Methane ameliorates post-operative cognitive dysfunction by inhibiting microglia NF-κB/MAPKs pathway and promoting IL-10 expression in aged mice

Abstract

Postoperative cognitive dysfunction (POCD) is one of the most common complications after surgery. Accumulating evidence suggests that postoperative neuro-inflammation plays a critical role in the mechanism of POCD. Recently, exogenous methane is reported to have anti-inflammatory properties and play a neuro-protective role in acute carbon monoxide poisoning injury. Therefore, we investigated the protective effect of methane on a POCD model induced by abdominal surgery and its underlying mechanism in aged mice. Methane-rich saline (MS) or normal saline (NS) (16 ml/kg) was injected intraperitoneally 30 min after the abdominal surgery. The result showed that methane attenuated spatial memory loss in Morris water maze (MWM) with decreasing pro-inflammatory cytokines production and activation of microglia in hippocampus after surgery. Meanwhile, methane treatment suppressed lipopolysaccharide (LPS)-stimulated phosphorylation of MAPKs pathways and its downstream target TNF-α and IL-6 in BV2 cells. Moreover, methane increased expression of IL-10 in the hippocampus 24 h after surgery, and blockade of IL-10 repressed the protective effect of methane on the cognitive impairments observed in MWM test, decreased microglial activation and the pro-inflammatory cytokine in plasma and hippocampal. Blockade of IL-10 abrogated the suppression effect of methane on the pro-inflammatory cytokine production and phosphorylation of NF-κB and p38MAPK both in hippocampus and in BV2 cells. In conclusion, our study suggests exogenous methane could be a novel agent for the therapy of POCD through its anti-inflammation properties.