PMID- 27497528 OWN - NLM STAT- MEDLINE DCOM- 20161227 LR - 20161230 IS - 1872-8111 (Electronic) IS - 0168-0102 (Linking) VI - 113 DP - 2016 Dec TI - Combined treatment with chondroitinase ABC and treadmill rehabilitation for chronic severe spinal cord injury in adult rats. PG - 37-47 LID - S0168-0102(16)30108-0 [pii] LID - 10.1016/j.neures.2016.07.005 [doi] AB - There are more than 50 times the number of chronic-phase spinal cord injury (SCI) patients than there are acute patients, and over half of all SCI patients are severely disabled. However, research focusing on chronic severe contusional SCI remains very rare. Here, we evaluated whether chondroitinase ABC (C-ABC), a degradative enzyme directed against chondroitin sulfate proteoglycans (CSPGs), and treadmill rehabilitation could exert synergistic therapeutic actions against chronic severe contusional SCI. First, we induced severe contusional SCI in adult rats, and administered C-ABC intrathecally at 6 weeks post-injury for a period of one week. Next, we performed treadmill rehabilitation from weeks 6 to 14 after SCI, for a total period of eight weeks. The initiation of treadmill rehabilitation triggered slight recovery between weeks 6 and 9, whereas C-ABC administration stimulated a third phase of recovery between weeks 12 and 14. Histologically, the C-ABC-treated rats showed an increase in the transverse residual tissue area and the extent of neuronal fiber regeneration at a site caudal to the lesion epicenter, and regrowth of putatively regenerating serotonergic fibers was significantly increased at the epicenter. We suggest that, when combined with intensive rehabilitation, C-ABC may play a beneficial role, even in severe and chronic SCI. CI - Copyright A(c) 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved. FAU - Shinozaki, Munehisa AU - Shinozaki M AD - Department of Physiology, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 1608582, Japan. FAU - Iwanami, Akio AU - Iwanami A AD - Department of Orthopedic Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 1608582, Japan. FAU - Fujiyoshi, Kanehiro AU - Fujiyoshi K AD - Department of Orthopedic Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 1608582, Japan. FAU - Tashiro, Syoichi AU - Tashiro S AD - Department of Rehabilitation, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 1608582, Japan. FAU - Kitamura, Kazuya AU - Kitamura K AD - Department of Orthopedic Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 1608582, Japan. FAU - Shibata, Shinsuke AU - Shibata S AD - Department of Physiology, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 1608582, Japan. FAU - Fujita, Hiroshi AU - Fujita H AD - Department of Glycoresearch, Central Research Laboratories, Seikagaku Corporation, 1253, Tateno 3-chome, Higashiyamato-shi, Tokyo 2070021, Japan. FAU - Nakamura, Masaya AU - Nakamura M AD - Department of Orthopedic Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 1608582, Japan. Electronic address: masa@a8.keio.jp. FAU - Okano, Hideyuki AU - Okano H AD - Department of Physiology, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 1608582, Japan. Electronic address: hidokano@a2.keio.jp. LA - eng PT - Journal Article DEP - 20160804 PL - Ireland TA - Neurosci Res JT - Neuroscience research JID - 8500749 RN - 0 (Chondroitin Sulfate Proteoglycans) RN - EC 4.2.2.20 (Chondroitin ABC Lyase) SB - IM MH - Animals MH - Axons/drug effects/physiology MH - Chondroitin ABC Lyase/*therapeutic use MH - Chondroitin Sulfate Proteoglycans/metabolism MH - Combined Modality Therapy MH - Female MH - Nerve Regeneration MH - *Physical Conditioning, Animal MH - Rats, Sprague-Dawley MH - Spinal Cord Injuries/*drug therapy/physiopathology/*rehabilitation OTO - NOTNLM OT - Axonal regeneration OT - Chondroitin sulfate proteoglycan OT - Glial scar OT - Neural plasticity EDAT- 2016/08/09 06:00 MHDA- 2016/12/28 06:00 CRDT- 2016/08/08 06:00 PHST- 2016/05/18 00:00 [received] PHST- 2016/07/20 00:00 [revised] PHST- 2016/07/26 00:00 [accepted] PHST- 2016/08/09 06:00 [pubmed] PHST- 2016/12/28 06:00 [medline] PHST- 2016/08/08 06:00 [entrez] AID - S0168-0102(16)30108-0 [pii] AID - 10.1016/j.neures.2016.07.005 [doi] PST - ppublish SO - Neurosci Res. 2016 Dec;113:37-47. doi: 10.1016/j.neures.2016.07.005. Epub 2016 Aug 4.