Dexamethasone can improve cognitive dysfunction by down-regulating the expression level of S100A8 after sevoflurane anaes-thesia in mice

Abstract

Objective To investigate the effect of dexamethasone on cognitive function after sevoflurane anaesthesia and its potential mechanism. Methods One hundred adult male C57BL/6 mice were randomly divided into 5 groups(n=20) using a random number table: control group(group C), sevoflurane group (group S), high dosage(20 mg/kg) of dexamethasone group(group H), middle dosage(2.0 mg/kg) of dexamethasone group (group M) and low dosage(0.2 mg/kg) of dexamethasone group(group L). Group C accepted no special treatment, while other groups were exposed in sevoflurane and had laparotomy surgery. Group H, group M and group L mice were given dexamethasone one hour before inhalation via intraperitoneal injection. After 24 h of the operation, 10 mice in each group were sacrificed randomly and tested for Iba1 expression using immunohistochemical staining in the mice's hippocampi. RT-PCR was used to detect the mRNA level of S100A8, Toll-like receptor 4(TLR4), IL-6, IL-1β and TNF-α. Expression of S100A8 protein was measured with Western blot. Other mice were subjected to a 5-day Morris water maze training and their escape latency, the frequency of crossing the platform and duration of swimming spent at the target quadrant were recorded. Results The escape latency period of group S mice was prolonged [5 d, (26.5±3.8) s] than the control group and the frequency of crossing platform was decreased(1.24±0.21) and the duration of swimming in the target quadrant was shortened[(9.1±1.7) s]. Expressions of Iba1 on microglia cells were increased, and the mRNA level of S100A8(3.10±0.18), TLR4(2.903±0.021), IL-6(2.63±0.13), IL-1β(3.733±0.160) and TNF-α(1.924±0.038) were increased as well(P<0.05). The frequency of crossing the original platform(2.38 ± 0.33) and duration of swimming spent at the target quadrant[(14.5±2.0) s] were increased in group M compared to group S and the escape latency[5 d, (17.8±2.3) s] was shortened(P<0.05). The expression of Iba1 on microglia cells were decreased, and the S100A8(1.11±0.12, 1.35±0.08), TLR4(0.872±0.112, 1.149±0.060), IL-6(1.13±0.06, 1.32±0.08), IL-1β(0.755±0.059, 0.941±0.133) and TNF-α(1.081±0.052, 1.041±0.021) mRNA level were decreased as well in both high dosage group and middle dosage group(P<0.05). Conclusions Intraperitoneal injection of dexamethasone (2.0 mg/kg) can improve the cognitive function after sevoflurane anaesthesia. The potential mechanism could be reducing the expression of S100A8, inhibiting the activity of microglia cells and reducing the expression of inflammatory cytokines. Key words: Dexamethasone; Sevoflurane; S100A8; Cognition disorders; Microglia