Athiraman Umeshkumar, Giri Tusar
Department of Anesthesiology, Washington University, St. Louis, MO, USA.
Department of Neurological Surgery, Washington University, St. Louis, MO, USA.
BJA Open. 2024 Mar 19;10:100268. doi: 10.1016/j.bjao.2024.100268. eCollection 2024 Jun.
Altered patterns of genetic expression induced by isoflurane preconditioning in mouse brain have not yet been investigated. The aim of our pilot study is to examine the temporal sequence of changes in the transcriptome of mouse brain cortex produced by isoflurane preconditioning.
Twelve-wk-old wild-type (C57BL/6J) male mice were randomly assigned for the experiments. Mice were exposed to isoflurane 2% in air for 1 h and brains were harvested at the following time points-immediately (0 h), and at 6, 12, 24, 36, 48, and 72 h after isoflurane exposure. A separate cohort of mice were exposed to three doses of isoflurane on days 1, 2, and 3 and brains were harvested after the third exposure. The NanoString mouse neuropathology panel was used to analyse isoflurane-induced gene expression in the cortex. The neuropathology panel included 760 genes covering pathways involved in neurodegeneration and other nervous system diseases, and 10 internal reference genes for data normalisation.
Genes involving several pathways were upregulated and downregulated by isoflurane preconditioning. Interestingly, a biphasic response was noted, meaning, an early expression of genes (until 6 h), followed by a transient pause (until 24 h), and a second wave of genomic response beginning at 36 h of isoflurane exposure was noted.
Isoflurane preconditioning induces significant alterations in the genes involved in neurodegeneration and other nervous system disorders in a temporal sequence. These data could aid in the identification of molecular mechanisms behind isoflurane preconditioning-induced neuroprotection in various central nervous system diseases.
异氟烷预处理诱导小鼠大脑基因表达模式的改变尚未得到研究。我们初步研究的目的是检测异氟烷预处理引起的小鼠大脑皮质转录组变化的时间顺序。
将12周龄野生型（C57BL/6J）雄性小鼠随机分组进行实验。小鼠暴露于含2%异氟烷的空气中1小时，在以下时间点采集大脑——即刻（0小时），以及异氟烷暴露后6、12、24、36、48和72小时。另一组小鼠在第1、2和3天暴露于三种剂量的异氟烷，在第三次暴露后采集大脑。使用NanoString小鼠神经病理学检测板分析异氟烷诱导的皮质基因表达。该神经病理学检测板包括760个涉及神经退行性变和其他神经系统疾病相关通路的基因，以及10个用于数据标准化的内部参照基因。
异氟烷预处理使涉及多个通路的基因上调和下调。有趣的是，观察到一种双相反应，即基因的早期表达（直至6小时），随后短暂停顿（直至24小时），并且注意到在异氟烷暴露36小时开始出现第二轮基因组反应。
异氟烷预处理按时间顺序诱导参与神经退行性变和其他神经系统疾病的基因发生显著改变。这些数据有助于确定异氟烷预处理在各种中枢神经系统疾病中诱导神经保护作用背后的分子机制。
