Department of Anesthesiology, First People's Hospital of Hangzhou, PR China.
Biochem Pharmacol. 2012 Aug 15;84(4):558-63. doi: 10.1016/j.bcp.2012.06.001. Epub 2012 Jun 15.
We developed a maternal fetal rat model to study the effects of isoflurane-induced neurotoxicity on the fetuses of pregnant rats exposed in utero. Pregnant rats at gestational day 14 were exposed to 1.3 or 3% isoflurane for 1h. At postnatal day 28, spatial learning and memory of the offspring were examined using the Morris Water Maze. The apoptosis was evaluated by caspase-3 immunohistochemistry in the hippocampal CA1 region. Simultaneously, the ultrastructure changes of synapse in the hippocampal CA1 and dentate gyrus region were observed by transmission electron microscopy (TEM). The 3% isoflurane treatment group showed significantly longer escape latency, less time spent in the third quadrant and fewer original platform crossings in the Morris Water Maze test, significantly increased number and optical densities of caspase-3 neurons. This treatment also produced remarkable changes in synaptic ultrastructure compared with the control and the 1.3% isoflurane groups. There were no differences in the Morris Water Maze test, densities of caspase-3 positive cells, or synaptic ultrastructure between the control and 1.3% isoflurane groups. High isoflurane concentration (3%) exposure during pregnancy caused spatial memory and learning impairments and more neurodegeneration in the offspring rats compared with control or lower isoflurane concentrations.
我们建立了一个母胎大鼠模型，以研究异氟醚诱导的神经毒性对宫内暴露的孕鼠胎儿的影响。在妊娠第 14 天，将孕鼠暴露于 1.3%或 3%异氟醚中 1 小时。在产后第 28 天，使用 Morris 水迷宫测试评估后代的空间学习和记忆能力。通过 caspase-3 免疫组织化学在海马 CA1 区评估细胞凋亡。同时，通过透射电子显微镜（TEM）观察海马 CA1 和齿状回区突触的超微结构变化。3%异氟醚处理组在 Morris 水迷宫测试中表现出明显更长的逃避潜伏期、更少的第三象限时间和更少的原始平台穿越次数，caspase-3 神经元的数量和光密度显著增加。与对照组和 1.3%异氟醚组相比，这种处理还导致突触超微结构发生了显著变化。在 Morris 水迷宫测试、caspase-3 阳性细胞密度或突触超微结构方面，对照组和 1.3%异氟醚组之间没有差异。与对照组或较低浓度异氟醚相比，妊娠期间高浓度（3%）异氟醚暴露导致后代大鼠的空间记忆和学习能力受损以及更多的神经退行性变。
