Brain Research Bulletin[JOURNAL]
Sun
200 papers
Corrigendum to "Regulation of angiogenesis in cerebral ischemic rats through ceRNA networks and its impact on cerebral ischemic stroke prognosis" [Brain Res. Bull. 235 (2026) 111703].
Cao W, Wang M, Chai W … +5 more , Luo C, Wang Y, Zhou X, Li J, Li L
Brain Res Bull · 2026 Jun · PMID 42309899 · Publisher ↗
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Temporal patterns of neurostimulation efficacy in drug-resistant epilepsy: A systematic review and meta-analysis.
Tian Y, Wei Z, Liu T … +3 more , Kuang S, Zhai F, Liang S
Brain Res Bull · 2026 Jun · PMID 42303163 · Publisher ↗
OBJECTIVE: To systematically evaluate the temporal efficacy trajectories and relative performance of four neurostimulation modalities (open-loop Vagus Nerve Stimulation [ol-VNS], closed-loop VNS [cl-VNS], Deep Brain Stim...
OBJECTIVE: To systematically evaluate the temporal efficacy trajectories and relative performance of four neurostimulation modalities (open-loop Vagus Nerve Stimulation [ol-VNS], closed-loop VNS [cl-VNS], Deep Brain Stimulation [DBS], and Responsive Neurostimulation [RNS]) in patients with drug-resistant epilepsy (DRE). METHODS: Following PRISMA guidelines, PubMed, Cochrane Library, and Web of Science were searched for studies published during the modern neuromodulation era (2014-2024). We included original studies of patients without prior resective surgery who received single-device implantation. Data were mapped into four standardized follow-up windows (3, 6, 12-18, and ≥21 months). Pooled responder rates (RRs, ≥50% seizure reduction) were calculated using a random-effects model. A mixed-effects meta-regression was conducted to explore the interaction between device modality and time. RESULTS: A total of 94 unique cohorts were included. Overall RRs demonstrated a robust, time-dependent improvement: 38.7% (95% CI: 29.9%-48.4%) at 3 months, 48.2% (95% CI: 42.3%-54.1%) at 6 months, 59.3% (95% CI: 56.2%-62.2%) at 12-18 months and peaking at 61.8% (95% CI: 57.6%-65.7%) at ≥ 21 months. Meta-regression (Q = 96.3, p < 0.0001) confirmed a highly significant main effect for follow-up duration. While numerical differences existed among devices (with cl-VNS, DBS, and RNS showing higher overall efficacy baselines compared to ol-VNS), the interaction terms between device type and follow-up duration were universally non-significant (all p > 0.05), indicating that the current data do not provide statistical evidence of diverging temporal trajectories across modalities. SIGNIFICANCE: Across all modalities, neurostimulation produced a robust, time-dependent improvement in responder rates, with progressive gains consolidating over 1-2 years. This temporal pattern is consistent with the hypothesis of delayed network remodeling, though the present data cannot confirm a shared mechanism. Numerical differences in baseline responder rates across devices are more likely attributable to patient selection and indication bias than to intrinsic hardware superiority.
Nao Tan Qing exerts neuroprotection against traumatic brain injury via multi-targeted immunomodulation and neurorestoration.
He R, Liu Y, Xiao R … +5 more , Lin Y, Zhang N, Liu Z, Li Q, Chen X
Brain Res Bull · 2026 Jun · PMID 42289235 · Publisher ↗
BACKGROUND: Traumatic brain injury (TBI) is a devastating neurological disorder with long-term functional deficits and limited effective therapies, where secondary injury driven by dysregulated immunity and disrupted sig...
BACKGROUND: Traumatic brain injury (TBI) is a devastating neurological disorder with long-term functional deficits and limited effective therapies, where secondary injury driven by dysregulated immunity and disrupted signaling is pathogenic; Nao Tan Qing (NTQ), a Chinese herbal formula guided by the traditional principle of "resolving phlegm and inducing resuscitation" for "brain collateral obstruction", shows neuroprotective potential, but its role and mechanism in TBI treatment remain unclear. AIM: This study aimed to systematically investigate the neuroprotective effects of NTQ against TBI model mice and elucidate its underlying molecular mechanisms. METHODS: A controlled cortical impact (CCI) mouse model of TBI was established, and animals received NTQ treatment for 28 consecutive days. NTQ's neuroprotective efficacy was comprehensively evaluated via behavioral tests (functional recovery), cerebral blood flow imaging (vascular integrity), and electromyography (neural activity). Post-treatment inflammatory levels in TBI mice were assessed by quantifying inflammatory cytokine expression using quantitative real-time PCR and detecting microglial activation via immunofluorescence. Mechanistic exploration integrated network pharmacology, transcriptomics and bioinformatics analyses to identify NTQ's active components, potential targets, and associated pathways in TBI. RESULTS: In vivo experiments demonstrated that NTQ significantly improved behavioral outcomes, restored cerebral blood flow, and enhanced neural activity in TBI mice. Concurrent with these functional benefits, NTQ robustly suppressed neuroinflammation, as evidenced by reduced pro-inflammatory cytokine expression and attenuated microglial activation. Integrated network pharmacology and transcriptomic analyses confirmed that NTQ acts primarily through immune regulation after TBI, modifying key immune-related molecules and pathways. Specifically, NTQ intervention elicited pronounced downregulation of immune-inflammatory mediators, including Cd3g, Cd5, Cd8a, Epcam, Slamf7, Il16, Il17r, Il18rap, Cxcl9, Cxcr6, Tnfsf11, and Tnfsf15. Further mechanistic dissection identified six putative bioactive constituents of NTQ, including nicotinamide, curcumin, baicalin, chrysin, daidzein, and apigenin, which may remodel the intracerebral immune microenvironment after TBI through three core pathways: amine ligand-binding receptors, nuclear receptor meta-pathways, and arachidonic acid metabolism. CONCLUSION: Taken together, our integrated analyses demonstrate that NTQ exerts neuroprotective effects in TBI by modulating immune responses and suppressing neuroinflammation, thereby establishing NTQ as a promising multi-target therapeutic agent for TBI.
Corrigendum to "Exploring post‑stroke depression: Exosomal proteomics reveals underlying mechanisms and potential plasma biomarkers" [Brain Res. Bull. 242 (2026) 111940].
Yue X, Zhang M, Li J … +5 more , Zhang H, Zhang C, Li R, Ding N, Zhang P
Brain Res Bull · 2026 Jun · PMID 42288453 · Publisher ↗
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Molecular contextualization of the neural correlates of episodic memory.
Fang Q, Chen J, Zhang Y … +4 more , Cai H, Wang J, Zhu J, Yu Y
Brain Res Bull · 2026 Jun · PMID 42288179 · Publisher ↗
BACKGROUND: Considerable neuroimaging effort has been dedicated to investigate the neural correlates of episodic memory, but the micro-scale molecular mechanisms that underlie the macro-scale neuroimaging correlates of e...
BACKGROUND: Considerable neuroimaging effort has been dedicated to investigate the neural correlates of episodic memory, but the micro-scale molecular mechanisms that underlie the macro-scale neuroimaging correlates of episodic memory are still unclear. METHODS: Resting-state functional MRI data were obtained from a large cohort of 510 healthy young adults to calculate regional homogeneity (ReHo) to reflect spontaneous intrinsic brain activity. We then explored the relationship between California Verbal Learning Test-Ⅱ performance and ReHo across participants to delineate the neural substrates of episodic memory. Finally, we conducted the spatial relationship analyses between the neural correlates with gene expression and neurotransmitter atlases to further explore their potential genetic architecture and neurochemical underpinnings. RESULTS: Our analysis revealed a significant negative correlation between episodic memory and ReHo in the bilateral precuneus. Additional spatial correlation analyses revealed that the identified neural correlates of episodic memory were associated with expression of gene categories predominantly implicating signal transduction, immune system process, cellular metabolic process and anatomical structure development, as well as were linked to serotonin transporter. CONCLUSIONS: These findings may not only offer novel insights into the molecular substrates underlying the neural basis of episodic memory, but also help inform prevention and intervention strategies for individuals in at-risk and early phases of dementia.
Assessing the effect of long-term high altitude exposure on human brain function: A resting-state functional magnetic resonance imaging study.
Wang Z, Chen J, Dai X … +10 more , Wang F, Jin L, Dang L, Nianzha D, Yang J, Li W, Wang W, Niu J, Liu J, Li Q
Brain Res Bull · 2026 Jun · PMID 42288178 · Publisher ↗
OBJECTIVE: This study uses resting-state functional magnetic resonance imaging (fMRI) to understand and compare the effects of hypoxic conditions at high and ultra-high altitudes. METHODS: Regional homogeneity (ReHo) and...
OBJECTIVE: This study uses resting-state functional magnetic resonance imaging (fMRI) to understand and compare the effects of hypoxic conditions at high and ultra-high altitudes. METHODS: Regional homogeneity (ReHo) and degree centrality (DC) values were calculated and compared between 47 low-altitude (LA, <500 m), 39 high-altitude (HA, 1520 m), and 34 ultra-high-altitude (UHA, 3650 m) healthy adults. Correlations with heart rate and blood oxygen saturation (SpO₂) were analyzed. RESULTS: Compared to the LA group, the UHA/HA group had significantly lower ReHo values in the bilateral basal ganglia, prefrontal lobes (left/right), left paracentral lobule, and these were positively correlated with SpO₂. Conversely, ReHo values were significantly higher in the bilateral posterior occipital and left superior parietal lobes, and were negatively correlated with SpO₂. DC values were significantly lower in the left orbitofrontal cortex, bilateral pallidum and left inferior frontal gyrus, and were positively correlated with SpO₂. Synchronous decreases in ReHo and DC were found in the left prefrontal cortex, bilateral pallidum and putamen. CONCLUSION: In high-altitude environments, functional activity is decreased in the basal ganglia, prefrontal cortex, and hippocampus, is accompanied by a compensatory increase in the occipital and superior parietal lobes. Concurrent reductions in DC and ReHo within the left prefrontal cortex, bilateral pallidum and putamen might serve as biomarkers for high-altitude hypoxic functional alterations and aid early detection and intervention of hypoxia-induced brain damage.
Multi-state neural dynamics encode antidepressant response: Fusion of resting and task networks.
Peng Y, Yu Y, Zhou N … +9 more , Fan X, Jiang L, He G, Li C, Yi C, Yao D, Shi K, Li F, Xu P
Brain Res Bull · 2026 Jun · PMID 42276172 · Publisher ↗
Although antidepressants demonstrate broad efficacy for major depressive disorder (MDD), treatment responses vary considerably across individuals. Consequently, pretreatment identification of eventual Responders (Res) ve...
Although antidepressants demonstrate broad efficacy for major depressive disorder (MDD), treatment responses vary considerably across individuals. Consequently, pretreatment identification of eventual Responders (Res) versus Non-responders (Non), alongside patient-specific prediction of symptomatic improvement under a given regimen, remains clinically imperative. Capitalizing on the complementary information provided by resting and task EEGs regarding MDD-related brain abnormalities, we pooled baseline data from four distinct centers to construct brain networks differentiating Res from Non, with subsequent extraction of spatial topological features. By fusing the spatial topological features (resting and task), we classified Res versus Non and forecasted long-term medication response. Baseline features distinguished Res from Non with 96.30% accuracy and enabled reliable patient-specific prediction of eight-week outcomes. Collectively, these results indicated that resting and task EEGs provided synergistic information, enhancing both diagnostic classification and prognostic prediction. This multidimensional approach provided a promising translational framework that, with further validation, may guide personalized antidepressant selection and potentially accelerate treatment response and reduce healthcare costs.
Characterizing excitatory-inhibitory balance in conscious rodents via paired pulse TMS.
Sharma G, Jain S, Kochhar KP
Brain Res Bull · 2026 Jun · PMID 42276171 · Publisher ↗
BACKGROUND: Transcranial magnetic stimulation is an established neuromodulation technique; however, its molecular and cellular mechanisms is still unknown. Most of the TMS studies in rodents have been conducted in anesth...
BACKGROUND: Transcranial magnetic stimulation is an established neuromodulation technique; however, its molecular and cellular mechanisms is still unknown. Most of the TMS studies in rodents have been conducted in anesthetized conditions, typically using single-pulse paradigms. NEW METHOD: We systematically evaluated both single-pulse and paired-pulse TMS parameters in unanaesthetised rats. All TMS protocols were recorded in awake and restrained rats. Motor thresholds & Motor-Evoked Potentials were determined by single-pulse stimulation. Paired-pulse protocols, including short-interval intracortical inhibition (SICI, 1-5 ms), intracortical facilitation (ICF, 20 ms), short-interval intracortical facilitation (SICF, 3 ms), and long-interval intracortical inhibition (LICI, 100 ms) were used to assess intracortical circuitry. RESULTS: The motor threshold (21.58 ± 2.9%) and latency (3.66 ± 0.46 ms) of MEPs obtained with a single pulse paradigm demonstrated consistent responses. The response to paired stimulation for SICI (ISI-2ms) was 218% higher than the unconditioned response while ICF, SICF, and LICI showed a 42% increase, 235% increase, and ∼90% decrease respectively. COMPARISON WITH EXISTING METHODS: In contrast to previous rodent TMS investigations conducted under anesthesia, this work recorded single-pulse and paired-pulse TMS measures in unanesthetized rats. This is the first report of paired-pulse TMS measurements in awake rats. Single-pulse TMS produced localized, stimulus-locked forelimb MEPs, similar to human research; in paired-pulse paradigms, ICF, LICI, and SICF showed human-like patterns, whereas SICI showed facilitation rather than inhibition. CONCLUSIONS: TMS single and paired pulse paradigms can be recorded and replicated in rodents in unanaesthetized state establishing a translational platform to investigate the mechanism of TMS.
Excessive mitochondrial fission induces postoperative delirium in mice undergoing high-altitude deacclimatization by exacerbating neuroinflammation and synaptic injury.
Ma H, Zhao Y, Yin M … +3 more , Ran X, Du Y, Zhou S
Brain Res Bull · 2026 Jun · PMID 42269727 · Publisher ↗
Postoperative delirium (POD) is a common complication after surgery. High-altitude deacclimatization (HADA), a physiological adaptation process, is associated with pathophysiological changes that may increase POD suscept...
Postoperative delirium (POD) is a common complication after surgery. High-altitude deacclimatization (HADA), a physiological adaptation process, is associated with pathophysiological changes that may increase POD susceptibility. However, the underlying molecular mechanisms remain poorly understood. This study investigated the role of mitochondrial dynamics in POD pathogenesis in mice undergoing HADA and explored the neuroprotective effects of the mitochondrial fission inhibitor, Mdivi-1. C57BL/6 mice were subjected to simulated high-altitude exposure for 4 weeks, followed by anesthesia and surgery to induce a POD model. Mice undergoing HADA and surgery exhibited significant postoperative delirium-like behaviors. These behavioral deficits were accompanied by excessive mitochondrial fission, exacerbated neuroinflammation (evidenced by microglial and astrocyte activation), and synaptic injury within the hippocampus. Notably, pretreatment with Mdivi-1 effectively attenuated these pathological changes. It reduced mitochondrial fission, suppressed neuroinflammation, restored key synaptic proteins, and consequently, alleviated the postoperative delirium-like behaviors. In conclusion, this study suggests that excessive mitochondrial fission contributes to HADA-associated POD, potentially via exacerbating neuroinflammation and synaptic damage. Targeting mitochondrial fission presents a potential therapeutic strategy to prevent this serious postoperative complication.
Reprint of: Effect of perioperative preemptive analgesia on hippocampal GABAA receptor α1/α5 balance in aged mild cognitive impairment rats.
Ren H, Zhang L, Yang C … +3 more , Wang X, Liu X, Wang H
Brain Res Bull · 2026 Jun · PMID 42263830 · Publisher ↗
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a frequent complication in elderly patients that delays recovery and increases long-term health risks. Preemptive analgesia may alleviate surgery-induced inflamma...
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a frequent complication in elderly patients that delays recovery and increases long-term health risks. Preemptive analgesia may alleviate surgery-induced inflammation and central sensitization, but its role in improving postoperative neurocognitive disorder (PND) through modulation of hippocampal Gamma-aminobutyric acid type A (GABAA) receptor α1/α5 subunits in aged rats with mild cognitive impairment (MCI) remains unclear. METHODS: Twenty-two-month-old male Sprague-Dawley (SD) rats were used to establish the MCI model via severe bilateral common carotid artery stenosis. After successful modeling, rats were randomly divided into five groups: Control (Con, only tibial exposure and suturing), Surgery (intravenous 0.9% normal saline), Nalbuphine (Nal, 10 mg/kg), Dezocine (Dez, 10 mg/kg), and Sufentanil (Suf, 10 μg/kg). Drugs were administered 1 h preoperatively. Anesthesia was induced with a subanesthetic regimen (0.7 MAC sevoflurane + 1.2 μg/ml propofol, validated previously), followed by tibial fracture open reduction and internal fixation (ORIF). Postoperative evaluations included pain indicators (paw withdrawal latency [PWL], paw withdrawal threshold [PWT]), cognitive function, and hippocampal GABAA α1/α5 and PSD95 expression levels. RESULTS: This study examined preemptive analgesia's effects on postoperative outcomes in aged MCI rats. Behavioral tests (PWL, PWT) showed it alleviated postoperative pain, while Y-maze and novel object recognition tests improved anesthesia/surgery-related cognitive decline on postoperative days 1, 3, 7. Western blot revealed ORIF model rats had reduced hippocampal GABAA α1/α5 ratio on postoperative days 1, partial recovery on postoperative days 3, 7, abnormal balance on postoperative days 7, and sustained PSD95 downregulation. Preemptive nalbuphine, dezocine, or sufentanil prevented GABAA α1/α5 imbalance and attenuated PSD95 reduction. HE staining indicated mitigated hippocampal neutrophil infiltration and structural damage induced by anesthesia/surgery. CONCLUSION: Perioperative preemptive analgesia effectively reduces postoperative pain and improves neurocognitive function in aged MCI rats, via a mechanism linked to maintaining hippocampal GABAA receptor α1/α5 subunit balance and ameliorating hippocampal neural dysfunction. This study provides foundational evidence for clinical postoperative pain management and cognitive protection in elderly MCI patients.
Multi-omics analysis identifies the miR-28a-5p/SerpinA3N/PI3K/AKT axis as a regulator of microglial neuroinflammation and cognitive decline in Alzheimer's disease.
Liu Y, Fu R, Ge C … +3 more , Long Z, Wang H, He G
Brain Res Bull · 2026 Jun · PMID 42263829 · Publisher ↗
INTRODUCTION: Neuroinflammation driven by microglial dysfunction is a central pathological feature of Alzheimer's disease (AD). However, the precise regulatory networks, particularly those involving post-transcriptional...
INTRODUCTION: Neuroinflammation driven by microglial dysfunction is a central pathological feature of Alzheimer's disease (AD). However, the precise regulatory networks, particularly those involving post-transcriptional control by microRNAs (miRNAs), remain incompletely understood. METHODS: We performed integrated multi-omics analysis (miRNA-seq, mRNA-seq, TMT-based proteomics) on hippocampal tissues from APP/PS1 and wild-type mice. Functional validation was conducted in vitro using BV2 microglial cells and in vivo via stereotaxic injection of miR-28a-5p agomir in APP/PS1 mice, combined with molecular, inflammatory, and behavioral assessments. RESULTS: Multi-omics integration identified SerpinA3N as a core upregulated target in a high-confidence miRNA-mRNA-protein network, with good discriminative ability across AD mouse models. SerpinA3N promoted microglial M1 polarization, enhanced TNF-α/IL-1β/IL-6 secretion, and suppressed the M2 marker Arg1 by inhibiting the PI3K/AKT pathway. miR-28a-5p was identified as a direct upstream repressor of SerpinA3N, and its downregulation in AD models contributed to SerpinA3N upregulation. Rescue experiments confirmed SerpinA3N mediates miR-28a-5p's neuroinflammatory effects. In vivo, miR-28a-5p overexpression reduced SerpinA3N, restored PI3K/AKT activity, alleviated neuroinflammation, and improved learning/memory deficits in APP/PS1 mice. CONCLUSION: Our study defines a novel miR-28a-5p/SerpinA3N/PI3K/AKT regulatory axis governing pro-inflammatory microglial activation and cognitive function in AD. SerpinA3N and miR-28a-5p show potential as preclinical research biomarkers in AD.
Unveiling the multi-target mechanisms of Zuo Gui Wan in Alzheimer's disease: An integrated study combining network pharmacology, Mendelian Randomization, and molecular docking.
Ma Z, Yang Z, Xiao Z … +2 more , Huang B, Wang X
Brain Res Bull · 2026 Jun · PMID 42259474 · Publisher ↗
PURPOSE: Zuo Gui Wan (ZGW), a traditional Chinese medicine formula, shows neuroprotective potential, but the mechanisms underlying its therapeutic effects on Alzheimer's disease (AD) remain unclear. This study aims to id...
PURPOSE: Zuo Gui Wan (ZGW), a traditional Chinese medicine formula, shows neuroprotective potential, but the mechanisms underlying its therapeutic effects on Alzheimer's disease (AD) remain unclear. This study aims to identify the active components, molecular targets, and biological pathways of ZGW in AD using an integrated systems pharmacology approach combining network analysis and causal inference. METHODS: Active ZGW ingredients and targets were sourced from TCMSP and BATMAN-TCM. Summary-data-based Mendelian Randomization (SMR) and colocalization analyses integrated eQTL and AD GWAS data to identify gene-AD associations. Network pharmacology, GO/KEGG enrichment, PPI analysis, and molecular docking were conducted. Selected targets were examined by CCK-8 assay and Western blot in an Aβ25-35-induced SH-SY5Y neuronal injury model treated with ZGW-containing rat serum. RESULTS: We identified 134 bioactive ZGW compounds targeting 391 AD-related genes. SMR prioritized six targets (ACE, SRC, STAT1, LEP, EGFR, and MAPK3) associated with neuroinflammatory and cardiovascular pathways. Molecular docking suggested strong interactions between key compounds and targets, notably berberine with SRC (-10.53 kcal/mol) and compound 1 (PubChem CID: 137704703) with MAPK3 (-17.22 kcal/mol). In the Aβ-induced neuronal model, ZGW-containing serum partially restored cell viability, reduced ERK1/2 and STAT1 phosphorylation, and increased ACE expression. CONCLUSION: Integrated computational analyses prioritized six potential AD-related targets of ZGW, including ACE, SRC, STAT1, LEP, EGFR, and MAPK3. Preliminary cellular experiments further supported the involvement of MAPK3/ERK and STAT1 signaling, with increased ACE expression observed after ZGW treatment. These findings provide mechanistic insight into the potential therapeutic effects of ZGW in AD.
Esketamine alleviates trigeminal neuralgia and anxiety-like behaviors in mice by inhibiting RIPK1/RIPK3/MLKL-mediated necroptosis.
Dong R, Liu J, Shen Y … +6 more , Wei M, Liu J, Liu P, Liu X, Zhao S, Wang X
Brain Res Bull · 2026 Aug · PMID 42250657 · Publisher ↗
BACKGROUND: Trigeminal neuralgia (TN) is a debilitating orofacial pain condition frequently complicated by anxiety and depression, forming a self-reinforcing pain-affect cycle with limited therapeutic options. METHODS: A...
BACKGROUND: Trigeminal neuralgia (TN) is a debilitating orofacial pain condition frequently complicated by anxiety and depression, forming a self-reinforcing pain-affect cycle with limited therapeutic options. METHODS: A TN mouse model with anxiety-like behavior was established using partial infraorbital nerve transection (pIONT). Esketamine (ES) (5 or 10 mg/kg) was administered intraperitoneally from postoperative day 14 for five days. Pain thresholds, anxiety-like behaviors, and despair-like behaviors were assessed. Neuronal injury and necroptosis-related molecules in the trigeminal ganglion and hippocampus were evaluated by histology, immunofluorescence, qRT-PCR, and western blotting. A necroptosis activator was used to verify the pathway involvement. RESULTS: ES dose-dependently alleviated mechanical allodynia and anxiety-like behaviors in pIONT mice. ES treatment ameliorated neuronal damage, increased Nissl body content, and restored dendritic spine density in the hippocampal dentate gyrus region. Mechanistically, pIONT induced the significant upregulation of RIPK1, RIPK3, and MLKL at both the mRNA and protein levels in the hippocampus, with increased colocalization of RIPK3 and MLKL with NeuN-positive neurons. Administration of ES markedly suppressed these changes. Co-administration of a necroptosis activator reversed the analgesic, anxiolytic, and neuroprotective effects of ES, confirming that the therapeutic effects are mediated via inhibition of the RIPK1/RIPK3/MLKL necroptosis pathway. CONCLUSIONS: ES alleviated pain and anxiety in pIONT mice by inhibiting hippocampal necroptosis via the RIPK1/RIPK3/MLKL pathway, highlighting necroptosis as a key mechanism in TN-associated emotional disorders and supporting ES repurposing as a dual-acting therapeutic strategy.
Non-invasive mapping of glioblastoma mass effect using digital volume correlation combined with MRI: Proof-of-concept.
Abbad Andaloussi M, Lontsie Zanmene M, Lavigne T … +4 more , Lubrano V, Urcun S, Hild F, Bordas S
Brain Res Bull · 2026 Aug · PMID 42250656 · Publisher ↗
Conventional imaging techniques lack the ability to quantify localized brain tissue displacements and strains associated with Glioblastoma (GBM) growth and treatment response. In this proof-of-concept study, a non-invasi...
Conventional imaging techniques lack the ability to quantify localized brain tissue displacements and strains associated with Glioblastoma (GBM) growth and treatment response. In this proof-of-concept study, a non-invasive approach is presented to map displacement and strain fields using Digital Volume Correlation (DVC) on serial T1-Gadolinium MRI scans of a GBM patient over 63 days. A comprehensive MRI pre-processing pipeline was applied, followed by the generation of meshes segmenting healthy brain tissue, tumor, and ventricles. Three distinct regularization scenarios were implemented to capture localized tissue deformations. DVC results were qualitatively compared to MRI anatomical changes and quantitatively validated against symmetric normalization (SyN) registration. DVC outperforms conventional SyN registration in capturing heterogeneous tissue deformations. These preliminary findings suggest greater sensitivity to biomechanical alterations induced by tumor progression and demonstrate the potential of DVC-augmented imaging to serve as a quantitative biomarker for assessing GBM-induced brain mechanics. By generating maps of ventricle deformation, the method provides new opportunities for early detection and monitoring of elevated intracranial pressure (ICP) in GBM patients.
The role of Th17 cells in the pathogenesis of Parkinson's disease: From immune dysregulation to neurodegeneration.
Zhao J, Liang H, Bi Y
Brain Res Bull · 2026 Aug · PMID 42248537 · Publisher ↗
Parkinson's disease (PD) is a neurological disorder with the fastest global growth rate, marked by the deterioration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of α-synuclei...
Parkinson's disease (PD) is a neurological disorder with the fastest global growth rate, marked by the deterioration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of α-synuclein (α-syn) deposits in neuronal cells. This progressive neurodegenerative disorder impacts both peripheral organs and the central nervous system (CNS), with neuroinflammation playing a pivotal role in its pathophysiological mechanisms. Research indicates that the adaptive immune response, particularly neuroinflammation mediated by T helper 17 (Th17) cells, a subset of CD4⁺ T cells characterized primarily by their secretion of interleukin-17 (IL-17), is strongly implicated in the pathological process of PD. Despite significant recent advances in mechanistic and translational research, a comprehensive synthesis integrating Th17 activation mechanisms, pathogenic crosstalk with other immune subsets, and the resultant Th17/Treg imbalance is currently lacking, thereby hindering the translation of immunological findings into targeted therapeutic interventions. This review considers in detail the mechanistic roles of Th17 cells in PD, including their activation mechanisms, pathogenic pathways, crosstalk with other immune cell subsets, and immune dysregulation with Tregs. Our analysis aims to offer an integrated perspective on the immunological mechanisms underlying Th17 cells in PD, thereby facilitating a deeper comprehension of disease pathogenesis and guiding the development of future immune-based therapeutic strategies.
Identification and validation of growth hormone-reactive gene markers in brain tissue during the recovery period of stroke.
Han W, Ke J, Cui M
Brain Res Bull · 2026 Jun · PMID 42248536 · Publisher ↗
BACKGROUND: Functional recovery after ischemic stroke is often incomplete, highlighting the need for therapies that enhance neural repair. Growth hormone (GH) has shown potential neuroprotective effects, but its molecula...
BACKGROUND: Functional recovery after ischemic stroke is often incomplete, highlighting the need for therapies that enhance neural repair. Growth hormone (GH) has shown potential neuroprotective effects, but its molecular mechanisms in the post-stroke brain remain unclear. This study aimed to identify and validate GH-responsive gene markers and explore their association with functional recovery. METHODS: A middle cerebral artery occlusion (MCAO) rat model was established. RNA sequencing of peri-infarct tissues was performed on days 7, 14, and 28 after recombinant human GH (rhGH) treatment to identify differentially expressed genes and enriched pathways. Neurological and behavioral assessments were conducted 14 days after rhGH administration. Histological staining was used to evaluate infarct volume, cortical damage, and neuronal apoptosis. Expression of GH-responsive genes was examined by RT-PCR and Western blot. Oxidative stress and inflammatory markers were measured by ELISA. Pathway specificity was verified using LY294002, a PI3K/Akt/mTOR pathway inhibitor. RESULTS: rhGH treatment induced a marked transcriptional response, peaking on day 14. rhGH upregulated growth-associated protein 43 (GAP43), insulin-like growth factor-1 (IGF1), brain-derived neurotrophic factor (BDNF), synapsin-1 (SYN1), and vascular endothelial growth factor (VEGFA), while downregulating matrix metalloproteinase-9 (MMP9). rhGH significantly improved neurological outcomes, reduced infarct-related histopathological damage, and inhibited neuronal apoptosis. It also suppressed oxidative stress and inflammatory responses. Moreover, rhGH activated the PI3K/Akt/mTOR pathway, whereas LY294002 attenuated its neuroprotective effects. CONCLUSION: GH promotes neurological recovery after ischemic stroke by reducing inflammation and oxidative stress and activating the PI3K/Akt/mTOR signaling pathway.
N-acetyltransferase 10 participates in dopaminergic neuronal apoptosis in Parkinson's disease through ac4C-mediated transcriptomic regulation.
Xue J, Jiang D, Zhai Y … +2 more , Wang Z, Tang Y
Brain Res Bull · 2026 Aug · PMID 42242584 · Publisher ↗
Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. However, the underlying pathogenic mechanisms of PD remain incompletely defined, and effective treatments...
Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. However, the underlying pathogenic mechanisms of PD remain incompletely defined, and effective treatments are lacking. N-acetyltransferase 10 (NAT10) catalyzes N4-acetylcytidine (ac4C) modification of mRNA, a process crucial for mRNA stability and translational efficiency. However, whether NAT10-mediated ac4C modification contributes to PD and the molecular mechanisms underlying its involvement remain unclear. This study aimed to investigate the role of NAT10 and its ac4C-mediated transcriptomic regulation in PD and to elucidate the underlying molecular mechanisms. In vivo and in vitro PD models were generated, and the expression levels of NAT10 and global ac4C modification were assessed. Experimental results revealed that NAT10 expression and global RNA ac4C levels were significantly increased in PD models and were positively associated with dopaminergic neuronal apoptosis. Knockdown of NAT10 reduced dopaminergic neuronal apoptosis, while overexpression exacerbated this apoptosis. Mechanistically, NAT10 may enhance ac4C modification of pyruvate dehydrogenase kinase 1 (PDK1) mRNA, thereby increasing its stability and translational efficiency. Upregulated PDK1 promoted phosphorylation of the pyruvate dehydrogenase (PDH) E1α subunit, leading to reduced PDH complex activity, decreased adenosine triphosphate (ATP) production, and increased lactate accumulation, possibly contributing to dopaminergic neuronal apoptosis. Importantly, treatment with the NAT10-targeting compound Remodelin alleviated dopaminergic neuron loss and improved motor deficits in PD models. Collectively, these findings suggest that NAT10/ac4C-associated dysfunction of the PDK1/PDH axis contributes to altered energy metabolism and dopaminergic neuronal apoptosis in PD models, supporting NAT10 as a potential intervention target for PD.
Subacute frontoinsular-cingulate tract changes in unvaccinated COVID-19 survivors: A tract-based spatial statistics study of diffusion tensor imaging.
Arendt CT, Klinsing S, Becke E … +9 more , Fahim M, Koepsell J, Jahnke K, Ronellenfitsch MW, Vehreschild MJ, Shrestha M, Deichmann R, Schüre JR, Hattingen E
Brain Res Bull · 2026 Aug · PMID 42235760 · Publisher ↗
BACKGROUND AND OBJECTIVES: Post-recovery brain changes following Coronavirus Disease 2019 (COVID-19) have been reported using various imaging techniques. The objective was to identify microstructural abnormalities betwee...
BACKGROUND AND OBJECTIVES: Post-recovery brain changes following Coronavirus Disease 2019 (COVID-19) have been reported using various imaging techniques. The objective was to identify microstructural abnormalities between groups in specific fiber tracts using tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI), along with region-specific quantitative analysis of T1 relaxation times (qT1) and volumes. METHODS: This single-center, prospective, observational case-control study included adults ≥ 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen positivity, matched by age and gender with seronegative controls, and categorized by initial infection severity and an age cut-off of 40. MRI included: (1) 2 mm DTI generating fractional anisotropy (FA), mean (MD), radial (RD), and axial diffusivity (AD) maps; (2) two 3D 1 mm³ gradient-echo datasets for mapping T1 relaxation times (qT1) and creating synthetic high-resolution T1 images; (3) 3 mm 2D fluid-attenuated inversion recovery (FLAIR) images. Baseline characteristics and neuro(psycho)logical assessments including olfactory function, Beck Depression Inventory, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, EQ-5D, and Montreal cognitive assessment were also recorded. RESULTS: Between November 2020 and December 2021, 145 unvaccinated subjects (median age, 46 years [IQR, 33.5-53]; 73 women) were consecutively evaluated. TBSS showed no significant FA differences between all 69 cases and 76 age- and sex-matched controls. However, participants ≥ 40 years that required hospitalization due to COVID-19 (n = 23) had decreased FA, increased RD, and reduced qT1 values (all P ≤ 0.001) in specific voxels compared to controls ≥ 40 years (n = 47). These microstructural measures appeared in predominantly right-sided lateral orbitofrontal, frontal inferior, anterior insular, and rostral anterior cingulate white matter (WM) regions, without visually detectable abnormalities or region-specific volume loss in WM or cortical gray matter. This subgroup also showed significantly higher presence of fatigue, depressive symptoms, poorer sleep quality and reduced health-related quality of life. DISCUSSION: Advanced MRI revealed microstructural abnormalities along frontoinsular-cingulate WM fiber tracts in unvaccinated participants aged ≥ 40 with a history of COVID-19 requiring hospitalization. These findings may suggest ongoing reduced fiber integrity and persistent oxidative stress within the salience network, potentially contributing to functional sequelae.
Handgrip strength relates to corticospinal tract microstructure in older adults.
Solis K, Shao M, Langley J … +3 more , Seitz AR, Hu X, Bennett IJ
Brain Res Bull · 2026 Aug · PMID 42235759 · Publisher ↗
Handgrip strength, an indicator of physical frailty, is lower in older age and in females than males, but its neural correlates remain understudied. The present study assessed whether handgrip strength relates to microst...
Handgrip strength, an indicator of physical frailty, is lower in older age and in females than males, but its neural correlates remain understudied. The present study assessed whether handgrip strength relates to microstructure of the corticospinal tract (CST), a white matter pathway for voluntary motor control that also degrades with age. Healthy older adults (n = 78; 60-87 years) underwent diffusion-weighted magnetic resonance imaging to measure CST microstructure. They also completed three sessions of handgrip squeezes on a dynamometer from which mean, maximum, and variability (standard deviation, coefficient of variation) measures of their maximum voluntary contractions (MVC) were calculated. Analyses replicated effects of age and sex on handgrip strength and CST microstructure. Independent of age and sex, results revealed that better handgrip strength (higher mean and maximum MVC) was related to better CST microstructure (higher intracellular, lower mean diffusivity). Finding that the CST is a neural correlate of handgrip strength suggests that its degradation may be a marker of physical frailty in older adults.
PVN oxytocin - VTA neurocircuit modulate the emergence of general anesthesia induced by isoflurane in mice.
Du T, Li Q, Jia L … +5 more , He J, Yin J, Ma K, Yin J, Li Y
Brain Res Bull · 2026 Aug · PMID 42229639 · Publisher ↗
AIMS: The paraventricular nucleus of the hypothalamus (PVN) plays a pivotal role in regulating consciousness transition, in which oxytocin neurons (OXT) are involved. The ventral tegmental area (VTA) is one of the import...
AIMS: The paraventricular nucleus of the hypothalamus (PVN) plays a pivotal role in regulating consciousness transition, in which oxytocin neurons (OXT) are involved. The ventral tegmental area (VTA) is one of the important projection regions of the PVN, closely related to the transition of anesthesia status. However, whether oxytocin neurons in the PVN and PVN-VTA pathway contribute to isoflurane-induced anesthetic state transitions is unknown. METHODS: Immunostaining and fiber photometry were used to verify the neuronal activity during the isoflurane anesthesia. Chemogenetic or optogenetic stimulation of PVN OXT neurons was then performed to verify their role in anesthesia, along with electroencephalography and behavioral recording. RESULTS: We found that isoflurane decreased the activity of PVN oxytocin neurons. Then, activation of PVN oxytocin neurons caused a reduction of the anesthesia emergence time with an increase in arousal-related power. Optogenetic inhibition of PVN oxytocin neurons caused a more isoflurane anesthesia recovery time along with an increase in low-frequency power. Similarly, activation or inhibition of PVN-VTA neural pathway produced similar effects. CONCLUSIONS: Collectively, oxytocin neurons in the PVN certainly modulate isoflurane anesthesia, in which the PVN-VTA pathway plays a significant and unique part.
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