title: 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: Department of Physiology and Pharmacology, Loma Linda University, School of Medicine, Loma Linda, CA 92354, USA.
authors: Anatol
authors: A
authors: Manaenko
authors: Nancy
authors: N
authors: Fathali
authors: Nikan H
authors: NH
authors: Khatibi
authors: Tim
authors: T
authors: Lekic
authors: Kenneth J
authors: KJ
authors: Shum
authors: Robert
authors: R
authors: Martin
authors: John H
authors: JH
authors: Zhang
authors: Jiping
authors: J
authors: Tang
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000150:complications / Q000517:prevention & control*; D017364:Collagenases / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007839:Functional Laterality / Q000187:drug effects; D006727:Hormone Antagonists / Q000008:administration & dosage*; D007211:Indoles / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D011597:Psychomotor Performance / Q000187:drug effects; D011759:Pyrrolidines / Q000008:administration & dosage*; D020521:Stroke / Q000150:complications; D013997:Time Factors
chemical_list: D006727:Hormone Antagonists; D007211:Indoles; D011759:Pyrrolidines; C082134:relcovaptan; D017364:Collagenases