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  4. The Dorsal Column Lesion Model of Spinal Cord Injury and Its Use in Deciphering the Neuron-Intrinsic Injury Response

The Dorsal Column Lesion Model of Spinal Cord Injury and Its Use in Deciphering the Neuron-Intrinsic Injury Response

Developmental Neurobiology, 2018 · DOI: 10.1002/dneu.22601 · Published: May 11, 2018

Spinal Cord InjuryRegenerative Medicine

Simple Explanation

The study focuses on the differences in how nerve cells in the peripheral nervous system (PNS) and central nervous system (CNS) respond to injury. PNS neurons can initiate a growth program to repair themselves, while CNS neurons often cannot. Researchers are exploring ways to enhance the neuron-intrinsic regenerative response to promote axon regeneration in the injured CNS. They use the dorsal column lesion model to study this. This model involves injuring the dorsal column of the spinal cord, which contains sensory neurons. These neurons behave differently depending on whether their peripheral or central branch is injured, making them ideal for studying neuron-intrinsic regeneration.

Study Duration
Not specified
Participants
Not specified
Evidence Level
Review

Key Findings

  • 1
    Peripheral nerve injury induces a strong regenerative response in DRG neurons, while central branch injury does not, highlighting the importance of neuron-intrinsic factors.
  • 2
    A 'conditioning lesion' (CL) of the peripheral nerve can enhance the regenerative capacity of the central branch of DRG neurons after a dorsal column lesion.
  • 3
    Manipulating neuron-intrinsic gene expression, particularly transcription factors, can promote axon regeneration in the dorsal column lesion model.

Research Summary

This review examines the dorsal column lesion model of spinal cord injury, focusing on its utility in studying neuron-intrinsic regenerative responses. It discusses the advantages and disadvantages of the model, surgical techniques, and methods to quantify regeneration and functional recovery. The review also explores experimental interventions aimed at enhancing the neuron-intrinsic injury response and manipulating the lesion environment to promote axonal regeneration.

Practical Implications

Understanding Neuron-Intrinsic Mechanisms

The dorsal column lesion model provides a valuable tool for dissecting the molecular mechanisms underlying successful axon regeneration, particularly the neuron-intrinsic factors that differentiate PNS and CNS neuron responses to injury.

Developing Targeted Therapies

By identifying key transcription factors and signaling pathways involved in the regenerative response, researchers can develop targeted therapies to enhance axon regeneration in the injured spinal cord.

Improving Functional Outcomes

Strategies that combine manipulation of neuron-intrinsic regenerative capacity with modification of the lesion environment may lead to improved functional outcomes after spinal cord injury.

Study Limitations

  • 1
    Functional deficits after DC lesion are often mild and spontaneously recover, complicating assessment.
  • 2
    Contusion models, while clinically relevant, can result in incomplete lesions, leading to spared fibers.
  • 3
    The regenerative response, even with interventions, often falls short of long-distance regeneration and functional reconnection.

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