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Journal of Neuroscience, Vol 16, 1083-1090, Copyright © 1996 by Society for Neuroscience
Immunohistochemical characterization of alterations in the distribution of amyloid precursor proteins and beta-amyloid peptide after experimental brain injury in the rat
JE Pierce, JQ Trojanowski, DI Graham, DH Smith and TK McIntosh
Division of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Recent reports suggest a relationship between traumatic brain injury and
the precocious development of neurodegenerative cascades, including diffuse
deposits of beta-amyloid peptides (A beta) in the injured brain. Because
the lateral fluid-percussion (FP) model of experimental brain injury
produces clinically relevant neuropathological sequelae in the rat brain,
we used this model together with a series of antibodies specific for
amyloid precursor proteins (APPs), APP-like proteins (APLPs), or A beta to
identify acute neurodegenerative changes after brain trauma. Male
Sprague-Dawley rats were anesthetized and subjected to lateral FP brain
injury of moderate to high severity. At 1 hr, 2 hr, 48 hr, 1 week, or 2
weeks after injury, animals were killed and their brains were removed for
immunohistochemical analysis. APP/APLP immunoreactivity increased in
specific brain regions as early as 1 hr after injury and persisted for at
least 2 weeks. Axons in the thalamus and subcortical white matter showed
the greatest APP/APLP accumulation. Injured cortex, striatum, cingulum, and
hippocampus also demonstrated significant axonal accumulations of APP/APLP.
Accumulation of APP/APLPs occurred primarily ipsilateral to the injury,
although bilateral changes were observed in some brain regions. No
deposition of A beta was observed in any brain region at any time point
examined. These results demonstrate a pattern of widespread axonal
pathology after lateral FP brain injury in the rat, characterized by
intra-axonal accumulations of APP/APLP immunoreactivity in the absence of
plaque- like deposits of A beta in the traumatized brain.
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