title: A combination of keratan sulfate digestion and rehabilitation promotes anatomical plasticity after rat spinal cord injury.
abstract: Functional recovery after neuronal injuries relies on neuronal network reconstruction which involves many repair processes, such as sealing of injured axon ends, axon regeneration/sprouting, and construction and refinement of synaptic connections. Chondroitin sulfate (CS) is a major inhibitor of axon regeneration/sprouting. It has been reported that the combination of task-specific rehabilitation and CS-digestion is much more effective than either treatment alone with regard to the promotion of functional and anatomical plasticity for dexterity in acute and chronic spinal cord injury models. We previously reported that keratan sulfate (KS) is another inhibitor and has a potency equal to CS. Here, we compared the effects of KS- or CS-digestion plus rehabilitation on recovery from spinal cord injury. Keratanase II or chondroitinase ABC was locally administered at the lesion after spinal cord injury at C3/4. Task-specific rehabilitation training, i.e., a single pellet reaching task using a Whishaw apparatus, was done for 3 weeks before injury, and then again at 1-6 weeks after injury. The combination of KS-digestion and rehabilitation yielded a better rate of pellet removal than either KS-digestion alone or rehabilitation alone, although these differences were not statistically significant. The combination of CS-digestion and rehabilitation showed similar results. Strikingly, both KS-digestion/rehabilitation and CS-digestion/rehabilitation showed significant increases in neurite growth in vivo as estimated by 5-hydroxytryptamine and GAP43 staining. Thus, KS-digestion and rehabilitation exerted a synergistic effect on anatomical plasticity, and this effect was comparable with that of CS-digestion/rehabilitation. KS-digestion might widen the therapeutic window of spinal cord injury if combined with rehabilitation.
authors.affiliation: Department of Biochemistry, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan; Department of Orthopedics, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Department of Biochemistry, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Imagama
authors.affiliation: Department of Developmental Molecular Anatomy, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ohgomori
authors.affiliation: Department of Biochemistry, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
authors.affiliation: Department of Orthopedics, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan. Electronic address: kkadoma@med.nagoya-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kadomatsu
mesh_terms: D000818:Animals; D002809:Chondroitin Sulfates / Q000627:therapeutic use; D005260:Female; D007632:Keratan Sulfate / Q000627:therapeutic use*; D009473:Neuronal Plasticity; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology / Q000534:rehabilitation*
chemical_list: D002809:Chondroitin Sulfates; D007632:Keratan Sulfate
keywords: Chondroitin sulfate; Chondroitinase ABC; Keratan sulfate; Keratanase II; Rehabilitation; Spinal cord injury