International Journal of Neuroscience最新文献

Aim: Drug interactions are crucial in understanding the efficacy and safety of co-administered antiepileptic drugs. This study aims to investigate drug interactions between carbamazepine (CBZ) and levetiracetam (LEV) and the factors associated with CBZ toxicity.

Methods: The present record-based case-control study analyzed data from 158 patients. A univariate analysis was done to identify the association of various factors with toxic trough CBZ concentrations. Frequentist disproportionality analysis was done to determine a signal for the association between concomitant LEV administration and CBZ toxicity. Receiver operating characteristic (ROC) analysis was done to identify the LEV:CBZ dose ratio to differentiate between toxic and non-toxic CBZ concentrations.

Results: The odds of developing manifestations of CBZ toxicity in CBZ + LEV versus CBZ group were 16.65 (95% confidence interval [CI]: 3.52-78.70; p < 0.001). The univariate analysis showed no association between CBZ dose and toxic trough CBZ levels, while an association between LEV administration and toxic trough CBZ levels was evident. A reporting odds ratio (ROR) of 2.25 (95% CI: 1.07-4.72; p = 0.030) and proportional reporting ratio (PRR) of 1.77(95% CI: 1.07-2.94) was observed for toxic levels of CBZ with co-administration of LEV.

A lev: CBZ dose ratio of 1.86 was identified as a threshold for differentiating between toxic and non-toxic serum concentrations with an accuracy of 72.9%.

Conclusions: There is a temporal association between LEV administration and toxic blood levels and toxic symptoms of CBZ, the chances of which significantly higher when the dose ratio of LEV:CBZ is 1.86.

Background: Ischemic stroke (IS) is a disease that causes necrosis of brain tissues by inadequate blood supply to the brain. Umbilical cord mesenchymal stem cells (UCMSCs)-derived exosomes (UCMSCs-Exo) have been reported to alleviate IS, and slit guidance ligand 2 (SLIT2) could promote neurological repair after IS. The aim of this research was to explore the potential mechanism of UCMSCs-derived exosomal SLIT2 on IS progression.

Methods: The middle cerebral artery occlusion (MCAO) rat and oxygen glucose deprivation/reperfusion (OGD/R)-induced cellular models were established, and then treated with UCMSCs-Exo. Cell viability and apoptosis were explored by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The expressions of ubiquitin specific peptidase 20 (USP20) and related apoptotic proteins were determined using Western blot. Immunofluorescence and immunohistochemistry were performed to evaluate the effect of SLIT2 on β-catenin nuclear translocation. The association between transcription factor 4 (TCF4) and USP20 promoter was investigated by chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assys.

Results: In the OGD/R-induced cell model, UCMSCs-derived exosomal SLIT2 increased cell viability, decreased apoptosis and promoted β-catenin nuclear translocation. Besides, β-catenin agonist (SKL2001) facilitated USP20 transcription by promoting TCF4 binding to USP20 promoter. Finally, TCF4 upregulated USP20 and inhibited OGD/R-induced cell damage. In the MCAO rat model, UCMSCs-derived exosomal SLIT2 mitigated IS by promoting β-catenin nuclear translocation, which activated the TCF4/USP20 pathway to inhibit apoptosis.

Conclusion: UCMSCs-derived exosomal SLIT2 activated TCF4 by promoting β-catenin nuclear translocation, which transcriptionally upregulated USP20 expression, thereby attenuating OGD/R-induced neuroncell damage and ultimately leading to inhibition of IS progression.

Piezo1 is a ubiquitously expressed non-selective cation channel protein found across various species. It possesses the ability to detect and respond to external mechanical forces, converting mechanical cues into intracellular bioelectrical events, thereby facilitating the propagation of electrochemical signals. Within the nervous system, Piezo1 is integral to synaptogenesis and myelination, modulation of pro-inflammatory mediators, neuropathic pain, cognitive processes, angiogenesis, and the regulation of cerebral hemodynamics, consequently impacting the pathogenesis and progression of neurological disorders. This review meticulously summarizes and synthesizes existing literature to provide an exhaustive overview of Piezo1's roles and mechanisms in a spectrum of neurological diseases, including neurodegenerative disorders, cerebrovascular accidents, traumatic brain injuries, gliomas, multiple sclerosis, and epilepsy. Additionally, it explores the potential therapeutic applications of targeting Piezo1. The discussion also encompasses the current research limitations, the imperative need for future investigations, and prospective strategies. Our analysis indicates that Piezo1 is a susceptibility gene for neurological conditions, and its expression inhibition may confer therapeutic benefits. In summary, this comprehensive review offers novel insights into the involvement of Piezo1 in neurological diseases and establishes a theoretical groundwork for the future development of Piezo1-targeted therapeutic interventions.

Duchenne muscular dystrophy is a common hereditary muscular dystrophy, virtual reality technology as an emerging therapeutic method has been gradually applied to the rehabilitation treatment of Duchenne muscular dystrophy patients. This paper reviews the current management status of Duchenne muscular dystrophy patients, the application effect of virtual reality technology in the rehabilitation treatment of Duchenne muscular dystrophy patients, and points out the challenges faced by the application of virtual reality technology in the field of Duchenne muscular dystrophy, aiming to provide a basis for the care of muscular dystrophy patients.

Aim: The existence of retrograde trans-synaptic degeneration (RTD) had been a controversial due to no structural continuity of two neurons in human. The study aimed to detect the macular retinal ganglion cell layer (mRGCL) loss in homonymous hemianopia (HH) patients caused by acquired cerebral lesions using optical coherence tomography (OCT) to explore RTD characteristics.

Methods: A total of 40 HH patients (80 eyes) were enrolled this study. All the patients underwent OCT examination to evaluate the peripapillary retinal nerve fiber layer (pRFNL) and mRGCL loss. Their VF defects (mean deviations [MDs]) were assessed by Humphrey Perimeter.

Results: pRNFL and mRGCL thicknesses in HH patients reduced markedly compared to that in healthy eyes. Temporal mRGCL thicknesses in ipsilateral eyes reduced 4.77 ± 7.98 μm (p = 0.002) in contrast to their contralateral eyes. Nasal mRGCL thickness in contralateral eyes reduced 5.75 ± 10.44 μm (p = 0.004), compared to their ipsilateral eyes. Additionally, trauma (p = 0.08) and tumor (p = 0.030) cerebral lesions caused more pRNFL loss than that of cerebrovascular diseases. VF defects (MD) had linear correlations to mRGCL thicknesses in nasal hemisphere in contralateral eyes (r = 0.397, p = 0.0404). The mRGCL and pRNFL loss occurred as early as 2-3 months after cerebral lesions occurred and progressed over time.

Conclusion: RTD caused by acquired cerebral lesions were objectively detected by OCT and its characteristics were consistent to anatomic features of visual pathway. The mRGCL loss due to RTD correlated to VF defects and trauma and tumors caused greater injuries in pRNFL. Visual pathway could be an ideal model and OCT is a useful tool for RTD.

Aim: Intracerebral hemorrhage (ICH) is a life-threatening stroke subtype where neuroinflammation plays a crucial role. However, the genetic basis for neuroinflammation in ICH remains unclear.

Methods: This study used Mendelian Randomization (MR) to investigate the causal impact of neuroinflammation-related genes on ICH risk. A two-sample MR analysis was conducted using genetic variants from large-scale genome-wide association studies (GWAS). The primary analytical methods included the inverse variance weighted (IVW) approach, supplemented by MR-Egger regression and the weighted median method. Protein-protein interaction (PPI) network analysis, Gene Ontology (GO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were employed to explore the biological mechanisms underlying these associations.

Results: Elevated expression of the CHUK gene was significantly associated with increased ICH risk (OR = 1.17, 95% CI 1.02-1.35, p = 0.0245 in the Ebi-ICH dataset; OR = 1.25, 95% CI 1.03-1.52, p = 0.0252 in the Finn-ICH dataset). Similarly, the CTLA4 gene showed a strong association with ICH (OR = 1.29, 95% CI 1.10-1.52, p < 0.01 in the Ebi-ICH dataset; OR = 1.23, 95% CI 1.02-1.47, p = 0.0264 in the Finn-ICH dataset). These results suggest that these genes contribute to ICH through mechanisms involving the NF-κB signaling pathway and immune regulation.

Conclusion: The findings reveal a significant genetic influence of CHUK and CTLA4 on ICH risk, provide potential targets for future therapeutic interventions, which could lead to the development of more effective treatment strategies for ICH.

Background and aims: Obesity has become a major public health burden worldwide due to the significant social and economic impacts of its associated comorbidities. Despite substantial advancements in obesity research, its prevalence continues to rise, and weight loss remains a persistent challenge despite numerous weight management programs. Food addiction has emerged as a novel factor contributing to obesity, garnering considerable attention. Some individuals consume specific foods in quantities exceeding their physiological needs, indicating a lack of control over their eating behavior. This study aimed to examine the possible synergistic effects of novel interventions (tDCS and oxytocin) on weight loss and food craving symptoms in obese individuals with food addiction.

Design: This randomized clinical trial study was conducted on obese individuals with food addiction.

Participants: Sixty individuals of both genders with obesity (BMI ≥ 30).

Setting: Participants were selected through purposive sampling and randomly assigned to four groups (19 participants each).

Intervention(s): Oxytocin nasal spray, Transcranial Direct Current Stimulation (tDCS), combined oxytocin & tDCS, and sham groups treated for 15 days.

Measurements: Body weight and food craving symptoms before and after treatment.

Comments: All three experimental interventions significantly improved weight control and food craving symptoms. No significant difference was observed between the mean scores of the tDCS and oxytocin groups. However, the combined tDCS and oxytocin group demonstrated significant differences compared to the other three groups. It can be concluded that the simultaneous application of two therapeutic approaches has a synergistic effect and can be effectively utilized in treating individuals with food addiction.

Background: Stroke is a common neurological disorder that leads to severe functional impairments and reduced quality of life. Early bedside rehabilitation plays a crucial role in recovery, but research on its effectiveness is limited.

Methods: This study aimed to assess the impact of early bedside rehabilitation on stroke patients. A total of 150 patients were randomly assigned to an intervention group (n = 75) and a control group (n = 75). The intervention group received physical therapy, occupational therapy, and speech therapy within 48 h of stroke onset. The control group received standard care. Assessments included activities of daily living (ADL), motor function, cognitive function, and quality of life.

Results: The intervention group showed significantly better outcomes in ADL, motor function, cognitive function, and quality of life compared to the control group. The intervention group had higher Barthel Index, modified Rankin Scale, Fugl-Meyer Assessment, Montreal Cognitive Assessment (MoCA), and Stroke-Specific Quality of Life Scale (SS-QOL) scores (p < 0.001).

Conclusion: Early bedside rehabilitation in the neurology department significantly improves stroke patients' recovery, including ADL, motor function, cognitive function, and quality of life. These findings highlight the importance of early rehabilitation and a comprehensive, multidisciplinary approach in stroke care, which can improve recovery outcomes and overall quality of care.

Objective: This study intends to investigate the protective impact of liproxstatin-1 against cerebral ischemia-reperfusion injury (CIRI) in rats and the corresponding underlying mechanism.

Methods: CIRI rat models were constructed. Pathological changes in tissues were assessed at multiple levels, including infarct area, neuronal activity, and iron content through 2,3,5-triphenyl tetrazolium chloride (TTC) staining, Nissl staining and Prussian blue (PB) staining. The expression of oxidative damage factors and key ferroptosis-related genes was assessed by enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (qPCR) or western blot (WB). Rat brain tissues were subjected to bulk RNA sequencing (bulk RNA-seq) analysis. Finally, in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) models were established, and the inhibitory effect of liproxstatin-1 on ferroptosis was identified by measuring cell viability, Fe²⁺ levels and lipid peroxidation.

Results: In vivo experiments demonstrated that liproxstatin-1 markedly improved neurological function and neuronal pathological damage in CIRI rats, while reducing iron content and oxidative damage. Bulk RNA-seq analysis revealed that differentially expressed genes (DEGs) were mainly enriched in the IL-17 signaling pathway, ether lipid metabolism, TNF signaling pathway and ferroptosis. Consistently, qPCR and WB results showed that liproxstatin-1 treatment increased the expression of FTH1 and GPX4, while decreasing the expression of NOX1, ACSL4, COX2 and TFR1 in rat brain tissues. In vitro experiments further demonstrated that liproxstatin-1 significantly enhanced cell viability and reduced Fe²⁺ and reactive oxygen species (ROS) levels.

Conclusions: Liproxstatin-1 inhibits the process of ferroptosis and alleviates CIRI in rats.

Introduction: Traumatic brain injury (TBI) remains a leading cause of disability and death worldwide, with no FDA-approved therapies capable of halting or reversing secondary injury cascades.

Areas covered: Recent years (2020-2025) have witnessed a surge in patent activity targeting diagnostic innovations, biomarker integration, and therapeutic strategies in TBI. Diagnostic advances include multimodal platforms that combine blood-based biomarkers, imaging modalities, and physiological monitoring to enhance early detection and stratification. Biomarker-driven patents, particularly those centered on glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), neurofilament light chain (NfL), and p-tau, have demonstrated translational value by enabling point-of-care testing and guiding therapeutic decisions. Therapeutic patents encompass a wide range of innovations, including anti-inflammatory and antioxidant agents, metabolic and vascular stabilizers, regenerative approaches, and advanced drug delivery systems designed to bypass the blood-brain barrier. Importantly, multimodal therapeutic strategies that integrate neuroprotection, neuro-restoration, and functional recovery are gaining momentum.

Expert opinion: Innovations in patents, such as breath-based sensors, eye-tracking systems, and non-invasive technologies, are expanding the possibilities for rapid, point-of-care testing. On the therapeutic side, patents focusing on monoclonal antibodies, neuroactive steroids, neuroprotective peptides, and site-specific delivery systems show promise; however, most candidates are still in preclinical or early clinical stages.