A mouse model of complete-crush transection spinal cord injury made by two operations

Ann Transl Med, 2020 · DOI: 10.21037/atm.2020.01.58 · Published: March 1, 2020

Spinal Cord Injury Surgery Research Methodology & Design

Simple Explanation

This study introduces a new mouse model for spinal cord injury (SCI) that mimics clinical treatment scenarios. The model involves creating a crush injury on the mouse's spinal cord, allowing scar tissue to form over six weeks, and then surgically removing the scar. The researchers validated this model by assessing the mice's motor function, electrophysiology, and histopathological changes. This includes observing tissue changes, performing HE staining, and conducting immunofluorescence staining to determine the extent of spinal cord segment to be removed. This new model allows for better assessment of treatments for SCI, including stem cell and biomaterial transplantation, by accurately simulating the clinical treatment process where scar tissue removal is often necessary.

Study Duration

6 weeks between the first and second operations

Participants

Forty-eight C57BL/6 mice

Evidence Level

Not specified

Key Findings

1
The initial crush injury model resulted in significant neurological deficits with limited natural recovery, as evidenced by behavioral scoring and electrophysiology.
2
Histopathological analysis revealed that a 2-mm spinal cord segment centered on the lesion core was appropriate for removal during the second surgery, based on scar range and inflammatory cell infiltration.
3
After the second operation, immunostaining showed no neurons or neurofilament residues in the lesion core, with astrocytes encapsulating immune cells to form dense glial scars.

Research Summary

The study established a mouse model of SCI involving a crush injury followed by scar removal to simulate clinical treatment of SCI. The model was validated using BMS scoring, electrophysiology, and histopathological analysis, showing it effectively mimics the chronic phase of SCI with scar formation. Gene expression analysis indicated potential for spontaneous nerve regeneration adjacent to the lesion core, suggesting the model's suitability for testing SCI treatments.

Practical Implications

Pre-clinical Testing Tool

The developed mouse model serves as a valuable tool for pre-clinical testing of SCI treatments, offering good simulation, feasibility, and reproducibility.

Scar Tissue Removal

The study highlights the importance of scar tissue removal in SCI treatment, providing a model to accurately simulate this clinical process.

Therapeutic Intervention

The model is suitable for assessing the effectiveness of stem cell and biomaterial transplantation therapies for SCI, particularly in the context of chronic injuries with scar formation.

Study Limitations

1
Mice are light in weight and have a small tissue structure, which makes surgery difficult.
2
Post-operative care such as that in pain relief, assisted urination, and nutrition enhancement, is very important.
3
the disorder of the wound healing structure and tissue adhesion in the first operation caused substantial difficulty for the second surgery.

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