搜索结果：Journal of integrative neuroscience

The perineuronal net (PNN) is an important extracellular environment around parvalbumin interneuron (PV IN) in the spinal cord. Chondroitin sulfate proteoglycan (CSPG) serves as a key factor mediating PNN effects on the spinal cord, primarily formed by covalently linked chondroitin sulfate glycosaminoglycan (CS-GAG) chains and diverse core proteins. Extensive research suggests that degradation of CS-GAG following nerve injury may contribute to severe spinal cord damage. Inhibiting CS-GAG degradation could enhance PNN stability and plasticity, thereby promoting recovery from nerve injury. Electroacupuncture (EA) intervention demonstrates significant neuroprotective effects, facilitating restoration of spinal cord nerve function and axonal regeneration. This study aims to observe the changes in CS-GAG and the expression of PV IN after spinal cord injury (SCI) in rats and explore the effect. An SCI model was established in Sprague-Dawley rats using an Infinite Horizon (IH) impactor, and EA was applied to the Jia-ji acupoints (EX-B2). The Basso-Beattie-Bresnahan (BBB) score of SCI rats was evaluated, and electromyography (EMG) of the gastrocnemius muscle of the hind limbs was performed. The protein expression levels of CS-GAG and glutamic acid decarboxylase (GAD) were detected using western blotting, and perineuronal nets (PNN) and PV IN were observed using immunofluorescence (IF). Fiber-optic calcium imaging was used to detect and analyze PV IN activity. Adeno-associated virus containing carbohydrate sulfotransferase 11 (Chst11) was injected into T9 and T10 spinal cord spaces using a microneedle, and changes in CS-GAG in the spinal cord of SCI rats before and after EA intervention were observed. CS-GAG and GAD expression levels were significantly decreased after SCI and PNN stability was reduced. Chondroitinase ABC (ChABC) treatment increased PV IN activity and GAD expression. EA effectively promoted an increase in CS-GAG and GAD, improved PNN stability and PV IN activity, and reversed the inhibitory effect of Chst11, thereby facilitating the rehabilitation of rats with SCI. The mechanisms and effects of EA on SCI repair were investigated. The results revealed that EA can regulate the recovery of PNN structure and function via CS-GAG and GAD, improve PV IN activity, and reverse the inhibitory effect of Chst11 to promote SCI rehabilitation in rats.

Neuroinflammation serves as a pivotal driver of pathology in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) - the widely used animal model of MS. A key contributor to this pathological process is neurotoxic A1-like reactive astrocytes, which play an essential role in disease progression. Although the antidiabetic drugs Metformin (Met) and Pioglitazone (Pio) exhibit anti-inflammatory properties, the effects of Met and Pio on A1-like reactive astrocytes in MS, as well as the underlying mechanisms, remain poorly defined. In this study, we investigated whether Met and Pio can attenuate neuroinflammation by modulating A1-like astrocyte activation to uncover the underlying signaling pathways involved in the process. Primary astrocytes were isolated from mice and then treated with interleukin‑17 (IL-17) to induce an A1-like reactive state. The effects of Met and Pio on A1-like astrocyte activation and inflammatory responses were evaluated. The role of the protein kinase B /mammalian target of rapamycin /signal transducer and activator of transcription 3 (AKT/mTOR/STAT3) signaling pathway was examined using Western blotting and immunofluorescence assay. Meanwhile, the experiments in vivo were performed in EAE mice, where Met and Pio administration was used to assess the therapeutic effects on neuroinflammation, demyelination, and disease progression. Both Met and Pio significantly suppressed the production of inflammatory cytokines and attenuated A1-like astrocyte activation in IL-17-stimulated primary astrocytes. These effects were mediated by the inhibition of the AKT/mTOR/STAT3 pathway. In EAE mice, drug treatment markedly reduced neuroinflammation and demyelination, thereby leading to a significant alleviation of clinical symptoms and pathological damage. Our findings suggest that Met and Pio downregulate the activated astrocyte-mediated inflammatory reaction to alleviate EAE pathogenesis through suppression of the AKT/mTOR/STAT3 pathway. Collectively, these results demonstrate a novel mechanism underlying the potential therapeutic effects of these drugs in MS and other neuroinflammatory disorders.

Executive dysfunction is the most prominent feature of cognitive impairment in patients with end-stage renal disease (ESRD). The dorsolateral prefrontal cortex (DLPFC) is a central region for the regulation of executive functions. The aim of our study was to examine alterations in neural activity and functional connectivity (FC) of the DLPFC in relation to cognitive assessments and clinical indicators in patients with ESRD using the resting-state functional magnetic resonance imaging (rs-fMRI) technique, and to further predict cognitive-related brain damage in this population. A total of 37 ESRD patients and 35 normal controls received MRI scans and neuropsychological assessments. Inter-group differences in fractional amplitude of low-frequency fluctuations (fALFF) and FC of the DLPFC were compared. Additionally, the relationships between DLPFC abnormalities and cognitive function were analyzed in ESRD patients, along with the clinical characteristics. Finally, we ascertained the potential of DLPFC abnormalities to predict cognitive-related brain damage using receiver operating characteristic (ROC) curve analysis. ESRD patients exhibited decreased fALFF in the bilateral DLPFC (p < 0.05, false discovery rate [FDR] corrected). These also showed abnormal FC with the frontoparietal cortex, cingulate cortex, cerebellar posterior lobe, inferior temporal gyrus, and rolandic operculum (p < 0.05, FDR corrected). Several alterations in the DLPFC were associated with cognitive assessments (p < 0.05) in ESRD patients, and were also correlated with the levels of uric acid and hemoglobin (p < 0.05). Importantly, ROC curve analysis showed the fALFF value of left DLPFC, and FC between right DLPFC and right middle frontal gyrus effectively predicted cognitive-related brain damage in patients with ESRD. This study demonstrated that the DLPFC is an important pathological brain region associated with the cognitive impairment of ESRD patients. Our results provide neuroimaging insights to further understand neural mechanisms of cognitive decline in this population.

Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide. Although the transcription-export (TREX) complex plays a central role in RNA maturation and nuclear export, the clinical and biological relevance of individual THO Complex Subunit (including THOC1, THOC2, THOC3, THOC5, THOC6, and THOC7) in LUAD is not well defined. We performed integrative analyses combining bulk transcriptomics from TCGA/GTEx and independent GEO cohorts, survival modeling, DNA methylation profiling, protein-level annotation from public resources, protein-protein interaction network analysis, immune infiltration estimation (TIMER), and single-cell RNA sequencing (scRNA-seq) to evaluate the relevance of THOC3 and THOC7 in LUAD. Across TCGA and external GEO validation datasets, THOC3 and THOC7 were consistently upregulated in LUAD and associated with poorer overall and disease-free survival, whereas other THO complex members showed weaker or inconsistent associations. Given these comparatively consistent and reproducible signals, we therefore prioritized THOC3 and THOC7 for downstream multi-layer analyses. Epigenetic profiling and interaction network analyses placed both genes within conserved RNA processing and export programs linked to genome maintenance pathways. Single-cell transcriptomic analysis provided additional resolution, demonstrating predominant enrichment of THOC3 and THOC7 in malignant epithelial clusters, with THOC3 aligning with transcriptional programs associated with DNA replication and repair, and THOC7 with proliferative and checkpoint-related states. Notably, expression of both genes was also detectable in myeloid and neutrophil subsets, and THOC7 expression remained elevated in recurrent LUAD samples, indicating association with aggressive and treatment-resistant disease states. Collectively, by integrating bulk, single-cell, epigenetic, and immune profiling across multiple independent cohorts, this study identifies THOC3 and THOC7 as reproducible molecular correlates of aggressive LUAD phenotypes. These highlight dysregulated RNA export programs as potential biomarkers of poor prognosis and motivate future functional studies to assess RNA export dependencies in LUAD.

Alzheimer's disease (AD) is a degenerative condition affecting the central nervous system and is the primary cause of dementia. Current therapies for AD are ineffective. Although brain regeneration via stem cell transplantation has therapeutic potential, suitable sources are limited. Hair follicle stem cells (HFSCs) are multi-potent cells and can differentiate into mesodermal and ectodermal lineages, and proliferate for extended periods. Nerve growth factor (NGF) is a neurotrophin that is vital for neuronal development and survival, and the regulation of apoptosis in neurodegenerative disorders. However, using HFSCs to treat AD has not been extensively investigated. Herein, we evaluated the therapeutic effects of HFSCs and the synergistic effect of NGF and HFSCs on AD. A rat model of AD was established by intrahippocampal injection of amyloid &#x3b2;-protein 1-42 (A&#x3b2;1-42). After 14 days, HFSCs and HFSCs overexpressing NGF were injected into the hippocampus of AD rats for therapy. The cognitive function of the treated AD rats was tested using the Morris water maze test. Congo red staining, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) were used to detect deposition, as well as soluble A&#x3b2;1-40 and A&#x3b2;1-42 levels. Additionally, western blotting was used to assess tau protein, the phosphoinositide-3 kinase (PI3K)/protein kinase B/glycogen synthase kinase-3&#x3b2; (Akt/GSK-3&#x3b2;) pathway, and the levels of synapse proteins. HFSCs and HFSCs/NGF transplantation not only significantly reduced A&#x3b2; deposition but also inhibited GSK-3&#x3b2; activity and reduced tau protein hyperphosphorylation by stimulating the PI3K/Akt signaling pathway. Moreover, HFSC and HFSC/NGF transplantation led to significant overexpression of the synaptophysin (SYP) and postsynaptic density protein 95 (PSD95) in the hippocampus of AD rats. HFSCs and NGF-modified HFSCs may become a promising treatment option for AD.

Dorsal repellent axon guidance protein (draxin) is a secreted protein that plays an establishment role in the formation of proper connections between neurons. Although draxin is known to regulate the elongation of axons from various types of neurons in vitro, its specific role in mature neurons remains unclear. Draxin expression in the hippocampal region of patients with Alzheimer's disease (AD) has been reported to be higher than in normal subjects. The present study investigated the effect of draxin on the expression of microtubule-associated protein 2 (MAP2) and neuronal nuclear antigen (NeuN), and on tau protein phosphorylation in mouse hippocampal neurons (HT22 cells) and AD cellular models. In addition, stereotactic techniques were used to inject neuronal-targeted adeno-associated virus (AAV) into the hippocampus of C57BL/6 mice to assess the effects of draxin overexpression on hippocampal neurons, as well as on behavioral and pathological features. In vitro experiments were conducted using mouse hippocampal neuronal cells (HT22 cells) and established AD cellular models, focusing on evaluating draxin's effects on the expression of neuronal markers (MAP2 and NeuN) and the phosphorylation status of tau protein. For in vivo validation, neuron-targeted AAV was delivered into the hippocampus of C57BL/6 mice via brain stereotactic injection to achieve draxin overexpression. Subsequent assessments included analyses of hippocampal neuronal integrity, behavioral tests (Y-maze and Morris water maze, to evaluate spatial learning and memory), and detection of AD-related pathological markers. In vitro experiments revealed that draxin overexpression decreased the cell survival rate, increased the apoptosis rate, decreased the expression of MAP2 and NeuN, and showed a trend for increased phosphorylation of tau protein compared with the control group. Notably, the spatial learning memory ability of mice with draxin overexpression in the brain, as determined by the Y-maze and Morris water maze tests, was significantly diminished compared with the control group. These mice also showed elevated tau protein phosphorylation and altered expression of wingless-related integration site (Wnt)/&#x3b2;-catenin/glycogen Synthase Kinase 3 beta (GSK-3&#x3b2;) pathway components. Our results suggest for the first time that neuronal overexpression of draxin may induce neuronal damage via the Wnt/&#x3b2;-catenin/GSK-3&#x3b2; signaling pathway, leading to AD-like neuropathological damage and cognitive dysfunction.

Intracranial space-occupying lesions (IOLs) often require precise surgical resection. Intraoperative neurophysiological monitoring (IONM), including somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs), is widely used to preserve neurological function. However, interpretation of IONM data still relies heavily on the experience of the surgeon. The aim of this study was to develop machine-learning (ML) models based on IONM data to support the assessment of lesion location relative to functional brain areas and surgical outcomes. We initially screened 377 patients undergoing microsurgical resection of IOLs. The clinical data on these patients included demographic characteristics, quantitative IONM parameters (SEP and MEP amplitude and latency), lesion localization, and postoperative adverse events. Four ML models were developed: support vector machine (SVM), decision tree, random forest, and na&#xef;ve Bayes. Model performance was evaluated using several metrics, including accuracy, sensitivity, specificity, precision, F1-score, and the area under the curve (AUC). Significant differences in SEP and MEP parameters were observed between patient groups with lesions located in functional and non-functional brain areas (all p < 0.05). SEP and MEP parameters were both associated with lesion localization and postoperative adverse events, with differential correlation patterns observed between the two modalities. The ML models demonstrated moderate discriminative performance in predicting lesion involvement in functional areas, with the highest accuracy of 79.2% in the training set and 65.00% in the test set. The models showed good performance in predicting serious adverse events, with the best accuracy of >78% in both datasets. ML models based on IONM data may help to assess lesion location relative to functional brain areas, as well as the prediction of postoperative outcomes. These findings suggest that ML-assisted analysis of IONM data may provide an exploratory framework for understanding lesion localization and postoperative outcomes, rather than a clinically deployable decision-support tool.

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease. No effective treatments have yet been found for ALS, primarily because the molecular mechanisms that underlie its pathogenesis are unknown. Although animal models are suitable for ALS research, species differences between these models and human spinal cord organs make it difficult to accurately predict the progression of disease in humans. Therefore, the development of more suitable models is urgently needed. Human stem cells have unlimited development potential and can be used to make three-dimensional organoid structures that mimic the architecture and function of actual organs. Organoid models can be used to overcome some of the species differences and accelerate experimental research, leading to the development of practical applications for the treatment of ALS. This article discusses the pathological mechanisms and cell types involved in ALS, as well as the genes associated with this disease. We also discuss the possible applications of spinal cord organoids (SCOs) in ALS research, such as the modeling of disease characteristics, study of pathological mechanisms, and drug screening. Finally, the prospects for SCOs in ALS treatment are highlighted, while acknowledging the need for further development of relevant technologies.

Global cerebral ischemia remains a major cause of neurological morbidity and mortality, yet effective neuroprotective strategies have shown limited translational success. Experimental studies frequently rely on ischemic duration as a primary determinant of injury severity, implicitly assuming equivalence across global brain ischemia-reperfusion (IR) and cardiac arrest with return of spontaneous circulation (CA/ROSC) models. However, increasing experimental evidence indicates that identical ischemic durations can lead to substantially different neuronal outcomes depending on the physiological and systemic context of ischemia. In brain-restricted global IR models, partial preservation of systemic circulation allows residual metabolic activity, delayed stress responses, and region-specific neuronal vulnerability, most notably delayed neuronal death in the hippocampal cornu ammonis 1 region. By contrast, CA/ROSC is characterized by complete systemic circulatory arrest followed by a biologically hostile reperfusion phase that includes profound mitochondrial dysfunction, heterogeneous reperfusion, blood-brain barrier disruption, and amplification of systemic inflammatory responses. As a result, these qualitative differences shift ischemic injury thresholds toward earlier onset and broader neuronal damage in CA/ROSC, even when ischemic durations are nominally comparable. This review integrates experimental evidence from rat models to examine how energy failure, reperfusion biology, proteostasis disruption, and brain-body interactions collectively determine neuronal vulnerability beyond ischemic duration alone. Through direct comparison of global IR and CA/ROSC paradigms, we highlight limitations of duration-centric interpretations and outline implications for experimental design and translational neuroprotection. Recognition of context-dependent ischemic mechanisms is essential for improving model selection and advancing therapeutic strategies for global cerebral ischemia.

Cerebral ischemia-reperfusion injury (CIRI) represents the most critical pathological event in the evolution of ischemic stroke (IS). Apoptosis is particularly important in CIRI pathophysiology. The interleukin-7 receptor (IL7R) is involved in various disease regulatory mechanisms; however, its specific role during CIRI remains unclear. We investigated the mechanistic function of IL7R in CIRI through a mouse model in vivo and through an astrocyte model in vitro. C57BL/6 mice were randomly allocated to one of five groups: (1) sham; (2) transient middle cerebral artery occlusion (tMCAO); (3) tMCAO + IL7R treatment; (4) tMCAO + negative control (NC); or (5) tMCAO + IL7R + the phosphatidylinositol 3-kinase (PI3K) pathway inhibitor (LY294002) (n = 3-7 per group) to evaluate the role of IL7R in CIRI. The in vitro study groups were (1) control; (2) oxygen-glucose deprivation/reoxygenation (OGD/R); (3) OGD/R + IL7R; (4) OGD/R + NC; and (5) OGD/R + IL7R + LY294002 groups. After IL7R overexpression was induced, the resulting changes in infarct volume, neurological score, cell viability, and expression of apoptosis-related proteins were assessed. IL7R overexpression significantly attenuated CIRI-induced apoptosis. In vivo, this intervention improved neurological function, alleviated cerebral edema, and decreased infarct volume in tMCAO mice. In vitro, after the overexpression of IL7R, flow cytometry analysis revealed a reduction in apoptosis rates post-OGD/R, whereas transmission electron microscopy revealed fewer morphological alterations associated with apoptosis. In addition, the level of Bcl-2-associated X protein (Bax) and cysteine-dependent aspartate-specific Protease-3 (caspase-3) were decreased, whereas that of B-cell lymphoma-2 (Bcl-2) was increased; these effects were reversed by LY294002. Overexpression of IL7R was shown to alleviate CIRI by suppressing apoptosis. These findings indicate IL7R as a novel target for IS treatment.

Secondary cerebral oedema following traumatic brain injury (TBI) is a major cause of poor prognosis, primarily driven by neuroinflammation. High-mobility group box 1 (HMGB1) is a key damage-associated molecular pattern that initiates a potent inflammatory cascade, yet targeted pharmacological interventions face clinical translation challenges. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has shown anti-inflammatory potential, but its efficacy and specific mechanisms in treating traumatic cerebral oedema remain unclear. A controlled cortical impact (CCI) model was established in male C57BL/6 mice. The animals were randomly divided into five groups: sham, TBI, TBI + taVNS, TBI + HMGB1 agonist (high glucose), and TBI + HMGB1 antagonist (glycyrrhizic acid). taVNS was administered daily for 7 days. Cerebral oedema volume was quantified via magnetic resonance imaging (MRI) on days 3 and 10 post-injury. Neurological function was assessed using the open field test and modified neurological sign score (mNSS). Molecular mechanisms were investigated through transcriptomic sequencing, enzyme-linked immunosorbent assay (ELISA), western blotting, and immunofluorescence to analyze HMGB1 and downstream inflammatory factors (interleukin-1&#x3b2; (IL-1&#x3b2;), interleukin-6 (IL-6)). Transcriptomic analysis revealed that taVNS reversed TBI-induced dysregulation of genes enriched in HMGB1-related pathways (e.g., Ras-associated protein-1 (Rap1), mitogen-activated protein kinase (MAPK)). Compared with the TBI group, taVNS significantly accelerated the resolution of cerebral oedema (reduction rate: 74.7 &#xb1; 12.1% vs 53.5 &#xb1; 16.2%, p < 0.05) and improved neurological function. Mechanistically, taVNS markedly suppressed the upregulation of HMGB1, IL-1&#x3b2;, and IL-6 in both serum and brain tissue. Crucially, the therapeutic effects of taVNS were abolished by HMGB1 agonism (high glucose), while HMGB1 antagonism (glycyrrhizic acid) alone mimicked the benefits of taVNS. This study demonstrates that taVNS effectively promotes the resolution of post-traumatic cerebral oedema and facilitates neurological recovery by specifically inhibiting the HMGB1-mediated inflammatory pathway. These findings position taVNS as a promising, non-invasive therapeutic strategy for the early management of secondary brain injury.

The objective identification of potential neurophysiological markers of schizotypal personality traits represents a major step toward improving early diagnostic strategies in psychiatry. In this study, we investigated the influence of schizotypal personality traits on the neural mechanisms underlying literal and figurative language comprehension, aiming to contribute to the development of neurophysiological markers of schizophrenia spectrum pathology. A total of 121 university students were assessed using the Schizotypal Personality Questionnaire (SPQ) and categorized into three groups: low-SPQ (scores <21; n = 60), intermediate-SPQ (scores 21-40; n = 44), and high-SPQ (scores &#x2265;41; n = 16). Participants evaluated 60 literal, 60 idiomatic, and 60 semantically incongruent phrases for meaningfulness, while event-related potentials (ERPs)-specifically N400 and post-N400 Positivity (PNP)-were recorded. The low-SPQ group showed clear N400 differentiation between idiomatic expressions and both incongruent and literal conditions, whereas intermediate-SPQ and high-SPQ groups demonstrated reduced N400 distinctions in the frontal area. At central and parietal sites, participants with increased SPQ scores retained partial differentiation between idiomatic and incongruent phrases, but they failed to differentiate between idiomatic and literal ones. Moreover, participants with intermediate SPQ scores exhibited larger frontal PNP differences between incongruent and idiomatic conditions relative to the low-SPQ group. These findings indicate that schizotypal traits are associated with poorly regulated semantic processing at the N400 stage, which is accompanied by compensatory activity at later stages of stimulus processing. These findings highlight ERP markers that may support early detection of vulnerability to schizophrenia spectrum disorders.

Electromagnetic field (EMF) exposure is increasingly common and has been implicated in a range of effects on human health. Conditioned fear memory plays a critical role in enabling organisms to respond appropriately to previously encountered threats. Despite growing interest in the neurobiological consequences of EMF exposure, its impact on the neural circuits underlying conditioned fear responses has not been clearly defined. Using a mouse model exposed to combined microwave and static magnetic fields, we examined the involvement of the primary auditory cortex-basolateral amygdala (Au1-BLA) circuit in EMF-associated alterations in conditioned fear retrieval. A multifaceted experimental approach was employed, including behavioral assays, viral tracing, genetically encoded calcium imaging, chemogenetic modulation, histopathological analysis, and immunofluorescence. Exposure was associated with reduced conditioned fear memory retrieval, pathological changes in Au1 and BLA tissue ultra-structures, and decreased Nissl bodies in Au1 neurons and Au1-BLA neuronal fiber projections. The attenuation of conditioned fear memory retrieval coincided with decreased calcium activity in Au1 and BLA neurons. Consistently, chemogenetic activation of Au1 calcium-dependent protein kinase II (CaMKII)-expressing neurons enhanced calcium activity in BLA neurons during fear retrieval and was accompanied by changes in cholinergic signaling in the BLA. These findings suggest that cholinergic neuronal populations downstream of the Au1-BLA circuit are sensitive to EMF exposure and may participate in EMF-related modulation of fear retrieval. Our findings support an association between EMF exposure and altered conditioned fear expression involving functional changes within the Au1-BLA circuit, especially for the changes in calcium activity and chemogenetic modulation of Au1 CaMKII-expressing neurons. This study provides direct experimental evidence linking EMF exposure to circuit-level functional interactions underlying fear memory retrieval.

The subjective limitations of neurobehavioral assessment cause a high misdiagnosis rate for disorders of consciousness (DoC). The purpose of this study was to identify the DoC level based on an analysis of multi-dimensional electroencephalogram (EEG) signals to assist with establishing a clinical diagnosis. Sixty-seven patients with DoC [coma, n = 19; vegetative state (VS), n = 23; and minimally conscious state (MCS), n = 25] were included to analyze resting state EEG characteristics. The EEG features were statistically compared among five band powers (delta, theta, alpha, beta, and gamma) and five brain regions (prefrontal, frontal, parietal, temporal, and occipital) by multidimensional analyses, including time-domain analysis, spectral analysis, and functional brain connectivity. Amplitude-integrated electroencephalography (aEEG) center amplitude showed significant differences between coma and MCS (p = 0.02688), with no significant differences observed for the other comparison. Spectral analysis revealed that delta and theta power decreased with higher consciousness levels, whereas alpha, beta, and gamma power increased. Relative power differed among groups across specific brain regions (prefrontal, frontal, parietal, temporal, and occipital) and frequency bands. Weighted Phase Lag Index (wPLI) based functional connectivity demonstrated frequency-specific network reorganization with theta band connectivity strongest in VS and alpha/beta/gamma band connectivity enhanced in MCS. Absolute power topographic maps showed expanding high-power regions from coma-to-MCS in high-frequency bands and the left dorsolateral prefrontal cortex (DLPFC) (F3 electrode) exhibited a consistent power gradient of coma < MCS < VS across all bands. Multidimensional EEG features have significant value in differentiating the levels of consciousness disorders. aEEG center amplitude discriminated MCS from coma; delta/gamma relative power separated VS from MCS, and alpha/beta relative power separated coma, VS, and MCS. Parieto-occipital connectivity matrix in the theta band distinguishes coma from VS, while absolute power topography of the left DLPFC shows potential for grading levels of impaired consciousness. These electrophysiologic biomarkers complement behavioral assessments, enhancing diagnostic accuracy.

This study aims to evaluate the global burden of adverse effects of medical treatment (AEMT) using data from the Global Burden of Disease Study (GBD) 2021. Data were extracted from the GBD 2021, covering 204 countries/territories from 1990 to 2021. AEMT was defined using ICD-9 and ICD-10 codes, encompassing complications from medical procedures, treatments, or healthcare exposures. Estimates were categorized into fatal and non-fatal outcomes and stratified by age, sex, year, and covariates, including the Socio-demographic Index (SDI). Mortality-incidence ratios (MIRs), defined as the ratio of mortality calculated by dividing the number of deaths by the total incident cases, were analyzed. In 2021, the global age-standardized prevalence, incidence, disability-adjusted life years (DALYs), and mortality rates of AEMT were 11.48 (95% uncertainty interval [UI], 8.86-14.13), 150.44 (131.19-171.81), 64.19 (51.06-73.11), and 1.53 (1.29-1.68) per 100,000 population, respectively. DALY rates were highest in the early neonatal group (4,789.47 per 100,000 population [95% UI, 3,682.00-5,963.30]), while mortality rates followed a U-shaped pattern across age groups. In 2021, MIRs were highest at both ends of the age range: the early neonatal group (0.58 [95% UI, 0.55-0.58]) and the 95+ age group (0.05 [0.04-0.06]). This pattern was consistent across all SDI quintiles, with higher MIRs observed in lower SDI quintiles. The significantly higher prevalence and incidence rates of AEMT among the older population in high SDI quintiles, compared to lower SDI quintiles, could be attributed to the healthcare overutilization, highlighting the need for policy adjustments.

Although pressing intervention is widely used clinically to alleviate pain associated with chronic myofascial trigger points (MTrPs), the mechanisms by which it modulates pain via sensory nerves remain unclear. This study aimed to investigate the effects of pressing intervention on transient receptor potential vanilloid 1 (TRPV1) channels in sensory nerves and to explore its potential analgesic mechanisms. Twenty-six male Sprague-Dawley rats were randomly divided into a blank group (n = 6) and a model establishment group (n = 20). Chronic MTrPs were induced in the model group by blunt strike combined with eccentric exercise. Eighteen successfully prepared were randomized into model, press, and press + capsaicin (TRPV1 agonist) groups (n = 6 per group). The press group received local pressing at MTrPs every two days for seven sessions, while the press + capsaicin group received intraperitoneal capsaicin prior to pressing. Pressure pain threshold (PPT) and soft tissue tension (STT), with STT quantified by the displacement at a loading force of 0.2 kg (D0.2), were measured before and after intervention. After treatment, the MTrPs tissue and the L2-L4 dorsal root ganglia (DRG) were collected for analysis. Skeletal muscle morphology was observed by hematoxylin-eosin (HE) staining. Inflammatory mediators in MTrPs tissue were measured by enzyme-linked immunosorbent assay (ELISA). TRPV1 protein expression in DRG was detected by Western blot. Immunofluorescence was used to detect TRPV1 on CGRP&#x207a; fibers in MTrPs and to quantify TRPV1+/c-Fos+ cells in DRG. Compared with the blank group, the model group showed reduced pain threshold, increased soft tissue tension, disorganized myocytes, inflammatory infiltration, elevated TRPV1 in nerve endings, increased interleukin-1&#x3b2; (IL-1&#x3b2;), prostaglandin E2 (PGE2), calcitonin gene-related peptide (CGRP), substance P (SP), decreased interleukin-10 (IL-10), and upregulated TRPV1 and TRPV1+/c-Fos+ cells in DRG (p < 0.01 or p < 0.05). Pressing reversed these changes, restored the pain threshold, soft tissue tension, and myocyte morphology, reduced TRPV1 and pro-inflammatory mediators, increased IL-10, and downregulated TRPV1 and TRPV1+/c-Fos+ cells in DRG (p < 0.01 or p < 0.05). These effects were partially blocked by capsaicin, as the press + capsaicin group exhibited reversed effects compared with pressing alone (p < 0.01 or p < 0.05). Pressing intervention increases the mechanical pain threshold and improves soft tissue tension in rats with MTrPs. The underlying mechanism may be associated with alleviating local inflammation, modulating the TRPV1 channel in unmyelinated C-type sensory nerve fibers, and inhibiting TRPV1 expression, thereby reducing sensory nerve excitability.

Accumulating evidence has demonstrated that bilingual experience shapes the intrinsic functional organization of the brain. However, the findings from different studies remain fragmented. This review synthesizes resting-state functional magnetic resonance imaging (fMRI) studies examining how distinct dimensions of bilingual experience, including the age of L2 acquisition (AoA-L2), L2 proficiency (PL-L2), and usage of L2 (Usage-L2), modulate the resting-state functional connectivity (RSFC) and the intrinsic organization of the functional network. Earlier AoA-L2 is associated with stronger RSFC involving the language, attentional, and subcortical systems, whereas later acquisition is linked to compensatory increases in control and cerebellar-subcortical circuits. The evidence for PL-L2 indicates that bilinguals with higher proficiency exhibit increased RSFC within attentional, subcortical, and cerebellar networks, along with a more efficient and integrated organization of the whole-brain functional network. The frequency and contextual diversity of real-world Usage-L2 dynamically reshape intrinsic connectivity, with socially diverse language engagement enhancing cross-network integration in control, subcortical, and cerebello-cortical circuits, whereas routine home use is linked to more reduced or localized connectivity patterns. The current evidence reveals meaningful but fragmented patterns linking bilingual experience to intrinsic functional connectivity, largely due to conceptual inconsistencies, limited linguistic diversity, small samples, methodological heterogeneity, and the scarcity of longitudinal or multimodal designs. This review identifies seven priorities for future research to address these constraints and move toward a more unified account of bilingual neuroplasticity: establishing standardized and multidimensional measures of bilingual experience; expanding linguistic and sociocultural diversity; increasing statistical power and reproducibility; implementing longitudinal, training-based, and experience-sampling designs; harmonizing resting-state preprocessing and analytical pipelines; modeling nonlinear and interactive brain-experience relationships; and integrating multimodal neuroimaging to elucidate mechanistic pathways. Advances in these directions will enable the field to move beyond descriptive findings toward explanatory models that illuminate how different dimensions of bilingual experience dynamically reorganize the intrinsic functional architecture of the brain.

Neurovascular coupling (NVC) is a fundamental physiological process that regulates cerebral blood flow in response to neuronal activity. This mechanism ensures the efficient delivery of oxygen and glucose to active brain regions while clearing metabolic byproducts, thus maintaining brain homeostasis and supporting optimal neural function. Disruptions in NVC are linked to complex molecular and cellular alterations and contribute significantly to a range of both acute and chronic neurological disorders, including Alzheimer's disease, ischemic stroke, cerebral small vessel disease, migraines, epilepsy, and cognitive deficits associated with diabetes. Gaining a deeper understanding of the pathological mechanisms underlying NVC dysfunction in these conditions is critical for developing novel diagnostic biomarkers and targeted therapeutic strategies. This review aims to provide a comprehensive exploration of the physiological basis of NVC in a healthy brain, alongside the methods used to study it. Additionally, it offers a detailed analysis of the molecular and cellular mechanisms driving NVC dysfunction in major neurological diseases, presenting a theoretical framework and new insights for the development of innovative diagnostic and therapeutic interventions.

Cerebral ischemia-reperfusion injury (CIRI) is a severe neurological condition where restoring neuronal mitochondrial function critically impacts prognosis. While electroacupuncture (EA) has demonstrated neuroprotective effects by improving mitochondrial function, the precise underlying mechanisms remain unclear. Emerging evidence suggests that astrocyte-to-neuron mitochondrial transfer, facilitated by mitochondrial Rho-GTPase 1 (Miro1), serves as a vital neuroprotective pathway. Therefore, this study investigates whether astrocytic Miro1 participates in the neuroprotective effects of EA against CIRI in mice by regulating the expression of the mitochondrial marker translocase of the outer mitochondrial membrane 40 (TOM40) and adenosine triphosphate (ATP) levels in damaged neurons. 126 C57BL/6 mice were randomly allocated into seven experimental groups (n = 18 per group): Sham-operated (Sham), middle cerebral artery occlusion (MCAO) model, EA, sham electroacupuncture (SEA), EA combined with astrocyte-specific Miro1 knockdown (GFAP: glial fibrillary acidic protein, EA+AAV-GFAP-shMiro1), astrocyte-specific Miro1 over-expression (AAV-GFAP-hiMiro1), and adenoviral empty vector control (AAV-GFAP-control). The CIRI model was induced using MCAO. Prior to model induction, the EA group received pretreatment with EA at the Baihui (GV20) acupoint. The SEA group underwent identical procedures to the EA group except for electrical stimulation. For the EA+AAV-GFAP-shMiro1, AAV-GFAP-hiMiro1, and AAV-GFAP-control groups, mice received intracerebroventricular injections of AAV-GFAP-shMiro1, AAV-GFAP-hiMiro1, or AAV-GFAP-control, respectively, 48 hours prior to EA treatment, with other procedures matching the EA group. At 24 hours post-reperfusion, neurological deficit scores, cerebral infarct volume, and neuronal survival in the peri-infarct penumbra were assessed. Astrocytes and neurons from the peri-infarct penumbra were isolated to measure ATP levels and expression of the mitochondrial-specific protein TOM40 in neurons, as well as ATP levels, TOM40, and Miro1 protein expression in astrocytes. Relative to the Sham group, the MCAO group displayed a significant increase in cerebral infarct volume and neurological deficit scores, accompanied by a marked reduction in neuronal viability, TOM40 expression, and ATP levels (p < 0.01). In contrast to the MCAO and SEA groups, the EA and AAV-GFAP-hiMiro1 groups demonstrated improved neurological scores, reduced infarct volume, enhanced neuronal viability, elevated neuronal ATP levels and TOM40 expression, as well as decreased astrocytic ATP and TOM40 levels, but significantly increased Miro1 expression in astrocytes (p < 0.01). When compared to the EA group, the EA+AAV-GFAP-shMiro1 group exhibited a reversal of all the aforementioned improvements (p < 0.01), while the AAV-GFAP-hiMiro1 group showed no significant changes (p > 0.05). EA exerts neuroprotective effects in MCAO mice by upregulating Miro1 protein expression in astrocytes and upregulating the mitochondrial marker TOM40 alongside ATP levels in neurons. Silencing Miro1 abolished the neuroprotective effects of EA and reduced neuronal TOM40 expression, while Miro1 overexpression increased this mitochondrial marker and mimicked EA-mediated neuroprotection. These findings identify Miro1 as a key effector of EA-induced neuroprotection, although the upstream signaling pathways linking EA to Miro1 upregulation require further investigation.