Gadjanski, Ivana

[["dc.bibliographiccitation.firstpage","81"],["dc.bibliographiccitation.journal","Annals of Neurology"],["dc.bibliographiccitation.lastpage","93"],["dc.bibliographiccitation.volume","66"],["dc.contributor.author","Gadjanski, Ivana"],["dc.contributor.author","Boretius, Susann"],["dc.contributor.author","Williams, Sarah K."],["dc.contributor.author","Lingor, Paul"],["dc.contributor.author","Knöferle, Johanna"],["dc.contributor.author","Sättler, Muriel B."],["dc.contributor.author","Fairless, Richard"],["dc.contributor.author","Hochmeister, Sonja"],["dc.contributor.author","Sühs, Kurt-Wolfram"],["dc.contributor.author","Michaelis, Thomas"],["dc.contributor.author","Frahm, Jens"],["dc.contributor.author","Storch, Maria K."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Diem, Ricarda"],["dc.date.accessioned","2019-07-09T11:52:52Z"],["dc.date.available","2019-07-09T11:52:52Z"],["dc.date.issued","2009"],["dc.description.abstract","Objective: The aim of this study was to investigate the role of voltage-dependent calcium channels (VDCCs) in axon degeneration during autoimmune optic neuritis. Methods: Calcium ion (Ca2 ) influx into the optic nerve (ON) through VDCCs was investigated in a rat model of optic neuritis using manganese-enhanced magnetic resonance imaging and in vivo calcium imaging. After having identified the most relevant channel subtype (N-type VDCCs), we correlated immunohistochemistry of channel expression with ON histopathology. In the confirmatory part of this work, we performed a treatment study using -conotoxin GVIA, an N-type specific blocker. Results: We observed that pathological Ca2 influx into ONs during optic neuritis is mediated via N-type VDCCs. By analyzing the expression of VDCCs in the inflamed ONs, we detected an upregulation of 1B, the pore-forming subunit of N-type VDCCs, in demyelinated axons. However, high expression levels were also found on macrophages/activated microglia, and lower levels were detected on astrocytes. The relevance of N-type VDCCs for inflammation-induced axonal degeneration and the severity of optic neuritis was corroborated by treatment with -conotoxin GVIA. This blocker led to decreased axon and myelin degeneration in the ONs together with a reduced number of macrophages/activated microglia. These protective effects were confirmed by analyzing the spinal cords of the same animals. Interpretation: We conclude that N-type VDCCs play an important role in inflammation-induced axon degeneration via two mechanisms: First, they directly mediate toxic Ca2 influx into the axons; and second, they contribute to macrophage/microglia function, thereby promoting secondary axonal damage."],["dc.identifier.doi","10.1002/ ana.21668"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6088"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60296"],["dc.language.iso","en"],["dc.subject.ddc","610"],["dc.title","Role of N-Type Voltage-Dependent Calcium Channels in Autoimmune Optic Neuritis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","MULTIPLE SCLEROSIS"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Gadjanski, I."],["dc.contributor.author","Boretius, Susann"],["dc.contributor.author","Michaelis, Thomas"],["dc.contributor.author","Frahm, Jens"],["dc.contributor.author","Baehr, M."],["dc.contributor.author","Diem, Ricarda"],["dc.date.accessioned","2018-11-07T09:22:33Z"],["dc.date.available","2018-11-07T09:22:33Z"],["dc.date.issued","2006"],["dc.format.extent","S9"],["dc.identifier.isi","000241921400028"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29368"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Sage Publications Ltd"],["dc.publisher.place","London"],["dc.relation.eventlocation","Madrid, SPAIN"],["dc.relation.issn","1352-4585"],["dc.title","Upregulated expression of N-type voltage dependent calcium channels (Cav2.2) in autoimmune optic neuritis detected by magnetic resonance imaging and immunochemistry"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","323"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","NeuroImage"],["dc.bibliographiccitation.lastpage","334"],["dc.bibliographiccitation.volume","41"],["dc.contributor.author","Boretius, Susann"],["dc.contributor.author","Gadjanski, Ivana"],["dc.contributor.author","Demmer, Iris"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Diem, Ricarda"],["dc.contributor.author","Michaelis, Thomas"],["dc.contributor.author","Frahm, Jens"],["dc.date.accessioned","2017-09-07T11:45:31Z"],["dc.date.available","2017-09-07T11:45:31Z"],["dc.date.issued","2008"],["dc.description.abstract","Neuritis of the optic nerve is one of the most frequent early symptoms ofmultiple sclerosis. There are only scarce data correlating magneticresonance imaging (MRI) contrast alterations with the underlyingpathology, that is inflammation, demyelination, and axonal damage.Here we studied optic neuritis in a rat model of experimental autoimmuneencephalomyelitis by comparingin vivoMRI findings from multipletechniques (T1, T2, proton density, magnetization transfer) to histo-pathology. We further assessed a breakdown of the blood–brain barrierby using Gd-DTPA and indirectly estimated the intracellular accumula-tion of calcium as a consequence of axonal damage by using manganese-enhanced MRI. Hyperintensity on T2-weighted images and signalenhancement after Gd-DTPA were highly sensitive to lesions of the opticnerve but did not differentiate between mild, moderate, and severedamage. Signal reduction on T1-weighted images was less sensitive butcorrelated well with the severity of tissue damage. No significant changesin magnetization transfer ratio were observed. Manganese ions tended toaccumulate in the central parts of the inflamed optic nerve. The resultingsignal enhancement at 24 h after administration positively correlated withthe severity of axonal loss. Thus, manganese might be an indicator ofintracellular calcium accumulation that is known to be associated withaxon damage. Although none of the methods alone distinguished betweeninflammation, demyelination, and reduced axon density, their specificcapabilities should prove useful for futurein vivoMRI studies of opticneuritis in both animal models and humans."],["dc.identifier.doi","10.1016/j.neuroimage.2008.02.021"],["dc.identifier.gro","3150382"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7140"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.issn","1053-8119"],["dc.subject","Optic neuritis; EAE; MRI; Manganese-enhanced MRI"],["dc.title","MRI of optic neuritis in a rat model"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]