The effect and possible mechanism of sevoflurane exposure on electroencephalographic seizures and long-term cognitive function in neonatal rats / 中华行为医学与脑科学杂志

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<0.01), the average duration of single epileptic wave ((1.575±2.349), (6.392±3.374), t=3.880, P< 0.01), the total duration increased significantly ((1.800±3.617), (10.957±6.028), t= 3.929, P<0.01) were all increased, the differences were statistically significant. Compared with sevoflurane group, the number of epileptic waves in EEG of male rats in NKCC1 blocker group decreased, the average duration of single epileptic wave decreased, and the total duration of epileptic wave shortened significantly, with statistical significance ((0.286±0.756), (0.925±1.733), (1.043±2.759), t=3.097, 4.404, 4.254, all P<0.01). There were no significant differences in female rat among the three groups (all 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<0.01), the total duration shortened ((10.957±6.028), (3.270±5.883), t=2.626, P<0.01), the difference was statistically significant.The behavioral results showed that, compared with the control group, the open arm dwell time of male rats in sevoflurane group was significantly shorter ( P<0.05), and the panic response in PPI group was significantly lower ( P<0.05), the difference was statistically significant.Compared with the sevoflurane group, the open arm dwell time in NKCC1 blocker group was significantly longer ( P<0.05), and the panic response in PPI group was significantly increased.The difference was statistically significant ( P<0.05). The change trend in female rats of each group was similar to that of male rats, but there was no significant difference (all 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.