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  1. Article ; Online: Repetitive head trauma, chronic traumatic encephalopathy and tau: Challenges in translating from mice to men.

    Ojo, Joseph O / Mouzon, Benoit C / Crawford, Fiona

    Experimental neurology

    2016  Volume 275 Pt 3, Page(s) 389–404

    Abstract: Chronic traumatic encephalopathy (CTE) is a neurological and psychiatric condition marked by preferential perivascular foci of neurofibrillary and glial tangles (composed of hyperphosphorylated-tau proteins) in the depths of the sulci. Recent ... ...

    Abstract Chronic traumatic encephalopathy (CTE) is a neurological and psychiatric condition marked by preferential perivascular foci of neurofibrillary and glial tangles (composed of hyperphosphorylated-tau proteins) in the depths of the sulci. Recent retrospective case series published over the last decade on athletes and military personnel have added considerably to our clinical and histopathological knowledge of CTE. This has marked a vital turning point in the traumatic brain injury (TBI) field, raising public awareness of the potential long-term effects of mild and moderate repetitive TBI, which has been recognized as one of the major risk factors associated with CTE. Although these human studies have been informative, their retrospective design carries certain inherent limitations that should be cautiously interpreted. In particular, the current overriding issue in the CTE literature remains confusing in regard to appropriate definitions of terminology, variability in individual pathologies and the potential case selection bias in autopsy based studies. There are currently no epidemiological or prospective studies on CTE. Controlled preclinical studies in animals therefore provide an alternative means for specifically interrogating aspects of CTE pathogenesis. In this article, we review the current literature and discuss difficulties and challenges of developing in-vivo TBI experimental paradigms to explore the link between repetitive head trauma and tau-dependent changes. We provide our current opinion list of recommended features to consider for successfully modeling CTE in animals to better understand the pathobiology and develop therapeutics and diagnostics, and critical factors, which might influence outcome. We finally discuss the possible directions of future experimental research in the repetitive TBI/CTE field.
    MeSH term(s) Animals ; Brain Injury, Chronic/etiology ; Brain Injury, Chronic/metabolism ; Brain Injury, Chronic/pathology ; Craniocerebral Trauma/complications ; Craniocerebral Trauma/metabolism ; Craniocerebral Trauma/pathology ; Disease Models, Animal ; Humans ; Mice ; Translational Medical Research/methods ; Translational Medical Research/trends ; tau Proteins/metabolism
    Chemical Substances tau Proteins
    Language English
    Publishing date 2016-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 207148-4
    ISSN 1090-2430 ; 0014-4886
    ISSN (online) 1090-2430
    ISSN 0014-4886
    DOI 10.1016/j.expneurol.2015.06.003
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  2. Article: Human amnionic progenitor cell secretome mitigates the consequence of traumatic optic neuropathy in a mouse model.

    McCartan, Robyn / Gratkowski, Arissa / Browning, Mackenzie / Hahn-Townsend, Coral / Ferguson, Scott / Morin, Alexander / Bachmeier, Corbin / Pearson, Andrew / Brown, Larry / Mullan, Michael / Crawford, Fiona / Tzekov, Radouil / Mouzon, Benoit

    Molecular therapy. Methods & clinical development

    2023  Volume 29, Page(s) 303–318

    Abstract: Traumatic optic neuropathy (TON) is a condition in which acute injury to the optic nerve from direct or indirect trauma results in vision loss. The most common cause of TON is indirect injury to the optic nerve caused by concussive forces that are ... ...

    Abstract Traumatic optic neuropathy (TON) is a condition in which acute injury to the optic nerve from direct or indirect trauma results in vision loss. The most common cause of TON is indirect injury to the optic nerve caused by concussive forces that are transmitted to the optic nerve. TON occurs in up to 5% of closed-head trauma patients and there is currently no known effective treatment. One potential treatment option for TON is ST266, a cell-free biological solution containing the secretome of amnion-derived multipotent progenitor (AMP) cells. We investigated the efficacy of intranasal ST266 in a mouse model of TON induced by blunt head trauma. Injured mice treated with a 10-day regimen of ST266 showed an improvement in spatial memory and learning, a significant preservation of retinal ganglion cells, and a decrease in neuropathological markers in the optic nerve, optic tract, and dorsal lateral geniculate nucleus. ST266 treatment effectively downregulated the NLRP3 inflammasome-mediated neuroinflammation pathway after blunt trauma. Overall, treatment with ST266 was shown to improve functional and pathological outcomes in a mouse model of TON, warranting future exploration of ST266 as a cell-free therapeutic candidate for testing in all optic neuropathies.
    Language English
    Publishing date 2023-04-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2872938-9
    ISSN 2329-0501 ; 2329-0501
    ISSN (online) 2329-0501
    ISSN 2329-0501
    DOI 10.1016/j.omtm.2023.04.002
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  3. Article ; Online: Influence of traumatic brain injury on extracellular tau elimination at the blood-brain barrier.

    Eisenbaum, Maxwell / Pearson, Andrew / Gratkowski, Arissa / Mouzon, Benoit / Mullan, Michael / Crawford, Fiona / Ojo, Joseph / Bachmeier, Corbin

    Fluids and barriers of the CNS

    2021  Volume 18, Issue 1, Page(s) 48

    Abstract: Repetitive head trauma has been associated with the accumulation of tau species in the brain. Our prior work showed brain vascular mural cells contribute to tau processing in the brain, and that these cells progressively degenerate following repetitive ... ...

    Abstract Repetitive head trauma has been associated with the accumulation of tau species in the brain. Our prior work showed brain vascular mural cells contribute to tau processing in the brain, and that these cells progressively degenerate following repetitive mild traumatic brain injury (r-mTBI). The current studies investigated the role of the cerebrovasculature in the elimination of extracellular tau from the brain, and the influence of r-mTBI on these processes. Following intracranial injection of biotin-labeled tau, the levels of exogenous labeled tau residing in the brain were elevated in a mouse model of r-mTBI at 12 months post-injury compared to r-sham mice, indicating reduced tau elimination from the brain following head trauma. This may be the result of decreased caveolin-1 mediated tau efflux at the blood-brain barrier (BBB), as the caveolin inhibitor, methyl-β-cyclodextrin, significantly reduced tau uptake in isolated cerebrovessels and significantly decreased the basolateral-to-apical transit of tau across an in vitro model of the BBB. Moreover, we found that the upstream regulator of endothelial caveolin-1, Mfsd2a, was elevated in r-mTBI cerebrovessels compared to r-sham, which coincided with a decreased expression of cerebrovascular caveolin-1 in the chronic phase following r-mTBI (> 3 months post-injury). Lastly, angiopoietin-1, a mural cell-derived protein governing endothelial Mfsd2a expression, was secreted from r-mTBI cerebrovessels to a greater extent than r-sham animals. Altogether, in the chronic phase post-injury, release of angiopoietin-1 from degenerating mural cells downregulates caveolin-1 expression in brain endothelia, resulting in decreased tau elimination across the BBB, which may describe the accumulation of tau species in the brain following head trauma.
    MeSH term(s) Animals ; Blood-Brain Barrier/metabolism ; Brain Injuries, Traumatic/metabolism ; Disease Models, Animal ; Female ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; tau Proteins/metabolism
    Chemical Substances tau Proteins
    Language English
    Publishing date 2021-10-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 2595406-4
    ISSN 2045-8118 ; 2045-8118
    ISSN (online) 2045-8118
    ISSN 2045-8118
    DOI 10.1186/s12987-021-00283-y
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  4. Article ; Online: Impact of gulf war toxic exposures after mild traumatic brain injury.

    Ferguson, Scott / McCartan, Robyn / Browning, Mackenzie / Hahn-Townsend, Coral / Gratkowski, Arissa / Morin, Alexander / Abdullah, Laila / Ait-Ghezala, Ghania / Ojo, Joseph / Sullivan, Kimberly / Mullan, Michael / Crawford, Fiona / Mouzon, Benoit

    Acta neuropathologica communications

    2022  Volume 10, Issue 1, Page(s) 147

    Abstract: Chemical and pharmaceutical exposures have been associated with the development of Gulf War Illness (GWI), but how these factors interact with the pathophysiology of traumatic brain injury (TBI) remains an area of study that has received little attention ...

    Abstract Chemical and pharmaceutical exposures have been associated with the development of Gulf War Illness (GWI), but how these factors interact with the pathophysiology of traumatic brain injury (TBI) remains an area of study that has received little attention thus far. We studied the effects of pyridostigmine bromide (an anti-nerve agent) and permethrin (a pesticide) exposure in a mouse model of repetitive mild TBI (r-mTBI), with 5 impacts over a 9-day period, followed by Gulf War (GW) toxicant exposure for 10 days beginning 30 days after the last head injury. We then assessed the chronic behavioral and pathological sequelae 5 months after GW agent exposure. We observed that r-mTBI and GWI cumulatively affect the spatial memory of mice in the Barnes maze and result in a shift of search strategies employed by r-mTBI/GW exposed mice. GW exposure also produced anxiety-like behavior in sham animals, but r-mTBI produced disinhibition in both the vehicle and GW treated mice. Pathologically, GW exposure worsened r-mTBI dependent axonal degeneration and neuroinflammation, increased oligodendrocyte cell counts, and increased r-mTBI dependent phosphorylated tau, which was found to colocalize with oligodendrocytes in the corpus callosum. These results suggest that GW exposures may worsen TBI-related deficits. Veterans with a history of both GW chemical exposures as well as TBI may be at higher risk for worse symptoms and outcomes. Subsequent exposure to various toxic substances can influence the chronic nature of mTBI and should be considered as an etiological factor influencing mTBI recovery.
    MeSH term(s) Mice ; Animals ; Gulf War ; Brain Concussion/complications ; Pyridostigmine Bromide/toxicity ; Permethrin/toxicity ; Disease Models, Animal ; Brain Injuries, Traumatic ; Pesticides ; Pharmaceutical Preparations
    Chemical Substances Pyridostigmine Bromide (KVI301NA53) ; Permethrin (509F88P9SZ) ; Pesticides ; Pharmaceutical Preparations
    Language English
    Publishing date 2022-10-18
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2715589-4
    ISSN 2051-5960 ; 2051-5960
    ISSN (online) 2051-5960
    ISSN 2051-5960
    DOI 10.1186/s40478-022-01449-x
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  5. Article: Chronic Hippocampal Abnormalities and Blunted HPA Axis in an Animal Model of Repeated Unpredictable Stress.

    Algamal, Moustafa / Ojo, Joseph O / Lungmus, Carlyn P / Muza, Phillip / Cammarata, Constance / Owens, Margaret J / Mouzon, Benoit C / Diamond, David M / Mullan, Michael / Crawford, Fiona

    Frontiers in behavioral neuroscience

    2018  Volume 12, Page(s) 150

    Abstract: Incidence of post-traumatic stress disorder (PTSD) ranges from 3 to 30% in individuals exposed to traumatic events, with the highest prevalence in groups exposed to combat, torture, or rape. To date, only a few FDA approved drugs are available to treat ... ...

    Abstract Incidence of post-traumatic stress disorder (PTSD) ranges from 3 to 30% in individuals exposed to traumatic events, with the highest prevalence in groups exposed to combat, torture, or rape. To date, only a few FDA approved drugs are available to treat PTSD, which only offer symptomatic relief and variable efficacy. There is, therefore, an urgent need to explore new concepts regarding the biological responses causing PTSD. Animal models are an appropriate platform for conducting such studies. Herein, we examined the chronic behavioral and neurobiological effects of repeated unpredictable stress (RUS) in a mouse model. 12 weeks-old C57BL/6J male mice were exposed to a 21-day RUS paradigm consisting of exposures to a predator odor (TMT) whilst under restraint, unstable social housing, inescapable footshocks and social isolation. Validity of the model was assessed by comprehensive examination of behavioral outcomes at an acute timepoint, 3 and 6 months post-RUS; and molecular profiling was also conducted on brain and plasma samples at the acute and 6 months timepoints. Stressed mice demonstrated recall of traumatic memories, passive stress coping behavior, acute anxiety, and weight gain deficits when compared to control mice. Immunoblotting of amygdala lysates showed a dysregulation in the p75NTR/ProBDNF, and glutamatergic signaling in stressed mice at the acute timepoint. At 6 months after RUS, stressed mice had lower plasma corticosterone, reduced hippocampal CA1 volume and reduced brain-derived neurotrophic factor levels. In addition, glucocorticoid regulatory protein FKBP5 was downregulated in the hypothalamus of stressed mice at the same timepoint, together implicating an impaired hypothalamus-pituitary-adrenal-axis. Our model demonstrates chronic behavioral and neurobiological outcomes consistent with those reported in human PTSD cases and thus presents a platform through which to understand the neurobiology of stress and explore new therapeutic interventions.
    Language English
    Publishing date 2018-07-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452960-6
    ISSN 1662-5153
    ISSN 1662-5153
    DOI 10.3389/fnbeh.2018.00150
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  6. Article ; Online: Ultrastructural Changes in the White and Gray Matter of Mice at Chronic Time Points After Repeated Concussive Head Injury.

    Ojo, Joseph O / Bachmeier, Corbin / Mouzon, Benoit C / Tzekov, Radouil / Mullan, Michael / Davies, Heather / Stewart, Michael G / Crawford, Fiona

    Journal of neuropathology and experimental neurology

    2015  Volume 74, Issue 10, Page(s) 1012–1035

    Abstract: Mild traumatic brain injury is a risk factor for neurodegenerative disease. We recently developed a model of repetitive concussive injury in mice that we have extensively characterized from 24 hours to 24 months after injury. Animals show evidence of ... ...

    Abstract Mild traumatic brain injury is a risk factor for neurodegenerative disease. We recently developed a model of repetitive concussive injury in mice that we have extensively characterized from 24 hours to 24 months after injury. Animals show evidence of progressive spatial memory deficits, thinning of the corpus callosum, axonal injury, and neuroglial activation. Here, we extended our neuropathologic characterization to the ultrastructural level in both a qualitative and a quantitative study. We focused on chronic (3 and 6 months) postinjury time points when the earliest stages of degenerative secondary changes were previously observed. In both C57BL/6 and hTau mice, we found white matter damage typified by axonal degeneration, microglial phagocytosis, and increased neuroglial cell density. In the cerebral cortex, we observed evidence of synaptic degeneration, dark neurons, altered dendritic microfilaments, subtle changes to the microvasculature, a mild augmentation of age-related features such as lipofuscin deposition, and electron-dense inclusions in microglial and perivascular cells. The majority of these ultrastructural features seemed to be more prominent at 3 versus 6 months after injury. Similar patterns were observed in C57BL/6 and hTau mice. These findings further support the relevance of our concussive injury model to the consequences of repetitive mild traumatic brain injury in humans.
    MeSH term(s) Animals ; Brain Injuries/pathology ; Disease Models, Animal ; Gray Matter/ultrastructure ; Mice ; Mice, Inbred C57BL ; Microscopy, Electron, Transmission ; White Matter/ultrastructure
    Language English
    Publishing date 2015-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3088-0
    ISSN 1554-6578 ; 0022-3069
    ISSN (online) 1554-6578
    ISSN 0022-3069
    DOI 10.1097/NEN.0000000000000247
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  7. Article: Negative Impact of Female Sex on Outcomes from Repetitive Mild Traumatic Brain Injury in hTau Mice Is Age Dependent: A Chronic Effects of Neurotrauma Consortium Study.

    Ferguson, Scott A / Mouzon, Benoit C / Lynch, Cillian / Lungmus, Carlyn / Morin, Alexander / Crynen, Gogce / Carper, Benjamin / Bieler, Gayle / Mufson, Elliott J / Stewart, William / Mullan, Michael / Crawford, Fiona

    Frontiers in aging neuroscience

    2017  Volume 9, Page(s) 416

    Abstract: Traumatic brain injury (TBI) is a serious public health concern which strikes someone every 15 s on average in the US. Even mild TBI, which comprise as many as 75% of all TBI cases, carries long term consequences. The effects of age and sex on long term ... ...

    Abstract Traumatic brain injury (TBI) is a serious public health concern which strikes someone every 15 s on average in the US. Even mild TBI, which comprise as many as 75% of all TBI cases, carries long term consequences. The effects of age and sex on long term outcome from TBI is not fully understood, but due to the increased risk for neurodegenerative diseases after TBI it is important to understand how these factors influence the outcome from TBI. This study examined the neurobehavioral and neuropathological effects of age and sex on the outcome 15 days following repetitive mild traumatic brain injury (r-mTBI) in mice transgenic for human tau (hTau). These mice express the six human isoforms of tau but do not express endogenous murine tau and they develop tau pathology and memory impairment in an age-dependent manner. After 5 mild impacts, aged female mice showed motor impairments that were absent in aged male mice, as well as younger animals. Conversely, aged female sham mice outperformed all other groups of aged mice in a Barnes maze spatial memory test. Pathologically, increases in IBA-1 and GFAP staining typically seen in this model of r-mTBI showed the expected increases with both injury and age, but phosphorylated tau stained with CP13 in the hippocampus (reduced in female sham mice compared to males) and PHF1 in the cortex (reduced in female TBI mice compared to male TBI mice) showed the only histological signs of sex-dependent differences in these mice.
    Language English
    Publishing date 2017-12-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2558898-9
    ISSN 1663-4365
    ISSN 1663-4365
    DOI 10.3389/fnagi.2017.00416
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  8. Article: Lifelong behavioral and neuropathological consequences of repetitive mild traumatic brain injury.

    Mouzon, Benoit C / Bachmeier, Corbin / Ojo, Joseph O / Acker, Christopher M / Ferguson, Scott / Paris, Daniel / Ait-Ghezala, Ghania / Crynen, Gogce / Davies, Peter / Mullan, Michael / Stewart, William / Crawford, Fiona

    Annals of clinical and translational neurology

    2017  Volume 5, Issue 1, Page(s) 64–80

    Abstract: Objective: Exposure to repetitive concussion, or mild traumatic brain injury (mTBI), has been linked with increased risk of long-term neurodegenerative changes, specifically chronic traumatic encephalopathy (CTE). To date, preclinical studies largely ... ...

    Abstract Objective: Exposure to repetitive concussion, or mild traumatic brain injury (mTBI), has been linked with increased risk of long-term neurodegenerative changes, specifically chronic traumatic encephalopathy (CTE). To date, preclinical studies largely have focused on the immediate aftermath of mTBI, with no literature on the lifelong consequences of mTBI in these models. This study provides the first account of lifelong neurobehavioral and histological consequences of repetitive mTBI providing unique insight into the constellation of evolving and ongoing pathologies with late survival.
    Methods: Male C57BL/6J mice (aged 2-3 months) were exposed to either single or repetitive mild TBI or sham procedure. Thereafter, animals were monitored and assessed at 24 months post last injury for measures of motor coordination, learning deficits, cognitive function, and anxiety-like behavior prior to euthanasia and preparation of the brains for detailed neuropathological and protein biochemical studies.
    Results: At 24 months survival animals exposed to r-mTBI showed clear evidence of learning and working memory impairment with a lack of spatial memory and vestibule-motor vestibulomotor deficits compared to sham animals. Associated with these late behavioral deficits there was evidence of ongoing axonal degeneration and neuroinflammation in subcortical white matter tracts. Notably, these changes were also observed after a single mTBI, albeit to a lesser degree than repetitive mTBI.
    Interpretation: In this context, our current data demonstrate, for the first time, that rather than an acute, time limited event, mild TBI can precipitate a lifelong degenerative process. These data therefore suggest that successful treatment strategies should consider both the acute and chronic nature of mTBI.
    Language English
    Publishing date 2017-12-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2740696-9
    ISSN 2328-9503
    ISSN 2328-9503
    DOI 10.1002/acn3.510
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  9. Article ; Online: Chronic White Matter Degeneration, but No Tau Pathology at One-Year Post-Repetitive Mild Traumatic Brain Injury in a Tau Transgenic Model.

    Mouzon, Benoit / Bachmeier, Corbin / Ojo, Joseph / Acker, Christopher / Ferguson, Scott / Crynen, Gogce / Davies, Peter / Mullan, Michael / Stewart, William / Crawford, Fiona

    Journal of neurotrauma

    2018  Volume 36, Issue 4, Page(s) 576–588

    Abstract: Tau pathology associated with chronic traumatic encephalopathy has been documented in the brains of individuals with a history of repetitive mild traumatic brain injury (r-mTBI). At this stage, the pathobiological role of tau in r-mTBI has not been ... ...

    Abstract Tau pathology associated with chronic traumatic encephalopathy has been documented in the brains of individuals with a history of repetitive mild traumatic brain injury (r-mTBI). At this stage, the pathobiological role of tau in r-mTBI has not been extensively explored in appropriate pre-clinical models. Here, we describe the acute and chronic behavioral and histopathological effects of single and repetitive mild TBI (five injuries given at 48 h intervals) in young adult (3 months old) hTau mice that express all six isoforms of hTau on a null murine tau background. Animals exposed to r-mTBI showed impaired visuospatial learning in the Barnes maze test that progressively worsened from two weeks to 12 months post-injury, which was also accompanied by significant deficits in visuospatial memory consolidation at 12 months post-injury. In contrast, only marginal changes were observed in visuospatial learning at six and 12 months after single mTBI. Histopathological analyses revealed that hTau mice developed axonal injury, thinning of the corpus callosum, microgliosis and astrogliosis in the white matter at acute and chronic time points after injury. Tau immunohistochemistry and enzyme-linked immunosorbent assay data suggest, however, only transient, injury-dependent increases in phosphorylated tau in the cerebral cortex beneath the impact site and in the CA1/CA3 subregion of the hippocampus after single or r-mTBI. This study implicates white matter degeneration as a prominent feature of survival from mTBI, while the role of tau pathology in the neuropathological sequelae of TBI remains elusive.
    MeSH term(s) Animals ; Chronic Traumatic Encephalopathy/pathology ; Disease Models, Animal ; Humans ; Male ; Maze Learning ; Mice ; Mice, Transgenic ; Nerve Degeneration/pathology ; White Matter/pathology ; tau Proteins/metabolism
    Chemical Substances MAPT protein, human ; tau Proteins
    Language English
    Publishing date 2018-09-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 645092-1
    ISSN 1557-9042 ; 0897-7151
    ISSN (online) 1557-9042
    ISSN 0897-7151
    DOI 10.1089/neu.2018.5720
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  10. Article ; Online: Subchronic Pathobiological Response Following Chronic Repetitive Mild Traumatic Brain Injury in an Aged Preclinical Model of Amyloid Pathogenesis.

    Ojo, Joseph O / Leary, Paige / Lungmus, Caryln / Algamal, Moustafa / Mouzon, Benoit / Bachmeier, Corbin / Mullan, Michael / Stewart, William / Crawford, Fiona

    Journal of neuropathology and experimental neurology

    2018  Volume 77, Issue 12, Page(s) 1144–1162

    Abstract: Repetitive mild traumatic brain injury (r-mTBI) is a risk factor for Alzheimer disease (AD). The precise nature of how r-mTBI leads to, or precipitates, AD pathogenesis remains unclear. In this study, we explore subchronic effects of chronic r-mTBI (12- ... ...

    Abstract Repetitive mild traumatic brain injury (r-mTBI) is a risk factor for Alzheimer disease (AD). The precise nature of how r-mTBI leads to, or precipitates, AD pathogenesis remains unclear. In this study, we explore subchronic effects of chronic r-mTBI (12-impacts) administered over 1-month in aged-PS1/APP mice and littermate controls. We investigate specific mechanisms that may elucidate the molecular link between AD and r-mTBI, focusing primarily on amyloid and tau pathology, amyloid processing, glial activation states, and associated clearance mechanisms. Herein, we demonstrate r-mTBI in aged PS1/APP mice does not augment, glial activation, amyloid burden, or tau pathology (with exception of pS202-positive Tau) 1 month after exposure to the last-injury. However, we observed a decrease in brain soluble Aβ42 levels without any appreciable change in peripheral soluble Aβ42 levels. This was accompanied by an increase in brain insoluble to soluble Aβ42 ratio in injured PS1/APP mice compared with sham injury. A parallel reduction in phagocytic receptor, triggering receptor expressed on myeloid cells 2, was also observed. This study demonstrates very subtle subchronic effects of r-mTBI on a preexisting amyloid pathology background, which may be on a continuum toward a slow and worsening neurodegenerative outcome compared with sham injury, and therefore, have many implications, especially in the elderly population exposed to TBI.
    MeSH term(s) Aging/genetics ; Aging/pathology ; Amyloid beta-Peptides/genetics ; Amyloidosis/etiology ; Amyloidosis/genetics ; Amyloidosis/pathology ; Animals ; Brain/pathology ; Brain Concussion/complications ; Brain Concussion/genetics ; Brain Concussion/pathology ; Disease Models, Animal ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Presenilin-1/genetics ; Random Allocation
    Chemical Substances Amyloid beta-Peptides ; Presenilin-1
    Language English
    Publishing date 2018-11-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3088-0
    ISSN 1554-6578 ; 0022-3069
    ISSN (online) 1554-6578
    ISSN 0022-3069
    DOI 10.1093/jnen/nly101
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