Middle Cerebral Artery Occlusion for Reproducible Stroke Models
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Solution Overview
Problem
Existing animal models for studying ischemic stroke and reperfusion injury suffer from high mortality rates, lack of reproducibility, and variability in infarct size and location, making it difficult to effectively study and develop treatments for stroke.
Innovation Solution
A method involving temporary occlusion of the middle cerebral artery at three specific locations, using sutures to block blood flow and allowing for controlled reperfusion, which reduces mortality and increases reproducibility of focal ischemic lesions in animal models.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If prior art animal models of ischemic stroke are used, then stroke research can be conducted, but high mortality rate and lack of reproducibility occur
Solution Approach 1:
The occlusion is divided into three distinct segments along the middle cerebral artery (first location proximal to bifurcation, second location at the bifurcation, third location distal to bifurcation). This segmentation allows controlled focal occlusion that reproduces consistent infarct patterns while reducing variability and mortality compared to single-point occlusion methods.
Solution Approach 2:
The patent applies occlusion at specific localized positions along the MCA rather than uniform or random occlusion. The three specific locations create a localized pattern of blood flow restriction that produces reproducible focal infarcts in the cerebral cortex, improving reliability while maintaining animal survival.
2Adaptability or versatility
If permanent occlusion of MCA is used, then ischemic effects can be studied, but reperfusion injury cannot be examined
Solution Approach 1:
The occlusion system is designed to be dynamic rather than permanent. The three occlusion points can be applied and removed controllably, allowing the system to transition between ischemic and reperfusion states. This enables versatile study of both ischemic injury mechanisms and reperfusion injury processes within the same model.
Solution Approach 2:
The patent enables periodic occlusion and reperfusion cycles by using removable occlusion at three MCA locations. This periodic action allows researchers to study ischemia during occlusion periods and reperfusion injury during release periods, providing adaptability to examine both pathological processes.
3Manufacturing precision
If single-point occlusion is used, then procedure is simple, but infarct variability is high
Solution Approach 1:
The occlusion is divided into three distinct segments along the middle cerebral artery (first location proximal to bifurcation, second location at the bifurcation, third location distal to bifurcation). This segmentation allows controlled focal occlusion that reproduces consistent infarct patterns while reducing variability and mortality compared to single-point occlusion methods.
Data Source
AI summary
An animal stroke model is provided. The model is useful in the study of brain ischemia and/or reperfusion injury and in identification and testing of compounds and interventions useful in the treatment of stroke. The method is carried out in a non-human mammal, such as rat. The method of inducing ischemia and/or reperfusion injury involves exposing a portion of the middle cerebral artery (MCA) and temporarily occluding it at one or more distinct locations, preferably three distinct locations. The model results in highly reproducible and focal infarct sizes, with low rate of mortality during the experimental procedure.