Axon Guidance Molecules and Neural Circuit Remodeling After Spinal Cord Injury

Neurotherapeutics, 2016 · DOI: 10.1007/s13311-015-0416-0 · Published: December 16, 2015

Spinal Cord Injury Neurology Regenerative Medicine & Stem Cells

Simple Explanation

The review discusses how molecular cues that guide the development of neural circuits are reactivated after spinal cord injury (SCI). However, these cues often hinder the functional rewiring of severed neural connections, presenting a challenge for promoting repair. The article explores how individual neural circuits respond to specific molecular cues post-injury and examines potential strategies for instigating functional repair or remodeling of the injured spinal cord, focusing on axon guidance molecules. The review emphasizes the importance of understanding how these guidance molecules affect neurons, glia, immune cells, and meningeal fibroblasts in the context of SCI to develop effective repair strategies.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Following SCI, the re-expression of axon guidance molecules like ephrins, semaphorins, and Wnts can inhibit neural circuit plasticity and functional recovery.
2
Inhibition of class 3 semaphorins has been associated with slight improvements in locomotor function following complete spinal cord transection in rodent models.
3
Blocking Wnt signaling after SCI enhances regeneration and axon plasticity of ascending dorsal column sensory axons after peripheral conditioning.

Research Summary

This review examines the role of axon guidance molecules, such as Wnts, semaphorins, and ephrins, in neural circuit remodeling after spinal cord injury (SCI). Following SCI, these molecules, which are crucial for development, are re-expressed and often inhibit regeneration and plasticity, particularly affecting the response of axons, glia, the vasculature, and the immune system. The review suggests that modulating guidance molecule signaling after injury, such as inhibiting repulsive responses or switching them towards attraction, is crucial for successful spinal tract regeneration and functional recovery.

Practical Implications

Therapeutic Targeting

Modulating the activity of axon guidance molecules, such as semaphorins and Wnts, could be a therapeutic strategy to promote axon regeneration and functional recovery after SCI.

Understanding Cellular Responses

A deeper understanding of how different cell types (neurons, glia, immune cells) respond to guidance molecules after SCI is crucial for developing effective treatments.

Enhancing Local Plasticity

Promoting local axon plasticity proximal to the injury site may enhance spontaneous recovery and could be a target for therapeutic interventions.

Study Limitations

1
Current knowledge of how axon guidance molecules affect individual circuits after SCI is limited.
2
The effects of guidance molecules on glia, immune cells, and meningeal fibroblasts need to be considered in attempts to repair damaged spinal cord circuits.
3
The intrinsic potential of affected axons to respond appropriately to proregenerative cues needs further exploration.

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