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

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.

• Authors: Anatol Manaenko, Nancy Fathali, Nikan H Khatibi, Tim Lekic, Kenneth J Shum, Robert Martin, John H Zhang, Jiping Tang
• Journal: Acta neurochirurgica. Supplement (Acta Neurochir Suppl) Vol. 111 Pg. 191-6 ( 2011) ISSN: 0065-1419 [Print] Austria
• PMID: 21725754 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Hormone Antagonists
• Indoles
• Pyrrolidines
• relcovaptan
• Collagenases

Topics

• Animals
• Brain (drug effects, pathology)
• Brain Edema (drug therapy)
• Cerebral Hemorrhage (chemically induced, complications, 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