Isoflurane does not cause neuroapoptosis but reduces astroglial processes in young adult mice.
Isoflurane does not cause neuroapoptosis but reduces astroglial processes in young adult mice.
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DOI：
10.1186/2045-9912-1-27
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发表时间：
2011-11-03
影响因子：
2.9
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Dallasen RM;Bowman JD;Xu Y
异氟醚是一种临床上广泛使用的挥发性麻醉剂，已被认为具有神经保护和神经毒性。关于异氟醚导致神经细胞凋亡的说法仍然存在争议。在这项研究中，我们研究了异氟烷暴露对年轻成年小鼠脑内细胞增殖和神经发生以及星形胶质细胞突起的影响。将60只6周龄小鼠随机分为4个麻醉浓度组(0组为对照组，0.6%、1.3%、2%组)，分别于异氟醚吸入后2 h、1 d、6 d、14 d恢复麻醉。免疫组织化学检测激活的caspase-3和抗凋亡信号，胶质纤维酸性蛋白(GFAP)和波形蛋白(Vimentin)用于反应性星形细胞增生，双皮质激素(DCX)用于神经发生，BrdU用于细胞增殖。与先前从新生啮齿动物研究中得出的结论相反，我们没有发现异氟醚诱导成年小鼠脑内细胞凋亡的证据。异氟醚不影响齿状回颗粒下层的神经发生。然而，在2%异氟醚暴露后，细胞增殖有减少的趋势。Vim和GFAP染色显示，异氟醚暴露导致海马区和齿状回星形胶质细胞突起迟发性减少。暴露在异氟醚中两小时并没有导致成人大脑中的神经细胞凋亡。异氟醚暴露后星形胶质细胞突起的延迟减少可能解释了为什么一些挥发性麻醉剂可以在实验性中风后提供神经保护，因为减少胶质瘢痕有助于更好的长期神经元恢复。
Isoflurane, a volatile anesthetic widely used clinically, has been implicated to be both neuroprotective and neurotoxic. The claim about isoflurane causing neural apoptosis remains controversial. In this study, we investigated the effects of isoflurane exposures on apoptotic and anti-apoptotic signals, cell proliferation and neurogenesis, and astroglial processes in young adult mouse brains. Sixty 6-week-old mice were randomly assigned to four anesthetic concentration groups (0 as control and 0.6%, 1.3%, and 2%) with four recovery times (2 h and 1, 6, and 14 d) after 2-h isoflurane exposure. Immunohistochemistry measurements of activated caspase-3 and Bcl-xl for apoptotic and anti-apoptotic signals, respectively, glial fibrillary acidic protein (GFAP) and vimentin for reactive astrocytosis, doublecortin (Dcx) for neurogenesis, and BrdU for cell proliferation were performed. Contrary to the previous conclusion derived from studies with neonatal rodents, we found no evidence of isoflurane-induced apoptosis in the adult mouse brain. Neurogenesis in the subgranule zone of the dentate gyrus was not affected by isoflurane. However, there is a tendency of reduced cell proliferation after 2% isoflurane exposure. VIM and GFAP staining showed that isoflurane exposure caused a delayed reduction of astroglial processes in the hippocampus and dentate gyrus. Two-hour exposure to isoflurane did not cause neuroapoptosis in adult brains. The delayed reduction in astroglial processes after isoflurane exposure may explain why some volatile anesthetics can confer neuroprotection after experimental stroke because reduced glial scarring facilitates better long-term neuronal recoveries.