Kim Greena, Love Kaitlyn, Connor-Stroud Fawn, Baxter Mark G, Alvarado Maria, Raper Jessica
Emory National Primate Research Center, Emory University, 954 Gatewood Rd NE, Atlanta GA 30329, USA.
Department of Pathology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem NC 27157, USA.
Neurotoxicol Teratol. 2025 Aug 5;110:107535. doi: 10.1016/j.ntt.2025.107535.
Animal models and human studies suggest that general anesthesia exposure during infancy results in long-lasting neurocognitive impairments. Because millions of children each year undergo procedures that require anesthesia, it is important to investigate the mechanism of anesthesia induced neurotoxicity to ultimately develop ways to protect the vulnerable developing brain. Animal models have played a key role in this investigation and have shown that neonatal general anesthesia exposure results in neuronal apoptosis, long-term mitochondrial dysfunction, and astrogliosis. The current study involved a rhesus macaque model of repeated sevoflurane exposure that has been shown to produce cognitive deficits, behavioral changes, and mitochondrial damage. This study sought to investigate whether prolonged sevoflurane exposure induced inflammation as measured in peripheral blood samples. Results found that sevoflurane exposure resulted in changing levels of inflammatory markers in the periphery. Specifically, interleukin 6 (IL-6) was increased immediately following sevoflurane exposure, but not at 24-h post-exposure. Plasma samples collected 24-h after exposure revealed increased granulocyte macrophage colony-stimulating factor (GM-CSF), but decreased monocyte chemoattractant protein-4 (MCP-4) and interferon gamma-induced protein 10 (IP-10) levels. Changes in these markers have been linked to cognitive impairment, and together these data suggest that plasma levels of cytokines and chemokines are a good potential medium to investigate anesthesia-induced inflammation in clinical populations.
动物模型和人体研究表明,婴儿期接受全身麻醉会导致长期的神经认知障碍。由于每年有数百万儿童接受需要麻醉的手术,因此研究麻醉诱导神经毒性的机制以最终找到保护脆弱发育中大脑的方法非常重要。动物模型在这项研究中发挥了关键作用,并已表明新生儿期接受全身麻醉会导致神经元凋亡、长期线粒体功能障碍和星形胶质细胞增生。当前的研究涉及恒河猴反复暴露于七氟醚的模型,该模型已被证明会产生认知缺陷、行为改变和线粒体损伤。本研究旨在调查长期暴露于七氟醚是否会在外周血样本中引发炎症。结果发现,七氟醚暴露导致外周炎症标志物水平发生变化。具体而言,七氟醚暴露后白细胞介素6(IL-6)立即升高,但暴露后24小时未升高。暴露后24小时采集的血浆样本显示粒细胞巨噬细胞集落刺激因子(GM-CSF)升高,但单核细胞趋化蛋白-4(MCP-4)和干扰素γ诱导蛋白10(IP-10)水平降低。这些标志物的变化与认知障碍有关,这些数据共同表明细胞因子和趋化因子的血浆水平是研究临床人群中麻醉诱导炎症的良好潜在介质。