Effect of fasudil on experimental autoimmune neuritis and its mechanisms of action

This study aimed to investigate the therapeutic effect of fasudil on treating experimental autoimmune neuritis (EAN). Twenty-four EAN mice were randomly assigned to fasudil treatment (Fasudil group) or saline treatment (EAN model group) for 28 days. Clinical symptom score was evaluated every other day; inflammatory cell infiltration, demyelination, anti-myelin basic protein (MBP), inflammatory cytokines, inducible nitric oxide synthase (iNOS), and arginase-1 were detected in sciatic nerves at day 28. Th1, Th2, Th17, and Tregs proportions in splenocytes were detected at day 28. Clinical symptom score was found to be attenuated in the Fasudil group compared to the EAN model group from day 12 to day 28. Sciatic nerve inflammatory cell counts by HE staining and demyelination by luxol fast blue staining were both reduced, while MBP was increased in the Fasudil group compared to the EAN model group at day 28. Interferon γ (IFN-γ) and interleukin (IL)-17 were reduced, while IL-4 and IL-10 were elevated in the Fasudil group at day 28. Sciatic nerve M1 macrophages marker iNOS was decreased while M2 macrophages marker arginase-1 was increased in the Fasudil group at day 28. CD4+IFN-γ+ (Th1) and CD4+IL-17+ (Th17) cell proportions were both decreased, CD4+IL-4+ (Th2) cell proportion was similar, while CD25+FOXP3+ (Treg) cell proportion in splenocytes was increased in the Fasudil group. In summary, fasudil presented a good therapeutic effect for treating EAN by attenuating Th1/Th17 cells and promoting Tregs activation as well as M2 macrophages polarization.

Capsaicin inhibits experimental autoimmune neuritis in rats through inhibition of autophagy activity / 中国药理学通报

Aim To observe the effect of capsaicin on the experimental autoimmune neuritis (EAN) in rats and explore the mechanism.Methods To induce EAN,male Lewis rats were immunized with peripheralnerve myelin sheath antigen (P257481) peptide and complete Freund's adjuvant (CFA) mixed liquor.Rapamycin (RAPA,2.5 mg · kg-1) was administered by intraperitoneal injection 0.5 h after immunization and capsaicin (1 mg · kg-1 · d-1) was administered by intragastric administration 1.0 h after immunization for 15 days.The incidence and clinical characteristics of EAN were observed.The clinical scores of neurological signs were completed and body weight was measured.Pathological morphology of sciatic nerve was observed by HE staining and Lauck fast blue staining.Ultrastructure of sciatic nerve was observed by transmission electron microscope.Levels of serum tumor necrosis factor alpha (TNF-α),interferon gamma (IFN-γ),interleukin 1β (IL-1β) and intedeukin-6 (IL-6) were tested by enzyme linked immunosorbent assay (ELISA).Expressions of autophagy related protein were measured by Western blot.Results Compared with EAN group,the clinical scores of neurological signs significantly decreased from day 7 to day 16 of post-immunization (P ＜ 0.05),body weight significantly increased from day 3 to day 16 of post-immunization (P ＜ 0.05),demyelination obviously decreased,inflammatory cell infiltration number obviously decreased (P ＜ 0.05),the levels of TNF-α,IFN-γ,IL-1β and IL-6 significantly decreased (P ＜ 0.05),the number of autophagosome in axon of sciatic nerve significantly decreased (P ＜ 0.05),and expressions of Beclin-1 and LC3-Ⅱ and the ratio of LC3-Ⅱ and LC3-Ⅰ were significantly down-regulated,and the expression of p62 was significantly up-regulated (P ＜ 0.05) in EAN + capsaicin group.Rapamycin partially reversed the action of capsaicin.Conclusions Capsaicin inhibits EAN in rats,and the mechanism may be related with the inhibition of autophagy activity.

Erythropoietin and autoimmune neuroinflammation: lessons from experimental autoimmune encephalomyelitis and experimental autoimmune neuritis / 대한해부학회지

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.

Increased expression of osteopontin in the spinal cords of Lewis rats with experimental autoimmune neuritis

To investigate the pattern of expression of osteopontin (OPN) in tissues of the central nervous system (CNS) responding to peripheral immunological stimulation, the expression of OPN was studied in the spinal cord of rats with experimental autoimmune neuritis (EAN). In this model system, the sciatic nerves and spinal nerve roots are the target organs of EAN and the spinal cord is a remote organ that may be indirectly affected. OPN was constitutively expressed in some astrocytes adjacent to the pia mater and neurons in normal rats. In rats with EAN, OPN was increased in the same cells and in some inflammatory cells, including macrophages in the subarachnoid space. Expression of CD44, a receptor of OPN, was weak in normal spinal cord tissue and increased in the entire spinal cord parenchyma in rats with EAN, as well as in inflammatory cells. These findings suggest that inflammatory cells as well as reactive astrocytes are major sources of OPN and CD44 in the spinal cord of rats with EAN. Further study is needed to elucidate the functional role of OPN in the spinal cord affected by EAN.

The mRNA expression of TLR4,TLR9 in experimental autoimmune neuritis induced by P0 180-199 and effects of TWP on it / 中国免疫学杂志

Objective:To observe the dynamic expression of mRNA of TLR4 and TLR9 in Lewis rats with experimental autoimmune neuritis(EAN) and the effect of TWP on the disease.Methods:Male Lewis rats were immunized with P0 180-199(100 microgram),TWP was profused into post-immunization rats’ stomach daily.The clinical signs of rats and pathological changes in the sciatic nerves were observed.TLR4 and TLR9 were detected by RT-PCR dynamically which spleens,sciatic nerves and peripheral blood lymphonodes as sample.Results:EAN group got the peak of clinical score at the 17 d.p.i,and ameliorated obviously at 33 d.p.i,and the mRNA expression of TLR4 got the peak at the 16 d.p.i,then reduced gradually(P

Preventive effect of immune tolerance induced by immature myeloid dendritic cell loading P2 58-73 peptide in experimental autoimmune neuritis / 临床神经病学杂志

Objective To observe the preventive effect of immune tolerance induced by immature myeloid dendritic cell(iMDC) loading P2 58-73 peptide(P2 58-73aa-iMDC) in experimental autoimmune neuritis(EAN),and the effect on the expression of IFN-? and IL-33 mRNA.Methods(1)The iMDC were cultured in vitro for loading P2 58-73aa.(2) 21 adult female Lewis rats were randomly divided into the EAN(A)group,iMDC(B)group and P2 58-73aa-iMDC(C)group,and subcutaneously injected PBS,iMDC and P2 58-73aa-iMDC respectively.After 7 d,all the rats were immunized with P2 53-78aa and complete freunds adjuvant(CFA) to inducing EAN.Then,the situation of onset were observed and clinical score were evaluated till 16 d(the crest-time of onset) after immunization.(3) The lymphocyte proliferative response were assayed by 3H-TdR incorporation.The expression of IL-33,IFN-? mRNA in sciatic nerves,spleen and lymph node were detected by RT-PCR.Results(1)In the crest-time of onset,the clinical scores in groups A,B and C were(7.4?1.9),(5.2?1.6) and(3.4?0.9) respectively.There were significant differences between each two groups(allP