title: Hypertonic resuscitation improves neuronal and behavioral outcomes after traumatic brain injury plus hemorrhage.
abstract: BACKGROUND
  : Resuscitation with hypertonic saline or hypertonic saline plus l-arginine acutely improves cerebral blood flow after traumatic brain injury (TBI) followed by hemorrhagic hypotension. The authors investigated whether hypertonic saline or hypertonic l-arginine would improve long-term neuronal survival and behavioral outcomes 15 days after TBI and hemorrhagic hypotension.
  
  
  METHODS
  : Mean arterial pressure, arterial blood gases, pH, plasma glucose, hematocrit, and hemoglobin were measured in male Sprague-Dawley rats before and after moderate (2.0 atm) fluid percussion TBI. Rats were assigned to one of six groups: (1) sham TBI, (2) hemorrhage only, (3) TBI only, (4) TBI plus hemorrhage and resuscitation with 0.9% saline, (5) TBI plus hemorrhage and resuscitation with hypertonic saline (7.5%), or (6) TBI plus hemorrhage and resuscitation with l-arginine (100 mg/kg) in hypertonic saline. On postinjury days 1-5, vestibulomotor function was assessed using beam balance and beam walking tasks. On postinjury days 11-15, spatial memory function was assessed using the Morris water maze. After behavioral testing, neuronal counting was performed bilaterally on specific hippocampal regions.
  
  
  RESULTS
  : Groups receiving hypertonic saline (P < 0.05, day 15 vs. day 11) or hypertonic l-arginine (P < 0.05, days 13-15 vs. day 11) showed improved performance over time on the Morris water maze, as well as significantly improved neuronal survival in the contralateral hippocampus (P < 0.05, hypertonic saline or hypertonic l-arginine vs. normal saline) compared with untreated TBI or normal saline-treated TBI plus hemorrhage groups.
  
  
  CONCLUSIONS
  : Hypertonic saline and hypertonic l-arginine were both effective at promoting long-term neuronal survival and behavioral recovery. The slightly earlier improvement in Morris water maze performance in the hypertonic l-arginine group warrants further studies to determine whether higher doses of l-arginine provide additional improvement. This study supports the therapeutic benefits of hypertonic resuscitation after TBI plus hemorrhagic hypotension.
authors.affiliation: Charles R. Allen Research Laboratories, Department of Anesthesiology, University of TexasMedical Branch, Galveston, Texas 77555-0830, USA.
authors.forename: Stacy L
authors.initials: SL
authors.lastname: Sell
authors.forename: Marcela A
authors.initials: MA
authors.lastname: Avila
authors.forename: Guangxiang
authors.initials: G
authors.lastname: Yu
authors.forename: Leoncio
authors.initials: L
authors.lastname: Vergara
authors.forename: Donald S
authors.initials: DS
authors.lastname: Prough
authors.forename: James J
authors.initials: JJ
authors.lastname: Grady
authors.forename: Douglas S
authors.initials: DS
authors.lastname: DeWitt
mesh_terms: D000818:Animals; D001120:Arginine / Q000627:therapeutic use; D001519:Behavior / Q000187:drug effects / Q000502:physiology; D001930:Brain Injuries / Q000150:complications* / Q000188:drug therapy* / Q000523:psychology; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000209:etiology* / Q000523:psychology; D004195:Disease Models, Animal; D006982:Hypertonic Solutions / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods*; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D006982:Hypertonic Solutions; D012462:Saline Solution, Hypertonic; D001120:Arginine