Encefalomielite aguda disseminada com provável etiologia de Bartonella henselae / Acute disseminated encephalomyelitis with probable Bartonella henselae etiology

RESUMO A encefalomielite aguda disseminada é uma doença rara, aguda, inflamatória e desmielinizante do sistema nervoso central, presumivelmente associada, em mais de três quartos dos casos, a infecções (virais, bacterianas ou inespecíficas) e imunizações ou sem qualquer antecedente indentificável. Habitualmente, apresenta um curso monofásico com início de sintomas inespecíficos na fase prodrómica, podendo evoluir com alterações neurológicas multifocais e até à perda total da acuidade visual. Descrevemos o caso de um menino de 9 anos com quadro inicial de edema de papila causado por encefalomielite aguda disseminada devido a Bartonella henselae. Apesar da gravidade da doença, o diagnóstico e o tratamento precoce proporcionaram bons desfechos.

ABSTRACT Acute disseminated encephalomyelitis is a rare, acute, inflammatory, and demyelinating disease of the central nervous system. Presumably associated in more than three quarters of cases by infections (viral, bacterial, or nonspecific) and immunizations or without any identifiable antecedent. It usually presents a monophasic course with onset of nonspecific symptoms in the prodromal phase and may evolve with multifocal neurological changes and even visual acuity loss. We describe a case of a 9-year-old boy with an initial picture of papillary edema caused by acute disseminated encephalomyelitis due to Bartonella henselae. Despite the severity of the disease, early diagnosis and treatment provided good outcomes.

Clinical spectrum of myelin oligodendrocyte glycoprotein antibody-associated disease in Brazil: a single-center experience / Espectro clínico de doença associada com anticorpos contra a glicoproteína de oligodendrócito de mielina no Brasil: uma experiencia de centro único

Abstract Background Anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibody-associated disease (MOGAD) is an immune-mediated neurological disorder with a broad spectrum of clinical presentation that is often difficult to distinguish from other demyelinating diseases, such as multiple sclerosis and neuromyelitis optica spectrum disorder. Objective To describe the clinical and paraclinical characteristics of MOGAD in a Brazilian tertiary center. Methods We retrospectively reviewed the records of adult and pediatric patients who tested positive for anti-MOG antibodies and presented with clinical and radiological diseases compatible with MOGAD. Results Forty-one patients (10 children) were included: 56% female, 58% Caucasian, mean age at onset 31 years (range 6-64), with a mean disease duration of 59.6 months (range 1-264 months). The most frequent onset presentation was optic neuritis (68%), acute disseminated encephalomyelitis (ADEM, 12%), and myelitis (10%). A monophasic disease course was observed in 49%. EDSS median was 2.1 at the last visit. Most patients (83%) were under continuous immunosuppressive treatment. Azathioprine was the first-line treatment in 59%. In all ADEM cases, conus, and root involvement was radiologically observed on MRI. Conclusion Brazilian MOGAD patients presented with a similar spectrum of previously reported MOGAD phenotypes. Conus and spinal root involvement seems to be frequently present in MOGAD-ADEM and could serve as radiologic characteristics of this clinical entity.

Resumo Antecedentes A doença associada ao anticorpo da glicoproteína da mielina de oligodendrócitos (anti-MOG; MOGAD) é uma doença neurológica imunomediada com um amplo espectro de apresentações clínicas que muitas vezes é difícil de distinguir de outras doenças desmielinizantes, como a esclerose múltipla e o distúrbio do espectro da neuromielite óptica. Objetivo Descrever as características clínicas e paraclínicas da MOGAD em um centro terciário brasileiro. Métodos Revisamos retrospectivamente os prontuários dos pacientes adultos e pediátricos que testaram positivos para anticorpos anti-MOG e apresentaram um quadro clínico e radiológico compatível com MOGAD. Resultados Quarenta e um pacientes (10 crianças) foram incluídos: 56% do sexo feminino, 58% caucasianos, idade média de início da doença foi 31 anos (intervalo de 6-64), com duração média da doença de 59,6 meses (intervalo de 1-264 meses). A apresentação inicial mais frequente foi neurite óptica (68%), seguida pela encefalomielite disseminada aguda (ADEM, 12%) e mielite (10%). Um curso monofásico da doença foi observado em 49%. EDSS foi de 2,1 na última visita. A maioria dos pacientes (83%) estava sob tratamento imunossupressor contínuo. Azatioprina foi o tratamento de primeira linha em 59%. Em todos os casos de ADEM, o envolvimento do cone medular e das raízes espinhais foi observado radiologicamente na ressonância magnética. Conclusão Os pacientes brasileiros com MOGAD apresentam um espectro clínico e radiológico semelhante aos fenótipos de MOGAD relatados anteriormente. O envolvimento do cone e das raízes espinhais parece estar frequentemente presente no MOGAD-ADEM e poderia servir como característica radiológica nesta entidade.

Myelin oligodendrocyte glycoprotein antibody-associated optic neuritis: an update / Neurite óptica associada com anticorpo contra a glicoproteína oligondendrócita da mielina: uma breve atualização

ABSTRACT Myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated optic neuritis has been established as a new entity of immune-mediated optic neuropathy. Patients usually present with recurrent optic neuritis, often bilaterally with initially severe vision loss and optic disc edema. However, in contrast to aquaporin 4-IgG-seropositive neuromyelitis optica spectrum disorder, visual recovery tends to be more favorable, with good response to steroid treatment. Another important differential diagnosis of myelin oligodendrocyte glycoprotein-IgG--associated optic neuritis is multiple sclerosis. Close monitoring for signs of relapse and long-term immunosuppression may be considered to maintain optimal visual function. The diagnosis can be made on the basis of the presence of a specific, usually serological, antibody against myelin oligodendrocyte glycoprotein (IgG; cell-based assay), and a demyelinating event (optic neuritis, myelitis, brainstem syndrome, or cortical lesions with seizures). The clinical spectrum of this newly recognized inflammatory demyelinating disease is expanding rapidly. We briefly review the epidemiological characteristics, clinical manifestations, diagnostic considerations, and treatment options of myelin oligodendrocyte glycoprotein-IgG-associated optic neuritis.

RESUMO A neurite óptica associada à glicoproteína de oligodendrócito de mielina-IgG foi estabelecida como uma nova entidade de neuropatia óptica imunomediada. Tipicamente os pacientes apresentam neurite óptica recorrente, muitas vezes bilateral, com perda de visão frequentemente severa e alta prevalência de edema do disco óptico na fase aguda. No entanto, em contraste com neuromyelitis optica spectrum disorder associada com presença de anticorpo contra aquaporina 4, a recuperação visual tende a ser mais favorável e responde bem ao tratamento com corticoide em altas doses. A esclerose múltipla representa outro importante diagnóstico diferencial de glicoproteína de oligodendrócito de mielina-IgG. O diagnóstico pode ser feito com base na presença de um anticorpo específico, geralmente sorológico contra glicoproteína de oligodendrócito de mielina (IgG, ensaio baseado em células), e presença de evento desmielinizante (neurite óptica, mielite, síndrome do tronco cerebral, lesões corticais com convulsões). O espectro clínico desta doença desmielinizante inflamatória recém-reconhecida está se expandindo rapidamente. Faremos uma breve revisão das características epidemiológicas, manifestações clínicas, considerações diagnósticas e opções de tratamento da neurite óptica associada à glicoproteína de oligodendrócito de mielina-IgG.

Neuromyelitis optica spectrum disorders: a review with a focus on children and adolescents / Espectro da neuromielite óptica: uma revisão com ênfase em crianças e adolescentes

Abstract Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe inflammatory disorder of the central nervous system (CNS). It is strongly associated with anti-aquaporin 4 antibodies (AQP4-IgG), and it mainly affects young women from non-white ethnicities. However, ~ 5 to 10% of all cases have onset during childhood. Children and adolescents share the same clinical, radiologic, and laboratory presentation as adults. Thus, the same NMOSD diagnostic criteria are also applied to pediatric-onset patients, but data on NMOSD in this population is still scarce. In seronegative pediatric patients, there is a high frequency of the antibody against myelin oligodendrocyte glycoprotein (MOG-IgG) indicating another disease group, but the clinical distinction between these two diseases may be challenging. Three drugs (eculizumab, satralizumab, and inebilizumab) have been recently approved for the treatment of adult patients with AQP4-IgG-positive NMOSD. Only satralizumab has recruited adolescents in one of the two pivotal clinical trials. Additional clinical trials in pediatric NMOSD are urgently required to evaluate the safety and efficacy of these drugs in this population.

Resumo O espectro da neuromielite óptica (ENMO) é uma rara e grave doença inflamatória do sistema nervoso central (SNC), fortemente associada ao anticorpo anti-aquaporina 4 (AQP4-IgG) e que afeta preferencialmente mulheres jovens de etnias não-caucasianas. No entanto, aproximadamente de 5 a 10% de todos os casos se iniciam na infância. Crianças e adolescentes compartilham as mesmas características clínicas, radiológicas e laboratoriais dos adultos. Além disso, o mesmo critério diagnóstico de ENMO é aplicado para pacientes com início na infância. No entanto, dados da população pediátrica são escassos. Em pacientes pediátricos soronegativos, existe uma alta frequência de positividade ao anticorpo contra a glicoproteína na mielina do oligodendrócito (MOG-IgG), indicando outra patologia; porém, a distinção clínica entre as duas doenças é desafiadora. Três medicações (eculizumabe, inebilizumabe e satralizumabe) foram recentemente aprovadas para pacientes adultos com AQP4-IgG. Apenas um dos ensaios pivotais do satralizumabe recrutou adolescentes. Novos ensaios clínicos em pacientes pediátricos com ENMO são necessários para avaliar a segurança e eficácia destas drogas nesta população.

Autoimmune optic neuropathy as the differential diagnosis of neuromyelitis optica spectrum disorders / Neuropatia óptica autoimune como diagnóstico diferencial do espectro da neuromielite óptica

ABSTRACT Optic neuritis is an important cause of decreased vision due to inflammation of the optic nerve. In view of its complex etiology, a thorough clinical evaluation is essential. Autoimmune optic neuropathy, a rare form of optic neuritis, is associated with progressive, painless, and severe visual loss. Severity depends on the inflammatory and ischemic components of the condition. Autoimmune optic neuropathy is ideally diagnosed with autoimmune disease markers (usually elevated levels of antinuclear antibodies). The treatment is immunosuppression with high doses of corticosteroids. Corticoid dependence is a characteristic of autoimmune optic neuropathy. In this report, we describe a patient with autoimmune optic neuropathy and discuss the importance of laboratory parameters and magnetic resonance imaging findings in the diagnosis of the disease.

RESUMO A Neurite óptica é uma importante causa de diminuição da visão devido à inflamação do nervo óptico. Por apresentar diversas etiologias faz-se necessário ampla investigação. A neuropatia óptica autoimune corresponde a uma doença rara que se manifesta com perda visual aguda, indolor e grave. A gravidade está associada a sua fisiopatogenia com componentes inflamatório e isquêmico. A positividade para marcadores de doenças autoimunes, mais comumente a elevação da titulação de anticorpos antinucleares, são fatores determinantes para o diagnóstico da neuropatia óptica autoimune. O tratamento é feito através de imunossupressão, com necessidade de altas doses de corticoide. Neste relato iremos descrever um paciente com neuropatia óptica autoimune. Discutiremos sobre a importância dos parâmetros laboratoriais e os achados de imagem da ressonância magnética para o diagnóstico.

Clinical Study of Neurodegenerative Treatment on Glaucoma by Insulin Intravitreal Injection

Purpose: Our trail was to study insulin intravitreal injection’s (IIV) efficacity and safety to treat glaucoma neurodegeneration.Methods: Eleven subjects (11eyes) were recruited;10 patients treated in a double masked randomized sham controlled including 5 patients received one IIV injection 3UI and 5 patients received one injection of balanced salt solution(BSS) 3UI. A follow up during 168days was realized using Optical Coherence Tomography(OCT) and visual field(VF).The eleventh patient received two IIV injection without masking the injection content within one month between each injection and followed up for 877days.All the patients have a correct ocular pressure and no ocular treatment was stopped.Results: The 5 patients who received IIV revealed a swift improvement of decibel (DB), and remains stable during the first month. The average improvement was 6.62DB during 168days.The 5 patients treated with one BSS injection showed no significant improvement regaining 1. 45DB.The last patient who received two injections showed increase from 7.54DB to 17.22DB with a functional amelioration of 9. 68DB.The OCT examination showed a structural improvement during the first month, then returned to the initial value. No complication was observed during and after the treatment.Conclusion: Insulin shows not only efficacity and safety but more than that, the visual field(VF) of the patients became stable and show no deterioration in all the follow up, which confirmed that insulin act to improve the function rather than structure. it means insulin reconnect the stoma and improve the neurite outgrowth This treatment will change the evolution of this pathology and protect the glaucomatous patients against blindness.

Qualidade de vida e condição clínica de indivíduos com hanseníase / Calidad de vida y estado clínico de las personas con lepra / Quality of life and clinical condition of individuals with leprosy

RESUMO Objetivo: analisar a qualidade de vida dos indivíduos com hanseníase em tratamento na rede de Atenção Básica e Especializada de saúde e realizar uma comparação de acordo com as condições clínicas dos pacientes. Método: estudo transversal, de caráter analítico, realizado na Atenção Básica e Especializada de saúde em João Pessoa, Paraíba, Brasil. A amostra foi coletada entre os meses de janeiro e março de 2017, sendo composta por 96 indivíduos em tratamento para doença, na faixa etária acima de 18 anos de idade. As informações foram coletadas a partir de um formulário semiestruturado contendo variáveis sociodemográficas e clínicas e o instrumento validado World Health Organization Quality of life Assessment bref. Os dados foram analisados com base nas técnicas de análise descritiva, tendo sido aplicados os testes de Normalidade (Kolmogorov-Smirnov), Levene, t paramétrico e ANOVA (teste post hoc tukey). Resultados: o escore geral para qualidade de vida entre os 96 participantes da pesquisa se manteve intermediário ( x ¯=57,04) sendo o domínio físico mais afetado negativamente ( x ¯=54,09). As questões contidas nos domínios "Recreação e lazer" ( x ¯=31,41), "Sentimentos negativos" ( x ¯=35,16), "Recursos Financeiros" ( x ¯=35,68) e "Dor e desconforto" ( x ¯=35,68) apresentaram menor escore médio. Pacientes com condições clínicas "osteoporose e artrose" (p = 0,011) e "neurite atual" (p = 0,001) obtiveram qualidade de vida em nível intermediário. Conclusão: evidenciou-se que pessoas com hanseníase têm qualidade de vida em nível intermediário, principalmente quando associada à neurite e a comorbidades, o que ressalva a necessidade de acompanhamento contínuo dos participantes da pesquisa.

RESUMEN Objetivo: analizar la calidad de vida de los individuos con lepra en tratamiento en la red de Atención Primaria y Especializada y su comparación según las condiciones clínicas de los pacientes. Método: estudio transversal, de carácter analítico, realizado en la Asistencia Sanitaria Básica y Especializada de João Pessoa, Paraíba, Brasil. La muestra se recogió entre enero y marzo de 2017, formada por 96 individuos en tratamiento por la enfermedad, mayores de 18 años. La información se recogió mediante un formulario semiestructurado que contenía variables sociodemográficas y clínicas, y el instrumento validado World Health Organization Quality of life Assessment bref. Los datos se analizaron a partir de las técnicas de análisis descriptivo y se aplicaron las pruebas de normalidad (Kolmogorov-Smirnov), Levene, t paramétrica y ANOVA (prueba de tukey post hoc). Resultados: la puntuación global de la calidad de vida entre los 96 participantes en la investigación se mantuvo en un nivel intermedio ( x ¯=57,04) y el dominio físico fue el más afectado negativamente ( x ¯=54,09). En cuanto a las preguntas contenidas en los dominios, "Recreación y ocio" ( x ¯=31,41), "Sentimientos negativos" ( x ¯=35,16), "Recursos económicos" ( x ¯=35,68) y "Dolor y malestar" ( x ¯=35,68) mostraron puntuaciones medias más bajas. Los pacientes con condiciones clínicas de "osteoporosis y artrosis" (p = 0,011) y "neuritis actual" (p = 0,001) obtuvieron una calidad de vida de nivel intermedio. Conclusión: se evidenció que las personas con lepra tienen un nivel intermedio de calidad de vida, especialmente cuando se asocia a neuritis y comorbilidades, lo que pone de manifiesto la necesidad de un seguimiento continuo de los participantes en la investigación.

ABSTRACT Objective: to analyze the quality of life of individuals with leprosy undergoing treatment in the Basic and Specialized Health Care network and to perform a comparison according to the clinical conditions of the patients. Method: cross-sectional, analytical study carried out in Primary and Specialized Health Care in João Pessoa, Paraíba, Brazil. The sample was collected between January and March 2017, consisting of 96 individuals undergoing treatment for the disease, aged over 18 years. Information was collected using a semi-structured form containing sociodemographic and clinical variables and the validated instrument World Health Organization Quality of life Assessment bref. Data were analyzed based on descriptive analysis techniques, using the Normality (Kolmogorov-Smirnov), Levene, parametric t and ANOVA (post hoc Tukey test) tests. Results: the overall score for quality of life among the 96 research subjects remained intermediate ( x ¯=57.04), with the Physical domain being most negatively affected ( x ¯=54.09). The questions contained in the domains "recreation and leisure" ( x ¯=31.41), "negative feelings" ( x ¯=35.16), "Financial Resources" ( x ¯=35.68) and "Pain and distress" ( x ¯= 35.68) had a lower mean score. Patients with clinical conditions "osteoporosis and arthrosis" (p = 0.011) and "current neuritis" (p = 0.001) had an intermediate quality of life. Conclusion: it was shown that people with leprosy have an intermediate quality of life, especially when associated with neuritis and comorbidities, which highlights the need for continuous monitoring of research subjects.

Diagnostic evolution of vestibular neuritis after long-term monitoring / Evolução diagnóstica da neurite vestibular após monitoração de longo prazo

Abstract Introduction The diagnosis of vestibular neuritis is based on clinical and laboratory findings after exclusion of other disease. There are occasional discrepancies between clinical impressions and laboratory results. It could be the first vertigo episode caused by other recurrent vestibular disease, other than vestibular neuritis. Objective This study aimed to analyze the clinical features and identify the diagnostic evolution of patients with clinically suspected vestibular neuritis. Methods A total of 201 patients clinically diagnosed with vestibular neuritis were included in this study. Clinical data on the symptoms and signs of vertigo along with the results of vestibular function test were analyzed retrospectively. Patients were categorized in terms of the results of caloric testing (CP - canal paresis) group; canal paresis ≥25%; (MCP -minimal canal paresis) group; canal paresis <25%). Clinical features were compared between the two groups and the final diagnosis was reviewed after long-term follow up of both groups. Results Out of 201 patients, 57 showed minimal canal paresis (CP < 25%) and 144 showed definite canal paresis (CP ≥ 25%). A total of 48 patients (23.8%) experienced another vertigo episode and were re-diagnosed. Recurring vestibular symptoms were seen more frequently in patients with minimal canal paresis (p = 0.027). Repeated symptoms were observed on the same affected side more frequently in the CP group. The proportion of final diagnosis were not different between two groups. Conclusions Patients with minimal CP are more likely to have recurrent vertigo than patients with definite CP. There was no significant difference in the distribution of the final diagnoses between two groups when the vertigo recurs.

Resumo Introdução O diagnóstico de neurite vestibular é baseado em achados clínicos e laboratoriais após exclusão de outra doença. Existem discrepâncias ocasionais entre a impressão clínica e os resultados laboratoriais. Pode ser o primeiro episódio de vertigem causado por outra doença vestibular recorrente, além da neurite vestibular. Objetivo Analisar as características clínicas e identificar a evolução diagnóstica de pacientes com suspeita clínica de neurite vestibular. Método Foram incluídos neste estudo 201 pacientes com diagnóstico clínico de neurite vestibular. Os dados clínicos sobre os sintomas e sinais de vertigem e os resultados dos testes de função vestibular foram analisados retrospectivamente. Os pacientes foram categorizados de acordo com os resultados das provas calóricos (Grupo PC: paresia do canal ≥ 25%; Grupo PMC: paresia mínima do canal < 25%). As características clínicas foram comparadas entre os dois grupos e o diagnóstico final foi revisado após o acompanhamento de longo prazo de ambos os grupos. Resultados De 201 pacientes, 57 apresentaram paresia mínima do canal (PC < 25%) e 144 apresentaram paresia definitiva do canal (PC ≥ 25%). Quarenta e oito pacientes (23,8%) apresentaram outro tipo de vertigem e foram diagnosticados novamente. Sintomas vestibulares recorrentes foram observados com mais frequência nos pacientes com paresia mínima do canal (p = 0,027). Sintomas recorrentes no mesmo lado afetado foram observados com mais frequência no Grupo PC. A proporção de diagnóstico final não foi diferente entre os dois grupos. Conclusão Os pacientes com paresia mínima do canal foram mais propensos a apresentar vertigem recorrente que os pacientes com paresia do canal definitiva. Não houve diferença significante na distribuição dos diagnósticos finais entre os dois grupos quando houve recorrência da vertigem.

The effect and mechanism of astragaloside Ⅳ on lysophosphatidic acid-induced neurite retraction of N1E-115 cells / 国际中医中药杂志

Objective:To observe the effect of astragaloside Ⅳ on lysophosphatidic acid(LPA)- induced neurite retraction of N1E-115 cells and its potential mechanism.Methods:N1E-115 cells were divided into blank group, model group, the low, medium and high dose groups of astragaloside Ⅳ. The blank group and model group was not intervened by astragaloside; while the low, medium and high dose groups were treated with 20,40 and 80 μg/ml astragaloside Ⅳ for 24 h. Each group was cultured with serum-free medium for 12 h. The model group and astragaloside Ⅳ groups were intervened by 40 μmol/L LPA for 10 min. Each group was observed and photographed with the inverted microscope, and the number of neurites in N1E-115 cells was counted by Image J software. The fluorescence expression of recombinant ras homolog gene family member A (RhoA), rho associated coiledcoil protein kinase 2 (ROCK2), phospho-rho associated coiledcoil protein kinase 2 (p-ROCK2) and phospho-myosin light chain 2 (p-MLC2) proteins was detected by immunohistochemistry. Real-time fluorescent quantitative polymerase chain reaction was used to detect the mRNA expression levels of RhoA and ROCK2 ; the protein expression levels of RhoA, ROCK2, p-MLC2 and myosin light chain 2 (MLC2) were detected by Western blotting.Results:Compared with 20 μg/ml astragaloside Ⅳ group, the inhibition rate of neurite retraction in 40 and 80 μg/ml astragalosideⅣ groups increased ( P<0.05). Compared with model group, the average fluorescence intensity of RhoA, p-ROCK2, p-MLC2 in 20, 40, 80 μg/ml astragaloside Ⅳ groups and the ROCK2 average fluorescence intensity in 40 μg/ml astragaloside Ⅳ group were decreased ( P<0.05, P<0.01); the expression of RhoA mRNA (0.89±0.09, 0.41±0.01, 0.09±0.03 vs. 1.50±0.01) and ROCK2 mRNA (0.89±0.09, 0.14±0.01, 0.20±0.01 vs. 1.62±0.17) decreased in 20, 40, 80 μg/ml astragaloside Ⅳ groups ( P<0.05, P<0.01); the ROCK2 protein (0.75±0.06, 0.57±0.02, 0.66±0.01 vs. 1.08±0.02), p-MLC2 protein (1.72±0.03, 1.40±0.04, 1.29±0.03 vs. 2.19±0.11), MLC2 protein (1.13±0.02, 0.68±0.03, 0.75±0.03 vs. 1.60±0.03) in 20, 40, 80 μg/ml astragaloside Ⅳ groups and the RhoA protein (0.35±0.01, 0.40±0.03 vs. 0.57±0.08) in 20, 40 μg/ml astragaloside Ⅳ groups were decreased ( P<0.05, P<0.01). Conclusion:Astragaloside Ⅳ can prevent LPA-induced neurite retraction and promote damaged nerve regeneration. The mechanism may down-regulae the protein expression levels of RhoA, ROCK2, p-ROCK2, p-MLC2 and MLC2 in RhoA-ROCK2 signaling pathway, and inhibite nerve growth cone collapse.

Effect of GSK-3β-mediated DRP1 on inhibition of primary hippocampal neuronal growth induced by aluminum / 环境与职业医学

Background Aluminum (Al) can cause irreversible damage to neurons and synapses function, and the mechanism may be connected to mitochondrial damage caused by glycogen synthase kinase-3β (GSK-3β) regulating dynamin-related protein 1 (DRP1), resulting in inhibition of the growth of neuronal protrusions. Objective To investigate the role of GSK-3β regulating DRP1 in the inhibition of primary hippocampal neurite growth induced by Al. Methods Neurons were extracted from the hippocampus of newborn mice (≤24 h old) for primary culture. On day 6, the purity of neurons was detected by immunofluorescence. On day 10, neurons with good growth state were selected for Al exposure and GSK-3β inhibitor SB216763 (SB) intervention. The experiment design included a blank control group, a dimethyl sulfoxide (DMSO) group, an Al (20 μmol·L−1) group, a SB (1 μmol·L−1) group, and a SB (1 μmol·L−1) + Al (20 μmol·L−1) group. After primary hippocampal neurons were treated with Al or SB for 48 h, cell viability was detected by CCK-8 assay, the mitochondrial morphology of primary hippocampal neurons was observed by transmission electron microscopy, the total protrusion length of primary hippocampal neurons was scanned and analyzed by laser confocal imaging, and their complexity was analyzed by Sholl analysis. The expression levels of phospho-GSK-3β, GSK-3β, and DRP1 were detected by Western blotting. Results The immunofluorescent results showed that the purity of primary neurons was higher than 90%. After the Al exposure and the SB intervention for 48 h, compared with the blank control group, there was no obvious difference in cell viability in the DMSO group and the SB group (P>0.05), and the Al group showed reduced cell viability (P=0.006); there was no obvious difference in cell viability between the SB+Al group and the Al group (P>0.05). Compared with the blank control group, there was no obvious difference in the average total length of protrusion in the DMSO group and the SB group (P>0.05), and the Al group showed reduced average total length of neurite (P<0.001); the average total neurite length in the SB+Al group was significantly increased compared with that in the Al group (P=0.001). The results of Sholl analysis revealed that, within 130 μm from the cytosol, the number of intersections of neurons in each group increased with the increase of distance. Above 130 μm from the cytosol, the number of intersections of neurons in each group decreased gradually with increase of distance. At 130 μm and 310 μm from the cytosol, compared with the blank control group, the number of neuronal intersections in the DMSO group and the SB group had no obvious difference (P>0.05), and that in the Al group was significantly reduced (P<0.05); there was no obvious difference in the number of neuronal intersections between the SB+Al group and the Al group (P>0.05). The mitochondrial structure of the blank control group was complete and the crest was clearly visible; there was no apparent variation in the mitochondrial structure in the DMSO group and the SB group; the mitochondria in the Al group were vacuolated and the crista disappeared; the SB+Al group showed clearer crista than the Al group. The difference in GSK-3β phosphorylation level among groups was statistically significant (F=45.841, P<0.001). Compared with the blank control group, the GSK-3β phosphorylation level showed not significantly different in the DMSO group (P>0.05), increased in the SB group (P=0.022), and significantly reduced in the Al group (P<0.001); the GSK-3β phosphorylation level was significantly higher in the SB+Al group than in the Al group (P<0.001). The difference in DRP1 protein level among groups was statistically significant (F=8.389, P=0.003). Compared with the blank control group, the DRP1 protein levels in the DMSO group and the SB group were not significantly different (P>0.05), and significantly increased in the Al group (P=0.001); the DRP1 protein level in the SB+Al group was significantly lower than that in the Al group (P=0.029). Conclusion Al may increase the level of DRP1 protein by activating GSK-3β, causing mitochondrial damage and inhibiting neuronal protrusions growth.

Síndrome de Parsonage Turner: um relato de caso / Parsonage-Turner Syndrome: a case report

A Síndrome de Parsonage-Turner (SPT) é uma doença rara que acomete a musculatura da cintura escapular, acarretando hipotrofia muscular e grande limitação funcional. A etiologia ainda é indeterminada; acredita-se que existam fatores autoimunes e infecciosos envolvidos. No presente caso foi aventada possível relação com a vacina da influenza. Os sintomas da SPT incluem dor abrupta de um lado da cintura escapular, sendo característico o despertar noturno. É uma condição de difícil diagnóstico, podendo ser confundida inicialmente com espondilose cervical, capsulite adesiva, radiculopatia cervical e bursite. Na investigação diagnóstica, foram realizados exames laboratoriais e ressonâncias magnéticas e eletroneuromiografia que auxiliou na definição diagnóstica. O tratamento envolve a abordagem da dor neuropática e reabilitação visando a recuperacao da força e da função muscular. O objetivo dessa descrição é revisar o assunto através de um relato de caso típico mas que, no entanto, não foi inicialmente considerado, servindo de alerta para que diante de quadros de dor aguda em membros superiors seja ponderado o diagnóstico de Parsonage Turner. Dessa forma o assunto se torna mais habitual no ofício médico, facilitando o diagnóstico precoce e oferecendo o prognóstico ao paciente, evitando exames e medicações desnecessárias.

Parsonage-Turner Syndrome (SPT) is a rare disease that affects the musculature of the shoulder girdle, resulting in muscle hypotrophy and functional limitation. The etiology is still undertermined: It is believed that exist autoimune disorders and infections involved. In this case a possible relationship with the influenza vacinne was suggest. The symptoms of SPT include acute onset pain in one side of the shoulder girdle and frequently awakens pacients from sleep, fact that occurred in this report. This disease has difficult diagnostic and can be confused initially with cervical spondylosis, adhesive capsulitis, cervical radiculopathy and bursitis. In the diagnostic investigation, laboratory exams, magnetic resonances and electroneuromyography were performed, of the latter deserves mention for assisting in the definitive diagnosis and determining the extent of the lesion. There is still no protocol for specific treatment, but it should be focused on reducing neuropathic pain and recovering muscle strength and function. The purpose of this description is to review the subject through a typical case report, which, however, was not initially considered, serving as a warning so that in the face of acute pain in upper limbs, the diagnosis of Parsonage Turner should be considered. Thus, the subject becomes more usual in the medical craft making the clinical evaluation more careful so that the diagnosis is early and offers a better prognosis to the patient, avoiding unnecessary exams and medications.

MicroRNA-146a inhibition promotes total neurite outgrowth and suppresses cell apoptosis, inflammation, and STAT1/MYC pathway in PC12 and cortical neuron cellular Alzheimer's disease models

This study aimed to explore the effect of microRNA (miR)-146a inhibition on regulating cell apoptosis, total neurite outgrowth, inflammation, and STAT1/MYC pathway in Alzheimer's disease (AD). PC12 and cortical neuron cellular AD models were constructed by Aβ1-42 insult. For the former model, nerve growth factor (NGF) stimulation was previously conducted. miR-146a inhibitor and negative-control (NC) inhibitor were transfected into the two cellular AD models, and then cells were named miR-inhibitor group and NC-inhibitor group, respectively. After transfection, cell apoptosis, total neurite outgrowth, supernatant inflammation cytokines, and STAT1/MYC pathway were detected. miR-146a expression was similar between PC12 cellular AD model and control cells (NGF-stimulated PC12 cells), while miR-146a expression was increased in cortical neuron cellular AD model compared with control cells (rat embryo primary cortical neurons). In both PC12 and cortical neuron cellular AD models, miR-146a expression was reduced in miR-inhibitor group compared with NC-inhibitor group after transfection. Furthermore, cell apoptosis was attenuated, while total neurite outgrowth was elevated in miR-inhibitor group compared with NC-inhibitor group. As for supernatant inflammatory cytokines, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-17 levels were lower in miR-inhibitor group than in NC-inhibitor group. Additionally, STAT1 and c-Myc mRNA and protein expressions were attenuated in miR-inhibitor group compared with NC-inhibitor group. In conclusion, miR-146a potentially represented a viable therapeutic target for AD.

Effects of Nogo-A and its receptor on the repair of sciatic nerve injury in rats

Regeneration of injured peripheral nerves is an extremely complex process. Nogo-A (neurite outgrowth inhibitor-A) inhibits axonal regeneration by interacting with Nogo receptor in the myelin sheath of the central nervous system (CNS). The aim of this study was to investigate the effects of Nogo-A and its receptor on the repair of sciatic nerve injury in rats. Sprague-Dawley rats (n=96) were randomly divided into 4 groups: control group (control), sciatic nerve transection group (model), immediate repair group (immediate repair), and delayed repair group (delayed repair). The rats were euthanized 1 week and 6 weeks after operation. The injured end tissues of the spinal cord and sciatic nerve were obtained. The protein expressions of Nogo-A and Nogo-66 receptor (NgR) were detected by immunohistochemistry. The protein expressions of Nogo-A, NgR, and Ras homolog family member A (RhoA) were detected by western blot. At 1 week after operation, the pathological changes in the immediate repaired group were less, and the protein expressions of Nogo-A, NgR, and RhoA in the spinal cord and sciatic nerve tissues were decreased (P<0.05) compared with the model group. After 6 weeks, the pathological changes in the immediate repair group and the delayed repair group were alleviated and the protein expressions decreased (P<0.05). The situation of the immediate repair group was better than that of the delayed repair group. Our data suggest that the expression of Nogo-A and its receptor increased after sciatic nerve injury, indicating that Nogo-A and its receptor play an inhibitory role in the repair process of sciatic nerve injury in rats.

Effect of aluminum-maltolate on primary hippocampal neuron neurite damage by regulating CRMP2 through GSK-3β in mice / 环境与职业医学

Background Aluminum can induce irreversible structural and synaptic functional damage, and the associated mechanism may be related to the neurite damage regulated by glycogen synthase kinase-3β (GSK-3β)/collapsin response mediator protein 2 (CRMP2). Objective This experiment is conducted to investigate the effect of aluminum-maltolate [Al(mal)3] on primary hippocampal neuron neurites in mice, and reveal the role of GSK-3β-CRMP2 in this process. Methods The hippocampus of newborn ICR mice (≤ 24 h old) was used for primary neuronal cultures. On the 5th day in vitro (DIV5), neuron purity detection were performed by confocal laser scanning microscopy. On DIV7, the neurons were transfected with lentiviral vector-mediated mNeonGreen. On DIV10, the neurons with mNeonGreen fluorescence in good growth state were treated with Al(mal)3. The stage I experimental groups were blank control group, maltol group, 10 µmol·L−1 Al group, 20 µmol·L−1 Al group, and 40 µmol·L−1 Al group. Then 20 µmol·L−1 Al was used to establish a model of neurite injury and for the intervention. The stage II experimental groups were blank control group, dimethyl sulfoxide (DMSO) group, Al (20 µmol·L−1) group, SB (GSK-3β inhibitor, 1 µmol·L−1), and SB (1 µmol·L−1)+Al (20 µmol·L−1) group. CCK-8 method was used to detect the viability of neurons. The primary hippocampal neurons of mice were scanned with high content analysis system at 0 h and 48 h after Al or SB treatment, and the density and length of neurites were analyzed. Western blotting was used to detect the expression and phosphorylation levels of CRMP2 and GSK-3β in primary hippocampal neurons of mice. Results The immunofluorescence results showed that the purity of primary neurons was more than 90%. Compared with the blank control group in stage I, the cell viability rates of the 10, 20, and 40 µmol·L−1 Al groups were decreased after 48h of Al(mal)3 treatment (P<0.05), while the cell viability rate of the maltol group had no significant change. There was no significant difference in cell viability rate among the DMSO group, the SB group, and the control group after 48h of SB treatment, and the viability rate of neurons in the SB+Al group was higher than that in the Al group (P<0.05) in stage II. The 48 h/0 h ratios of average number and length of neurites in the control group were 90.13%±11.70% and 113.24%±8.34%, respectively. The 48 h/0 h ratios in the Al group were 56.47%±16.36% and 62.06%±6.75%, respectively, which were lower than those in the control group (P<0.05). The 48 h/0 h ratios of average number of neurites in the SB group (99.03%±21.83%) was not significantly different from that in the control group, but the 48 h/0 h ratio of average length of neurites in the SB group (128.72%±15.39%) was higher than that in the control group (P<0.05). The 48 h/0 h ratios of average number (72.59%±10.89%) and length of neurites (93.84%±14.65%) in the SB+Al group were significantly increased compared with those in the Al group (P<0.05). Western blotting results showed that: There was no significant difference in GSK-3β protein level among all groups; compared with the control group (1.00±0.18), the protein level of p-GSK-3β in the Al group (0.45±0.05) was significantly decreased, and that in the SB group (1.32±0.23) was significantly increased; the protein level of p-GSK-3β in the SB+Al group (0.80±0.05) was significantly higher than that in the Al group (P<0.05). Compared with the control group (1.00±0.07), the CRMP2 protein level in the Al group (0.66±0.11) was significantly decreased (P<0.05), while that in the SB group (1.01±0.02) was not significantly changed. Compared with the control group (1.00±0.13), the p-CRMP2 protein level in the Al group (1.50±2.18) was significantly increased, and that in the SB group (0.62±0.09) was significantly decreased (P<0.05); the protein level of p-CRMP2 in the SB+Al group (1.28±0.24) was lower than that in the Al group (P<0.05). Conclusion Aluminum may activate GSK-3β, increase CRMP2 phosphorylation level, and damage neurite growth.

Brain tissue microstructure parameters estimation method based on proximal gradient network / 生物医学工程学杂志

Diffusion tensor imaging technology can provide information on the white matter of the brain, which can be used to explore changes in brain tissue structure, but it lacks the specific description of the microstructure information of brain tissue. The neurite orientation dispersion and density imaging make up for its shortcomings. But in order to accurately estimate the brain microstructure, a large number of diffusion gradients are needed, and the calculation is complex and time-consuming through maximum likelihood fitting. Therefore, this paper proposes a kind of microstructure parameters estimation method based on the proximal gradient network, which further avoids the classic fitting paradigm. The method can accurately estimate the parameters while reducing the number of diffusion gradients, and achieve the purpose of imaging quality better than the neurite orientation dispersion and density imaging model and accelerated microstructure imaging via convex optimization model.

Human placental laminin: Role in neuronal differentiation, cell adhesion and proliferation

Human placental extract has wound healing potential. Immuno-blots revealed presence of laminin in placentalextract (70 ± 0.257 lg/ml; n=3). It was purified using immuno-affinity chromatography. SDS-PAGE and SEHPLC indicated a188 kDa protein with some small peptides. Since placental laminin existed in its truncatedform, its roles in cellular migration, differentiation and wound healing were verified. Induction of cellularmigration and motility in rat fibroblasts were enhanced by placental laminin as observed from scratch woundassay. Promotion of neuronal differentiation of PC12 cells by placental laminin was observed by phase contrastmicroscopy. Confocal images showed presence of laminin on the cell surface and along the axonal processes.Significant interaction between integrin receptors and laminin responsible for cellular differentiation wasdemonstrated from co-localization experiments. Union between integrin receptor and its synthetic antagonistrevealed retarded pattern of neurite outgrowth in laminin treated cells. Animal model studies revealed fasterwound healing in the presence of placental laminin. Induction of re-epithelialization and angiogenesis inwound area by cellular proliferation and adhesion were observed. The cytokine levels showed an initial riseand gradual fall over the duration of wound healing on application of the fragmented laminin. Thus, roles ofplacental laminin in neuronal differentiation and wound healing were indicated.

Perdas visuais agudas: uma revisão dos últimos 10 anos de causas não infecciosas e não maculares / Acute visual loss: a review from the last 10 years of non-infectious and non-macular causes

Objetivo: o conhecimento das principais causas de perda visual aguda possibilita o diagnóstico precoce do paciente, o que favorece o tratamento mais rápido e eficaz, a fim de preservar a acuidade visual. Neste artigo de revisão, as principais causas não infeciosas e não oriundas da mácula são abordadas, a fim de buscar e revisar os tópicos mais pertinentes sobre cada tema, como as manifestações clínicas e os tratamentos mais utilizados. Métodos: trata-se de uma revisão de literatura, com 30 artigos selecionados e revisados da plataforma MEDLINE. Resultados: as causas de perda visual aguda discutidas são cinco. Primeiro, as por baixa acuidade visual, súbita, unilateral, sem dor e sem hiperemia: hemorragia vítrea, descolamento de retina, oclusão vascular de retina e neuropatia óptica isquêmica anterior. Posteriormente, por baixa acuidade visual, súbita, unilateral, com dor e sem hiperemia: neurite óptica. Por meio deste estudo, alguns fatores de risco podem ser evidenciados e os principais tratamentos destacados. Conclusão: o diagnóstico precoce das perdas visuais agudas deve ser realizado, com os exames físicos adequados, como a fundoscopia e os exames complementares necessários solicitados. Além disso, o encaminhamento ao oftalmologista é de extrema importância para minimizar sequelas e evitar complicações.

Objective: The knowledge of the main causes of acute visual loss enables the early diagnosis of the patient, which favors faster and more effective treatment in order to preserve visual acuity. In this review article, the main non-infectious causes not originating from the macula are addressed in order to search and review the most relevant topics on each theme, such as the clinical manifestations and the most used treatments. Methods: This is a literature review with 30 articles selected and reviewed from the MEDLINE platform. Results: Five causes of acute visual loss are discussed. First, those for sudden, unilateral, without pain, and without hyperemia low visual acuity are reviewed: vitreous hemorrhage, retinal detachment, retinal vascular occlusion, and anterior ischemic optic neuropathy. Subsequently, one due to low visual acuity, sudden, unilateral, with pain and without hyperemia is evaluated: optic neuritis. Through this study, some risk factors and main treatments can be highlighted. Conclusion: The early diagnosis of acute visual loss should be performed with appropriate physical exams, such as fundoscopy and the necessary complementary exams. In addition, referral to an ophthalmologist is extremely important to minimize sequelae and avoid complications.

Paired Immunoglobulin-like Receptor B Inhibition in Müller Cells Promotes Neurite Regeneration After Retinal Ganglion Cell Injury in vitro / 神经科学通报·英文版

In the central nervous system (CNS), three types of myelin-associated inhibitors (MAIs) have major inhibitory effects on nerve regeneration. They include Nogo-A, myelin-associated glycoprotein, and oligodendrocyte-myelin glycoprotein. MAIs possess two co-receptors, Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PirB). Previous studies have confirmed that the inhibition of NgR only results in a modest increase in regeneration in the CNS; however, the inhibitory effects of PirB with regard to nerve regeneration after binding to MAIs remain controversial. In this study, we demonstrated that PirB is expressed in primary cultures of retinal ganglion cells (RGCs), and the inhibitory effects of the three MAIs on the growth of RGC neurites are not significantly decreased after direct PirB knockdown using adenovirus PirB shRNA. Interestingly, we found that retinal Müller cells expressed PirB and that its knockdown enhanced the regeneration of co-cultured RGC neurites. PirB knockdown also activated the JAK/Stat3 signaling pathway in Müller cells and upregulated ciliary neurotrophic factor levels. These findings indicate that PirB plays a novel role in retinal Müller cells and that its action in these cells may indirectly affect the growth of RGC neurites. The results also reveal that PirB in Müller cells affects RGC neurite regeneration. Our findings provide a novel basis for the use of PirB as a target molecule to promote nerve regeneration.

Paired Immunoglobulin-like Receptor B Inhibition in Müller Cells Promotes Neurite Regeneration After Retinal Ganglion Cell Injury in vitro / 神经科学通报·英文版

In the central nervous system (CNS), three types of myelin-associated inhibitors (MAIs) have major inhibitory effects on nerve regeneration. They include Nogo-A, myelin-associated glycoprotein, and oligodendrocyte-myelin glycoprotein. MAIs possess two co-receptors, Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PirB). Previous studies have confirmed that the inhibition of NgR only results in a modest increase in regeneration in the CNS; however, the inhibitory effects of PirB with regard to nerve regeneration after binding to MAIs remain controversial. In this study, we demonstrated that PirB is expressed in primary cultures of retinal ganglion cells (RGCs), and the inhibitory effects of the three MAIs on the growth of RGC neurites are not significantly decreased after direct PirB knockdown using adenovirus PirB shRNA. Interestingly, we found that retinal Müller cells expressed PirB and that its knockdown enhanced the regeneration of co-cultured RGC neurites. PirB knockdown also activated the JAK/Stat3 signaling pathway in Müller cells and upregulated ciliary neurotrophic factor levels. These findings indicate that PirB plays a novel role in retinal Müller cells and that its action in these cells may indirectly affect the growth of RGC neurites. The results also reveal that PirB in Müller cells affects RGC neurite regeneration. Our findings provide a novel basis for the use of PirB as a target molecule to promote nerve regeneration.

Effect of acupuncture intervention on neurological function, cerebral microglia activation and secondary nerve damage in traumatic brain injury rats / 针刺研究

OBJECTIVE: To observe the effect of acupuncture on activities of microglia in traumatic brain injury (TBI) rats. METHODS: Fifty-four male SD rats were randomly and equally divided into normal control, model and acupuncture groups according to the random number table (n＝18 rats in each group). The TBI model was established by using a free fall brain injury striking device after exposing the local cranial bone (to induce the left parietal cerebral contusion). Acupoints "Baihui" (GV20), "Shuigou" (GV26), "Fengfu" (GV16), "Yamen" (GV15) and bilateral "Hegu" (LII4) were stimulated intensively by twirling the filiform needles with force at a range of >360° and a frequency of 160－180 cycles/min for 10 sec in every acupoint, once every 5 min during the 15 minutes' needle retaining. The treatment was given once every day for successive 14 days. The rats of the normal and model groups were grabbed and fixed with the same procedure. The behavioral changes were tested using modified neurological severity score (mNSS). The histopathological changes of the injured cerebral cortex tissues were observed by using hematoxylin-eosin (H.E.) staining, and the fluorescence intensity of Iba-1 (marker of microglia) positive products in the surrounding tissue of the cerebral focus was displayed by immunofluorescence staining, and the contents of neuron specific enolate (NSE) and neurite outgrowth inhibitor-A (Nogo-A) in serum (indicating a secondary nerve damage) were assayed by ELISA. RESULTS: The mNSS scores were significantly increased on day 1, 3, 7 and 14 in the model group in comparison with the normal group (P<0.01) and considerably decreased at the 4 time-points after acupuncture intervention relevant to the model group (P<0.05, P<0.01). H．E. staining showed that modeling induced pathological changes such as the excursion of cell nucleus, cellular swel-ling, vacuole-like change, neuron death, karyopyknosis dissolution, and proliferation of fibrous tissue were relatively milder in the acupuncture group. The average fluorescence intensity values of Iba-1-positive products, serum NSE and Nogo-A contents on day 3, 7 and 14 were significantly higher in the model group than in the normal group (P<0.05, P<0.01), and notably down-regulated in the acupuncture group than in the model group (P<0.05, P<0.01, except Nogo-A on day 3). CONCLUSION: Acupuncture intervention may accelerate neurological function recovery in TBI rats, which is closely related to its effects in inhibiting the activation of microglia and secondary nerve damage.