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  1. Article ; Online: Abrogation of atypical neurogenesis and vascular-derived EphA4 prevents repeated mild TBI-induced learning and memory impairments.

    Greer, Kisha / Basso, Erwin Kristobal Gudenschwager / Kelly, Colin / Cash, Alison / Kowalski, Elizabeth / Cerna, Steven / Ocampo, Collin Tanchanco / Wang, Xia / Theus, Michelle H

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 15374

    Abstract: Brain injury resulting from repeated mild traumatic insult is associated with cognitive dysfunction and other chronic co-morbidities. The current study tested the effects of aberrant neurogenesis in a mouse model of repeated mild traumatic brain injury ( ... ...

    Abstract Brain injury resulting from repeated mild traumatic insult is associated with cognitive dysfunction and other chronic co-morbidities. The current study tested the effects of aberrant neurogenesis in a mouse model of repeated mild traumatic brain injury (rmTBI). Using Barnes Maze analysis, we found a significant reduction in spatial learning and memory at 24 days post-rmTBI compared to repeated sham (rSham) injury. Cell fate analysis showed a greater number of BrdU-labeled cells which co-expressed Prox-1 in the DG of rmTBI-injured mice which coincided with enhanced cFos expression for neuronal activity. We then selectively ablated dividing neural progenitor cells using a 7-day continuous infusion of Ara-C prior to rSham or rmTBI. This resulted in attenuation of cFos and BrdU-labeled cell changes and prevented associated learning and memory deficits. We further showed this phenotype was ameliorated in EphA4f.
    MeSH term(s) Animals ; Brain Concussion/complications ; Brain Concussion/metabolism ; Brain Concussion/pathology ; Disease Models, Animal ; Learning Disabilities/etiology ; Learning Disabilities/metabolism ; Learning Disabilities/pathology ; Male ; Maze Learning/physiology ; Memory/physiology ; Memory Disorders/etiology ; Memory Disorders/metabolism ; Memory Disorders/pathology ; Mice ; Neurogenesis/physiology ; Neurons/metabolism ; Neurons/physiology ; Receptor, EphA4/metabolism ; Spatial Learning/physiology
    Chemical Substances Receptor, EphA4 (EC 2.7.10.1)
    Language English
    Publishing date 2020-09-21
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-72380-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Extracellular vesicle concentrations of glial fibrillary acidic protein and neurofilament light measured 1 year after traumatic brain injury.

    Flynn, Spencer / Leete, Jacqueline / Shahim, Pashtun / Pattinson, Cassandra / Guedes, Vivian A / Lai, Chen / Devoto, Christina / Qu, Bao-Xi / Greer, Kisha / Moore, Brian / van der Merwe, Andre / Ekanayake, Vindhya / Gill, Jessica / Chan, Leighton

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 3896

    Abstract: Traumatic brain injury (TBI) is linked to long-term symptoms in a sub-set of patients who sustain an injury, but this risk is not universal, leading us and others to question the nature of individual variability in recovery trajectories. Extracellular ... ...

    Abstract Traumatic brain injury (TBI) is linked to long-term symptoms in a sub-set of patients who sustain an injury, but this risk is not universal, leading us and others to question the nature of individual variability in recovery trajectories. Extracellular vesicles (EVs) are a promising, novel avenue to identify blood-based biomarkers for TBI. Here, our aim was to determine if glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) measured 1-year postinjury in EVs could distinguish patients from controls, and whether these biomarkers relate to TBI severity or recovery outcomes. EV GFAP and EV NfL were measured using an ultrasensitive assay in 72 TBI patients and 20 controls. EV GFAP concentrations were elevated in moderate and severe TBI compared to controls (p's < 0.001) and could distinguish controls from moderate (AUC = 0.86) or severe TBI (AUC = 0.88). Increased EV GFAP and EV NfL levels were associated with lower 1-year Glasgow Outcome Scale-Extended (GOS-E) score (p's < 0.05). These findings suggest that blood-derived EV concentrations of GFAP and NfL drawn even 1 year after injury are higher in TBI patients compared to controls, and are related to injury severity and poor recovery outcomes, suggesting that TBIs alter the activity of these biomarkers, likely contributing to individual variability in recovery.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Biomarkers/metabolism ; Brain Injuries, Traumatic/metabolism ; Case-Control Studies ; Extracellular Vesicles/metabolism ; Female ; Glial Fibrillary Acidic Protein/metabolism ; Humans ; Male ; Middle Aged ; Neurofilament Proteins/metabolism ; Recovery of Function ; Young Adult
    Chemical Substances Biomarkers ; GFAP protein, human ; Glial Fibrillary Acidic Protein ; Neurofilament Proteins ; neurofilament protein L
    Language English
    Publishing date 2021-02-16
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-82875-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Extracellular vesicle neurofilament light is elevated within the first 12-months following traumatic brain injury in a U.S military population.

    Guedes, Vivian A / Lange, Rael T / Lippa, Sara M / Lai, Chen / Greer, Kisha / Mithani, Sara / Devoto, Christina / A Edwards, Katie / Wagner, Chelsea L / Martin, Carina A / Driscoll, Angela E / Wright, Megan M / Gillow, Kelly C / Baschenis, Samantha M / Brickell, Tracey A / French, Louis M / Gill, Jessica M

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 4002

    Abstract: Traumatic brain injury (TBI) can be associated with long-term neurobehavioral symptoms. Here, we examined levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in extracellular vesicles isolated from blood, and their ... ...

    Abstract Traumatic brain injury (TBI) can be associated with long-term neurobehavioral symptoms. Here, we examined levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in extracellular vesicles isolated from blood, and their relationship with TBI severity and neurobehavioral symptom reporting. Participants were 218 service members and veterans who sustained uncomplicated mild TBIs (mTBI, n = 107); complicated mild, moderate, or severe TBIs (smcTBI, n = 66); or Injured controls (IC, orthopedic injury without TBI, n = 45). Within one year after injury, but not after, NfL was higher in the smcTBI group than mTBI (p = 0.001, d = 0.66) and IC (p = 0.001, d = 0.35) groups, which remained after controlling for demographics and injury characteristics. NfL also discriminated the smcTBI group from IC (AUC:77.5%, p < 0.001) and mTBI (AUC:76.1%, p < 0.001) groups. No other group differences were observed for NfL or GFAP at either timepoint. NfL correlated with post-concussion symptoms (r
    MeSH term(s) Brain Injuries, Traumatic/complications ; Extracellular Vesicles ; Humans ; Intermediate Filaments ; Military Personnel ; Post-Concussion Syndrome ; Veterans
    Language English
    Publishing date 2022-03-07
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-05772-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Modulation of gap junction-associated Cx43 in neural stem/progenitor cells following traumatic brain injury.

    Greer, Kisha / Chen, Jiang / Brickler, Thomas / Gourdie, Robert / Theus, Michelle H

    Brain research bulletin

    2017  Volume 134, Page(s) 38–46

    Abstract: Restoration of learning and memory deficits following traumatic brain injury (TBI) is attributed, in part, to enhanced neural stem/progenitor cell (NSPCs) function. Recent findings suggest gap junction (GJ)-associated connexin 43 (Cx43) plays a key role ... ...

    Abstract Restoration of learning and memory deficits following traumatic brain injury (TBI) is attributed, in part, to enhanced neural stem/progenitor cell (NSPCs) function. Recent findings suggest gap junction (GJ)-associated connexin 43 (Cx43) plays a key role in the cell cycle regulation and function of NSPCs and is modulated following TBI. Here, we demonstrate that Cx43 is up-regulated in the dentate gyrus following TBI and is expressed on vimentin-positive cells in the subgranular zone. To test the role of Cx43 on NSPCs, we exposed primary cultures to the α-connexin Carboxyl Terminal (αCT1) peptide which selectively modulates GJ-associated Cx43. Treatment with αCT1 substantially reduced proliferation and increased caspase 3/7 expression on NSPCs in a dose-dependent manner. αCT1 exposure also reduced overall expression of Cx43 and phospho (p)-Serine368. These findings demonstrate that Cx43 positively regulates adult NPSCs; the modulation of which may influence changes in the dentate gyrus following TBI.
    MeSH term(s) Animals ; Apoptosis/drug effects ; Apoptosis/physiology ; Blotting, Western ; Brain Injuries, Traumatic/metabolism ; Brain Injuries, Traumatic/pathology ; Bromodeoxyuridine ; Caspase 3/metabolism ; Caspase 7/metabolism ; Cell Proliferation/drug effects ; Cell Proliferation/physiology ; Cells, Cultured ; Connexin 43/metabolism ; Disease Models, Animal ; Gap Junctions/drug effects ; Gap Junctions/metabolism ; Hippocampus/drug effects ; Hippocampus/metabolism ; Hippocampus/pathology ; Immunohistochemistry ; Male ; Mice ; Microscopy, Confocal ; Neural Stem Cells/drug effects ; Neural Stem Cells/metabolism ; Neural Stem Cells/pathology ; Phosphorylation/drug effects ; Vimentin/metabolism
    Chemical Substances Connexin 43 ; GJA1 protein, mouse ; Vimentin ; Casp3 protein, mouse (EC 3.4.22.-) ; Casp7 protein, mouse (EC 3.4.22.-) ; Caspase 3 (EC 3.4.22.-) ; Caspase 7 (EC 3.4.22.-) ; Bromodeoxyuridine (G34N38R2N1)
    Language English
    Publishing date 2017-06-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 197620-5
    ISSN 1873-2747 ; 0361-9230
    ISSN (online) 1873-2747
    ISSN 0361-9230
    DOI 10.1016/j.brainresbull.2017.06.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Neuronally-derived tau is increased in experienced breachers and is associated with neurobehavioral symptoms.

    Edwards, Katie A / Greer, Kisha / Leete, Jacqueline / Lai, Chen / Devoto, Christina / Qu, Bao-Xi / Yarnell, Angela M / Polejaeva, Elena / Dell, Kristine C / LoPresti, Matthew L / Walker, Peter / Wassermann, Eric M / Carr, Walter / Stone, James R / Ahlers, Stephen T / Vorn, Rany / Martin, Carina / Gill, Jessica M

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 19527

    Abstract: Military and law enforcement breachers are exposed to many low-level blasts during their training and occupational experiences in which they detonate explosives to force entry into secured structures. There is a concern that exposure to these repetitive ... ...

    Abstract Military and law enforcement breachers are exposed to many low-level blasts during their training and occupational experiences in which they detonate explosives to force entry into secured structures. There is a concern that exposure to these repetitive blast events in career breachers could result in cumulative neurological effects. This study aimed to determine concentrations of neurofilament light (NF-L), tau, and amyloid-beta 42 (Aβ42) in serum and in neuronal-derived extracellular vesicles (EVs) in an experienced breacher population, and to examine biomarker associations with neurobehavioral symptoms. Thirty-four participants enrolled in the study: 20 experienced breachers and 14 matched military or civilian law enforcement controls. EV tau concentrations were significantly elevated in experienced breachers (0.3301 ± 0.5225) compared to controls (-0.4279 ± 0.7557; F = 10.43, p = 0.003). No statistically significant changes were observed in EV levels of NF-L or Aβ42 or in serum levels of NF-L, tau, or Aβ42 (p's > 0.05). Elevated EV tau concentrations correlated with increased Neurobehavioral Symptom Inventory (NSI) score in experienced breachers (r = 0.596, p = 0.015) and predicted higher NSI score (F(1,14) = 7.702, p = 0.015, R
    MeSH term(s) Adult ; Amyloid beta-Peptides/blood ; Amyloid beta-Peptides/metabolism ; Biomarkers ; Blast Injuries/complications ; Brain Injuries, Traumatic ; Disease Susceptibility ; Female ; Humans ; Male ; Middle Aged ; Military Personnel ; Nervous System Diseases/diagnosis ; Nervous System Diseases/etiology ; Nervous System Diseases/metabolism ; Neurofilament Proteins/blood ; Neurofilament Proteins/metabolism ; Neurons/metabolism ; Symptom Assessment ; tau Proteins/blood ; tau Proteins/metabolism
    Chemical Substances Amyloid beta-Peptides ; Biomarkers ; Neurofilament Proteins ; tau Proteins
    Language English
    Publishing date 2021-09-30
    Publishing country England
    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 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-97913-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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