Brain Research Bulletin[JOURNAL]
Sun
200 papers
Electroacupuncture alleviates pain in rats with Cervical Spondylotic Radiculopathy by promoting M2 polarization of spinal macrophages through suppression of Piezo1 protein expression.
Huang W, Wang T, Su H … +9 more , Huang X, Li X, Zheng G, Yin L, Huang Y, Xu Z, Wei G, Li X, Su S
Brain Res Bull · 2026 Apr · PMID 41850498 · Publisher ↗
BACKGROUND: Macrophage polarization regulates CSR pain. Piezo1, a mechanosensitive channel, modulates this process. Acupuncture promotes M2 polarization, and our team found electroacupuncture (EA) alleviates CSR pain. Ho...
BACKGROUND: Macrophage polarization regulates CSR pain. Piezo1, a mechanosensitive channel, modulates this process. Acupuncture promotes M2 polarization, and our team found electroacupuncture (EA) alleviates CSR pain. However, whether EA acts via Piezo1 remains unclear. METHODS: CSR was induced in rats by inserting a nylon filament into the cervical spinal canal to compress the nerve roots. On day 6 post-surgery, gait scoring and thermal pain threshold tests confirmed successful modeling. Rats were assigned to Sham, CSR, EA, and EA+Yoda1 groups. From day 7, the EA and EA+Yoda1 groups received 20 min of EA at bilateral LI4 and LR3 daily for 7 days. The EA+Yoda1 group was injected intraperitoneally with Yoda1 (1.5 mg/kg) before each session; the EA group received vehicle. After treatment, behavioral tests were repeated, and spinal cords were collected. Histopathology was assessed by Hematoxylin and eosin (H&E) staining. Piezo1 and polarization-related markers were detected by immunofluorescence, Western blot(WB), and ELISA. RESULTS: EA improved motor behavior and thermal pain thresholds in CSR rats. It suppressed the expression of Piezo1 in the spinal cord, as well as the levels of CD86, iNOS, IL-6, NF-κB, and p-NF-κB, while promoting the expression of CD206, Arg1, TGF-β, and IL-10. These effects were reversed by treatment with Yoda1, suggesting that electroacupuncture alleviates neuropathic pain in CSR rats by downregulating Piezo1 expression and promoting macrophage polarization toward the M2 phenotype.
Altered properties of dynamic functional connectivity and cortical volume of visual cortex after treatment in children with anisometropic amblyopia.
Ma W, Zou Q, Luo K … +3 more , Cao J, Liu R, Zhao L
Brain Res Bull · 2026 May · PMID 41850497 · Publisher ↗
OBJECTIVE: To investigate treatment-induced neuroplasticity in anisometropic amblyopia (AA), this study integrated voxel-based morphometry (VBM) and dynamic functional connectivity (dFC) to characterize longitudinal chan...
OBJECTIVE: To investigate treatment-induced neuroplasticity in anisometropic amblyopia (AA), this study integrated voxel-based morphometry (VBM) and dynamic functional connectivity (dFC) to characterize longitudinal changes in cortical gray matter volume and temporal dynamics of functional connectivity within the visual centers, and to assess their correlations with clinical visual outcomes. METHODS: Twenty-two children with AA underwent comprehensive ophthalmic assessment, resting-state functional MRI, and 3D-T1WI at baseline and one month post-treatment. We applied VBM to quantify structural changes in visual cortical regions and employed a Hidden Markov Model (HMM) to identify recurrent dFC states. Dynamic temporal properties-including fractional occupancy(FO), mean dwell time(MDT), switching rate (SR), and transition probabilities-were computed for each state. Paired t-tests were used to evaluate pre-post differences in gray matter volume and dFC metrics, and correlation analyses were performed to relate these neural changes to ophthalmic indicators. RESULTS: Following treatment, AA children exhibited increased gray matter volume in the left inferior occipital gyrus and decreased volume in the left middle occipital gyrus. dFC analysis revealed significant reconfiguration in both striate and extrastriate cortices, characterized by increased fractional occupancy and mean dwell time in States 11, and decreased temporal metrics in States 6 and 10. These states were associated with enhanced connectivity between striate and extrastriate regions, despite lower overall functional activity. Key dynamic metrics were correlated with improvements in ophthalmic parameters. CONCLUSIONS: Treatment in AA children is associated with structural reorganization and dynamic functional reconfiguration in visual cortices. The observed gray matter volume alterations, along with shifts in dFC state dynamics and strengthened network interactions, suggest that multimodal neuroadaptive processes underpin functional recovery in amblyopia. These findings provide objective imaging-based evidence for the neural mechanisms that support treatment-induced rehabilitation in AA.
Limbic structural markers of language delay in late-preterm children by NeuroQuant and machine learning.
Lee SH, Lee HJ, Kim H … +2 more , Kim SJ, Kim HH
Brain Res Bull · 2026 Apr · PMID 41850496 · Publisher ↗
Language development relies on distributed neural systems that include temporal and limbic-striatal circuits, yet the neuroanatomical substrates of language delay in late-preterm children remain incompletely characterize...
Language development relies on distributed neural systems that include temporal and limbic-striatal circuits, yet the neuroanatomical substrates of language delay in late-preterm children remain incompletely characterized. This study investigated structural brain differences associated with language delay in late-preterm children using quantitative automated volumetry at term-equivalent age and an interpretable analytical approach to identify neuroanatomical correlates of later language outcomes. In this retrospective cohort study, late-preterm children with language delay (n = 31) and without language delay (n = 120) were included. T1-weighted MRI scans acquired at term-equivalent age were analyzed using NeuroQuant. Exploratory feature selection and prioritization were performed to identify volumetric features associated with language delay, followed by multivariable logistic regression analyses adjusting for relevant clinical covariates. Compared with controls, language delay was associated with increased left amygdalar volume and decreased hippocampal volume. Receptive language delay was associated with reduced right nucleus accumbens volume, whereas expressive language delay was associated with increased left amygdalar volume and reduced hippocampal volume. These findings indicate that distinct limbic and striatal brain structures are differentially associated with receptive and expressive language domains in late-preterm children. Quantitative automated volumetry may help characterize limbic-striatal neuroanatomical patterns related to language outcomes and generate testable hypotheses for future longitudinal neurodevelopmental studies.
Optimized CNN-based facial analysis for depression detection: Managing mental disorder in education.
Wang M, Wu Y, Rezaee K … +1 more , Khosravi M
Brain Res Bull · 2026 Apr · PMID 41845968 · Publisher ↗
Major Depressive Disorder (MDD) is frequently under-identified in educational contexts, including arts and design programs, where limited clinical resources and privacy concerns restrict routine screening. Studio-based c...
Major Depressive Disorder (MDD) is frequently under-identified in educational contexts, including arts and design programs, where limited clinical resources and privacy concerns restrict routine screening. Studio-based curricula may introduce critique- and portfolio-driven stressors, motivating low-burden decision support for triage rather than diagnosis. Face-based machine learning can provide a non-intrusive signal when designed to be privacy-preserving and compute-efficient; however, prior work often relies on multimodal inputs, under-reports calibration/robustness, and is not optimized for on-device deployment. We present OCFA (Optimized CNN-Based Facial Analysis), a lightweight face-only pipeline that integrates (1) a RobFaceNet-style backbone with Adapt-Coordinate Attention, (2) multi-objective evolutionary model selection under explicit efficiency and reliability constraints, and (3) post-hoc temperature scaling to improve probabilistic calibration with zero inference-time FLOPs. Because supervision is available at the interview/session level rather than per frame, OCFA aggregates frame-level evidence into a session score (pooling/MIL variants) while enforcing strict subject/session-wise separation to prevent identity leakage. Experiments use the DAIC-WOZ depression subset with PHQ-8-derived labels (binary screening cutoff PHQ-8 ≥ 10) and official train/dev/test partitions; cross-domain generalization is assessed on E-DAIC as an external benchmark with a controlled shift in interview dynamics (WoZ-controlled vs AI-controlled sessions). On the official DAIC-WOZ test split, OCFA achieves 82.98% accuracy, 82.61% F1, AUROC= 0.886, and post-scaling ECE≈ 0.040 at 0.065 GMac (112×112) with 3.80 M parameters. Under the same frozen operating point (no external-set re-tuning), OCFA attains 81.10% accuracy, 80.20% F1, and AUROC= 0.874 on E-DAIC. For privacy-aligned interpretability, we report SHAP-based global feature importance without exposing identifiable face imagery. OCFA is designed as a calibrated, on-device compatible risk estimator for human-in-the-loop screening workflows (including art and design schools). Prospective validation under real educational capture conditions remains necessary before operational deployment.
Dynamic functional connectivity changes in noise-induced hearing loss: A resting-state fMRI study with machine learning-based classification.
Wang A, Yang B, Huang R … +3 more , Pan X, Bao X, Zhang G
Brain Res Bull · 2026 Apr · PMID 41833699 · Publisher ↗
OBJECTIVE: Noise-induced hearing loss impacts brain health and cognition, with dynamic functional connectivity analysis offering a promising but underexplored method for studying whole-brain activity. Therefore, this stu...
OBJECTIVE: Noise-induced hearing loss impacts brain health and cognition, with dynamic functional connectivity analysis offering a promising but underexplored method for studying whole-brain activity. Therefore, this study aimed to utilise dynamic functional connectivity analysis to investigate abnormal temporal variability in whole-brain functional connectivity in patients with noise-induced hearing loss. METHODS: In this observational study, 58 patients with noise-induced hearing loss and 42 healthy male controls, matched for age and education, underwent resting-state functional magnetic resonance imaging. The sliding window approach was employed to evaluate dynamic functional connectivity between region pairs, and k-means clustering was used to identify dynamic functional connectivity states. A two-sample t-test was used to compare differences in dynamic functional connectivity variability and state metrics between patients with noise-induced hearing loss and healthy male controls (P < 0.05). Abnormal brain dynamic functional connectivity features were identified using false discovery rate correction and least absolute shrinkage and selection operator classifier. These features were used to construct support vector machine classifiers. RESULTS: Compared with healthy male controls, patients with noise-induced hearing loss demonstrated decreased dynamic functional connectivity between the right supplementary motor area and bilateral cuneus and increased dynamic functional connectivity between the supplementary motor area and left inferior parietal gyrus. The support vector machine classifier based on abnormal dynamic functional connectivity features selected by false discovery rate correction successfully distinguished between patients with noise-induced hearing loss and healthy male controls with an accuracy of 82.5%. The accuracy of the support vector machine classifier based on least absolute shrinkage and selection operator-selected abnormal dynamic functional connectivity features reached 96.8%. CONCLUSION: This study revealed abnormal dynamic functional connectivity patterns in patients with noise-induced hearing loss, offering insights into the complex neuropathological mechanisms underlying long-term brain network changes associated with this disease.
Functional heterogeneity of medial septal GABAergic neurons in theta rhythm modulation and septo-hippocampal communication.
Huang S, Wang Y, Ma X … +2 more , Lin L, Xu J
Brain Res Bull · 2026 Apr · PMID 41833698 · Publisher ↗
The medial septum (MS) acts as a primary pacemaker for hippocampal theta rhythms. However, the functional diversity of MS GABAergic neurons and their roles in septo-hippocampal communication remain elusive. We combined o...
The medial septum (MS) acts as a primary pacemaker for hippocampal theta rhythms. However, the functional diversity of MS GABAergic neurons and their roles in septo-hippocampal communication remain elusive. We combined optogenetic manipulation with multi-channel in vivo electrophysiological recordings in freely moving mice to characterize such heterogeneity. Rhythmic MS GABAergic neurons could be characterized into distinct functional subgroups based on their directional coupling with hippocampal theta oscillations. Granger causality analysis identified a "driver" subpopulation exerting strong causal influence on hippocampal theta, and a "follower" subgroup primarily receiving feedback from the hippocampus. Furthermore, optogenetic inhibition revealed two distinct response patterns, resembling "driver" and "follower" subpopulations. These findings provided evidence for a bidirectional septo-hippocampal inhibitory loop, suggesting that MS GABAergic neurons orchestrate theta rhythms through coordinated drive and feedback mechanisms.
Functional gradient reorganization and its impact on spatial working memory after acute sleep deprivation.
Xu L, Yan J, Zhang H … +3 more , Zhang J, Zhang X, Zhang J
Brain Res Bull · 2026 Apr · PMID 41833697 · Publisher ↗
BACKGROUND: Although resting-state functional magnetic resonance imaging (rs-fMRI)-derived functional gradients have been widely used to describe cortical hierarchical organization, their application has rarely targeted...
BACKGROUND: Although resting-state functional magnetic resonance imaging (rs-fMRI)-derived functional gradients have been widely used to describe cortical hierarchical organization, their application has rarely targeted acute sleep deprivation (ASD)-related cognitive vulnerability. In particular, whether ASD induces systematic reorganization of gradient architecture and whether this reorganization contributes to spatial working memory (SWM) impairment have not yet been systematically examined. METHODS: Fifty healthy young adult males were recruited. A 1-back task was administered to assess SWM performance before and after ASD. T1-weighted and rs-fMRI data were acquired. Functional gradient-based metrics, including standard deviation of gradient values, range of gradient values, network gradient values, and inter-network relative distances, were computed to characterize cortical hierarchical organization and were subsequently correlated with SWM behavioral performance. RESULTS: Compared with the rested wakefulness condition, ASD significantly impaired SWM performance. Functional gradient analysis revealed significant alterations in both global (standard deviation and range) and local (gradient values of specific subnetworks) features of the top three principal gradients. Notably, the standard deviation of Gradient 2 was significantly negatively correlated with omission rate. In addition, relative distances between multiple networks within Gradient 2 and 3 were also closely associated with SWM performance. CONCLUSION: From the perspective of functional gradients, the present study highlights the global and local gradient reorganization following ASD, as well as the importance of maintaining a balance between functional segregation and integration across subnetworks in sustaining SWM performance.
SYK-dependent lipid handling in monocyte-derived macrophages governs functional recovery after spinal cord injury.
Zhao Y, Hu H, Wang J … +9 more , Hu Y, Yang L, Wu Z, Zhao S, Wang X, Mu Y, Zheng M, Tian D, Cheng L
Brain Res Bull · 2026 Apr · PMID 41831796 · Publisher ↗
After spinal cord injury (SCI), monocyte-derived macrophages and resident microglia play critical, yet potentially distinct, roles in sculpting the lesion milieu via phagocytosis. However, the underlying mechanisms remai...
After spinal cord injury (SCI), monocyte-derived macrophages and resident microglia play critical, yet potentially distinct, roles in sculpting the lesion milieu via phagocytosis. However, the underlying mechanisms remain unclear. While spleen tyrosine kinase (SYK) has emerged as a master switch for microglial neuroprotection, its function in macrophages after SCI is unknown. Here, we show that SYK expression increases after SCI, peaking at 7 days post-injury (dpi) and persisting until 28 dpi, predominantly within Cx3cr1-GFPF4/80 macrophages rather than Cx3cr1-GFPF4/80 microglia. Pharmacological blockade of SYK with intraperitoneal Entospletinib impaired macrophage phagocytosis, triggered intracellular lipid droplet accumulation, and impeded axonal regrowth and functional recovery. Conversely, SYK agonism with Pustulan injection boosted myelin phagocytosis, accelerated lipid metabolism, and enhanced locomotor outcomes. Notably, in triggering receptor expressed on myeloid cell 2 (TREM2) knockout mice, Pustulan treatment restored macrophage phagocytic competence and lipid droplet clearance, identifying TREM2-SYK signaling as the critical axis governing post-SCI macrophage function. Our findings establish SYK as a therapeutic target for reprogramming macrophage lipid metabolism and promoting repair following SCI.
Remimazolam alleviates blood-brain barrier damage by regulating the PI3K/AKT signaling pathway in sepsis-associated encephalopathy mice.
Xu B, Wang X, Liu S … +6 more , Guo Y, Dong Q, Tao Y, Zhang M, Ni P, Xie Y
Brain Res Bull · 2026 Apr · PMID 41831795 · Publisher ↗
Sepsis-associated encephalopathy (SAE) is a common neurological complication in critically ill patients. However, therapeutic strategies for SAE remain limited. Increasing evidence suggests that impairment of the blood-b...
Sepsis-associated encephalopathy (SAE) is a common neurological complication in critically ill patients. However, therapeutic strategies for SAE remain limited. Increasing evidence suggests that impairment of the blood-brain barrier (BBB) plays a crucial role in the progression of SAE. Remimazolam has been demonstrated in previous studies to exert neuroprotective effects through the modulation of neuroinflammatory responses. This study aimed to determine whether remimazolam alleviates BBB disruption in a murine model of SAE and to elucidate the underlying signaling mechanisms. A murine model of SAE was established by intraperitoneal administration of lipopolysaccharide (LPS), followed by treatment with remimazolam. To investigate the involvement of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway, the specific PI3K inhibitor LY294002 was co-administered. BBB integrity, expression of ZO-1 and Occludin, levels of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6), and microglial activation were systematically evaluated. Our results indicate that LPS increases blood-brain barrier permeability, downregulates the expression of ZO-1 and Occludin, elevates brain levels of pro-inflammatory cytokines IL-1β and IL-6, and induces microglial activation. In contrast, remimazolam treatment significantly attenuated LPS-induced BBB dysfunction, as evidenced by reduced Evans blue extravasation, restoration of ZO-1 and Occludin expression, decreased production of IL-1β and IL-6, and suppression of microglial overactivation. Moreover, remimazolam reversed LPS-induced inhibition of the PI3K/AKT signaling pathway. Notably, co-administration of LY294002 abolished the protective effects of remimazolam, indicating a critical role for PI3K/AKT signaling in mediating its neuroprotective actions. These findings suggest that remimazolam may represent a promising therapeutic candidate for targeting the pathogenesis of SAE.
Acupuncture improves neuronal ferroptosis and synaptic damage in a rat model of traumatic brain injury.
Wu M, Pu J, Wang C … +4 more , Sun H, Zhang S, Huang Y, Gong Y
Brain Res Bull · 2026 Apr · PMID 41825615 · Publisher ↗
The neuropathologic process underlying secondary brain injury post-TBI is complex, and neurotransmitter changes and synaptic plasticity damage are the main potential factors. N-methyl-d-aspartate receptor (NMDAR) has bee...
The neuropathologic process underlying secondary brain injury post-TBI is complex, and neurotransmitter changes and synaptic plasticity damage are the main potential factors. N-methyl-d-aspartate receptor (NMDAR) has been reported to be closely related to synaptic plasticity. Acupuncture can inhibit ferroptosis of nerve cells and enhance synaptic plasticity. This study aims to elucidate the effects of acupuncture on reducing neuronal ferroptosis, reducing synaptic damage, and improving secondary brain injury after TBI. The results showed that the mNSS scores of the TBI group were significantly higher than those in the Sham group. Rotarod test duration, as well as the frequency and time of platform crossing in the TBI group, were significantly reduced compared to the Sham group. Ferroptosis and synaptic damage injury increased after TBI. Acupuncture can reverse the above results and reduce the expression of the activated NMDAR post-TBI. Acupuncture can alleviate synaptic damage and restore neural function deficit after TBI, which may play an anti-ferroptosis role by inhibiting NMDAR.
PDGF-BB mitigates pericyte injury by activating the PHF19-PRC2 complex via the miR-221/BRCA1 signaling axis in Alzheimer's disease.
Yang H, Zhou H, Zhao K … +5 more , Shi L, Li Y, Zhao Q, Ya J, Wu C
Brain Res Bull · 2026 Apr · PMID 41825614 · Publisher ↗
BACKGROUND: Platelet-derived growth factor-BB (PDGF-BB) is a critical factor in maintaining pericyte function. Damage to pericytes has been shown to accelerate the progression of Alzheimer's disease (AD). This study aime...
BACKGROUND: Platelet-derived growth factor-BB (PDGF-BB) is a critical factor in maintaining pericyte function. Damage to pericytes has been shown to accelerate the progression of Alzheimer's disease (AD). This study aimed to investigate the role of PDGF-BB in the pathogenesis of AD. METHODS: Pericytes were treated with Aβ1-42 alone or in combination with PDGF-BB. Cell viability, proliferation, and apoptosis were assessed using the CCK-8 assay, EdU assay, and flow cytometry, respectively. Co-immunoprecipitation was performed to investigate the interactions among BRCA1, PHF19, EZH2, EED, SUZ12, and RbAp46/48. The relationships among BRCA1, miR-221-3p, and miR-222-3p were evaluated using a luciferase reporter assay. APP/PS1 transgenic mice were administered PDGF-BB, and behavioral performance was assessed via the Morris water maze test. Immunofluorescence staining and Evans Blue assay were employed to examine pericyte coverage and blood-brain barrier (BBB) integrity. RESULTS: PDGF-BB enhanced cell viability and proliferation while inhibiting apoptosis in Aβ1-42-treated pericytes; these effects were reversed by BRCA1 overexpression. BRCA1 expression was upregulated in pericytes exposed to Aβ1-42. Furthermore, PDGF-BB treatment resulted in the downregulation of BRCA1 and the upregulation of members of the PHF19-PRC2 complex, including PHF19, EZH2, EED, SUZ12, and RbAp46/48. BRCA1 was found to interact with these PHF19-PRC2 complex components. Additionally, miR-221 suppressed BRCA1 expression by directly targeting BRCA1, whereas miR-222 interacted with BRCA1 without affecting its expression. In vivo, PDGF-BB administration improved learning and memory abilities, increased pericyte coverage, and enhanced blood-brain barrier integrity in an Alzheimer's disease mouse model. CONCLUSION: PDGF-BB activated PHF19-PRC2 complex through the regulation of the miR-221/BRCA1 axis, thereby decreasing blood-brain barrier permeability and improving learning and memory abilities in AD mouse models. Consequently, PDGF-BB may have a therapeutic potential in the progression of AD.
Longitudinal voxel-based FDG PET assessment of chemotherapy effects on brain metabolism in lung cancer.
Cheng HW, Hsiao IT, Huang TW … +6 more , Lee Y, Yang QF, Chen IF, Chiu CH, Cheng CY, Lin LF
Brain Res Bull · 2026 Apr · PMID 41819474 · Publisher ↗
BACKGROUND: Chemotherapy-induced cognitive impairment (CICI) is a frequently reported complication in lung cancer patients, yet the underlying cerebral metabolic changes remain poorly characterized. This study aimed to e...
BACKGROUND: Chemotherapy-induced cognitive impairment (CICI) is a frequently reported complication in lung cancer patients, yet the underlying cerebral metabolic changes remain poorly characterized. This study aimed to evaluate chemotherapy-related alterations in brain glucose metabolism in patients with non-small cell lung cancer (NSCLC) using a longitudinal, within-subject voxel-based F-FDG PET approach. METHODS: Forty NSCLC patients who underwent both pre- and post-chemotherapy FDG PET imaging were retrospectively enrolled. Voxel-wise comparisons were performed using SPM12 to identify regional metabolic changes. Patients were stratified based on chemotherapy intensity (standard: ≥4 cycles; short-course: 1-3 cycles) and recovery interval (short: <6 months; long: ≥6 months), with subgroup and interaction analyses conducted accordingly. RESULTS: Compared with baseline, post-treatment scans revealed regional metabolic reductions, predominantly in the right thalamus, left frontal lobe, and bilateral temporal regions. Patients receiving standard chemotherapy exhibited more extensive metabolic reductions than those receiving short-course treatment, particularly in the bilateral temporal and cingulate regions. Furthermore, patients scanned within six months post-chemotherapy showed more pronounced reductions than those with longer recovery intervals, suggesting a potential trend of metabolic recovery over time. In contrast, patients with limited initial metabolic changes (i.e., short-course group) exhibited minimal changes across intervals. CONCLUSION: This within-subject FDG PET study provides longitudinal evidence that chemotherapy independently contributes to brain metabolic alterations in NSCLC patients, predominantly involving the frontal, temporal, and limbic regions. These findings highlight vulnerable neural substrates and underscore the clinical value of functional neuroimaging in cancer survivorship research.
Long-term variable photoperiod disrupts serotonin signaling in prefrontal cortex and hippocampus, contributing to mood and cognitive deficits.
Hou Y, Zhang Y, Han C … +2 more , Sun H, Meng P
Brain Res Bull · 2026 Apr · PMID 41819473 · Publisher ↗
Circadian rhythm misalignment is strongly linked to mood and cognitive impairments, but the related molecular pathways are not fully elucidated. This research examined how long-term variable photoperiod (L-VP) influences...
Circadian rhythm misalignment is strongly linked to mood and cognitive impairments, but the related molecular pathways are not fully elucidated. This research examined how long-term variable photoperiod (L-VP) influences emotional and cognitive functions, along with changes in serotonin (5-HT) signaling in the prefrontal cortex (PFC) and hippocampus of Wistar rats. Behavioral assessments revealed that L-VP induced anxiety-like behaviors, depressive phenotypes, and cognitive impairments, particularly during the subjective active phase (ZT12). Additionally, L-VP altered 5-HT metabolism, reducing 5-hydroxyindoleacetic acid (5-HIAA) levels and the 5-HIAA/5-HT ratio, indicating impaired serotonergic transmission. Expression of 5-HT receptors (5-HTR1A and 5-HTR2A) also exhibited circadian dysregulation, with reduced 5-HTR2A levels in the PFC. These findings suggest that chronic circadian misalignment disrupts 5-HT signaling in emotion- and cognition-related brain regions, contributing to mood and cognitive deficits. This study highlights the PFC and hippocampus as critical hubs for integrating circadian and emotional functions and explores potential therapeutic targets for circadian-related neuropsychiatric disorders.
SERPINE1 drives neuropathic pain in a resiniferatoxin-induced model via AKT-mediated neuronal apoptosis.
Wang D, Xu L, Sun Y … +2 more , Yue J, Li L
Brain Res Bull · 2026 Apr · PMID 41806904 · Publisher ↗
Postherpetic neuralgia (PHN) is a persistent neuropathic pain condition resulting from varicella-zoster virus reactivation, yet remains inadequately treated. Here, we elucidate a pathogenic function of Serpin Family E Me...
Postherpetic neuralgia (PHN) is a persistent neuropathic pain condition resulting from varicella-zoster virus reactivation, yet remains inadequately treated. Here, we elucidate a pathogenic function of Serpin Family E Member 1 (SERPINE1) in neuropathic pain using a resiniferatoxin (RTX)-induced neuropathic pain to simulate PHN. RTX administration triggered sustained mechanical allodynia and thermal hyposensitivity, accompanied by damage in the dorsal root ganglion (DRG) and sciatic nerve. Transcriptomic analysis identified SERPINE1 as a prominently upregulated gene in DRG following RTX challenge. Pharmacological inhibition of SERPINE1 with TM5441 alleviated pain-related behaviors in a dose-dependent manner, restored vanilloid 1 (TRPV1)-positive neuronal populations, and mitigated ultrastructural nerve pathology. Mechanistically, SERPINE1 suppression attenuated neuronal apoptosis (lowered caspase‑3) in the DRG. This anti‑apoptotic effect was associated with inhibition of the AKT pathway, evidenced by decreased AKT phosphorylation in both DRG tissues from RTX‑treated rats and RTX‑stimulated SH‑SY5Y cells. Our findings demonstrate that SERPINE1 drives neuropathic pain in the RTX model and highlight its pharmacological inhibition as a promising therapeutic strategy.
Born under a cloud: Neurophysiological consequences of maternal smoking on neonatal sleep and EEG patterns.
Kavčič A, Demšar J, Štihec M … +2 more , Mlakar Ž, Soltirovska-Šalamon A
Brain Res Bull · 2026 Apr · PMID 41802577 · Publisher ↗
STUDY OBJECTIVES: Sleep is a fundamental physiological process critical for central nervous system maturation and optimal cognitive development. It is known that nicotine, as a psychoactive substance, alters central sign...
STUDY OBJECTIVES: Sleep is a fundamental physiological process critical for central nervous system maturation and optimal cognitive development. It is known that nicotine, as a psychoactive substance, alters central signaling pathways and sleep physiology. Therefore, smoke exposure during pregnancy and breastfeeding is believed to negatively impact the newborn's sleep architecture. METHODS: In this study, we investigated the effects of indirect prenatal and postnatal nicotine exposure on sleep architecture and quantitative EEG characteristics in 28 newborns (≥37 weeks postmenstrual age), including 14 newborns born to mothers who smoked, and 14 newborns born to non-smoking mothers. Each newborn underwent a three-hour observational sleep assessment and a 64-channel EEG recording. We compared the duration of sleep stages and quantitative EEG parameters between the two groups. RESULTS: Newborns of smoking mothers spent a greater proportion of time in wakefulness and drowsiness and a reduced proportion in quiet sleep. Quantitative EEG analysis revealed that these newborns exhibited increased power in the theta and alpha frequency bands, decreased power in the delta frequency band, elevated spectral edge frequency (SEF 90), reduced global brain network efficiency in the alpha frequency band, and diminished fronto-temporal connectivity in the right hemisphere within the delta frequency band. CONCLUSIONS: Our findings indicate that maternal smoking alters sleep patterns and brain activity in newborns, which could potentially have a long-term influence on central nervous system development in infancy and childhood.
The role of the Toll-like receptor family in stroke: functions, mechanisms and therapeutic targets.
Tang H, Zhang Y, Liao D … +5 more , Hu J, Zhang M, Li S, Pu Y, Bai X
Brain Res Bull · 2026 Apr · PMID 41796908 · Publisher ↗
Toll-like receptors (TLRs) are pivotal pattern recognition receptors in the innate immune system, primarily responsible for detecting pathogen-associated molecular patterns (PAMPs) and damage-associated molecular pattern...
Toll-like receptors (TLRs) are pivotal pattern recognition receptors in the innate immune system, primarily responsible for detecting pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). This review comprehensively examines the dual role of TLRs in stroke pathophysiology, wherein they exacerbate inflammatory brain injury yet also harbor neuroprotective potential. We delve into the core signaling mechanisms, specifically the MyD88-dependent and TRIF-dependent pathways, and evaluate their relevance as therapeutic targets. Furthermore, we synthesize emerging insights into novel regulators of TLR activity, including dietary components via the gut-brain axis and exosome-mediated intercellular communication. By integrating evidence from other inflammatory diseases, we propose targeted strategies to balance the detrimental and beneficial effects of TLR activation. The therapeutic potential of TLR agonists, antagonists, and combination therapies is critically appraised. Finally, we delineate future research priorities, including the optimization of TLR modulation, exploration of combination therapies, and cross-disease mechanistic studies, to fully realize the translational promise of TLRs in stroke therapy.
Effects and mechanisms of cannabidiol in attenuating orofacial inflammatory pain and ameliorating pain-related affective deficits.
Wang W, Xie G, Xu B … +7 more , Xie J, Cao D, Song X, Zou W, Wu N, Li J, Han X
Brain Res Bull · 2026 Apr · PMID 41796907 · Publisher ↗
BACKGROUND/OBJECTIVES: Orofacial inflammatory pain remains a significant clinical challenge due to the lack of effective therapeutic agents that specifically target its complex pathophysiology. Conventional analgesics of...
BACKGROUND/OBJECTIVES: Orofacial inflammatory pain remains a significant clinical challenge due to the lack of effective therapeutic agents that specifically target its complex pathophysiology. Conventional analgesics often provide inadequate relief and fail to address the profound negative affective states that frequently accompany chronic pain, further diminishing patients' quality of life. This study evaluated the therapeutic potential of cannabidiol (CBD) in mitigating sensory and affective dimensions of inflammatory pain and elucidated its underlying mechanisms. METHODS: Acute orofacial inflammatory pain was induced via subcutaneous formalin injection into the upper lip of mice. Chronic inflammatory pain and associated negative affect were modeled using intraplantar injection of complete Freund's adjuvant (CFA). A comprehensive behavioral battery-including von Frey filament testing, open field test, elevated plus maze, forced swim test, tail suspension test, sucrose preference test, and Y-maze-was employed to assess nociception and affective states. Mechanistic studies involved RT-qPCR, ELISA, LC-MS/MS, immunofluorescence and in vivo fiber photometry was employed to examine inflammatory, oxidative, endocannabinoid, and serotonergic pathways. RESULTS: Local administration of CBD significantly suppressed formalin-induced acute orofacial pain, specifically attenuating Phase II inflammatory sensitization. At the peripheral level, CBD downregulated FAAH and PGE2, reduced levels of pro-inflammatory cytokines (IL-1β, TNF-α) and oxidative stress markers, and increased levels of endocannabinoids in the blood-effects mediated primarily through CB2 receptor activation. Central actions of CBD were evidenced by reduced neuronal activation (c-Fos) in the spinal trigeminal nucleus caudalis (Sp5C) and anterior cingulate cortex, as well as increased anandamide (AEA) in the Sp5C and periaqueductal gray, which were mediated through CB1 receptor signaling. In the CFA-induced chronic pain model, systemic CBD administration not only alleviated mechanical allodynia but also markedly ameliorated anxiety- and depression-like behaviors and restored cognitive performance. Fiber photometry further revealed that CBD normalized deficits in serotonin transient activity in the central amygdala. CONCLUSIONS: CBD exerts robust multi-dimensional therapeutic effects across sensory, affective, and cognitive domains in inflammatory pain models. The findings underscore the translational potential of CBD as a novel therapeutic strategy for comprehensive management of orofacial pain and pain-related debilitating emotional comorbidities.
Epigallocatechin gallate ameliorates brain injuries after intracerebral hemorrhage by inhibiting ferroptosis through upregulation of Nrf2-Keap1 pathway.
Zhou SY, Guo ZN, Sun YY … +5 more , Jia WB, Zhu HJ, Liu J, Qu Y, Jin H
Brain Res Bull · 2026 Apr · PMID 41796906 · Publisher ↗
Intracerebral hemorrhage (ICH) has high mortality and disability with limited efficient therapies. The inhibition of ferroptosis is implicated in the prognosis of ICH. Epigallocatechin gallate (EGCG) has iron chelating,...
Intracerebral hemorrhage (ICH) has high mortality and disability with limited efficient therapies. The inhibition of ferroptosis is implicated in the prognosis of ICH. Epigallocatechin gallate (EGCG) has iron chelating, anti-inflammatory and free radical scavenging properties, which connected with Nrf2-Keap1 pathway in previous researches. Our investigation aimed to identify the role of EGCG on ferroptosis in ICH rats and the underlying mechanisms through Nrf2-Keap1 pathway. In this study we observed that EGCG treatment effectively reduced hematoma volume, cellular destruction of brain tissue and ferroptosis in neuronal cells, and improved neurobehavioral outcomes in rat model of ICH. Our further studies showed that EGCG promoted the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), stimulated Nrf2-Keap1 complex releasing Nrf2 and promoted the translocation of Nrf2 from the cytoplasm to the nucleus, and regulated the downstream ferroptosis-regulated proteins to inhibit ferroptosis, while Nrf2 inhibitor reversed the anti-ferroptosis effect, suggesting that EGCG inhibit ferroptosis by upregulating Nrf2. Moreover, ultilizing the in vitro ICH model, we revealed that when Keap1 is silenced, the regulation of ferroptosis-related mRNA by EGCG through Nrf2 was enhanced, which is direct opposite of the Nrf2 silencing result, indicating that Nrf2-Keap1 pathway plays an important role in EGCG treatment after ICH. Our study confirmed for the first time that EGCG could reduce the iron deposition by regulating downstream ferroptosis-related proteins via Nrf2-Keap1 pathway and inhibit ferroptosis after ICH, indicating that EGCG could be a potential drug for the treatment of ICH.
Irisin reduces neurodegeneration and neuroinflammation in the 6-hydroxydopamine rat model of Parkinson's disease.
Kamidai NM, Britto LRG, Ferreira AFF
Brain Res Bull · 2026 Apr · PMID 41796905 · Publisher ↗
Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects millions of individuals worldwide. With the number of cases expected to continue rising, there is an urgent need for new treatments. Irisi...
Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects millions of individuals worldwide. With the number of cases expected to continue rising, there is an urgent need for new treatments. Irisin, a peptide released by skeletal muscle during exercise, has been proposed as a key mediator of the beneficial effects of physical activity on the brain. However, its potential neuroprotective role in PD remains unclear. Here, we established a PD model by injecting 6-hydroxydopamine into the right striatum of rats, followed by irisin administration into both cerebral lateral ventricles. Motor behavior was assessed, and brain tissue was collected for analysis of nigral dopaminergic neuron numbers in the substantia nigra pars compacta (SNc), axonal terminal density in the striatum (CPu), and glial cell reactivity. Our findings showed that irisin-treated PD animals exhibited a higher number of dopaminergic neurons (n = 6/group; +11,8 ± 3,6%; p = 0.013), increased terminal density in the striatum (n = 6/group; +18,8 ± 5,1%; p < 0.001), and reduced the number of asymmetrical rotations when compared to untreated rats (n = 6/group; -73,6 ± 32,4%; p < 0.001). Additionally, irisin reduced microglia (n = 6/group; SNc: -27.8 ± 4.5%; p = 0.030; CPu: -25.1 ± 2.8%; p = 0.019) and astrocytes (n = 6/group; SNc: -30.9 ± 5.3%; p = 0.013; CPu: -55.0 ± 7.5%; p < 0.001) density and alleviated morphological alterations (n = 30 cells/group; increased number of branches and endpoints of glia cells; p < 0.01 in all cases) indicating an anti-inflammatory effect. These results suggest that irisin exerts neuroprotective and anti-inflammatory effects in the 6-hydroxydopamine rat model of PD, highlighting its potential as a promising tool in the management of PD.
Derivation of machine learning brain aging biomarkers for a set of forty thousand functional connectomes.
Honnorat N, Wang D, Ho NH … +10 more , Martinez D, Brandigampala SR, Heckbert SR, Bahrami M, Himali JJ, DeCarli C, Beiser A, Hughes TM, Seshadri S, Habes M
Brain Res Bull · 2026 Apr · PMID 41794271 · Full text
Various Magnetic Resonance Imaging modalities were developed to explore the brain. Among them, functional MRI is of key importance for studying brain activity and its neural substrates. Recent works have pointed out that...
Various Magnetic Resonance Imaging modalities were developed to explore the brain. Among them, functional MRI is of key importance for studying brain activity and its neural substrates. Recent works have pointed out that machine learning can use neuroimaging data to predict brain age. This approach is crucial not only for understanding the effects of aging but also for refining diagnostics because many chronic and neurodegenerative diseases appear as accelerated aging. Unfortunately, the prediction of brain age is particularly challenging for functional data due to the large dimension of the high-resolution connectomes usually derived to summarize the functional organization of the brain and their particular mathematical properties. In this work, we investigate the prediction of brain age from functional data on a large scale by creating a set of forty thousand functional connectomes via the processing of the resting-state fMRI scans of four cohort studies. This dataset is used to explore the ability of various connectome transformations and machine learning strategies to achieve accurate age predictions. We hope that our results will open the way for more reliable functional brain age measures.
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