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

Experimental autoimmune encephalomyelitis (EAE) in Lewis rats is characterized by transient paralysis followed by recovery. To evaluate whether transient paralysis in EAE affects bone density, tibiae of EAE rats were morphologically investigated using micro-computed tomography and histology. The parameters of bone health were significantly reduced at the peak stage of EAE rats relative to those of controls (p < 0.05). The reduction of bone density was found to remain unchanged, even in the recovery stage. Collectively, the present data suggest that osteoporosis occurs in paralytic rats with monophasic EAE, possibly through the disuse of hindlimbs and/or autoimmune inflammation.
Animals ; Autoimmunity ; Bone Density ; Encephalomyelitis, Autoimmune, Experimental* ; Hindlimb ; Inflammation ; Osteoporosis* ; Paralysis ; Rats* ; Tibia

OBJECTIVETo observe the pathological changes of axonal injury in a rat model of experimental allergic encephalomyelitis (EAE).

METHODSWith HE, luxol fast blue and Bielschowsky staining, the expression of APP, MBP, SMI-32 and MBP in the brain and spinal cord of EAE rats using double-labeling indirect immunofluorescence.

RESULTSExtensive cuffing lesions of inflammatory cell infiltrations were found in the brain and spinal cord of the rats, accompanied by multiple lesions of demyelination, axonal disarrangement with vesicular loss. SMI-32 staining identified numerous nonphosphorylated neurofilament, indicating the presence of axonal injury. Axonal oval bodies formed by APP accumulation were found in the white matters of the spinal cord 14 days after EAE, suggesting that neuraxial damage occurred in the early stage of EAE which was not synchronous with myelin loss.

CONCLUSIONDifferent levels of inflammation occur in different stages of EAE, and inflammatory cell infiltration is the most obvious at the peak of EAE. Axonal injury occurs in the early stage of EAE and progresses over the entire disease course.

Animals ; Axons ; pathology ; Brain ; pathology ; Encephalomyelitis, Autoimmune, Experimental ; pathology ; Female ; Rats ; Rats, Wistar ; Spinal Cord ; pathology

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

Peroxisome proliferator-activated receptor gamma (PPARgamma) was identified as a cell-intrinsic regulator of Th17 cell differentiation. Th17 cells have been associated with several autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), inflammatory bowel disease (IBD), and collagen-induced arthritis. In this study, we confirmed PPARgamma-mediated inhibition of Th17 cell differentiation and cytokine production at an early stage. Treatment with ciglitazone, a PPARgamma ligand, reduced both IL-1beta-mediated enhancement of Th17 differentiation and activation of Th17 cells after polarization. For Th17 cell differentiation, we found that ciglitazone-treated cells had a relatively low proliferative activity and produced a lower amount of cytokines, regardless of the presence of IL-1beta. The inhibitory activity of ciglitazone might be due to decrease of CCNB1 expression, which regulates the cell cycle in T cells. Hence, we postulate that a pharmaceutical PPARgamma activator might be a potent candidate for treatment of Th17-mediated autoimmune disease patients.
Arthritis, Experimental ; Autoimmune Diseases ; Cell Cycle ; Cell Proliferation ; Cytokines ; Encephalomyelitis, Autoimmune, Experimental ; Humans ; Inflammatory Bowel Diseases ; Interleukin-17 ; PPAR gamma* ; T-Lymphocytes ; Th17 Cells*

Experimental autoimmune encephalomyelitis (EAE) in Lewis rats is an acute monophasic paralytic central nervous system disease, in which most rats spontaneously recover from paralysis. EAE in Lewis rats is induced by encephalitogenic antigens, including myelin basic protein. EAE is mediated by CD4+ Th1 cells, which secrete pro-inflammatory mediators, and spontaneous recovery is mediated by regulatory T cells. Recently, it was established that classically activated macrophages (M1 phenotype) play an important role in the initiation of EAE, while alternatively activated macrophages (M2 phenotype) contribute to spontaneous recovery from rat EAE. This review will summarize the neuroimmunological aspects of active monophasic EAE, which manifests as neuroinflammation followed by neuroimmunomodulation and/or neuroprotection, with a focus on the role of alternatively activated macrophages.
Animals ; Central Nervous System ; Encephalomyelitis, Autoimmune, Experimental ; Macrophages ; Myelin Basic Protein ; Neuroimmunomodulation ; Paralysis ; Rats ; T-Lymphocytes, Regulatory ; Th1 Cells

AIMTo observe the dynamic changes of heme oxygenase-1 (HO-1) mRNA and protein express in subfornical organ in rats with experimental allergic encephalomyelitis (EAE) to confirm that SFO is one of the sites for blood-bearing signaling molecules entering into brain.

METHODSEAE was induced by CFA-GPSCH on Wistar rats, we observed the levels of HO-1 mRNA and its protein expression with immunohistochemistry and in situ hybridization technology on 1 d, 7 d, 14 d, and 21 d after EAE induction in SFO of rats. The relationship between HO-1 and symptoms of EAE was also investigated.

RESULTSThe expression levels of HO-1 mRNA and its protein expression were very low in the brains of the control group, whereas they were enhanced gradually with pathological course in the brain and onsets of symptoms, signs of EAE. On 1 d after induction of EAE, positive cells of HO-1 mRNA and its protein expression were observed at SFO, but the labeled cells were rarely seen in the other brain regions. On 7 d, the positive cells increased markedly. On 14 d the levels of HO-1 mRNA and its protein expression in the brains reached the peak, the positive cells of HO-1 were mainly located at the choroid plexuses and SFO, as well as the regions around "sleeve-like" lesion foci, all of which were coincident with the locations of lesions of EAE. The changes of incidence, symptom, reduction of the body weight, and pathology lesions of EAE in rat brains were the most significant. On 21 d, the levels of HO-1 mRNA and its protein expression reduced gradually, which was in parallel with remitted symptoms of EAE. When a specific inhibitor of HO-1, Snpp9, was applied, the symptoms and pathological lesions of EAE in brains were mitigated markedly.

CONCLUSIONSFO may be one of the earliest sites for blood-bearing signaling molecules entering into brain. The dynamic changes of HO-1 mRNA and its protein expression are in parallel with the changes of symptoms and pathological lesions of EAE in the brains. Application of some inhibitors of HO-1 may be one of potential therapeutic methods for prevention and treatment of EAE.

Animals ; Encephalomyelitis, Autoimmune, Experimental ; metabolism ; Female ; Heme Oxygenase (Decyclizing) ; genetics ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; Subfornical Organ ; metabolism

Experimental allergic encephalomyelitis (EAE) lesions by autoimmune inflammatory mechanism are characterized by the activation of microglia and astrocytes during the peak symptomatic stage of the disease. Besides it is well known that ROS and nitric oxide (NO), which is come out from activated inflammatory cells, play important role in the pathogenesis of EAE lesions. And vitamin C (L-ascorbic acid), which may protect from the deleterious effect by reducing iron (Fe2+) or copper (Cu2+) ions and maintain tissue homeostasis by removing of oxygen free radical, is inevitable to help many enzymatic reactions of cells. Previous report already investigated expression and functional analysis on various vitamin C transporters of vitamin C in many cell types. However, the researches for the vitamin C transporters are mostly performed in the normal state but not disease model yet. Therefore, for the first time, we investigated to know whether the SVCT1, 2 immunoreactivity may be observed in the astrocyte of EAE rat spinal cord. In the comparison of control and peak time group, the number of SVCT1, 2 immunoreactive cell was inclined to increase (P<0.05) as respectively 100+/-29.93, 135+/-34.62 in the control group, and 179+/-54.29, 349+/-73.56 in the peak time group. SVCT2 immunoreactivity was not doubly colocalized with GFAP antibody in the control group. In contrast, the astrocytes of the peak time group showed SVCT2 immunoreactivity in the perivascualr region and the cell number of doubly (SVCT2, GFAP) colocalized was 15+/-5.67 (P<0.05). We are firstly demonstrated that, in the evolving processes of EAE, astrocytes are able to use the vitamin C via the SVCT2. Taken all findings into consideration, the present data on the typical anti-oxidant vitamin C and its transporters, which may play a role in removing ROS, could be considered as a target to the therapeutic strategy of EAE and is also very useful to identify the characterization of vitamin C in the biological organism.
Animals ; Ascorbic Acid ; Astrocytes ; Cell Count ; Copper ; Encephalomyelitis, Autoimmune, Experimental* ; Homeostasis ; Ions ; Iron ; Microglia ; Nitric Oxide ; Oxygen ; Rats ; Spinal Cord*

OBJECTIVE: We studied effects of dexamethasone on neurogenic bladder and paralysis in experimental autoimmune encephalomyelitis (EAE) rat model for multiple sclerosis. METHOD: Thirty-five female Lewis rats were used in the study. Thirteen rats used as normal cystometrogram controls. Twenty-two rats induced EAE were divided into two groups: ten rats as control and twelve rats as dexamethasone injection group. Bladder dysfunction by cystometrogram, severity of weakness, and duration of paralysis were evaluated every other day after the onset of paralysis. RESULTS: Dexamethasone injection group compared to control group presented short duration of bladder dysfunction (2.5 vs. 4.2 day, p<0.05) and paralysis (4.5 vs. 7.3 day, p<0.05). There was a trend for lesser paralysis in the dexamethasone injection group, than control group (weakness scores were 2.4 vs. 3.6, p>0.05), but it was not statistically significant. CONCLUSION: Dexamethasone ameliorates the course of paralysis and bladder dysfunction in EAE. We suggest that dexamethasone treatment is an effective method in treating neurogenic bladder and paralysis in multiple sclerosis.
Animals ; Dexamethasone* ; Encephalomyelitis, Autoimmune, Experimental* ; Female ; Humans ; Models, Animal ; Multiple Sclerosis ; Paralysis ; Rats* ; Urinary Bladder ; Urinary Bladder, Neurogenic*

The primary chemical components of Astragalus membranaceus include polysaccharides, saponins, flavonoids, and amino acids. Recent studies have shown that Astragalus membranaceus has multiple functions, including improving immune function and exerting antioxidative, anti-radiation, anti-tumor, antibacterial, antiviral, and hormone-like effects. Astragalus membranaceus and its extracts are widely used in clinical practice because they have obvious therapeutic effects against various autoimmune diseases and relatively less adverse reaction. Multiple sclerosis (MS) is an autoimmune disease of central nervous system (CNS), which mainly caused by immune disorder that leads to inflammatory demyelination, inflammatory cell infiltration, and axonal degeneration in the CNS. In this review, the authors analyzed the clinical manifestations of MS and experimental autoimmune encephalomyelitis (EAE) and focused on the efficacy of Astragalus membranaceus and its chemical components in the treatment of MS/EAE.
Animals ; Humans ; Astragalus propinquus/chemistry* ; Multiple Sclerosis/drug therapy* ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Drugs, Chinese Herbal/chemistry* ; Polysaccharides