Pub Date : 2025-04-14DOI: 10.1016/j.jneuroim.2025.578618
Qiuju Li , Bin Liu , Yangtai Guan, Yuhui Wang
Autoimmune gastritis (AIG) is characterized by the destruction of gastric parietal cells, leading to vitamin B12 deficiency and potentially causing subacute combined degeneration of the spinal cord (SCD). We present a case of a 61-year-old male with AIG who developed SCD and underwent three sessions of double filtration plasmapheresis (DFPP), resulting in significant reduction of autoantibody titers and improvement in neurological symptoms. DFPP demonstrated efficacy in treating AIG complicated by SCD, offering potentially faster clinical response than conventional therapies by rapidly reducing autoantibody levels. This case underscores the importance of early diagnosis and intervention in preventing irreversible neurological damage, suggesting DFPP as a promising adjunctive treatment for AIG with SCD and warranting further investigation into its mechanisms and applications in autoimmune diseases.
{"title":"Double filtration plasmapheresis in autoimmune gastritis with subacute combined degeneration of the spinal cord: A case report","authors":"Qiuju Li , Bin Liu , Yangtai Guan, Yuhui Wang","doi":"10.1016/j.jneuroim.2025.578618","DOIUrl":"10.1016/j.jneuroim.2025.578618","url":null,"abstract":"<div><div>Autoimmune gastritis (AIG) is characterized by the destruction of gastric parietal cells, leading to vitamin B12 deficiency and potentially causing subacute combined degeneration of the spinal cord (SCD). We present a case of a 61-year-old male with AIG who developed SCD and underwent three sessions of double filtration plasmapheresis (DFPP), resulting in significant reduction of autoantibody titers and improvement in neurological symptoms. DFPP demonstrated efficacy in treating AIG complicated by SCD, offering potentially faster clinical response than conventional therapies by rapidly reducing autoantibody levels. This case underscores the importance of early diagnosis and intervention in preventing irreversible neurological damage, suggesting DFPP as a promising adjunctive treatment for AIG with SCD and warranting further investigation into its mechanisms and applications in autoimmune diseases.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"403 ","pages":"Article 578618"},"PeriodicalIF":2.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838704","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}
Pub Date : 2025-04-13DOI: 10.1016/j.jneuroim.2025.578615
Yuka Inoue , Takayuki Fujii , Kaoru Yoshida Kashu , Mitsuru Watanabe , Katsuhisa Masaki , Eizo Tanaka , Yuu-ichi Kira , Hajime Takeuchi , Ken Yamaura , Noriko Isobe
Neuromyelitis optica spectrum disorders (NMOSD) are characterized by severe inflammation-mediated astrocytopathy in the central nervous system. Neuropathic pain (NP) is highly prevalent among patients with NMOSD, and significantly impairs their quality of life. Alpha-calcitonin gene-related peptide (α-CGRP) is a neuropeptide related to pain and neuroinflammation in the central and peripheral nerves; however, the involvement of α-CGRP in NMOSD pathophysiology remains unexplored. Here, we measured serum levels of α-CGRP in 33 patients with NMOSD and 36 healthy controls by enzyme-linked immunosorbent assay to clarify associations between serum α-CGRP levels and clinical NMOSD features, including NP. The NMOSD patients showed significantly higher serum α-CGRP levels than healthy controls [median (interquartile range), ng/mL; 1.89 (1.66–2.39) vs 1.54 (1.34–1.87), p = 0.008]. NMOSD patients with sensory or bowel and bladder dysfunction had elevated serum α-CGRP levels compared with those without [2.02 (1.76–2.80) vs 1.76 (1.44–1.95), p = 0.049; 2.19 (1.96–2.86) vs 1.71 (1.40–1.90), p < 0.001, respectively]. Serum α-CGRP levels were higher in NMOSD patients with neuropathic pain than in those without [2.00 (1.71–2.76) vs 1.78 (1.51–1.97), p = 0.120]. NMOSD patients with spinal cord lesions on magnetic resonance imaging showed significantly higher serum α-CGRP levels compared with those without [2.02 (1.73–2.83) vs 1.73 (1.36–1.87), p = 0.044]. These findings indicate an association between α-CGRP and NMOSD pathophysiological status, especially sensory and bowel and bladder dysfunction derived from spinal cord lesions.
{"title":"Associations between serum levels of alpha-calcitonin gene-related peptide and clinical features of neuromyelitis optica spectrum disorders","authors":"Yuka Inoue , Takayuki Fujii , Kaoru Yoshida Kashu , Mitsuru Watanabe , Katsuhisa Masaki , Eizo Tanaka , Yuu-ichi Kira , Hajime Takeuchi , Ken Yamaura , Noriko Isobe","doi":"10.1016/j.jneuroim.2025.578615","DOIUrl":"10.1016/j.jneuroim.2025.578615","url":null,"abstract":"<div><div>Neuromyelitis optica spectrum disorders (NMOSD) are characterized by severe inflammation-mediated astrocytopathy in the central nervous system. Neuropathic pain (NP) is highly prevalent among patients with NMOSD, and significantly impairs their quality of life. Alpha-calcitonin gene-related peptide (α-CGRP) is a neuropeptide related to pain and neuroinflammation in the central and peripheral nerves; however, the involvement of α-CGRP in NMOSD pathophysiology remains unexplored. Here, we measured serum levels of α-CGRP in 33 patients with NMOSD and 36 healthy controls by enzyme-linked immunosorbent assay to clarify associations between serum α-CGRP levels and clinical NMOSD features, including NP. The NMOSD patients showed significantly higher serum α-CGRP levels than healthy controls [median (interquartile range), ng/mL; 1.89 (1.66–2.39) vs 1.54 (1.34–1.87), <em>p</em> = 0.008]. NMOSD patients with sensory or bowel and bladder dysfunction had elevated serum α-CGRP levels compared with those without [2.02 (1.76–2.80) vs 1.76 (1.44–1.95), <em>p</em> = 0.049; 2.19 (1.96–2.86) vs 1.71 (1.40–1.90), <em>p</em> < 0.001, respectively]. Serum α-CGRP levels were higher in NMOSD patients with neuropathic pain than in those without [2.00 (1.71–2.76) vs 1.78 (1.51–1.97), <em>p</em> = 0.120]. NMOSD patients with spinal cord lesions on magnetic resonance imaging showed significantly higher serum α-CGRP levels compared with those without [2.02 (1.73–2.83) vs 1.73 (1.36–1.87), <em>p</em> = 0.044]. These findings indicate an association between α-CGRP and NMOSD pathophysiological status, especially sensory and bowel and bladder dysfunction derived from spinal cord lesions.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"404 ","pages":"Article 578615"},"PeriodicalIF":2.9,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844106","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}
Pub Date : 2025-04-12DOI: 10.1016/j.jneuroim.2025.578617
Tichakorn Singto , Alisa Sergeeva , Viviane Filor , Jonathan Vidak , Burkhard Kleuser , Vitaly Belik , Fabian Schumacher , Wolfgang Bäumer
The interaction between the neuroimmune system plays a crucial role in itch sensation, yet most research has focused on immune cells within the skin. Our study seeks to explore the presence and functions of immune cells within the dorsal root ganglia (DRG) in the context of allergic contact dermatitis (ACD). Immunofluorescence and histological staining techniques were employed to identify immune cells, including T-cells, basophils, mast cells, and dendritic cells (DCs), within the DRG of BALB/c mice sensitized and challenged with toluene diisocyanate (TDI). Our findings revealed an increase in mast cells and DCs within the DRG under ACD condition. Additionally, when DRG neurons were cultured with mast cells, a higher proportion of neurons exhibited responses to non-histaminergic pruritogens compared to neurons cultured alone. This suggests that mast cells may contribute to heightened sensitivity to non-histaminergic pruritogens. Furthermore, we conducted transcriptomic analysis of DCs within the DRG using RNA sequencing, followed by pathway enrichment analysis. Our analysis revealed that sorted DCs are implicated in immune responses, inflammation, and itch, with notable upregulation of Cathepsin S (Ctss) and sphingosine-1-phosphate (S1P) phosphatase 2 (Sgpp2). Subsequent functional experiments targeting CTSS in co-culture studies validated suppressed response to pruritogen and agonists of TRPA1 and TRPV1, indicating a potential role in peripheral sensitization. Additionally, the co-culture study indicated that the neuroimmune interaction between DCs and DRG neurons might involve S1P metabolism and S1P receptor signaling. In conclusion, targeting DCs and exploring the non-histaminergic functions of mast cells within the DRG, holds promise as novel targets for treating pruritus.
{"title":"Immune cells in dorsal root ganglia are associated with pruritus in a mouse model of allergic contact dermatitis and co-culture study","authors":"Tichakorn Singto , Alisa Sergeeva , Viviane Filor , Jonathan Vidak , Burkhard Kleuser , Vitaly Belik , Fabian Schumacher , Wolfgang Bäumer","doi":"10.1016/j.jneuroim.2025.578617","DOIUrl":"10.1016/j.jneuroim.2025.578617","url":null,"abstract":"<div><div>The interaction between the neuroimmune system plays a crucial role in itch sensation, yet most research has focused on immune cells within the skin. Our study seeks to explore the presence and functions of immune cells within the dorsal root ganglia (DRG) in the context of allergic contact dermatitis (ACD). Immunofluorescence and histological staining techniques were employed to identify immune cells, including T-cells, basophils, mast cells, and dendritic cells (DCs), within the DRG of BALB/c mice sensitized and challenged with toluene diisocyanate (TDI). Our findings revealed an increase in mast cells and DCs within the DRG under ACD condition. Additionally, when DRG neurons were cultured with mast cells, a higher proportion of neurons exhibited responses to non-histaminergic pruritogens compared to neurons cultured alone. This suggests that mast cells may contribute to heightened sensitivity to non-histaminergic pruritogens. Furthermore, we conducted transcriptomic analysis of DCs within the DRG using RNA sequencing, followed by pathway enrichment analysis. Our analysis revealed that sorted DCs are implicated in immune responses, inflammation, and itch, with notable upregulation of Cathepsin S (<em>Ctss</em>) and sphingosine-1-phosphate (S1P) phosphatase 2 (<em>Sgpp2</em>). Subsequent functional experiments targeting CTSS in co-culture studies validated suppressed response to pruritogen and agonists of TRPA1 and TRPV1, indicating a potential role in peripheral sensitization. Additionally, the co-culture study indicated that the neuroimmune interaction between DCs and DRG neurons might involve S1P metabolism and S1P receptor signaling. In conclusion, targeting DCs and exploring the non-histaminergic functions of mast cells within the DRG, holds promise as novel targets for treating pruritus.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"404 ","pages":"Article 578617"},"PeriodicalIF":2.9,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839207","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}
Pub Date : 2025-04-11DOI: 10.1016/j.jneuroim.2025.578616
Yury Zharikov , Anna Shitova , Polina Melnikova , Ilya Voloshin , Maria Orliuk , Anna Olsufieva , André Pontes-Silva , Tatiana Zharikova
HIV-associated neurocognitive disorders are a common manifestation of HIV infection, affecting more than half of HIV-infected individuals, including those receiving targeted antiviral therapy. A common feature of the course of HIV infection during therapy is large-scale immune responses in the brain. Several pathways are involved in the neuropathogenesis of HIV infection: Cellular entry, inflammatory processes in microglia, activation of astroglia, myeloid cells, and damage to brain vessels leading to neurocirculatory disorders. Data on vascular diseases that influence the development of neurocognitive impairment in HIV-positive patients will also be examined, as well as better intervention strategies for complex neurocognitive disorders and neurodegenerative processes in HIV infection.
{"title":"Autoantibody-mediated disorders of the central and peripheral nervous system: Overview Infection","authors":"Yury Zharikov , Anna Shitova , Polina Melnikova , Ilya Voloshin , Maria Orliuk , Anna Olsufieva , André Pontes-Silva , Tatiana Zharikova","doi":"10.1016/j.jneuroim.2025.578616","DOIUrl":"10.1016/j.jneuroim.2025.578616","url":null,"abstract":"<div><div>HIV-associated neurocognitive disorders are a common manifestation of HIV infection, affecting more than half of HIV-infected individuals, including those receiving targeted antiviral therapy. A common feature of the course of HIV infection during therapy is large-scale immune responses in the brain. Several pathways are involved in the neuropathogenesis of HIV infection: Cellular entry, inflammatory processes in microglia, activation of astroglia, myeloid cells, and damage to brain vessels leading to neurocirculatory disorders. Data on vascular diseases that influence the development of neurocognitive impairment in HIV-positive patients will also be examined, as well as better intervention strategies for complex neurocognitive disorders and neurodegenerative processes in HIV infection.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"403 ","pages":"Article 578616"},"PeriodicalIF":2.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838703","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}
Pub Date : 2025-04-10DOI: 10.1016/j.jneuroim.2025.578607
Sahla El Mahdaoui , Signe Refstrup Husted , Malene Bredahl Hansen , Stefan Cobanovic , Mie Reith Mahler , Sophie Buhelt , Marina Rode von Essen , Finn Sellebjerg , Jeppe Romme Christensen
{"title":"Corrigendum to “Cerebrospinal fluid soluble CD27 is associated with CD8+ T cells, B cells and biomarkers of B cell activity in relapsing-remitting multiple sclerosis” [Journal of neuroimmunology vol. 381 (2023): 578128]","authors":"Sahla El Mahdaoui , Signe Refstrup Husted , Malene Bredahl Hansen , Stefan Cobanovic , Mie Reith Mahler , Sophie Buhelt , Marina Rode von Essen , Finn Sellebjerg , Jeppe Romme Christensen","doi":"10.1016/j.jneuroim.2025.578607","DOIUrl":"10.1016/j.jneuroim.2025.578607","url":null,"abstract":"","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"403 ","pages":"Article 578607"},"PeriodicalIF":2.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817241","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}
Pub Date : 2025-04-08DOI: 10.1016/j.jneuroim.2025.578612
Maria Staykova
{"title":"An enjoyable career in science","authors":"Maria Staykova","doi":"10.1016/j.jneuroim.2025.578612","DOIUrl":"10.1016/j.jneuroim.2025.578612","url":null,"abstract":"","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"404 ","pages":"Article 578612"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816783","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}
Pub Date : 2025-04-08DOI: 10.1016/j.jneuroim.2025.578611
Giang T. Tran , Sukhandep Bedi , Prateek Rakesh , Nirupama D. Verma , Nicole Carter , Catherine M. Robinson , Ranje Al-Atiyah , Bruce M. Hall , Suzanne J. Hodgkinson
Experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin basic protein (MBP) is a self-limiting disease model of multiple sclerosis. CD4+CD25+Foxp3+T cells play a role in limiting autoimmune disease but treatment with antigen naïve CD4+CD25+ cells does not reduce EAE.
This study examined if in vitro activation by MBP and rIL-2 induced CD4+CD25+Foxp3+ cells that could inhibit EAE. Culture of CD4+CD8-CD25+cells from naïve rats with MBP and rIL-2 induced activated Treg that reduced the severity of clinical EAE and infiltration of CD8+T cells and macrophage into brain stem. CD4+CD25+T cells activated by an irrelevant autoantigen and rIL-2 did not suppress EAE. Resting CD4+CD25+T cells activated by autoantigen and rIL-2 have mRNA for Infgr, Il12rb2, Il5 but not Tbet, Gata3, Ilr5ra or Ifng. These changes in mRNA expression are the markers of Ts1 cells.
A proportion of CD4+CD8-CD25+ cells activated by MBP/rIL-2 were induced to express CD8α, CD8β and CD62L. Depletion of CD4+CD8α+CD25+ cells removed the capacity of MBP and rIL-2 activated CD4+CD25+T cells to suppress EAE.
This study demonstrated that in vitro activation of CD4+CD8-CD25+ cells by MBP/rIL-2 induced relevant antigen-specific Treg within days, which expressed CD8α, CD8β and CD62L with a Ts1 phenotype and that had greater potency than freshly isolated antigen naive CD4+CD25+Treg in suppressing clinical severity of EAE and immune inflammation in CNS. These findings may guide development of antigen-specific Treg for therapy.
{"title":"Autoantigen and IL-2 activated CD4+CD25+T regulatory cells are induced to express CD8 and are autoantigen specific in inhibiting experimental autoimmune encephalomyelitis","authors":"Giang T. Tran , Sukhandep Bedi , Prateek Rakesh , Nirupama D. Verma , Nicole Carter , Catherine M. Robinson , Ranje Al-Atiyah , Bruce M. Hall , Suzanne J. Hodgkinson","doi":"10.1016/j.jneuroim.2025.578611","DOIUrl":"10.1016/j.jneuroim.2025.578611","url":null,"abstract":"<div><div>Experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin basic protein (MBP) is a self-limiting disease model of multiple sclerosis. CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup>T cells play a role in limiting autoimmune disease but treatment with antigen naïve CD4<sup>+</sup>CD25<sup>+</sup> cells does not reduce EAE.</div><div>This study examined if in vitro activation by MBP and rIL-2 induced CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> cells that could inhibit EAE. Culture of CD4<sup>+</sup>CD8<sup>-</sup>CD25<sup>+</sup>cells from naïve rats with MBP and rIL-2 induced activated Treg that reduced the severity of clinical EAE and infiltration of CD8<sup>+</sup>T cells and macrophage into brain stem. CD4<sup>+</sup>CD25<sup>+</sup>T cells activated by an irrelevant autoantigen and rIL-2 did not suppress EAE. Resting CD4<sup>+</sup>CD25<sup>+</sup>T cells activated by autoantigen and rIL-2 have mRNA for <em>Infgr, Il12rb2, Il5</em> but not <em>Tbet, Gata3, Ilr5ra</em> or <em>Ifng.</em> These changes in mRNA expression are the markers of Ts1 cells.</div><div>A proportion of CD4<sup>+</sup>CD8<sup>-</sup>CD25<sup>+</sup> cells activated by MBP/rIL-2 were induced to express CD8α, CD8β and CD62L. Depletion of CD4<sup>+</sup>CD8α<sup>+</sup>CD25<sup>+</sup> cells removed the capacity of MBP and rIL-2 activated CD4<sup>+</sup>CD25<sup>+</sup>T cells to suppress EAE.</div><div>This study demonstrated that in vitro activation of CD4<sup>+</sup>CD8<sup>-</sup>CD25<sup>+</sup> cells by MBP/rIL-2 induced relevant antigen-specific Treg within days, which expressed CD8α, CD8β and CD62L with a Ts1 phenotype and that had greater potency than freshly isolated antigen naive CD4<sup>+</sup>CD25<sup>+</sup>Treg in suppressing clinical severity of EAE and immune inflammation in CNS. These findings may guide development of antigen-specific Treg for therapy.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"404 ","pages":"Article 578611"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826395","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}
Pub Date : 2025-04-08DOI: 10.1016/j.jneuroim.2025.578614
Jiatong Li , Zexu Chen , Liu Yang , Tianshu Guan , Hai Yu , Wenbo Yang , Jia You , Weikang Gong , Jianfeng Feng , Xiangjun Chen
Background
Early diagnosis and differentiation of demyelinating diseases of the central nervous system (CNS) are essential for timely treatment but challenged with the limited availability of non-invasive, real-time methods to assess the architecture of the CNS. This study compared the retinal layers between patients with CNS demyelinating diseases and the general population and evaluated the predictive value of these structures in prospective diagnosis.
Methods
This UK Biobank study, incorporating optical coherence tomography images, analyzed patients with CNS demyelinating diseases identified at recruitment and during follow-up. Cross-sectionally, baseline retinal structures were compared, with diagnostic models constructed following cross-validation. Cox regression was used to assess the risk of future diagnosis in the prospective cohort.
Results
34,230 individuals were included, comprising 61 diagnosed patients. The thickness of the macular ganglion cell-inner plexiform layer (mGCIPL; p = 4.91 × 10−10), papillary retinal nerve fiber layer (pRNFL; p = 9.92 × 10−6), and non-central macular subfields (p value ranging from 1.16 × 10−2 to 1.18 × 10−10) were significantly thinner in the patient group. A diagnostic model incorporating mGCIPL, pRNFL and outer temporal macular thickness achieved the area under the curve of 0.779. During follow-up, 96 patients were newly diagnosed. Multivariable Cox regression revealed thinner mGCIPL (HR: 0.960, 95 % CI: 0.936 to 0.984, p = 0.001) and thinner outer nasal macula (HR: 0.990 95 % CI: 0.983 to 0.997, p = 0.006) as high risk predictors of future diagnosis.
Conclusions
Retinal structure can serve as non-invasive biomarker for CNS demyelinating diseases and has prospective diagnostic value in identifying pre-clinical and sub-clinical patients.
{"title":"Retinal layer thinning as a predictor of demyelinating diseases of the central nervous system: Insights from a decade-long cohort study","authors":"Jiatong Li , Zexu Chen , Liu Yang , Tianshu Guan , Hai Yu , Wenbo Yang , Jia You , Weikang Gong , Jianfeng Feng , Xiangjun Chen","doi":"10.1016/j.jneuroim.2025.578614","DOIUrl":"10.1016/j.jneuroim.2025.578614","url":null,"abstract":"<div><h3>Background</h3><div>Early diagnosis and differentiation of demyelinating diseases of the central nervous system (CNS) are essential for timely treatment but challenged with the limited availability of non-invasive, real-time methods to assess the architecture of the CNS. This study compared the retinal layers between patients with CNS demyelinating diseases and the general population and evaluated the predictive value of these structures in prospective diagnosis.</div></div><div><h3>Methods</h3><div>This UK Biobank study, incorporating optical coherence tomography images, analyzed patients with CNS demyelinating diseases identified at recruitment and during follow-up. Cross-sectionally, baseline retinal structures were compared, with diagnostic models constructed following cross-validation. Cox regression was used to assess the risk of future diagnosis in the prospective cohort.</div></div><div><h3>Results</h3><div>34,230 individuals were included, comprising 61 diagnosed patients. The thickness of the macular ganglion cell-inner plexiform layer (mGCIPL; <em>p</em> = 4.91 × 10<sup>−10</sup>), papillary retinal nerve fiber layer (pRNFL; <em>p</em> = 9.92 × 10<sup>−6</sup>), and non-central macular subfields (<em>p</em> value ranging from 1.16 × 10<sup>−2</sup> to 1.18 × 10<sup>−10</sup>) were significantly thinner in the patient group. A diagnostic model incorporating mGCIPL, pRNFL and outer temporal macular thickness achieved the area under the curve of 0.779. During follow-up, 96 patients were newly diagnosed. Multivariable Cox regression revealed thinner mGCIPL (HR: 0.960, 95 % CI: 0.936 to 0.984, <em>p =</em> 0.001) and thinner outer nasal macula (HR: 0.990 95 % CI: 0.983 to 0.997, <em>p =</em> 0.006) as high risk predictors of future diagnosis.</div></div><div><h3>Conclusions</h3><div>Retinal structure can serve as non-invasive biomarker for CNS demyelinating diseases and has prospective diagnostic value in identifying pre-clinical and sub-clinical patients.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"404 ","pages":"Article 578614"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839208","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}
Intrathecal injection (IT) of autologous mesenchymal stem cells (MSC) showed robust beneficial effects a previous randomized study from our center, in patients with progressive multiple sclerosis (MS) (NCT02166021). We evaluated here the effect of repeated MSC-NG01 transplantations on serum biomarkers of neuroinflammation and neurodegeneration, namely, neurofilaments light chains (NFL) and glial fibrillary acidic protein (GFAP), in an open-label extension trial.
Methods
23 patients with progressive types of MS, who participated in the NCT02166021-trial, were included. Patients were treated with 2–3 intrathecal injections of MSC-NG01 and followed up for a period of >12 months. Safety/tolerability and various efficacy measurements, including EDSS/FS, timed 25-ft (T25FW) walking, cognitive functions, and serum levels of the biomarkers NFL and GFAP, were assessed.
Results
Serum levels of NFL and GFAP showed a gradual and consistent reduction after the intrathecal treatments with MSC-NG01, in multiple measurements. The mean NFL reduction at last observation after one year was 33.2 % (p < 0.001, Wilcoxon-paired test). Serum levels of GFAP were reduced in all tested patients (p < 0.0004, Wilcoxon-paired test). A significant improvement was observed in T25-FW and in the sum of all functional systems (FS) at the final visit of 12 months. SDMT cognitive test was also improved by a mean of >3 degrees (p = 0.0008).
Conclusion
Treatment of progressive MS patients with IT injections of autologous MSC-NG01 induced a reduction in both NFL and GFAP biomarkers levels, paralleled by beneficial effects on cognition, neurological functional tests and quality of life. These data indicate significant effects of MSC-transplantation on neurodegeneration and neuroinflammation.
{"title":"Kinetics of serum NFL and GFAP and changes in cognitive functions, in MS patients treated with repeated administrations of autologous mesenchymal stem cells (MSC-NG01)","authors":"Panayiota Petrou, Ibrahim Kassis, Yarden Levi, Nour Yaghmour, Tehila Epstein, Ariel Ginzberg, Dimitrios Karussis","doi":"10.1016/j.jneuroim.2025.578613","DOIUrl":"10.1016/j.jneuroim.2025.578613","url":null,"abstract":"<div><h3>Background</h3><div>Intrathecal injection (IT) of autologous mesenchymal stem cells (MSC) showed robust beneficial effects a previous randomized study from our center, in patients with progressive multiple sclerosis (MS) (<span><span>NCT02166021</span><svg><path></path></svg></span>). We evaluated here the effect of repeated MSC-NG01 transplantations on serum biomarkers of neuroinflammation and neurodegeneration, namely, neurofilaments light chains (NFL) and glial fibrillary acidic protein (GFAP), in an open-label extension trial.</div></div><div><h3>Methods</h3><div>23 patients with progressive types of MS, who participated in the <span><span>NCT02166021</span><svg><path></path></svg></span>-trial, were included. Patients were treated with 2–3 intrathecal injections of MSC-NG01 and followed up for a period of >12 months. Safety/tolerability and various efficacy measurements, including EDSS/FS, timed 25-ft (T25FW) walking, cognitive functions, and serum levels of the biomarkers NFL and GFAP, were assessed.</div></div><div><h3>Results</h3><div>Serum levels of NFL and GFAP showed a gradual and consistent reduction after the intrathecal treatments with MSC-NG01, in multiple measurements. The mean NFL reduction at last observation after one year was 33.2 % (<em>p</em> < 0.001, Wilcoxon-paired test). Serum levels of GFAP were reduced in all tested patients (<em>p</em> < 0.0004, Wilcoxon-paired test). A significant improvement was observed in T25-FW and in the sum of all functional systems (FS) at the final visit of 12 months. SDMT cognitive test was also improved by a mean of >3 degrees (<em>p</em> = 0.0008).</div></div><div><h3>Conclusion</h3><div>Treatment of progressive MS patients with IT injections of autologous MSC-NG01 induced a reduction in both NFL and GFAP biomarkers levels, paralleled by beneficial effects on cognition, neurological functional tests and quality of life. These data indicate significant effects of MSC-transplantation on neurodegeneration and neuroinflammation.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"403 ","pages":"Article 578613"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817240","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}
Pub Date : 2025-04-07DOI: 10.1016/j.jneuroim.2025.578609
Yesha A. Dave , Marta Koperska , Kelsey E. Lucerne , Ava L. Shipman , Sharon M. Zeldin , Aya Osman , Rebecca S. Hofford , Drew D. Kiraly
Cocaine use disorder is a chronic relapsing condition with no FDA-approved biological treatments. The gut microbiome has emerged as a key modulator of neurobehavioral responses to drugs of abuse, yet its role in female animals has been under studied. Here, we investigated the effects of gut microbiome depletion on cocaine-induced behavioral and transcriptional responses in female mice. Adult female C57BL/6 J mice were treated with a non-absorbable oral antibiotic (Abx) cocktail for two weeks to deplete the gut microbiome, followed by behavioral assays assessing locomotor sensitization and conditioned place preference (CPP) to cocaine. Abx-treated females displayed reduced locomotor sensitization and a shifted CPP dose-response curve, characterized by attenuated preference at higher cocaine doses. Transcriptional analysis of the nucleus accumbens (NAc) revealed that microbiome depletion suppressed cocaine-induced expression of immediate early genes (c-Fos, FosB, Nr4a1, Egr4) and altered dopamine-related (Drd1) and microglial (Cx3cr1) markers. These findings contrast with prior studies in males, where microbiome depletion enhanced cocaine-induced behavioral plasticity. The observed effects suggest distinct gut-brain signaling as an important contributor to cocaine reinforcement and neuroadaptations in females. This study provides novel insights into microbiome regulation of addiction-relevant behaviors and highlights the necessity of sex-specific investigations in neuropsychiatric disorders. Further research is needed to elucidate the molecular pathways linking gut dysbiosis to substance use vulnerability in females.
{"title":"Gut microbiome depletion modulates cocaine-induced behavioral and transcriptional responses in female mice","authors":"Yesha A. Dave , Marta Koperska , Kelsey E. Lucerne , Ava L. Shipman , Sharon M. Zeldin , Aya Osman , Rebecca S. Hofford , Drew D. Kiraly","doi":"10.1016/j.jneuroim.2025.578609","DOIUrl":"10.1016/j.jneuroim.2025.578609","url":null,"abstract":"<div><div>Cocaine use disorder is a chronic relapsing condition with no FDA-approved biological treatments. The gut microbiome has emerged as a key modulator of neurobehavioral responses to drugs of abuse, yet its role in female animals has been under studied. Here, we investigated the effects of gut microbiome depletion on cocaine-induced behavioral and transcriptional responses in female mice. Adult female C57BL/6 J mice were treated with a non-absorbable oral antibiotic (Abx) cocktail for two weeks to deplete the gut microbiome, followed by behavioral assays assessing locomotor sensitization and conditioned place preference (CPP) to cocaine. Abx-treated females displayed reduced locomotor sensitization and a shifted CPP dose-response curve, characterized by attenuated preference at higher cocaine doses. Transcriptional analysis of the nucleus accumbens (NAc) revealed that microbiome depletion suppressed cocaine-induced expression of immediate early genes (<em>c-Fos</em>, <em>FosB</em>, <em>Nr4a1</em>, <em>Egr4</em>) and altered dopamine-related (<em>Drd1</em>) and microglial (<em>Cx3cr1</em>) markers. These findings contrast with prior studies in males, where microbiome depletion enhanced cocaine-induced behavioral plasticity. The observed effects suggest distinct gut-brain signaling as an important contributor to cocaine reinforcement and neuroadaptations in females. This study provides novel insights into microbiome regulation of addiction-relevant behaviors and highlights the necessity of sex-specific investigations in neuropsychiatric disorders. Further research is needed to elucidate the molecular pathways linking gut dysbiosis to substance use vulnerability in females.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"403 ","pages":"Article 578609"},"PeriodicalIF":2.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143820779","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号