The effect and possible mechanism of sevoflurane exposure on electroencephalographic seizures and long-term cognitive function in neonatal rats

Abstract

Objective To investigate the effect of sevoflurane anesthesia on electroencephalographic (EEG) seizures and long-term behavior and possible mechanism in neonatal rats. Methods A total of 141 postnatal days 4-6 Sprague-Dawley rats (66 male, 75 female) were divided into 3 groups (n=47 in each group) according to random number table method: control group, sevoflurane group, and NKCC1 inhibitor group, with 22 males and 25 females in each group. Rats in the control group were fed in normal cage without anesthesia; rats in the sevoflurane group were anesthetized with 2.1% sevoflurane for 6 hours; rats in the NKCC1 blocker group received intraperitoneal injection of 1.82 mg / kg bumetanide 30 minutes before anesthesia with 2.1% sevoflurane. The rats in the control group and sevoflurane group were injected subcutaneously with the same dose of DMSO at the same time when the NKCC1 blocker group received the drug intervention, so as to eliminate the influence caused by the solvent. The rats were observed for 30 minutes after recovery from anesthesia and then continued to breastfeed normally. Some of the new born rats received EEG monitoring from 9 to 11 days after being raised; the other rats received EPM and PPI respectively at 60 and 70 days after being raised. Results The results of EEG showed that, compared with the control group, the number of epileptic waves((0.429±0.787), (1.571±0.787), t=2.753, P 0.05). Compared with male rats, the average duration of female rats in sevoflurane group decreased ((6.392±3.374), (2.515±2.992), t=3.044, P 0.05). Comparison between male and female rats: compared with male rats in sevoflurane group, the female rats in sevoflurane group had a longer open arm stay time in EPM experiment (P<0.05), the difference was statistically significant. Conclusion Sevoflurane anesthesia for 6 hours can significantly increase the generation of epileptic waves in EEG of male newborn rats, and cause behavioral abnormalities in adult male rats, which may be related to NKCC1.And male rats are more vulnerable to the negative effects of sevoflurane anesthesia on brain nerve development. Key words: Sevoflurane; Neonatal anesthesia; Bumetanide; Gender; Electroencephalo-graphic; Behaviour; Rat