Hypertonic saline ameliorates cerebral edema through downregulation of aquaporin-4 expression in the astrocytes

Neuroscience. 2010 Mar 31;166(3):878-85. doi: 10.1016/j.neuroscience.2009.12.076. Epub 2010 Jan 18.

Abstract

Osmotherapy with 10% hypertonic saline (HS) alleviates cerebral edema through osmotic force. Aquaporin-4 (AQP4) has been reported to be implicated in the pathogenesis of cerebral edema resulting from a variety of brain injury. This study aimed to determine if 10% hypertonic saline ameliorates cerebral edema through downregulation of AQP4 expression in the perivascular astrocytes in the ischemic cerebral edema. Adult male Sprague-Dawley (SD) rats were subjected to permanent right-sided middle cerebral artery occlusion (MCAO) and treated with a continuous i.v. infusion of 10% HS. Brain water content (BWC) analyzed by wet-to-dry ratios in the ischemic hemisphere of SD rats was attenuated after 10% HS treatment. This was coupled with the reduction of neuronal apoptosis in the peri-ischemic brain tissue. Concomitantly, downregulated expression of AQP4 in the perivascular astrocytes after 10% HS treatment was observed. Our results suggest that in addition to its osmotic force, 10% HS exerts anti-edema effects possibly through downregulation of AQP4 expression in the perivascular astrocytes. The reduction of brain edema after 10% HS administration can prevent ischemic brain damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Aquaporin 4 / biosynthesis*
  • Aquaporin 4 / genetics
  • Astrocytes / metabolism*
  • Brain / metabolism
  • Brain / pathology
  • Brain Edema / etiology
  • Brain Edema / metabolism
  • Brain Edema / therapy*
  • Down-Regulation
  • Infarction, Middle Cerebral Artery / complications
  • Male
  • Neurons / pathology
  • Osmosis
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Saline Solution, Hypertonic / pharmacology*
  • Saline Solution, Hypertonic / therapeutic use

Substances

  • Aquaporin 4
  • RNA, Messenger
  • Saline Solution, Hypertonic