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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
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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
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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
Diffuse Axonal Injury in Head Trauma
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Self-citationPathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences
Bramlett, H., & Dietrich, W. (2004) · Journal of Cerebral Blood Flow and Metabolism · doi:10.1097/01.wcb.0000111614.19196.04 · Cited by 622
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BackgroundTraumatic brain injury and amyloid-β pathology: a link to Alzheimer's disease?
Johnson, V. E., Stewart, W., & Smith, D. H. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2808 · Cited by 587
Self-citationLateral Fluid Percussion Brain Injury: A 15-Year Review and Evaluation
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“…Conti et al., 1998; Pierce et al., 1998; Saatman et al., 1998; Carbonell et al., 1998; Sato et al., 2001; Raghupathi et al., 2003), medial septum (Sinson et al., 1997; Smith et al., 1997a), striatum (Hicks et al., 1996; Pierce et al., 1996; Hallam et al., 2004), and amygdala (Hallam et al., 2004).”
Self-citationConti, A., Raghupathi, R., Trojanowski, J., & McIntosh, T. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-15-05663.1998 · Cited by 543
Self-citationBramlett, H. M., & Dietrich, W. D. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2014.3352 · Cited by 590
The duality of the inflammatory response to traumatic brain injury
McIntosh, T. K., Lenzlinger, P. M., Morganti-Kossmann, M.-C., & Laurer, H. L. (2001) · Molecular Neurobiology · doi:10.1385/mn:24:1-3:169 · Cited by 428
Self-citationAlzheimer's pathology in human temporal cortex surgically excised after severe brain injury
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Self-citationSheng, J. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(03)00069-x · Cited by 388
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Self-citationAxonal Damage in Traumatic Brain Injury
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Self-citationMild head injury increasing the brain's vulnerability to a second concussive impact
Laurer, H. L., Bareyre, F. M., Lee, V. M. Y. C., Trojanowski, J. Q., Longhi, L., Hoover, R., Saatman, K. E., Raghupathi, R., Hoshino, S., Grady, M. S., et al. (2001) · Journal of Neurosurgery · doi:10.3171/jns.2001.95.5.0859 · Cited by 313
Self-citationMouzon, B., Chaytow, H., Crynen, G. C., Bachmeier, C. J., Stewart, J., MULLAN, M. J., Stewart, W. B., Jr., & Crawford, F. (2012) · Journal of Neurotrauma · doi:10.1089/neu.2012.2498 · Cited by 298
“Axonal injury following trauma results in swollen and tortuous axons that can be detected by the accumulation of APP as early as 35min after brain injury, 46 and in our model, a single impact resulted in APP-immunoreactive axons localized to the CC, evident at 24 h after injury.”
Chen, X.-H., Siman, R., Iwata, A., Meaney, D. F., Trojanowski, J. Q., & Smith, D. H. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63303-2 · Cited by 271
“It has long been suspected that accumulated APP in damaged axons could provide ample substrate for A production.(18,34,35) Indeed, immunohistochemical detection of APP accumulation in axons throughout the white matter has become a standard method to identify DAI in human brains.”
MethodSelf-citationMacrophages and neurodegeneration
Hendriks, J. J. A., Teunissen, C. E., de Vries, H. E., & Dijkstra, C. D. (2005) · Brain Research Reviews · doi:10.1016/j.brainresrev.2004.12.008 · Cited by 247
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Functional Differentiation of Multiple Perilesional Zones after Focal Cerebral Ischemia
Witte, O., Bidmon, H.-J., Schiene, K., Redecker, C., & Hagemann, G. (2000) · Journal of Cerebral Blood Flow and Metabolism · doi:10.1097/00004647-200008000-00001 · Cited by 260
“In addition, a rapid contralateral activation of NOS-I and a longer lasting up-regulation of APP and neurofilament 68 have been found in rodents (Pierce et al., 1996), whereas in humans a transient contralateral phosphorylation of neurofilament H occurs (Hedreen et al.”
BackgroundTraumatic brain injury and Alzheimer's disease: a review
van den Heuvel, C., Thornton, E., & Vink, R. (2007) · Progress in brain research · doi:10.1016/s0079-6123(06)61021-2 · Cited by 215
Bramlett, H. M., & Dietrich, W. D. (2001) · Journal of Neurotrauma · doi:10.1089/089771501750451811 · Cited by 213
“Various laboratories have reported increases in b -APP immunoreactivity after clinical and experimental brain injury (Bramlett et al., 1997; Pierce et al., 1996; Roberts et al., 1994).”
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Cerebrospinal Fluid Markers for Alzheimer's Disease Evaluated after Acute Ischemic Stroke
Hesse, C., Rosengren, L., Vanmechelen, E., Vanderstichele, H., Jensen, C., Davidsson, P., & Blennow, K. (2000) · Journal of Alzheimer s Disease · doi:10.3233/jad-2000-23-402 · Cited by 215
Amyloid β accumulation in axons after traumatic brain injury in humans
Smith, D. H., Chen, X.-H., Iwata, A., & Graham, D. (2003) · Journal of neurosurgery · doi:10.3171/jns.2003.98.5.1072 · Cited by 196
Self-citationBramlett, H. M., Dietrich, W. D., Green, E. J., & Busto, R. (1997) · Acta Neuropathologica · doi:10.1007/s004010050602 · Cited by 189
Therapy Development for Diffuse Axonal Injury
Smith, D. H., Hicks, R. R., & Povlishock, J. T. (2012) · Journal of Neurotrauma · doi:10.1089/neu.2012.2825 · Cited by 191
Self-citationArendt, T. (2003) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2003.09.007 · Cited by 189
Blasko, I., Beer, R., Bigl, M., Apelt, J., Franz, G., Rudzki, D., Ransmayr, G. N., Kampfl, A., & Schliebs, R. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-003-0095-6 · Cited by 188
“…Ab levels in cerebrospinal fluid (Emmerling et al., 2000; Raby et al., 1998), and marked overproduction of the amyloid beta precursor protein (AbPP) in neurons of injured humans or experimental animals have also been observed (Lewen et al., 1995; Pierce et al., 1996; Sherriff et al., 1994).”
BackgroundProlonged Activation of NF-κB Following Traumatic Brain Injury in Rats
NONAKA, M., CHEN, X.-H., PIERCE, J. E. S., LEONI, M. J., McINTOSH, T. K., WOLF, J. A., & SMITH, D. H. (1999) · Journal of Neurotrauma · doi:10.1089/neu.1999.16.1023 · Cited by 176
“In addition, amyloid precursor protein (APP), which has been found to accumulate up to 1 year following brain trauma in the rat (Pierce et al., 1996, 1998), may also activate NF-kB (Barger and Harmon, 1997).”
Self-citationFluid-percussion–induced traumatic brain injury model in rats
Kabadi, S. V., Hilton, G. D., Stoica, B. A., Zapple, D. N., & Faden, A. I. (2010) · Nature Protocols · doi:10.1038/nprot.2010.112 · Cited by 170
Protein Accumulation in Traumatic Brain Injury
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Self-citationBALDWIN, S. A., GIBSON, T., CALLIHAN, C. T., SULLIVAN, P. G., PALMER, E., & SCHEFF, S. W. (1997) · Journal of Neurotrauma · doi:10.1089/neu.1997.14.385 · Cited by 120
“These models have been em-al., 1995; Posmantur et al., 1996; Mocchetti and Wrathall, ployed to characterize ionic and metabolic changes 1995; Pierce et al., 1996), cerebrovascular response Sanders-Brown Center on Aging, Department of Anatomy and Neurobiology, University of Kentucky, Lexington,…”
Experimental traumatic brain injury
Albert-Weißenberger, C., & Sirén, A. (2010) · Experimental & Translational Stroke Medicine · doi:10.1186/2040-7378-2-16 · Cited by 139
“For instance, initial studies using LFP detected an ipsilateral brain injury [64] whereas some later studies detected a widespread, bilateral brain injury [65-67].”
ResultAlzheimer Disease and Its Growing Epidemic
Hickman, R. A., Faustin, A., & Wısnıewskı, T. (2016) · Neurologic Clinics · doi:10.1016/j.ncl.2016.06.009 · Cited by 163
“First, APP expression is noticeably increased post-TBI.(83,84) APP is particularly prominent at the axon terminals where there has been axonal transection and axonal transection is known to occur even in mild cases of TBI.”
BackgroundSmith, D. H., Nakamura, M., McIntosh, T. K., Wang, J., Rodríguez, A., Chen, X.-H., Raghupathi, R., Saatman, K. E., Clemens, J., Schmidt, M. L., et al. (1998) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65643-x · Cited by 143
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“The primary antibodies used were cis mAb (clone #113) and trans mAb (clone #25)48, tau tangle-related mAbs AT180, AT8, AT100 (all from Innogenetics, Alpharetta, GA), oligomeric tau T22 polyclonal antibodies (EMD Millipore, Billerica, MA), anti-tau rabbit mAb (E178, Abcam), anti-PHF-1 (ab109390, Abcam), Von Willerbrand…”
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“…et al. (2011a,b); similar IHC staining pattern APP Anti-rabbit Amyloid precursor protein 51 2700: Invitrogen Coporation, Camarillo, CA, USA WB Pierce et al. (1996), Wang et al. (2011); similar IHC staining pattern CC1 Anti-mouse Mature OLs ab16794: Abcam, Cambridge, UK ICC,…”
Spain, A., Daumas, S., Lifshitz, J., Rhodes, J. K. J., Andrews, P., Horsburgh, K. J., & Fowler, J. H. (2010) · Journal of Neurotrauma · doi:10.1089/neu.2010.1288 · Cited by 139
“Moststudies have focused on moderate to severe levels of injury, which produce gross damage to grey and white matter regions, particularly the hippocampus (Carbonell et al., 1998; Holland et al., 2008; Pierce et al., 1998, 1996; Tran et al., 2006; Witgen et al., 2005).”
Aβ as a bioflocculant: implications for the amyloid hypothesis of Alzheimer’s disease
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Apolipoprotein E &egr;4 and short-term recovery from predominantly mild brain injury
Liberman, J., Stewart, W., Wesnes, K., & Troncoso, J. (2002) · Neurology · doi:10.1212/wnl.58.7.1038 · Cited by 129
The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease
Kokiko-Cochran, O. N., & Godbout, J. P. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00672 · Cited by 128
“Although Aβ deposition is apparent following rotational acceleration TBI in pigs (132, 133) and rabbits (134), 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).”
BackgroundHerrero-Herranz, E., Pardo, L., Gold, R., & Linker, R. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.01.001 · Cited by 124
“APP is a well characterized marker for acute axonal injury in neurodegenerative diseases, but also MS (Kuhlmann et al., 2002; Pierce et al., 1996).”
BackgroundIwata, A., Chen, X., McIntosh, T. K., Browne, K. D., & Smith, D. H. (2002) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/61.12.1056 · Cited by 116
Self-citationNitric oxide generators produce accumulation of chelatable zinc in hippocampal neuronal perikarya
Cuajungco, M. P., & Lees, G. J. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00463-6 · Cited by 116
Traumatic brain injury: cause or risk of Alzheimer’s disease? A review of experimental studies
Szczygielski, J., Mautes, A. E. M., Steudel, W. I., Falkai, P., Bayer, T. A., & Wirths, O. (2005) · Journal of Neural Transmission · doi:10.1007/s00702-005-0326-0 · Cited by 75
“Nevertheless, APP immunostaining remains to be so far the best method to visualise injured axons, both in experimental (Bramlett et al., 1997; Pierce et al., 1996; Stone et al., 1999; Hoshino et al., 2003) and medical settings (Gentleman et al., 1993b; Sherriff et al., 1994a, b; Blumbergs et al.,…”
BackgroundMethodInfluentialLifshitz, J., Kelley, B., & Povlishock, J. (2007) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/01.jnen.0000248558.75950.4d · Cited by 114
“To date, the long-term fate of neurons subjected to perisomatic axotomy has not been followed over a prolonged time course because of the persistent evolution of the injury cavity after focal injuries and the resorption of axonal pathology after diffuse injury (3, 6).”
BackgroundAnimal Models of Post-Traumatic Epilepsy
Pitkänen, A., & McIntosh, T. (2006) · Journal of Neurotrauma · doi:10.1089/neu.2006.23.241 · Cited by 112
“…that axonal injury continues for weeks to months post-injury in the major fiber pathways in mice, rats, and humans, and therefore, occurs in parallel with axonal sprouting (Roberts et al., 1991; Graham et al., 1995; Pierce et al., 1996; Carbonnell and Grady, 1999; Bramlett and Dietrich, 2002).”
Self-citationRodent Model of Direct Cranial Blast Injury
Kuehn, R. B., Simard, P. F., Driscoll, I., Keledjian, K., Ivanova, S. A., Tosun, Ç., Williams, A. N., Bochicchio, G., Gerzanich, V., & Simard, J. M. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2010.1532 · Cited by 109
“Both axonal and neuronal abnormalities were identified that were broadly similar to findings reported in other forms of TBI (Blumbergs et al., 1995; Bramlett et al., 1997; Itoh et al., 2009; Kilbourne et al., 2009; Pierce et al., 1996; Stone et al., 2000).”
Brain injury, neuroinflammation and Alzheimer's disease
Breunig, J. J., Guillot‐Sestier, M., & Town, T. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00026 · Cited by 106
“…models have relatively low abundance of brain endogenous Aβ species that do not reach a critical threshold for aggregation (Lewen et al., 1995; Pierce et al., 1996; Bramlett et al., 1997; Hoshino et al., 1998; Iwata et al., 2002; Stone et al., 2002; Hamberger et al., 2003; Abrahamson et al.,…”
BackgroundEffects of Low-Level Blast Exposure on the Nervous System: Is There Really a Controversy?
Elder, G. A., Stone, J. R., & Ahlers, S. T. (2014) · Frontiers in Neurology · doi:10.3389/fneur.2014.00269 · Cited by 113
Tsitsopoulos, P. P., & Marklund, N. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00079 · Cited by 120
“In addition, increased neuronal APP expression has also been observed in human and animal models and across the spectrum of severe TBI (Otsuka et al., 1991; Sola et al., 1993; Lewen et al., 1995; Pierce et al., 1996; Murakami et al., 1998; Ciallella et al., 2002; Itoh et al., 2009).”
BackgroundInfluentialNovel Model of Frontal Impact Closed Head Injury in the Rat
Kilbourne, M., Kuehn, R. B., Tosun, Ç., Caridi, J., Keledjian, K., Bochicchio, G., Scalea, T., Gerzanich, V., & Simard, J. M. (2009) · Journal of Neurotrauma · doi:10.1089/neu.2009.0968 · Cited by 107
“Diffuse axonal injury (DAI) is characterized by the accumulation of b-APP in injured axons in a pattern that resembles a string of beads (Blumbergs et al., 1995; Bramlett et al., 1997; Pierce et al., 1996; Stone et al., 2000).”
Mechanisms of amyloid plaque pathogenesis
Fiala, J. C. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0284-8 · Cited by 99
Washington, P. M., Morffy, N., Parsadanian, M., Zapple, D. N., & Burns, M. P. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2013.3017 · Cited by 103
Rodriguez-Paez, A. C., Brunschwig, J. P., & Bramlett, H. M. (2005) · Acta Neuropathologica · doi:10.1007/s00401-005-1010-z · Cited by 94
“b-Amyloid precursor protein (bAPP), an effective marker for axonal damage [10, 31, 34, 44, 69, 76], is transported by fast axoplasmic flow and accumulates following cytoskeletal disruption [58].”
Sanderson, K. L., Raghupathi, R., Saatman, K. E., Martin, D., Miller, G., & McIntosh, T. K. (1999) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199910000-00008 · Cited by 98
Self-citationThe Neuroprotective Properties of the Amyloid Precursor Protein Following Traumatic Brain Injury
Plummer, S. L., van den Heuvel, C., Thornton, E., Corrigan, F., & Cappai, R. (2016) · Aging and Disease · doi:10.14336/ad.2015.0907 · Cited by 103
“The amyloid precursor protein (APP) has a long association with TBI as its expression is dramatically upregulated in the brain following injury [3-6].”
BackgroundResultInfluentialGenetic vulnerability following traumatic brain injury: the role of apolipoprotein E
Nathoo, N. (2003) · Molecular Pathology · doi:10.1136/mp.56.3.132 · Cited by 96
Apoptotic and behavioral sequelae of mild brain trauma in mice
Tweedie, D., Milman, A., Holloway, H., Li, Y.-Z., Harvey, B., Shen, H., Pistell, P., Lahiri, D., Hoffer, B., Wang, Y., et al. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21160 · Cited by 96
Stone, J., Walker, S. A., & Povlishock, J. (1999) · Acta Neuropathologica · doi:10.1007/s004010050996 · Cited by 95
Ciallella, J. R., Ikonomovic, M. D., Paljug, W. R., Wilbur, Y. I., Dixon, C. E., Kochanek, P. M., Marion, D. W., & DeKosky, S. T. (2002) · Journal of Neurotrauma · doi:10.1089/089771502762300229 · Cited by 94
“However, A b deposits were not detected at any time post-injury in any brain region examined, consistent with studies using fluid-per-cussion (Pierce et al., 1996; Masumura et al., 2000) or weight-drop (Lewen et al., 1996) models of brain Because we found no A b deposits in brain regions analyzed…”
InfluentialBehavioral consequences of minimal traumatic brain injury in mice.
Zohar, O., Rubovitch, V., Milman, A., Schreiber, S., & Pick, C. G. (2011) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-2011-1821 · Cited by 93
“Studies utilizing various experimental models of TBI indicate that the primary brain damage triggers cellular pathologies, which in turn lead to long-lasting secondary neuronal and glial damage (Pierce et al. 1996, 1998, Berger et al. 1999, Graham et al. 2000, Albensi 2001).”
MethodMorrison, B., Eberwine, J., Meaney, D., & McIntosh, T. (2000) · Neuroscience · doi:10.1016/s0306-4522(99)00537-0 · Cited by 92
Self-citationBrain Trauma in Aged Transgenic Mice Induces Regression of Established Aβ Deposits
Nakagawa, Y., Reed, L., Nakamura, M., McIntosh, T. K., Smith, D. H., Saatman, K. E., Raghupathi, R., Clemens, J., Saido, T. C., Lee, V. M.-Y., et al. (2000) · Experimental Neurology · doi:10.1006/exnr.2000.7375 · Cited by 91
Self-citationAbrahamson, E. E., Ikonomovic, M. D., Ciallella, J. R., Hope, C. E., Paljug, W. R., Isanski, B. A., Flood, D. G., Clark, R. S. B., & DeKosky, S. T. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2005.10.011 · Cited by 90
APP as a Protective Factor in Acute Neuronal Insults
Hefter, D., & Draguhn, A. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00022 · Cited by 97
“…fluid percussion model of diffuse brain injury in adult rats APP expression was globally elevated in cortex and hippocampus within hours following the insult (Murakami et al., 1998); in a lateral fluid percussion model APP was overexpressed as early as 1 h after the insult (Pierce et al., 1996).”
BackgroundAnimal models of traumatic brain injury
Johnson, V. E., Meaney, D. F., Cullen, D. K., & Smith, D. H. (2015) · Handbook of clinical neurology · doi:10.1016/b978-0-444-52892-6.00008-8 · Cited by 151
“Similarly, neuronal loss and axonal pathology has been observed in regions distant to the contusion site (Dixon et al., 1991; Pierce et al., 1996).”
BackgroundSelf-citationVink, R., Mullins, P. G., Temple, M. D., Bao, W.-L., & Faden, A. (2001) · Journal of Neurotrauma · doi:10.1089/089771501316919201 · Cited by 87
“This observation of bilateral damage was supported in a later publication reporting that significant accumulations of amyloid precursor proteins occur in the ipsilateral hemisphere with changes some-times observed in the contralateral hemisphere as well (Pierce et al., 1996).”
Delayed Phospholipid Degradation in Rat Brain After Traumatic Brain Injury
Homayoun, P., de Turco, E., Parkins, N. E., Lane, D. C., Soblosky, J., Carey, M. E., & Bazan, N. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69010199.x · Cited by 85
Povlishock, J., Buki, A., Koiziumi, H., Stone, J., & Okonkwo, D. (1999) · Acta neurochirurgica. Supplement · doi:10.1007/978-3-7091-6391-7_3 · Cited by 84
Extracellular association of APP and tau fibrils induces intracellular aggregate formation of tau
Takahashi, M., Miyata, H., Kametani, F., Nonaka, T., Akiyama, H., Hisanaga, S., & Hasegawa, M. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1415-2 · Cited by 101
“It is not yet clear whether or not there is any increase in the expression levels of APP in brains of patients with sporadic AD, but it has been reported that the APP expression is increased in brains of post-traumatic injury patients [13, 47, 48] and animal models [21, 30, 43, 45, 59].”
BackgroundSchouten, J. W., Fulp, C. T., Royo, N. C., Saatman, K. E., Watson, D. J., Snyder, E. Y., Trojanowski, J. Q., Prockop, D. J., Maas, A. I. R., & McIntosh, T. K. (2004) · Journal of Neurotrauma · doi:10.1089/neu.2004.21.1501 · Cited by 74
“Secondary or delayed axotomy has been shown as early as 2–3 h after injury in clinical (McKenzie et al., 1996) and experimental (Pierce et al., 1996; Bramlett and Dietrich, 2002) TBI using amyloid precursor protein (APP) accumulation as a measure of axonal transport dysfunction.”
Self-citationBidmon, H.-J., Kato, K., Schleicher, A., Witte, O. W., & Zilles, K. (1998) · Stroke · doi:10.1161/01.str.29.1.203 · Cited by 82
Injury cascades in TBI-related neurodegeneration
DeKosky, S. T., & Asken, B. M. (2017) · Brain Injury · doi:10.1080/02699052.2017.1312528 · Cited by 96
OLIGODENDROCYTE VULNERABILITY FOLLOWING TRAUMATIC BRAIN INJURY IN RATS
Lotocki, G., Vaccari, J. P. D. R., Alonso, O., Molano, J. S., Nixon, R., Safavi, P., Dietrich, W., & Bramlett, H. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.05.056 · Cited by 79
Association of Chronic Vascular Changes with Functional Outcome after Traumatic Brain Injury in Rats
Hayward, N., Immonen, R. J., Tuunanen, P. I., Ndode‐Ekane, X. E., Gröhn, O. H. J., & Pitkänen, A. (2010) · Journal of Neurotrauma · doi:10.1089/neu.2010.1448 · Cited by 80
“…that axonal injury in the thalamus after LFP injury is associated with chronic APP accumulation, which can lead to enhanced amyloid beta levels in the absence of plaques, as well as expression of enzymes processing APP (Bramlett et al., 1997; Johnson et al., 2010; Pierce, Trojanowski, et al. 1996).”
Alsop, D., Murai, H., Detre, J., McIntosh, T. K., & Smith, D. H. (1996) · Journal of Neurotrauma · doi:10.1089/neu.1996.13.515 · Cited by 79
“Since the understanding of diffusion is in such a primitive state, it is premature to assert that diffusion changes directly reflect axonal or dendritic damage but the close correlation between the distribution of acute diffusion change and the distribution of early axonal and dendritic damage as measured with /3APP a…”
InfluentialSelf-citationGensel, J. C., Wang, Y., Guan, Z., Beckwith, K. A., Braun, K. J., Wei, P. Y., McTigue, D. M., & Popovich, P. G. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0337-15.2015 · Cited by 78
“-APP is a sensitive measure of axon injury (Pierce et al., 1996).”
BackgroundBidmon, H.-J., Jancsik, V, Schleicher, A., Hagemann, G., Witte, O. W., Woodhams, P., & Zilles, K. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00289-3 · Cited by 74
Raghupathi, R., & McIntosh, T. K. (1996) · Molecular Brain Research · doi:10.1016/0169-328x(95)00289-5 · Cited by 72
Self-citationBaker, A. J., Phan, N., Moulton, R. J., Fehlings, M. G., Yücel, Y., Zhao, M., Liu, E., & Tian, G.-F. (2002) · Journal of Neurotrauma · doi:10.1089/089771502753754064 · Cited by 73
“Advantages include the availability of immunohistochemical techniques (Stone et al., 2000; Pierce et al., 1996) and the rapid appearance of increased staining following injury (McKenzie et al., 1996; Graham et al., 1995).”
McDermott, K. L., Raghupathi, R., Fernandez, S. C., Saatman, K. E., Protter, A. A., Finklestein, S. P., Sinson, G. P., Smith, D. H., & McIntosh, T. K. (1997) · Journal of Neurotrauma · doi:10.1089/neu.1997.14.191 · Cited by 73
“Although we did not quantitatively assess the cell loss in the thalamus, previous studies have reported both acute and delayed degeneration of thalamic neurons following FP brain injury (Hicks et al., 1996; Pierce et al., 1996).”
Self-citationEkmark‐Lewén, S., Flygt, J., Kiwanuka, O., Meyerson, B. J., Lewén, A., Hillered, L., & Marklund, N. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-44 · Cited by 67
“Increased β-APP immunostaining in white matter tracts is a consistent feature of experimental TBI models including the Marmarou impact acceleration and lateral fluid percussion injury (lFPI) models in rats [53-55].”
BackgroundSchultz, V., van der Meer, F., Wrzos, C., Scheidt, U., Bahn, E., Stadelmann, C., Brück, W., & Junker, A. (2017) · Glia · doi:10.1002/glia.23167 · Cited by 75
Harkany, T., Dijkstra, I. M., Oosterink, B. J., Horvath, K. M., Ábrahám, I. M., Keijser, J. N., van der Zee, E. A., & Luiten, P. G. M. (2000) · Neuroscience · doi:10.1016/s0306-4522(00)00296-7 · Cited by 55
Elder, G. A., Ehrlich, M. E., & Gandy, S. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134294 · Cited by 76
Amyloid precursor protein potentiates the neurotrophic activity of NGF.
Wallace, W. C., Akar, C. A., & Lyons, W. E. (1997) · Brain Research. Molecular Brain Research · doi:10.1016/s0169-328x(97)00258-1 · Cited by 66
Lenzlinger, P. M., Shimizu, S., Marklund, N., Thompson, H. J., Schwab, M., Saatman, K., Hoover, R., Bareyre, F., Motta, M., Luginbuhl, A., et al. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.04.048 · Cited by 65
Self-citationHamberger, A., Huang, Y.-L., Zhu, H., Bao, F., Ding, M., Blennow, K., Olsson, A., Hansson, H.-A., Viano, D., & Haglid, K. G. (2003) · Journal of Neurotrauma · doi:10.1089/08977150360547080 · Cited by 64
“It has been suggested that species differences in the processing of b APP and A b , and the characteristics of the antibodies used, are responsible for such discrepancies (Pierce et al., 1996; Smith et al., 1999).”
In Vivo Regulation of Amyloid Precursor Protein Secretion in Rat Neocortex by Cholinergic Activity
Roßner, S., Ueberham, U., Yu, J., Kirazov, L., Schliebs, R., Perez-Polo, J. R., & Bigl, V. (1997) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1997.tb01379.x · Cited by 61
Decourt, B., D’Souza, G. X., Shi, J., Ritter, A., Suazo, J., & Sabbagh, M. N. (2022) · Aging and disease · doi:10.14336/ad.2021.0529 · Cited by 69
“Interestingly, astrocytes and microglia can also produce high amounts of Aβ during CNS insults [25].”
BackgroundSaatman, K., Zhang, C., Bartus, R., & Mcintosh, T. K. (2000) · Journal of Cerebral Blood Flow and Metabolism · doi:10.1097/00004647-200001000-00010 · Cited by 62
Self-citationHiltunen, M. O., van Groen, T., & Jolkkonen, J. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1154 · Cited by 62
“Brain insults, such as stroke and trauma, lead to a variable upregulation and accumulation of A β PP/ A β [2,3].”
Influential
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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