Construction of pathways to promote axon growth within the adult central nervous system

Brain Res Bull, 2011 · DOI: 10.1016/j.brainresbull.2010.05.013 · Published: March 10, 2011

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

After spinal cord injury, it's hard to get axons to grow or regenerate because the environment isn't supportive and neurons don't have much ability to grow on their own. Neurotrophins can help sensory axons regenerate after certain injuries, but they don't always go to the right place. To help axons grow in the right direction, scientists have tried building pathways using a combination of treatments. These treatments aim to increase the growth potential of neurons, create a bridge across the injury site, and provide a supportive surface for axons to grow out of the bridge and back into the surrounding tissue. In cases where nerve circuits are lost, pre-made supportive pathways can help transplanted neurons grow axons over long distances to reach their targets.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Not specified

Key Findings

1
Neurotrophins alone can induce regeneration of sensory axons, but they may not terminate in appropriate target regions without additional guidance signals.
2
Combined treatments that increase intrinsic growth properties of neurons, provide a bridge across the lesion site, and supply a growth-supportive substrate can support good regeneration.
3
Preformed growth-supportive pathways can sustain long-distance axon growth from a neuronal transplant to distal target locations in disorders where neuronal circuits are lost.

Research Summary

The adult mammalian central nervous system (CNS) faces challenges in recovering from neurotrauma and disease due to axon disruption, neuronal death, target denervation, and functional deficits. Construction of pathways using combined treatments support good regeneration when they increase the intrinsic growth properties of neurons, provide a bridge across the lesion site, and supply a growth supportive substrate to induce axon growth out of the bridge and back into the host. In summary, the construction of neurotrophin gradients distal to the lesion supports regeneration of sensory axons into the spinal cord after dorsal root rhizotomies and out of cellular bridges after CNS lesions.

Practical Implications

Targeted Therapies

Combined therapies that address multiple aspects of axon regeneration, such as intrinsic growth ability, lesion bridging, and growth substrate provision, hold promise for spinal cord injury treatment.

Clinical Translation

Findings from animal models need careful consideration for translation to human clinical trials, particularly regarding cell type selection, delivery methods, and post-surgical assessments.

Neurotrophin Gradients

Creating controlled neurotrophin gradients can enhance axon outgrowth and targeting, but careful attention must be paid to avoid inappropriate targeting due to overexpression or incorrect placement.

Study Limitations

1
Limited axon growth out of bridges back into the host tissue.
2
High levels of neurotrophin expressed over multiple target locations could mask endogenous guidance properties within the adult nervous system and prevent specific targeting of regenerating axons.
3
Combining multiple peripheral nerves grafts from injured white matter to gray matter with fibrin glue containing fibroblast growth factor 1 was not found to be anatomically or functionally therapeutic when used in non-human primates with lesioned spinal cords.

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