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Mitochondrial function and brain Metabolic Score (BMS) in ischemic Stroke: Evaluation of "neuroprotectants" safety
Avraham Mayevsky1, Hofit Kutai-Asis1, Michael Tolmasov1
1The Mina & Everard Goodman Faculty of Life-Sciences and The Leslie & Susan Gonda Multidisciplinary Brain Research Center Bar-Ilan University, Ramat-Gan 5290002, Israel.
Abstract:
The initial and significant event developed in ischemic stroke is the sudden decrease in blood flow and oxygen supply to brain tissue, leading to dysfunction of the mitochondria. Many attempts were and are being made to develop new drugs and treatments that will save the ischemic brain, but the efficacy is not optimal and in many patients, irreversible damage to the brain will persist. We review a unique approach to evaluate mitochondrial function and microcirculatory hemodynamic in real time in vivo. Three out of four monitored physiological parameters are integrated into a new Brain Metabolic Score (BMS) calculated in real time and is correlated to Brain Oxygen Balance. The technology was adapted to various experimental as well as clinical situations for monitoring the brain in real time. The developed protocols could be used in testing the efficacy and safety of new drugs in experimental animals. Few models of brain monitoring during partial or complete ischemia were developed and used in naive animals or under brain activation protocols. It was found that mitochondrial function/dysfunction is the major and dominant parameter affecting the calculated Brain Metabolic Score. Using our monitoring system and protocols will provide direct information regarding the ability of the tested brain to provide enough oxygen consumed by the mitochondria in the "resting" or in the "activated" brain in vivo and in real-time. Preliminary studies, indicated that testing the efficacy and safety of new neuroprotectant drugs provided significant results to the R&D studies of ischemic stroke related to mitochondrial function.
Insights
A novel Brain Metabolic Score (BMS) monitors mitochondrial function in real-time, offering a new way to assess brain health during ischemic stroke and evaluate neuroprotective drugs.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Cardiovascular System
Background:
- Ischemic stroke causes sudden brain tissue damage due to reduced blood flow and oxygen.
- Mitochondrial dysfunction is a key factor in ischemic brain injury.
- Current treatments for ischemic stroke have suboptimal efficacy, leading to persistent brain damage.
Purpose of the Study:
- To introduce a novel real-time in vivo monitoring system for brain mitochondrial function and microcirculatory hemodynamics.
- To develop a Brain Metabolic Score (BMS) for assessing brain oxygen balance.
- To evaluate the potential of this system in drug development for ischemic stroke.
Main Methods:
- Developed a monitoring system to track physiological parameters in real-time.
- Integrated three key parameters into a Brain Metabolic Score (BMS).
- Adapted the technology for experimental and clinical use in various brain monitoring scenarios.
Main Results:
- The Brain Metabolic Score (BMS) effectively correlates with Brain Oxygen Balance.
- Mitochondrial function/dysfunction was identified as the dominant factor influencing the BMS.
- The system demonstrated utility in monitoring brain states during ischemia and activation.
Conclusions:
- The real-time monitoring system provides crucial insights into mitochondrial oxygen consumption in the brain.
- This technology can significantly aid in testing the efficacy and safety of new neuroprotective drugs for ischemic stroke.
- The developed protocols offer a valuable tool for research and development in stroke-related mitochondrial dysfunction.
