scholarly journals Acute or Delayed Treatment with Anatabine Improves Spatial Memory and Reduces Pathological Sequelae at Late Time-Points after Repetitive Mild Traumatic Brain Injury

2017 ◽  
Vol 34 (8) ◽  
pp. 1676-1691 ◽  
Author(s):  
Scott Ferguson ◽  
Benoit Mouzon ◽  
Daniel Paris ◽  
Destinee Aponte ◽  
Laila Abdullah ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Spatial Memory ◽  
Mild Traumatic Brain Injury ◽  
Late Time ◽  
Delayed Treatment ◽  
Time Points

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.

scholarly journals Chronic gliosis and behavioral deficits in mice following repetitive mild traumatic brain injury

2014 ◽  
Vol 121 (6) ◽  
pp. 1342-1350 ◽  
Author(s):  
Rebekah Mannix ◽  
Jacqueline Berglass ◽  
Justin Berkner ◽  
Philippe Moleus ◽  
Jianhua Qiu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Spatial Memory ◽  
Mild Traumatic Brain Injury ◽  
Exploratory Behavior ◽  
Clinical Syndrome ◽  
Therapeutic Interventions ◽  
Behavioral Testing ◽  
Behavioral Deficits ◽  
Structural Brain Damage

Object With the recent increasing interest in outcomes after repetitive mild traumatic brain injury (rmTBI; e.g., sports concussions), several models of rmTBI have been established. Characterizing these models in terms of behavioral and histopathological outcomes is vital to assess their clinical translatability. The purpose of this study is to provide an in-depth behavioral and histopathological phenotype of a clinically relevant model of rmTBI. Methods The authors used a previously published weight-drop model of rmTBI (7 injuries in 9 days) in 2- to 3-month-old mice that produces cognitive deficits without persistent loss of consciousness, seizures, gross structural imaging findings, or microscopic evidence of structural brain damage. Injured and sham-injured (anesthesia only) mice were subjected to a battery of behavioral testing, including tests of balance (rotarod), spatial memory (Morris water maze), anxiety (open field plus maze), and exploratory behavior (hole-board test). After behavioral testing, brains were assessed for histopathological outcomes, including brain volume and microglial and astrocyte immunolabeling. Results Compared with sham-injured mice, mice subjected to rmTBI showed increased exploratory behavior and had impaired balance and worse spatial memory that persisted up to 3 months after injury. Long-term behavioral deficits were associated with chronic increased astrocytosis and microgliosis but no volume changes. Conclusions The authors demonstrate that their rmTBI model results in a characteristic behavioral phenotype that correlates with the clinical syndrome of concussion and repetitive concussion. This model offers a platform from which to study therapeutic interventions for rmTBI.

Repeated mild traumatic brain injury produces neuroinflammation, anxiety-like behaviour and impaired spatial memory in mice

Brain Injury ◽  
2017 ◽  
Vol 32 (1) ◽  
pp. 113-122 ◽  
Author(s):  
John I Broussard ◽  
Laura Acion ◽  
Héctor De Jesús-Cortés ◽  
Terry Yin ◽  
Jeremiah K Britt ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Spatial Memory ◽  
Mild Traumatic Brain Injury

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 Post-Concussion Symptoms in Complicated vs. Uncomplicated Mild Traumatic Brain Injury Patients at Three and Six Months Post-Injury: Results from the CENTER-TBI Study

2019 ◽  
Vol 8 (11) ◽  
pp. 1921 ◽  
Author(s):  
Daphne C. Voormolen ◽  
Juanita A. Haagsma ◽  
Suzanne Polinder ◽  
Andrew I.R. Maas ◽  
Ewout W. Steyerberg ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Odds Ratio ◽  
Post Injury ◽  
Chi Square ◽  
Time Points ◽  
Post Concussion Syndrome ◽  
Icd 10 ◽  
Baseline Covariates

The aim of this study was to assess the occurrence of post-concussion symptoms and post-concussion syndrome (PCS) in a large cohort of patients after complicated and uncomplicated mild traumatic brain injury (mTBI) at three and six months post-injury. Patients were included through the prospective cohort study: Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI). Patients enrolled with mTBI (Glasgow Coma Scale 13–15) were further differentiated into complicated and uncomplicated mTBI based on the presence or absence of computed tomography abnormalities, respectively. The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) assessed post-concussion symptoms and PCS according to the mapped ICD-10 classification method. The occurrence of post-concussion symptoms and syndrome at both time points was calculated. Chi square tests were used to test for differences between and within groups. Logistic regression was performed to analyse the association between complicated versus uncomplicated mTBI and the prevalence of PCS. Patients after complicated mTBI reported slightly more post-concussion symptoms compared to those after uncomplicated mTBI. A higher percentage of patients after complicated mTBI were classified as having PCS at three (complicated: 46% vs. uncomplicated: 35%) and six months (complicated: 43% vs. uncomplicated 34%). After adjusting for baseline covariates, the effect of complicated versus uncomplicated mTBI at three months appeared minimal: odds ratio 1.25 (95% confidence interval: 0.95–1.66). Although patients after complicated mTBI report slightly more post-concussion symptoms and show higher PCS rates compared to those after uncomplicated mTBI at three and six months, complicated mTBI was only found a weak indicator for these problems.

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.

The Speech-Language Pathologists' Role in Mild Traumatic Brain Injury for Middle and High School–Age Children: Viewpoints on Guidelines From the Centers for Disease Control and Prevention

2019 ◽  
Vol 28 (3) ◽  
pp. 1363-1370 ◽  
Author(s):  
Jessica Brown ◽  
Katy O'Brien ◽  
Kelly Knollman-Porter ◽  
Tracey Wallace
Keyword(s):  
High School ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Disease Control ◽  
Mild Traumatic Brain Injury ◽  
School Age Children ◽  
School Age ◽  
Speech Language Pathologists ◽  
Control And Prevention ◽  
Centers For Disease Control

Purpose The Centers for Disease Control and Prevention (CDC) recently released guidelines for rehabilitation professionals regarding the care of children with mild traumatic brain injury (mTBI). Given that mTBI impacts millions of children each year and can be particularly detrimental to children in middle and high school age groups, access to universal recommendations for management of postinjury symptoms is ideal. Method This viewpoint article examines the CDC guidelines and applies these recommendations directly to speech-language pathology practices. In particular, education, assessment, treatment, team management, and ongoing monitoring are discussed. In addition, suggested timelines regarding implementation of services by speech-language pathologists (SLPs) are provided. Specific focus is placed on adolescents (i.e., middle and high school–age children). Results SLPs are critical members of the rehabilitation team working with children with mTBI and should be involved in education, symptom monitoring, and assessment early in the recovery process. SLPs can also provide unique insight into the cognitive and linguistic challenges of these students and can serve to bridge the gap among rehabilitation and school-based professionals, the adolescent with brain injury, and their parents. Conclusion The guidelines provided by the CDC, along with evidence from the field of speech pathology, can guide SLPs to advocate for involvement in the care of adolescents with mTBI. More research is needed to enhance the evidence base for direct assessment and treatment with this population; however, SLPs can use their extensive knowledge and experience working with individuals with traumatic brain injury as a starting point for post-mTBI care.

Assessment of Cognitive-Communicative Disorders of Mild Traumatic Brain Injury Sustained in Combat

2009 ◽  
Vol 19 (2) ◽  
pp. 47-57 ◽  
Author(s):  
Christine Parrish ◽  
Carole Roth ◽  
Brooke Roberts ◽  
Gail Davie
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Psychological Health ◽  
Communication Disorders ◽  
Service Members ◽  
Patient Questionnaire ◽  
Speech Language Pathologists ◽  
Test Protocol ◽  
Communication Deficits

Abstract Background: Mild traumatic brain injury (mTBI) is recognized as the signature injury of the current conflicts in Iraq and Afghanistan, yet there remains limited understanding of the persisting cognitive deficits of mTBI sustained in combat. Speech-language pathologists (SLPs) have traditionally been responsible for evaluating and treating the cognitive-communication disorders following severe brain injuries. The evaluation instruments historically used are insensitive to the subtle deficits found in individuals with mTBI. Objectives: Based on the limited literature and clinical evidence describing traditional and current tests for measuring cognitive-communication deficits (CCD) of TBI, the strengths and weaknesses of the instruments are discussed relative to their use with mTBI. It is necessary to understand the nature and severity of CCD associated with mTBI for treatment planning and goal setting. Yet, the complexity of mTBI sustained in combat, which often co-occurs with PTSD and other psychological health and physiological issues, creates a clinical challenge for speech-language pathologists worldwide. The purpose of the paper is to explore methods for substantiating the nature and severity of CCD described by service members returning from combat. Methods: To better understand the nature of the functional cognitive-communication deficits described by service members returning from combat, a patient questionnaire and a test protocol were designed and administered to over 200 patients. Preliminary impressions are described addressing the nature of the deficits and the challenges faced in differentiating the etiologies of the CCD. Conclusions: Speech-language pathologists are challenged with evaluating, diagnosing, and treating the cognitive-communication deficits of mTBI resulting from combat-related injuries. Assessments that are sensitive to the functional deficits of mTBI are recommended. An interdisciplinary rehabilitation model is essential for differentially diagnosing the consequences of mTBI, PTSD, and other psychological and physical health concerns.

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