How does chondroitinase promote functional recovery in the damaged CNS?
A number of recent studies have established that the bacterial enzyme chondroitinase ABC promotes functional recovery in the injured CNS. The issue of how it works is rarely addressed, however. The effects of the enzyme are presumed to be due to the degradation of inhibitory chondroitin sulphate GAG chains. Here we review what is known about the composition, structure and distribution of the extracellular matrix in the CNS, and how it changes in response to injury. We summarize the data pertaining to the ability of chondroitinase to promote functional recovery, both in the context of axon regeneration and the reactivation of plasticity. We also present preliminary data on the persistence of the effects of the enzyme in vivo, and its hyaluronan-degrading activity in CNS homogenates in vitro. We then consider precisely how the enzyme might influence functional recovery in the CNS. The ability of chondroitinase to degrade hyaluronan is likely to result in greater matrix disruption than the degradation of chondroitin sulphate alone.
Crespo
Dámaso
D
Cambridge University Centre for Brain Repair, Forvie Site, Robinson Way, Cambridge, CB2 2PY, UK.
Asher
Richard A
RA
Lin
Rachel
R
Rhodes
Kate E
KE
Fawcett
James W
JW
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism; D019765:Chondroitin ABC Lyase / Q000494:pharmacology* / Q000627:therapeutic use; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005911:Gliosis / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology
D006820:Hyaluronic Acid; D019765:Chondroitin ABC Lyase