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  4. A Neonatal Mouse Spinal Cord Injury Model for Assessing Post-Injury Adaptive Plasticity and Human Stem Cell Integration

A Neonatal Mouse Spinal Cord Injury Model for Assessing Post-Injury Adaptive Plasticity and Human Stem Cell Integration

PLoS ONE, 2013 · DOI: 10.1371/journal.pone.0071701 · Published: August 19, 2013

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

This paper introduces a new model for studying spinal cord injuries in newborn mice. Researchers created a spinal cord compression injury to mimic real-world injuries. This model allows for the study of how the young spinal cord can reorganize itself after injury. The model also serves as a platform to test how human stem cells can be used to repair spinal cord damage. The researchers injected human stem cells into the injured spinal cord of the mice and observed how well these cells integrated into the damaged tissue. The results showed that the injured mice recovered some movement and that the human stem cells were able to survive and begin to develop into specialized cells within the mouse spinal cord. This model helps scientists to better understand spinal cord injury and potential treatments.

Study Duration
1-2 Weeks for behavioral recovery assessment, up to a month for stem cell integration
Participants
104 ICR and 19 SCID-ICR mice
Evidence Level
Not specified

Key Findings

  • 1
    Dramatic degeneration of axons and synaptic contacts was evident within 24 hours of SCC, and loss of neurons in the injured segment was evident for at least a month thereafter.
  • 2
    Within 4 days of SCC and progressively thereafter, hindlimb motility began to be restored and descending inputs reappeared, but with examples of atypical synaptic connections indicating a reorganization of circuitry.
  • 3
    Genetically labeled human fetal neural progenitor cells injected into the injured spinal cord survived for at least a month, integrated into the host tissue and began to differentiate morphologically.

Research Summary

The study developed a neonatal mouse spinal cord compression (SCC) injury model to investigate adaptive plasticity and human stem cell integration after injury. The model allows for high-throughput assessment of functional synaptic connectivity. Results showed substantial behavioral recovery after SCC, with hindlimb motility approaching sham control levels within 1-2 weeks. Electrophysiological and optical recording demonstrated recovery of descending inputs to lumbar motoneurons. Human fetal neural progenitor cells transplanted into the injured spinal cord survived, integrated, and showed morphological differentiation. The model offers insights into adaptive plasticity mechanisms and the potential for stem cell-based therapies.

Practical Implications

Understanding Pediatric SCI

The model provides a platform that more likely reflects the pathogenetic and recovery processes characteristic of the developing human than do adult animal SCI models.

Advancing Stem Cell Therapies

The model is useful for testing the capacity of human stem and progenitor cell-derived neurons to integrate functionally into spinal neural circuits.

Exploring Adaptive Plasticity

The integrative, multi-methodological platform employing the neonatal mouse should provide novel insight into the scope of adaptive plasticity in the developing mammalian spinal cord.

Study Limitations

  • 1
    The model uses lateral compression, which may not fully replicate dorsoventral compression seen in many clinical cases.
  • 2
    Neonatal spinal cord differs from adult spinal cord in myelination and other factors, limiting direct extrapolation to adult SCI.
  • 3
    The clip compression strength may decrease with use.

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