Weishaupt, Jochen Hans

[["dc.bibliographiccitation.artnumber","e43963"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","PlosOne"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Dibaj, Payam"],["dc.contributor.author","Zschüntzsch, Jana"],["dc.contributor.author","Steffens, Heinz"],["dc.contributor.author","Scheffel, Jörg"],["dc.contributor.author","Göricke, Bettina"],["dc.contributor.author","Weishaupt, Jochen H."],["dc.contributor.author","Le Meur, Karim"],["dc.contributor.author","Kirchhoff, Frank"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Schomburg, Eike D."],["dc.contributor.author","Neusch, Clemens"],["dc.date.accessioned","2019-07-09T11:53:39Z"],["dc.date.available","2019-07-09T11:53:39Z"],["dc.date.issued","2012"],["dc.description.abstract","Mutations in SOD1 cause hereditary variants of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS). Pathophysiology of the disease is non-cell-autonomous, with toxicity deriving also from glia. In particular, microglia contribute to disease progression. Methylene blue (MB) inhibits the effect of nitric oxide, which mediates microglial responses to injury. In vivo 2P-LSM imaging was performed in ALS-linked transgenic SOD1G93A mice to investigate the effect of MB on microglia-mediated inflammation in the spinal cord. Local superfusion of the lateral spinal cord with MB inhibited the microglial reaction directed at a laser-induced axon transection in control and SOD1G93A mice. In vitro, MB at high concentrations inhibited cytokine and chemokine release from microglia of control and advanced clinical SOD1G93A mice. Systemic MB-treatment of SOD1G93A mice at early preclinical stages significantly delayed disease onset and motor dysfunction. However, an increase of MB dose had no additional effect on disease progression; this was unexpected in view of the local anti-inflammatory effects. Furthermore, in vivo imaging of systemically MB-treated mice also showed no alterations of microglia activity in response to local lesions. Thus although systemic MB treatment had no effect on microgliosis, instead, its use revealed an important influence on motor neuron survival as indicated by an increased number of lumbar anterior horn neurons present at the time of disease onset. Thus, potentially beneficial effects of locally applied MB on inflammatory events contributing to disease progression could not be reproduced in SOD1G93A mice via systemic administration, whereas systemic MB application delayed disease onset via neuroprotection."],["dc.format.extent","13"],["dc.identifier.doi","10.1371/journal.phone.0043963"],["dc.identifier.fs","592827"],["dc.identifier.pmid","22952827"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7861"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60471"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Influence of Methylene Blue on Microglia-Induced Inflammation and Motor Neuron Degeneration in the SOD1G93A Model for ALS"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","BMC Neuroscience"],["dc.contributor.author","Weishaupt, Jochen Hans"],["dc.contributor.author","Dietz, Gunnar"],["dc.contributor.author","Göricke, Bettina"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Frank, Tobias"],["dc.contributor.author","Schlachetzki, Johannes C. M."],["dc.contributor.author","Meuer, Katrin"],["dc.contributor.author","Rohde, Gundula"],["dc.contributor.author","Schneider, Armin"],["dc.date.accessioned","2019-07-10T08:13:27Z"],["dc.date.available","2019-07-10T08:13:27Z"],["dc.date.issued","2009"],["dc.description.abstract","Background: The hematopoietic Granulocyte-Colony Stimulating Factor (G-CSF) plays a crucial role in controlling the number of neutrophil progenitor cells. Its function is mediated via the G-CSF receptor, which was recently found to be expressed also in the central nervous system. In addition, G-CSF provided neuroprotection in models of neuronal cell death. Here we used the retinal ganglion cell (RGC) axotomy model to compare effects of local and systemic application of neuroprotective molecules. Results: We found that the G-CSF receptor is robustly expressed by RGCs in vivo and in vitro. We thus evaluated G-CSF as a neuroprotectant for RGCs and found a dose-dependent neuroprotective effect of G-CSF on axotomized RGCs when given subcutaneously. As stem stell mobilization had previously been discussed as a possible contributor to the neuroprotective effects of G-CSF, we compared the local treatment of RGCs by injection of G-CSF into the vitreous body with systemic delivery by subcutaneous application. Both routes of application reduced retinal ganglion cell death to a comparable extent. Moreover, G-CSF enhanced the survival of immunopurified RGCs in vitro. Conclusion: We thus show that G-CSF neuroprotection is at least partially independent of potential systemic effects and provide further evidence that the clinically applicable G-CSF could become a treatment option for both neurodegenerative diseases and glaucoma"],["dc.identifier.fs","568091"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5954"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61250"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1471-2202"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Both systemic and local application of granulocyte-colony stimulating factor (G-CSF) is neuroprotective after retinal ganglion cell axotomy."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]