title: Improvement of cerebral metabolism mediated by Ro5-4864 is associated with relief of intracranial pressure and mitochondrial protective effect in experimental brain injury.
abstract: OBJECTIVE
  To 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.
  
  
  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.
authors.affiliation: Acute Brain Injury Research Laboratory, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. j_soustiel@rambam.health.gov.il
authors.forename: Jean F
authors.initials: JF
authors.lastname: Soustiel
authors.forename: Eugene
authors.initials: E
authors.lastname: Vlodavsky
authors.forename: Felix
authors.initials: F
authors.lastname: Milman
authors.forename: Moshe
authors.initials: M
authors.lastname: Gavish
authors.forename: Menashe
authors.initials: M
authors.lastname: Zaaroor
mesh_terms: D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D007427:Intracranial Pressure / Q000187:drug effects* / Q000502:physiology; D008297:Male; D017551:Microdialysis; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009460:Neurologic Examination / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001570:Benzodiazepinones; D020011:Protective Agents; C028513:4'-chlorodiazepam