International Journal of Neuroscience最新文献

Aim: Neurovascular unit (NVU) dysfunction is a central determinant of tissue injury, reperfusion failure, and long-term neurological outcomes after ischemic stroke. This review critically examines the cellular and molecular mechanisms underlying NVU disruption, with a particular focus on inflammation, oxidative stress and blood-brain barrier (BBB) integrity, and evaluates emerging NVU-targeted therapeutic strategies.

Methods: A focused narrative review synthesized studies on ischemic stroke-related NVU alterations, integrating cellular mechanisms, biomarkers and phase-specific therapeutic strategies targeting BBB dysfunction, inflammation, oxidative stress and neurorestoration.

Results: Acute ischemic injury induces endothelial tight-junction disruption, pericyte constriction and loss, astrocytic activation and microglial-driven inflammation, resulting in BBB breakdown, impaired neurovascular coupling (NVC) and restricted microvascular reperfusion. These processes facilitate leukocyte infiltration, exacerbate secondary neuronal damage and increase hemorrhagic transformation risk. Circulating and cerebrospinal fluid (CSF) biomarkers, including MMP-9, GFAP, S100B and pro-inflammatory cytokines, reflect NVU injury severity and correlate with functional outcomes. In the chronic phase, persistent BBB permeability, maladaptive VEGF signaling and sustained low-grade inflammation contribute to white matter injury, impaired neuroplasticity and post-stroke cognitive decline. Therapeutic strategies targeting NVU dysfunction include anti-inflammatory agents, COX-2 inhibitors and NADPH oxidase (NOX) inhibitors, alongside stem cell-based and extracellular vesicle-mediated approaches that promote vascular stabilization and repair. Neuroplasticity-enhancing interventions and nanoparticle-based drug delivery systems further support functional recovery.

Conclusions: NVU dysfunction underlies both acute injury amplification and chronic recovery failure after stroke. Biomarker-guided, phase-specific therapeutic strategies targeting inflammation, oxidative stress and BBB instability represent a promising framework for personalized stroke management.

Introduction: Postoperative delirium (POD) frequently occurs in patients following cardiac valve surgery in the intensive care unit (ICU), and is linked to adverse outcomes and extended hospitalization. The purpose of this study was to establish and validate a model for predicting high-risk individuals.

Methods: This retrospective analysis enrolled adult patients who had cardiac valve surgery and subsequent ICU admission. Potential predictors were screened using LASSO logistic regression with cross-validation, followed by multivariable logistic regression, and a nomogram was developed from the final model. Model performance was assessed by receiver operating characteristic (ROC) curve analysis, calibration plots and decision curve analysis (DCA), and was benchmarked against the Sequential Organ Failure Assessment (SOFA) score.

Results: In total, 3249 patients were analyzed, of whom 535 (16.5%) developed POD. Significant predictors identified were oxygen saturation, respiratory rate, urea nitrogen, INR, white blood cell (WBC) count, hemoglobin, SOFA score, myocardial infarction, diabetes and hyperlipidemia. The nomogram yielded AUCs of 0.766 (95% CI: 0.738-0.794) in the training cohort and 0.789 (95% CI: 0.750-0.828) in the validation cohort, showing significantly better predictive accuracy than the SOFA score (p < 0.05).

Conclusions: The proposed model demonstrates strong predictive ability for POD in cardiac valve surgery patients and may aid clinicians in early risk stratification and targeted intervention. Further prospective validation is needed.

Objective: To evaluate the safety and efficacy of Edaravone-Dexborneol as a neuroprotective agent in patients with acute ischemic stroke (AIS).

Methods: We conducted a comprehensive search in PubMed, Scopus, Web of Science, and Cochrane CENTRAL until January 22, 2026, including clinical trials and observational studies comparing Edaravone-Dexborneol with Edaravone monotherapy, standard treatment, and placebo. Data on functional recovery (Modified Rankin Scale [mRS], National Institutes of Health Stroke Scale [NIHSS], Barthel Index [BI]), safety outcomes, and mortality were extracted. A random effects model was used for statistical analysis.

Results: Overall, 13 studies (5 cohort studies and 8 randomized controlled trials) involving 7,846 patients were included, demonstrating that Edaravone-Dexborneol significantly improved 90-day mRS scores (0-1) compared with Edaravone alone (RD: 0.08, 95% CI: [0.03, 0.13], P = 0.001). When compared with standard treatment, NIHSS scores were significantly lower in the Edaravone-Dexborneol group (MD: -2.18, 95% CI: [-3.75, -0.62], P = 0.006), and no significant difference was observed in mRS (0-1) or the risk of symptomatic intracranial hemorrhage (sICH). Safety outcomes showed a possible dose-dependent adverse event (AE), including hyperhomocysteinemia and hypokalemia.

Conclusion: Edaravone-Dexborneol might be an effective treatment for improving functional recovery in patients with AIS and appears to have a relatively favorable safety profile. However, careful dosing is necessary to minimize AEs. Future research should focus on large-scale trials, long-term outcomes, and mechanistic studies to optimize treatment protocols.

Aim: To evaluate the clinical value of combining alteplase, aspirin, and clopidogrel in patients with stroke, with changes in the National Institutes of Health Stroke Scale (NIHSS) score as the primary efficacy assessment indicator.

Methods: Clinical data of 122 patients with stroke who received pharmacological treatment between January 2022 and June 2024 were retrospectively collected from the hospital's health information technology (HIT) system. Patients were assigned to two groups according to treatment protocols: a dual-agent group (n = 61; aspirin plus alteplase) and a triple-agent group (n = 61; alteplase, aspirin, and clopidogrel).

Results: At 24 h, 3 days, and 5 days of treatment, NIHSS scores were lower in the triple-agent group than in the dual-agent group, with a significantly higher NIHSS improvement rate at 5 days (85.0% vs. 75.0%, p = 0.022). At 5 days and at 90-day follow-up, Montreal Cognitive Assessment (MoCA) scores were significantly higher in the triple-agent group (p = 0.002, p < 0.001). The dual-agent group had a longer duration of hospitalization but lower average medical costs than the triple-agent group (p = 0.025). No significant difference in 90-day complication incidence was observed between the groups (p > 0.05). At the 90-day follow-up, the triple-agent group demonstrated significantly better upper and lower limb function and higher Barthel scores compared with the dual-agent group (p < 0.001).

Conclusion: Triple-agent therapy, with alteplase, aspirin, and clopidogrel, may reduce neurological impairment, improve cognitive outcomes, and enhance early functional recovery in patients with stroke, although at the expense of higher medical costs.

Background: Dizziness/vertigo is a multifactorial neurological disorder with complex ge-netic and cellular bases, yet its molecular mechanisms remain unclear. Understanding how gene regulation contributes to dizziness/vertigo may reveal novel neurobiological and therapeutic insights.

Methods: We established a multi-omics integrative framework combining genome-wide association study (GWAS) data with expression quantitative trait loci (eQTL) from brain single-cell types, CD4⁺ T cells, oneK1K immune cells, and plasma. Two-sample Mendelian randomization (MR) and colocalization analyses were applied to identify causal genes. Single-cell RNA sequencing (scRNA-seq) of the auditory nerve was used to as-sess cell type-specific expression, intercellular communication, and pseudotime dynam-ics. Gene-gene interaction and drug-target networks were further constructed to identify potential therapeutic candidates.

Results: Six key genes-Activin A Receptor Type 2A (ACVR2A), Phospholipid Transfer Protein (PLTP), Androgen Dependent TFPI Regulating Protein (ADTRP), Methylenetetrahydrofolate Dehydrogenase (NADP + Dependent) 1 Like (MTHFD1L), Collagen Type VII Alpha 1 Chain (COL7A1), and Pantothenate Kinase 4 (PANK4)-showed strong causal and colocalization evidence for dizziness/vertigo. Single-cell analysis revealed distinct cell type-specific expression, with fibroblasts and adipocytes playing central roles in signaling and gene regulation. Pseudo-time trajectories indicated coordinated upregulation of ACVR2A, MTHFD1L, PANK4, and PLTP during later developmental stages. Interaction network analysis positioned these genes as major hubs, and DrugBank screening identified Sotatercept as a promising candidate targeting ACVR2A.

Conclusion: This integrative analysis links gene expres-sion regulation to dizziness/vertigo across neuroimmune and metabolic systems. The findings uncover coordinated molecular pathways underlying disease susceptibility and highlight novel therapeutic targets, providing a foundation for precision treatment strate-gies.

Aims: The present study investigated the causal associations of artificial sweetener consumption on the risk of stroke.

Methods: We applied a two-sample Mendelian randomization (MR) design using genome-wide association study (GWAS) summary data for artificial sweetener intake (added to coffee, tea, and cereal) and stroke. The primary inverse variance weighted (IVW) analysis was complemented by sensitivity tests (Cochran's Q-test, MR-Egger, MR-PRESSO, and leave-one-out analysis) and multivariate MR (MVMR) to address heterogeneity, pleiotropy, and potential confounding.

Results: Artificial sweeteners added to tea nominally increased small vessel stroke risk (OR = 3.01, 95%CI: 1.28-7.07, P = 0.0115, P-FDR = 0.20). Low-calorie drink intake (OR = 1.71, 95%CI: 1.12-2.63, P = 0.014, P-FDR = 0.20) and sucralose metabolite levels (OR = 1.14, 95%CI: 1.02-1.27, P = 0.029, P-FDR = 0.20) were nominally associated with cardioembolic stroke. MVMR analysis revealed that after adjusting for coffee intake, the association between intake of artificial sweeteners added to tea and small vessel stroke (OR = 2.90, P = 0.024) remained statistically significant. And after adjusting for blood glucose levels, the association between sucralose metabolite levels and cardioembolic stroke reversed direction and remained statistically significant (OR = 0.73, P = 0.024).

Conclusion: This MR study indicated that artificial sweeteners, particularly those added to tea and sucralose metabolites, were associated with small vessel and cardioembolic stroke, respectively. However, these associations were attenuated after adjusting for BMI or tea consumption, indicating potential confounding by adiposity or beverage habits. Findings should be interpreted cautiously and warrant further investigation.

Aim: To investigate the transcriptional changes and cell interactions following trigeminal neuralgia (TN) in different cell types in rostral ventromedial medulla (RVM).Methods: In this study, trigeminal neuropathic pain was induced in mice by ligating the left infraorbital nerve. Ten days after nerve ligation, we performed single-nucleus RNA sequencing of the RVM cells from the Sham and TN groups.Results: We identified neurons, astrocytes, microglial cells, oligodendrocytes, oligodendrocyte progenitor cells, Purkinje cells, neuroblasts, endothelial cells and fibroblasts in RVM tissue. After analyzing the cell-type-specific transcriptional changes in the RVM following nerve ligation, we found that the number of neurons and Purkinje cells in the RVM increased. Furthermore, the differentially expressed genes (DEGs) in neurons and astrocytes between the two groups was identified. The downregulated DEGs in neurons were significantly enriched in GABAergic synapse (such as Gabrg3 and Gabra2). The upregulated DEGs in neurons were enriched in glutamatergic synapse and voltage-gated ion channels. The downregulated DEGs in astrocytes involved in regulation of the postsynaptic membrane and synaptic membrane were enriched. Notably, the CellChat analysis highlights the Slit2-Robo 1/2 signaling pathway as a key route of communication between neurons and astrocytes after nerve ligation.Conclusions: This study analyzed cell-type-specific transcriptional responses to pain, and identified the possible key genes involved in TN. We inferred cell-state-specific communication in various cell types. Our findings provide potential targets, such as Slit2-Robo 1/2, Gabrg3, Gabra2, Grm4, Grik2, Cadps2 and Camk4 on therapeutic strategies for neuropathic or orofacial pain.

While there are many studies on the neural bases of obsessive-compulsive disorder (OCD), there is a dire need for a neurocomputational framework to explain its symptoms. To this end, we use the Expected Value of Control (EVC) theory to conceptualize the information processing deficits underlying OCD. Specifically, we argue that when experiencing obsessions, weak cognitive control is favored due to the affective cost of disregarding anxiety-provoking obsessions (akin to ignoring a fire alarm). This affective cost leads to the overvaluation of the cost of cognitive control (deeming it expensive), favoring automatic responses in the form of compulsions. We also exercise other ways by which OCD symptoms can be explained within the same theoretical framework. We ground our EVC-based neuroeconomic account in different neural systems implicated in OCD, including the orbitofrontal cortex, dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex, and basal ganglia, which refer to different EVC constituents. Finally, we argue that input from the bed nucleus of the stria terminalis to dACC introduces the key affective cost information to the estimation of EVC.

Objective: The National Institutes of Health Stroke Scale (NIHSS) is a known risk factor for post-stroke depression (PSD). However, more objective indicators are needed. The role of neuron-specific enolase (NSE) in PSD development remains unclear. This study aimed to ascertain the correlation of NIHSS score and NSE with PSD risk, and establish a novel nomogram combining NSE and NIHSS for early PSD prediction.

Methods: A total of 172 patients with acute ischemic stroke (AIS) were involved. Baseline clinical data including NSE and NIHSS were collected. At 3-month follow-up, patients were categorized into PSD and non-PSD groups. Logistic models and restricted cubic spline curve were used to investigate the correlation between NIHSS, NSE and PSD. A corresponding nomogram was formulated.

Results: Among 172 patients with AIS, 63 (36.63%) were diagnosed with PSD, while 109 (63.37%) were non-PSD. The baseline NIHSS and NSE were positively correlated with the risk of 3-month PSD (P < 0.05). Multivariate logistic regression revealed that sex (OR= 2.168, 95% CI 1.038 ∼ 4.526), age (OR= 1.035, 95% CI 1.002 ∼ 1.070), NIHSS (OR= 1.164, 95% CI 1.022 ∼ 1.325) and NSE (OR= 1.180, 95% CI 1.037 ∼ 1.343) were independently associated with 3-month PSD (all P < 0.05). The nomogram constructed using sex, age, baseline NIHSS score and NSE showed good discrimination, calibration, and clinical utility.

Conclusion: NSE is a valuable tool for early identification of PSD risk. A combined prediction model incorporating NIHSS and NSE has been established for the personalized prevention and intervention of PSD.

Objective: To evaluate the ability of median nerve stimulation (MNS)-induced high gamma band (HGB) activity in mapping the hand motor cortex at different states of consciousness.

Methods: Five patients undergoing awake craniotomy were recruited. MNS-induced electrocorticographic signals were recorded from awake to anesthetic states, with the loss of consciousness (LOC) session divided into three stages (LOC1, LOC2, and LOC3) based on conscious level. HGB signals were analyzed to localize hand motor cortex. Linear models were applied to analyze HGB dynamics during LOC.

Results: The sensitivity of hand motor cortex mapping based on HGB average envelope at short-latency period was 100%, 96.67%±3.33%, 83.47%±8.19%, and 82.22%±11.44% for the awake, LOC1, LOC2 and LOC3 stages. The sensitivity for HGB average envelope at long-latency period was 92.67%±4.52%, 90.85%±4.13%, 72.27%±17.07%, and 40.53%±12.82% across the same stages. The sensitivity based on HGB average power at short-latency period decreased from 100% in awake stage to 72.83%±12.95%, 48.11%±15.95%, and 21.12%±5.70% across LOC stages. The sensitivity for HGB average power at long-latency period dropped from 92.67%±4.52% in awake stage to 70.94%±10.79%, 58.37%±17.49%, and 25.71%±14.95% in the subsequent LOC stages. The slope coefficient of the simple linear model for long-latency average envelope was significantly smaller than that for short-latency. In the linear mixed effects model, the Condition × Sliding Window estimate coefficient was -0.794.

Conclusion: In awake state, HGB average envelope and average power both effectively localized hand motor cortex. With declining consciousness, the mapping ability of average power significantly deteriorated, while the mapping ability of short-latency average envelope remained relatively stable.