Toll-like receptors 4 (TLR4) contributes to the pathogenesis of some neurodegenerative diseases. However, little is known about whether TLR4 is associated with sevoflurane-induced cognitive decline. This investigation aims to address the effect of global TLR4 gene knockout on cognitive decline following sevoflurane exposure to mice. Wild-type and TLR4^−/− mice were exposed to 3% sevoflurane. Novel object recognition test and Y-maze test were used to analyze cognitive function. Tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in plasma and hippocampus were measured by ELISA. Peripheral administration of recombinant TNF-α to TLR4^−/− mice was used to observed the role of TNF-α in cognitive function following sevoflurane. Our results showed that, in contrast to wild-type mice, TLR4 deficiency protected against the cognitive function impairment following sevoflurane exposure, and abrogated IL-1β, IL-6 and TNF-α response to sevoflurane in the system and the hippocampus. Subcutaneous administration of recombinant TNF-α elevated these cytokine levels in the hippocampus, and resulted in cognitive decline in TLR4^−/− mice exposed to sevoflurane. Taken together, our results identify the crucial role of TLR4 in sevoflurane-induced cognitive decline, and showed that TLR4 mediated pro-inflammatory cytokine response to sevoflurane, and consequent cognitive decline in aged mice exposed to sevoflurane, and imply a novel target for improvement and therapy of sevoflurane-associated cognitive decline.

Toll 样受体 4 (TLR4) 有助于一些神经退行性疾病的发病机制。然而，关于 TLR4 是否与七氟醚引起的认知能力下降有关，我们知之甚少。这项调查旨在解决全球 TLR4 基因敲除对小鼠七氟醚暴露后认知能力下降的影响。野生型和 TLR4 ^-/-小鼠暴露于 3% 七氟醚。新物体识别测试和Y-迷宫测试用于分析认知功能。通过ELISA测量血浆和海马中的肿瘤坏死因子α（TNF-α），白细胞介素1β（IL-1β）和白细胞介素6（IL-6）。将重组 TNF-α 外周给药至 TLR4 ^-/-小鼠用于观察七氟醚后TNF-α在认知功能中的作用。我们的结果表明，与野生型小鼠相比，TLR4 缺乏可防止七氟醚暴露后的认知功能障碍，并消除系统和海马中对七氟醚的 IL-1β、IL-6 和 TNF-α 反应。重组 TNF-α 的皮下给药提高了海马中这些细胞因子的水平，并导致 TLR4 ^{-/- 的}认知能力下降暴露于七氟烷的小鼠。总之，我们的结果确定了 TLR4 在七氟醚诱导的认知能力下降中的关键作用，并表明 TLR4 介导了对七氟醚的促炎细胞因子反应，以及随之而来的暴露于七氟醚的老年小鼠的认知能力下降，这意味着一个新的改善目标和七氟醚相关认知能力下降的治疗。