Clinical features and visual outcomes of pediatric optic neuritis in the Indian population: A prospective study

Purpose: Optic neuritis, defined as inflammation of the optic nerve, is the most common optic neuropathy affecting adults. Various studies in Southeast Asia have shown that the clinical profile of optic neuritis might differ in these regions from that reported in the western literature. Through this study, we evaluate the clinical profile of pediatric optic neuritis (PON) in the Indian population. Methods: This was a hospital?based prospective observational study. Patients with optic neuritis younger than 16 years who attended the neuro?ophthalmology clinic from May 2016 to April 2017 were included in the study. Results: This study included 54 eyes of 38 patients. The mean age of presentation was 10.6 years. Unilateral disease (58%) was found to be more common, and a slight female preponderance (58%) was noted. The most common feature was visual loss (96.3%). Pupillary light reflex abnormality was seen in most patients. Fundus examination revealed disk edema (77.7%) to be the most common feature. Neuroimaging was performed in 34 patients, and multiple sclerosis was diagnosed in four patients. At 3 months follow?up after treatment, 89% of eyes had best correct visual acuity of 6/9 or better (P < 0.001). Conclusion: In our study, we found the clinical profile of PON to be similar to that seen in western studies as well as those done previously in the Indian population, although with a few differences

Mielitis transversa aguda asociada con infección por SARS-CoV-2 / Acute Transverse Myelitis Associated to SARS-CoV-2 Infection

Resumen Además de provocar problemas respiratorios, la infección con el SARS-CoV-2 puede causar un espectro amplio de complicaciones neurológicas como son cefalea, ageusia, anosmia, encefalopatía, enfermedad cerebrovascular, síndrome de Guillain-Barré y otras polineuropatías, meningoencefalitis, encefalopatía hemorrágica necrotizante aguda y síndromes del sistema nervioso central asociados a inflamación. En esta revisión presentamos 39 casos de mielitis transversa aguda (MTA) asociados a infección por el SARS-CoV-2, confirmado por una prueba de reacción en cadena de la polimerasa (PCR) por hisopado nasofaríngeo y/o de antígeno en plasma. Los análisis bioquímicos de los pacientes confirmaron la ausencia de otros patógenos y de autoanticuerpos involucrados en inflamación del sistema nervioso, excepto por 2 casos, uno con autoanticuerpos contra la glicoproteína de la mielina de los oligodendrocitos (anti-MOG IgG) y otro con anti-MOG IgG y antidescarboxilasa del ácido glutámico (anti-GAD65), indicativos de una enfermedad autoinmune del sistema nervioso central. Los estudios de imagenología de resonancia magnética (RMN) confirmaron el diagnóstico de MTA. Aunque no se puede inferir causalidad, es muy probable que los casos aislados de MTA sean consecuencia de un proceso para o postinfeccioso en la COVID-19. La comprensión de los mecanismos que desencadenan estos trastornos neurológicos durante o al final de la infección viral, ayudarán a optimizar las estrategias terapéuticas para el manejo del paciente.

Abstract In addition to causing respiratory problems, SARS-CoV-2 can cause a wide spectrum of neurological complications such as headaches, ageusia, anosmia, encephalopathy, cerebrovascular disease, Guillain-Barré syndrome and other polyneuropathies, meningoencephalitis, acute necrotizing hemorrhagic encephalopathy, and central nervous system syndromes associated with inflammation. In this review we present 39 cases of acute transverse myelitis (ATM) associated to SARS-CoV-2 infection. All cases had a positive polymerase chain reaction (PCR) nasopharyngeal swab and/or antigen test. Biochemical analyses confirmed the absence of other pathogens and autoantibody-mediated neuroinflammatory disease, except for two cases, one with autoantibodies against the oligodendrocyte myelin glycoprotein (anti-MOG IgG) and another with anti-MOG IgG and anti-glutamic acid decarboxylase (anti-GAD65). Magnetic Resonance Imaging (MRI) studies confirmed the diagnosis of ATM. Although causality cannot be inferred, it is likely that isolated cases of ATM are the consequence of a para or post-infectious process in SARS-CoV-2. In this work, the probable causes of ATM associated with SARS-CoV-2 are discussed. The understanding of the mechanisms behind these neurological disorders triggered by a viral infection will help to optimize the therapeutic strategies for patient management.

Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells / 中国结合医学杂志

OBJECTIVE@#To examine the anti-inflammatory effect of grape seed extract (GSE) in animal and cellular models and explore its mechanism of action.@*METHODS@#This study determined the inhibitory effect of GSE on macrophage inflammation and Th1 and Th17 polarization in vitro. Based on the in vitro results, the effects and mechanisms of GSE on multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE) mice model were further explored. The C57BL/6 mice were intragastrically administered with 50 mg/kg of GSE once a day from the 3rd day to the 27th day after immunization. The activation of microglia, the polarization of Th1 and Th17 and the inflammatory factors such as tumor necrosis factor- α (TNF- α), interleukin-1 β (IL-1 β), IL-6, IL-12, IL-17 and interferon-γ (IFN-γ) secreted by them were detected in vitro and in vivo by flow cytometry, enzyme linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot, respectively.@*RESULTS@#GSE reduced the secretion of TNF-α, IL-1 β and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide (P<0.01), inhibited the secretion of TNF-α, IL-1 β, IL-6, IL-12, IL-17 and IFN-γ in spleen cells of EAE mice immunized for 9 days (P<0.05 or P<0.01), and reduced the differentiation of Th1 and Th17 mediated by CD3 and CD28 factors (P<0.01). GSE significantly improved the clinical symptoms of EAE mice, and inhibited spinal cord demyelination and inflammatory cell infiltration. Peripherally, GSE downregulated the expression of toll-like-receptor 4 (TLR4) and Rho-associated kinase (ROCKII, P<0.05 or P<0.01), and inhibited the secretion of inflammatory factors (P<0.01 or P<0.05). In the central nervous system, GSE inhibited the infiltration of CD45+CD11b+ and CD45+CD4+ cells, and weakened the differentiation of Th1 and Th17 (P<0.05). Moreover, it reduced the secretion of inflammatory factors (P<0.01), and prevented the activation of microglia (P<0.05).@*CONCLUSION@#GSE had a beneficial effect on the pathogenesis and progression of EAE by inhibiting inflammatory response as a potential drug and strategy for the treatment of MS.

4-hydroxy-2-nonenal as a marker of the oxidative stress in brains of dogs with canine distemper / 4-hidroxi-2-nonenal como marcador de estresse oxidativo no cérebro de cães com cinomose

Canine Distemper is a disease caused by Canine morbillivirus (CM), a pantropic virus that can affect the central nervous system (CNS), causing demyelination. However, the pathogenesis of this lesion remains to be clarified. Brain samples of 14 naturally infected dogs by CM were analyzed to evaluate the presence of oxidative stress and demyelination. RT-PCR assay was performed to confirm a diagnosis of canine distemper in the brain, immunohistochemistry anti-CM was used to localize the viral proteins in the tissue, and anti-4-hydroxy-2-nonenal (4-HNE) was a marker of a product of lipid peroxidation. The results showed the presence of viral proteins in the demyelinated area with the presence of 4-HNE. Our results suggest that the CM virus infection causes oxidative stress leading to lipid peroxidation, which causes tissue damage and demyelination. In conclusion, oxidative stress plays a significant role in canine distemper pathogenesis in the CNS.(AU)

A cinomose canina é uma doença causada pelo Morbilivírus canino (CM), um vírus pantrópico que pode afetar o sistema nervoso central (SNC), causando desmielinização. No entanto, a patogênese dessa lesão não está totalmente esclarecida. RT-PCR e imuno-histoquímica foram realizadas para confirmação do diagnóstico de cinomose em amostras de encéfalo de 14 cães naturalmente infectados. Após confirmação, foi realizada uma avaliação do estresse oxidativo por imuno-histoquímica com uso de anti-4-hidroxi-nonenal (4HNE) como marcador de produtos resultantes da peroxidação lipídica. Os resultados sugerem que a infecção pelo CM causa estresse oxidativo no tecido, levando a peroxidação lipídica, a qual causa danos ao tecido, culminando com desmielinização. Conclui-se que o estresse oxidativo tem papel importante na patogênese da cinomose canina no sistema nervoso central.(AU)

Effects of low frequency magnetic stimulation on myelin and inflammation in demyelinated mice / 中华物理医学与康复杂志

Objective:To explore the effect of low frequency magnetic stimulation on myelin and inflammation in the callosum of demyelinated mice.Methods:Thirty-six 6 to 8-week-old male C57BL/6J mice were randomly divided into a control group, a cuprizone (CPZ) group and a magnetic therapy group. The CPZ group and the magnetic therapy group had demyelination induced by feeding a mixed diet containing 0.3% CPZ for 6 weeks, while the control group was given conventional food. The magnetic therapy group was given 50Hz 10mT magnetic stimulation during the 6 weeks for 20min daily, 5 days a week. The body mass of each mouse was observed every 7 days. At the end of the 6th week elevated cross maze experiments were conducted to observe any anxiety state. The myelin sheath in the corpus callosum was observed using Luxol fast blue staining and myelin basic protein (MBP) immunohistochemistry Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the corpus callosum were detected using enzyme-linked immunosorbent assays.Results:After the 6 weeks of treatment, the average body mass of the mice in the magnetic therapy group had improved significantly compared with the CPZ group. The CPZ group′s times in the elevated cross maze experiments were significantly shorter than those of the control group and also shorter than those of the magnetic therapy group. The Luxol staining showed significant myelin loss in the corpus callosum of the CPZ group, but compared with the CPZ group the average loss of myelin in the magnetic therapy group was significantly less. This was further confirmed by the MBP immunohistochemistry. Compared with the control group, the average expression of MBP in the CPZ group was significantly reduced, while in the magnetic therapy group it was significantly increased. Compared with the control group, the average TNF-α and IL-1β levels in the corpus callosum of the CPZ group increased significantly, but compared with the CPZ group the average levels in the magnetic therapy group had decreased significantly.Conclusions:Low frequency magnetic stimulation improves the body weight and anxiety state of mice. That is probably related to less myelin loss and inhibited inflammatory response in the corpus callosum.

Conditional Deletion of Foxg1 Alleviates Demyelination and Facilitates Remyelination via the Wnt Signaling Pathway in Cuprizone-Induced Demyelinated Mice / 神经科学通报·英文版

The massive loss of oligodendrocytes caused by various pathological factors is a basic feature of many demyelinating diseases of the central nervous system (CNS). Based on a variety of studies, it is now well established that impairment of oligodendrocyte precursor cells (OPCs) to differentiate and remyelinate axons is a vital event in the failed treatment of demyelinating diseases. Recent evidence suggests that Foxg1 is essential for the proliferation of certain precursors and inhibits premature neurogenesis during brain development. To date, very little attention has been paid to the role of Foxg1 in the proliferation and differentiation of OPCs in demyelinating diseases of the CNS. Here, for the first time, we examined the effects of Foxg1 on demyelination and remyelination in the brain using a cuprizone (CPZ)-induced mouse model. In this work, 7-week-old Foxg1 conditional knockout and wild-type (WT) mice were fed a diet containing 0.2% CPZ w/w for 5 weeks, after which CPZ was withdrawn to enable remyelination. Our results demonstrated that, compared with WT mice, Foxg1-knockout mice exhibited not only alleviated demyelination but also accelerated remyelination of the demyelinated corpus callosum. Furthermore, we found that Foxg1 knockout decreased the proliferation of OPCs and accelerated their differentiation into mature oligodendrocytes both in vivo and in vitro. Wnt signaling plays a critical role in development and in a variety of diseases. GSK-3β, a key regulatory kinase in the Wnt pathway, regulates the ability of β-catenin to enter nuclei, where it activates the expression of Wnt target genes. We then used SB216763, a selective inhibitor of GSK-3β activity, to further demonstrate the regulatory mechanism by which Foxg1 affects OPCs in vitro. The results showed that SB216763 clearly inhibited the expression of GSK-3β, which abolished the effect of the proliferation and differentiation of OPCs caused by the knockdown of Foxg1. These results suggest that Foxg1 is involved in the proliferation and differentiation of OPCs through the Wnt signaling pathway. The present experimental results are some of the first to suggest that Foxg1 is a new therapeutic target for the treatment of demyelinating diseases of the CNS.

Dicer Deletion in Astrocytes Inhibits Oligodendroglial Differentiation and Myelination / 神经科学通报·英文版

Increasing evidence has shown that astrocytes are implicated in regulating oligodendrocyte myelination, but the underlying mechanisms remain largely unknown. To understand whether microRNAs in astrocytes function in regulating oligodendroglial differentiation and myelination in the developing and adult CNS, we generated inducible astrocyte-specific Dicer conditional knockout mice (hGFAP-CreERT; Dicer fl/fl). By using a reporter mouse line (mT/mG), we confirmed that hGFAP-CreERT drives an efficient and astrocyte-specific recombination in the developing CNS, upon tamoxifen treatment from postnatal day 3 (P3) to P7. The Dicer deletion in astrocytes resulted in inhibited oligodendroglial differentiation and myelination in the developing CNS of Dicer cKO mice at P10 and P14, and did not alter the densities of neurons or axons, indicating that Dicer in astrocytes is required for oligodendrocyte myelination. Consequently, the Dicer deletion in astrocytes at P3 resulted in impaired spatial memory and motor coordination at the age of 9 weeks. To understand whether Dicer in astrocytes is also required for remyelination, we induced Dicer deletion in 3-month-old mice and then injected lysolecithin into the corpus callosum to induce demyelination. The Dicer deletion in astrocytes blocked remyelination in the corpus callosum 14 days after induced demyelination. Together, our results indicate that Dicer in astrocytes is required for oligodendroglia myelination in both the developing and adult CNS.

Neuropsychiatric manifestations in multiple sclerosis: clinical case report and review of literature

Background: Multiple sclerosis (MS) is a neurological disability affecting young and middle-aged adults. Neuropsychiatric manifestations in the background of multiple sclerosis had been reported as a sporadic occurrence. Case description: Here, we report the case of a 57-year-old man who developed neuropsychiatric manifestations during the course of MS. Discussion: In our case, the presence of MS might be a possible reason for the neuropsychiatric manifestations. However, not many case reports have previously acknowledged wherein a patient developed neuropsychiatric symptoms secondary to multiple sclerosis. Conclusion: Hence, this case stresses the need for future studies assessing the relationship between multiple sclerosis and psychosis.

Yoga as an intervention to manage multiple sclerosis symptoms

Multiple sclerosis (MS) is an autoimmune, demyelinating, inflammatory disease of central nervoussystem (CNS) which is characterized by spasticity, fatigue, depression, anxiety, bowel and bladderdysfunction, impaired mobility, cognitive impairment etc. and affects approximately 2.5 million peopleworldwide. Disease modifying therapies for MS which help in preventing accumulation of lesions inwhite matter of CNS are costly and have significant adverse effects. Therefore, patients with MS are usingcomplementary and alternative medicine (CAM) and Yoga is one of the most popular form of CAM whichis being used immensely to reduce or overcome the symptoms of MS. In the current review attempted topresent the potential impact of yoga practices on reducing MS related symptoms.© 2019 The Authors. Published by Elsevier B.V. on behalf of Institute of Transdisciplinary Health Sciencesand Technology and World Ayurveda Foundation. This is an open access article under the CC BY-NC-ND

Demyelination in experimental intraventricular neurocysticercosis / Desmielinização na neurocisticercose intraventricular experimental

Abstract Neurocysticercosis (NCC) is classified as a neglected tropical disease, which affects mainly Latin America and Africa in spite of some reports in North America and Europe. NCC represents the cause of up to 30% of the reported cases of epilepsy in endemic countries. The NCC injuries present direct relation to the development stage, location, and number of parasites as well as to the host immune response. This study aimed the characterization of the inflammatory response and tissue injuries by means of the analyses of the periventricular and parenchymatous demyelination through the experimental intraventricular NCC infection. Therefore, BALB/c mice were submitted to experimental NCC inoculation with Taenia crassiceps cysticerci. Their brains were removed at 7, 30, 60, and 90 days after the inoculation (DAI), and analyzed after staining with hematoxylin and eosin (HE), Luxol Fast Blue, and Nissl. It was possible to observe ventriculomegaly, inflammatory infiltration composed by polymorphonuclear and mononuclear cells, and foamy macrophages. The presence of inflammatory cells was associated with neurodegeneration detected by the areas with demyelination observed initially in the periventricular area and lately in the parenchyma. In conclusion, the presence of cysticerci and the consequent inflammation were able to promote initial periventricular demyelination followed by parenchymatous demyelination as the infection progressed.

Resumo A neurocisticercose (NCC) é classificada como uma doença tropical negligenciada que afeta principalmente a América Latina e a África, apesar de alguns relatos na América do Norte e na Europa. A NCC é responsável por cerca de 30% dos casos de epilepsia em países endêmicos. Estas lesões parecem ter estreita relação com o estádio de desenvolvimento, com a localização e o número de parasitas, bem como a resposta imune do hospedeiro. O presente estudo objetivou caracterizar a resposta de células inflamatórias e as lesões teciduais pela análise da desmielinização periventricular e parenquimatosa ao longo da infecção experimental de NCC intraventricular. Para tanto, camundongos BALB/c foram submetidos a NCC experimental através da inoculação de cisticercos de Taenia crassiceps. O encéfalo foi retirado aos 7, 30, 60 e 90 dias após inoculação (DAI) e analisado após coloração por Hematoxilina e Eosina (HE), Luxol Fast Blue e Nissl. Observou-se ventriculomegalia, processo de infiltração inflamatório composto por células polimorfonucleares, mononucleares e macrófagos espumosos. A presença de células inflamatórias foi associada com neurodegeneração, observada pelas áreas de desmielinização que foram inicialmente periventricular e mais tardiamente no parênquima. Em conclusão, observa-se que a presença dos cisticercos e a inflamação foram capazes de promover desmielinização periventricular inicial e parenquimatosa conforme houve progressão tardia da infecção.

Repair effect of cannabinoid on myelin sheath of demyelination model mice induced by cuprizone / 吉林大学学报(医学版)

Objective: To investigate the repair effect of cannabinoid (WIN55212-2) on the myelin sheath of the demyelination model mice induced by cuprizone, and to elucidate its possible mechanism. Methods: A total of 95 C57BL/6 mice were randomly divided into blank control group, model group (0.2% cuprizone for 6 weeks), DMSO group (intraperitoneally injected with the same amount of DMSO mixture from the 3rd week of feeding 0.2% cuprizone) and treatment group (intraperitoneally injected with 1 mg · kg-1 WIN55212-2 from the 3rd week of feeding 0.2% cuprizone). The myelin sheath tissue of the mice was stained by Black-gold II staining technique, and its histomorphology was observed. The expression levels of juxtanodin (JN), myelin basic protein (MBP) and Nkx2. 2 proteins in mouse brain tissue were detected by Western blotting method. Results: The results of Black-gold I staining showed that the corpus callosum of the brain of the mice in blank control group had significant coloration, while the corpus callosum of the mice in model group showed less coloration. Compared with blank control group, the expression levels of JN and MBP proteins in brain tissue of the mice in model group were significantly decreased (P<0.05). Compared with model group and DMSO group, the expression level of JN and Nkx2. 2 proteins in brain tissue of the mice in treatment group were significantly increased (P

Different pathological processes for acute white matter lesions in multiple sclerosis

@#Introduction: Multiple sclerosis (MS) has variable clinical presentations, prognoses, pathogeneses, and pathological patterns. We conducted a pathological review of acute MS-associated lesions that focused on the degree of axonal injury, myelin loss, and glial reaction to determine whether the observed demyelination was of the primary or secondary type. Materials and Methods: After searching the records for a 15-year period at the London Health Sciences Centre Pathology Department, we identified 8 cases of surgical acute lesion biopsies in which clinical MS diagnoses were made before or after the biopsy. Results: The white matter pathologies in these cases could be sorted into 3 morphological patterns. The first pattern, which represents typical demyelinated plaques, was observed in 4 cases and was characterised by nearly complete demyelination accompanied by variable degrees of axon preservation and axonal swelling. The second pattern was observed in 3 cases and was characterised by demyelinating lesions containing variable numbers of myelinated axons mixed with a few demyelinated axons and variable numbers of axonal swellings. The myelinated axons ranged from scattered fibres to bands of variable thickness, and the demyelination was a mixture of primary and secondary demyelination. The third pattern was observed in 1 case and was characterised by well-demarcated areas of reduced myelin staining and numerous apoptotic nuclei. Axonal staining revealed many fragmented axons with reduced myelin staining but no definitely demyelinated axons. Conclusion: This report shows that the predominant pathology underlying acute MS-related lesions is not limited to demyelination but can include axonal degeneration alone or in combination with primary demyelination which reflect different pathogenesis for these acute lesions.

Isolamento e diferenciação das células-tronco da polpa dentária canina em células progenitoras neurais / Isolation and differentiation of canine dental pulp stem cells in neural progenitor cells

O objetivo deste estudo foi verificar a capacidade de diferenciação das células-tronco da polpa dentária canina em células progenitoras neurais bem como quantificar obtenção e viabilidade celular, durante três passagens em cultura. As células foram extraídas da polpa dentária de dois cadáveres caninos, com aproximadamente dez meses de idade, que foram a óbito em decorrência de traumatismo automotivo. Após três subculturas, realizou-se avaliação da viabilidade celular por quantificação em câmara de Neubauer. A partir disso, induziu-se diferenciação neural em meio de cultura neurobasal (Gibco™), com células aderidas ao plástico ou suspensas em placas tratadas com agarose. Após sete e 14 dias em cultivo indutor, observou-se morfologia e perfil imunofenotípico utilizando citometria de fluxo e imunocitoquímica fluorescente. Aos 14 dias as células apresentaram alto grau de expressão para marcadores anti-nestina e anti-glial fibrillary acidic protein (anti-GFAP). Anteriormente, obteve-se ao 25º dia, média de 18x106 células viáveis indiferenciadas oriundas do tecido pulpar. Sugere-se que as células-tronco indiferenciadas da polpa dentária canina apresentem índices satisfatórios de diferenciação em células progenitoras neurais, aderidas ou suspensas em cultura. A polpa dentária dos dentes decíduos caninos, fornece células indiferenciadas viáveis em quantidade adequada.(AU)

The objective of this study was to verify the differentiation capacity of canine tooth pulp stem cells in neural progenitor cells as well as to quantify the attainment and viability during three culture passages. The cells were extracted from the dental pulp of two canine cadavers, with approximately ten months of age, which died due to automotive trauma. After three subcultures, cell viability evaluation was performed by Neubauer chamber quantification. Neural differentiation was induced in neurobasal culture medium (Gibco ™), with cells adhered to the plastic or suspended in agarose-treated plates. After seven and 14 days in inducer culture, morphology and immunophenotypic profile were observed using flow cytometry and fluorescent immunocytochemistry. At 14 days the cells had a high degree of expression for anti-nestin and anti-glial fibrillary acidic (anti-GFAP) markers. Previously, an average of 18x106 undifferentiated viable cells from the pulp tissue were obtained on the 25th day. It is suggested that the undifferentiated canine pulp stem cells present satisfactory differentiation indices in neural progenitor cells, adhered or suspended in culture. The dental pulp of deciduous canine teeth provides viable undifferentiated cells in adequate quantity.(AU)

The effect of intermittent fasting diet on the hippocampus of adult male mouse after inducing demyelination by ethidium bromide injection / Efecto de la dieta de ayuno intermitente en el hipocampo de ratón macho adulto después de inducir la desmielinización por inyección de bromuro de etidio

Intermittent fasting diet (IF) as a restrictive regimen prevents neural degeneration and stimulates overexpression of various neurotropic factors in the hippocampus of animal models. This study evaluates the potential effect of the IF in the prevention of learning and memory dysfunction and improving the alterations in the number and volume of neurons in an ethidium bromide (EB) induced mouse model of demyelination.Mice were randomly assigned into N group (Normal Diet and normal saline injection), F group (IF and normal saline injection), EBN group (Normal Diet and EB injection), EBF group (IF and EB injection). The hidden platform test was carried out based on path length, escape latency and swim speeds of mice. Stereological studies were determined by the Cavalieri and the Optical Dissector technique. Maintenance of mice on the IF results in significantly decreased the body weight and biochemical parameters, increased total number of neurons and volume of the hippocampus, and improved learning and memory parameters of adult male mice. However, IF in EBF group did not show as excellently as F group. The EBF group displayed significantly spatial memory improvement than that in EBN group. There were no statistically significant differences between EBF and EBN groups in stereological and learning parameters, though the EBF group displayed faster escape latencies, and swam faster and shorter path lengths than the EBN group in these parameters. Therefore as a conclusion, The IF fairly improved some adverse effects of EB in experimental demyelination models.

La dieta de ayuno intermitente (AI) como régimen restrictivo, previene la degeneración neural y la estimación de la presencia de diversos factores neurotrópicos en el hipocampo de modelos animales. Este estudio evalúa el efecto potencial de la AI en la prevención del aprendizaje y la disfunción de la memoria y mejora las alteraciones en el número y el volumen de las neuronas en un modelo de desmielinización, en ratón, inducido con bromuro de etidio (BE). Los ratones se asignaron al azar en el grupo N (dieta normal e inyección salina normal), Grupo A (AI e inyección salina normal), Grupo BEN (dieta normal e inyección BE), Grupo EBF (inyección AI y BE). La prueba de la plataforma oculta se llevó a cabo en función de la longitud del trayecto, la latencia de escape y la velocidad de nado de los ratones. Los estudios estereológicos fueron determinados por la técnica de Cavalieri y la técnica del disector óptico. En el grupo AI disminuyeron significativamente el peso corporal de los ratones, los parámetros bioquímicos, el número total de neuronas y el volumen del hipocampo, y los parámetros de aprendizaje y la memoria de los ratones machos adultos. Sin embargo, el grupo AI en BEF no se mostró tan bien como el grupo A. El grupo EBF mostró una mejora en la memoria espacial significativamente mayor que la del grupo BEN. No hubo diferencias estadísticamente significativas entre los grupos A, BE y BEN en los parámetros estereológicos y de aprendizaje, aunque el grupo EBF mostró latencias de escape más rápidas, y nado en las rutas más rápidas y más cortas que el grupo BEN en estos parámetros. Por lo tanto, como conclusión, el grupo AI mejoró bastante algunos efectos adversos de la BE en los modelos de desmielinización experimental.

Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice / 神经科学通报·英文版

The obstacle to successful remyelination in demyelinating diseases, such as multiple sclerosis, mainly lies in the inability of oligodendrocyte precursor cells (OPCs) to differentiate, since OPCs and oligodendrocyte-lineage cells that are unable to fully differentiate are found in the areas of demyelination. Thus, promoting the differentiation of OPCs is vital for the treatment of demyelinating diseases. Shikimic acid (SA) is mainly derived from star anise, and is reported to have anti-influenza, anti-oxidation, and anti-tumor effects. In the present study, we found that SA significantly promoted the differentiation of cultured rat OPCs without affecting their proliferation and apoptosis. In mice, SA exerted therapeutic effects on experimental autoimmune encephalomyelitis (EAE), such as alleviating clinical EAE scores, inhibiting inflammation, and reducing demyelination in the CNS. SA also promoted the differentiation of OPCs as well as their remyelination after lysolecithin-induced demyelination. Furthermore, we showed that the promotion effect of SA on OPC differentiation was associated with the up-regulation of phosphorylated mTOR. Taken together, our results demonstrated that SA could act as a potential drug candidate for the treatment of demyelinating diseases.

Changes of myelin basic protein expression in the white matter of young rats with sepsis / 中国小儿急救医学

Sixty-four healthy Wistar rats(18 days old),weighting 30 ～ 40 g,were randomly divided into two groups:control group and lipopolysaccharide(LPS) group. LPS group was intraperitoneally injected with 5 mg/ kg LPS to prepare rat sepsis model. The control group received intraperitoneal injection of saline of equal volume. All surving animals were anesthetized at the set time 2 h,4 h,6 h and 12 h after administration(8 rats at each time point),and craniotomy after taking blood from the heart. Myelin injury was staining by luxol fast blue. Immunohistochemical staining and Western blot were used to detect the expression of myelin basic protein(MBP) in rat brain at different time points. The expression of the MBP protein in serum detected by enzyme-linked immunosorbent assay( ELISA). Results Observed under light microscope after luxol fast blue staining,the myelin sheath of the white matter in the brain was disordered,sparse and stained lightly from 6 to 12 hours in LPS group. Western blot analysis and immunohistochemical test results showed that the expression of MBP protein in the LPS group was decreased compared with the control group at 2 h,4 h and 6 h after LPS administration ( P < 0. 05). The expression of MBP protein in LPS group at 12 h was not significantly different from that in the control group(P > 0. 05). The serum ELISA results showed that the serum MBP levels in the LPS group increased at 2 h,4 h,6 h and 12 h after LPS administration(P < 0. 05). Conclusion In rat sepsis model,MBP protein expression in the white matter decreases,serum MBP protein content increases,and the decreasing of MBP protein expression is associated with matter myelin injury.

miR-381 Attenuates Peripheral Neuropathic Phenotype Caused by Overexpression of PMP22

Charcot-Marie Tooth disease type 1A (CMT1A), the major type of CMT, is caused by duplication of peripheral myelin protein 22 (PMP22) gene whose overexpression causes structural and functional abnormalities in myelination. We investigated whether miRNA-mediated regulation of PMP22 expression could reduce the expression level of PMP22, thereby alleviating the demyelinating neuropathic phenotype of CMT1A. We found that several miRNAs were down-regulated in C22 mouse, a CMT1A mouse model. Among them, miR-381 could target 3′ untranslated region (3′UTR) of PMP22 in vitro based on Western botting and quantitative Real Time-PCR (qRT-PCR) results. In vivo efficacy of miR-381 was assessed by administration of LV-miR-381, an miR-381 expressing lentiviral vector, into the sciatic nerve of C22 mice by a single injection at postnatal day 6 (p6). Administration of LV-miR-381 reduced expression level of PMP22 along with elevated level of miR-381 in the sciatic nerve. Rotarod performance analysis revealed that locomotor coordination of LV-miR-381 administered C22 mice was significantly enhanced from 8 weeks post administration. Electrophysiologically, increased motor nerve conduction velocity was observed in treated mice. Histologically, toluidine blue staining and electron microscopy revealed that structural abnormalities of myelination were improved in sciatic nerves of LV-miR-381 treated mice. Therefore, delivery of miR-381 ameliorated the phenotype of peripheral neuropathy in CMT1A mouse model by down-regulating PMP22 expression. These data suggest that miRNA can be used as a potent therapeutic strategy to control diseases with copy number variations such as CMT1A.

Clinical features of central nerve system inflammatory demyelinating diseases associated with anti-myelin oligodendrocyte glycoprotein antibodies in children / 中华实用儿科临床杂志

Objective@#To describe the clinical manifestations of central nerve system inflammatory demyelinating disease associated with anti-myelin oligodendrocyte glycoprotein antibody (MOG-IDD) in children, and to explore the clinical characteristics of the children.@*Methods@#The clinical and laboratory characteristics of the patients diagnosed in Beijing Children′s Hospital, Capital Medical University, from October 2016 to August 2018 were described, and the clinical data of the patients with unipolar and recurrent diseases were compared.@*Results@#A total of 50 patients were included, among whom the ratio of male to female was 24:26, and the average age of onset was (6.7±3.1) years old (0.4-12.6 years old). There was no significant difference in the age of onset between boys and girls(t=0.712, P=0.480). The main symptoms included fever (31/50 cases), encephalopathy (26/50 cases) and optic neuritis (22/50 cases), etc.In the last follow-up, 26 patients (52.0%) had a monophasic course and 24 patients (48.0%) had a recurrent course.There were age differences in encephalopathy and ataxia in the first episode of [(5.7±2.8) years old vs.(8.1±3.0) years old, (5.0±2.5) years old vs. (7.7±3.0) years old](t=2.746, P=0.009; t=2.837, P=0.007). The average number of recurrence was (2.1±1.4) times (1-7 times), in which 17 cases (70.8%) of recurrence presented within 12 months and 20 cases (83.3%) of recurrence presented within 24 months after onset.Convulsion incidences of recurrent cases were 10 cases and 13 cases respectively in the first episode and recurrent courses, which were significantly higher than those of monophasic cases (4 cases, 4 cases)(χ2=7.912, P=0.005; χ2=8.365, P=0.004). All patients were sensitive to first-line immunotherapy.Seven patients with recu-rrence were treated with mycophenolatemofetil, and 17 patients with repeated first-line therapy.In the last follow-up, all patients were in remission and 2 patients had mild neurological dysfunction.@*Conclusions@#MOG-IDD can occur in childhood.Encephalopathy and optic neuritis are the most common symptoms.Encephalopathy and ataxia are more common in young children.Convulsions may indicate the course of recurrence.

Glial response following diffuse axonal injury / 解剖学报

Objective To explore the glial response and the relationship with secondary axonal degeneration in rats after diffuse axonal injury (DAI). Methods Adult male Sprague-Dawley rats were randomly assigned to control or DAI groups sacrificed at 1, 2, 3, 5 and 7 days with 10 rats in each group. DAI model was made referring to modified Marmarou method and glial fibrillary acidic protein (G F A P), ionized calcium binding adaptor molecule-1 (Ibal), recombinant oligodendrocyte lineage transcription factor 2 (Olig2), CC-1, NG2 immunohistochemistry, TUNEL staining and transmission electron microscopy were performed in brain stem. Results The number of Ibal labeled positive cells was significantly increased at day 3 and day 7 after injury. Moreover, different hypertrophic morphology was identified after injury. There was no effect of DAI on GFAP expression in brain stem. Numbers of mature oligodendrocyte marker CC-1 immunoreactivity cells within brain stem were significantly decreased at each of the time points after injury. The number of TUNEL positive cells in brain stem was significantly increased with injured time. Olig2 expression was significantly increased throughout the first week and reached peak at day 3 after injury in brain stem. The number of NG2 labeled positive cells was significantly increased at day 3 and day 7 after DAI. Ultrastructural evidence showed myelin release then further developed as widespread delamination and collapse, and leading to degeneration of axonal partner. Conclusion Mature oligodendrocytes are vulnerable in DAI and myelin loss may contribute to axonal degeneration. OPCs proliferate with activation of microglia. This insight of glial response will further explain the pathophysiological mechanism of secondary axonal damage in DAI.