engleski

Sialoglycans Regulate Axon Regeneration after Central Nervous System Injury – the Therapeutic Potential of Sialidase

The adult central nervous system (CNS) is inhibitory for axon regeneration, limiting recovery from CNS injuries. This is due, in part, to endogenous axon regeneration inhibitors that accumulate at CNS injury sites, including myelin-associated glycoprotein (MAG, Siglec 4). MAG on residual myelin binds to sialoglycans on axons to halt regeneration. MAG inhibition of axon outgrowth from neurons cultured in vitro is reversed by sialidase treatment, suggesting the same treatment might enhance regeneration in vivo. We tested this in two animal models. In one, rat nerve roots were cut as they exited the spinal cord and a peripheral nerve graft was inserted. Sialidase was delivered to the graft site for 14 days via osmotic pump. Dye tracking was used to quantify spinal axon outgrowth. Sialidase-treated rats had 2.6-fold greater spinal axon outgrowth (p < 0.005) than did control rats (Yang, et al., Proc. Natl. Acad. Sci. USA 103, 11057 (2006)). In a second model, rats were subjected to spinal cord contusion, a common form of spinal cord injury in humans. Sialidase was delivered intrathecally for 14 days. Animals were monitored for motor behavior for 5 weeks, then were tested for renal sympathetic nerve activity in response to blood pressure changes, a circuit compromised by spinal cord injury. Preliminary results indicate a therapeutic benefit from sialidase delivery in this model. The results imply that axonal sialoglycans are required for inhibition of axon regeneration, and that sialidase may improve recovery from CNS injuries.

gangliosides; sialidase; axonal regeneration

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