Many studies have shown that prolonged or repeated use of general anesthesia early in life can cause an increase in neurodegeneration and lasting changes in behavior. While short periods of general anesthesia appear to be safe, there is a concern about the neurotoxic potential of prolonged or repeated general anesthesia in young children. Unfortunately, the use of general anesthesia in children cannot be avoided. It would be a great benefit to develop a strategy to reduce or reverse anesthesia mitigated neurotoxicity. The mechanisms behind anesthesia related neurotoxicity are unknown, but evidence suggests that mitochondrial dysfunction and abnormal energy utilization are involved. Recent research suggests that a class of compounds known as carnitines may be effective at preventing anesthesia related neurotoxicity by influencing fatty acid metabolism in the mitochondria. However, it is unknown if carnitines can provide protection against changes in behavior associated with early life exposure to anesthesia. Accordingly, we evaluated the neuroprotective potential of acetyl-l-carnitine in 7-day old rats. Rat pups were exposed to 6 h of general anesthesia with sevoflurane or a control condition, with and without acetyl-l-carnitine. The oxygenation level of animals was continually monitored during sevoflurane exposure, and any animal showing signs of hypoxia was removed from the study. Animals exposed to sevoflurane showed clear signs of neurodegeneration 2 h after sevoflurane exposure. The hippocampus, cortex, thalamus, and caudate putamen all had elevated levels of Fluoro-Jade C staining. Despite the elevated levels of Fluoro-Jade C, few behavioral changes were observed in an independent cohort of animals treated with sevoflurane. Furthermore, acetyl-l-carnitine had little impact on levels of Fluoro-Jade C staining in animals treated with sevoflurane. These data suggest that acetyl-l-carnitine may offer little protection again anesthesia related neurotoxicity in fully oxygenated animals.

中文翻译：

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在长期新生儿麻醉的啮齿动物模型中，乙酰左旋肉碱不能预防神经变性。

许多研究表明，在生命早期长期或反复使用全身麻醉会导致神经变性增加和行为的持久变化。虽然短期全身麻醉似乎是安全的，但人们担心长时间或反复全身麻醉对幼儿的神经毒性潜力。不幸的是，在儿童中使用全身麻醉是不可避免的。开发一种减少或逆转麻醉减轻神经毒性的策略将是一个巨大的好处。麻醉相关神经毒性背后的机制尚不清楚，但有证据表明线粒体功能障碍和能量利用异常有关。最近的研究表明，一类被称为肉碱的化合物可能通过影响线粒体中的脂肪酸代谢来有效预防与麻醉相关的神经毒性。然而，尚不清楚肉碱是否可以提供保护，防止与生命早期暴露于麻醉相关的行为变化。因此，我们评估了乙酰左旋肉碱对 7 天大大鼠的神经保护潜力。大鼠幼崽暴露于七氟醚全身麻醉或对照条件下 6 小时，有和没有乙酰-l-肉碱。在七氟醚暴露期间持续监测动物的氧合水平，并且从研究中移除任何表现出缺氧迹象的动物。暴露于七氟醚的动物在七氟醚暴露后 2 小时表现出明显的神经变性迹象。海马体、皮层、丘脑、尾壳核和尾壳核的 Fluoro-Jade C 染色水平均升高。尽管氟玉 C 水平升高，但在用七氟醚治疗的独立动物队列中观察到的行为变化很少。此外，乙酰左旋肉碱对用七氟醚治疗的动物的 Fluoro-Jade C 染色水平几乎没有影响。这些数据表明，乙酰左旋肉碱对完全充氧动物的麻醉相关神经毒性几乎没有保护作用。