Isoflurane preconditioning effects on brain damage induced by electromagnetic pulse radiation through epigenetic modification of BDNF gene transcription.

Abstract

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.