Department of Anaesthesiology, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Anaesthesiology, Shengjing Hospital of China Medical University, Shenyang, China.
Biomed Pharmacother. 2020 Nov;131:110733. doi: 10.1016/j.biopha.2020.110733. Epub 2020 Sep 18.
General anaesthesia may impose significant neurocognitive risks on the developing brain. As brain injury in preterm neonates has a particular predilection for cerebral white matter, we aimed to evaluate the effects of sevoflurane on oligodendrocyte maturation and myelination in a preterm-equivalent rat model. Two-day-old postnatal (P2) Sprague-Dawley rats were exposed to 3.3 % (approximately 1 minimum alveolar concentration [MAC]) or 4.9 % (approximately 1.5 MAC) sevoflurane for 2 h. Physiologic parameters were measured at the end of sevoflurane anaesthesia. Oligodendrocyte proliferation, maturation, and myelination were evaluated by immunofluorescence with specific markers at different time points. Open field test and Morris water maze tests were performed to access behavior changes from P29 to P36. Arterial blood gases values and blood glucose levels were within the normal physiologic range. As compared to control, 4.9 %, but not 3.3 % sevoflurane disturbed oligodendrocyte maturation at P14, resulting in hypomyelination and axonal damage in cerebral white matter at P28. Rats exposed to 4.9 %, but not 3.3 % sevoflurane showed decreased explorative activity and increased anxiety-like behaviour, as well as learning and memory impairments. Furthermore, 4.9 %, but not 3.3 % sevoflurane inhibited oligodendrocyte proliferation in the developing white matter of the rat brain at 12 h post-anaesthesia, with further evidence of widespread reactive astrogliosis. High concentration of sevoflurane (4.9 %) exposure in early postnatal rats may disrupt oligodendrocyte maturation and myelination. Our study has aimed a spotlight on the need for safe and rational use of analgesics in neonates, especially preterm infants.
全身麻醉可能会对发育中的大脑造成显著的神经认知风险。由于早产儿的脑损伤特别偏爱脑白质，我们旨在评估七氟醚在早产儿等效大鼠模型中对少突胶质细胞成熟和髓鞘形成的影响。新生后 2 天（P2）的 Sprague-Dawley 大鼠暴露于 3.3%（约 1 个最小肺泡浓度 [MAC]）或 4.9%（约 1.5 MAC）七氟醚中 2 小时。在七氟醚麻醉结束时测量生理参数。在不同时间点用特定标志物通过免疫荧光评估少突胶质细胞增殖、成熟和髓鞘形成。从 P29 到 P36 进行旷场试验和 Morris 水迷宫试验以评估行为变化。动脉血气值和血糖水平在正常生理范围内。与对照组相比，4.9%而非 3.3%的七氟醚在 P14 时干扰少突胶质细胞成熟，导致 P28 时脑白质髓鞘形成不良和轴突损伤。暴露于 4.9%而非 3.3%七氟醚的大鼠表现出探索活动减少和焦虑样行为增加，以及学习和记忆障碍。此外，4.9%而非 3.3%的七氟醚在麻醉后 12 小时抑制大鼠脑发育白质中的少突胶质细胞增殖，并有广泛的反应性星形胶质细胞增生的进一步证据。新生后早期高浓度七氟醚（4.9%）暴露可能会破坏少突胶质细胞的成熟和髓鞘形成。我们的研究强调了在新生儿中安全和合理使用镇痛药的必要性，尤其是早产儿。
