Night-shift nurses experience chronic sleep deprivation, which impairs cognitive functions crucial for patient safety. However, the underlying reorganization of brain functional networks remains poorly understood. This study aimed to investigate the task-specific effects of sleep deprivation on brain network topology during sustained attention and working memory in night-shift female nurses.

Ischemic stroke is associated with high disability rates, underscoring the urgent need for effective rehabilitation strategies. While exercise rehabilitation promotes functional recovery, the differential therapeutic effects of distinct exercise modalities and their underlying mechanisms remain incompletely understood. Our previous proteomic study showed that exercise administered after cerebral ischemia-reperfusion (CI/RP) strongly inhibited major neutrophil-driven biological processes in the penumbra region, including neutrophil extracellular traps (NETs) formation and integrin-cell surface interactions. Subsequent experimental results demonstrated that forced exercise (F-Ex) more significantly reduced neutrophil infiltration and NETs formation, attenuated blood-brain barrier（BBB）leakage, and upregulated tight junction proteins (TJPs) compared to voluntary exercise (V-Ex). Furthermore, previous studies have established that matrix metalloproteinases (MMPs) are closely linked to BBB disruption. In our study, matrix metalloproteinase-25 (MMP-25/MT6-MMP), was recognized among the most differentially expressed proteins (DEPs) and its expression was associated with neutrophil infiltration. However, the role of MMP-25 in cerebral ischemia remains understudied. Overall, F-Ex conferred greater neurological improvement in early-stage CI/RP injury compared to V-Ex. These results provide evidence-based insights for selecting optimal exercise interventions in post-stroke rehabilitation, elucidate a novel mechanism underlying F-Ex-mediated protection against ischemic brain injury, and implicate MMP-25 as a potential therapeutic target for ischemic stroke.

Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis, present major global health challenges due to their progressive and incurable nature. Early and accurate diagnosis is critical to slow disease progression and optimize therapeutic interventions, yet conventional diagnostic approaches-such as neuroimaging, cerebrospinal fluid biomarker analysis, and clinical evaluation-are often inadequate at the prodromal stage. Recent advances in artificial intelligence, particularly machine learning (ML), have provided new opportunities for precision diagnosis and treatment in neurology, using large data and multimodal biomarkers. Applications of ML to data from neuroimaging, electrophysiology, behavioral functions, speech and handwriting analysis, and molecular biomarkers have shown promising improvements in diagnostic accuracy, patient classification, and therapeutic recommendations. However, significant challenges remain, including data heterogeneity, model interpretability, population diversity, and ethical concerns surrounding patients' privacy. The purpose of this review is to examine current applications of ML in the diagnosis and management of neurodegenerative diseases through various data, highlight its strengths and limitations, and discuss future directions for using these approaches in clinical practice. We also outline emerging directions, including multimodal fusion with longitudinal data, federated and privacy-preserving learning, and the potential of explainable AI (XAI) and large language models (LLMs) in clinical decision support.

Research over the past few decades has focused on elucidating the role of the blood-brain barrier (BBB) in neuroprotection, regulation of the brain microenvironment, and mediation of the selective permeability of substances, including drug molecules. This has highlighted its significance in preclinical research, particularly in the screening of novel chemical entities with neuromodulatory properties. The BBB is not a static barrier but a dynamic, multicellular interface known as the neurovascular unit (NVU), which actively regulates brain homeostasis. A persistent challenge in neurotherapeutics is the translatability crisis, where promising results from traditional preclinical models fail to materialize in human trials. Current in vivo models, such as those using rodents and zebrafish, replicate the complexity of the human BBB and demonstrate satisfactory reproducibility, but are limited by their cost, time-consuming nature, and critical issues of interspecies translatability, particularly in the expression and function of key drug transporters. This has driven the development of in vitro models. In recent years, organ-on-a-chip technologies, which utilize the principles of microfluidics, have emerged at the forefront. These models are robust, cost-effective, and enable high-throughput screening of experimental results. By incorporating human-derived cells, physiological shear stress, and 3D architecture, these platforms are evolving from simple permeability-screening tools into sophisticated "pathophysiology-in-a-dish" systems. They combine the advantages of both in vivo and in vitro systems and offer promising scalability for modeling neurodegenerative diseases, neuroinflammation, and cancer, thereby enabling more predictive screening of therapeutic candidates. This review aims to provide a perspective on the current understanding of the BBB and its associated transport mechanisms, followed by a discussion of various contemporary models with the potential to transform the drug discovery landscape. The application of microfluidics in designing these models, along with noteworthy case studies in disease modeling, is explored. Finally, a brief overview of current challenges in the field, including the need for standardization, and exciting future directions spurred by regulatory shifts toward non-animal alternative methods is presented.

Although previous neuroimaging studies have characterized static brain activity in bone metastasis pain (BMP), its dynamic functional properties remain largely unexplored. This study aimed to investigate the dynamic brain activity in BMP patients.

To characterize the dynamic functional network connectivity (dFNC) patterns in children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and to uncover potential abnormalities in neural regulation and related functional impairments.

Neuroinflammation plays a role in the overall pathophysiological process of stroke. Developing preventive stroke drugs that target neuroinflammation may be a promising strategy. The aim of our study was to investigate the effect of salvianolic acid A (SAA) administered preventively on the regulation of neuroinflammation and apoptosis and to evaluate its underlying mechanisms during stroke. An autologous thrombus stroke model was established in SD rats using electrocoagulation, and an oxygen-glucose deprivation (OGD) injury model was created in human brain microvascular endothelial cells (HBMECs). SAA (10 mg/kg) was administered orally twice a day for 5 days prior to the operation. The supernatant of lipopolysaccharide (LPS) -treated BV2 cells was used as conditioned medium (CM). HBMECs were co-cultured with CM for 6 h. Our results showed that pretreatment with SAA alleviated cerebral infarction, decreased the levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α), inhibited the polarization of M1 microglia, promoted the polarization of M2 microglia, inhibited apoptosis, and balanced the expression of Bax and Bcl-2 proteins both in vivo and in vitro. Furthermore, we found that SAA inhibited the activation of the HMGB1/NF-κB signaling pathway. In conclusion, our results indicate that SAA prevents neuroinflammation and apoptosis caused by acute ischemic stroke through the inhibition of the HMGB1/NF-κB signaling pathway. Pretreatment with SAA is a potential strategy for the prevention of ischemic stroke.

In this study, experiments were conducted to investigate how primed theta-burst (PBs) and a theta pulse (TPS; 5 Hz trains for 3 min) stimulation along with pentylenetetrazol (PTZ) induced seizure like activity modulate long-term potentiation (LTP) in CA1 field recordings and whether extracellular adenosine plays a role in this modulation. Population spike (PS) was significantly enhanced for at least 1 h by short-term PTZ exposure (3 mM, 10 min), whereas the slope of the field excitatory postsynaptic potential (fEPSP) was not altered. PBs alone or in combination with short-term PTZ exposure induced LTP in fEPSP slope and PS amplitude. TPS was applied 3 min after PBs and 7 min after short-term PTZ exposure or PBs + PTZ, caused an immediate attenuation of the potentiated synaptic responses. TPS was applied 30 min after PBs or PTZ washout in the presence of EHNA (10 µM), an adenosine deaminase (ADA) inhibitor, had no effect on potentiated synaptic responses. Interestingly, when TPS was applied 30 min after PBs + PTZ, it was found that TPS-induced depotentiation was suppressed in the presence of ADA inhibitor. This effect was blocked by the adenosine A1 receptor (A1R) antagonist, CPX (200 nM). We showed that abnormal LTP induced under epileptogenic conditions can be modulated by theta-patterned stimulation and that ADA inhibition and A1R blockade alter the ability of such stimulation to induce depotentiation. These findings suggest involvement of extracellular adenosine in the regulating of aberrant synaptic plasticity, which could have implications for understanding hippocampal dysfunction associated with epileptic activity.

Central nervous system (CNS) diseases are characterized by high morbidity, long disease courses, and irreversible neurological impairment, often resulting from damage to the neurovascular unit (NVU). Tissue inhibitor of metalloproteinase-1 (TIMP-1), the endogenous inhibitor of matrix metalloproteinase-9 (MMP-9), plays a pivotal role in maintaining extracellular matrix (ECM) homeostasis and regulating NVU integrity. Beyond its canonical MMP-inhibitory function, TIMP-1 exerts a wide spectrum of MMP-independent effects as a multifunctional cytokine that interacts with cell surface receptors such as CD63/β1-integrin and low-density lipoprotein receptor-related protein-1 (LRP-1). Through activation of FAK/PI3K-Akt and MAPK signaling pathways, TIMP-1 modulates astrocyte proliferation, neural stem cell adhesion and migration, endothelial barrier stability, and myelin regeneration. Altered TIMP-1 expression is closely associated with the onset, progression, and prognosis of major CNS disorders, including ischemic stroke, epilepsy, multiple sclerosis, and neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Accumulating evidence highlights its dual, context-dependent roles-protective in acute neuroinflammatory and ischemic injury, yet potentially profibrotic or maladaptive under chronic pathological conditions. This review comprehensively summarizes recent advances in understanding the molecular mechanisms and biological functions of TIMP-1 in CNS diseases, emphasizing its regulatory networks in neuroinflammation, neuroprotection, and neuroregeneration. A deeper understanding of TIMP-1 signaling dynamics will accelerate its translational application as a diagnostic biomarker and therapeutic target for restoring neurovascular unit function in CNS disorders.

Sepsis-associated encephalopathy (SAE) is a frequent but underrecognized complication of systemic infection, characterized by acute brain dysfunction and long-term cognitive impairment in the absence of direct central nervous system infection. Despite its high morbidity and mortality, the mechanistic basis of SAE remains poorly defined, limiting early diagnosis and targeted intervention. This review synthesizes recent advances in the molecular and cellular pathophysiology of SAE, with emphasis on blood-brain barrier (BBB) disruption, neuroinflammation, glial cell activation, mitochondrial dysfunction, and neurotransmitter imbalance. We highlight the central role of BBB breakdown in facilitating peripheral-to-central immune signaling, which triggers a cascade of neuroinflammatory and metabolic events that collectively disrupt synaptic homeostasis and neuronal integrity. Emerging evidence also supports the existence of biologically distinct SAE subphenotypes, such as ischemic-hypoxic, inflammatory-dominant, and metabolic-degenerative types-each associated with specific molecular features and clinical outcomes. These insights underscore the need for biomarker-driven patient stratification and mechanism-targeted therapeutic strategies. Future research should prioritize the development of integrated diagnostic platforms, molecular phenotyping tools, and neuroprotective therapies that address the heterogeneous nature of SAE. A refined understanding of its pathogenesis holds promise for transforming the clinical management of SAE and improving long-term neurological recovery in sepsis survivors.

The thalamus, which consists of multiple subregions, has been of particular interest in the study of minimal hepatic encephalopathy (MHE). This study aimed to identify abnormalities of the thalamic subregions in patients with MHE and their associations with cognitive performance.

Migraine without aura (MWoA) is linked to abnormal subcortical/cortical network activity and neurotransmitter dysregulation. However, the alteration of functional integration and the information flow between brain networks participated in pain sensory pathway and the patterns of neurotransmitter dysregulation during the interictal period remain unclear.

In recent years, the increasing frequency of traumatic events has drawn greater attention to post-traumatic stress disorder (PTSD). However, its underlying biological mechanisms remain poorly understood. N6-methyladenosine (m6A) methylation is among the most common RNA modifications, yet to our knowledge, no studies to date have reported alterations in m6A methylation in PTSD. We enrolled 27 individuals with PTSD and 32 healthy controls. Quantitative real-time PCR (qRT-PCR) was used to examine expression differences of m6A methyltransferases. MeRIP-seq and RNA-seq were employed to investigate m6A methylation modifications and differentially expressed genes between PTSD patients and controls, followed by bioinformatic analysis. Our findings revealed decreased expression of METTL3 and FTO in peripheral blood mononuclear cells of PTSD patients, along with reduced global m6A methylation levels. MeRIP-seq analysis identified 1243 differentially expressed m6A peaks between groups. These peaks were annotated to 1054 differentially m6A-methylated genes, among which 183 exhibited hypermethylation and 871 showed hypomethylation in the PTSD group. RNA-seq analysis detected 662 differentially expressed genes, including 449 up-regulated and 213 down-regulated genes. In the differentially expressed lncRNA profile, 818 genes were identified, comprising 562 up-regulated and 256 down-regulated genes. GO and KEGG analyses indicated that the differentially methylated genes, mRNAs, and lncRNAs were primarily associated with inflammatory response, myelination alterations, and autonomic nervous system activation. In summary, m6A modification plays a critical role in the development and progression of PTSD. This study provides new insights into the biological mechanisms underlying the disorder.

Depression is a common emotional and affective disorder in clinical practice. Its core symptoms include significant and persistent low mood, decreased interest, etc. To date, the treatment approaches for depression primarily consist of pharmacotherapy, psychological counseling and treatment, as well as physical therapy. Drug therapy is the main treatment method in clinical practice, but it is limited by slow onset, low response rate, and many adverse reactions. Electroacupuncture (EA) therapy in traditional medicine has significant advantages of multi-pathway, multi-level, and multi-target in the intervention of depression, but its mechanisms are not fully understood.

Sepsis-associated encephalopathy is a frequent complication in critically ill patients and is associated with long-term cognitive impairments. However, the pathophysiology of septic encephalopathy underlying cerebral metabolism, cognition, learning, and memory capabilities is poorly understood. In this study, LC/MS-MS-based metabolomics was used to investigate the cognitive deficit mechanism underlying bacterial lipopolysaccharide (LPS)-induced sepsis-associated encephalopathy. Mice were randomly divided into the vehicle (control), LPS, and LPS + minocycline (LPS+Mino) groups. Minocycline was administered 30min after the LPS administration and daily afterward for 2 days. Behavioral tests were performed starting from day 6 with open field, fear conditioning tests, and T-maze, respectively. LPS-induced sepsis caused a profound alteration of the lipid profile in multiple brain regions. Analyses of lipid profiles revealed that the lipidome was differentially affected among the different brain areas in the LPS-induced septic brain. Following the injection of LPS, more lipid categories were impacted in the cerebral cortex. And glycerophospholipids contributed to a large proportion of those significantly modified lipids in the nucleus accumbens (NAc) and hippocampus. Furthermore, the length and unsaturation of fatty acids were also differentially affected in the LPS-induced septic brain. After being treated with minocycline, the dysregulated lipidomic profiles can be partially reversed, demonstrating the critical roles of dysregulated lipidome in sepsis-associated encephalopathy. Collectively, our results show that sepsis-associated encephalopathy differentially reprograms the lipidomic metabolism among the brain areas, which may underlie its cognitive deficits.

Prolonged stress has been identified as a primary contributor to neurodegenerative conditions, affecting key regions of the brain like the hippocampus and frontal cortex. Curcumin, a natural substance with numerous biological properties such as antioxidant, antibacterial, and anti-inflammatory effects, has limited application due to its hydrophobic nature. By studying male Wistar rats, this research explored how nanocurcumin impacts neuronal damage caused by chronic stress in the frontal cortex and hippocampus. This study involved 24 adult male rats, which were categorized into three groups: control, stress (four hours of daily restraint stress for two weeks), and stress + nanocurcumin (received 100 mg/kg nanocurcumin before stress). After the treatment period, cognitive impairment was assessed using the Barnes maze. Subsequently, the animals were sacrificed, and biochemical and histological evaluations were performed. The Barnes maze parameters were enhanced in the stress + nanocurcumin group relative to the stress animals. In the stress + nanocurcumin group, blood levels of catalase (CAT), glutathione (GSH), and total antioxidant capacity (TAC) diminished, although serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD) escalated in comparison to the stress group. Administration of nanocurcumin resulted in reduced GSH levels and elevated MDA levels in the brain. Moreover, in the stressed group administered nanocurcumin, the density of neuronal spines in the dentate gyrus (DG), CA1 and CA3 areas of the hippocampus exhibited an increase relative to the stress group. Nanocurcumin dramatically diminished stress-induced neuronal damage in the CA1, CA3, DG of the hippocampus, and prefrontal cortex. Based on these results, the administration of nanocurcumin exerts neuroprotective effects against chronic stress-induced neurodegeneration by targeting oxidative stress and improving memory impairment. Therefore, nanocurcumin can be considered a potential complementary option for preventing neurodegenerative disorders induced by chronic stress and associated memory impairment.

Men and women generally exhibit different sleep patterns and structures. These differences also extend to how each sex responds to sleep deprivation, a condition linked to various health issues. Although estradiol is known to influence sleep patterns, its sex-specific effects on sleep characteristics and the responses to sleep deprivation are not well understood. In our study, we used a genetic estrogen deficiency mouse model with aromatase deficiency (Ar) to explore estrogens' sex-specific role in reactions to acute sleep deprivation (SD). Initially, we identified a sex difference in SD-induced sleep-wake proportions and sleep patterns in wild type (WT) mice. Then, we found that estrogens deficiency caused alterations of normal sleep pattern in females, characterized by less wakefulness and more NREM time, but not in males at baseline compared to WT mice. While SD led to significant alterations in circadian rhythm, sleep patterns, and sleep rebound in both male and female Ar mice, sex differences were evident in specific responses to SD. Female Ar mice exhibited a quicker and longer-lasting post-SD sleep rebound, with reduced wake time, increased sleep time, and less fragmented sleep, whereas male Ar mice showed a delayed sleep rebound except for REM sleep time and REM sleep spectral alterations compared to WT mice. Our findings underscore the crucial role of endogenous estrogens in sleep regulation and its sex-specific response to sleep deprivation, which could be significant for precision sleep medicine.

To evaluate the efficacy of entacapone (EN) combined with high-frequency repetitive transcranial magnetic stimulation (rTMS) in treating pain in patients with Parkinson's disease (PD), with the primary outcome defined as the change in pain severity assessed by the Visual Analog Scale (VAS).Secondary outcomes included motor function (UPDRS), other pain dimensions (KPPS), depressive symptoms (HAMD), and levels of inflammatory markers (TNF-α and IL-6).

This study aimed to identify whether a novel brain-derived peptide, hypoxic ischemic brain damage-associated peptide (HIBDAP), which was identified by our research group in previous studies through peptidome analysis, has a protective effect on the neonatal brain under hypoxic ischemia (HI), and to elucidate the underlying mechanism in a neonatal hypoxic-ischemic brain damage (HIBD) rat model.

Recent studies have demonstrated that subanesthetic dose of ketamine or its S-enantiomer, esketamine, can paradoxically accelerate the recovery of consciousness in rodents following general anesthesia. However, the neural mechanisms underlying this "awakening-promoting" effect remain poorly understood.

Activating transcription factor 3 (ATF3) and solute carrier family 7 member 11 (SLC7A11) have been implicated in ferroptosis following ischemic stroke. However, the precise regulatory mechanisms between ATF3 and SLC7A11 remain incompletely understood. This study aims to investigate the regulatory mechanism of ATF3 and SLC7A11 in ferroptosis during ischemic stroke. The stroke-related microarray dataset GSE58294 was downloaded from the GEO database. Differential gene expression analysis was performed to identify ferroptosis-related differentially expressed genes (FRDEGs). Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network construction, were conducted. Key hub genes were validated in both a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) and a cellular model of oxygen-glucose deprivation/reoxygenation (OGD/R) using BV2 microglia. Cell viability was assessed by CCK-8 assay. Ferroptosis-related proteins were analyzed by Western blot, and apoptosis was detected by flow cytometry. Levels of reactive oxygen species (ROS) and Fe were measured using immunofluorescence and ELISA, respectively. Bioinformatic analysis identified SLC7A11 as a significantly altered gene in stroke. The PPI network predicted ATF3 as a key transcription factor regulating SLC7A11. In vitro, transfection with si-ATF3 downregulated GPX4 and FTH1 levels while upregulating IREB2 and ALOX15. Furthermore, si-ATF3 transfection reduced ROS levels and iron concentration in microglia, effects that were reversed by the ferroptosis inducer erastin. Notably, SLC7A11 expression was significantly increased following ATF3 knockdown. Our findings demonstrate that ATF3 preliminarily promotes ferroptosis by binding to the SLC7A11 promoter and inhibiting its expression, providing a novel mechanistic insight into ischemic stroke pathology.