Frontiers In Cellular Neuroscience[JOURNAL]
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200 papers
Correction: Histone deacetylase inhibitors are protective in acute but not in chronic models of ototoxicity.
Yang CH, Liu Z, Dong D … +3 more , Schacht J, Arya D, Sha SH
Front Cell Neurosci · 2026 · PMID 41993672 · Full text
[This corrects the article DOI: 10.3389/fncel.2017.00315.].
[This corrects the article DOI: 10.3389/fncel.2017.00315.].
Systematic review of literature regarding the isolation of mesenchymal adult stem cells from the olfactory epithelium.
Pipolo C, La Rubia P, Cozzi A … +3 more , Karki P, Saibene AM, Bottai D
Front Cell Neurosci · 2026 · PMID 41988390 · Full text
BACKGROUND: The olfactory mucosa has emerged as a promising source of mesenchymal stem cells with neurogenic potential. These cells exhibit neural, glial, and mesenchymal properties, making them attractive candidates for...
BACKGROUND: The olfactory mucosa has emerged as a promising source of mesenchymal stem cells with neurogenic potential. These cells exhibit neural, glial, and mesenchymal properties, making them attractive candidates for regenerative medicine, particularly in treating neurodegenerative and immunemediated disorders. METHODS: This systematic review analyzed existing literature on the isolation, characterization, and therapeutic applications of olfactory mucosa mesenchymal stem cells. The review assessed variations in isolation techniques, culture conditions, and differentiation potential, as well as preclinical and clinical applications. RESULTS: Olfactory mucosa mesenchymal stem cells express key neural and mesenchymal markers, including Nestin, SRY-box 2, , CD44, and CD105, confirming their multilineage differentiation capacity. Their ability to secrete neurotrophic factors such as Brain-Derived Neurotrophic Factor, Nerve Growth Factor, and Glial Cell Derived Neurotrophic Factor underscores their role in neural repair. While most studies successfully isolated olfactory mucosa mesenchymal stem cells via biopsy, differences in sampling depth and culture media influenced cell yield and growth patterns. Preclinical studies suggest that olfactory mucosa mesenchymal stem cells (OM-MSCs) may represent a promising experimental model for neurological disorders-including Parkinson's disease, spinal cord injury, schizophrenia, and retinal diseases-although current evidence remains preliminary and translational efficacy has not yet been established. However, challenges remain in standardizing protocols, addressing donor variability, and ensuring clinical safety. CONCLUSION: Olfactory mucosa mesenchymal stem cells represent a promising avenue for neurological and regenerative therapies. Despite their potential, further research is needed to optimize isolation techniques, enhance reproducibility, and navigate regulatory hurdles. Collaborative efforts between researchers, clinicians, and regulatory bodies will be essential to translating OM-MSC research into viable clinical applications.
The neurobiological regulatory mechanism of brain edema.
Tian M, Li M, Zhang C … +3 more , Luo Q, Wang A, Li D
Front Cell Neurosci · 2026 · PMID 41988389 · Full text
Cerebral edema is a common pathological condition associated with a variety of neurological disorders, and its development involves numerous neurobiological mechanisms. This review explores the neurobiological regulatory...
Cerebral edema is a common pathological condition associated with a variety of neurological disorders, and its development involves numerous neurobiological mechanisms. This review explores the neurobiological regulatory mechanisms underlying cerebral edema, including the disruption of the blood-brain barrier, inflammatory responses, alterations in vascular permeability, and intracellular edema. We will investigate the formation mechanisms of cerebral edema under different pathological states and discuss potential therapeutic strategies, aiming to provide insights for clinical treatment. Current research highlights the complexity of the interactions between these mechanisms and the need for targeted interventions to mitigate the impact of cerebral edema on patient outcomes. This review aims to synthesize existing knowledge and encourage further exploration in this critical area of neuroscience, ultimately contributing to more effective management of cerebral edema.
Recreating the human brain: Are assembloids merely descriptive models?
Izhiman Y, Anamala C, Nauman EA … +1 more , Liaudanskaya V
Front Cell Neurosci · 2026 · PMID 41969527 · Full text
Assembloids, engineered fusions of region-specific brain 3D constructs, have emerged as powerful platforms to study neurodevelopment and neurological diseases. Unlike first-generation organoids, assembloids enable direct...
Assembloids, engineered fusions of region-specific brain 3D constructs, have emerged as powerful platforms to study neurodevelopment and neurological diseases. Unlike first-generation organoids, assembloids enable direct modeling of interregional communication, allowing investigation of higher-order brain functions that depend on circuit-level interactions. Over the past 5 years, rapid advances in human-derived assembloid systems have demonstrated their ability to recapitulate key features of human brain organization, including long-range projection formation, region-specific signaling, neurovascular coupling, and progressive network dysfunction. The primary application of assembloid modeling remains the study of neurodevelopment, specifically focusing on mapping biological mechanisms driving the human brain development. Another major application of assembloids is the study and modeling of neurological diseases. Recent studies have integrated multiple neural regions, alongside vascular and glial components, and disease-relevant genetic backgrounds to recreate circuit-level interactions underlying pathology. These approaches have further highlighted the importance of neuroglial interactions in shaping development, connectivity, and disease progression in the human brain. Across models and disease contexts, a consistent theme has emerged: pathological phenotypes arise primarily from disrupted intercellular communication rather than isolated cellular and more purely neuronal, defects. Despite these strengths, current assembloid platforms remain limited by incomplete maturation, variability in reproducibility, and challenges in modeling long-term disease trajectories. Together, existing evidence positions assembloids as a promising next-generation platform for studying human brain development and neurodegeneration, while highlighting the need for continued refinement to improve physiological relevance as model complexity increases.
Editorial: Reviews in non-neuronal cells 2024 & 2025.
Qiu Q, Hu B
Front Cell Neurosci · 2026 · PMID 41969526 · Full text
Abstract loading — click title to view on PubMed.
Neuropeptide and cytokines expression in long COVID-19 related neuropsychological sequelae: insights into NK1R-mediated neuroinflammation and therapeutic targeting.
Abdullah M, Naz A, Reznikov LR … +4 more , Qureshi JA, Hasnain A, Obaid A, Ali A
Front Cell Neurosci · 2026 · PMID 41969525 · Full text
BACKGROUND: Long COVID-19 causes neurophysiological, cardiopulmonary, and musculoskeletal issues. Increased neuropeptides and cytokines lead to neuroinflammation, resulting in neurocognitive impairments, fatigue, depress...
BACKGROUND: Long COVID-19 causes neurophysiological, cardiopulmonary, and musculoskeletal issues. Increased neuropeptides and cytokines lead to neuroinflammation, resulting in neurocognitive impairments, fatigue, depression, anxiety, and severe cognitive deficits. The Neurokinin 1 receptor (NK1R) is a cellular receptor for the neuropeptide Substance P, and its dysregulation links to neuropsychological issues despite antipsychotic use. OBJECTIVES: In the present study, neuropsychological sequelae related to long COVID-19 were screened and the expression of related neuropeptides and cytokines was evaluated. Additionally, potential drugs have been evaluated computationally to reduce neuroinflammation in long COVID-19. METHODS: After informed consent, subjects were screened by a medical physician for long COVID-19 in an outdoor patient clinic. Various biological scales were used to assess and categorize the severity of neuropsychological symptoms related to long COVID-19. After that, peripheral blood samples were collected from subjects using ELISA and RT-qPCR. Nine drugs were selected and subjected to virtual screening to identify potential drug antagonists for NK1R. The key drug-like properties, safety profile, pharmacokinetic analysis, and biological activity of the identified hits were assessed. RESULTS: In this study the mean age of 90 patients (60% males and 40% females), was 33 ± 5 years in the symptomatic group and 31 ± 6 years in the asymptomatic long COVID-19 group for <40 years age-group. Whereas, the mean age of >40 years age-group was 58 ± 10 years in the symptomatic group and 54 ± 11 years in the asymptomatic long COVID-19 group. The minimum persistence of duration of long COVID-19 related symptoms in the <30 weeks group was observed to be 19 ± 6 weeks, while 44 ± 6 weeks in the >30 weeks group of symptomatic long COVID-19. A total of 48% patients had fatigue, 47% complained about headache, 28% had anxiety, 25% faced depression, 20% had psychosocial distress, 20% felt discomfort, and 13% had cognitive impairment. A total of 10% had reported dizziness sequelae among long COVID-19 survivors. Experimental data showed upregulation of IL-6, IL-10, and SP in both symptomatic and asymptomatic individuals compared with controls ( < 0.001). Drug screening analyses revealed aprepitant (-9.3 kcal/mol) and N- acetyl- L- tryptophan (-8.7 kcal/mol) stable interactions with NK1R and maintaining molecular dynamics stability (RMSD: 1.5-2.2 Å; RMSF 0.8-1.4 Å; Rg approximately 21.6 Å). These compounds also demonstrated favorable blood-brain barrier permeability and pharmacokinetic profiles, suggesting their potential as therapeutic antagonists for treating prolonged COVID-related neuroinflammation. CONCLUSION: IL-6, IL-10, and SP are found to be deregulated in long COVID-19 leading to neurophysiological sequelae. To overcome neuropsychological sequelae, binding of SP to NK1R can be hindered using aprepitant and N-Acetyl-L tryptophan which has been evaluated computationally and may require further and studies for validation.
The GPR68-NINJ1 axis: an emerging mechano-chemical checkpoint in blood-brain barrier disruption-a hypothetical framework and therapeutic promise.
Bai B, Feng H, Yang H … +2 more , Huang M, Wang Y
Front Cell Neurosci · 2026 · PMID 41969524 · Full text
The blood-brain barrier (BBB) is a critical interface whose failure is a convergent pathological feature of traumatic, ischemic, and neurodegenerative neurological diseases. Current paradigms often overlook the synergist...
The blood-brain barrier (BBB) is a critical interface whose failure is a convergent pathological feature of traumatic, ischemic, and neurodegenerative neurological diseases. Current paradigms often overlook the synergistic interplay between mechanical forces and biochemical cues, such as acidosis, that drive BBB disruption. This perspective synthesizes groundbreaking, yet largely independent, discoveries on two key molecules: GPR68 (OGR1), a proton-sensing GPCR with unique millisecond-level mechanosensitivity to shear stress, and NINJ1, a recently defined executor of plasma membrane rupture during lytic cell death. We propose a testable novel hypothesis: that these proteins form a functional "GPR68-NINJ1 axis," creating a self-amplifying mechano-chemical circuit that initiates and exacerbates BBB breakdown. We detail the molecular logic of this axis-from GPR68's sensing of pathological acidosis (pH ≤ 6.4) and shear stress to NINJ1's oligomerization and DAMP release-and explore its potential role in unifying the pathophysiology of diverse disorders like TBI, stroke, MS, and AD. Finally, we translate this framework into a roadmap for future research and therapeutic intervention, discussing targeted inhibitors, precision chronotherapy, and the critical experiments needed to validate this emerging paradigm.
Immaturity of the neuromuscular junction in spinal muscular atrophy mouse models.
Tabares L, Fuentes-Moliz A, Cano R … +2 more , Ruiz R, Arumugam S
Front Cell Neurosci · 2026 · PMID 41969523 · Full text
Spinal muscular atrophy (SMA) is caused by deficiency of the survival motor neuron (SMN) protein and is classically defined by degeneration of lower motor neurons. Extensive evidence from mouse models and human tissue de...
Spinal muscular atrophy (SMA) is caused by deficiency of the survival motor neuron (SMN) protein and is classically defined by degeneration of lower motor neurons. Extensive evidence from mouse models and human tissue demonstrates that dysfunction at the neuromuscular junction (NMJ) emerges early and precedes overt denervation. Here, we review structural, molecular, and functional studies showing that SMA NMJs fail to complete key postnatal maturation programmes that normally scale presynaptic release capacity to muscle growth and increasing functional demand. SMA motor terminals retain multiple features of developmental immaturity, including reduced active zone number, limited synaptic vesicle pool extension, altered cytoskeletal organisation, incomplete molecular specialization, and impaired recruitment of functional release sites, resulting in constrained neurotransmitter release and reduced presynaptic reserve. These defects are highly muscle- and region-specific and preferentially affect vulnerable motor units. We propose a conceptual framework in which delayed and incomplete NMJ maturation increases susceptibility to superimposed degenerative processes, ultimately leading to synaptic destabilisation and denervation. This integrated view reconciles early synaptic dysfunction with later neurodegeneration and has important implications for understanding SMA pathogenesis, identifying sensitive biomarkers, and optimizing the timing and targets of therapeutic intervention.
(Ba,Ca)(Ti,Sn)O-based piezoelectric ceramics promotes neuroprotection by regulating microglial IL-6/JAK2/STAT3 signaling pathway.
Song H, Tang G, Li Y … +4 more , Sun B, Yu Z, Zhang M, Yang D
Front Cell Neurosci · 2026 · PMID 41958828 · Full text
OBJECTIVE: To investigate whether (Ba,Ca)(Ti,Sn)O-based piezoelectric ceramics (BCTS) provide neuroprotection by inhibiting the IL-6/JAK2/STAT3 signaling pathway in microglia. METHODS: BCTS surface morphology and element...
OBJECTIVE: To investigate whether (Ba,Ca)(Ti,Sn)O-based piezoelectric ceramics (BCTS) provide neuroprotection by inhibiting the IL-6/JAK2/STAT3 signaling pathway in microglia. METHODS: BCTS surface morphology and elemental distribution were analyzed using Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectroscopy (EDX), phase composition was determined via X-ray diffraction (XRD), and hydrophilicity was measured through contact angle analysis. Immunofluorescence (IF), Western blot, and ELISA were employed to evaluate the expression of microglial markers and inflammatory factors in the BV2 injury model and in spinal cord injury rats. Behavioral tests were conducted to evaluate motor function recovery in spinal cord injury rats. PC12 cells were cultured with BCTS-CM (supernatant from BCTS-treated BV2 cells) to assess the IL-6/JAK2/STAT3 signaling pathway expression and its effects on LDH release, antioxidant enzyme activity, apoptotic proteins, and β-III-tubulin expression. RESULTS: BCTS exhibited a pure perovskite phase, densely packed grains, and favorable hydrophilicity. It did not affect BV2 cell viability but inhibited LPS-induced M1 microglial activation, reducing the expression of TNF-α, IL-1β, and IL-6. Simultaneously, BCTS promoted M2 microglial polarization, upregulating IL-4, IL-10, and TGF-β1. In PC12 cells, BCTS-CM increased cell survival, antioxidant activities, Bcl-2, and β-III-tubulin expression, while decreasing LDH release, MDA content, BAX and Cleaved Caspase-3 expression. BCTS-induced neuroprotection is mediated by the suppression of the IL-6/JAK2/STAT3 signaling pathway, as evidenced by the fact that IL-6 supplementation counteracts this protection while AG490 treatment further reinforces it compared to BCTS-CM alone. In the spinal cord injury rat model, BCTS inhibited the expression of microglia and inflammatory factors at the injury site, while improving the BBB score and reducing the error rate in the grid walking test. CONCLUSION: (Ba,Ca)(Ti,Sn)O-based piezoelectric ceramics exhibit neuroprotective effects by inhibiting IL-6 secretion from microglia, thereby preventing the activation of the IL-6/JAK2/STAT3 signaling pathway in neurons.
Etifoxine drives macrophage M2 polarization via Schwann cell-derived progesterone activation of PPARγ to accelerate peripheral nerve repair.
Guo C, Liu S
Front Cell Neurosci · 2026 · PMID 41958827 · Full text
BACKGROUND: Peripheral nerve injury (PNI) presents a significant clinical challenge due to limited endogenous regenerative capacity. The translocator protein (TSPO) ligand etifoxine (ETX) has shown promise in promoting n...
BACKGROUND: Peripheral nerve injury (PNI) presents a significant clinical challenge due to limited endogenous regenerative capacity. The translocator protein (TSPO) ligand etifoxine (ETX) has shown promise in promoting nerve repair, but the underlying cellular and molecular mechanisms remain incompletely understood. METHODS: Utilizing in vitro co-culture systems with human Schwann cells (HSCs) and THP-1-derived macrophages, TSPO-knockdown HSCs, conditioned medium experiments, and an in vivo rat sciatic nerve crush injury model, we investigated the effects of ETX on cellular crosstalk and macrophage polarization. Molecular analyses included RNA sequencing, western blotting, fatty acid oxidation (FAO) assays, and a Mito-QC reporter system to assess mitophagy. Functional recovery was evaluated through behavioral tests (hindlimb grip strength, mechanical pain threshold), immunofluorescence, and retrograde tracing. RESULTS: ETX specifically activated TSPO on Schwann cells, stimulating progesterone synthesis and secretion. This Schwann cell-derived progesterone acted as a paracrine signal on macrophages, activating the PPARγ-PGC1α axis. This activation triggered dual reprogramming in macrophages: a metabolic shift toward FAO and induction of BNIP3L-mediated mitophagy, both essential for sustaining a pro-regenerative M2 phenotype. These effects were significantly attenuated by the progesterone receptor antagonist RU486 or the PPARγ antagonist GW9662. In vivo, ETX treatment accelerated functional recovery, enhanced axonal regeneration, and increased infiltration of M2 macrophages at the injury site, effects that were partially reversed by RU486 or GW9662 co-administration. CONCLUSION: ETX facilitates peripheral nerve repair by promoting Schwann cell-derived progesterone, which drives macrophage PPARγ pathway activation, orchestrating metabolic-autophagic reprogramming necessary for sustained M2 polarization. These findings identify a novel Schwann cell-macrophage metabolic crosstalk mechanism and support the therapeutic potential of targeting this axis in PNI.
Retraction: Long non-coding RNA TUSC7, a target of miR-23b, plays tumor-suppressing roles in human gliomas.
Frontiers Editorial Office
Front Cell Neurosci · 2026 · PMID 41958826 · Full text
[This retracts the article DOI: 10.3389/fncel.2016.00235.].
[This retracts the article DOI: 10.3389/fncel.2016.00235.].
Impaired myelination in multiple sclerosis organoids: p21 links oligodendrocyte dysfunction to disease subtype.
Sadiq SA, Mehta T, Holzman W … +2 more , McDermott A, Daviaud N
Front Cell Neurosci · 2026 · PMID 41953255 · Full text
Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system. The cause of the disease is unknown but both genetic and environmental factors are strongly involved in its pathogenesis. We de...
Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system. The cause of the disease is unknown but both genetic and environmental factors are strongly involved in its pathogenesis. We derived cerebral and spinal cord organoids from induced pluripotent stem cells (iPSC) from healthy controls as well as from primary progressive MS (PPMS), secondary progressive MS (SPMS) and relapsing-remitting MS (RRMS) patients to investigate and compare oligodendrocyte differentiation and myelination capacity. In MS organoids, particularly in PPMS, we observed a decrease in p21 expression associated with a dysregulation of PAK1 and E2F1 expression. In parallel, a decrease in oligodendrocyte maturation was detected in long-term cultured cerebral and spinal cord organoids, especially in PPMS, leading to a reduced myelination capacity. Disruption of astrocyte and neuronal populations was also observed. Our findings demonstrate that in MS, inherent deficits in the p21 pathway may alter glial and neuronal cell populations and may contribute to the disease pathogenesis by reducing the capacity for myelin repair.
Stochasticity in action potential backpropagation: consequences for neuronal computation.
Antic SD, Milicevic KD, Lytton WW
Front Cell Neurosci · 2026 · PMID 41948461 · Full text
In cortical and hippocampal pyramidal neurons, backpropagating action potentials (bAPs) play a central role in dendritic signaling, synaptic integration, and spike-timing-dependent plasticity (STDP). In most experimental...
In cortical and hippocampal pyramidal neurons, backpropagating action potentials (bAPs) play a central role in dendritic signaling, synaptic integration, and spike-timing-dependent plasticity (STDP). In most experimental and theoretical frameworks, bAPs are implicitly treated as reliable signals that faithfully inform dendritic synapses of somatic spiking. Here, we review experimental evidence demonstrating that this assumption is often violated. In large portions of the pyramidal neuron dendritic tree, particularly in distal apical branches and apical tuft dendrites, bAP amplitude exhibits pronounced spatial and temporal variability, including: (i) activity-dependent attenuation, (ii) frequency-dependent amplification, (iii) branch-specific propagation failures, and (iv) trial-to-trial stochastic AP flickering. We summarize five experimentally documented forms of bAP variability and discuss how stochastic backpropagation may shape synaptic plasticity in computational neuroscience, especially STDP, by introducing probabilistic gates that limit the coincidence of: (i) dendritic depolarization (bAP) and (ii) synaptic input (EPSP). Finally, we consider broader implications of the AP flickering in dendrites for cortical information processing, including redundancy, averaging, evidence accumulation, and error-correcting strategies in cortical circuits.
miR-19a-3p and miR-19b-3p repress Nurr1 and Nur77 to promote microglial inflammation after spinal cord injury.
Sahebdel F, Zia A, Quintá HR … +4 more , Stucky A, Morse LR, Olson JK, Battaglino RA
Front Cell Neurosci · 2026 · PMID 41948460 · Full text
BACKGROUND: Spinal cord injury (SCI)-induced neuropathic pain affects up to 60% of individuals with SCI and is closely linked to microglia-driven neuroinflammation. Neuroinflammatory processes after SCI are major contrib...
BACKGROUND: Spinal cord injury (SCI)-induced neuropathic pain affects up to 60% of individuals with SCI and is closely linked to microglia-driven neuroinflammation. Neuroinflammatory processes after SCI are major contributors to the development and persistence of chronic pain. MicroRNAs (miRNAs) have emerged as regulators of neuroinflammation. There are higher levels of circulating miR-19a and miR-19b in persons living with SCI with neuropathic pain compared to those with no pain. These miRNAs are associated with altered the neuroprotective genes Nurr1 and Nur77. METHODS: Primary microglia cultures and a rat spinal cord injury model were used to investigate the regulatory effects of miR-19a and miR-19b on Nurr1 and Nur77 expression. RESULTS: Our study shows that miR-19a and miR-19b and their binding sites in Nurr1's 3' UTR are highly conserved across vertebrates, suggesting functional importance. Through microglia cultures and rat SCI models, we demonstrate that these miRNAs negatively regulate Nurr1, Nur77, and inflammatory gene expression. Protein-protein interaction network analysis highlights transcription factors such as MYC, RUNX1, and STAT3 as central to this regulatory network. CONCLUSION: These findings support a model in which miR-19a and miR-19b contribute to microglia-driven neuroinflammation after SCI and highlight their potential as therapeutic targets to reduce neuropathic pain.
Serum NfL and GFAP in post-COVID syndrome: minimal evidence of CNS injury after adjusting for confounders.
Wunderle M, Ribeiro A, Lethen I … +9 more , Wicklein R, Feneberg E, Wöhnl A, Negele J, Kesseler V, Niedermayer S, Lech M, Wallraven T, Schmaderer C
Front Cell Neurosci · 2026 · PMID 41939132 · Full text
BACKGROUND: Post-COVID syndrome (PCS) often includes neurological symptoms, but evidence for persistent CNS injury remains inconsistent. Serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) ar...
BACKGROUND: Post-COVID syndrome (PCS) often includes neurological symptoms, but evidence for persistent CNS injury remains inconsistent. Serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are biomarkers of neuronal and astroglial injury. We investigated whether serum NfL and GFAP differ between PCS patients and recovered controls after adjusting for age and renal function. METHODS: In this prospective single-center case-control study, serum NfL and GFAP were quantified using Simoa® (Quanterix) in 102 PCS patients and 102 recovered controls. Group comparisons employed Mann-Whitney tests and ANCOVA-style multivariable linear regression of log-transformed biomarkers adjusted for age, sex, and eGFR. Associations with eGFR were examined in multivariable models, and findings were validated in an age- and sex-matched cohort. RESULTS: Age emerged as the primary determinant of NfL and GFAP concentrations. The inverse correlations with renal function (NfL = -0.23; GFAP = -0.33) and the initially higher GFAP in PCS (60.4 vs. 52.3 pg/mL; = 0.002) were largely explained by age. After adjustment for age, sex, and eGFR, neither biomarker showed independent differences between groups (adjusted GMRs: NfL 1.04 [0.91-1.18], = 0.59; GFAP 1.10 [0.96-1.26], = 0.15). In an age- and sex-matched cohort (71 pairs), adjusted analyses confirmed no difference in NfL ( = 0.48), while GFAP demonstrated a significant increase in PCS ( = 0.15, = 0.025). CONCLUSION: GFAP concentrations were modestly elevated in PCS in an age- and sex-matched cohort and persisted after adjustment for kidney function, whereas NfL showed no group differences. These findings argue against widespread neuroaxonal injury in PCS and suggest only a subtle astroglial signal in a subset of patients. Rigorous adjustment for confounders-particularly age, sex, and renal function-is essential for valid interpretation of serum neuroinjury biomarkers in PCS.
Blood-spinal cord barrier disruption after spinal cord injury: a time-dependent mechanistic review.
Jiang Z, Zhang C, Zhao Z … +1 more , Ning B
Front Cell Neurosci · 2026 · PMID 41939131 · Full text
The blood-spinal cord barrier (BSCB) is a specialized vascular interface that preserves spinal cord homeostasis by regulating molecular and cellular trafficking between blood and neural tissue. Disruption of BSCB integri...
The blood-spinal cord barrier (BSCB) is a specialized vascular interface that preserves spinal cord homeostasis by regulating molecular and cellular trafficking between blood and neural tissue. Disruption of BSCB integrity is a critical pathological event follow-ing spinal cord injury (SCI), leading to increased permeability, inflammatory cell infil-tration, and secondary neurodegeneration. Increasing evidence indicates that BSCB breakdown is not a single event but a dynamic, time-dependent process. In this review, we summarize the molecular and cellular mechanisms responsible for BSCB disruption after SCI in a chronological manner. Key pathological events occurring during the acute, subacute, and chronic phases are discussed, including pathological hemody-namic changes, endothelial stress responses, epigenetic regulation, inflammatory me-diators, immune cell-endothelial interactions, and extracellular matrix remodeling. We further highlight endogenous protective and reparative mechanisms that emerge at later stages. A comprehensive understanding of the temporal characteristics of BSCB disruption may facilitate the development of phase-specific therapeutic strate-gies aimed at preserving barrier integrity, limiting secondary injury, and improving neurological recovery after SCI. This temporal perspective underscores the need for stage-specific interventions to preserve BSCB integrity and improve outcomes after SCI.
Transcriptomic signatures in tetrapartite brain region identifies shared and unique gene signatures for substance-use.
Veerappa A, Guda C
Front Cell Neurosci · 2026 · PMID 41929436 · Full text
INTRODUCTION: Chronic substance use is a neuropsychiatric disorder marked by persistent craving, reward seeking, and progression to addiction. The midbrain governs hunger, reward, and pleasure; the DLPFC modulates cravin...
INTRODUCTION: Chronic substance use is a neuropsychiatric disorder marked by persistent craving, reward seeking, and progression to addiction. The midbrain governs hunger, reward, and pleasure; the DLPFC modulates craving, decision making, and tolerance; the NAc influences feeding, reward, stress, and drug self-administration; and the amygdala regulates emotion and memory. METHODS: To understand these complex and dynamic events in the context of substance use disorders, we profiled transcriptomes from these four regions and integrated clustering, biclustering, WGCNA, and pathway enrichment analyses. RESULTS: Upregulation of gene expression was dominant in all four brain regions of cases versus controls. Distinct differential transcriptomic signatures were both unique to individual regions and shared across regions, identifying 186 genes exclusive to midbrain, 29 to DLPFC, 160 to NAc, and 442 in amygdala. Network analysis revealed DEGs across all regions interconnected via a neuropeptide-neurotransmitter axis, suggesting substances disrupt the equilibrium between neurotransmitters and neuropeptides. Significant upregulation of CSF3, GADD45B, SOCS3, and NPAS4 across all four regions enriched the CREB Signaling in Neurons pathway, supporting their involvement in long-lasting maladaptations of neurocircuitry due to chronic substance use. DISCUSSION: By unraveling unique and shared transcriptomic signatures, our study advances understanding of crosstalk among key players in each brain region in substance use, implying that induction and exclusion signals drive distinct pathway signaling and sustain addiction behavior. Alongside known genes in substance biology and addiction, we also identified several novel biomarkers that could confer susceptibility for addiction risk.
O-GlcNAc transferase controls excitatory synapse development and AMPA receptor expression in an activity-dependent manner.
Han L, Lagerlöf O
Front Cell Neurosci · 2026 · PMID 41924559 · Full text
Brain development and neural circuit function depend on the formation and termination of excitatory synapses. The regulation of excitatory synapse plasticity has long been associated with neuronal activity. In addition t...
Brain development and neural circuit function depend on the formation and termination of excitatory synapses. The regulation of excitatory synapse plasticity has long been associated with neuronal activity. In addition to neuronal activity, emerging data show that body metabolism affects synaptic plasticity. However, it is unclear how neuronal activity and metabolic signaling may interact to control the number and function of excitatory synapses. The nutrient sensor O-GlcNAc transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of cytoplasmic and nuclear proteins depending on the metabolic state of the body, has been implicated in excitatory synapse maturation, but its activity-dependent roles and underlying mechanisms are unclear. Here, we investigated how OGT regulates excitatory synapse structure, number and AMPA-type glutamate receptors (AMPARs) in cultured hippocampal neurons under normal and activity-suppressed conditions. We show that OGT overexpression selectively enhances accumulation of the AMPARs subunit GluA1 in dendritic spines at a mature developmental stage (DIV14), but not during early development (DIV7). Chronic suppression of neuronal activity with tetrodotoxin (TTX) abolished the OGT-dependent increase in GluA1 expression, indicating that OGT-mediated regulation of AMPARs is activity-dependent. In parallel, OGT overexpression promoted coordinated growth and maturation of excitatory synapses, increasing the size and intensity of postsynaptic PSD-95 and presynaptic vGluT1 puncta, particularly at colocalized synaptic sites. These structural effects, as well as OGT-induced increases in excitatory synapse number, were eliminated by activity blockade. Together, our findings identify the nutrient sensor OGT as an activity-dependent regulator of excitatory synapse maturation and AMPARs accumulation, revealing a molecular mechanism by which neuronal activity and metabolic signaling can be integrated to shape synaptic connectivity and function.
Establishing an experimental model approach to thermal-induced spinal cord injury in mice.
Mashima A, Yokota K, Kobayakawa K … +10 more , Saiwai H, Kitade K, Kishikawa J, Sugano M, Sasaguri S, Tarukado K, Kawaguchi K, Ono G, Maeda T, Nakashima Y
Front Cell Neurosci · 2026 · PMID 41924558 · Full text
Neurological deficits following spinal surgery represent a severe complication, and thermal damage from high-speed drills is considered a potential cause, but the underlying pathophysiology remains poorly understood. Her...
Neurological deficits following spinal surgery represent a severe complication, and thermal damage from high-speed drills is considered a potential cause, but the underlying pathophysiology remains poorly understood. Here, we aimed to develop and characterize a novel mouse model of thermal-induced spinal cord injury (TiSCI). Given that surgical drilling can generate temperatures of 90 °C, we created a TiSCI model by applying a controlled thermal exposure (90 °C for 1 min) to the exposed thoracic cord in mice. The TiSCI model induced significant and persistent hindlimb motor deficits, accompanied by marked demyelination and progressive collagen deposition at the lesion site. Transcriptomic analysis by RNA-sequencing revealed that this pathology was associated with a significant upregulation of pro-fibrotic genes, including Col1a1, Col1a2, Tgfβ1, and Acta2. Using Col1a2-EGFP transgenic mice, we identified a prominent fibrotic scar composed of Type I collagen-producing cells at the lesion site, evident by 7 and 14 days post-injury, which spatially overlapped with demyelinated regions devoid of axons. KEGG pathway analysis highlighted pathways related to extracellular matrix organization, phagocytosis, and fibroblast activation. Notably, Scarb3 and Actg2 were upregulated early, while Itgax and Fzd7 were induced later, implicating both immune cell responses and Wnt/β-catenin signaling in fibrotic scar progression. In conclusion, this study established an experimental platform for investigating TiSCI in mice, providing first direct evidence that a thermal insult causes persistent neurological deficits by inducing a robust fibrotic response. The resulting collagenous scar acts as a physical barrier to axonal connectivity, establishing the fibrotic process as a key therapeutic target.
Editorial: Ion channels in the nervous system.
Urrutia J, Villarroel A, Revuelta M
Front Cell Neurosci · 2026 · PMID 41924557 · Full text
Abstract loading — click title to view on PubMed.
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