Enduring cognitive, neurobehavioral and histopathological changes persist for up to one year following severe experimental brain injury in rats

• Published in: Neuroscience 1998-11, Vol.87 (2), p.359-369
• Main Authors: Pierce, J.E.S, Smith, D.H, Trojanowski, J.Q, McIntosh, T.K
• Format: Article
• Language: English
• Subjects: Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - metabolism; amyloid precursor protein; Animals; Behavior, Animal - physiology; Biological and medical sciences; Brain - pathology; Brain Chemistry - physiology; Brain Injuries - metabolism; Brain Injuries - pathology; Brain Injuries - psychology; Cognition Disorders - etiology; Cognition Disorders - prevention & control; fluid-percussion brain injury; Forelimb - physiology; Injuries of the nervous system and the skull. Diseases due to physical agents; Male; Maze Learning - physiology; Medical sciences; Morris water maze; neurodegeneration; neurologic motor score; Psychomotor Performance - physiology; Rats; Rats, Sprague-Dawley; Traumas. Diseases due to physical agents; traumatic brain injury
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(98)00142-0

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.