Normothermic Ex Vivo Brain Preservation Perfusion System
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Solution Overview
Problem
Current methods fail to effectively preserve cellular structure and function in the intact mammalian brain after global ischemia, with existing technologies unable to maintain cell viability and prevent irreversible cell death following cerebral perfusion cessation.
Innovation Solution
A perfusate composition including glucose, amino acids, water-soluble salts, vitamins, artificial oxygen carriers, and compounds that inhibit cytotoxicity, inflammation, and apoptosis, combined with a system for normothermic ex vivo brain preservation using a perfusion device that regulates temperature and perfusion parameters.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If conventional preservation methods are used after global ischemia, then cell death occurs rapidly, but the invention aims to extend the viable time window for preservation
Solution Approach 1:
The perfusate is prepared with pre-selected combinations of compounds (anti-cytotoxic, antioxidants, anti-necrotic, antiexcitotoxic, anti-inflammatory, anti-apoptotic agents) before ischemic events occur. This preliminary formulation ensures that when preservation is needed, the complete protective mechanism is immediately available to counteract multiple death pathways simultaneously, extending viable duration without compromising survival reliability
Solution Approach 2:
The invention uses composite perfusate formulations containing multiple types of protective compounds working synergistically. The perfusate combines anti-cytotoxic compounds, antioxidants, anti-necrotic compounds, antiexcitotoxic compounds, anti-inflammatory compounds, and anti-apoptotic compounds in specific concentrations. This composite approach addresses multiple cell death mechanisms concurrently, achieving both extended preservation duration and high cell survival rates
2Reliability
If the brain is preserved at normothermic conditions, then metabolic needs continue to be supported, but energy consumption increases compared to hypothermic methods
Solution Approach 1:
The invention changes the temperature parameter from hypothermic to normothermic conditions while compensating for increased metabolic demands through enhanced perfusate composition. The normothermic temperature (37°C) maintains optimal enzymatic activity and metabolic function, and the perfusate's enriched composition with multiple protective compounds and nutrients provides the necessary energy substrates to support this higher metabolic rate, achieving reliable metabolic support without excessive energy consumption
3Ease of manufacture
If a simple perfusate composition is used, then the system is easier to implement, but it cannot prevent multiple pathways of cell death
Solution Approach 1:
The perfusate formulation is designed as a universal solution that simultaneously addresses multiple cell death pathways through a single integrated composition. The perfusate contains anti-cytotoxic compounds, antioxidants, anti-necrotic compounds, antiexcitotoxic compounds, anti-inflammatory compounds, and anti-apoptotic compounds, all working together to prevent various harmful effects. This multi-functional approach protects against multiple death mechanisms while maintaining straightforward preparation procedures, achieving both ease of manufacture and comprehensive protection
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 solution maintains morphofunctional integrity and cellular viability of the brain for extended periods post-mortem or after ischemia, reducing reperfusion injury and supporting metabolic needs, thereby preserving neural function and structure.
Implementation Method 1
one or more artificial oxygen carrier compounds
Implementation Method 2
normothermic ex vivo preservation
Data Source
AI summary
The invention provides a system for normothermic, ex vivo restoration and preservation of an intact mammalian brain, and other organs. In certain aspects, the system is capable of preserving a brain as well as other organs, maintaining cellular integrity and cellular function for hours post mortem or after global ischemia. The invention also provides synthetic brain perfusate formulations, including a novel brain perfusion medium (BPM), which are able to reduce reperfusion injury, stimulate recovery from hypoxia, prevent edema and metabolically support the energy needs of brain function.