Rapid chemical clearing of white matter in the post-mortem human brain by 1,2-hexanediol delipidation |
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| Affiliation: | 1. Department of System Pathology for Neurological Disorders, Center for Bioresources, Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata 951-8585, Japan;2. Department of Pathology, Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata 951-8585, Japan;1. Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan;2. PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan;3. Laboratory for Synthetic Biology, RIKEN Quantitative Biology Center (QBiC), 1-3, Yamadaoka, Suita, Osaka 565-0874, Japan;4. AMED-CREST, Japan Agency for Medical Research and Development (AMED), 1-7-1, Ohte-machi, Chiyoda-ku, Tokyo, 100-0004, Japan;1. Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA;2. Laboratory of Brain Development and Repair, The Rockefeller University, New York, NY 10065, USA;1. Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan;2. Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan;3. Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata 951-8585, Japan;4. Laboratory for Synthetic Biology, RIKEN Quantitative Biology Center, 1-3 Yamadaoka, Suita, Osaka 565-5241, Japan;1. Harvard Center for Biological Imaging, Harvard University, Cambridge, MA 02138, USA;2. Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA;3. Center for Brain Science, Harvard University, Cambridge, MA 02138, USA;1. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA;2. Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA;3. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA;4. Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA;5. Simons Center for Data Analysis, 160 Fifth Avenue, 8th Floor, New York, NY 10010, USA;6. C.S. Kubik Laboratory of Neuropathology, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA;7. Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA;8. Princeton Neuroscience Institute and Computer Science Department, Princeton University, Princeton, NJ 08544, USA;9. Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02142, USA;1. Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Dr., Ashburn, VA 20147, USA |
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| Abstract: | Three-dimensional (3D) imaging based on chemical tissue clearing in the post-mortem human brain is a promising approach for stereoscopic understanding of central nervous system diseases. Especially, delipidation of lipid-rich white matter (WM) is a rate-determining step in human brain clearing by hydrophilic reagents. In this study, we described the rapid delipidation of WM by a 1,2-hexanediol (HxD)-based aqueous solution. HxD delipidation enabled rapid clearing of a formalin-fixed human brain specimen including the WM. Although harsh HxD delipidation was applied to the brain tissue, conventional pathological staining patterns and various types of antigenicity were sufficiently preserved. Furthermore, HxD delipidation was compatible with 3D imaging of fluorescently-labeled tissue samples. HxD delipidation could be useful in future 3D neuropathological diagnosis. |
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| Keywords: | Chemical tissue clearing White matter Delipidation 1,2-Hexanediol Neuropathology |
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