Respiratory axon regeneration in the chronically injured spinal cord

Neurobiol Dis., 2021 · DOI: 10.1016/j.nbd.2021.105389 · Published: July 1, 2021

Spinal Cord Injury Pulmonology Neurology

Simple Explanation

This study investigates whether a peptide (PAP4) can help restore breathing function after chronic spinal cord injury (SCI). The peptide targets a protein (PTEN) that inhibits axon growth. The researchers tested whether PAP4 could reconnect damaged nerve circuits in the spinal cord, specifically those controlling the diaphragm, a key muscle for breathing. The study found that PAP4 promoted the growth of damaged nerve fibers (axons) but only resulted in minimal recovery of diaphragm function, suggesting challenges in reconnecting these fibers in the chronically injured spinal cord.

Study Duration

24 weeks

Participants

Rats (n = 4-12 per group) with C2 hemisection SCI

Evidence Level

Not specified

Key Findings

1
Systemic delivery of PAP4 starting at 8 weeks after C2 hemisection promoted substantial, long-distance regeneration of injured bulbospinal rostral Ventral Respiratory Group (rVRG) axons.
2
PAP4 stimulated only minimal recovery of diaphragm function.
3
There was minimal formation of putative excitatory monosynaptic connections between regrowing rVRG axons and PhMN targets.

Research Summary

The study investigates the effectiveness of PAP4 in promoting respiratory axon regeneration and functional recovery in a rat model of chronic cervical spinal cord injury (SCI). PAP4 administration led to significant regeneration of injured respiratory axons through the lesion site, but only resulted in limited recovery of diaphragm function. The limited functional recovery was attributed to a lack of synaptic reconnection between the regenerated axons and their target motor neurons in the spinal cord.

Practical Implications

Therapeutic Potential

PTEN inhibition can promote axon regeneration in chronic SCI, suggesting potential for therapeutic interventions.

Combination Therapies

Combining PTEN inhibition with other interventions to promote synapse formation may enhance functional recovery in chronic SCI.

Challenges in Chronic SCI

The study highlights the challenges of achieving functional circuit restoration in the chronically injured spinal cord, particularly concerning synaptogenesis.

Study Limitations

1
Limited functional recovery despite axon regeneration.
2
Minimal synaptic reconnectivity between regrowing axons and motor neuron targets.
3
Study conducted only on younger rats.

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