title: Cognitive impairment and synaptosomal choline uptake in rats following impact acceleration injury.
abstract: Traumatic brain injury is well known to cause deficits in learning and memory, which typically improve with time. Animal studies with fluid percussion or controlled cortical impact injury have identified transient disturbances in forebrain cholinergic innervation which may contribute to such cognitive problems. This study examines the extent to which water maze performance and forebrain synaptosomal choline uptake are affected one week after injury using the newly developed impact acceleration injury model. Injury or sham injury was delivered to adult male Sprague-Dawley rats under halothane anesthesia using a 500-g 2.1-m weight drop. Based on righting reflex, injured rats were divided into moderate (< or = 12 min) or severe (>12 min) groups. Water maze testing was performed on days 5-7 postinjury. On day 7, choline uptake was determined in synaptosomes from hippocampus, a parietal cortex, and entorhinal cortex. Maze learning was severely impaired in the severe injury group but not in the moderate injury group. Learning retention was slightly impaired in the moderate injury group and severely affected in the severe injury group. There was a very strong correlation between the severity of injury as determined by prolongation of righting times and disruption of maze learning at 1 week postinjury. There was no change in synaptosomal choline uptake in any of the forebrain regions in the severe injury group, but a slight (14%) decrease in the hippocampus and parietal cortex of the moderate injury group. Correlation analysis showed no relationship between synaptosomal choline uptake in any brain region and performance in either water maze learning or retention. This study shows that the impact acceleration model produces cognitive impairments equivalent to those seen with fluid percussion injury and controlled cortical impact. Compared with those models, the impact acceleration model does not produce a similar disruption of forebrain cholinergic nerve terminals.
authors.affiliation: Department of Neurosurgery, University of Utah, Salt Lake City 84132, USA. rhs@suzy.med.utah.edu
authors.forename: R H
authors.initials: RH
authors.lastname: Schmidt
authors.forename: K J
authors.initials: KJ
authors.lastname: Scholten
authors.forename: P H
authors.initials: PH
authors.lastname: Maughan
mesh_terms: D000054:Acceleration / Q000009:adverse effects; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology*; D002794:Choline / Q000378:metabolism*; D003072:Cognition Disorders / Q000209:etiology*; D008297:Male; D018782:Maze Learning; D009420:Nervous System / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013550:Swimming; D013574:Synaptosomes / Q000378:metabolism*; D014949:Wounds, Nonpenetrating / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology*
chemical_list: D002794:Choline