A Mouse Model of Spinal Cord Hypoperfusion with Immediate Paralysis Caused by Endovascular Repair of Thoracic Aortic Aneurysm

Anesthesiology, 2023 · DOI: 10.1097/ALN.0000000000004515 · Published: April 1, 2023

Spinal Cord Injury Cardiovascular Science Research Methodology & Design

Simple Explanation

This study created a mouse model to simulate spinal cord injury that can occur during thoracic endovascular aortic repair (TEVAR) in humans. Researchers ligated intercostal arteries in mice to mimic the reduced blood flow to the spinal cord that can happen during TEVAR. The procedure caused paralysis in the mice, with varying degrees of severity, similar to what is observed in human patients undergoing TEVAR. The researchers then analyzed the spinal cords of the mice to observe the damage caused by the reduced blood flow. This mouse model can be used to study the mechanisms of spinal cord injury during TEVAR and to develop new treatments to prevent or reduce the severity of this complication.

Study Duration

2 weeks

Participants

Adult C57BL/6 mice (sham, n=53; ligation, n=60)

Evidence Level

Not specified

Key Findings

1
Ligation of intercostal arteries induced a significant and instantaneous drop in blood flow in both the intercostal arteries and the thoracic spinal cord.
2
The model resulted in variable degrees of paralysis, ranging from mild to severe, mirroring the clinical presentation in human patients undergoing TEVAR.
3
Histopathological analysis revealed ischemic spinal cord damage, with activation of astrocytes and microglia, and electron microscopy confirmed cellular damage in the spinal cord tissue.

Research Summary

The study successfully developed a mouse model of spinal cord hypoperfusion induced by ligation of intercostal arteries, mimicking the ischemic spinal cord injury observed in humans after TEVAR. The mouse model exhibited immediate paralysis of varying degrees, similar to clinical findings in human patients, and demonstrated reproducible spinal cord hypoperfusion and histopathological ischemic damage. This model provides a valuable tool for studying the mechanisms underlying TEVAR-induced spinal cord injury and for developing potential neuroprotective strategies.

Practical Implications

Drug Development

The mouse model can be used to test and develop new neuroprotective drugs and therapeutics for ischemic spinal cord injury following TEVAR.

Predictive Screening

The model suggests that the pre-TEVAR degree of patency and development of collaterals around the spinal cord may predict post-procedure paralysis severity, potentially aiding clinical screening.

Mechanistic Study

The model facilitates mechanistic study of thoracic endovascular aortic repair-induced spinal cord hypoperfusion.

Study Limitations

1
Lack of pre-experiment sample size calculation.
2
Histopathological results showed posterior spinal cord lesions, suggesting that sensory tests may have revealed additional mice demonstrating deficit; multi-modal sensory testing is recommended for future studies.
3
No autopsies were performed on expired mice to establish actual cause of death.

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