Neuropathic pain is frequently comorbid with anxiety and depression, yet the mechanisms linking immune signaling to affective brain circuits remain poorly understood. Here, we identify a neuroimmune circuit in which peripheral nerve injury activates microglia in the midbrain ventrolateral periaqueductal gray/dorsal raphe (vlPAG/DRN), triggering an NLRP3-IL-1β-dependent inflammatory cascade. Direct optogenetic or chemogenetic activation of vlPAG/DRN microglia is sufficient to drive negative affective behaviors. We show that local VGLUT2+ glutamatergic neurons (vlPAG/DRNGlu) are the principal IL-1R1-expressing targets; IL-1β activates these neurons to drive anxiety- and depression-like states. Conversely, microglia-specific Nlrp3 deletion or local IL-1R1 blockade prevents neuropathic pain-induced affective deficits. Furthermore, circuit mapping and functional manipulation reveal an excitatory vlPAG/DRNGlu to the bed nucleus of the stria terminalis (BNSTGABA) pathway that is both sufficient to induce and required to maintain the affective component of neuropathic pain. Together, our findings delineate a microglia-vlPAG/DRNGlu-BNSTGABA axis that translates peripheral injury into maladaptive emotional states, revealing a discrete neuroimmune circuit substrate for mood comorbidity in chronic pain.

Background: Insomnia is a common and heritable neurological condition that lacks clearly defined causal molecular drivers. Identifying brain cell–specific genes with protective effects may uncover new therapeutic targets for sleep-related disorders. Methods: We integrated brain single-cell gene expression profiles with insomnia genome-wide association data from the UK Biobank (109,548 cases, 277,440 controls). Using Wald ratio–based Mendelian randomization (MR), we estimated the causal effects of cell type-specific gene expression on insomnia. Significant genes were evaluated via Bayesian colocalization and Steiger filtering to confirm shared causal variants and correct expression-to-trait directionality. Independent replication used the FinnGen cohort (6,776 cases, 490,763 controls). Phenotype specificity and anatomical expression were assessed using phenome-wide association studies (PheWAS) and The Human Protein Atlas. Results: Among multiple cell type–specific associations, GFM1 emerged as a protective gene for insomnia in excitatory neurons (OR=0.90, FDR=0.0109), and was independently replicated in FinnGen (OR=0.77, P=0.0019). Colocalization analysis supported a shared causal variant at the GFM1 locus (PP.H4=0.717), and Steiger directionality filtering confirmed the causal path from gene expression to phenotype. PheWAS showed phenotype specificity without evidence of horizontal pleiotropy. GFM1 was predominantly expressed in sleep-regulating brain regions such as the cerebral cortex, midbrain, and hypothalamus, supporting its functional relevance in sleep biology. Conclusion: This integrative analysis identifies GFM1 as a robust, brain cell–specific protective gene for insomnia, with cross-dataset replication and functional support from colocalization, PheWAS, and expression atlases. Given its role in mitochondrial translation, GFM1 may represent a novel target for interventions aimed at sleep-related neurological conditions.

Background: The signaling pathways of inflammatory pain are widely explored, but practical clinical approaches to ameliorate pain remain inadequate. Methods: Quantitative PCR (qPCR) and ELISA methods were applied to measure the concentration of interleukin (IL)-27 in the inflammatory pain mouse model. Flow cytometry was conducted to identify the source of IL-27. Bone marrow-derived macrophages were stimulated by IL-27, IL-4, lipopolysaccharide, and/or interferon-gamma, followed by qPCR to assess pro-inflammatory and pro-resolving markers' dynamic expression. Then, the molecule profiling of IL-27-primed macrophages was determined using transcriptomic and proteomic sequencing. The Agilent Seahorse XF analyzer calculated energy metabolism indicators. The adoptive cell transfer method was used to verify that forkhead box class O3 (FoxO3) mediates alternatively activated macrophage differentiation induced by IL-27-Ucp2, contributing to alleviating pain sensation in mice. Results: IL-27 is highly expressed centrally and peripherally in rodent pain models. Selective downregulation of IL-27 intensifies pain sensitivity in mice. In macrophages, IL-27 promotes the secretion of anti-inflammatory molecules, such as Arginase-1. Further, transcriptome, energy metabolic examination, and proteome analyses identified that IL-27 restructures the metabolism in macrophages, which is mediated by uncoupling protein 2 (Ucp2) and subsequently activates transcription factor FoxO3. Conditional knockdown of FoxO3 (si-FoxO3) in macrophages refrains the production of anti-inflammatory genes in vitro; meanwhile, adoptive transfer of macrophages with si-FoxO3 but no wild-type macrophages (or IL-27 primed macrophages) prolongs mechanical hyperalgesia in mice. Conclusions: These findings reveal that the IL-27-Ucp2-FoxO3 axis regulates macrophage plasticity distinct from the canonical IL-4-mediated pathway through metabolic rewiring and facilitates alleviating Inflammatory pain.

Purpose:This study evaluated whether oxycodone alone could substitute for fentanyl combined with remifentanil for general anesthesia in laparoscopic uterine myoma surgery. Patients and Methods:90 adult female patients were randomized into three groups: oxycodone 0.35 mg/kg (Group A), oxycodone 0.30 mg/kg (Group B), or fentanyl 5 μg/kg (Group C) for induction. Anesthesia was maintained with propofol plus saline (Groups A/B) or remifentanil (Group C). Primary outcomes included Numerical Rating Scale (NRS) pain scores in the Post-Anesthesia Care Unit (PACU). Secondary outcomes were intubation reaction, vital signs, extubation/PACU times, Ramsey Sedation Scores (RSS) in PACU, NRS pain scores and adverse events within 48 hours postoperatively. Results:Intubation reactions were rare (one case each in Groups B/C, none in Group A). Group B had significantly lower PACU NRS scores than Group C (0.6 ± 0.7 vs 1.3 ± 1.4, P = 0.011), while Group A showed a nonsignificant trend (0.8 ± 0.9 vs 1.3 ± 1.4, P = 0.051). RSS scores, extubation/PACU times, and 48-hour NRS scores were comparable. However, oxycodone groups had longer postoperative evacuation times than fentanyl group (Group A vs Group C: 20.0 ± 7.3 hours vs 16.5 ± 5.1 hours, P=0.038; Group B vs Group C: 20.3 ± 8.2 hours vs 16.5 ± 5.1 hours, P=0.034). Conclusion:Oxycodone alone provides superior early postoperative analgesia compared to fentanyl-remifentanil in laparoscopic myoma surgery but may delay bowel recovery.

Background:Remimazolam is widely employed in surgical abortions. However, its dosing references from clinical studies such as gastrointestinal and bronchoscopic anesthesia have resulted in high incidence of physical movement. Purpose:Determining the optimal dosage (the 90% effective dose [ED90]) for preventing physical movement during surgical abortions. Patients and Methods:Fifty-seven individuals aged 18 to 45 undergoing surgical abortion were included. Remimazolam, combined with remifentanil, was utilized for anesthesia induction. Commencing at an initial dose of 0.25 mg/kg of remimazolam, subsequent adjustments relied on the preceding patient's response, employing an up-down sequential allocation utilizing a biased-coin design. Results:Patients received remimazolam doses ranging from 0.25 to 0.65 mg/kg. The estimated ED90, along with its 95% confidence interval (CI), for preventing physical movement was 0.615 mg/kg (0.398-0.629 mg/kg). Patients maintained stable circulation, and no significant adverse events were recorded. Patients reported a satisfaction score of 4.63 ± 0.62 points. Anesthesiologists rated their satisfaction at 4.19 ± 0.61 points, and endoscopists expressed a satisfaction level of 4.53 ± 0.57 points (based on a full score of 5 points, with a minimum of 1 point). Conclusion:The ED90 of remimazolam during surgical abortion to prevent physical movement was determined to be 0.615 mg/kg (95% CI, 0.398-0.629 mg/kg).

Postoperative cognitive dysfunction (POCD) is a prevalent complication following major surgery, particularly in older adults, and is associated with increased morbidity, prolonged hospitalization, and reduced quality of life. Although blood-brain barrier (BBB) disruption has been implicated in POCD pathogenesis, the molecular mechanisms remain poorly defined. In this study, we identify Caveolin-1 (Cav-1), a membrane scaffolding protein highly expressed in endothelial cells (ECs), as a key regulator of BBB integrity and cognitive function following surgical trauma. Using a tibial fracture internal fixation model in mice, we observed a significant upregulation of Cav-1 in the hippocampus, accompanied by reduced expression of tight junctions (TJs) proteins (Claudin-5 and ZO-1), increased BBB permeability, and impaired performance in behavioral assays indicative of cognitive decline. Pharmacological inhibition of Cav-1 via methyl-β-cyclodextrin (MβCD) attenuated these effects, restoring TJs expression, reducing BBB leakage, and improving cognitive outcomes. To elucidate the underlying mechanism, we employed an in vitro inflammation model using LPS-stimulated brain microvascular ECs. Cav-1 upregulation was found to increase the expression of matrix metalloproteinases MMP2 and MMP9, which in turn degraded TJs. Inhibition of Cav-1 suppressed MMP2/9 expression and preserved barrier integrity, confirming a Cav-1/MMP2/9 signaling axis. These findings demonstrate that Cav-1 plays a central role in mediating BBB breakdown and postoperative cognitive impairment via MMP-dependent degradation of TJs. Targeting Cav-1 may offer a novel therapeutic strategy to preserve BBB function and reduce the incidence of POCD in surgical patients.

Cancer is one of the leading causes of morbidity and mortality in the global population. The effective management of cancer-associated pain and anesthesia are critical aspects of comprehensive cancer treatment. However, the role and mechanism of anesthesia and analgesia-related drugs in tumors remain controversial. In this study, the efficacy of 16 commonly used analgesics and anesthetics against non-small cell lung cancer (NSCLC) was evaluated. Among the 16 examined injections, butorphanol tartrate injection significantly inhibited the proliferation of NSCLC cells and increased the sensitivity of the EGFR-TKI-resistant H1975 cell line to gefitinib. Benzethonium chloride (BC) is the main active antitumor ingredient of butorphanol tartrate injection. BC may regulate the cell cycle, apoptosis and EMT signaling pathways by modulating the P53 signaling pathway. Our study reveals the therapeutic value of butorphanol tartrate injection and BC in the treatment of NSCLC and provides a theoretical basis for comprehensive therapies for NSCLC.

INTRODUCTION:Laparoscopic hepatectomy (LH) poses a high risk of carbon dioxide embolism due to extensive hepatic transection, long surgery duration, and dissection of the large hepatic veins or vena cava. PATIENT CONCERNS:A 65-year-old man was scheduled to undergo LH. Following intraperitoneal carbon dioxide (CO2) insufflation and hepatic portal occlusion, the patient developed severe hemodynamic collapse accompanied by a decrease in the pulse oxygen saturation (SpO2). DIAGNOSIS:Although a decrease in end-tidal carbon dioxide (ETCO2) was not observed, CO2 embolism was still suspected because of the symptoms. INTERVENTIONS AND OUTCOMES:The patient was successfully resuscitated after the immediate discontinuation of CO2 insufflation and inotrope administration. CO2 embolism must always be suspected during laparoscopic surgery whenever sudden hemodynamic collapse associated with decreased pulse oxygen saturation occurs, regardless of whether ETCO2 changes. Instant arterial blood gas analysis is imperative, and a significant difference between PaCO2 and ETCO2 is indicative of carbon dioxide embolism. CONCLUSION:Instant arterial blood gas analysis is imperative, and a significant difference between PaCO2 and ETCO2 is indicative of carbon dioxide embolism.

Purposes SARS-CoV-2 have become widespread worldwide since the outbreak. Respiratory function deteriorates rapidly in critically ill patients infected with SARS-CoV-2. Endotracheal intubation is an indispensable therapeutic measure during the development of the disease. This study was intended to describe the experience of endotracheal intubation from front-line anesthesiologists and clinical prognosis of patients infected with Coronavirus disease-19 (COVID-19). Methods Fourteen critical patients infected with COVID-19 who underwent endotracheal intubation were included in this study. We collate and analyze the blood gas results before and after tracheal intubation of patients and clinical prognostic indicators such as length of stay and. mortality. The experience of anesthesiologists who intubated patients has also been recorded in detail. Results Patients had a mean time of 10.6 days from initial symptoms to endotracheal intubation. Most intubated patients had one or more underlying conditions: hypertension (8, 57.14%), diabetes (5, 35.71%), and cardiovascular and cerebrovascular diseases (2, 14.29%). The oxygenation index increased significantly after intubation compared with before intubation (148.80 ± 42.25 vs 284.43 ± 60.17 p < 0.001). 85.72% of patients required extra-corporeal membrane oxygenation (ECMO) due to inability to maintain oxygen saturation with standard therapeutic measures. Two patients underwent lung transplantation because their lungs were essentially nonfunctional, and they recovered well after surgery. As of this writing, all patients were discharged after satisfactory recovery. Conclusions Reasonable selection of intubation timing is particularly important. It is crucial to increase the patient's oxygen supply and reduce oxygen consumption as much as possible during endotracheal intubation. In addition, the personal protective measures of medical personnel participating in treatment should be scientific and standardized. Graphical Abstract

BACKGROUND:Empty sella is an anatomical and radiological finding of the herniation of the subarachnoid space into the pituitary fossa leading to a flattened pituitary gland. Patients with empty sella may present with various symptoms, including headache due to intracranial hypertension and endocrine symptoms related to the specific pituitary hormones affected. Here, we report a female patient who developed persistent postoperative hypotension caused by subclinical empty sella syndrome after a simple surgery.CASE SUMMARY:A 47-year-old woman underwent vocal cord polypectomy under general anesthesia with endotracheal intubation. She denied any medical history, and her vital signs were normal before the surgery. Anesthesia and surgery were uneventful. However, she developed dizziness, headache and persistent hypotension in the ward. Thus, intravenous dopamine was started to maintain normal blood pressure, which improved her symptoms. However, she remained dependent on dopamine for over 24 h without any obvious anesthesia- and surgery-related complications. An endocrine etiology was then suspected, and further examination showed a high prolactin level, a low normal adrenocorticotropic hormone level and a low cortisol level. Magnetic resonance imaging of the brain revealed an empty sella. Therefore, she was diagnosed with empty sella syndrome and secondary adrenal insufficiency. Her symptoms disappeared one week later after daily glucocorticoid supplement.CONCLUSION:Endocrine etiologies such as pituitary and adrenal-related dysfunction should be considered in patients showing persistent postoperative hypotension when anesthesia- and surgery-related factors are excluded.

(1) Background: Acute kidney injury (AKI) is related to adverse outcomes in critical illness and cardiovascular surgery. In this study, a systematic literature review and meta-analysis was carried out to evaluate the incidence and associations of AKI as a postoperative complication of thoracic (including lung resection and esophageal) surgical procedures. (2) Methods: Adopting a systematic strategy, the electronic reference databases (PubMed, EMBASE, and Cochrane Library) were searched for articles researching postoperative renal outcomes that were diagnosed using RIFLE, AKIN or KDIGO consensus criteria in the context of a thoracic operation. A random-effects model was applied to estimate the incidence of AKI and, where reported, the pooled relative risk of mortality and non-renal complications after AKI. The meta-analysis is registered in PROSPERO under the number CRD42021274166. (3) Results: In total, 20 studies with information gathered from 34,826 patients after thoracic surgery were covered. Comprehensively, the incidence of AKI was estimated to be 8.8% (95% CI: 6.7–10.8%). A significant difference was found in the mortality of patients with and without AKI (RR = 2.93, 95% CI: 1.79–4.79, p < 0.001). Additionally, in patients experiencing AKI, cardiovascular and respiratory complications were more common (p = 0.01 and p < 0.001, respectively). (4) Conclusions: AKI is a common complication associated with adverse outcomes following general thoracic surgery. An important issue in perioperative care, AKI should be considered as a highly significant prognostic indicator and an attractive target for potential therapeutic interventions, especially in high-risk populations.

Background Postoperative sleep disturbance (PSD) is a prevalent clinical complication that may arise due to various factors. The purpose of this investigation is to identify the risk factors for PSD in spinal surgery and establish a risk prediction nomogram. Methods The clinical records of individuals who underwent spinal surgery from January 2020 to January 2021 were gathered prospectively. The least absolute shrinkage and selection operator (LASSO) regression, along with multivariate logistic regression analysis, was employed to establish independent risk factors. A nomogram prediction model was devised based on these factors. The nomogram’s effectiveness was evaluated and verified via the receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA). Results A total of 640 patients who underwent spinal surgery were analyzed in this investigation, among which 393 patients experienced PSD with an incidence rate of 61.4%. After conducting LASSO regression and logistic regression analyses using R software on the variables in training set, 8 independent risk factors associated to PSD were identified, including female, preoperative sleep disorder, high preoperative anxiety score, high intraoperative bleeding volume, high postoperative pain score, dissatisfaction with ward sleep environment, non-use of dexmedetomidine and non-use of erector spinae plane block (ESPB). The nomogram and online dynamic nomogram were constructed after incorporating these variables. In the training and validation sets, the area under the curve (AUC) in the receiver operating characteristic (ROC) curves were 0.806 (0.768–0.844) and 0.755 (0.667–0.844), respectively. The calibration plots indicated that the mean absolute error (MAE) values in both sets were respectively 1.2% and 1.7%. The decision curve analysis demonstrated the model had a substantial net benefit within the range of threshold probabilities between 20% and 90%. Conclusions The nomogram model proposed in this study included eight frequently observed clinical factors and exhibited favorable accuracy and calibration. Trial registration The study was retrospectively registered with the Chinese Clinical Trial Registry (ChiCTR2200061257, 18/06/2022).

Background Medullary thyroid carcinoma (MTC) and pheochromocytoma are rare neuroendocrine tumors, which are diagnosed simultaneously in approximately 35% of patients. Heart failure and Takotsubo Syndrome (TTS) are rare and life-threatening cardiovascular complications of pheochromocytoma. Case presentation: A 42-year-old woman was admitted to the hospital for surgery because of a thyroid nodule detected on physical examination. After surgery, she presented with acute heart failure in the general ward. The clinical manifestations combined with electrocardiogram, echocardiography, coronary angiography, and myocardial enzyme examination were consistent with the diagnosis of TTS. Postoperative abdominal enhanced CT and catecholamine levels at the time of heart failure supported that acute heart failure and TTS are due to enhanced adrenal pheochromocytoma activity. Conclusions MTC may be complicated with pheochromocytoma. Preoperative examination should be completed. It is recommended to perform pheochromocytoma surgery before MTC resection. In addition, acute heart failure and TTS are rare and serious complications of pheochromocytoma. Further studies are needed on the treatment and pathogenesis of TTS.

Cortical neural dynamics mediate information processing for the cerebral cortex, which is implicated in fundamental biological processes such as vision and olfaction, in addition to neurological and psychiatric diseases. Spontaneous pain is a key feature of human neuropathic pain. Whether spontaneous pain pushes the cortical network into an aberrant state and, if so, whether it can be brought back to a "normal" operating range to ameliorate pain are unknown. Using a clinically relevant mouse model of neuropathic pain with spontaneous pain-like behavior, we report that orofacial spontaneous pain activated a specific area within the primary somatosensory cortex (S1), displaying synchronized neural dynamics revealed by intravital two-photon calcium imaging. This synchronization was underpinned by local GABAergic interneuron hypoactivity. Pain-induced cortical synchronization could be attenuated by manipulating local S1 networks or clinically effective pain therapies. Specifically, both chemogenetic inhibition of pain-related c-Fos-expressing neurons and selective activation of GABAergic interneurons significantly attenuated S1 synchronization. Clinically effective pain therapies including carbamazepine and nerve root decompression could also dampen S1 synchronization. More important, restoring a "normal" range of neural dynamics through attenuation of pain-induced S1 synchronization alleviated pain-like behavior. These results suggest that spontaneous pain pushed the S1 regional network into a synchronized state, whereas reversal of this synchronization alleviated pain.

Background: We conducted a prospective study of surgical inpatients at a teaching hospital to assess the incidence and potential risk factors for major complications of caudal anesthesia in anorectal surgery.Methods: A total of 973 patients undergoing anorectal surgery under caudal block were included in this prospective, observer-blinded trial after providing consent. Demographic information, detailed perioperative information, anesthesia-related complications and postoperative follow-up information were recorded. Meanwhile, the incidence and risk factors for major caudal anesthesia-related complications were analyzed.Results: A total of 973 patients underwent caudal block. The effective rate was 95.38% (928 cases). However, there were still 38 (3.91%) cases with insufficient block and 7 (0.72%) cases with no block. The major anesthesia-related complications were local anesthetic systemic toxicity (9, 0.92%), cauda equine syndrome (1, 0.10%), transient neurological symptoms (3, 0.31%) and localized pain at the caudal insertion site (30, 3.08%). The identified risk factor for local anesthetic systemic toxicity was multiple attempts locating the caudal space (OR= 5.30; 1.21-23.29). The identified risk factor for localized pain at the caudal insertion site was multiple attempts locating the caudal space (OR= 10.57; 4.89-22.86).Conclusion: The main complications of caudal block are transient neurological symptoms, cauda equine syndrome, serious local anesthetic systemic toxicity and localized pain at the caudal insertion site. Localized pain at the caudal insertion site is an easily overlooked complication. Multiple punctures during the block procedure was an independent influencing factor for both local anesthetic systemic toxicity and localized pain at the caudal insertion site. It is worth avoiding multiple attempts to locate the caudal space. Caudal block is still a safe and reliable method for anesthesia in adult anorectal surgery.

Interleukin-37 (IL-37) is an effective anti-inflammatory factor and acts through intracellular and extracellular pathways, inhibiting the effects of other inflammatory cytokines, such as IL-1β, IL-6, and tumor necrosis factor-α (TNF-α), thereby exerting powerful anti-inflammatory effects. In numerous recent studies, the anti-inflammatory effects of IL-37 have been described in many autoimmune diseases, colitis, and tumors. However, the current research on IL-37 in the field of the central nervous system (CNS) is not only less, but mainly for clinical research and little discussion of the mechanism. In this review, the role of IL-37 and its associated inflammatory factors in common CNS diseases are summarized, and their therapeutic potential in CNS diseases identified.

Although folate and vitamin B12 status have long been implicated in cognitive function, there is no consensus on the threshold of folate and vitamin B12 for assessing their impacts on cognition. The goal of this study was to detail the association between folate and vitamin B12 with cognitive performance. We analyzed cross-sectional data of older adults (≥60 y; n = 2204) from the NHANES (National Health and Nutrition Examination Surveys) cohort from 2011–2014. The restricted cubic spline model was used for describing the associations between serum total folate, RBC folate, 5-methyltetrahydrofolate, and vitamin B12 and the Consortium to Establish a Registry for Alzheimer’s Disease Word Learning (CERAD-WL) and Delayed Recall (CERAD-DR) tests, the Animal Fluency (AF) test, and the Digit Symbol Substitution Test (DSST), respectively. Older adults with a different folate and vitamin B12 status were clustered by artificial intelligence unsupervised learning. The statistically significant non-linear relationships between the markers of folate or vitamin B12 status and cognitive function were found after adjustments for potential confounders. Inverse U-shaped associations between folate/vitamin B12 status and cognitive function were observed, and the estimated breakpoint was described. No statistically significant interaction between vitamin B12 and folate status on cognitive function was observed in the current models. In addition, based on the biochemical examination of these four markers, older adults could be assigned into three clusters representing relatively low, medium, and high folate/vitamin B12 status with significantly different scores on the CERAD-DR and DSST. Low or high folate and vitamin B12 status affected selective domains of cognition, and was associated with suboptimal cognitive test outcomes.

乳腺癌是威胁女性健康的"头号杀手",发病率逐渐上升.手术是治疗乳腺癌的重要手段,而麻醉药物的使用对乳腺癌患者围手术期的治疗、康复、生活质量等方面产生重要影响.不同的麻醉药物对乳腺癌手术过程中残留肿瘤细胞的存活和生长具有非常重要的影响.本文总结了目前关于麻醉药物与乳腺癌生长及预后的研究,探讨不同麻醉药物影响肿瘤生长的分子机制及临床预后相关性.

Background Perioperative neurocognitive disorders (PNDs) are common complications observed among surgical patients. Accumulating evidence suggests that neuroinflammation is one of the major contributors to the development of PNDs, but the underlying mechanisms remain unclear. Methods qPCR and ELISA analysis were used for detecting LCN2 and cytokine levels. cx3cr1(CreER/-):: R26(iDTR/-) crossed mouse line was used for microglia depletion; intracranial injection of recombinant LCN2 (rLCN2) and adeno-associated viruses (AAV)-mediated shRNA silencing approaches were used for gain and loss of function, respectively. Combing with in vitro microglia cell culture, we have studied the role of LCN2 in surgery-induced cognitive decline in mice. Results We revealed that Lcn2 mRNA and protein levels were greatly increased in mouse hippocampal neurons after surgery. This surgery-induced elevation of LCN2 was independent of the presence of microglia. Gain of function by intracranial injection of rLCN2 protein into hippocampus disrupted fear memory in naive mice without surgery. Conversely, silencing LCN2 in hippocampus by AAV-shRNA protected mice from surgery-induced microglia morphological changes, neuroinflammation and cognitive decline. In vitro, application of rLCN2 protein induced the expression of several pro-inflammatory cytokines in both BV-2 and primary microglia culture. Conclusions These data suggest LCN2 acts as a signal from neuron to induce proinflammatory microglia, which contributes to surgery-induced neuroinflammation and cognitive decline in mice.

Surgical pain is associated with delirium in patients, and acupuncture can treat pain. However, whether electroacupuncture can attenuate the surgical pain-associated delirium via the gut–brain axis remains unknown. Leveraging a mouse model of foot incision-induced surgical pain and delirium-like behavior, we found that electroacupuncture stimulation at specific acupoints (e.g., DU20+KI1) attenuated both surgical pain and delirium-like behavior in mice. Mechanistically, mice with incision-induced surgical pain and delirium-like behavior showed gut microbiota imbalance, microglia activation in the spinal cord, somatosensory cortex, and hippocampus, as well as an enhanced dendritic spine elimination in cortex revealed by two-photon imaging. The electroacupuncture regimen that alleviated surgical pain and delirium-like behavior in mice also effectively restored the gut microbiota balance, prevented the microglia activation, and reversed the dendritic spine elimination. These data demonstrated a potentially important gut–brain interactive mechanism underlying the surgical pain-induced delirium in mice. Pending further studies, these findings revealed a possible therapeutic approach in preventing and/or treating postoperative delirium by using perioperative electroacupuncture stimulation in patients.