Eleutheroside E attenuates isoflurane-induced cognitive dysfunction by regulating the α7-nAChR-NMDAR pathway.

There is growing evidence that cognitive dysfunction induced by anesthetics is adversely affecting a large number of elderly surgical patients. Eleutheroside E (EE), a principal component of Eleutherococcus senticosus, exerts obvious protective effects on cognition. The aim of this study was to investigate the neuroprotective effect of EE on isoflurane (ISO)-induced cognitive dysfunction and explore the possible mechanisms. Learning and memory are assessed in novel object recognition and Morris water maze. We found that with ISO exposure, aged rats had a lower preference for the new object and spent less time in the target quarter. However, the amnesia can be alleviated by EE (50 mg/kg, intraperitoneally). Further research focused on the possible protective molecules associated with learning and memory, such as acetylcholine (ACh) and choline acetyltransferase (ChAT), nicotinic acetylcholine receptors (α7-nAChR), and NR2B, is required. The ACh in the hippocampus and serum was decreased after ISO exposure; meanwhile, the expression of ChAT, α7-nAChRs, and NR2B was downregulated. This abnormal state can be reversed by the administration of EE. Here, our results suggested that EE may be a potential therapeutic agent against ISO-induced cognitive dysfunction. The possible mechanism can be attributed to its neuroprotection through enhancing ChAT, which promotes the synthesis of ACh, further influencing the expression of the α7-nAChR-NR2B complex.

Effect of electro-acupuncture stimulation of Ximen (PC4) and Neiguan (PC6) on remifentanil-induced breakthrough pain following thoracal esophagectomy / 华中科技大学学报（医学）（英德文版）

The clinical analgesic effect of electro-acupuncture (EA) stimulation (EAS) on breakthrough pain induced by remifentanil in patients undergoing radical thoracic esophagectomy, and the mechanisms were assessed. Sixty patients (ASAIII) scheduled for elective radical esophagectomy were randomized into three groups: group A (control) receiving a general anesthesia only; group B (sham) given EA needles at PC4 (Ximen) and PC6 (Neiguan) but no stimulation; and group C (EAS) electrically given EAS of the ipsilateral PC4 and PC6 throughout the surgery. The EAS consisting of a disperse-dense wave with a low frequency of 2 Hz and a high frequency of 20 Hz, was performed 30 min prior to induction of general anesthesia and continued through the surgery. At the emergence, sufentanil infusion was given for postoperative analgesia with loading dose of 7.5 μg, followed by a continuous infusion of 2.25 μg/h. The patient self-administration of sufentanil was 0.75 μg with a lockout of 15 min as needed. Additional breakthrough pain was treated with dezocine (5 mg) intravenously at the patient's request. Blood samples were collected before (T1), 2 h (T2), 24 h (T3), and 48 h (T4) after operation to measure the plasma β-EP, PGE2, and 5-HT. The operative time, the total dose of sufentanil and the dose of self-administration, and the rescue doses of dezocine were recorded. Visual Analogue Scale (VAS) scores at 2, 12, 24 and 48 h postoperatively and the incidence of apnea and severe hypotension were recorded. The results showed that the gender, age, weight, operative time and remifentanil consumption were comparable among 3 groups. Patients in EAS group had the lowest VAS scores postoperatively among the three groups (P0.05). No apnea or severe hypotension was observed in any group. It was concluded that intraoperative ipsilateral EAS at PC4 and PC6 provides effective postoperative analgesia for patients undergoing radical esophagectomy with remifentanil anesthesia and significantly decrease requirement for parental narcotics. The underlying mechanism may be related to stimulation of the release of endogenous β-EP and inhibition of inflammatory mediators (5-HT and PGE2).

Effect of electro-acupuncture stimulation of Ximen (PC4) and Neiguan (PC6) on remifentanil-induced breakthrough pain following thoracal esophagectomy / 华中科技大学学报（医学）（英德文版）

The clinical analgesic effect of electro-acupuncture (EA) stimulation (EAS) on breakthrough pain induced by remifentanil in patients undergoing radical thoracic esophagectomy, and the mechanisms were assessed. Sixty patients (ASAIII) scheduled for elective radical esophagectomy were randomized into three groups: group A (control) receiving a general anesthesia only; group B (sham) given EA needles at PC4 (Ximen) and PC6 (Neiguan) but no stimulation; and group C (EAS) electrically given EAS of the ipsilateral PC4 and PC6 throughout the surgery. The EAS consisting of a disperse-dense wave with a low frequency of 2 Hz and a high frequency of 20 Hz, was performed 30 min prior to induction of general anesthesia and continued through the surgery. At the emergence, sufentanil infusion was given for postoperative analgesia with loading dose of 7.5 μg, followed by a continuous infusion of 2.25 μg/h. The patient self-administration of sufentanil was 0.75 μg with a lockout of 15 min as needed. Additional breakthrough pain was treated with dezocine (5 mg) intravenously at the patient's request. Blood samples were collected before (T1), 2 h (T2), 24 h (T3), and 48 h (T4) after operation to measure the plasma β-EP, PGE2, and 5-HT. The operative time, the total dose of sufentanil and the dose of self-administration, and the rescue doses of dezocine were recorded. Visual Analogue Scale (VAS) scores at 2, 12, 24 and 48 h postoperatively and the incidence of apnea and severe hypotension were recorded. The results showed that the gender, age, weight, operative time and remifentanil consumption were comparable among 3 groups. Patients in EAS group had the lowest VAS scores postoperatively among the three groups (P<0.05). The total dose of sufentanil was 115±6.0 μg in EAS group, significantly lower than that in control (134.3±5.9 μg) and sham (133.5±7.0 μg) groups. Similarly, the rescue dose of dezocine was the least in EAS group (P<0.05) among the three groups. Plasma β-EP levels in EAS group at T3 (176.90±45.73) and T4 (162.96±35.00 pg/mL) were significantly higher than those in control (132.33±36.75 and 128.79±41.24 pg/mL) and sham (136.56±45.80 and 129.85±36.14 pg/mL) groups, P<0.05 for all. EAS could decrease the release of PGE2. Plasma PGE2 levels in EAS group at T2 and T3 (41±5 and 40±5 pg/mL respectively) were significantly lower than those in control (64±5 and 62±7 pg/mL) and sham (66±6 and 62±6 pg/mL) groups. Plasma 5-HT levels in EAS group at T2 (133.66±40.85) and T3 (154.66±52.49 ng/mL) were significantly lower than those in control (168.33±56.94 and 225.28±82.03) and sham (164.54±47.53 and 217.74±76.45 ng/mL) groups. For intra-group comparison, plasma 5-HT and PGE2 levels in control and sham groups at T2 and T3, and β-EP in EAS group at T3 and T4 were significantly higher than those at T1 (P<0.05); PGE2 and 5-HT levels in EAS group showed no significant difference among the different time points (P>0.05). No apnea or severe hypotension was observed in any group. It was concluded that intraoperative ipsilateral EAS at PC4 and PC6 provides effective postoperative analgesia for patients undergoing radical esophagectomy with remifentanil anesthesia and significantly decrease requirement for parental narcotics. The underlying mechanism may be related to stimulation of the release of endogenous β-EP and inhibition of inflammatory mediators (5-HT and PGE2).