Kerschensteiner, Martin

[["dc.bibliographiccitation.firstpage","2683"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","2695"],["dc.bibliographiccitation.volume","144"],["dc.contributor.author","Mahler, Christoph"],["dc.contributor.author","Schumacher, Adrian-Minh"],["dc.contributor.author","Unterrainer, Marcus"],["dc.contributor.author","Kaiser, Lena"],["dc.contributor.author","Höllbacher, Thomas"],["dc.contributor.author","Lindner, Simon"],["dc.contributor.author","Havla, Joachim"],["dc.contributor.author","Ertl-Wagner, Birgit"],["dc.contributor.author","Patzig, Maximilian"],["dc.contributor.author","Seelos, Klaus"],["dc.contributor.author","Kerschensteiner, Martin"],["dc.date.accessioned","2022-02-01T10:31:20Z"],["dc.date.available","2022-02-01T10:31:20Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Progressive multifocal leukoencephalopathy (PML) is a severe infection of the CNS caused by the polyomavirus JC that can occur in multiple sclerosis patients treated with natalizumab. Clinical management of patients with natalizumab-associated PML is challenging not least because current imaging tools for the early detection, longitudinal monitoring and differential diagnosis of PML lesions are limited. Here we evaluate whether translocator protein (TSPO) PET imaging can be applied to monitor the inflammatory activity of PML lesions over time and differentiate them from multiple sclerosis lesions. For this monocentre pilot study we followed eight patients with natalizumab-associated PML with PET imaging using the TSPO radioligand 18F-GE-180 combined with frequent 3 T MRI. In addition we compared TSPO PET signals in PML lesions with the signal pattern of multiple sclerosis lesions from 17 independent multiple sclerosis patients. We evaluated the standardized uptake value ratio as well as the morphometry of the TSPO uptake for putative PML and multiple sclerosis lesions areas compared to a radiologically unaffected pseudo-reference region in the cerebrum. Furthermore, TSPO expression in situ was immunohistochemically verified by determining the density and cellular identity of TSPO-expressing cells in brain sections from four patients with early natalizumab-associated PML as well as five patients with other forms of PML and six patients with inflammatory demyelinating CNS lesions (clinically isolated syndrome/multiple sclerosis). Histological analysis revealed a reticular accumulation of TSPO expressing phagocytes in PML lesions, while such phagocytes showed a more homogeneous distribution in putative multiple sclerosis lesions. TSPO PET imaging showed an enhanced tracer uptake in natalizumab-associated PML lesions that was present from the early to the chronic stages (up to 52 months after PML diagnosis). While gadolinium enhancement on MRI rapidly declined to baseline levels, TSPO tracer uptake followed a slow one phase decay curve. A TSPO-based 3D diagnostic matrix taking into account the uptake levels as well as the shape and texture of the TSPO signal differentiated >96% of PML and multiple sclerosis lesions. Indeed, treatment with rituximab after natalizumab-associated PML in three patients did not affect tracer uptake in the assigned PML lesions but reverted tracer uptake to baseline in the assigned active multiple sclerosis lesions. Taken together our study suggests that TSPO PET imaging can reveal CNS inflammation in natalizumab-associated PML. TSPO PET may facilitate longitudinal monitoring of disease activity and help to distinguish recurrent multiple sclerosis activity from PML progression."],["dc.description.abstract","Abstract Progressive multifocal leukoencephalopathy (PML) is a severe infection of the CNS caused by the polyomavirus JC that can occur in multiple sclerosis patients treated with natalizumab. Clinical management of patients with natalizumab-associated PML is challenging not least because current imaging tools for the early detection, longitudinal monitoring and differential diagnosis of PML lesions are limited. Here we evaluate whether translocator protein (TSPO) PET imaging can be applied to monitor the inflammatory activity of PML lesions over time and differentiate them from multiple sclerosis lesions. For this monocentre pilot study we followed eight patients with natalizumab-associated PML with PET imaging using the TSPO radioligand 18F-GE-180 combined with frequent 3 T MRI. In addition we compared TSPO PET signals in PML lesions with the signal pattern of multiple sclerosis lesions from 17 independent multiple sclerosis patients. We evaluated the standardized uptake value ratio as well as the morphometry of the TSPO uptake for putative PML and multiple sclerosis lesions areas compared to a radiologically unaffected pseudo-reference region in the cerebrum. Furthermore, TSPO expression in situ was immunohistochemically verified by determining the density and cellular identity of TSPO-expressing cells in brain sections from four patients with early natalizumab-associated PML as well as five patients with other forms of PML and six patients with inflammatory demyelinating CNS lesions (clinically isolated syndrome/multiple sclerosis). Histological analysis revealed a reticular accumulation of TSPO expressing phagocytes in PML lesions, while such phagocytes showed a more homogeneous distribution in putative multiple sclerosis lesions. TSPO PET imaging showed an enhanced tracer uptake in natalizumab-associated PML lesions that was present from the early to the chronic stages (up to 52 months after PML diagnosis). While gadolinium enhancement on MRI rapidly declined to baseline levels, TSPO tracer uptake followed a slow one phase decay curve. A TSPO-based 3D diagnostic matrix taking into account the uptake levels as well as the shape and texture of the TSPO signal differentiated >96% of PML and multiple sclerosis lesions. Indeed, treatment with rituximab after natalizumab-associated PML in three patients did not affect tracer uptake in the assigned PML lesions but reverted tracer uptake to baseline in the assigned active multiple sclerosis lesions. Taken together our study suggests that TSPO PET imaging can reveal CNS inflammation in natalizumab-associated PML. TSPO PET may facilitate longitudinal monitoring of disease activity and help to distinguish recurrent multiple sclerosis activity from PML progression."],["dc.identifier.doi","10.1093/brain/awab127"],["dc.identifier.pmid","33757118"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/98835"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/20"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-517"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | C02: In vivo detection and targeting of calcium clearance and axonal membrane repair after acute CNS insults"],["dc.relation.eissn","1460-2156"],["dc.relation.issn","0006-8950"],["dc.relation.workinggroup","RG Brück"],["dc.relation.workinggroup","RG Kerschensteiner (Neuroimmune Interactions)"],["dc.relation.workinggroup","RG Stadelmann-Nessler"],["dc.title","TSPO PET imaging of natalizumab-associated progressive multifocal leukoencephalopathy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2461"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Annals of Clinical and Translational Neurology"],["dc.bibliographiccitation.lastpage","2466"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Penkert, Horst"],["dc.contributor.author","Lauber, Chris"],["dc.contributor.author","Gerl, Mathias J."],["dc.contributor.author","Klose, Christian"],["dc.contributor.author","Damm, Markus"],["dc.contributor.author","Fitzner, Dirk"],["dc.contributor.author","Flierl‐Hecht, Andrea"],["dc.contributor.author","Kümpfel, Tania"],["dc.contributor.author","Kerschensteiner, Martin"],["dc.contributor.author","Hohlfeld, Reinhard"],["dc.contributor.author","Gerdes, Lisa A."],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2021-04-14T08:32:24Z"],["dc.date.available","2021-04-14T08:32:24Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1002/acn3.51216"],["dc.identifier.pmid","33159711"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83910"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/1"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B01: The role of inflammatory cytokine signaling for efficient remyelination in multiple sclerosis"],["dc.relation","TRR 274 | C02: In vivo detection and targeting of calcium clearance and axonal membrane repair after acute CNS insults"],["dc.relation.issn","2328-9503"],["dc.relation.workinggroup","RG Kerschensteiner (Neuroimmune Interactions)"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.title","Plasma lipidomics of monozygotic twins discordant for multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","355"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Nature Neuroscience"],["dc.bibliographiccitation.lastpage","367"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Jafari, Mehrnoosh"],["dc.contributor.author","Schumacher, Adrian-Minh"],["dc.contributor.author","Snaidero, Nicolas"],["dc.contributor.author","Ullrich Gavilanes, Emily M."],["dc.contributor.author","Neziraj, Tradite"],["dc.contributor.author","Kocsis-Jutka, Virág"],["dc.contributor.author","Engels, Daniel"],["dc.contributor.author","Jürgens, Tanja"],["dc.contributor.author","Wagner, Ingrid"],["dc.contributor.author","Weidinger, Juan Daniel Flórez"],["dc.contributor.author","Schmidt, Stephanie S."],["dc.contributor.author","Beltrán, Eduardo"],["dc.contributor.author","Hagan, Nellwyn"],["dc.contributor.author","Woodworth, Lisa"],["dc.contributor.author","Ofengeim, Dimitry"],["dc.contributor.author","Gans, Joseph"],["dc.contributor.author","Wolf, Fred"],["dc.contributor.author","Kreutzfeldt, Mario"],["dc.contributor.author","Portugues, Ruben"],["dc.contributor.author","Merkler, Doron"],["dc.contributor.author","Misgeld, Thomas"],["dc.contributor.author","Kerschensteiner, Martin"],["dc.date.accessioned","2021-04-14T08:30:17Z"],["dc.date.available","2021-04-14T08:30:17Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1038/s41593-020-00780-7"],["dc.identifier.pmid","33495636"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83177"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/12"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/103"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B03: Checkpoints of recovery after primary astrocytic lesions in neuromyelitis optica and related animal models"],["dc.relation","TRR 274 | C02: In vivo detection and targeting of calcium clearance and axonal membrane repair after acute CNS insults"],["dc.relation","TRR 274 | C05: Checkpoints for circuit integration of nascent neurons in the injured brain"],["dc.relation","TRR 274 | Z01: Bioimaging Platform"],["dc.relation","TRR 274 | Z02: Genomics and Bioinformatics Platform"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | C02: Aktive Zonendesigns und -dynamiken, die auf das synaptische Arbeitsgedächtnis zugeschnitten sind"],["dc.relation.eissn","1546-1726"],["dc.relation.issn","1097-6256"],["dc.relation.workinggroup","RG Kerschensteiner (Neuroimmune Interactions)"],["dc.relation.workinggroup","RG Misgeld"],["dc.relation.workinggroup","RG Portugues (Sensorimotor Control)"],["dc.relation.workinggroup","RG Wolf"],["dc.title","Phagocyte-mediated synapse removal in cortical neuroinflammation is promoted by local calcium accumulation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4901"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Snaidero, Nicolas"],["dc.contributor.author","Schifferer, Martina"],["dc.contributor.author","Mezydlo, Aleksandra"],["dc.contributor.author","Zalc, Bernard"],["dc.contributor.author","Kerschensteiner, Martin"],["dc.contributor.author","Misgeld, Thomas"],["dc.date.accessioned","2022-08-18T13:29:08Z"],["dc.date.available","2022-08-18T13:29:08Z"],["dc.date.issued","2020"],["dc.description.abstract","Myelin, rather than being a static insulator of axons, is emerging as an active participant in circuit plasticity. This requires precise regulation of oligodendrocyte numbers and myelination patterns. Here, by devising a laser ablation approach of single oligodendrocytes, followed by in vivo imaging and correlated ultrastructural reconstructions, we report that in mouse cortex demyelination as subtle as the loss of a single oligodendrocyte can trigger robust cell replacement and remyelination timed by myelin breakdown. This results in reliable reestablishment of the original myelin pattern along continuously myelinated axons, while in parallel, patchy isolated internodes emerge on previously unmyelinated axons. Therefore, in mammalian cortex, internodes along partially myelinated cortical axons are typically not reestablished, suggesting that the cues that guide patchy myelination are not preserved through cycles of de- and remyelination. In contrast, myelin sheaths forming continuous patterns show remarkable homeostatic resilience and remyelinate with single axon precision."],["dc.identifier.doi","10.1038/s41467-020-18632-0"],["dc.identifier.pmid","32994410"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113004"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/7"],["dc.language.iso","en"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B02: Inflammatory neurodegeneration and repair mechanisms in childhood onset autoimmune and neurometabolic demyelinating CNS disease"],["dc.relation","TRR 274 | C02: In vivo detection and targeting of calcium clearance and axonal membrane repair after acute CNS insults"],["dc.relation","TRR 274 | C05: Checkpoints for circuit integration of nascent neurons in the injured brain"],["dc.relation","TRR 274 | Z01: Bioimaging Platform"],["dc.relation.issn","2041-1723"],["dc.relation.workinggroup","RG Kerschensteiner (Neuroimmune Interactions)"],["dc.relation.workinggroup","RG Misgeld"],["dc.relation.workinggroup","RG Schifferer"],["dc.title","Myelin replacement triggered by single-cell demyelination in mouse cortex"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","100232"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","STAR Protocols"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Kislinger, Georg"],["dc.contributor.author","Gnägi, Helmut"],["dc.contributor.author","Kerschensteiner, Martin"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Misgeld, Thomas"],["dc.contributor.author","Schifferer, Martina"],["dc.date.accessioned","2022-08-19T06:32:51Z"],["dc.date.available","2022-08-19T06:32:51Z"],["dc.date.issued","2020"],["dc.description.abstract","Here, we describe a detailed workflow for ATUM-FIB microscopy, a hybrid method that combines serial-sectioning scanning electron microscopy (SEM) with focused ion beam SEM (FIB-SEM). This detailed protocol is optimized for mouse cortex samples. The main processing steps include the generation of semi-thick sections from sequentially cured resin blocks using a heated microtomy approach. We demonstrate the different imaging modalities, including serial light and electron microscopy for target recognition and FIB-SEM for isotropic imaging of regions of interest. For complete details on the use and execution of this protocol, please refer to Kislinger et al. (2020)."],["dc.identifier.doi","10.1016/j.xpro.2020.100232"],["dc.identifier.pmid","33377119"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113013"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/33"],["dc.language.iso","en"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B03: Checkpoints of recovery after primary astrocytic lesions in neuromyelitis optica and related animal models"],["dc.relation","TRR 274 | C02: In vivo detection and targeting of calcium clearance and axonal membrane repair after acute CNS insults"],["dc.relation","TRR 274 | Z01: Bioimaging Platform"],["dc.relation.eissn","2666-1667"],["dc.relation.workinggroup","RG Kerschensteiner (Neuroimmune Interactions)"],["dc.relation.workinggroup","RG Misgeld"],["dc.relation.workinggroup","RG Schifferer"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.title","ATUM-FIB microscopy for targeting and multiscale imaging of rare events in mouse cortex"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","101290"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","iScience"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Kislinger, Georg"],["dc.contributor.author","Gnägi, Helmut"],["dc.contributor.author","Kerschensteiner, Martin"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Misgeld, Thomas"],["dc.contributor.author","Schifferer, Martina"],["dc.date.accessioned","2022-08-18T13:58:23Z"],["dc.date.available","2022-08-18T13:58:23Z"],["dc.date.issued","2020-07-24"],["dc.description.abstract","Volume electron microscopy enables the ultrastructural analysis of biological tissue. Currently, the techniques involving ultramicrotomy (ATUM, ssTEM) allow large fields of view but afford only limited z-resolution, whereas ion beam-milling approaches (FIB-SEM) yield isotropic voxels but are restricted in volume size. Now we present a hybrid method, named ATUM-FIB, which combines the advantages of both approaches. ATUM-FIB is based on serial sectioning of tissue into \"semithick\" (2-10 μm) sections collected onto tape. Serial light and electron microscopy allows the identification of regions of interest that are then directly accessible for targeted FIB-SEM. The set of semithick sections thus represents a tissue \"library\" which provides three-dimensional context information that can be probed \"on demand\" by local high-resolution analysis. We demonstrate the potential of this technique to reveal the ultrastructure of rare but pathologically important events by identifying microglia contact sites with amyloid plaques in a mouse model of familial Alzheimer's disease."],["dc.identifier.doi","10.1016/j.isci.2020.101290"],["dc.identifier.pmid","32622266"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113006"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/15"],["dc.language.iso","en"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B03: Checkpoints of recovery after primary astrocytic lesions in neuromyelitis optica and related animal models"],["dc.relation","TRR 274 | C02: In vivo detection and targeting of calcium clearance and axonal membrane repair after acute CNS insults"],["dc.relation","TRR 274 | Z01: Bioimaging Platform"],["dc.relation.eissn","2589-0042"],["dc.relation.workinggroup","RG Kerschensteiner (Neuroimmune Interactions)"],["dc.relation.workinggroup","RG Misgeld"],["dc.relation.workinggroup","RG Schifferer"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.title","Multiscale ATUM-FIB Microscopy Enables Targeted Ultrastructural Analysis at Isotropic Resolution"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]