Journal of Neuroinflammation最新文献

{"title":"LAPF enhances lysosomal acidification to promote TLR9 and cGAS-STING-mediated antiviral immunity and attenuate HSV-1-induced neuroinflammatory pain.","authors":"Erliang Kong, Mengqiu Deng, Ruifeng Ding, Mei Yang, Yongchang Li, Xudong Feng, Honghao Song, Huawei Wei, Xin Jiang, Hongbin Yuan, Chaofeng Han","doi":"10.1186/s12974-026-03856-6","DOIUrl":"https://doi.org/10.1186/s12974-026-03856-6","url":null,"abstract":"<p><p>Postherpetic neuralgia (PHN) is characterized by neural injury and neuroinflammation resulting from viral infection and reactivation. Herpes simplex virus type 1 (HSV-1) is capable of inducing virus-associated PHN-like neuropathic pain and has been widely used as a model for studying virus-induced neuroinflammatory pain. However, the immune mechanisms underlying virus-induced neuroinflammation and pain remain incompletely understood. In this study, we used an HSV-1-induced neuroinflammatory pain model and observed reduced Lapf expression following HSV-1 infection through transcriptome sequencing, which was further confirmed to be localized in microglia of the spinal dorsal horn by immunofluorescence staining. Lapf microglia-specific deficiency aggravated neuroinflammation and promoted mechanical allodynia by impairing antiviral innate immunity both in vivo and in vitro. Overexpression of Lapf in microglia strengthened antiviral innate immunity and suppressed HSV-1 replication. Mechanistically, transcriptome sequencing of Lapf microglia-specific deficient mice identified lysosomal endocytosis as a critical pathway in LAPF-mediated antiviral innate immunity. Lapf deficiency decreased lysosomal acidity, resulting in reduced TLR9 activation, thereby impairing viral DNA sensing and IFN-I production. Lapf deficiency also reduced lysosomal membrane stability, facilitating the escape of HSV-1 DNA into the cytoplasm, where it could amplify and reactivate. Conversely, Lapf overexpression enhanced lysosomal acidity and membrane stability, promoting TLR9 activation and antiviral innate immunity. Furthermore, Lapf deficiency markedly reduced the phosphorylation of STING, TBK1, and IRF3, whereas Lapf overexpression restored cGAS-STING signaling. This effect was abolished by lysosomal acidification inhibitor chloroquine (CQ), supporting that LAPF promotes lysosomal acidification-dependent antiviral immunity via TLR9 and cGAS-STING pathways. Pharmacological enhancement of LAPF activity using the dephosphorylation inhibitor SHP099 alleviated neuroinflammation and mechanical allodynia in HSV-1-induced neuroinflammatory pain model mice, suggesting potential therapeutic implications. In conclusion, our findings demonstrate that LAPF enhances lysosomal acidification to promote dual antiviral innate immune responses via TLR9 and cGAS-STING pathways in HSV-1 infection, thereby attenuating HSV-1-induced neuroinflammatory pain. These results provide mechanistic insights and potential therapeutic targets for virus-associated neuroinflammatory pain.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNF-α and IFN-γ impair neural oscillations and induce neurodegeneration by microglial nitric oxide, metabolic and oxidative stress.","authors":"Nikolai Malorny, Bruno Chausse, Babak Khodaie, Amr Elgez, Lennart Söder, Andrea Lewen, Alexei V Egorov, Oliver Kann","doi":"10.1186/s12974-026-03835-x","DOIUrl":"https://doi.org/10.1186/s12974-026-03835-x","url":null,"abstract":"<p><strong>Background: </strong>The cytokine tumor necrosis factor-alpha (TNF-α) regulates inflammatory responses in infectious and neurodegenerative diseases and also affects neuronal function. The role of TNF-α in the activation of microglial cells (resident central nervous system macrophages), including the impact on neuronal survival, excitability, and synaptic transmission is incompletely defined, however. We explored the effects of chronic TNF-α exposure (72 h) on microglia and neurons in organotypic hippocampal slice cultures from male and female rats, i.e., postnatal cortex tissue lacking leukocyte invasion and adaptive immunity.</p><p><strong>Methods: </strong>We applied gene expression analysis, biochemical assays, immunohistochemistry, electrophysiology by extracellular (local field potential) and intracellular (intrinsic membrane properties) recordings, and pharmacological ablation of the microglial cell population. We mainly focused on carbachol-induced neural network oscillations (brain waves) in the gamma frequency band (30-70 Hz) that underlie higher cognitive functions such as perception, attention, and memory.</p><p><strong>Results: </strong>TNF-α induced microglial proliferation and upregulation of genes related to inflammation and oxidative stress such as Il6 (interleukin-6), Nos2 [inducible nitric oxide (NO) synthase, iNOS] and Sod2 (superoxide dismutase 2), which was accompanied by a decreased number of slices showing gamma oscillations in extracellular recordings. Notably, a fraction of slices presented neural bursting reflecting hyperexcitability in the tissue. Neuronal dysfunction was absent during acute TNF-α exposure (30 min). When paired with the lymphocyte cytokine interferon-gamma (IFN-γ), TNF-α induced an amplified neuroinflammation response dominated by bursting or loss of electrical activity. In intracellular recordings, neurons showed a brief burst of action potentials followed by slowing of spiking with pronounced afterhyperpolarization (switch from regular to burst firing behavior) during depolarizing current injection. Notably, the impairments could be attenuated by inhibition of iNOS and NADPH oxidase, glucose supplementation, microglial depletion or blockade of TNF receptor 1 (TNFR1) signaling with small molecule drugs, RIPA-56 and ICCB-19.</p><p><strong>Conclusions: </strong>Our data provide mechanistic insight into TNF-α- and IFN-γ-induced neuronal impairments mediated by microglial NO, metabolic and oxidative stress, and demonstrate functional neuroprotection by pharmacology. Our study extends the pathophysiological understanding of diseases such as sepsis, multiple sclerosis, Alzheimer's disease, depression and schizophrenia featuring activated microglia, infiltrating monocytes and T cells, and/or blood-brain barrier leakage.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic insights and therapeutic potential of targeting the cGAS-STING pathway in neurodegenerative diseases.","authors":"Huilin Liu, Chun Hu, Hongdou Liu, Ziqing Gong, Shilong Jiang, Junkai Xie, Yongtao Li, Chong Liu, Ying Wang, Chan Zou, Guoping Yang","doi":"10.1186/s12974-026-03815-1","DOIUrl":"https://doi.org/10.1186/s12974-026-03815-1","url":null,"abstract":"<p><p>The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a central cytosolic DNA-sensing module that links DNA damage and mitochondrial dysfunction to innate immune activation. Here, we focus on canonical cGAS-STING signaling in the central nervous system (CNS) and discuss non-canonical branches only when directly relevant to neurodegeneration. We summarize structural and activation-termination mechanisms and synthesize cell-type-biased outputs across microglia, astrocytes, neurons, and oligodendroglial lineage cells. We then integrate Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease by mapping shared DNA-stress triggers to multicellular amplification loops and by grading causal evidence from genetic perturbation, pharmacological pathway interference, and correlative human datasets. Finally, we classify inhibitor modalities and emerging enabling technologies while emphasizing translational constraints, including blood-brain barrier (BBB) delivery, long-term safety, human STING-allele diversity, and pharmacodynamic biomarkers. Collectively, we propose an evidence-calibrated framework for judging when cGAS-STING is most plausibly positioned as a causal node, a permissive amplifier, or a secondary correlate in neurodegenerative disease, and where therapeutic translation should proceed cautiously.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iba1 deficiency impairs microglial synaptic remodeling and neuronal survival after axonal injury.","authors":"Koji Sekiguchi, Hirotaka Shoji, Tomoko Shindo, Jumpei Sasabe, Daiki Tokuyasu, Jin Nakahara, Tsuyoshi Miyakawa, Daisuke Ito","doi":"10.1186/s12974-026-03848-6","DOIUrl":"https://doi.org/10.1186/s12974-026-03848-6","url":null,"abstract":"<p><strong>Background: </strong>Microglia remodel neuronal circuits in pathological conditions; however, the molecular requirements for these responses and their consequences for motoneuron survival remain unclear.</p><p><strong>Methods: </strong>Aif1 (Iba1) knockout mice were generated using CRISPR/Cas9-mediated deletion, and baseline phenotypes and responses to unilateral facial nerve axotomy were assessed using immunohistochemistry, transmission electron microscopy, and single-nucleus RNA sequencing of the facial motor nucleus. Motoneuron survival and nuclear γH2AX foci were evaluated 28 days post-axotomy.</p><p><strong>Findings: </strong>Under baseline conditions, Iba1^-/- mice had reduced body weights and mild behavioral abnormalities compared to wild-type mice. After axotomy, microglial ensheathment of ChAT-positive facial motoneurons was reduced, with fewer neurons showing extensive perisomatic microglial coverage than in Iba1^+/+ mice. Ultrastructurally, somatic synapse loss observed after injury in wild-type mice was not detected in Iba1^-/- mice, and fewer injured motoneurons were in contact with microglial processes. Single-nucleus transcriptomics showed an exaggerated expansion of an interferon-responsive microglial state in Iba1-/- mice after axotomy, whereas injured motoneurons displayed altered transcriptional programs related to synapse organization and neurotransmission. At 28 days, Iba1-/- mice showed reduced motoneuron survival, lower ChAT expression, and increased nuclear γH2AX foci.</p><p><strong>Interpretation: </strong>Iba1 supports microglia-neuron cross-talk that enables effective perisomatic remodefling after axonal injury; disruption of this response is accompanied by inflammatory-state shifts and compromised motoneuron survival.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Otilonium bromide ameliorates paclitaxel-induced peripheral neuropathy by targeting phosphatase PPM1A.","authors":"Xiaojing Liu, Meng Zhang, Yue Zhang, Yining Hao, Dayun Lu, Wenjun Li, Xu Shen","doi":"10.1186/s12974-026-03845-9","DOIUrl":"https://doi.org/10.1186/s12974-026-03845-9","url":null,"abstract":"<p><p>Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) is a severe side effect lacking effective treatment, largely due to its complex and poorly understood pathogenesis. Here, we observed the pathological inhibition of phosphatase PPM1A activity in the dorsal root ganglia (DRG) tissues of PIPN mice. We also found that otilonium bromide (OB), as a PPM1A activator, ameliorated the PIPN-like pathology in mice, as evidenced by the alleviation of sensory dysfunction, myelin sheath injury, intraepidermal nerve fiber loss and vascular lesions. Using PPM1A-specific knockdown mice, we demonstrated that OB suppresses pro-inflammatory M1 macrophage polarization in the DRG through the PPM1A/NF-κB/NLRP3/IL-1β pathway, thereby alleviating axonal degeneration and neuronal apoptosis. In vitro experiments revealed that PTX-damaged DRG neurons release high-mobility group box 1 (HMGB1) to promote pro-inflammatory macrophage polarization, while OB disrupts this neuron-macrophage interaction by limiting HMGB1 release and subsequent macrophage activation. Together, our findings highlight PPM1A activation as a promising therapeutic strategy for PIPN and identify OB as a potential agent for treating this clinical side effect.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of astrocytic Bmal1 promotes blood-brain barrier disruption and synaptic dysfunction during systemic inflammation.","authors":"Changjun Lee, Yelin Lee, Woo Chan Jeong, Inhwa Hwang, Harin Bae, Do-Wan Shim, Hyeji Jung, Ji Won Um, Je-Wook Yu","doi":"10.1186/s12974-026-03841-z","DOIUrl":"https://doi.org/10.1186/s12974-026-03841-z","url":null,"abstract":"<p><p>Circadian rhythm disruption has been associated with the exaggerated inflammatory responses in peripheral tissues; however, its impact on neuroinflammation and blood-brain barrier (BBB) integrity remains unclear. Here, we identify the astrocytic circadian clock as a key regulator of BBB homeostasis during systemic inflammation. In a mouse model, circadian rhythm disruption for three weeks markedly increased BBB permeability in male mice, as evidenced by Evans blue leakage and myeloid cell infiltration into the brain parenchyma following lipopolysaccharide (LPS) challenge. Transcriptomic analyses using public datasets revealed that astrocytes exhibit the highest expression of core circadian clock genes among brain cell types. Accordingly, we generated tamoxifen-inducible, astrocyte-specific Bmal1-knockout (KO) mice. Deletion of Bmal1 in astrocytes significantly enhanced BBB leakage, astrogliosis and pericyte loss after LPS administration. Mechanistically, Bmal1-deficient astrocytes produced elevated levels of the chemokine CXCL5, which promoted CXCR2-dependent neutrophil recruitment into the brain. Pharmacological blockade of CXCR2 with SB225002 restored pericyte coverage and attenuated BBB disruption in astrocytic Bmal1 KO mice. Functionally, these mice exhibited impaired excitatory synaptic transmission following systemic inflammation, suggesting that astrocytic Bmal1 loss compromises neurovascular and synaptic integrity. Taken together, our findings demonstrate that astrocytic Bmal1 maintains BBB integrity and synaptic stability under inflammatory stress. This work also highlights astrocyte-intrinsic circadian regulation as a critical mechanism linking chemokine production to neurovascular vulnerability.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperactive basolateral amygdala mediates comorbid anxiety in chronic rhinosinusitis.","authors":"Xiaojun Zhang, Wensi Wu, Haomiao Zhao, Yimeng Chang, Xinyi Ma, Xueyun Shi, Wenshuang Li, Binxiang Tang, Pin Wang, Chen Duan, Min Jin, Xin Feng","doi":"10.1186/s12974-026-03850-y","DOIUrl":"https://doi.org/10.1186/s12974-026-03850-y","url":null,"abstract":"<p><strong>Rationale: </strong>Anxiety disorder is a common but often overlooked comorbidity in patients with chronic rhinosinusitis (CRS). However, it remains unclear which specific brain regions are involved in CRS-related anxiety-like behaviors, as well as how neural-immune interactions contribute to the progression of comorbid anxiety in CRS.</p><p><strong>Methods: </strong>Anxiety symptoms in CRS patients were evaluated using the Hospital Anxiety and Depression Scale (HADS). A papain-induced CRS mouse model was established to examine anxiety-like behaviors and associated neural and immunological alterations. Behavioral assays were combined with immunohistochemistry, in vivo fiber photometry, electrophysiology, viral tracing, and chemogenetic manipulation to identify brain regions and circuits. Peripheral inflammation, sympathetic activity, blood-brain barrier (BBB) integrity and the effects of IL-33 neutralization on peripheral inflammation, anxiety-like behaviors, and neuronal excitability were also examined.</p><p><strong>Results: </strong>Persistent anxiety was observed in CRS patients and mice, even after improvement of sinonasal inflammation. In CRS mice, anxiety-like behaviors were linked to selective hyperactivation of BLA CaMKIIα-positive neurons, with increased intrinsic excitability and excitatory synaptic input shifting the excitation-inhibition balance toward excitation. Chemogenetic inhibition of BLA neurons alleviated anxiety-like behaviors and reduced sympathetic nerve fiber density, norepinephrine release, and nasal eosinophilic inflammation, whereas activation produced the opposite effects. Functional analyses implicate a BLA-centered network involving the vHPC and premammillary nucleus (PMN) in regulating peripheral sympathetic and immune responses. Additionally, CRS mice exhibited impaired BBB integrity, and IL-33 neutralization mitigated peripheral inflammation, improved anxiety-like behaviors, and decreased BLA hyperexcitability.</p><p><strong>Conclusions: </strong>Dysregulated excitatory activity in the BLA underlies anxiety comorbidity in CRS. Our findings support the involvement of a BLA-centered functional network encompassing the vHPC and PMN in the regulation of sympathetic activity and peripheral inflammation.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 infection is associated with hypothalamic orexin suppression and persistent cortical NeuN attenuation.","authors":"Gun Young Yoon, Young Cheul Chung, Ji Hyun Choi, Yun Ha, Se Yeon Seo, Keun Bon Ku, Do Yeon Kim, Woo Yeon Hwang, Gi Uk Jeong, Dae-Gyun Ahn, Kyun-Do Kim, Je-Keun Rhee, Won-Ho Shin, Young-Chan Kwon","doi":"10.1186/s12974-026-03842-y","DOIUrl":"https://doi.org/10.1186/s12974-026-03842-y","url":null,"abstract":"<p><p>Long COVID frequently presents with persistent neurological symptoms, including cognitive impairment, fatigue, and sleep disturbances; however, its underlying mechanisms remain unclear. Here, we show that SARS-CoV-2 infection induces lasting cortical neuronal injury and hypothalamic orexin (hypocretin) dysfunction in vivo. In K18-hACE2 and wild-type BALB/c mice, viral RNA persisted in the brain and coincided with focal loss of Neuronal Nuclei (NeuN)-positive cortical neurons beyond acute infection. SARS-CoV-2, but not the influenza A virus, triggered rapid and sustained suppression of hypothalamic orexin expression, defining a virus-specific neuropathological signature. Considering the downregulation of orexin and focal cortical NeuN attenuation, we found that exogenous orexin-A/B supplementation increased NeuN abundance in vitro and in vivo under the tested conditions. Overall, these findings identify the orexin system as a candidate neural vulnerability to SARS-CoV-2 and suggest that orexinergic dysfunction may contribute to the neurological manifestations of Long COVID.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An unrecognized mechanism of neuroprotection by microglial TIA1-mediated stress granules to prevent neuroinflammation and demyelination in experimental autoimmune encephalomyelitis mice through sequestering ApoE mRNA.","authors":"Qinjiao Fu, Yanzhu Liu, Fangfang Li, Yanjiao Wang, Juanqing Yue, Yingyi Chen, Shufang Wu, Jingjing Zhang, Mengxian Jia, Yaozhi He, Jiawei Wang, Zhihui Huang, Ying Wang","doi":"10.1186/s12974-026-03833-z","DOIUrl":"https://doi.org/10.1186/s12974-026-03833-z","url":null,"abstract":"<p><p>Microglia contribute to the pathogenesis of multiple sclerosis (MS) by promoting inflammatory cascades, mediating demyelination and regulating autoimmune responses, however, the molecular mechanisms connecting cellular stress to microglia-mediated immune responses in MS remain elusive. Stress granules (SGs) serve as an adaptive response of cells to various stressors such as viral infection and oxidative stress. In this study, we found that microglial T-cell intracellular antigen 1 (TIA1), a core SG component, was upregulated in MS patients and experimental autoimmune encephalomyelitis (EAE) mice. The neuroinflammation, demyelination and clinical deficits were exacerbated in Tia1^Cx3cr1-CKO (TIA1 knockout in microglia and monocyte-derived macrophages) EAE mice. Furthermore, TIA1^-/- microglia exhibited the heightened activation characterized by increased proliferation, enhanced phagocytic activity, and a sustained polarization toward a pro-inflammatory phenotype. Notably, in an in vitro model of NaAsO₂-induced stress, TIA1 deficiency in BV2 cells and primary cultured microglia resulted in both enhanced phagocytic capacity and a pro-inflammatory phenotypic shift. Mechanistically, upon to stresses, microglial TIA1-mediated SGs formation was enhanced, leading to sequester ApoE mRNA into SGs to reduce ApoE expression, which in turn prevented excessive activation of microglia and inhibited demyelination in EAE mice. These findings uncover a previously unrecognized neuroprotective mechanism wherein TIA1-mediated SGs in microglia dynamically restrain neuroinflammation via post-transcriptional control of ApoE, revealing a new therapeutic avenue for MS.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility of multimodal metabolic analysis for detecting early changes in acute neuroinflammation.","authors":"James T Grist, Ilia Evstafev, Dominika Olesova, Signe E Nynäs, Matej Orešič, Alex M Dickens, Damian J Tyler, Yvonne Couch","doi":"10.1186/s12974-026-03839-7","DOIUrl":"https://doi.org/10.1186/s12974-026-03839-7","url":null,"abstract":"<p><p>Given the prevalence of metabolic perturbations in a variety of neurological and neurodegenerative diseases, understanding and monitoring brain metabolism is a key step in our advancement of therapies. The details of the citric acid cycle were established at the beginning of the last century but only recently have its metabolic intermediates been observed in vivo in the brain. In this study, we employed orthogonal analyses to investigate metabolic alterations in response to acute neuroinflammation in vivo, demonstrating a multi-technique approach that could be used for future studies.Hyperpolarized [1-¹³C] pyruvate spectroscopy revealed an early decline in pyruvate metabolism via pyruvate dehydrogenase (PDH), leading to reduced ¹³C-bicarbonate formation. This metabolic disruption occurred despite the absence of structural or perfusion changes on conventional MRI. Further analysis of polar metabolites in the ipsilateral hemisphere confirmed ongoing inflammatory processes. These findings highlight the potential of this dual technique approach to inform upon metabolic changes due to neuroinflammation.Combining methods to probe metabolism in invasive (metabolomics) and non-invasive (hyperpolarized MRI) manners, this represents a promising translational approach for real-time metabolic assessments in an area of the body, the brain, where studying processes such as metabolism has traditionally been challenging. This study has demonstrated the approach to monitor changes in metabolism in response to inflammation in the brain.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}