title: Differential effects of endothelin receptor A and B antagonism on behavioral outcome following traumatic brain injury.
abstract: OBJECTIVE
  Previously we have reported that endothelin receptor A and B antagonists elicit differential effects on cerebral blood flow and cellular damage. In summary, endothelin receptor A antagonists restore microcirculation and diminish cellular damage after injury, while endothelin receptor B antagonists had no effect on either parameter. However, what is not known is the effect of either antagonist on behavioral outcome. Therefore, this work was designed to test the effects of endothelin receptor A and B antagonism on behavioral outcome following traumatic brain injury (TBI).
  
  
  METHODS
  A total of 48 male Sprague-Dawley rats (400-450 g) were used in this study. Four groups (n = 12 per group) were generated as follows: sham operation, trauma+vehicle (0·9% saline), trauma+40 nmol BQ-123 (a selective endothelin receptor A antagonist) and trauma +20 nmol BQ-788 (a selective endothelin receptor B antagonist). All treatments were delivered via intracerebroventricular injection. Trauma was induced using a weight acceleration impact device. Twenty-four hours post-injection animals were tested for 21 days on a radial arm maze task to determine cognitive outcome.
  
  
  RESULTS
  Our data indicated that endothelin receptor A antagonism significantly reduced the extent of behavioral deficits following TBI while endothelin receptor B and vehicle injection had no effect.
  
  
  CONCLUSIONS
  The results suggest that endothelin receptor A, but not endothelin receptor B, antagonism improves behavioral outcome following TBI. Furthermore, these data provide a functional correlate to previously published findings in our laboratory showing that endothelin receptor A antagonism improves both blood flow and cellular outcome following TBI. In a broader sense, this work demonstrates that hypoperfusion following TBI likely contributes to poor outcome following head injury.
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Reynolds
authors.forename: Steven
authors.initials: S
authors.lastname: Schafer
authors.forename: Ryan
authors.initials: R
authors.lastname: Pirooz
authors.forename: Alex
authors.initials: A
authors.lastname: Marinica
authors.forename: Ali
authors.initials: A
authors.lastname: Chbib
authors.forename: Christopher
authors.initials: C
authors.lastname: Bedford
authors.forename: Michael
authors.initials: M
authors.lastname: Fronczak
authors.forename: José A
authors.initials: JA
authors.lastname: Rafols
authors.forename: Donald
authors.initials: D
authors.lastname: Kuhn
authors.forename: Christian W
authors.initials: CW
authors.lastname: Kreipke
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000502:physiology; D044023:Receptor, Endothelin B / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B