title: Clazosentan, a novel endothelin A antagonist, improves cerebral blood flow and behavior after traumatic brain injury.
abstract: OBJECTIVE
  The purpose of this study was to test the efficacy of a novel endothelin receptor A antagonist on blood flow and behavioral outcome given 30 minutes following traumatic brain injury.
  
  
  METHODS
  Male Sprague-Dawley rats (400-450 g) were used in this study. All animals were scanned for initial blood flow using arterial spin labeling magnetic resonance imaging (n = 72 total). Half were subjected to traumatic brain injury using a weight acceleration impact device (n = 36 total). Sham operated animals were used as control (n = 36 total). Thirty minutes following traumatic brain injury, animals were given one intravenous injection of vehicle (0·9% saline) or 1·0 mg/kg clazosentan, a novel endothelin receptor A antagonist, for a total of four groups. At 4, 24, and 48 hours post-traumatic brain injury, blood flow determination continued. On the second day post-traumatic brain injury/sham operation, behavioral testing commenced using a radial arm maze to assess cognitive function.
  
  
  RESULTS
  Our results indicate that 1·0 mg/kg clazosentan was effective in ameliorating hypoperfusion seen after traumatic brain injury. Saline had no effect. Furthermore, clazosentan treatment was effective in significantly improving behavioral outcome following traumatic brain injury.
  
  
  CONCLUSIONS
  Collectively, these results indicate that clazosentan, given at 30 minutes post-traumatic brain injury, is effective in improving outcome following injury.
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Wayne State University, Detroit, MI 48201, USA. ckreipke@med.wayne.edu
authors.forename: Christian W
authors.initials: CW
authors.lastname: Kreipke
authors.forename: José A
authors.initials: JA
authors.lastname: Rafols
authors.forename: Christian A
authors.initials: CA
authors.lastname: Reynolds
authors.forename: Steven
authors.initials: S
authors.lastname: Schafer
authors.forename: Alex
authors.initials: A
authors.lastname: Marinica
authors.forename: Christopher
authors.initials: C
authors.lastname: Bedford
authors.forename: Michael
authors.initials: M
authors.lastname: Fronczak
authors.forename: Donald
authors.initials: D
authors.lastname: Kuhn
authors.forename: William M
authors.initials: WM
authors.lastname: Armstead
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D004146:Dioxanes / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D004146:Dioxanes; D065130:Endothelin A Receptor Antagonists; D011725:Pyridines; D011743:Pyrimidines; D044022:Receptor, Endothelin A; D013449:Sulfonamides; D013777:Tetrazoles; D014665:Vasodilator Agents; C109641:clazosentan