Alzheimer's pathology in human temporal cortex surgically excised after severe brain injury

Ikonomović, Miloš D.; Uryu, Kunihiro; Abrahamson, Eric E.; Ciallella, John R.; Trojanowski, John Q.; Lee, Virginia M.‐Y.; Clark, Robert S. B.; Marion, Donald W.; Wisniewski, Stephen R.; DeKosky, Steven T.

doi:10.1016/j.expneurol.2004.06.011

Cited by 366 publications

(318 citation statements)

References 69 publications

Supporting

Mentioning

288

Contrasting

Unclassified

Order By: Relevance

“…20 Ab accumulates very quickly after TBI because Ab deposits can be identified within as little as 2 h post-injury in the human brain. 13,15 Further, this accumulation of Ab also occurs in animal models of TBI, 12,17 including mouse CCI. 12,14,22. In the present study, we again report that CCI causes a significant and rapid accumulation of soluble Ab 40 species.…”

Section: Discussionmentioning

confidence: 99%

“…The rapid accumulation of Ab after TBI is well documented in both humans and experimental animal models. [12][13][14][15][16][17] Excess Ab is detrimental to dendritic spine health both in vivo 18 and in vitro 19 and, similar to spine loss after TBI, Ab-induced dendritic spine loss can be prevented with the calcineurin inhibitor FK506. 20 These data suggest that spine retraction after Ab and TBI may have a common mechanism of action through calcineurin activation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Controlled Cortical Impact Results in an Extensive Loss of Dendritic Spines that Is Not Mediated by Injury-Induced Amyloid-Beta Accumulation

Winston

Chellappa

Wilkins

et al. 2013

Journal of Neurotrauma

View full text Add to dashboard Cite

The clinical manifestations that occur after traumatic brain injury (TBI) include a wide range of cognitive, emotional, and behavioral deficits. The loss of excitatory synapses could potentially explain why such diverse symptoms occur after TBI, and a recent preclinical study has demonstrated a loss of dendritic spines, the postsynaptic site of the excitatory synapse, after fluid percussion injury. The objective of this study was to determine if controlled cortical impact (CCI) also resulted in dendritic spine retraction and to probe the underlying mechanisms of this spine loss. We used a unilateral CCI and visualized neurons and dendtritic spines at 24 h post-injury using Golgi stain. We found that TBI caused a 32% reduction of dendritic spines in layer II/III of the ipsilateral cortex and a 20% reduction in the dendritic spines of the ipsilateral dentate gyrus. Spine loss was not restricted to the ipsilateral hemisphere, however, with similar reductions in spine numbers recorded in the contralateral cortex (25% reduction) and hippocampus (23% reduction). Amyloid-b (Ab), a neurotoxic peptide commonly associated with Alzheimer disease, accumulates rapidly after TBI and is also known to cause synaptic loss. To determine if Ab contributes to spine loss after brain injury, we administered a c-secretase inhibitor LY450139 after TBI. We found that while LY450139 administration could attenuate the TBI-induced increase in Ab, it had no effect on dendritic spine loss after TBI. We conclude that the acute, global loss of dendritic spines after TBI is independent of c-secretase activity or TBI-induced Ab accumulation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Controlled Cortical Impact Results in an Extensive Loss of Dendritic Spines that Is Not Mediated by Injury-Induced Amyloid-Beta Accumulation

Winston

Chellappa

Wilkins

et al. 2013

Journal of Neurotrauma

View full text Add to dashboard Cite

show abstract

“…Samples were kept frozen and stored at -80°C for Western blot analysis and/ or fixed in 4% paraformaldehyde for immunohistochemistry as described in previous studies. [21][22][23][24][25] Postmortem control samples of frontal cortex tissue from subjects without neurodegenerative disease were processed in a like manner.…”

Section: Subjectsmentioning

confidence: 99%

Expression of ATP-Binding Cassette Transporters B1 and C1 after Severe Traumatic Brain Injury in Humans

Willyerd

Empey

Philbrick

et al. 2016

Journal of Neurotrauma

Self Cite

View full text Add to dashboard Cite

Adenosine triphosphate-binding cassette (ABC) transport proteins ABCC1 and ABCB1 (also known as multidrug resistance-associated protein 1 and p-glycoprotein, respectively), are key membrane efflux transporters of drugs and endogenous substrates, including in the brain. The impact of traumatic brain injury (TBI) on ABCC1 and ABCB1 expression in humans is unknown. We hypothesized that ABCC1 and ABCB1 expression would be altered in brain tissue from patients acutely after severe TBI. Archived TBI samples (n = 10) from our Brain Trauma Research Center and control samples (n = 7) from our Alzheimer Disease Research Center were obtained under Institutional Review Board approval. Protein was extracted from fresh frozen cortical brain tissue for Western blot analysis and sections were obtained from fixed cortical tissue for immunohistochemistry. Relative abundance of ABCC1 was increased in samples from TBI versus controls (2.8 -2.5 fold; p = 0.005). ABCC1 immunohistochemistry was consistent with Western blot data, with increased immunoreactivity in cerebral blood vessel walls, as well as cells with the morphological appearance of neurons and glia in TBI versus controls. Relative abundance of ABCB1 was similar between TBI and controls ( p = 0.76), and ABCB1 immunoreactivity was primarily associated with cerebral blood vessels in both groups. These human data show that TBI increases ABCC1 expression in the brain, consistent with possible implications for both patients receiving pharmacological inhibitors and/or substrates of ABCC1 after TBI.

show abstract

“…Both of these conditions in humans have been associated with delayed events including an increased risk of developing dementia (Burri et al, 2013;Ikonomovic et al, 2004;Vincent et al, 2014), and this is supported by data derived from animal studies (Uryu et al, 2002;Tran et al, 2011). The animal studies also suggest that anti-inflammatory and antioxidant compounds such as simvastatin, or the flavonoid, luteolin can blunt the effects of TBI (Abrahamson et al, 2009;Sawmiller et al, 2014).…”

Section: Oxidative Stress In Penetrating Tbimentioning

confidence: 82%

Common biochemical defects linkage between post-traumatic stress disorders, mild traumatic brain injury (TBI) and penetrating TBI

Prasad¹,

Bondy

2015

Brain Research

View full text Add to dashboard Cite

AnxietyPsychological damage a b s t r a c t Post-traumatic stress disorder (PTSD) is a complex mental disorder with psychological and emotional components, caused by exposure to single or repeated extreme traumatic events found in war, terrorist attacks, natural or man-caused disasters, and by violent personal assaults and accidents. Mild traumatic brain injury (TBI) occurs when the brain is violently rocked back and forth within the skull following a blow to the head or neck as in contact sports, or when in close proximity to a blast pressure wave following detonation of explosives in the battlefield. Penetrating TBI occurs when an object penetrates the skull and damages the brain, and is caused by vehicle crashes, gunshot wound to the head, and exposure to solid fragments in the proximity of explosions, and other combat-related head injuries. Despite clinical studies and improved understanding of the mechanisms of cellular damage, prevention and treatment strategies for patients with PTSD and TBI remain unsatisfactory. To develop an improved plan for treating and impeding progression of PTSD and TBI, it is important to identify underlying biochemical changes that may play key role in the initiation and progression of these disorders. This review identifies three common biochemical events, namely oxidative stress, chronic inflammation and excitotoxicity that participate in the initiation and progression of these conditions. While these features are separately discussed, in many instances, they overlap. This review also addresses the goal of developing novel treatments and drug regimens, aimed at combating this triad of events common to, and underlying, injury to the brain.

show abstract

Alzheimer's pathology in human temporal cortex surgically excised after severe brain injury

Cited by 366 publications

References 69 publications

Controlled Cortical Impact Results in an Extensive Loss of Dendritic Spines that Is Not Mediated by Injury-Induced Amyloid-Beta Accumulation

Controlled Cortical Impact Results in an Extensive Loss of Dendritic Spines that Is Not Mediated by Injury-Induced Amyloid-Beta Accumulation

Expression of ATP-Binding Cassette Transporters B1 and C1 after Severe Traumatic Brain Injury in Humans

Common biochemical defects linkage between post-traumatic stress disorders, mild traumatic brain injury (TBI) and penetrating TBI

Contact Info

Product

Resources

About