Reduction of brain edema and expression of aquaporins with acute ethanol treatment after traumatic brain injury

J Neurosurg. 2013 Feb;118(2):390-6. doi: 10.3171/2012.8.JNS12736. Epub 2012 Nov 30.

Abstract

Object: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporin 4 / genetics*
  • Aquaporin 4 / metabolism
  • Aquaporins / genetics*
  • Aquaporins / metabolism
  • Brain Edema / drug therapy*
  • Brain Edema / genetics
  • Brain Edema / metabolism
  • Brain Injuries / drug therapy*
  • Brain Injuries / genetics
  • Brain Injuries / metabolism
  • Central Nervous System Depressants / pharmacology
  • Cognition / drug effects
  • Ethanol / pharmacology*
  • Gene Expression / drug effects
  • Male
  • Motor Activity / drug effects
  • Neuroprotective Agents / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Aqp4 protein, rat
  • Aqp9 protein, rat
  • Aquaporin 4
  • Aquaporins
  • Central Nervous System Depressants
  • Neuroprotective Agents
  • RNA, Messenger
  • Ethanol