Postoperative cognitive dysfunction (POCD) is a disturbing neurological complication in patients undergoing anesthesia and surgical procedures. Brain-derived neurotrophic factor (BDNF) and its precursor proBDNF binding to their corresponding receptors tyrosine kinase (TrkB) and p75 neurotrophin receptor (p75NTR) exert quite an opposite biological function in neuron survival and synaptic function. This study aimed to demonstrate the critical role of the BDNF/proBDNF ratio in modulating synaptic plasticity, which further leads to anesthesia-/surgery-induced POCD. It also showed that the exogenous BDNF or p75NTR inhibitor could ameliorate cognitive dysfunction. In detail, 16-month-old C57BL/6 mice were subjected to a stabilized tibial fracture surgery with isoflurane anesthesia to establish the POCD animal model. The mice were then microinjected with either p75NTR inhibitor or exogenous BDNF into the dorsal hippocampus. Behavioral experiments were performed by open field and fear conditioning tests (FCTs). Western blotting was also used to measure the expression levels of BDNF, proBDNF, TrkB, p-TrkB, p75NTR, and synapse proteins. Golgi staining and electrophysiology were applied to evaluate the neuronal synaptic plasticity. Here, we demonstrated that anesthesia/surgery induced a reduction of BDNF/proBDNF, which negatively regulates the synaptic function in hippocampus, subsequently leading to cognitive impairment in aged mice. P75NTR inhibitor and exogenous BDNF could attenuate cognitive deficits by rescuing the dendritic spine loss and long-term potentiation (LTP) via altering the BDNF/proBDNF ratio. This study unveiled that the BDNF/proBDNF ratio in the hippocampus played a key role in anesthesia-/surgery-induced POCD. Thereby, tuning the ratio of BDNF/proBDNF is supposed to be a promising therapeutic target for POCD.

Background Intravenous and inhalational agents are commonly used in general anesthesia. However, it is still controversial which technique is superior for the quality of postoperative recovery. This meta-analysis aimed at comparing impact of total intravenous anesthesia (TIVA) versus inhalational maintenance of anesthesia on the quality of recovery in patients undergoing non-cardiac surgery. Methods We systematically searched EMBASE, PubMed, and Cochrane library for randomized controlled trials (RCTs), with no language or publication status restriction. Two authors independently performed data extraction and assessed risk of bias. The outcomes were expressed as mean difference (MD) with 95% confidence interval (CI) based on a random-effect model. We performed trial sequential analysis (TSA) for total QoR-40 scores and calculated the required information size (RIS) to correct the increased type I error. Results A total of 156 records were identified, and 9 RCTs consisting of 922 patients were reviewed and included in the meta-analysis. It revealed a significant increase in total QoR-40 score on the day of surgery with TIVA (MD, 5.91 points; 95% CI, 2.14 to 9.68 points; P = 0.002; I2 = 0.0%). The main improvement was in four dimensions, including “physical comfort”, “emotional status”, “psychological support” and “physical independence”. There was no significant difference between groups in total QoR-40 score (P = 0.120) or scores of each dimension on POD1. The TSA showed that the estimated required information size for total QoR-40 scores was not surpassed by recovered evidence in our meta-analysis. And the adjusted Z-curves did not cross the conventional boundary and the TSA monitoring boundary. Conclusion Low-certainty evidence suggests that propofol-based TIVA may improve the QoR-40 score on the day of surgery. But more evidence is needed for a firm conclusion and clinical significance.

RPostCT significantly decreased myocardial infarction size via neurogenic transmission and various signaling pathways. This study describes a new cardiac I/R injury prevention method that might lead to the development of therapies that are more clinically relevant for myocardial I/R injury.

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