• Jean F Soustiel, Eugene Vlodavsky, Felix Milman, Moshe Gavish, and Menashe Zaaroor.
• Acute Brain Injury Research Laboratory, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. j_soustiel@rambam.health.gov.il
• Pharm. Res. 2011 Nov 1; 28 (11): 2945-53.

PurposeTo investigate the possible impact of reduction of mitochondrial membrane permeabilization by modulation of the 18 kDa translocator protein mediated by Ro5-4864 over post-traumatic cerebral edema and metabolic crisis.MethodsCerebral 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.ResultsRo5-4864 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.ConclusionsThe 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.

37 keywords...

hide…