Propofol is a widely used intravenous anesthetic agent with potential neuroprotective effect in diverse models of neuronal injury, including ischemic stroke and traumatic brain injury. However, few studies have been carried out to determine the effects and molecular mechanisms of propofol in classic microglial activation (M1 activation) related to neuronal injury. This study explored the anti-inflammatory effects of propofol in LPS-activated BV microglia. Propofol potently decreased the pro-inflammatory mediators, such as nitric oxide, TNF-α, and IL-6, at both the transcriptional and translational levels. Furthermore, propofol suppressed the expression of miR-155 in LPS-activated cells. Knockdown of miR-155 attenuated the anti-inflammatory effect of propofol in cells after LPS exposure. miR-155 was also confirmed as a negative regulator of SOCS1 expression. The inhibitory effect of propofol on LPS-induced inflammation involved the upregulation of SOCS1. Overall, these results suggest that propofol can suppress the neuroinflammatory response of microglia to LPS through the regulation of the miR-155/SOCS1 pathway.

Perioperative neurocognitive disorders have been widely recognized as common adverse events after surgical intervention. Aging is one of the most important independent risk factors for worsened cognitive outcome, and this deterioration is linked to exacerbated microglia‐mediated neuroinflammation in the aged brain. Under pathological stimulation, microglia are capable of polarizing toward proinflammatory M1 and anti‐inflammatory M2 phenotypes. In the present study, we examined how aging affects microglial responses and neuroinflammation following peripheral surgery. Adult (2‐3 months) and aged (18 months old) male C57/BL6 mice were subjected to tibial fracture or sham surgery. Aged mice exhibited higher level of tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) in the hippocampus. The expression of synaptic protein synaptophysin (SYP) was also markedly reduced in the aged brain after the surgery. Both adult and aged mice showed significant increases in M1 microglial polarization (CD16/32). In contrast, tibial fracture surgery induced a decreased M2 microglial polarization (CD206, Ym1/2, Arg1) in aged brain but enhanced M2 microglial polarization in adult brain. Aged mice have upregulated voltage‐gated proton channel (Hv1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit expression compared with adult mice. The percentage of CD16/32‐positive M1 microglia colabeling with Hv1 was higher in aged mice after tibial fracture surgery. Thus, Hv1/NADPH oxidase upregulation in the aged brain may shift the dynamic equilibrium of microglial activation toward M1 polarization and exaggerate postoperative neuroinflammatory responses after peripheral surgical intervention.