Mitochondrial function and brain Metabolic Score (BMS) in ischemic Stroke: Evaluation of "neuroprotectants" safety and efficacy.

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.