Inhibition of central axon regeneration: perspective from chondroitin sulfate proteoglycans in lamprey spinal cord injury

After spinal cord injury (SCI), axon regeneration fails, leading to paralysis. Chondroitin sulfate proteoglycans (CSPGs) are secreted at the injury site and were initially considered a physical barrier. These CSPGs interact with receptors, initiating inhibitory signaling that prevents regeneration. Studies show that removing CSPGs with chondroitinase ABC (ChABC) reduces their inhibitory effects and promotes axon growth and functional recovery. ChABC treatment enhances axon sprouting after SCI. Experiments in lampreys, which have identifiable reticulospinal (RS) neurons, show that CSPG digestion reduces apoptotic signaling and enhances axon regeneration after spinal cord transection.

• 1
  Digestion of CSPGs with ChABC reduces retrograde apoptotic signaling and enhances true axon regeneration in lampreys after spinal cord transection.
• 2
  Upregulation of PTPσ mRNA in RS neurons after SCI is partly due to the actions of elevated CSPGs at the injury site, indicating a retrograde effect.
• 3
  ChABC treatment promotes axonal regeneration after SCI and is accompanied by enhanced Akt activation, protecting RS neurons from retrograde apoptosis.