Resveratrol attenuates behavioral impairments and reduces cortical and hippocampal loss in a rat controlled cortical impact model of traumatic brain injury.
Resveratrol (3,5,4'-trihydroxystilbene) is a plant-derived small molecule that is protective against multiple neurological and systemic insults. To date, no studies have explored the potential for resveratrol to provide behavioral protection in adult animals in the setting of traumatic brain injury (TBI). Using 50 male Sprague-Dawley rats, we employed the controlled cortical impact (CCI) model to ascertain whether post-injury administration of resveratrol would reduce the severity of the well-described cognitive and motor deficits associated with the model. Contusion volumes and hippocampal neuronal numbers were also measured to characterize the tissue and neuronal-sparing properties, respectively, of resveratrol. We found that 100 mg/kg, but not 10 mg/kg, of intraperitoneal resveratrol administered after injury provides significant behavioral protection in rats sustaining CCI. Specifically, rodents treated with 100 mg/kg of resveratrol showed improvements in motor performance (beam balance and beam walking) and testing of visuospatial memory (Morris water maze). Behavioral protection was correlated with significantly reduced contusion volumes, preservation of CA1 and CA3 hippocampal neurons, and protection from overt hippocampal loss as a result of incorporation into the overlying cortical contusion in resveratrol-treated animals. Although the mechanisms by which resveratrol mediates its neuroprotection is unclear, the current study adds to the growing literature identifying resveratrol as a potential therapy for human brain injury.
Singleton
Richard H
RH
Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
Yan
Hong Q
HQ
Fellows-Mayle
Wendy
W
Dixon
C Edward
CE
D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use
D018696:Neuroprotective Agents; D013267:Stilbenes; D000077185:Resveratrol