title: Repeated resveratrol administration confers lasting protection against neuronal damage but induces dose-related alterations of behavioral impairments after global ischemia.
abstract: Resveratrol, a naturally occurring polyphenol, has been shown to protect the heart and brain against ischemic injury. The current study investigated the effects of administration with either a 1 or 10-mg/kg dose of resveratrol on CA1 neuronal injury and behavioral/cognitive impairments after 10-min global ischemia in rats. The open-field, eight-arm radial maze and object recognition tests served to evaluate effects of resveratrol treatment on ischemia-induced locomotor activity, and spatial and recognition memory impairments, respectively. CA1 and CA3 neuronal injury was assessed upon completion of behavioral testing, 85 days postischemia. A separate series of groups served to assess neuronal injury at 7 days postischemia. Global ischemia (10 min) led to approximately 50% CA1 cell injury, which was prevented at both short (7 days) and long (85 days) postischemic intervals by resveratrol treatment. Importantly, despite comparable neuronal protection, the two resveratrol doses showed distinct behavioral effects. Thus, the 10-mg/kg resveratrol dose led to an enhanced locomotor activity in the open-field 4-days postischemia and an impaired spatial memory in the delayed nonmatching to sample and delayed matching to sample radial-maze tasks initiated on day 13 postischemia. These findings suggest independent actions of resveratrol on distinct physiological systems mediating cellular survival and functional recovery and dose-related actions of the polyphenol on behavioral and memory processes.
authors.affiliation: Department of Psychology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Catrinel
authors.initials: C
authors.lastname: Girbovan
authors.forename: Lucie
authors.initials: L
authors.lastname: Morin
authors.forename: Hélène
authors.initials: H
authors.lastname: Plamondon
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D018696:Neuroprotective Agents; D013267:Stilbenes; D000077185:Resveratrol