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|Title:||Characterisation of the effect of knockout of the amyloid precursor protein on outcome following mild traumatic brain injury|
Van Den Heuvel, C.
|Citation:||Brain Research, 2012; 1451:87-99|
|Publisher:||Elsevier Science Bv|
|Frances Corrigan, Robert Vink, Peter C. Blumbergs, Colin L. Masters, Roberto Cappai and Corinna Van Den Heuvel|
|Abstract:||The amyloid precursor protein (APP) increases following traumatic brain injury (TBI), although the functional significance of this remains unclear largely because the functions of the subsequent APP metabolites are so different: Aβ is neurotoxic whilst sAPPα is neuroprotective. To investigate this further, APP wildtype and knockout mice were subjected to mild diffuse TBI and their outcomes compared. APP knockout mice displayed significantly worse cognitive and motor deficits, as demonstrated by the Barnes Maze and rotarod respectively, than APP wildtype mice. This was associated with a significant increase in hippocampal and cortical cell loss, as well as axonal injury, in APP knockout mice and an impaired neuroreparative response as indicated by diminished GAP-43 immunoreactivity when compared to APP wildtype mice. This study is the first to demonstrate that endogenous APP is beneficial following mild TBI, suggesting that the upregulation of APP observed following injury is an acute protective response.|
|Keywords:||Hippocampus; Cerebral Cortex; Neurons; Axons; Animals; Mice, Knockout; Mice; Brain Injuries; Amyloid beta-Protein Precursor; Rotarod Performance Test; Maze Learning; Motor Skills; Recovery of Function; Caspase 3|
|Rights:||© 2012 Elsevier B.V. All rights reserved.|
|Appears in Collections:||Medical Sciences publications|
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