Combined treatment with chondroitinase ABC and treadmill rehabilitation for chronic severe spinal cord injury in adult rats

Munehisa Shinozaki, Akio Iwanami, Kanehiro Fujiyoshi, Syoichi Tashiro, Kazuya Kitamura, Shinsuke Shibata, Hiroshi Fujita, Masaya Nakamura, Hideyuki Okano

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)37-47
Number of pages11
JournalNeuroscience Research
Volume113
DOIs
Publication statusPublished - 2016 Dec 1

Fingerprint

Chondroitin ABC Lyase
Spinal Cord Injuries
Rehabilitation
Therapeutics
Chondroitin Sulfate Proteoglycans
Regeneration
Wounds and Injuries
Enzymes

Keywords

  • Axonal regeneration
  • Chondroitin sulfate proteoglycan
  • Glial scar
  • Neural plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Combined treatment with chondroitinase ABC and treadmill rehabilitation for chronic severe spinal cord injury in adult rats. / Shinozaki, Munehisa; Iwanami, Akio; Fujiyoshi, Kanehiro; Tashiro, Syoichi; Kitamura, Kazuya; Shibata, Shinsuke; Fujita, Hiroshi; Nakamura, Masaya; Okano, Hideyuki.

In: Neuroscience Research, Vol. 113, 01.12.2016, p. 37-47.

Research output: Contribution to journalArticle

Shinozaki, Munehisa ; Iwanami, Akio ; Fujiyoshi, Kanehiro ; Tashiro, Syoichi ; Kitamura, Kazuya ; Shibata, Shinsuke ; Fujita, Hiroshi ; Nakamura, Masaya ; Okano, Hideyuki. / Combined treatment with chondroitinase ABC and treadmill rehabilitation for chronic severe spinal cord injury in adult rats. In: Neuroscience Research. 2016 ; Vol. 113. pp. 37-47.
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