Sialidase, chondroitinase ABC, and combination therapy after spinal cord contusion injury

Andrea Mountney, Matthew R. Zahner, Elizabeth R. Sturgill, Christopher J. Riley, Jeffrey W. Aston, Martin Oudega, Lawrence P. Schramm, Andres Hurtado, Ronald L. Schnaar

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Axon regeneration in the central nervous system is severely hampered, limiting functional recovery. This is in part because of endogenous axon regeneration inhibitors that accumulate at the injury site. Therapeutic targeting of these inhibitors and their receptors may facilitate axon outgrowth and enhance recovery. A rat model of spinal cord contusion injury was used to test the effects of two bacterial enzyme therapies that target independent axon regeneration inhibitors, sialidase (Vibrio cholerae) and chondroitinase ABC (ChABC, Proteus vulgaris). The two enzymes, individually and in combination, were infused for 2 weeks via implanted osmotic pumps to the site of a moderate thoracic spinal cord contusion injury. Sialidase was completely stable, whereas ChABC retained>30% of its activity in vivo over the 2 week infusion period. Immunohistochemistry revealed that infused sialidase acted robustly throughout the spinal cord gray and white matter, whereas ChABC activity was more intense superficially. Sialidase treatment alone resulted in improved behavioral and anatomical outcomes. Rats treated exclusively with sialidase showed significantly increased hindlimb motor function, evidenced by higher Basso Beattie and Bresnahan (BBB) and BBB subscores, and fewer stepping errors on a horizontal ladder. Sialidase-treated rats also had increased serotonergic axons caudal to the injury. ChABC treatment, in contrast, did not enhance functional recovery or alter axon numbers after moderate spinal cord contusion injury, and dampened the response of sialidase in the dual enzyme treatment group. We conclude that sialidase infusion enhanced recovery from spinal cord contusion injury, and that combining sialidase with ChABC failed to improve outcomes.

Original languageEnglish (US)
Pages (from-to)181-190
Number of pages10
JournalJournal of Neurotrauma
Volume30
Issue number3
DOIs
StatePublished - Feb 1 2013
Externally publishedYes

Fingerprint

Chondroitin ABC Lyase
Neuraminidase
Spinal Cord Injuries
Axons
Regeneration
Therapeutics
Proteus vulgaris
Enzyme Therapy
Vibrio cholerae
Wounds and Injuries
Enzymes
Hindlimb
Spinal Cord
Thorax
Central Nervous System
Immunohistochemistry

Keywords

  • axon regeneration
  • chondroitin sulfate
  • ganglioside
  • motor behavior
  • serotonergic axons

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Mountney, A., Zahner, M. R., Sturgill, E. R., Riley, C. J., Aston, J. W., Oudega, M., ... Schnaar, R. L. (2013). Sialidase, chondroitinase ABC, and combination therapy after spinal cord contusion injury. Journal of Neurotrauma, 30(3), 181-190. https://doi.org/10.1089/neu.2012.2353

Sialidase, chondroitinase ABC, and combination therapy after spinal cord contusion injury. / Mountney, Andrea; Zahner, Matthew R.; Sturgill, Elizabeth R.; Riley, Christopher J.; Aston, Jeffrey W.; Oudega, Martin; Schramm, Lawrence P.; Hurtado, Andres; Schnaar, Ronald L.

In: Journal of Neurotrauma, Vol. 30, No. 3, 01.02.2013, p. 181-190.

Research output: Contribution to journalArticle

Mountney, A, Zahner, MR, Sturgill, ER, Riley, CJ, Aston, JW, Oudega, M, Schramm, LP, Hurtado, A & Schnaar, RL 2013, 'Sialidase, chondroitinase ABC, and combination therapy after spinal cord contusion injury', Journal of Neurotrauma, vol. 30, no. 3, pp. 181-190. https://doi.org/10.1089/neu.2012.2353
Mountney, Andrea ; Zahner, Matthew R. ; Sturgill, Elizabeth R. ; Riley, Christopher J. ; Aston, Jeffrey W. ; Oudega, Martin ; Schramm, Lawrence P. ; Hurtado, Andres ; Schnaar, Ronald L. / Sialidase, chondroitinase ABC, and combination therapy after spinal cord contusion injury. In: Journal of Neurotrauma. 2013 ; Vol. 30, No. 3. pp. 181-190.
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