A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FI,-70211 Kuopio, Finland.
Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, FI,-70211 Kuopio, Finland.
Neuroimage. 2021 Jul 1;234:117987. doi: 10.1016/j.neuroimage.2021.117987. Epub 2021 Mar 21.
Isoflurane, the most commonly used preclinical anesthetic, induces brain plasticity and long-term cellular and molecular changes leading to behavioral and/or cognitive consequences. These changes are most likely associated with network-level changes in brain function. To elucidate the mechanisms underlying long-term effects of isoflurane, we investigated the influence of a single isoflurane exposure on functional connectivity, brain electrical activity, and gene expression. Male Wistar rats (n = 22) were exposed to 1.8% isoflurane for 3 h. Control rats (n = 22) spent 3 h in the same room without exposure to anesthesia. After 1 month, functional connectivity was evaluated with resting-state functional magnetic resonance imaging (fMRI; n = 6 + 6) and local field potential measurements (n = 6 + 6) in anesthetized animals. A whole genome expression analysis (n = 10+10) was also conducted with mRNA-sequencing from cortical and hippocampal tissue samples. Isoflurane treatment strengthened thalamo-cortical and hippocampal-cortical functional connectivity. Cortical low-frequency fMRI power was also significantly increased in response to the isoflurane treatment. The local field potential results indicating strengthened hippocampal-cortical alpha and beta coherence were in good agreement with the fMRI findings. Furthermore, altered expression was found in 20 cortical genes, several of which are involved in neuronal signal transmission, but no gene expression changes were noted in the hippocampus. Isoflurane induced prolonged changes in thalamo-cortical and hippocampal-cortical function and expression of genes contributing to signal transmission in the cortex. Further studies are required to investigate whether these changes are associated with the postoperative behavioral and cognitive symptoms commonly observed in patients and animals.
异氟醚是最常用于临床前麻醉的药物，可诱导大脑可塑性和长期的细胞和分子变化，导致行为和/或认知后果。这些变化很可能与大脑功能的网络水平变化有关。为了阐明异氟醚长期作用的机制，我们研究了单次异氟醚暴露对功能连接、脑电活动和基因表达的影响。雄性 Wistar 大鼠（n=22）暴露于 1.8%异氟醚中 3 小时。对照组大鼠（n=22）在相同的房间中待 3 小时，不接触麻醉剂。1 个月后，通过静息态功能磁共振成像（fMRI；n=6+6）和麻醉动物的局部场电位测量（n=6+6）评估功能连接。还进行了全基因组表达分析（n=10+10），用皮质和海马组织样本的 mRNA 测序进行分析。异氟醚处理增强了丘脑-皮质和海马-皮质的功能连接。皮质低频 fMRI 功率也因异氟醚处理而显著增加。局部场电位结果表明，海马-皮质的 alpha 和 beta 相干性增强，与 fMRI 结果一致。此外，在 20 个皮质基因中发现了表达改变，其中几个基因参与神经元信号传递，但在海马体中未观察到基因表达变化。异氟醚诱导了丘脑-皮质和海马-皮质功能以及参与皮质信号传递的基因表达的长期变化。需要进一步研究这些变化是否与术后患者和动物中常见的行为和认知症状有关。
