Abstract
Isoflurane can elicit cognitive impairment. However, the pathogenesis in the brain remains inconclusive. The present study investigated the mechanism of glutamate neurotoxicity in adolescent male rats that underwent postnatal isoflurane exposure and the role of sodium butyrate (NaB) in cognitive impairment induced by isoflurane exposure. Seven-day-old rats were exposed to 1.7% isoflurane for 35min every day for four consecutive days, and then glutamate neurotoxicity was examined in the hippocampus. Morris water maze analysis showed cognitive impairments in isoflurane-exposed rats. High-performance liquid chromatography found higher hippocampal glutamate concentrations following in vitro and in vivo isoflurane exposure. The percentage of early apoptotic hippocampal neurons was markedly increased after isoflurane exposure. Decreased acetylation and increased HDAC2 activity were observed in the hippocampus of isoflurane-exposed rats and hippocampal neurons. Furthermore, postnatal isoflurane exposure decreased histone acetylation of hippocampal neurons in the promoter regions of GLT-1 and mGLuR1/5, but not mGLuR2/3. Treatment with NaB not only restored the histone acetylation of the GLT-1 and mGLuR1/5 promoter regions and glutamate excitatory neurotoxicity in hippocampal neurons, but also improved cognitive impairment in vivo. Moreover, NaB may be a potential therapeutic drug for cognitive impairment caused by isoflurane exposure. These results suggest that postnatal isoflurane exposure contributes to cognitive impairment via decreasing histone acetylation of glutamatergic systems in the hippocampus of adolescent rats.
Published Version
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