Parkinson's disease (PD), a prevailing neurodegenerative disorder, is marked by the depletion of dopaminergic neurons in the substantia nigra of the brain. Current therapeutic approaches for PD only offer symptomatic relief, temporarily enhancing the patient's quality of life. In recent time, mesenchymal stem cells (MSCs) have exhibited promise as a new regimen for PD due to their capacity to morph into various cell types and release neurotrophic factors that foster neuronal survival and regeneration. Human umbilical cord derived mesenchymal stem cells (hUCMSCs) is gaining attention as a viable cellular therapy for treating PD, given their ethical and non-invasive isolation, low immunogenicity, minimal senescence, high proliferation rate and regenerative potential. Numerous studies have demonstrated the ability of hUCMSCs in improving underlying pathophysiological factors implicated in PD such as cognitive functions, behavioral and motor recovery, modulation of microenvironment by secreting tropic factors and exosomes, differentiation into dopaminergic neuron-like cells, neuroprotection, reduction in apoptosis and oxidative stress. The purpose of this review is to critically analzye the progress in preclinical and clinical studies of hUCMSCs based therapy for PD.
{"title":"Advances in Parkinson's disease management using umbilical cord-derived mesenchymal stem cells.","authors":"Nishant Mante, Vaishali Undale, Avinash Sanap, Ramesh Bhonde, Supriya Kheur, Pratima Tambe, Avinash Kharat","doi":"10.1016/j.jneuroim.2026.578911","DOIUrl":"https://doi.org/10.1016/j.jneuroim.2026.578911","url":null,"abstract":"<p><p>Parkinson's disease (PD), a prevailing neurodegenerative disorder, is marked by the depletion of dopaminergic neurons in the substantia nigra of the brain. Current therapeutic approaches for PD only offer symptomatic relief, temporarily enhancing the patient's quality of life. In recent time, mesenchymal stem cells (MSCs) have exhibited promise as a new regimen for PD due to their capacity to morph into various cell types and release neurotrophic factors that foster neuronal survival and regeneration. Human umbilical cord derived mesenchymal stem cells (hUCMSCs) is gaining attention as a viable cellular therapy for treating PD, given their ethical and non-invasive isolation, low immunogenicity, minimal senescence, high proliferation rate and regenerative potential. Numerous studies have demonstrated the ability of hUCMSCs in improving underlying pathophysiological factors implicated in PD such as cognitive functions, behavioral and motor recovery, modulation of microenvironment by secreting tropic factors and exosomes, differentiation into dopaminergic neuron-like cells, neuroprotection, reduction in apoptosis and oxidative stress. The purpose of this review is to critically analzye the progress in preclinical and clinical studies of hUCMSCs based therapy for PD.</p>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"416 ","pages":"578911"},"PeriodicalIF":2.5,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491390","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 : 2026-03-12DOI: 10.1016/j.jneuroim.2026.578909
João Henrique Correa Kanan, Larissa D Bobermin, Vanessa-Fernanda da Silva, Júlia Krebs-Rosa, Marina Silveira Martins Kessler, Marina C Leite, Adriana Fernanda K Vizuete, Patrícia Sesterheim, André Quincozes-Santos, Carlos-Alberto Gonçalves
The complement system is a set of membrane-bound and circulating proteins (predominantly synthesized in the liver), whose function is to warn of a microbial invasion (as do the receptors for pathogens and damage-associated molecular patterns, PAMPs and DAMPs, respectively) and initiate the defense response, by tagging foreign or self-entities with C3 fragments, promoting phagocytosis and lysis of the membrane of the "invading" organisms. This system is also used by some tissues for structural reorganization, to induce and remove apoptotic cells. In the central nervous system (CNS), synapses are constantly undergoing remodeling via the elimination and formation of new synapses, which is mediated, in part, by complement system proteins produced by microglia and astrocytes. This elimination process (synaptic pruning) appears to be particularly pronounced in neurodegenerative diseases. In this short review, we aim to discuss the role of the complement system in the CNS, particularly in the very prevalent psychiatric disorder, major depressive disorder, emphasizing the importance of astrocytes, as well as the need to advance our understanding of the specificities of the glial complement system proteins for diagnostic and therapeutic purposes.
{"title":"Changes in the complement system are involved in synaptic pruning in major depressive disorder.","authors":"João Henrique Correa Kanan, Larissa D Bobermin, Vanessa-Fernanda da Silva, Júlia Krebs-Rosa, Marina Silveira Martins Kessler, Marina C Leite, Adriana Fernanda K Vizuete, Patrícia Sesterheim, André Quincozes-Santos, Carlos-Alberto Gonçalves","doi":"10.1016/j.jneuroim.2026.578909","DOIUrl":"https://doi.org/10.1016/j.jneuroim.2026.578909","url":null,"abstract":"<p><p>The complement system is a set of membrane-bound and circulating proteins (predominantly synthesized in the liver), whose function is to warn of a microbial invasion (as do the receptors for pathogens and damage-associated molecular patterns, PAMPs and DAMPs, respectively) and initiate the defense response, by tagging foreign or self-entities with C3 fragments, promoting phagocytosis and lysis of the membrane of the \"invading\" organisms. This system is also used by some tissues for structural reorganization, to induce and remove apoptotic cells. In the central nervous system (CNS), synapses are constantly undergoing remodeling via the elimination and formation of new synapses, which is mediated, in part, by complement system proteins produced by microglia and astrocytes. This elimination process (synaptic pruning) appears to be particularly pronounced in neurodegenerative diseases. In this short review, we aim to discuss the role of the complement system in the CNS, particularly in the very prevalent psychiatric disorder, major depressive disorder, emphasizing the importance of astrocytes, as well as the need to advance our understanding of the specificities of the glial complement system proteins for diagnostic and therapeutic purposes.</p>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"415 ","pages":"578909"},"PeriodicalIF":2.5,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147474126","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}
Diabetic neuropathy is a debilitating complication of type 2 diabetes mellitus (T2DM), largely driven by systemic inflammation and metabolic disturbances. This cross-sectional study assessed the relationship between interleukin-6 (IL-6), vitamin B12, lipid profile, and nerve conduction parameters in T2DM patients with and without neuropathy. Sixty participants were divided evenly into two groups: T2DM without neuropathy (control) and T2DM with confirmed neuropathy (case). Biochemical parameters measured included fasting and postprandial glucose, glycated hemoglobin (HbA1c), vitamin B12, IL-6, renal function, and detailed lipid profiling. Nerve conduction studies assessed sensory and motor nerves in upper and lower limbs. The neuropathy group showed higher IL-6 levels, lower vitamin B12 concentrations, and an atherogenic lipid profile characterised by increased triglycerides, VLDL, and non-HDL cholesterol. Marked reductions in nerve conduction velocities were evident in both sensory and motor nerves, especially in the common peroneal and posterior tibial nerves, which had high diagnostic accuracy with AUC values of 0.88 and 0.84, respectively. Univariate regression identified IL-6 as significantly associated with decreased conduction velocity in radial sensory and posterior tibial nerves. Supporting these clinical findings, in silico pathway enrichment analyses highlighted key roles for IL-6 signalling, vitamin B12 metabolism, lipid pathways, and myelination in diabetic neuropathy pathogenesis. These integrated data underscore inflammation and metabolic dysfunction as pivotal drivers, with IL-6 and nerve conduction studies serving as promising early biomarkers and therapeutic targets.
{"title":"Neuroinflammation and metabolic dysfunction drive nerve conduction deficits in diabetic neuropathy: Clinical and in silico insights","authors":"Faaz Bin Razi , Sangeeta Singhal , Hamid Ashraf , Shagufta Moin","doi":"10.1016/j.jneuroim.2025.578849","DOIUrl":"10.1016/j.jneuroim.2025.578849","url":null,"abstract":"<div><div>Diabetic neuropathy is a debilitating complication of type 2 diabetes mellitus (T2DM), largely driven by systemic inflammation and metabolic disturbances. This cross-sectional study assessed the relationship between interleukin-6 (IL-6), vitamin B12, lipid profile, and nerve conduction parameters in T2DM patients with and without neuropathy. Sixty participants were divided evenly into two groups: T2DM without neuropathy (control) and T2DM with confirmed neuropathy (case). Biochemical parameters measured included fasting and postprandial glucose, glycated hemoglobin (HbA1c), vitamin B12, IL-6, renal function, and detailed lipid profiling. Nerve conduction studies assessed sensory and motor nerves in upper and lower limbs. The neuropathy group showed higher IL-6 levels, lower vitamin B12 concentrations, and an atherogenic lipid profile characterised by increased triglycerides, VLDL, and non-HDL cholesterol. Marked reductions in nerve conduction velocities were evident in both sensory and motor nerves, especially in the common peroneal and posterior tibial nerves, which had high diagnostic accuracy with AUC values of 0.88 and 0.84, respectively. Univariate regression identified IL-6 as significantly associated with decreased conduction velocity in radial sensory and posterior tibial nerves. Supporting these clinical findings, in silico pathway enrichment analyses highlighted key roles for IL-6 signalling, vitamin B12 metabolism, lipid pathways, and myelination in diabetic neuropathy pathogenesis. These integrated data underscore inflammation and metabolic dysfunction as pivotal drivers, with IL-6 and nerve conduction studies serving as promising early biomarkers and therapeutic targets.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"412 ","pages":"Article 578849"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849488","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}
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous immune-mediated neuropathy. The activation of the complement system has been implicated in CIDP, but it remains unclear which complement pathway activation is essential for the pathogenesis of CIDP. We therefore examined the deposition and production of several activated complement factors in tissues and serum of CIDP, respectively.
Methods
We immunohistochemically stained C4d, C3c, and C5b-9 using sural nerve specimens of CIDP and controls. Images were evaluated for the density and fluorescence intensity of complement factor deposition. Serum complement factors (factor H, Ba, sC5b-9, C3, C4 and CH50) were measured in CIDP and in controls. We also investigated clinical data in relation to complement deposition and serum complement factors.
Results
C4d was deposited on the myelin sheaths in all patients with CIDP, with significantly higher density and intensity than in controls. C3c was detected in three of the nine patients with CIDP, while C5b-9 was not detected. Serum levels of sC5b-9 were higher than the normal range in some patients, but no significant differences in serum complement levels were observed between those with CIDP and controls. The C4d density and serum C3 levels were positively correlated with Hughes functional grading scale scores.
Conclusions
C4d deposition was observed in all patients with CIDP. Few patients showed the activated terminal pathway. The classical and/or lectin pathways are predominantly involved in CIDP pathogenesis. Sural nerve pathology and activated complement factors in the plasma may be useful for selecting therapeutic agents including C2 inhibitors.
{"title":"The activation of classical and/or lectin complement pathway for the pathogenesis of chronic inflammatory demyelinating polyradiculoneuropathy","authors":"Keishu Murakami , Hiroshi Tsujimoto , Yoshiaki Nakayama , Hiroki Takeuchi , Kenji Yamamoto , Kei-Ichi Katayama , Yusuke Inada , Yutaka Inaba , Masatoshi Jinnin , Nobuyuki Oka , Norimitsu Inoue , Katsuichi Miyamoto","doi":"10.1016/j.jneuroim.2025.578848","DOIUrl":"10.1016/j.jneuroim.2025.578848","url":null,"abstract":"<div><h3>Background</h3><div>Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous immune-mediated neuropathy. The activation of the complement system has been implicated in CIDP, but it remains unclear which complement pathway activation is essential for the pathogenesis of CIDP. We therefore examined the deposition and production of several activated complement factors in tissues and serum of CIDP, respectively.</div></div><div><h3>Methods</h3><div>We immunohistochemically stained C4d, C3c, and C5b-9 using sural nerve specimens of CIDP and controls. Images were evaluated for the density and fluorescence intensity of complement factor deposition. Serum complement factors (factor H, Ba, sC5b-9, C3, C4 and CH50) were measured in CIDP and in controls. We also investigated clinical data in relation to complement deposition and serum complement factors.</div></div><div><h3>Results</h3><div>C4d was deposited on the myelin sheaths in all patients with CIDP, with significantly higher density and intensity than in controls. C3c was detected in three of the nine patients with CIDP, while C5b-9 was not detected. Serum levels of sC5b-9 were higher than the normal range in some patients, but no significant differences in serum complement levels were observed between those with CIDP and controls. The C4d density and serum C3 levels were positively correlated with Hughes functional grading scale scores.</div></div><div><h3>Conclusions</h3><div>C4d deposition was observed in all patients with CIDP. Few patients showed the activated terminal pathway. The classical and/or lectin pathways are predominantly involved in CIDP pathogenesis. Sural nerve pathology and activated complement factors in the plasma may be useful for selecting therapeutic agents including C2 inhibitors.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"412 ","pages":"Article 578848"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839090","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 : 2026-03-01Epub Date: 2025-12-25DOI: 10.1016/j.jneuroim.2025.578847
Jeseong Won , Judong Kim , S.M. Touhidul Islam , Fei Qiao , Avtar K. Singh , Inderjit Singh
B cell-activating factor (BAFF) is a key mediator of B cell-driven autoimmune pathology. In mice with experimental autoimmune encephalomyelitis (EAE), a widely used model of multiple sclerosis (MS), we observed a pronounced accumulation of B cells within the spinal cord, alongside elevated BAFF expression, particularly in GFAP+ activated astrocytes located in the subpial-region. This upregulation of BAFF coincided with the infiltration of CD4+ T cells, notably Th1 cells producing IFNγ, a cytokine critical for inducing BAFF gene expression in astrocytes. Concurrently, elevated BAFF levels in the spinal cords of EAE mice were associated with increased expression of S-nitrosoglutathione (GSNO) reductase (GSNOR), the enzyme that degrades GSNO, a molecule known for its anti-inflammatory properties. Pharmacological inhibition of GSNOR using N6022, a reversible inhibitor, significantly reduced BAFF expression and decreased B cell accumulation in the CNS. In vitro, both GSNO and N6022 suppressed IFNγ- and TNFα-induced BAFF expression in cultured astrocytes by inhibiting STAT1 and NF-κB activation. Furthermore, co-culture of B cells with IFNγ/TNFα-stimulated astrocytes, or exposure to their conditioned media, resulted in an increased number of B cells and enhanced IL-6 production. These effects were attenuated either by pretreating astrocytes with GSNO or by applying BAFF-neutralizing antibodies to B cells. Collectively, these findings suggest that GSNOR modulates astrocytic BAFF expression, thereby influencing B cell activation and their IL-6-mediated functions in EAE. Modulation of this pathway may represent a promising avenue for future investigation into immune regulation in MS and related autoimmune conditions.
{"title":"The potential role of S-nitrosoglutathione reductase in astrocyte BAFF expression and B cell activation in experimental autoimmune encephalomyelitis","authors":"Jeseong Won , Judong Kim , S.M. Touhidul Islam , Fei Qiao , Avtar K. Singh , Inderjit Singh","doi":"10.1016/j.jneuroim.2025.578847","DOIUrl":"10.1016/j.jneuroim.2025.578847","url":null,"abstract":"<div><div>B cell-activating factor (BAFF) is a key mediator of B cell-driven autoimmune pathology. In mice with experimental autoimmune encephalomyelitis (EAE), a widely used model of multiple sclerosis (MS), we observed a pronounced accumulation of B cells within the spinal cord, alongside elevated BAFF expression, particularly in GFAP<sup>+</sup> activated astrocytes located in the subpial-region. This upregulation of BAFF coincided with the infiltration of CD4<sup>+</sup> T cells, notably Th1 cells producing IFNγ, a cytokine critical for inducing BAFF gene expression in astrocytes. Concurrently, elevated BAFF levels in the spinal cords of EAE mice were associated with increased expression of S-nitrosoglutathione (GSNO) reductase (GSNOR), the enzyme that degrades GSNO, a molecule known for its anti-inflammatory properties. Pharmacological inhibition of GSNOR using N6022, a reversible inhibitor, significantly reduced BAFF expression and decreased B cell accumulation in the CNS. In vitro, both GSNO and N6022 suppressed IFNγ- and TNFα-induced BAFF expression in cultured astrocytes by inhibiting STAT1 and NF-κB activation. Furthermore, co-culture of B cells with IFNγ/TNFα-stimulated astrocytes, or exposure to their conditioned media, resulted in an increased number of B cells and enhanced IL-6 production. These effects were attenuated either by pretreating astrocytes with GSNO or by applying BAFF-neutralizing antibodies to B cells. Collectively, these findings suggest that GSNOR modulates astrocytic BAFF expression, thereby influencing B cell activation and their IL-6-mediated functions in EAE. Modulation of this pathway may represent a promising avenue for future investigation into immune regulation in MS and related autoimmune conditions.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"412 ","pages":"Article 578847"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145882028","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 : 2026-03-01Epub Date: 2025-12-06DOI: 10.1016/j.jneuroim.2025.578834
Silvia Sperandei , Lorenzo Gaetani , Giorgia Manni , Marco Gargaro , Giuseppe Vittorio De Socio , Maria Cristina Gallina , Andrea Fiacca , Cinzia Costa , Andrea Mancini , Lucilla Parnetti , Francesca Fallarino , Massimiliano Di Filippo
Encephalopathy with cytotoxic lesions of the corpus callosum (CLOCCs) represents a clinical-radiological entity characterized by MRI evidence of lesions involving the splenium of the corpus callosum and a collection of neurological symptoms ranging from consciousness impairment to seizures and focal neurological signs. The most widely accepted pathophysiological mechanism underlying CLOCCs is thought to be represented by a phenomenon of cytokine-induced cytotoxic edema but its exact immune pathogenesis is still unravelled and targeted treatments are lacking.
Here, we report the case of a 18-year-old male with CLOCCs associated with acute Epstein-Barr virus (EBV) infection, in whom the systemic immune response across acute and post-acute phases was characterized for the first time through longitudinal cytokine profiling. The obtained data pave the way to a more precise comprehension of CLOCCs pathogenesis and an individualized treatment of this potentially severe condition.
{"title":"Immune profiling unveils the systemic cytokine milieu associated with acute reversible encephalopathy with cytotoxic lesions of the corpus callosum (CLOCCs)","authors":"Silvia Sperandei , Lorenzo Gaetani , Giorgia Manni , Marco Gargaro , Giuseppe Vittorio De Socio , Maria Cristina Gallina , Andrea Fiacca , Cinzia Costa , Andrea Mancini , Lucilla Parnetti , Francesca Fallarino , Massimiliano Di Filippo","doi":"10.1016/j.jneuroim.2025.578834","DOIUrl":"10.1016/j.jneuroim.2025.578834","url":null,"abstract":"<div><div>Encephalopathy with cytotoxic lesions of the corpus callosum (CLOCCs) represents a clinical-radiological entity characterized by MRI evidence of lesions involving the splenium of the corpus callosum and a collection of neurological symptoms ranging from consciousness impairment to seizures and focal neurological signs. The most widely accepted pathophysiological mechanism underlying CLOCCs is thought to be represented by a phenomenon of cytokine-induced cytotoxic edema but its exact immune pathogenesis is still unravelled and targeted treatments are lacking.</div><div>Here, we report the case of a 18-year-old male with CLOCCs associated with acute Epstein-Barr virus (EBV) infection, in whom the systemic immune response across acute and post-acute phases was characterized for the first time through longitudinal cytokine profiling. The obtained data pave the way to a more precise comprehension of CLOCCs pathogenesis and an individualized treatment of this potentially severe condition.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"412 ","pages":"Article 578834"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145771843","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 : 2026-03-01Epub Date: 2025-12-26DOI: 10.1016/j.jneuroim.2025.578850
Kristen Simone , Nabeela Nathoo , Allyssa Hooper , Albert Aboseif , Andrew Blake Buletko , Niranjala Satkunam , Jennifer A. McCombe , Sophia Pin
Anti-N-methyl-d-aspartate receptor autoimmune encephalitis (NMDAR-AIE) is an immune-mediated neurological disease with manifestations including altered mental status, neuropsychiatric disturbance, movement disorders, seizure, and dysautonomia. NMDAR-AIE is associated with ovarian teratoma in half of cases, typically mature teratoma. NMDAR-AIE is rarely associated with immature ovarian teratomas. Here, we describe three cases of NMDAR-AIE associated with immature ovarian teratomas. We review diagnosis and management of immature ovarian teratomas in NMDAR-AIE as a collaboration between gynecology and neurology, with multi-disciplinary recommendations provided regarding workup and management.
{"title":"Immature ovarian teratomas in anti-NMDA receptor encephalitis","authors":"Kristen Simone , Nabeela Nathoo , Allyssa Hooper , Albert Aboseif , Andrew Blake Buletko , Niranjala Satkunam , Jennifer A. McCombe , Sophia Pin","doi":"10.1016/j.jneuroim.2025.578850","DOIUrl":"10.1016/j.jneuroim.2025.578850","url":null,"abstract":"<div><div>Anti-<em>N</em>-methyl-<span>d</span>-aspartate receptor autoimmune encephalitis (NMDAR-AIE) is an immune-mediated neurological disease with manifestations including altered mental status, neuropsychiatric disturbance, movement disorders, seizure, and dysautonomia. NMDAR-AIE is associated with ovarian teratoma in half of cases, typically mature teratoma. NMDAR-AIE is rarely associated with immature ovarian teratomas. Here, we describe three cases of NMDAR-AIE associated with immature ovarian teratomas. We review diagnosis and management of immature ovarian teratomas in NMDAR-AIE as a collaboration between gynecology and neurology, with multi-disciplinary recommendations provided regarding workup and management.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"412 ","pages":"Article 578850"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849394","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 : 2026-03-01Epub Date: 2025-12-31DOI: 10.1016/j.jneuroim.2025.578851
Xiaoli Liao , Jingqi Shao , Zhihui Chen
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder influenced by both genetic predispositions and environmental insults. However, the precise molecular mechanisms linking prenatal environmental perturbations to neurodevelopmental impairments remain poorly defined. This study investigates the role of mitochondrial dysfunction and metabolic disturbances in ASD pathogenesis using various preclinical models, including the maternal immune activation (MIA) and ASD high-risk gene knockout models. We performed transcriptomic profiling on mouse brain tissues to identify differentially expressed genes (DEGs) associated with mitochondrial and metabolic pathways. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), revealed significant disruptions in pathways such as oxidative phosphorylation, tricarboxylic acid, and energy metabolism. These findings point to mitochondrial dysfunction as a central mechanism contributing to metabolic imbalances in ASD. Comparative analysis with publicly available RNA-seq datasets from PTEN knockout model revealed both shared and unique metabolic signatures. Single-cell RNA-seq data from the MIA model further identified cell-type-specific metabolic alterations in distinct neuronal and glial populations. Additionally, analysis of the Human Fetal Single-Cell Atlas highlighted the relevance of these metabolic pathways in human brain development. Collectively, these results emphasize mitochondrial metabolism as a potential therapeutic target for ASD, offering insights into the molecular basis of this disorder.
{"title":"Mitochondrial dysregulation as a central mechanism in autism spectrum disorder pathogenesis","authors":"Xiaoli Liao , Jingqi Shao , Zhihui Chen","doi":"10.1016/j.jneuroim.2025.578851","DOIUrl":"10.1016/j.jneuroim.2025.578851","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder influenced by both genetic predispositions and environmental insults. However, the precise molecular mechanisms linking prenatal environmental perturbations to neurodevelopmental impairments remain poorly defined. This study investigates the role of mitochondrial dysfunction and metabolic disturbances in ASD pathogenesis using various preclinical models, including the maternal immune activation (MIA) and ASD high-risk gene knockout models. We performed transcriptomic profiling on mouse brain tissues to identify differentially expressed genes (DEGs) associated with mitochondrial and metabolic pathways. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), revealed significant disruptions in pathways such as oxidative phosphorylation, tricarboxylic acid, and energy metabolism. These findings point to mitochondrial dysfunction as a central mechanism contributing to metabolic imbalances in ASD. Comparative analysis with publicly available RNA-seq datasets from PTEN knockout model revealed both shared and unique metabolic signatures. Single-cell RNA-seq data from the MIA model further identified cell-type-specific metabolic alterations in distinct neuronal and glial populations. Additionally, analysis of the Human Fetal Single-Cell Atlas highlighted the relevance of these metabolic pathways in human brain development. Collectively, these results emphasize mitochondrial metabolism as a potential therapeutic target for ASD, offering insights into the molecular basis of this disorder.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"412 ","pages":"Article 578851"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912017","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 : 2026-03-01Epub Date: 2025-12-31DOI: 10.1016/j.jneuroim.2025.578852
Mohamed Y. Abdelgaied , Omar Abdelgawad , Mohamed Hamed Rashad , Mohamed H. Solayman , Hend M. El-Tayebi
Background
Neurodegeneration and inflammation can accelerate the demyelination process in multiple sclerosis (MS). We aimed to investigate the efficacy and tolerability of metformin as an add-on treatment to interferon Beta 1a (IFNβ-1a) in Egyptian patients with relapsing-remitting multiple sclerosis (RRMS).
Method
Thirty RRMS patients were divided into two groups: the experimental arm receiving IFNβ-1a plus 2 g of metformin once daily and the control arm receiving IFNβ-1a alone. Tolerance to metformin was measured for the intervention group. Following 6 months period, serum neurofilament light chain (sNFL) and nuclear factor Kappa B (NF-κB), T2 lesions in magnetic resonance imaging (MRI), and expanded disability status scale (EDSS) were measured.
Results
There were no statistically significant differences between the two groups in the change in the median (interquartile range) of the blood biomarkers (sNFL; −32.8 (21) vs −32.8 (13.4), p = 0.99) and NF-κB; −64.9 (35.1) vs −61.6 (35.7), p = 0.8, respectively). In clinical outcomes, there was no statistically significant in the mean (standard deviation) change of EDSS (0 vs 0, p = 1). For MRI results, 11 patients had a stationary and regressive course 1 patient had a progressive course in the metformin group vs 6 patients had a stationary and regressive course and 2 had a progressive course in the control group, p = 0.23. All outcomes were measured after 6-month follow-ups. The most common side effects of metformin were diarrhea and abdominal pain without incidence of lactic acidosis.
Conclusion
Receiving metformin as an add-on therapy to IFNβ-1a did not result in a significant improvement in neurodegeneration and inflammation blood biomarkers and clinical outcomes. A high dose of metformin (2 g/day) is safe and well tolerated in patients with MS. Additional studies involving larger populations are necessary to confirm or disprove these findings.
Trial registration
ClinicalTrials.gov ID: NCT06812585
背景：神经变性和炎症可加速多发性硬化症（MS）的脱髓鞘过程。我们的目的是研究二甲双胍作为干扰素β 1a （IFNβ-1a）附加治疗在埃及复发-缓解型多发性硬化症（RRMS）患者中的疗效和耐受性。方法30例RRMS患者分为两组，实验组给予IFNβ-1a + 2 g二甲双胍每日1次，对照组单独给予IFNβ-1a治疗。测量干预组对二甲双胍的耐受性。随访6个月，检测血清神经丝轻链（sNFL）、核因子κB （NF-κB）、磁共振成像（MRI） T2病变、扩展残疾状态量表（EDSS）。结果两组患者血液生物标志物(sNFL: - 32.8 （21) vs - 32.8 (13.4), p = 0.99）和NF-κB的中位数（四分位数范围）变化差异无统计学意义；61.6 vs−−64.9(35.1)(35.7),分别为p = 0.8)。在临床结局方面，EDSS的平均（标准差）变化无统计学意义（0 vs 0, p = 1）。MRI结果显示，二甲双胍组11例患者病程平稳消退，1例进展，对照组6例患者病程平稳消退，2例进展，p = 0.23。所有结果在6个月的随访后测量。二甲双胍最常见的副作用是腹泻和腹痛，无乳酸性酸中毒的发生。结论接受二甲双胍作为IFNβ-1a的附加治疗并未导致神经变性和炎症血液生物标志物以及临床结果的显着改善。高剂量二甲双胍（2g /天）对ms患者是安全且耐受性良好的，需要更多的涉及更大人群的研究来证实或反驳这些发现。临床试验注册。gov ID: NCT06812585
{"title":"Efficacy and tolerability of metformin as an adjuvant therapy in patients with relapse-remitting multiple sclerosis receiving interferon Beta 1a: A randomized pilot trial","authors":"Mohamed Y. Abdelgaied , Omar Abdelgawad , Mohamed Hamed Rashad , Mohamed H. Solayman , Hend M. El-Tayebi","doi":"10.1016/j.jneuroim.2025.578852","DOIUrl":"10.1016/j.jneuroim.2025.578852","url":null,"abstract":"<div><h3>Background</h3><div>Neurodegeneration and inflammation can accelerate the demyelination process in multiple sclerosis (MS). We aimed to investigate the efficacy and tolerability of metformin as an add-on treatment to interferon Beta 1a (IFNβ-1a) in Egyptian patients with relapsing-remitting multiple sclerosis (RRMS).</div></div><div><h3>Method</h3><div>Thirty RRMS patients were divided into two groups: the experimental arm receiving IFNβ-1a plus 2 g of metformin once daily and the control arm receiving IFNβ-1a alone. Tolerance to metformin was measured for the intervention group. Following 6 months period, serum neurofilament light chain (sNFL) and nuclear factor Kappa B (NF-κB), T2 lesions in magnetic resonance imaging (MRI), and expanded disability status scale (EDSS) were measured.</div></div><div><h3>Results</h3><div>There were no statistically significant differences between the two groups in the change in the median (interquartile range) of the blood biomarkers (sNFL; −32.8 (21) vs −32.8 (13.4), <em>p</em> = 0.99) and NF-κB; −64.9 (35.1) vs −61.6 (35.7), <em>p</em> = 0.8, respectively). In clinical outcomes, there was no statistically significant in the mean (standard deviation) change of EDSS (0 vs 0, <em>p</em> = 1)<strong>.</strong> For MRI results, 11 patients had a stationary and regressive course 1 patient had a progressive course in the metformin group vs 6 patients had a stationary and regressive course and 2 had a progressive course in the control group, <em>p</em> = 0.23. All outcomes were measured after 6-month follow-ups. The most common side effects of metformin were diarrhea and abdominal pain without incidence of lactic acidosis.</div></div><div><h3>Conclusion</h3><div>Receiving metformin as an add-on therapy to IFNβ-1a did not result in a significant improvement in neurodegeneration and inflammation blood biomarkers and clinical outcomes. A high dose of metformin (2 g/day) is safe and well tolerated in patients with MS. Additional studies involving larger populations are necessary to confirm or disprove these findings.</div></div><div><h3>Trial registration</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> ID: <span><span>NCT06812585</span><svg><path></path></svg></span></div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"412 ","pages":"Article 578852"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145882029","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}
Homer-3-IgG autoimmunity is a rare diagnosis typically presenting with subacute cerebellar ataxia. Here, we report a patient presenting insidiously with cerebellar ataxia and mild cognitive impairment, referred to the Mayo Clinic for a second opinion of her initial diagnosis of parkinsonism. Considering autoimmune cerebellar ataxia as the correct diagnosis, the patient's cerebrospinal fluid (CSF) and serum samples were sent for Movement Disorders Autoimmune/Paraneoplastic Evaluation neural antibody testing. Murine tissue-based indirect immunofluorescence assay of serum and CSF revealed a unique cerebellar molecular layer-predominant ‘medusa head’ staining pattern. Protein microarray disclosed Homer-3 as high ranking hits. Serological diagnosis was confirmed by Homer-3-specific line blot assay. The patient was treated with a 12-week regimen of intravenous methylprednisolone. She had limited improvement, though at 6-month follow-up she had not progressed further off treatment. This patient is the third detected case with Homer-3-IgG in the Neuroimmunology laboratory of the Mayo Clinic, and the only one clinically evaluated at Mayo Clinic. Histories for the two other cases were unavailable. This case adds to the limited number of reports on Homer-3-IgG autoimmunity, with our literature review identifying 15 other cases reported to date. Neurological presentations include cerebellar ataxia (15/16), cognitive impairment (4/16), REM sleep behavior disorder (2/16), seizures (2/16), myeloradiculopathy (1/16), radiculoneuropathy (1/16), and psychosis (1/16). The most common treatment used was corticosteroids (15/16), followed by IVIg (7/16), mycophenolate mofetil (MMF) (4/16), plasma exchange (3/16), and rituximab (1/16). Reported outcomes have varied, with partial improvement being most common (7/15).
{"title":"A case of Homer-3 IgG cerebellar ataxia & literature review of 15 reported cases","authors":"Diana Anissian , Divyanshu Dubey , Nisa Vorasoot , Ramona Miske , Anastasia Zekeridou , Andrew McKeon","doi":"10.1016/j.jneuroim.2025.578846","DOIUrl":"10.1016/j.jneuroim.2025.578846","url":null,"abstract":"<div><div>Homer-3-IgG autoimmunity is a rare diagnosis typically presenting with subacute cerebellar ataxia. Here, we report a patient presenting insidiously with cerebellar ataxia and mild cognitive impairment, referred to the Mayo Clinic for a second opinion of her initial diagnosis of parkinsonism. Considering autoimmune cerebellar ataxia as the correct diagnosis, the patient's cerebrospinal fluid (CSF) and serum samples were sent for Movement Disorders Autoimmune/Paraneoplastic Evaluation neural antibody testing. Murine tissue-based indirect immunofluorescence assay of serum and CSF revealed a unique cerebellar molecular layer-predominant ‘medusa head’ staining pattern. Protein microarray disclosed Homer-3 as high ranking hits. Serological diagnosis was confirmed by Homer-3-specific line blot assay. The patient was treated with a 12-week regimen of intravenous methylprednisolone. She had limited improvement, though at 6-month follow-up she had not progressed further off treatment. This patient is the third detected case with Homer-3-IgG in the Neuroimmunology laboratory of the Mayo Clinic, and the only one clinically evaluated at Mayo Clinic. Histories for the two other cases were unavailable. This case adds to the limited number of reports on Homer-3-IgG autoimmunity, with our literature review identifying 15 other cases reported to date. Neurological presentations include cerebellar ataxia (15/16), cognitive impairment (4/16), REM sleep behavior disorder (2/16), seizures (2/16), myeloradiculopathy (1/16), radiculoneuropathy (1/16), and psychosis (1/16). The most common treatment used was corticosteroids (15/16), followed by IVIg (7/16), mycophenolate mofetil (MMF) (4/16), plasma exchange (3/16), and rituximab (1/16). Reported outcomes have varied, with partial improvement being most common (7/15).</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"412 ","pages":"Article 578846"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839091","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}
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