Sialidase Enhances Spinal Axon Outgrowth in vivo

The adult CNS is an inhibitory environment for axon outgrowth, severely limiting recovery from traumatic injury. This limitation is due, in part, to endogenous axon regeneration inhibitors (ARIs) that accumulate at CNS injury sites. ARIs include myelin-associated glycoprotein, Nogo, oligodendrocyte-...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-07, Vol.103 (29), p.11057-11062
Main Authors: Yang, Lynda J. S., Lorenzini, Ileana, Vajn, Katarina, Mountney, Andrea, Schramm, Lawrence P., Schnaar, Ronald L.
Format: Article
Language:English
Subjects:
Animals
Axons
Axons - drug effects
Axons - enzymology
Biological Sciences
Brachial plexus
Clostridium perfringens
Enzymes
Glycoproteins
Male
Nerve Regeneration
Nerves
Neuraminidase - metabolism
Neuraminidase - pharmacology
Neurites - drug effects
Neurites - enzymology
Neurons
Peripheral nerves
Physical trauma
Rats
Rats, Sprague-Dawley
Receptors
Reflexes
Spinal cord
Spinal Cord - drug effects
Spinal Cord - enzymology
Spinal cord injuries
Tissue grafting
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The adult CNS is an inhibitory environment for axon outgrowth, severely limiting recovery from traumatic injury. This limitation is due, in part, to endogenous axon regeneration inhibitors (ARIs) that accumulate at CNS injury sites. ARIs include myelin-associated glycoprotein, Nogo, oligodendrocyte-myelin glycoprotein, and chondroitin sulfate proteoglycans (CSPGs). Some ARIs bind to specific receptors on the axon growth cone to halt outgrowth. Reversing or blocking the actions of ARIs may promote recovery after CNS injury. We report that treatment with sialidase, an enzyme that cleaves one class of axonal receptors for myelinassociated glycoprotein, enhances spinal axon outgrowth into implanted peripheral nerve grafts in a rat model of brachial plexus avulsion, a traumatic injury in which nerve roots are torn from the spinal cord. Repair using peripheral nerve grafts is a promising restorative surgical treatment in humans, although functional improvement remains limited. To model brachial plexus avulsion in the rat, C8 nerve roots were cut flush to the spinal cord and a peroneal nerve graft was inserted into the lateral spinal cord at the lesion site. Infusion of Clostridium perfringens sialidase to the injury site markedly increased the number of spinal axons that grew into the graft (2.6-fold). Chondroitinase ABC, an enzyme that cleaves a different ARI (CSPGs), also enhanced axon outgrowth in this model. In contrast, phosphatidylinositol-specific phospholipase C, which cleaves oligodendrocyte-myelin glycoprotein and Nogo receptors, was without benefit. Molecular therapies targeting sialoglycoconjugates and CSPGs may aid functional recovery after brachial plexus avulsion or other nervous system injuries and diseases.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0604613103