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The gold standard for the histopathological analysis of mTLE is histology, which is a two-dimensional technique. To fill this gap, we propose complementary three-dimensional (3D) X-ray histology. Herein, we used synchrotron radiation-based phase-contrast microtomography with 1.6 \u03bcm-wide voxels for the post mortem visualization of tissue microstructure in an intrahippocampal-kainate mouse model for mTLE. We demonstrated that the 3D X-ray histology of unstained, unsectioned, paraffin-embedded brain hemispheres can identify hippocampal sclerosis through the loss of pyramidal neurons in the first and third regions of the Cornu ammonis as well as granule cell dispersion within the dentate gyrus. Morphology and density changes during epileptogenesis were quantified by segmentations from a deep convolutional neural network. Compared to control mice, the total dentate gyrus volume doubled and the granular layer volume quadrupled 21 days after injecting kainate. Subsequent sectioning of the same mouse brains allowed for benchmarking 3D X-ray histology against well-established histochemical and immunofluorescence stainings. Thus, 3D X-ray histology is a complementary neuroimaging tool to unlock the third dimension for the cellular-resolution histopathological analysis of mTLE.<\/jats:p>","DOI":"10.1093\/micmic\/ozad082","type":"journal-article","created":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T13:29:48Z","timestamp":1692192588000},"page":"1730-1745","source":"Crossref","is-referenced-by-count":6,"title":["3D X-ray Histology for the Investigation of Temporal Lobe Epilepsy in a Mouse Model"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0814-8467","authenticated-orcid":false,"given":"Griffin","family":"Rodgers","sequence":"first","affiliation":[{"name":"Biomaterials Science Center, Department of Biomedical Engineering, University of Basel , 4123 Allschwil , Switzerland"},{"name":"Biomaterials Science Center, Department of Clinical Research, University Hospital Basel , 4031 Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9620-8700","authenticated-orcid":false,"given":"Christos","family":"Bikis","sequence":"additional","affiliation":[{"name":"Biomaterials Science Center, Department of Biomedical Engineering, University of Basel , 4123 Allschwil , Switzerland"},{"name":"Integrierte Psychiatrie Winterthur\u2014Z\u00fcrcher Unterland , 8408 Winterthur , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6472-2956","authenticated-orcid":false,"given":"Philipp","family":"Janz","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Experimental Epilepsy Research, Department of Neurosurgery, Medical Center\u2014University of Freiburg , 79106 Freiburg , Germany"},{"name":"Faculty of Biology, University of Freiburg , 79106 Freiburg , Germany"},{"name":"BrainLinks-BrainTools Center, University of Freiburg , 79106 Freiburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6541-2629","authenticated-orcid":false,"given":"Christine","family":"Tanner","sequence":"additional","affiliation":[{"name":"Biomaterials Science Center, Department of Biomedical Engineering, University of Basel , 4123 Allschwil , Switzerland"},{"name":"Biomaterials Science Center, Department of Clinical Research, University Hospital Basel , 4031 Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9598-6295","authenticated-orcid":false,"given":"Georg","family":"Schulz","sequence":"additional","affiliation":[{"name":"Biomaterials Science Center, Department of Biomedical Engineering, University of Basel , 4123 Allschwil , Switzerland"},{"name":"Biomaterials Science Center, Department of Clinical Research, University Hospital Basel , 4031 Basel , Switzerland"},{"name":"Core Facility Micro- and Nanotomography, Department of Biomedical Engineering, University of Basel , 4123 Allschwil , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Thalmann","sequence":"additional","affiliation":[{"name":"Biomaterials Science Center, Department of Biomedical Engineering, University of Basel , 4123 Allschwil , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7022-4136","authenticated-orcid":false,"given":"Carola A","family":"Haas","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Experimental Epilepsy Research, Department of Neurosurgery, Medical Center\u2014University of Freiburg , 79106 Freiburg , Germany"},{"name":"BrainLinks-BrainTools Center, University of Freiburg , 79106 Freiburg , Germany"},{"name":"Center of Basics in NeuroModulation, Faculty of Medicine, University of Freiburg , 79114 Freiburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4078-9109","authenticated-orcid":false,"given":"Bert","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Biomaterials Science Center, Department of Biomedical Engineering, University of Basel , 4123 Allschwil , Switzerland"},{"name":"Biomaterials Science Center, Department of Clinical Research, University Hospital Basel , 4031 Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,8,16]]},"reference":[{"issue":"1","key":"2023100116021506800_ozad082-B1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.expneurol.2005.01.029","article-title":"Epileptogenesis and chronic seizures in a mouse model of temporal lobe epilepsy are associated with distinct EEG patterns and selective neurochemical alterations in the contralateral 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