A combination of keratan sulfate digestion and rehabilitation promotes anatomical plasticity after rat spinal cord injury

Yoshimoto Ishikawa, Shiro Imagama, Tomohiro Ohgomori, Naoki Ishiguro, Kenji Kadomatsu

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)13-18
Number of pages6
JournalNeuroscience Letters
Volume593
DOIs
Publication statusPublished - Apr 3 2015

Fingerprint

Keratan Sulfate
Spinal Cord Injuries
Digestion
Rehabilitation
Chondroitin Sulfates
Axons
Regeneration
Wounds and Injuries
Chondroitin ABC Lyase
Neurites
Serotonin

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

A combination of keratan sulfate digestion and rehabilitation promotes anatomical plasticity after rat spinal cord injury. / Ishikawa, Yoshimoto; Imagama, Shiro; Ohgomori, Tomohiro; Ishiguro, Naoki; Kadomatsu, Kenji.

In: Neuroscience Letters, Vol. 593, 03.04.2015, p. 13-18.

Research output: Contribution to journalArticle

Ishikawa, Yoshimoto ; Imagama, Shiro ; Ohgomori, Tomohiro ; Ishiguro, Naoki ; Kadomatsu, Kenji. / A combination of keratan sulfate digestion and rehabilitation promotes anatomical plasticity after rat spinal cord injury. In: Neuroscience Letters. 2015 ; Vol. 593. pp. 13-18.
@article{06a820cd5bb64618921c72d76010baaa,
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.",
author = "Yoshimoto Ishikawa and Shiro Imagama and Tomohiro Ohgomori and Naoki Ishiguro and Kenji Kadomatsu",
year = "2015",
month = "4",
day = "3",
doi = "10.1016/j.neulet.2015.03.015",
language = "English",
volume = "593",
pages = "13--18",
journal = "Neuroscience Letters",
issn = "0304-3940",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - A combination of keratan sulfate digestion and rehabilitation promotes anatomical plasticity after rat spinal cord injury

AU - Ishikawa, Yoshimoto

AU - Imagama, Shiro

AU - Ohgomori, Tomohiro

AU - Ishiguro, Naoki

AU - Kadomatsu, Kenji

PY - 2015/4/3

Y1 - 2015/4/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84924953392&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924953392&partnerID=8YFLogxK

U2 - 10.1016/j.neulet.2015.03.015

DO - 10.1016/j.neulet.2015.03.015

M3 - Article

C2 - 25770829

AN - SCOPUS:84924953392

VL - 593

SP - 13

EP - 18

JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

ER -