scholarly journals Glutamate and GABA concentrations following mild traumatic brain injury: a pilot study

2018 ◽  
Vol 120 (3) ◽  
pp. 1318-1322 ◽  
Author(s):  
Alia L. Yasen ◽  
Jolinda Smith ◽  
Anita D. Christie
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Primary Motor Cortex ◽  
Brain Regions ◽  
Resonance Spectroscopy ◽  
Multiple Time ◽  
Time Points ◽  
The Brain

Animal models of mild traumatic brain injury (mTBI) suggest that metabolic changes in the brain occur immediately after a mechanical injury to the head. Proton magnetic resonance spectroscopy (1H-MRS) can be used to determine relative concentrations of metabolites in vivo in the human brain. The purpose of this study was to determine concentrations of glutamate and GABA in the brain acutely after mTBI and throughout 2 mo of recovery. Concentrations of glutamate and GABA were obtained using 1H-MRS in nine individuals who had suffered an mTBI and nine control individuals in two brain regions of interest: the primary motor cortex (M1), and the dorsolateral prefrontal cortex (DLPFC), and at three different time points postinjury: 72 h, 2 wk, and 2 mo postinjury. There were no differences between groups in concentrations of glutamate or GABA, or the ratio of glutamate to GABA, in M1. In the DLPFC, glutamate concentration was lower in the mTBI group compared with controls at 72 h postinjury (d = 1.02), and GABA concentration was lower in the mTBI group at 72 h and 2 wk postinjury (d = 0.81 and d = 1.21, respectively). The ratio of glutamate to GABA in the DLPFC was higher in the mTBI group at 2 wk postinjury (d = 1.63). These results suggest that changes in glutamate and GABA concentrations in the brain may be region-specific and may depend on the amount of time that has elapsed postinjury. NEW & NOTEWORTHY To our knowledge, this is the first study to examine neurotransmitter concentrations in vivo at multiple time points throughout recovery from mild traumatic brain injury in humans.

scholarly journals Diverse Changes in Microglia Morphology and Axonal Pathology Over One Year after Mild Traumatic Brain Injury in Pigs

2020 ◽  
Author(s):  
Michael R. Grovola ◽  
Nicholas Paleologos ◽  
Daniel P. Brown ◽  
Nathan Tran ◽  
Kathryn L. Wofford ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Mild Traumatic Brain Injury ◽  
Periventricular White Matter ◽  
Post Injury ◽  
Mild Tbi ◽  
Time Points ◽  
Axonal Pathology ◽  
The Brain

AbstractOver 2.8 million people experience mild traumatic brain injury (TBI) in the United States each year, which may lead to long-term neurological dysfunction. The mechanical forces that occur due to TBI propagate through the brain to produce diffuse axonal injury (DAI) and trigger secondary neuroinflammatory cascades. The cascades may persist from acute to chronic time points after injury, altering the homeostasis of the brain. However, the relationship between the hallmark axonal pathology of diffuse TBI and potential changes in glial cell activation or morphology have not been established in a clinically relevant large animal model at chronic time points. In this study, we assessed tissue from pigs subjected to rapid head rotation in the coronal plane to generate mild TBI. Neuropathological assessments for axonal pathology, microglial morphological changes, and astrocyte reactivity were conducted in specimens out to 1 year post injury. We detected an increase in overall amyloid precursor protein pathology, as well as periventricular white matter and fimbria/fornix pathology after a single mild TBI. We did not detect changes in corpus callosum integrity or astrocyte reactivity. However, detailed microglial skeletal analysis revealed changes in morphology, most notably increases in the number of microglial branches, junctions, and endpoints. These subtle changes were most evident in periventricular white matter and certain hippocampal subfields, and were observed out to 1 year post injury in some cases. These ongoing morphological alterations suggest persistent change in neuroimmune homeostasis. Additional studies are needed to characterize the underlying molecular and neurophysiological alterations, as well as potential contributions to neurological deficits.

scholarly journals Machine Learning Classification of Mild Traumatic Brain Injury Using Whole-Brain Functional Activity: A Radiomics Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Xiaoping Luo ◽  
Dezhao Lin ◽  
Shengwei Xia ◽  
Dongyu Wang ◽  
Xinmang Weng ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Short Range ◽  
Low Frequency ◽  
Brain Regions ◽  
Classification Performance ◽  
Imaging Parameters ◽  
The Brain ◽  
Normal Controls

Objectives. To investigate the classification performance of support vector machine in mild traumatic brain injury (mTBI) from normal controls. Methods. Twenty-four mTBI patients (15 males and 9 females; mean age, 38.88 ± 13.33 years) and 24 age and sex-matched normal controls (13 males and 11 females; mean age, 40.46 ± 11.4 years) underwent resting-state functional MRI examination. Seven imaging parameters, including amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), degree centrality (DC), voxel-mirrored homotopic connectivity (VMHC), long-range functional connectivity density (FCD), and short-range FCD, were entered into the classification model to distinguish the mTBI from normal controls. Results. The ability for any single imaging parameters to distinguish the two groups is lower than multiparameter combinations. The combination of ALFF, fALFF, DC, VMHC, and short-range FCD showed the best classification performance for distinguishing the two groups with optimal AUC value of 0.778, accuracy rate of 81.11%, sensitivity of 88%, and specificity of 75%. The brain regions with the highest contributions to this classification mainly include bilateral cerebellum, left orbitofrontal cortex, left cuneus, left temporal pole, right inferior occipital cortex, bilateral parietal lobe, and left supplementary motor area. Conclusions. Multiparameter combinations could improve the classification performance of mTBI from normal controls by using the brain regions associated with emotion and cognition.

Analysis of magnetic resonance spectroscopy relative metabolite ratios in mild traumatic brain injury and normative controls

2019 ◽  
pp. 291-297
Author(s):  
Peter E. Cartwright ◽  
◽  
Thomas G. Perkins ◽  
Steffanie H. Wilson ◽  
Lindell K. Weaver ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Mild Traumatic Brain Injury ◽  
Military Personnel ◽  
Resonance Spectroscopy ◽  
Automatic Data ◽  
The Brain ◽  
Over Time

Introduction: We evaluated magnetic resonance spectroscopy (MRS) in United States military personnel with persistent symptoms after mild traumatic brain injury (mTBI), comparing over time two groups randomized to receive hyperbaric oxygen or sham chamber sessions and a third group of normative controls. Methods: Active-duty or veteran military personnel and normative controls underwent MRS outcome measures at baseline, 13 weeks (mTBI group only), and six months. Participants received 3.0 Tesla brain MRS for analysis of water-suppressed two-dimensional (2D) multivoxel 1H-MRS of the brain using point resolved spectroscopy (PRESS) with volume selection localized above the lateral ventricles and within the brain parenchyma, of which one voxel was chosen in each hemisphere without artifact. Script-based automatic data processing was used to assess N-acetylaspartate (NAA), creatine (Cr), and choline (Cho). Metabolite ratios for white matter were then calculated for NAA/Cr (Area), Cho/Cr (Area), and Cho/NAA (Area). These ratios were compared using standard analysis methodology. Results: There were no observable differences between participants with mTBI and normative controls nor any observable changes over time in the NAA/Cr (area), Cho/Cr (area), and Cho/NAA (area) ratios. Similarly, the control and injured participants were indistinguishable. Discussion: While participants with mild TBI showed no difference in MRS compared to normative controls, our results are limited by the few voxels chosen and potentially by less sensitive MRS markers.

Providing Care of Mild Traumatic Brain Injury by the Family Practice/Primary Care Optometrist

2018 ◽  
pp. 110-119
Keyword(s):  
Primary Care ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Family Practice ◽  
Advanced Training ◽  
Entry Level ◽  
The Family ◽  
Basic Understanding ◽  
The Brain

Primary Objectives: By extending the scope of knowledge of the primary care optometrist, the brain injury population will have expanded access to entry level neurooptometric care by optometric providers who have a basic understanding of their neurovisual problems, be able to provide some treatment and know when to refer to their colleagues who have advanced training in neuro-optometric rehabilitation.

scholarly journals What are the strongest indicators of intracerebral hemorrhage in mild traumatic brain injury?

2021 ◽  
Vol 6 (1) ◽  
pp. e000717
Author(s):  
Panu Teeratakulpisarn ◽  
Phati Angkasith ◽  
Thanakorn Wannakul ◽  
Parichat Tanmit ◽  
Supatcha Prasertcharoensuk ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
High Risk ◽  
Ct Scan ◽  
Mild Traumatic Brain Injury ◽  
Skull Fracture ◽  
Brain Ct ◽  
Baseline Characteristics ◽  
Gcs Score ◽  
The Brain

BackgroundAlthough there are eight factors known to indicate a high risk of intracranial hemorrhage (ICH) in mild traumatic brain injury (TBI), identification of the strongest of these factors may optimize the utility of brain CT in clinical practice. This study aimed to evaluate the predictors of ICH based on baseline characteristics/mode of injury, indications for brain CT, and a combination of both to determine the strongest indicator.MethodsThis was a descriptive, retrospective, analytical study. The inclusion criteria were diagnosis of mild TBI, high risk of ICH, and having undergone a CT scan of the brain. The outcome of the study was any type of ICH. Stepwise logistic regression analysis was used to find the strongest predictors according to three models: (1) injury pattern and baseline characteristics, (2) indications for CT scan of the brain, and (3) a combination of models 1 and 2.ResultsThere were 100 patients determined to be at risk of ICH based on indications for CT of the brain in patients with acute head injury. Of these, 24 (24.00%) had ICH. Model 1 found that injury due to motor vehicle crash was a significant predictor of ICH, with an adjusted OR (95% CI) of 11.53 (3.05 to 43.58). Models 2 and 3 showed Glasgow Coma Scale (GCS) score of 13 to 14 after 2 hours of observation and open skull or base of skull fracture to be independent predictors, with adjusted OR (95% CI) of 11.77 (1.32 to 104.96) and 5.88 (1.08 to 31.99) according to model 2.DiscussionOpen skull or base of skull fracture and GCS score of 13 to 14 after 2 hours of observation were the two strongest predictors of ICH in mild TBI.Level of evidenceIII.

scholarly journals GPR110 ligands reduce chronic optic tract gliosis and visual deficit following repetitive mild traumatic brain injury in mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Huazhen Chen ◽  
Karl Kevala ◽  
Elma Aflaki ◽  
Juan Marugan ◽  
Hee-Yong Kim
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Visual Evoked Potential ◽  
Evoked Potential ◽  
Optic Tract ◽  
Primary Microglia ◽  
Visual Dysfunction ◽  
The Brain

Abstract Background Repetitive mild traumatic brain injury (mTBI) can result in chronic visual dysfunction. G-protein receptor 110 (GPR110, ADGRF1) is the target receptor of N-docosahexaenoylethanolamine (synaptamide) mediating the anti-neuroinflammatory function of synaptamide. In this study, we evaluated the effect of an endogenous and a synthetic ligand of GPR110, synaptamide and (4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-hydroxy-2-methylpropyl) docosa-4,7,10,13,16,19-hexaenamide (dimethylsynaptamide, A8), on the mTBI-induced long-term optic tract histopathology and visual dysfunction using Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA), a clinically relevant model of mTBI. Methods The brain injury in wild-type (WT) and GPR110 knockout (KO) mice was induced by CHIMERA applied daily for 3 days, and GPR110 ligands were intraperitoneally injected immediately following each impact. The expression of GPR110 and proinflammatory mediator tumor necrosis factor (TNF) in the brain was measured by using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in an acute phase. Chronic inflammatory responses in the optic tract and visual dysfunction were assessed by immunostaining for Iba-1 and GFAP and visual evoked potential (VEP), respectively. The effect of GPR110 ligands in vitro was evaluated by the cyclic adenosine monophosphate (cAMP) production in primary microglia isolated from adult WT or KO mouse brains. Results CHIMERA injury acutely upregulated the GPR110 and TNF gene level in mouse brain. Repetitive CHIMERA (rCHIMERA) increased the GFAP and Iba-1 immunostaining of glia cells and silver staining of degenerating axons in the optic tract with significant reduction of N1 amplitude of visual evoked potential at up to 3.5 months after injury. Both GPR110 ligands dose- and GPR110-dependently increased cAMP in cultured primary microglia with A8, a ligand with improved stability, being more effective than synaptamide. Intraperitoneal injection of A8 at 1 mg/kg or synaptamide at 5 mg/kg significantly reduced the acute expression of TNF mRNA in the brain and ameliorated chronic optic tract microgliosis, astrogliosis, and axonal degeneration as well as visual deficit caused by injury in WT but not in GPR110 KO mice. Conclusion Our data demonstrate that ligand-induced activation of the GPR110/cAMP system upregulated after injury ameliorates the long-term optic tract histopathology and visual impairment caused by rCHIMERA. Based on the anti-inflammatory nature of GPR110 activation, we suggest that GPR110 ligands may have therapeutic potential for chronic visual dysfunction associated with mTBI.

scholarly journals Neuromodulation for Mild Traumatic Brain Injury Rehabilitation: A Systematic Review

2020 ◽  
Vol 14 ◽  
Author(s):  
Francesca Buhagiar ◽  
Melinda Fitzgerald ◽  
Jason Bell ◽  
Fiona Allanson ◽  
Carmela Pestell
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Post Intervention ◽  
Persistent Symptoms ◽  
Positive Effects ◽  
The Brain

Background: Mild traumatic brain injury (mTBI) results from an external force to the head or body causing neurophysiological changes within the brain. The number and severity of symptoms can vary, with some individuals experiencing rapid recovery, and others having persistent symptoms for months to years, impacting their quality of life. Current rehabilitation is limited in its ability to treat persistent symptoms and novel approaches are being sought to improve outcomes following mTBI. Neuromodulation is one technique used to encourage adaptive neuroplasticity within the brain.Objective: To systematically review the literature on the efficacy of neuromodulation in the mTBI population.Method: A systematic review was conducted using Medline, Embase, PsycINFO, PsycARTICLES and EBM Review. Preferred Reporting Items for Systematic Reviews and the Synthesis Without Meta-analysis reporting guidelines were used and a narrative review of the selected studies was completed. Fourteen articles fulfilled the inclusion criteria which were published in English, investigating an adult sample and using a pre- and post-intervention design. Studies were excluded if they included non-mild TBI severities, pediatric or older adult populations.Results: Thirteen of fourteen studies reported positive reductions in mTBI symptomatology following neuromodulation. Specifically, improvements were reported in post-concussion symptom ratings, headaches, dizziness, depression, anxiety, sleep disturbance, general disability, cognition, return to work and quality of life. Normalization of working memory activation patterns, vestibular field potentials, hemodynamics of the dorsolateral prefrontal cortex and excessive delta wave activity were also seen. The studies reviewed had several methodological limitations including small, heterogenous samples and varied intervention protocols, limiting generalisability. Further research is required to understand the context in which neuromodulation may be beneficial.Conclusions: While these positive effects are observed, limitations included unequal representation of neuromodulation modalities in the literature, and lack of literature describing the efficacy of neuromodulation on the development or duration of persistent mTBI symptoms. Better clarity regarding neuromodulation efficacy could have a significant impact on mTBI patients, researchers, clinicians, and policy makers, facilitating a more productive post-mTBI population. Despite the limitations, the literature indicates that neuromodulation warrants further investigation. PROSPERO registration number: CRD42020161279.

scholarly journals Highly Sensitive Single Molecular Array Immunoassay Measurement of t-Tau, NF-L, GFAP, and UCH-L1 Biomarkers in Acute Concussion/Mild Traumatic Brain Injury (mTBI) Patient Serum and Saliva Samples

Neurology ◽  
2019 ◽  
Vol 93 (14 Supplement 1) ◽  
pp. S19.3-S20
Author(s):  
Ahmed Chenna ◽  
Christos Petropoulos ◽  
John Winslow
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Limited Information ◽  
Post Injury ◽  
Time Points ◽  
Highly Sensitive ◽  
Biomarker Analysis ◽  
T Tau ◽  
Control Samples

ObjectiveTo determine if t-Tau, NF-L, GFAP and UCH-L1 protein biomarkers are elevated in early time points of acute concussion/mild traumatic brain injury patient serum and saliva, relative to control samples.Backgroundt-Tau, NF-L, GFAP and UCH-L1 levels have been reported to increase in cerebral spinal fluid (CSF) and blood following head trauma within 24 hours or longer, and are candidate diagnostic and prognostic biomarkers of concussion and mild to moderate TBI. However, limited information exists on the relationship between these biomarkers at short time points post-injury, and detectability in saliva of mTBI patients.Design/MethodsBiomarker analysis of serum from a total of 120 participants, derived from two independent sample groups consisting of 60 concussion/mTBI patients each, with blood collected within 1-4 hr and 8-16 hr post-injury, respectively, was compared with 30 healthy control sera. Saliva samples were collected after 8-16 hr post-injury from a n = 30 subset of the same patients. Quanterix Simoa 4-plex immunoassay was used for highly sensitive measurements of these biomarkers.ResultsMedian levels of NF-L, GFAP and UCH-L1 were significantly higher in independent sets of patient serum samples (n = 60 each), both at early (1–4 hr) and later (8–16 hr) time points post-mTBI/concussion, relative to control samples (n = 30) (p < 0.0001, = 0.0001, <0.0001, respectively). Low levels of t-Tau are detected, but are significantly elevated post-concussion relative to controls (p = 0.0001). Significant correlations were observed between levels of t-Tau and UCH-L1, NF-L and GFAP, and t-Tau and GFAP in both post-injury time-point groups, and between NF-L and UCH-L1 levels in the 8-16 hr group. The four biomarkers were detected in saliva from concussion/mTBI patients (n = 30).ConclusionsThis study supports the utility of ultra-sensitive multiplex immunoassays to detect increases in CNS proteins at high sensitivity in serum and saliva within 1-4 and 8-16 hr of concussion/mTBI.

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