Sialidase enhances recovery from spinal cord contusion injury

Andrea Mountney, Matthew R. Zahner, Ileana Lorenzini, Martin Oudega, Lawrence P. Schramm, Ronald L. Schnaar

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Axons fail to regenerate in the injured spinal cord, limiting motor and autonomic recovery and contributing to long-term morbidity. Endogenous inhibitors, including those on residual myelin, contribute to regeneration failure. One inhibitor, myelin-associated glycoprotein (MAG), binds to sialoglycans and other receptors on axons. MAG inhibition of axon outgrowth in some neurons is reversed by treatment with sialidase, an enzyme that hydrolyzes sialic acids and eliminates MAG-sialoglycan binding. We delivered recombinant sialidase intrathecally to rats following a spinal cord contusive injury. Sialidase (or saline solution) was infused to the injury site continuously for 2 wk and then motor behavior, autonomic physiology, and anatomic outcomes were determined 3 wk later. Sialidase treatment significantly enhanced hindlimb motor function, improved bulbospinally mediated autonomic reflexes, and increased axon sprouting. These findings validate sialoglycans as therapeutic targets and sialidase as a candidate therapy for spinal cord injury.

Original languageEnglish (US)
Pages (from-to)11561-11566
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number25
DOIs
StatePublished - Jun 22 2010
Externally publishedYes

Fingerprint

Neuraminidase
Spinal Cord Injuries
Myelin-Associated Glycoprotein
Axons
Sialic Acids
Therapeutics
Hindlimb
Myelin Sheath
Sodium Chloride
Reflex
Regeneration
Spinal Cord
Morbidity
Neurons
Wounds and Injuries
Enzymes

Keywords

  • Axon regeneration
  • Ganglioside
  • Myelin-associated glycoprotein
  • Serotonergic axons
  • Sialoglycan

ASJC Scopus subject areas

  • General

Cite this

Sialidase enhances recovery from spinal cord contusion injury. / Mountney, Andrea; Zahner, Matthew R.; Lorenzini, Ileana; Oudega, Martin; Schramm, Lawrence P.; Schnaar, Ronald L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 25, 22.06.2010, p. 11561-11566.

Research output: Contribution to journalArticle

Mountney, Andrea ; Zahner, Matthew R. ; Lorenzini, Ileana ; Oudega, Martin ; Schramm, Lawrence P. ; Schnaar, Ronald L. / Sialidase enhances recovery from spinal cord contusion injury. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 25. pp. 11561-11566.
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