Tolvaptan attenuated brain edema in experimental intracerebral hemorrhage

Brain Res. 2019 Jul 15:1715:41-46. doi: 10.1016/j.brainres.2019.01.033. Epub 2019 Jan 28.

Abstract

Arginine-vasopressin (AVP) is believed to be positively correlated with the brain edema formation, but the underlying mechanism is still unclear. In this study, we explored the role of the V2 receptors antagonist tolvaptan on brain edema following intracerebral hemorrhage (ICH) with a rat model. Animals were randomly given tolvaptan or vehicle through oral gavage at 12 h, 36 h, and 60 h after ICH surgery. Brain swelling (%), brain water content(BWC), neurological scores, Evans blue fluorescence and blood-brain barrier (BBB) tight junction proteins were measured to evaluate the effect of tolvaptan in ICH. We found that tolvaptan alleviated the brain swelling (%), decreased the BWC growth, and attenuated the neurological deficits after ICH (p < 0.05, vs vehicle). What's more, tolvaptan increased the expression of ZO-1 and occludin (p < 0.05, vs vehicle), which might be attributed to the down-regulated effects of tolvaptan on MMP-9. These results provided evidence supporting the use of tolvaptan for ICH-induced brain edema. Large animal experiments are required to further explore the efficacy and mechanism of tolvaptan in ICH treatment.

Keywords: Arginine-vasopressin; Blood brain barrier; Brain edema; Tolvaptan; V1 receptors; V2 receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Blood-Brain Barrier / drug effects
  • Brain / metabolism
  • Brain Edema / drug therapy*
  • Brain Edema / metabolism
  • Cerebral Hemorrhage / drug therapy*
  • Cerebral Hemorrhage / metabolism
  • Disease Models, Animal
  • Male
  • Occludin / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Vasopressin / metabolism
  • Tolvaptan / therapeutic use*

Substances

  • Occludin
  • Receptors, Vasopressin
  • Tolvaptan