Journal of neuroimmunology最新文献

{"title":"Exercise ameliorates microglial activation and cognitive impairment induced by GFAT1 knockdown after traumatic brain injury","authors":"Tianyu Zai ,&nbsp;Mengqi Liu ,&nbsp;Weiguan Chen ,&nbsp;Chengwei Duan ,&nbsp;Jiahao Zhang ,&nbsp;Baohao Zheng ,&nbsp;Hongjian Lu","doi":"10.1016/j.jneuroim.2026.578868","DOIUrl":"10.1016/j.jneuroim.2026.578868","url":null,"abstract":"<div><h3>Background</h3><div>The potential of exercise to prevent traumatic brain injury (TBI) has been extensively studied. Microglia play a critical role in TBI pathogenesis. Glutamine-fructose-6-phosphate transaminase 1 (GFAT1), the key enzyme regulating the hexosamine biosynthetic pathway (HBP), not only controls glucose influx but also plays an important role in the neuroinflammatory process. However, the relationship between GFAT1 expression and microglial metabolic activity during treadmill exercise in TBI mice remains unclear.</div></div><div><h3>Methods</h3><div>A mouse TBI model was established via needle puncture, with mice randomly divided into sedentary and 14-day voluntary treadmill-running exercise groups. GFAT1 knockdown was achieved using GFAT1 shRNA lentivirus. Behavioral tests, electrophysiological recordings, immunohistochemistry, immunofluorescence, and Western blotting evaluated microglial activation and neurological function. An in vitro cell model was constructed with irisin and LPS, using Western blotting and TUNEL staining to assess inflammatory proteins and neuronal apoptosis.</div></div><div><h3>Results</h3><div>The TBI group showed higher GFAT1 expression than the sham group. Following TBI induction, GFAT1 knockdown increased Interleukin-6(IL-6) expression and aggravate cognitive impairment. While exercise training promoted cognitive function recovery, reduced IL-6 expression, and upregulated the expressions of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). In vitro LPS stimulation induced the expression of GFAT1, IL-6, and iNOS; however, GFAT1 knockdown further exacerbated the expression of IL-6 and iNOS. Furthermore, irisin pretreatment led to a reduction in neuronal apoptosis, an increase in Nrf2 and HO-1 expression, and a decrease in IL-6 and iNOS expression<strong>.</strong></div></div><div><h3>Conclusion</h3><div>Exercise ameliorates microglial activation and cognitive impairment induced by GFAT1 knockdown after traumatic brain injury.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578868"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain tumor detection using HyGSNet and feature extraction with DWT-based GDP","authors":"Ponlatha Sambandham ,&nbsp;Someswari Perla ,&nbsp;Katakam Venkateswara Rao ,&nbsp;Ganji Ramanjaiah","doi":"10.1016/j.jneuroim.2026.578869","DOIUrl":"10.1016/j.jneuroim.2026.578869","url":null,"abstract":"<div><div>A life-threatening condition that impacts neurological function is brain tumors, which can lead to psychiatric complications such as depression and panic attacks. Timely and accurate detection, followed by appropriate treatment, is essential to improve the quality of life. Quick and early recognition of brain tumors significantly enhances treatment outcomes and promotes effective healing. In this context, medical image processing plays a critical role in assisting clinicians to detect and classify brain abnormalities. However, the manual process is time-consuming and heavily reliant on the expertise of physicians. Therefore, an intelligent system for brain tumor detection is essential to support clinical decision-making. This research presented a Hybrid Google SpinalNet (HyGSNet) to automatically detect brain tumors from Magnetic resonance imaging (MRI) images. Here, the proposed HyGSNet model is the hybridization of GoogleNet and SpinalNet. Initially, the Adaptive Wiener filter is used for pre-processing the input image, and the UNeXt is used for the segmentation of the filtered image. Then, the image augmentation process is followed by feature extraction to extract the essential features. Finally, the extracted features are passed to the HyGSNet for detecting brain tumor. Here, the performance of HyGSNet is evaluated with various evaluation metrics. The HyGSNet approach recorded high performance with specificity of 93%, accuracy of 93%, and sensitivity of 93.7%. The experimental results demonstrate that the proposed approach achieves consistently high performance across key evaluation metrics, indicating its robustness and reliability for brain tumor detection.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578869"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146064435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postbiotics and the gut–brain axis: A mechanistic review on modulating neuroinflammation and cognitive aging","authors":"Rijhul Lahariya ,&nbsp;Gargee Anand ,&nbsp;Bandana Kumari ,&nbsp;Ketan Priyadarshi","doi":"10.1016/j.jneuroim.2026.578870","DOIUrl":"10.1016/j.jneuroim.2026.578870","url":null,"abstract":"<div><div>Aging triggers gut microbiota dysbiosis that disrupts the gut-brain axis (GBA), promoting neuroinflammation and neurodegeneration. Elderly exhibit reduced microbial diversity, depleted beneficial bacteria, and expanded pathobionts, elevating neurotoxic metabolites—lipopolysaccharides (LPS), trimethylamine-N-oxide, kynurenine derivatives, and secondary bile acids. These drive “inflammaging,” blood-brain barrier breakdown, microglial activation, mitochondrial impairment, and proteinopathies in Alzheimer's and Parkinson's disease. Conversely, neuroprotective metabolites from commensals—short-chain fatty acids, indole-3-propionic acid, and urolithins—preserve gut integrity, suppress inflammation, upregulate BDNF for synaptic plasticity, and enhance mitophagy. Postbiotics, stable probiotic-derived bioactives (butyrate, polyphenol metabolites, and lactate derivatives), surpass live probiotics in safety and precision. They modulate GBA via histone deacetylase inhibition, GPR41/43 signaling, NF-κB blockade, and microglial M2 shift, blocking LPS translocation and bolstering neuronal resilience. Preclinical rodent studies demonstrate robust neuroprotection, but human translation reveals challenges: inter-individual microbiota variability (diet/genetics/comorbidities), inconsistent metabolite absorption/brain penetration between species, methodological limitations (16S rRNA vs. functional metagenomics), postbiotic standardization barriers, and sparse Phase I/II trials showing biomarker benefits without cognitive endpoints. This review synthesizes gut dysbiosis-metabolite-brain aging mechanisms, positioning postbiotics as precision therapeutics. Multi-omics stratified controlled trials are essential to validate long-term efficacy for delaying neurodegeneration and extending cognitive health.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578870"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibodies in Creutzfeldt-Jakob disease: A systematic review of patient characteristics, diagnostics, and clinical implications","authors":"Raluca Bilavu ,&nbsp;Marius Benta ,&nbsp;Amalia Cornea ,&nbsp;Lucian Vasiluta ,&nbsp;Elena Cecilia Rosca","doi":"10.1016/j.jneuroim.2026.578865","DOIUrl":"10.1016/j.jneuroim.2026.578865","url":null,"abstract":"<div><h3>Background</h3><div>Creutzfeldt–Jakob disease (CJD) is a rare, rapidly progressive prion neurodegenerative disorder causing fatal dementia. Recently, reports have identified various autoantibodies in confirmed CJD patients, raising questions about their significance. We performed a scoping review of published CJD cases with co-occurring antibodies, including antineuronal (e.g., NMDAR, LGI1, CASPR2, VGKC, GAD65, GlyR), anti-thyroid peroxidase, antinuclear, and infection-related antibodies, to characterize patient demographics, clinical and diagnostic features, and outcomes, and explore the pathophysiological implications of this association.</div></div><div><h3>Methods</h3><div>We searched PubMed and Scopus databases up to June 2024, following a published protocol. We included definite/probable CJD cases in which serum/CSF testing detected autoantibodies. Demographic information, clinical presentations, diagnostic findings, treatments, and outcomes were analyzed.</div></div><div><h3>Results</h3><div>We identified 65 CJD patients with co-occurring antibodies and reported an additional case of a 58-year-old woman with genetic CJD and co-existing anti-TPO and weakly positive CASPR2 antibodies. The median age was 61 years (range 28–82), with NMDAR-Ab patients older and LGI1/CASPR2-Ab cases younger. Most were diagnosed with sporadic CJD (86%) and confirmed by CJD biomarkers (RT-QuIC 100%, 14–3-3 92.6%, Tau 91.7%). Antibodies were mainly found in serum (87.2% vs. 29.8% in CSF). Rapidly progressive dementia was universal, with gait impairment (71.9%) and movement disorders (59.4%) being common. Most cases showed no improvement with immunotherapy, indicating that antibodies may be an epiphenomenon. However, a few cases had transient or partial improvement, suggesting a possible modulatory role or dual pathology.</div></div><div><h3>Conclusion</h3><div>Antibodies are increasingly noted in CJD as a secondary effect of neurodegeneration. They complicate diagnosis and rarely suggest treatable aspects of the disease. More research is needed to clarify their complex role.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578865"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum from patients with acetylcholine receptor antibody–positive myasthenia gravis triggers pathogenic changes in human myotube cells","authors":"Keisuke Tanaka ,&nbsp;Akiyuki Uzawa ,&nbsp;Manato Yasuda ,&nbsp;Yosuke Onishi ,&nbsp;Hiroyuki Akamine ,&nbsp;Hideo Handa ,&nbsp;Etsuko Ogaya ,&nbsp;Shota Miyake ,&nbsp;Masayuki Baba ,&nbsp;Hiroto Abe ,&nbsp;Koki Nagaoka ,&nbsp;Yuko Nakatake-Furuie ,&nbsp;Kenichi Serizawa ,&nbsp;Satoshi Kuwabara","doi":"10.1016/j.jneuroim.2026.578871","DOIUrl":"10.1016/j.jneuroim.2026.578871","url":null,"abstract":"<div><h3>Background</h3><div>Some patients with myasthenia gravis (MG) are refractory to available treatments, highlighting the need to further understand the pathogenesis of the disease. This study aimed to determine whether components in the serum from patients with acetylcholine receptor (AChR) antibody–positive MG affect myotubes, to explore their possible role in disease pathogenesis beyond the inhibition of acetylcholine signal transmission.</div></div><div><h3>Methods</h3><div>Serum was collected from 14 patients with AChR antibody–positive MG. The differentiated human myotubes were stimulated with 10% serum from healthy controls or patients with MG. After 24 h, ribonucleic acid extraction/sequencing was performed, and differentially expressed genes (DEGs) were extracted. Pathway analysis was completed using DEGs that were downregulated by stimulation with serum from patients with MG. Expression of genes important for muscle contraction was measured and myotube diameter was determined by immunostaining.</div></div><div><h3>Results</h3><div>Approximately 1200 DEGs were extracted by comparing gene expression in cultured human myotube cells stimulated with serum from healthy controls and patients with MG. Gene ontology terms linked with muscle function were suppressed in myotube cells stimulated with patient serum. Suppression of pathways associated with muscle atrophy/weakness, decreased expression of genes associated with muscle contraction, and smaller myotube diameter were confirmed in myotube cells stimulated with serum from patients versus healthy controls.</div></div><div><h3>Conclusion</h3><div>Factors other than acetylcholine signal transmission inhibition may contribute to the pathogenesis of AChR antibody–positive MG. Further research is needed to clarify the pathways involved, potentially leading to more tailored pharmacotherapies.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578871"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic stress, gut dysbiosis, and cholesterol metabolism: Implications for Alzheimer's disease","authors":"Ashmita Das ,&nbsp;Navya P. ,&nbsp;Durlav Chowdhury ,&nbsp;Arijit Das ,&nbsp;Rahul Manna ,&nbsp;Surendra H. Bodakhe","doi":"10.1016/j.jneuroim.2026.578853","DOIUrl":"10.1016/j.jneuroim.2026.578853","url":null,"abstract":"<div><div>Alzheimer's disease is a degenerative neurological condition that gradually worsens and is the predominant type of dementia evident in millions of individuals globally. The intricate origin and development of this condition includes multiple genetic and environmental risk factors, alterations in gene expression, and activation of detrimental pathways. Chronic stress can adversely affect brain structure and function, leading to diminished cognitive ability, impaired decision-making, and poor mood regulation. The gut-brain axis, influenced by dietary and early life variables, significantly affects the control of stress responses. The human microbiota forms a symbiotic interaction with the host, impacting protective cell barriers, metabolic processes, and immune functions in the intestines. Chronic stress and high-cholesterol diets can alter gut microbiota composition, influencing behaviour, immune responses, and intestinal function. Oxysterols affect gut health and inflammation through the alteration of tight junctions and the stimulation of proinflammatory bacterial proliferation. This review provides a thorough explanation of the structure and function of the dietary stress system, its relationship with the central nervous system (CNS) and endocrine axis, and evidence connecting stress to the core processes of stress-related illnesses impacting AD. A thorough comprehension of the complex interplay among chronic stress, gut dysbiosis, and Alzheimer's disease progression could provide novel insights for the formulation of targeted therapeutic interventions.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578853"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145929195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Free light chains analysis in cerebrospinal fluid for the diagnosis of multiple sclerosis: A study in the Israeli population","authors":"Alina Ostrovsky,&nbsp;Amos J. Simon,&nbsp;Batia Kaplan","doi":"10.1016/j.jneuroim.2026.578873","DOIUrl":"10.1016/j.jneuroim.2026.578873","url":null,"abstract":"<div><h3>Background</h3><div>The 2024 revision of the McDonald criteria for multiple sclerosis (MS) recognized kappa free light chain (FLCκ) as a quantitative biomarker of intrathecal immunoglobulin synthesis equivalent to oligoclonal bands (OCB). However, diagnostic performance of reported FLC thresholds vary across laboratories due to differences in instrumentation, assay type, population and regional characteristics.</div></div><div><h3>Objectives</h3><div>Assessing of the utility of nephelometric FLC assay for MS diagnosis in an Israeli cohort.</div></div><div><h3>Methods</h3><div>A total of 135 patients with MS, non-MS demyelinating/inflammatory and non-demyelinating neurological disorders were tested using FLC assay and OCB technique. FLCκ and λ concentration and their index values were estimated. Statistical analysis methods included Mann-Whitney and Kruskal-Wallis tests, Spearman correlation, and receiver operating characteristic (ROC) curves.</div></div><div><h3>Results</h3><div>FLCκ metrics outperformed FLCλ in diagnosing MS. Using FLCκ index, a threshold 7.0 yielded 82% specificity and 77.1% sensitivity, while 72% specificity and 82% sensitivity was achieved using κ concentration cut-off 0.19 mg/L. Specificity of OCB test (84%) was similar to that of FLCκ index, though OCB sensitivity (88.6%) exceeded the FLC-based metrics. Specifically, cases with κ index &gt;11 and concentration &gt; 0.2 mg/L were MS or OCB-positive, whereas cases with κ concentration &lt; 0.1 mg/L were non-MS or OCB-negative. Hence, 60% of the cases may be safely excluded from OCB testing.</div></div><div><h3>Conclusions</h3><div>Optimized FLCκ thresholds effectively assist MS diagnosis within Israeli population. Combined FLC thresholds (κ index and concentration values) were established for screening clearly defined/unequivocal cases that may not require time-consuming operator-dependent OCB analysis. Rapid quantitative FLC assay holds promise as a screening tool for unequivocal cases prior to OCB testing.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578873"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect on disease activity of ofatumumab in the treatment of glial fibrillary acidic protein astrocytopathy and 18F-DPA714 PET/MRI imaging assessment","authors":"Yingbo Han ,&nbsp;Xiaoyu Chen ,&nbsp;Qinming Zhou ,&nbsp;Ruifen Duan ,&nbsp;Mengmeng Zhang ,&nbsp;Sheng Chen ,&nbsp;Huanyu Meng","doi":"10.1016/j.jneuroim.2026.578862","DOIUrl":"10.1016/j.jneuroim.2026.578862","url":null,"abstract":"<div><div>A 49-year-old male with Glial Fibrillary Acidic Protein Astrocytopathy (GFAP-A) presented with progressive cognitive decline, visual hallucinations, and bowel/bladder incontinence. Brain MRI revealed extensive white matter hyperintensities on T2-FLAIR sequences. After suboptimal response to first-line treatments including corticosteroids and intravenous immunoglobulin (IVIg), the patient was initiated on Ofatumumab (OFA) therapy. Treatment response was systematically monitored through validated clinical assessment tools (MMSE, MoCA, mRS, and CASE) and advanced neuroimaging, including conventional MRI and ¹⁸F-DPA714 PET. Following OFA treatment, the patient demonstrated marked clinical improvement and radiological resolution. Notably, ¹⁸F-DPA714 PET imaging captured dynamic changes in neuroinflammation and revealed distinct patterns not apparent on conventional MRI. This case demonstrates the potential effect on disease activity and safety of OFA in GFAP-A treatment while highlighting the value of ¹⁸F-DPA714 PET as an innovative tool for monitoring neuroinflammation and therapeutic response. To our knowledge, this represents the first comprehensive multimodal assessment using ¹⁸F-DPA714 PET/MRI in a GFAP-A patient treated with ofatumumab.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578862"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B cell tolerance checkpoint function in multiple sclerosis and transient CD52 depletion","authors":"Anastasia Alexaki ,&nbsp;Fotis Baltoumas ,&nbsp;Dimitrios Tzanetakos ,&nbsp;Chrysoula Zografou ,&nbsp;Theodoros Dame ,&nbsp;Chrysoula Michaletou ,&nbsp;Galini Kyriakaki ,&nbsp;Aglaia G. Vakrakou ,&nbsp;Maria Anagnostouli ,&nbsp;Georgia Karadima ,&nbsp;Marianna Tzanoudaki ,&nbsp;Marinos C. Dalakas ,&nbsp;Leonidas Stefanis ,&nbsp;Konstantinos Kilidireas ,&nbsp;Kevin C. O'Connor ,&nbsp;Georgios Pavlopoulos ,&nbsp;Panos Stathopoulos","doi":"10.1016/j.jneuroim.2026.578854","DOIUrl":"10.1016/j.jneuroim.2026.578854","url":null,"abstract":"<div><div>Transient CD52 immune cell depletion with the monoclonal antibody alemtuzumab is highly effective in treating relapsing-remitting multiple sclerosis but often leads to secondary autoimmunity. Whether these effects are linked to an alteration of B cell tolerance mechanisms is currently not known. To evaluate peripheral B cell tolerance checkpoint integrity in patients and controls, we constructed 138 recombinant mAbs from single mature naïve B cells and tested their poly- and autoreactivity. We examined three healthy donors (HDs), three immunotherapy-naïve MS patients, and six patients treated with alemtuzumab at comparable time points post-treatment (mean ± SD 3.8 ± 0.39 years). Moreover, we investigated B cell receptor (BCR) repertoire parameters associated with tolerance mechanisms in the same subject groups. Polyreactive and autoreactive fraction means did not differ significantly among the three subgroups. Presence of a high or low autoreactive fraction of naïve B cells in patients treated with alemtuzumab did not correlate with secondary autoimmunity at the time of sampling and with future MS activity, and therefore most likely reflects stochastic variation in the context of immune reconstitution. In BCR repertoire analysis, alemtuzumab-treated patients showed lower mean naïve complementarity-determining region 3 (CDR3) net charge compared to HDs (<em>P</em> = 0.0036), an interesting yet isolated finding warranting further investigation. Overall, transient CD52 depletion did not seem to affect major changes in peripheral B cell tolerance checkpoint function as assessed with naïve B cell cloning and BCR NGS, while observations in the described setting may also apply to other immune reconstitution therapies.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578854"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The NEDD8-activating enzyme inhibitor MLN4924 reduces inflammation, blood-brain barrier disruption and brain injury after intracerebral hemorrhage in mice","authors":"Yu Huang ,&nbsp;Zihan Wang ,&nbsp;Shaochen Wang ,&nbsp;Chenxi Liu ,&nbsp;Luping Chang ,&nbsp;Xue Geng ,&nbsp;Pengyue Du ,&nbsp;Yong-Chen Wang ,&nbsp;Wenying Fan ,&nbsp;Bing-Qiao Zhao","doi":"10.1016/j.jneuroim.2026.578872","DOIUrl":"10.1016/j.jneuroim.2026.578872","url":null,"abstract":"<div><div>Inflammation is a key factor leading to secondary brain injury after intracerebral hemorrhage (ICH). Neddylation, a post-translational modification that attaches NEDD8 (neuronal precursor cell-expressed developmentally downregulated protein 8) to targets, regulates diverse cellular processes. Neddylation is overactivated in various cancers and linked to atherosclerosis and inflammatory disorders, but its role in ICH remains unclear. In this study, mice were subjected to ICH by injection of collagenase. The NEDD8-activating enzyme inhibitor MLN4924 was administered subcutaneously post-ICH. We found that NEDD8 expression was upregulated in macrophages and microglia after ICH. Treatment with MLN4924 reduced NEDD8 expression, cullin-1 neddylation, macrophage infiltration, microglial activation, and the production of proinflammatory cytokines. These anti-inflammatory effects were accompanied by attenuated loss of tight junction proteins, blood-brain barrier (BBB) damage, neuronal degeneration and brain injury, and improved neurological function. Furthermore, MLN4924 treatment induced the accumulation of the cullin-RING E3 ligase substrates, including phosphorylated ERK5 and KLF2, and reduced ICAM-1 expression. Inhibiting ERK5 reversed the beneficial effects of MLN4924 on inflammation, BBB disruption, and neurobehavioral deficits. Collectively, inhibition of the NEDD8 pathway by MLN4924 attenuates inflammation, BBB disruption, and neurological deficits via the p-ERK5-KLF2-ICAM-1 axis, highlighting NEDD8 pathway as a potential therapeutic target for ICH.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"413 ","pages":"Article 578872"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}