Asunto(s)
Lateralidad Funcional/fisiología , Enfermedad de la Neurona Motora/diagnóstico , Enfermedad de la Neurona Motora/fisiopatología , Vías Nerviosas/fisiopatología , Reflejo Anormal/fisiología , Telencéfalo/patología , Telencéfalo/fisiopatología , Músculos Faciales/inervación , Músculos Faciales/fisiopatología , Nervio Facial/fisiopatología , Humanos , Enfermedad de la Neurona Motora/patología , Vías Nerviosas/patología , Examen Neurológico/métodos , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Tractos Piramidales/patología , Tractos Piramidales/fisiopatología , Tractos Espinotalámicos/patología , Tractos Espinotalámicos/fisiopatologíaAsunto(s)
Esclerosis Amiotrófica Lateral/inmunología , Autoanticuerpos/sangre , Gangliósido G(M1)/inmunología , Anciano , Esclerosis Amiotrófica Lateral/genética , Especificidad de Anticuerpos , Autoanticuerpos/biosíntesis , Autoanticuerpos/inmunología , Progresión de la Enfermedad , Femenino , Humanos , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Axonal injury initiates a process of neuronal degeneration, with resulting death of neuronal cell bodies. We show here that in C57BL/6J mice, previously shown to have a limited ability to manifest a post-traumatic protective immunity, the rate of neuronal survival is increased if IL-6 is deficient during the first 24 hours after optic nerve injury. Immunocytochemical staining preformed 7 days after the injury revealed an increased number of activated microglia in the IL-6-deficient mice compared to the wild-type mice. In addition, IL-6-deficient mice showed an increased resistance to glutamate toxicity. These findings suggest that the presence of IL-6 during the early post-traumatic phase, at least in mice that are susceptible to autoimmune disease development, has a negative effect on neuronal survival. This further substantiates the contention that whether immune-derived factors are beneficial or harmful for nerve recovery after injury depends on the phenotype of the immune cells and the timing and nature of their dialog with the damaged neural tissue.
Asunto(s)
Interleucina-6/deficiencia , Neuronas/fisiología , Traumatismos del Nervio Óptico/fisiopatología , Animales , Supervivencia Celular/efectos de los fármacos , Resistencia a Medicamentos , Encefalomielitis Autoinmune Experimental/genética , Femenino , Predisposición Genética a la Enfermedad , Ácido Glutámico/envenenamiento , Interleucina-6/genética , Interleucina-6/farmacología , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados/genética , Compresión Nerviosa , Degeneración Nerviosa/etiología , Traumatismos del Nervio Óptico/patología , Células Ganglionares de la Retina/patología , Células Ganglionares de la Retina/fisiologíaRESUMEN
Induction of myelin gene expression denotes the last stage of differentiation of myelinating glial cells. Following peripheral nerve transection, Schwann cells (SC) lose myelin gene expression and proliferate, resembling premyelinating embryonic SC (eSC). We show that a fusion protein of the soluble interleukin-6 receptor to interleukin-6 (IL6RIL6), a potent activator of the gp130 signaling receptor, is an inducer of MBP and Po gene products in rat E18 embryonic dorsal root ganglia (DRG) 3 day cultures. Cells whose growth is dependent on the IL6RIL6 chimera were isolated from DRG. These cells (designated CH cells) express Krox-20, as do promyelinating and myelinating SC (mSC). IL6RIL6 induces Po and MBP in CH cells and their cocultures with neurons. In addition, IL6RIL6 leads to a disappearance of Pax-3, a marker of eSC and nonmyelinating Schwann cells (nmSC). Glial fibrillary acidic protein, present in nmSC, is not significantly induced by IL6RIL6. The CH cells acquire glial morphology when exposed to IL6RIL6 and cover axons in cocultures. In a sciatic nerve-derived SC line, IL6RIL6 also induces Po and triggers a rapid attachment along axons. In vivo administration of IL6RIL6 intraperitoneally to rats after sciatic nerve transection and resuture increases 4-fold the number of myelinated nerve fibers (MF) measured on day 12, 2.5-5 mm distal to the suture. The stimulation by IL6RIL6 treatment is highest (7.1-fold) at the more distant 5 mm site, and the thickness of myelin sheaths is increased. Compared to known SC growth factors, the gp130 activator IL6RIL6 appears to combine both in vitro mitogenic effects and promotion of myelin gene expression.
Asunto(s)
Interleucina-6/metabolismo , Proteína Básica de Mielina/genética , Vaina de Mielina/fisiología , Regeneración Nerviosa/fisiología , Receptores de Interleucina-6/metabolismo , Nervio Ciático/fisiología , Animales , Diferenciación Celular/fisiología , Células Cultivadas , Ganglios Espinales/citología , Expresión Génica/fisiología , Técnicas In Vitro , Interleucina-6/genética , Microscopía Electrónica , Proteína P0 de la Mielina/genética , Fibras Nerviosas Mielínicas/fisiología , Fibras Nerviosas Mielínicas/ultraestructura , Ratas , Ratas Endogámicas Lew , Receptores de Interleucina-6/genética , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Células de Schwann/citología , Células de Schwann/fisiología , Células de Schwann/ultraestructura , Nervio Ciático/cirugíaRESUMEN
OBJECTIVE: Recently, a strong correlation between the increase in hypointense lesion load on T1 weighted spin echo images, and the increase in disability was reported. Although the effect of interferon-beta has been demonstrated both in reducing exacerbation rate, frequency of enhancing lesions, and accumulation of disease burden on T2 weighted images, the impact on the accumulation of hypointense lesions has not yet been evaluated. The aims of the present study were: (a) to assess for the first time the effect of interferon-beta-1a on T1 weighted MRI hypointense lesion volume; and (b) to evaluate the relation between changes on hypointense, hyperintense, and enhancing lesion volume before and during interferon-beta-1a treatment in relapsing-remitting multiple sclerosis. METHODS: After a baseline scan and 6 month pretreatment period, 67 patients with relapsing-remitting multiple sclerosis were treated with interferon-beta-1a by subcutaneous injection three times a week during a 12 month treatment period. All patients had MRI every month during the 6 month pretreatment period and for the first 9 months of the treatment period. A final MRI was also performed at the end of the 12 month treatment period. RESULTS: There was a significant increase in the mean hyperintense lesion volume during the pretreatment phase (6 months) and a slight decrease during the treatment period (12 months), whereas the hypointense lesion volume increased significantly before treatment and remained substantially stable during treatment. There was a significant correlation between changes in hypointense and hyperintense lesion volume during the observation period, but not during treatment. The monthly mean volume of Gadolinium-DTPA enhancing lesions was significantly higher during the pretreatment than the treatment period, and the enhancing lesion volume correlated with changes of hyperintense and hypointense lesion volumes only during the observation period. CONCLUSION: These data suggest that interferon-beta-1a has a stabilising effect on T1 weighted hypointense lesion volume.
Asunto(s)
Encéfalo/patología , Interferón beta/uso terapéutico , Imagen por Resonancia Magnética , Esclerosis Múltiple/tratamiento farmacológico , Adulto , Personas con Discapacidad , Femenino , Gadolinio DTPA , Humanos , Interferón beta/farmacología , Masculino , Esclerosis Múltiple/patología , Valor Predictivo de las Pruebas , Pronóstico , Resultado del TratamientoRESUMEN
Expression of myelin basic protein (MBP) and Po gene products is induced during the final postnatal maturation of Schwann cells and reinduced during nerve regeneration. We show that a chimeric protein containing interleukin-6 fused to its soluble receptor (IL6RIL6 chimera) induces MBP and Po RNAs and proteins in cultures of dorsal root ganglia (DRG) from 14 day old mouse embryos. Activation of gp130 signaling by IL6RIL6 appears comparable to cyclic AMP elevating agents to induce the myelin gene products in DRG and in pure Schwann cell cultures.