Clinical anesthesia causes permanent damage to the fetal guinea pig brain
Clinical anesthesia causes permanent damage to the fetal guinea pig brain
复制标题
DOI：
10.1111/j.1750-3639.2007.00116.x
复制
发表时间：
2008-04-01
期刊：
影响因子：
6.4
通讯作者：
Jevtovic-Todorovic, Vesna
中科院分区：
文献类型：
--
作者：
Rizzi, Sabina;Carter, Lisa B.;Jevtovic-Todorovic, Vesna
将未成熟的大脑暴露于全身麻醉是常见的。鉴于全身麻醉剂可能损害发育中的哺乳动物神经元的证据，这种做法的安全性最近受到了挑战。关于未成熟大鼠的初步报告提出了关于该物种可能独特的脆弱性，其大脑发育持续时间短以及麻醉期间缺乏对营养和心肺稳态的密切监测的批评。因此，我们研究了麻醉对豚鼠的神经毒性作用，豚鼠的大脑发育时间较长，主要是产前现象，因此可以通过麻醉妊娠雌性猪进行麻醉诱导的胎脑神经毒性研究。由于它们的体型大，这些动物使得侵入性监测母体和间接监测胎儿健康在技术上是可行的。尽管母体体内平衡得到充分维持，但在胎仔突触形成高峰期，母体单次短时间暴露于异氟烷（单独或与一氧化二氮和/或咪达唑仑一起），可诱导胎仔豚鼠大脑发生严重的神经细胞凋亡。正如在出生后早期发现的那样，这导致了脆弱大脑区域的许多神经元的损失，表明麻醉诱导的神经细胞凋亡可能导致永久性脑损伤。
Exposure of the immature brain to general anesthesia is common. The safety of this practice has recently been challenged in view of evidence that general anesthetics can damage developing mammalian neurons. Initial reports on immature rats raised criticism regarding the possibly unique vulnerability of this species, short duration of their brain development and a lack of close monitoring of nutritional and cardiopulmonary homeostasis during anesthesia. Therefore, we studied the neurotoxic effects of anesthesia in guinea pigs, whose brain development is longer and is mostly a prenatal phenomenon, so that anesthesia-induced neurotoxicity studies of the fetal brain can be performed by anesthetizing pregnant female pigs. Because of their large size, these animals made invasive monitoring of maternal and, indirectly, fetal well-being technically feasible. Despite adequate maintenance of maternal homeostasis, a single short maternal exposure to isoflurane, whether alone or with nitrous oxide and/or midazolam at the peak of fetal synaptogenesis, induced severe neuroapoptosis in the fetal guinea pig brain. As detected early in post-natal life, this resulted in the loss of many neurons from vulnerable brain regions, demonstrating that anesthesia-induced neuroapoptosis can cause permanent brain damage.