*Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutes, Baltimore, MD †Department of Anesthesiology, Columbia University, New York, NY.
J Neurosurg Anesthesiol. 2014 Oct;26(4):363-8. doi: 10.1097/ANA.0000000000000119.
There is growing concern that pediatric exposure to anesthetic agents may cause long-lasting deficits in learning by impairing brain development. Most studies to date on this topic have focused on the direct effects of anesthetics on developing neurons. Relatively little attention has been paid to possible effects of anesthetics on astrocytes, a glial cell type that plays an important supporting role in neuronal development.
Astrocytes were exposed to isoflurane and then cocultured with unexposed neurons to test for astrocyte-specific toxic effects on neuronal growth. Axon length was measured in the cocultured neurons to assess neuronal growth.
We found that neurons cocultured with astrocytes exposed to isoflurane exhibited a 30% reduction in axon outgrowth. Further experimentation showed that this effect is likely due to reduced levels of brain-derived neurotrophic factor in the coculture media.
Isoflurane interferes with the ability of cultured astrocytes to support neuronal growth. This finding represents a potentially novel mechanism through which general anesthetics may interfere with brain development.
越来越多的人担心,儿科患者接触麻醉剂可能会通过损害大脑发育而导致学习能力的长期缺陷。迄今为止,关于这一主题的大多数研究都集中在麻醉剂对发育中的神经元的直接影响上。相对较少关注麻醉剂对星形胶质细胞(一种在神经元发育中起重要支持作用的神经胶质细胞类型)的可能影响。
将星形胶质细胞暴露于异氟烷中,然后与未暴露的神经元共培养,以测试麻醉剂对神经元生长的特定毒性作用。在共培养的神经元中测量轴突长度以评估神经元生长。
我们发现与暴露于异氟烷的星形胶质细胞共培养的神经元的轴突生长减少了 30%。进一步的实验表明,这种效应可能是由于共培养培养基中脑源性神经营养因子水平降低所致。
异氟烷干扰了培养的星形胶质细胞支持神经元生长的能力。这一发现代表了一种潜在的新机制,即全身麻醉可能会干扰大脑发育。