Background: Microglial polarization toward pro-inflammatory M1 phenotype are major contributors to the development of perioperative neurocognitive disorders (PNDs). Metabolic reprogramming plays an important role in regulating microglial polarization. We therefore hypothesized that surgical trauma can activate microglial M1 polarization by metabolic reprogramming to induce hippocampal neuroinflammation and subsequent postoperative cognitive impairment. Methods: We used aged mice to establish a model of PNDs, and investigated whether surgical trauma induced metabolic reprograming in hippocampus using PET/CT and GC/TOF–MS based metabolomic analysis. We then determined the effect of the glycolytic inhibitor 2-deoxy-d-glucose (2-DG) on hippocampal microglial M1 polarization, neuroinflammation, and cognitive function at 3 d after surgery. Results: We found that surgery group had less context-related freezing time than either control or anesthesia group (P < 0.05) without significant difference in tone-related freezing time (P > 0.05). The level of Iba-1 fluorescence intensity in hippocampus were significantly increased in surgery group than that in control group (P < 0.05) accompanied by activated morphological changes of microglia and increased expression of iNOS/CD86 (M1 marker) in enriched microglia from hippocampus (P < 0.05). PET/CT and metabolomics analysis indicated that surgical trauma provoked the metabolic reprogramming from oxidative phosphorylation to glycolysis in hippocampus. Inhibition of glycolysis by 2-DG significantly alleviated the surgical trauma induced increase of M1 (CD86⁺CD206⁻) phenotype in enriched microglia from hippocampus and up-regulation of pro-inflammatory mediators (IL-1β and IL-6) expression in hippocampus. Furthermore, glycolytic inhibition by 2-DG ameliorated the hippocampus dependent cognitive deficit caused by surgical trauma. Conclusions: Metabolic reprogramming is crucial for regulating hippocampal microglial M1 polarization and neuroinflammation in PNDs. Manipulating microglial metabolism might provide a valuable therapeutic strategy for treating PNDs.

Background: Continuous nerve block with ropivacaine is commonly performed after repair surgery for traumatic peripheral nerve injuries. After peripheral nerve injury, tetrodotoxin-resistant voltage-gated sodium channel Nav1.8 is upregulated and contributes to macrophage inflammation. This study investigated whether ropivacaine promotes peripheral nerve regeneration through Nav1.8-mediated macrophage signaling. Methods: A sciatic nerve transection-repair (SNT) model was established in adult Sprague–Dawley rats of both sexes. The rats received 0.2% ropivacaine or 10 μM Nav1.8-selective inhibitor A-803467 around the injured site or near the sacrum for 3 days. Nerve regeneration was evaluated using behavioral, electrophysiologic, and morphological examinations. Moreover, myelin debris removal, macrophage phenotype, Nav1.8 expression, and neuropeptide expression were assessed using immunostaining, enzyme-linked immunosorbent assay, and Western blotting. Results: Compared to the SNT-plus-vehicle group, the sensory, motor, and sensory–motor coordination functions of the two ropivacaine groups were significantly improved. Electrophysiologic (mean ± SD: recovery index of amplitude, vehicle 0.43 ± 0.17 vs. ropivacaine 0.83 ± 0.25, n = 11, P < 0.001) and histological analysis collectively indicated that ropivacaine significantly promoted axonal regrowth (percentage of neurofilament 200 [NF-200]–positive area: vehicle 19.88 ± 2.81 vs. ropivacaine 31.07 ± 2.62, n = 6, P < 0.001). The authors also found that, compared to the SNT-plus-vehicle group, the SNT-plus-ropivacaine group showed faster clearance of myelin debris, accompanied by significantly increased macrophage infiltration and transition from the M1 to M2 phenotype. Moreover, ropivacaine significantly attenuated Nav1.8 upregulation at 9 days after sciatic nerve transection (vehicle 4.12 ± 0.30-fold vs. ropivacaine 2.75 ± 0.36-fold, n = 5, P < 0.001), which coincided with the increased expression of chemokine ligand 2 and substance P. Similar changes were observed when using the selective Nav1.8 channel inhibitor A-803467. Conclusions: Continuous nerve block with ropivacaine promotes the structural and functional recovery of injured sciatic nerves, possibly by regulating Nav1.8-mediated macrophage signaling. Editor’s Perspective: What We Already Know about This Topic: What This Article Tells Us That Is New:

Background. Postoperative cognitive dysfunction (POCD) is a common complication after abdominal surgery. Several studies have reported that POCD is related to neuroinflammation caused by surgery. Omega‐3 polyunsaturated fatty acids (PUFAs) can effectively inhibit the systematic inflammatory response. So, we use fish oil to study the effect of fish oil on inflammation, immunity, and cognitive behavior after splenectomy in rats. Methods. 60 SD (Sprague‐Dawley) rats were randomly divided into control group (group C, n = 20), surgery group (group S, n = 20), and omega‐3 (fish oil) intervention group (group F, n = 20). Omega‐3 PUFA was injected intraperitoneally from 3 days before operation to 7 days after operation in group F, and normal saline was injected simultaneously in group S. Rats in group S and group F received splenectomy under general anesthesia. Morris water maze behavioral evaluation was performed on the first, third, fifth, and seventh day after operation. The levels of IL‐1β (interleukin‐1β), IL‐6 (interleukin‐6), TNF‐α (tumor necrosis factor‐α), SOD (superoxide dismutase), and GSH‐PX (glutathione peroxidase) were detected. Results. Serums IL‐1β, IL‐6, and TNF‐α concentrations in group S and group F were higher than those in group C (P < 0.01), while those inflammatory cytokines in group F were significantly lower than those in group S (P < 0.01); serum GSH‐PX levels in group F were higher than group S (P < 0.01). The Morris water maze behavior test performance of group F was better than that of group S (P < 0.05). Conclusion. Omega‐3 PUFA can effectively improve postoperative inflammatory response, reduce the damage of antioxidant defense system, and improve postoperative cognitive function.

Prior studies have indicated that the neuroprotective effects of dexmedetomidine (DEX) in cerebral ischemia, yet its mechanisms remain elusive. Using multi-omics approaches (RNA-seq, metabolomics, and single-cell RNA-seq), we discovered that DEX pretreatment significantly reduced cerebral infarct volume and improved neurological function in middle cerebral artery occlusion (MCAO) mice compared to PBS controls. Single-cell analysis revealed that DEX preserved microglial phagocytic function via metabolic regulation, leading to reduced microglial apoptosis and attenuated immune dysregulation—including decreased chemotactic neutrophils, B cells, and antigen-presenting fibroblasts. These cellular changes were corroborated by transcriptomic and metabolic profiles showing suppressed apoptosis and inflammation. Mechanistically, we identified HK2 (hexokinase 2) as a key regulator of microglial homeostasis, with its expression correlating with microglial migration, proliferation, and inflammation, findings validated in oxygen–glucose deprivation models. Collectively, our results demonstrate that DEX protects against cerebral ischemia–reperfusion injury by maintaining immune microenvironment homeostasis through microglial metabolic reprogramming mediated by HK2. This multi-omics study provides mechanistic insights supporting DEX’s translational potential in ischemic stroke therapy.

It is believed that neural information representation and processing relies on the neural population instead of a single neuron. In neuromorphic photonics, photonic neurons in the form of nonlinear responses have been extensively studied in single devices and temporal nodes. However, to construct a photonic neural population (PNP), the process of scaling up and massive interconnections remain challenging considering the physical complexity and response latency. Here, we propose a comb-based PNP interconnected by carrier coupling with superior scalability. Two unique properties of neural population are theoretically and experimentally demonstrated in the comb-based PNP, including nonlinear response curves and population activities coding. A classification task of three input patterns with dual radio-frequency (RF) tones is successfully implemented in a time-efficient manner, which allows the comb-based PNP to make effective use of the ultra-broad bandwidth of photonics for parallel and nonlinear processing.

Introduction: Fospropofol disodium is a novel prodrug that has improved pharmacokinetic and pharmacodynamic properties when compared with propofol. This trial aims to compare the efficacy and safety of fospropofol versus propofol sedation for same-day bidirectional endoscopy in elderly patients.Methods and analysis: This is a prospective, single-center, double-blind, randomized, propofol-controlled, non-inferiority trial. A total of 256 patients aged 65 years or older, who are scheduled for same-day bidirectional endoscopy under sedation, will be randomly allocated, in a 1:1 ratio, to either fospropofol group or propofol group (n = 128 in each group). All patients will receive analgesic pre-treatment with sufentanil 5 μg. Two minutes later, an initial bolus dose of fospropofol 6.5 mg/kg or 1.5 mg/kg propofol and supplemental doses of fospropofol 1.6 mg/kg or 0.5 mg/kg propofol will be titrated as needed to achieve target sedation levels during the procedures. The primary outcome is the success rate of same-day bidirectional endoscopy. Secondary outcomes include the time to successful induction of sedation, duration, time to being fully alert, time to patient discharge, endoscopist satisfaction, patient satisfaction, and the top-up frequency and dosage of sedative medications. The safety endpoints consist of adverse events concerning cough reflex, gag reflexes, body movement, muscular tremor, and pain on injection. Sedation-related AEs, including episodes of desaturation, severe desaturation (SpO₂ < 90%), hypotension, severe hypotension (decrease in MBP ≥30% of baseline), and bradycardia, will also be recorded. Data will be analyzed on an intention-to-treat basis.Discussion: We hypothesize that the efficacy and safety of fospropofol sedation for elderly patients undergoing same-visit bidirectional endoscopy will not be inferior to that of propofol. Our findings will potentially provide a new sedation regimen for same-visit bidirectional endoscopy in elderly patients.Clinical Trial Registration: clinicaltrials.gov, identifier NCT02875639