Immunohistochemical characterization of alterations in the distribution of amyloid precursor proteins and beta-amyloid peptide after experimental brain injury in the rat.
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.
Pierce
J E
JE
Division of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Trojanowski
J Q
JQ
Graham
D I
DI
Smith
D H
DH
McIntosh
T K
TK
D016229:Amyloid beta-Peptides / Q000032:analysis*; D016564:Amyloid beta-Protein Precursor / Q000032:analysis*; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008297:Male; D009410:Nerve Degeneration; D009419:Nerve Tissue Proteins / Q000032:analysis*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000378:metabolism / Q000473:pathology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins