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Immunohistochemical characterization of alterations in the distribution of amyloid precursor proteins and beta-amyloid peptide after experimental brain injury in the rat
Open accessAbstract
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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“For example, APP expression increases in striatal and hippocampal axons along with cortical and thalamic neurons within the first 24 h after experimental impact and fluid percussion TBI (121–123)”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [121]
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“a majority of rodent studies fail to show this association in non-transgenic animals using CCI, FPI, and weight drop models (121, 122, 124, 125, 135).”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [121]
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Citations
Cites
Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein
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“One such transgenic mouse expressing human APP developed spontaneous deposits of A/3 that form amyloid fibrils (Games et al., 1995).”
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“Our laboratory has established a model of experimental lateral fluid-percussion (FP) brain injury in the rat (McIntosh et al., 1989) that produces reproducible and clinically relevant his- topathological changes, including extensive neuronal loss and degeneration accompanied by gliosis in cortical…”
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Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport.
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MethodSelf-citationAccumulation of the beta amyloid precursor protein at sites of ischemic injury in rat brain.
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BackgroundExpression of APP in the early stage of brain damage
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“The extent of DA1 increases in parallel with the severity of TBI and correlates with measures of postinjury morbidity and mortality (Gennarelli et al., 1982a; Pilz, 1983; Adams et al., 1989; Povlishock, 1992; Povlishock et al., 1992; Blumbergs et al., 1994).”
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Self-citationAMYLOID β-PROTEIN PRECURSOR DEPOSITION IN RAT HIPPOCAMPUS LESIONED BY IBOTENIC ACID INJECTION
Nakamura, Y., Takeda, M., Niigawa, H., Hariguchi, S., Kitajima, S., & Nishimura, T. (1992) · doi:10.1097/00002826-199202001-00908 · Cited by 76
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Expression of c-fos in the Hippocampus Following Mild and Moderate Fluid Percussion Brain Injury
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BackgroundThe nootropic compound BMY-21502 improves spatial learning ability in brain injured rats
Pierce, J. E. S., Smith, D. H., Eison, M. S., & McIntosh, T. K. (1993) · Brain Research · doi:10.1016/0006-8993(93)90078-2 · Cited by 36
Self-citationGenetically engineered animal models of human neurodegenerative diseases.
Higgins, L., & Cordell, B. (1995) · Neurodegeneration · doi:10.1006/neur.1995.0015 · Cited by 15 · cited 1×
“Future studies using transgenic mice that develop AD-like pathology (for review, set Higgins and Cordell, 1995) may provide insights into the role of TBI in the pathogenesis of AD.”
Background
Cited by
Sorted by citations
Chronic traumatic encephalopathy in athletes: Progressive tauopathy after repetitive head injury
McKee, A. C., Cantu, R. C., Nowinski, C. J., Hedley-Whyte, E. T., Gavett, B. E., Budson, A. E., Santini, V. E., Lee, H.-S., Kubilus, C. A., & Stern, R. A. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181a9d503 · Cited by 2,295
Atwood, C. S., Moir, R. D., Huang, X., Scarpa, R. C., Bacarra, N. M. E., Romano, D. M., Hartshorn, M. A., Tanzi, R. E., & Bush, A. I. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.21.12817 · Cited by 1,009
Acute axonal injury in multiple sclerosis: Correlation with demyelination and inflammation
Bitsch, A. (2000) · Brain · doi:10.1093/brain/123.6.1174 · Cited by 898
“Studies of severe head trauma and ischaemic cerebral infarction demonstrated that the accumulation of APP in the proximal ends of transected axons is restricted to a period of 30 days after an acute injury and, therefore, is well suited as a marker of acute axonal damage (Li et al., 1995; Pierce et al., 1996; Bramlett…”
BackgroundKuhlmann, T., Lingfeld, G., Bitsch, A., Schuchardt, J., & Brück, W. (2002) · Brain : a journal of neurology · doi:10.1093/brain/awf235 · Cited by 851
“It persists in transected axons for a period of <30 days (Li et al., 1995; Pierce et al., 1996; Bramlett et al., 1997; Yam et al., 1997) In histopathological studies, a signi®cant reduction of axon density was found in multiple sclerosis lesions (Lovas et al.”
BackgroundTraumatic Brain Injuries: Pathophysiology and Potential Therapeutic Targets
Ng, S. Y., & Lee, A. Y. W. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00528 · Cited by 906
Metadata
- Authors
- Pierce, J., Trojanowski, J., Graham, D., Smith, D., & McIntosh, T.
- Affiliations
- University of Pennsylvania (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1996-02-01
- Volume
- 16
- Issue
- 3
- Pages
- 1083-1090
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6578806
- OpenAlex
- W1879457624
- Cited by
- 239
- References
- 75
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 8 · 2018: 7 · 2017: 8 · 2016: 5 · 2015: 15 · 2014: 4 · 2013: 10 · 2012: 8
- FWCI
- 10.01
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P30AG010124, AG-10124)
- National Institute of Neurological Disorders and Stroke (NS-08803, NS26818)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Keywords
- amyloid precursor protein, amyloid-beta, traumatic brain injury, fluid percussion injury, axonal pathology, neurodegeneration, thalamus, white matter, hippocampus, striatum
- MeSH terms
- Animals, Brain Injuries, Hippocampus, Male, Nerve Degeneration, Nerve Tissue Proteins, Pressure, Thalamus, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Rats, Sprague-Dawley, Rats
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