CONDITIONING LESIONS BEFORE OR AFTER SPINAL CORD INJURY RECRUIT BROAD GENETIC MECHANISMS THAT SUSTAIN AXONAL REGENERATION: SUPERIORITY TO CAMP- MEDIATED EFFECTS

Exp Neurol, 2012 · DOI: 10.1016/j.expneurol.2011.12.037 · Published: May 1, 2012

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates how damage to a peripheral nerve, called a conditioning lesion, affects the ability of nerve fibers in the spinal cord to regenerate after injury. The researchers compared the effects of these lesions to treatments that increase levels of a molecule called cAMP, which is known to promote nerve regeneration. The study found that conditioning lesions were more effective than cAMP-elevating treatments in promoting the regeneration of nerve fibers in the spinal cord, even when the lesions were applied after the spinal cord injury. The researchers also found that conditioning lesions activated a wider range of genes involved in nerve regeneration compared to cAMP treatments. These findings suggest that conditioning lesions promote nerve regeneration through multiple mechanisms, not just by increasing cAMP levels. This has important implications for developing new treatments to promote nerve regeneration after spinal cord injury.

Study Duration

4 weeks

Participants

210 rats

Evidence Level

Level 2: Experimental study

Key Findings

1
Conditioning lesions are more effective than cAMP elevations on central axonal regeneration, especially when combined with cellular grafts and viral neurotrophin delivery.
2
The effects of conditioning lesions persist whether applied before or shortly after spinal cord injury.
3
Conditioning lesions recruit greater sets of genetic mechanisms relevant to axonal regeneration compared to cAMP administration, and these changes are sustained for longer periods.

Research Summary

This study compares the efficacy of peripheral nerve conditioning lesions to cAMP elevations on central sensory axonal regeneration when administered either before or after cervical spinal cord lesions. The study found significantly greater effects of conditioning lesions compared to cAMP elevations on central axonal regeneration when combined with cellular grafts at the lesion site and viral neurotrophin delivery. The study concludes that cAMP-mediated mechanisms account for only a portion of the potency of conditioning lesions on central axonal regeneration, and that broader genetic mechanisms can extend the effect and duration of cellular events that support axonal growth.

Practical Implications

Targeting Intracellular Mechanisms

Findings have important implications for targeting intraneuronal mechanisms to enhance regeneration in a time frame of practical relevance.

Combination Therapies

Combining conditioning lesions with neurotrophin delivery shows promise for enhancing axonal regeneration after spinal cord injury.

Timing of Intervention

Conditioning lesions are effective even when administered shortly after central lesions, providing a broader window for therapeutic intervention.

Study Limitations

1
The distance of axonal growth (2–2.5 mm) beyond the lesion site was insufficient for regenerating axons to reach their brainstem target nuclei and is therefore unlikely to have functional effects.
2
More extended growth might require the inactivation or neutralization of inhibitory cues present in the injured spinal cord and/or a decrease in NT-3 expression.
3
The study focused on sensory axons; the effects on motor axons may differ.

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