Intraneural Injection of ATP Stimulates Regeneration of Primary Sensory Axons in the Spinal Cord

The Journal of Neuroscience, 2018 · DOI: 10.1523/JNEUROSCI.1660-17.2017 · Published: February 7, 2018

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates whether injecting ATP into a peripheral nerve can stimulate the regeneration of sensory nerve fibers in the spinal cord, similar to what happens after a peripheral nerve injury. The researchers found that injecting ATP into the sciatic nerve of rats increased the number of axons growing into a spinal cord lesion after a dorsal column transection. The study also showed that ATP injection increased the expression of proteins associated with nerve regeneration in sensory neurons, and that P2Y2 receptors are involved in this process.

Study Duration

6 weeks

Participants

Female Wister rats (200–250 g, 6–8 rats per group) and P2X7R_KO and P2Y2R_KO mice

Evidence Level

Not specified

Key Findings

1
A single injection of ATP into the sciatic nerve quadrupled the number of axons growing into a lesion epicenter in the spinal cord after a dorsal column transection.
2
A second ATP injection one week after the first markedly reinforced the stimulatory effect of a single injection.
3
P2Y2 receptors are involved in the activation of STAT3 after ATP injection or conditioning lesion, whereas P2X7 receptors are not.

Research Summary

This study demonstrates that intraneural injection of ATP can elevate the regenerative state of DRG neurons and stimulate the growth of their central axons in injured spinal cord. ATP injection is also able to activate transcription factor STAT3 and increase the expression of GAP43 in DRG neurons in the same way as nerve injury does. The data from this study also suggest that intraneural ATP injection could be developed into a clinically applicable treatment for overcoming one of the major obstacles to axonal regeneration in the adult mammalian CNS.

Practical Implications

Therapeutic Potential

Intraneural ATP injection could be developed into a clinically applicable treatment for spinal cord injury to promote axon regeneration.

Underlying Mechanisms

The study reveals possible mechanisms underlying the stimulation of regenerative programs, involving ATP release as an injury signal and activation of the STAT3 signaling pathway.

Combination Therapy

ATP injection can be combined with other strategies such as blocking myelin-associated inhibitors to achieve more profound axonal regeneration.

Study Limitations

1
Spinal cord injury and ATP injection were performed concomitantly, which will not occur in clinical practice.
2
The efficacy of ATP injection needs to be tested in subacute and chronic injury animal models.
3
Any successful therapeutic strategies will also have to deal with the poor cellular environment in the CNS and the challenge of directing axons to their original synaptic targets.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury