Isoflurane-induced apoptosis of neurons and oligodendrocytes in the fetal rhesus macaque brain.
Isoflurane-induced apoptosis of neurons and oligodendrocytes in the fetal rhesus macaque brain.
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DOI：
10.1097/aln.0000000000000037
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发表时间：
2014-03
期刊：
影响因子：
8.8
通讯作者：
Brambrink AM
中科院分区：
文献类型：
--
作者：
Creeley CE;Dikranian KT;Dissen GA;Back SA;Olney JW;Brambrink AM
作者先前已经表明，新生非人灵长类动物（NHP）大脑暴露于异氟烷5小时会导致神经元和少突胶质细胞广泛的急性凋亡变性。本研究探讨了异氟烷在胎儿NHP脑中的潜在致癫痫作用。胎龄为120天（G120）的胎恒河猴在子宫内暴露于异氟烷麻醉（n = 5）或无麻醉（对照条件; n = 4）5 h，3 h后系统评价脑的所有区域，以寻找神经元或神经胶质细胞凋亡变性的证据。暴露的G120胎儿NHP脑异氟烷引起的神经元和少突胶质细胞的凋亡显着增加的阶段时，少突胶质细胞刚刚开始髓鞘轴突。神经细胞凋亡反应在小脑、尾状核、壳核、杏仁核和几个皮质区最为突出。少突胶质细胞凋亡弥漫分布于多个白色区。异氟烷暴露的大脑中的细胞凋亡（神经元+少突胶质细胞）的总数增加了4.1倍，与药物初治对照组相比。异氟醚去除的少突胶质细胞总数高于去除的神经元数量。异氟醚麻醉5小时导致G120胎NHP脑中神经元和少突胶质细胞死亡。在胎儿脑中，正如作者先前在新生儿NHP脑中发现的那样，当少突胶质细胞刚刚达到髓鞘形成能力时，它们变得脆弱。在NHP脑中，异氟烷的神经毒性潜力在妊娠晚期（G120）和新生儿期之间增加。
The authors have previously shown that exposure of the neonatal nonhuman primate (NHP) brain to isoflurane for 5 h causes widespread acute apoptotic degeneration of neurons and oligodendrocyte. The current study explored the potential apoptogenic action of isoflurane in the fetal NHP brain. Fetal rhesus macaques at gestational age of 120 days (G120) were exposed in utero for 5 h to isoflurane anesthesia (n = 5) or to no anesthesia (control condition; n = 4), and all regions of the brain were systematically evaluated 3 h later for evidence of apoptotic degeneration of neurons or glia. Exposure of the G120 fetal NHP brain to isoflurane caused a significant increase in apoptosis of neurons and of oligodendrocytes at a stage when oligodendrocytes were just beginning to myelinate axons. The neuroapoptosis response was most prominent in the cerebellum, caudate, putamen, amygdala, and several cerebrocortical regions. Oligodendrocyte apoptosis was diffusely distributed over many white matter regions. The total number of apoptotic profiles (neurons + oligodendrocytes) in the isoflurane-exposed brains was increased 4.1-fold, compared with the brains from drug-naive controls. The total number of oligodendrocytes deleted by isoflurane was higher than the number of neurons deleted. Isoflurane anesthesia for 5 h causes death of neurons and oligodendrocytes in the G120 fetal NHP brain. In the fetal brain, as the authors previously found in the neonatal NHP brain, oligodendrocytes become vulnerable when they are just achieving myelination competence. The neurotoxic potential of isoflurane increases between the third trimester (G120) and the neonatal period in the NHP brain.