Behavioral and Histological Effects of Traumatic Brain Injury on Alzheimer\u27s Disease Transgenic Mice

The main objective of this study was to elucidate the possible mechanistic link between traumatic brain injury (TBI) and Alzheimer\u27s disease (AD) using an animal model. We examined behavioral and histological effects of TBI in pre-symptomatic AD-transgenic mice (C57B6/SJL/SwissWebster/B6D2F1). In previous studies, these mice displayed AD-like behavioral deficits by 15-17 months of age and AD-like neuropathology as early as six months of age. To clarify the effects of TBI on these mice, the present study began when they were about three months of age and the study ended when they were about five months of age. As a control, non-transgenic (NT) mice were also evaluated in this study. To assess behavioral changes following TBI, all mice were subjected to 14 days of pre-TBI training of a spatial memory task, the radial arm water maze (RAWM). After training, there were no performance differences between AD-transgenic mice and NT mice. Then, half of the AD-transgenic mice, as well as half of the NT mice, received an experimental TBI at the right parietal cortex using a pneumatic impactor. The other half of these mice received sham surgery. At two, four, and six weeks after surgery, all mice were tested in the same water maze task and the numbers of errors were recorded. AD-transgenic mice with TBI made significantly more errors than AD-transgenic mice without TBI and NT mice regardless of TBI. Furthermore, deficits were observed at both two and six weeks after TBI surgery. To assess histological changes following TBI, we used a monoclonal antibody against beta-amyloid to detect AD-like plaques and an antibody against NeuN to evaluate the total neuronal loss. There were no clear group differences in terms of the beta amyloid expression pattern, although one AD-transgenic mouse with TBI showed AD-like beta amyloid plaques throughout the entire cortex and hippocampus. These results suggest that TBI precipitated behavioral deficits in a spatial memory task in pre-symptomatic AD-transgenic mice, but not control mice. Further studies are warranted for histological effects of TBI