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1.
J Neuroimmunol ; 361: 577726, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34628135

RESUMO

We describe a case of a 28-year-old man who developed a cervical myelitis while exposed to ixekizumab (IL-17 inhibitor) for psoriatic arthritis. Spinal MRI showed a T2 hyperintense lesion at the C4-C5 level while brain MRI was unspecific. Oligoclonal bands were absent and extensive screening for autoimmunity was negative. Rechallenge with ixekizumab was positive corroborating a relation between drug exposure and the neurological event. To the best of our knowledge, this is the first case of CNS inflammatory adverse event associated with ixekizumab. We also provide a review of case reports of demyelinating disorders associated with the use of biologic drugs for the treatment of psoriasis and psoriatic arthritis.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Fatores Imunológicos/efeitos adversos , Mielite/induzido quimicamente , Adolescente , Corticosteroides/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/efeitos adversos , Artrite Psoriásica/tratamento farmacológico , Mapeamento Encefálico , Substituição de Medicamentos , Feminino , Humanos , Hipestesia/induzido quimicamente , Fatores Imunológicos/uso terapêutico , Interleucina-17/antagonistas & inibidores , Perna (Membro)/inervação , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mielite/diagnóstico por imagem , Mielite/tratamento farmacológico , Paresia/induzido quimicamente , Medula Espinal/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto Jovem
2.
J Neuroimmunol ; 359: 577686, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34392078

RESUMO

A 44-year-old previously healthy woman developed acute myelitis in close temporal relationship with ChAdOx1 nCoV-19 vaccine first-dose administration. The neurological involvement was mainly sensory with neuroimaging showing two mono-metameric lesions involving the posterior and lateral cord at dorsal level. Significant improvement was promptly recorded with high-dose intravenous steroids, with complete recovery within one month. The strict temporal relationship between vaccination and myelitis, together with the absence of clues pointing to alternative diagnoses, might suggest a conceivable role for anti-SARS-CoV-2 vaccine as immunological trigger, although a causal relationship has yet to be established and our preliminary observation suggests caution.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Mielite/diagnóstico por imagem , Doença Aguda , Adulto , Vacinas contra COVID-19/efeitos adversos , ChAdOx1 nCoV-19 , Feminino , Humanos , Mielite/induzido quimicamente
4.
J Neuroimmunol ; 354: 577533, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33684832

RESUMO

Tumor necrosis factor-alpha (TNF-α) inhibitors are increasingly used for various autoimmune diseases. Demyelinating events in the CNS, including myelitis, are reportedly associated with TNF-α inhibitor exposure. Behcet's disease rarely involves the spinal cord. A 51-year-old Japanese woman presented with back pain, leg weakness, and numbness during golimumab administration, a TNF-α inhibitor, for Behcet's disease. Magnetic resonance imaging revealed multifocal myelitis in the cervical and thoracic spinal cords. Discontinuation of golimumab and steroid therapy were effective and the symptoms have not relapsed. Although it is possible that the patient's myelitis was part of the symptoms of neuro-Behcet's disease, we believe that golimumab likely played a role in the myelitis development.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Síndrome de Behçet/tratamento farmacológico , Mielite/induzido quimicamente , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Doenças Desmielinizantes/induzido quimicamente , Feminino , Humanos , Pessoa de Meia-Idade
5.
Rinsho Shinkeigaku ; 61(2): 109-114, 2021 Feb 23.
Artigo em Japonês | MEDLINE | ID: mdl-33504748

RESUMO

SMON (subacute myelo-optico-neuropathy) is toxic neurological disease which had a profound impact on the population in Japan in 1960's. The clinical characteristics of SMON includes an ascending sensory disturbance, spasticity, and visual impairment typically following abdominal symptoms. Infection was first suspected as an underlying cause of this epidemic. The disorder was ultimately attributed to the overuse of clioquinol, based on the analysis of green urine from affected patients and confirmed by the epidemiological surveys and experimental animal studies. The factors that contributed to the prevalence of SMON which remains the worst example of drug-associated toxicity in Japan to date include the conversion of clioquinol from a purely topical agent to an orally-administered drug, dogma associated with drug safety, relatively limited regulation of drug use, an increase in the number of prescriptions due to the availability of universal insurance, as well as the complexity of the associated abdominal symptoms. Periodical examination of the patients diagnosed with SMON continues to this day. As such, it is important to have a better understanding of clioquinol-induced neurotoxicity together with the mechanisms underlying drug susceptibility; we should not permit the memory of this severe and prominent drug-associated toxicity fade from view.


Assuntos
Clioquinol/efeitos adversos , Mielite/induzido quimicamente , Mielite/diagnóstico , Neurite Óptica/induzido quimicamente , Neurite Óptica/diagnóstico , Doença Aguda , Administração Oral , Animais , Clioquinol/administração & dosagem , Clioquinol/toxicidade , Diagnóstico Diferencial , Humanos , Japão/epidemiologia , Mielite/epidemiologia , Neurite Óptica/epidemiologia , Prevalência , Fatores de Tempo
8.
Pharmacol Ther ; 199: 155-163, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30898518

RESUMO

Clioquinol, one of the first mass-produced drugs, was considered safe and efficacious for many years. It was used as an antifungal and an antiprotozoal drug until it was linked to an outbreak of subacute myelo-optic neuropathy (SMON), a debilitating disease almost exclusively confined to Japan. Today, new information regarding clioquinol targets and its mechanism of action, as well as genetic variation (SNPs) in efflux transporters in the Japanese population, provide a unique interpretation of the existing phenomena. Further understanding of clioquinol's role in the inhibition of cAMP efflux and promoting apoptosis might offer promise for the treatment of cancer and/or neurodegenerative diseases. Here, we highlight recent developments in the field and discuss possible connections, hypotheses and perspectives in clioquinol-related research.


Assuntos
Anti-Infecciosos/uso terapêutico , Clioquinol/uso terapêutico , Neoplasias/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Anti-Infecciosos/efeitos adversos , Povo Asiático/genética , Clioquinol/efeitos adversos , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Humanos , Mielite/induzido quimicamente , Mielite/genética , Doenças Neurodegenerativas/metabolismo , Neurite Óptica/induzido quimicamente , Neurite Óptica/genética , Polimorfismo de Nucleotídeo Único , Síndrome
9.
Ann Hematol ; 98(1): 205-207, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29804266
10.
Med Sci Monit ; 24: 9187-9195, 2018 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-30559337

RESUMO

BACKGROUND Recent data have demonstrated the potential immunosuppressive roles of interleukin-37 (IL-37) in several diseases, but whether it is involved in the pathogenesis of inflammatory myopathy has not been elucidated. MATERIAL AND METHODS An experimental autoimmune myositis (EAM) model was built by subcutaneous injections of pertussis toxin (PTX) and purified rabbit myosin (10mg/kg) emulsified with an equal volume of conventional complete Freund's adjuvant (CFA) in a Lewis model. Autoimmune myositis Lewis model rats were divided into 3 groups: group A rats (control group) were injected with CFA in saline weekly; group B (IL-37 group) rats were injected with saline with IL-37 and CFA in saline weekly; and group C (IL-37 + SIS3 group) rats were injected with IL-37, CFA, and SIS3. ELISA was also used to assess the expressions of TNF-α, IL-6, IL-1ß, TGF-ß1, and CK. HE staining was performed to assess pathological changes in lung and muscle tissues. RESULTS The expressions of TNF-α, IL-6, IL-1ß, TGF-ß1, and CK significantly increased in autoimmune myositis Lewis model rats. After IL-37 treatment, the expression of TNF-α, IL-6, IL-1ß, TGF-ß1, and CK was significantly reduced, as were the inflammatory responses of lung and muscle. However, SIS3 reduced the effects of IL-37 on the autoimmune myositis Lewis model rats. CONCLUSIONS These findings indicate that IL-37 protects against inflammatory response via regulating Smad3 in autoimmune myositis Lewis model rats.


Assuntos
Interleucina-1/farmacologia , Mielite/tratamento farmacológico , Mielite/imunologia , Animais , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Modelos Animais de Doenças , Feminino , Adjuvante de Freund/farmacologia , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-1/metabolismo , Interleucina-1beta/metabolismo , Mielite/induzido quimicamente , Toxina Pertussis , Engenharia de Proteínas/métodos , Ratos , Ratos Endogâmicos Lew , Fator de Crescimento Transformador beta1/biossíntese , Fator de Necrose Tumoral alfa/biossíntese
11.
Intern Med ; 57(18): 2641-2645, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29780125

RESUMO

Objective The aim of this study was to clarify the clinical conditions related to the depressive mental states in Japanese patients with subacute myelo-optico-neuropathy (SMON), caused by clioquinol intoxication more than 40 years previously. Methods The changes in the mental states with aging were investigated in 25 Japanese SMON patients (mean age: 77.2 years old, range: 53-90) using a Japanese version of the Zung Self-rating Depression Scale (J-SDS) questionnaires with supportive interviews by the clinical psychotherapist and medical checkup records. These mental and medical examinations were repeated more than twice within 2 to 11 years' interval. The J-SDS questionnaires were also examined in 25 age-matched non-SMON elderly people. Results The total J-SDS scores of most of the SMON patients decreased with age without significant changes in the mean Barthel index scores during this study period. The mean J-SDS scores at the first and latest studies were significantly higher than in the age-matched healthy elderly people. The total J-SDS scores of the latest study were significantly correlated with the degree of physical disability, such as the inverse total Barthel index scores, severity of SMON or gait disturbance, but not with the age. Conclusion The total J-SDS scores of most of the SMON patients tended to decrease with age. Repeating mental supportive interviews and medical examinations by experts helped to improve the depressive mental state and revealed close relationship between the mental state and the physical disabilities of the SMON patients.


Assuntos
Transtorno Depressivo/etiologia , Mielite/psicologia , Doenças do Nervo Óptico/psicologia , Doenças do Sistema Nervoso Periférico/psicologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Clioquinol/efeitos adversos , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mielite/induzido quimicamente , Doenças do Nervo Óptico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Inquéritos e Questionários
12.
Neurosci Bull ; 34(1): 13-21, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28265898

RESUMO

Mounting evidence supports an important role of chemokines, produced by spinal cord astrocytes, in promoting central sensitization and chronic pain. In particular, CCL2 (C-C motif chemokine ligand 2) has been shown to enhance N-methyl-D-aspartate (NMDA)-induced currents in spinal outer lamina II (IIo) neurons. However, the exact molecular, synaptic, and cellular mechanisms by which CCL2 modulates central sensitization are still unclear. We found that spinal injection of the CCR2 antagonist RS504393 attenuated CCL2- and inflammation-induced hyperalgesia. Single-cell RT-PCR revealed CCR2 expression in excitatory vesicular glutamate transporter subtype 2-positive (VGLUT2+) neurons. CCL2 increased NMDA-induced currents in CCR2+/VGLUT2+ neurons in lamina IIo; it also enhanced the synaptic NMDA currents evoked by dorsal root stimulation; and furthermore, it increased the total and synaptic NMDA currents in somatostatin-expressing excitatory neurons. Finally, intrathecal RS504393 reversed the long-term potentiation evoked in the spinal cord by C-fiber stimulation. Our findings suggest that CCL2 directly modulates synaptic plasticity in CCR2-expressing excitatory neurons in spinal lamina IIo, and this underlies the generation of central sensitization in pathological pain.


Assuntos
Quimiocina CCL2/metabolismo , Hiperalgesia/metabolismo , Potenciação de Longa Duração/fisiologia , Mielite/metabolismo , Animais , Benzoxazinas/farmacologia , Benzoxazinas/uso terapêutico , Quimiocina CCL2/antagonistas & inibidores , Quimiocina CCL2/genética , Quimiocina CCL2/farmacologia , Fármacos Atuantes sobre Aminoácidos Excitatórios/farmacologia , Agonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Adjuvante de Freund/toxicidade , Hiperalgesia/induzido quimicamente , Hiperalgesia/prevenção & controle , Potenciação de Longa Duração/efeitos dos fármacos , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mielite/induzido quimicamente , Mielite/tratamento farmacológico , Neurônios/efeitos dos fármacos , Manejo da Dor , Somatostatina/genética , Somatostatina/metabolismo , Medula Espinal/citologia , Compostos de Espiro/farmacologia , Compostos de Espiro/uso terapêutico , Proteína Vesicular 2 de Transporte de Glutamato/genética , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/genética , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismo
13.
J Comp Neurol ; 525(16): 3414-3428, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28649695

RESUMO

In both acute and chronic pain conditions, women tend to be more sensitive than men. This sex difference may be regulated by estrogens, such as estradiol, that are synthesized in the spinal cord and brainstem and act locally to influence pain processing. To identify a potential cellular source of local estrogen, here we examined the expression of aromatase, the enzyme that catalyzes the conversion of testosterone to estradiol. Our studies focused on primary afferent neurons and on their central targets in the spinal cord and medulla as well as in the nucleus of the solitary tract, the target of nodose ganglion-derived visceral afferents. Immunohistochemical staining in an aromatase reporter mouse revealed that many neurons in laminae I and V of the spinal cord dorsal horn and caudal spinal trigeminal nucleus and in the nucleus of the solitary tract express aromatase. The great majority of these cells also express inhibitory interneuron markers. We did not find sex differences in aromatase expression and neither the pattern nor the number of neurons changed in a sciatic nerve transection model of neuropathic pain or in the Complete Freund's adjuvant model of inflammatory pain. A few aromatase neurons express Fos after cheek injection of capsaicin, formalin, or chloroquine. In total, given their location, these aromatase neurons are poised to engage nociceptive circuits, whether it is through local estrogen synthesis or inhibitory neurotransmitter release.


Assuntos
Aromatase/genética , Aromatase/metabolismo , Regulação da Expressão Gênica , Bulbo/citologia , Neurônios/enzimologia , Ciática/enzimologia , Corno Dorsal da Medula Espinal/citologia , Vias Aferentes/fisiologia , Animais , Modelos Animais de Doenças , Adjuvante de Freund/toxicidade , Camundongos , Camundongos Transgênicos , Mielite/induzido quimicamente , Mielite/enzimologia , Proteínas do Tecido Nervoso/metabolismo , Fosfopiruvato Hidratase/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Estilbamidinas/metabolismo , Canais de Cátion TRPV/metabolismo
14.
Mult Scler ; 23(9): 1297-1300, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28391740

RESUMO

We report two cases of neuromyelitis optica spectrum disorder (NMOSD) who were misdiagnosed as multiple sclerosis (MS) and developed catastrophic relapses following initiation of dimethyl fumarate. Both patients developed a severe myelitis extending from the cervical cord to the medulla with significant cord swelling, resulting in complete quadriplegia and respiratory difficulties, in addition to severe bilateral visual loss in one patient. It is of note that both catastrophic relapses occurred 2 and 3 months following initiation of dimethyl fumarate.


Assuntos
Cegueira/induzido quimicamente , Erros de Diagnóstico , Fumarato de Dimetilo/efeitos adversos , Imunossupressores/efeitos adversos , Mielite/induzido quimicamente , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/tratamento farmacológico , Quadriplegia/induzido quimicamente , Adulto , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/tratamento farmacológico , Recidiva
15.
Bioorg Med Chem ; 25(9): 2643-2656, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28341402

RESUMO

Protein arginine deiminases (PAD) are implicated in a variety of inflammatory and neurodegenerative diseases including multiple sclerosis (MS). Following the discovery of an in silico hit containing hydantoin and a piperidine moiety, we hypothesized that a 2-carbon linker on the hydantoin would be necessary for a 5-membered heterocycle for optimal PAD inhibitory activity. We designed thirteen compounds as potential inhibitors of PAD2 and PAD4 enzymes-two important PAD enzymes implicated in MS. Two compounds, one with an imidazole moiety (22) and the other with a tetrazole moiety (24) showed good inhibition of PAD isozymes in vitro and in the EAE mouse model of MS in vivo. Further experiments suggested that compound 22, a non-covalent inhibitor of PAD2 and PAD4, exhibits dose-dependent efficacy in the EAE mouse model and in the cuprizone-mediated demyelination model.


Assuntos
Inibidores Enzimáticos/uso terapêutico , Hidantoínas/uso terapêutico , Hidrolases/antagonistas & inibidores , Imidazóis/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Tetrazóis/uso terapêutico , Animais , Encéfalo/patologia , Domínio Catalítico , Cuprizona , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/tratamento farmacológico , Encefalite/induzido quimicamente , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacocinética , Feminino , Meia-Vida , Humanos , Hidantoínas/administração & dosagem , Hidantoínas/química , Hidantoínas/farmacocinética , Imidazóis/administração & dosagem , Imidazóis/química , Imidazóis/farmacocinética , Isoenzimas/antagonistas & inibidores , Masculino , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Mielite/induzido quimicamente , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacocinética , Fármacos Neuroprotetores/uso terapêutico , Medula Espinal/patologia , Tetrazóis/administração & dosagem , Tetrazóis/química , Tetrazóis/farmacocinética
16.
Exp Neurol ; 291: 62-73, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28179153

RESUMO

Neuropeptide FF (NPFF) is recognized as an opioid modulating peptide that regulates morphine-induced analgesia. The aim of this study was to delineate the role of NPFFR2 in pain transmission. We found the expression levels of NPFF and NPFFR2 were increased in the lumbar dorsal horn of animals with CFA- and carrageenan-induced inflammation and both NPFFR2 over-expressing transgenic (NPFFR2-Tg) and NPFFR2 agonist-treated mice displayed hyperalgesia. BOLD signals from functional MRI showed that NPFFR2-Tg mice exhibited increased activation of pain-related brain regions after painful stimulation when compared to WT mice. Inflammatory mediators within the spinal cord, calcitonin gene-related peptide (CGRP) and substance P (SP), were up-regulated in NPFFR2-Tg and chronic NPFFR2 agonist-treated mice. In DRG cultures, treatment with an NPFFR2 agonist induced the expression and release of CGRP, an action which was blocked by NPFFR2 siRNA. Furthermore, treatment with a CGRP antagonist ameliorated the pain hyperalgesia in NPFFR2-Tg mice, returning the pain threshold to a control level. However, treatment with a SP antagonist reduced the pain responses in both WT and NPFFR2-Tg mice and did not suppress pain hypersensitivity in NPFFR2-Tg mice. Together, these results demonstrate that NPFFR2 activation modulates pain transmission by up-regulating the pain mediator CGRP, leading to hyperalgesia.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Regulação da Expressão Gênica/genética , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Mielite/complicações , Receptores Acoplados a Proteínas G/metabolismo , Animais , Carragenina/toxicidade , Células Cultivadas , Córtex Cerebral/diagnóstico por imagem , Modelos Animais de Doenças , Membro Anterior/inervação , Adjuvante de Freund/toxicidade , Gânglios Espinais/citologia , Hidrazinas/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mielite/induzido quimicamente , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurotransmissores/metabolismo , Oxigênio/sangue , Medição da Dor , Receptores Acoplados a Proteínas G/genética , Fatores de Tempo
17.
Hum Vaccin Immunother ; 13(3): 572-573, 2017 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-27668461

RESUMO

We report the case of a 57 year-old woman who developed transverse myelitis and acute HSV-2 reactivation following influenza vaccination. Over the next 5 years, she experienced a fluctuating course of improvement and regression for both myelitis and herpes.


Assuntos
Herpes Genital/induzido quimicamente , Herpes Genital/patologia , Vacinas contra Influenza/efeitos adversos , Mielite/induzido quimicamente , Mielite/patologia , Vacinação/efeitos adversos , Feminino , Humanos , Vacinas contra Influenza/administração & dosagem , Pessoa de Meia-Idade
18.
Rinsho Shinkeigaku ; 56(4): 265-9, 2016 04 28.
Artigo em Japonês | MEDLINE | ID: mdl-27010093

RESUMO

A previously healthy 16-year-old girl developed sudden eye pain and visual loss in her right eye. On day 7 from onset her right visual acuity had decreased to light perception, and she underwent 5 courses of intravenous methylprednisolone therapy (IVMP, 1 g/day for 3 consecutive days per week). Her eye pain and her visual acuity had improved immediately. Eleven months later, follow-up MRI revealed three T2-hyperintense plaques involving subcortical white matter in the left occipital lobe, right frontal lobe, right thalamus, and thoracic spinal cord. We suspected the diagnosis as multiple sclerosis and treated with fingolimod. She developed recurrent optic neuritis (ON) on day 19 from fingolimod therapy, and we stopped fingolimod. For two years from onset she was admitted five times due to recurrences of ON and appearance of white matter lesion and myelitis. At 22 months, anti-myelin oligodendrocyte glycoprotein (MOG) antibodies revealed to be positive in her sera from the onset to the present. Our case report suggests that fingolimod might not be effective in anti-MOG antibody-related disorders together with anti-aquaporin-4 (AQP4) antibody-positive group.


Assuntos
Autoanticorpos , Cloridrato de Fingolimode/efeitos adversos , Glicoproteína Mielina-Oligodendrócito/imunologia , Neurite Óptica/induzido quimicamente , Adolescente , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Infusões Intravenosas , Imageamento por Ressonância Magnética , Metilprednisolona/administração & dosagem , Mielite/induzido quimicamente , Neurite Óptica/tratamento farmacológico , Recidiva , Medula Espinal/diagnóstico por imagem
19.
J Neuroimmunol ; 286: 59-70, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26298325

RESUMO

Neuropathic pain is a debilitating condition in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Specific myelin basic protein (MBP) peptides are encephalitogenic, and myelin-derived altered peptide ligands (APLs) are capable of preventing and ameliorating EAE. We investigated the effects of active immunisation with a weakly encephalitogenic epitope of MBP (MBP87-99) and its mutant APL (Cyclo-87-99[A(91),A(96)]MBP87-99) on pain hypersensitivity and neuroinflammation in Lewis rats. MBP-treated rats exhibited significant mechanical and thermal pain hypersensitivity associated with infiltration of T cells, MHC class II expression and microglia activation in the spinal cord, without developing clinical signs of paralysis. Co-immunisation with APL significantly decreased pain hypersensitivity and neuroinflammation emphasising the important role of neuroimmune crosstalk in neuropathic pain.


Assuntos
Hipersensibilidade/etiologia , Proteína Básica da Mielina/toxicidade , Mielite , Dor/fisiopatologia , Fragmentos de Peptídeos/toxicidade , Animais , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Adjuvante de Freund/toxicidade , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Hipersensibilidade/metabolismo , Ligantes , Ativação Linfocitária/imunologia , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Proteína Básica da Mielina/imunologia , Mielite/induzido quimicamente , Mielite/complicações , Mielite/imunologia , Dor/induzido quimicamente , Medição da Dor , Limiar da Dor , Fragmentos de Peptídeos/imunologia , Ratos , Ratos Endogâmicos Lew , Medula Espinal/metabolismo , Medula Espinal/patologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Fatores de Tempo , Vacinação/efeitos adversos
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