BackgroundPostoperative cognitive dysfunction (POCD) is a common complication after surgery, especially amongst elderly patients. Neuroinflammation and iron homeostasis are key hallmarks of several neurological disorders. In this study, we investigated the role of deferoxamine (DFO), a clinically used iron chelator, in a mouse model of surgery-induced cognitive dysfunction and assessed its neuroprotective effects on neuroinflammation, oxidative stress, and memory function.MethodsA model of laparotomy under general anesthesia and analgesia was used to study POCD. Twelve to 14 months C57BL/6J male mice were treated with DFO, and changes in iron signaling, microglia activity, oxidative stress, inflammatory cytokines, and neurotrophic factors were assessed in the hippocampus on postoperative days 3, 7, and 14. Memory function was evaluated using fear conditioning and Morris water maze tests. BV2 microglia cells were used to test the anti-inflammatory and neuroprotective effects of DFO.ResultsPeripheral surgical trauma triggered changes in hippocampal iron homeostasis including ferric iron deposition, increase in hepcidin and divalent metal transporter-1, reduction in ferroportin and ferritin, and oxidative stress. Microglia activation, inflammatory cytokines, brain-derived neurotropic factor impairments, and cognitive dysfunction were found up to day 14 after surgery. Treatment with DFO significantly reduced neuroinflammation and improved cognitive decline by modulating p38 MAPK signaling, reactive oxygen species, and pro-inflammatory cytokines release.ConclusionsIron imbalance represents a novel mechanism underlying surgery-induced neuroinflammation and cognitive decline. DFO treatment regulates neuroinflammation and microglia activity after surgery.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0740-2) contains supplementary material, which is available to authorized users.
Mechanical trauma (MT) causes myocardial injury and cardiac dysfunction.However, the underlying mechanism remains largely unclear. This study investigated the role of mitochondrial dynamics in post-traumatic cardiac dysfunction and the protective effects of melatonin. Adult male Sprague Dawley rats were subjected to
K E Y W O R D Scardiac dysfunction, Drp1, mechanical trauma, melatonin, mitochondrial dynamics
Caspase-3 inhibition alleviates pulmonary injury, thereby preventing angiogenesis as well as the development of HPS in CBDL rats. These effects are related to the regulation of the Akt and ERK1 pathways.
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