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.

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.

Dynamic change OX40/OX40L mRNA in experimental allergic neuritis / 中南大学学报(医学版)

OBJECTIVE@#To examine the expression of mRNA of Oxford 40(OX40) and Oxford 40 ligand(OX40L) in the sciatic nerve, spleen, peripheral blood mononuclear cells and lymph nodes of experimental allegic neuritis (EAN).@*METHODS@#Thirty-six Lewis rats were randomly assigned into an EAN group and a CFA group. The rats were sacrificed on 9th, 17th, and 26th day after immunization. OX40 and OX40L mRNA was detected by reverse transcription polymerase chain reaction in the spleen, sciatic nerves, peripheral blood mononuclear cells and lymphonodes.@*RESULTS@#The peak of clinical course came on 17th day after the immunization in EAN. The mRNA expression of OX40/OX40L was higher on 8th day and 17th day than that on 26th day after the immunization (P<0.05). There was significant difference between the EAN group and the CFA group at the 3 time points (P<0.05); rats in the CFA group didn't have any clinical manifestations. The mRNA expression of OX40 and OX40L in the EAN group raised in the sciatic nerves and lymph nodes at the above 3 time points (P<0.05). Weak expression was seen in the peripheral blood mononuclear cells.@*CONCLUSION@#OX40 and OX40L may play a role in the pathogenesis of experimental allegic neuritis.

Increased phosphorylation of c-Jun NH (2)-terminal protein kinase in the sciatic nerves of Lewis rats with experimental autoimmune neuritis

The phosphorylation of c-Jun NH (2)-terminal protein kinase (JNK), one of the mitogen-activated protein kinases, was analyzed in the sciatic nerves of Lewis rats with experimental autoimmune neuritis (EAN). Western blot analysis showed that the expression levels of both phosphorylated JNK1 (p-JNK1, approximately 46 kDa) and phosphorylated JNK2 (p-JNK2, approximately 54 kDa) in the sciatic nerves of rats with EAN increased significantly (p < 0.05) at day 14 post-immunization (PI) and remained at this level at days 24 and 30 PI, with a slight decrease. In EANaffected sciatic nerves, there was intense immunostaining for p-JNK in the infiltrating inflammatory cells (especially ED1- positive macrophages) and Schwann cells on days 14-24 PI, compared with those of controls. Some macrophages with increased p-JNK immunoreactivity was shown to be apoptotic, while some Schwann cells remained survived in this rat EAN model, suggesting that JNK is differentially involved in the EAN-affected sciatic nerves. These findings suggest that JNK phosphorylation is closely associated with the clearance of inflammatory cells as well as the activation of Schwann cells in the EAN affected sciatic nerves.

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.

Expression and significance of integrin alpha6beta4 in experimental allergic neuritis / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expression of the integrin alpha6beta4 in experimental allergic neuritis (EAN) and the relationship of the integrin alpha6beta4 with functional states of Schwann cells (Sc) as well as the injury and repair of the myelin during EAN.</p><p><b>METHODS</b>EAN was induced in Lewis rats and sciatic nerves were resected in 18 EAN and 3 normal rats. The expression of tissue integrin alpha6beta4 was analyzed during the course of EAN induction and in controls by in situ hybridization and semi-quantitative RT-PCR.</p><p><b>RESULTS</b>The detection of integrin alpha6 and beta4 subunit by hybridization in situ demonstrated that expression of alpha6 subunit present no significant changes during the course of EAN, while expression of beta4 declined in the early phase, showing less positive signals than those of the control, and restored its expression in the later or recovery phase. The changes of expression of integrin alpha6 and beta4 in EAN were confirmed by semi-quantitative PT-PCR, using GAPDH as the internal standard.</p><p><b>CONCLUSIONS</b>The degeneration and injury of Sc caused by inflammation affect the expression of integrin, which shows similar changes in Sc during embryogenesis, indicating alpha6beta4 may be a marker of Sc differentiation and at least an important molecule to mark the course of EAN. The expression of alpha6beta4 correlate with the injury and repair of myelin during EAN.</p>

Síndrome de Guillain-Barré: etiología y patogénesis / Guillain-Barre syndrome: etiology and pathogenesis

Guillain-Barre syndrome (GBS) is a reactive, self-limited, monophasic disease triggered by a preceding bacterial or viral infection. GBS has also been linked to underlying systemic diseases, certain malignancies, surgery, pregnancy, trauma severe infection, and tissue transplantation (bone marrow and organs). Although its pathogenesis is unclear, it is likely to be a consequence of an immune mediated process. Therefore, we believe that GBS results from an aberrant immune response that somehow mistakenly attacks the nerve tissue of its host, most probably by recognizing a molecular similar epitope mechanism (molecular mimicry). Immune reactions against these epitopes result in acute inflammatory demyelinating neuropathy or acute axonal forms. GBS has a worldwide distribution with an annual incidence of approximately 1.2-8.6 cases per 100,000 people. Both genders are at similar risk (but there is a slight male predominance). All ages are affected, although the distribution is bimodal. The supporting measures are critically important to provide optimal treatment. Immunomodulation with plasma exchange and intravenous immunoglobulin treatments shorten the disease course. Outcome is generally good, with virtually full recovery in 70-80 of the patients. In this review physiopathological aspects and clinical implications of GBS are fully discussed.

Liquen plano generalizado tratado con talidomida: reporte de cuatro casos y revisión de la literatura / Lichen planus generalized treated with talidomide: report four case and review of the literature

La Talidomida (agente hipnótico) ha sido utilizado en un gran número de afecciones dermatológicas de tipo inflamatorio como reacción leprosa, prúrigo actínico, prúrigo nodularis de hyde y pioderma gangrenoso con probada utilidad. Su efecto beneficioso se debe a su probable acción inmunomoduladora y/o antiinflamatoria. En vista de las dificultades terapéuticas y el rol inmunológico en la etiología del liquen plano, nosotros decidimos administrar un esquema terapéutico con Talidomida, en cuatro pacientes (hombres y mujer postmenopáusica debido a su potencial teratogénico) con lesiones extensas y sintomáticas, obteniendo buenos resultados