Postoperative cognitive dysfunction increases mortality and morbidity in perioperative patients and has become a major concern for patients and caregivers. Previous studies demonstrated that synaptic plasticity is closely related to cognitive function, anesthesia and surgery inhibit synaptic function. In central nervous system, autophagy is vital to synaptic plasticity, homeostasis of synapticproteins, synapse elimination, spine pruning, proper axon guidance, and when dysregulated, is associated with behavioral and memory functions disorders. The mammalian target of rapamycin (mTOR) negatively regulates the process of autophagy. This study aimed to explore whether rapamycin can ameliorate anesthesia/surgery-induced cognitive deficits by inhibiting mTOR, activating autophagy and rising synaptic plasticity-related proteins in the hippocampus. Aged C57BL/6J mice were used to establish POCD models with exploratory laparotomy under isoflurane anesthesia. The Morris Water Maze (MWM) was used to measure reference memory after anesthesia and surgery. The levels of mTOR phosphorylation (p-mTOR), Beclin-1 and LC3-II were examined on postoperative days 1, 3 and 7 by western blotting. The levels of synaptophysin (SYN) and postsynaptic density protein 95 (PSD-95) in the hippocampus were also examined by western blotting. Here we showed that anesthesia/surgery impaired reference memory and induced the activation of mTOR, decreased the expression of autophagy-related proteins such as Beclin-1 and LC3-II. A corresponding decline in the expression of neuronal/synaptic, plasticity-related proteins such as SYN and PSD-95 was also observed. Pretreating mice with rapamycin inhibited the activation of mTOR and restored autophagy function, also increased the expression of SYN and PSD-95. Furthermore, anesthesia/surgery-induced learning and memory deficits were also reversed by rapamycin pretreatment. In conclusion, anesthesia/surgery induced mTOR hyperactivation and autophagy impairments, and then reduced the levels of SYN and PSD-95 in the hippocampus. An mTOR inhibitor, rapamycin, ameliorated anesthesia/surgery-related cognitive impairments by inhibiting the mTOR activity, inducing activation of autophagy, enhancing SYN and PSD-95 expression.

Perioperative sleep disturbance is a risk factor for persistent pain after surgery. Clinical studies have shown that patients with insufficient sleep before and after surgery experience more intense and long-lasting postoperative pain. We hypothesize that sleep deprivation alters L-type calcium channels in the dorsal root ganglia (DRG), thus delaying the recovery from post-surgical pain. To verify this hypothesis, and to identify new predictors and therapeutic targets for persistent postoperative pain, we first established a model of postsurgical pain with perioperative sleep deprivation (SD) by administering hind paw plantar incision to sleep deprivation rats. Then we conducted behavioral tests, including tests with von Frey filaments and a laser heat test, to verify sensory pain, measured the expression of L-type calcium channels using western blotting and immunofluorescence of dorsal root ganglia (an important neural target for peripheral nociception), and examined the activity of L-type calcium channels and neuron excitability using electrophysiological measurements. We validated the findings by performing intraperitoneal injections of calcium channel blockers and microinjections of dorsal root ganglion cells with adeno-associated virus. We found that short-term sleep deprivation before and after surgery increased expression and activity of L-type calcium channels in the lumbar dorsal root ganglia, and delayed recovery from postsurgical pain. Blocking these channels reduced impact of sleep deprivation. We conclude that the increased expression and activity of L-type calcium channels is associated with the sleep deprivation-mediated prolongation of postoperative pain. L-type calcium channels are thus a potential target for management of postoperative pain.

Postoperative cognitive dysfunction (POCD) may last for days, months or even years, leading to prolonged hospitalization and increased costs, increased mortality, and poor quality of life. Although POCD is an important clinical problem, its prevention, treatment strategies and effects are still limited. Therefore, this study aims to investigate the preventive effect of perioperative probiotic intervention on POCD in elderly patients, and further explore the mechanism of probiotics in improving postoperative cognitive function. After obtaining ethical approval and written informed consent, 190 patients aged 65 years or older scheduled for elective lower-extremity orthopedic surgery were enrolled in this randomized, single-center, double-blind trial. Enrolled patients were randomized to probiotic or control groups receiving either probiotics or placebo (210 mgx4/dose orally, 2 times/day) from 1 day before surgery to 5 days after surgery. The primary outcome was the cognitive function assessed by Mini-mental State Examination (MMSE) on admission, the first day, the third day and the seventh day after surgery. The secondary outcomes included perioperative changes in plasma IL-1β, IL-6 and BDNF, postoperative pain intensity, perioperative activities of daily living (ADL), faecal microbiota composition and changes of intestinal metabolites The incidence of POCD in the probiotic group was significantly lower than in the control group (6 of 90 patients [6.7%] vs. 16 of 93 patients [17.2%], P = 0.028). In addition, the plasma levels of proinflammatory cytokines IL-1β and IL-6 were significantly lower and BDNF levels were significantly higher in the probiotic group than in the control group 1–2 days after surgery (U = 173.0, P < 0.01; U = 139.0, P < 0.01; U = 207.0, P < 0.01). Perioperative probiotic intervention can reduce the incidence of POCD in elderly patients, which may improve cognitive function by inhibiting inflammatory response after anesthesia and surgery, and altering the composition of the postoperative gut microbiota and intestinal metabolites.

Postoperative cognitive dysfunction increases mortality and morbidity in perioperative patients. Numerous studies have demonstrated that multiple surgery/anesthesia during the neurodevelopmental period affects cognitive function, whereas a single anesthesia/surgery rarely causes cognitive dysfunction in adults. However, whether adults who undergo multiple anesthesia/surgery over a short period will experience cognitive dysfunction remains unclear. In this study, central nervous system inflammation and changes in cholinergic markers were investigated in adult mice subjected to multiple laparotomy procedures over a short period of time. The results showed that despite the increased expression of IL-6 and TNF-α in the hippocampus after multiple operations and the activation of microglia, multiple anesthesia/surgery did not cause a decline in cognitive function in adult mice. There were no changes in the cholinergic markers after multiple anesthesia/surgery.

Background: To evaluate the effect of perioperative subanesthetic dose of esketamine on the postoperative recovery quality in patients undergoing laparoscopic gastrointestinal surgery. Methods: A total of 144 patients undergoing elective surgery for gastrointestinal tumors were selected and randomly assigned to either the esketamine group or the control group, with 72 patients in each group. Based on the standardized general anesthesia protocols, the esketamine group received an intravenous injection of esketamine at a dose of 0.2 mg/kg during the induction of anesthesia and an additional 0.2 mg/kg 30 minutes before the end of the surgery. Patient-controlled intravenous analgesia (PCIA) was administered for 48 hours, the esketamine group was treated with sufentanil (0.04 μg/kg/h) combined with esketamine (0.02 mg/kg/h) and sufentanil (0.04 μg/kg/h) was used as the control group. The scores of 40-items Quality of Recovery Scale (QoR-40) were recorded one day before surgery, one day after surgery, three days after surgery, and five days after surgery. Numerical Rating Scale (NRS) pain scores were recorded at postoperative intervals of 6 hours, 24 hours, 36 hours, and 48 hours. Levels of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and brain-derived neurotrophic factor (BDNF) in venous blood were analyzed prior to entering the operating room, upon arrival at the recovery room, and on the second postoperative day. Results: A total of 140 patients completed this study. Compared to the control group, the QoR-40 scores in the esketamine group were significantly higher at 1, 3, and 5 days post-surgery (Z = − 10.080, Z = − 8.178, Z = − 4.139, P < 0.05). In addition, the resting NRS scores were significantly lower at 6 hours, 24 hours, 36 hours, and 48 hours post-surgery in the esketamine group (Z=− 6.322, Z=− 5.736, Z=− 6.563, Z=− 5.920, P < 0.05). Conclusion: This study found that the perioperative use of subanesthetic esketamine improved early postoperative recovery quality and reduced postoperative pain levels in patients undergoing laparoscopic gastrointestinal surgery.