Department of Anesthesiology, Huashan Hospital, Fudan University, No. 12, Urumqi Central Rd., Shanghai 200040, PR China.
Med Hypotheses. 2011 Aug;77(2):223-9. doi: 10.1016/j.mehy.2011.04.018. Epub 2011 May 6.
The commonly used volatile anesthetic isoflurane or sevoflurane has been shown to be both neuroprotective and neurotoxic in various cell cultures and animal models. Some possible mechanisms have been raised to elucidate volatile anesthetics-induced neuroprotection or neurotoxicity, respectively. However, none of these can reconcile the linkage between their dual effects. Similar to volatile anesthetics, some drugs and nonpharmacological factors also can produce neuroprotection and neurotoxicity, which is associated with bioenergetic metabolism of neuronal cells. Here we present a uniform mechanism, bioenergetic homeostasis hypothesis, to explain neuroprotection and neurotoxicity induced by volatile anesthetics. The numerous evidences have shown that volatile anesthetics could affect mitochondrial electron transport complexes and glycolysis related pathways in cells, which could alter intracellular calcium homeostasis, ROS production and adenosine triphosphate (ATP) synthesis. Duration and concentration of exposure to volatile anesthetics could play a role on severity of bioenergy inhibition. Mild bioenergetic metabolism inhibition trigger signaling events involving preconditioning on neurons, and further bioenergy impairment could lead to neuronal cellular apoptosis, inhibition of neurogenesis and elevated β-Secretase, which drive pathogenesis of neurodegeneration.
在各种细胞培养物和动物模型中，常用的挥发性麻醉剂异氟醚或七氟醚已被证明具有神经保护作用和神经毒性作用。已经提出了一些可能的机制来分别阐明挥发性麻醉剂诱导的神经保护或神经毒性作用。然而，这些机制都无法解释它们双重作用之间的联系。类似于挥发性麻醉剂，一些药物和非药物因素也可以产生神经保护和神经毒性作用，这与神经元细胞的生物能量代谢有关。在这里，我们提出了一个统一的机制，即生物能量代谢稳态假说，来解释挥发性麻醉剂诱导的神经保护和神经毒性作用。大量证据表明，挥发性麻醉剂可以影响细胞中线粒体电子传递复合物和糖酵解相关途径，从而改变细胞内钙稳态、ROS 产生和三磷酸腺苷 (ATP) 合成。暴露于挥发性麻醉剂的持续时间和浓度可能对生物能量抑制的严重程度起作用。轻度生物能量代谢抑制会触发涉及神经元预处理的信号事件，进一步的生物能量损伤可能导致神经元细胞凋亡、神经发生抑制和β-分泌酶升高，从而导致神经退行性变的发病机制。
