title: Enduring cognitive, neurobehavioral and histopathological changes persist for up to one year following severe experimental brain injury in rats.
abstract: Clinical studies have demonstrated that patients sustain prolonged behavioral deficits following traumatic brain injury, in some cases culminating in the cognitive and histopathological hallmarks of Alzheimer's disease. However, few studies have examined the long-term consequences of experimental traumatic brain injury. In the present study, anesthetized male Sprague-Dawley rats (n = 185) were subjected to severe lateral fluid-percussion brain injury (n = 115) or sham injury (n = 70) and evaluated up to one year post-injury for cognitive and neurological deficits and histopathological changes. Compared with sham-injured controls, brain-injured animals showed a spatial learning impairment that persisted up to one year post-injury. In addition, deficits in specific neurologic motor function tasks also persisted up to one year post-injury. Immunohistochemistry using multiple antibodies to the amyloid precursor protein and/or amyloid precursor protein-like proteins revealed novel axonal degeneration in the striatum, corpus callosum and injured cortex up to one year post-injury and in the thalamus up to six months post-injury. Histologic evaluation of injured brains demonstrated a progressive expansion of the cortical cavity, enlargement of the lateral ventricles, deformation of the hippocampus, and thalamic calcifications. Taken together, these findings indicate that experimental traumatic brain injury can cause long-term cognitive and neurologic motor dysfunction accompanied by continuing neurodegeneration.
authors.affiliation: Division of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Pierce
authors.forename: D H
authors.initials: DH
authors.lastname: Smith
authors.forename: J Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: T K
authors.initials: TK
authors.lastname: McIntosh
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry / Q000502:physiology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology* / Q000523:psychology*; D003072:Cognition Disorders / Q000209:etiology* / Q000517:prevention & control*; D005552:Forelimb / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor