title: Trans-sodium crocetinate improves outcomes in rodent models of occlusive and hemorrhagic stroke.
abstract: Trans-sodium crocetinate (TSC) is a novel carotenoid compound capable of enhancing the diffusion of small molecules in aqueous solutions. TSC improves the diffusion of oxygen and glucose, and increases oxygenation in ischemic brain tissue. TSC also dampens the intensity of an ischemic challenge during an ongoing ischemic event. The current study examined the impact of TSC in rat models of ischemic and hemorrhagic stroke. Rat three vessel occlusion (3VO), and combined 3VO and one vessel occlusion (3VO/1VO) models of ischemic stroke were evaluated for structural and behavioral outcomes. The effects of TSC were also tested in a rat model of intracerebral hemorrhage (ICH). Delayed treatment with TSC reduced infarct volume in a rodent model of transient focal ischemia involving either 2 or 6h of ischemia. Neurological outcomes, based on a multi-scale assessment and automated gait analysis, also were improved by TSC treatment. Additionally, TSC reduced edema and hemorrhagic volume in a rat model of ICH. An optimal therapeutic candidate for early intervention in ischemic stroke should be effective when administered on a delayed basis and should not aggravate outcomes associated with hemorrhagic stroke. The current findings demonstrate that delayed TSC treatment improves outcomes in experimental models of both ischemic and hemorrhagic stroke. Together, these findings suggest that TSC may be a safe and beneficial therapeutic modality for early stroke intervention, irrespective of the type of stroke involved.
authors.affiliation: Department of Neuroscience, University of Virginia, Charlottesville, VA, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neuroscience, University of Virginia, Charlottesville, VA, USA.
authors.forename: Ryo
authors.initials: R
authors.lastname: Yoshimura
authors.affiliation: Department of Neuroscience, University of Virginia, Charlottesville, VA, USA.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Manabe
authors.affiliation: Department of Neuroscience, University of Virginia, Charlottesville, VA, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Schretter
authors.affiliation: Department of Neuroscience, University of Virginia, Charlottesville, VA, USA; Neuroscience Graduate Program, University of Virginia, Charlottesville, VA, USA.
authors.forename: Ryon
authors.initials: R
authors.lastname: Clarke
authors.affiliation: Department of Neuroscience, University of Virginia, Charlottesville, VA, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Neuroscience, University of Virginia, Charlottesville, VA, USA; Neuroscience Graduate Program, University of Virginia, Charlottesville, VA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Fitzgerald
authors.affiliation: Department of Neuroscience, University of Virginia, Charlottesville, VA, USA; Neuroscience Graduate Program, University of Virginia, Charlottesville, VA, USA; Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA. Electronic address: ksl3h@virginia.edu.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Lee
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002338:Carotenoids; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005684:Gait / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010363:Pattern Recognition, Automated; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016896:Treatment Outcome; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018696:Neuroprotective Agents; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids
keywords: Hemorrhage; Ischemia; Rat; Stroke; Therapy; Trans sodium crocetinate