271081 20240811004519.0 10.7554/eLife.90565 doi pmid:39102289 pmid pmc:PMC11299977 pmc altmetric:155287117 altmetric DZNE-2024-00953 English 600 Kislinger, Georg P:(DE-2719)9000614 0 First author dzne Combining array tomography with electron tomography provides insights into leakiness of the blood-brain barrier in mouse cortex. Cambridge 2024 eLife Sciences Publications article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1723114479_2211 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Like other volume electron microscopy approaches, automated tape-collecting ultramicrotomy (ATUM) enables imaging of serial sections deposited on thick plastic tapes by scanning electron microscopy (SEM). ATUM is unique in enabling hierarchical imaging and thus efficient screening for target structures, as needed for correlative light and electron microscopy. However, SEM of sections on tape can only access the section surface, thereby limiting the axial resolution to the typical size of cellular vesicles with an order of magnitude lower than the acquired xy resolution. In contrast, serial-section electron tomography (ET), a transmission electron microscopy-based approach, yields isotropic voxels at full EM resolution, but requires deposition of sections on electron-stable thin and fragile films, thus making screening of large section libraries difficult and prone to section loss. To combine the strength of both approaches, we developed 'ATUM-Tomo, a hybrid method, where sections are first reversibly attached to plastic tape via a dissolvable coating, and after screening detached and transferred to the ET-compatible thin films. As a proof-of-principle, we applied correlative ATUM-Tomo to study ultrastructural features of blood-brain barrier (BBB) leakiness around microthrombi in a mouse model of traumatic brain injury. Microthrombi and associated sites of BBB leakiness were identified by confocal imaging of injected fluorescent and electron-dense nanoparticles, then relocalized by ATUM-SEM, and finally interrogated by correlative ATUM-Tomo. Overall, our new ATUM-Tomo approach will substantially advance ultrastructural analysis of biological phenomena that require cell- and tissue-level contextualization of the finest subcellular textures. 351 - Brain Function (POF4-351) G:(DE-HGF)POF4-351 POF4-351 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de CLEM Other array tomography Other blood brain barrier Other cell biology Other correlation Other imaging Other mouse Other neuroscience Other volume electron microscopy Other Animals MeSH Mice MeSH Electron Microscope Tomography: methods MeSH Blood-Brain Barrier: ultrastructure MeSH Cerebral Cortex: diagnostic imaging MeSH Cerebral Cortex: ultrastructure MeSH Mice, Inbred C57BL MeSH Male MeSH Microscopy, Electron, Scanning: methods MeSH Microtomy MeSH Fabig, Gunar 0000-0003-3017-0978 1 Wehn, Antonia 2 Rodriguez, Lucia P:(DE-2719)9001702 3 dzne Jiang, Hanyi P:(DE-2719)9001710 4 dzne Niemann, Cornelia P:(DE-2719)9001883 5 dzne Klymchenko, Andrey S 6 Plesnila, Nikolaus P:(DE-2719)9000853 7 Misgeld, Thomas P:(DE-2719)2810727 8 Müller-Reichert, Thomas 0000-0003-0203-1436 9 Khalin, Igor 10 Schifferer, Martina P:(DE-2719)2812260 11 Last author 10.7554/eLife.90565 Vol. 12, p. RP90565 PERI:(DE-600)2687154-3 RP90565 eLife 12 2024 2050-084X OpenAccess http://pub.dzne.de/record/271081/files/DZNE-2024-00953%2BSUP.pdf OpenAccess pdfa http://pub.dzne.de/record/271081/files/DZNE-2024-00953%2BSUP.pdf?subformat=pdfa oai:pub.dzne.de:271081 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 0 P:(DE-2719)9000614 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)9001702 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 4 P:(DE-2719)9001710 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 5 P:(DE-2719)9001883 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 8 P:(DE-2719)2810727 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 11 P:(DE-2719)2812260 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-351 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Brain Function 0 2024 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2023-08-22 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2023-08-22 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2023-08-22 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2023-08-22 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2023-08-22 DBCoverage StatID:(DE-HGF)1040 StatID Zoological Record 2023-08-22 JCR StatID:(DE-HGF)0100 StatID ELIFE : 2022 2023-08-22 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2022-09-23T12:20:44Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2022-09-23T12:20:44Z WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2023-08-22 Fees StatID:(DE-HGF)0700 StatID 2023-08-22 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2023-08-22 Creative Commons Attribution CC BY 4.0 LIC:(DE-HGF)CCBY4 HGFVOC OpenAccess StatID:(DE-HGF)0510 StatID Peer Review StatID:(DE-HGF)0030 StatID ASC 2023-08-22 Article Processing Charges StatID:(DE-HGF)0561 StatID 2023-08-22 IF >= 5 StatID:(DE-HGF)9905 StatID ELIFE : 2022 2023-08-22 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2023-08-22 DBCoverage StatID:(DE-HGF)0320 StatID PubMed Central 2023-08-22 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2023-08-22 Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Anonymous peer review 2022-09-23T12:20:44Z I:(DE-2719)1110000-4 AG Misgeld Neuronal Cell Biology 0 I:(DE-2719)1110008 AG Simons Molecular Neurobiology 1 journal VDB UNRESTRICTED I:(DE-2719)1110000-4 I:(DE-2719)1110008 FullTexts