Primate Cerebral Infarction Model for Chronic Motor Dysfunction
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a lack of a nonhuman primate animal model of cerebral infarction that can be used for the screening and evaluation of therapeutic agents, particularly for cerebral infarction at a subacute to chronic stage, and a method for producing such a model, as well as a therapeutic agent for penetrating branch infarction.
Innovation Solution
A method involving the administration of endothelin to the basal ganglia and thalamic region of nonhuman primates to induce basal ganglia, thalamus, and internal capsule damage, creating a nonhuman primate animal model of cerebral infarction, and using NeuroD1 as a therapeutic agent for penetrating branch infarction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If a rodent cerebral infarction model is used for therapeutic agent evaluation, then the model can be produced with established protocols, but the discrepancy between nonclinical trial results and clinical trial results increases due to differences in microcirculation and brain structure between rodents and humans
Solution Approach 1:
The patent creates a nonhuman primate model that copies human cerebral infarction characteristics more accurately than rodent models. The model reproduces similar microcirculation patterns, brain structure, and infarction outcomes as human stroke, thereby improving predictive validity for clinical trials while maintaining experimental feasibility.
2Ease of manufacture
If a nonhuman primate MCAO model is used, then the model can be produced with artificial blockage of the middle cerebral artery, but the model gradually recovers spontaneously within 28-30 days, making it unsuitable for evaluating therapeutic agents for chronic stage cerebral infarction
Solution Approach 1:
The patent applies local quality by targeting specific deep brain structures (basal ganglia, thalamus, internal capsule) for infarction induction rather than using general MCAO. This localized approach creates persistent damage in critical areas that maintains motor dysfunction long-term, enabling evaluation of chronic stage therapeutic agents while preserving the feasibility of controlled model production.
3Ease of manufacture
If endothelin is administered to the surface of the middle cerebral artery in rodents, then cerebral infarction can be induced, but the model does not adequately represent human penetrating branch infarction characteristics
Solution Approach 1:
The patent applies local quality by precisely targeting deep brain structures (basal ganglia, thalamus, internal capsule) for infarction induction through controlled endothelin administration. This localized approach creates infarctions that precisely match human penetrating branch infarction characteristics, improving both the accuracy of the model and the precision of infarction site placement.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The method produces a nonhuman primate model with high reproducibility and maintains motor dysfunction for a long period, enabling effective evaluation of therapeutic agents for cerebral infarction at a subacute to chronic stage, and NeuroD1 shows efficacy in treating penetrating branch infarction.
Implementation Method 1
administration of endothelin having a strong vasoconstrictive effect to the surface of the middle cerebral artery
Data Source
AI summary
The present invention relates to a method for producing a nonhuman primate animal model of cerebral infarction, comprising administering endothelin to basal ganglia and thalamic region of a nonhuman primate, and thereby inducing basal ganglia damage, thalamus damage, and internal capsule damage; and a pharmaceutical composition for the treatment of cerebral infarction at a subacute to chronic stage, penetrating branch infarction, or cerebral infarction having brain damage in a penetrating branch territory, comprising a NeuroD1 protein or a polynucleotide encoding the NeuroD1 protein.