Erythropoietin Enhances Nerve Repair in Anti-Ganglioside Antibody-Mediated Models of Immune Neuropathy

Zhang, Gang; Lehmann, Helmar C.; Богданова, Н. А.; Gao, Tong; Zhang, Jiangyang; Sheikh, Kazim A.

doi:10.1371/journal.pone.0027067

Cited by 25 publications

(18 citation statements)

References 64 publications

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“…Prednisolone or intravenous methylprednisolone treatment in GBS patients did not improve patient outcomes [87,88]. Plasmapheresis and IVIg are the only known effective treatments for GBS.…”

Section: Treatmentmentioning

confidence: 94%

Guillain-Barré syndrome: causes, immunopathogenic mechanisms and treatment

Jasti

Selmi

Sarmiento-Monroy

et al. 2016

Expert Review of Clinical Immunology

114

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Guillain-Barré syndrome is a rare disease representing the most frequent cause of acute flaccid symmetrical weakness of the limbs and areflexia usually reaching its peak within a month. The etiology and pathogenesis remain largely enigmatic and the syndrome results in death or severe disability in 9-17% of cases despite immunotherapy. Areas covered: In terms of etiology, Guillain-Barré syndrome is linked to Campylobacter infection but less than 0.1% of infections result in the syndrome. In terms of pathogenesis, activated macrophages and T cells and serum antibodies against gangliosides are observed but their significance is unclear. Expert commentary: Guillain-Barré syndrome is a heterogeneous condition with numerous subtypes and recent data point towards the role of ganglioside epitopes by immunohistochemical methods. Ultimately, the syndrome results from a permissive genetic background on which environmental factors, including infections, vaccination and the influence of aging, lead to disease.

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“…Prednisolone or intravenous methylprednisolone treatment in GBS patients did not improve patient outcomes [87,88]. Plasmapheresis and IVIg are the only known effective treatments for GBS.…”

Section: Treatmentmentioning

confidence: 94%

Guillain-Barré syndrome: causes, immunopathogenic mechanisms and treatment

Jasti

Selmi

Sarmiento-Monroy

et al. 2016

Expert Review of Clinical Immunology

114

View full text Add to dashboard Cite

show abstract

“…Positive effects of external EPO on neuronal survival and function have been shown in other animal models, e.g. in diabetic retinopathy or autoimmune neuropathy [22], [23]. Given that EPO is also elevated in the retina of diabetic patients in comparison to non diabetics, this might be a compensatory mechanism [24].…”

Section: Discussionmentioning

confidence: 91%

Systemic Treatment with Erythropoietin Protects the Neurovascular Unit in a Rat Model of Retinal Neurodegeneration

et al. 2014

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Rats expressing a transgenic polycystic kidney disease (PKD) gene develop photoreceptor degeneration and subsequent vasoregression, as well as activation of retinal microglia and macroglia. To target the whole neuroglialvascular unit, neuro- and vasoprotective Erythropoietin (EPO) was intraperitoneally injected into four –week old male heterozygous PKD rats three times a week at a dose of 256 IU/kg body weight. For comparison EPO-like peptide, lacking unwanted side effects of EPO treatment, was given five times a week at a dose of 10 µg/kg body weight. Matched EPO treated Sprague Dawley and water-injected PKD rats were held as controls. After four weeks of treatment the animals were sacrificed and analysis of the neurovascular morphology, glial cell activity and pAkt localization was performed. The number of endothelial cells and pericytes did not change after treatment with EPO or EPO-like peptide. There was a nonsignificant reduction of migrating pericytes by 23% and 49%, respectively. Formation of acellular capillaries was significantly reduced by 49% (p<0.001) or 40% (p<0.05). EPO-treatment protected against thinning of the central retina by 10% (p<0.05), a composite of an increase of the outer nuclear layer by 12% (p<0.01) and in the outer segments of photoreceptors by 26% (p<0.001). Quantification of cell nuclei revealed no difference. Microglial activity, shown by gene expression of CD74, decreased by 67% (p<0.01) after EPO and 36% (n.s.) after EPO-like peptide treatment. In conclusion, EPO safeguards the neuroglialvascular unit in a model of retinal neurodegeneration and secondary vasoregression. This finding strengthens EPO in its protective capability for the whole neuroglialvascular unit.

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“…These signaling pathways also have been shown to be activated by EPO in neurons (21)(22)(23)28,57,60). Even if iPS cell-derived pNPCs expressed EPOR mRNA and functional EPOR-associated intracellular signaling pathways, neither inhibition of MAPK nor PI3K/AKT counteracted the effect of EPO on iPS pNPC proliferation.…”

Section: Discussionmentioning

confidence: 99%

Effects of Erythropoietin in Murine-Induced Pluripotent Cell-Derived Panneural Progenitor Cells

Offen

Flemming

Kamawal

et al. 2013

Mol Med

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Induced cell fate changes by reprogramming of somatic cells offers an efficient strategy to generate autologous pluripotent stem (iPS) cells from any adult cell type. The potential of iPS cells to differentiate into various cell types is well established, however the efficiency to produce functional neurons from iPS cells remains modest. Here, we generated panneural progenitor cells (pNPCs) from mouse iPS cells and investigated the effect of the neurotrophic growth factor erythropoietin (EPO) on their survival, proliferation and neurodifferentiation. Under neural differentiation conditions, iPS-derived pNPCs gave rise to microtubule-associated protein-2 positive neuronlike cells (34% to 43%) and platelet-derived growth factor receptor positive oligodendrocytelike cells (21% to 25%) while less than 1% of the cells expressed the astrocytic marker glial fibrillary acidic protein. Neuronlike cells generated action potentials and developed active presynaptic terminals. The pNPCs expressed EPO receptor (EPOR) mRNA and displayed functional EPOR signaling. In proliferating cultures, EPO (0.1-3 U/mL) slightly improved pNPC survival but reduced cell proliferation and neurosphere formation in a concentration-dependent manner. In differentiating cultures EPO facilitated neurodifferentiation as assessed by the increased number of β-III-tubulin positive neurons. Our results show that EPO inhibits iPS pNPC self-renewal and promotes neurogenesis.

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Erythropoietin Enhances Nerve Repair in Anti-Ganglioside Antibody-Mediated Models of Immune Neuropathy

Cited by 25 publications

References 64 publications

Guillain-Barré syndrome: causes, immunopathogenic mechanisms and treatment

Guillain-Barré syndrome: causes, immunopathogenic mechanisms and treatment

Systemic Treatment with Erythropoietin Protects the Neurovascular Unit in a Rat Model of Retinal Neurodegeneration

Effects of Erythropoietin in Murine-Induced Pluripotent Cell-Derived Panneural Progenitor Cells

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