Sialidase enhances recovery from spinal cord contusion injury.
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.
Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Andrea
A
Mountney
Matthew R
MR
Zahner
Ileana
I
Lorenzini
Martin
M
Oudega
Lawrence P
LP
Schramm
Ronald L
RL
Schnaar
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D001522:Behavior, Animal; D003288:Contusions / Q000188:drug therapy* / Q000503:physiopathology; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D007278:Injections, Spinal; D009186:Myelin Sheath / Q000378:metabolism*; D009439:Neuraminidase / Q000378:metabolism*; D009995:Osmosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D014734:Vibrio cholerae / Q000378:metabolism
D006023:Glycoproteins; D009439:Neuraminidase