Scholarlink

Background <p>Perioperative use of dexmedetomidine (DEX) reduces the incidence of Delayed Neurocognitive Recovery (DNR) in elderly patients, though mechanisms remain unclear. This study investigated whether DEX improves DNR by inhibiting microglial activation and explored the cholinergic anti-inflammatory pathway’s role.</p> Methods <p>An exploratory laparotomy model was established in aged C57BL/6J mice, with preoperative treatment using DEX or DEX combined with α-bungarotoxin. Cognitive function was assessed through the novel object recognition (NOR) and Morris water maze (MWM) tests, while immunofluorescence was used to observe microglial morphology, and qPCR and ELISA were employed to detect inflammatory factor expression.</p> Results <p>DEX pretreatment significantly reduced the escape latency of aged mice on postoperative days 3–5 (50.50 ± 3.73 vs. 55.01 ± 4.01, <i>P</i> = 0.04; 36.36 ± 4.31 vs. 43.42 ± 5.64, <i>P</i> = 0.01; 27.00 ± 3.94 vs. 34.50 ± 5.54, <i>P</i> = 0.006), increased number of times crossing the previous platform location (2.50 ± 1.31 vs. 1.08 ± 0.90, <i>P</i> = 0.02), and percentage of dwell time in the target quadrant (37.87 ± 9.66 vs. 25.00 ± 4.48, <i>P</i> &lt; 0.001). DEX pretreatment also reduced the expression of pro-inflammatory cytokines in the hippocampus (TNF-α, 604.10 ± 165.40 vs. 915.30 ± 97.64, <i>P</i> = 0.002; IL-6, 145.30 ± 12.11 vs. 176.50 ± 16.15, <i>P</i> = 0.002; IL-1β, 59.68 ± 4.29 vs. 68.73 ± 3.11, <i>P</i> = 0.001) of aged mice postoperatively, as well as in the spleen and serum. Additionally, DEX pretreatment reduces microglia count (96.60 ± 11.84 vs. 136.20 ± 32.62, <i>P</i> = 0.05), fluorescence (0.96 ± 0.06 vs. 1.10 ± 0.02, <i>P</i> &lt; 0.001), morphology (7.20 ± 2.17 vs.12.80 ± 2.28, <i>P</i> = 0.002) in aged mice post-surgery. Pre-administration of α-bungarotoxin before DEX pretreatment partially reversed these effects.</p> Conclusions <p>DEX pretreatment ameliorated DNR in aged mice is related to inhibition of microglial activation, which was at least partially attributed to activation of the cholinergic anti-inflammatory pathway.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Dexmedetomidine pretreatment improves postsurgical delay in neurocognitive recovery in aged mice by inhibiting hippocampal microglial activation via activation of cholinergic anti-inflammatory pathways

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月15日

查看全文
  • Qidi Zhang,
  • Shiyu Hao,
  • Guicheng Wang,
  • Chengxiao Liu,
  • Gongming Wang,
  • Jie Zhang,
  • Jinyang Zhao,
  • Xiaowei Li,
  • Jingjing Li,
  • Jiangnan Wu,
  • Xu Wang

摘要

Background

Perioperative use of dexmedetomidine (DEX) reduces the incidence of Delayed Neurocognitive Recovery (DNR) in elderly patients, though mechanisms remain unclear. This study investigated whether DEX improves DNR by inhibiting microglial activation and explored the cholinergic anti-inflammatory pathway’s role.

Methods

An exploratory laparotomy model was established in aged C57BL/6J mice, with preoperative treatment using DEX or DEX combined with α-bungarotoxin. Cognitive function was assessed through the novel object recognition (NOR) and Morris water maze (MWM) tests, while immunofluorescence was used to observe microglial morphology, and qPCR and ELISA were employed to detect inflammatory factor expression.

Results

DEX pretreatment significantly reduced the escape latency of aged mice on postoperative days 3–5 (50.50 ± 3.73 vs. 55.01 ± 4.01, P = 0.04; 36.36 ± 4.31 vs. 43.42 ± 5.64, P = 0.01; 27.00 ± 3.94 vs. 34.50 ± 5.54, P = 0.006), increased number of times crossing the previous platform location (2.50 ± 1.31 vs. 1.08 ± 0.90, P = 0.02), and percentage of dwell time in the target quadrant (37.87 ± 9.66 vs. 25.00 ± 4.48, P < 0.001). DEX pretreatment also reduced the expression of pro-inflammatory cytokines in the hippocampus (TNF-α, 604.10 ± 165.40 vs. 915.30 ± 97.64, P = 0.002; IL-6, 145.30 ± 12.11 vs. 176.50 ± 16.15, P = 0.002; IL-1β, 59.68 ± 4.29 vs. 68.73 ± 3.11, P = 0.001) of aged mice postoperatively, as well as in the spleen and serum. Additionally, DEX pretreatment reduces microglia count (96.60 ± 11.84 vs. 136.20 ± 32.62, P = 0.05), fluorescence (0.96 ± 0.06 vs. 1.10 ± 0.02, P < 0.001), morphology (7.20 ± 2.17 vs.12.80 ± 2.28, P = 0.002) in aged mice post-surgery. Pre-administration of α-bungarotoxin before DEX pretreatment partially reversed these effects.

Conclusions

DEX pretreatment ameliorated DNR in aged mice is related to inhibition of microglial activation, which was at least partially attributed to activation of the cholinergic anti-inflammatory pathway.