title: Combined treatment with chondroitinase ABC and treadmill rehabilitation for chronic severe spinal cord injury in adult rats.
abstract: 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.
authors: Department of Physiology, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 1608582, Japan.
authors: Munehisa
authors: M
authors: Shinozaki
authors: Department of Orthopedic Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 1608582, Japan.
authors: Akio
authors: A
authors: Iwanami
authors: Department of Orthopedic Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 1608582, Japan.
authors: Kanehiro
authors: K
authors: Fujiyoshi
authors: Department of Rehabilitation, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 1608582, Japan.
authors: Syoichi
authors: S
authors: Tashiro
authors: Department of Orthopedic Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 1608582, Japan.
authors: Kazuya
authors: K
authors: Kitamura
authors: Department of Physiology, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 1608582, Japan.
authors: Shinsuke
authors: S
authors: Shibata
authors: Department of Glycoresearch, Central Research Laboratories, Seikagaku Corporation, 1253, Tateno 3-chome, Higashiyamato-shi, Tokyo 2070021, Japan.
authors: Hiroshi
authors: H
authors: Fujita
authors: Department of Orthopedic Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 1608582, Japan. Electronic address: masa@a8.keio.jp.
authors: Masaya
authors: M
authors: Nakamura
authors: Department of Physiology, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 1608582, Japan. Electronic address: hidokano@a2.keio.jp.
authors: Hideyuki
authors: H
authors: Okano
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D019765:Chondroitin ABC Lyase / Q000627:therapeutic use*; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D003131:Combined Modality Therapy; D005260:Female; D009416:Nerve Regeneration; D010805:Physical Conditioning, Animal; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology / Q000534:rehabilitation*
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D019765:Chondroitin ABC Lyase
keywords: Axonal regeneration; Chondroitin sulfate proteoglycan; Glial scar; Neural plasticity