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1.
BMC Pediatr ; 23(1): 15, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36627589

RESUMO

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a post-viral inflammatory vasculopathy characterized by persistent fever, multiorgan dysfunction, significant laboratory markers of inflammation, lack of an alternative diagnosis, and prior SARS-CoV-2 infection or exposure in children and adolescents. The most common early symptoms include a prolonged fever, as well as dermatologic, mucocutaneous, and gastrointestinal symptoms such abdominal pain, vomiting, and diarrhea. CASE PRESENTATION: We present a pediatric patient with multisystem inflammatory syndrome with the development of abdominal pain and seizure who was found to have a circumferential wall thickening of the terminal ileum and ileocecal junction in abdominal CT scan. The brain MRI of the patient showed cytotoxic lesions of the corpus callosum (CLOCC) which had hypersignal intensity with a few diffusion restrictions in the splenium of the corpus callosum. CONCLUSION: This case is being reported to raise awareness of MIS-C presenting characteristics. Given the rising number of MIS-C patients and a lack of understanding regarding early diagnostic clinical characteristics and therapy, further research into clinical presentations, treatment, and outcomes is urgently needed.


Assuntos
COVID-19 , Doença de Crohn , Adolescente , Humanos , Criança , SARS-CoV-2 , Doença de Crohn/patologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Dor Abdominal/etiologia , Dor Abdominal/patologia
2.
Exp Neurol ; 359: 114241, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36240881

RESUMO

Traumatic brain injury (TBI) acutely damages the brain; this injury can evolve into chronic neurodegeneration. While much is known about the chronic effects arising from multiple mild TBIs, far less is known about the long-term effects of a single moderate to severe TBI. We found that a single moderate closed head injury to mice induces diffuse axonal injury within 1-day post-injury (DPI). At 14 DPI, injured animals have atrophy of ipsilesional cortex, thalamus, and corpus callosum, with bilateral atrophy of the dorsal fornix. Atrophy of the ipsilesional corpus callosum is accompanied by decreased fractional anisotropy and increased mean and radial diffusivity that remains unchanged between 14 and 180 DPI. Injured animals show an increased density of phospho-tau immunoreactive (pTau+) cells in the ipsilesional cortex and thalamus, and bilaterally in corpus callosum. Between 14 and 180 DPI, atrophy occurs in the ipsilesional ventral fornix, contralesional corpus callosum, and bilateral internal capsule. Diffusion tensor MRI parameters remain unchanged in white matter regions with delayed atrophy. Between 14 and 180 DPI, pTau+ cell density increases bilaterally in corpus callosum, but decreases in cortex and thalamus. The location of pTau+ cells within the ipsilesional corpus callosum changes between 14 and 180 DPI; density of all cells increases including pTau+ or pTau- cells. >90% of the pTau+ cells are in the oligodendrocyte lineage in both gray and white matter. Density of thioflavin-S+ cells in thalamus increases by 180 DPI. These data suggest a single closed head impact produces multiple forms of chronic neurodegeneration. Gray and white matter regions proximal to the impact site undergo early atrophy. More distal white matter regions undergo chronic, progressive white matter atrophy with an increasing density of oligodendrocytes containing pTau. These data suggest a complex chronic neurodegenerative process arising from a single moderate closed head injury.


Assuntos
Lesões Encefálicas Traumáticas , Traumatismos Cranianos Fechados , Substância Branca , Animais , Camundongos , Masculino , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Imagem de Tensor de Difusão , Lesões Encefálicas Traumáticas/patologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Oligodendroglia , Atrofia/patologia , Traumatismos Cranianos Fechados/patologia
3.
Ann Clin Transl Neurol ; 10(1): 32-47, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36480557

RESUMO

OBJECTIVE: Neonatal imaging studies report corpus callosum abnormalities after neonatal hypoxic-ischaemic encephalopathy (HIE), but corpus callosum development and relation to cognition in childhood are unknown. Using magnetic resonance imaging (MRI), we examined the relationship between corpus callosum size, microstructure and cognitive and motor outcomes at early school-age children cooled for HIE (cases) without cerebral palsy compared to healthy, matched controls. A secondary aim was to examine the impact of HIE-related neonatal brain injury on corpus callosum size, microstructure and growth. METHODS: Participants aged 6-8 years underwent MRI, the Movement Assessment Battery for Children Second Edition and Wechsler Intelligence Scale for Children Fourth Edition. Cross-sectional area, volume, fractional anisotropy and radial diffusivity of the corpus callosum and five subdivisions were measured. Multivariable regression was used to assess associations between total motor score, full-scale IQ (FSIQ) and imaging metrics. RESULTS: Adjusting for age, sex and intracranial volume, cases (N = 40) compared to controls (N = 39) demonstrated reduced whole corpus callosum area (ß = -26.9, 95% confidence interval [CI] = -53.17, -0.58), volume (ß = -138.5, 95% CI = -267.54, -9.56), fractional anisotropy and increased radial diffusivity (P < 0.05) within segments II-V. In cases, segment V area (ß = 0.18, 95% CI = 0.004, 0.35), volume (ß = 0.04, 95% CI = 0.001, 0.079), whole corpus callosum fractional anisotropy (ß = 13.8 95% CI = 0.6, 27.1) and radial diffusivity (ß = -11.3, 95% CI = -22.22, -0.42) were associated with FSIQ. Growth of the corpus callosum was restricted in cases with a FSIQ ≤85, and volume was reduced in cases with mild neonatal multifocal injury compared to white matter injury alone. INTERPRETATION: Following neonatal HIE, morphological and microstructural changes in the corpus callosum are associated with reduced cognitive function at early school age.


Assuntos
Lesões Encefálicas , Cognição , Corpo Caloso , Criança , Humanos , Recém-Nascido , Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Cognição/fisiologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Imagem de Difusão por Ressonância Magnética , Imageamento por Ressonância Magnética , Estudos de Casos e Controles
4.
BMC Neurol ; 22(1): 453, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36471320

RESUMO

BACKGROUND: To determine whether restricted diffusion of the callosal splenium is specific for seizure activity in neonates. METHODS: We performed a retrospective chart review of 123 neonates who had a diagnosis of hypoxic ischemic encephalopathy (HIE) who underwent therapeutic cooling and had magnetic resonance imaging (MRI) within the first 10 days of life. The regions examined for injury include the callosal splenium, cortex, deep gray matter, and subcortical white matter. Neurodevelopmental outcomes were secondarily assessed using the Bayley Scales of Infant Development at 12 to 18 months of age and > 18 months of age. APGAR scores and pH, two important markers of hypoxia/ischemia and encephalopathy, were also analyzed in relation to these outcomes. RESULTS: Approximately 41% of the neonates had at least one abnormal region on brain MRI, and 21% had abnormal signal in the splenium. Clinical and/or electrographic seizures were documented in 32%. Changes in the splenium had a sensitivity of 54%, specificity of 94%, and positive predictive value of 81% for seizure presence. The presence of seizures and splenium lesion was associated poor developmental outcomes at 12 to 18 months of age. APGAR scores at 10 minutes, but not lowest pH was associated with splenial changes. CONCLUSIONS: Restricted diffusion of the callosal splenium is specific for recent seizures in neonates with HIE. Seizures and splenial lesion represent risk factors for poor neurodevelopmental outcomes. Child neurologists and neonatologists should consider splenial signal abnormality in their assessment of neonates at risk for seizures and counsel families about likely outcomes accordingly.


Assuntos
Hipóxia-Isquemia Encefálica , Lactente , Recém-Nascido , Criança , Humanos , Estudos Retrospectivos , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Convulsões/etiologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Imageamento por Ressonância Magnética/métodos
5.
Clin Med (Lond) ; 22(5): 493-495, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36507823

RESUMO

A 26-year-old man was diagnosed with epilepsy a few months previously and admitted with status epilepticus. Computed tomography (CT) of the brain and CT venography were unremarkable. Magnetic resonance imaging (MRI) of the brain showed evidence of possible acute focal infarction in the splenium of the corpus callosum that showed a true restricted diffusion. The patient had no vascular risk factors and no focal neurological deficit on examination to explain the occurrence of an acute infarction. MRI of the brain was repeated 1 month later to assess for progression of that lesion and showed resolution of it. This case highlights the association of cytotoxic lesions of the corpus callosum that show true restricted diffusion with status epilepticus. It also emphasises the importance of medical reasoning and not being solely dependent on diagnostic investigations without reasonably linking them to the history and examination.


Assuntos
Epilepsia , Estado Epiléptico , Masculino , Humanos , Adulto , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Imageamento por Ressonância Magnética , Infarto/patologia
6.
BMJ Case Rep ; 15(12)2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36585049

RESUMO

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinicoradiologic syndrome diagnosed by temporary hyperintense lesion in the area, including the splenium of the corpus callosum, on diffusion-weighted imaging and neuropsychiatric symptoms that recover without sequelae. MERS is rare in adults, especially elderly people. We herein report a man in his 60s diagnosed with MERS caused by Legionella pneumonia. He completely recovered with only the administration of levofloxacin and azithromycin despite the risk factors of an advanced age, medical history of untreated hypertension, bilateral spontaneous pneumothoraxes, smoking and drinking habits and pulmonary emphysema. To our knowledge, this is the oldest case of MERS due to Legionella pneumonia and extremely old among total MERS cases. Our research revealed that Legionella species are the most common pathogens of adult-onset MERS, while viruses are the main causative factors in children. This case helps clarify the features of MERS in high-risk adults.


Assuntos
Encefalopatias , Encefalite , Legionella , Doença dos Legionários , Pneumonia , Masculino , Adulto , Criança , Humanos , Idoso , Encefalopatias/complicações , Encefalite/diagnóstico por imagem , Encefalite/etiologia , Doença dos Legionários/complicações , Doença dos Legionários/diagnóstico , Doença dos Legionários/tratamento farmacológico , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Pneumonia/complicações , Imageamento por Ressonância Magnética
9.
Turk J Med Sci ; 52(5): 1506-1512, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36422480

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) mostly manifests with fever, shortness of breath, and cough, has also been found to cause some neurological symptoms, such as anosmia and ageusia. The aim of the study was to present the magnetic resonance imaging (MRI) findings of patients with anosmia-hyposmia symptoms and to discuss potential mechanisms in light of these findings. METHODS: Of the 2412 patients diagnosed with COVID-19-related pneumonia (RT-PCR at least once + clinically confirmed) between March and December 2020, 15 patients underwent olfactory MRI to investigate the cause of ongoing anosmia/ hyposmia symptoms were included in the study. RESULTS: Eleven (73.3%) patients were female and four (26.7%) were male. A total of eight patients (53.3%) showed thickening in the olfactory cleft region, where the olfactory epithelium is located. In nine patients (60%), enhancement was observed in the olfactory cleft region. Diffusion-weighted imaging showed restricted diffusion in three patients (20%) (corpus callosum splenium in one patient, thalamus mediodorsal nucleus in one patient, and mesencephalon in one patient). DISCUSSION: This study revealed that there is a relationship between anosmia and MRI findings. Larger studies can enlighten the pathophysiological mechanism and shed light on both diagnosis and new treatments.


Assuntos
COVID-19 , Transtornos do Olfato , Humanos , Masculino , Feminino , Anosmia/diagnóstico por imagem , Anosmia/etiologia , COVID-19/complicações , COVID-19/diagnóstico por imagem , Transtornos do Olfato/diagnóstico por imagem , Transtornos do Olfato/etiologia , Imageamento por Ressonância Magnética , Corpo Caloso/patologia
10.
Brain Behav ; 12(11): e2726, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36278400

RESUMO

BACKGROUND: Brain atrophy is an important feature in dementia and is meaningful to explore a brain atrophy model to predict dementia. Using machine learning algorithm to establish a dementia model and cognitive function model based on brain atrophy characteristics is unstoppable. METHOD: We acquired 157 dementia and 156 normal old people.s clinical information and MRI data, which contains 44 brain atrophy features, including visual scale assessment of brain atrophy and multiple linear measurement indexes and brain atrophy index. Five machine learning models were used to establish prediction models for dementia, general cognition, and subcognitive domains. RESULTS: The extreme Gradient Boosting (XGBoost) model had the best effect in predicting dementia, with a sensitivity of 0.645, a specificity of 0.839, and the area under curve (AUC) of 0.784. In this model, the important brain atrophy features for predicting dementia were temporal horn ratio, cella media index, suprasellar cistern ratio, and the thickness of the corpus callosum genu. CONCLUSION: For nonstroke elderly people, the machine learning model based on clinical head MRI brain atrophy features had good predictive value for dementia, general cognitive impairment, immediate memory impairment, word fluency disorder, executive dysfunction, and visualspatial disorder.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Atrofia/patologia , Cognição , Disfunção Cognitiva/diagnóstico , Doença de Alzheimer/patologia , Corpo Caloso/patologia
11.
Turk J Med Sci ; 52(2): 405-412, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36161629

RESUMO

BACKGROUND: Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a rare clinicoradiological syndrome that typically presents with central nervous system symptoms such as loss of consciousness, seizure, headache, and ophthalmoparesis. METHODS: Here, we highlight the characteristics of this syndrome together with the clinical and MRI findings of 6 pediatric patients with MERS. RESULTS: Between January 2017 and October 2020, 6 patients with MERS (3 boys and 3 girls) presented to our center. The mean age was 122 ± 54.6 (min-max: 44-180) months. None of the patients had a chronic disease. In our study, infectious agents were detected in 4 patients (66.6%), while noninfectious causes (one seizure and the other hyponatremia) were detected in two patients. All of our cases were discharged without any sequelae after an average of 12.1 ± 7 (min-max: 4-20) days of hospitalization. In 1 patient (case 6), control MRI could not be performed, and the radiological recovery of our other patients was shown to be between 14 days and 2 months. DISCUSSION: MERS is an acute encephalopathy with good prognosis and should be considered by neurologists in differential diagnosis due to its variable clinical presentation and specific MRI findings.


Assuntos
Encefalopatias , Encefalite , Encefalopatias/complicações , Encefalopatias/etiologia , Criança , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Encefalite/diagnóstico , Encefalite/etiologia , Encefalite/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Convulsões , Síndrome
13.
Neurobiol Dis ; 174: 105858, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36096339

RESUMO

Mutations in SPG11, encoding spatacsin, constitute the major cause of autosomal recessive Hereditary Spastic Paraplegia (HSP) with thinning of the corpus callosum. Previous studies showed that spatacsin orchestrates cellular traffic events through the formation of a coat-like complex and its loss of function results in lysosomal and axonal transport impairments. However, the upstream mechanisms that regulate spatacsin trafficking are unknown. Here, using proteomics and CRISPR/Cas9-mediated tagging of endogenous spatacsin, we identified a subset of 14-3-3 proteins as physiological interactors of spatacsin. The interaction is modulated by Protein Kinase A (PKA)-dependent phosphorylation of spatacsin at Ser1955, which initiates spatacsin trafficking from the plasma membrane to the intracellular space. Our study provides novel insight in understanding spatacsin physio-pathological roles with mechanistic dissection of its associated pathways.


Assuntos
Proteínas 14-3-3 , Paraplegia Espástica Hereditária , Humanos , Proteínas 14-3-3/genética , Proteínas Quinases Dependentes de AMP Cíclico/genética , Paraplegia Espástica Hereditária/genética , Mutação , Corpo Caloso/patologia , Proteínas/genética
15.
Zh Nevrol Psikhiatr Im S S Korsakova ; 122(9. Vyp. 2): 32-36, 2022.
Artigo em Russo | MEDLINE | ID: mdl-36170096

RESUMO

Mild encephalopathy with a reversible splenial lesion (MERS) is a clinical and radiological syndrome that can be caused by infectious and non-infectious factors. The most common neurological symptoms are impaired consciousness, impaired speech, convulsions, muscle weakness, ophthalmoplegia, facial paralysis, and headache. A case of a 5-year-old child with a leading clinical symptom of bilateral transient blindness and radiological characteristics of MERS syndrome is presented.


Assuntos
Encefalopatias , Corpo Caloso , Encefalopatias/diagnóstico , Pré-Escolar , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Cefaleia/patologia , Humanos , Imageamento por Ressonância Magnética , Síndrome
16.
Artigo em Inglês | MEDLINE | ID: mdl-36011475

RESUMO

The corpus callosum plays a vital role in brain function. In particular, in the trunk of the corpus callosum, in the course of various diseases, there may be temporary, reversible changes (reversible splenial lesion syndrome (RESLES)), as well as partially reversible and irreversible changes. This article discusses the differentiation of RESLES and other conditions with changes in the corpus callosum lobe, as well as the accompanying clinical symptoms. Moreover, a case report of a patient in whom the above changes appeared in the nuclear magnetic resonance (NMR) image is presented. A 20-year-old patient with the diagnosis of Ehlers-Danlos syndrome type VI was admitted to the psychiatric ward in an emergency because of psychomotor agitation, refusal to take food and fluids, delusional statements with a message, grandeur, and auditory hallucinations. In the performed magnetic resonance imaging (MRI) of the brain, the corpus callosum non-characteristic in T2-weighted images revealed a hyperintensive area, which was significantly hyperintensive in diffusion magnetic resonance (DWI) sequences and in apparent diffusion coefficient (ADC) sequences with reduced signal intensity and no signs of bleeding. The hypothesis of subacute ischemic stroke of the corpus callosum was presented. In the control MRI of the brain, changes in the corpus callosum completely regressed, thus excluding an ischemic etiology and favoring the diagnosis of RESLES. During hospitalization, the patient experienced significant fluctuations in mental status, with the dominant symptoms typical of the paranoid syndrome in the form of disturbances in the course and structure of thinking and perception, and a clear and stable improvement was obtained after the administration of long-acting intramuscular olanzapine. Taking into account the clinical and radiological picture, the age of the episode, the rapidity of the disease development, the persistence of its clinical symptoms after the withdrawal of radiological changes in the brain NMR image, as well as the significant improvement in the clinical condition after the introduction of antipsychotic drugs, the final diagnosis was made of schizophrenia.


Assuntos
Encefalopatias , Adulto , Encefalopatias/diagnóstico , Casuísmo , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Imagem de Difusão por Ressonância Magnética/efeitos adversos , Humanos , Imageamento por Ressonância Magnética/efeitos adversos , Síndrome , Adulto Jovem
17.
Neurotoxicology ; 92: 200-211, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35995272

RESUMO

Exposure to environmental contaminants is an important public health concern for the Inuit population of northern Québec, who have been exposed to mercury (Hg), polychlorinated biphenyls (PCBs) and lead (Pb). During the last 25 years, the Nunavik Child Development Study (NCDS) birth cohort has reported adverse associations between these exposures and brain function outcomes. In the current study, we aimed to determine whether contaminant exposure is associated with alterations of the corpus callosum (CC), which plays an important role in various cognitive, motor and sensory function processes. Magnetic resonance imaging (MRI) was administered to 89 NCDS participants (mean age ± SD = 18.4 ± 1.2). Diffusion-weighted imaging was assessed to characterize the microstructure of the CC white matter in 7 structurally and functionally distinct regions of interest (ROIs) using a tractography-based segmentation approach. The following metrics were computed: fiber tract density, fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD). Multiple linear regression models adjusted for sex, age, current alcohol/drug use and fish nutrients (omega-3 fatty acids and selenium) were conducted to assess the association between diffusion-weighted imaging metrics and Hg, PCB 153 and Pb concentrations obtained at birth in the cord blood and postnatally (mean values from blood samples at 11 and 18 years of age). Exposures were not associated with fiber tract density. Nor were significant associations found with cord and postnatal blood Pb concentrations for FA. However, pre- and postnatal Hg and PCB concentrations were significantly associated with higher FA of several regions of the CC, namely anterior midbody, posterior midbody, isthmus, and splenium, with the most pronounced effects observed in the splenium. FA results were mainly associated with lower RD. This study shows that exposure to Hg and PCB 153 alters the posterior microstructure of the CC, providing neuroimaging evidence of how developmental exposure to environmental chemicals can impair brain function and behavior in late adolescence.


Assuntos
Ácidos Graxos Ômega-3 , Mercúrio , Bifenilos Policlorados , Selênio , Animais , Anisotropia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão/métodos , Humanos , Chumbo , Bifenilos Policlorados/toxicidade
18.
Aging (Albany NY) ; 14(18): 7263-7281, 2022 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-35997651

RESUMO

Aging may be associated with motor decline that is attributed to deteriorating white matter microstructure of the corpus callosum (CC), among other brain-related factors. Similar to motor functioning, executive functioning (EF) typically declines during aging, with age-associated changes in EF likewise being linked to altered white matter connectivity in the CC. Given that both motor and executive functions rely on white matter connectivity via the CC, and that bimanual control is thought to rely on EF, the question arises whether EF can at least party account for the proposed link between CC-connectivity and motor control in older adults. To address this, diffusion magnetic resonance imaging data were obtained from 84 older adults. A fiber-specific approach was used to obtain fiber density (FD), fiber cross-section (FC), and a combination of both metrics in eight transcallosal white matter tracts. Motor control was assessed using a bimanual coordination task. EF was determined by a domain-general latent EF-factor extracted from multiple EF tasks, based on a comprehensive test battery. FD of transcallosal prefrontal fibers was associated with cognitive and motor performance. EF partly accounted for the relationship between FD of prefrontal transcallosal pathways and motor control. Our results underscore the multidimensional interrelations between callosal white matter connectivity (especially in prefrontal brain regions), EF across multiple domains, and motor control in the older population. They also highlight the importance of considering EF when investigating brain-motor behavior associations in older adults.


Assuntos
Substância Branca , Cognição , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Imagem de Tensor de Difusão/métodos , Função Executiva , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
19.
J Mol Neurosci ; 72(10): 2081-2093, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35976486

RESUMO

In multiple sclerosis patients, long-term inflammation makes the oligodendrocyte progenitor cells (OPCs) exhausted; therefore, a new therapy that makes them responsive to insults to participate in remyelination is highly in demand. Here, we investigated the effect of ursolic acid (UA) on myelin repair after mid-term and long-term demyelination periods induced by 6 or 12 weeks of cuprizone treatment followed by 2 weeks of recovery with or without UA. Immunohistochemistry studies and myelin genes expression assessment were used to evaluate the myelination status of mouse corpora callosa and the cellular mechanisms of myelin repair. Results showed that UA significantly promoted recovery from myelin loss after discontinuing 6 or 12 weeks of cuprizone feeding, as measured by luxol fast blue (LFB), fluoroMyelin (FM), anti-myelin basic protein (MBP) staining, and oligodendrocyte progenitor cell counts. It led to reduced inflammation and gliosis as evaluated by glial fibrillary acidic protein (GFAP), Iba1, or other marker gene transcripts. Following long-term demyelination, gliosis and TNF-α were observed as potential players in lesion pathology, which were restored by UA. An increased IL-10 may contribute to UA anti-inflammatory effect and making responsive the exhausted OPCs. UA increased the number of new oligodendrocyte lineage cells and myelination. Our findings indicated that UA can enhance myelin repair after cuprizone challenge through the prevention of gliosis and increasing the newly generated myelin.


Assuntos
Doenças Desmielinizantes , Células Precursoras de Oligodendrócitos , Animais , Camundongos , Cuprizona/toxicidade , Células Precursoras de Oligodendrócitos/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Interleucina-10/metabolismo , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/metabolismo , Gliose , Fator de Necrose Tumoral alfa/metabolismo , Bainha de Mielina/metabolismo , Oligodendroglia/metabolismo , Corpo Caloso/patologia , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
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