Singh, Shailender Narayan

[["dc.bibliographiccitation.artnumber","156"],["dc.bibliographiccitation.journal","Journal of Neuroinflammation"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","van Horssen, Jack"],["dc.contributor.author","Singh, Shailender"],["dc.contributor.author","van der Pol, Susanne"],["dc.contributor.author","Kipp, Markus"],["dc.contributor.author","Lim, Jamie L."],["dc.contributor.author","Peferoen, Laura"],["dc.contributor.author","Gerritsen, Wouter"],["dc.contributor.author","Kooi, Evert-Jan"],["dc.contributor.author","Witte, Maarten E."],["dc.contributor.author","Geurts, Jeroen J. G."],["dc.contributor.author","de Vries, Helga E."],["dc.contributor.author","Peferoen-Baert, Regina"],["dc.contributor.author","van den Elsen, Peter J."],["dc.contributor.author","van der Valk, Paul"],["dc.contributor.author","Amor, Sandra"],["dc.date.accessioned","2018-11-07T09:08:16Z"],["dc.date.available","2018-11-07T09:08:16Z"],["dc.date.issued","2012"],["dc.description.abstract","Background: In brain tissues from multiple sclerosis (MS) patients, clusters of activated HLA-DR-expressing microglia, also referred to as preactive lesions, are located throughout the normal-appearing white matter. The aim of this study was to gain more insight into the frequency, distribution and cellular architecture of preactive lesions using a large cohort of well-characterized MS brain samples. Methods: Here, we document the frequency of preactive lesions and their association with distinct white matter lesions in a cohort of 21 MS patients. Immunohistochemistry was used to gain further insight into the cellular and molecular composition of preactive lesions. Results: Preactive lesions were observed in a majority of MS patients (67%) irrespective of disease duration, gender or subtype of disease. Microglial clusters were predominantly observed in the vicinity of active demyelinating lesions and are not associated with T cell infiltrates, axonal alterations, activated astrocytes or blood-brain barrier disruption. Microglia in preactive lesions consistently express interleukin-10 and TNF-alpha, but not interleukin-4, whereas matrix metalloproteases-2 and -9 are virtually absent in microglial nodules. Interestingly, key subunits of the free-radical-generating enzyme NADPH oxidase-2 were abundantly expressed in microglial clusters. Conclusions: The high frequency of preactive lesions suggests that it is unlikely that most of them will progress into full-blown demyelinating lesions. Preactive lesions are not associated with blood-brain barrier disruption, suggesting that an intrinsic trigger of innate immune activation, rather than extrinsic factors crossing a damaged blood-brain barrier, induces the formation of clusters of activated microglia."],["dc.identifier.doi","10.1186/1742-2094-9-156"],["dc.identifier.isi","000307447800002"],["dc.identifier.pmid","22747960"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8916"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25992"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1742-2094"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Clusters of activated microglia in normal-appearing white matter show signs of innate immune activation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","595"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","608"],["dc.bibliographiccitation.volume","125"],["dc.contributor.author","Singh, Shailender"],["dc.contributor.author","Metz, Imke"],["dc.contributor.author","Amor, Sandra"],["dc.contributor.author","van der Valk, Paul"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Brueck, Wolfgang"],["dc.date.accessioned","2018-11-07T09:26:35Z"],["dc.date.available","2018-11-07T09:26:35Z"],["dc.date.issued","2013"],["dc.description.abstract","Microglial nodules in the normal-appearing white matter have been suggested as the earliest stage(s) of multiple sclerosis (MS) lesion formation. Such nodules are characterized by an absence of leukocyte infiltration, astrogliosis or demyelination, and may develop into active demyelinating MS lesions. Although the etiology of MS is still not known, inflammation and autoimmunity are considered to be the central components of this disease. Previous studies provide evidence that Wallerian degeneration, occurring as a consequence of structural damage in MS lesions, might be responsible for observed pathological abnormalities in connected normal-appearing white matter. As innate immune cells, microglia/macrophages are the first to react to even minor pathological changes in the CNS. Biopsy tissue from 27 MS patients and autopsy and biopsy tissue from 22 normal and pathological controls were analyzed to determine the incidence of microglial nodules. We assessed MS periplaque white matter tissue from early disease stages to determine whether microglial nodules are associated with altered axons. With immunohistochemical methods, the spatial relation of the two phenomena was visualized using HLA-DR antibody for MHC II expression by activated microglia/macrophages and by applying antibodies against damaged axons, i.e., SMI32 (non-phosphorylated neurofilaments) and amyloid precursor protein as well as neuropeptide Y receptor Y1, which marks axons undergoing Wallerian degeneration. Our data demonstrate that the occurrence of microglial nodules is not specific to MS and is associated with degenerating as well as damaged axons in early MS. In addition, we show that early MS microglial nodules exhibit both pro- and antiinflammatory phenotypes."],["dc.identifier.doi","10.1007/s00401-013-1082-0"],["dc.identifier.isi","000317071500009"],["dc.identifier.pmid","23354834"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10302"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30334"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0001-6322"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]