Tian Li-Ying, Cai Cheng-Kui, Zhang Xia-Jing, Sun Xu-De
Department of Anesthesiology, The Second Affiliated Hospital of Air Force Medical University, Xi'an, China.
Department of Orthopedics, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, China.
Ann Palliat Med. 2020 Sep;9(5):3418-3427. doi: 10.21037/apm-20-1655.
The effects of electromagnetic pulse (EMP) radiation on cognitive impairment have attracted much attention, but the mechanism is still unclear. Regulation of brain-derived neurotrophic factor (BDNF) gene expression has been found to promote memory formation and neuronal survival. Isoflurane preconditioning (IP) was reported to have a neuroprotective effect. In this study, we verified the protective effect of IP against brain injury induced by EMP exposure and examined the relation of this effect with BDNF gene regulation.
Twenty-four hours before EMP exposure, rats were pretreated with 2% inhaled isoflurane for 30 minutes. At 24 hours after EMP injury, the Morris water maze test was carried out. Meanwhile, the other rats were executed and their brain tissues were used for Nissl staining, qRT-PCR, western blot and chromatin immunoprecipitation.
The Morris water maze results showed that 2% IP improved the spatial learning and memory ability of the rats. The Nissl staining results showed 2% of IP alleviated neuronal damage. Also, we detected the mRNA and protein expression of BDNF, and 2% IP significantly increased the expression of BDNF. We also found the expression level of histone deacetylase 2 (HDAC2) was increased and that EMP exposure significantly decreased H3 acetylation, while 2% IP reversed these phenomena, individually, BDNF transcription was activated, and neurogenesis after EMP exposure was alleviated.
Our results suggested that 2% of IP alleviates cognitive impairment induced by EMP exposure in rats. Also, the sustained elevated level of BDNF gene transcription may be an essential mechanism for stimulating neurogenesis because of the increased level of HDAC2-dependent H3 acetylation.
电磁脉冲（EMP）辐射对认知功能损害的影响已引起广泛关注，但其机制仍不清楚。研究发现，调节脑源性神经营养因子（BDNF）基因表达可促进记忆形成和神经元存活。据报道，异氟烷预处理（IP）具有神经保护作用。在本研究中，我们验证了IP对EMP暴露所致脑损伤的保护作用，并探讨了这种作用与BDNF基因调控的关系。
在EMP暴露前24小时，用2%吸入异氟烷预处理大鼠30分钟。EMP损伤后24小时，进行Morris水迷宫试验。同时，处死其他大鼠，取脑组织进行尼氏染色、qRT-PCR、蛋白质免疫印迹和染色质免疫沉淀分析。
Morris水迷宫试验结果显示，2%IP可改善大鼠的空间学习和记忆能力。尼氏染色结果显示，2%IP减轻了神经元损伤。此外，我们检测了BDNF的mRNA和蛋白表达，2%IP显著增加了BDNF的表达。我们还发现组蛋白去乙酰化酶2（HDAC2）的表达水平升高，EMP暴露显著降低H3乙酰化水平，而2%IP可逆转这些现象，单独来看，BDNF转录被激活，EMP暴露后的神经发生得到缓解。
我们的结果表明，2%IP可减轻EMP暴露所致的大鼠认知功能损害。此外，BDNF基因转录水平的持续升高可能是刺激神经发生的重要机制，这是由于HDAC2依赖性H3乙酰化水平升高所致。
