title: Reduction of brain edema and expression of aquaporins with acute ethanol treatment after traumatic brain injury.
abstract: OBJECTIVE
  Previous studies have demonstrated that traumatic brain injury (TBI) causes brain edema by allowing excessive water passage through aquaporin (AQP) proteins. To establish the potential neuroprotective properties of ethanol as a post-TBI therapy, in the present study the authors determined the effect of ethanol on brain edema, AQP expression, and functional outcomes in a post-TBI setting.
  
  
  METHODS
  Adult male Sprague-Dawley rats weighing between 425 and 475 g received a closed head TBI in which Maramarou's impact-acceleration method was used. Animals were given a subsequent intraperitoneal injection of 0.5 g/kg or 1.5 g/kg ethanol at 60 minutes post-TBI and were killed 24 hours after TBI. Brains were subsequently examined for edema along with AQP mRNA and protein expression. Additional animals treated with either 0.5 g/kg or 1.5 g/kg ethanol at 60 minutes post-TBI were designated for cognitive and motor testing for 3 weeks.
  
  
  RESULTS
  Ethanol administration post-TBI led to significantly (p < 0.05) lower levels of brain edema as measured by brain water content. This downregulation in brain edema was associated with significantly (p < 0.05) reduced levels of AQP mRNA and protein expression as compared with TBI without treatment. These findings concur with cognitive studies in which ethanol-treated animals exhibited significantly (p < 0.05) faster radial maze completion times. Motor behavioral testing additionally demonstrated significant (p < 0.05) beneficial effects of ethanol, with treated animals displaying improved motor coordination when compared with untreated animals.
  
  
  CONCLUSIONS
  The present findings suggest that acute ethanol administration after a TBI decreases AQP expression, which may lead to reduced cerebral edema. Ethanol-treated animals additionally showed improved cognitive and motor outcomes compared with untreated animals.
authors.affiliation: Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Wang
authors.forename: David Yu-Te
authors.initials: DY
authors.lastname: Chou
authors.forename: Jamie Y
authors.initials: JY
authors.lastname: Ding
authors.forename: Vance
authors.initials: V
authors.lastname: Fredrickson
authors.forename: Changya
authors.initials: C
authors.lastname: Peng
authors.forename: Steven
authors.initials: S
authors.lastname: Schafer
authors.forename: Murali
authors.initials: M
authors.lastname: Guthikonda
authors.forename: Christian
authors.initials: C
authors.lastname: Kreipke
authors.forename: José A
authors.initials: JA
authors.lastname: Rafols
authors.forename: Yuchuan
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics* / Q000378:metabolism; D020346:Aquaporins / Q000235:genetics* / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C496032:Aqp4 protein, rat; C491637:Aqp9 protein, rat; D051401:Aquaporin 4; D020346:Aquaporins; D002492:Central Nervous System Depressants; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D000431:Ethanol