Three-dimensional imaging of the unsectioned adult spinal cord to assess axon regeneration and glial responses after injury

Nature Medicine
Ali ErtürkFrank Bradke

Abstract

Studying regeneration in the central nervous system (CNS) is hampered by current histological and imaging techniques because they provide only partial information about axonal and glial reactions. Here we developed a tetrahydrofuran-based clearing procedure that renders fixed and unsectioned adult CNS tissue transparent and fully penetrable for optical imaging. In large spinal cord segments, we imaged fluorescently labeled cells by 'ultramicroscopy' and two-photon microscopy without the need for histological sectioning. We found that more than a year after injury growth-competent axons regenerated abundantly through the injury site. A few growth-incompetent axons could also regenerate when they bypassed the lesion. Moreover, we accurately determined quantitative changes of glial cells after spinal cord injury. Thus, clearing CNS tissue enables an unambiguous evaluation of axon regeneration and glial reactions. Our clearing procedure also renders other organs transparent, which makes this approach useful for a large number of preclinical paradigms.

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Citations

Oct 19, 2013·Bulletin of Experimental Biology and Medicine·A A LazutkinK V Anokhin
Oct 13, 2012·Nature Protocols·Ali ErtürkHans-Ulrich Dodt
Dec 1, 2012·International Journal of Biomedical Imaging·Monish PimpalkhareXavier Intes
Nov 13, 2012·The Journal of Clinical Investigation·Christian BredeAndreas Beilhack
Apr 6, 2012·PloS One·Klaus BeckerHans-Ulrich Dodt
Jun 28, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yu-Shang LeeJerry Silver
Jul 23, 2014·The Journal of Experimental Medicine·Matthew C WoodruffMichael C Carroll
Mar 2, 2016·Plant & Cell Physiology·Junko HasegawaSachihiro Matsunaga
Nov 7, 2015·The Journal of Physiological Sciences : JPS·Takeshi KandaHiromasa Funato
Feb 6, 2015·Microscopy·Atsushi Miyawaki
Oct 9, 2015·Nature Protocols·Etsuo A SusakiHiroki R Ueda
Sep 13, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yasuo TakashimaAtsushi Suzuki
Apr 16, 2014·The International Journal of Neuroscience·Ewa Rojczyk-GołębiewskaRyszard Wiaderkiewicz
Jun 16, 2015·Frontiers in Neuroanatomy·Jing YuanQingming Luo
Jun 16, 2015·Frontiers in Neuroanatomy·Ludovico SilvestriFrancesco S Pavone
Jan 16, 2014·Experimental Neurology·Jared M CreggJerry Silver
Oct 31, 2014·International Journal of Neural Systems·Jérémie Cabessa, Hava T Siegelmann
Mar 12, 2015·Frontiers in Neuroanatomy·Bing HouTianzi Jiang
Aug 17, 2014·Tissue Engineering. Part C, Methods·Molly E Boutin, Diane Hoffman-Kim
Oct 29, 2014·Molecular Psychiatry·A M StewartA V Kalueff
Oct 11, 2016·IEEE Journal of Selected Topics in Quantum Electronics : a Publication of the IEEE Lasers and Electro-optics Society·Jing MenChao Zhou
May 29, 2015·PloS One·Nina JährlingHans-Ulrich Dodt
Aug 13, 2013·Journal of Neuroimmunology·Vinciane ToppetsNadine Antoine
Aug 23, 2016·Nature Methods·Chenchen PanAli Ertürk
Sep 7, 2016·Scientific Reports·Kristian H R Jensen, Rune W Berg
Mar 17, 2017·Acta Cirúrgica Brasileira·Jéssica Rodrigues OrlandinValéria Maria Lara
Dec 13, 2016·Neuroscience Letters·Brett J HiltonWolfram Tetzlaff
Nov 9, 2016·Neuroscience Letters·Caitlin E Hill
Feb 18, 2017·Scientific Reports·Maxence FrétaudViolette Thermes
Jul 19, 2017·Experimental Neurology·Dietmar FischerKevin K Park

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