Multiple sclerosis (MS) is a T-lymphocyte-mediated autoimmune disease that is characterized by inflammation in the central nervous system (CNS). Although many disease-modifying therapies (DMTs) are presumed effective in patients with MS, studies on the efficacy and safety of DMTs for preventing MS relapse are limited. Therefore, we tested the immunosuppressive anti-inflammatory effects of oral-formulated tacrolimus (FK506) on MS in a mouse model of experimental autoimmune encephalomyelitis (EAE). The mice were randomly divided into 3 experimental groups: an untreated EAE group, a low-dose tacrolimus-treated EAE group, and a high-dose tacrolimus-treated EAE group. After autoimmunization of the EAE mice with myelin oligodendrocyte glycoprotein, symptom severity scores, immunohistochemistry of the myelination of the spinal cord, and western blotting were used to evaluate the EAE mice. After the autoimmunization, the symptom scores of each EAE group significantly differed at times. The group treated with the larger tacrolimus dose had the lowest symptom scores. The tacrolimus-treated EAE groups exhibited less demyelination and inflammation and weak immunoreactivity for all of the immunization biomarkers. Our results revealed that oral-formulated tacrolimus inhibited the autoimmunization in MS pathogenesis by inactivating inflammatory cells.
Animals ; Autoimmune Diseases ; Biomarkers ; Blotting, Western ; Central Nervous System ; Demyelinating Diseases ; Encephalomyelitis, Autoimmune, Experimental* ; Humans ; Immunization ; Immunohistochemistry ; Inflammation ; Mice* ; Multiple Sclerosis ; Myelin Sheath ; Myelin-Oligodendrocyte Glycoprotein ; Neuromyelitis Optica ; Recurrence ; Spinal Cord ; Tacrolimus*

Acute disseminated encephalomyelitis(ADEM) and acute relapsing disseminated encephalomyelitis(ARDEM) are representative demyelination diseases that occur among young children with a fulminant onset similar to encephalitis or meningitis. The diseases often occur after some viral infection of immunization and the etiology of these diseases is considered to be an autoimmune response because of the similarity in pathologic findings to experimental allergic encephalomyelitis. Cerebral computed tomography(CT) findings of demyelination in ADEM or ARDEM show normal to low density areas in the white matter. In cerebral MRI findings, a scattered distinct high intensity lesion considered to be demyelination is observed in 72-weighted imaging even in the early stages. ADEM is usually monophasic, but recurrent episodes may occure. When ADEM is reccurent, the distinction from multiple sclerosis becomes difficult. We report here a case of acute relapsing disseminated encephalomyelitis(ARDEM) in a 9 years old male child who experence ADEM, 3 times.
Autoimmunity ; Child ; Demyelinating Diseases ; Encephalitis ; Encephalomyelitis, Acute Disseminated* ; Encephalomyelitis, Autoimmune, Experimental ; Humans ; Immunization ; Magnetic Resonance Imaging ; Male ; Meningitis ; Multiple Sclerosis

BACKGROUND: Multiple sclerosis (MS) is an immune-associated inflammatory disorder of the central nervous system and results in serious disability. Although many disease-modifying therapy drugs have been developed, these drugs have shown limited clinical efficacy and some adverse effects in previous studies, therefore, there has been reasonable need for less harmful and cost-effective therapeutics. Herein, we tested the anti-inflammatory effect of sulforaphane (SFN) in a mouse model of experimental autoimmune encephalomyelitis (EAE). METHODS: The EAE mice were randomly assigned into two experimental groups: the phosphate-buffered saline (PBS)-treated EAE group and SFN-treated EAE group. After EAE mice induction by auto-immunization against the myelin oligodendrocyte glycoprotein peptide, we evaluated EAE symptom scores and biochemical analyses such as infiltration of inflammatory cells and demyelination of the spinal cord. Furthermore, western blotting was performed using the spinal cords of EAE mice. RESULTS: In the behavioral study, the SFN-treated EAE mice showed favorable clinical scores compared with PBS-treated EAE mice at the 13th day (1.30 ± 0.15 vs. 1.90 ± 0.18; P = 0.043) and 14th day (1.80 ± 0.13 vs. 2.75 ± 0.17; P = 0.003). Additionally, the biochemical studies revealed that SFN treatment inhibited the inflammatory infiltration, demyelinating injury of the spinal cords, and the up-regulation of inducible nitric oxide synthase in the EAE mice. CONCLUSION: The SFN treatment showed anti-inflammatory and anti-oxidative effects in the EAE mice. Conclusively, this study suggests that SFN has neuroprotective effects via anti-inflammatory processing, so it could be a new therapeutic or nutritional supplement for MS.
Animals ; Blotting, Western ; Central Nervous System ; Demyelinating Diseases ; Encephalomyelitis, Autoimmune, Experimental ; Mice ; Multiple Sclerosis ; Myelin-Oligodendrocyte Glycoprotein ; Neuromyelitis Optica ; Neuroprotective Agents ; Nitric Oxide Synthase Type II ; Spinal Cord ; Treatment Outcome ; Up-Regulation

Erythropoietin (EPO) is known to have numerous biological functions. While its primary function is during haematopoiesis, recent studies have shown that EPO plays important role in cytoprotection, immunomodulation, and antiapoptosis. These secondary functions of EPO are integral to tissue protection following hypoxic injury, ischemia-reperfusion injury, and spinal cord injury in the central nervous system. This review focuses on experimental evidence documenting the neuroprotective effects of EPO in organ-specific autoimmune nervous system disorders such as experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune neuritis (EAN). In addition, the immunomodulatory role of EPO in the pathogenesis of EAE and EAN animal models of human multiple sclerosis and Guillain-Barre syndrome, respectively, will be discussed.
Autoimmune Diseases ; Central Nervous System ; Cytoprotection ; Encephalomyelitis ; Encephalomyelitis, Autoimmune, Experimental ; Erythropoietin ; Guillain-Barre Syndrome ; Hematopoiesis ; Humans ; Immunomodulation ; Models, Animal ; Multiple Sclerosis ; Nervous System Diseases ; Neuritis, Autoimmune, Experimental ; Neuroprotective Agents ; Reperfusion Injury ; Spinal Cord Injuries

The International Pediatric Multiple Sclerosis Study Group (IPMSSG) put forward the 2007 version of the diagnostic criteria for multiple sclerosis and other immune-mediated demyelinating diseases of the central nervous system in children in 2007 ("2007 version" for short). In 2012, IPMSSG proposed the new diagnostic criteria with reference to the latest research achievements of 150 members ("2012 version" for short). The 2012 version of the consensus statements covers the diagnostic criteria for acute disseminated encephalomyelitis, clinically isolated syndrome, neuromyelitis optica, and multiple sclerosis in children. As the two IPMSSG members in China, the authors give an interpretation of the 2012 version of the consensus statements with reference to related literature and clinical and scientific experience. The authors focus on how the 2012 version comprehensively and thoroughly elaborates on the clinical features, diagnostic criteria, influencing factors, and new ideas of acute demyelinating diseases of the central nervous system in children. These become more operable in clinical diagnosis and treatment of multiple sclerosis and other immune-mediated demyelinating diseases of the central nervous system in children.
Child ; Consensus ; Demyelinating Diseases ; diagnosis ; Encephalomyelitis, Acute Disseminated ; diagnosis ; Humans ; Multiple Sclerosis ; diagnosis ; Neuromyelitis Optica ; diagnosis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination, focal infiltration of inflammatory cells and axonal injury, which leads to loss of neurological function. The exact cause of the disease remains unclear, but an autoimmune response directed against CNS antigens is suspected. Studies in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, have provided important insights into mechanisms of T cell-mediated CNS autoimmune disease. It appears likely that when a genetically susceptible host encounters a common environmental antigen (such as an infectious organism), a process called 'molecular mimicry' results in the peripheral activation of cross-reactive T cells that can migrate to the CNS and mount pro-inflammatory responses to myelin epitopes. This review describes the current understanding on the immunopathogenesis of MS and the mechanisms of action of currently available disease-modifying therapies in the context of the underlying immunopathogenic processes they are thought to affect.
Autoimmune Diseases ; Autoimmunity ; Axons ; Central Nervous System ; Demyelinating Diseases ; Encephalomyelitis, Autoimmune, Experimental ; Epitopes ; Models, Animal ; Multiple Sclerosis* ; Myelin Sheath ; T-Lymphocytes

Schilder's disease or myelinoclastic diffuse sclerosis (MDS) is a rare variant of multiple sclerosis. We report a 66-year-old woman with progressive motor weakness and diffuse white matter degeneration on MRI, which satisfies the Poser's restrictive criteria of MDS. As previously reported cases of probable Schilder's disease did not meet the criteria correctly, we consider our patient is the first pathology-proven case of MDS in Korea.
Aged ; Demyelinating Diseases ; Diffuse Cerebral Sclerosis of Schilder ; Female ; Humans ; Multiple Sclerosis

No abstract available.
Diffuse Cerebral Sclerosis of Schilder*

Balo's concentric sclerosis is regarded as a rare variant of multiple sclerosis. Traditionally, Balo's concentric sclerosis was a post-mortem diagnosis, but the recent introduction of brain magnetic resonance imaging (MRI) scans may allow noninvasive access without biopsy. Brain MRI findings of Balo's concentric sclerosis is characteristic concentric configuration of alternating bands of white matter of different pathology, with relatively preserved myelination alternating with regions of demyelination in the cerebral white matter. We report a case of Balo's concentric sclerosis with recurrent optic neuritis.
Biopsy ; Brain ; Demyelinating Diseases ; Diagnosis ; Diffuse Cerebral Sclerosis of Schilder* ; Humans ; Magnetic Resonance Imaging ; Multiple Sclerosis ; Myelin Sheath ; Optic Neuritis* ; Pathology

Experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), reflects pathophysiologic steps in MS such as the influence of T cells and antibodies reactive to the myelin sheath, and the cytotoxic effect of cytokines. Galectin-9 (Gal-9) is a member of animal lectins that plays an essential role in various biological functions. The expression of Gal-9 is significantly enhanced in MS lesions; however, its role in autoimmune disease has not been fully elucidated. To identify the role of Gal-9 in EAE, we measured changes in mRNA and protein expression of Gal-9 as EAE progressed. Expression increased with disease progression, with a sharp rise occurring at its peak. Gal-9 immunoreactivity was mainly expressed in astrocytes and microglia of the central nervous system (CNS) and macrophages of spleen. Flow cytometric analysis revealed that Gal-9+CD11b+ cells were dramatically increased in the spleen at the peak of disease. Increased expression of tumor necrosis factor (TNF)-R1 and p-Jun N-terminal kinase (JNK) was observed in the CNS of EAE mice, suggesting that TNF-R1 and p-JNK might be key regulators contributing to the expression of Gal-9 during EAE. These results suggest that identification of the relationship between Gal-9 and EAE progression is critical for better understanding Gal-9 biology in autoimmune disease.
Animals ; Antibodies ; Astrocytes ; Autoimmune Diseases ; Biology ; Central Nervous System ; Cytokines ; Disease Progression ; Encephalomyelitis, Autoimmune, Experimental* ; Humans ; Lectins ; Macrophages ; Mice ; Microglia ; Models, Animal ; Multiple Sclerosis ; Myelin Sheath ; Phosphotransferases ; RNA, Messenger ; Spleen ; T-Lymphocytes ; Tumor Necrosis Factor-alpha