Isoflurane causes greater neurodegeneration than an equivalent exposure of sevoflurane in the developing brain of neonatal mice.
Isoflurane causes greater neurodegeneration than an equivalent exposure of sevoflurane in the developing brain of neonatal mice.
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DOI：
10.1097/aln.0b013e3181d94da5
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发表时间：
2010-06
期刊：
影响因子：
8.8
通讯作者：
Wei H
中科院分区：
文献类型：
--
作者：
Liang G;Ward C;Peng J;Zhao Y;Huang B;Wei H
根据我们之前的细胞培养研究，我们假设异氟醚比七氟醚在新生小鼠大脑发育中更能诱导神经变性。我们用 0.75% 异氟烷或 1.1% 七氟烷（~0.5 最低肺泡浓度）治疗 7 日龄小鼠 6 小时，然后在麻醉治疗后 2 小时获取血液和脑样本，用于测定不同脑区域的神经细胞凋亡和血液中的神经退行性生物标志物 S100β。还通过测定细胞周期的蛋白表达和凋亡相关蛋白来比较异氟烷或七氟烷诱导的神经变性机制。在不同的组中，在出生后第 7 天进行麻醉治疗后，通过在出生后第 42 天对小鼠进行莫里斯水迷宫测试来评估记忆和学习能力。异氟烷（而非七氟烷）显着增加了血液中的神经退行性生物标志物 S100β。异氟烷治疗显着增加了细胞凋亡，这通过激活不同脑区域的 caspase-3 和聚 (ADP-核糖) 聚合酶的升高来表明。等量暴露的七氟醚往往会增加海马和皮质区域的细胞凋亡，但其效力明显低于异氟醚。异氟醚和七氟醚均未显着改变 3-磷酸甘油醛脱氢酶、β 位点淀粉样蛋白 β 前体蛋白裂解酶和细胞周期调节蛋白（CDK4、细胞周期蛋白 D1）的蛋白质水平。异氟烷和七氟烷在选定的暴露量下不会显着改变记忆和学习能力。在等量暴露下，异氟醚比七氟醚更能引起新生小鼠发育中大脑的神经变性。
We hypothesized that isoflurane has a greater potency to induce neurodegeneration than sevoflurane in the developing brains of neonatal mice based on our previous studies in cell culture. We treated 7-day-old mice with either 0.75% isoflurane or 1.1% sevoflurane (~0.5 Minimum Alveolar Concentration) for 6 h and then obtained blood and brain samples at 2 h after the anesthesia treatment for determination of neuroapoptosis in different brain regions and the neurodegenerative biomarker S100β in the blood. The mechanisms of neurodegeneration induced by isoflurane or sevoflurane were also compared by determining protein expressions of the cell cycle, and apoptosis related proteins. In separate groups, memory and learning ability were evaluated through the use of Morris Water Maze testing in mice at postnatal day 42 after anesthesia treatment at postnatal day 7. Isoflurane but not sevoflurane significantly increased the neurodegenerative biomarker S100β in the blood. Isoflurane treatments significantly increased apoptosis indicated by the activation of caspase-3 and elevation of Poly-(ADP-ribose) polymerase in different brain regions. An equipotent exposure of sevoflurane tended to increase apoptosis in hippocampal and cortex areas but was significantly less potent than isoflurane. Neither isoflurane nor sevoflurane changed protein levels of glyceraldehyde-3-phosphate dehydrogenase, beta-site amyloid beta precursor protein cleaving enzyme and cell cycle regulatory proteins (CDK4, cyclin D1) significantly. Isoflurane and sevoflurane at the selected exposures did not significantly alter memory and learning ability. At equipotent exposures, isoflurane has a greater potency than sevoflurane to cause neurodegeneration in the developing brains of neonatal mice.