title: The Effects of Clinically Relevant Hypertonic Saline and Conivaptan Administration on Ischemic Stroke.
abstract: Cerebral edema after stroke is associated with poor neurological outcomes. Current therapies are limited to osmotic agents, such as hypertonic saline (HS), which reduce intracranial pressure. Although studies have demonstrated edema reductions following HS, tissue survival has not been thoroughly examined. Additionally, the efficacy of promising pharmacological agents has not been evaluated for synergy with osmotic agents. Conivaptan is an FDA-approved vasopressin receptor antagonist that may exert both osmotic and anti-inflammatory effects. In this study, rats were subjected to middle cerebral artery occlusion prior to treatment with 5 % HS bolus +5 % HS maintenance (HS), conivaptan alone (Con), conivaptan +5 % HS maintenance (Con + HS), or conivaptan +5 % HS bolus +5 % maintenance (Con + HSb). Treatments were initiated at six (Early) or 24 h (Late) following stroke and rats were euthanized at 48 h to evaluate infarct volume, brain edema, and microglia/macrophage activation. Infarct volume and brain edema in the Early HS, Early Con, and Late HS groups were significantly reduced compared with controls. Interestingly, only the Early Con group demonstrated reduced microglia/macrophage activation. These data suggest an anti-inflammatory mechanism for conivaptan and provide support for a multipronged approach combining osmotic agents with compounds that inhibit the neuroinflammatory response to stroke.
authors.affiliation: Department of Neurology, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL, 33612, USA.
authors.forename: David
authors.initials: D
authors.lastname: Decker
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL, 33612, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Collier
authors.affiliation: Department of Neurology, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL, 33612, USA.
authors.forename: Tsz
authors.initials: T
authors.lastname: Lau
authors.affiliation: Department of Neurology, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL, 33612, USA.
authors.forename: Raul
authors.initials: R
authors.lastname: Olivera
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL, 33612, USA.
authors.forename: Glenn
authors.initials: G
authors.lastname: Roma
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL, 33612, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Leonardo
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL, 33612, USA.
authors.forename: Hilary
authors.initials: H
authors.lastname: Seifert
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL, 33612, USA.
authors.forename: Derrick
authors.initials: D
authors.lastname: Rowe
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL, 33612, USA. kpennypa@health.usf.edu.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Pennypacker
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology; D017078:Laser-Doppler Flowmetry; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D017628:Microglia / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D005452:Fluoresceins; D005456:Fluorescent Dyes; D012462:Saline Solution, Hypertonic; C435731:fluoro jade; C106389:conivaptan
keywords: Central nervous system; Inflammation; Osmotherapy; Rodent; Swelling; Vasopressin