Dataset Information

The Temporal Pattern of Changes in Serum Biomarker Levels Reveals Complex and Dynamically Changing Pathologies after Exposure to a Single Low-Intensity Blast in Mice.

ABSTRACT: Time-dependent changes in blood-based protein biomarkers can help identify the -pathological processes in blast-induced traumatic brain injury (bTBI), assess injury severity, and monitor disease progression. We obtained blood from control and injured mice (exposed to a single, low-intensity blast) at 2-h, 1-day, 1-week, and 1-month post-injury. We then determined the serum levels of biomarkers related to metabolism (4-HNE, HIF-1?, ceruloplasmin), vascular function (AQP1, AQP4, VEGF, vWF, Flk-1), inflammation (OPN, CINC1, fibrinogen, MIP-1a, OX-44, p38, MMP-8, MCP-1 CCR5, CRP, galectin-1), cell adhesion and the extracellular matrix (integrin ?6, TIMP1, TIMP4, Ncad, connexin-43), and axonal (NF-H, Tau), neuronal (NSE, CK-BB) and glial damage (GFAP, S100?, MBP) at various post-injury time points. Our findings indicate that the exposure to a single, low-intensity blast results in metabolic and vascular changes, altered cell adhesion, and axonal and neuronal injury in the mouse model of bTBI. Interestingly, serum levels of several inflammatory and astroglial markers were either unchanged or elevated only during the acute and subacute phases of injury. Conversely, serum levels of the majority of biomarkers related to metabolic and vascular functions, cell adhesion, as well as neuronal and axonal damage remained elevated at the termination of the experiment (1?month), indicating long-term systemic and cerebral alterations due to blast. Our findings show that the exposure to a single, low-intensity blast induces complex pathological processes with distinct temporal profiles. Hence, monitoring serum biomarker levels at various post-injury time points may provide enhanced diagnostics in blast-related neurological and multi-system deficits.

SUBMITTER: Ahmed F

PROVIDER: S-EPMC4464198 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Temporal Pattern of Changes in Serum Biomarker Levels Reveals Complex and Dynamically Changing Pathologies after Exposure to a Single Low-Intensity Blast in Mice.

Ahmed Farid F Plantman Stefan S Cernak Ibolja I Agoston Denes V DV

Frontiers in neurology 20150612

Time-dependent changes in blood-based protein biomarkers can help identify the -pathological processes in blast-induced traumatic brain injury (bTBI), assess injury severity, and monitor disease progression. We obtained blood from control and injured mice (exposed to a single, low-intensity blast) at 2-h, 1-day, 1-week, and 1-month post-injury. We then determined the serum levels of biomarkers related to metabolism (4-HNE, HIF-1α, ceruloplasmin), vascular function (AQP1, AQP4, VEGF, vWF, Flk-1), ...[more]

PMID: 26124743

Similar Datasets

Project description:Music tempo is closely connected to listeners' musical emotion and multifunctional neural activities. Music with increasing tempo evokes higher emotional responses and music with decreasing tempo enhances relaxation. However, the neural substrate of emotion evoked by dynamically changing tempo is still unclear. To investigate the spatial connectivity and temporal dynamic functional network connectivity (dFNC) of musical emotion evoked by dynamically changing tempo, we collected dynamic emotional ratings and conducted group independent component analysis (ICA), sliding time window correlations, and k-means clustering to assess the FNC of emotion evoked by music with decreasing tempo (180-65 bpm) and increasing tempo (60-180 bpm). Music with decreasing tempo (with more stable dynamic valences) evoked higher valence than increasing tempo both with stronger independent components (ICs) in the default mode network (DMN) and sensorimotor network (SMN). The dFNC analysis showed that with time-decreasing FNC across the whole brain, emotion evoked by decreasing music was associated with strong spatial connectivity within the DMN and SMN. Meanwhile, it was associated with strong FNC between the DMN-frontoparietal network (FPN) and DMN-cingulate-opercular network (CON). The paired t-test showed that music with a decreasing tempo evokes stronger activation of ICs within DMN and SMN than that with an increasing tempo, which indicated that faster music is more likely to enhance listeners' emotions with multifunctional brain activities even when the tempo is slowing down. With increasing FNC across the whole brain, music with an increasing tempo was associated with strong connectivity within FPN; time-decreasing connectivity was found within CON, SMN, VIS, and between CON and SMN, which explained its unstable valence during the dynamic valence rating. Overall, the FNC can help uncover the spatial and temporal neural substrates of musical emotions evoked by dynamically changing tempi.

Project description:Service members during military actions or combat training are frequently exposed to primary blasts by weaponry. Most studies have investigated moderate or severe brain injuries from blasts generating overpressures >100?kPa, whereas understanding the pathophysiology of low-intensity blast (LIB)-induced mild traumatic brain injury (mTBI) leading to neurological deficits remains elusive. Our recent studies, using an open-field LIB-induced mTBI mouse model with a peak overpressure at 46.6?kPa, demonstrated behavioral impairments and brain nanoscale damages, notably mitochondrial and axonal ultrastructural changes. In this study, we used tandem mass tagged (TMT) quantitative proteomics and bioinformatics analysis to seek insights into the molecular mechanisms underlying ultrastructural pathology. Changes in global- and phospho-proteomes were determined at 3 and 24?h and at 7 and 30 days post injury (DPI), in order to investigate the biochemical and molecular correlates of mitochondrial dysfunction. Results showed striking dynamic changes in a total of 2216 proteins and 459 phosphorylated proteins at vary time points after blast. Disruption of key canonical pathways included evidence of mitochondrial dysfunction, oxidative stress, axonal/cytoskeletal/synaptic dysregulation, and neurodegeneration. Bioinformatic analysis identified blast-induced trends in networks related to cellular growth/development/movement/assembly and cell-to-cell signaling interactions. With observations of proteomic changes, we found LIB-induced oxidative stress associated with mitochondrial dysfunction mainly at 7 and 30 DPI. These dysfunctions included impaired fission-fusion dynamics, diminished mitophagy, decreased oxidative phosphorylation, and compensated respiration-relevant enzyme activities. Insights on the early pathogenesis of primary LIB-induced brain damage provide a template for further characterization of its chronic effects, identification of potential biomarkers, and targets for intervention.

Dataset Information

The Temporal Pattern of Changes in Serum Biomarker Levels Reveals Complex and Dynamically Changing Pathologies after Exposure to a Single Low-Intensity Blast in Mice.

Publications

The Temporal Pattern of Changes in Serum Biomarker Levels Reveals Complex and Dynamically Changing Pathologies after Exposure to a Single Low-Intensity Blast in Mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets