CNS Regeneration: Only on One Condition

Curr Biol, 2009 · DOI: 10.1016/j.cub.2009.04.026 · Published: June 9, 2009

Simple Explanation

The central nervous system (CNS) in mammals typically lacks the ability to regenerate after injury. However, scientists have discovered that if dorsal root ganglion neurons are 'conditioned' by first injuring their peripheral axons, their central axons can regenerate within the spinal cord. New research indicates that even if the order of injury is reversed, regeneration through a CNS lesion can occur rapidly under specific circumstances. This finding challenges previous assumptions about the limitations of CNS regeneration. The key condition for this regeneration is that the initial lesion in the CNS must be small enough to avoid scarring. When scarring is minimized, the subsequent conditioning can promote axon regeneration through the primary lesion.

Study Duration

Not specified

Participants

Adult rats and transgenic mice

Evidence Level

Not specified

Key Findings

1
DRG neurons can be conditioned peripherally even after a central lesion has occurred, upregulating regeneration-associated genes (RAGs) similarly to conditioning before CNS injury.
2
Axons from conditioned DRG neurons can regenerate in vivo across a relatively large, fresh lesion, but the initial lesion inhibits regeneration.
3
Axon regeneration can occur rather quickly through a primary central lesion upon subsequent conditioning, but this is contingent on the lesion being small enough to avoid scarring.

Research Summary

The mammalian CNS typically does not regenerate well after injury. However, prior research showed that a 'conditioning lesion' to peripheral axons of dorsal root ganglion (DRG) neurons can promote regeneration of their central axons within the spinal cord. This paper discusses recent findings that demonstrate that DRG neurons can be conditioned peripherally even after a central lesion, leading to the upregulation of regeneration-associated genes and the potential for axonal regeneration across lesions. The crucial condition for successful regeneration after a central lesion is minimizing the initial lesion size to prevent scarring, suggesting that the lesion environment is a critical factor in regeneration failure.

Practical Implications

Therapeutic Potential

The finding that conditioning can occur after a central lesion opens new avenues for therapeutic interventions aimed at promoting CNS regeneration after injury.

Scarring Mitigation

Understanding the role of scarring in inhibiting regeneration emphasizes the importance of developing strategies to minimize or modify scar formation after CNS injuries.

Targeted Protein Identification

The paper's insights can guide the identification of specific proteins critical for the conditioning effect, potentially leading to targeted therapies to enhance regeneration.

Study Limitations

1
The study focuses primarily on DRG neurons; the findings may not be directly applicable to all types of neurons in the CNS.
2
The success of regeneration is highly dependent on the size of the initial lesion, limiting the applicability to larger, more traumatic injuries.
3
The mechanisms underlying the conditioning effect are not fully understood, requiring further research to optimize its therapeutic potential.

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