Departments of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR 97239-3098, USA.
Ann Neurol. 2012 Oct;72(4):525-35. doi: 10.1002/ana.23652.
Previously we reported that exposure of 6-day-old (P6) rhesus macaques to isoflurane for 5 hours triggers a robust neuroapoptosis response in developing brain. We have also observed (unpublished data) that isoflurane causes apoptosis of cellular profiles in the white matter that resemble glia. We analyzed the cellular identity of the apoptotic white matter profiles and determined the magnitude of this cell death response to isoflurane.
Neonatal (P6) rhesus macaques were exposed for 5 hours to isoflurane anesthesia according to current clinical standards in pediatric anesthesia. Brains were collected 3 hours later and examined immunohistochemically to analyze apoptotic neuronal and glial death.
Brains exposed to isoflurane displayed significant apoptosis in both the white and gray matter throughout the central nervous system. Approximately 52% of the dying cells were glia, and 48% were neurons. Oligodendrocytes (OLs) engaged in myelinogenesis were selectively vulnerable, in contrast to OL progenitors, astrocytes, microglia, and interstitial neurons. When adjusted for control rates of OL apoptosis, the percentage of OLs that degenerated in the forebrain white matter of the isoflurane-treated group was 6.3% of the total population of myelinating OLs.
Exposure of the infant rhesus macaque brain to isoflurane for 5 hours is sufficient to cause widespread apoptosis of neurons and OLs throughout the developing brain. Deletion of OLs at a stage when they are just beginning to myelinate axons could potentially have adverse long-term neurobehavioral consequences that might be additive to the potential consequences of isoflurane-induced neuroapoptosis.
此前我们曾报道，6 日龄（P6）恒河猴接触 5 小时异氟醚可引发发育中大脑强烈的神经细胞凋亡反应。我们还观察到（未发表数据）异氟醚可引起白质中类似于神经胶质的细胞形态凋亡。我们分析了凋亡性白质形态的细胞特征，并确定了异氟醚诱导的这种细胞死亡反应的程度。
根据小儿麻醉的当前临床标准，将新生（P6）恒河猴暴露于异氟醚麻醉 5 小时。3 小时后收集大脑，进行免疫组织化学分析以分析凋亡的神经元和神经胶质死亡。
暴露于异氟醚的大脑在中枢神经系统的白质和灰质中均显示出明显的细胞凋亡。大约 52%的死亡细胞是神经胶质，48%是神经元。参与髓鞘形成的少突胶质细胞（OLs）特别易受影响，而 OL 祖细胞、星形胶质细胞、小胶质细胞和间质神经元则不受影响。与对照组 OL 凋亡率相比，异氟醚处理组前脑白质中变性的 OL 百分比为髓鞘形成 OL 总数的 6.3%。
6 日龄恒河猴大脑接触 5 小时异氟醚足以引起整个发育中大脑的神经元和 OL 广泛凋亡。在开始髓鞘化轴突的阶段删除 OL，可能会对长期神经行为产生不利影响，这可能会增加异氟醚诱导的神经细胞凋亡的潜在后果。
