Brain Res. [JOURNAL]
Sun
200 papers
Profiling tRNA-derived fragments in LPS-induced microglia and their influence on immune response.
Arioz BI, Binokay L, Kocakusak H … +2 more , Karakülah G, Genc S
Brain Res · 2026 Oct · PMID 42314895 · Publisher ↗
The resident macrophages of the brain, microglia, react to immunological responses and preserve homeostasis in the central nervous system. Microglia play a critical role in neuroinflammation, which occurs in neurological...
The resident macrophages of the brain, microglia, react to immunological responses and preserve homeostasis in the central nervous system. Microglia play a critical role in neuroinflammation, which occurs in neurological and neurodegenerative diseases. Microglial responses are associated with neurodegenerative diseases, autoimmune diseases, and cancer, and therefore require strict regulation. Transfer RNA-derived fragments (tRFs) are small non-coding regulatory RNA molecules generated from the cleavage of transfer RNAs. tRFs have recently emerged as one of the key regulators of gene expression and cellular function in various biological processes. Understanding the content of tRFs altered in microglia due to LPS exposure may provide insights into the mechanisms involved in disease pathogenesis, where neuroinflammation plays a role. We used next-generation sequencing to determine tRF profiles of three different fractions (lysate, extracellular vesicles, and extracellular vesicles-free supernatant) of LPS-induced microglial cells. A total of 345 tRFs were differentially expressed across these fractions after LPS stimulation, including 13 DE-tRFs shared by all three compartments. Gene Ontology analysis of these 13 tRFs suggests their potential involvement in the inflammatory responses of microglia. Among the 13 consistently dysregulated DE-tRFs, tDR-1:33-Glu-CTC-1-M2 was selected for preliminary candidate-level assessment based on its consistent differential expression across all three fractions in our NGS data and previous reports linking this fragment to neuroinflammatory contexts.Increased expression pattern of tDR-1:33-Glu-CTC-1-M2 was further confirmed in lysate samples of LPS-induced microglial cells via RT-qPCR. Inhibition of tDR-1:33-Glu-CTC-1-M2 attenuated LPS-induced cytokine expression and release in microglia, supporting an association between this candidate tRF and inflammatory readouts in this model.
cGAS-STING signaling pathway: a central pathological mechanism and emerging therapeutic target for postoperative cognitive dysfunction.
Wu X, Zhong B, Xu Y … +2 more , Lai Y, Wen X
Brain Res · 2026 Oct · PMID 42309183 · Publisher ↗
Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication in older patients following surgery. However, the upstream molecular triggers of perioperative neuroinflammation, a key factor in its pa...
Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication in older patients following surgery. However, the upstream molecular triggers of perioperative neuroinflammation, a key factor in its pathogenesis, remain insufficiently understood. This review systematically examines the emerging evidence implicating the cGAS-STING signaling pathway as a potentially central mediator in the pathological progression of POCD. Integrating recent advancements, we outline a critical pathological cascade in POCD: perioperative stressors, including anesthesia and surgical trauma, induce mitochondrial injury, resulting in the release of mitochondrial DNA (mtDNA) into the cytosol. This leaked mtDNA functions as an endogenous danger signal, activating the cGAS-STING pathway in brain microglia. Activation of this pathway drives neuroinflammation, characterized by proinflammatory (M1-like) microglial polarization, regulated cell death (e.g., pyroptosis), and a self-perpetuating cycle of mitochondrial dysfunction, ultimately leading to neuronal damage and cognitive decline. We propose the mtDNA-cGAS-STING axis as a candidate pivotal link between perioperative stress and the neuropathology of POCD, based on converging preclinical evidence. Therapeutic strategies targeting this pathway, such as cGAS-STING inhibition or the promotion of mitophagy, have shown significant neuroprotective effects in preclinical studies. These findings offer promising avenues for the prevention and treatment of POCD and highlight potential implications for perioperative neuroprotection in older adults.
Comprehensive analysis of brain tissue transcriptome and serum miRNA reveals molecular signatures of cognitive impairment after traumatic brain injury.
Ou Z, Tan T, Liang F
Brain Res · 2026 Oct · PMID 42303152 · Publisher ↗
BACKGROUND: Cognitive impairment after traumatic brain injury (TBI) lacks early biomarkers. Integrating brain transcriptome and serum miRNA data may reveal molecular signatures for early prediction. METHODS: We analyzed...
BACKGROUND: Cognitive impairment after traumatic brain injury (TBI) lacks early biomarkers. Integrating brain transcriptome and serum miRNA data may reveal molecular signatures for early prediction. METHODS: We analyzed GEO datasets GSE104687 (brain transcriptome, n = 376) and GSE123336 (serum miRNA, n = 218). Brain samples were grouped into TBI with cognitive impairment (TBI-CI, n = 101), TBI without cognitive impairment (TBI-nonCI, n = 93), and healthy controls (n = 103). Differential expression and GSEA were performed. miRNA-target gene networks were constructed using TargetScan and miRTarBase. An independent cohort (n = 64) validated key miRNAs. RESULTS: Ten core genes differentiated TBI-CI from TBI-nonCI, enriched in NF-κB/TNF immune pathways and ribosomal inhibition. Serum miRNA analysis identified 35 differentially expressed miRNAs, with miR-146a-3p and miR-203a-3p significantly downregulated. Integrated network analysis highlighted miR-146a-3p targeting PCK1, RPS28P7, and ANKRD20A4. In the validation cohort, both miRNAs correlated positively with MoCA scores (rho = 0.748 and 0.770, P < 0.001) and distinguished TBI-CI from TBI-nonCI with AUCs of 0.82 and 0.79 (combined AUC = 0.88). CONCLUSION: Downregulation of miR-146a-3p and miR-203a-3p and upregulation of their targets characterize post-TBI cognitive impairment, involving immune-inflammatory activation and ribosomal dysfunction, offering potential diagnostic biomarkers.
Musicians are better at using sounds as spatial body anchors.
Paromov D, Azar C, Maheu M … +3 more , Bacon BA, Sharp A, Champoux F
Brain Res · 2026 Oct · PMID 42303151 · Publisher ↗
Musicians are known to possess superior multisensory integration abilities but the extent to which these enhanced abilities extend beyond the context of music remains unclear. A recent study suggests that musicians might...
Musicians are known to possess superior multisensory integration abilities but the extent to which these enhanced abilities extend beyond the context of music remains unclear. A recent study suggests that musicians might be making better use of environmental sounds in representing their bodies in space. If this is indeed the case, the enhanced use of sound sources for body representation could arguably allow for better control of posture. In the present study, we aimed to investigate the impact of sound stimuli on postural control in musicians versus non-musicians. Participants were asked to perform a challenging postural task in the presence, and absence of auditory input. No differences in sway parameters were observed between groups in the absence of auditory input. As expected, the addition of auditory cues significantly enhanced postural control performance in both groups. However, this enhanced performance in the presence of sound was significantly more pronounced in musicians as compared to non-musicians. This effect was associated with decreased activity in frequency bands known to be linked to anticipatory mechanisms, vestibular inflow and feedback-corrective mechanisms. These results support the idea that musicianship enhances postural control through the integration of auditory spatial anchors. Even more importantly, these results suggest that the positive impact of musical training extends far beyond the context of music, even going so far as to positively influence spatial abilities.
Ultra-high-field 7T MRI reveals neural abnormalities of attention networks in relation to cognitive impairment in hypertension.
Kong Y, Guo QH, Tang Y … +19 more , Xia SJ, Xu TY, Zhang JR, Wang J, Cheng YB, Chen Y, Zhao MQ, Zhou L, Sun YW, Wang DY, Li SY, Nie QY, Wang XY, Xing Y, Han L, Zhou N, Wang JG, Sun YH, Ma CS
Brain Res · 2026 Oct · PMID 42303150 · Publisher ↗
Hypertension is a significant risk factor for cognitive impairment (CI), yet the corresponding neural network abnormalities remain underexplored. In this study, we examined the associations among global and domain-specif...
Hypertension is a significant risk factor for cognitive impairment (CI), yet the corresponding neural network abnormalities remain underexplored. In this study, we examined the associations among global and domain-specific cognitive dysfunction, neuroimaging measures, and blood pressure in a subgroup of hypertensive patients with CI (N = 41) from a randomized controlled trial who underwent ultra-high-field 7 T MRI. Structural atrophy related to CI was localized to regions overlapping the attention networks. Both whole-brain and within-network dysfunction of the attention networks were associated with worse global cognitive performance. Notably, hyperconnectivity within key attention network hubs, including the right anterior insula and posterior intraparietal sulcus, was associated with declined processing speed in hypertensive patients, mediating the association between pulse pressure and processing speed. These findings provide new insights into the neural pathophysiology of hypertension-related CI and suggest potential network-based targets for intervention.
Tumor cell extracellular vesicles derived lncRNA XIST regulates the blood-brain barrier and NSCLC brain metastasis via miR-19b-3p/EPN2.
Cao Y, Chai W, Liu S … +5 more , Xu Y, Tang D, Deng X, Luo Y, Long J
Brain Res · 2026 Oct · PMID 42285197 · Publisher ↗
This study aimed to investigate the function and molecular mechanism of long non-coding RNA XIST derived from tumor extracellular vesicles (EVs) in brain metastasis of non-small cell lung cancer (NSCLC). Serum samples we...
This study aimed to investigate the function and molecular mechanism of long non-coding RNA XIST derived from tumor extracellular vesicles (EVs) in brain metastasis of non-small cell lung cancer (NSCLC). Serum samples were collected from NSCLC patients with brain metastasis and healthy controls to detect the expression levels of XIST, miR-19b-3p, and EPN2 mRNA. EVs were isolated from A549 cells, and their morphology and particle size were characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot analysis. An in vitro blood-brain barrier (BBB) model was constructed using human brain microvascular endothelial cells (HBMECs) and astrocytes. After a 24-h treatment with EVs, PKH67 staining was employed to observe EV uptake by HBMECs and astrocytes. The role of XIST in BBB integrity and NSCLC cell invasion was evaluated through RT-qPCR, Western blot, transendothelial electrical resistance (TEER) measurement, rhodamine-dextran permeability assay, immunofluorescence staining, Transwell migration assay, and interactive video imaging system. The binding interactions among XIST, miR-19b-3p, and EPN2 were confirmed by dual-luciferase reporter assay and RNA immunoprecipitation. Results revealed that EVs derived from A549 cells exhibited typical characteristics and were efficiently internalized by HBMECs, leading to reduced TEER values, decreased tight junction proteins expression, and increased rhodamine-dextran permeability. XIST was overexpressed in NSCLC patients with brain metastasis and in A549 and H1299 cells, and its knockdown in A549 cells alleviated BBB disruption and suppressed A549 and H1299 cell invasion. Knockdown of EPN2 in HBMECs produced effects similar to those observed with XIST knockdown. Notably, knockdown of miR-19b-3p partially reversed the effects of EPN2 knockdown on both BBB integrity and NSCLC cell invasion. In vivo experiments demonstrated that XIST inhibition attenuated NSCLC brain metastasis by improving BBB integrity. Mechanistically, XIST positively regulated EPN2 expression by sponging miR-19b-3p. In conclusion, inhibition of XIST in A549 cells mitigates BBB damage and suppresses NSCLC brain metastasis by modulating the miR-19b-3p/EPN2 axis.
Network pharmacology-based investigation and in vitro validation of the endothelial protective mechanisms of GZFLW against cerebral ischemia/reperfusion injury.
Ou F, Qiu Y, Yu S … +1 more , Huang Y
Brain Res · 2026 Oct · PMID 42276186 · Publisher ↗
OBJECTIVE: To investigate the protective effects and potential mechanisms of Guizhi-Fuling Wan (GZFLW) against cerebral ischemia/reperfusion injury (CIRI). METHODS: Active compounds and predicted targets of GZFLW were id...
OBJECTIVE: To investigate the protective effects and potential mechanisms of Guizhi-Fuling Wan (GZFLW) against cerebral ischemia/reperfusion injury (CIRI). METHODS: Active compounds and predicted targets of GZFLW were identified from TCMSP and BATMAN-TCM, while CIRI-related targets were obtained from GeneCards. Overlapping targets were analyzed using protein-protein interaction (PPI) network and GO/KEGG enrichment analyses. Molecular docking was applied to assess binding between key compounds and core targets. An oxygen-glucose deprivation/reoxygenation (OGD/R) model was established in rat brain microvascular endothelial cells (BMECs). Cell viability, apoptosis, transendothelial electrical resistance (TEER), and FITC-Dextran permeability were assessed. Western blotting was used to examine proteins related to PI3K/AKT signaling, apoptosis regulation, and blood-brain barrier (BBB)-associated tight junction integrity. RESULTS: A total of 43 active compounds and 108 shared targets related to GZFLW and CIRI were identified. Network analysis highlighted AKT1, BCL-2, TNF, IL6, IL1B, TP53, CASP3, and ESR1 as key targets. Major compounds such as quercetin, β-sitosterol, kaempferol, and hederagenin showed strong predicted binding to core targets. In the OGD/R model, GZFLW-containing serum improved BMEC viability, suppressed apoptosis, enhanced TEER, and reduced FITC-Dextran permeability. It also activated PI3K/AKT signaling, upregulated BCL-2 and Claudin-5, and downregulated Bax and p-FOXO1/FOXO1. The PI3K inhibitor LY294002 partially reversed these protective effects. CONCLUSION: GZFLW alleviated OGD/R-induced BMEC injury and improved endothelial barrier integrity, possibly through modulation of PI3K/AKT signaling, the BCL-2/Bax apoptotic pathway, and the FOXO1/Claudin-5 pathway, providing evidence for its therapeutic potential against CIRI.
Acute cardiovascular exercise and circulating neurotrophic factors in humans: A systematic review and meta-analysis of mechanisms and methodological moderators.
Moreau D, Chapple-De Lange BT
Brain Res · 2026 Oct · PMID 42276185 · Publisher ↗
Acute cardiovascular exercise is widely proposed to modulate neurotrophic factors implicated in brain plasticity, yet empirical findings remain inconsistent and difficult to interpret. This systematic review and meta-ana...
Acute cardiovascular exercise is widely proposed to modulate neurotrophic factors implicated in brain plasticity, yet empirical findings remain inconsistent and difficult to interpret. This systematic review and meta-analysis synthesized evidence on the acute effects of a single bout of cardiovascular exercise on circulating neurotrophic factors in healthy adults and identified methodological sources of variability. We searched PubMed, Web of Science, Scopus, Embase, PsycINFO, ScienceDirect, and SPORTDiscus, supplemented by gray literature sources. Eligible studies included healthy adults undergoing a single exercise bout with peripheral neurotrophic outcomes. Study selection, data extraction, and risk of bias assessment were conducted by two reviewers. Findings were synthesized narratively, and a focused random-effects meta-analysis was conducted for the subset of studies reporting extractable pre- and post-exercise BDNF data. Twenty-two studies (N = 628) were included, assessing brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1). Acute exercise was consistently associated with transient increases in BDNF, particularly following moderate-to-vigorous intensities and immediate post-exercise sampling. The meta-analysis confirmed a moderate, statistically significant increase in circulating BDNF (pooled Hedges' g = 0.48, 95 % CI [0.29, 0.68], p < 0.001), with directionally larger effects following higher-intensity exercise and in younger adults. In contrast, evidence for VEGF and IGF-1 was limited and inconsistent, and too sparse to pool. Exercise intensity, biological sample type, and sampling timing emerged as key moderators. Overall confidence in the evidence appears moderate for BDNF and low for VEGF and IGF-1, reflecting differences in study volume, consistency, and methodological variability.
Brain entangled quantum states in radical pairs: a possible link to consciousness.
Cavelier G
Brain Res · 2026 Oct · PMID 42264167 · Publisher ↗
Current approaches to the study of consciousness have significantly advanced our understanding of this widespread phenomenon in neurocognitive science. Research involving EEG oscillatory dynamics and electromagnetic fiel...
Current approaches to the study of consciousness have significantly advanced our understanding of this widespread phenomenon in neurocognitive science. Research involving EEG oscillatory dynamics and electromagnetic field activity within brain tissue has provided increasingly detailed insights into arousal states. The neuro-molecular bases of conscious experience have been further clarified, including investigations exploring potential quantum mechanical contributions. However, the precise location, origin, and mechanisms of consciousness within the brain, as well as its connection to fundamental biophysical principles, remain elusive. In this work, we investigate the possible involvement of quantum effects in consciousness by extending rigorous scientific equations and quantum information formalisms-specifically those describing electronic quantum wavefunctions and their parameters-to connect abstract quantum information and photons, atomic, molecular, and neuronal circuit activity, with brain spiking patterns and frequency coding. Testable hypothesis 1: A conscious experience-such as a strong human emotional experience globally connected to sensory perception and the corresponding physical and temporal environment-is registered by the brain through its embedding in N-Methyl-D-Aspartate (NMDA) receptor (NMDAR)-based radical pairs. Local intracranial EEG (iEEG) - Electron Paramagnetic Resonance (EPR) measurements help in supporting the occurrence of such embedding. Hypothesis 1 assessment - Empirical observations that would falsify it: Measurable or inferred parameter values that support the embedding of conscious experience are listed in Tables 1 and 2 and should comply with the ranges and conditions specified therein. Testable hypotheses 2: The NMDAR micropopulation of entangled spin states within relevant radical pairs encodes and transfers sensory and cognitive information of conscious experiences into measurable, stable nanoscale parameters of the quantum iEEG wavefunction. These parameters are transmitted in biconditional manner to the corresponding neuronal spike frequency and timing codes of associated neural circuits. Hypothesis 2 assessment - Empirical observations that would falsify it: iEEG, EEG, EPR, and related radical-pair parameter measurements should comply biconditionally with the relevant neuronal, molecular, and nanoscale measurements and conditions in Tables 1 and 2.
Early-life maternal separation enhances vulnerability to adolescent social isolation: behavioral and structural alterations of the anterior cingulate cortex.
Ranaivomanana CP, Chaibi I, Ait-Mansour I … +3 more , Moubarrad Lamghari FZ, Bennis M, Ba-M'hamed S
Brain Res · 2026 Oct · PMID 42263980 · Publisher ↗
Pathological aggression often results from the interaction between early-life adversity and later psychosocial stress. Maternal separation (MS) is an early-life stress model that increases vulnerability to aggression. Ho...
Pathological aggression often results from the interaction between early-life adversity and later psychosocial stress. Maternal separation (MS) is an early-life stress model that increases vulnerability to aggression. However, social isolation (SI) is a paradigm for inducing aggressive behaviors and anterior cingulate cortex (ACC) alterations. Yet, the relationship between MS to adult behavior and ACC structure, and the modulatory role of SI during adolescence, remain unclear. This study examined the effects of MS, with or without SI, on aggression, anxiety, sensory sensitivity, and ACC morphology. Swiss albino pups underwent MS (4 h/day, PND2-20) and were later housed at PND46 for two weeks under standard or isolated conditions, which resulted four groups per sex: MS/SI, MS/SI, MS/SI, and MS/SI. Behavioral assessments were conducted in adulthood (PND60-62). The Resident-Intruder test indicated increased aggression exclusively in MS+/SI+ males, while social behavior declined in both sexes of MS/SI and MS/SI. The elevated plus maze showed increased anxiety specifically in MS/SI females. Mechanical allodynia, assessed by the von Frey test, was observed in MS+/SI- and MS+/SI+ groups, with no changes in thermal sensitivity measured by the hot plate test. Morphological analyses using Nissl and Golgi-Cox staining revealed ACC alterations in MS+/SI- and MS+/SI+ mice of both sexes, including reduced neuronal density, shorter dendritic length, diminished branching, lower spine density, and decreased arborization complexity of pyramidal neurons. These results highlight a synergistic effect between MS and SI: MS predisposes individuals to SI's detrimental impact, while SI amplifies MS induced behavioral and neurobiological alterations. The ACC emerges as a critical substrate mediating the cumulative effects of stress on pathological aggression and its comorbidities.
FTO knockdown confers neuroprotection in intracerebral hemorrhage rats by suppressing ferroptosis via inhibiting autophagy.
Xiao Q, Guo H, Yu H … +2 more , Huang Z, Luo M
Brain Res · 2026 Oct · PMID 42248290 · Publisher ↗
OBJECTIVE: Intracerebral hemorrhage (ICH) has high disability rates and fatality. This study aims to investigate whether fat mass and obesity-associated protein (FTO) exacerbate ICH-induced brain injury by regulating aut...
OBJECTIVE: Intracerebral hemorrhage (ICH) has high disability rates and fatality. This study aims to investigate whether fat mass and obesity-associated protein (FTO) exacerbate ICH-induced brain injury by regulating autophagy-dependent ferroptosis and to identify potential therapeutic targets. METHODS: An ICH model was established in rats via autologous blood injection. FTO expression was knocked down using adeno-associated virus-delivered short hairpin RNA (shRNA). Neurological scores, brain edema, and histopathology were assessed. Autophagy, oxidative stress, and ferroptosis markers were measured by Western blot and enzyme-linked immunosorbent assay (ELISA).Immunofluorescence was performed for FTO with neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), LC3, and GPX4/microtubule-associated protein 2 (MAP2). RESULTS: FTO expression was significantly upregulated post-ICH, correlating with neurological deterioration, cerebral edema, neuronal loss, and inflammatory infiltration. Immunofluorescence showed FTO colocalized with NeuN. FTO knockdown attenuated neurological deficits, reduced cerebral edema, and suppressed neuronal loss. FTO knockdown inhibited autophagy-related protein (ATG5)/microtubule-associated protein 1 light chain 3B (LC3B)-mediated autophagy activation, thereby mitigating iron overload, lipid peroxidation, and ferroptosis markers (decreased glutathione peroxidase 4 [GPX4], elevated acyl-CoA synthetase long-chain family member 4 [ACSL4], and cyclooxygenase-2 [COX2]). FTO knockdown also reduced LC3 fluorescence and restored GPX4/MAP2 colocalization. Rescue experiments further confirmed that ATG5 overexpression reversed the neuroprotective effects of FTO knockdown. CONCLUSION: FTO aggravates ICH-induced brain injury by promoting ATG5/LC3B-mediated autophagy and subsequent ferroptosis. Targeting FTO represents a promising therapeutic strategy to mitigate secondary brain damage post-ICH.
Differential effects of hypothalamic ET receptor blockade in fever, hypolocomotion and serotonin release during systemic inflammation in male and female rats.
Alencar TS, Santos MO, Schneider VMM … +5 more , Fernandes SMA, Borges AP, Guaita GO, Costa RA, Zampronio AR
Brain Res · 2026 Oct · PMID 42242457 · Publisher ↗
Systemic inflammation triggers a set of physiological and behavioral changes known as sickness behavior, including fever and hypolocomotion. Previous studies demonstrated that lipopolysaccharide (LPS) induces these respo...
Systemic inflammation triggers a set of physiological and behavioral changes known as sickness behavior, including fever and hypolocomotion. Previous studies demonstrated that lipopolysaccharide (LPS) induces these responses in both sexes, with sex-specific alterations in hypothalamic serotonin (5-HT) levels-decreased in males and increased in females. These effects were reversed by intracerebroventricular (i.c.v.) administration of BQ788, an endothelin-1 type B (ET) receptor antagonist. This study investigated whether direct intra-hypothalamic (i.h.) administration of BQ788 could modulate 5-HT levels and attenuate sickness behavior. Wistar rats were implanted with temperature sensors and received hypothalamic microinjections of BQ788 or saline, followed by intraperitoneal LPS or vehicle. Body temperature was monitored for five hours, locomotor activity assessed via open field test, and hypothalamic 5-HT and its metabolite 5- hydroxyindoleacetic acid (5-HIAA) levels quantified by HPLC. LPS induced fever and hypolocomotion in both sexes, with reduced 5-HT/5-HIAA in males and increased levels in females. In males, i.h. BQ788 reversed these effects, suggesting direct hypothalamic action. In females, i.h. BQ788 normalized 5-HT levels but did not affect fever or hypolocomotion. However, i.c.v. BQ788 reduced these responses in females, indicating that ET-1 signaling sites differ between sexes. These findings highlight a sexually dimorphic neuroimmune response to systemic inflammation, with hypothalamic ET-1 signaling mediating sickness behavior in males, but not in females. This underscores the importance of sex-specific approaches in neuroinflammatory research.
Electroacupuncture attenuates PVN-SCG sympathetic hyperactivation to improve cardiac function in myocardial infarction mice.
Peng R, Lu X, Jiang M … +9 more , Zhu Y, Liu X, Li J, Chen J, Guo Y, Yu M, Fu S, Zou L, Lu S
Brain Res · 2026 Oct · PMID 42235844 · Publisher ↗
Myocardial infarction (MI) triggers maladaptive sympathetic overactivation, which acts as a key driver of adverse cardiac remodeling and progression to heart failure. Electroacupuncture (EA) at the Neiguan (PC6) acupoint...
Myocardial infarction (MI) triggers maladaptive sympathetic overactivation, which acts as a key driver of adverse cardiac remodeling and progression to heart failure. Electroacupuncture (EA) at the Neiguan (PC6) acupoint exhibits reliable cardioprotective effects, yet its central neural mechanisms remain incompletely clarified. This study investigated whether EA at PC6 improves post-MI outcomes by modulating the hypothalamic paraventricular nucleus-superior cervical ganglion (PVN-SCG) sympathetic axis. MI was surgically induced by permanent ligation of the left anterior descending coronary artery in mice, followed by consecutive EA treatment at PC6. Cardiac function was assessed by echocardiography, while sympathetic activity was evaluated via heart rate variability (HRV) analysis and norepinephrine levels of serum and heart. Myocardial fibrosis and key molecular markers within the PVN-SCG axis were systematically analyzed. In this mice MI model, EA at PC6 significantly improved cardiac function as indicated by ejection fraction and attenuated ventricular dilation. Mechanistically, EA suppressed systemic sympathetic activity, as evidenced by decreased serum and cardiac norepinephrine levels as well as normalized HRV parameters. Notably, EA markedly inhibited neuronal hyperactivity (c-fos expression) in both the PVN and SCG. Peripherally, EA mitigated cardiac sympathetic remodeling by downregulating tyrosine hydroxylase (TH) and synaptophysin (SYN) expression, accompanied by reduced myocardial fibrosis and collagen deposition. These findings demonstrate that EA at PC6 exerts s potent cardioprotection against post-MI injury by specifically inhibiting sympathetic hyperactivation at both central (PVN-SCG axis) and peripheral levels. This study identifies a novel neuromodulatory mechanism underlying EA therapy and supports PC6 EA as a promising non-pharmacological strategy for post-MI cardiac protection.
Adipose tissue as a systemic modulator of brain aging: mechanistic links between metabolism, inflammation and neurodegeneration.
Andreea-Ramona T, Mirabela MM
Brain Res · 2026 Sep · PMID 42229697 · Publisher ↗
Brain aging involves progressive declines in neuroplasticity, metabolic flexibility, cerebrovascular integrity and immune homeostasis. Although traditionally viewed as brain-intrinsic, growing evidence indicates that per...
Brain aging involves progressive declines in neuroplasticity, metabolic flexibility, cerebrovascular integrity and immune homeostasis. Although traditionally viewed as brain-intrinsic, growing evidence indicates that peripheral metabolic organs substantially influence neural aging trajectories. Among these, adipose tissue is increasingly recognized as a dynamic endocrine and immune organ capable of modulating central nervous system (CNS) structure and function across the lifespan. Epidemiological, neuroimaging and experimental studies consistently link adipose tissue dysfunction, particularly the expansion and inflammatory remodeling of visceral fat depots, to accelerated brain aging, cognitive decline and increased susceptibility to neurodegenerative disease. These relationships extend beyond conventional cardiometabolic risk, implicating adipose-derived mechanisms with direct relevance for neural aging. Chronic low-grade inflammation, impaired insulin signaling, dyslipidemia, adipokine imbalance and senescence-associated secretory activity originating in adipose tissue act on the aging brain by promoting microglial dysfunction, cerebrovascular impairment, blood-brain barrier (BBB) disruption and synaptic vulnerability. In parallel, adipose-derived extracellular vesicles and microRNAs have been identified as direct molecular mediators of adipose-brain communication. Importantly, adipose tissue is structurally and functionally heterogeneous, and its impact on brain aging is strongly depot- and context-dependent. While dysfunctional visceral adipose tissue amplifies neuroinflammatory and neurodegenerative processes, preserved subcutaneous and thermogenic depots may support brain resilience by sustaining metabolic homeostasis and neurotrophic signaling. By integrating molecular, translational and human evidence, this review frames adipose tissue as a central and modifiable systemic determinant of brain aging. Framing brain aging within a peripheral metabolic context reconciles findings across disciplines and highlights adipose-targeted interventions as promising strategies for preserving cognitive function and reducing neurodegenerative risk.
Inhibition of the IRE1α/ASK1/JNK signaling pathway ameliorates perioperative neurocognitive disorder in aged mice following abdominal surgery.
Zhang W, Liu C, Xu R … +8 more , Li Z, Xu Y, Yin J, Han F, Meng Q, Duan M, Zhang Z, Wang X
Brain Res · 2026 Oct · PMID 42229696 · Publisher ↗
BACKGROUND: Perioperative neurocognitive disorder (PND) is a common postoperative complication, although its pathophysiological mechanisms remain incompletely understood. Inositol-requiring enzyme 1α (IRE1α) is an endopl...
BACKGROUND: Perioperative neurocognitive disorder (PND) is a common postoperative complication, although its pathophysiological mechanisms remain incompletely understood. Inositol-requiring enzyme 1α (IRE1α) is an endoplasmic reticulum (ER) membrane sensor that participates in the pathogenesis of cognitive disorders through ER stress. However, its relationship with PND remains unclear. This study aimed to investigate whether IRE1α contributes to PND through surgery-induced ER stress. METHODS: An abdominal surgery model was used to investigate the postoperative effects of surgery on the mouse hippocampus. Behavioral tests, mRNA sequencing of hippocampal tissue, protein detection, Nissl staining, immunohistochemistry, immunofluorescence staining, and electron microscopy were performed. Aged mice in the surgery group received intraperitoneal injection of an IRE1α inhibitor. RESULTS: Surgery-induced cognitive impairment was mainly observed in aged mice. Surgery-induced ER stress was associated with activation of the IRE1α/ASK1/JNK pathway, increased microglial activation, enhanced release of inflammatory factors, and mitochondrial damage. Treatment with the IRE1α inhibitor improved these outcomes. CONCLUSION: Surgery-induced ER stress was associated with IRE1α overactivation and postoperative cognitive impairment in aged mice. Suppression of the IRE1α/ASK1/JNK pathway ameliorated postoperative neuroinflammation, mitochondrial pathology, and microglial activation, thereby improving postoperative cognitive function in aged mice.
Early and sustained Intervention with YKB Modulates the Cerebro-Retinal-Synaptic Network to Ameliorate Memory Deficits in Alzheimer's Disease.
Liu Y, Li L, Pu J … +9 more , Xiong Y, Feng T, Liu Z, Zhou C, Xu H, Sayami N, Yang J, Zhou H, Gan P
Brain Res · 2026 Oct · PMID 42219140 · Publisher ↗
This study investigates whether early and sustained intervention with the Chinese herbal formula Yi Kang Bu Yuan (YKB) can modulate integrated networks to counteract Alzheimer 's disease (AD) progression. In APPswe/PSEN1...
This study investigates whether early and sustained intervention with the Chinese herbal formula Yi Kang Bu Yuan (YKB) can modulate integrated networks to counteract Alzheimer 's disease (AD) progression. In APPswe/PSEN1dE9 transgenic mice, chronic YKB administration prevented both short- and long-term memory decline. This cognitive protection was supported by a coordinated rescue of pathology across the brain-retina axis: YKB restored vascular structural remodeling, as evidenced by increased cerebrovascular collagen IV and retinal CD31 endothelia density. These vascular improvements occurred in parallel with short-term memory gain. Concurrently, YKB upregulated hippocampal PSD-95, which correlated with long-term fear memory rescue, and suppressed hippocampal GFAP astrogliosis. These results define a novel, multi-target therapeutic axis for YKB in early AD, demonstrating that coordinated modulation of the neurovascular unit and synaptic circuits can effectively ameliorate multifactorial deficits.
Divergent neurovascular protection: Histone deacetylase inhibition preserves neuronal ultrastructure while hypoxia-inducible factor activation maintains vascular integrity after ischemic stroke.
Amin N, Hussein AB, Yuan X … +5 more , Lu Q, Shen G, Xu Q, Yang Q, Fang M
Brain Res · 2026 Sep · PMID 42219139 · Publisher ↗
Ischemic stroke triggers severe disruption of the neurovascular unit (NVU), with pathology evident at the ultrastructural level. Hypoxia-inducible factor-1α (HIF-1α) activators such as Prolyl hydroxylase inhibitors e.g.,...
Ischemic stroke triggers severe disruption of the neurovascular unit (NVU), with pathology evident at the ultrastructural level. Hypoxia-inducible factor-1α (HIF-1α) activators such as Prolyl hydroxylase inhibitors e.g., dimethyloxalylglycine (DMOG) and histone deacetylase inhibitors (e.g., Apicidin) are promising therapeutic candidates, but their specific impact on subcellular architecture remains poorly characterized. Endothelin-1 (ET-1) model was used to induce ischemic stroke. Animals were treated intraperitoneally with either DMOG (40 mg/kg), Apicidin (1 mg/kg), or vehicle at reperfusion onset. After 7 days, behavioral analysis was conducted, Cytochrome-C immunohistochemistry and cortical tissue was processed for transmission electron microscopy (TEM) to assess ultrastructural integrity. Severe ultrastructural pathology, such as pyknotic neuronal soma, broken axons, enlarged mitochondria, synaptic disintegration, and reactive microglia and oligodendrocytes, was seen in model animals. With relatively slight improvements in synaptic and glial function and ongoing somatic, axonal, and mitochondrial damage, DMOG therapy offered little protection for neurons. With intact soma and axons, decreased mitochondrial swelling, increased synaptic vesicle density, and enhanced oligodendrocyte and microglial morphology, Apicidin therapy, on the other hand, showed strong neuronal preservation. While Apicidin is more effective at maintaining the integrity of neurons and synapses, DMOG mainly stabilizes the vascular compartment. These results imply that better neuroprotection may be provided by combination therapy that targets both vascular and neuronal components.
Task interruptions impair visuospatial working memory: Behavioral and EEG evidence for feature-specific cognitive interference.
Ülkü S, Arslan C, Getzmann S … +2 more , Wascher E, Schneider D
Brain Res · 2026 Oct · PMID 42219138 · Publisher ↗
Working memory (WM) is vulnerable to interferences, especially from task interruptions that redirect the focus of attention to secondary tasks. Here, we used a visuospatial WM task to investigate how the modality and cog...
Working memory (WM) is vulnerable to interferences, especially from task interruptions that redirect the focus of attention to secondary tasks. Here, we used a visuospatial WM task to investigate how the modality and cognitive domain of interruptions affect performance. Twenty-eight participants memorized orientations of colored bars and reported one after a retrospective cue. During the maintenance phase, interrupting tasks varying in modality and cognitive domain occurred: visual arithmetic, auditory arithmetic, or visuospatial discrimination. Interruptions generally impaired memory performance, with the visuospatial discrimination task, which included low-level sensory feature overlap, causing the greatest decline. Further, target orientation's proximity to the horizontal axis was a good predictor in recall error, which showed a significant interaction only with visuospatial interruptions. EEG data showed reduced theta activity and weaker alpha/beta suppression to the retrospective cue following interruptions. After the visuospatial interruption, stronger posterior alpha asymmetries emerged, reflecting greater attentional demands for reorienting attention to the interrupted task. These results highlight that overlapping features between primary and interrupting tasks critically influence WM interference.
Fluid-based biomarkers of amyotrophic lateral sclerosis: recent advances and future prospects.
Jiang Y, Hu S, Yang B … +4 more , Zhang L, Wang Y, Yang G, Zhang H
Brain Res · 2026 Oct · PMID 42217760 · Publisher ↗
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder with no definitive cure. The absence of specific diagnostic biomarkers leads to diagnostic delays, hindering early intervention and manageme...
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder with no definitive cure. The absence of specific diagnostic biomarkers leads to diagnostic delays, hindering early intervention and management. This review provides a critical appraisal of fluid-based biomarkers for ALS across multiple sources-cerebrospinal fluid (CSF), blood, urine, saliva, and tears-with emphasis on their diagnostic and prognostic potential, limitations, and readiness for clinical translation. While neurofilaments (NfL, pNfH) are well-established as sensitive indicators of neuroaxonal injury and are increasingly used as prognostic and pharmacodynamic markers in clinical trials, they lack disease specificity. Biomarkers reflecting ALS-specific pathology, such as TDP-43 species and C9orf72 dipeptide repeat proteins (DPRs), show promise but remain in early validation stages with limited multicenter data. Emerging markers from non-invasive sources (urine p75ECD, salivary chromogranin A, tear metabolomics) offer potential for repeated sampling but require rigorous external validation before clinical adoption. To address current gaps, we introduce a standardized evidence grading framework (Tier 1-3) and a comprehensive reporting template for biomarker studies, including explicit performance metrics (AUC, sensitivity, specificity, confidence intervals) and validation status. We also propose minimum reporting standards for study design, pre-analytical variables, and statistical rigor, modeled on REMARK guidelines. A roadmap for biomarker validation and a cross-fluid comparison matrix are provided to guide future research. Despite considerable progress, significant challenges remain, including biological heterogeneity, pre-analytical variability, and insufficient external validation. Future efforts should prioritize multicenter prospective studies, assay harmonization, ethical frameworks for early diagnosis, and integration of emerging technologies such as artificial intelligence and digital twins. Fluid-based biomarkers, while not yet replacing clinical evaluation, are essential tools for accelerating drug development, enabling patient stratification, and moving toward personalized medicine in ALS.
Cytokine levels in serum and cerebrospinal fluid of patients with idiopathic intracranial hypertension.
Kaur K, Awasthy AK, Takkar A … +9 more , Kaur P, Kumar A, Karthik VM, Tigari B, Ahuja C, Saikia B, Singh R, Puri GD, Lal V
Brain Res · 2026 Sep · PMID 42214536 · Publisher ↗
Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure (ICP) without an identifiable intracranial lesion, yet its underlying pathophysiology remains poorly defined. Emerging evidenc...
Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure (ICP) without an identifiable intracranial lesion, yet its underlying pathophysiology remains poorly defined. Emerging evidence suggests that immune-mediated mechanisms may contribute to disease onset and progression. We conducted a prospective case-control study including 100 adult patients with IIH and 100 age- and sex-matched controls at a tertiary care center in India. The study received Institutional Ethics Committee approval (IEC-03/2019-1141) and was registered with the Clinical Trials Registry of India (CTRI/2020/03/023920). Serum and cerebrospinal fluid (CSF) samples were analyzed for key pro- and anti-inflammatory cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, IFN-γ) using BD™ Cytometric Bead Array technology. Cytokine profiles were evaluated in relation to disease severity, treatment response, and clinical outcomes. Distinct inflammatory alterations were observed in patients with IIH, suggesting a disease-associated immune signature. These findings support a potential role of immune dysregulation in IIH pathogenesis and highlight cytokine profiling as a promising approach for identifying biomarkers of disease activity and prognosis.
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