Chondroitinase Enhances Regeneration
1.Dorsal overhemisection
2.Intrathecal Chondroitinase ABC
3.CST axons regenerate
4.DRG upregulate GAP-43
5.Evoked potentials across scar
6.
Scar with secreted
CS-6-PG
•The glial scar contains extracellular matrix molecules including chondroitin sulphate proteoglycans (CSPGs), which inhibit axon growth in vitro. Regenerating axons stop at CSPG-rich regions in vivo.
•Chondroitinase ABC (ChABC) inactivates CSPG by removing glycosaminoglycan (GAG) chains.
• Intrathecal delivery of ChABC in rats that received a dorsal overhemisection degraded CS-GAG at the injury site, upregulated GAP-43 in DRG cells and enhanced regeneration of ascending sensory and descending corticospinal tract axons.
•ChABC treatment also restored post-synaptic responses below the lesion after electrical stimulation of corticospinal neurons, and enhanced recovery of locomotor and proprioceptive functions.
Bradbury EJ, Moon LD, Popat RJ, King VR, Bennett GS, Patel PN, Fawcett JW, McMahon SB. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 416:636-40, 2002.