caa a22 4500 445314486 CHVBK 20180317142641.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s11095-011-0463-0 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0463-0 Improvement of Cerebral Metabolism Mediated by Ro5-4864 is Associated with Relief of Intracranial Pressure and Mitochondrial Protective Effect in Experimental Brain Injury [Elektronische Daten] [Jean Soustiel, Eugene Vlodavsky, Felix Milman, Moshe Gavish, Menashe Zaaroor] ABSTRACT: Purpose: To investigate the possible impact of reduction of mitochondrial membrane permeabilization by modulation of the 18kDa translocator protein mediated by Ro5-4864 over post-traumatic cerebral edema and metabolic crisis. Methods: Cerebral microdialysis and intracranial pressure (ICP) monitoring were performed in Sprague-Dawley rats treated by intraperitoneal injection of either dimethylsulfoxide (vehicle) or Ro5-4864 following cortical contusion and further correlated with quantitative assessment of mitochondrial damage, water content in the injured tissue, modified neurological severity score, and lesion size. Results: Ro5-4864 resulted in a profound decrease in ICP that correlated with improved cerebral metabolism characterized by significantly higher glucose and pyruvate and lower lactate concentrations in the pericontusional area in comparison with vehicle-treated animals. Reduced ICP correlated with reduced water content in the injured tissue; improved metabolism was associated with reduced mitochondrial damage evidenced by electron microscopy. Both effects were associated with a profound and significant reduction in glycerol release and lesion size, and correlated with improved neurological recovery. Conclusions: The present study shows that Ro5-4864 has a favorable effect on the fate of injured brain, presumably mediated by improvement of metabolism. It further suggests that improvement of metabolism may contribute to ICP relief. Springer Science+Business Media, LLC, 2011 18kDa translocator protein nationallicence intracranial pressure nationallicence microdialysis nationallicence mitochondria nationallicence traumatic brain injury nationallicence Soustiel Jean Acute Brain Injury Research Laboratory, Faculty of Medicine, Technion — Israel Institute of Technology, Haifa, Israel aut Vlodavsky Eugene Institute of Pathology, Rambam Medical Center, Faculty of Medicine, Technion — Israel Institute of Technology, Haifa, Israel aut Milman Felix Acute Brain Injury Research Laboratory, Faculty of Medicine, Technion — Israel Institute of Technology, Haifa, Israel aut Gavish Moshe Department of Molecular Pharmacology, Faculty of Medicine, Technion — Israel Institute of Technology, Haifa, Israel aut Zaaroor Menashe Acute Brain Injury Research Laboratory, Faculty of Medicine, Technion — Israel Institute of Technology, Haifa, Israel aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/11(2011-11-01), 2945-2953 0724-8741 28:11<2945 2011 28 11095 https://doi.org/10.1007/s11095-011-0463-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0463-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Soustiel Jean Acute Brain Injury Research Laboratory, Faculty of Medicine, Technion — Israel Institute of Technology, Haifa, Israel aut NATIONALLICENCE 700 1- Vlodavsky Eugene Institute of Pathology, Rambam Medical Center, Faculty of Medicine, Technion — Israel Institute of Technology, Haifa, Israel aut NATIONALLICENCE 700 1- Milman Felix Acute Brain Injury Research Laboratory, Faculty of Medicine, Technion — Israel Institute of Technology, Haifa, Israel aut NATIONALLICENCE 700 1- Gavish Moshe Department of Molecular Pharmacology, Faculty of Medicine, Technion — Israel Institute of Technology, Haifa, Israel aut NATIONALLICENCE 700 1- Zaaroor Menashe Acute Brain Injury Research Laboratory, Faculty of Medicine, Technion — Israel Institute of Technology, Haifa, Israel aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/11(2011-11-01), 2945-2953 0724-8741 28:11<2945 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer