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Postoperative cognitive dysfunction (POCD), common in elderly patients, refers to a decline in cognitive function following surgery, which may persist or even evolve into Alzheimer's disease (AD). Despite great efforts, the mechanism of POCD remains unclear. In the present study, we tested the hypothesis that Toll-like receptor 4 (TLR4) on microglia contributes to POCD. Shortly after surgery, aged rats demonstrated significant deficits in memory and learning, accompanied by the activation of microglia, marked upregulation of TLR4 on microglia in the hippocampus, as well as an increased expression of two downstream factors [myeloid differentiation factor 88 (MyD88) and TIR-domain-containing adapter-inducing interferon-β (TRIF)] and pro-inflammatory cytokines [including tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)]. With an increase in time following surgery, the expression of TLR4 and the aforementioned factors and pro-inflammatory cytokines gradually returned to normal, as did the cognitive function of the aged rats. In conclusion, our study suggests that the activation of TLR4 signaling on microglia may act as an underlying mechanism of POCD.

The role of the TLR4 signaling pathway in cognitive deficits following surgery in aged rats