Protection Effect of Dexamethasone on the Memory Impairment and Neuronal Damage of Neonate Rats that Repeatedly Suffered Sevoflurane Exposure

  Objective  To investigate the protection effect of dexamethasone (DXMS) on the memory impairment and neuronal damage of neonate rats that caused by sevoflurane (SEVO) exposure.

  Methods  5-days-old newborn SD rats were randomly divided into normal group (NC group) (10 rats), SEVO group (10 rats) and SEVO+DXMS group (10 rats). Rats of SEVO group and SEVO+DXMS group were exposed to 2.5% SEVO 2 h per day for 1 week, meanwhile the rats of SEVO+DXMS group were given 20 mg/kg DXMS treatment before exposure and the normal group was given the same amount of placebo and carrier gas as control. All rats were fed normally till infancy. Then the Morris water maze test was used to assess the learning and memory function of rats of each group. HE and Nissl staining were used to observe the histomorphology and neuronal changes in the hippocampus of rats. ELISA was performed to test the changes in nitric oxide (NO), superoxide dismutase (SOD) and malondialdehyde (MDA) level in brain tissues. The expression of silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), fork head protein transcription factor 3α (FOXO3α) mRNA in brain tissue was detected by qRT-PCR. Western blot was used to explore the changes in SIRT1 and caspase-3 protein expression of hippocampus.

  Results  Compared with the NC group, the pathologic damage of hippocampus tissues was severely in SEVO group, and the number of neuronal cells was decreased as well. After SEVO intervention, the degree of pathologic damage was alleviated, and the number of neuronal cells was significantly increased. The Morris water maze test showed that the escape latency, number of platform crossing and target quadrant retention time between SEVO group and SEVO+DXMS group were significant different. The level of NO and MDA in brain of SEVO+DXMS group was significantly decreased than that of SEVO group, while the level of SOD was increased. qRT-PCR showed that the mRNA levels of SIRT1, PGC-1α and FOXO3α in SEVO+DXMS group were significantly higher those in SEVO group, but mRNA level of SIRT1 was still significantly lower than that of NC group. Western blot showed that the expression of SIRT1 protein in SEVO+DXMS group was significantly higher than that of SEVO group, and the expression of caspase-3 was reduced in SEVO+DXMS compared with SEVO group.

  Conclusion  DXMS could reduce the level of oxidative stress and suppress the apoptosis of neuronal cells, reduce SEVO-induced brain damage in neonatal rats and improve learning and memory ability in infant rats.