Immediate Anti-tumor Necrosis Factor-α (Etanercept) Therapy Enhances Axonal Regeneration After Sciatic Nerve Crush

J Neurosci Res, 2010 · DOI: 10.1002/jnr.22202 · Published: February 1, 2010

Simple Explanation

Peripheral nerves can regenerate after injury, unlike those in the central nervous system. This study investigates how early treatments can affect nerve repair by looking at tumor necrosis factor-alpha (TNF-α). The study found that TNF-α levels increase briefly after a nerve injury and then return to normal. Blocking TNF-α immediately after injury with etanercept, a TNF-α antagonist, enhances nerve regeneration. The results suggest that TNF-α plays a crucial role in the early stages after nerve injury, and that intervening with a TNF-α antagonist can promote better and faster nerve repair.

Study Duration

60 days

Participants

127 adult female Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
TNF-α mRNA expression is induced at 1 day and returned to baseline at 5 days after injury in nerve and the corresponding dorsal root ganglia (DRG).
2
Immediate therapy with the TNF-α antagonist etanercept enhanced the rate of axonal regeneration, as determined by nerve pinch test.
3
Increased GAP-43 expression was found in the injured nerve and in the corresponding DRG and ventral spinal cord after systemic etanercept compared with vehicle treatments.

Research Summary

This study investigates the effect of immediate anti-TNF-α (etanercept) therapy on nerve regeneration after sciatic nerve crush injury in rats. The researchers found that TNF-α mRNA expression increased transiently after nerve crush and that etanercept treatment enhanced axonal regeneration and GAP-43 expression. The study concludes that immediate anti-TNF-α therapy supports peripheral nerve regeneration and may offer a new therapeutic strategy for nerve repair.

Practical Implications

Therapeutic Potential

Immediate etanercept therapy could be a potential therapeutic strategy for enhancing nerve regeneration after peripheral nerve injuries.

Understanding TNF-α Role

Further research is needed to fully elucidate the role of TNF-α in axonal degeneration and regrowth to optimize therapeutic interventions.

Clinical Translation

Caution is advised when extrapolating the effective etanercept doses from rodent studies to clinical use due to differences in physiology and drug metabolism.

Study Limitations

1
Future studies should assess the effect of immediate etanercept therapy on the late stages of functional regeneration.
2
The mechanisms by which its systemic therapy produces a GAP-43 increase in motor neurons of the spinal cord and its effect on the functional locomotive recovery that is not assessed by nerve pinch testing (Seijffers et al., 2007) remain to be elucidated.
3
The direct role of TNF-α on axonal outgrowth must be considered.

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