The use of anesthetics is a well-known treatment for severely injured patients. In the present study we tested the pathophysiology of several levels of injury damage in a rat model and also tested the effect of Equithesin on brain vitality in these models. Traumatic Brain Injury (TBI) was induced using the fluid percussion injury model in four levels: mild, moderate and two levels of severe TBI. Brain real-time evaluation was performed by the multiparametric monitoring assembly (MPA) which enable cerebral blood flow (CBF) monitoring by laser Doppler flowmetry, mitochondrial NADH (Nicotinamide adenine dinucleotide) monitoring by the fluorometric technique, ionic homehostasis using special mini-electrodes, intracranial pressure (ICP) by the ICP camino device and needle electrodes for ECoG (Electrocorticogram) recording. Our results showed high correlation between the level of impact and the extent of changes in the physiological properties of the injury as indicated by the changes in all parameters monitored using the MPA device. Moreover, Equithesin improved CBF, ionic extracellular level and mitochondrial redox state following mild and moderate TBI while in severe TBI, Equithesin did not improve the metabolic state of the cerebral cortex, although it decreased the mortality rate from 66% to 20%, and following extra-severe TBI level, Equithesin did not improve survival rate. In conclusion it seems that Equithesin's protective effect exists under mild to moderate levels of injury and not in case of severe injuries.

Severe body stress induced by hypoxemia and hypotension may lead to total body energy state deterioration. The perfusion of the most vital organs is maintained at the expense of “less vital” organs. In the present study, we used a multi-site multiparametric (MSMP) monitoring system for real-time evaluation of tissue blood flow (TBF) and mitochondrial NADH fluorescence of the brain and the small intestine following hemorrhage. In Group 1, uncontrolled hemorrhage, mean arterial pressure (MAP) was decreased to 40mmHg within 2 minutes and shed blood was re-infused after 30minutes. In Group 2, controlled hemorrhage, during the 30minutes of hemorrhage, MAP was kept at 40mmHg. During hemorrhage, in both groups, the intestinal TBF and NADH deteriorated, while the brain remained relatively well protected. In Group 1, all parameters partly recovered within the hemorrhage phase, while in Group 2, complete recovery occurred only after resuscitation. At the end of the experiment, both models showed a decrease in intestinal viability (TBF decreased, NADH increased), while the brain metabolic state in Group 2 declined slightly. Our unique multi-parametric monitoring device demonstrated that, under hemorrhage, the small intestine responded entirely differently from the brain. This may suggest the potential usefulness of the monitoring of less vital organs, as proxy organs, in critical conditions such as massive hemorrhage. The present study also highlights the importance of mitochondrial function monitoring in similar conditions in the clinical environment.

Focal ischemia due to reduction of cerebral blood flow (CBF), creates 2 zones of damage: the core area, which suffers severe damage, and penumbra area, which surrounds the core and suffers intermediate levels of injury. Objectives: A novel method is introduced, which evaluates mitochondrial function in the core and in the penumbra, during focal cerebral ischemia. Methods: Wistar rats underwent focal cerebral ischemia by middle cerebral artery occlusion (MCAO) for 60 minutes, followed by 60 minutes of reperfusion. Mitochondrial function was assessed by a unique Multi-Site — Multi-Parametric (MSMP) monitoring system, which measures mitochondrial NADH using fluorometric technique, and CBF using Laser Doppler Flowmetry (LDF). Results: At the onset of occlusion, CBF dropped and NADH increased significantly only in the right hemisphere. CBF levels were significantly lower and NADH significantly higher in the core than in the penumbra. After reperfusion, CBF and NADH recovered correspondingly to the intensity of ischemia. Conclusion: Application of the MSMP system can add significant information for the understanding of the cerebral metabolic state under ischemic conditions, with an emphasis on mitochondrial function.