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1.
Neurosciences (Riyadh) ; 29(3): 153-160, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38981633

RESUMO

Tumefactive demyelinating lesion is a variant of multiple sclerosis that is a diagnostic challenge. Tumefactive demyelinating lesion requires extensive work-up as its clinical and radiological features are often indistinguishable from other central nervous system lesions, such as tumors. Diagnosis is further complicated by the increasing recognition that tumefactive demyelinating lesions can occur alongside, evolve into, or develop from numerous conditions other than multiple sclerosis, pointing to a possible overlapping etiology. We review herein relevant studies from 2017 onwards to provide a current view on the pathogenesis, clinical and imaging findings, novel diagnostic techniques for differential diagnoses, and management of tumefactive demyelinating lesions.


Assuntos
Doenças Desmielinizantes , Esclerose Múltipla , Humanos , Doenças Desmielinizantes/diagnóstico por imagem , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/diagnóstico , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/patologia , Diagnóstico Diferencial , Imageamento por Ressonância Magnética
2.
Commun Biol ; 7(1): 813, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965401

RESUMO

Strategies for treating progressive multiple sclerosis (MS) remain limited. Here, we found that miR-145-5p is overabundant uniquely in chronic lesion tissues from secondary progressive MS patients. We induced both acute and chronic demyelination in miR-145 knockout mice to determine its contributions to remyelination failure. Following acute demyelination, no advantage to miR-145 loss could be detected. However, after chronic demyelination, animals with miR-145 loss demonstrated increased remyelination and functional recovery, coincident with altered presence of astrocytes and microglia within the corpus callosum relative to wild-type animals. This improved response in miR-145 knockout animals coincided with a pathological upregulation of miR-145-5p in wild-type animals with chronic cuprizone exposure, paralleling human chronic lesions. Furthermore, miR-145 overexpression specifically in oligodendrocytes (OLs) severely stunted differentiation and negatively impacted survival. RNAseq analysis showed altered transcriptome in these cells with downregulated major pathways involved in myelination. Our data suggest that pathological accumulation of miR-145-5p is a distinctive feature of chronic demyelination and is strongly implicated in the failure of remyelination, possibly due to the inhibition of OL differentiation together with alterations in other glial cells. This is mirrored in chronic MS lesions, and thus miR-145-5p serves as a potential relevant therapeutic target in progressive forms of MS.


Assuntos
Doenças Desmielinizantes , Modelos Animais de Doenças , Camundongos Knockout , MicroRNAs , Remielinização , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Remielinização/genética , Camundongos , Doenças Desmielinizantes/genética , Doenças Desmielinizantes/metabolismo , Doenças Desmielinizantes/patologia , Humanos , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Recuperação de Função Fisiológica , Masculino , Camundongos Endogâmicos C57BL , Cuprizona/toxicidade , Feminino , Doença Crônica , Bainha de Mielina/metabolismo
3.
Niger J Clin Pract ; 27(6): 696-701, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38943292

RESUMO

BACKGROUND: Demyelinating disorders of the central nervous system (CNS) are rare disorders characterized by inflammation and the selective destruction of CNS myelin. The incidence of this disorder is increasing in developed countries. Nigerian studies on the pediatric population on the subject are very scarce. AIMS: The aim of the study was to document the epidemiology, clinical profile, and impact of late presentation on the treatment outcome of demyelinating diseases of the CNS in pediatric patients. METHODS: The retrospective review of patients aged 1-15 years admitted in a tertiary hospital from January 2018 to December 2022 with various symptoms suggestive of demyelinating CNS disorders. The diagnosis was clinically and radiologically confirmed. Information retrieved from the case notes included patients' demographics, clinical symptoms and signs, number of days with symptoms to presentation in the hospital, results of the magnetic resonance imaging (MRI), treatment, and treatment outcomes. Data were entered in Excel sheet and results were presented in tables and percentages. RESULTS: The incidence of demyelinating disorders over the period was 0.013% (10 out of 769 patients admitted over the period). Acute demyelinating encephalomyelitis (ADEM) was the most common disorder seen in the study population (60%, n = 6), followed by transverse myelitis and two (20%) had optic neuritis (ON). Most of the patients with ADEM were in the 1-5-year age group. The female-to-male ratio was 2.3:1. Paraplegia, visual impairment, and ataxia were the most common clinical presentations in the study population. One of the patients met the criteria for the diagnosis of multiple sclerosis during follow-up. Human immunodeficiency virus (HIV) was identified as the cause of demyelination in one case. Most of the patients improved with steroids. CONCLUSION: ADEM was the most common clinical phenotype seen in this study. Patients with ADEM and ON had a better prognosis than transverse myelitis. Late presentation was also identified as a poor prognostic factor. Follow-up of cases is very important to monitor disease progression to multiple sclerosis.


Assuntos
Doenças Desmielinizantes , Humanos , Nigéria/epidemiologia , Criança , Feminino , Masculino , Adolescente , Pré-Escolar , Estudos Retrospectivos , Lactente , Doenças Desmielinizantes/epidemiologia , Doenças Desmielinizantes/diagnóstico , Imageamento por Ressonância Magnética , Incidência , Resultado do Tratamento , Mielite Transversa/epidemiologia , Mielite Transversa/diagnóstico , Neurite Óptica/epidemiologia , Neurite Óptica/diagnóstico
5.
Clin Nutr ESPEN ; 62: 108-114, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38901931

RESUMO

Diet and inflammation may contribute to the development of multiple sclerosis (MS). The aim of this systematic review and meta-analysis was to assess the association between proinflammatory diet, as estimated by the Dietary Inflammatory Index (DII®), and the likelihood of developing MS or other demyelinating autoimmune diseases. A systematic search was performed of search engines and databases (PubMed, ISI Web of Sciences, Scopus, and Embase) to identify relevant studies before 10th June 2023. The search identified 182 potential studies, from which 39 full-text articles were screened for relevance. Five articles with case-control design (n = 4,322, intervention group: 1714; control group: 2608) met the study inclusion criteria. The exposure variable was DII, with studies using two distinct models: quartile-based comparisons of DII and assessment of continuous DII. The meta-analysis of high versus low quartiles of DII with four effect sizes showed a significant association with MS/demyelinating autoimmune disease likelihood, with an odds ratio (OR) of 3.26 (95% confidence interval (CI) 1.16, 9.10). The meta-analysis of four studies with DII fit as a continuous variable showed a 31% increased likelihood of MS per unit increment; which was not statistically significant at the nominal alpha equals 0.05 (OR 1.31; 95% CI 0.95, 1.81). In conclusion, this systematic review and meta-analysis provides evidence of a positive association between higher DII scores with the likelihood of developing MS, highlighting that diet-induced inflammation could play a role in MS or other demyelinating autoimmune diseases risk.


Assuntos
Dieta , Inflamação , Esclerose Múltipla , Humanos , Doenças Desmielinizantes , Doenças Autoimunes , Fatores de Risco
6.
Sci Rep ; 14(1): 14649, 2024 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918552

RESUMO

Cognitive impairment (CI) is prevalent in central nervous system demyelinating diseases, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We developed a novel tablet-based modified digital Symbol Digit Modalities Test (MD-SDMT) with adjustable protocols that feature alternating symbol-digit combinations in each trial, lasting one or two minutes. We assessed 144 patients (99 with MS and 45 with NMOSD) using both MD-SDMT protocols and the traditional paper-based SDMT. We also gathered participants' feedback through a questionnaire regarding their preferences and perceived reliability. The results showed strong correlations between MD-SDMT and paper-based SDMT scores (Pearsons correlation: 0.88 for 2 min; 0.85 for 1 min, both p < 0.001). Among the 120 respondents, the majority preferred the digitalized SDMT (55% for the 2 min, 39% for the 1 min) over the paper-based version (6%), with the 2 min MD-SDMT reported as the most reliable test. Notably, patients with NMOSD and older individuals exhibited a preference for the paper-based test, as compared to those with MS and younger patients. In summary, even with short test durations, the digitalized SDMT effectively evaluates cognitive function in MS and NMOSD patients, and is generally preferred over the paper-based method, although preferences may vary with patient characteristics.


Assuntos
Esclerose Múltipla , Neuromielite Óptica , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Esclerose Múltipla/psicologia , Esclerose Múltipla/fisiopatologia , Neuromielite Óptica/fisiopatologia , Testes Neuropsicológicos , Disfunção Cognitiva/diagnóstico , Reprodutibilidade dos Testes , Idoso , Doenças Desmielinizantes , Inquéritos e Questionários , Adulto Jovem , Computadores de Mão
7.
Lipids Health Dis ; 23(1): 194, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909243

RESUMO

BACKGROUND: Lipid droplet (LD)-laden microglia is a key pathological hallmark of multiple sclerosis. The recent discovery of this novel microglial subtype, lipid-droplet-accumulating microglia (LDAM), is notable for increased inflammatory factor secretion and diminished phagocytic capability. Lipophagy, the autophagy-mediated selective degradation of LDs, plays a critical role in this context. This study investigated the involvement of microRNAs (miRNAs) in lipophagy during demyelinating diseases, assessed their capacity to modulate LDAM subtypes, and elucidated the potential underlying mechanisms involved. METHODS: C57BL/6 mice were used for in vivo experiments. Two weeks post demyelination induction at cervical level 4 (C4), histological assessments and confocal imaging were performed to examine LD accumulation in microglia within the lesion site. Autophagic changes were observed using transmission electron microscopy. miRNA and mRNA multi-omics analyses identified differentially expressed miRNAs and mRNAs under demyelinating conditions and the related autophagy target genes. The role of miR-223 in lipophagy under these conditions was specifically explored. In vitro studies, including miR-223 upregulation in BV2 cells via lentiviral infection, validated the bioinformatics findings. Immunofluorescence staining was used to measure LD accumulation, autophagy levels, target gene expression, and inflammatory mediator levels to elucidate the mechanisms of action of miR-223 in LDAM. RESULTS: Oil Red O staining and confocal imaging revealed substantial LD accumulation in the demyelinated spinal cord. Transmission electron microscopy revealed increased numbers of autophagic vacuoles at the injury site. Multi-omics analysis revealed miR-223 as a crucial regulatory gene in lipophagy during demyelination. It was identified that cathepsin B (CTSB) targets miR-223 in autophagy to integrate miRNA, mRNA, and autophagy gene databases. In vitro, miR-223 upregulation suppressed CTSB expression in BV2 cells, augmented autophagy, alleviated LD accumulation, and decreased the expression of the inflammatory mediator IL-1ß. CONCLUSION: These findings indicate that miR-223 plays a pivotal role in lipophagy under demyelinating conditions. By inhibiting CTSB, miR-223 promotes selective LD degradation, thereby reducing the lipid burden and inflammatory phenotype in LDAM. This study broadens the understanding of the molecular mechanisms of lipophagy and proposes lipophagy induction as a potential therapeutic approach to mitigate inflammatory responses in demyelinating diseases.


Assuntos
Autofagia , Catepsina B , Doenças Desmielinizantes , Gotículas Lipídicas , Lisofosfatidilcolinas , Camundongos Endogâmicos C57BL , MicroRNAs , Microglia , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Microglia/metabolismo , Microglia/patologia , Camundongos , Gotículas Lipídicas/metabolismo , Doenças Desmielinizantes/metabolismo , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/genética , Doenças Desmielinizantes/patologia , Catepsina B/metabolismo , Catepsina B/genética , Lisofosfatidilcolinas/metabolismo , Modelos Animais de Doenças , Masculino , Regulação da Expressão Gênica , Linhagem Celular
8.
J Neuroinflammation ; 21(1): 157, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879499

RESUMO

BACKGROUND: Cystatin F is a secreted lysosomal cysteine protease inhibitor that has been implicated in affecting the severity of demyelination and enhancing remyelination in pre-clinical models of immune-mediated demyelination. How cystatin F impacts neurologic disease severity following viral infection of the central nervous system (CNS) has not been well characterized and was the focus of this study. We used cystatin F null-mutant mice (Cst7-/-) with a well-established model of murine coronavirus-induced neurologic disease to evaluate the contributions of cystatin F in host defense, demyelination and remyelination. METHODS: Wildtype controls and Cst7-/- mice were intracranially (i.c.) infected with a sublethal dose of the neurotropic JHM strain of mouse hepatitis virus (JHMV), with disease progression and survival monitored daily. Viral plaque assays and qPCR were used to assess viral levels in CNS. Immune cell infiltration into the CNS and immune cell activation were determined by flow cytometry and 10X genomics chromium 3' single cell RNA sequencing (scRNA-seq). Spinal cord demyelination was determined by luxol fast blue (LFB) and Hematoxylin/Eosin (H&E) staining and axonal damage assessed by immunohistochemical staining for SMI-32. Remyelination was evaluated by electron microscopy (EM) and calculation of g-ratios. RESULTS: JHMV-infected Cst7-/- mice were able to control viral replication within the CNS, indicating that cystatin F is not essential for an effective Th1 anti-viral immune response. Infiltration of T cells into the spinal cords of JHMV-infected Cst7-/- mice was increased compared to infected controls, and this correlated with increased axonal damage and demyelination associated with impaired remyelination. Single-cell RNA-seq of CD45 + cells enriched from spinal cords of infected Cst7-/- and control mice revealed enhanced expression of transcripts encoding T cell chemoattractants, Cxcl9 and Cxcl10, combined with elevated expression of interferon-g (Ifng) and perforin (Prf1) transcripts in CD8 + T cells from Cst7-/- mice compared to controls. CONCLUSIONS: Cystatin F is not required for immune-mediated control of JHMV replication within the CNS. However, JHMV-infected Cst7-/- mice exhibited more severe clinical disease associated with increased demyelination and impaired remyelination. The increase in disease severity was associated with elevated expression of T cell chemoattractant chemokines, concurrent with increased neuroinflammation. These findings support the idea that cystatin F influences expression of proinflammatory gene expression impacting neuroinflammation, T cell activation and/or glia cell responses ultimately impacting neuroinflammation and neurologic disease.


Assuntos
Infecções por Coronavirus , Cistatinas , Doenças Desmielinizantes , Camundongos Knockout , Vírus da Hepatite Murina , Animais , Camundongos , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/metabolismo , Doenças Desmielinizantes/virologia , Doenças Desmielinizantes/imunologia , Vírus da Hepatite Murina/patogenicidade , Cistatinas/genética , Cistatinas/metabolismo , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/patologia , Doenças Neuroinflamatórias/metabolismo
9.
Sci Rep ; 14(1): 13988, 2024 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-38886527

RESUMO

Demyelination is generated in several nervous system illnesses. Developing strategies for effective clinical treatments requires the discovery of promyelinating drugs. Increased GABAergic signaling through γ-aminobutyric acid type A receptor (GABAAR) activation in oligodendrocytes has been proposed as a promyelinating condition. GABAAR expressed in oligodendroglia is strongly potentiated by n-butyl-ß-carboline-3-carboxylate (ß-CCB) compared to that in neurons. Here, mice were subjected to 0.3% cuprizone (CPZ) added in the food to induce central nervous system demyelination, a well-known model for multiple sclerosis. Then ß-CCB (1 mg/Kg) was systemically administered to analyze the remyelination status in white and gray matter areas. Myelin content was evaluated using Black-Gold II (BGII) staining, immunofluorescence (IF), and magnetic resonance imaging (MRI). Evidence indicates that ß-CCB treatment of CPZ-demyelinated animals promoted remyelination in several white matter structures, such as the fimbria, corpus callosum, internal capsule, and cerebellar peduncles. Moreover, using IF, it was observed that CPZ intake induced an increase in NG2+ and a decrease in CC1+ cell populations, alterations that were importantly retrieved by ß-CCB treatment. Thus, the promyelinating character of ß-CCB was confirmed in a generalized demyelination model, strengthening the idea that it has clinical potential as a therapeutic drug.


Assuntos
Carbolinas , Cuprizona , Doenças Desmielinizantes , Modelos Animais de Doenças , Remielinização , Animais , Cuprizona/toxicidade , Remielinização/efeitos dos fármacos , Camundongos , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/metabolismo , Carbolinas/farmacologia , Carbolinas/administração & dosagem , Bainha de Mielina/metabolismo , Bainha de Mielina/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/metabolismo , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/metabolismo , Esclerose Múltipla/induzido quimicamente , Esclerose Múltipla/patologia , Substância Branca/efeitos dos fármacos , Substância Branca/metabolismo , Substância Branca/patologia , Imageamento por Ressonância Magnética
10.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(3): 487-494, 2024 Jun 18.
Artigo em Chinês | MEDLINE | ID: mdl-38864135

RESUMO

OBJECTIVE: To unveil the pathological changes associated with demyelination in schizophrenia (SZ) and its consequential impact on interstitial fluid (ISF) drainage, and to investigate the therapeutic efficacy of ursolic acid (UA) in treating demyelination and the ensuing abnormalities in ISF drainage in SZ. METHODS: Female C57BL/6J mice, aged 6-8 weeks and weighing (20±2) g, were randomly divided into three groups: control, SZ model, and UA treatment. The control group received intraperitoneal injection (ip) of physiological saline and intragastric administration (ig) of 1% carboxymethylcellulose sodium (CMC-Na). The SZ model group was subjected to ip injection of 2 mg/kg dizocilpine maleate (MK-801) and ig administration of 1% CMC-Na. The UA treatment group underwent ig administration of 25 mg/kg UA and ip injection of 2 mg/kg MK-801. The treatment group received UA pretreatment via ig administration for one week, followed by a two-week drug intervention for all the three groups. Behavioral assessments, including the open field test and prepulse inhibition experiment, were conducted post-modeling. Subsequently, changes in the ISF partition drainage were investigated through fluorescent tracer injection into specific brain regions. Immunofluorescence analysis was employed to examine alterations in aquaporin 4 (AQP4) polarity distribution in the brain and changes in protein expression. Myelin reflex imaging using Laser Scanning Confocal Microscopy (LSCM) was utilized to study modifications in myelin within the mouse brain. Quantitative data underwent one-way ANOVA, followed by TukeyHSD for post hoc pairwise comparisons between the groups. RESULTS: The open field test revealed a significantly longer total distance [(7 949.39±1 140.55) cm vs. (2 831.01±1 212.72) cm, P < 0.001] and increased central area duration [(88.43±22.06) s vs. (56.85±18.58) s, P=0.011] for the SZ model group compared with the controls. The UA treatment group exhibited signifi-cantly reduced total distance [(2 415.80±646.95) cm vs. (7 949.39±1 140.55) cm, P < 0.001] and increased central area duration [(54.78±11.66) s vs. (88.43±22.06) s, P=0.007] compared with the model group. Prepulse inhibition test results demonstrated a markedly lower inhibition rate of the startle reflex in the model group relative to the controls (P < 0.001 for both), with the treatment group displaying significant improvement (P < 0.001 for both). Myelin sheath analysis indicated significant demyelination in the model group, while UA treatment reversed this effect. Fluorescence tracing exhibited a significantly larger tracer diffusion area towards the rostral cortex and reflux area towards the caudal thalamus in the model group relative to the controls [(13.93±3.35) mm2 vs. (2.79±0.94) mm2, P < 0.001 for diffusion area; (2.48±0.38) mm2 vs. (0.05±0.12) mm2, P < 0.001 for reflux area], with significant impairment of drainage in brain regions. The treatment group demonstrated significantly reduced tracer diffusion and reflux areas [(7.93±2.48) mm2 vs. (13.93±3.35) mm2, P < 0.001 for diffusion area; (0.50±0.30) mm2 vs. (2.48±0.38) mm2, P < 0.001 for reflux area]. Immunofluorescence staining revealed disrupted AQP4 polarity distribution and reduced AQP4 protein expression in the model group compared with the controls [(3 663.88±733.77) µm2 vs. (13 354.92±4 054.05) µm2, P < 0.001]. The treatment group exhibited restored AQP4 polarity distribution and elevated AQP4 protein expression [(11 104.68±3 200.04) µm2 vs. (3 663.88±733.77) µm2, P < 0.001]. CONCLUSION: UA intervention ameliorates behavioral performance in SZ mice, Thus alleviating hyperactivity and anxiety symptoms and restoring sensorimotor gating function. The underlying mechanism may involve the improvement of demyelination and ISF drainage dysregulation in SZ mice.


Assuntos
Doenças Desmielinizantes , Modelos Animais de Doenças , Líquido Extracelular , Camundongos Endogâmicos C57BL , Esquizofrenia , Triterpenos , Ácido Ursólico , Animais , Camundongos , Triterpenos/uso terapêutico , Triterpenos/farmacologia , Esquizofrenia/tratamento farmacológico , Feminino , Doenças Desmielinizantes/tratamento farmacológico , Líquido Extracelular/efeitos dos fármacos , Líquido Extracelular/metabolismo , Maleato de Dizocilpina , Aquaporina 4/metabolismo
11.
Continuum (Minneap Minn) ; 30(3): 781-817, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38830071

RESUMO

OBJECTIVE: This article reviews the various conditions that can present with acute and severe central nervous system demyelination, the broad differential diagnosis of these conditions, the most appropriate diagnostic workup, and the acute treatment regimens to be administered to help achieve the best possible patient outcomes. LATEST DEVELOPMENTS: The discovery of anti-aquaporin 4 (AQP4) antibodies and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in the past two decades has revolutionized our understanding of acute demyelinating disorders, their evaluation, and their management. ESSENTIAL POINTS: Demyelinating disorders comprise a large category of neurologic disorders seen by practicing neurologists. In the majority of cases, patients with these conditions do not require care in an intensive care unit. However, certain disorders may cause severe demyelination that necessitates intensive care unit admission because of numerous simultaneous multifocal lesions, tumefactive lesions, or lesions in certain brain locations that lead to acute severe neurologic dysfunction. Intensive care may be necessary for the management and prevention of complications for patients who have severely altered mental status, rapidly progressive neurologic worsening, elevated intracranial pressure, severe cerebral edema, status epilepticus, or respiratory failure.


Assuntos
Doenças Desmielinizantes , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/terapia , Gerenciamento Clínico , Adulto Jovem
12.
Neuromolecular Med ; 26(1): 22, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824254

RESUMO

Stroke is a significant public health issue, and research has consistently focused on studying the mechanisms of injury and identifying new targets. As a CDK5 activator, p39 plays a crucial role in various diseases. In this article, we will explore the role and mechanism of p39 in cerebral ischemic injury. We measured the level of p39 using western blot and QPCR at various time points following cerebral ischemia-reperfusion (I/R) injury. The results indicated a significant reduction in the level of p39. TTC staining and behavioral results indicate that the knockout of p39 (p39KO) provides neuroprotection in the short-term. Interestingly, the behavioral dysfunction in p39KO mice was exacerbated after the repair phase of I/R. Further study revealed that this deterioration may be due to demyelination induced by elevated p35 levels. In summary, our study offers profound insights into the significance of p39 in both the acute and repair stages of ischemic injury recovery and a theoretical foundation for future therapeutic drug exploration.


Assuntos
Camundongos Endogâmicos C57BL , Camundongos Knockout , Bainha de Mielina , Traumatismo por Reperfusão , Animais , Masculino , Camundongos , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/genética , Infarto da Artéria Cerebral Média/patologia , Fosfotransferases , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
13.
Neuroimaging Clin N Am ; 34(3): 335-357, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38942520

RESUMO

In recent decades, advances in neuroimaging have profoundly transformed our comprehension of central nervous system demyelinating diseases. Remarkable technological progress has enabled the integration of cutting-edge acquisition and postprocessing techniques, proving instrumental in characterizing subtle focal changes, diffuse microstructural alterations, and macroscopic pathologic processes. This review delves into state-of-the-art modalities applied to multiple sclerosis, neuromyelitis optica spectrum disorders, and myelin oligodendrocyte glycoprotein antibody-associated disease. Furthermore, it explores how this dynamic landscape holds significant promise for the development of effective and personalized clinical management strategies, encompassing support for differential diagnosis, prognosis, monitoring treatment response, and patient stratification.


Assuntos
Encéfalo , Neuroimagem , Humanos , Neuroimagem/métodos , Encéfalo/diagnóstico por imagem , Doenças Desmielinizantes/diagnóstico por imagem , Neuromielite Óptica/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico por imagem
14.
Neuroimaging Clin N Am ; 34(3): 421-438, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38942525

RESUMO

Atypical demyelinating lesions (ADLs) can be idiopathic, occurring as isolated and self-limited events, or can appear in different stages of relapsing demyelinating diseases. Not infrequently, ADLs occur in inflammatory syndromes associated with exogenous or endogenous toxic factors, metabolic imbalance, or infectious agents. It is important to recognize imaging patterns that indicate an inflammatory/demyelinating substrate in central nervous system lesions and to investigate potential triggers or complicating factors that might be associated. The prognostic and treatment strategies of ADLs are influenced by the underlying etiopathogenesis.


Assuntos
Encéfalo , Doenças Desmielinizantes , Imageamento por Ressonância Magnética , Humanos , Doenças Desmielinizantes/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem
15.
Neuroimaging Clin N Am ; 34(3): 317-334, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38942519

RESUMO

Standardized MR imaging protocols are important for the diagnosis and monitoring of patients with multiple sclerosis (MS) and the appropriate use of MR imaging in routine clinical practice. Advances in using MR imaging to establish an earlier diagnosis of MS, safety concerns regarding intravenous gadolinium-based contrast agents, and the value of spinal cord MR imaging for diagnostic, prognostic, and monitoring purposes suggest a changing role of MR imaging for the management and care of MS patients. The MR imaging protocol emphasizes 3 dimensional acquisitions for optimal comparison over time.


Assuntos
Doenças Desmielinizantes , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Doenças Desmielinizantes/diagnóstico por imagem , Esclerose Múltipla/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Meios de Contraste
19.
Cell Rep ; 43(5): 114226, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38733586

RESUMO

Cognitive dysfunction is a feature in multiple sclerosis (MS), a chronic inflammatory demyelinating disorder. A notable aspect of MS brains is hippocampal demyelination, which is closely associated with cognitive decline. However, the mechanisms underlying this phenomenon remain unclear. Chitinase-3-like (CHI3L1), secreted by activated astrocytes, has been identified as a biomarker for MS progression. Our study investigates CHI3L1's function within the demyelinating hippocampus and demonstrates a correlation between CHI3L1 expression and cognitive impairment in patients with MS. Activated astrocytes release CHI3L1 in reaction to induced demyelination, which adversely affects the proliferation and differentiation of neural stem cells and impairs dendritic growth, complexity, and spine formation in neurons. Our findings indicate that the astrocytic deletion of CHI3L1 can mitigate neurogenic deficits and cognitive dysfunction. We showed that CHI3L1 interacts with CRTH2/receptor for advanced glycation end (RAGE) by attenuating ß-catenin signaling. The reactivation of ß-catenin signaling can revitalize neurogenesis, which holds promise for therapy of inflammatory demyelination.


Assuntos
Astrócitos , Proteína 1 Semelhante à Quitinase-3 , Cognição , Hipocampo , Neurogênese , Transdução de Sinais , Proteína 1 Semelhante à Quitinase-3/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Animais , Astrócitos/metabolismo , Humanos , Camundongos , Cognição/fisiologia , Doenças Desmielinizantes/metabolismo , Doenças Desmielinizantes/patologia , Masculino , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Feminino , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , beta Catenina/metabolismo , Proliferação de Células , Diferenciação Celular
20.
Mult Scler ; 30(7): 800-811, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38751221

RESUMO

BACKGROUND: Conventional magnetic resonance imaging (MRI) does not account for all disability in multiple sclerosis. OBJECTIVE: The objective was to assess the ability of graph metrics from diffusion-based structural connectomes to explain motor function beyond conventional MRI in early demyelinating clinically isolated syndrome (CIS). METHODS: A total of 73 people with CIS underwent conventional MRI, diffusion-weighted imaging and clinical assessment within 3 months from onset. A total of 28 healthy controls underwent MRI. Structural connectomes were produced. Differences between patients and controls were explored; clinical associations were assessed in patients. Linear regression models were compared to establish relevance of graph metrics over conventional MRI. RESULTS: Local efficiency (p = 0.045), clustering (p = 0.034) and transitivity (p = 0.036) were reduced in patients. Higher assortativity was associated with higher Expanded Disability Status Scale (EDSS) (ß = 74.9, p = 0.026) scores. Faster timed 25-foot walk (T25FW) was associated with higher assortativity (ß = 5.39, p = 0.026), local efficiency (ß = 27.1, p = 0.041) and clustering (ß = 36.1, p = 0.032) and lower small-worldness (ß = -3.27, p = 0.015). Adding graph metrics to conventional MRI improved EDSS (p = 0.045, ΔR2 = 4) and T25FW (p < 0.001, ΔR2 = 13.6) prediction. CONCLUSION: Graph metrics are relevant early in demyelination. They show differences between patients and controls and have relationships with clinical outcomes. Segregation (local efficiency, clustering, transitivity) was particularly relevant. Combining graph metrics with conventional MRI better explained disability.


Assuntos
Conectoma , Doenças Desmielinizantes , Humanos , Masculino , Feminino , Adulto , Doenças Desmielinizantes/diagnóstico por imagem , Doenças Desmielinizantes/fisiopatologia , Pessoa de Meia-Idade , Imagem de Difusão por Ressonância Magnética , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/fisiopatologia , Avaliação da Deficiência , Imageamento por Ressonância Magnética , Adulto Jovem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Encéfalo/patologia
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