title: Endothelin and the neurovascular unit in pediatric traumatic brain injury.
abstract: OBJECTIVE
  This study characterized the association between endothelin-1, cerebral hemodynamics, and histopathology after fluid percussion brain injury in the newborn pig.
  
  
  METHODS
  Lateral fluid percussion injury was induced in newborn pigs equipped with a closed cranial window. Cerebral blood flow was determined with radiolabeled microspheres and cerebrospinal fluid endothelin-1 was measured by radioimmunoassay.
  
  
  RESULTS
  Cerebrospinal fluid endothelin-1 was increased from 26±4 to 296±37 pg/ml (∼10(-10) M) at 8 hours following fluid percussion injury. Post-injury treatment (30 minutes) with the endothelin-1 antagonist BQ-123 (1 mg/kg, intravenous) blocked pial artery vasoconstriction to topical endothelin-1 (∼10(-10) M) and blunted fluid percussion injury-induced reductions in cerebral blood flow at 8 hours post-insult (56±6 and 26±4 ml/minute versus 57±6 and 40± ml/minute; 100 g for cerebral blood flow before injury and 8 hours post-fluid percussion injury in vehicle and BQ-123 post-treated animals, respectively). Fluid percussion injury resulted in neuronal cell loss and decreased microtubule associated protein 2 immunoreactivity in the parietal cortex, which were blunted by BQ-123.
  
  
  CONCLUSIONS
  These data indicate that fluid percussion injury-induced changes in cerebral hemodynamics are associated with neuronal damage and that endothelin-1 contributes to fluid percussion injury-induced histopathologic changes.
authors.affiliation: Department of Anesthesiology and Critical Care and Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA. armsteaw@uphs.upenn.edu
authors.forename: William M
authors.initials: WM
authors.lastname: Armstead
authors.forename: Ramesh
authors.initials: R
authors.lastname: Raghupathi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D002648:Child; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000134:cerebrospinal fluid* / Q000633:toxicity; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D034421:Sus scrofa
chemical_list: D019332:Endothelin-1