scholarly journals Transcriptional Pathology Evolves Over Time in Rat Hippocampus Following Lateral Fluid Percussion Traumatic Brain Injury

2021 ◽  
Author(s):  
Rinaldo Catta-Preta ◽  
Iva Zdillar ◽  
Bradley Jenner ◽  
Emily T. Doisy ◽  
Kayleen Tercovich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Cell Death ◽  
Brain Injury ◽  
Injury Severity ◽  
Cholesterol Metabolism ◽  
Fluid Percussion ◽  
Differential Gene ◽  
Lateral Fluid Percussion ◽  
The Brain

Traumatic brain injury (TBI) causes acute and lasting impacts on the brain, driving pathology along anatomical, cellular, and behavioral dimensions. Rodent models offer the opportunity to study TBI in a controlled setting, and enable analysis of the temporal progression that occurs from injury to recovery. We applied transcriptomic and epigenomic analysis, characterize gene expression and in ipsilateral hippocampus at 1 and 14 days following moderate lateral fluid percussion (LFP) injury. This approach enabled us to identify differential gene expression (DEG) modules with distinct expression trajectories across the two time points. The major DEG modules represented genes that were up- or downregulated acutely, but largely recovered by 14 days. As expected, DEG modules with acute upregulation were associated with cell death and astrocytosis. Interestingly, acutely downregulated DEGs related to neurotransmission mostly recovered by two weeks. Upregulated DEG modules related to inflammation were not necessarily elevated acutely, but were strongly upregulated after two weeks. We identified a smaller DEG module with delayed upregulation at 14 days including genes related to cholesterol metabolism and amyloid beta clearance. Finally, differential expression was paralleled by changes in H3K4me3 at the promoters of differentially expressed genes at one day following TBI. Following TBI, changes in cell viability, function and ultimately behavior are dynamic processes. Our results show how transcriptomics in the preclinical setting has the potential to identify biomarkers for injury severity and/or recovery, to identify potential therapeutic targets, and, in the future, to evaluate efficacy of an intervention beyond measures of cell death or spatial learning.

scholarly journals The role of salivary vesicles as a potential inflammatory biomarker to detect traumatic brain injury in mixed martial artists

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rani Matuk ◽  
Mandy Pereira ◽  
Janette Baird ◽  
Mark Dooner ◽  
Yan Cheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Head Injury ◽  
Injury Severity ◽  
Expression Profiles ◽  
High Impact ◽  
Impact Mechanism ◽  
Inflammatory Biomarker ◽  
Potential Biomarker

AbstractTraumatic brain injury (TBI) is of significant concern in the realm of high impact contact sports, including mixed martial arts (MMA). Extracellular vesicles (EVs) travel between the brain and oral cavity and may be isolated from salivary samples as a noninvasive biomarker of TBI. Salivary EVs may highlight acute neurocognitive or neuropathological changes, which may be particularly useful as a biomarker in high impact sports. Pre and post-fight samples of saliva were isolated from 8 MMA fighters and 7 from controls. Real-time PCR of salivary EVs was done using the TaqMan Human Inflammatory array. Gene expression profiles were compared pre-fight to post-fight as well as pre-fight to controls. Largest signals were noted for fighters sustaining a loss by technical knockout (higher impact mechanism of injury) or a full match culminating in referee decision (longer length of fight), while smaller signals were noted for fighters winning by joint or choke submission (lower impact mechanism as well as less time). A correlation was observed between absolute gene information signals and fight related markers of head injury severity. Gene expression was also significantly different in MMA fighters pre-fight compared to controls. Our findings suggest that salivary EVs as a potential biomarker in the acute period following head injury to identify injury severity and can help elucidate pathophysiological processes involved in TBI.

scholarly journals Differential Gene Expression Associated with Meningeal Injury in Acute Mild Traumatic Brain Injury

2017 ◽  
Vol 34 (4) ◽  
pp. 853-860 ◽  
Author(s):  
Whitney S. Livingston ◽  
Jessica M. Gill ◽  
Martin R. Cota ◽  
Anlys Olivera ◽  
Jessica L. O'Keefe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Differential Gene Expression ◽  
Mild Traumatic Brain Injury ◽  
Differential Gene

scholarly journals TT-301 Inhibits Microglial Activation and Improves Outcome after Central Nervous System Injury in Adult Mice

2012 ◽  
Vol 116 (6) ◽  
pp. 1299-1311 ◽  
Author(s):  
Michael L. James ◽  
Haichen Wang ◽  
Viviana Cantillana ◽  
Beilei Lei ◽  
Dawn N. Kernagis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Functional Outcome ◽  
Differential Gene Expression ◽  
Morris Water Maze ◽  
Water Maze ◽  
Murine Models ◽  
Differential Gene

Background Microglial inhibition may reduce secondary tissue injury and improve functional outcome following acute brain injury. Utilizing clinically relevant murine models of traumatic brain injury and intracerebral hemorrhage, neuroinflammatory responses and functional outcome were examined in the presence of a potential microglial inhibitor, TT-301. Methods TT-301 or saline was administered following traumatic brain injury or intracerebral hemorrhage, and then for four subsequent days. The effect of TT-301 on neuroinflammatory responses and neuronal viability was assessed, as well as short-term vestibulomotor deficit (Rotorod) and long-term neurocognitive impairment (Morris water maze). Finally differential gene expression profiles of mice treated with TT-301 were compared with those of vehicle. Results Reduction in F4/80+ staining was demonstrated at 1 and 10 days, but not 28 days, after injury in mice treated with TT-301 (n = 6). These histologic findings were associated with improved neurologic function as assessed by Rotorod, which improved by 52.7% in the treated group by day 7, and Morris water maze latencies, which improved by 232.5% as a function of treatment (n = 12; P < 0.05). Similar benefit was demonstrated following intracerebral hemorrhage, in which treatment with TT-301 was associated with functional neurologic improvement of 39.6% improvement in Rotorod and a reduction in cerebral edema that was independent of hematoma volume (n = 12; P < 0.05). Differential gene expression was evaluated following treatment with TT-301, and hierarchical cluster analysis implicated involvement of the Janus kinase-Signal Transducer and Activator of Transcription pathway after administration of TT-301 (n = 3/group). Conclusions Modulation of neuroinflammatory responses through TT-301 administration improved histologic and functional parameters in murine models of acute neurologic injury.

A rapid lateral fluid percussion injury rodent model of traumatic brain injury and post-traumatic epilepsy

Neuroreport ◽  
2014 ◽  
pp. 1 ◽  
Author(s):  
Mustafa Q. Hameed ◽  
Grant S. Goodrich ◽  
Sameer C. Dhamne ◽  
Asa Amandusson ◽  
Tsung-Hsun Hsieh ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Rodent Model ◽  
Fluid Percussion ◽  
Fluid Percussion Injury ◽  
Post Traumatic ◽  
Lateral Fluid Percussion ◽  
Post Traumatic Epilepsy ◽  
Traumatic Epilepsy

scholarly journals Correlation of Cerebral and Subcutaneous Glycerol in Severe Traumatic Brain Injury and Association with Tissue Damage

2021 ◽  
Author(s):  
Linda Hägglund ◽  
Magnus Olivecrona ◽  
Lars-Owe D. Koskinen
Keyword(s):  
Computed Tomography ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Injury Severity Score ◽  
Severe Traumatic Brain Injury ◽  
Tissue Damage ◽  
Injury Severity ◽  
Health Evaluation ◽  
Brain Tissue Damage ◽  
The Brain

Abstract Background This study is a substudy of a prospective consecutive double-blinded randomized study on the effect of prostacyclin in severe traumatic brain injury (sTBI). The aims of the present study were to investigate whether there was a correlation between brain and subcutaneous glycerol levels and whether the ratio of interstitial glycerol in the brain and subcutaneous tissue (glycerolbrain/sc) was associated with tissue damage in the brain, measured by using the Rotterdam score, S-100B, neuron-specific enolase (NSE), the Injury Severity Score (ISS), the Acute Physiology and Chronic Health Evaluation Score (APACHE II), and trauma type. A potential association with clinical outcome was explored. Methods Patients with sTBI aged 15–70 years presenting with a Glasgow Coma Scale Score ≤ 8 were included. Brain and subcutaneous adipose tissue glycerol levels were measured through microdialysis in 48 patients, of whom 42 had complete data for analysis. Brain tissue damage was also evaluated by using the Rotterdam classification of brain computed tomography scans and the biochemical biomarkers S-100B and NSE. Results In 60% of the patients, a positive relationship in glycerolbrain/sc was observed. Patients with a positive correlation of glycerolbrain/sc had slightly higher brain glycerol levels compared with the group with a negative correlation. There was no significant association between the computed tomography Rotterdam score and glycerolbrain/sc. S-100B and NSE were associated with the profile of glycerolbrain/sc. Our results cannot be explained by the general severity of the trauma as measured by using the Injury Severity Score or Acute Physiology and Chronic Health Evaluation Score. Conclusions We have shown that peripheral glycerol may flux into the brain. This effect is associated with worse brain tissue damage. This flux complicates the interpretation of brain interstitial glycerol levels. We remind the clinicians that a damaged blood–brain barrier, as seen in sTBI, may alter the concentrations of various substances, including glycerol in the brain. Awareness of this is important in the interpretation of the data bedside as well in research.

Treatment of traumatic brain injury with 17α-ethinylestradiol-3-sulfate in a rat model

2017 ◽  
Vol 127 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Harrison Kim ◽  
Tao Yu ◽  
Betul Cam-Etoz ◽  
Thomas van Groen ◽  
William J. Hubbard ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Body Weight ◽  
Brain Injury ◽  
Diffusion Tensor ◽  
T2 Mapping ◽  
Water Soluble ◽  
Fluid Percussion ◽  
The Mean ◽  
Lateral Fluid Percussion ◽  
Center Area

OBJECTIVE17α-ethynylestradiol-3-sulfate (EE-3-SO4) is a highly water-soluble synthetic estrogen that has an extended half-life (∼ 10 hours) over that of naturally occurring estrogen (∼ 10 minutes). In this study, EE-3-SO4 was evaluated in a lateral fluid percussion–induced traumatic brain injury (TBI) model in rats.METHODSA total of 9 groups of Sprague-Dawley rats underwent craniectomy. Twenty-four hours later, lateral fluid percussion was applied to 6 groups of animals to induce TBI; the remaining 3 groups served as sham control groups. EE-3-SO4 (1 mg/kg body weight in 0.4 ml/kg body weight) or saline (vehicle control) was injected intravenously 1 hour after TBI; saline was injected in all sham animals. One day after EE-3-SO4/saline injection, intracranial pressure (ICP), cerebral perfusion pressure (CPP), and partial brain oxygen pressure (PbtO2) were measured in Groups 1–3 (2 TBI groups and 1 sham group), and brain edema, diffusion axonal injury, and cerebral glycolysis were assessed in Groups 4–6 using MRI T2 mapping, diffusion tensor imaging (DTI), and FDG-PET imaging, respectively. Four days after dosing, the open-field anxiety of animals was assessed in Groups 7–9 by measuring the duration that each animal spent in the center area of an open chamber during 4 minutes of monitoring.RESULTSEE-3-SO4 significantly lowered ICP while raising CPP and PbtO2, compared with vehicle treatment in TBI-induced animals (p < 0.05). The mean size of cerebral edema of TBI animals treated with EE-3-SO4 was 25 ± 3 mm3 (mean ± SE), which was significantly smaller than that of vehicle-treated animals (67 ± 6 mm3, p < 0.001). Also, EE-3-SO4 treatment significantly increased the fractional anisotropy of the white matter in the ipsilateral side (p = 0.003) and cerebral glycolysis (p = 0.014). The mean duration that EE-3-SO4-treated animals spent in the center area was 12 ± 2 seconds, which was significantly longer than that of vehicle-treated animals (4 ± 1 seconds; p = 0.008) but not different from that of sham animals (11 ± 3 seconds; p > 0.05).CONCLUSIONSThese data support the clinical use of EE-3-SO4 for early TBI treatment.

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