1) is an important inflammatory factor that is closely related to mortality in patients with sepsis. High magnesium therapy has been proved to reduce sepsis-related mortality and sepsis-induced pathologic complications. These effects result from reduced expression and release of many inflammatory cytokines, although it is not clear whether high magnesium affects the expression and release of HMGB1. In the present study, we explored the effect of magnesium sulfate on the expression and release of HMGB1 in lipopolysaccharide (LPS)-activated macrophages. ⋯ Our study has demonstrated that magnesium sulfate inhibits the translocation of HMGB1 from the nucleus to the cytoplasm and the expression of HMGB1 mRNA in a dose-dependent manner. The mechanism responsible for these effects involves the NF-κB signaling pathway.
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Complement is invariably activated during trauma and contributes to tissue injury. Recombinant human decay-accelerating factor (DAF), a complement regulatory protein that inhibits both classical and alternative pathways, improves survival and reduces tissue damage in animal models of tissue injury. The extent to which DAF may facilitate resuscitation in hemorrhaged large animals is not known. ⋯ DAF improved survival and reduced early Hextend fluid resuscitation requirements in swine subjected to hemorrhagic shock. These benefits are attributed to decreased complement deposition and limited organ damage.
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Spinal cord injuries (SCIs) are serious and debilitating health problems that lead to severe and permanent neurological deficits resulting from the primary mechanical impact followed by secondary tissue injury. During the acute stage after an SCI, the expression of autophagy and inflammatory responses contribute to the development of secondary injury. In the present study, we examined the multifaceted effects of rapamycin on outcomes of rats after an SCI. ⋯ Rapamycin is a novel neuroprotectant with multifaceted effects on the rat spinal cord after injury. Use of such a clinically established drug could facilitate early clinical trials in selected cases of human SCIs.