Does CNS Myelin Inhibit Axon Regeneration?

The central nervous system (CNS) often fails to regenerate axons after injury, unlike the peripheral nervous system (PNS). One reason may be the presence of inhibitory molecules in CNS myelin, produced by oligodendrocytes, which block axon growth. Research has shown that adult sensory neurons can regenerate axons in the brain's white matter, even without blocking these inhibitory factors, suggesting that the glial scar and molecules secreted by reactive astrocytes also play a role in inhibiting axon regeneration. Two important aspects that differ in the PNS and CNS are that when an axon in the PNS is severed, the chain of Schwann cells remains, providing a pathway that guides axon regrowth, which is not available in the CNS.

• 1
  Molecules derived from myelin inhibit axon outgrowth. A high-molecular-weight membrane protein (NI-35/250) has been found in rat, bovine, and human myelin as a main neurite growth inhibitory factor.
• 2
  Reactive astrocytes in the CNS, unlike Schwann cells in the PNS, form a glial scar that inhibits axon regeneration both physically and through the secretion of inhibitory molecules into the extracellular matrix, particularly chondroitin sulfate proteoglycans.
• 3
  Adult DRG neurons transplanted into CNS white matter can regenerate axons rapidly, suggesting that the inhibitory effects of myelin can be overcome, especially when the inflammatory response and glial scarring are minimized.