The vulnerable period to neurotoxicity of isoflurane overlaps with a developmental stage characterized by programmed neuronal death. STAT3 has been identified as a crucial molecule involved in survival pathways during this period. We aimed to investigate the role of STAT3 in cellular vulnerability to isoflurane. C57/BL6 mice on postnatal day 7 or 21, primary neurons derived from mice embryos at gestational days 14–16 and cultured for 5 or 14 days, as well as human neuroglioma U251 cells were treated with isoflurane. A plasmid containing human wild-type STAT3, STAT3 anti-sense oligonucleotide, STAT3 specific inhibitor STA21, proteasome inhibitor MG-132 and calcineurin inhibitor FK506 were utilized to evaluate the influence of STAT3 levels on isoflurane-induced cytotoxicity. The levels of Western blot results, mRNA, intracellular ROS, apoptotic rate, and calcineurin activity were analyzed using unpaired Student's t-test or one-way ANOVA followed by Bonferroni post hoc test, as appropriate. Elevated levels of STAT3, reduced activity of calcineurin, as well as a diminished response to isoflurane-induced calcineurin activation and neuroapoptosis were observed in more mature brain or neurons. Isoflurane accelerated the degradation of ubiquitin-conjugated proteins but did not facilitate ubiquitin conjugation to proteins. STAT3 was of particular importance in the all ubiquitin-conjugated proteins degraded by isoflurane. Knockdown or inhibition of STAT3 nuclear translocation exacerbated isoflurane-induced oxidative injury and apoptosis, while STAT3 overexpression mitigated these effects. Finally, this study demonstrated that FK506 pretreatment mitigated the apoptosis, ROS accumulation, and the impairment of neurite growth in primary neurons after exposed to isoflurane. These findings indicate that specific regulation of STAT3 was closely related with the cellular vulnerability to isoflurane via an antioxidative pathway.

Yan Yang

Shiyu Song

Hongwei Wang

Zhengliang Ma

Qian Gao

BMC Neuroscience

BMC NEUROSCIENCE 是一本开放获取、同行评审的期刊，它考虑神经科学各个方面的文章，欢迎研究提供深入了解神经系统功能的分子、细胞、发育、遗传和基因组、系统、网络、认知和行为方面的研究。健康和疾病。实验和理论研究都在范围内，描述监测或操纵神经系统功能的方法学方法的研究也在范围内。

BMC Neuroscience is an open access, peer-reviewed journal that covers all aspects of neuroscience. We welcome submissions that provide in-depth insights into the functioning of the nervous system, including research in molecular, cellular, developmental, genetic and genomic, systems, network, cognitive, and behavioral neuroscience. Studies related to both health and disease are within scope, and both experimental and theoretical research are encouraged. Methodological studies that describe monitoring or manipulating nervous system functions are also considered.

BMC Neuroscience 是一本开放获取、同行评审的期刊，涵盖神经科学的各个方面。我们欢迎研究者提交能够深入理解神经系统功能的文章，涉及分子、细胞、发育、遗传与基因组、系统、网络、认知和行为等领域的研究。无论是健康还是疾病相关的研究，实验和理论研究均在我们的范围之内。此外，描述监测或操纵神经系统功能的方法学研究也被纳入考虑。

Category	Quartile
医学	4
医学, 神经科学	4

The antioxidative effect of STAT3 involved in cellular vulnerability to isoflurane

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