Hanisch, Uwe-Karsten

[["dc.bibliographiccitation.journal","Multiple Sclerosis Journal"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Kramann, N."],["dc.contributor.author","Menken, Lena"],["dc.contributor.author","Hayardeny, Liat"],["dc.contributor.author","Hanisch, U-K"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Wegner, C."],["dc.date.accessioned","2018-11-07T09:35:28Z"],["dc.date.available","2018-11-07T09:35:28Z"],["dc.date.issued","2014"],["dc.format.extent","382"],["dc.identifier.isi","000354441300878"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32389"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Sage Publications Ltd"],["dc.publisher.place","London"],["dc.relation.conference","Joint ACTRIMS-ECTRIMS Meeting"],["dc.relation.eventlocation","Boston, MA"],["dc.relation.issn","1477-0970"],["dc.relation.issn","1352-4585"],["dc.title","Laquinimod treatment prevents cuprizone-induced demyelination independent of Toll-like receptor signaling via MyD88 and TRIF"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1083"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","1099"],["dc.bibliographiccitation.volume","63"],["dc.contributor.author","Menzfeld, Christiane"],["dc.contributor.author","John, Michael"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Scheffel, Joerg"],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Goetz, Alexander A."],["dc.contributor.author","Ribes, Sandra"],["dc.contributor.author","Nau, Roland"],["dc.contributor.author","Borisch, Angela"],["dc.contributor.author","Boutin, Philippe"],["dc.contributor.author","Neumann, Konstantin"],["dc.contributor.author","Bremes, Vanessa"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Tischner, Denise"],["dc.contributor.author","Waetzig, Vicky"],["dc.contributor.author","Herdegen, Thomas"],["dc.contributor.author","Teismann, Peter"],["dc.contributor.author","Greig, Iain"],["dc.contributor.author","Mueller, Michael"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Mildner, Alexander"],["dc.contributor.author","Kettenmann, Helmut"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Prinz, Marco R."],["dc.contributor.author","Rotshenker, Shlomo"],["dc.contributor.author","Weber, Martin S."],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.date.accessioned","2018-11-07T09:56:53Z"],["dc.date.available","2018-11-07T09:56:53Z"],["dc.date.issued","2015"],["dc.description.abstract","The putative protein tyrosine kinase (PTK) inhibitor tyrphostin AG126 has proven beneficial in various models of inflammatory disease. Yet molecular targets and cellular mechanisms remained enigmatic. We demonstrate here that AG126 treatment has beneficial effects in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. AG126 alleviates the clinical symptoms, diminishes encephalitogenic Th17 differentiation, reduces inflammatory CNS infiltration as well as microglia activation and attenuates myelin damage. We show that AG126 directly inhibits Bruton's tyrosine kinase (BTK), a PTK associated with B cell receptor and Toll-like receptor (TLR) signaling. However, BTK inhibition cannot account for the entire activity spectrum. Effects on TLR-induced proinflammatory cytokine expression in microglia involve AG126 hydrolysis and conversion of its dinitrile side chain to malononitrile (MN). Notably, while liberated MN can subsequently mediate critical AG126 features, full protection in EAE still requires delivery of intact AG126. Its anti-inflammatory potential and especially interference with TLR signaling thus rely on a dual mechanism encompassing BTK and a novel MN-sensitive target. Both principles bear great potential for the therapeutic management of disturbed innate and adaptive immune functions. GLIA 2015;63:1083-1099"],["dc.identifier.doi","10.1002/glia.22803"],["dc.identifier.isi","000353244400011"],["dc.identifier.pmid","25731696"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37056"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1098-1136"],["dc.relation.issn","0894-1491"],["dc.title","Tyrphostin AG126 Exerts Neuroprotection in CNS Inflammation by a Dual Mechanism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.volume","57"],["dc.contributor.author","Menzfeld, Christiane"],["dc.contributor.author","John, Michael"],["dc.contributor.author","Neumann, K."],["dc.contributor.author","Tischner, Denise"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Rotshenker, Shlomo"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.date.accessioned","2018-11-07T11:23:41Z"],["dc.date.available","2018-11-07T11:23:41Z"],["dc.date.issued","2009"],["dc.format.extent","S66"],["dc.identifier.isi","000270075500275"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56240"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.publisher.place","Hoboken"],["dc.relation.conference","9th European Meeting on Glial Cells in Health and Disease"],["dc.relation.eventlocation","Paris, FRANCE"],["dc.relation.issn","0894-1491"],["dc.title","TYRPHOSTIN AG126 MODULATES TOLL-LIKE RECEPTOR (TLR)-ACTIVATED RESPONSES IN MICROGLIA"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","MULTIPLE SCLEROSIS"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Mildner, Alexander"],["dc.contributor.author","Schmidt, H."],["dc.contributor.author","Nitsche, M."],["dc.contributor.author","Mekler, D."],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Mack, Matthias"],["dc.contributor.author","Heikenwalder, Mathias"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Priller, Josef"],["dc.contributor.author","Prinz, Marco R."],["dc.date.accessioned","2018-11-07T10:58:20Z"],["dc.date.available","2018-11-07T10:58:20Z"],["dc.date.issued","2007"],["dc.format.extent","S255"],["dc.identifier.isi","000251423400794"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50454"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Sage Publications Ltd"],["dc.publisher.place","London"],["dc.relation.conference","23rd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis/12th Annual Conference of Rehabilitation in MS"],["dc.relation.eventlocation","Prague, CZECH REPUBLIC"],["dc.relation.issn","1352-4585"],["dc.title","Microglia in the adult brain arise from Ly-6Chi monocytes only under defined host conditions"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Ribes, Sandra"],["dc.contributor.author","Goetz, Alexander A."],["dc.contributor.author","Nau, R."],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Hanisch, U-K"],["dc.date.accessioned","2018-11-07T09:23:23Z"],["dc.date.available","2018-11-07T09:23:23Z"],["dc.date.issued","2013"],["dc.format.extent","S181"],["dc.identifier.isi","000320408400581"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29563"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.conference","11th European Meeting on Glial Cell Function in Health and Disease"],["dc.relation.eventlocation","Berlin, GERMANY"],["dc.relation.issn","0894-1491"],["dc.title","CD14 AS A KEY REGULATOR OF TLR-MEDIATED RESPONSES OF MICROGLIA"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1930"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","1943"],["dc.bibliographiccitation.volume","60"],["dc.contributor.author","Scheffel, Joerg"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Seifert, Stefanie"],["dc.contributor.author","Ribes, Sandra"],["dc.contributor.author","Nau, Roland"],["dc.contributor.author","Parsa, Roham"],["dc.contributor.author","Harris, Robert A."],["dc.contributor.author","Boddeke, Hendrikus W. G. M."],["dc.contributor.author","Chuang, Han-Ning"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Wessels, Johannes Theodor"],["dc.contributor.author","Juergens, Tanja"],["dc.contributor.author","Merkler, Doron"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Schnaars, Mareike"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Kettenmann, Helmut"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.date.accessioned","2018-11-07T09:03:06Z"],["dc.date.available","2018-11-07T09:03:06Z"],["dc.date.issued","2012"],["dc.description.abstract","The sentinel and immune functions of microglia require rapid and appropriate reactions to infection and damage. Their Toll-like receptors (TLRs) sense both as threats. However, whether activated microglia mount uniform responses or whether subsets conduct selective tasks is unknown. We demonstrate that murine microglia reorganize their responses to TLR activations postnatally and that this process comes with a maturation of TLR4-organized functions. Although induction of MHCI for antigen presentation remains as a pan-populational feature, synthesis of TNFa becomes restricted to a subset, even within adult central nervous system regions. Response heterogeneity is evident ex vivo, in situ, and in vivo, but is not limited to TNFa production or to TLR-triggered functions. Also, clearance activities for myelin under physiological and pathophysiological conditions, IFN >> factors reveal dissimilar microglial contributions. Notably, response heterogeneity is also confirmed in human brain tissue. Our findings suggest that microglia divide by constitutive and inducible capacities. Privileged production of inflammatory mediators assigns a master control to subsets. Sequestration of clearance of endogenous material versus antigen presentation in exclusive compartments can separate potentially interfering functions. Finally, subsets rather than a uniform population of microglia may assemble the reactive phenotypes in responses during infection, injury, and rebuilding, warranting consideration in experimental manipulation and therapeutic strategies. (c) 2012 Wiley Periodicals, Inc."],["dc.identifier.doi","10.1002/glia.22409"],["dc.identifier.isi","000310262600010"],["dc.identifier.pmid","22911652"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24833"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0894-1491"],["dc.title","Toll-like receptor activation reveals developmental reorganization and unmasks responder subsets of microglia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4841"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Infection and Immunity"],["dc.bibliographiccitation.lastpage","4848"],["dc.bibliographiccitation.volume","74"],["dc.contributor.author","Hermann, Isabel"],["dc.contributor.author","Kellert, Markus"],["dc.contributor.author","Schmidt, Hauke"],["dc.contributor.author","Mildner, Alexander"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Prinz, Marco R."],["dc.contributor.author","Nau, Roland"],["dc.date.accessioned","2018-11-07T09:28:40Z"],["dc.date.available","2018-11-07T09:28:40Z"],["dc.date.issued","2006"],["dc.description.abstract","The course of autoimmune inflammatory diseases of the central nervous system (CNS) can be influenced by infections. Here we assessed the disease-modulating effects of the most frequent respiratory pathogen Streptococcus pneumonia on the course of experimental autoimmune encephalomyelitis (EAE). Mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG(35-55)) peptide, challenged intraperitoneally with live S. pneumoniae type 3, and then treated with ceftriaxone. EAE was monitored by a clinical score for 35 days after immunization. EAE was unaltered in mice infected with S. pneumoniae 2 days before and 21 days after the first MOG(35-55) injection but was more severe in animals infected 7 days after the first MOG(35-55) injection. The antigen-driven systemic T-cell response was unaltered, and the intraspinal Th1 cytokine mRNA concentrations at the peak of disease were unchanged. The composition of CNS-infiltrating cells and subsequent tissue destruction were only slightly increased after S. pneumoniae infection. In contrast, the serum levels of tumor necrosis factor alpha and interleukin-6 and spinal interleukin-6 levels were elevated, and the expression of major histocompatibility complex class II molecules, CD80, and CD86 on splenic dendritic cells were enhanced early after infection. Serum cytokine concentrations were not elevated, and EAE was not aggravated by S. pneumoniae infection in Toll-like receptor 2 (TLR2)-deficient mice. In conclusion, infection with S. pneumoniae worsens EAE probably by elevation of proinflammatory cytokines and activation of dendritic cells in the systemic circulation via TLR2 and cross talk through the blood-brain barrier."],["dc.identifier.doi","10.1128/IAI.00026-06"],["dc.identifier.isi","000239381400049"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30836"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Microbiology"],["dc.relation.issn","0019-9567"],["dc.title","Streptococcus pneumoniae infection aggravates experimental autoimmune encephalomyelitis via toll-like receptor 2"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Cytokine"],["dc.bibliographiccitation.volume","43"],["dc.contributor.author","Scheffel, Joerg"],["dc.contributor.author","Rossum van, Denise"],["dc.contributor.author","Weinstein, Jonathan R."],["dc.contributor.author","Dihazi, Hassan"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Kettenmann, Helmut"],["dc.contributor.author","Prinz, Marco R."],["dc.contributor.author","Moeller, Thomas"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.date.accessioned","2018-11-07T11:11:15Z"],["dc.date.available","2018-11-07T11:11:15Z"],["dc.date.issued","2008"],["dc.format.extent","315"],["dc.identifier.doi","10.1016/j.cyto.2008.07.386"],["dc.identifier.isi","000260212900351"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53386"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Ltd Elsevier Science Ltd"],["dc.publisher.place","London"],["dc.relation.conference","7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research"],["dc.relation.eventlocation","Montreal, CANADA"],["dc.relation.issn","1043-4666"],["dc.title","Toll-like receptor 4/MyD88 pathway mediates microglial proinflammatory cytokine responses to thrombin-associated coagulation protein complexes"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","153"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.lastpage","154"],["dc.bibliographiccitation.volume","178"],["dc.contributor.author","Prinz, Marco R."],["dc.contributor.author","Schmidt, Hauke"],["dc.contributor.author","Detje, Claudia N."],["dc.contributor.author","Mildner, Alexander"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Becher, Burkhard"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Kalinke, Ulrich"],["dc.date.accessioned","2018-11-07T09:21:15Z"],["dc.date.available","2018-11-07T09:21:15Z"],["dc.date.issued","2006"],["dc.identifier.isi","000241633101059"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29069"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.publisher.place","Amsterdam"],["dc.relation.conference","8th International Conference of Neuroimmunology"],["dc.relation.eventlocation","Nagoya, JAPAN"],["dc.relation.issn","0165-5728"],["dc.title","Type 1 interferon receptor (IFNAR)-dependent modulation of myeloid cell activation determines the course of experimental autoimmune encephalomyelitis"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","411"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","424"],["dc.bibliographiccitation.volume","124"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Pfoertner, Ramona"],["dc.contributor.author","Pham, Trinh"],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Hayardeny, Liat"],["dc.contributor.author","Piryatinsky, Victor"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Rossum, Denise van"],["dc.contributor.author","Brakelmann, Lars"],["dc.contributor.author","Hagemeier, Karin"],["dc.contributor.author","Kuhlmann, Tanja"],["dc.contributor.author","Stadelmann-Nessler, Christine"],["dc.contributor.author","John, Gareth R."],["dc.contributor.author","Kramann, Nadine"],["dc.contributor.author","Wegner, Christiane"],["dc.date.accessioned","2018-11-07T09:06:50Z"],["dc.date.available","2018-11-07T09:06:50Z"],["dc.date.issued","2012"],["dc.description.abstract","Laquinimod (LAQ) is a new oral immunomodulatory compound that reduces relapse rate, brain atrophy and disability progression in multiple sclerosis (MS). LAQ has well-documented effects on inflammation in the periphery, but little is known about its direct activity within the central nervous system (CNS). To elucidate the impact of LAQ on CNS-intrinsic inflammation, we investigated the effects of LAQ on cuprizone-induced demyelination in mice in vivo and on primary CNS cells in vitro. Demyelination, inflammation, axonal damage and glial pathology were evaluated in LAQ-treated wild type and Rag-1-deficient mice after cuprizone challenge. Using primary cells we tested for effects of LAQ on oligodendroglial survival as well as on cytokine secretion and NF-kappa B activation in astrocytes and microglia. LAQ prevented cuprizone-induced demyelination, microglial activation, axonal transections, reactive gliosis and oligodendroglial apoptoses in wild type and Rag-1-deficient mice. LAQ significantly decreased pro-inflammatory factors in stimulated astrocytes, but not in microglia. Oligodendroglial survival was not affected by LAQ in vitro. Astrocytic, but not microglial, NF-kappa B activation was markedly reduced by LAQ as evidenced by NF-kappa B reporter assay. LAQ also significantly decreased astrocytic NF-kappa B activation in cuprizone-treated mice. Our data indicate that LAQ prevents cuprizone-induced demyelination by attenuating astrocytic NF-kappa B activation. These effects are CNS-intrinsic and not mediated by peripheral immune cells. Therefore, LAQ downregulation of the astrocytic pro-inflammatory response may be an important mechanism underlying its protective effects on myelin, oligodendrocytes and axons. Modulation of astrocyte activation may be an attractive therapeutic target to prevent tissue damage in MS."],["dc.identifier.doi","10.1007/s00401-012-1009-1"],["dc.identifier.isi","000307757200010"],["dc.identifier.pmid","22766690"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9468"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25641"],["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","CC BY-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.title","Reduced astrocytic NF-kappa B activation by laquinimod protects from cuprizone-induced demyelination"],["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"]]