Post-treatment with SR49059 improves outcomes following an intracerebral hemorrhagic stroke in mice

Acta Neurochir Suppl. 2011:111:191-6. doi: 10.1007/978-3-7091-0693-8_32.

Abstract

Intracerebral hemorrhage (ICH) is a devastating stroke subtype characterized by severe brain edema formation leading to cerebral blood flow compromise and parenchymal damage. Arginine vasopressin (AVP), a non-peptide antidiuretic hormone, has recently been implicated as a modulator of brain edema following injury. In this study, we investigated the effects of SR49059, a highly specific AVP V1a receptor antagonist, on brain injury outcomes following ICH, specifically assessing the ability of SR49059 in reducing brain edema and improving neurobehavioral deficits. Male CD1 mice (n=35) were randomly assigned to the following groups: sham, ICH, ICH with SR49059 at 0.5 mg/kg, and ICH with SR49059 at 2 mg/kg. ICH was induced by using the collagenase injection model, and treatment was given 1 h after surgery. Post-assessment was conducted at 24 and 72 h after surgery, and included brain water content and neurobehavioral testing. The study found that SR49059 significantly reduced cerebral edema at 24 and 72 h post-ICH injury and improved neurobehavioral deficits at 72 h. Our study suggests that blockage of the AVP V1a receptor is a promising treatment target for improving ICH-induced brain injury. Further studies will be needed to confirm this relationship and determine future clinical direction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / pathology
  • Brain Edema / drug therapy
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / prevention & control*
  • Collagenases / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Functional Laterality / drug effects
  • Hormone Antagonists / administration & dosage*
  • Indoles / administration & dosage*
  • Male
  • Mice
  • Psychomotor Performance / drug effects
  • Pyrrolidines / administration & dosage*
  • Stroke / complications
  • Time Factors

Substances

  • Hormone Antagonists
  • Indoles
  • Pyrrolidines
  • relcovaptan
  • Collagenases