Mouse Model of Spinal Cord Hypoperfusion via Intercostal Artery Ligation
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Solution Overview
Problem
Current animal models for thoracic endovascular aortic repair-induced ischemic spinal cord injury are inadequate, lacking a clinically relevant model for mechanistic study and therapeutic screening, due to high costs, morbidity, and limited utility in replicating large animal models.
Innovation Solution
A method involving the ligation of specific intercostal arteries in a vertebrate animal to reduce spinal cord blood flow, inducing ischemic spinal cord injury or brain injury, which can be used to screen therapeutic agents for CNS injuries, by dissecting and ligating specific intercostal arteries to mimic the effects of thoracic endovascular aortic repair.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional open repair or large animal models are used to study thoracic aortic aneurysm repair-induced ischemic spinal cord injury, then the model can replicate human pathology, but the cost and morbidity are excessively high and the models are ill-suited for mechanistic study and therapeutic screening
Solution Approach 1:
The patent creates a simplified mouse model that copies the essential pathological features of human ischemic spinal cord injury caused by thoracic aortic aneurysm repair. By ligating specific intercostal arteries (typically T8-T10) in mice, the model replicates the hypoperfusion and ischemic damage to the spinal cord without requiring expensive large animal models or complex surgical procedures, making it suitable for mechanistic study and therapeutic screening
Solution Approach 2:
The patent employs mice as a cost-effective alternative to expensive large animal models. Mice are inexpensive, easy to house, and suitable for high-throughput therapeutic screening. The model accepts that the animals have limited lifespan and are used for specific research purposes rather than long-term study, maximizing the value obtained from each subject while minimizing overall research costs
2Reliability
If intercostal arteries are ligated to induce spinal cord hypoperfusion, then the model reproduces immediate paralysis and histopathological damage, but the surgical procedure becomes more complex
Solution Approach 1:
The patent divides the spinal cord blood supply into segmental units by identifying and ligating specific intercostal arteries at defined thoracic levels (T8-T10). This segmentation approach allows precise control over which spinal cord segments are affected, reproducing the focal nature of clinical ischemic injuries while simplifying the surgical procedure compared to more extensive vascular manipulation
Solution Approach 2:
The patent performs preliminary identification and exposure of the target intercostal arteries before ligation. By carefully dissecting and exposing the arteries at the predetermined thoracic levels, the surgeon ensures accurate placement of ligatures to achieve the desired hypoperfusion pattern. This preliminary action prevents unnecessary tissue damage and reduces surgical complexity by avoiding trial-and-error approaches
Data Source
AI summary
The present disclosure relates to methods of inducing central nervous system (CNS) injuries in an animal model for use of identifying and/or screening CNS therapeutic compositions.