260 research outputs found
Methylprednisolone increases neuronal apoptosis during autoimmune CNS inflammation by inhibition of an endogenous neuroprotective pathway
No full textOptic neuritis is one of the most common clinical manifestations of multiple sclerosis ( MS), a chronic inflammatory disease of the CNS. High-dosage methylprednisolone treatment has been established as the standard therapy of acute inflammation of the optic nerve ( ON). The rationale for corticosteroid treatment lies in the antiinflammatory and immunosuppressive properties of these drugs, as shown in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. To investigate the influence of methylprednisolone therapy on the survival of retinal ganglion cells (RGCs), the neurons that form the axons of the ON, we used a rat model of myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Optic neuritis was diagnosed by recording visual evoked potentials, and RGC function was monitored by measuring electroretinograms. Methylprednisolone treatment significantly increased RGC apoptosis during MOG-EAE. By Western blot analysis, we identified the underlying molecular mechanism: a suppression of mitogen-activated protein kinase ( MAPK) phosphorylation, which is a key event in an endogenous neuroprotective pathway. The methylprednisolone-induced inhibition of MAPK phosphorylation was calcium dependent. Hence, we provide evidence for negative effects of steroid treatment on neuronal survival during chronic inflammatory autoimmune disease of the CNS, which should result in a reevaluation of the current therapy regimen
Methylprednisolone increases neuronal apoptosis during autoimmune CNS inflammation by inhibition of an endogenous neuroprotective pathway
No full textOptic neuritis is one of the most common clinical manifestations of multiple sclerosis ( MS), a chronic inflammatory disease of the CNS. High-dosage methylprednisolone treatment has been established as the standard therapy of acute inflammation of the optic nerve ( ON). The rationale for corticosteroid treatment lies in the antiinflammatory and immunosuppressive properties of these drugs, as shown in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. To investigate the influence of methylprednisolone therapy on the survival of retinal ganglion cells (RGCs), the neurons that form the axons of the ON, we used a rat model of myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Optic neuritis was diagnosed by recording visual evoked potentials, and RGC function was monitored by measuring electroretinograms. Methylprednisolone treatment significantly increased RGC apoptosis during MOG-EAE. By Western blot analysis, we identified the underlying molecular mechanism: a suppression of mitogen-activated protein kinase ( MAPK) phosphorylation, which is a key event in an endogenous neuroprotective pathway. The methylprednisolone-induced inhibition of MAPK phosphorylation was calcium dependent. Hence, we provide evidence for negative effects of steroid treatment on neuronal survival during chronic inflammatory autoimmune disease of the CNS, which should result in a reevaluation of the current therapy regimen
Mechanisms and Time Course of Neuronal Degeneration in Experimental Autoimmune Encephalomyelitis
No full textNeuronal and axonal damage is considered to be the main cause for long-term disability in multiple sclerosis. We analyzed the mechanisms and kinetics of neuronal cell death in experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG) by combining an electrophysiological in vivo assessment of the optic pathway with the investigation of retinal ganglion cell (RGC) counts. In accordance with our previous findings in this animal model, neuritis of the optic nerve (ON) leads to apoptotic RGC death. By further investigating the time course of RGC apoptosis in the present study, we found that neuronal cell death together with decreased visual acuity values occurred before the onset of clinical symptoms. Simultaneously with the time course of RGC apoptosis, we found a down-regulation of phospho-Akt as well as a shift in the relation of 2 proteins of the Bcl-2 family Bax and Bcl-2, towards a more proapoptotic ratio in these cells. Comparing the kinetics and mechanisms of RGC death during MOG-EAE with those following complete surgical transection of the ON, we found significant agreement. We hypothesize that the main reason for RGC loss in MOG-EAE is the inflammatory attack but RGC death also occurs independently of histopathological ON changes
Acute neuronal apoptosis in a rat model of multiple sclerosis
No full textDemyelination caused by inflammation of the CNS has been considered to be a major hallmark of multiple sclerosis (MS). Using experimental autoimmune encephalomyelitis, a model of MS, we demonstrate that an immune-mediated attack of the optic nerve is accompanied by an early degeneration of retinal ganglion cells (RGCs). The decrease of neuronal cell density was correlated with functional disabilities as assessed by visual evoked cortical potentials and electroretinogram. Visual acuity was significantly reduced. DNA degradation and activation of caspase-3 in RGCs indicate that cell death of RGCs is apoptotic. These findings show for the first time that an inflammatory attack against myelin components can lead to acute neuronal cell loss by apoptosis
Acute neuronal apoptosis in a rat model of multiple sclerosis
No full textDemyelination caused by inflammation of the CNS has been considered to be a major hallmark of multiple sclerosis (MS). Using experimental autoimmune encephalomyelitis, a model of MS, we demonstrate that an immune-mediated attack of the optic nerve is accompanied by an early degeneration of retinal ganglion cells (RGCs). The decrease of neuronal cell density was correlated with functional disabilities as assessed by visual evoked cortical potentials and electroretinogram. Visual acuity was significantly reduced. DNA degradation and activation of caspase-3 in RGCs indicate that cell death of RGCs is apoptotic. These findings show for the first time that an inflammatory attack against myelin components can lead to acute neuronal cell loss by apoptosis
Processors for ALOS Optical Data: Deconvolution, DEM Generation, Orthorectification, and Atmospheric Correction
No full textThe German Aerospace Center (DLR) is responsible for the development of prototype processors for PRISM and AVNIR-2 data under a contract of the European Space Agency. The PRISM processor comprises the radiometric correction, an optional deconvolution to improve image quality, the generation of a digital elevation model, and orthorectification. The AVNIR-2 processor comprises radiometric correction, orthorectification, and atmospheric correction over land. Here, we present the methodologies applied during these processing steps as well as the results achieved using the processors
Comment l’Europe parlait français (2) : Copenhague, 1797
No full textAprès un premier billet où j’ai présenté l’intérêt d’un parcours bibliographique parmi les méthodes de langues modernes dans le contexte d’une réflexion sur le statut de la langue française dans l’Europe du 18e siècle, il est temps maintenant de lire l’un de ces manuels : ce sera les Principes généraux de la langue danoise, avec un abrégé des curiosités de la ville de Copenhague et des environs de cette capitale (Copenhague et Leipsig, Proft & Storch, 1797) par Mathias Hagerup, professeur à l..
Comment l’Europe parlait français (2) : Copenhague, 1797
No full textAprès un premier billet où j’ai présenté l’intérêt d’un parcours bibliographique parmi les méthodes de langues modernes dans le contexte d’une réflexion sur le statut de la langue française dans l’Europe du 18e siècle, il est temps maintenant de lire l’un de ces manuels : ce sera les Principes généraux de la langue danoise, avec un abrégé des curiosités de la ville de Copenhague et des environs de cette capitale (Copenhague et Leipsig, Proft & Storch, 1797) par Mathias Hagerup, professeur à l..
Ciliary neurotrophic factor protects retinal ganglion cells from secondary cell death during acute autoimmune optic neuritis in rats
No full textMultiple sclerosis (MS) is a chronic inflammatory disease of the CNS which leads to demyelination, axonal destruction and neuronal loss in the early stages. Available therapies mainly target the inflammatory component of the disease but fail to prevent neurodegeneration. To investigate the effect of ciliary neurotrophic factor (CNTF) on the survival of retinal ganglion cells (RGCs), the neurons that form the axons of the optic nerve, we used a rat model of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. Optic neuritis in this model was diagnosed by recording visual evoked potentials, and RGC function was monitored by measuring electroretinograms. This study demonstrates that CNTF has a neuroprotective effect on affected RGCs during acute optic neuritis. Furthermore, we demonstrate that CNTF exerts its neuroprotective effect through activation of the Janus kinase/signal transducer and activator of transcription pathway, mitogen activated protein kinases and a shift in the Bcl-2 family of proteins towards the anti-apoptotic side. In summary, our results demonstrate that CNTF can serve as an effective neuroprotective treatment in a rat model of MS that especially reflects the neurodegenerative aspects of this disease
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