Remyelination Regulated by microRNAs in Neurodegenerative Diseases： A Review / 中国实验方剂学杂志

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.

Research status and prospect of remyelination in multiple sclerosis based on "inflammation-tissue" homeostatic coupling / 中国中药杂志

Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.

Transcriptome Analysis of Schwann Cells at Various Stages of Myelination Implicates Chromatin Regulator Sin3A in Control of Myelination Identity / 神经科学通报·英文版

Enhancing remyelination after injury is of utmost importance for optimizing the recovery of nerve function. While the formation of myelin by Schwann cells (SCs) is critical for the function of the peripheral nervous system, the temporal dynamics and regulatory mechanisms that control the progress of the SC lineage through myelination require further elucidation. Here, using in vitro co-culture models, gene expression profiling of laser capture-microdissected SCs at various stages of myelination, and multilevel bioinformatic analysis, we demonstrated that SCs exhibit three distinct transcriptional characteristics during myelination: the immature, promyelinating, and myelinating states. We showed that suppressor interacting 3a (Sin3A) and 16 other transcription factors and chromatin regulators play important roles in the progress of myelination. Sin3A knockdown in the sciatic nerve or specifically in SCs reduced or delayed the myelination of regenerating axons in a rat crushed sciatic nerve model, while overexpression of Sin3A greatly promoted the remyelination of axons. Further, in vitro experiments revealed that Sin3A silencing inhibited SC migration and differentiation at the promyelination stage and promoted SC proliferation at the immature stage. In addition, SC differentiation and maturation may be regulated by the Sin3A/histone deacetylase2 (HDAC2) complex functionally cooperating with Sox10, as demonstrated by rescue assays. Together, these results complement the recent genome and proteome analyses of SCs during peripheral nerve myelin formation. The results also reveal a key role of Sin3A-dependent chromatin organization in promoting myelinogenic programs and SC differentiation to control peripheral myelination and repair. These findings may inform new treatments for enhancing remyelination and nerve regeneration.

Protective effect and mechanism of ginsenoside Rb1 on repairing sciatic nerve injury in mice / 解剖学报

Objective To explore the effect and mechanism of ginsenoside Rb1 on the repair of sciatic nerve injury (SNI) in mice. Methods Seventy-eight adult male Kunming mice were randomly divided into sham group (26), SNI group (26), SNI+Rb1 group (26). The SNI+Rb1 group was given 10 mg/kg ginsenoside Rb1 (i.p.), and the SNI group and the sham group were given the same volume of normal saline. The injury method was established by squeezing the sciatic nerve. Sciatic functional index (SFI) was used to evaluate sciatic nerve function. Growth associated protein 43 (GAP43) immunofluorescent staining was used to detect neural regeneration and repair on day 14, and the structure changes of the myelin sheath of the injured segment were observed under transmission electron microscope. Ki67 and S100β were used to detect the proliferation and migration ability of Schwann cells, and Real-time PCR was used to detect the mRNA expression levels after crush on day 3 and day 7. Results SFI of SNI+Rb1 group was higher than SNI group. The HE result showed that the sciatic nerve was uniform in the SNI + Rb1 group. The result of immunofluorescent staining displayed that Rb1 enhanced GAP43

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.

Pinocembrin Promotes OPC Differentiation and Remyelination via the mTOR Signaling Pathway / 神经科学通报·英文版

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.

Advances about perineuronal nets in the repair of nerve function after spinal cord injury / 中国骨伤

Perineuronal nets (PNNs) is a complex network composed of highly condensed extracellular matrix molecules surrounding neurons. It plays an important role in maintaining the performance of neurons and protecting them from harmful substances. However, after spinal cord injury, PNNs forms a physical barrier that surrounds the neuron and limits neuroplasticity, impedes axonal regeneration and myelin formation, and promotes local neuroinflammatory uptake. This paper mainly describes the composition and function of PNNs of neurons and its regulatory effects on axonal regeneration, myelin formation and neuroinflammation after spinal cord injury.

Pinocembrin Promotes OPC Differentiation and Remyelination via the mTOR Signaling Pathway / 神经科学通报·英文版

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.

Study on the mechanism of quercetin promoting myelin regeneration in CPZ induced demyelinating mice model / 国际中医中药杂志

Objective@#To observe the effect of quercetin on myelin regeneration in desyelinating mice induced by cuprizone (CPZ).@*Methods@#A total of 50 C57BL/6J mice were randomly divided into normal control group, model group, low, medium and high dose quercetin groups, 10 mice in each group. In addition to the normal control group, mice demyelinating model was induced by feeding with 0.2% CPZ rodent feed. Quercetin solution was administered to the low, medium and high dose quercetin groups at 25, 50 and 100 mg/kg, and to the normal control group and the model group at 1 time/d. After 5 weeks of continuous gavage, the weight of mice was recorded every week, and the experiment of rotating bar was carried out. After 5 weeks, the changes of the myelin sheath in the corpus callosum of mice were observed by luxol fast blue (LFB) and transmission electron microscope (TEM). Immunofluorescence method was used to determine the protein expressions of myelin basic protein (MBP) and oligodendrocyte transcription 2actor (Olig2) in mouse brain tissue. The expression of MBP and cyclic nucleotide-3'phosphate hydrolase (CNPase) in mouse corpus callosum was determined by Western blot.@*Results@#After 2-5 weeks, compared with the model group, the body mass of the medium and high dose quercetin groups significantly increased (P<0.01), and the score of turning rod significantly increased (P<0.01). The LFB observation showed that the demyelination score of corpus callosum in low, medium and high dose quercetin groups (2.23 ± 0.25, 1.50 ± 0.15, 1.14 ± 0.97 vs. 2.83 ± 0.18) significantly decreased (P<0.01). TEM observation showed that the G-ratio value in low, medium and high dose quercetin groups (0.75 ± 0.05, 0.75 ± 0.08, 0.73 ± 0.08 vs. 0.87 ± 0.05) significantly reduced (P<0.01). Immunofluorescence observation showed that the positive expression of MBP (37.40 ± 2.41, 37.40 ± 1.14 vs. 24.40 ± 3.65) and Olig2 (7.40 ± 1.14, 4.60 ± 1.14 vs. 2.80 ± 0.84) in the medium and high dose quercetin groups significantly increased (P<0.05). WB showed that the expression of MBP protein (1.32 ± 0.12, 0.80 ± 0.34 vs. 0.21 ± 0.07) and CNPase protein (0.72 ± 0.13, 1.06 ± 0.36 vs. 0.36 ± 0.21) in the medium and high dose quercetin groups significantly increased (P<0.05).@*Conclusions@#Quercetin (50-100 mg/kg) can reduce myelin injury and promote myelin regeneration in CPZ mice, as a neuroprotective effect on CPZ mice.

Mechanisms underlying remyelination with special focus on demyelination models of multiple sclerosis / 浙江大学学报·医学版

Failure to remyelinate and rewrap the demyelinated axons has been revealed as the major hurdle for treatment of multiple sclerosis (MS), and the bottleneck is the inability of oligodendrocyte progenitor cell (OPC) to differentiate into mature oligodendrocyte. Remyelination is a spontaneous regenerative process, which includes activation, migration and differentiation of OPC, and is believed to protect the axon and further halt neurodegeneration. In recent years, studies have identified many potential drug targets for efficiently promoting OPC differentiation in demyelination models, such as metformin, clemostine, and drug targets as myelin transcription factor 1-like protein (Myt1L), N-methyl-D-aspartic acid (NMDA) receptor, connexin 43 (Cx43), G protein coupled receptor 17 (GPR17), κ opioid receptor (KOR), sterol 14α-demethylase (CYP51), Δ14-sterol reductase (TM7SF2), emopamil-binding protein (EBP). This review summarizes the recent progress on the mechanisms underlying the activation, migration and differentiation of OPC in remyelination with special focus on studies using demyelination models of MS, which may provide insights of further exploring new therapeutic strategies for MS.

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.

Novel Thermosensitive Heparin-poloxamer Hydrogel Bridge NGF to Treat Peripheral Nerve Injury in Diabetics Rats / 中国药学杂志

OBJECTIVE: To investigate the effects of NGF-HP thermosensitive hydrogel on facilitating structural and functional regeneration in diabetic rats with sciatic nerve crush injury. METHODS: Eight-week-old male SD rats (200-220 g) were intraperitoneally injected wither steptozocin(STZ) to induce diabetes. After success of model establishment, the sciatic nerve of the diabetes rats were made crushed through two vascular clips force. Muscle and skin were then closed with 5-0 stitches. Following surgery, the rats were randomly divided into three groups: PNI-diabetics group, free NGF group and NGF-HP hygrogel group. Each group received corresponding therapeutic drugs through a microsyringe. The motor recovery in all tested rats was assessed using Basso-Beattie-Bresnahan (BBB) locomotion scale and inclined plane test at indicated time points. After 30 d, rats were sacrificed, the crushed nerve and corresponding gastrocnemius muscle were harvested and the pathology index was assessed.The expressions of structural and functional proteins were detected through immunoblotting.The improvement of axon and myelination regeneration were evaluated via immunofluorescence, Masson′s trichrom stain and transmission electron microscope. RESULTS: NGF-HP not only had a good affinity for a certain amounts of nerve growth factor (NGF), but also controlled its release in a steady fashion in vitro. In vivo, compared with administration of direct free NGF, single injection of NGF-HP hydrogel was more effective at upregulating the expression of nerve associated structural and functional proteins, enhancing axonal regeneration and remyelination, as well as improving motor function recovery. CONCLUSION: This new type of hydrogel loaded with NGF shows striking effects on functional and morphometric recovery on peripheral nerve injury (PNI) following diabetes,which may provide a theoretical basis strategies for remedying PNI-diabetes in clinical populations.

Myt1L Promotes Differentiation of Oligodendrocyte Precursor Cells and is Necessary for Remyelination After Lysolecithin-Induced Demyelination / 神经科学通报·英文版

The differentiation and maturation of oligodendrocyte precursor cells (OPCs) is essential for myelination and remyelination in the CNS. The failure of OPCs to achieve terminal differentiation in demyelinating lesions often results in unsuccessful remyelination in a variety of human demyelinating diseases. However, the molecular mechanisms controlling OPC differentiation under pathological conditions remain largely unknown. Myt1L (myelin transcription factor 1-like), mainly expressed in neurons, has been associated with intellectual disability, schizophrenia, and depression. In the present study, we found that Myt1L was expressed in oligodendrocyte lineage cells during myelination and remyelination. The expression level of Myt1L in neuron/glia antigen 2-positive (NG2) OPCs was significantly higher than that in mature CC1 oligodendrocytes. In primary cultured OPCs, overexpression of Myt1L promoted, while knockdown inhibited OPC differentiation. Moreover, Myt1L was potently involved in promoting remyelination after lysolecithin-induced demyelination in vivo. ChIP assays showed that Myt1L bound to the promoter of Olig1 and transcriptionally regulated Olig1 expression. Taken together, our findings demonstrate that Myt1L is an essential regulator of OPC differentiation, thereby supporting Myt1L as a potential therapeutic target for demyelinating diseases.

Advances in mechanisms of microglial function on demyelination and remyelination in EAE model / 中国免疫学杂志

Inflammatory cells infiltration and demyelination in the central nervous system (CNS) are the main pathological characteristics of multiple sclerosis(MS),an autoimmune disease in the CNS.Most of the related pathological studies are carried out in the animal model experimental autoimmune encephalomyelitis(EAE).Microglia(MG) are the primary immune effector cells of the CNS and their activation can play complex roles in demyelination and remyelination during EAE.In detail,M1 phenotype is an important cause of demyelination and detrimental to remyelination while M2 phenotype can promote remyelination and inhibit demyelination.In this review,we not only focus on advances in the direct mechanisms of microglial function on demyelination and remyelination in EAE model,also the indirect mechanisms by astrocytes.

Targeting G protein-coupled receptors for the treatment of autoimmune diseases / 中国药理学与毒理学杂志

Our group is interested in the biological functions of G protein-coupled receptor (GPCR) and their roles in major diseases including autoimmune disease, neurodegenerative diseases, metabolic diseases, etc. In addition to the mechanism study, we also screen and develop drugs targeting GPCRs. In recent years, we also seek to study the mechanism of fate determination of stem cells with small molecule compounds. One of the autoimmune diseases we're particularly interested is Multiple Sclerosis (MS). MS is an inflammatory disease that is characterized by immune-mediated demyelin?ation and degeneration of the central nervous system. In the past few years, we've discovered that two GPCRs (CysLT1 and A2B) are critically involved in the development of MS by regulating the differentia?tion or function of immune cells. Blocking these receptors alleviates clinical symptoms of EAE, a mouse model of MS, indicating these receptors are potential drug targets for MS. Current drugs for MS all targets immune system. Although effective in reducing the relapse rate and the formation of new lesions, these drugs have very limited effects in preventing the progression of disability. Promoting oligodendrocyte progenitor cell differentiation, remyelination and subsequent functional recovery of the neurons have been proposed to be the new direction of MS therapy. Our recent study demonstrated that KOR, an opioid receptor, is important for oligodendrocyte-mediated remyelination in EAE, suggesting KOR might be a target to develop new MS therapies from a regenerative point of view.

Propentofylline reverses delayed remyelination in streptozotocin-induced diabetic rats

Objective The diabetic state induced by streptozotocin injection is known to impair oligodendroglial remyelination in the rat brainstem following intracisternal injection with the gliotoxic agent ethidium bromide (EB). In such experimental model, propentofylline (PPF) recently showed to improve myelin repair, probably due to its neuroprotective, antiinflammatory and antioxidant effects. The aim of this study was to evaluate the effect of PPF administration in diabetic rats submitted to the EB-demyelinating model. Materials and methods Adult male rats, diabetic or not, received a single injection of 10 microlitres of 0.1% EB solution into the cisterna pontis. For induction of diabetes mellitus the streptozotocin-diabetogenic model was used (50 mg/kg, intraperitoneal route – IP). Some diabetic rats were treated with PPF (12.5 mg/kg/day, IP route) during the experimental period. The animals were anesthetized and perfused from 7 to 31 days after EB injection and brainstem sections were collected for analysis of the lesions by light and transmission electron microscopy. Results Diabetic rats injected with EB showed larger amounts of myelin-derived membranes in the central areas of the lesions and considerable delay in the remyelinating process played by surviving oligodendrocytes and invading Schwann cells after the 15th day. On the other hand, diabetic rats that received PPF presented lesions similar to those of non-diabetic animals, with rapid remyelination at the edges of the lesion site and fast clearance of myelin debris from the central area. Conclusion The administration of PPF apparently reversed the impairment in remyelination induced by the diabetic state. Arch Endocrinol Metab. 2015;59(1):47-53 .

Esclerosis múltiple: enfermedad neurológica de alto impacto social: de vuelta al antiguo tratamiento / Multiple sclerosis, neurological disease with high social impact: back to the old treatment

Resumen La esclerosis múltiple (EM) es una enfermedad inmune-inflamatoria y crónico-degenerativa, que afecta a personas jóvenes y tiene un alto impacto social por los costos directos e indirectos. Objetivo: Regular el proceso neurodegenerativo a través de una adecuada modulación de los factores inflamatorios mediante el uso de metilprednisolona y la evaluación con estudios de resonancia magnética. Pacientes y métodos: Pacientes mujeres que se encuentran entre la 1ª y 5ª década de la vida, con diagnóstico de EM, que se incluyeron por cumplir con los criterios diagnósticos de McDonald 2010 (sobre todo la diseminación en tiempo y espacio). Se les administraron bolos de metilprednisolona de manera regular, aun cuando no presentaran recaídas y se evaluaron con estudios de resonancia magnética (RM) anual, con un seguimiento de hasta 15 años. Resultados: Se observa una marcada disminución de las lesiones en función del tiempo y la administración de los bolos de metilprednisolona, y entre los 3 y 10 años las lesiones desaparecen en su totalidad. Conclusiones: La administración de bolos de metilprednisolona de manera regular atenúa el proceso inflamatorio y el daño a la barrera hematoencefálica, y por lo tanto, coadyuva en la remielinización y previene la neurodegeneración.

Abstract Multiple sclerosis (MS) is a chronic inflammatory and immune-degenerative disease that affects young people and has a high social impact due to direct and indirect costs. Objective: Regulate neurodegenerative process through a suitable modulation of inflammatory factors by using methylprednisolone and evaluation with Magnetic Resonance studies. Patients and methods: Female patients between the 1st and 5th decade of life, with diagnosis of Multiple Sclerosis, were included in the study if they met the criteria of McDonal 2010 (specially space and time monitoring) methylprednisolone boluses were administered regularly, even when the patient had no relapses, and the patients were then evaluated with Magnetic Resonance per annum, with a follow-up of up to 15 years. Results: There is a marked decrease of lesion in function of time and the bolus administration of methylprednisolone, and lesions disappeared entirely after 3 to 10 years of administration. Conclusions: The regular bolus administration of methylprednisolone attenuates the inflammatory process and the damage to the blood brain barrier and thus contributes in preventing neurodegeneration and is coadyuvant in remyelination.

Expression pattern of transcription factor Olig2 in cuprizone-induced mouse model of acute demyelination / 中国实验动物学报

Objective To investigate the expression pattern of transcription factor Olig 2 in cuprizone-induced mouse model of acute demyelination .Methods C57BL/6 mice were fed with 0.2%cuprizone to induce acute demyelina-tion.Immunofluorescence and qRT-PCR were used, and Olig2, MBP and GFAP were detected in the brain tissues of con-trol group and cuprizone-treated groups for 6 weeks and recovery for 2 weeks.Results Severe demyelination occurred in the corpus callosum following 6-weeks exposure to cuprizone , while remyelination was detected in the white matter after the mice were given diet without cuprizone .In the normal mice , Olig2 was expressed in a low level , while the experessions of Olig2 and GFAP were significantly increased , and Olig2 +/GFAP+cells were detected after demyelination .But the expres-sion of MBP was below the normal level with demyelination .After recovery for 2 weeks, the experession of Olig2 was lower, but the experessions of MBP and GFAP were increased .Conclusions Olig2 may play an important role in the glial differ-entiation from neural progenitor cells into active astrocytes , and in the glial scar formation .

The Research Progress of Tumor Necrosis Factor Alpha in Multiple Sclerosis and Remyelination / 天津医药

Tumor necrosis factor (TNF)-αis a pleiotropic inflammatory cytokine, which is produced chiefly by acti?vated macrophages. Two forms of TNF-α, soluble and transmembrane, can bind tumor necrosis factor receptor (TNFR) 1 or TNFR2, respectively. Recently, a concept has emerged that TNF-α/TNFR pathway plays an important role in the pathogene?sis of multiple sclerosis and remyelination. TNFR1 induces death of oligodendrocytes via death receptor-mediated apoptosis, which leads to demyelination or other neurodegenerative changes. However, TNFR2 has a positive effect on multiple sclero?sis. It facilitates the proliferation and differentiation of oligodendrocyte precursor cells, thus promoting remyelination.