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  1. Traumatic Brain Injury (TBI)

    MedlinePlus

    ... A. (2008). Mild traumatic brain injury in U.S. soldiers returning from Iraq. New England Journal of Medicine, 358, 453–463. ... and Spotlights U.S. hospitals miss followup for suspected child abuse Q&A with NICHD Acting Director Catherine ...

  2. Traumatic Brain Injury (TBI) Data and Statistics

    MedlinePlus

    ... data.cdc.gov . Emergency Department Visits, Hospitalizations, and Deaths Rates of TBI-related Emergency Department Visits, Hospitalizations, ... related Hospitalizations by Age Group and Injury Mechanism Deaths Rates of TBI-related Deaths by Sex Rates ...

  3. How Do Health Care Providers Diagnose Traumatic Brain Injury (TBI)?

    MedlinePlus

    ... Information Clinical Trials Resources and Publications How do health care providers diagnose traumatic brain injury (TBI)? Skip sharing ... links Share this: Page Content To diagnose TBI, health care providers may use one or more tests that ...

  4. Neuroimaging biomarkers in mild traumatic brain injury (mTBI).

    PubMed

    Bigler, Erin D

    2013-09-01

    Reviewed herein are contemporary neuroimaging methods that detect abnormalities associated with mild traumatic brain injury (mTBI). Despite advances in demonstrating underlying neuropathology in a subset of individuals who sustain mTBI, considerable disagreement persists in neuropsychology about mTBI outcome and metrics for evaluation. This review outlines a thesis for the select use of sensitive neuroimaging methods as potential biomarkers of brain injury recognizing that the majority of individuals who sustain an mTBI recover without neuroimaging signs or neuropsychological sequelae detected with methods currently applied. Magnetic resonance imaging (MRI) provides several measures that could serve as mTBI biomarkers including the detection of hemosiderin and white matter abnormalities, assessment of white matter integrity derived from diffusion tensor imaging (DTI), and quantitative measures that directly assess neuroanatomy. Improved prediction of neuropsychological outcomes in mTBI may be achieved with the use of targeted neuroimaging markers.

  5. Genetics and outcomes after traumatic brain injury (TBI): What do we know about pediatric TBI?

    PubMed Central

    Kurowski, Brad; Martin, Lisa J.; Wade, Shari L.

    2013-01-01

    Human genetic association studies in individuals with traumatic brain injury (TBI) have increased rapidly over the past few years. Recently, several review articles evaluated the association of genetics with outcomes after TBI. However, almost all of the articles discussed in these reviews focused on adult TBI. The primary objective of this review is to gain a better understanding of which genes and/or genetic polymorphisms have been evaluated in pediatric TBI. Our initial search identified 113 articles. After review of these articles only 5 genetic association studies specific to pediatric TBI were identified. All five of these studies evaluated the apolipoprotein (APOE) gene. The study design and methods of these identified papers will be discussed. An additional search was then performed to evaluate genes beyond APOE that have been evaluated in adult TBI; findings from these studies are highlighted. Larger genetic studies will need to be performed in the future to better elucidate the association of APOE and other genes with outcomes after TBI in children. There is great potential to utilized genetic information to inform prognosis and management after TBI in children; however, we have much work ahead of us to reach the goal of individualized management. PMID:23023254

  6. TBI-ROC Part One: Understanding Traumatic Brain Injury--An Introduction

    ERIC Educational Resources Information Center

    Trudel, Tina M.; Scherer, Marcia J.; Elias, Eileen

    2011-01-01

    This article is the first of a multi-part series on traumatic brain injury (TBI). Historically, TBI has received very limited national public policy attention and support. However since it has become the signature injury of the military conflicts in Iraq and Afghanistan, TBI has gained the attention of elected officials, military leaders,…

  7. Increased brain activation during working memory processing after pediatric mild traumatic brain injury (mTBI)

    PubMed Central

    Westfall, Daniel R.; West, John D.; Bailey, Jessica N.; Arnold, Todd W.; Kersey, Patrick A.; Saykin, Andrew J.; McDonald, Brenna C.

    2016-01-01

    Purpose The neural substrate of post-concussive symptoms following the initial injury period after mild traumatic brain injury (mTBI) in pediatric populations remains poorly elucidated. This study examined neuropsychological, behavioral, and brain functioning in adolescents post-mTBI to assess whether persistent differences were detectable up to a year post-injury. Methods Nineteen adolescents (mean age 14.7 years) who experienced mTBI 3–12 months previously (mean 7.5 months) and 19 matched healthy controls (mean age 14.0 years) completed neuropsychological testing and an fMRI auditory-verbal N-back working memory task. Parents completed behavioral ratings. Results No between-group differences were found for cognition, behavior, or N-back task performance, though the expected decreased accuracy and increased reaction time as task difficulty increased were apparent. However, the mTBI group showed significantly greater brain activation than controls during the most difficult working memory task condition. Conclusion Greater working memory task-related activation was found in adolescents up to one year post-mTBI relative to controls, potentially indicating compensatory activation to support normal task performance. Differences in brain activation in the mTBI group so long after injury may indicate residual alterations in brain function much later than would be expected based on the typical pattern of natural recovery, which could have important clinical implications. PMID:26684070

  8. Mental Health Implications of Traumatic Brain Injury (TBI) in Children and Youth

    PubMed Central

    Schachar, Russell James; Park, Laura Seohyun; Dennis, Maureen

    2015-01-01

    Objective: Traumatic brain injury (TBI) is the most common cause of death and disability in children and adolescents. Psychopathology is an established risk factor for, and a frequent consequence of, TBI. This paper reviews the literature relating psychopathology and TBI. Method: Selective literature review. Results: The risk of sustaining a TBI is increased by pre-existing psychopathology (particularly ADHD and aggression) and psychosocial adversity. Even among individuals with no psychopathology prior to the injury, TBI is frequently followed by mental illness especially ADHD, personality change, conduct disorder and, less frequently, by post-traumatic stress and anxiety disorders. The outcome of TBI can be partially predicted by pre-injury adjustment and injury severity, but less well by age at injury. Few individuals receive treatment for mental illness following TBI. Conclusion: TBI has substantial relevance to mental health professionals and their clinical practice. Available evidence, while limited, indicates that the risk for TBI in children and adolescents is increased in the presence of several, potentially treatable mental health conditions and that the outcome of TBI involves a range of mental health problems, many of which are treatable. Prevention and management efforts targeting psychiatric risks and outcomes are an urgent priority. Child and adolescent mental health professionals can play a critical role in the prevention and treatment of TBI through advocacy, education, policy development and clinical practice. PMID:26379721

  9. The Impact of Previous Traumatic Brain Injury on Health and Functioning: A TRACK-TBI Study

    PubMed Central

    Spielman, Lisa; Singh, Ayushi; Gordon, Wayne A.; Lingsma, Hester F.; Maas, Andrew I.R.; Manley, Geoffrey T.; Mukherjee, Pratik; Okonkwo, David O.; Puccio, Ava M.; Schnyer, David M.; Valadka, Alex B.; Yue, John K.; Yuh, Esther L.; Casey, and the TRACK-TBI Investigators including: Scott S.; Cooper, Shelly R.; Cheong, Maxwell; Hricik, Allison J.; Knight, Emily E.; Menon, David K.; Morabito, Diane J.; Pacheco, Jennifer L.; Sinha, Tuhin K.; Vassar, Mary J.

    2013-01-01

    Abstract The idea that multiple traumatic brain injury (TBI) can have a cumulative detrimental effect on functioning is widely accepted. Most research supporting this idea comes from athlete samples, and it is not known whether remote history of previous TBI affects functioning after subsequent TBI in community-based samples. This study investigates whether a previous history of TBI with loss of consciousness (LOC) is associated with worse health and functioning in a sample of individuals who require emergency department care for current TBI. Twenty-three percent of the 586 individuals with current TBI in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study reported having sustained a previous TBI with LOC. Individuals with previous TBI were more likely to be unemployed (χ2=17.86; p=0.000), report a variety of chronic medical and psychiatric conditions (4.75≤χ2≥24.16; p<0.05), and report substance use (16.35≤χ2≥27.57; p<0.01) before the acute injury, compared to those with no previous TBI history. Those with a previous TBI had less-severe acute injuries, but experienced worse outcomes at 6-month follow-up. Results of a series of regression analyses controlling for demographics and acute injury severity indicated that individuals with previous TBI reported more mood symptoms, more postconcussive symptoms, lower life satisfaction, and had slower processing speed and poorer verbal learning, compared to those with no previous TBI history. These findings suggest that history of TBI with LOC may have important implications for health and psychological functioning after TBI in community-based samples. PMID:23924069

  10. Common biochemical defects linkage between post-traumatic stress disorders, mild traumatic brain injury (TBI) and penetrating TBI.

    PubMed

    Prasad, Kedar N; Bondy, Stephen C

    2015-03-01

    Post-traumatic stress disorder (PTSD) is a complex mental disorder with psychological and emotional components, caused by exposure to single or repeated extreme traumatic events found in war, terrorist attacks, natural or man-caused disasters, and by violent personal assaults and accidents. Mild traumatic brain injury (TBI) occurs when the brain is violently rocked back and forth within the skull following a blow to the head or neck as in contact sports, or when in close proximity to a blast pressure wave following detonation of explosives in the battlefield. Penetrating TBI occurs when an object penetrates the skull and damages the brain, and is caused by vehicle crashes, gunshot wound to the head, and exposure to solid fragments in the proximity of explosions, and other combat-related head injuries. Despite clinical studies and improved understanding of the mechanisms of cellular damage, prevention and treatment strategies for patients with PTSD and TBI remain unsatisfactory. To develop an improved plan for treating and impeding progression of PTSD and TBI, it is important to identify underlying biochemical changes that may play key role in the initiation and progression of these disorders. This review identifies three common biochemical events, namely oxidative stress, chronic inflammation and excitotoxicity that participate in the initiation and progression of these conditions. While these features are separately discussed, in many instances, they overlap. This review also addresses the goal of developing novel treatments and drug regimens, aimed at combating this triad of events common to, and underlying, injury to the brain.

  11. TBI-ROC Part Seven: Traumatic Brain Injury--Technologies to Support Memory and Cognition

    ERIC Educational Resources Information Center

    Scherer, Marcia; Elias, Eileen; Weider, Katie

    2010-01-01

    This article is the seventh of a multi-part series on traumatic brain injury (TBI). The six earlier articles in this series have discussed the individualized nature of TBI and its consequences, the rehabilitation continuum, and interventions at various points along the continuum. As noted throughout the articles, many individuals with TBI…

  12. What Are Common Traumatic Brain Injury (TBI) Symptoms?

    MedlinePlus

    ... person with TBI may or may not lose consciousness—loss of consciousness is not always a sign of severe TBI. ... with memory, concentration, attention, or thinking Loss of consciousness lasting a few seconds to minutes 1 Sensitivity ...

  13. The ABCs of TBI. Evidence-based guidelines for adult traumatic brain injury care.

    PubMed

    Dewall, Jeremy

    2010-04-01

    The images of Olympic athlete Nodar Kumaritasvili flying off his luge and contacting a fixed steel beam at the recent Winter Olympics in Vancouver, British Columbia, were shocking. But the resultant injuries and death of the young athlete were not surprising to EMS personnel who witnessed the incident, because training and experience with similar mechanisms of injury intuitively teach us that these types of patients are susceptible to traumatic brain injury (TBI). Worldwide, TBI is the leading injury cause of death and permanent disability. In the U.S. alone, 1.4 million cases of TBI present to emergency services every year. Many more cases go unreported and untreated. These TBIs lead to 235,000 hospitalizations and, ultimately, 50,000 deaths.(1) For instance, blunt trauma alone kills 1% of those affected, but when a TBI is also involved, the mortality rate increases to 30%.(2) Some 50% of those who die from TBI do so within the first two hours of injury, making emergent prehospital intervention critical.(3) Preventing secondary injury by proper prehospital management can save brain function and lives. PMID:20399377

  14. Managing behavioral health needs of veterans with traumatic brain injury (TBI) in primary care.

    PubMed

    King, Paul R; Wray, Laura O

    2012-12-01

    Traumatic brain injury (TBI) is a frequent occurrence in the United States, and has been given particular attention in the veteran population. Recent accounts have estimated TBI incidence rates as high as 20 % among US veterans who served in Afghanistan or Iraq, and many of these veterans experience a host of co-morbid concerns, including psychiatric complaints (such as depression and post-traumatic stress disorder), sleep disturbance, and substance abuse which may warrant referral to behavioral health specialists working in primary care settings. This paper reviews many common behavioral health concerns co-morbid with TBI, and suggests areas in which behavioral health specialists may assess, intervene, and help to facilitate holistic patient care beyond the acute phase of injury. The primary focus is on sequelae common to mild and moderate TBI which may more readily present in primary care clinics.

  15. Complementary and alternative medicine (CAM) following traumatic brain injury (TBI): Opportunities and challenges.

    PubMed

    Hernández, Theresa D; Brenner, Lisa A; Walter, Kristen H; Bormann, Jill E; Johansson, Birgitta

    2016-06-01

    Traumatic brain injury (TBI) is highly prevalent and occurs in a variety of populations. Because of the complexity of its sequelae, treatment strategies pose a challenge. Given this complexity, TBI provides a unique target of opportunity for complementary and alternative medicine (CAM) treatments. The present review describes and discusses current opportunitites and challenges associated with CAM research and clinical applications in civilian, veteran and military service populations. In addition to a brief overview of CAM, the translational capacity from basic to clinical research to clinical practice will be described. Finally, a systematic approach to developing an adoptable evidence base, with proof of effectiveness based on the literature will be discussed. Inherent in this discussion will be the methodological and ethical challenges associated with CAM research in those with TBI and associated comorbidities, specifically in terms of how these challenges relate to practice and policy issues, implementation and dissemination. This article is part of a Special Issue entitled SI:Brain injury and recovery.

  16. Combined SCI and TBI: Recovery of forelimb function after unilateral cervical spinal cord injury (SCI) is retarded by contralateral traumatic brain injury (TBI), and ipsilateral TBI balances the effects of SCI on paw placement

    PubMed Central

    Inoue, Tomoo; Lin, Amity; Ma, Xiaokui; McKenna, Stephen L.; Creasey, Graham H.; Manley, Geoffrey T.; Ferguson, Adam R.; Bresnahan, Jacqueline C.; Beattie, Michael S.

    2015-01-01

    A significant proportion (estimates range from 16–74%) of patients with spinal cord injury (SCI) have concomitant traumatic brain injury (TBI), and the combination often produces difficulties in planning and implementing rehabilitation strategies and drug therapies. For example, many of the drugs used to treat SCI may interfere with cognitive rehabilitation, and conversely drugs that are used to control seizures in TBI patients may undermine locomotor recovery after SCI. The current paper presents an experimental animal model for combined SCI and TBI to help drive mechanistic studies of dual diagnosis. Rats received a unilateral SCI (75 kdyn) at C5 vertebral level, a unilateral TBI (2.0 mm depth, 4.0 m/s velocity impact on the forelimb sensori-motor cortex), or both SCI + TBI. TBI was placed either contralateral or ipsilateral to the SCI. Behavioral recovery was examined using paw placement in a cylinder, grooming, open field locomotion, and the IBB cereal eating test. Over 6 weeks, in the paw placement test, SCI + contralateral TBI produced a profound deficit that failed to recover, but SCI + ipsilateral TBI increased the relative use of the paw on the SCI side. In the grooming test, SCI + contralateral TBI produced worse recovery than either lesion alone even though contralateral TBI alone produced no observable deficit. In the IBB forelimb test, SCI + contralateral TBI revealed a severe deficit that recovered in 3 weeks. For open field locomotion, SCI alone or in combination with TBI resulted in an initial deficit that recovered in 2 weeks. Thus, TBI and SCI affected forelimb function differently depending upon the test, reflecting different neural substrates underlying, for example, exploratory paw placement and stereotyped grooming. Concurrent SCI and TBI had significantly different effects on outcomes and recovery, depending upon laterality of the two lesions. Recovery of function after cervical SCI was retarded by the addition of a moderate TBI in the

  17. Patient Characterization Protocols for Psychophysiological Studies of Traumatic Brain Injury and Post-TBI Psychiatric Disorders

    PubMed Central

    Rapp, Paul E.; Rosenberg, Brenna M.; Keyser, David O.; Nathan, Dominic; Toruno, Kevin M.; Cellucci, Christopher J.; Albano, Alfonso M.; Wylie, Scott A.; Gibson, Douglas; Gilpin, Adele M. K.; Bashore, Theodore R.

    2013-01-01

    Psychophysiological investigations of traumatic brain injury (TBI) are being conducted for several reasons, including the objective of learning more about the underlying physiological mechanisms of the pathological processes that can be initiated by a head injury. Additional goals include the development of objective physiologically based measures that can be used to monitor the response to treatment and to identify minimally symptomatic individuals who are at risk of delayed-onset neuropsychiatric disorders following injury. Research programs studying TBI search for relationships between psychophysiological measures, particularly ERP (event-related potential) component properties (e.g., timing, amplitude, scalp distribution), and a participant’s clinical condition. Moreover, the complex relationships between brain injury and psychiatric disorders are receiving increased research attention, and ERP technologies are making contributions to this effort. This review has two objectives supporting such research efforts. The first is to review evidence indicating that TBI is a significant risk factor for post-injury neuropsychiatric disorders. The second objective is to introduce ERP researchers who are not familiar with neuropsychiatric assessment to the instruments that are available for characterizing TBI, post-concussion syndrome, and psychiatric disorders. Specific recommendations within this very large literature are made. We have proceeded on the assumption that, as is typically the case in an ERP laboratory, the investigators are not clinically qualified and that they will not have access to participant medical records. PMID:23885250

  18. Statistical machine learning to identify traumatic brain injury (TBI) from structural disconnections of white matter networks.

    PubMed

    Mitra, Jhimli; Shen, Kai-kai; Ghose, Soumya; Bourgeat, Pierrick; Fripp, Jurgen; Salvado, Olivier; Pannek, Kerstin; Taylor, D Jamie; Mathias, Jane L; Rose, Stephen

    2016-04-01

    Identifying diffuse axonal injury (DAI) in patients with traumatic brain injury (TBI) presenting with normal appearing radiological MRI presents a significant challenge. Neuroimaging methods such as diffusion MRI and probabilistic tractography, which probe the connectivity of neural networks, show significant promise. We present a machine learning approach to classify TBI participants primarily with mild traumatic brain injury (mTBI) based on altered structural connectivity patterns derived through the network based statistical analysis of structural connectomes generated from TBI and age-matched control groups. In this approach, higher order diffusion models were used to map white matter connections between 116 cortical and subcortical regions. Tracts between these regions were generated using probabilistic tracking and mean fractional anisotropy (FA) measures along these connections were encoded in the connectivity matrices. Network-based statistical analysis of the connectivity matrices was performed to identify the network differences between a representative subset of the two groups. The affected network connections provided the feature vectors for principal component analysis and subsequent classification by random forest. The validity of the approach was tested using data acquired from a total of 179 TBI patients and 146 controls participants. The analysis revealed altered connectivity within a number of intra- and inter-hemispheric white matter pathways associated with DAI, in consensus with existing literature. A mean classification accuracy of 68.16%±1.81% and mean sensitivity of 80.0%±2.36% were achieved in correctly classifying the TBI patients evaluated on the subset of the participants that was not used for the statistical analysis, in a 10-fold cross-validation framework. These results highlight the potential for statistical machine learning approaches applied to structural connectomes to identify patients with diffusive axonal injury. PMID

  19. Longitudinal outcome and recovery of social problems after pediatric traumatic brain injury (TBI): Contribution of brain insult and family environment.

    PubMed

    Ryan, Nicholas P; van Bijnen, Loeka; Catroppa, Cathy; Beauchamp, Miriam H; Crossley, Louise; Hearps, Stephen; Anderson, Vicki

    2016-04-01

    Pediatric traumatic brain injury (TBI) can result in a range of social impairments, however longitudinal recovery is not well characterized, and clinicians are poorly equipped to identify children at risk for persisting difficulties. Using a longitudinal prospective design, this study aimed to evaluate the contribution of injury and non-injury related risk and resilience factors to longitudinal outcome and recovery of social problems from 12- to 24-months post-TBI. 78 children with TBI (injury age: 5.0-15.0 years) and 40 age and gender-matched typically developing (TD) children underwent magnetic resonance imaging including a susceptibility-weighted imaging (SWI) sequence 2-8 weeks post-injury (M=39.25, SD=27.64 days). At 12 and 24-months post- injury, parents completed questionnaires rating their child's social functioning, and environmental factors including socioeconomic status, caregiver mental health and family functioning. Results revealed that longitudinal recovery profiles differed as a function of injury severity, such that among children with severe TBI, social problems significantly increased from 12- to 24-months post-injury, and were found to be significantly worse than TD controls and children with mild and moderate TBI. In contrast, children with mild and moderate injuries showed few problems at 12-months post-injury and little change over time. Pre-injury environment and SWI did not significantly contribute to outcome at 24-months, however concurrent caregiver mental health and family functioning explained a large and significant proportion of variance in these outcomes. Overall, this study shows that longitudinal recovery profiles differ as a function of injury severity, with evidence for late-emerging social problems among children with severe TBI. Poorer long-term social outcomes were associated with family dysfunction and poorer caregiver mental health at 24-months post injury, suggesting that efforts to optimize the child's environment and

  20. Longitudinal outcome and recovery of social problems after pediatric traumatic brain injury (TBI): Contribution of brain insult and family environment.

    PubMed

    Ryan, Nicholas P; van Bijnen, Loeka; Catroppa, Cathy; Beauchamp, Miriam H; Crossley, Louise; Hearps, Stephen; Anderson, Vicki

    2016-04-01

    Pediatric traumatic brain injury (TBI) can result in a range of social impairments, however longitudinal recovery is not well characterized, and clinicians are poorly equipped to identify children at risk for persisting difficulties. Using a longitudinal prospective design, this study aimed to evaluate the contribution of injury and non-injury related risk and resilience factors to longitudinal outcome and recovery of social problems from 12- to 24-months post-TBI. 78 children with TBI (injury age: 5.0-15.0 years) and 40 age and gender-matched typically developing (TD) children underwent magnetic resonance imaging including a susceptibility-weighted imaging (SWI) sequence 2-8 weeks post-injury (M=39.25, SD=27.64 days). At 12 and 24-months post- injury, parents completed questionnaires rating their child's social functioning, and environmental factors including socioeconomic status, caregiver mental health and family functioning. Results revealed that longitudinal recovery profiles differed as a function of injury severity, such that among children with severe TBI, social problems significantly increased from 12- to 24-months post-injury, and were found to be significantly worse than TD controls and children with mild and moderate TBI. In contrast, children with mild and moderate injuries showed few problems at 12-months post-injury and little change over time. Pre-injury environment and SWI did not significantly contribute to outcome at 24-months, however concurrent caregiver mental health and family functioning explained a large and significant proportion of variance in these outcomes. Overall, this study shows that longitudinal recovery profiles differ as a function of injury severity, with evidence for late-emerging social problems among children with severe TBI. Poorer long-term social outcomes were associated with family dysfunction and poorer caregiver mental health at 24-months post injury, suggesting that efforts to optimize the child's environment and

  1. NIR light propagation in a digital head model for traumatic brain injury (TBI).

    PubMed

    Francis, Robert; Khan, Bilal; Alexandrakis, George; Florence, James; MacFarlane, Duncan

    2015-09-01

    Near infrared spectroscopy (NIRS) is capable of detecting and monitoring acute changes in cerebral blood volume and oxygenation associated with traumatic brain injury (TBI). Wavelength selection, source-detector separation, optode density, and detector sensitivity are key design parameters that determine the imaging depth, chromophore separability, and, ultimately, clinical usefulness of a NIRS instrument. We present simulation results of NIR light propagation in a digital head model as it relates to the ability to detect intracranial hematomas and monitor the peri-hematomal tissue viability. These results inform NIRS instrument design specific to TBI diagnosis and monitoring.

  2. NIR light propagation in a digital head model for traumatic brain injury (TBI).

    PubMed

    Francis, Robert; Khan, Bilal; Alexandrakis, George; Florence, James; MacFarlane, Duncan

    2015-09-01

    Near infrared spectroscopy (NIRS) is capable of detecting and monitoring acute changes in cerebral blood volume and oxygenation associated with traumatic brain injury (TBI). Wavelength selection, source-detector separation, optode density, and detector sensitivity are key design parameters that determine the imaging depth, chromophore separability, and, ultimately, clinical usefulness of a NIRS instrument. We present simulation results of NIR light propagation in a digital head model as it relates to the ability to detect intracranial hematomas and monitor the peri-hematomal tissue viability. These results inform NIRS instrument design specific to TBI diagnosis and monitoring. PMID:26417498

  3. NIR light propagation in a digital head model for traumatic brain injury (TBI)

    PubMed Central

    Francis, Robert; Khan, Bilal; Alexandrakis, George; Florence, James; MacFarlane, Duncan

    2015-01-01

    Near infrared spectroscopy (NIRS) is capable of detecting and monitoring acute changes in cerebral blood volume and oxygenation associated with traumatic brain injury (TBI). Wavelength selection, source-detector separation, optode density, and detector sensitivity are key design parameters that determine the imaging depth, chromophore separability, and, ultimately, clinical usefulness of a NIRS instrument. We present simulation results of NIR light propagation in a digital head model as it relates to the ability to detect intracranial hematomas and monitor the peri-hematomal tissue viability. These results inform NIRS instrument design specific to TBI diagnosis and monitoring. PMID:26417498

  4. Thioredoxin-Mimetic-Peptides Protect Cognitive Function after Mild Traumatic Brain Injury (mTBI)

    PubMed Central

    Baratz-Goldstein, Renana; Deselms, Hanna; Heim, Leore Raphael; Khomski, Lena; Hoffer, Barry J.

    2016-01-01

    Mild traumatic brain injury (mTBI) is recognized as a common injury among children, sportsmen, and elderly population. mTBI lacks visible objective structural brain damage but patients frequently suffer from long-lasting cognitive, behavioral and emotional difficulties associated with biochemical and cellular changes. Currently there is no effective treatment for patients with mTBI. The thioredoxin reductase/thioredoxin pathway (TrxR/Trx1) has both anti-inflammatory and anti-oxidative properties. If the system is compromised, Trx1 remains oxidized and triggers cell death via an ASK1-Trx1 signal transduction mechanism. We previously showed tri and tetra peptides which were derived from the canonical -CxxC- motif of the Trx1-active site, called thioredoxin mimetic (TXM) peptides, reversed inflammatory and oxidative stress damage mimicking Trx1 activity. Here, TXM-peptides were examined for protecting cognitive function following weight drop closed-head injury in a mouse model of mTBI. TXM-CB3 (AcCys-Pro-CysNH2), TXM-CB13 (DY-70; AcCys-Met-Lys-CysNH2) or AD4 (ACysNH2) were administered at 50 mg/kg, 60 min after injury and cognitive performance was monitored by the novel-object-recognition and Y-maze tests. Behavioral deficits subsequent to mTBI injury were reversed by a single dose of TXM-CB3, TXM-CB13 and, to a lesser extent, by AD4. TXM-CB13 similar to TXM-CB3 and AD4 reversed oxidative stress-induced phosphorylation of mitogen-activated kinases, p38MAPK and c-Jun N-terminal kinase, (JNK) in human neuronal SH-SY5Y cells. We conclude that significantly improved cognitive behavior post mTBI by the TXM-peptides could result from anti-apoptotic, and/or anti-inflammatory activities. Future preclinical studies are required to establish the TXM-peptides as potential therapeutic drugs for brain injuries. PMID:27285176

  5. Thioredoxin-Mimetic-Peptides Protect Cognitive Function after Mild Traumatic Brain Injury (mTBI).

    PubMed

    Baratz-Goldstein, Renana; Deselms, Hanna; Heim, Leore Raphael; Khomski, Lena; Hoffer, Barry J; Atlas, Daphne; Pick, Chaim G

    2016-01-01

    Mild traumatic brain injury (mTBI) is recognized as a common injury among children, sportsmen, and elderly population. mTBI lacks visible objective structural brain damage but patients frequently suffer from long-lasting cognitive, behavioral and emotional difficulties associated with biochemical and cellular changes. Currently there is no effective treatment for patients with mTBI. The thioredoxin reductase/thioredoxin pathway (TrxR/Trx1) has both anti-inflammatory and anti-oxidative properties. If the system is compromised, Trx1 remains oxidized and triggers cell death via an ASK1-Trx1 signal transduction mechanism. We previously showed tri and tetra peptides which were derived from the canonical -CxxC- motif of the Trx1-active site, called thioredoxin mimetic (TXM) peptides, reversed inflammatory and oxidative stress damage mimicking Trx1 activity. Here, TXM-peptides were examined for protecting cognitive function following weight drop closed-head injury in a mouse model of mTBI. TXM-CB3 (AcCys-Pro-CysNH2), TXM-CB13 (DY-70; AcCys-Met-Lys-CysNH2) or AD4 (ACysNH2) were administered at 50 mg/kg, 60 min after injury and cognitive performance was monitored by the novel-object-recognition and Y-maze tests. Behavioral deficits subsequent to mTBI injury were reversed by a single dose of TXM-CB3, TXM-CB13 and, to a lesser extent, by AD4. TXM-CB13 similar to TXM-CB3 and AD4 reversed oxidative stress-induced phosphorylation of mitogen-activated kinases, p38MAPK and c-Jun N-terminal kinase, (JNK) in human neuronal SH-SY5Y cells. We conclude that significantly improved cognitive behavior post mTBI by the TXM-peptides could result from anti-apoptotic, and/or anti-inflammatory activities. Future preclinical studies are required to establish the TXM-peptides as potential therapeutic drugs for brain injuries. PMID:27285176

  6. Chapter 1 Common Data Elements and Federal Interagency Traumatic Brain Injury Research Informatics System for TBI Research.

    PubMed

    Thompson, Hilaire J; Vavilala, Monica S; Rivara, Frederick P

    2015-01-01

    Despite increased attention to traumatic brain injury (TBI), there remains no specific treatment and available interventions focus rather on the prevention of secondary injury. One of the reasons posited for the lack of a successful therapy is the amalgamation of various types of injuries under the same severity category in clinical trials. Informatics approaches have been suggested as a means to develop an improved classification system for TBI. As a result of federal interagency efforts, common data elements (CDEs) for TBI have now been developed. Further, the Federal Interagency Traumatic Brain Injury Research Informatics System (FITBIR) has been created and is now available for TBI researchers to both add and retrieve data. This chapter will discuss the goals, development, and evolution of the CDEs and FITBIR and discuss how these tools can be used to support TBI research. A specific exemplar using the CDEs and lessons learned from working with the CDEs and FITBIR are included to aid future researchers.

  7. TBI-QOL: Development and Calibration of Item Banks to Measure Patient Reported Outcomes Following Traumatic Brain Injury

    PubMed Central

    Tulsky, David S.; Kisala, Pamela A.; Victorson, David; Carlozzi, Noelle; Bushnik, Tamara; Sherer, Mark; Choi, Seung W.; Heinemann, Allen W.; Chiaravalloti, Nancy; Sander, Angelle M.; Englander, Jeffrey; Hanks, Robin; Kolakowsky-Hayner, Stephanie; Roth, Elliot; Gershon, Richard; Rosenthal, Mitchell; Cella, David

    2016-01-01

    Objective: To use a patient-centered approach or participatory action research design combined with advanced psychometrics to develop a comprehensive patient-reported outcomes (PRO) measurement system specifically for individuals with traumatic brain injury (TBI). This TBI Quality-of-Life (TBI-QOL) measurement system expands the work of other large PRO measurement initiatives, that is, the Patient-Reported Outcomes Measurement Information System and the Neurology Quality-of-Life measurement initiative. Setting: Five TBI Model Systems centers across the United States. Participants: Adults with TBI. Design: Classical and modern test development methodologies were used. Qualitative input was obtained from individuals with TBI, TBI clinicians, and caregivers of individuals with TBI through multiple methods, including focus groups, individual interviews, patient consultation, and cognitive debriefing interviews. Item pools were field tested in a large multisite sample (n = 675) and calibrated using item response theory methods. Main Outcomes Measures: Twenty-two TBI-QOL item banks/scales. Results: The TBI-QOL consists of 20 independent calibrated item banks and 2 uncalibrated scales that measure physical, emotional, cognitive, and social aspects of health-related quality of life. Conclusions: The TBI-QOL measurement system has potential as a common data element in TBI research and to enhance collection of health-related quality-of-life and PRO data in rehabilitation research and clinical settings. PMID:25931184

  8. [Late-onset Neurodegenerative Diseases Following Traumatic Brain Injury: Chronic Traumatic Encephalopathy (CTE) and Alzheimer's Disease Secondary to TBI (AD-TBI)].

    PubMed

    Takahata, Keisuke; Tabuchi, Hajime; Mimura, Masaru

    2016-07-01

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease, which is associated with mild repetitive traumatic brain injury (TBI). This long-term and progressive symptom due to TBI was initially called punch-drunk syndrome or dementia pugilistica, since it was believed to be associated with boxing. However, serial neuropathological studies of mild repetitive TBI in the last decade have revealed that CTE occurs not only in boxers but also in a wider population including American football players, wrestlers, and military personnel. CTE has gained large public interest owing to dramatic cases involving retired professional athletes wherein serious behavioral problems and tragic incidents were reported. Unlike mild repetitive TBI, a single episode of severe TBI can cause another type of late-onset neuropsychiatric disease including Alzheimer's disease (AD). Several epidemiological studies have shown that a single episode of severe TBI is one of the major risk factors of AD. Pathologically, both AD and CTE are characterized by abnormal accumulations of hyperphosphorylated tau proteins. However, recent neuropathological studies revealed that CTE demonstrates a unique pattern of tau pathology in neurons and astrocytes, and accumulation of other misfolded proteins such as TDP-43. Currently, no reliable biomarkers of late-onset neurodegenerative diseases following TBI are available, and a definitive diagnosis can be made only via postmortem neuropathological examination. Development in neuroimaging techniques such as tau and amyloid positron emission tomography imaging might not only enable early diagnosis of CTE, but also contribute to the interventions for prevention of late-onset neurodegenerative diseases following TBI. Further studies are necessary to elucidate the mechanisms of neurodegeneration in the living brain of patients with TBI. PMID:27395469

  9. Functional MRI of mild traumatic brain injury (mTBI): progress and perspectives from the first decade of studies

    PubMed Central

    Saykin, Andrew J.; McAllister, Thomas W.

    2014-01-01

    Mild traumatic brain injury (mTBI) represents the great majority of traumatic brain injuries, and is a common medical problem affecting cognitive and vocational functioning as well as quality of life in some individuals. Functional MRI (fMRI) is an important research method for investigating the neuroanatomic substrates of cognitive disorders and their treatment. Surprisingly, however, relatively little research has utilized fMRI to examine alterations in brain functioning after mTBI. This article provides a critical overview of the published fMRI research on mTBI to date. These topics include examination of frontal lobe/ executive functions such as working memory, as well as episodic memory and resting state/functional connectivity. mTBI has also been investigated in military populations where studies have focused on effects of blast injury and comorbid conditions such as post-traumatic stress disorder and major depressive disorder. Finally, we address fMRI evaluations of response to behavioral or pharmacological challenges and interventions targeting cognitive and behavioral sequelae of mTBI. The review concludes with identification and discussion of gaps in current knowledge and future directions for fMRI studies of mTBI. The authors conclude that fMRI in combination with related methods can be expected to play an increasing role in research related to studies of pathophysiological mechanisms of the sequelae of mTBI as well as in diagnosis and treatment monitoring. PMID:22618832

  10. Characterizing the spatial distribution of microhemorrhages resulting from Traumatic Brain Injury (TBI)

    NASA Astrophysics Data System (ADS)

    Li, Ningzhi; Chou, Yi-Yu; Shiee, Navid; Chan, Leighton; Pham, Dzung L.; Butman, John A.

    2014-03-01

    This study examines the spatial distribution of microhemorrhages defined using susceptibility weighted images (SWI) in 46 patients with Traumatic Brain Injury (TBI) and applying region of interest (ROI) analysis using a brain atlas. SWI and 3D T1-weighted images were acquired on a 3T clinical Siemens scanner. A neuroradiologist reviewed all SWI images and manually labeled all identified microhemorrhages. To characterize the spatial distribution of microhemorrhages in standard Montreal Neurological Institute (MNI) space, the T1-weighted images were nonlinearly registered to the MNI template. This transformation was then applied to the co-registered SWI images and to the microhemorrhage coordinates. The frequencies of microhemorrhages were determined in major structures from ROIs defined in the digital Talairach brain atlas and in white matter tracts defined using a diffusion tensor imaging atlas. A total of 629 microhemorrhages were found with an average of 22±42 (range=1-179) in the 24 positive TBI patients. Microhemorrhages mostly congregated around the periphery of the brain and were fairly symmetrically distributed, although a number were found in the corpus callosum. From Talairach ROI analysis, microhemorrhages were most prevalent in the frontal lobes (65.1%). Restricting the analysis to WM tracts, microhemorrhages were primarily found in the corpus callosum (56.9%).

  11. Symptomatology and functional outcome in mild traumatic brain injury: results from the prospective TRACK-TBI study.

    PubMed

    McMahon, Paul; Hricik, Allison; Yue, John K; Puccio, Ava M; Inoue, Tomoo; Lingsma, Hester F; Beers, Sue R; Gordon, Wayne A; Valadka, Alex B; Manley, Geoffrey T; Okonkwo, David O

    2014-01-01

    Mild Traumatic Brain Injury (mTBI), or concussion, is a major public health concern. There is controversy in the literature regarding the true incidence of postconcussion syndrome (PCS), with the constellation of physical, cognitive, emotional, and sleep symptoms after mTBI. In the current study, we report on the incidence and evolution of PCS symptoms and patient outcomes after mTBI at 3, 6, and 12 months in a large, prospective cohort of mTBI patients. Participants were identified as part of the prospective, multi-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study. The study population was mTBI patients (Glasgow Coma Scale score of 13-15) presenting to the emergency department, including patients with a negative head computed tomography discharged to home without admission to hospital; 375 mTBI subjects were included in the analysis. At both 6 and 12 months after mTBI, 82% (n=250 of 305 and n=163 of 199, respectively) of patients reported at least one PCS symptom. Further, 44.5 and 40.3% of patients had significantly reduced Satisfaction With Life scores at 6 and 12 months, respectively. At 3 months after injury, 33% of the mTBI subjects were functionally impaired (Glasgow Outcome Scale-Extended score ≤6); 22.4% of the mTBI subjects available for follow-up were still below full functional status at 1 year after injury. The term "mild" continues to be a misnomer for this patient population and underscores the critical need for evolving classification strategies for TBI for targeted therapy.

  12. Neuronal damage and functional deficits are ameliorated by inhibition of aquaporin and HIF1α after traumatic brain injury (TBI).

    PubMed

    Shenaq, Mohammed; Kassem, Hassan; Peng, Changya; Schafer, Steven; Ding, Jamie Y; Fredrickson, Vance; Guthikonda, Murali; Kreipke, Christian W; Rafols, José A; Ding, Yuchuan

    2012-12-15

    The present study, using a rodent model of closed-head diffuse traumatic brain injury (TBI), investigated the role of dysregulated aquaporins (AQP) 4 and 9, as well as hypoxia inducible factor -1α(HIF-1α) on brain edema formation, neuronal injury, and functional deficits. TBI was induced in adult (400-425 g), male Sprague-Dawley rats using a modified Marmarou's head impact-acceleration device (450 g weight dropped from 2m height). Animals in each treatment group were administered intravenous anti-AQP4 or -AQP9 antibodies or 2-Methoxyestradiol (2ME2, an inhibitor of HIF-1α) 30 min after injury. At 24h post-TBI, animals (n=6 each group) were sacrificed to examine the extent of brain edema by water content, as well as protein expression of AQP and HIF-1α by Western immune-blotting. At 48-hours post-TBI, neuronal injury (n=8 each group) was assessed by FluoroJade (FJ) histochemistry. Spatial learning and memory deficits were evaluated by radial arm maze (n=8 each group) up to 21 days post-TBI. Compared to non-injured controls, significant (p<0.05) increases in the expression of AQP4 and -9 were detected in the brains of injured animals. In addition, significant (p<0.05) brain edema after TBI was associated with increases (p <0.05) both in neuronal injury (FJ labeling) and neurobehavioral deficits. Selective inhibition of either AQP4 or -9, or HIF-1α significantly (p<0.05) decreased the expression of the proteins. In addition, inhibition of the AQPs and HIF-1α significantly (p<0.05) ameliorated brain edema, as well as the number of injured neurons in cortical layers II/III and V/VI, striatum and hippocampal regions CA1/CA3. Finally, compared to the non-treated TBI animals, AQP or HIF-1α inhibition significantly (p<0.01) improved neurobehavioral outcomes after TBI. Taken together, the present data supports a causal relation between HIF-AQP mediated cerebral edema, secondary neuronal injury, and tertiary behavioral deficits post-TBI. The data further suggests that

  13. Greater neurobehavioral deficits occur in adult mice after repeated, as compared to single, mild traumatic brain injury (mTBI).

    PubMed

    Nichols, Jessica N; Deshane, Alok S; Niedzielko, Tracy L; Smith, Cory D; Floyd, Candace L

    2016-02-01

    Mild traumatic brain injury (mTBI) accounts for the majority of all brain injuries and affected individuals typically experience some extent of cognitive and/or neuropsychiatric deficits. Given that repeated mTBIs often result in worsened prognosis, the cumulative effect of repeated mTBIs is an area of clinical concern and on-going pre-clinical research. Animal models are critical in elucidating the underlying mechanisms of single and repeated mTBI-associated deficits, but the neurobehavioral sequelae produced by these models have not been well characterized. Thus, we sought to evaluate the behavioral changes incurred after single and repeated mTBIs in mice utilizing a modified impact-acceleration model. Mice in the mTBI group received 1 impact while the repeated mTBI group received 3 impacts with an inter-injury interval of 24h. Classic behavior evaluations included the Morris water maze (MWM) to assess learning and memory, elevated plus maze (EPM) for anxiety, and forced swim test (FST) for depression/helplessness. Additionally, species-typical behaviors were evaluated with the marble-burying and nestlet shredding tests to determine motivation and apathy. Non-invasive vibration platforms were used to examine sleep patterns post-mTBI. We found that the repeated mTBI mice demonstrated deficits in MWM testing and poorer performance on species-typical behaviors. While neither single nor repeated mTBI affected behavior in the EPM or FST, sleep disturbances were observed after both single and repeated mTBI. Here, we conclude that behavioral alterations shown after repeated mTBI resemble several of the deficits or disturbances reported by patients, thus demonstrating the relevance of this murine model to study repeated mTBIs.

  14. Greater neurobehavioral deficits occur in adult mice after repeated, as compared to single, mild traumatic brain injury (mTBI).

    PubMed

    Nichols, Jessica N; Deshane, Alok S; Niedzielko, Tracy L; Smith, Cory D; Floyd, Candace L

    2016-02-01

    Mild traumatic brain injury (mTBI) accounts for the majority of all brain injuries and affected individuals typically experience some extent of cognitive and/or neuropsychiatric deficits. Given that repeated mTBIs often result in worsened prognosis, the cumulative effect of repeated mTBIs is an area of clinical concern and on-going pre-clinical research. Animal models are critical in elucidating the underlying mechanisms of single and repeated mTBI-associated deficits, but the neurobehavioral sequelae produced by these models have not been well characterized. Thus, we sought to evaluate the behavioral changes incurred after single and repeated mTBIs in mice utilizing a modified impact-acceleration model. Mice in the mTBI group received 1 impact while the repeated mTBI group received 3 impacts with an inter-injury interval of 24h. Classic behavior evaluations included the Morris water maze (MWM) to assess learning and memory, elevated plus maze (EPM) for anxiety, and forced swim test (FST) for depression/helplessness. Additionally, species-typical behaviors were evaluated with the marble-burying and nestlet shredding tests to determine motivation and apathy. Non-invasive vibration platforms were used to examine sleep patterns post-mTBI. We found that the repeated mTBI mice demonstrated deficits in MWM testing and poorer performance on species-typical behaviors. While neither single nor repeated mTBI affected behavior in the EPM or FST, sleep disturbances were observed after both single and repeated mTBI. Here, we conclude that behavioral alterations shown after repeated mTBI resemble several of the deficits or disturbances reported by patients, thus demonstrating the relevance of this murine model to study repeated mTBIs. PMID:26542813

  15. Diffusion Tensor Imaging for Outcome Prediction in Mild Traumatic Brain Injury: A TRACK-TBI Study

    PubMed Central

    Yuh, Esther L.; Cooper, Shelly R.; Mukherjee, Pratik; Yue, John K.; Lingsma, Hester F.; Gordon, Wayne A.; Valadka, Alex B.; Okonkwo, David O.; Schnyer, David M.; Vassar, Mary J.; Maas, Andrew I.R.; Casey, Scott S.; Cheong, Maxwell; Dams-O'Connor, Kristen; Hricik, Allison J.; Inoue, Tomoo; Menon, David K.; Morabito, Diane J.; Pacheco, Jennifer L.; Puccio, Ava M.; Sinha, Tuhin K.

    2014-01-01

    Abstract We evaluated 3T diffusion tensor imaging (DTI) for white matter injury in 76 adult mild traumatic brain injury (mTBI) patients at the semiacute stage (11.2±3.3 days), employing both whole-brain voxel-wise and region-of-interest (ROI) approaches. The subgroup of 32 patients with any traumatic intracranial lesion on either day-of-injury computed tomography (CT) or semiacute magnetic resonance imaging (MRI) demonstrated reduced fractional anisotropy (FA) in numerous white matter tracts, compared to 50 control subjects. In contrast, 44 CT/MRI-negative mTBI patients demonstrated no significant difference in any DTI parameter, compared to controls. To determine the clinical relevance of DTI, we evaluated correlations between 3- and 6-month outcome and imaging, demographic/socioeconomic, and clinical predictors. Statistically significant univariable predictors of 3-month Glasgow Outcome Scale-Extended (GOS-E) included MRI evidence for contusion (odds ratio [OR] 4.9 per unit decrease in GOS-E; p=0.01), ≥1 ROI with severely reduced FA (OR, 3.9; p=0.005), neuropsychiatric history (OR, 3.3; p=0.02), age (OR, 1.07/year; p=0.002), and years of education (OR, 0.79/year; p=0.01). Significant predictors of 6-month GOS-E included ≥1 ROI with severely reduced FA (OR, 2.7; p=0.048), neuropsychiatric history (OR, 3.7; p=0.01), and years of education (OR, 0.82/year; p=0.03). For the subset of 37 patients lacking neuropsychiatric and substance abuse history, MRI surpassed all other predictors for both 3- and 6-month outcome prediction. This is the first study to compare DTI in individual mTBI patients to conventional imaging, clinical, and demographic/socioeconomic characteristics for outcome prediction. DTI demonstrated utility in an inclusive group of patients with heterogeneous backgrounds, as well as in a subset of patients without neuropsychiatric or substance abuse history. PMID:24742275

  16. Post-traumatic anosmia in patients with mild traumatic brain injury (mTBI): A systematic and illustrated review

    PubMed Central

    Proskynitopoulos, Phileas J.; Stippler, Martina; Kasper, Ekkehard M.

    2016-01-01

    Background: Olfactory dysfunction (OD) is a disorder associated with traumatic brain injury (TBI), which is prevalent in up to 20% of patients suffering from TBI. Nevertheless, most studies focusing on the relationship between OD and TBIs do not differentiate between the different types of TBI (mild, medium, and severe). In this paper, we conducted a comprehensive and systematic review of the existing literature for the association between mild TBI (mTBI) and OD in order to examine their relationship, focusing on its neurosurgical management and the radiographic characteristics. Methods: The MEDLINE database was systematically reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We found 66 articles, of which 10 fulfilled our criteria. Results: All except two studies reported a significant association between trauma severity and olfaction. Two studies found a negative correlation between TBI severity and olfactory bulb volume with one reporting an r value of −0.62). Three studies reported an association between the observation of radiographic intracranial hemorrhage or skull base fractures and the history of TBI. Conclusion: According to our search results, we conclude that OD is a prevalent but underdiagnosed problem in mTBI. Because OD is associated with a significant decrease in quality of life, we think that neurosurgical teams need to asses olfactory function in mTBI patients when they report to clinics. To illustrate this scenario, we include two distinct cases of patients with anosmia after mTBI in this review. Finally, we suggest a treatment algorithm for patients with mTBI so that a possible OD can be diagnosed and treated as early as possible. PMID:27213113

  17. Sustained attention in traumatic brain injury (TBI) and healthy controls: enhanced sensitivity with dual-task load.

    PubMed

    Dockree, Paul M; Bellgrove, Mark A; O'Keeffe, Fiadhnait M; Moloney, Pauline; Aimola, Lina; Carton, Simone; Robertson, Ian H

    2006-01-01

    Poor sustained attention or alertness is a common consequence of traumatic brain injury (TBI) and has a considerable impact on the recovery and adjustment of TBI patients. Here, we describe the development of a sensitive laboratory task in healthy subjects (Experiment 1) and its enhanced sensitivity to sustained attention errors in TBI patients (Experiment 2). The task involves withholding a key press to an infrequent no-go target embedded within a predictable sequence of numbers (primary goal) and detecting grey-coloured targets within the sequence (secondary goal). In Experiment 1, we report that neurologically healthy subjects are more likely to experience a lapse of attention and neglect the primary task goal, despite ceiling performance on the secondary task. Further, attentional lapses on the task correlated with everyday attentional failures and variability of response time. In Experiment 2, the task discriminates between TBI patients and controls with a large effect size. The dual-task yields more errors in both groups than a simple task involving only the primary goal that is commonly used to detect sustained attention deficits in neurologically impaired groups. TBI patients' errors also correlated with everyday cognitive failures and variability of response time. This was not the case in the simple version of the task. We conclude that the dual-task demand associated with this task enhances its sensitivity as a measure of sustained attention in TBI patients and neurologically healthy controls that relates to everyday slips of attention.

  18. Early Cerebral Circulation Disturbance in Patients Suffering from Severe Traumatic Brain Injury (TBI): A Xenon CT and Perfusion CT Study

    PubMed Central

    HONDA, Mitsuru; ICHIBAYASHI, Ryo; YOKOMURO, Hiroki; YOSHIHARA, Katsunori; MASUDA, Hiroyuki; HAGA, Daisuke; SEIKI, Yoshikatsu; KUDOH, Chiaki; KISHI, Taichi

    2016-01-01

    Traumatic brain injury (TBI) is widely known to cause dynamic changes in cerebral blood flow (CBF). Ischemia is a common and deleterious secondary injury following TBI. Detecting early ischemia in TBI patients is important to prevent further advancement and deterioration of the brain tissue. The purpose of this study was to clarify the cerebral circulatory disturbance during the early phase and whether it can be used to predict patient outcome. A total of 90 patients with TBI underwent a xenon-computed tomography (Xe-CT) and subsequently perfusion CT to evaluate the cerebral circulation on days 1–3. We measured CBF using Xe-CT and mean transit time (MTT: the width between two inflection points [maximum upward slope and maximum downward slope from inflow to outflow of the contrast agent]) using perfusion CT and calculated the cerebral blood volume (CBV) using the AZ-7000W98 computer system. The relationships of the hemodynamic parameters CBF, MTT, and CBV to the Glasgow Coma Scale (GCS) score and the Glasgow Outcome Scale (GOS) score were examined. There were no significant differences in CBF, MTT, and CBV among GCS3–4, GCS5–6, and GCS7–8 groups. The patients with a favorable outcome (GR and MD) had significantly higher CBF and lower MTT than those with an unfavorable one (SD, VS, or D). The discriminant analysis of these parameters could predict patient outcome with a probability of 70.6%. During the early phase, CBF reduction and MTT prolongation might influence the clinical outcome of TBI. These parameters are helpful for evaluating the severity of cerebral circulatory disturbance and predicting the outcome of TBI patients. PMID:27356957

  19. Early Cerebral Circulation Disturbance in Patients Suffering from Severe Traumatic Brain Injury (TBI): A Xenon CT and Perfusion CT Study.

    PubMed

    Honda, Mitsuru; Ichibayashi, Ryo; Yokomuro, Hiroki; Yoshihara, Katsunori; Masuda, Hiroyuki; Haga, Daisuke; Seiki, Yoshikatsu; Kudoh, Chiaki; Kishi, Taichi

    2016-08-15

    Traumatic brain injury (TBI) is widely known to cause dynamic changes in cerebral blood flow (CBF). Ischemia is a common and deleterious secondary injury following TBI. Detecting early ischemia in TBI patients is important to prevent further advancement and deterioration of the brain tissue. The purpose of this study was to clarify the cerebral circulatory disturbance during the early phase and whether it can be used to predict patient outcome. A total of 90 patients with TBI underwent a xenon-computed tomography (Xe-CT) and subsequently perfusion CT to evaluate the cerebral circulation on days 1-3. We measured CBF using Xe-CT and mean transit time (MTT: the width between two inflection points [maximum upward slope and maximum downward slope from inflow to outflow of the contrast agent]) using perfusion CT and calculated the cerebral blood volume (CBV) using the AZ-7000W98 computer system. The relationships of the hemodynamic parameters CBF, MTT, and CBV to the Glasgow Coma Scale (GCS) score and the Glasgow Outcome Scale (GOS) score were examined. There were no significant differences in CBF, MTT, and CBV among GCS3-4, GCS5-6, and GCS7-8 groups. The patients with a favorable outcome (GR and MD) had significantly higher CBF and lower MTT than those with an unfavorable one (SD, VS, or D). The discriminant analysis of these parameters could predict patient outcome with a probability of 70.6%. During the early phase, CBF reduction and MTT prolongation might influence the clinical outcome of TBI. These parameters are helpful for evaluating the severity of cerebral circulatory disturbance and predicting the outcome of TBI patients. PMID:27356957

  20. Traumatic Brain Injury. Fact Sheet = Lesion Cerebral Traumatica (TBI). Hojas Informativas Sobre Discapacidades.

    ERIC Educational Resources Information Center

    National Information Center for Children and Youth with Disabilities, Washington, DC.

    This fact sheet, written in both English and Spanish, offers general information about traumatic brain injury. Information includes a definition, incidence, individual characteristics, and educational implications. The signs of traumatic brain injury are listed and include physical disabilities, difficulties with thinking, and social, behavioral,…

  1. A meta-analysis of response inhibition and Stroop interference control deficits in adults with traumatic brain injury (TBI).

    PubMed

    Dimoska-Di Marco, Aneta; McDonald, Skye; Kelly, Michelle; Tate, Robyn; Johnstone, Stuart

    2011-04-01

    The prominent clinical feature of behavioral impulsivity following traumatic brain injury (TBI) suggests impairment of frontal inhibitory control processes. This meta-analysis consolidates the recent surge in studies across two forms of "effortful" inhibition, employing well-defined paradigms of response inhibition (N = 20; i.e., go/no-go, sustained attention to response, stop-signal, Conners' continuous performance tasks) and response interference control (N = 21, i.e., Stroop color word tasks). Across 41 effect sizes involving 989 adults with mild to severe TBI and 969 controls, the overall effect of TBI on reduced inhibitory control was small to moderate (d = 0.3) and significant. The effect was larger in studies measuring response inhibition performance (d = 0.5), while Stroop interference control yielded a nonsignificant overall effect size (d = 0.05). Further analysis of the latter finding revealed a large effect size when Stroop task studies used the outcome measure "total time on task" (d = 1.4), but not "RT per trial" or "number of stimuli" (d = -0.8 and -0.9). Response speed in these tasks was impaired to a large degree (d = 0.96). Together these findings support a response inhibition deficit following TBI but suggest factors other than interference control, such as poor processing speed, fatigue, and underarousal, may underlie poor performance in Stroop tasks.

  2. A study on the mechanism by which MDMA protects against dopaminergic dysfunction after minimal traumatic brain injury (mTBI) in mice.

    PubMed

    Edut, S; Rubovitch, V; Rehavi, M; Schreiber, S; Pick, C G

    2014-12-01

    Driving under methylenedioxymethamphetamine (MDMA) influence increases the risk of being involved in a car accident, which in turn can lead to traumatic brain injury. The behavioral deficits after traumatic brain injury (TBI) are closely connected to dopamine pathway dysregulation. We have previously demonstrated in mice that low MDMA doses prior to mTBI can lead to better performances in cognitive tests. The purpose of this study was to assess in mice the changes in the dopamine system that occurs after both MDMA and minimal traumatic brain injury (mTBI). Experimental mTBI was induced using a concussive head trauma device. One hour before injury, animals were subjected to MDMA. Administration of MDMA before injury normalized the alterations in tyrosine hydroxylase (TH) levels that were observed in mTBI mice. This normalization was also able to lower the elevated dopamine receptor type 2 (D2) levels observed after mTBI. Brain-derived neurotrophic factor (BDNF) levels did not change following injury alone, but in mice subjected to MDMA and mTBI, significant elevations were observed. In the behavioral tests, haloperidol reversed the neuroprotection seen when MDMA was administered prior to injury. Altered catecholamine synthesis and high D2 receptor levels contribute to cognitive dysfunction, and strategies to normalize TH signaling and D2 levels may provide relief for the deficits observed after injury. Pretreatment with MDMA kept TH and D2 receptor at normal levels, allowing regular dopamine system activity. While the beneficial effect we observe was due to a dangerous recreational drug, understanding the alterations in dopamine and the mechanism of dysfunction at a cellular level can lead to legal therapies and potential candidates for clinical use.

  3. Outcome Prediction after Mild and Complicated Mild Traumatic Brain Injury: External Validation of Existing Models and Identification of New Predictors Using the TRACK-TBI Pilot Study

    PubMed Central

    Lingsma, Hester F.; Yue, John K.; Maas, Andrew I.R.; Steyerberg, Ewout W.; Cooper, Shelly R.; Dams-O'Connor, Kristen; Gordon, Wayne A.; Menon, David K.; Mukherjee, Pratik; Okonkwo, David O.; Puccio, Ava M.; Schnyer, David M.; Valadka, Alex B.; Vassar, Mary J.; Yuh, Esther L.

    2015-01-01

    Abstract Although the majority of patients with mild traumatic brain injury (mTBI) recover completely, some still suffer from disabling ailments at 3 or 6 months. We validated existing prognostic models for mTBI and explored predictors of poor outcome after mTBI. We selected patients with mTBI from TRACK-TBI Pilot, an unselected observational cohort of TBI patients from three centers in the United States. We validated two prognostic models for the Glasgow Outcome Scale Extended (GOS-E) at 6 months after injury. One model was based on the CRASH study data and another from Nijmegen, The Netherlands. Possible predictors of 3- and 6-month GOS-E were analyzed with univariate and multi-variable proportional odds regression models. Of the 386 of 485 patients included in the study (median age, 44 years; interquartile range, 27–58), 75% (n=290) presented with a Glasgow Coma Score (GCS) of 15. In this mTBI population, both previously developed models had a poor performance (area under the receiver operating characteristic curve, 0.49–0.56). In multivariable analyses, the strongest predictors of lower 3- and 6-month GOS-E were older age, pre-existing psychiatric conditions, and lower education. Injury caused by assault, extracranial injuries, and lower GCS were also predictive of lower GOS-E. Existing models for mTBI performed unsatisfactorily. Our study shows that, for mTBI, different predictors are relevant as for moderate and severe TBI. These include age, pre-existing psychiatric conditions, and lower education. Development of a valid prediction model for mTBI patients requires further research efforts. PMID:25025611

  4. Social communication mediates the relationship between emotion perception and externalizing behaviors in young adult survivors of pediatric traumatic brain injury (TBI).

    PubMed

    Ryan, Nicholas P; Anderson, Vicki; Godfrey, Celia; Eren, Senem; Rosema, Stefanie; Taylor, Kaitlyn; Catroppa, Cathy

    2013-12-01

    Traumatic brain injury (TBI) is a common cause of childhood disability, and is associated with elevated risk for long-term social impairment. Though social (pragmatic) communication deficits may be among the most debilitating consequences of childhood TBI, few studies have examined very long-term communication outcomes as children with TBI make the transition to young adulthood. In addition, the extent to which reduced social function contributes to externalizing behaviors in survivors of childhood TBI remains poorly understood. The present study aimed to evaluate the extent of social communication difficulty among young adult survivors of childhood TBI (n=34, injury age: 1.0-7.0 years; M time since injury: 16.55 years) and examine relations among aspects of social function including emotion perception, social communication and externalizing behaviors rated by close-other proxies. Compared to controls the TBI group had significantly greater social communication difficulty, which was associated with more frequent externalizing behaviors and poorer emotion perception. Analyses demonstrated that reduced social communication mediated the association between poorer emotion perception and more frequent externalizing behaviors. Our findings indicate that socio-cognitive impairments may indirectly increase the risk for externalizing behaviors among young adult survivors of childhood TBI, and underscore the need for targeted social skills interventions delivered soon after injury, and into the very long-term.

  5. Meta-analytic methods and the importance of non-TBI factors related to outcome in mild traumatic brain injury: response to Bigler et al. (2013).

    PubMed

    Larrabee, Glenn J; Binder, Laurence M; Rohling, Martin L; Ploetz, Danielle M

    2013-01-01

    Bigler et al. (2013, The Clinical Neuropsychologist) contend that weak methodology and poor quality of the studies comprising our recent meta-analysis led us to miss detecting a subgroup of mild traumatic brain injury (mTBI) characterized by persisting symptomatic complaint and positive biomarkers for neurological damage. Our computation of non-significant Q, tau(2), and I(2) statistics contradicts the existence of a subgroup of mTBI with poor outcome, or variation in effect size as a function of quality of research design. Consistent with this conclusion, the largest single contributor to our meta-analysis, Dikmen, Machamer, Winn, and Temkin (1995, Neuropsychology, 9, 80) yielded an effect size, -0.02, that was smaller than our overall effect size of -0.07 despite using the most liberal definition of mTBI: loss of consciousness less than 1 hour, with no exclusion of subjects who had positive CT scans. The evidence is weak for biomarkers of mTBI, such as diffusion tensor imaging and for demonstrable neuropathology in uncomplicated mTBI. Postconcussive symptoms, and reduced neuropsychological test scores are not specific to mTBI but can result from pre-existing psychosocial and psychiatric problems, expectancy effects and diagnosis threat. Moreover, neuropsychological impairment is seen in a variety of primary psychiatric disorders, which themselves are predictive of persistent complaints following mTBI. We urge use of prospective studies with orthopedic trauma controls in future investigations of mTBI to control for these confounding factors.

  6. Global Outcome Trajectories After TBI Among Survivors and Nonsurvivors: A National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems Study

    PubMed Central

    Dams-O’Connor, Kristen; Pretz, Christopher; Billah, Tausif; Hammond, Flora M.; Harrison-Felix, Cynthia

    2014-01-01

    Objective To compare long-term functional outcome trajectories of individuals with traumatic brain injury (TBI) who survive with those who expire more than 5 years postinjury, using individual growth curve analysis. Design Secondary analysis of data from a multicenter longitudinal cohort study. Setting Acute inpatient rehabilitation facilities that are current or former TBI Model Systems. Participants Individuals 16 years and older with a primary diagnosis of TBI. Main Outcome Measures Glasgow Outcome Scale–Extended; Disability Rating Scale. Results Individuals in the TBI Model Systems who expire several years after injury demonstrate worse functional status at baseline and a steeper rate of decline over time as measured by both the Glasgow Outcome Scale–Extended and the Disability Rating Scale. There was significant variability in each growth parameter (P < .05) for both instruments. A reduced model was built for each outcome, including all covariates that related significantly to the growth parameters. An interactive tool was created for each outcome to generate individual-level trajectories based on various combinations of covariate values. Conclusion Individuals with TBI who die several years after injury demonstrate functional trajectories that differ markedly from those of survivors. Opportunities should be sought for health management interventions to improve health and longevity after TBI. PMID:24922043

  7. A mild traumatic brain injury (mTBI) induces secondary attention-deficit hyperactivity disorder-like symptomology in young rats.

    PubMed

    Mychasiuk, Richelle; Hehar, Harleen; Esser, Michael J

    2015-06-01

    Although attention-deficit hyperactivity disorder (ADHD) is commonly reported after moderate and severe traumatic brain injury (TBI), research is struggling to find a strong link between mild TBI or concussion and ADHD. Epidemiological studies often generate conflicting results which may be related to the difficulty identifying the lingering symptoms of mTBI, the lack of baseline knowledge and the possible exacerbation of pre-existing ADHD symptomology, and/or differential diagnostic criteria for secondary ADHD. The purpose of this study was to determine if a mild TBI/concussion in the juvenile period (postnatal day 30) could induce ADHD-like symptoms in young rodents. Using the Go/No-Go paradigm of the 5-choice serial reaction task, sustained attention, impulsivity, and response inhibition was measured. The open field was also used to measure activity levels at two time points. Animals that experienced an mTBI in the juvenile period exhibited ADHD symptomology, with sex-differences present on one of the tasks. Significant deficits were identified in sustained attention, response inhibition, and impulsivity. Immediately after the mTBI, all rats were hypoactive in the open field, and while male animals exhibited a trend toward hyperactivity in the long-term, females continued to trend toward hypoactivity for the duration of the experiment. These findings provide a unique platform upon which preventative and therapeutic strategies can be implemented and tested in an effort to improve ADHD-like symptoms following mTBI.

  8. Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study

    PubMed Central

    Cnossen, Maryse C.; Polinder, Suzanne; Lingsma, Hester F.; Maas, Andrew I. R.; Menon, David; Steyerberg, Ewout W.

    2016-01-01

    Introduction The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Methods We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. Results All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. Conclusion Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches. PMID:27571205

  9. Traumatic Brain Injury

    MedlinePlus

    Traumatic brain injury (TBI) happens when a bump, blow, jolt, or other head injury causes damage to the brain. Every year, millions of people in the U.S. suffer brain injuries. More than half are bad enough that ...

  10. Traumatic Brain Injury

    MedlinePlus

    ... Center PTACs Workspaces Log-in Search for: Traumatic Brain Injury A legacy resource from NICHCY Disability Fact ... in her. Back to top What is Traumatic Brain Injury? A traumatic brain injury (TBI) is an ...

  11. Cognitive control of conscious error awareness: error awareness and error positivity (Pe) amplitude in moderate-to-severe traumatic brain injury (TBI).

    PubMed

    Logan, Dustin M; Hill, Kyle R; Larson, Michael J

    2015-01-01

    Poor awareness has been linked to worse recovery and rehabilitation outcomes following moderate-to-severe traumatic brain injury (M/S TBI). The error positivity (Pe) component of the event-related potential (ERP) is linked to error awareness and cognitive control. Participants included 37 neurologically healthy controls and 24 individuals with M/S TBI who completed a brief neuropsychological battery and the error awareness task (EAT), a modified Stroop go/no-go task that elicits aware and unaware errors. Analyses compared between-group no-go accuracy (including accuracy between the first and second halves of the task to measure attention and fatigue), error awareness performance, and Pe amplitude by level of awareness. The M/S TBI group decreased in accuracy and maintained error awareness over time; control participants improved both accuracy and error awareness during the course of the task. Pe amplitude was larger for aware than unaware errors for both groups; however, consistent with previous research on the Pe and TBI, there were no significant between-group differences for Pe amplitudes. Findings suggest possible attention difficulties and low improvement of performance over time may influence specific aspects of error awareness in M/S TBI. PMID:26217212

  12. Cognitive control of conscious error awareness: error awareness and error positivity (Pe) amplitude in moderate-to-severe traumatic brain injury (TBI)

    PubMed Central

    Logan, Dustin M.; Hill, Kyle R.; Larson, Michael J.

    2015-01-01

    Poor awareness has been linked to worse recovery and rehabilitation outcomes following moderate-to-severe traumatic brain injury (M/S TBI). The error positivity (Pe) component of the event-related potential (ERP) is linked to error awareness and cognitive control. Participants included 37 neurologically healthy controls and 24 individuals with M/S TBI who completed a brief neuropsychological battery and the error awareness task (EAT), a modified Stroop go/no-go task that elicits aware and unaware errors. Analyses compared between-group no-go accuracy (including accuracy between the first and second halves of the task to measure attention and fatigue), error awareness performance, and Pe amplitude by level of awareness. The M/S TBI group decreased in accuracy and maintained error awareness over time; control participants improved both accuracy and error awareness during the course of the task. Pe amplitude was larger for aware than unaware errors for both groups; however, consistent with previous research on the Pe and TBI, there were no significant between-group differences for Pe amplitudes. Findings suggest possible attention difficulties and low improvement of performance over time may influence specific aspects of error awareness in M/S TBI. PMID:26217212

  13. Changes in Diffusion Kurtosis Imaging and Magnetic Resonance Spectroscopy in a Direct Cranial Blast Traumatic Brain Injury (dc-bTBI) Model.

    PubMed

    Zhuo, Jiachen; Keledjian, Kaspar; Xu, Su; Pampori, Adam; Gerzanich, Volodymyr; Simard, J Marc; Gullapalli, Rao P

    2015-01-01

    Explosive blast-related injuries are one of the hallmark injuries of veterans returning from recent wars, but the effects of a blast overpressure on the brain are poorly understood. In this study, we used in vivo diffusion kurtosis imaging (DKI) and proton magnetic resonance spectroscopy (MRS) to investigate tissue microstructure and metabolic changes in a novel, direct cranial blast traumatic brain injury (dc-bTBI) rat model. Imaging was performed on rats before injury and 1, 7, 14 and 28 days after blast exposure (~517 kPa peak overpressure to the dorsum of the head). No brain parenchyma abnormalities were visible on conventional T2-weighted MRI, but microstructural and metabolic changes were observed with DKI and proton MRS, respectively. Increased mean kurtosis, which peaked at 21 days post injury, was observed in the hippocampus and the internal capsule. Concomitant increases in myo-Inositol (Ins) and Taurine (Tau) were also observed in the hippocampus, while early changes at 1 day in the Glutamine (Gln) were observed in the internal capsule, all indicating glial abnormality in these regions. Neurofunctional testing on a separate but similarly treated group of rats showed early disturbances in vestibulomotor functions (days 1-14), which were associated with imaging changes in the internal capsule. Delayed impairments in spatial memory and in rapid learning, as assessed by Morris Water Maze paradigms (days 14-19), were associated with delayed changes in the hippocampus. Significant microglial activation and neurodegeneration were observed at 28 days in the hippocampus. Overall, our findings indicate delayed neurofunctional and pathological abnormalities following dc-bTBI that are silent on conventional T2-weighted imaging, but are detectable using DKI and proton MRS. PMID:26301778

  14. Stretch and/or oxygen glucose deprivation (OGD) in an in vitro traumatic brain injury (TBI) model induces calcium alteration and inflammatory cascade

    PubMed Central

    Salvador, Ellaine; Burek, Malgorzata; Förster, Carola Y.

    2015-01-01

    The blood-brain barrier (BBB), made up of endothelial cells of capillaries in the brain, maintains the microenvironment of the central nervous system. During ischemia and traumatic brain injury (TBI), cellular disruption leading to mechanical insult results to the BBB being compromised. Oxygen glucose deprivation (OGD) is the most commonly used in vitro model for ischemia. On the other hand, stretch injury is currently being used to model TBI in vitro. In this paper, the two methods are used alone or in combination, to assess their effects on cerebrovascular endothelial cells cEND in the presence or absence of astrocytic factors. Applying severe stretch and/or OGD to cEND cells in our experiments resulted to cell swelling and distortion. Damage to the cells induced release of lactate dehydrogenase enzyme (LDH) and nitric oxide (NO) into the cell culture medium. In addition, mRNA expression of inflammatory markers interleukin (I L)-6, IL-1α, chemokine (C-C motif) ligand 2 (CCL2) and tumor necrosis factor (TNF)-α also increased. These events could lead to the opening of calcium ion channels resulting to excitotoxicity. This could be demonstrated by increased calcium level in OGD-subjected cEND cells incubated with astrocyte-conditioned medium. Furthermore, reduction of cell membrane integrity decreased tight junction proteins claudin-5 and occludin expression. In addition, permeability of the endothelial cell monolayer increased. Also, since cell damage requires an increased uptake of glucose, expression of glucose transporter glut1 was found to increase at the mRNA level after OGD. Overall, the effects of OGD on cEND cells appear to be more prominent than that of stretch with regards to TJ proteins, NO, glut1 expression, and calcium level. Astrocytes potentiate these effects on calcium level in cEND cells. Combining both methods to model TBI in vitro shows a promising improvement to currently available models. PMID:26347611

  15. ED disposition of the Glasgow Coma Scale 13 to 15 traumatic brain injury patient: analysis of the Transforming Research and Clinical Knowledge in TBI study☆,☆☆

    PubMed Central

    Adeoye, Opeolu; Lindsell, Christopher J.; Hart, Kimberly W.; Pancioli, Arthur; McMullan, Jason T.; Yue, John K.; Nishijima, Daniel K.; Gordon, Wayne A.; Valadka, Alex B.; Okonkwo, David O.; Lingsma, Hester F.; Maas, Andrew I.R.

    2014-01-01

    Objective Mild traumatic brain injury (mTBI) patients are frequently admitted to high levels of care despite limited evidence suggesting benefit. Such decisions may contribute to the significant cost of caring for mTBI patients. Understanding the factors that drive disposition decision making and how disposition is associated with outcomes is necessary for developing an evidence-base supporting disposition decisions. We evaluated factors associated with emergency department triage of mTBI patients to 1 of 3 levels of care: home, inpatient floor, or intensive care unit (ICU). Methods This multicenter, prospective, cohort study included patients with isolated head trauma, a cranial computed tomography as part of routine care, and a Glasgow Coma Scale (GCS) score of 13 to 15. Data analysis was performed using multinomial logistic regression. Results Of the 304 patients included, 167 (55%) were discharged home, 76 (25%) were admitted to the inpatient floor, and 61 (20%) were admitted to the ICU. In the multivariable model, admission to the ICU, compared with floor admission, varied by study site, odds ratio (OR) 0.18 (95% confidence interval [CI], 0.06–0.57); antiplatelet/anticoagulation therapy, OR 7.46 (95% CI, 1.79–31.13); skull fracture, OR 7.60 (95% CI, 2.44–23.73); and lower GCS, OR 2.36 (95% CI, 1.05–5.30). No difference in outcome was observed between the 3 levels of care. Conclusion Clinical characteristics and local practice patterns contribute to mTBI disposition decisions. Level of care was not associated with outcomes. Intracranial hemorrhage, GCS 13 to 14, skull fracture, and current antiplatelet/anticoagulant therapy influenced disposition decisions. PMID:24857248

  16. Defense and Veterans Brain Injury Center

    MedlinePlus

    ... Headache Following Concussion/Mild TBI Clinical Recommendation DCoE Blog TBI Highlights Give Concussion the Red Card (link ... of TBI (link is external) Read more DCoE blog articles » Defense and Veterans Brain Injury Center Crisis ...

  17. Impact of Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) and Positron Emission Tomography/Computed Tomography (PET/CT) in the Diagnosis of Traumatic Brain Injury (TBI): Case Report.

    PubMed

    Molina-Vicenty, Irma L; Santiago-Sánchez, Michelaldemar; Vélez-Miró, Iván; Motta-Valencia, Keryl

    2016-09-01

    Traumatic brain injury (TBI) is defined as damage to the brain resulting from an external force. TBI, a global leading cause of death and disability, is associated with serious social, economic, and health problems. In cases of mild-to-moderate brain damage, conventional anatomical imaging modalities may or may not detect the cascade of metabolic changes that have occurred or are occurring at the intracellular level. Functional nuclear medicine imaging and neurophysiological parameters can be used to characterize brain damage, as the former provides direct visualization of brain function, even in the absence of overt behavioral manifestations or anatomical findings. We report the case of a 30-year-old Hispanic male veteran who, after 2 traumatic brain injury events, developed cognitive and neuropsychological problems with no clear etiology in the presence of negative computed tomography (CT) findings. PMID:27623144

  18. When Injury Clouds Understanding of Others: Theory of Mind after Mild TBI in Preschool Children.

    PubMed

    Bellerose, Jenny; Bernier, Annie; Beaudoin, Cindy; Gravel, Jocelyn; Beauchamp, Miriam H

    2015-08-01

    There is evidence to suggest that social skills, such as the ability to understand the perspective of others (theory of mind), may be affected by childhood traumatic brain injuries; however, studies to date have only considered moderate and severe traumatic brain injury (TBI). This study aimed to assess theory of mind after early, mild TBI (mTBI). Fifty-one children who sustained mTBI between 18 and 60 months were evaluated 6 months post-injury on emotion and desires reasoning and false-belief understanding tasks. Their results were compared to that of 50 typically developing children. The two groups did not differ on baseline characteristics, except for pre- and post-injury externalizing behavior. The mTBI group obtained poorer scores relative to controls on both the emotion and desires task and the false-belief understanding task, even after controlling for pre-injury externalizing behavior. No correlations were found between TBI injury characteristics and theory of mind. This is the first evidence that mTBI in preschool children is associated with theory of mind difficulties. Reduced perspective taking abilities could be linked with the social impairments that have been shown to arise following TBI.

  19. When Injury Clouds Understanding of Others: Theory of Mind after Mild TBI in Preschool Children.

    PubMed

    Bellerose, Jenny; Bernier, Annie; Beaudoin, Cindy; Gravel, Jocelyn; Beauchamp, Miriam H

    2015-08-01

    There is evidence to suggest that social skills, such as the ability to understand the perspective of others (theory of mind), may be affected by childhood traumatic brain injuries; however, studies to date have only considered moderate and severe traumatic brain injury (TBI). This study aimed to assess theory of mind after early, mild TBI (mTBI). Fifty-one children who sustained mTBI between 18 and 60 months were evaluated 6 months post-injury on emotion and desires reasoning and false-belief understanding tasks. Their results were compared to that of 50 typically developing children. The two groups did not differ on baseline characteristics, except for pre- and post-injury externalizing behavior. The mTBI group obtained poorer scores relative to controls on both the emotion and desires task and the false-belief understanding task, even after controlling for pre-injury externalizing behavior. No correlations were found between TBI injury characteristics and theory of mind. This is the first evidence that mTBI in preschool children is associated with theory of mind difficulties. Reduced perspective taking abilities could be linked with the social impairments that have been shown to arise following TBI. PMID:26243654

  20. Traumatic Brain Injury Inpatient Rehabilitation

    ERIC Educational Resources Information Center

    Im, Brian; Schrer, Marcia J.; Gaeta, Raphael; Elias, Eileen

    2010-01-01

    Traumatic brain injuries (TBI) can cause multiple medical and functional problems. As the brain is involved in regulating nearly every bodily function, a TBI can affect any part of the body and aspect of cognitive, behavioral, and physical functioning. However, TBI affects each individual differently. Optimal management requires understanding the…

  1. Understanding Traumatic Brain Injury: An Introduction

    ERIC Educational Resources Information Center

    Trudel, Tina M.; Scherer, Marcia J.; Elias, Eileen

    2009-01-01

    This article is the first of a multi-part series on traumatic brain injury (TBI). Historically, TBI has received very limited national public policy attention and support. However since it has become the signature injury of the military conflicts in Iraq and Afghanistan, TBI has gained the attention of elected officials, military leaders,…

  2. Traumatic Brain Injury: Looking Back, Looking Forward

    ERIC Educational Resources Information Center

    Bartlett, Sue; Lorenz, Laura; Rankin, Theresa; Elias, Eileen; Weider, Katie

    2011-01-01

    This article is the eighth of a multi-part series on traumatic brain injury (TBI). Historically, TBI has received limited national attention and support. However, since it is the signature injury of the military conflicts in Iraq and Afghanistan, TBI has gained attention of elected officials, military leaders, policymakers, and the public. The…

  3. Preconditioning for traumatic brain injury

    PubMed Central

    Yokobori, Shoji; Mazzeo, Anna T; Hosein, Khadil; Gajavelli, Shyam; Dietrich, W. Dalton; Bullock, M. Ross

    2016-01-01

    Traumatic brain injury (TBI) treatment is now focused on the prevention of primary injury and reduction of secondary injury. However, no single effective treatment is available as yet for the mitigation of traumatic brain damage in humans. Both chemical and environmental stresses applied before injury, have been shown to induce consequent protection against post-TBI neuronal death. This concept termed “preconditioning” is achieved by exposure to different pre-injury stressors, to achieve the induction of “tolerance” to the effect of the TBI. However, the precise mechanisms underlying this “tolerance” phenomenon are not fully understood in TBI, and therefore even less information is available about possible indications in clinical TBI patients. In this review we will summarize TBI pathophysiology, and discuss existing animal studies demonstrating the efficacy of preconditioning in diffuse and focal type of TBI. We will also review other non-TBI preconditionng studies, including ischemic, environmental, and chemical preconditioning, which maybe relevant to TBI. To date, no clinical studies exist in this field, and we speculate on possible futureclinical situation, in which pre-TBI preconditioning could be considered. PMID:24323189

  4. Performance Monitoring in Children following Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Ornstein, Tisha J.; Levin, Harvey S.; Chen, Shirley; Hanten, Gerri; Ewing-Cobbs, Linda; Dennis, Maureen; Barnes, Marcia; Max, Jeffrey E.; Logan, Gordon D.; Schachar, Russell

    2009-01-01

    Background: Executive control deficits are common sequelae of childhood traumatic brain injury (TBI). The goal of the current study was to assess a specific executive control function, performance monitoring, in children following TBI. Methods: Thirty-one children with mild-moderate TBI, 18 with severe TBI, and 37 control children without TBI, of…

  5. Traumatic brain injury and criminal behaviour.

    PubMed

    Diaz, F G

    1995-01-01

    The clinical characteristics of traumatic brain injury (TBI), the association of TBI with lasting behavioural problems and neuropsychological deficits, and the use of the insanity defense in criminal proceedings in relation to TBI are discussed. Furthermore, the possible abuse of the incidental association of a TBI to the commission of a crime is explored. A framework of evaluation is described to determine the relevance of the association of TBI and the ultimate commission of a crime.

  6. TBI-ROC Part Nine: Diagnosing TBI and Psychiatric Disorders

    ERIC Educational Resources Information Center

    Elias, Eileen; Weider, Katie; Mustafa, Ruman

    2011-01-01

    This article is the ninth of a multi-part series on traumatic brain injury (TBI). It focuses on the process of diagnosing TBI and psychiatric disorders. Diagnosing traumatic brain injury can be challenging. It can be difficult differentiating TBI and psychiatric symptoms, as both have similar symptoms (e.g., memory problems, emotional outbursts,…

  7. LOW BRAIN DHA CONTENT WORSENS SENSORIMOTOR OUTCOMES AFTER TBI AND DECREASES TBI-INDUCED TIMP1 EXPRESSION IN JUVENILE RATS

    PubMed Central

    Russell, Kristin L.; Berman, Nancy E. J.; Levant, Beth

    2013-01-01

    SUMMARY The effects of dietary modulation of brain DHA content on outcomes after TBI were examined in a juvenile rat model. Long-Evans rats with normal or diet-induced decreases in brain DHA were subjected to a controlled cortical impact or sham surgery on postnatal day 17. Rats with the greatest decreases in brain DHA had the poorest sensorimotor outcomes after TBI. Ccl2, Gfap, and Mmp 9 mRNA levels, and MMP-2 and −9 enzymatic activities were increased after TBI regardless of brain DHA level. Lesion volume was not affected by brain DHA level. In contrast, TBI-induced Timp1 expression was lower in rats on the Deficient diet and correlated with brain DHA level. These data suggest that decreased brain DHA content contributes to poorer sensorimotor outcomes after TBI through a mechanism involving modulation of Timp1 expression. PMID:23796971

  8. Neuroepidemiology of traumatic brain injury.

    PubMed

    Gardner, A J; Zafonte, R

    2016-01-01

    Traumatic brain injury (TBI) is a significant public-health concern. TBI is defined as an acute brain injury resulting from mechanical energy to the head from external physical forces. Some of the leading causes of TBI include falls, assaults, motor vehicle or traffic accidents, and sport-related concussion. Two of the most common identified risk factors are sex (males are nearly three times more likely to suffer a TBI than females); and a bimodal age pattern (persons 65 years and older, and children under 14 years old). It is estimated that approximately 1.5-2 million Americans suffer from TBI annually. TBIs account for around 1.4 million emergency room visits, 275 000 hospital admissions, and 52 000 deaths in the USA each year. TBI contributes to approximately 30% of all deaths in the USA annually. In Australia, it is estimated that approximately 338 700 individuals (1.9% of the population) suffer from a disability related to TBI. Of these, 160 200 were severely or profoundly affected by acquired brain injury, requiring daily support. In the UK, TBI accounted for 3.4% of all emergency department attendances annually. An overall rate of 453 per 100 000 was found for all TBI severities, of which 40 per 100 000 (10.9%) were moderate to severe. TBI often results in residual symptoms that affect an individual's cognition, movement, sensation, and/or emotional functioning. Recovery and rehabilitation from TBI may require considerable resources and may take years. Some individuals never fully recover, and some require lifetime ongoing care and support. TBI has an enormous social and financial cost, with estimates of the annual financial burden associated with TBI ranging between 9 and 10 billion US dollars. PMID:27637960

  9. Microglia in the TBI brain: The good, the bad, and the dysregulated.

    PubMed

    Loane, David J; Kumar, Alok

    2016-01-01

    As the major cellular component of the innate immune system in the central nervous system (CNS) and the first line of defense whenever injury or disease occurs, microglia play a critical role in neuroinflammation following a traumatic brain injury (TBI). In the injured brain microglia can produce neuroprotective factors, clear cellular debris and orchestrate neurorestorative processes that are beneficial for neurological recovery after TBI. However, microglia can also become dysregulated and can produce high levels of pro-inflammatory and cytotoxic mediators that hinder CNS repair and contribute to neuronal dysfunction and cell death. The dual role of microglial activation in promoting beneficial and detrimental effects on neurons may be accounted for by their polarization state and functional responses after injury. In this review article we discuss emerging research on microglial activation phenotypes in the context of acute brain injury, and the potential role of microglia in phenotype-specific neurorestorative processes such as neurogenesis, angiogenesis, oligodendrogenesis and regeneration. We also describe some of the known molecular mechanisms that regulate phenotype switching, and highlight new therapeutic approaches that alter microglial activation state balance to enhance long-term functional recovery after TBI. An improved understanding of the regulatory mechanisms that control microglial phenotypic shifts may advance our knowledge of post-injury recovery and repair, and provide opportunities for the development of novel therapeutic strategies for TBI.

  10. Traumatic brain injury

    PubMed Central

    Risdall, Jane E.; Menon, David K.

    2011-01-01

    There is an increasing incidence of military traumatic brain injury (TBI), and similar injuries are seen in civilians in war zones or terrorist incidents. Indeed, blast-induced mild TBI has been referred to as the signature injury of the conflicts in Iraq and Afghanistan. Assessment involves schemes that are common in civilcian practice but, in common with civilian TBI, takes little account of information available from modern imaging (particularly diffusion tensor magnetic resonance imaging) and emerging biomarkers. The efficient logistics of clinical care delivery in the field may have a role in optimizing outcome. Clinical care has much in common with civilian TBI, but intracranial pressure monitoring is not always available, and protocols need to be modified to take account of this. In addition, severe early oedema has led to increasing use of decompressive craniectomy, and blast TBI may be associated with a higher incidence of vasospasm and pseudoaneurysm formation. Visual and/or auditory deficits are common, and there is a significant risk of post-traumatic epilepsy. TBI is rarely an isolated finding in this setting, and persistent post-concussive symptoms are commonly associated with post-traumatic stress disorder and chronic pain, a constellation of findings that has been called the polytrauma clinical triad. PMID:21149359

  11. Traumatic Brain Injury and Personality Change

    ERIC Educational Resources Information Center

    Fowler, Marc; McCabe, Paul C.

    2011-01-01

    Traumatic brain injury (TBI) is the leading cause of death and lifelong disability in the United States for individuals below the age of 45. Current estimates from the Center for Disease Control (CDC) indicate that at least 1.4 million Americans sustain a TBI annually. TBI affects 475,000 children under age 14 each year in the United States alone.…

  12. Working with Students with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Lucas, Matthew D.

    2010-01-01

    The participation of a student with Traumatic Brain Injury (TBI) in general physical education can often be challenging and rewarding for the student and physical education teacher. This article addresses common characteristics of students with TBI and presents basic solutions to improve the education of students with TBI in the general physical…

  13. Narrative Language in Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Marini, Andrea; Galetto, Valentina; Zampieri, Elisa; Vorano, Lorenza; Zettin, Marina; Carlomagno, Sergio

    2011-01-01

    Persons with traumatic brain injury (TBI) often show impaired linguistic and/or narrative abilities. The present study aimed to document the features of narrative discourse impairment in a group of adults with TBI. 14 severe TBI non-aphasic speakers (GCS less than 8) in the phase of neurological stability and 14 neurologically intact participants…

  14. Traumatic Brain Injury: A Challenge for Educators

    ERIC Educational Resources Information Center

    Bullock, Lyndal M.; Gable, Robert A.; Mohr, J. Darrell

    2005-01-01

    In this article, the authors provide information designed to enhance the knowledge and understanding of school personnel about traumatic brain injury (TBI). The authors specifically define TBI and enumerate common characteristics associated with traumatic brain injury, discuss briefly the growth and type of services provided, and offer some…

  15. Imaging of Traumatic Brain Injury.

    PubMed

    Bodanapally, Uttam K; Sours, Chandler; Zhuo, Jiachen; Shanmuganathan, Kathirkamanathan

    2015-07-01

    Imaging plays an important role in the management of patients with traumatic brain injury (TBI). Computed tomography (CT) is the first-line imaging technique allowing rapid detection of primary structural brain lesions that require surgical intervention. CT also detects various deleterious secondary insults allowing early medical and surgical management. Serial imaging is critical to identifying secondary injuries. MR imaging is indicated in patients with acute TBI when CT fails to explain neurologic findings. However, MR imaging is superior in patients with subacute and chronic TBI and also predicts neurocognitive outcome.

  16. TBI-ROC Part Six: Lifelong Living after TBI

    ERIC Educational Resources Information Center

    Boeing, Marianne; Barton, Barbara; Zinsmeister, Paula; Brouwers, Lynn; Trudel, Tina M.; Elias, Eileen; Weider, Katie

    2010-01-01

    This article is the sixth of a multi-part series on traumatic brain injury (TBI) and discusses lifelong living after TBI. Following TBI, lifelong outcomes vary depending on the individual affected, treatment provided and severity of injury. Fortunately, many individuals who experience mild concussions common to childhood have no lasting symptoms.…

  17. Evaluation after Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Trudel, Tina M.; Halper, James; Pines, Hayley; Cancro, Lorraine

    2010-01-01

    It is important to determine if a traumatic brain injury (TBI) has occurred when an individual is assessed in a hospital emergency room after a car accident, fall, or other injury that affects the head. This determination influences decisions about treatment. It is essential to screen for the injury, because the sooner they begin appropriate…

  18. Traumatic Brain Injury and Sleep Disorders

    PubMed Central

    Viola-Saltzman, Mari; Watson, Nathaniel F.

    2012-01-01

    SYNOPSIS Sleep disturbance is common following traumatic brain injury (TBI), affecting 30–70% of individuals, many occurring after mild injuries. Insomnia, fatigue and sleepiness are the most frequent post-TBI sleep complaints with narcolepsy (with or without cataplexy), sleep apnea (obstructive and/or central), periodic limb movement disorder, and parasomnias occurring less commonly. In addition, depression, anxiety and pain are common TBI co-morbidities with substantial influence on sleep quality. Two types of TBI negatively impact sleep: contact injuries causing focal brain damage and acceleration/deceleration injuries causing more generalized brain damage. Diagnosis of sleep disorders after TBI may involve polysomnography, multiple sleep latency testing and/or actigraphy. Treatment is disorder specific and may include the use of medications, continuous positive airway pressure (or similar device) and/or behavioral modifications. Unfortunately, treatment of sleep disorders associated with TBI often does not improve sleepiness or neuropsychological function. PMID:23099139

  19. Neurostimulation for traumatic brain injury.

    PubMed

    Shin, Samuel S; Dixon, C Edward; Okonkwo, David O; Richardson, R Mark

    2014-11-01

    Traumatic brain injury (TBI) remains a significant public health problem and is a leading cause of death and disability in many countries. Durable treatments for neurological function deficits following TBI have been elusive, as there are currently no FDA-approved therapeutic modalities for mitigating the consequences of TBI. Neurostimulation strategies using various forms of electrical stimulation have recently been applied to treat functional deficits in animal models and clinical stroke trials. The results from these studies suggest that neurostimulation may augment improvements in both motor and cognitive deficits after brain injury. Several studies have taken this approach in animal models of TBI, showing both behavioral enhancement and biological evidence of recovery. There have been only a few studies using deep brain stimulation (DBS) in human TBI patients, and future studies are warranted to validate the feasibility of this technique in the clinical treatment of TBI. In this review, the authors summarize insights from studies employing neurostimulation techniques in the setting of brain injury. Moreover, they relate these findings to the future prospect of using DBS to ameliorate motor and cognitive deficits following TBI.

  20. Traumatic Brain Injury: When Children Return to School.

    ERIC Educational Resources Information Center

    Williams, Dennis

    This guide addresses issues concerned with the reintegration of students with traumatic brain injuries (TBI) into the classroom. It first provides a definition of TBI and identifies characteristics of students with TBI. The guide then discusses cognitive consequences of TBI, with emphasis on deficits of executive function, attention, and memory.…

  1. Ulinastatin attenuates brain edema after traumatic brain injury in rats.

    PubMed

    Cui, Tao; Zhu, Gangyi

    2015-03-01

    Traumatic brain injury (TBI) remains the leading cause of injury-related death and disability. Brain edema, one of the most major complications of TBI, contributes to elevated intracranial pressure, and poor prognosis following TBI. The objective of this study was to evaluate whether Ulinastatin (UTI), a serine protease inhibitor, attenuates brain edema following TBI. Our results showed that treatment with UTI at a dose of 50,000 U/kg attenuated the brain edema, as assayed by water content 24 h after TBI induction. This attenuation was associated with a significant decrease of the expression level of aquaporin-4. In addition, we showed that UTI treatment also markedly inhibited the expression of pro-inflammatory cytokines including IL-1β and TNF-α as well as activity of NF-κB. Collectively, our findings suggested that UTI may be a promising strategy to treat brain edema following TBI.

  2. The King's Outcome Scale for Childhood Head Injury and Injury Severity and Outcome Measures in Children with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Calvert, Sophie; Miller, Helen E.; Curran, Andrew; Hameed, Biju; McCarter, Renee; Edwards, Richard J.; Hunt, Linda; Sharples, Peta Mary

    2008-01-01

    The aim of this study was to relate discharge King's Outcome Scale for Childhood Head Injury (KOSCHI) category to injury severity and detailed outcome measures obtained in the first year post-traumatic brain injury (TBI). We used a prospective cohort study. Eighty-one children with TBI were studied: 29 had severe, 15 moderate, and 37 mild TBI. The…

  3. Mild Traumatic Brain Injury in Translation

    PubMed Central

    Robertson, Claudia S.

    2013-01-01

    Abstract This Introduction to a Special Issue on Mild Traumatic Brain Injury (mTBI) highlights the methodological challenges in outcome studies and clinical trials involving patients who sustain mTBI. Recent advances in brain imaging and portable, computerized cognitive tasks have contributed to protocols that are sensitive to the effects of mTBI and efficient in time for completion. Investigation of civilian mTBI has been extended to single and repeated injuries in athletes and blast-related mTBI in service members and veterans. Despite differences in mechanism of injury, there is evidence for similar effects of acceleration-deceleration and blast mechanisms of mTBI on cognition. Investigation of repetitive mTBI suggests that the effects may be cumulative and that repeated mTBI and repeated subconcussive head trauma may lead to neurodegenerative conditions. Although animal models of mTBI using cortical impact and fluid percussion injury in rodents have been able to reproduce some of the cognitive deficits frequently exhibited by patients after mTBI, modeling post-concussion symptoms is difficult. Recent use of closed head and blast injury animal models may more closely approximate clinical mTBI. Translation of interventions that are developed in animal models to patients with mTBI is a priority for the research agenda. This Special Issue on mTBI integrates basic neuroscience studies using animal models with studies of human mTBI, including the cognitive sequelae, persisting symptoms, brain imaging, and host factors that facilitate recovery. PMID:23046349

  4. An automatic MEG low-frequency source imaging approach for detecting injuries in mild and moderate TBI patients with blast and non-blast causes.

    PubMed

    Huang, Ming-Xiong; Nichols, Sharon; Robb, Ashley; Angeles, Annemarie; Drake, Angela; Holland, Martin; Asmussen, Sarah; D'Andrea, John; Chun, Won; Levy, Michael; Cui, Li; Song, Tao; Baker, Dewleen G; Hammer, Paul; McLay, Robert; Theilmann, Rebecca J; Coimbra, Raul; Diwakar, Mithun; Boyd, Cynthia; Neff, John; Liu, Thomas T; Webb-Murphy, Jennifer; Farinpour, Roxanna; Cheung, Catherine; Harrington, Deborah L; Heister, David; Lee, Roland R

    2012-07-16

    Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild (and some moderate) TBI can be difficult to diagnose because the injuries are often not detectable on conventional MRI or CT. Injured brain tissues in TBI patients generate abnormal low-frequency magnetic activity (ALFMA, peaked at 1-4 Hz) that can be measured and localized by magnetoencephalography (MEG). We developed a new automated MEG low-frequency source imaging method and applied this method in 45 mild TBI (23 from combat-related blasts, and 22 from non-blast causes) and 10 moderate TBI patients (non-blast causes). Seventeen of the patients with mild TBI from blasts had tertiary injuries resulting from the blast. The results show our method detected abnormalities at the rates of 87% for the mild TBI group (blast-induced plus non-blast causes) and 100% for the moderate group. Among the mild TBI patients, the rates of abnormalities were 96% and 77% for the blast and non-blast TBI groups, respectively. The spatial characteristics of abnormal slow-wave generation measured by Z scores in the mild blast TBI group significantly correlated with those in non-blast mild TBI group. Among 96 cortical regions, the likelihood of abnormal slow-wave generation was less in the mild TBI patients with blast than in the mild non-blast TBI patients, suggesting possible protective effects due to the military helmet and armor. Finally, the number of cortical regions that generated abnormal slow-waves correlated significantly with the total post-concussive symptom scores in TBI patients. This study provides a foundation for using MEG low-frequency source imaging to support the clinical diagnosis of TBI. PMID:22542638

  5. Neuropathology of explosive blast traumatic brain injury.

    PubMed

    Magnuson, John; Leonessa, Fabio; Ling, Geoffrey S F

    2012-10-01

    During the conflicts of the Global War on Terror, which are Operation Enduring Freedom (OEF) in Afghanistan and Operation Iraqi Freedom (OIF), there have been over a quarter of a million diagnosed cases of traumatic brain injury (TBI). The vast majority are due to explosive blast. Although explosive blast TBI (bTBI) shares many clinical features with closed head TBI (cTBI) and penetrating TBI (pTBI), it has unique features, such as early cerebral edema and prolonged cerebral vasospasm. Evolving work suggests that diffuse axonal injury (DAI) seen following explosive blast exposure is different than DAI from focal impact injury. These unique features support the notion that bTBI is a separate and distinct form of TBI. This review summarizes the current state of knowledge pertaining to bTBI. Areas of discussion are: the physics of explosive blast generation, blast wave interaction with the bony calvarium and brain tissue, gross tissue pathophysiology, regional brain injury, and cellular and molecular mechanisms of explosive blast neurotrauma.

  6. Clinical Traumatic Brain Injury in the Preclinical Setting.

    PubMed

    Berkner, Justin; Mannix, Rebekah; Qiu, Jianhua

    2016-01-01

    Traumatic brain injury (TBI) is the leading cause of death and disability for people under 45 years of age. Clinical TBI is often the result of disparate forces resulting in heterogeneous injuries. Preclinical modeling of TBI is a vital tool for studying the complex cascade of metabolic, cellular, and molecular post-TBI events collectively termed secondary injury. Preclinical models also provide an important platform for studying therapeutic interventions. However, modeling TBI in the preclinical setting is challenging, and most models replicate only certain aspects of clinical TBI. This chapter details the most widely used models of preclinical TBI, including the controlled cortical impact, fluid percussion, blast, and closed head models. Each of these models replicates particular critical aspects of clinical TBI. Prior to selecting a preclinical TBI model, it is important to address what aspect of human TBI is being sought to evaluate. PMID:27604710

  7. Hypothermia in Traumatic Brain Injury.

    PubMed

    Ahmed, Aminul I; Bullock, M Ross; Dietrich, W Dalton

    2016-10-01

    For over 50 years, clinicians have used hypothermia to manage traumatic brain injury (TBI). In the last two decades numerous trials have assessed whether hypothermia is of benefit in patients. Mild to moderate hypothermia reduces the intracranial pressure (ICP). Randomized control trials for short-term hypothermia indicate no benefit in outcome after severe TBI, whereas longer-term hypothermia could be of benefit by reducing ICP. This article summarises current evidence and gives recommendations based upon the conclusions. PMID:27637398

  8. Neuropsychological Consequences of Traumatic Brain Injury in Children and Adolescents.

    ERIC Educational Resources Information Center

    Lord-Maes, Janiece; Obrzut, John E.

    1996-01-01

    This article discusses recent findings concerning cognitive outcomes in traumatic brain injury (TBI) in children and adolescents, with a particular focus on age differences with TBI. It suggests a relationship between specific learning disorders and brain dysfunction, addresses differential hemispheric functioning with TBI, and outlines recent…

  9. Use of magnesium in traumatic brain injury.

    PubMed

    Sen, Ananda P; Gulati, Anil

    2010-01-01

    Depletion of magnesium is observed in animal brain and in human blood after brain injury. Treatment with magnesium attenuates the pathological and behavioral changes in rats with brain injury; however, the therapeutic effect of magnesium has not been consistently observed in humans with traumatic brain injury (TBI). Secondary brain insults are observed in patients with brain injury, which adversely affect clinical outcome. Systemic administration studies in rats have shown that magnesium enters the brain; however, inducing hypermagnesemia in humans did not concomitantly increase magnesium levels in the CSF. We hypothesize that the neuroprotective effects of magnesium in TBI patients could be observed by increasing its brain bioavailability with mannitol. Here, we review the role of magnesium in brain injury, preclinical studies in brain injury, clinical safety and efficacy studies in TBI patients, brain bioavailability studies in rat, and pharmacokinetic studies in humans with brain injury. Neurodegeneration after brain injury involves multiple biochemical pathways. Treatment with a single agent has often resulted in poor efficacy at a safe dose or toxicity at a therapeutic dose. A successful neuroprotective therapy needs to be aimed at homeostatic control of these pathways with multiple agents. Other pharmacological agents, such as dexanabinol and progesterone, and physiological interventions, with hypothermia and hyperoxia, have been studied for the treatment of brain injury. Treatment with magnesium and hypothermia has shown favorable outcome in rats with cerebral ischemia. We conclude that coadministration of magnesium and mannitol with pharmacological and physiological agents could be an effective neuroprotective regimen for the treatment of TBI. PMID:20129501

  10. Imaging Evaluation of Acute Traumatic Brain Injury.

    PubMed

    Mutch, Christopher A; Talbott, Jason F; Gean, Alisa

    2016-10-01

    Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Imaging plays an important role in the evaluation, diagnosis, and triage of patients with TBI. Recent studies suggest that it also helps predict patient outcomes. TBI consists of multiple pathoanatomic entities. This article reviews the current state of TBI imaging including its indications, benefits and limitations of the modalities, imaging protocols, and imaging findings for each of these pathoanatomic entities. Also briefly surveyed are advanced imaging techniques, which include several promising areas of TBI research. PMID:27637393

  11. Traumatic brain injury and reserve.

    PubMed

    Bigler, Erin D; Stern, Yaakov

    2015-01-01

    The potential role of brain and cognitive reserve in traumatic brain injury (TBI) is reviewed. Brain reserve capacity (BRC) refers to preinjury quantitative measures such as brain size that relate to outcome. Higher BRC implies threshold differences when clinical deficits will become apparent after injury, where those individuals with higher BRC require more pathology to reach that threshold. Cognitive reserve (CR) refers to how flexibly and efficiently the individual makes use of available brain resources. The CR model suggests the brain actively attempts to cope with brain damage by using pre-existing cognitive processing approaches or by enlisting compensatory approaches. Standard proxies for CR include education and IQ although this has expanded to include literacy, occupational attainment, engagement in leisure activities, and the integrity of social networks. Most research on BRC and CR has taken place in aging and degenerative disease but these concepts likely apply to the effects of TBI, especially with regards to recovery. Since high rates of TBI occur in those under age 35, both CR and BRC factors likely relate to how the individual copes with TBI over the lifespan. These factors may be particularly relevant to the relationship of developing dementia in the individual who has sustained a TBI earlier in life.

  12. The gut reaction to traumatic brain injury

    PubMed Central

    Katzenberger, Rebeccah J; Ganetzky, Barry; Wassarman, David A

    2015-01-01

    Traumatic brain injury (TBI) is a complex disorder that affects millions of people worldwide. The complexity of TBI partly stems from the fact that injuries to the brain instigate non-neurological injuries to other organs such as the intestine. Additionally, genetic variation is thought to play a large role in determining the nature and severity of non-neurological injuries. We recently reported that TBI in flies, as in humans, increases permeability of the intestinal epithelial barrier resulting in hyperglycemia and a higher risk of death. Furthermore, we demonstrated that genetic variation in flies is also pertinent to the complexity of non-neurological injuries following TBI. The goals of this review are to place our findings in the context of what is known about TBI-induced intestinal permeability from studies of TBI patients and rodent TBI models and to draw attention to how studies of the fly TBI model can provide unique insights that may facilitate diagnosis and treatment of TBI. PMID:26291482

  13. Pathology of traumatic brain injury.

    PubMed

    Finnie, John W

    2014-12-01

    Although traumatic brain injury (TBI) is frequently encountered in veterinary practice in companion animals, livestock and horses, inflicted head injury is a common method of euthanasia in domestic livestock, and malicious head trauma can lead to forensic investigation, the pathology of TBI has generally received little attention in the veterinary literature. This review highlights the pathology and pathogenesis of cerebral lesions produced by blunt, non-missile and penetrating, missile head injuries as an aid to the more accurate diagnosis of neurotrauma cases. If more cases of TBI in animals that result in fatality or euthanasia are subjected to rigorous neuropathological examination, this will lead to a better understanding of the nature and development of brain lesions in these species, rather than extrapolating data from human studies. PMID:25178417

  14. Inflammatory neuroprotection following traumatic brain injury.

    PubMed

    Russo, Matthew V; McGavern, Dorian B

    2016-08-19

    Traumatic brain injury (TBI) elicits an inflammatory response in the central nervous system (CNS) that involves both resident and peripheral immune cells. Neuroinflammation can persist for years following a single TBI and may contribute to neurodegeneration. However, administration of anti-inflammatory drugs shortly after injury was not effective in the treatment of TBI patients. Some components of the neuroinflammatory response seem to play a beneficial role in the acute phase of TBI. Indeed, following CNS injury, early inflammation can set the stage for proper tissue regeneration and recovery, which can, perhaps, explain why general immunosuppression in TBI patients is disadvantageous. Here, we discuss some positive attributes of neuroinflammation and propose that inflammation be therapeutically guided in TBI patients rather than globally suppressed. PMID:27540166

  15. Primary blast causes mild, moderate, severe and lethal TBI with increasing blast overpressures: Experimental rat injury model

    PubMed Central

    Mishra, Vikas; Skotak, Maciej; Schuetz, Heather; Heller, Abi; Haorah, James; Chandra, Namas

    2016-01-01

    Injury severity in blast induced Traumatic Brain Injury (bTBI) increases with blast overpressure (BOP) and impulse in dose-dependent manner. Pure primary blast waves were simulated in compressed gas shock-tubes in discrete increments. Present work demonstrates 24 hour survival of rats in 0–450 kPa (0–800 Pa∙s impulse) range at 10 discrete levels (60, 100, 130, 160, 190, 230, 250, 290, 350 and 420 kPa) and determines the mortality rate as a non-linear function of BOP. Using logistic regression model, predicted mortality rate (PMR) function was calculated, and used to establish TBI severities. We determined a BOP of 145 kPa as upper mild TBI threshold (5% PMR). Also we determined 146–220 kPa and 221–290 kPa levels as moderate and severe TBI based on 35%, and 70% PMR, respectively, while BOP above 290 kPa is lethal. Since there are no standards for animal bTBI injury severity, these thresholds need further refinements using histopathology, immunohistochemistry and behavior. Further, we specifically investigated mild TBI range (0–145 kPa) using physiological (heart rate), pathological (lung injury), immuno-histochemical (oxidative/nitrosative and blood-brain barrier markers) as well as blood borne biomarkers. With these additional data, we conclude that mild bTBI occurs in rats when the BOP is in the range of 85–145 kPa. PMID:27270403

  16. Primary blast causes mild, moderate, severe and lethal TBI with increasing blast overpressures: Experimental rat injury model

    NASA Astrophysics Data System (ADS)

    Mishra, Vikas; Skotak, Maciej; Schuetz, Heather; Heller, Abi; Haorah, James; Chandra, Namas

    2016-06-01

    Injury severity in blast induced Traumatic Brain Injury (bTBI) increases with blast overpressure (BOP) and impulse in dose-dependent manner. Pure primary blast waves were simulated in compressed gas shock-tubes in discrete increments. Present work demonstrates 24 hour survival of rats in 0–450 kPa (0–800 Pa•s impulse) range at 10 discrete levels (60, 100, 130, 160, 190, 230, 250, 290, 350 and 420 kPa) and determines the mortality rate as a non-linear function of BOP. Using logistic regression model, predicted mortality rate (PMR) function was calculated, and used to establish TBI severities. We determined a BOP of 145 kPa as upper mild TBI threshold (5% PMR). Also we determined 146–220 kPa and 221–290 kPa levels as moderate and severe TBI based on 35%, and 70% PMR, respectively, while BOP above 290 kPa is lethal. Since there are no standards for animal bTBI injury severity, these thresholds need further refinements using histopathology, immunohistochemistry and behavior. Further, we specifically investigated mild TBI range (0–145 kPa) using physiological (heart rate), pathological (lung injury), immuno-histochemical (oxidative/nitrosative and blood-brain barrier markers) as well as blood borne biomarkers. With these additional data, we conclude that mild bTBI occurs in rats when the BOP is in the range of 85–145 kPa.

  17. Primary blast causes mild, moderate, severe and lethal TBI with increasing blast overpressures: Experimental rat injury model.

    PubMed

    Mishra, Vikas; Skotak, Maciej; Schuetz, Heather; Heller, Abi; Haorah, James; Chandra, Namas

    2016-01-01

    Injury severity in blast induced Traumatic Brain Injury (bTBI) increases with blast overpressure (BOP) and impulse in dose-dependent manner. Pure primary blast waves were simulated in compressed gas shock-tubes in discrete increments. Present work demonstrates 24 hour survival of rats in 0-450 kPa (0-800 Pa∙s impulse) range at 10 discrete levels (60, 100, 130, 160, 190, 230, 250, 290, 350 and 420 kPa) and determines the mortality rate as a non-linear function of BOP. Using logistic regression model, predicted mortality rate (PMR) function was calculated, and used to establish TBI severities. We determined a BOP of 145 kPa as upper mild TBI threshold (5% PMR). Also we determined 146-220 kPa and 221-290 kPa levels as moderate and severe TBI based on 35%, and 70% PMR, respectively, while BOP above 290 kPa is lethal. Since there are no standards for animal bTBI injury severity, these thresholds need further refinements using histopathology, immunohistochemistry and behavior. Further, we specifically investigated mild TBI range (0-145 kPa) using physiological (heart rate), pathological (lung injury), immuno-histochemical (oxidative/nitrosative and blood-brain barrier markers) as well as blood borne biomarkers. With these additional data, we conclude that mild bTBI occurs in rats when the BOP is in the range of 85-145 kPa. PMID:27270403

  18. Traumatic brain injury, neuroimaging, and neurodegeneration

    PubMed Central

    Bigler, Erin D.

    2012-01-01

    Depending on severity, traumatic brain injury (TBI) induces immediate neuropathological effects that in the mildest form may be transient but as severity increases results in neural damage and degeneration. The first phase of neural degeneration is explainable by the primary acute and secondary neuropathological effects initiated by the injury; however, neuroimaging studies demonstrate a prolonged period of pathological changes that progressively occur even during the chronic phase. This review examines how neuroimaging may be used in TBI to understand (1) the dynamic changes that occur in brain development relevant to understanding the effects of TBI and how these relate to developmental stage when the brain is injured, (2) how TBI interferes with age-typical brain development and the effects of aging thereafter, and (3) how TBI results in greater frontotemporolimbic damage, results in cerebral atrophy, and is more disruptive to white matter neural connectivity. Neuroimaging quantification in TBI demonstrates degenerative effects from brain injury over time. An adverse synergistic influence of TBI with aging may predispose the brain injured individual for the development of neuropsychiatric and neurodegenerative disorders long after surviving the brain injury. PMID:23964217

  19. Traumatic brain injury, neuroimaging, and neurodegeneration.

    PubMed

    Bigler, Erin D

    2013-01-01

    Depending on severity, traumatic brain injury (TBI) induces immediate neuropathological effects that in the mildest form may be transient but as severity increases results in neural damage and degeneration. The first phase of neural degeneration is explainable by the primary acute and secondary neuropathological effects initiated by the injury; however, neuroimaging studies demonstrate a prolonged period of pathological changes that progressively occur even during the chronic phase. This review examines how neuroimaging may be used in TBI to understand (1) the dynamic changes that occur in brain development relevant to understanding the effects of TBI and how these relate to developmental stage when the brain is injured, (2) how TBI interferes with age-typical brain development and the effects of aging thereafter, and (3) how TBI results in greater frontotemporolimbic damage, results in cerebral atrophy, and is more disruptive to white matter neural connectivity. Neuroimaging quantification in TBI demonstrates degenerative effects from brain injury over time. An adverse synergistic influence of TBI with aging may predispose the brain injured individual for the development of neuropsychiatric and neurodegenerative disorders long after surviving the brain injury.

  20. Mild traumatic brain injury.

    PubMed

    Katz, Douglas I; Cohen, Sara I; Alexander, Michael P

    2015-01-01

    Mild traumatic brain injury (TBI) is common but accurate diagnosis and defining criteria for mild TBI and its clinical consequences have been problematic. Mild TBI causes transient neurophysiologic brain dysfunction, sometimes with structural axonal and neuronal damage. Biomarkers, such as newer imaging technologies and protein markers, are promising indicators of brain injury but are not ready for clinical use. Diagnosis relies on clinical criteria regarding depth and duration of impaired consciousness and amnesia. These criteria are particularly difficult to confirm at the least severe end of the mild TBI continuum, especially when relying on subjective, retrospective accounts. The postconcussive syndrome is a controversial concept because of varying criteria, inconsistent symptom clusters and the evidence that similar symptom profiles occur with other disorders, and even in a proportion of healthy individuals. The clinical consequences of mild TBI can be conceptualized as two multidimensional disorders: (1) a constellation of acute symptoms that might be termed early phase post-traumatic disorder (e.g., headache, dizziness, imbalance, fatigue, sleep disruption, impaired cognition), that typically resolve in days to weeks and are largely related to brain trauma and concomitant injuries; (2) a later set of symptoms, a late phase post-traumatic disorder, evolving out of the early phase in a minority of patients, with a more prolonged (months to years), sometimes worsening set of somatic, emotional, and cognitive symptoms. The later phase disorder is highly influenced by a variety of psychosocial factors and has little specificity for brain injury, although a history of multiple concussions seems to increase the risk of more severe and longer duration symptoms. Effective early phase management may prevent or limit the later phase disorder and should include education about symptoms and expectations for recovery, as well as recommendations for activity modifications

  1. Reality Lessons in Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Adams, Elaine Parker; Adams, Albert A., Jr.

    2008-01-01

    This article goes beyond the typical guidance on how to address the educational needs of students with traumatic brain injury (TBI). A survivor of TBI and his parent advocate describe real-life encounters in the education arena and offer ways to respond to the problems depicted in the situations. Their candor enhances educator awareness of the…

  2. School Reentry Following Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Deidrick, Kathleen K. M.; Farmer, Janet E.

    2005-01-01

    Successful school reentry following traumatic brain injury (TBI) is critical to recovery. Physical, cognitive, behavioral, academic, and social problems can affect a child's school performance after a TBI. However, early intervention has the potential to improve child academic outcomes and promote effective coping with any persistent changes in…

  3. Magnetic Resonance Imaging in Experimental Traumatic Brain Injury.

    PubMed

    Shen, Qiang; Watts, Lora Tally; Li, Wei; Duong, Timothy Q

    2016-01-01

    Traumatic brain injury (TBI) is a leading cause of death and disability in the USA. Common causes of TBI include falls, violence, injuries from wars, and vehicular and sporting accidents. The initial direct mechanical damage in TBI is followed by progressive secondary injuries such as brain swelling, perturbed cerebral blood flow (CBF), abnormal cerebrovascular reactivity (CR), metabolic dysfunction, blood-brain-barrier disruption, inflammation, oxidative stress, and excitotoxicity, among others. Magnetic resonance imaging (MRI) offers the means to noninvasively probe many of these secondary injuries. MRI has been used to image anatomical, physiological, and functional changes associated with TBI in a longitudinal manner. This chapter describes controlled cortical impact (CCI) TBI surgical procedures, a few common MRI protocols used in TBI imaging, and, finally, image analysis pertaining to experimental TBI imaging in rats. PMID:27604743

  4. Discriminating military and civilian traumatic brain injuries.

    PubMed

    Reid, Matthew W; Velez, Carmen S

    2015-05-01

    Traumatic brain injury (TBI) occurs at higher rates among service members than civilians. Explosions from improvised explosive devices and mines are the leading cause of TBI in the military. As such, TBI is frequently accompanied by other injuries, which makes its diagnosis and treatment difficult. In addition to postconcussion symptoms, those who sustain a TBI commonly report chronic pain and posttraumatic stress symptoms. This combination of symptoms is so typical they have been referred to as the "polytrauma clinical triad" among injured service members. We explore whether these symptoms discriminate civilian occurrences of TBI from those of service members, as well as the possibility that repeated blast exposure contributes to the development of chronic traumatic encephalopathy (CTE). This article is part of a Special Issue entitled 'Traumatic Brain Injury'.

  5. Is genistein neuroprotective in traumatic brain injury?

    PubMed

    Soltani, Zahra; Khaksari, Mohammad; Jafari, Elham; Iranpour, Maryam; Shahrokhi, Nader

    2015-12-01

    The concerns about negative consequences of estrogen therapy have led to introduce other strategies to obtain estrogen's benefits in the brain. The present study tests the hypothesis that a major isoflavone of soy; genistein with estrogen-like activity can be neuroprotective in traumatic brain injury (TBI). The male Wistar rats were randomly divided to four groups: sham, TBI, vehicle and genistein. The TBI was induced by Marmarou method. The brain edema and the disruption of blood-brain-barrier (BBB) were evaluated 48 h post-TBI. Genistein (15 mg/kg) or dimethyl sulfoxide (DMSO) was injected i.p., twice after TBI. The intracranial pressure (ICP), the motor performance, and the beam-walk task (WB) were determined before trauma, on trauma day (D0), and first (D1) and second (D2) days post-TBI. Genistein inhibited a development of brain edema and a BBB permeability in TBI animals. An increase of ICP and a defect in motor and WB performance were showed following TBI, in all times evaluated. An increase of ICP induced by TBI was suppressed by genistein on D1 and D2 times. Genistein improved a motor disorder induced by TBI, on D1 and D2 times. Also an increase of traversal time in WB task was suppressed by genistein in TBI animals, on D1 and D2 times. The results of this study demonstrated that genistein can be neuroprotective in TBI. Genistein inhibited the disruption of BBB, the brain edema and the increase of ICP, and the disturbance of neurobehavioral performance in TBI. PMID:26367454

  6. Neurobiological consequences of traumatic brain injury

    PubMed Central

    McAllister, Thomas W.

    2011-01-01

    Traumatic brain injury (TBI) is a worldwide public health problem typically caused by contact and inertial forces acting on the brain. Recent attention has also focused on the mechanisms of injury associated with exposure to blast events or explosions. Advances in the understanding of the neuropathophysiology of TBI suggest that these forces initiate an elaborate and complex array of cellular and subcellular events related to alterations in Ca++ homeostasis and signaling. Furthermore, there is a fairly predictable profile of brain regions that are impacted by neurotrauma and the related events. This profile of brain damage accurately predicts the acute and chronic sequelae that TBI survivors suffer from, although there is enough variation to suggest that individual differences such as genetic polymorphisms and factors governing resiliency play a role in modulating outcome. This paper reviews our current understanding of the neuropathophysiology of TBI and how this relates to the common clinical presentation of neurobehavioral difficulties seen after an injury. PMID:22033563

  7. Enhancing the Schooling of Students with Traumatic Brain Injury.

    ERIC Educational Resources Information Center

    Keyser-Marcus, Lori; Briel, Lori; Sherron-Targett, Pam; Yasuda, Satoko; Johnson, Susan; Wehman, Paul

    2002-01-01

    This article explores how to identify students with traumatic brain injury (TBI), difficulties students with TBI may face in the classroom, where the best placements might be, and what teaching strategies are effective. A classroom observation checklist for students with TBI is provided, along with advice on developing instructional plans.…

  8. Brain Imaging and Behavioral Outcome in Traumatic Brain Injury.

    ERIC Educational Resources Information Center

    Bigler, Erin D.

    1996-01-01

    This review explores the cellular pathology associated with traumatic brain injury (TBI) and its relation to neurobehavioral outcomes, the relationship of brain imaging findings to underlying pathology, brain imaging techniques, various image analysis procedures and how they relate to neuropsychological testing, and the importance of brain imaging…

  9. [Guidelines for the management of severe traumatic brain injury. Part 3. Surgical management of severe traumatic brain injury (Options)].

    PubMed

    Potapov, A A; Krylov, V V; Gavrilov, A G; Kravchuk, A D; Likhterman, L B; Petrikov, S S; Talypov, A E; Zakharova, N E; Solodov, A A

    2016-01-01

    Traumatic brain injury (TBI) is one of the main causes of mortality and severe disability in young and middle age patients. Patients with severe TBI, who are in coma, are of particular concern. Adequate diagnosis of primary brain injuries and timely prevention and treatment of secondary injury mechanisms markedly affect the possibility of reducing mortality and severe disability. The present guidelines are based on the authors' experience in developing international and national recommendations for the diagnosis and treatment of mild TBI, penetrating gunshot wounds of the skull and brain, severe TBI, and severe consequences of brain injury, including a vegetative state. In addition, we used the materials of international and national guidelines for the diagnosis, intensive care, and surgical treatment of severe TBI, which were published in recent years. The proposed recommendations for surgical treatment of severe TBI in adults are addressed primarily to neurosurgeons, neurologists, neuroradiologists, anesthesiologists, and intensivists who are routinely involved in treating these patients.

  10. [Guidelines for the management of severe traumatic brain injury. Part 3. Surgical management of severe traumatic brain injury (Options)].

    PubMed

    Potapov, A A; Krylov, V V; Gavrilov, A G; Kravchuk, A D; Likhterman, L B; Petrikov, S S; Talypov, A E; Zakharova, N E; Solodov, A A

    2016-01-01

    Traumatic brain injury (TBI) is one of the main causes of mortality and severe disability in young and middle age patients. Patients with severe TBI, who are in coma, are of particular concern. Adequate diagnosis of primary brain injuries and timely prevention and treatment of secondary injury mechanisms markedly affect the possibility of reducing mortality and severe disability. The present guidelines are based on the authors' experience in developing international and national recommendations for the diagnosis and treatment of mild TBI, penetrating gunshot wounds of the skull and brain, severe TBI, and severe consequences of brain injury, including a vegetative state. In addition, we used the materials of international and national guidelines for the diagnosis, intensive care, and surgical treatment of severe TBI, which were published in recent years. The proposed recommendations for surgical treatment of severe TBI in adults are addressed primarily to neurosurgeons, neurologists, neuroradiologists, anesthesiologists, and intensivists who are routinely involved in treating these patients. PMID:27070263

  11. Impact of Posttraumatic Stress Disorder and Injury Severity on Recovery in Children with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Kenardy, Justin; Le Brocque, Robyne; Hendrikz, Joan; Iselin, Greg; Anderson, Vicki; McKinlay, Lynne

    2012-01-01

    The adverse impact on recovery of posttraumatic stress disorder (PTSD) in mild traumatic brain injury (TBI) has been demonstrated in returned veterans. The study assessed this effect in children's health outcomes following TBI and extended previous work by including a full range of TBI severity, and improved assessment of PTSD within a…

  12. Behavioral Considerations Associated with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Mayfield, Joan; Homack, Susan

    2005-01-01

    Children who sustain traumatic brain injury (TBI) can experience significant cognitive deficits. These deficits may significantly impair their functioning in the classroom, resulting in the need for academic and behavioral modifications. Behavior and social problems can be the direct or indirect result of brain injury. Difficulties in paying…

  13. Motor Vehicle Crash Brain Injury in Infants and Toddlers: A Suitable Model for Inflicted Head Injury?

    ERIC Educational Resources Information Center

    Shah, Mahim; Vavilala, Monica S.; Feldman, Kenneth W.; Hallam, Daniel K.

    2005-01-01

    Objective: Children involved in motor vehicle crash (MVC) events might experience angular accelerations similar to those experienced by children with inflicted traumatic brain injury (iTBI). This is a pilot study to determine whether the progression of signs and symptoms and radiographic findings of MVC brain injury (mvcTBI) in children of the age…

  14. Getting My Bearings, Returning to School: Issues Facing Adolescents with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Schilling, Ethan J.; Getch, Yvette Q.

    2012-01-01

    Traumatic brain injury (TBI) is characterized by a blow to the head or other penetrating head injury resulting in impairment of the brain's functioning. Despite the high incidence of TBI in adolescents, many educators still consider TBI to be a low-incidence disability. In addition, school personnel often report receiving little to no pre-service…

  15. Managing traumatic brain injury secondary to explosions

    PubMed Central

    Burgess, Paula; E Sullivent, Ernest; M Sasser, Scott; M Wald, Marlena; Ossmann, Eric; Kapil, Vikas

    2010-01-01

    Explosions and bombings are the most common deliberate cause of disasters with large numbers of casualties. Despite this fact, disaster medical response training has traditionally focused on the management of injuries following natural disasters and terrorist attacks with biological, chemical, and nuclear agents. The following article is a clinical primer for physicians regarding traumatic brain injury (TBI) caused by explosions and bombings. The history, physics, and treatment of TBI are outlined. PMID:20606794

  16. TBI and Sex: Crucial role of progesterone protecting the brain in an omega-3 deficient condition

    PubMed Central

    Tyagi, Ethika; Agrawal, Rahul; Ying, Zhe; Gomez-Pinilla, Fernando

    2014-01-01

    We assessed whether the protective action of progesterone on traumatic brain injury (TBI) could be influenced by the consumption of omega-3 fatty acids during early life. Pregnant Sprague Dawley rats were fed on omega-3 adequate or deficient diet from 3rd day of pregnancy and their female offspring were kept on the same diets up to the age of 15 weeks. Ovariectomy was performed at the age of 12 weeks to deprive animals from endogenous steroids until the time of a fluid percussion injury (FPI). Dietary n-3 fatty acid deficiency increased anxiety in sham animals and TBI aggravated the effects of the deficiency. Progesterone replacement counteracted the effects of TBI on the animals reared under n-3 deficiency. A similar pattern was observed for markers of membrane homeostasis such as 4-Hydroxynonenal (HNE) and secreted phospholipases A2 (sPLA2), synaptic plasticity such as brain derived neurotrophic factor (BDNF), syntaxin (STX)-3 and growth associated protein (GAP)-43, and for growth inhibitory molecules such as myelin-associated glycoprotein (MAG) and Nogo-A. Results that progesterone had no effects on sham n-3 deficient animals suggest that the availability of progesterone is essential under injury conditions. Progesterone treatment counteracted several parameters related to synaptic plasticity and membrane stability reduced by FPI and n-3 deficiency suggest potential targets for therapeutic applications. These results reveal the importance of n-3 preconditioning during early life and the efficacy of progesterone therapy during adulthood to counteract weaknesses in neuronal and behavioral plasticity. PMID:24361060

  17. Comparative Effectiveness of Family Problem-Solving Therapy (F-PST) for Adolescent TBI

    ClinicalTrials.gov

    2016-07-25

    Tbi; Intracranial Edema; Brain Edema; Craniocerebral Trauma; Head Injury; Brain Hemorrhage, Traumatic; Subdural Hematoma; Brain Concussion; Head Injuries, Closed; Epidural Hematoma; Cortical Contusion; Wounds and Injuries; Disorders of Environmental Origin; Trauma, Nervous System; Brain Injuries

  18. Early coagulation events induce acute lung injury in a rat model of blunt traumatic brain injury.

    PubMed

    Yasui, Hideki; Donahue, Deborah L; Walsh, Mark; Castellino, Francis J; Ploplis, Victoria A

    2016-07-01

    Acute lung injury (ALI) and systemic coagulopathy are serious complications of traumatic brain injury (TBI) that frequently lead to poor clinical outcomes. Although the release of tissue factor (TF), a potent initiator of the extrinsic pathway of coagulation, from the injured brain is thought to play a key role in coagulopathy after TBI, its function in ALI following TBI remains unclear. In this study, we investigated whether the systemic appearance of TF correlated with the ensuing coagulopathy that follows TBI in ALI using an anesthetized rat blunt trauma TBI model. Blood and lung samples were obtained after TBI. Compared with controls, pulmonary edema and increased pulmonary permeability were observed as early as 5 min after TBI without evidence of norepinephrine involvement. Systemic TF increased at 5 min and then diminished 60 min after TBI. Lung injury and alveolar hemorrhaging were also observed as early as 5 min after TBI. A biphasic elevation of TF was observed in the lungs after TBI, and TF-positive microparticles (MPs) were detected in the alveolar spaces. Fibrin(ogen) deposition was also observed in the lungs within 60 min after TBI. Additionally, preadministration of a direct thrombin inhibitor, Refludan, attenuated lung injuries, thus implicating thrombin as a direct participant in ALI after TBI. The results from this study demonstrated that enhanced systemic TF may be an initiator of coagulation activation that contributes to ALI after TBI. PMID:27190065

  19. Pituitary dysfunction following traumatic brain injury: clinical perspectives

    PubMed Central

    Tanriverdi, Fatih; Kelestimur, Fahrettin

    2015-01-01

    Traumatic brain injury (TBI) is a well recognized public health problem worldwide. TBI has previously been considered as a rare cause of hypopituitarism, but an increased prevalence of neuroendocrine dysfunction in patients with TBI has been reported during the last 15 years in most of the retrospective and prospective studies. Based on data in the current literature, approximately 15%–20% of TBI patients develop chronic hypopituitarism, which clearly suggests that TBI-induced hypopituitarism is frequent in contrast with previous assumptions. This review summarizes the current data on TBI-induced hypopituitarism and briefly discusses some clinical perspectives on post-traumatic anterior pituitary hormone deficiency. PMID:26251600

  20. Health Care Costs 1 Year After Pediatric Traumatic Brain Injury

    PubMed Central

    Rivara, Frederick P.; Vavilala, Monica S.

    2015-01-01

    Objectives. This study sought to estimate total health care costs for mild, moderate, and severe pediatric traumatic brain injury (TBI) and to compare individual- and population-level costs across levels of TBI severity. Methods. Using 2007 to 2010 MarketScan Commercial Claims and Encounters data, we estimated total quarterly health care costs 1 year after TBI among enrollees (aged < 18 years). We compared costs across levels of TBI severity using generalized linear models. Results. Mild TBI accounted for 96.6% of the 319 103 enrollees with TBI; moderate and severe TBI accounted for 1.7% and 1.6%, respectively. Adjusted individual health care costs for moderate and severe TBI were significantly higher than mild TBI in the year after injury (P < .01). At the population level, moderate and severe TBI costs were 88% and 75% less than mild TBI, respectively. Conclusions. Individually, moderate and severe TBI initially generated costs that were markedly higher than those of mild TBI. At the population level, costs following mild TBI far exceeded those of more severe cases, a result of the extremely high population burden of mild TBI. PMID:26270293

  1. Neuropathology of mild traumatic brain injury: relationship to neuroimaging findings.

    PubMed

    Bigler, Erin D; Maxwell, William L

    2012-06-01

    Neuroimaging identified abnormalities associated with traumatic brain injury (TBI) are but gross indicators that reflect underlying trauma-induced neuropathology at the cellular level. This review examines how cellular pathology relates to neuroimaging findings with the objective of more closely relating how neuroimaging findings reveal underlying neuropathology. Throughout this review an attempt will be made to relate what is directly known from post-mortem microscopic and gross anatomical studies of TBI of all severity levels to the types of lesions and abnormalities observed in contemporary neuroimaging of TBI, with an emphasis on mild traumatic brain injury (mTBI). However, it is impossible to discuss the neuropathology of mTBI without discussing what occurs with more severe injury and viewing pathological changes on some continuum from the mildest to the most severe. Historical milestones in understanding the neuropathology of mTBI are reviewed along with implications for future directions in the examination of neuroimaging and neuropathological correlates of TBI.

  2. Linguistic outcomes following traumatic brain injury in children.

    PubMed

    Ewing-Cobbs, Linda; Barnes, Marcia

    2002-09-01

    Recent studies of outcome after traumatic brain injury (TBI) emphasize the adverse effect of diffuse brain injury on linguistic development. This article reviews studies of lexical development, discourse processes, and reading in children and adolescents with TBI. The child's developmental level at the time of injury is related to the pattern of deficits. Young children who sustain severe TBI are particularly vulnerable to linguistic deficits at both lexical and discourse levels. TBI in older children and adolescents preferentially disrupts higher-order discourse functions. The contribution of deficits in fundamental processes, such as working memory and processing speed, to linguistic outcomes requires further investigation.

  3. Linguistic outcomes following traumatic brain injury in children.

    PubMed

    Ewing-Cobbs, Linda; Barnes, Marcia

    2002-09-01

    Recent studies of outcome after traumatic brain injury (TBI) emphasize the adverse effect of diffuse brain injury on linguistic development. This article reviews studies of lexical development, discourse processes, and reading in children and adolescents with TBI. The child's developmental level at the time of injury is related to the pattern of deficits. Young children who sustain severe TBI are particularly vulnerable to linguistic deficits at both lexical and discourse levels. TBI in older children and adolescents preferentially disrupts higher-order discourse functions. The contribution of deficits in fundamental processes, such as working memory and processing speed, to linguistic outcomes requires further investigation. PMID:12350042

  4. Traumatic brain injury and forensic neuropsychology.

    PubMed

    Bigler, Erin D; Brooks, Michael

    2009-01-01

    As part of a special issue of The Journal of Head Trauma Rehabilitation, forensic neuropsychology is reviewed as it applies to traumatic brain injury (TBI) and other types of acquired brain injury in which clinical neuropsychologists and rehabilitation psychologists may be asked to render professional opinions about the neurobehavioral effects and outcome of a brain injury. The article introduces and overviews the topic focusing on the process of forensic neuropsychological consultation and practice as it applies to patients with TBI or other types of acquired brain injury. The emphasis is on the application of scientist-practitioner standards as they apply to legal questions about the status of a TBI patient and how best that may be achieved. This article introduces each topic area covered in this special edition.

  5. Relation of Executive Functioning to Pragmatic Outcome following Severe Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Douglas, Jacinta M.

    2010-01-01

    Purpose: This study was designed to explore the behavioral nature of pragmatic impairment following severe traumatic brain injury (TBI) and to evaluate the contribution of executive skills to the experience of pragmatic difficulties after TBI. Method: Participants were grouped into 43 TBI dyads (TBI adults and close relatives) and 43 control…

  6. Traumatic Brain Injury Models in Animals.

    PubMed

    Rostami, Elham

    2016-01-01

    Traumatic brain injury (TBI) is the leading cause of death in young adults in industrialized nations and in the developing world the WHO considers TBI a silent epidemic caused by an increasing number of traffic accidents. Despite the major improvement of TBI outcome in the acute setting in the past 20 years, the assessment, therapeutic interventions, and prevention of long-term complications remain a challenge. In order to get a deeper insight into the pathology of TBI and advancement of medical understanding and clinical progress experimental animal models are an essential requirement. This chapter provides an overview of most commonly used experimental animal TBI models and the pathobiological findings based on current data. In addition, limitations and advantages of each TBI model are mentioned. This will hopefully give an insight into the possibilities of each model and be of value in choosing one when designing a study. PMID:27604712

  7. Traumatic brain injury among North Carolina's veterans.

    PubMed

    Hooker, James Stewart; Moore, Daniel P

    2015-04-01

    This article describes the difficulty of diagnosing traumatic brain injury (TBI), treatment protocols provided through the military, an alternative therapy with scientific evidence of its effectiveness in repairing injured brain tissue, challenges faced by brain-injured veterans seeking community reintegration, and state services that are available to help veterans.

  8. Traumatic Alterations in Consciousness: Traumatic Brain Injury

    PubMed Central

    Blyth, Brian J.; Bazarian, Jeffrey J.

    2010-01-01

    Mild traumatic brain injury (mTBI) refers to the clinical condition of transient alteration of consciousness as a result of traumatic injury to the brain. The priority of emergency care is to identify and facilitate the treatment of rare but potentially life threatening intra-cranial injuries associated with mTBI through the judicious application of appropriate imaging studies and neurosurgical consultation. Although post-mTBI symptoms quickly and completely resolve in the vast majority of cases, a significant number of patients will complain of lasting problems that may cause significant disability. Simple and early interventions such as patient education and appropriate referral can reduce the likelihood of chronic symptoms. Although definitive evidence is lacking, mTBI is likely to be related to significant long-term sequelae such as Alzheimer's disease and other neurodegenerative processes. PMID:20709244

  9. Using the public health model to address unintentional injuries and TBI: A perspective from the Centers for Disease Control and Prevention (CDC).

    PubMed

    Baldwin, Grant; Breiding, Matt; Sleet, David

    2016-06-30

    Traumatic brain injury (TBI) can have long term effects on mental and physical health, and can disrupt vocational, educational, and social functioning. TBIs can range from mild to severe and their effects can last many years after the initial injury. CDC seeks to reduce the burden of TBI from unintentional injuries through a focus on primary prevention, improved recognition and management, and intervening to improve health outcomes after TBI. CDC uses a 4-stage public health model to guide TBI prevention, moving from 1) surveillance of TBI, 2) identification of risk and protective factors for TBI, 3) development and testing of evidence-based interventions, to 4) bringing effective intervention to scale through widespread adoption. CDC's unintentional injury prevention activities focus on the prevention of sports-related concussions, motor vehicle crashes, and older adult falls. For concussion prevention, CDC developed Heads Up - an awareness initiative focusing on ways to prevent a concussion in sports, and identifying how to recognize and manage potential concussions. In motor vehicle injury prevention, CDC has developed a tool (MV PICCS) to calculate the expected number of injuries prevented and lives saved using various evidence-based motor vehicle crash prevention strategies. To help prevent TBI related to older adult falls, CDC has developed STEADI, an initiative to help primary care providers identify their patients' falls risk and provide effective interventions. In the future, CDC is focused on advancing our understanding of the public health burden of TBI through improved surveillance in order to produce more comprehensive estimates of the public health burden of TBI.

  10. Using the public health model to address unintentional injuries and TBI: A perspective from the Centers for Disease Control and Prevention (CDC).

    PubMed

    Baldwin, Grant; Breiding, Matt; Sleet, David

    2016-06-30

    Traumatic brain injury (TBI) can have long term effects on mental and physical health, and can disrupt vocational, educational, and social functioning. TBIs can range from mild to severe and their effects can last many years after the initial injury. CDC seeks to reduce the burden of TBI from unintentional injuries through a focus on primary prevention, improved recognition and management, and intervening to improve health outcomes after TBI. CDC uses a 4-stage public health model to guide TBI prevention, moving from 1) surveillance of TBI, 2) identification of risk and protective factors for TBI, 3) development and testing of evidence-based interventions, to 4) bringing effective intervention to scale through widespread adoption. CDC's unintentional injury prevention activities focus on the prevention of sports-related concussions, motor vehicle crashes, and older adult falls. For concussion prevention, CDC developed Heads Up - an awareness initiative focusing on ways to prevent a concussion in sports, and identifying how to recognize and manage potential concussions. In motor vehicle injury prevention, CDC has developed a tool (MV PICCS) to calculate the expected number of injuries prevented and lives saved using various evidence-based motor vehicle crash prevention strategies. To help prevent TBI related to older adult falls, CDC has developed STEADI, an initiative to help primary care providers identify their patients' falls risk and provide effective interventions. In the future, CDC is focused on advancing our understanding of the public health burden of TBI through improved surveillance in order to produce more comprehensive estimates of the public health burden of TBI. PMID:27497467

  11. Using anesthetics and analgesics in experimental traumatic brain injury.

    PubMed

    Rowe, Rachel K; Harrison, Jordan L; Thomas, Theresa C; Pauly, James R; Adelson, P David; Lifshitz, Jonathan

    2013-08-01

    Valid modeling of traumatic brain injury (TBI) requires accurate replication of both the mechanical forces that cause the primary injury and the conditions that lead to secondary injuries observed in human patients. The use of animals in TBI research is justified by the lack of in vitro or computer models that can sufficiently replicate the complex pathological processes involved. Measures to reduce nociception and distress must be implemented, but the administration of anesthetics and analgesics can influence TBI outcomes, threatening the validity of the research. In this review, the authors present evidence for the interference of anesthetics and analgesics in the natural course of brain injury in animal models of TBI. They suggest that drugs should be selected for or excluded from experimental TBI protocols on the basis of IACUC-approved experimental objectives in order to protect animal welfare and preserve the validity of TBI models. PMID:23877609

  12. Emerging Therapies in Traumatic Brain Injury

    PubMed Central

    Kochanek, Patrick M.; Jackson, Travis C.; Ferguson, Nikki Miller; Carlson, Shaun W.; Simon, Dennis W.; Brockman, Erik C.; Ji, Jing; Bayir, Hülya; Poloyac, Samuel M.; Wagner, Amy K.; Kline, Anthony E.; Empey, Philip E.; Clark, Robert S.B.; Jackson, Edwin K.; Dixon, C. Edward

    2015-01-01

    Despite decades of basic and clinical research, treatments to improve outcomes after traumatic brain injury (TBI) are limited. However, based on the recent recognition of the prevalence of mild TBI, and its potential link to neurodegenerative disease, many new and exciting secondary injury mechanisms have been identified and several new therapies are being evaluated targeting both classic and novel paradigms. This includes a robust increase in both preclinical and clinical investigations. Using a mechanism-based approach the authors define the targets and emerging therapies for TBI. They address putative new therapies for TBI across both the spectrum of injury severity and the continuum of care, from the field to rehabilitation. They discuss TBI therapy using 11 categories, namely, (1) excitotoxicity and neuronal death, (2) brain edema, (3) mitochondria and oxidative stress, (4) axonal injury, (5) inflammation, (6) ischemia and cerebral blood flow dysregulation, (7) cognitive enhancement, (8) augmentation of endogenous neuroprotection, (9) cellular therapies, (10) combination therapy, and (11) TBI resuscitation. The current golden age of TBI research represents a special opportunity for the development of breakthroughs in the field. PMID:25714870

  13. Traumatic brain injury in modern war

    NASA Astrophysics Data System (ADS)

    Ling, Geoffrey S. F.; Hawley, Jason; Grimes, Jamie; Macedonia, Christian; Hancock, James; Jaffee, Michael; Dombroski, Todd; Ecklund, James M.

    2013-05-01

    Traumatic brain injury (TBI) is common and especially with military service. In Iraq and Afghanistan, explosive blast related TBI has become prominent and is mainly from improvised explosive devices (IED). Civilian standard of care clinical practice guidelines (CPG) were appropriate has been applied to the combat setting. When such CPGs do not exist or are not applicable, new practice standards for the military are created, as for TBI. Thus, CPGs for prehospital care of combat TBI CPG [1] and mild TBI/concussion [2] were introduced as was a DoD system-wide clinical care program, the first large scale system wide effort to address all severities of TBI in a comprehensive organized way. As TBI remains incompletely understood, substantial research is underway. For the DoD, leading this effort are The Defense and Veterans Brain Injury Center, National Intrepid Center of Excellence and the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury. This program is a beginning, a work in progress ready to leverage advances made scientifically and always with the intent of providing the best care to its military beneficiaries.

  14. The Impact of Traumatic Brain Injury on the Aging Brain.

    PubMed

    Young, Jacob S; Hobbs, Jonathan G; Bailes, Julian E

    2016-09-01

    Traumatic brain injury (TBI) has come to the forefront of both the scientific and popular culture. Specifically, sports-related concussions or mild TBI (mTBI) has become the center of scientific scrutiny with a large amount of research focusing on the long-term sequela of this type of injury. As the populace continues to age, the impact of TBI on the aging brain will become clearer. Currently, reports have come to light that link TBI to neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, as well as certain psychiatric diseases. Whether these associations are causations, however, is yet to be determined. Other long-term sequelae, such as chronic traumatic encephalopathy (CTE), appear to be associated with repetitive injuries. Going forward, as we gain better understanding of the pathophysiological process involved in TBI and subclinical head traumas, and individual traits that influence susceptibility to neurocognitive diseases, a clearer, more comprehensive understanding of the connection between brain injury and resultant disease processes in the aging brain will become evident. PMID:27432348

  15. Emerging narrative discourse skills 18 months after traumatic brain injury in early childhood

    PubMed Central

    Walz, Nicolay Chertkoff; Yeates, Keith Owen; Taylor, H. Gerry; Stancin, Terry; Wade, Shari L.

    2013-01-01

    This study examined the longer term effect of traumatic brain injury (TBI), approximately 18 months post-injury, on emerging narrative discourse skills of 85 children with orthopaedic injury (OI), 43 children with moderate TBI, and 19 children with severe TBI who were between 3 years and 6 years 11 months at injury. Children with TBI performed worse than children with OI on most discourse indices. Children with severe TBI were less proficient than children with moderate TBI at identifying unimportant story information. Age and pragmatic skills were predictors of discourse performance. PMID:22257728

  16. Traumatic Brain Injury: Persistent Misconceptions and Knowledge Gaps among Educators

    ERIC Educational Resources Information Center

    Ettel, Deborah; Glang, Ann E.; Todis, Bonnie; Davies, Susan C.

    2016-01-01

    Each year approximately 700,000 U.S. children aged 0-19 years sustain a traumatic brain injury (TBI) placing them at risk for academic, cognitive, and behavioural challenges. Although TBI has been a special education disability category for 25 years, prevalence studies show that of the 145,000 students each year who sustain long-term injury from…

  17. The Changed Brain: Teacher Awareness of Traumatic Brain Injury and Instruction Methods to Enhance Cognitive Processing in Mathematics

    ERIC Educational Resources Information Center

    Stahl, Judith M.

    2008-01-01

    Traumatic brain injury (TBI) has come to subjugate and exert its authority on education as some survivors re-enter the academic arena. A key component of a TBI student's academic success is dependent upon a teacher's awareness of the TBI learner and a willingness to modify curriculum to promote the uniqueness of the changed brain and therefore,…

  18. Post-traumatic stress disorder vs traumatic brain injury

    PubMed Central

    Bryant, Richard

    2011-01-01

    Post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) often coexist because brain injuries are often sustained in traumatic experiences. This review outlines the significant overlap between PTSD and TBI by commencing with a critical outline of the overlapping symptoms and problems of differential diagnosis. The impact of TBI on PTSD is then described, with increasing evidence suggesting that mild TBI can increase risk for PTSD. Several explanations are offered for this enhanced risk. Recent evidence suggests that impairment secondary to mild TBI is largely attributable to stress reactions after TBI, which challenges the long-held belief that postconcussive symptoms are a function of neurological insult This recent evidence is pointing to new directions for treatment of postconcussive symptoms that acknowledge that treating stress factors following TBI may be the optimal means to manage the effects of many TBIs, PMID:22034252

  19. Critical care management of severe traumatic brain injury in adults

    PubMed Central

    2012-01-01

    Traumatic brain injury (TBI) is a major medical and socio-economic problem, and is the leading cause of death in children and young adults. The critical care management of severe TBI is largely derived from the "Guidelines for the Management of Severe Traumatic Brain Injury" that have been published by the Brain Trauma Foundation. The main objectives are prevention and treatment of intracranial hypertension and secondary brain insults, preservation of cerebral perfusion pressure (CPP), and optimization of cerebral oxygenation. In this review, the critical care management of severe TBI will be discussed with focus on monitoring, avoidance and minimization of secondary brain insults, and optimization of cerebral oxygenation and CPP. PMID:22304785

  20. Pediatric Rodent Models of Traumatic Brain Injury.

    PubMed

    Semple, Bridgette D; Carlson, Jaclyn; Noble-Haeusslein, Linda J

    2016-01-01

    Due to a high incidence of traumatic brain injury (TBI) in children and adolescents, age-specific studies are necessary to fully understand the long-term consequences of injuries to the immature brain. Preclinical and translational research can help elucidate the vulnerabilities of the developing brain to insult, and provide model systems to formulate and evaluate potential treatments aimed at minimizing the adverse effects of TBI. Several experimental TBI models have therefore been scaled down from adult rodents for use in juvenile animals. The following chapter discusses these adapted models for pediatric TBI, and the importance of age equivalence across species during model development and interpretation. Many neurodevelopmental processes are ongoing throughout childhood and adolescence, such that neuropathological mechanisms secondary to a brain insult, including oxidative stress, metabolic dysfunction and inflammation, may be influenced by the age at the time of insult. The long-term evaluation of clinically relevant functional outcomes is imperative to better understand the persistence and evolution of behavioral deficits over time after injury to the developing brain. Strategies to modify or protect against the chronic consequences of pediatric TBI, by supporting the trajectory of normal brain development, have the potential to improve quality of life for brain-injured children. PMID:27604726

  1. Post mTBI fatigue is associated with abnormal brain functional connectivity.

    PubMed

    Nordin, Love Engström; Möller, Marika Christina; Julin, Per; Bartfai, Aniko; Hashim, Farouk; Li, Tie-Qiang

    2016-02-16

    This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants' fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject's fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system.

  2. Post mTBI fatigue is associated with abnormal brain functional connectivity

    PubMed Central

    Nordin, Love Engström; Möller, Marika Christina; Julin, Per; Bartfai, Aniko; Hashim, Farouk; Li, Tie-Qiang

    2016-01-01

    This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants’ fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject’s fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system. PMID:26878885

  3. Post mTBI fatigue is associated with abnormal brain functional connectivity.

    PubMed

    Nordin, Love Engström; Möller, Marika Christina; Julin, Per; Bartfai, Aniko; Hashim, Farouk; Li, Tie-Qiang

    2016-01-01

    This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants' fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject's fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system. PMID:26878885

  4. Frequency and impact of recurrent traumatic brain injury in a population-based sample.

    PubMed

    Theadom, Alice; Parmar, Priya; Jones, Kelly; Barker-Collo, Suzanne; Starkey, Nicola J; McPherson, Kathryn M; Ameratunga, Shanthi; Feigin, Valery L

    2015-05-15

    The aim of this study was to determine the frequency, mechanism(s), and impact of recurrent traumatic brain injury (TBI) over a 1-year period. Population-based TBI incidence and 1-year outcomes study with embedded case-control analysis. All participants (adults and children) who experienced a recurrent TBI (more than one) in the 12 months after an index injury and matched controls who sustained one TBI within the same period were enrolled in a population-based TBI incidence and outcomes study. Details of all recurrent TBIs sustained within 12 months of the initial index injury were recorded. Each recurrent TBI case was matched to a case sustaining one TBI based on age (±2 years), gender, and index TBI severity. Cognitive ability, disability, and postconcussion symptoms (PCS) were assessed 1 year after the index injury. Overall, 9.9% (n=72) of TBI cases experienced at least one recurrent TBI within the year after initial index injury. Males, people <35 years of age, and those who had experienced a TBI before their index injury were at highest risk of recurrent TBI. Recurrent TBI cases reported significantly increased PCS at 1 year, compared to the matched controls (n=72) sustaining one TBI. There was no difference in overall cognitive ability and disability between the two groups. People experiencing recurrent TBIs are more likely to experience increased frequency and severity of PCS. Greater public awareness of the potential effects of recurrent brain injury is needed. PMID:25334048

  5. Model Family Professional Partnerships for Interventions in Children with Traumatic Brain Injury.

    ERIC Educational Resources Information Center

    Pieper, Betty; Singer, George

    A meeting of professional experts in pediatric traumatic brain injury (TBI) focused on gathering current expert opinion regarding assistance to families with a child having such an injury. Quantitative data from an ethnographic survey of 214 parents on the effects of TBI on the family is summarized. Then, normalization for families of TBI children…

  6. Long-Term Attention Problems in Children with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Yeates, Keith Owen; Armstrong, Kira; Janusz, Jennifer; Taylor, H. Gerry; Wade, Shari; Stancin, Terry; Drotar, Dennis

    2005-01-01

    Objective: To examine long-term attention problems and their cognitive correlates after childhood traumatic brain injury (TBI). Method: Data were drawn from a prospective, longitudinal study conducted between 1992 and 2002. Participants included 41 children with severe TBI, 41 with moderate TBI, and 50 with orthopedic injury (OI), who were all…

  7. Differences in Brain Metabolic Impairment between Chronic Mild/Moderate TBI Patients with and without Visible Brain Lesions Based on MRI

    PubMed Central

    Asano, Yoshitaka; Ikegame, Yuka

    2016-01-01

    Introduction. Many patients with mild/moderate traumatic brain injury (m/mTBI) in the chronic stage suffer from executive brain function impairment. Analyzing brain metabolism is important for elucidating the pathological mechanisms associated with their symptoms. This study aimed to determine the differences in brain glucose metabolism between m/mTBI patients with and without visible traumatic brain lesions based on MRI. Methods. Ninety patients with chronic m/mTBI due to traffic accidents were enrolled and divided into two groups based on their MRI findings. Group A comprised 50 patients with visible lesions. Group B comprised 40 patients without visible lesions. Patients underwent FDG-PET scans following cognitive tests. FDG-PET images were analyzed using voxel-by-voxel univariate statistical tests. Results. There were no significant differences in the cognitive tests between Group A and Group B. Based on FDG-PET findings, brain metabolism significantly decreased in the orbital gyrus, cingulate gyrus, and medial thalamus but increased in the parietal and occipital convexity in Group A compared with that in the control. Compared with the control, patients in Group B exhibited no significant changes. Conclusions. These results suggest that different pathological mechanisms may underlie cognitive impairment in m/mTBI patients with and without organic brain damage. PMID:27529067

  8. Differences in Brain Metabolic Impairment between Chronic Mild/Moderate TBI Patients with and without Visible Brain Lesions Based on MRI.

    PubMed

    Ito, Keiichi; Asano, Yoshitaka; Ikegame, Yuka; Shinoda, Jun

    2016-01-01

    Introduction. Many patients with mild/moderate traumatic brain injury (m/mTBI) in the chronic stage suffer from executive brain function impairment. Analyzing brain metabolism is important for elucidating the pathological mechanisms associated with their symptoms. This study aimed to determine the differences in brain glucose metabolism between m/mTBI patients with and without visible traumatic brain lesions based on MRI. Methods. Ninety patients with chronic m/mTBI due to traffic accidents were enrolled and divided into two groups based on their MRI findings. Group A comprised 50 patients with visible lesions. Group B comprised 40 patients without visible lesions. Patients underwent FDG-PET scans following cognitive tests. FDG-PET images were analyzed using voxel-by-voxel univariate statistical tests. Results. There were no significant differences in the cognitive tests between Group A and Group B. Based on FDG-PET findings, brain metabolism significantly decreased in the orbital gyrus, cingulate gyrus, and medial thalamus but increased in the parietal and occipital convexity in Group A compared with that in the control. Compared with the control, patients in Group B exhibited no significant changes. Conclusions. These results suggest that different pathological mechanisms may underlie cognitive impairment in m/mTBI patients with and without organic brain damage. PMID:27529067

  9. Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury

    NASA Astrophysics Data System (ADS)

    Sturdivant, Nasya M.; Smith, Sean G.; Ali, Syed F.; Wolchok, Jeffrey C.; Balachandran, Kartik

    2016-09-01

    Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality.

  10. Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury

    PubMed Central

    Sturdivant, Nasya M.; Smith, Sean G.; Ali, Syed F.; Wolchok, Jeffrey C.; Balachandran, Kartik

    2016-01-01

    Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality. PMID:27623738

  11. Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury.

    PubMed

    Sturdivant, Nasya M; Smith, Sean G; Ali, Syed F; Wolchok, Jeffrey C; Balachandran, Kartik

    2016-01-01

    Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality. PMID:27623738

  12. Hydrogen-rich water attenuates brain damage and inflammation after traumatic brain injury in rats.

    PubMed

    Tian, Runfa; Hou, Zonggang; Hao, Shuyu; Wu, Weichuan; Mao, Xiang; Tao, Xiaogang; Lu, Te; Liu, Baiyun

    2016-04-15

    Inflammation and oxidative stress are the two major causes of apoptosis after traumatic brain injury (TBI). Most previous studies of the neuroprotective effects of hydrogen-rich water on TBI primarily focused on antioxidant effects. The present study investigated whether hydrogen-rich water (HRW) could attenuate brain damage and inflammation after traumatic brain injury in rats. A TBI model was induced using a controlled cortical impact injury. HRW or distilled water was injected intraperitoneally daily following surgery. We measured survival rate, brain edema, blood-brain barrier (BBB) breakdown and neurological dysfunction in all animals. Changes in inflammatory cytokines, inflammatory cells and Cho/Cr metabolites in brain tissues were also detected. Our results demonstrated that TBI-challenged rats exhibited significant brain injuries that were characterized by decreased survival rate and increased BBB permeability, brain edema, and neurological dysfunction, while HRW treatment ameliorated the consequences of TBI. HRW treatment also decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1β and HMGB1), inflammatory cell number (Iba1) and inflammatory metabolites (Cho) and increased the levels of an anti-inflammatory cytokine (IL-10) in the brain tissues of TBI-challenged rats. In conclusion, HRW could exert a neuroprotective effect against TBI and attenuate inflammation, which suggests HRW as an effective therapeutic strategy for TBI patients. PMID:26826009

  13. Imatinib treatment reduces brain injury in a murine model of traumatic brain injury

    PubMed Central

    Su, Enming J.; Fredriksson, Linda; Kanzawa, Mia; Moore, Shannon; Folestad, Erika; Stevenson, Tamara K.; Nilsson, Ingrid; Sashindranath, Maithili; Schielke, Gerald P.; Warnock, Mark; Ragsdale, Margaret; Mann, Kris; Lawrence, Anna-Lisa E.; Medcalf, Robert L.; Eriksson, Ulf; Murphy, Geoffrey G.; Lawrence, Daniel A.

    2015-01-01

    Current therapies for Traumatic brain injury (TBI) focus on stabilizing individuals and on preventing further damage from the secondary consequences of TBI. A major complication of TBI is cerebral edema, which can be caused by the loss of blood brain barrier (BBB) integrity. Recent studies in several CNS pathologies have shown that activation of latent platelet derived growth factor-CC (PDGF-CC) within the brain can promote BBB permeability through PDGF receptor α (PDGFRα) signaling, and that blocking this pathway improves outcomes. In this study we examine the efficacy for the treatment of TBI of an FDA approved antagonist of the PDGFRα, Imatinib. Using a murine model we show that Imatinib treatment, begun 45 min after TBI and given twice daily for 5 days, significantly reduces BBB dysfunction. This is associated with significantly reduced lesion size 24 h, 7 days, and 21 days after TBI, reduced cerebral edema, determined from apparent diffusion co-efficient (ADC) measurements, and with the preservation of cognitive function. Finally, analysis of cerebrospinal fluid (CSF) from human TBI patients suggests a possible correlation between high PDGF-CC levels and increased injury severity. Thus, our data suggests a novel strategy for the treatment of TBI with an existing FDA approved antagonist of the PDGFRα. PMID:26500491

  14. Animal models of traumatic brain injury

    PubMed Central

    Xiong, Ye; Mahmood, Asim; Chopp, Michael

    2014-01-01

    Traumatic brain injury (TBI) is a leading cause of mortality and morbidity in both civilian life and the battlefield worldwide. Survivors of TBI frequently experience long-term disabling changes in cognition, sensorimotor function and personality. Over the past three decades, animal models have been developed to replicate the various aspects of human TBI, to better understand the underlying pathophysiology and to explore potential treatments. Nevertheless, promising neuroprotective drugs, which were identified to be effective in animal TBI models, have all failed in phase II or phase III clinical trials. This failure in clinical translation of preclinical studies highlights a compelling need to revisit the current status of animal models of TBI and therapeutic strategies. PMID:23329160

  15. Biophysical mechanisms of traumatic brain injuries.

    PubMed

    Young, Lee Ann; Rule, Gregory T; Bocchieri, Robert T; Burns, Jennie M

    2015-02-01

    Despite years of effort to prevent traumatic brain injuries (TBIs), the occurrence of TBI in the United States alone has reached epidemic proportions. When an external force is applied to the head, it is converted into stresses that must be absorbed into the brain or redirected by a helmet or other protective equipment. Complex interactions of the head, neck, and jaw kinematics result in strains in the brain. Even relatively mild mechanical trauma to these tissues can initiate a neurochemical cascade that leads to TBI. Civilians and warfighters can experience head injuries in both combat and noncombat situations from a variety of threats, including ballistic and blunt impact, acceleration, and blast. It is critical to understand the physics created by these threats to develop meaningful improvements to clinical care, injury prevention, and mitigation. Here the authors review the current state of understanding of the complex loading conditions that lead to TBI and characterize how these loads are transmitted through soft tissue, the skull and into the brain, resulting in TBI. In addition, gaps in knowledge and injury thresholds are reviewed, as these must be addressed to better design strategies that reduce TBI incidence and severity. PMID:25714862

  16. Biophysical mechanisms of traumatic brain injuries.

    PubMed

    Young, Lee Ann; Rule, Gregory T; Bocchieri, Robert T; Burns, Jennie M

    2015-02-01

    Despite years of effort to prevent traumatic brain injuries (TBIs), the occurrence of TBI in the United States alone has reached epidemic proportions. When an external force is applied to the head, it is converted into stresses that must be absorbed into the brain or redirected by a helmet or other protective equipment. Complex interactions of the head, neck, and jaw kinematics result in strains in the brain. Even relatively mild mechanical trauma to these tissues can initiate a neurochemical cascade that leads to TBI. Civilians and warfighters can experience head injuries in both combat and noncombat situations from a variety of threats, including ballistic and blunt impact, acceleration, and blast. It is critical to understand the physics created by these threats to develop meaningful improvements to clinical care, injury prevention, and mitigation. Here the authors review the current state of understanding of the complex loading conditions that lead to TBI and characterize how these loads are transmitted through soft tissue, the skull and into the brain, resulting in TBI. In addition, gaps in knowledge and injury thresholds are reviewed, as these must be addressed to better design strategies that reduce TBI incidence and severity.

  17. Persistent cognitive dysfunction after traumatic brain injury: A dopamine hypothesis

    PubMed Central

    Bales, James W.; Wagner, Amy K.; Kline, Anthony E.; Dixon, C. Edward

    2010-01-01

    Traumatic brain injury (TBI) represents a significant cause of death and disability in industrialized countries. Of particular importance to patients the chronic effect that TBI has on cognitive function. Therapeutic strategies have been difficult to evaluate because of the complexity of injuries and variety of patient presentations within a TBI population. However, pharmacotherapies targeting dopamine (DA) have consistently shown benefits in attention, behavioral outcome, executive function, and memory. Still it remains unclear what aspect of TBI pathology is targeted by DA therapies and what time-course of treatment is most beneficial for patient outcomes. Fortunately, ongoing research in animal models has begun to elucidate the pathophysiology of DA alterations after TBI. The purpose of this review is to discuss clinical and experimental research examining DAergic therapies after TBI, which will in turn elucidate the importance of DA for cognitive function/dysfunction after TBI as well as highlight the areas that require further study. PMID:19580914

  18. Traumatic brain injury and obesity induce persistent central insulin resistance.

    PubMed

    Karelina, Kate; Sarac, Benjamin; Freeman, Lindsey M; Gaier, Kristopher R; Weil, Zachary M

    2016-04-01

    Traumatic brain injury (TBI)-induced impairments in cerebral energy metabolism impede tissue repair and contribute to delayed functional recovery. Moreover, the transient alteration in brain glucose utilization corresponds to a period of increased vulnerability to the negative effects of a subsequent TBI. In order to better understand the factors contributing to TBI-induced central metabolic dysfunction, we examined the effect of single and repeated TBIs on brain insulin signalling. Here we show that TBI induced acute brain insulin resistance, which resolved within 7 days following a single injury but persisted until 28 days following repeated injuries. Obesity, which causes brain insulin resistance and neuroinflammation, exacerbated the consequences of TBI. Obese mice that underwent a TBI exhibited a prolonged reduction of Akt (also known as protein kinase B) signalling, exacerbated neuroinflammation (microglial activation), learning and memory deficits, and anxiety-like behaviours. Taken together, the transient changes in brain insulin sensitivity following TBI suggest a reduced capacity of the injured brain to respond to the neuroprotective and anti-inflammatory actions of insulin and Akt signalling, and thus may be a contributing factor for the damaging neuroinflammation and long-lasting deficits that occur following TBI. PMID:26833850

  19. Brain activation profiles in mTBI: Evidence from combined resting-state EEG and MEG activity.

    PubMed

    Lianyang Li; Pagnotta, Mattia F; Arakaki, Xianghong; Tran, Thao; Strickland, David; Harrington, Michael; Zouridakis, George

    2015-01-01

    In this study, we compared the brain activation profiles obtained from resting state Electroencephalographic (EEG) and Magnetoencephalographic (MEG) activity in six mild traumatic brain injury (mTBI) patients and five orthopedic controls, using power spectral density (PSD) analysis. We first estimated intracranial dipolar EEG/MEG sources on a dense grid on the cortical surface and then projected these sources on a standardized atlas with 68 regions of interest (ROIs). Averaging the PSD values of all sources in each ROI across all control subjects resulted in a normative database that was used to convert the PSD values of mTBI patients into z-scores in eight distinct frequency bands. We found that mTBI patients exhibited statistically significant overactivation in the delta, theta, and low alpha bands. Additionally, the MEG modality seemed to better characterize the group of individual subjects. These findings suggest that resting-state EEG/MEG activation maps may be used as specific biomarkers that can help with the diagnosis of and assess the efficacy of intervention in mTBI patients. PMID:26737894

  20. Current pre-hospital traumatic brain injury management in China

    PubMed Central

    Kou, Kou; Hou, Xiang-yu; Sun, Jian-dong; Chu, Kevin

    2014-01-01

    BACKGROUND: Traumatic brain injury (TBI) is associated with most trauma-related deaths. Secondary brain injury is the leading cause of in-hospital deaths after traumatic brain injury. By early prevention and slowing of the initial pathophysiological mechanism of secondary brain injury, pre-hospital service can significantly reduce case-fatality rates of TBI. In China, the incidence of TBI is increasing and the proportion of severe TBI is much higher than that in other countries. The objective of this paper is to review the pre-hospital management of TBI in China. DATA SOURCES: A literature search was conducted in January 2014 using the China National Knowledge Infrastructure (CNKI). Articles on the assessment and treatment of TBI in pre-hospital settings practiced by Chinese doctors were identified. The information on the assessment and treatment of hypoxemia, hypotension, and brain herniation was extracted from the identified articles. RESULTS: Of the 471 articles identified, 65 met the selection criteria. The existing literature indicated that current practices of pre-hospital TBI management in China were sub-optimal and varied considerably across different regions. CONCLUSION: Since pre-hospital care is the weakest part of Chinese emergency care, appropriate training programs on pre-hospital TBI management are urgently needed in China. PMID:25548596

  1. The Wechsler Adult Intelligence Scale-III and Malingering in Traumatic Brain Injury: Classification Accuracy in Known Groups

    ERIC Educational Resources Information Center

    Curtis, Kelly L.; Greve, Kevin W.; Bianchini, Kevin J.

    2009-01-01

    A known-groups design was used to determine the classification accuracy of Wechsler Adult Intelligence Scale-III (WAIS-III) variables in detecting malingered neurocognitive dysfunction (MND) in traumatic brain injury (TBI). TBI patients were classified into the following groups: (a) mild TBI not-MND (n = 26), (b) mild TBI MND (n = 31), and (c)…

  2. Chapter 2 traumatic brain injury research in military populations.

    PubMed

    Kasper, Christine E

    2015-01-01

    Traumatic brain injury (TBI) in all of its forms--blast, concussive, and penetrating--has been an unfortunate sequela of warfare since ancient times. The continued evolution of military munitions and armor on the battlefield, as well as the insurgent use of improvised explosive devices, has led to blast-related TBI whose long-term effects on behavior and cognition are not yet known. Advances in medical care have greatly increased survival from these types of injuries. Therefore, an understanding of the potential health effects of TBI is essential. This review focuses on specific aspects of military-related TBI. There exists a large body of literature reporting the environmental conditions, forces, and staging of injury. Many of these studies are focused on the neuropathology of TBI, due to blast overpressure waves, and the emergence of large numbers of mild blast-related TBI cases. PMID:25946382

  3. What Can I Do to Help Prevent Traumatic Brain Injury?

    MedlinePlus

    ... to Congress: Epidemiology and Rehabilitation Report to Congress: Military Personnel TBI in the US: Emergency Department Visits, Hospitalizations ... sustaining a traumatic brain injury, including: Buckling your child in the car using a child safety seat, ...

  4. Chronic cerebrovascular dysfunction after traumatic brain injury.

    PubMed

    Jullienne, Amandine; Obenaus, Andre; Ichkova, Aleksandra; Savona-Baron, Catherine; Pearce, William J; Badaut, Jerome

    2016-07-01

    Traumatic brain injuries (TBI) often involve vascular dysfunction that leads to long-term alterations in physiological and cognitive functions of the brain. Indeed, all the cells that form blood vessels and that are involved in maintaining their proper function can be altered by TBI. This Review focuses on the different types of cerebrovascular dysfunction that occur after TBI, including cerebral blood flow alterations, autoregulation impairments, subarachnoid hemorrhage, vasospasms, blood-brain barrier disruption, and edema formation. We also discuss the mechanisms that mediate these dysfunctions, focusing on the cellular components of cerebral blood vessels (endothelial cells, smooth muscle cells, astrocytes, pericytes, perivascular nerves) and their known and potential roles in the secondary injury cascade. © 2016 Wiley Periodicals, Inc. PMID:27117494

  5. Experimental models of repetitive brain injuries.

    PubMed

    Weber, John T

    2007-01-01

    Repetitive traumatic brain injury (TBI) occurs in a significant portion of trauma patients, especially in specific populations, such as child abuse victims or athletes involved in contact sports (e.g. boxing, football, hockey, and soccer). A continually emerging hypothesis is that repeated mild injuries may cause cumulative damage to the brain, resulting in long-term cognitive dysfunction. The growing attention to this hypothesis is reflected in several recent experimental studies of repeated mild TBI in vivo. These reports generally demonstrate cellular and cognitive dysfunction after repetitive injury using rodent TBI models. In some cases, data suggests that the effects of a second mild TBI may be synergistic, rather than additive. In addition, some studies have found increases in cellular markers associated with Alzheimer's disease after repeated mild injuries, which demonstrates a direct experimental link between repetitive TBI and neurodegenerative disease. To complement the findings from humans and in vivo experimentation, my laboratory group has investigated the effects of repeated trauma in cultured brain cells using a model of stretch-induced mechanical injury in vitro. In these studies, hippocampal cells exhibited cumulative damage when mild stretch injuries were repeated at either 1-h or 24-h intervals. Interestingly, the extent of damage to the cells was dependent on the time between repeated injuries. Also, a very low level of stretch, which produced no cell damage on its own, induced cell damage when it was repeated several times at a short interval (every 2 min). Although direct comparisons to the clinical situation are difficult, these types of repetitive, low-level, mechanical stresses may be similar to the insults received by certain athletes, such as boxers, or hockey and soccer players. This type of in vitro model could provide a reliable system in which to study the mechanisms underlying cellular dysfunction following repeated injuries. As

  6. [The characteristics of blast traumatic brain injury].

    PubMed

    Matsumoto, Yoshihisa; Hatano, Ben; Matsushita, Yoshitaro; Nawashiro, Hiroshi; Shima, Katsuji

    2010-08-01

    With the increase in terrorist activity in recent times, the number of blast injuries has also increased in civilian and military settings. In a recent war, the number of patients who suffered blast traumatic brain injury (bTBI) increased, so treatment of bTBI is currently a very important issue. Blast injury is complicated and can be divided into 4 categories: primary, secondary, tertiary, and quaternary. Primary blast injury results from exposure to blast waves; secondary blast injury is trauma caused by fragments of explosive devices; tertiary blast injury is the result of collision with objects; and quaternary blast injury is the result of exposure to toxic and other substances. Blast waves mainly injure air-containing organs such as the lung, bowel, and ear. The brain may also be affected by blast waves. From the clinical perspective, hyperemia and severe cerebral edema occur frequently in patients who sustain significant bTBI. Penetrating or closed head injury caused by the explosion may be associated with vasospasm and pseudoaneurysm formation. Mild traumatic brain injury during war can be associated with posttraumatic stress disorder. To elucidate the mechanism of bTBI, many research works using animal models and computer analysis are underway. Such studies have so far shown that blast waves can cause damage to the brain tissue and cognitive deficits; however, detailed investigations on this topic are still required. Treatment of bTBI patients may require clinical knowledge and skills related to intensive care, neurology, and neurosurgery. Moreover, further research is required in this field. PMID:20697143

  7. Traumatic Brain Injury: An Educator's Manual. [Revised Edition.

    ERIC Educational Resources Information Center

    Fiegenbaum, Ed, Ed.; And Others

    This manual for the Portland (Oregon) Public Schools presents basic information on providing educational services to children with traumatic brain injury (TBI). Individual sections cover the following topics: the brain, central nervous system and behavior; physical, psychological and emotional implication; traumatic brain injury in children versus…

  8. Narrative Skills Following Traumatic Brain Injury in Children and Adults.

    ERIC Educational Resources Information Center

    Biddle, Kathleen R.; And Others

    1996-01-01

    This study used dependency analysis to document and describe the narrative discourse impairments of 10 children (mean age 12) and 10 adults (mean age 35) with traumatic brain injury (TBI), and matched controls. Individuals with TBI were significantly more disfluent than controls and their narrative performance required a significant listener…

  9. Classroom Interventions for Students with Traumatic Brain Injuries

    ERIC Educational Resources Information Center

    Bowen, Julie M.

    2005-01-01

    Students who have sustained a traumatic brain injury (TBI) return to the school setting with a range of cognitive, psychosocial, and physical deficits that can significantly affect their academic functioning. Successful educational reintegration for students with TBI requires careful assessment of each child's unique needs and abilities and the…

  10. Intervention Strategies for Serving Students with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Arroyos-Jurado, Elsa; Savage, Todd A.

    2008-01-01

    As school-age children are at the highest risk for sustaining a traumatic brain injury (TBI), educational professionals working in school settings will encounter students dealing with the after-effects of a TBI. These effects can influence students' ability to navigate the behavioral, social, and academic demands of the classroom. This article…

  11. Traumatic Brain Injury in Early Childhood: Developmental Effects and Interventions.

    ERIC Educational Resources Information Center

    Lowenthal, Barbara; Lowenthal, Barbara

    1998-01-01

    Describes the unique effects of traumatic brain injury (TBI) on development in early childhood and offers suggestions for interventions in the cognitive, language, social-emotional, motor, and adaptive domains. Urges more intensive, long-term studies on the immediate and long-term effects of TBI. (Author/DB)

  12. GH and Pituitary Hormone Alterations After Traumatic Brain Injury.

    PubMed

    Karaca, Züleyha; Tanrıverdi, Fatih; Ünlühızarcı, Kürşad; Kelestimur, Fahrettin

    2016-01-01

    Traumatic brain injury (TBI) is a crucially important public health problem around the world, which gives rise to increased mortality and is the leading cause of physical and psychological disability in young adults, in particular. Pituitary dysfunction due to TBI was first described 95 years ago. However, until recently, only a few papers have been published in the literature and for this reason, TBI-induced hypopituitarism has been neglected for a long time. Recent studies have revealed that TBI is one of the leading causes of hypopituitarism. TBI which causes hypopituitarism may be characterized by a single head injury such as from a traffic accident or by chronic repetitive head trauma as seen in combative sports including boxing, kickboxing, and football. Vascular damage, hypoxic insult, direct trauma, genetic predisposition, autoimmunity, and neuroinflammatory changes may have a role in the development of hypopituitarism after TBI. Because of the exceptional structure of the hypothalamo-pituitary vasculature and the special anatomic location of anterior pituitary cells, GH is the most commonly lost hormone after TBI, and the frequency of isolated GHD is considerably high. TBI-induced pituitary dysfunction remains undiagnosed and therefore untreated in most patients because of the nonspecific and subtle clinical manifestations of hypopituitarism. Treatment of TBI-induced hypopituitarism depends on the deficient anterior pituitary hormones. GH replacement therapy has some beneficial effects on metabolic parameters and neurocognitive dysfunction. Patients with TBI without neuroendocrine changes and those with TBI-induced hypopituitarism share the same clinical manifestations, such as attention deficits, impulsion impairment, depression, sleep abnormalities, and cognitive disorders. For this reason, TBI-induced hypopituitarism may be neglected in TBI victims and it would be expected that underlying hypopituitarism would aggravate the clinical picture of TBI

  13. Screening for Traumatic Brain Injury: Findings and Public Health Implications

    PubMed Central

    Dams-O’Connor, Kristen; Cantor, Joshua B.; Brown, Margaret; Dijkers, Marcel P.; Spielman, Lisa A.; Gordon, Wayne A.

    2016-01-01

    Objective To provide an overview of a series of projects that used a structured self-report screening tool in diverse settings and samples to screen for lifetime history of traumatic brain injury (TBI). Setting Diverse community settings. Participants Homeless persons (n = 111), individuals with HIV seeking vocational rehabilitation (n = 173), youth in the juvenile justice system (n = 271), public schoolchildren (n = 174), substance users (n = 845), intercollegiate athletes (n = 90), and other community-based samples (n = 396). Design Cross-sectional. Main Measure Brain Injury Screening Questionnaire. Results Screening using the Brain Injury Screening Questionnaire finds that 27% to 54% of those in high-risk populations report a history of TBI with chronic symptoms. Associations between TBI and social, academic, or other problems are evident in several studies. In non–high-risk community samples, 9% to 12% of individuals report TBI with chronic symptoms. Conclusion Systematic TBI screening can be implemented efficiently and inexpensively in a variety of settings. Lifetime TBI history data gathered using a structured self-report instrument can augment existing estimates of the prevalence of TBI, both as an acute event and as a chronic condition. Identification of individuals with TBI can facilitate primary prevention efforts, such as reducing risk for reinjury in high-risk groups, and provide access to appropriate interventions that can reduce the personal and societal costs of TBI (tertiary prevention). PMID:25370440

  14. Endocannabinoids and traumatic brain injury

    PubMed Central

    Shohami, Esther; Cohen-Yeshurun, Ayelet; Magid, Lital; Algali, Merav; Mechoulam, Raphael

    2011-01-01

    Traumatic brain injury (TBI) represents the leading cause of death in young individuals. It triggers the accumulation of harmful mediators, leading to secondary damage, yet protective mechanisms are also set in motion. The endocannabinoid (eCB) system consists of ligands, such as anandamide and 2-arachidonoyl-glycerol (2-AG), receptors (e.g. CB1, CB2), transporters and enzymes, which are responsible for the ‘on-demand’ synthesis and degradation of these lipid mediators. There is a large body of evidence showing that eCB are markedly increased in response to pathogenic events. This fact, as well as numerous studies on experimental models of brain toxicity, neuroinflammation and trauma supports the notion that the eCB are part of the brain's compensatory or repair mechanisms. These are mediated via CB receptors signalling pathways that are linked to neuronal survival and repair. The levels of 2-AG, the most highly abundant eCB, are significantly elevated after TBI and when administered to TBI mice, 2-AG decreases brain oedema, inflammation and infarct volume and improves clinical recovery. The role of CB1 in mediating these effects was demonstrated using selective antagonists or CB1 knockout mice. CB2 were shown in other models of brain insults to reduce white blood cell rolling and adhesion, to reduce infarct size and to improve motor function. This review is focused on the role the eCB system plays as a self-neuroprotective mechanism and its potential as a basis for the development of novel therapeutic modality for the treatment of CNS pathologies with special emphasis on TBI. LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-7 PMID:21418185

  15. Outcome measures for traumatic brain injury.

    PubMed

    Shukla, Dhaval; Devi, B Indira; Agrawal, Amit

    2011-07-01

    Traumatic brain injury (TBI) is a major public health problem resulting in death and disabilities of young and productive people. Though the mortality of TBI has decreased substantially in recent years the disability due to TBI has not appreciably reduced. Various outcome scales have been proposed and used to assess disability after TBI. A few, commonly used are Glasgow Outcome Scale (GOS) with or without extended scores, Disability Rating Scale (DRS), Functional Independence Measure (FIM), Community Integration Questionnaire (CIQ), and the Functional Status Examination (FSE). These scales assess disability resulting from physical and cognitive impairments. For patients with good physical recovery a cognitive and neuropsychological outcome measure is required. Such measures include Neurobehavioural Function Inventory and specific neuropsychological tests like Rey Complex Figure for visuoconstruction and memory, Controlled Oral Word Association for verbal fluency, Symbol Digit Modalities (verbal) for sustained attention and Grooved Pegboard for fine motor dexterity. A more holistic and complete outcome measure is Quality of Life (QOL). Disease specific QOL measure for TBI, Quality of Life after Brain Injury (QOLIBRI) has also been recently proposed. The problems with outcome measures include poor operational definitions, lack of sensitivity or low ceiling effects, inability to evaluate patients who cannot report, lack of integration of morbidity and mortality categories, and limited domains of functioning assessed. GOSE-E satisfies most of the criteria of good outcome scale and in combination with neuropsychological tests is a near complete instrument for assessment of outcome after TBI. PMID:21440363

  16. Cardiac dysfunction following brain death after severe pediatric traumatic brain injury: A preliminary study of 32 children

    PubMed Central

    Krishnamoorthy, Vijay; Prathep, Sumidtra; Sharma, Deepak; Fujita, Yasuki; Armstead, William; Vavilala, Monica S.

    2015-01-01

    Background: Cardiac dysfunction after brain death has been described in a variety of brain injury paradigms but is not well understood after severe pediatric traumatic brain injury (TBI). Cardiac dysfunction may have implications for organ donation in this patient population. Materials and Methods: We conducted a retrospective cohort study of pediatric patients with severe TBI, both with and without a diagnosis of brain death, who underwent echocardiography during the first 2 weeks after TBI, between the period of 2003–2011. We examined cardiac dysfunction in patients with and without a diagnosis of brain death. Results: In all, 32 (2.3%) of 1,413 severe pediatric TBI patients underwent echocardiogram evaluation. Most patients had head abbreviated injury score 5 (range 2–6) and subdural hematoma (34.4%). Ten patients with TBI had brain death compared with 22 severe TBI patients who did not have brain death. Four (40%) of 10 pediatric TBI patients with brain death had a low ejection fraction (EF) compared with 1 (4.5%) of 22 pediatric TBI patients without brain death who had low EF (OR = 14, P = 0.024). Conclusions: The incidence of cardiac dysfunction is higher among pediatric severe TBI patients with a diagnosis of brain death, as compared to patients without brain death. This finding may have implications for cardiac organ donation from this population and deserves further study. PMID:26157654

  17. Traumatic Brain Injury: Perspectives from Educational Professionals

    ERIC Educational Resources Information Center

    Mohr, J. Darrell; Bullock, Lyndal M.

    2005-01-01

    This article reports the outcomes from 2 focus groups conducted to ascertain professional educators' perceptions regarding their (a) level of preparedness for working with students with traumatic brain injury (TBI), (b) ideas regarding ways to improve support to students and families, and (c) concerns about meeting the diverse needs of children…

  18. Seizures Following Traumatic Brain Injury in Childhood.

    ERIC Educational Resources Information Center

    Williams, Dennis

    This guide provides information on seizures in students with traumatic brain injury (TBI) and offers guidelines for classroom management. First, a classification system for seizures is presented with specific types of seizures explained. Post-traumatic seizures are specifically addressed as is the importance of seizure prevention when possible.…

  19. Traumatic Brain Injury in Children and Adolescents: Academic and Intellectual Outcomes Following Injury

    ERIC Educational Resources Information Center

    Arroyos-Jurado, Elsa; Paulsen, Jane S.; Ehly, Stewart; Max, Jeffrey E.

    2006-01-01

    This study was conducted to examine the impact of childhood traumatic brain injury (TBI) on intellectual and academic outcomes postinjury. A comprehensive assessment of cognition, achievement, learning, and memory was administered to 27 children and adolescents 6 to 8 years post-TBI. Findings revealed that parent ratings of premorbid achievement…

  20. Diagnosing pseudobulbar affect in traumatic brain injury

    PubMed Central

    Engelman, William; Hammond, Flora M; Malec, James F

    2014-01-01

    Pseudobulbar affect (PBA) is defined by episodes of involuntary crying and/or laughing as a result of brain injury or other neurological disease. Epidemiology studies show that 5.3%–48.2% of people with traumatic brain injury (TBI) may have symptoms consistent with (or suggestive of) PBA. Yet it is a difficult and often overlooked condition in individuals with TBI, and is easily confused with depression or other mood disorders. As a result, it may be undertreated and persist for longer than it should. This review presents the signs and symptoms of PBA in patients with existing TBI and outlines how to distinguish PBA from other similar conditions. It also compares and contrasts the different diagnostic criteria found in the literature and briefly mentions appropriate treatments. This review follows a composite case with respect to the clinical course and treatment for PBA and presents typical challenges posed to a provider when diagnosing PBA. PMID:25336956

  1. Neural Correlates of Motor Dysfunction in Children with Traumatic Brain Injury: Exploration of Compensatory Recruitment Patterns

    ERIC Educational Resources Information Center

    Caeyenberghs, K.; Wenderoth, N.; Smits-Engelsman, B. C. M.; Sunaert, S.; Swinnen, S. P.

    2009-01-01

    Traumatic brain injury (TBI) is a common form of disability in children. Persistent deficits in motor control have been documented following TBI but there has been less emphasis on changes in functional cerebral activity. In the present study, children with moderate to severe TBI (n = 9) and controls (n = 17) were scanned while performing cyclical…

  2. Best Practices in Assessment and Programming for Students with Traumatic Brain Injuries.

    ERIC Educational Resources Information Center

    North Carolina State Dept. of Public Instruction, Raleigh. Div. for Exceptional Children.

    This manual is intended to give teachers a basic understanding of traumatic brain injury (TBI) and an in-depth understanding of techniques for evaluating the student with TBI in order to provide appropriate programming. Section 1 introduces a definition of TBI including incidence and causes, an overview of neuroanatomy, primary and secondary…

  3. Decoding Hippocampal Signaling Deficits after Traumatic Brain Injury

    PubMed Central

    Atkins, Coleen M.

    2012-01-01

    There are more than 3.17 million people coping with long-term disabilities due to traumatic brain injury (TBI) in the United States. The majority of TBI research is focused on developing acute neuroprotective treatments to prevent or minimize these long-term disabilities. Therefore, chronic TBI survivors represent a large, underserved population that could significantly benefit from a therapy that capitalizes on the endogenous recovery mechanisms occurring during the weeks to months following brain trauma. Previous studies have found that the hippocampus is highly vulnerable to brain injury, in both experimental models of TBI and during human TBI. Although often not directly mechanically injured by the head injury, in the weeks to months following TBI, the hippocampus undergoes atrophy and exhibits deficits in long-term potentiation (LTP), a persistent increase in synaptic strength that is considered to be a model of learning and memory. Decoding the chronic hippocampal LTP and cell signaling deficits after brain trauma will provide new insights into the molecular mechanisms of hippocampal-dependent learning impairments caused by TBI and facilitate the development of effective therapeutic strategies to improve hippocampal-dependent learning for chronic survivors of TBI. PMID:23227133

  4. Combined Neurotrauma Models: Experimental Models Combining Traumatic Brain Injury and Secondary Insults.

    PubMed

    Simon, Dennis W; Vagni, Vincent M; Kochanek, Patrick M; Clark, Robert S B

    2016-01-01

    Patients with severe traumatic brain injury (TBI) frequently present with concomitant injuries that may cause secondary brain injury and impact outcomes. Animal models have been developed that combine contemporary models of TBI with a secondary neurologic insult such as hypoxia, shock, long bone fracture, and radiation exposure. Combined injury models may be particularly useful when modeling treatment strategies and in efforts to map basic research to a heterogeneous patient population. Here, we review these models and their collective contribution to the literature on TBI. In addition, we provide protocols and notes for two well-characterized models of TBI plus hemorrhagic shock. PMID:27604730

  5. Traumatic Brain Injury: A Look at Alcohol and Other Drug Abuse Prevention.

    ERIC Educational Resources Information Center

    VSA Educational Services, Washington, DC. Resource Center on Substance Abuse Prevention and Disability.

    This leaflet examines alcohol and other drug abuse prevention for individuals with traumatic brain injury. The characteristics and incidence of traumatic brain injury (TBI) are noted. The implications of alcohol and other drug use are discussed, emphasizing that TBI is often related to lifestyles where alcohol and other drug abuse and risk taking…

  6. Investigating Metacognition, Cognition, and Behavioral Deficits of College Students with Acute Traumatic Brain Injuries

    ERIC Educational Resources Information Center

    Martinez, Sarah; Davalos, Deana

    2016-01-01

    Objective: Executive dysfunction in college students who have had an acute traumatic brain injury (TBI) was investigated. The cognitive, behavioral, and metacognitive effects on college students who endorsed experiencing a brain injury were specifically explored. Participants: Participants were 121 college students who endorsed a mild TBI, and 121…

  7. The Nature of Services Provided Students with Traumatic Brain Injury in Virginia.

    ERIC Educational Resources Information Center

    Virginia State Dept. of Education, Richmond.

    A survey of Virginia's local school divisions was conducted to obtain data on the number of students in Virginia with traumatic brain injury (TBI) and the nature of the services provided to them. A definition of traumatic brain injury is presented, and disorders resulting from TBI are listed, followed by a list of services required by this…

  8. Progesterone for Neuroprotection in Pediatric Traumatic Brain Injury

    PubMed Central

    Robertson, Courtney L.; Fidan, Emin; Stanley, Rachel M.; MHSA; Noje, Corina; Bayir, Hülya

    2016-01-01

    Objective To provide an overview of the preclinical literature on progesterone for neuroprotection after traumatic brain injury (TBI), and to describe unique features of developmental brain injury that should be considered when evaluating the therapeutic potential for progesterone treatment after pediatric TBI. Data Sources National Library of Medicine PubMed literature review. Data Selection The mechanisms of neuroprotection by progesterone are reviewed, and the preclinical literature using progesterone treatment in adult animal models of TBI are summarized. Unique features of the developing brain that could either enhance or limit the efficacy of neuroprotection by progesterone are discussed, and the limited preclinical literature using progesterone after acute injury to the developing brain is described. Finally, the current status of clinical trials of progesterone for adult TBI is reviewed. Data Extraction and Synthesis Progesterone is a pleotropic agent with beneficial effects on secondary injury cascades that occur after TBI, including cerebral edema, neuroinflammation, oxidative stress, and excitotoxicity. More than 40 studies have used progesterone for treatment after TBI in adult animal models, with results summarized in tabular form. However, very few studies have evaluated progesterone in pediatric animal models of brain injury. To date, two human Phase II trials of progesterone for adult TBI have been published, and two multi-center Phase III trials are underway. Conclusions The unique features of the developing brain from that of a mature adult brain make it necessary to independently study progesterone in clinically relevant, immature animal models of TBI. Additional preclinical studies could lead to the development of a novel neuroprotective therapy that could reduce the long-term disability in head-injured children, and could potentially provide benefit in other forms of pediatric brain injury (global ischemia, stroke, statue epilepticus). PMID

  9. Impaired Visual Integration in Children with Traumatic Brain Injury: An Observational Study

    PubMed Central

    Weeda, Wouter D.; van Heurn, L. W. Ernest; Vermeulen, R. Jeroen; Goslings, J. Carel; Luitse, Jan S. K.; Poll-Thé, Bwee Tien; Beelen, Anita; van der Wees, Marleen; Kemps, Rachèl J. J. K.; Catsman-Berrevoets, Coriene E.

    2015-01-01

    Background Axonal injury after traumatic brain injury (TBI) may cause impaired sensory integration. We aim to determine the effects of childhood TBI on visual integration in relation to general neurocognitive functioning. Methods We compared children aged 6–13 diagnosed with TBI (n = 103; M = 1.7 years post-injury) to children with traumatic control (TC) injury (n = 44). Three TBI severity groups were distinguished: mild TBI without risk factors for complicated TBI (mildRF- TBI, n = 22), mild TBI with ≥1 risk factor (mildRF+ TBI, n = 46) or moderate/severe TBI (n = 35). An experimental paradigm measured speed and accuracy of goal-directed behavior depending on: (1) visual identification; (2) visual localization; or (3) both, measuring visual integration. Group-differences on reaction time (RT) or accuracy were tracked down to task strategy, visual processing efficiency and extra-decisional processes (e.g. response execution) using diffusion model analysis. General neurocognitive functioning was measured by a Wechsler Intelligence Scale short form. Results The TBI group had poorer accuracy of visual identification and visual integration than the TC group (Ps ≤ .03; ds ≤ -0.40). Analyses differentiating TBI severity revealed that visual identification accuracy was impaired in the moderate/severe TBI group (P = .05, d = -0.50) and that visual integration accuracy was impaired in the mildRF+ TBI group and moderate/severe TBI group (Ps < .02, ds ≤ -0.56). Diffusion model analyses tracked impaired visual integration accuracy down to lower visual integration efficiency in the mildRF+ TBI group and moderate/severe TBI group (Ps < .001, ds ≤ -0.73). Importantly, intelligence impairments observed in the TBI group (P = .009, d = -0.48) were statistically explained by visual integration efficiency (P = .002). Conclusions Children with mildRF+ TBI or moderate/severe TBI have impaired visual integration efficiency, which may contribute to poorer general

  10. Practitioner Review: Beyond Shaken Baby Syndrome--What Influences the Outcomes for Infants following Traumatic Brain Injury?

    ERIC Educational Resources Information Center

    Ashton, Rebecca

    2010-01-01

    Background: Traumatic brain injury (TBI) in infancy is relatively common, and is likely to lead to poorer outcomes than injuries sustained later in childhood. While the headlines have been grabbed by infant TBI caused by abuse, often known as shaken baby syndrome, the evidence base for how to support children following TBI in infancy is thin.…

  11. Prediction of brain age suggests accelerated atrophy after traumatic brain injury

    PubMed Central

    Cole, James H; Leech, Robert; Sharp, David J

    2015-01-01

    Objective The long-term effects of traumatic brain injury (TBI) can resemble observed in normal ageing, suggesting that TBI may accelerate the ageing process. We investigate this using a neuroimaging model that predicts brain age in healthy individuals and then apply it to TBI patients. We define individuals' differences in chronological and predicted structural "brain age," and test whether TBI produces progressive atrophy and how this relates to cognitive function. Methods A predictive model of normal ageing was defined using machine learning in 1,537 healthy individuals, based on magnetic resonance imaging–derived estimates of gray matter (GM) and white matter (WM). This ageing model was then applied to test 99 TBI patients and 113 healthy controls to estimate brain age. Results The initial model accurately predicted age in healthy individuals (r * 0.92). TBI brains were estimated to be "older," with a mean predicted age difference (PAD) between chronological and estimated brain age of 4.66 years (±10.8) for GM and 5.97 years (±11.22) for WM. This PAD predicted cognitive impairment and correlated strongly with the time since TBI, indicating that brain tissue loss increases throughout the chronic postinjury phase. Interpretation TBI patients' brains were estimated to be older than their chronological age. This discrepancy increases with time since injury, suggesting that TBI accelerates the rate of brain atrophy. This may be an important factor in the increased susceptibility in TBI patients for dementia and other age-associated conditions, motivating further research into the age-like effects of brain injury and other neurological diseases. PMID:25623048

  12. Hypothermia following Pediatric Traumatic Brain Injury

    PubMed Central

    2009-01-01

    Abstract Preclinical as well as clinical studies in traumatic brain injury (TBI) have established the likely association of secondary injury and outcome in adults in children following severe injury. Similarly, there is growing evidence in experimental laboratory studies that moderate hypothermia has a beneficial effect on outcome, though the exact mechanisms remain to be absolutely defined. The Pediatric TBI Guidelines provided the knowledge and background for standard management of children following severe TBI and highlighted that there are very few clinical studies to date. In particular with respect to temperature regulation and the use of hypothermia, initial findings of case series of small numbers were promising. Further preliminary randomized clinical trials, both single institution and multicenter, have provided the initial data on safety and efficacy, though larger, Phase III studies are necessary to ensure both the safety and efficacy of hypothermia in pediatric TBI prior to implementation as part of the standard of care. It is expected that hypothermia initiated early after severe TBI will have a protective effect on the pediatric brain and can be done safely, but this still remains to be definitively tested. PMID:19271965

  13. Correlation of brain levels of progesterone and dehydroepiandrosterone with neurological recovery after traumatic brain injury in female mice.

    PubMed

    Lopez-Rodriguez, Ana Belen; Acaz-Fonseca, Estefania; Giatti, Silvia; Caruso, Donatella; Viveros, Maria-Paz; Melcangi, Roberto C; Garcia-Segura, Luis M

    2015-06-01

    Traumatic brain injury (TBI) is an important cause of disability in humans. Neuroactive steroids, such as progesterone and dehydroepiandrosterone (DHEA), are neuroprotective in TBI models. However in order to design potential neuroprotective strategies based on neuroactive steroids it is important to determine whether its brain levels are altered by TBI. In this study we have used a weight-drop model of TBI in young adult female mice to determine the levels of neuroactive steroids in the brain and plasma at 24h, 72 h and 2 weeks after injury. We have also analyzed whether the levels of neuroactive steroids after TBI correlated with the neurological score of the animals. TBI caused neurological deficit detectable at 24 and 72 h, which recovered by 2 weeks after injury. Brain levels of progesterone, tetrahydroprogesterone (THP), isopregnanolone and 17β-estradiol were decreased 24h, 72 h and 2 weeks after TBI. DHEA and brain testosterone levels presented a transient decrease at 24h after lesion. Brain levels of progesterone and DHEA showed a positive correlation with neurological recovery. Plasma analyses showed that progesterone was decreased 72 h after lesion but, in contrast with brain progesterone, its levels did not correlate with neurological deficit. These findings indicate that TBI alters the levels of neuroactive steroids in the brain with independence of its plasma levels and suggest that the pharmacological increase in the brain of the levels of progesterone and DHEA may result in the improvement of neurological recovery after TBI.

  14. Alteration in synaptic junction proteins following traumatic brain injury.

    PubMed

    Merlo, Lucia; Cimino, Francesco; Angileri, Filippo Flavio; La Torre, Domenico; Conti, Alfredo; Cardali, Salvatore Massimiliano; Saija, Antonella; Germanò, Antonino

    2014-08-15

    Extensive research and scientific efforts have been focused on the elucidation of the pathobiology of cellular and axonal damage following traumatic brain injury (TBI). Conversely, few studies have specifically addressed the issue of synaptic dysfunction. Synaptic junction proteins may be involved in post-TBI alterations, leading to synaptic loss or disrupted plasticity. A Synapse Protein Database on synapse ontology identified 109 domains implicated in synaptic activities and over 5000 proteins, but few of these demonstrated to play a role in the synaptic dysfunction after TBI. These proteins are involved in neuroplasticity and neuromodulation and, most importantly, may be used as novel neuronal markers of TBI for specific intervention.

  15. The experience of traumatic brain injury in Botswana.

    PubMed

    Mbakile-Mahlanza, Lingani; Manderson, Lenore; Ponsford, Jennie

    2015-01-01

    Whilst the consequences of traumatic brain injury (TBI) are understood in Western countries, it is not known how cultural background and beliefs affect response and outcome following TBI in low and middle income countries. This study aimed to explore the experiences of TBI in Botswana. Participants included 21 individuals with moderate to severe TBI (68% males, mean age 35.2 years), 18 caregivers and 25 healthcare workers. Qualitative semi-structured interviews were transcribed, translated and thematically coded. Thematic analysis indicated several themes: Injury-related changes, attributions and beliefs about the cause of the injury, family reactions, attitudes, and resources. Participants described the common injury-related effects of TBI. Many participants attributed their injury to supernatural causes. Immediate family members of participants with TBI expressed a sense of love and devotion towards the injured person. Communication was characterised by inadequate information given to those injured and their caregivers. Provision of care was impeded by insufficient staff, limited supplies and lack of training of nurses. The current healthcare system would therefore appear to be ill-equipped to meet the needs of TBI survivors in Botswana. This study will improve understanding of cultural responses and approaches to brain injuries in Botswana which may, in turn, inform improved practice. PMID:25558888

  16. Detecting Behavioral Deficits Post Traumatic Brain Injury in Rats.

    PubMed

    Awwad, Hibah O

    2016-01-01

    Traumatic brain injury (TBI), ranging from mild to severe, almost always elicits an array of behavioral deficits in injured subjects. Some of these TBI-induced behavioral deficits include cognitive and vestibulomotor deficits as well as anxiety and other consequences. Rodent models of TBI have been (and still are) fundamental in establishing many of the pathophysiological mechanisms of TBI. Animal models are also utilized in screening and testing pharmacological effects of potential therapeutic agents for brain injury treatment. This chapter details validated protocols for each of these behavioral deficits post traumatic brain injury in Sprague-Dawley male rats. The elevated plus maze (EPM) protocol is described for assessing anxiety-like behavior; the Morris water maze protocol for assessing cognitive deficits in learning memory and spatial working memory and the rotarod test for assessing vestibulomotor deficits. PMID:27604739

  17. Classification of Traumatic Brain Injury for Targeted Therapies

    PubMed Central

    Saatman, Kathryn E.; Duhaime, Ann-Christine; Bullock, Ross; Maas, Andrew I.R.; Valadka, Alex

    2008-01-01

    Abstract The heterogeneity of traumatic brain injury (TBI) is considered one of the most significant barriers to finding effective therapeutic interventions. In October, 2007, the National Institute of Neurological Disorders and Stroke, with support from the Brain Injury Association of America, the Defense and Veterans Brain Injury Center, and the National Institute of Disability and Rehabilitation Research, convened a workshop to outline the steps needed to develop a reliable, efficient and valid classification system for TBI that could be used to link specific patterns of brain and neurovascular injury with appropriate therapeutic interventions. Currently, the Glasgow Coma Scale (GCS) is the primary selection criterion for inclusion in most TBI clinical trials. While the GCS is extremely useful in the clinical management and prognosis of TBI, it does not provide specific information about the pathophysiologic mechanisms which are responsible for neurological deficits and targeted by interventions. On the premise that brain injuries with similar pathoanatomic features are likely to share common pathophysiologic mechanisms, participants proposed that a new, multidimensional classification system should be developed for TBI clinical trials. It was agreed that preclinical models were vital in establishing pathophysiologic mechanisms relevant to specific pathoanatomic types of TBI and verifying that a given therapeutic approach improves outcome in these targeted TBI types. In a clinical trial, patients with the targeted pathoanatomic injury type would be selected using an initial diagnostic entry criterion, including their severity of injury. Coexisting brain injury types would be identified and multivariate prognostic modeling used for refinement of inclusion/exclusion criteria and patient stratification. Outcome assessment would utilize endpoints relevant to the targeted injury type. Advantages and disadvantages of currently available diagnostic, monitoring, and

  18. Mechanical Injury Induces Brain Endothelial-Derived Microvesicle Release: Implications for Cerebral Vascular Injury during Traumatic Brain Injury.

    PubMed

    Andrews, Allison M; Lutton, Evan M; Merkel, Steven F; Razmpour, Roshanak; Ramirez, Servio H

    2016-01-01

    It is well established that the endothelium responds to mechanical forces induced by changes in shear stress and strain. However, our understanding of vascular remodeling following traumatic brain injury (TBI) remains incomplete. Recently published studies have revealed that lung and umbilical endothelial cells produce extracellular microvesicles (eMVs), such as microparticles, in response to changes in mechanical forces (blood flow and mechanical injury). Yet, to date, no studies have shown whether brain endothelial cells produce eMVs following TBI. The brain endothelium is highly specialized and forms the blood-brain barrier (BBB), which regulates diffusion and transport of solutes into the brain. This specialization is largely due to the presence of tight junction proteins (TJPs) between neighboring endothelial cells. Following TBI, a breakdown in tight junction complexes at the BBB leads to increased permeability, which greatly contributes to the secondary phase of injury. We have therefore tested the hypothesis that brain endothelium responds to mechanical injury, by producing eMVs that contain brain endothelial proteins, specifically TJPs. In our study, primary human adult brain microvascular endothelial cells (BMVEC) were subjected to rapid mechanical injury to simulate the abrupt endothelial disruption that can occur in the primary injury phase of TBI. eMVs were isolated from the media following injury at 2, 6, 24, and 48 h. Western blot analysis of eMVs demonstrated a time-dependent increase in TJP occludin, PECAM-1 and ICAM-1 following mechanical injury. In addition, activation of ARF6, a small GTPase linked to extracellular vesicle production, was increased after injury. To confirm these results in vivo, mice were subjected to sham surgery or TBI and blood plasma was collected 24 h post-injury. Isolation and analysis of eMVs from blood plasma using cryo-EM and flow cytometry revealed elevated levels of vesicles containing occludin following brain trauma

  19. Mechanical Injury Induces Brain Endothelial-Derived Microvesicle Release: Implications for Cerebral Vascular Injury during Traumatic Brain Injury

    PubMed Central

    Andrews, Allison M.; Lutton, Evan M.; Merkel, Steven F.; Razmpour, Roshanak; Ramirez, Servio H.

    2016-01-01

    It is well established that the endothelium responds to mechanical forces induced by changes in shear stress and strain. However, our understanding of vascular remodeling following traumatic brain injury (TBI) remains incomplete. Recently published studies have revealed that lung and umbilical endothelial cells produce extracellular microvesicles (eMVs), such as microparticles, in response to changes in mechanical forces (blood flow and mechanical injury). Yet, to date, no studies have shown whether brain endothelial cells produce eMVs following TBI. The brain endothelium is highly specialized and forms the blood-brain barrier (BBB), which regulates diffusion and transport of solutes into the brain. This specialization is largely due to the presence of tight junction proteins (TJPs) between neighboring endothelial cells. Following TBI, a breakdown in tight junction complexes at the BBB leads to increased permeability, which greatly contributes to the secondary phase of injury. We have therefore tested the hypothesis that brain endothelium responds to mechanical injury, by producing eMVs that contain brain endothelial proteins, specifically TJPs. In our study, primary human adult brain microvascular endothelial cells (BMVEC) were subjected to rapid mechanical injury to simulate the abrupt endothelial disruption that can occur in the primary injury phase of TBI. eMVs were isolated from the media following injury at 2, 6, 24, and 48 h. Western blot analysis of eMVs demonstrated a time-dependent increase in TJP occludin, PECAM-1 and ICAM-1 following mechanical injury. In addition, activation of ARF6, a small GTPase linked to extracellular vesicle production, was increased after injury. To confirm these results in vivo, mice were subjected to sham surgery or TBI and blood plasma was collected 24 h post-injury. Isolation and analysis of eMVs from blood plasma using cryo-EM and flow cytometry revealed elevated levels of vesicles containing occludin following brain trauma

  20. Neurological consequences of traumatic brain injuries in sports.

    PubMed

    Ling, Helen; Hardy, John; Zetterberg, Henrik

    2015-05-01

    Traumatic brain injury (TBI) is common in boxing and other contact sports. The long term irreversible and progressive aftermath of TBI in boxers depicted as punch drunk syndrome was described almost a century ago and is now widely referred as chronic traumatic encephalopathy (CTE). The short term sequelae of acute brain injury including subdural haematoma and catastrophic brain injury may lead to death, whereas mild TBI, or concussion, causes functional disturbance and axonal injury rather than gross structural brain damage. Following concussion, symptoms such as dizziness, nausea, reduced attention, amnesia and headache tend to develop acutely but usually resolve within a week or two. Severe concussion can also lead to loss of consciousness. Despite the transient nature of the clinical symptoms, functional neuroimaging, electrophysiological, neuropsychological and neurochemical assessments indicate that the disturbance of concussion takes over a month to return to baseline and neuropathological evaluation shows that concussion-induced axonopathy may persist for years. The developing brains in children and adolescents are more susceptible to concussion than adult brain. The mechanism by which acute TBI may lead to the neurodegenerative process of CTE associated with tau hyperphosphorylation and the development of neurofibrillary tangles (NFTs) remains speculative. Focal tau-positive NFTs and neurites in close proximity to focal axonal injury and foci of microhaemorrhage and the predilection of CTE-tau pathology for perivascular and subcortical regions suggest that acute TBI-related axonal injury, loss of microvascular integrity, breach of the blood brain barrier, resulting inflammatory cascade and microglia and astrocyte activation are likely to be the basis of the mechanistic link of TBI and CTE. This article provides an overview of the acute and long-term neurological consequences of TBI in sports. Clinical, neuropathological and the possible pathophysiological

  1. Traumatic brain injury: endocrine consequences in children and adults.

    PubMed

    Richmond, Erick; Rogol, Alan D

    2014-02-01

    Traumatic brain injury (TBI) is a common cause of death and disability in young adults with consequences ranging from physical disabilities to long-term cognitive, behavioral, psychological and social defects. Recent data suggest that pituitary hormone deficiency is not infrequent among TBI survivors; the prevalence of reported hypopituitarism following TBI varies widely among published studies. The most common cause of TBI is motor vehicle accidents, including pedestrian-car and bicycle car encounters, falls, child abuse, violence and sports injuries. Prevalence of hypopituitarism, from total to isolated pituitary deficiency, ranges from 5 to 90 %. The time interval between TBI and pituitary function evaluation is one of the major factors responsible for variations in the prevalence of hypopituitarism reported. Endocrine dysfunction after TBI in children and adolescents is common. Adolescence is a time of growth, freedom and adjustment, consequently TBI is also common in this group. Sports-related TBI is an important public health concern, but many cases are unrecognized and unreported. Sports that are associated with an increased risk of TBI include those involving contact and/or collisions such as boxing, football, soccer, ice hockey, rugby, and the martial arts, as well as high velocity sports such as cycling, motor racing, equestrian sports, skiing and roller skating. The aim of this paper is to summarize the best evidence of TBI as a cause of pituitary deficiency in children and adults. PMID:24030696

  2. Case Identification of Work-Related Traumatic Brain Injury Using the Occupational Injury and Illness Classification System (OIICS)

    PubMed Central

    Graves, Janessa M.; Blanar, Laura; Bowman, Stephen M.

    2013-01-01

    Objective Traumatic brain injury (TBI) is one of the most common, costly, and disabling occupational injuries. Objectives included determining whether work-related TBI could be reliably identified using the Occupational Injury and Illness Classification System (OIICS) and describing challenges in developing an OIICS-based TBI case definition. Methods Washington State trauma registry reports and workers’ compensation claims were linked (1998–2008). Trauma registry diagnoses were used as the gold standard for six OIICS-based TBI case definitions. Results OIICS-based case definitions were highly specific but had low sensitivity, capturing less than a third of fatal and nonfatal TBI. Conclusions The use of OIICS versus ICD-9-CM codes underestimated TBI and changed the attributable cause distribution, with potential implications for prevention efforts. Surveillance methods that can more fully and accurately capture the impact of work-related TBI across the U.S are needed. PMID:23618883

  3. Transcranial amelioration of inflammation and cell death after brain injury

    NASA Astrophysics Data System (ADS)

    Roth, Theodore L.; Nayak, Debasis; Atanasijevic, Tatjana; Koretsky, Alan P.; Latour, Lawrence L.; McGavern, Dorian B.

    2014-01-01

    Traumatic brain injury (TBI) is increasingly appreciated to be highly prevalent and deleterious to neurological function. At present, no effective treatment options are available, and little is known about the complex cellular response to TBI during its acute phase. To gain insights into TBI pathogenesis, we developed a novel murine closed-skull brain injury model that mirrors some pathological features associated with mild TBI in humans and used long-term intravital microscopy to study the dynamics of the injury response from its inception. Here we demonstrate that acute brain injury induces vascular damage, meningeal cell death, and the generation of reactive oxygen species (ROS) that ultimately breach the glial limitans and promote spread of the injury into the parenchyma. In response, the brain elicits a neuroprotective, purinergic-receptor-dependent inflammatory response characterized by meningeal neutrophil swarming and microglial reconstitution of the damaged glial limitans. We also show that the skull bone is permeable to small-molecular-weight compounds, and use this delivery route to modulate inflammation and therapeutically ameliorate brain injury through transcranial administration of the ROS scavenger, glutathione. Our results shed light on the acute cellular response to TBI and provide a means to locally deliver therapeutic compounds to the site of injury.

  4. TRANSCRANIAL AMELIORATION OF INFLAMMATION AND CELL DEATH FOLLOWING BRAIN INJURY

    PubMed Central

    Roth, Theodore L.; Nayak, Debasis; Atanasijevic, Tatjana; Koretsky, Alan P.; Latour, Lawrence L.; McGavern, Dorian B.

    2014-01-01

    Traumatic brain injury (TBI) is increasingly appreciated to be highly prevalent and deleterious to neurological function 1, 2. At present no effective treatment options are available, and little is known about the complex cellular response to TBI during its acute phase. To gain novel insights into TBI pathogenesis, we developed a novel closed-skull brain injury model that mirrors some pathological features associated with mild TBI in humans and used long-term intravital microscopy to study the dynamics of the injury response from its inception. Here we demonstrate that acute brain injury induces vascular damage, meningeal cell death, and the generation of reactive oxygen species (ROS) that ultimately breach the glial limitans and promote spread of the injury into the parenchyma. In response, the brain elicits a neuroprotective, purinergic receptor dependent inflammatory response characterized by meningeal neutrophil swarming and microglial reconstitution of the damaged glial limitans. We additionally show that the skull bone is permeable to small molecular weight compounds and use this delivery route to modulate inflammation and therapeutically ameliorate brain injury through transcranial administration of the ROS scavenger, glutathione. Our results provide novel insights into the acute cellular response to TBI and a means to locally deliver therapeutic compounds to the site of injury. PMID:24317693

  5. TBI Patient, Injury, Therapy, and Ancillary Treatments Associated with Outcomes at Discharge and 9 Months Post-discharge

    PubMed Central

    Horn, Susan D.; Corrigan, John D.; Beaulieu, Cynthia L.; Bogner, Jennifer; Barrett, Ryan S.; Giuffrida, Clare G.; Ryser, David K.; Cooper, Kelli; Carroll, Deborah M.; Deutscher, Daniel

    2015-01-01

    Objective To examine associations of patient and injury characteristics, inpatient rehabilitation therapy activities, and neurotropic medications with outcomes at discharge and 9 months post-discharge for patients with traumatic brain injury (TBI) Design Prospective, longitudinal observational study Setting 10 inpatient rehabilitation centers (9 US, 1 Canada) Participants Consecutive patients (n=2130) enrolled between 2008 and 2011, admitted for inpatient rehabilitation after an index TBI injury Interventions Not applicable Main Outcome Measures Rehabilitation length of stay, discharge to home, and Functional Independence Measure (FIM) at discharge and 9 months post-discharge Results The admission FIM Cognitive score was used to create 5 relatively homogeneous subgroups for subsequent analysis of treatment outcomes. Within each subgroup, significant associations were found between outcomes and patient and injury characteristics, time spent in therapy activities, and medications used. Patient and injury characteristics explained on average 35.7% of the variation in discharge outcomes and 22.3% in 9-month outcomes. Adding time spent and level of effort in therapy activities, as well as percent of stay using specific medications, explained approximately 20.0% more variation for discharge outcomes and 12.9% for 9-month outcomes. After patient, injury, and treatment characteristics were used to predict outcomes, center differences added only approximately 1.9% additional variance explained. Conclusions At discharge, greater effort during therapy sessions, time spent in more complex therapy activities, and use of specific medications were associated with better outcomes for patients in all admission FIM Cognitive subgroups. At 9 months post-discharge, similar but less pervasive associations were observed for therapy activities, but not classes of medications. Further research is warranted to examine more specific combinations of therapy activities and medications that

  6. The prehospital management of traumatic brain injury.

    PubMed

    Goldberg, Scott A; Rojanasarntikul, Dhanadol; Jagoda, Andrew

    2015-01-01

    Traumatic brain injury (TBI) is an important cause of death and disability, particularly in younger populations. The prehospital evaluation and management of TBI is a vital link between insult and definitive care and can have dramatic implications for subsequent morbidity. Following a TBI the brain is at high risk for further ischemic injury, with prehospital interventions targeted at reducing this secondary injury while optimizing cerebral physiology. In the following chapter we discuss the prehospital assessment and management of the brain-injured patient. The initial evaluation and physical examination are discussed with a focus on interpretation of specific physical examination findings and interpretation of vital signs. We evaluate patient management strategies including indications for advanced airway management, oxygenation, ventilation, and fluid resuscitation, as well as prehospital strategies for the management of suspected or impending cerebral herniation including hyperventilation and brain-directed hyperosmolar therapy. Transport decisions including the role of triage models and trauma centers are discussed. Finally, future directions in the prehospital management of traumatic brain injury are explored.

  7. Skull Flexure from Blast Waves: A Mechanism for Brain Injury with Implications for Helmet Design

    NASA Astrophysics Data System (ADS)

    Moss, William C.; King, Michael J.; Blackman, Eric G.

    2009-09-01

    Traumatic brain injury (TBI) has become a signature injury of current military conflicts, with debilitating, costly, and long-lasting effects. Although mechanisms by which head impacts cause TBI have been well researched, the mechanisms by which blasts cause TBI are not understood. From numerical hydrodynamic simulations, we have discovered that nonlethal blasts can induce sufficient skull flexure to generate potentially damaging loads in the brain, even without a head impact. The possibility that this mechanism may contribute to TBI has implications for injury diagnosis and armor design.

  8. Skull flexure from blast waves: a mechanism for brain injury with implications for helmet design.

    PubMed

    Moss, William C; King, Michael J; Blackman, Eric G

    2009-09-01

    Traumatic brain injury (TBI) has become a signature injury of current military conflicts, with debilitating, costly, and long-lasting effects. Although mechanisms by which head impacts cause TBI have been well researched, the mechanisms by which blasts cause TBI are not understood. From numerical hydrodynamic simulations, we have discovered that nonlethal blasts can induce sufficient skull flexure to generate potentially damaging loads in the brain, even without a head impact. The possibility that this mechanism may contribute to TBI has implications for injury diagnosis and armor design. PMID:19792349

  9. Skull Flexure from Blast Waves: A Mechanism for Brain Injury with Implications for Helmet Design

    SciTech Connect

    Moss, W C; King, M J; Blackman, E G

    2009-04-30

    Traumatic brain injury [TBI] has become a signature injury of current military conflicts, with debilitating, costly, and long-lasting effects. Although mechanisms by which head impacts cause TBI have been well-researched, the mechanisms by which blasts cause TBI are not understood. From numerical hydrodynamic simulations, we have discovered that non-lethal blasts can induce sufficient skull flexure to generate potentially damaging loads in the brain, even without a head impact. The possibility that this mechanism may contribute to TBI has implications for injury diagnosis and armor design.

  10. Magnetic micelles for DNA delivery to rat brains after mild traumatic brain injury.

    PubMed

    Das, Mahasweta; Wang, Chunyan; Bedi, Raminder; Mohapatra, Shyam S; Mohapatra, Subhra

    2014-10-01

    Traumatic brain injury (TBI) causes significant mortality, long term disability and psychological symptoms. Gene therapy is a promising approach for treatment of different pathological conditions. Here we tested chitosan and polyethyleneimine (PEI)-coated magnetic micelles (CP-mag micelles or CPMMs), a potential MRI contrast agent, to deliver a reporter DNA to the brain after mild TBI (mTBI). CPMM-tomato plasmid (ptd) conjugate expressing a red-fluorescent protein (RFP) was administered intranasally immediately after mTBI or sham surgery in male SD rats. Evans blue extravasation following mTBI suggested CPMM-ptd entry into the brain via the compromised blood-brain barrier. Magnetofection increased the concentration of CPMMs in the brain. RFP expression was observed in the brain (cortex and hippocampus), lung and liver 48 h after mTBI. CPMM did not evoke any inflammatory response by themselves and were excreted from the body. These results indicate the possibility of using intranasally administered CPMM as a theranostic vehicle for mTBI. From the clinical editor: In this study, chitosan and PEI-coated magnetic micelles (CPMM) were demonstrated as potentially useful vehicles in traumatic brain injury in a rodent model. Magnetofection increased the concentration of CPMMs in the brain and, after intranasal delivery, CPMM did not evoke any inflammatory response and were excreted from the body. PMID:24486465

  11. Brain injury, neuroinflammation and Alzheimer's disease

    PubMed Central

    Breunig, Joshua J.; Guillot-Sestier, Marie-Victoire; Town, Terrence

    2013-01-01

    With as many as 300,000 United States troops in Iraq and Afghanistan having suffered head injuries (Miller, 2012), traumatic brain injury (TBI) has garnered much recent attention. While the cause and severity of these injuries is variable, severe cases can lead to lifelong disability or even death. While aging is the greatest risk factor for Alzheimer's disease (AD), it is now becoming clear that a history of TBI predisposes the individual to AD later in life (Sivanandam and Thakur, 2012). In this review article, we begin by defining hallmark pathological features of AD and the various forms of TBI. Putative mechanisms underlying the risk relationship between these two neurological disorders are then critically considered. Such mechanisms include precipitation and ‘spreading’ of cerebral amyloid pathology and the role of neuroinflammation. The combined problems of TBI and AD represent significant burdens to public health. A thorough, mechanistic understanding of the precise relationship between TBI and AD is of utmost importance in order to illuminate new therapeutic targets. Mechanistic investigations and the development of preclinical therapeutics are reliant upon a clearer understanding of these human diseases and accurate modeling of pathological hallmarks in animal systems. PMID:23874297

  12. Pharmacology of traumatic brain injury: where is the "golden bullet"?

    PubMed

    Beauchamp, Kathryn; Mutlak, Haitham; Smith, Wade R; Shohami, Esther; Stahel, Philip F

    2008-01-01

    Traumatic brain injury (TBI) represents a major health care problem and a significant socioeconomic challenge worldwide. In the United States alone, approximately 1.5 million patients are affected each year, and the mortality of severe TBI remains as high as 35%-40%. These statistics underline the urgent need for efficient treatment modalities to improve posttraumatic morbidity and mortality. Despite advances in basic and clinical research as well as improved neurological intensive care in recent years, no specific pharmacological therapy for TBI is available that would improve the outcome of these patients. Understanding of the cellular and molecular mechanisms underlying the pathophysiological events after TBI has resulted in the identification of new potential therapeutic targets. Nevertheless, the extrapolation from basic research data to clinical application in TBI patients has invariably failed, and results from prospective clinical trials are disappointing. We review the published prospective clinical trials on pharmacological treatment modalities for TBI patients and outline future promising therapeutic avenues in the field.

  13. Mental Health in Women With Traumatic Brain Injury: A Systematic Review on Depression and Hope.

    PubMed

    Oyesanya, Tolu O; Ward, Earlise C

    2016-01-01

    The prevalence of traumatic brain injury (TBI) in women has recently increased from 25% to 40%. Current literature inadequately captures challenges women face after injury, including depression. The limited focus on depression is problematic as rates of depression are increasing simultaneously with rates of TBI. A disabling symptom of depression is lack of hope; thus, depression, comorbid with TBI, leads to disability among women. Unfortunately, depression and hope among women with TBI has yet to be systematically examined. The purpose of this systematic review is to examine and synthesize current literature focusing on women with TBI, comorbid with depression, and hope.

  14. Cerebral Lactate Metabolism After Traumatic Brain Injury.

    PubMed

    Patet, Camille; Suys, Tamarah; Carteron, Laurent; Oddo, Mauro

    2016-04-01

    Cerebral energy dysfunction has emerged as an important determinant of prognosis following traumatic brain injury (TBI). A number of studies using cerebral microdialysis, positron emission tomography, and jugular bulb oximetry to explore cerebral metabolism in patients with TBI have demonstrated a critical decrease in the availability of the main energy substrate of brain cells (i.e., glucose). Energy dysfunction induces adaptations of cerebral metabolism that include the utilization of alternative energy resources that the brain constitutively has, such as lactate. Two decades of experimental and human investigations have convincingly shown that lactate stands as a major actor of cerebral metabolism. Glutamate-induced activation of glycolysis stimulates lactate production from glucose in astrocytes, with subsequent lactate transfer to neurons (astrocyte-neuron lactate shuttle). Lactate is not only used as an extra energy substrate but also acts as a signaling molecule and regulator of systemic and brain glucose use in the cerebral circulation. In animal models of brain injury (e.g., TBI, stroke), supplementation with exogenous lactate exerts significant neuroprotection. Here, we summarize the main clinical studies showing the pivotal role of lactate and cerebral lactate metabolism after TBI. We also review pilot interventional studies that examined exogenous lactate supplementation in patients with TBI and found hypertonic lactate infusions had several beneficial properties on the injured brain, including decrease of brain edema, improvement of neuroenergetics via a "cerebral glucose-sparing effect," and increase of cerebral blood flow. Hypertonic lactate represents a promising area of therapeutic investigation; however, larger studies are needed to further examine mechanisms of action and impact on outcome. PMID:26898683

  15. Amyloid pathology and axonal injury after brain trauma

    PubMed Central

    Scott, Gregory; Ramlackhansingh, Anil F.; Edison, Paul; Hellyer, Peter; Cole, James; Veronese, Mattia; Leech, Rob; Greenwood, Richard J.; Turkheimer, Federico E.; Gentleman, Steve M.; Heckemann, Rolf A.; Matthews, Paul M.; Brooks, David J.

    2016-01-01

    Objective: To image β-amyloid (Aβ) plaque burden in long-term survivors of traumatic brain injury (TBI), test whether traumatic axonal injury and Aβ are correlated, and compare the spatial distribution of Aβ to Alzheimer disease (AD). Methods: Patients 11 months to 17 years after moderate–severe TBI underwent 11C-Pittsburgh compound B (11C-PiB)-PET, structural and diffusion MRI, and neuropsychological examination. Healthy aged controls and patients with AD underwent PET and structural MRI. Binding potential (BPND) images of 11C-PiB, which index Aβ plaque density, were computed using an automatic reference region extraction procedure. Voxelwise and regional differences in BPND were assessed. In TBI, a measure of white matter integrity, fractional anisotropy, was estimated and correlated with 11C-PiB BPND. Results: Twenty-eight participants (9 with TBI, 9 controls, 10 with AD) were assessed. Increased 11C-PiB BPND was found in TBI vs controls in the posterior cingulate cortex and cerebellum. Binding in the posterior cingulate cortex increased with decreasing fractional anisotropy of associated white matter tracts and increased with time since injury. Compared to AD, binding after TBI was lower in neocortical regions but increased in the cerebellum. Conclusions: Increased Aβ burden was observed in TBI. The distribution overlaps with, but is distinct from, that of AD. This suggests a mechanistic link between TBI and the development of neuropathologic features of dementia, which may relate to axonal damage produced by the injury. PMID:26843562

  16. Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury

    PubMed Central

    Reifschneider, Kent; Auble, Bethany A.; Rose, Susan R.

    2015-01-01

    Traumatic brain injuries (TBI) are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children’s quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6–12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life. PMID:26287247

  17. Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury.

    PubMed

    Reifschneider, Kent; Auble, Bethany A; Rose, Susan R

    2015-01-01

    Traumatic brain injuries (TBI) are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children's quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6-12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life. PMID:26287247

  18. Optical microangiography enabling visualization of change in meninges after traumatic brain injury in mice in vivo

    NASA Astrophysics Data System (ADS)

    Choi, Woo June; Qin, Wan; Qi, Xiaoli; Wang, Ruikang K.

    2016-03-01

    Traumatic brain injury (TBI) is a form of brain injury caused by sudden impact on brain by an external mechanical force. Following the damage caused at the moment of injury, TBI influences pathophysiology in the brain that takes place within the minutes or hours involving alterations in the brain tissue morphology, cerebral blood flow (CBF), and pressure within skull, which become important contributors to morbidity after TBI. While many studies for the TBI pathophysiology have been investigated with brain cortex, the effect of trauma on intracranial tissues has been poorly studied. Here, we report use of high-resolution optical microangiography (OMAG) to monitor the changes in cranial meninges beneath the skull of mouse after TBI. TBI is induced on a brain of anesthetized mouse by thinning the skull using a soft drill where a series of drilling exert mechanical stress on the brain through the skull, resulting in mild brain injury. Intracranial OMAG imaging of the injured mouse brain during post-TBI phase shows interesting pathophysiological findings in the meningeal layers such as widening of subdural space as well as vasodilation of subarachnoid vessels. These processes are acute and reversible within hours. The results indicate potential of OMAG to explore mechanism involved following TBI on small animals in vivo.

  19. Traumatic Brain Injury and Behavior: A Practical Approach.

    PubMed

    McGee, Jeanie; Alekseeva, Nadejda; Chernyshev, Oleg; Minagar, Alireza

    2016-02-01

    Traumatic brain injury (TBI) is a complex neurologic and neuropathologic process that may affect the patient's behavior permanently. Clinically, TBI is associated with a wide gamut of neurologic and psychiatric disorders, such as amnesia, cognitive decline, seizures, attention and concentration deficits, depression, manic behavior, psychosis, hostile and violent behavior, and personality alterations. Therapy and rehabilitative efforts should be designed based on the type of injury and the patient's specific needs. Gaining familiarity with the behavioral disorders outlined in this article and understanding how to identify and treat them plays a significant role in the management of patients with TBI. PMID:26613995

  20. Tibial fracture exacerbates traumatic brain injury outcomes and neuroinflammation in a novel mouse model of multitrauma.

    PubMed

    Shultz, Sandy R; Sun, Mujun; Wright, David K; Brady, Rhys D; Liu, Shijie; Beynon, Sinead; Schmidt, Shannon F; Kaye, Andrew H; Hamilton, John A; O'Brien, Terence J; Grills, Brian L; McDonald, Stuart J

    2015-08-01

    Multitrauma is a common medical problem worldwide, and often involves concurrent traumatic brain injury (TBI) and bone fracture. Despite the high incidence of combined TBI and fracture, preclinical TBI research commonly employs independent injury models that fail to incorporate the pathophysiologic interactions occurring in multitrauma. Here, we developed a novel mouse model of multitrauma, and investigated whether bone fracture worsened TBI outcomes. Male mice were assigned into four groups: sham-TBI+sham-fracture (SHAM); sham-TBI+fracture (FX); TBI+sham-fracture (TBI); and TBI+fracture (MULTI). The injury methods included a closed-skull weight-drop TBI model and a closed tibial fracture. After a 35-day recovery, mice underwent behavioral testing and magnetic resonance imaging (MRI). MULTI mice displayed abnormal behaviors in the open-field compared with all other groups. On MRI, MULTI mice had enlarged ventricles and diffusion abnormalities compared with all other groups. These changes occurred in the presence of heightened neuroinflammation in MULTI mice at 24 hours and 35 days after injury, and elevated edema and blood-brain barrier disruption at 24 hours after injury. Together, these findings indicate that tibial fracture worsens TBI outcomes, and that exacerbated neuroinflammation may be an important factor that contributes to these effects, which warrants further investigation.

  1. Official position of the military TBI task force on the role of neuropsychology and rehabilitation psychology in the evaluation, management, and research of military veterans with traumatic brain injury.

    PubMed

    McCrea, Michael; Pliskin, Neil; Barth, Jeffrey; Cox, David; Fink, Joseph; French, Louis; Hammeke, Thomas; Hess, David; Hopewell, Alan; Orme, Daniel; Powell, Matthew; Ruff, Ron; Schrock, Barbara; Terryberry-Spohr, Lori; Vanderploeg, Rodney; Yoash-Gantz, Ruth

    2008-01-01

    This Position Statement is a summary of the literature and learning regarding current issues raised by the occurrence, treatment, and study of traumatic brain injury in military service members and veterans. The Report has been approved by the American Academy of Clinical Neuropsychology (AACN), Divisions 40 (Neuropsychology) and 22 (Rehabilitation Psychology) of the American Psychological Association (APA), and the National Academy of Neuropsychology (NAN), with the goal of providing information of relevance on an important public policy matter within their respective areas of expertise. The Report is not intended to establish guidelines or standards for the professional practice of psychology, nor has it been adopted as official policy by the American Psychological Association or any other division or subunit of APA.

  2. Neuropathophysiology of Brain Injury.

    PubMed

    Quillinan, Nidia; Herson, Paco S; Traystman, Richard J

    2016-09-01

    Every year in the United States, millions of individuals incur ischemic brain injury from stroke, cardiac arrest, or traumatic brain injury. These acquired brain injuries can lead to death or long-term neurologic and neuropsychological impairments. The mechanisms of ischemic and traumatic brain injury that lead to these deficiencies result from a complex interplay of interdependent molecular pathways, including excitotoxicity, acidotoxicity, ionic imbalance, oxidative stress, inflammation, and apoptosis. This article reviews several mechanisms of brain injury and discusses recent developments. Although much is known from animal models of injury, it has been difficult to translate these effects to humans. PMID:27521191

  3. Chapter 3 animal models of traumatic brain injury: is there an optimal model that parallels human brain injury?

    PubMed

    Briones, Teresita L

    2015-01-01

    Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in the younger population worldwide. Survivors of TBI often experience long-term disability in the form of cognitive, sensorimotor, and affective impairments. Despite the high prevalence in, and cost of TBI to, both individuals and society, some of its underlying pathophysiology is not completely understood. Animal models have been developed over the past few decades to closely replicate the different facets of TBI in humans to better understand the underlying pathophysiology and behavioral impairments and assess potential therapies that can promote neuroprotection. However, no effective treatment for TBI has been established to date in the clinical setting, despite promising results generated in preclinical studies in the use of neuroprotective strategies. The failure to translate results from preclinical studies to the clinical setting underscores a compelling need to revisit the current state of knowledge in the use of animal models in TBI.

  4. Fatal traumatic brain injury, West Virginia, 1989-1998.

    PubMed Central

    Adekoya, Nelson; Majumder, Ranjit

    2004-01-01

    OBJECTIVE: The objective of this study was to describe fatal cases of traumatic brain injury (TBI) among West Virginia residents. METHODS: The authors analyzed data from the National Center for Health Statistics Multiple Cause of Death tapes for the period 1989-1998. They compared West Virginia's annualized average TBI death rate with the rates of other states and with the rate among U.S. residents for the same period. U.S. Bureau of Census population estimates were used as denominators. RESULTS: A total of 4,416 TBI deaths occurred in West Virginia in 1989-1998, for an annual average death rate of 23.6 per 100,000 population. From 1989 to 1998, TBI death rates declined 5% (p=0.4042). Seventy-five percent (n=3,315) of fatalities occurred among men. Adults > or =65 years of age accounted for the highest percentage of fatal injuries (n=1,135). The leading external causes of fatal TBI were: firearm-related (39% of reported fatalities), motor vehicles-related (34%), and fall-related (10%). Firearm-related TBI became the leading cause of TBI fatalities in 1991, surpassing motor vehicle-related TBI. Seventy-five percent of firearm-related TBI deaths were suicides (n=1,302). West Virginia's TBI death rate (23.6 per 100,000) was higher than the national rate (20.6 per 100,000). In 23 states, the average TBI death rates over the 10-year period were higher than West Virginia's. Whereas modest declines in TBI death rates occurred for motor vehicle-related and firearm-related causes in West Virginia, a concomitant 38% increase occurred in the fall-related TBI death rate during the decade. CONCLUSION: Data presented in this report can be used to develop targeted prevention programs in West Virginia. PMID:15313112

  5. Effect of lacosamide on structural damage and functional recovery after traumatic brain injury in rats.

    PubMed

    Pitkänen, A; Immonen, R; Ndode-Ekane, X; Gröhn, O; Stöhr, T; Nissinen, J

    2014-05-01

    In a subgroup of patients, traumatic brain injury (TBI) results in the occurrence of acute epileptic seizures or even status epilepticus, which are treated with antiepileptic drugs (AEDs). Recent experimental data, however, suggest that administration of AEDs at the early post-injury phase can compromise the recovery process. The present study was designed to assess the profile of a novel anticonvulsant, lacosamide (Vimpat) on post-TBI structural, motor and cognitive outcomes. Moderate TBI was induced by lateral fluid-percussion injury in adult rats. Treatment with 0.9% saline or lacosamide (30 mg/kg, i.p.) was started at 30 min post-injury and continued at 8h intervals for 3d (total daily dose 90 mg/kg/d). Rats were randomly assigned to 4 treatment groups: sham-operated controls treated with vehicle (Sham-Veh) or lacosamide (Sham-LCM) and injured animals treated with vehicle (TBI-Veh) or lacosamide (TBI-LCM). As functional outcomes we tested motor recovery with composite neuroscore and beam-walking at 2, 7, and 15 d post-injury. Cognitive recovery was tested with the Morris water-maze at 12-14 d post-TBI. To assess the structural outcome, animals underwent magnetic resonance imaging (MRI) at 2 d post-TBI. At 16d post-TBI, rats were perfused for histology to analyze cortical and hippocampal neurodegeneration and axonal damage. Our data show that at 2 d post-TBI, both the TBI-Veh and TBI-LCM groups were equally impaired in neuroscore. Thereafter, motor recovery occurred similarly during the first week. At 2 wk post-TBI, recovery of the TBI-LCM group lagged behind that in the TBI-VEH group (p<0.05). Performance in beam-walking did not differ between the TBI-Veh and TBI-LCM groups. Both TBI groups were similarly impaired in the Morris water-maze at 2 wk post-TBI. MRI and histology did not reveal any differences in the cortical or hippocampal damage between the TBI-Veh and TBI-LCM groups. Taken together, acute treatment with LCM had no protective effects on post-TBI

  6. Aging, Neurodegenerative Disease, and Traumatic Brain Injury: The Role of Neuroimaging

    PubMed Central

    Levine, Brian

    2015-01-01

    Abstract Traumatic brain injury (TBI) is a highly prevalent condition with significant effects on cognition and behavior. While the acute and sub-acute effects of TBI recover over time, relatively little is known about the long-term effects of TBI in relation to neurodegenerative disease. This issue has recently garnered a great deal of attention due to publicity surrounding chronic traumatic encephalopathy (CTE) in professional athletes, although CTE is but one of several neurodegenerative disorders associated with a history of TBI. Here, we review the literative on neurodegenerative disorders linked to remote TBI. We also review the evidence for neuroimaging changes associated with unhealthy brain aging in the context of remote TBI. We conclude that neuroimaging biomarkers have significant potential to increase understanding of the mechanisms of unhealthy brain aging and neurodegeneration following TBI, with potential for identifying those at risk for unhealthy brain aging prior to the clinical manifestation of neurodegenerative disease. PMID:25192426

  7. Neuroimaging Correlates of Novel Psychiatric Disorders after Pediatric Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Max, Jeffrey E.; Wilde, Elisabeth A.; Bigler, Erin D.; Thompson, Wesley K.; MacLeod, Marianne; Vasquez, Ana C.; Merkley, Tricia L.; Hunter, Jill V.; Chu, Zili D.; Yallampalli, Ragini; Hotz, Gillian; Chapman, Sandra B.; Yang, Tony T.; Levin, Harvey S.

    2012-01-01

    Objective: To study magnetic resonance imaging (MRI) correlates of novel (new-onset) psychiatric disorders (NPD) after traumatic brain injury (TBI) and orthopedic injury (OI). Method: Participants were 7 to 17 years of age at the time of hospitalization for either TBI or OI. The study used a prospective, longitudinal, controlled design with…

  8. When Service Members with Traumatic Brain Injury Become Students: Methods to Advance Learning

    ERIC Educational Resources Information Center

    Helms, Kimberly Turner; Libertz, Daniel

    2014-01-01

    The purpose of this paper is to explain which evidence-based interventions in study strategies have been successful in helping soldiers and veterans with traumatic brain injury (TBI) return to the classroom. Military leaders have specifically identified TBI as one of the signature injuries of the wars in Afghanistan and Iraq with over a quarter of…

  9. Sentence Processing in Traumatic Brain Injury: Evidence from the P600

    ERIC Educational Resources Information Center

    Key-DeLyria, Sarah E.

    2016-01-01

    Purpose: Sentence processing can be affected following a traumatic brain injury (TBI) due to linguistic or cognitive deficits. Language-related event-related potentials (ERPs), particularly the P600, have not been described in individuals with TBI history. Method: Four young adults with a history of closed head injury participated. Two had severe…

  10. Circulating Brain-Derived Neurotrophic Factor Has Diagnostic and Prognostic Value in Traumatic Brain Injury.

    PubMed

    Korley, Frederick K; Diaz-Arrastia, Ramon; Wu, Alan H B; Yue, John K; Manley, Geoffrey T; Sair, Haris I; Van Eyk, Jennifer; Everett, Allen D; Okonkwo, David O; Valadka, Alex B; Gordon, Wayne A; Maas, Andrew I R; Mukherjee, Pratik; Yuh, Esther L; Lingsma, Hester F; Puccio, Ava M; Schnyer, David M

    2016-01-15

    Brain-derived neurotrophic factor (BDNF) is important for neuronal survival and regeneration. We investigated the diagnostic and prognostic values of serum BDNF in traumatic brain injury (TBI). We examined serum BDNF in two independent cohorts of TBI cases presenting to the emergency departments (EDs) of the Johns Hopkins Hospital (JHH; n = 76) and San Francisco General Hospital (SFGH, n = 80), and a control group of JHH ED patients without TBI (n = 150). Findings were subsequently validated in the prospective, multi-center Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Pilot study (n = 159). We investigated the association between BDNF, glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 (UCH-L1) and recovery from TBI at 6 months in the TRACK-TBI Pilot cohort. Incomplete recovery was defined as having either post-concussive syndrome or a Glasgow Outcome Scale Extended score <8 at 6 months. Median day-of-injury BDNF concentrations (ng/mL) were lower among TBI cases (JHH TBI, 17.5 and SFGH TBI, 13.8) than in JHH controls (60.3; p = 0.0001). Among TRACK-TBI Pilot subjects, median BDNF concentrations (ng/mL) were higher in mild (8.3) than in moderate (4.3) or severe TBI (4.0; p = 0.004. In the TRACK-TBI cohort, the 75 (71.4%) subjects with very low BDNF values (i.e., TBI controls, <14.2 ng/mL) had higher odds of incomplete recovery than those who did not have very low values (odds ratio, 4.0; 95% confidence interval [CI]: 1.5-11.0). The area under the receiver operator curve for discriminating complete and incomplete recovery was 0.65 (95% CI: 0.52-0.78) for BDNF, 0.61 (95% CI: 0.49-0.73) for GFAP, and 0.55 (95% CI: 0.43-0.66) for UCH-L1. The addition of GFAP/UCH-L1 to BDNF did not improve outcome prediction significantly. Day-of-injury serum BDNF is associated with TBI diagnosis and also provides 6-month prognostic information regarding recovery from TBI. Thus, day-of-injury

  11. Traumatic brain injury in operation enduring freedom/operation iraqi freedom: a primer.

    PubMed

    Fabrizio, Katherine S; Keltner, Norman L

    2010-12-01

    In greater numbers than in prior conflicts, service members deployed as part of Operation Enduring Freedom and Operation Iraqi Freedom have an increased risk of experiencing a traumatic brain injury (TBI). The basics of TBI are discussed, with particular attention paid to blast-related events, as this is a common mechanism of injury in this population. Particular attention is focused on the pharmacologic treatment of the sequlae of TBI and common comorbid conditions.

  12. The Chaos of Combat: An Overview of Challenges in Military Mild Traumatic Brain Injury Research.

    PubMed

    Davenport, Nicholas D

    2016-01-01

    Mild traumatic brain injury (mTBI), or concussion, is among the most common injuries affecting Veterans of recent combat deployments. Military mTBI differs from civilian mTBI in fundamental ways that make assessment and diagnosis difficult, including a reliance on retrospective self-report and the potential influence of comorbid psychopathology. These unique features and their implications for research and clinical practice are summarized, and neuroimaging studies are discussed in the context of these complicating factors. PMID:27242555

  13. The Chaos of Combat: An Overview of Challenges in Military Mild Traumatic Brain Injury Research

    PubMed Central

    Davenport, Nicholas D.

    2016-01-01

    Mild traumatic brain injury (mTBI), or concussion, is among the most common injuries affecting Veterans of recent combat deployments. Military mTBI differs from civilian mTBI in fundamental ways that make assessment and diagnosis difficult, including a reliance on retrospective self-report and the potential influence of comorbid psychopathology. These unique features and their implications for research and clinical practice are summarized, and neuroimaging studies are discussed in the context of these complicating factors. PMID:27242555

  14. Occult retinal detachment after mild traumatic brain injury: case report and literature review.

    PubMed

    Bedgood, Alysia; Rand, Scott E; Major, James

    2015-01-01

    Concussions, or mild traumatic brain injuries (mTBI), are on the forefront of sports medicine. There is a spectrum of symptoms associated with mTBI, some of which include blurriness, double vision, and light sensitivity. Further evaluation for nonconcussion-related causes is warranted if vision changes do not improve concurrently with other symptoms. Keeping in mind other less obvious injuries, including retinal detachment, is important when performing an initial evaluation or follow-up of an mTBI.

  15. Glucocorticoids modulate the NGF mRNA response in the rat hippocampus after traumatic brain injury.

    PubMed

    Grundy, P L; Patel, N; Harbuz, M S; Lightman, S L; Sharples, P M

    2001-02-23

    Nerve growth factor (NGF) expression in the rat hippocampus is increased after experimental traumatic brain injury (TBI) and is neuroprotective. Glucocorticoids are regulators of brain neurotrophin levels and are often prescribed following TBI. The effect of adrenalectomy (ADX) and corticosterone (CORT) replacement on the expression of NGF mRNA in the hippocampus after TBI has not been investigated to date. We used fluid percussion injury and in situ hybridisation to evaluate the expression of NGF mRNA in the hippocampus 4 h after TBI in adrenal-intact or adrenalectomised rats (with or without CORT replacement). TBI increased expression of NGF mRNA in sham-ADX rats, but not in ADX rats. Furthermore, CORT replacement in ADX rats restored the increase in NGF mRNA induced by TBI. These findings suggest that glucocorticoids have an important role in the induction of hippocampal NGF mRNA after TBI.

  16. Role of microvascular disruption in brain damage from traumatic brain injury

    PubMed Central

    Logsdon, Aric F.; Lucke-Wold, Brandon P.; Turner, Ryan C.; Huber, Jason D.; Rosen, Charles L.; Simpkins, James W.

    2015-01-01

    Traumatic brain injury (TBI) is acquired from an external force, which can inflict devastating effects to the brain vasculature and neighboring neuronal cells. Disruption of vasculature is a primary effect that can lead to a host of secondary injury cascades. The primary effects of TBI are rapidly occurring while secondary effects can be activated at later time points and may be more amenable to targeting. Primary effects of TBI include diffuse axonal shearing, changes in blood brain barrier (BBB) permeability, and brain contusions. These mechanical events, especially changes to the BBB, can induce calcium perturbations within brain cells producing secondary effects, which include cellular stress, inflammation, and apoptosis. These secondary effects can be potentially targeted to preserve the tissue surviving the initial impact of TBI. In the past, TBI research had focused on neurons without any regard for glial cells and the cerebrovasculature. Now a greater emphasis is being placed on the vasculature and the neurovascular unit following TBI. A paradigm shift in the importance of the vascular response to injury has opened new avenues of drug treatment strategies for TBI. However, a connection between the vascular response to TBI and the development of chronic disease has yet to be elucidated. Long-term cognitive deficits are common amongst those sustaining severe or multiple mild TBIs. Understanding the mechanisms of cellular responses following TBI is important to prevent the development of neuropsychiatric symptoms. With appropriate intervention following TBI, the vascular network can perhaps be maintained and the cellular repair process possibly improved to aid in the recovery of cellular homeostasis. PMID:26140712

  17. The challenge of mild traumatic brain injury: role of biochemical markers in diagnosis of brain damage.

    PubMed

    Mondello, Stefania; Schmid, Kara; Berger, Rachel P; Kobeissy, Firas; Italiano, Domenico; Jeromin, Andreas; Hayes, Ronal L; Tortella, Frank C; Buki, Andras

    2014-05-01

    During the past decade there has been an increasing recognition of the incidence of mild traumatic brain injury (mTBI) and a better understanding of the subtle neurological and cognitive deficits that may result from it. A substantial, albeit suboptimal, effort has been made to define diagnostic criteria for mTBI and improve diagnostic accuracy. Thus, biomarkers that can accurately and objectively detect brain injury after mTBI and, ideally, aid in clinical management are needed. In this review, we discuss the current research on serum biomarkers for mTBI including their rationale and diagnostic performances. Sensitive and specific biomarkers reflecting brain injury can provide important information regarding TBI pathophysiology and serve as candidate markers for predicting abnormal computed tomography findings and/or the development of residual deficits in patients who sustain an mTBI. We also outline the roles of biomarkers in settings of specific interest including pediatric TBI, sports concussions and military injuries, and provide perspectives on the validation of such markers for use in the clinic. Finally, emerging proteomics-based strategies for identifying novel markers will be discussed.

  18. Brain injury from explosive blast: description and clinical management.

    PubMed

    Ling, G; Ecklund, J M; Bandak, F A

    2015-01-01

    Accumulating clinical experience is indicating that explosive blast brain injury is becoming recognized as a disease distinct from the penetrating form of blast injury as well as the classic closed head injury (CHI). In recent US conflicts in Iraq and Afghanistan, over 60% of combat casualties were from explosive blast with the hallmark explosive weapon being the improvised explosive device (IED). Explosive blast TBI is a condition afflicting many combat injured warfighters potentially constituting another category of TBI. Clinically, it shares many features with conventional TBI but possesses some unique aspects. In its mild form, it also shares many clinical features with PTSD but here again has distinct aspects. Although military medical providers depend on civilian standard of care guidelines when managing explosive blast mTBI, they are continually adapting their medical practice in order to optimize the treatment of this disease, particularly in a theater of war. It is clear that further rigorous scientific study of explosive blast mTBI at both the basic science and clinical levels is needed. This research must include improved understanding of the causes and mechanisms of explosive blast TBI as well as comprehensive epidemiologic studies to determine the prevalence of this disease and its risk factors. A widely accepted unambiguous clinical description of explosive blast mTBI with diagnostic criteria would greatly improve diagnosis. It is hoped that through appropriate research meaningful prevention, mitigation, and treatment strategies for explosive blast mTBI can be speedily realized.

  19. Substance P immunoreactivity increases following human traumatic brain injury.

    PubMed

    Zacest, Andrew C; Vink, Robert; Manavis, Jim; Sarvestani, Ghafar T; Blumbergs, Peter C

    2010-01-01

    Recent experimental evidence suggests that neuropeptides, and in particular substance P (SP), are released following traumatic brain injury (TBI) and may play a significant role in the aetiology of cerebral edema and increased intracranial pressure. Whether SP may play a similar role in clinical TBI remains unknown and was investigated in the current study. Archival post-mortem material was selected from patients who had sustained TBI, had died and had undergone post-mortem and detailed neuropathological examination (n = 13). A second cohort of patients who had died, but who showed no neuropathological abnormality (n = 10), served as case controls. Changes in SP immunoreactivity were examined in the cerebral cortex directly beneath the subdural haematoma in 7 TBI cases and in proximity to contusions in the other 6 cases. Increased SP perivascular immunoreactivity was observed after TBI in 10/13 cases, cortical neurones in 12/13 and astrocytes in 10/13 cases. Perivascular axonal injury was observed by amyloid precursor protein (APP) immunoreactivity in 6/13 TBI cases. Co-localization of SP and APP in a small subset of perivascular fibres suggests perivascular axonal injury could be a mechanism of release of this neuropeptide. The abundance of SP fibres around the human cerebral microvasculature, particularly post capillary venules, together with the changes observed following TBI in perivascular axons, cortical neurones and astrocytes suggest a potentially important role for substance P in neurogenic inflammation following human TBI. PMID:19812951

  20. Brain injury from explosive blast: description and clinical management.

    PubMed

    Ling, G; Ecklund, J M; Bandak, F A

    2015-01-01

    Accumulating clinical experience is indicating that explosive blast brain injury is becoming recognized as a disease distinct from the penetrating form of blast injury as well as the classic closed head injury (CHI). In recent US conflicts in Iraq and Afghanistan, over 60% of combat casualties were from explosive blast with the hallmark explosive weapon being the improvised explosive device (IED). Explosive blast TBI is a condition afflicting many combat injured warfighters potentially constituting another category of TBI. Clinically, it shares many features with conventional TBI but possesses some unique aspects. In its mild form, it also shares many clinical features with PTSD but here again has distinct aspects. Although military medical providers depend on civilian standard of care guidelines when managing explosive blast mTBI, they are continually adapting their medical practice in order to optimize the treatment of this disease, particularly in a theater of war. It is clear that further rigorous scientific study of explosive blast mTBI at both the basic science and clinical levels is needed. This research must include improved understanding of the causes and mechanisms of explosive blast TBI as well as comprehensive epidemiologic studies to determine the prevalence of this disease and its risk factors. A widely accepted unambiguous clinical description of explosive blast mTBI with diagnostic criteria would greatly improve diagnosis. It is hoped that through appropriate research meaningful prevention, mitigation, and treatment strategies for explosive blast mTBI can be speedily realized. PMID:25702216

  1. Energy Drinks, Alcohol, Sports and Traumatic Brain Injuries among Adolescents

    PubMed Central

    Ilie, Gabriela; Boak, Angela; Mann, Robert E.; Adlaf, Edward M.; Hamilton, Hayley; Asbridge, Mark; Rehm, Jürgen; Cusimano, Michael D.

    2015-01-01

    Importance The high prevalence of traumatic brain injuries (TBI) among adolescents has brought much focus to this area in recent years. Sports injuries have been identified as a main mechanism. Although energy drinks, including those mixed with alcohol, are often used by young athletes and other adolescents they have not been examined in relation to TBI. Objective We report on the prevalence of adolescent TBI and its associations with energy drinks, alcohol and energy drink mixed in with alcohol consumption. Design, Settings and Participants Data were derived from the Centre for Addiction and Mental Health’s 2013 Ontario Student Drug Use and Health Survey (OSDUHS). This population-based cross-sectional school survey included 10,272 7th to 12th graders (ages 11–20) who completed anonymous self-administered questionnaires in classrooms. Main Outcome Measures Mild to severe TBI were defined as those resulting in a loss of consciousness for at least five minutes, or being hospitalized for at least one night. Mechanism of TBI, prevalence estimates of TBI, and odds of energy drink consumption, alcohol use, and consumption of energy drinks mixed with alcohol are assessed. Results Among all students, 22.4% (95% CI: 20.7, 24.1) reported a history of TBI. Sports injuries remain the main mechanism of a recent (past year) TBI (45.5%, 95% CI: 41.0, 50.1). Multinomial logistic regression showed that relative to adolescents who never sustained a TBI, the odds of sustaining a recent TBI were greater for those consuming alcohol, energy drinks, and energy drinks mixed in with alcohol than abstainers. Odds ratios were higher for these behaviors among students who sustained a recent TBI than those who sustained a former TBI (lifetime but not past 12 months). Relative to recent TBI due to other causes of injury, adolescents who sustained a recent TBI while playing sports had higher odds of recent energy drinks consumption than abstainers. Conclusions and Relevance TBI remains a

  2. Neuroimaging in Pediatric Traumatic Brain Injury: Current and Future Predictors of Functional Outcome

    ERIC Educational Resources Information Center

    Suskauer, Stacy J.; Huisman, Thierry A. G. M.

    2009-01-01

    Although neuroimaging has long played a role in the acute management of pediatric traumatic brain injury (TBI), until recently, its use as a tool for understanding and predicting long-term brain-behavior relationships after TBI has been limited by the relatively poor sensitivity of routine clinical imaging for detecting diffuse axonal injury…

  3. Synaptic Mechanisms of Blast-Induced Brain Injury.

    PubMed

    Przekwas, Andrzej; Somayaji, Mahadevabharath R; Gupta, Raj K

    2016-01-01

    Blast wave-induced traumatic brain injury (TBI) is one of the most common injuries to military personnel. Brain tissue compression/tension due to blast-induced cranial deformations and shear waves due to head rotation may generate diffuse micro-damage to neuro-axonal structures and trigger a cascade of neurobiological events culminating in cognitive and neurodegenerative disorders. Although diffuse axonal injury is regarded as a signature wound of mild TBI (mTBI), blast loads may also cause synaptic injury wherein neuronal synapses are stretched and sheared. This synaptic injury may result in temporary disconnect of the neural circuitry and transient loss in neuronal communication. We hypothesize that mTBI symptoms such as loss of consciousness or dizziness, which start immediately after the insult, could be attributed to synaptic injury. Although empirical evidence is beginning to emerge; the detailed mechanisms underlying synaptic injury are still elusive. Coordinated in vitro-in vivo experiments and mathematical modeling studies can shed light into the synaptic injury mechanisms and their role in the potentiation of mTBI symptoms. PMID:26834697

  4. Synaptic Mechanisms of Blast-Induced Brain Injury

    PubMed Central

    Przekwas, Andrzej; Somayaji, Mahadevabharath R.; Gupta, Raj K.

    2016-01-01

    Blast wave-induced traumatic brain injury (TBI) is one of the most common injuries to military personnel. Brain tissue compression/tension due to blast-induced cranial deformations and shear waves due to head rotation may generate diffuse micro-damage to neuro-axonal structures and trigger a cascade of neurobiological events culminating in cognitive and neurodegenerative disorders. Although diffuse axonal injury is regarded as a signature wound of mild TBI (mTBI), blast loads may also cause synaptic injury wherein neuronal synapses are stretched and sheared. This synaptic injury may result in temporary disconnect of the neural circuitry and transient loss in neuronal communication. We hypothesize that mTBI symptoms such as loss of consciousness or dizziness, which start immediately after the insult, could be attributed to synaptic injury. Although empirical evidence is beginning to emerge; the detailed mechanisms underlying synaptic injury are still elusive. Coordinated in vitro–in vivo experiments and mathematical modeling studies can shed light into the synaptic injury mechanisms and their role in the potentiation of mTBI symptoms. PMID:26834697

  5. Experimental traumatic brain injury

    PubMed Central

    2010-01-01

    Traumatic brain injury, a leading cause of death and disability, is a result of an outside force causing mechanical disruption of brain tissue and delayed pathogenic events which collectively exacerbate the injury. These pathogenic injury processes are poorly understood and accordingly no effective neuroprotective treatment is available so far. Experimental models are essential for further clarification of the highly complex pathology of traumatic brain injury towards the development of novel treatments. Among the rodent models of traumatic brain injury the most commonly used are the weight-drop, the fluid percussion, and the cortical contusion injury models. As the entire spectrum of events that might occur in traumatic brain injury cannot be covered by one single rodent model, the design and choice of a specific model represents a major challenge for neuroscientists. This review summarizes and evaluates the strengths and weaknesses of the currently available rodent models for traumatic brain injury. PMID:20707892

  6. Long-Term Ability to Interpret Facial Expression after Traumatic Brain Injury and Its Relation to Social Integration

    ERIC Educational Resources Information Center

    Knox, Lucy; Douglas, Jacinta

    2009-01-01

    There is considerable evidence that individuals with traumatic brain injury (TBI) experience problems interpreting the emotional state of others. However, the functional implications of these changes have not been fully investigated. A study of 13 individuals with severe TBI and an equal number of matched controls found that TBI participants had…

  7. 78 FR 76196 - Secondary Service Connection for Diagnosable Illnesses Associated With Traumatic Brain Injury

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-17

    ... Traumatic Brain Injury AGENCY: Department of Veterans Affairs. ACTION: Final rule. SUMMARY: The Department... and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury, regarding the association between traumatic brain injury (TBI) and five diagnosable illnesses. This amendment establishes that if...

  8. 78 FR 9929 - Current Traumatic Brain Injury State Implementation Partnership Grantees; Non-Competitive One...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... HUMAN SERVICES Health Resources and Services Administration Current Traumatic Brain Injury State...-Competitive One-Year Extension Funds for Current Traumatic Brain Injury (TBI) State Implementation Partnership... by the Traumatic Brain Injury Act of 1996 (Pub. L. 104-166) and was most recently reauthorized by...

  9. A better mild traumatic brain injury model in the rat.

    PubMed

    Takeuchi, Satoru; Nawashiro, Hiroshi; Sato, Shunichi; Kawauchi, Satoko; Nagatani, Kimihiro; Kobayashi, Hiroaki; Otani, Naoki; Osada, Hideo; Wada, Kojiro; Shima, Katsuji

    2013-01-01

    The primary pathology associated with mild -traumatic brain injury (TBI) is selective axonal injury, which may characterize the vast majority of blast-induced TBIs. Axonal injuries in cases of mild TBI have been considered to be the main factors responsible for the long-lasting memory or attentional impairment in affected subjects. Among these axonal injuries, recent attention has been focused on the cingulum bundle (CB). Furthermore, recent studies with diffusion tensor MR imaging have shown the presence of injuries of the CB in cases of mild TBI in humans. This study aimed to provide a better laboratory model of mild TBI.Sprague-Dawley rats were subjected to mild TBI using laser-induced shock waves (LISW) (sham, 0.5 J/cm(2), or 1.0 J/cm(2); n = 4 per group). Bodian-stained brain sections 14 days after LISW at 0.5 J/cm(2) or 1.0 J/cm(2) showed a decrease in the CB axonal density compared with the sham group, whereas there were no differences in the axonal density of the corpus callosum.The present study shows that this model is capable of reproducing the histological changes associated with mild TBI. PMID:23564112

  10. Persuasive Discourse Impairments in Traumatic Brain Injury

    PubMed Central

    Ghayoumi, Zahra; Yadegari, Fariba; Mahmoodi-Bakhtiari, Behrooz; Fakharian, Esmaeil; Rahgozar, Mehdi; Rasouli, Maryam

    2015-01-01

    Background: Considering the cognitive and linguistic complexity of discourse production, it is expected that individuals with traumatic brain injury (TBI) should face difficulties in this task. Therefore, clinical examination of discourse has become a useful tool for studying and assessment of communication skills of people suffering from TBI. Among different genres of discourse, persuasive discourse is considered as a more cognitively demanding task. However, little is known about persuasive discourse in individuals suffering from TBI. Objectives: The purpose of this study was to evaluate the performance of adults with TBI on a task of spoken persuasive discourse to determine the impaired linguistic measures. Patients and Methods: Thirteen TBI nonaphasic Persian speaking individuals, ranged between 19 to 40 years (Mean = 25.64 years; SD = 6.10) and 59 healthy adults matched by age, were asked to perform the persuasive discourse task. The task included asking the participants to express their opinion on a topic, and after the analysis of the produced discourse, the two groups were compared on the basis of their language productivity, sentential complexity, maze ratio and cohesion ratio. Results: The TBI group produced discourses with less productivity, sentential complexity, cohesion ratio and more maze ratio compared the control group. Conclusions: As it is important to consider acquired communication disorders particularly discourse impairment of brain injured patients along with their other clinical impairments and regarding the fact that persuasive discourse is crucial in academic and social situations, the persuasive discourse task presented in this study could be a useful tool for speech therapists, intending to evaluate communication disorders in patients with TBI. PMID:25798418

  11. Development of an Ontology for Rehabilitation: Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Grove, Michael J.

    2013-01-01

    Traumatic Brain Injury (TBI) rehabilitation interventions are very heterogeneous due to injury characteristics and pathology, patient demographics, healthcare settings, caregiver variability, and individualized, multi-discipline treatment plans. Consequently, comparing and generalizing the effectiveness of interventions is limited largely due to…

  12. Traumatic brain injury and NADPH oxidase: a deep relationship.

    PubMed

    Angeloni, Cristina; Prata, Cecilia; Dalla Sega, Francesco Vieceli; Piperno, Roberto; Hrelia, Silvana

    2015-01-01

    Traumatic brain injury (TBI) represents one of the major causes of mortality and disability in the world. TBI is characterized by primary damage resulting from the mechanical forces applied to the head as a direct result of the trauma and by the subsequent secondary injury due to a complex cascade of biochemical events that eventually lead to neuronal cell death. Oxidative stress plays a pivotal role in the genesis of the delayed harmful effects contributing to permanent damage. NADPH oxidases (Nox), ubiquitary membrane multisubunit enzymes whose unique function is the production of reactive oxygen species (ROS), have been shown to be a major source of ROS in the brain and to be involved in several neurological diseases. Emerging evidence demonstrates that Nox is upregulated after TBI, suggesting Nox critical role in the onset and development of this pathology. In this review, we summarize the current evidence about the role of Nox enzymes in the pathophysiology of TBI.

  13. Traumatic Brain Injury and NADPH Oxidase: A Deep Relationship

    PubMed Central

    Prata, Cecilia; Vieceli Dalla Sega, Francesco; Piperno, Roberto; Hrelia, Silvana

    2015-01-01

    Traumatic brain injury (TBI) represents one of the major causes of mortality and disability in the world. TBI is characterized by primary damage resulting from the mechanical forces applied to the head as a direct result of the trauma and by the subsequent secondary injury due to a complex cascade of biochemical events that eventually lead to neuronal cell death. Oxidative stress plays a pivotal role in the genesis of the delayed harmful effects contributing to permanent damage. NADPH oxidases (Nox), ubiquitary membrane multisubunit enzymes whose unique function is the production of reactive oxygen species (ROS), have been shown to be a major source of ROS in the brain and to be involved in several neurological diseases. Emerging evidence demonstrates that Nox is upregulated after TBI, suggesting Nox critical role in the onset and development of this pathology. In this review, we summarize the current evidence about the role of Nox enzymes in the pathophysiology of TBI. PMID:25918580

  14. Traumatic Brain Injury and Dystonia

    MedlinePlus

    ... various neurological symptoms, often including dystonia and other movement disorders. Symptoms • Symptoms of a TBI can be mild, ... following an injury. Symptoms of dystonia and other movement disorders may be delayed by several months or years ...

  15. Novel DTI Methodology to Detect and Quantify Injured Regions and Affected Brain Pathways in Traumatic Brain Injury

    PubMed Central

    Singh, Manbir; Jeong, Jeongwon; Hwang, Darryl; Sungkarat, Witaya; Gruen, Peter

    2009-01-01

    Purpose To develop and apply DTI based normalization methodology for the detection and quantification of traumatic brain injury (TBI) and the impact of injury along specific brain pathways in: a) individual TBI subjects, and b) a TBI group. Materials and Methods Normalized DTI tractography was conducted in the native space of 12 TBI and 10 age-matched control subjects using the same number of seeds in each subject, distributed at anatomically equivalent locations. Whole-brain tracts from the control group were mapped onto the head of each TBI subject. Differences in the Fractional Anisotropy (FA) maps between each TBI subject and the control group were computed in a common space using a t-test, transformed back to the individual TBI subject's head-space, and thresholded to form Regions of Interest (ROIs) that were used to sort tracts from the control group and the individual TBI subject. Tract-counts for a given ROI in each TBI subject were compared to group mean for the same ROI to quantify impact of injury along affected pathways. Same procedure was used to compare TBI group to control group in a common space. Results Sites of injury within individual TBI subjects and affected pathways included hippocampal/fornix, inferior fronto-occipital, inferior longitudinal fasciculus, corpus callosum (genu and splenium), cortico-spinal tracts and the uncinate fasciculus. Most of these regions were also detected in the group study. Conclusions The DTI normalization methodology presented here enables automatic delineation of ROIs within the heads of individual subjects (or in a group). These ROIs not only localize and quantify the extent of injury, but also quantify the impact of injury on affected pathways in an individual or a group of TBI subjects. PMID:19608369

  16. A new avenue for lithium: intervention in traumatic brain injury.

    PubMed

    Leeds, Peter R; Yu, Fengshan; Wang, Zhifei; Chiu, Chi-Tso; Zhang, Yumin; Leng, Yan; Linares, Gabriel R; Chuang, De-Maw

    2014-06-18

    Traumatic brain injury (TBI) is a leading cause of disability and death from trauma to central nervous system (CNS) tissues. For patients who survive the initial injury, TBI can lead to neurodegeneration as well as cognitive and motor deficits, and is even a risk factor for the future development of neurodegenerative disorders such as Alzheimer's disease. Preclinical studies of multiple neuropathological and neurodegenerative disorders have shown that lithium, which is primarily used to treat bipolar disorder, has considerable neuroprotective effects. Indeed, emerging evidence now suggests that lithium can also mitigate neurological deficits incurred from TBI. Lithium exerts neuroprotective effects and stimulates neurogenesis via multiple signaling pathways; it inhibits glycogen synthase kinase-3 (GSK-3), upregulates neurotrophins and growth factors (e.g., brain-derived neurotrophic factor (BDNF)), modulates inflammatory molecules, upregulates neuroprotective factors (e.g., B-cell lymphoma-2 (Bcl-2), heat shock protein 70 (HSP-70)), and concomitantly downregulates pro-apoptotic factors. In various experimental TBI paradigms, lithium has been shown to reduce neuronal death, microglial activation, cyclooxygenase-2 induction, amyloid-β (Aβ), and hyperphosphorylated tau levels, to preserve blood-brain barrier integrity, to mitigate neurological deficits and psychiatric disturbance, and to improve learning and memory outcome. Given that lithium exerts multiple therapeutic effects across an array of CNS disorders, including promising results in preclinical models of TBI, additional clinical research is clearly warranted to determine its therapeutic attributes for combating TBI. Here, we review lithium's exciting potential in ameliorating physiological as well as cognitive deficits induced by TBI.

  17. The impact of injury severity on executive function 7-10 years following pediatric traumatic brain injury.

    PubMed

    Muscara, Frank; Catroppa, Cathy; Anderson, Vicki

    2008-01-01

    The impact of pediatric traumatic brain injury (TBI) on executive function (EF) development is well documented, with more severe injury associated with poorer outcome. Few studies have investigated the impact of pediatric TBI on EF in the long-term post-injury. The current study explored the relationship between injury severity and EF in participants with childhood TBI, following the transition into adulthood. The sample included 36 participants who had sustained TBI between 8-12 years of age. At 7-10 years post-injury, they now ranged between 16-22 years of age. Findings indicated that adolescents and young adults who suffered a more severe TBI during childhood tended to display a higher degree of executive dysfunction, but only in specific EF domains. PMID:18788014

  18. Blast traumatic brain injury in the rat using a blast overpressure model.

    PubMed

    Yarnell, Angela M; Shaughness, Michael C; Barry, Erin S; Ahlers, Stephen T; McCarron, Richard M; Grunberg, Neil E

    2013-01-01

    Traumatic brain injury (TBI) is a serious health concern for civilians and military populations, and blast-induced TBI (bTBI) has become an increasing problem for military personnel over the past 10 years. To understand the biological and psychological effects of blast-induced injuries and to examine potential interventions that may help to prevent, attenuate, and treat effects of bTBI, it is valuable to conduct controlled animal experiments. This unit discusses available paradigms to model traumatic brain injury in animals, with an emphasis on the relevance of these various models to study blast-induced traumatic brain injury (bTBI). This paper describes the detailed methods of a blast overpressure (BOP) paradigm that has been used to conduct experiments with rats to model blast exposure. This particular paradigm models the pressure wave created by explosions, including improvised explosive devices (IEDs).

  19. Early Neuropsychological Tests as Correlates of Productivity 1 Year after Traumatic Brain Injury: A Preliminary Matched Case-Control Study

    ERIC Educational Resources Information Center

    Ryu, Won Hyung A.; Cullen, Nora K.; Bayley, Mark T.

    2010-01-01

    This study explored the relative strength of five neuropsychological tests in correlating with productivity 1 year after traumatic brain injury (TBI). Six moderate-to-severe TBI patients who returned to work at 1-year post-injury were matched with six controls who were unemployed after 1 year based on age, severity of injury, and Functional…

  20. Molecular mechanisms of cognitive dysfunction following traumatic brain injury

    PubMed Central

    Walker, Kendall R.; Tesco, Giuseppina

    2013-01-01

    Traumatic brain injury (TBI) results in significant disability due to cognitive deficits particularly in attention, learning and memory, and higher-order executive functions. The role of TBI in chronic neurodegeneration and the development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and most recently chronic traumatic encephalopathy (CTE) is of particular importance. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. In this review, we present experimental evidence of the known secondary injury mechanisms which contribute to neuronal cell loss, axonal injury, and synaptic dysfunction and hence cognitive impairment both acutely and chronically following TBI. In particular we focus on the mechanisms linking TBI to the development of two forms of dementia: AD and CTE. We provide evidence of potential molecular mechanisms involved in modulating Aβ and Tau following TBI and provide evidence of the role of these mechanisms in AD pathology. Additionally we propose a mechanism by which Aβ generated as a direct result of TBI is capable of exacerbating secondary injury mechanisms thereby establishing a neurotoxic cascade that leads to chronic neurodegeneration. PMID:23847533

  1. Traumatic Brain Injury Precipitates Cognitive Impairment and Extracellular Aβ Aggregation in Alzheimer's Disease Transgenic Mice

    PubMed Central

    Shimizu, Toru; Arendash, Gary W.; Borlongan, Cesar V.

    2013-01-01

    Traumatic brain injury (TBI) has become a signature wound of the wars in Iraq and Afghanistan. Many American soldiers, even those undiagnosed but likely suffering from mild TBI, display Alzheimer's disease (AD)-like cognitive impairments, suggesting a pathological overlap between TBI and AD. This study examined the cognitive and neurohistological effects of TBI in presymptomatic APP/PS1 AD-transgenic mice. AD mice and non-transgenic (NT) mice received an experimental TBI on the right parietal cortex using the controlled cortical impact model. Animals were trained in a water maze task for spatial memory before TBI, and then reevaluated in the same task at two and six weeks post-TBI. The results showed that AD mice with TBI made significantly more errors in the task than AD mice without TBI and NT mice regardless of TBI. A separate group of AD mice and NT mice were evaluated neurohistologically at six weeks after TBI. The number of extracellular beta-amyloid (Aβ)-deposits significantly increased by at least one fold in the cortex of AD mice that received TBI compared to the NT mice that received TBI or the AD and NT mice that underwent sham surgery. A significant decrease in MAP2 positive cells, indicating neuronal loss, was observed in the cortex of both the AD and NT mice that received TBI compared to the AD and NT mice subjected to sham surgery. Similar changes in extracellular Aβ deposits and MAP2 positive cells were also seen in the hippocampus. These results demonstrate for the first time that TBI precipitates cognitive impairment in presymptomatic AD mice, while also confirming extracellular Aβ deposits following TBI. The recognition of this pathological link between TBI and AD should aid in developing novel treatments directed at abrogating cellular injury and extracellular Aβ deposition in the brain. PMID:24223856

  2. Traumatic brain injury precipitates cognitive impairment and extracellular Aβ aggregation in Alzheimer's disease transgenic mice.

    PubMed

    Tajiri, Naoki; Kellogg, S Leilani; Shimizu, Toru; Arendash, Gary W; Borlongan, Cesar V

    2013-01-01

    Traumatic brain injury (TBI) has become a signature wound of the wars in Iraq and Afghanistan. Many American soldiers, even those undiagnosed but likely suffering from mild TBI, display Alzheimer's disease (AD)-like cognitive impairments, suggesting a pathological overlap between TBI and AD. This study examined the cognitive and neurohistological effects of TBI in presymptomatic APP/PS1 AD-transgenic mice. AD mice and non-transgenic (NT) mice received an experimental TBI on the right parietal cortex using the controlled cortical impact model. Animals were trained in a water maze task for spatial memory before TBI, and then reevaluated in the same task at two and six weeks post-TBI. The results showed that AD mice with TBI made significantly more errors in the task than AD mice without TBI and NT mice regardless of TBI. A separate group of AD mice and NT mice were evaluated neurohistologically at six weeks after TBI. The number of extracellular beta-amyloid (Aβ)-deposits significantly increased by at least one fold in the cortex of AD mice that received TBI compared to the NT mice that received TBI or the AD and NT mice that underwent sham surgery. A significant decrease in MAP2 positive cells, indicating neuronal loss, was observed in the cortex of both the AD and NT mice that received TBI compared to the AD and NT mice subjected to sham surgery. Similar changes in extracellular Aβ deposits and MAP2 positive cells were also seen in the hippocampus. These results demonstrate for the first time that TBI precipitates cognitive impairment in presymptomatic AD mice, while also confirming extracellular Aβ deposits following TBI. The recognition of this pathological link between TBI and AD should aid in developing novel treatments directed at abrogating cellular injury and extracellular Aβ deposition in the brain. PMID:24223856

  3. Comment: importance of cognitive reserve in traumatic brain injury.

    PubMed

    Bigler, Erin D

    2014-05-01

    The expectation for moderate to severe traumatic brain injury (TBI) is permanent damage and lasting deficits. However, in a multicenter investigation, Schneider et al.(1) show that by 1 year postinjury, one-fourth of patients with TBI achieve disability-free recovery (DFR), defined as a score of zero on the Disability Rating Scale. Of importance, cognitive reserve (CR) in the form of educational attainment was related to DFR.

  4. Alcohol exposure after mild focal traumatic brain injury impairs neurological recovery and exacerbates localized neuroinflammation.

    PubMed

    Teng, Sophie X; Katz, Paige S; Maxi, John K; Mayeux, Jacques P; Gilpin, Nicholas W; Molina, Patricia E

    2015-03-01

    Traumatic brain injury (TBI) represents a leading cause of morbidity and mortality among young individuals. Alcohol abuse is a risk factor associated with increased TBI incidence. In addition, up to 26% of TBI patients engage in alcohol consumption after TBI. Limited preclinical studies have examined the impact of post-injury alcohol exposure on TBI recovery. The aim of this study was to determine the isolated and combined effects of TBI and alcohol on cognitive, behavioral, and physical recovery, as well as on associated neuroinflammatory changes. Male Sprague-Dawley rats (∼300g) were subjected to a mild focal TBI by lateral fluid percussion (∼30PSI, ∼25ms) under isoflurane anesthesia. On day 4 after TBI, animals were exposed to either sub-chronic intermittent alcohol vapor (95% ethanol 14h on/10h off; BAL∼200mg/dL) or room air for 10days. TBI induced neurological dysfunction reflected by an increased neurological severity score (NSS) showed progressive improvement in injured animals exposed to room air (TBI/air). In contrast, TBI animals exposed to alcohol vapor (TBI/alcohol) showed impaired NSS recovery throughout the 10-day period of alcohol exposure. Open-field exploration test revealed an increased anxiety-like behavior in TBI/alcohol group compared to TBI/air group. Additionally, alcohol-exposed animals showed decreased locomotion and impaired novel object recognition. Immunofluorescence showed enhanced reactive astrocytes, microglial activation, and HMGB1 expression localized to the injured cortex of TBI/alcohol as compared to TBI/air animals. The expression of neuroinflammatory markers showed significant positive correlation with NSS. These findings indicated a close relationship between accentuated neuroinflammation and impaired neurological recovery from post-TBI alcohol exposure. The clinical implications of long-term consequences in TBI patients exposed to alcohol during recovery warrant further investigation.

  5. Alcohol Exposure after Mild Focal Traumatic Brain Injury Impairs Neurological Recovery and Exacerbates Localized Neuroinflammation

    PubMed Central

    Teng, Sophie X; Katz, Paige S; Maxi, John K; Mayeux, Jacques P; Gilpin, Nicholas W; Molina, Patricia E

    2014-01-01

    Traumatic brain injury (TBI) represents a leading cause of morbidity and mortality among young individuals. Alcohol abuse is a risk factor associated with increased TBI incidence. In addition, up to 26% of TBI patients engage in alcohol consumption after TBI. Limited preclinical studies have examined the impact of post-injury alcohol exposure on TBI recovery. The aim of this study was to determine the isolated and combined effects of TBI and alcohol on cognitive, behavioral, and physical recovery, as well as on associated neuroinflammatory changes. Male Sprague-Dawley rats (~300 g) were subjected to a mild focal TBI by lateral fluid percussion (~30 PSI, ~25 ms) under isoflurane anesthesia. On day 4 after TBI, animals were exposed to either sub-chronic intermittent alcohol vapor (95% ethanol 14h on /10h off; BAL~200 mg/dL) or room air for 10 days. TBI induced neurological dysfunction reflected by an increased neurological severity score (NSS) showed progressive improvement in injured animals exposed to room air (TBI/air). In contrast, TBI animals exposed to alcohol vapor (TBI/alcohol) showed impaired NSS recovery throughout the 10-day period of alcohol exposure. Open-field exploration test revealed an increased anxiety-like behavior in TBI/alcohol group compared to TBI/air group. Additionally, alcohol-exposed animals showed decreased locomotion and impaired novel object recognition. Immunofluorescence showed enhanced reactive astrocytes, microglial activation, and HMGB1 expression localized to the injured cortex of TBI/alcohol as compared to TBI/air animals. The expression of neuroinflammatory markers showed significant positive correlation with NSS. These findings indicated a close relationship between accentuated neuroinflammation and impaired neurological recovery from post-TBI alcohol exposure. The clinical implications of long-term consequences in TBI patients exposed to alcohol during recovery warrant further investigation. PMID:25489880

  6. Traumatic Brain Injury

    MedlinePlus

    ... a concussion may feel dazed and may lose vision or balance for a while after the injury A brain contusion is a bruise of the brain. This ... consciousness Headache Confusion Feeling dizzy or lightheaded Blurry vision ... or severe traumatic brain injury include all of the symptoms listed above ...

  7. Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model

    PubMed Central

    Lau, Tsz; Kaneko, Yuji; van Loveren, Harry; Borlongan, Cesario V.

    2012-01-01

    Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI. PMID:22438975

  8. Volumetrics relate to the development of depression after traumatic brain injury.

    PubMed

    Maller, Jerome J; Thomson, Richard H S; Pannek, Kerstin; Bailey, Neil; Lewis, Philip M; Fitzgerald, Paul B

    2014-09-01

    Previous research suggests that many people who sustain a traumatic brain injury (TBI), even of the mild form, will develop major depression (MD). We previously reported white matter integrity differences between those who did and did not develop MD after mild TBI. In this current paper, we aimed to investigate whether there were also volumetric differences between these groups, as suggested by previous volumetric studies in mild TBI populations. A sample of TBI-with-MD subjects (N=14), TBI-without-MD subjects (N=12), MD-without-TBI (N=26) and control subjects (no TBI or MD, N=23), received structural MRI brain scans. T1-weighted data were analysed using the Freesurfer software package which produces automated volumetric results. The findings of this study indicate that (1) TBI patients who develop MD have reduced volume in temporal, parietal and lingual regions compared to TBI patients who do not develop MD, and (2) MD patients with a history of TBI have decreased volume in the temporal region compared to those who had MD but without a history of TBI. We also found that more severe MD in those with TBI-with-MD significantly correlated with reduced volume in anterior cingulate, temporal lobe and insula. These findings suggest that volumetric reduction to specific regions, including parietal, temporal and occipital lobes, after a mild TBI may underlie the susceptibility of these patients developing major depression, in addition to altered white matter integrity. PMID:24886777

  9. Diffusion tensor imaging in mild traumatic brain injury litigation.

    PubMed

    Wortzel, Hal S; Kraus, Marilyn F; Filley, Christopher M; Anderson, C Alan; Arciniegas, David B

    2011-01-01

    A growing body of literature addresses the application of diffusion tensor imaging (DTI) to traumatic brain injury (TBI). Most TBIs are of mild severity, and their diagnosis and prognosis are often challenging. These challenges may be exacerbated in medicolegal contexts, where plaintiffs seek to present objective evidence that supports a clinical diagnosis of mild (m)TBI. Because DTI permits quantification of white matter integrity and because TBI frequently involves white matter injury, DTI represents a conceptually appealing method of demonstrating white matter pathology attributable to mTBI. However, alterations in white matter integrity are not specific to TBI, and their presence does not necessarily confirm a diagnosis of mTBI. Guided by rules of evidence shaped by Daubert v. Merrell Dow Pharmaceuticals, Inc., we reviewed and analyzed the literature describing DTI findings in mTBI and related neuropsychiatric disorders. Based on this review, we suggest that expert testimony regarding DTI findings will seldom be appropriate in legal proceedings focused on mTBI. PMID:22159979

  10. Effects of hydroxysafflor yellow A on the experimental traumatic brain injury in rats.

    PubMed

    Bie, Xiao-Dong; Han, Jue; Dai, Hai-Bin

    2010-03-01

    This paper explores the effects of hydroxysafflor yellow A (HSYA) on traumatic brain injury (TBI). Rats were divided into four groups: control, TBI, TBI combined with HSYA, and TBI combined with nimodipine. Saline, HSYA, or nimodipine was i.v. injected at 30 min before and 6 h after the onset of TBI. The contusion volume of brain, mitochondrial ATPase activity, brain malondialdehyde (MDA) content, and the concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in the blood plasma were investigated. The results showed that the inhibitory rate of HSYA at a dose of 4 mg/kg was 59.2% compared with the TBI group. After the insult by TBI for 48 h, the activity of Na(+), K(+)-ATPase, Ca(2+)-ATPase, and Mg(2+)-ATPase decreased to 31, 35, and 38% of control group. HSYA increased these ATPase activities by 162, 96, and 131% of TBI group. HSYA also increased superoxide dismutase activity and decreased MDA content in the right parietal lobe adjacent to contusion foci in TBI rats. HSYA enhanced the t-PA activity by 64.64%, decreased the PAI-1 activity by 71.88%, and decreased the MMP-9 expression to 49.11% in the hippocampus of the TBI group at 12 h. In conclusion, HSYA may exert a potential therapeutic strategy to improve the outcome following TBI injury.

  11. Controlled cortical impact model for traumatic brain injury.

    PubMed

    Romine, Jennifer; Gao, Xiang; Chen, Jinhui

    2014-08-05

    Every year over a million Americans suffer a traumatic brain injury (TBI). Combined with the incidence of TBIs worldwide, the physical, emotional, social, and economical effects are staggering. Therefore, further research into the effects of TBI and effective treatments is necessary. The controlled cortical impact (CCI) model induces traumatic brain injuries ranging from mild to severe. This method uses a rigid impactor to deliver mechanical energy to an intact dura exposed following a craniectomy. Impact is made under precise parameters at a set velocity to achieve a pre-determined deformation depth. Although other TBI models, such as weight drop and fluid percussion, exist, CCI is more accurate, easier to control, and most importantly, produces traumatic brain injuries similar to those seen in humans. However, no TBI model is currently able to reproduce pathological changes identical to those seen in human patients. The CCI model allows investigation into the short-term and long-term effects of TBI, such as neuronal death, memory deficits, and cerebral edema, as well as potential therapeutic treatments for TBI.

  12. Challenges associated with screening for traumatic brain injury among US veterans seeking homeless services.

    PubMed

    Russell, Leah M; Devore, Maria D; Barnes, Sean M; Forster, Jeri E; Hostetter, Trisha A; Montgomery, Ann Elizabeth; Casey, Roger; Kane, Vincent; Brenner, Lisa A

    2013-12-01

    We identified the prevalence of traumatic brain injury (TBI) among homeless veterans and assessed the TBI-4, a screening tool created to identify TBI history. Between May 2010 and October 2011, 800 US veterans from two hospitals, one eastern (n = 122) and one western (n = 678) completed some or all measures. Findings suggested that 47% of veterans seeking homeless services had a probable history of TBI (data for prevalence obtained only at the western hospital). However, psychometric results from the screening measure suggested that this may be an underestimate and supported comprehensive assessment of TBI in this population. PMID:24148060

  13. Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats.

    PubMed

    Zhao, Jinbing; Chen, Zhi; Xi, Guohua; Keep, Richard F; Hua, Ya

    2014-10-01

    Acute post-traumatic ventricular dilation and hydrocephalus are relatively frequent consequences of traumatic brain injury (TBI). Several recent studies have indicated that high iron levels in brain may relate to hydrocephalus development after intracranial hemorrhage. However, the role of iron in the development of post-traumatic hydrocephalus is still unclear. This study was to determine whether or not iron has a role in hydrocephalus development after TBI. TBI was induced by lateral fluid-percussion in male Sprague-Dawley rats. Some rats had intraventricular injection of iron. Acute hydrocephalus was measured by magnetic resonance T2-weighted imaging and brain hemorrhage was determined by T2* gradient-echo sequence imaging and brain hemoglobin levels. The effect of deferoxamine on TBI-induced hydrocephalus was examined. TBI resulted in acute hydrocephalus at 24 h (lateral ventricle volume: 24.1 ± 3.0 vs. 9.9 ± 0.2 mm(3) in sham group). Intraventricular injection of iron also caused hydrocephalus (25.7 ± 3.4 vs. 9.0 ± 0.6 mm(3) in saline group). Deferoxamine treatment attenuated TBI-induced hydrocephalus and heme oxygenase-1 upregulation. In conclusion, iron may contribute to acute hydrocephalus after TBI.

  14. Paclitaxel improves outcome from traumatic brain injury

    PubMed Central

    Cross, Donna J.; Garwin, Gregory G.; Cline, Marcella M.; Richards, Todd L.; Yarnykh, Vasily; Mourad, Pierre D.; Ho, Rodney J.Y.; Minoshima, Satoshi

    2016-01-01

    Pharmacologic interventions for traumatic brain injury (TBI) hold promise to improve outcome. The purpose of this study was to determine if the microtubule stabilizing therapeutic paclitaxel used for more than 20 years in chemotherapy would improve outcome after TBI. We assessed neurological outcome in mice that received direct application of paclitaxel to brain injury from controlled cortical impact (CCI). Magnetic resonance imaging was used to assess injury-related morphological changes. Catwalk Gait analysis showed significant improvement in the paclitaxel group on a variety of parameters compared to the saline group. MRI analysis revealed that paclitaxel treatment resulted in significantly reduced edema volume at site-of-injury (11.92 ± 3.0 and 8.86 ± 2.2 mm3 for saline vs. paclitaxel respectively, as determined by T2-weighted analysis; p ≤ 0.05), and significantly increased myelin tissue preservation (9.45 ± 0.4 vs. 8.95 ± 0.3, p ≤ 0.05). Our findings indicate that paclitaxel treatment resulted in improvement of neurological outcome and MR imaging biomarkers of injury. These results could have a significant impact on therapeutic developments to treat traumatic brain injury. PMID:26086366

  15. Neural evidence that conscious awareness of errors is reduced in depression following a traumatic brain injury.

    PubMed

    Bailey, N W; Hoy, K E; Maller, J J; Upton, D J; Segrave, R A; Fitzgibbon, B M; Fitzgerald, P B

    2015-03-01

    Impaired error awareness is related to poorer outcome following traumatic brain injury (TBI). Error awareness deficits are also found in major depressive disorder (MDD), but have not been examined in the MDD that follows a TBI (TBI-MDD). This study assessed neural activity related to error awareness in TBI-MDD. Four groups completed a response inhibition task while EEG was recorded- healthy controls (N = 15), MDD-only (N = 15), TBI-only (N = 16), and TBI-MDD (N = 12). Error related EEG activity was compared using powerful randomisation statistics that included all electrodes and time points. Participants with TBI-MDD displayed less frontally distributed neural activity, suggesting reduced contribution from frontal generating sources. Neural activity during this time window is thought to reflect conscious awareness of errors. The TBI-only and MDD-only groups did not differ from controls, and early error processing was unaffected, suggesting early error detection is intact.

  16. Proteomics: in pursuit of effective traumatic brain injury therapeutics

    PubMed Central

    Lizhnyak, Pavel N.; Ottens, Andrew K.

    2015-01-01

    Summary Effective traumatic brain injury (TBI) therapeutics remain stubbornly elusive. Efforts in the field have been challenged by the heterogeneity of clinical TBI, with greater complexity among underlying molecular phenotypes than initially conceived. Future research must confront the multitude of factors comprising this heterogeneity, representing a big data challenge befitting the coming informatics age. Proteomics is poised to serve a central role in prescriptive therapeutic development, as it offers an efficient endpoint within which to assess post-TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and the particular importance of temporal profiling in defining biochemical sequences and guiding therapeutic development. Lastly, we offer perspective on repurposing biofluid proteomics to develop theragnostic assays with which to prescribe, monitor and assess pharmaceutics for improved translation and outcome for TBI patients. PMID:25603864

  17. Neuropsychology of Neuroendocrine Dysregulation after Traumatic Brain Injury.

    PubMed

    Zihl, Josef; Almeida, Osborne F X

    2015-05-20

    Endocrine dysfunction is a common effect of traumatic brain injury (TBI). In addition to affecting the regulation of important body functions, the disruption of endocrine physiology can significantly impair mental functions, such as attention, memory, executive function, and mood. This mini-review focuses on alterations in mental functioning that are associated with neuroendocrine disturbances in adults who suffered TBI. It summarizes the contribution of hormones to the regulation of mental functions, the consequences of TBI on mental health and neuroendocrine homeostasis, and the effects of hormone substitution on mental dysfunction caused by TBI. The available empirical evidence suggests that comprehensive assessment of mental functions should be standard in TBI subjects presenting with hormone deficiency and that hormone replacement therapy should be accompanied by pre- and post-assessments.

  18. Social dysfunction after pediatric traumatic brain injury: A translational perspective.

    PubMed

    Ryan, Nicholas P; Catroppa, Cathy; Godfrey, Celia; Noble-Haeusslein, Linda J; Shultz, Sandy R; O'Brien, Terence J; Anderson, Vicki; Semple, Bridgette D

    2016-05-01

    Social dysfunction is common after traumatic brain injury (TBI), contributing to reduced quality of life for survivors. Factors which influence the development or persistence of social deficits after injury remain poorly understood, particularly in the context of ongoing brain maturation during childhood and adolescence. Aberrant social interactions have recently been modeled in adult and juvenile rodents after experimental TBI, providing an opportunity to gain new insights into the underlying neurobiology of these behaviors. Here, we review our current understanding of social dysfunction in both humans and rodent models of TBI, with a focus on brain injuries acquired during early development. Modulators of social outcomes are discussed, including injury-related and environmental risk and resilience factors. Disruption of social brain network connectivity and aberrant neuroendocrine function are identified as potential mechanisms of social impairments after pediatric TBI. Throughout, we highlight the overlap and disparities between outcome measures and findings from clinical and experimental approaches, and explore the translational potential of future research to prevent or ameliorate social dysfunction after childhood TBI. PMID:26949224

  19. Magnetic Micelles for DNA delivery to rat brains after mild traumatic brain injury

    PubMed Central

    Das, Mahasweta; Wang, Chunyan; Bedi, Raminder; Mohapatra, Shyam S.; Mohapatra, Subhra

    2014-01-01

    Traumatic brain injury (TBI) causes significant mortality, long term disability and psychological symptoms. Gene therapy is a promising approach for treatment of different pathological conditions. Here we tested chitosan and polyethyleneimine (PEI)-coated magnetic micelles (CPmag micelles or CPMMs), a potential MRI contrast agent, to deliver a reporter DNA to the brain after mild TBI (mTBI). CPMM - tomato plasmid (ptd) conjugate expressing a red-fluorescent protein (RFP) was administered intranasally immediately after mTBI or sham surgery in male SD rats. Evans blue extravasation following mTBI suggested CPMM-ptd entry into the brain via the compromised blood-brain barrier. Magnetofection increased the concentration of CPMMs in the brain. RFP expression was observed in the brain (cortex and hippocampus), lung and liver 48 hours after mTBI. CPMM did not evoke any inflammatory response by themselves and were excreted from the body. These results indicate the possibility of using intranasally administered CPMM as a theranostic vehicle for mTBI. PMID:24486465

  20. Aqueous Date Fruit Efficiency as Preventing Traumatic Brain Deterioration and Improving Pathological Parameters after Traumatic Brain Injury in Male Rats

    PubMed Central

    Badeli, Hamze; Shahrokhi, Nader; KhoshNazar, Mahdieosadat; Asadi-Shekaari, Majid; Shabani, Mohammad; Eftekhar Vaghefi, Hassan; Khaksari, Mohammad; Basiri, Mohsen

    2016-01-01

    Objective Following traumatic brain injury, disruption of blood-brain-barrier and consequent brain edema are critical events which might lead to increasing intracranial pressure (ICP), and nerve damage. The current study assessed the effects of aqueous date fruit extract (ADFE) on the aforementioned parameters. Materials and Methods In this experimental study, diffused traumatic brain injury (TBI) was generated in adult male rats using Marmarou’s method. Experimental groups include two pre-treatment (oral ADFE, 4 and 8 mL/kg for 14 days), vehicle (distilled water, for 14 days) and sham groups. Brain edema and neuronal injury were measured 72 hours after TBI. Veterinary coma scale (VCS) and ICP were determined at -1, 4, 24, 48 and 72 hours after TBI. Differences among multiple groups were assessed using ANOVA. Turkey’s test was employed for the ANOVA post-hoc analysis. The criterion of statistical significance was sign at P<0.05. Results Brain water content in ADFE-treated groups was decreased in comparison with the TBI+vehicle group. VCS at 24, 48 and 72 hours after TBI showed a significant increase in ADFE groups in comparison with the TBI+vehicle group. ICP at 24, 48 and 72 hours after TBI, was decreased in ADFE groups, compared to the TBI+vehicle. Brain edema, ICP and neuronal injury were also decreased in ADFE group, but VCS was increased following on TBI. Conclusion ADFE pre-treatment demonstrated an efficient method for preventing traumatic brain deterioration and improving pathological parameters after TBI.

  1. Aqueous Date Fruit Efficiency as Preventing Traumatic Brain Deterioration and Improving Pathological Parameters after Traumatic Brain Injury in Male Rats

    PubMed Central

    Badeli, Hamze; Shahrokhi, Nader; KhoshNazar, Mahdieosadat; Asadi-Shekaari, Majid; Shabani, Mohammad; Eftekhar Vaghefi, Hassan; Khaksari, Mohammad; Basiri, Mohsen

    2016-01-01

    Objective Following traumatic brain injury, disruption of blood-brain-barrier and consequent brain edema are critical events which might lead to increasing intracranial pressure (ICP), and nerve damage. The current study assessed the effects of aqueous date fruit extract (ADFE) on the aforementioned parameters. Materials and Methods In this experimental study, diffused traumatic brain injury (TBI) was generated in adult male rats using Marmarou’s method. Experimental groups include two pre-treatment (oral ADFE, 4 and 8 mL/kg for 14 days), vehicle (distilled water, for 14 days) and sham groups. Brain edema and neuronal injury were measured 72 hours after TBI. Veterinary coma scale (VCS) and ICP were determined at -1, 4, 24, 48 and 72 hours after TBI. Differences among multiple groups were assessed using ANOVA. Turkey’s test was employed for the ANOVA post-hoc analysis. The criterion of statistical significance was sign at P<0.05. Results Brain water content in ADFE-treated groups was decreased in comparison with the TBI+vehicle group. VCS at 24, 48 and 72 hours after TBI showed a significant increase in ADFE groups in comparison with the TBI+vehicle group. ICP at 24, 48 and 72 hours after TBI, was decreased in ADFE groups, compared to the TBI+vehicle. Brain edema, ICP and neuronal injury were also decreased in ADFE group, but VCS was increased following on TBI. Conclusion ADFE pre-treatment demonstrated an efficient method for preventing traumatic brain deterioration and improving pathological parameters after TBI. PMID:27602324

  2. Supporting the literacy skills of adolescents with traumatic brain injury.

    PubMed

    Krause, Miriam; Byom, Lindsey; Meulenbroek, Peter; Richards, Stephanie; O'Brien, Katy

    2015-02-01

    Traumatic brain injury (TBI) can affect developmental trajectories as well as language, attention, memory, executive functions, and other cognitive skills related to literacy. Literacy demands change through adolescence and into young adulthood, with academic literacy demands increasing and vocational literacy demands being introduced. Speech-language pathology services must evolve with the literacy needs of each client. This article discusses assessment and treatment approaches designed for adolescents with TBI and recommendations for adapting literacy interventions from the learning disabilities literature. Through proper assessment and intervention, speech-language pathologists can have a meaningful impact on the academic and vocational literacy needs of adolescents with TBI. PMID:25633145

  3. Assessing Quantitative Changes in Intrinsic Thalamic Networks in Blast and Nonblast Mild Traumatic Brain Injury: Implications for Mechanisms of Injury.

    PubMed

    Nathan, Dominic E; Bellgowan, Julie F; Oakes, Terrence R; French, Louis M; Nadar, Sreenivasan R; Sham, Elyssa B; Liu, Wei; Riedy, Gerard

    2016-06-01

    In the global war on terror, the increased use of improvised explosive devices has resulted in increased incidence of blast-related mild traumatic brain injury (mTBI). Diagnosing mTBI is both challenging and controversial due to heterogeneity of injury location, trauma intensity, transient symptoms, and absence of focal biomarkers on standard clinical imaging modalities. The goal of this study is to identify a brain biomarker that is sensitive to mTBI injury. Research suggests the thalamus may be sensitive to changes induced by mTBI. A significant number of connections to and from various brain regions converge at the thalamus. In addition, the thalamus is involved in information processing, integration, and regulation of specific behaviors and mood. In this study, changes in task-free thalamic networks as quantified by graph theory measures in mTBI blast (N = 186), mTBI nonblast (N = 80), and controls (N = 21) were compared. Results show that the blast mTBI group had significant hyper-connectivity compared with the controls and nonblast mTBI group. However, after controlling for post-traumatic stress symptoms (PTSS), the blast mTBI group was not different from the controls, but the nonblast mTBI group showed significant hypo-connectivity. The results suggest that there are differences in the mechanisms of injury related to mTBI as reflected in the architecture of the thalamic networks. However, the effect of PTSS and its relationship to mTBI is difficult to distinguish and warrants more research.

  4. The Effects of Mild Traumatic Brain Injury, Post-Traumatic Stress Disorder, and Combined Mild Traumatic Brain Injury/Post-Traumatic Stress Disorder on Returning Veterans.

    PubMed

    Combs, Hannah L; Berry, David T R; Pape, Theresa; Babcock-Parziale, Judith; Smith, Bridget; Schleenbaker, Randal; Shandera-Ochsner, Anne; Harp, Jordan P; High, Walter M

    2015-07-01

    United States veterans of the Iraqi (Operation Iraqi Freedom [OIF]) and Afghanistan (Operation Enduring Freedom [OEF]) conflicts have frequently returned from deployment after sustaining mild traumatic brain injury (mTBI) and enduring stressful events resulting in post-traumatic stress disorder (PTSD). A large number of returning service members have been diagnosed with both a history of mTBI and current PTSD. Substantial literature exists on the neuropsychological factors associated with mTBI and PTSD occurring separately; far less research has explored the combined effects of PTSD and mTBI. The current study employed neuropsychological and psychological measures in a sample of 251 OIF/OEF veterans to determine whether participants with a history of mTBI and current PTSD (mTBI+PTSD) have poorer cognitive and psychological outcomes than participants with mTBI only (mTBI-o), PTSD only (PTSD-o), or veteran controls (VC), when groups are comparable on intelligence quotient, education, and age. The mTBI+PTSD group performed more poorly than VC, mTBI-o, and PTSD-o groups on several neuropsychological measures. Effect size comparisons suggest small deleterious effects for mTBI-o on measures of processing speed and visual attention and small effects for PTSD-o on measures of verbal memory, with moderate effects for mTBI+PTSD on the same variables. Additionally, the mTBI+PTSD group was significantly more psychologically distressed than the PTSD-o group, and PTSD-o group was more distressed than VC and mTBI-o groups. These findings suggest that veterans with mTBI+PTSD perform significantly lower on neuropsychological and psychiatric measures than veterans with mTBI-o or PTSD-o. The results also raise the possibility of mild but persisting cognitive changes following mTBI sustained during deployment.

  5. The Effects of Mild Traumatic Brain Injury, Post-Traumatic Stress Disorder, and Combined Mild Traumatic Brain Injury/Post-Traumatic Stress Disorder on Returning Veterans

    PubMed Central

    Combs, Hannah L.; Berry, David T. R.; Pape, Theresa; Babcock-Parziale, Judith; Smith, Bridget; Schleenbaker, Randal; Shandera-Ochsner, Anne; Harp, Jordan P.

    2015-01-01

    Abstract United States veterans of the Iraqi (Operation Iraqi Freedom [OIF]) and Afghanistan (Operation Enduring Freedom [OEF]) conflicts have frequently returned from deployment after sustaining mild traumatic brain injury (mTBI) and enduring stressful events resulting in post-traumatic stress disorder (PTSD). A large number of returning service members have been diagnosed with both a history of mTBI and current PTSD. Substantial literature exists on the neuropsychological factors associated with mTBI and PTSD occurring separately; far less research has explored the combined effects of PTSD and mTBI. The current study employed neuropsychological and psychological measures in a sample of 251 OIF/OEF veterans to determine whether participants with a history of mTBI and current PTSD (mTBI+PTSD) have poorer cognitive and psychological outcomes than participants with mTBI only (mTBI-o), PTSD only (PTSD-o), or veteran controls (VC), when groups are comparable on intelligence quotient, education, and age. The mTBI+PTSD group performed more poorly than VC, mTBI-o, and PTSD-o groups on several neuropsychological measures. Effect size comparisons suggest small deleterious effects for mTBI-o on measures of processing speed and visual attention and small effects for PTSD-o on measures of verbal memory, with moderate effects for mTBI+PTSD on the same variables. Additionally, the mTBI+PTSD group was significantly more psychologically distressed than the PTSD-o group, and PTSD-o group was more distressed than VC and mTBI-o groups. These findings suggest that veterans with mTBI+PTSD perform significantly lower on neuropsychological and psychiatric measures than veterans with mTBI-o or PTSD-o. The results also raise the possibility of mild but persisting cognitive changes following mTBI sustained during deployment. PMID:25350012

  6. The Effects of Mild Traumatic Brain Injury, Post-Traumatic Stress Disorder, and Combined Mild Traumatic Brain Injury/Post-Traumatic Stress Disorder on Returning Veterans.

    PubMed

    Combs, Hannah L; Berry, David T R; Pape, Theresa; Babcock-Parziale, Judith; Smith, Bridget; Schleenbaker, Randal; Shandera-Ochsner, Anne; Harp, Jordan P; High, Walter M

    2015-07-01

    United States veterans of the Iraqi (Operation Iraqi Freedom [OIF]) and Afghanistan (Operation Enduring Freedom [OEF]) conflicts have frequently returned from deployment after sustaining mild traumatic brain injury (mTBI) and enduring stressful events resulting in post-traumatic stress disorder (PTSD). A large number of returning service members have been diagnosed with both a history of mTBI and current PTSD. Substantial literature exists on the neuropsychological factors associated with mTBI and PTSD occurring separately; far less research has explored the combined effects of PTSD and mTBI. The current study employed neuropsychological and psychological measures in a sample of 251 OIF/OEF veterans to determine whether participants with a history of mTBI and current PTSD (mTBI+PTSD) have poorer cognitive and psychological outcomes than participants with mTBI only (mTBI-o), PTSD only (PTSD-o), or veteran controls (VC), when groups are comparable on intelligence quotient, education, and age. The mTBI+PTSD group performed more poorly than VC, mTBI-o, and PTSD-o groups on several neuropsychological measures. Effect size comparisons suggest small deleterious effects for mTBI-o on measures of processing speed and visual attention and small effects for PTSD-o on measures of verbal memory, with moderate effects for mTBI+PTSD on the same variables. Additionally, the mTBI+PTSD group was significantly more psychologically distressed than the PTSD-o group, and PTSD-o group was more distressed than VC and mTBI-o groups. These findings suggest that veterans with mTBI+PTSD perform significantly lower on neuropsychological and psychiatric measures than veterans with mTBI-o or PTSD-o. The results also raise the possibility of mild but persisting cognitive changes following mTBI sustained during deployment. PMID:25350012

  7. Mild Traumatic Brain Injury Update: Forensic Neuropsychiatric Implications.

    PubMed

    Wortzel, Hal S; Granacher, Robert P

    2015-12-01

    Traumatic brain injury (TBI) involves a wide range of potential neuropsychiatric outcomes, from death or profound impairment to full and fast recovery. This circumstance has contributed to an atmosphere with considerable potential for both clinical confusion and unjustified medicolegal outcomes. Given that mild (m)TBI accounts for most (∼80%) TBI events and is generally associated with an excellent prognosis, the risk for erroneous clinical formulations and unmerited legal outcomes seems particularly high in cases involving mTBI. In this article, we summarize the recent results published by the International Collaboration on Mild Traumatic Brain Injury Prognosis (ICMTBIP) and the new approach of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, to TBI, and we explore the clinical and medicolegal implications. Symptoms that emerge after mTBI remain nonspecific, and potential etiologies are diverse. Clinicians and medicolegal experts should be familiar with the natural history of mTBI, able to recognize atypical outcomes, and willing to search for alternative explanations when confronted with persistent or severe impairment.

  8. Epileptogenesis after traumatic brain injury in Plau-deficient mice.

    PubMed

    Bolkvadze, Tamuna; Rantala, Jukka; Puhakka, Noora; Andrade, Pedro; Pitkänen, Asla

    2015-10-01

    Several components of the urokinase-type plasminogen activator receptor (uPAR)-interactome, including uPAR and its ligand sushi-repeat protein 2, X-linked (SRPX2), are linked to susceptibility to epileptogenesis in animal models and/or humans. Recent evidence indicates that urokinase-type plasminogen activator (uPA), a uPAR ligand with focal proteinase activity in the extracellular matrix, contributes to recovery-enhancing brain plasticity after various epileptogenic insults such as traumatic brain injury (TBI) and status epilepticus. Here, we examined whether deficiency of the uPA-encoding gene Plau augments epileptogenesis after TBI. Traumatic brain injury was induced by controlled cortical impact in the somatosensory cortex of adult male wild-type and Plau-deficient mice. Development of epilepsy and seizure susceptibility were assessed with a 3-week continuous video-electroencephalography monitoring and a pentylenetetrazol test, respectively. Traumatic brain injury-induced cortical or hippocampal pathology did not differ between genotypes. The pentylenetetrazol test revealed increased seizure susceptibility after TBI (p<0.05) in injured mice. Epileptogenesis was not exacerbated, however, in Plau-deficient mice. Taken together, Plau deficiency did not worsen controlled cortical impact-induced brain pathology or epileptogenesis caused by TBI when assessed at chronic timepoints. These data expand previous observations on Plau deficiency in models of status epilepticus and suggest that inhibition of focal extracellular proteinase activity resulting from uPA-uPAR interactions does not modify epileptogenesis after TBI. PMID:26253597

  9. The blood-brain barrier as a target in traumatic brain injury treatment.

    PubMed

    Thal, Serge C; Neuhaus, Winfried

    2014-11-01

    Traumatic brain injury (TBI) is one of the most frequent causes of death in the young population. Several clinical trials have unsuccessfully focused on direct neuroprotective therapies. Recently immunotherapeutic strategies shifted into focus of translational research in acute CNS diseases. Cross-talk between activated microglia and blood-brain barrier (BBB) could initiate opening of the BBB and subsequent recruitment of systemic immune cells and mediators into the brain. Stabilization of the BBB after TBI could be a promising strategy to limit neuronal inflammation, secondary brain damage and acute neurodegeneration. This review provides an overview on the pathophysiology of TBI and brain edema formation including definitions and classification of TBI, current clinical treatment strategies, as well as current understanding on the underlying cellular processes. A summary of in vivo and in vitro models to study different aspects of TBI is presented. Three mechanisms proposed for stabilization of the BBB, myosin light chain kinases, glucocorticoid receptors and peroxisome proliferator-activated receptors are reviewed for their influence on barrier-integrity and outcome after TBI. In conclusion, the BBB is recommended as a promising target for the treatment of traumatic brain injury, and it is suggested that a combination of BBB stabilization and neuroprotectants may improve therapeutic success. PMID:25446615

  10. Traumatic Brain Injury Upregulates Phosphodiesterase Expression in the Hippocampus.

    PubMed

    Wilson, Nicole M; Titus, David J; Oliva, Anthony A; Furones, Concepcion; Atkins, Coleen M

    2016-01-01

    Traumatic brain injury (TBI) results in significant impairments in hippocampal synaptic plasticity. A molecule critically involved in hippocampal synaptic plasticity, 3',5'-cyclic adenosine monophosphate, is downregulated in the hippocampus after TBI, but the mechanism that underlies this decrease is unknown. To address this question, we determined whether phosphodiesterase (PDE) expression in the hippocampus is altered by TBI. Young adult male Sprague Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury. Animals were analyzed by western blotting for changes in PDE expression levels in the hippocampus. We found that PDE1A levels were significantly increased at 30 min, 1 h and 6 h after TBI. PDE4B2 and 4D2 were also significantly increased at 1, 6, and 24 h after TBI. Additionally, phosphorylation of PDE4A was significantly increased at 6 and 24 h after TBI. No significant changes were observed in levels of PDE1B, 1C, 3A, 8A, or 8B between 30 min to 7 days after TBI. To determine the spatial profile of these increases, we used immunohistochemistry and flow cytometry at 24 h after TBI. PDE1A and phospho-PDE4A localized to neuronal cell bodies. PDE4B2 was expressed in neuronal dendrites, microglia and infiltrating CD11b(+) immune cells. PDE4D was predominantly found in microglia and infiltrating CD11b(+) immune cells. To determine if inhibition of PDE4 would improve hippocampal synaptic plasticity deficits after TBI, we treated hippocampal slices with rolipram, a pan-PDE4 inhibitor. Rolipram partially rescued the depression in basal synaptic transmission and converted a decaying form of long-term potentiation (LTP) into long-lasting LTP. Overall, these results identify several possible PDE targets for reducing hippocampal synaptic plasticity deficits and improving cognitive function acutely after TBI. PMID:26903822

  11. Systematic Review of Traumatic Brain Injury Animal Models.

    PubMed

    Phipps, Helen W

    2016-01-01

    The goals of this chapter are to provide an introduction into the variety of animal models available for studying traumatic brain injury (TBI) and to provide a concise systematic review of the general materials and methods involved in each model. Materials and methods were obtained from a literature search of relevant peer-reviewed articles. Strengths and weaknesses of each animal choice were presented to include relative cost, anatomical and physiological features, and mechanism of injury desired. Further, a variety of homologous, isomorphic/induced, and predictive animal models were defined, described, and compared with respect to their relative ease of use, characteristics, range, adjustability (e.g., amplitude, duration, mass/size, velocity, and pressure), and rough order of magnitude cost. Just as the primary mechanism of action of TBI is limitless, so are the animal models available to study TBI. With such a wide variety of available animals, types of injury models, along with the research needs, there exists no single "gold standard" model of TBI rendering cross-comparison of data extremely difficult. Therefore, this chapter reflects a representative sampling of the TBI animal models available and is not an exhaustive comparison of every possible model and associated parameters. Throughout this chapter, special considerations for animal choice and TBI animal model classification are discussed. Criteria central to choosing appropriate animal models of TBI include ethics, funding, complexity (ease of use, safety, and controlled access requirements), type of model, model characteristics, and range of control (scope). PMID:27604713

  12. Structural and functional effects of social isolation on the hippocampus of rats with traumatic brain injury.

    PubMed

    Khodaie, Babak; Lotfinia, Ahmad Ali; Ahmadi, Milad; Lotfinia, Mahmoud; Jafarian, Maryam; Karimzadeh, Fariba; Coulon, Philippe; Gorji, Ali

    2015-02-01

    Social isolation has significant long-term psychological and physiological consequences. Both social isolation and traumatic brain injury (TBI) alter normal brain function and structure. However, the influence of social isolation on recovery from TBI is unclear. This study aims to evaluate if social isolation exacerbates the anatomical and functional deficits after TBI in young rats. Juvenile male rats were divided into four groups; sham operated control with social contacts, sham control with social isolation, TBI with social contacts, and TBI with social isolation. During four weeks after brain injury in juvenile rats, we evaluated the animal behaviors by T-maze and open-field tests, recorded brain activity with electrocorticograms and assessed structural changes by histological procedures in the hippocampal dentate gyrus, CA1, and CA3 areas. Our findings revealed significant memory impairments and hyperactivity conditions in rats with TBI and social isolation compared to the other groups. Histological assessments showed an increase of the mean number of dark neurons, apoptotic cells, and caspase-3 positive cells in all tested areas of the hippocampus in TBI rats with and without social isolation compared to sham rats. Furthermore, social isolation significantly increased the number of dark cells, apoptotic neurons, and caspase-3 positive cells in the hippocampal CA3 region in rats with TBI. This study indicates the harmful effect of social isolation on anatomical and functional deficits induced by TBI in juvenile rats. Prevention of social isolation may improve the outcome of TBI.

  13. Pathophysiology of hypopituitarism in the setting of brain injury.

    PubMed

    Dusick, Joshua R; Wang, Christina; Cohan, Pejman; Swerdloff, Ronald; Kelly, Daniel F

    2012-03-01

    The complex pathophysiology of traumatic brain injury (TBI) involves not only the primary mechanical event but also secondary insults such as hypotension, hypoxia, raised intracranial pressure and changes in cerebral blood flow and metabolism. It is increasingly evident that these initial insults as well as transient events and treatments during the early injury phase can impact hypothalamic-pituitary function both acutely and chronically after injury. In turn, untreated pituitary hormonal dysfunction itself can further hinder recovery from brain injury. Secondary adrenal insufficiency, although typically reversible, occurs in up to 50% of intubated TBI victims and is associated with lower systemic blood pressure. Chronic anterior hypopituitarism, although reversible in some patients, persists in 25-40% of moderate and severe TBI survivors and likely contributes to long-term neurobehavioral and quality of life impairment. While the rates and risk factors of acute and chronic pituitary dysfunction have been documented for moderate and severe TBI victims in numerous recent studies, the pathophysiology remains ill-defined. Herein we discuss the hypotheses and available data concerning hypothalamic-pituitary vulnerability in the setting of head injury. Four possible pathophysiological mechanisms are considered: (1) the primary brain injury event, (2) secondary brain insults, (3) the stress of critical illness and (4) medication effects. Although each of these factors appears to be important in determining which hormonal axes are affected, the severity of dysfunction, their time course and possible reversibility, this process remains incompletely understood. PMID:18481181

  14. Sleep Disturbances in Traumatic Brain Injury: A Meta-Analysis

    PubMed Central

    Grima, Natalie; Ponsford, Jennie; Rajaratnam, Shantha M.; Mansfield, Darren; Pase, Matthew P.

    2016-01-01

    Study Objectives: Sleep disturbances are frequently reported following traumatic brain injury (TBI); however, the exact disturbances remain unclear. This meta-analysis aimed to characterize sleep disturbance in community dwelling patients with TBI as compared to controls. Methods: Two investigators independently conducted a systematic search of multiple electronic databases from inception to May 27, 2015. Studies were selected if they compared sleep in community dwelling individuals with TBI relative to a control population without head injury. Data were pooled in meta-analysis with outcomes expressed as the standard mean difference (SMD) and 95% confidence interval (CI). The primary outcomes were derived from polysomnography and secondary outcomes were derived from subjective sleep measures. Results: Sixteen studies were included, combining 637 TBI patients and 567 controls, all of whom were community dwelling. Pooled polysomnography data revealed that TBI patients had poorer sleep efficiency (SMD = −0.47, CI: −0.89, −0.06), shorter total sleep duration (SMD = −0.37, CI: −0.59, −0.16), and greater wake after sleep onset time (SMD = 0.60, CI: 0.33, 0.87). Although sleep architecture was similar between the groups, a trend suggested that TBI patients may spend less time in REM sleep (SMD = −0.22, CI: −0.45, 0.01). Consistent with polysomnographic derangement, TBI patients reported greater subjective sleepiness and poorer perceived sleep quality. Conclusions: The evidence suggests that TBI is associated with widespread objective and subjective sleep deficits. The present results highlight the need for physicians to monitor and address sleep deficits following TBI. Citation: Grima N, Ponsford J, Rajaratnam SM, Mansfield D, Pase MP. Sleep disturbances in traumatic brain injury: a meta-analysis. J Clin Sleep Med 2016;12(3):419–428. PMID:26564384

  15. Diffusion tensor imaging and magnetic resonance spectroscopy in traumatic brain injury: a review of recent literature.

    PubMed

    Xiong, Kun-lin; Zhu, Yong-shan; Zhang, Wei-guo

    2014-12-01

    Concussion is the most common form of traumatic brain injury (TBI), but diagnosis remains controversial because the brain appears quite normal in conventional computed tomography and magnetic resonance imaging (MRI). These conventional tools are not sensitive enough to detect diffuse traumatic axonal injury, and cannot depict aberrations in mild TBIs. Advanced MRI modalities including diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS), make it possible to detect brain injuries in TBI. The purpose of this review is to provide the latest information regarding the visualization and quantification of important abnormalities in TBI and new insights into their clinical significance. Advanced imaging modalities allow the discovery of biomarkers of injury and the detection of changes in brain injury over time. Such tools will likely be used to evaluate treatment efficacy in research. Combining multiple imaging modalities would not only provide greater insight into the underlying physiological changes in TBI, but also improve diagnostic accuracy in predicting outcomes. In this review we present evidence of brain abnormalities in TBI based on investigations using MRI, including DTI and MRS. Our review provides a summary of some of the important studies published from 2002 to 2012 on the topic of MRI findings in head trauma. With the growing realization that even mild head injury can lead to neurocognitive deficits, medical imaging has assumed preeminence for detecting abnormalities associated with TBI. Advanced MRI modalities such as DTI and MRS have an important role in the diagnosis of lesions for TBI patients.

  16. Severe Traumatic Brain Injury

    MedlinePlus

    ... to Congress: Epidemiology and Rehabilitation Report to Congress: Military Personnel TBI in the US: Emergency Department Visits, Hospitalizations ... a leading cause of TBI for active duty military personnel in war zones. 15 CDC estimates of TBI ...

  17. Genetic predictors of outcome following traumatic brain injury.

    PubMed

    Lipsky, Robert H; Lin, Mingkuan

    2015-01-01

    The nature of traumatic brain injury (TBI) has acute and chronic outcomes for those who survive. Over time, the chronic process of injury impacts multiple organ systems that may lead to disease. We discuss possible mechanisms and methodological issues in the context of candidate gene association studies using TBI patient populations. Because study population sizes have been generally limited, we discussed results on genes that have been the focus of independent studies. We also present a justification for testing more speculative candidate genes in recovery from TBI, such as those involved in circadian rhythm, to outline the importance of prioritizing functional variants in genes that may modulate recovery or provide neuroprotection from TBI. Finally, we provide a perspective on how future research will integrate population level genetic findings with the biological basis of disease in order to create a resource of predictive outcome measures for individual patients.

  18. Recovery of educational skills following paediatric traumatic brain injury.

    PubMed

    Catroppa, C; Anderson, V

    1999-01-01

    Academic success in the classroom is often dependent upon a child's ability in the areas of literacy, such as reading and spelling, and arithmetic. Following traumatic brain injury these skills are often compromised. The present study examined the recovery of educational skills (reading accuracy, reading comprehension, spelling and arithmetic) over 24 months post-injury, in a group of children who had sustained a mild, moderate or severe TBI. Results showed that the severe TBI group exhibited greater deficits on reading comprehension and arithmetic, while the moderate and severe TBI groups performed similarly in the areas of reading accuracy and spelling. Future research is required to further investigate predictors of educational outcome post-TBI. PMID:10819429

  19. Clinimetric measurement in traumatic brain injuries.

    PubMed

    Opara, J A; Małecka, E; Szczygiel, J

    2014-06-15

    Traumatic brain injury is a leading cause of death and disability worldwide. Every year, about 1.5 million affected people die and several millions receive emergency treatment. Most of the burden (90%) is in low and middle-income countries. The costs of care depend on the level of disability. The burden of care after traumatic brain injury is caused by disability as well as by psychosocial and emotional sequelae of injury. The final consequence of brain injury is the reduction of quality of life. It is very difficult to predict the outcome after traumatic brain injury. The basic clinical model included four predictors: age, score in Glasgow coma scale, pupil reactivity, and the presence of major extracranial injury. These are the neuroradiological markers of recovery after TBI (CT, MRI and PET) and biomarkers: genetic markers of ApoE Gene, ectoenzyme CD 38 (cluster of differentiation 38), serum S100B, myelin basic protein (MBP), neuron specific endolase (NSE), and glial fibrillary acidic protein (GPAP). These are many clinimetric scales which are helpful in prognosing after head injury. In this review paper, the most commonly used scales evaluating the level of consciousness after traumatic brain injury have been presented.

  20. The profile of head injuries and traumatic brain injury deaths in Kashmir.

    PubMed

    Yattoo, Gh; Tabish, Amin

    2008-06-21

    This study was conducted on patients of head injury admitted through Accident & Emergency Department of Sher-i-Kashmir Institute of Medical Sciences during the year 2004 to determine the number of head injury patients, nature of head injuries, condition at presentation, treatment given in hospital and the outcome of intervention. Traumatic brain injury (TBI) deaths were also studied retrospectively for a period of eight years (1996 to 2003).The traumatic brain injury deaths showed a steady increase in number from year 1996 to 2003 except for 1999 that showed decline in TBI deaths. TBI deaths were highest in age group of 21-30 years (18.8%), followed by 11-20 years age group (17.8%) and 31-40 years (14.3%). The TBI death was more common in males. Maximum number of traumatic brain injury deaths was from rural areas as compared to urban areas.To minimize the morbidity and mortality resulting from head injury there is a need for better maintenance of roads, improvement of road visibility and lighting, proper mechanical maintenance of automobile and other vehicles, rigid enforcement of traffic rules, compulsory wearing of crash helmets by motor cyclist and scooterists and shoulder belt in cars and imparting compulsory road safety education to school children from primary education level. Moreover, appropriate medical care facilities (including trauma centres) need to be established at district level, sub-divisional and block levels to provide prompt and quality care to head injury patients.

  1. The profile of head injuries and traumatic brain injury deaths in Kashmir

    PubMed Central

    Yattoo, GH; Tabish, Amin

    2008-01-01

    This study was conducted on patients of head injury admitted through Accident & Emergency Department of Sher-i-Kashmir Institute of Medical Sciences during the year 2004 to determine the number of head injury patients, nature of head injuries, condition at presentation, treatment given in hospital and the outcome of intervention. Traumatic brain injury (TBI) deaths were also studied retrospectively for a period of eight years (1996 to 2003). The traumatic brain injury deaths showed a steady increase in number from year 1996 to 2003 except for 1999 that showed decline in TBI deaths. TBI deaths were highest in age group of 21–30 years (18.8%), followed by 11–20 years age group (17.8%) and 31–40 years (14.3%). The TBI death was more common in males. Maximum number of traumatic brain injury deaths was from rural areas as compared to urban areas. To minimize the morbidity and mortality resulting from head injury there is a need for better maintenance of roads, improvement of road visibility and lighting, proper mechanical maintenance of automobile and other vehicles, rigid enforcement of traffic rules, compulsory wearing of crash helmets by motor cyclist and scooterists and shoulder belt in cars and imparting compulsory road safety education to school children from primary education level. Moreover, appropriate medical care facilities (including trauma centres) need to be established at district level, sub-divisional and block levels to provide prompt and quality care to head injury patients PMID:18570674

  2. Experimental traumatic brain injury alters ethanol consumption and sensitivity.

    PubMed

    Lowing, Jennifer L; Susick, Laura L; Caruso, James P; Provenzano, Anthony M; Raghupathi, Ramesh; Conti, Alana C

    2014-10-15

    Altered alcohol consumption patterns after traumatic brain injury (TBI) can lead to significant impairments in TBI recovery. Few preclinical models have been used to examine alcohol use across distinct phases of the post-injury period, leaving mechanistic questions unanswered. To address this, the aim of this study was to describe the histological and behavioral outcomes of a noncontusive closed-head TBI in the mouse, after which sensitivity to and consumption of alcohol were quantified, in addition to dopaminergic signaling markers. We hypothesized that TBI would alter alcohol consumption patterns and related signal transduction pathways that were congruent to clinical observations. After midline impact to the skull, latency to right after injury, motor deficits, traumatic axonal injury, and reactive astrogliosis were evaluated in C57BL/6J mice. Amyloid precursor protein (APP) accumulation was observed in white matter tracts at 6, 24, and 72 h post-TBI. Increased intensity of glial fibrillary acidic protein (GFAP) immunoreactivity was observed by 24 h, primarily under the impact site and in the nucleus accumbens, a striatal subregion, as early as 72 h, persisting to 7 days, after TBI. At 14 days post-TBI, when mice were tested for ethanol sensitivity after acute high-dose ethanol (4 g/kg, intraperitoneally), brain-injured mice exhibited increased sedation time compared with uninjured mice, which was accompanied by deficits in striatal dopamine- and cAMP-regulated neuronal phosphoprotein, 32 kDa (DARPP-32) phosphorylation. At 17 days post-TBI, ethanol intake was assessed using the Drinking-in-the-Dark paradigm. Intake across 7 days of consumption was significantly reduced in TBI mice compared with sham controls, paralleling the reduction in alcohol consumption observed clinically in the initial post-injury period. These data demonstrate that TBI increases sensitivity to ethanol-induced sedation and affects downstream signaling mediators of striatal

  3. Normobaric oxygen worsens outcome after a moderate traumatic brain injury.

    PubMed

    Talley Watts, Lora; Long, Justin Alexander; Manga, Venkata Hemanth; Huang, Shiliang; Shen, Qiang; Duong, Timothy Q

    2015-07-01

    Traumatic brain injury (TBI) is a multifaceted injury and a leading cause of death in children, young adults, and increasingly in Veterans. However, there are no neuroprotective agents clinically available to counteract damage or promote repair after brain trauma. This study investigated the neuroprotective effects of normobaric oxygen (NBO) after a controlled cortical impact in rats. The central hypothesis was that NBO treatment would reduce lesion volume and functional deficits compared with air-treated animals after TBI by increasing brain oxygenation thereby minimizing ischemic injury. In a randomized double-blinded design, animals received either NBO (n = 8) or normal air (n = 8) after TBI. Magnetic resonance imaging (MRI) was performed 0 to 3 hours, and 1, 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. Behavioral assessments were performed before injury induction and before MRI scans on days 2, 7, and 14. Nissl staining was performed on day 14 to corroborate the lesion volume detected from MRI. Contrary to our hypothesis, we found that NBO treatment increased lesion volume in a rat model of moderate TBI and had no positive effect on behavioral measures. Our results do not promote the acute use of NBO in patients with moderate TBI. PMID:25690469

  4. Normobaric oxygen worsens outcome after a moderate traumatic brain injury.

    PubMed

    Talley Watts, Lora; Long, Justin Alexander; Manga, Venkata Hemanth; Huang, Shiliang; Shen, Qiang; Duong, Timothy Q

    2015-07-01

    Traumatic brain injury (TBI) is a multifaceted injury and a leading cause of death in children, young adults, and increasingly in Veterans. However, there are no neuroprotective agents clinically available to counteract damage or promote repair after brain trauma. This study investigated the neuroprotective effects of normobaric oxygen (NBO) after a controlled cortical impact in rats. The central hypothesis was that NBO treatment would reduce lesion volume and functional deficits compared with air-treated animals after TBI by increasing brain oxygenation thereby minimizing ischemic injury. In a randomized double-blinded design, animals received either NBO (n = 8) or normal air (n = 8) after TBI. Magnetic resonance imaging (MRI) was performed 0 to 3 hours, and 1, 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. Behavioral assessments were performed before injury induction and before MRI scans on days 2, 7, and 14. Nissl staining was performed on day 14 to corroborate the lesion volume detected from MRI. Contrary to our hypothesis, we found that NBO treatment increased lesion volume in a rat model of moderate TBI and had no positive effect on behavioral measures. Our results do not promote the acute use of NBO in patients with moderate TBI.

  5. Normobaric oxygen worsens outcome after a moderate traumatic brain injury

    PubMed Central

    Talley Watts, Lora; Long, Justin Alexander; Manga, Venkata Hemanth; Huang, Shiliang; Shen, Qiang; Duong, Timothy Q

    2015-01-01

    Traumatic brain injury (TBI) is a multifaceted injury and a leading cause of death in children, young adults, and increasingly in Veterans. However, there are no neuroprotective agents clinically available to counteract damage or promote repair after brain trauma. This study investigated the neuroprotective effects of normobaric oxygen (NBO) after a controlled cortical impact in rats. The central hypothesis was that NBO treatment would reduce lesion volume and functional deficits compared with air-treated animals after TBI by increasing brain oxygenation thereby minimizing ischemic injury. In a randomized double-blinded design, animals received either NBO (n=8) or normal air (n=8) after TBI. Magnetic resonance imaging (MRI) was performed 0 to 3 hours, and 1, 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. Behavioral assessments were performed before injury induction and before MRI scans on days 2, 7, and 14. Nissl staining was performed on day 14 to corroborate the lesion volume detected from MRI. Contrary to our hypothesis, we found that NBO treatment increased lesion volume in a rat model of moderate TBI and had no positive effect on behavioral measures. Our results do not promote the acute use of NBO in patients with moderate TBI. PMID:25690469

  6. Midline (Central) Fluid Percussion Model of Traumatic Brain Injury.

    PubMed

    Rowe, Rachel K; Griffiths, Daniel R; Lifshitz, Jonathan

    2016-01-01

    Research models of traumatic brain injury (TBI) hold significant validity towards the human condition, with each model replicating a subset of clinical features and symptoms. After 30 years of characterization and implementation, fluid percussion injury (FPI) is firmly recognized as a clinically relevant model of TBI, encompassing concussion through severe injury. The midline variation of FPI may best represent mild and diffuse clinical brain injury, because of the acute behavioral deficits, the late onset of subtle behavioral morbidities, and the absence of gross histopathology. This chapter outlines the procedures for midline (diffuse) FPI in adult male rats and mice. With these procedures, it becomes possible to generate brain-injured laboratory animals for studies of injury-induced pathophysiology and behavioral deficits, for which rational therapeutic interventions can be implemented. PMID:27604721

  7. Pathophysiological links between traumatic brain injury and post-traumatic headaches.

    PubMed

    Ruff, Robert L; Blake, Kayla

    2016-01-01

    This article reviews possible ways that traumatic brain injury (TBI) can induce migraine-type post-traumatic headaches (PTHs) in children, adults, civilians, and military personnel. Several cerebral alterations resulting from TBI can foster the development of PTH, including neuroinflammation that can activate neural systems associated with migraine. TBI can also compromise the intrinsic pain modulation system and this would increase the level of perceived pain associated with PTH. Depression and anxiety disorders, especially post-traumatic stress disorder (PTSD), are associated with TBI and these psychological conditions can directly intensify PTH. Additionally, depression and PTSD alter sleep and this will increase headache severity and foster the genesis of PTH. This article also reviews the anatomic loci of injury associated with TBI and notes the overlap between areas of injury associated with TBI and PTSD. PMID:27635228

  8. Pathophysiological links between traumatic brain injury and post-traumatic headaches

    PubMed Central

    Ruff, Robert L.; Blake, Kayla

    2016-01-01

    This article reviews possible ways that traumatic brain injury (TBI) can induce migraine-type post-traumatic headaches (PTHs) in children, adults, civilians, and military personnel. Several cerebral alterations resulting from TBI can foster the development of PTH, including neuroinflammation that can activate neural systems associated with migraine. TBI can also compromise the intrinsic pain modulation system and this would increase the level of perceived pain associated with PTH. Depression and anxiety disorders, especially post-traumatic stress disorder (PTSD), are associated with TBI and these psychological conditions can directly intensify PTH. Additionally, depression and PTSD alter sleep and this will increase headache severity and foster the genesis of PTH. This article also reviews the anatomic loci of injury associated with TBI and notes the overlap between areas of injury associated with TBI and PTSD. PMID:27635228

  9. Pathophysiological links between traumatic brain injury and post-traumatic headaches

    PubMed Central

    Ruff, Robert L.; Blake, Kayla

    2016-01-01

    This article reviews possible ways that traumatic brain injury (TBI) can induce migraine-type post-traumatic headaches (PTHs) in children, adults, civilians, and military personnel. Several cerebral alterations resulting from TBI can foster the development of PTH, including neuroinflammation that can activate neural systems associated with migraine. TBI can also compromise the intrinsic pain modulation system and this would increase the level of perceived pain associated with PTH. Depression and anxiety disorders, especially post-traumatic stress disorder (PTSD), are associated with TBI and these psychological conditions can directly intensify PTH. Additionally, depression and PTSD alter sleep and this will increase headache severity and foster the genesis of PTH. This article also reviews the anatomic loci of injury associated with TBI and notes the overlap between areas of injury associated with TBI and PTSD.

  10. Pathophysiological links between traumatic brain injury and post-traumatic headaches.

    PubMed

    Ruff, Robert L; Blake, Kayla

    2016-01-01

    This article reviews possible ways that traumatic brain injury (TBI) can induce migraine-type post-traumatic headaches (PTHs) in children, adults, civilians, and military personnel. Several cerebral alterations resulting from TBI can foster the development of PTH, including neuroinflammation that can activate neural systems associated with migraine. TBI can also compromise the intrinsic pain modulation system and this would increase the level of perceived pain associated with PTH. Depression and anxiety disorders, especially post-traumatic stress disorder (PTSD), are associated with TBI and these psychological conditions can directly intensify PTH. Additionally, depression and PTSD alter sleep and this will increase headache severity and foster the genesis of PTH. This article also reviews the anatomic loci of injury associated with TBI and notes the overlap between areas of injury associated with TBI and PTSD.

  11. The role of free radicals in traumatic brain injury.

    PubMed

    O'Connell, Karen M; Littleton-Kearney, Marguerite T

    2013-07-01

    Traumatic brain injury (TBI) is a significant cause of death and disability in both the civilian and the military populations. The primary impact causes initial tissue damage, which initiates biochemical cascades, known as secondary injury, that expand the damage. Free radicals are implicated as major contributors to the secondary injury. Our review of recent rodent and human research reveals the prominent role of the free radicals superoxide anion, nitric oxide, and peroxynitrite in secondary brain injury. Much of our current knowledge is based on rodent studies, and the authors identified a gap in the translation of findings from rodent to human TBI. Rodent models are an effective method for elucidating specific mechanisms of free radical-induced injury at the cellular level in a well-controlled environment. However, human TBI does not occur in a vacuum, and variables controlled in the laboratory may affect the injury progression. Additionally, multiple experimental TBI models are accepted in rodent research, and no one model fully reproduces the heterogeneous injury seen in humans. Free radical levels are measured indirectly in human studies based on assumptions from the findings from rodent studies that use direct free radical measurements. Further study in humans should be directed toward large samples to validate the findings in rodent studies. Data obtained from these studies may lead to more targeted treatment to interrupt the secondary injury cascades.

  12. Gallic acid improved behavior, brain electrophysiology, and inflammation in a rat model of traumatic brain injury.

    PubMed

    Sarkaki, Alireza; Farbood, Yaghoub; Gharib-Naseri, Mohammad Kazem; Badavi, Mohammad; Mansouri, Mohammad Taghi; Haghparast, Abbas; Mirshekar, Mohammad Ali

    2015-08-01

    Traumatic brain injury (TBI) is one of the main causes of intellectual and cognitive disabilities. In the clinic it is essential to limit the development of cognitive impairment after TBI. In this study, the effects of gallic acid (GA; 100 mg/kg, per oral, from 7 days before to 2 days after TBI induction) on neurological score, passive avoidance memory, long-term potentiation (LTP) deficits, and levels of proinflammatory cytokines including interleukin-1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) in the brain have been evaluated. Brain injury was induced following Marmarou's method. Data were analyzed by one-way and repeated measures ANOVA followed by Tukey's post-hoc test. The results indicated that memory was significantly impaired (p < 0.001) in the group treated with TBI + vehicle, together with deterioration of the hippocampal LTP and increased brain tissue levels of IL-1β, IL-6, and TNF-α. GA treatment significantly improved memory and LTP in the TBI rats. The brain tissue levels of IL-1β, IL-6, and TNF-α were significantly reduced (p < 0.001) in the group treated with GA. The results suggest that GA has neuroprotective properties against TBI-induced behavioral, electrophysiological, and inflammatory disorders, probably via the decrease of cerebral proinflammatory cytokines.

  13. Ethyl Pyruvate Protects against Blood-Brain Barrier Damage and Improves Long-Term Neurological Outcomes in a Rat Model of Traumatic Brain Injury

    PubMed Central

    Shi, Hong; Wang, Hailian; Pu, Hongjian; Shi, Yejie; Zhang, Jia; Zhang, Wenting; Wang, Guohua; Hu, Xiaoming; Leak, Rehana K.; Chen, Jun; Gao, Yanqin

    2015-01-01

    Aims Many traumatic brain injury (TBI) survivors sustain neurological disability and cognitive impairments due to the lack of defined therapies to reduce TBI-induced long-term brain damage. Ethyl pyruvate (EP) has shown neuroprotection in several models of acute brain injury. The present study therefore investigated the potential beneficial effect of EP on long-term outcomes after TBI and the underlying mechanisms. Methods Male adult rats were subjected to unilateral controlled cortical impact injury. EP was injected intraperitoneally 15 min after TBI and again at 12, 24, 36, 48, and 60 h after TBI. Neurological deficits, blood-brain barrier (BBB) integrity and neuroinflammation were assessed. Results EP improved sensorimotor and cognitive functions and ameliorated brain tissue damage up to 28 d post-TBI. BBB breach and brain edema were attenuated by EP at 48 h after TBI. EP suppressed matrix metalloproteinase (MMP)-9 production from peripheral neutrophils and reduced the number of MMP-9-overproducing neutrophils in the spleen, and therefore mitigated MMP-9-mediated BBB breakdown. Moreover, EP exerted potent anti-inflammatory effects in cultured microglia and inhibited the elevation of inflammatory mediators in the brain after TBI. Conclusion EP confers long-term neuroprotection against TBI, possibly through breaking the vicious cycle among MMP-9-mediated BBB disruption, neuroinflammation and long-lasting brain damage. PMID:25533312

  14. A New Rabbit Model of Pediatric Traumatic Brain Injury

    PubMed Central

    Zhang, Zhi; Saraswati, Manda; Koehler, Raymond C.; Robertson, Courtney

    2015-01-01

    Abstract Traumatic brain injury (TBI) is a common cause of disability in childhood, resulting in numerous physical, behavioral, and cognitive sequelae, which can influence development through the lifespan. The mechanisms by which TBI influences normal development and maturation remain largely unknown. Pediatric rodent models of TBI often do not demonstrate the spectrum of motor and cognitive deficits seen in patients. To address this problem, we developed a New Zealand white rabbit model of pediatric TBI that better mimics the neurological injury seen after TBI in children. On postnatal Day 5-7 (P5-7), rabbits were injured by a controlled cortical impact (6-mm impactor tip; 5.5 m/sec, 2-mm depth, 50-msec duration). Rabbits from the same litter served as naïve (no injury) and sham (craniotomy alone) controls. Functional abilities and activity levels were measured 1 and 5 d after injury. Maturation level was monitored daily. We performed cognitive tests during P14-24 and sacrificed the animals at 1, 3, 7, and 21 d after injury to evaluate lesion volume and microglia. TBI kits exhibited delayed achievement of normal developmental milestones. They also demonstrated significant cognitive deficits, with lower percentage of correct alternation rate in the T-maze (n=9-15/group; p<0.001) and less discrimination between novel and old objects (p<0.001). Lesion volume increased from 16% at Day 3 to 30% at Day 7 after injury, indicating ongoing secondary injury. Activated microglia were noted at the injury site and also in white matter regions of the ipsilateral and contralateral hemispheres. The neurologic and histologic changes in this model are comparable to those reported clinically. Thus, this rabbit model provides a novel platform for evaluating neuroprotective therapies in pediatric TBI. PMID:25758339

  15. Electroencephalographic inverse localization of brain activity in acute traumatic brain injury as a guide to surgery, monitoring and treatment

    PubMed Central

    Irimia, Andrei; Goh, S.-Y. Matthew; Torgerson, Carinna M.; Stein, Nathan R.; Chambers, Micah C.; Vespa, Paul M.; Van Horn, John D.

    2013-01-01

    Objective To inverse-localize epileptiform cortical electrical activity recorded from severe traumatic brain injury (TBI) patients using electroencephalography (EEG). Methods Three acute TBI cases were imaged using computed tomography (CT) and multimodal magnetic resonance imaging (MRI). Semi-automatic segmentation was performed to partition the complete TBI head into 25 distinct tissue types, including 6 tissue types accounting for pathology. Segmentations were employed to generate a finite element method model of the head, and EEG activity generators were modeled as dipolar currents distributed over the cortical surface. Results We demonstrate anatomically faithful localization of EEG generators responsible for epileptiform discharges in severe TBI. By accounting for injury-related tissue conductivity changes, our work offers the most realistic implementation currently available for the inverse estimation of cortical activity in TBI. Conclusion Whereas standard localization techniques are available for electrical activity mapping in uninjured brains, they are rarely applied to acute TBI. Modern models of TBI-induced pathology can inform the localization of epileptogenic foci, improve surgical efficacy, contribute to the improvement of critical care monitoring and provide guidance for patient-tailored treatment. With approaches such as this, neurosurgeons and neurologists can study brain activity in acute TBI and obtain insights regarding injury effects upon brain metabolism and clinical outcome. PMID:24011495

  16. Head motions while riding roller coasters: implications for brain injury.

    PubMed

    Pfister, Bryan J; Chickola, Larry; Smith, Douglas H

    2009-12-01

    The risk of traumatic brain injury (TBI) while riding roller coasters has received substantial attention. Case reports of TBI around the time of riding roller coasters have led many medical professionals to assert that the high gravitational forces (G-forces) induced by roller coasters pose a significant TBI risk. Head injury research, however, has shown that G-forces alone cannot predict TBI. Established head injury criterions and procedures were employed to compare the potential of TBI between daily activities and roller coaster riding. Three-dimensional head motions were measured during 3 different roller coaster rides, a pillow fight, and car crash simulations. Data was analyzed and compared with published data, using similar analyses of head motions. An 8.05 m/s car crash lead to the largest head injury criterion measure of 28.1 and head impact power of 3.41, over 6 times larger than the roller coaster rides of 4.1 and 0.36. Notably, the linear and rotational components of head acceleration during roller coaster rides were milder than those induced by many common activities. As such, there appears to be an extremely low risk of TBI due to the head motions induced by roller coaster rides. PMID:19901817

  17. Head motions while riding roller coasters: Implications for brain injury

    PubMed Central

    Chickola, Larry; Smith, Douglas H.

    2009-01-01

    The risk of traumatic brain injury (TBI) while riding roller coasters has received substantial attention. Case reports of TBI around the time of riding roller coasters have led many medical professionals to assert that the high gravitational forces (G-forces) induced by roller coasters pose a significant TBI risk. Head injury research, however, has shown that G-forces alone cannot predict TBI. Established head injury criterions and procedures were employed to compare the potential of TBI between daily activities and roller coaster riding. Three dimensional head motions were measured during three different roller coaster rides, a pillow fight, and car crash simulations. Data was analyzed and compared to published data using similar analyses of head motions. An 8.05m/s car crash lead to the largest head injury criterion measure (HIC15) of 28.1 and head impact factor (HIP) of 3.41, over six times larger than the roller coaster rides of 4.1 and 0.36. Notably, the linear and rotational components of head acceleration during roller coaster rides were milder than those induced by many common activities. As such, there appears to be an extremely low risk of TBI due to the head motions induced by roller coaster rides. PMID:19901817

  18. TBI-the most complex disease in the most complex organ: the CENTER-TBI trial-a commentary.

    PubMed

    Wheble, Joanna L C; Menon, D K

    2016-04-01

    Each year, approximately 2.5 million people experience some form of traumatic brain injury (TBI) in Europe. One million of these are admitted to hospital and 75 000 will die. TBI represents a major cause of death and disability, particularly among those of working age. Substantial investments have been made in an effort to improve diagnosis, management and survival in TBI, but with little success. The Collaborative European Neuro-Trauma Effectiveness Research in TBI (CENTER-TBI) study promises to use the natural variability seen in the management of TBI across Europe with the application of Comparative Effectiveness Research (CER). It will generate repositories of baseline and comprehensive TBI patient data, neuroimaging, neurogenetics and biomarkers, which aim to improve the diagnosis, stratification, management and prognostication of patients with TBI.

  19. Epidemiological shifts in elderly traumatic brain injury: 18-year trends in Pennsylvania.

    PubMed

    Ramanathan, Deepa M; McWilliams, Nathan; Schatz, Philip; Hillary, Frank G

    2012-05-01

    Older adults tend to have poorer outcomes compared to younger adults following moderate-to-severe traumatic brain injury (TBI). Currently, there is a need for research focusing on how elderly TBI has changed as the U.S. population shifts. This study provides a statewide account of moderate-to-severe TBI in regard to injury-related variables and incidence rates in the elderly. Data from Pennsylvania accredited trauma centers collected in the Pennsylvania Trauma Outcome Study between 1992 and 2009 were used in the current study. Incidence rates for TBI were calculated using U.S. Census Bureau estimates for individuals aged 65-90 years (separated into three subgroups: ages 65-73, 74-82, and 83-90 years). In addition, we focused on describing the following injury-related variables: mechanism of injury, injury severity, hospital length of stay, and functional status at discharge. The results indicate that the incidence of elderly TBI has approximately doubled in the past 18 years, and that the increase in elderly TBI is greatest for individuals between the ages of 83 and 90. Furthermore, this age group had the poorest outcomes following TBI. Prevention and awareness of TBI in the elderly is imperative in reducing the likelihood of injury and disability. Continued statewide work is needed to demonstrate trends in elderly TBI nationwide to further add to the knowledge base used for prevention and rehabilitation work.

  20. WAIS Digit Span-Based Indicators of Malingered Neurocognitive Dysfunction: Classification Accuracy in Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Heinly, Matthew T.; Greve, Kevin W.; Bianchini, Kevin J.; Love, Jeffrey M.; Brennan, Adrianne

    2005-01-01

    The present study determined specificity and sensitivity to malingered neurocognitive dysfunction (MND) in traumatic brain injury (TBI) for several Wechsler Adult Intelligence Scale (WAIS) Digit Span scores. TBI patients (n = 344) were categorized into one of five groups: no incentive, incentive only, suspect, probable MND, and definite MND.…

  1. Physicians' Initial Forensic Impressions of Hypothetical Cases of Pediatric Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Laskey, Antoinette L.; Sheridan, Michael J.; Hymel, Kent P.

    2007-01-01

    Objective: To describe physicians' initial forensic impressions of hypothetical cases of pediatric traumatic brain injury (TBI) and to compare the responses of pathologists and pediatricians. Method: A survey was administered to physicians who attended workshops on pediatric TBI; were members of two national internet list serves; and were members…

  2. Services and Supports for Students with Traumatic Brain Injury: Survey of State Educational Agencies

    ERIC Educational Resources Information Center

    Glang, Ann; Ettel, Deborah; Todis, Bonnie; Gordon, Wayne A.; Oswald, Jennifer M.; Vaughn, Susan L.; Connors, Susan H.; Brown, Margaret

    2015-01-01

    Long-term follow-up studies conducted during the K-12 school years suggest that challenges related to childhood traumatic brain injury (TBI) tend to persist or worsen over time. A 1999 survey of State Directors of Special Education revealed that most states had emerging initiatives for children with TBI and were expanding their capacity to serve…

  3. Assessing Children with Traumatic Brain Injury during Rehabilitation: Promoting School and Community Reentry.

    ERIC Educational Resources Information Center

    Farmer, Janet E.; And Others

    1996-01-01

    Evaluating children with traumatic brain injury (TBI) in order to facilitate their transition to school is reviewed. A process-oriented approach to assessing TBI children during rehabilitation is suggested. The major areas of functioning important to school reentry are discussed. The need for families and professionals to communicate about the…

  4. Mirror Asymmetry of Category and Letter Fluency in Traumatic Brain Injury and Alzheimer's Patients

    ERIC Educational Resources Information Center

    Capitani, Erminio; Rosci, Chiara; Saetti, Maria Cristina; Laiacona, Marcella

    2009-01-01

    In this study we contrasted the Category fluency and Letter fluency performance of 198 normal subjects, 57 Alzheimer's patients and 57 patients affected by traumatic brain injury (TBI). The aim was to check whether, besides the prevalence of Category fluency deficit often reported among Alzheimer's patients, the TBI group presented the opposite…

  5. An Online Family Intervention to Reduce Parental Distress Following Pediatric Brain Injury

    ERIC Educational Resources Information Center

    Wade, Shari L.; Carey, Joanne; Wolfe, Christopher R.

    2006-01-01

    This study examined whether an online problem-solving intervention could improve parental adjustment following pediatric traumatic brain injury (TBI). Families of children with moderate-to-severe TBI were recruited from the trauma registry of a large children's hospital and randomly assigned to receive online family problem solving therapy (FPS; n…

  6. Predictors of Attention-Deficit/Hyperactivity Disorder within 6 Months after Pediatric Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Max, Jeffrey E.; Schachar, Russell J.; Levin, Harvey S.; Ewing-Cobbs, Linda; Chapman, Sandra B.; Dennis, Maureen; Saunders, Ann; Landis, Julie

    2005-01-01

    Objective: To assess the phenomenology and predictive factors of attention-deficit/hyperactivity disorder (ADHD) after traumatic brain injury (TBI), also called secondary ADHD (SADHD). Method: Children without preinjury ADHD 5-14 years old with TBI from consecutive admissions (n = 143) to five trauma centers were observed prospectively for 6…

  7. Preschool Traumatic Brain Injury: A Review for the Early Childhood Special Educator

    ERIC Educational Resources Information Center

    Wetherington, Crista E.; Hooper, Stephen R.

    2006-01-01

    This article reviews an emergent area of traumatic brain injury (TBI) literature; namely, developmental outcomes of TBI sustained during the early childhood and preschool period. The developmental time period from birth through age 5 years is one of significant growth and maturity, particularly in the neurological development of the child. An…

  8. Academic and Language Outcomes in Children after Traumatic Brain Injury: A Meta-Analysis

    ERIC Educational Resources Information Center

    Vu, Jennifer A.; Babikian, Talin; Asarnow, Robert F .

    2011-01-01

    Expanding on Babikian and Asarnow's (2009) meta-analytic study examining neurocognitive domains, this current meta-analysis examined academic and language outcomes at different time points post-traumatic brain injury (TBI) in children and adolescents. Although children with mild TBI exhibited no significant deficits, studies indicate that children…

  9. Traumatic Brain Injury in K-12 Students: Where Have All the Children Gone?

    ERIC Educational Resources Information Center

    Schutz, Larry E.; Rivers, Kenyatta O.; McNamara, Elizabeth; Schutz, Judith A.; Lobato, Emilio J.

    2010-01-01

    When children who are permanently disabled by traumatic brain injury (TBI) return to school, most are placed in mainstream classrooms and incorrectly presumed capable of resuming their education. Only one to two percent are classified as students with TBI, qualifying them for the services they need for their education. The failure to properly…

  10. Posttraumatic Stress Disorder, Traumatic Brain Injury, and Suicide Attempt History among Veterans Receiving Mental Health Services

    ERIC Educational Resources Information Center

    Brenner, Lisa A.; Betthauser, Lisa M.; Homaifar, Beeta Y.; Villarreal, Edgar; Harwood, Jeri E. F.; Staves, Pamela J.; Huggins, Joseph A.

    2011-01-01

    History of posttraumatic stress disorder (PTSD) or traumatic brain injury (TBI) has been found to increase risk of suicidal behavior. The association between suicide attempt history among veterans with PTSD and/or TBI was explored. Cases (N = 81) and 2:1 matched controls (N = 160) were randomly selected from a Veterans Affairs Medical Center…

  11. Interpersonal Relatedness and Psychological Functioning Following Traumatic Brain Injury: Implications for Marital and Family Therapists

    ERIC Educational Resources Information Center

    Bay, Esther H.; Blow, Adrian J.; Yan, Xie

    2012-01-01

    Recovery from a mild-to-moderate traumatic brain injury (TBI) is a challenging process for injured persons and their families. Guided by attachment theory, we investigated whether relationship conflict, social support, or sense of belonging were associated with psychological functioning. Community-dwelling persons with TBI (N = 75) and their…

  12. Traumatic Brain Injury and Grief: Considerations and Practical Strategies for School Psychologists

    ERIC Educational Resources Information Center

    Jantz, Paul B.; Comerchero, Victoria A.; Canto, Angela I.; Pierson, Eric

    2015-01-01

    Traumatic brain injury (TBI) can result in a range of social, emotional, neurological, cognitive, and behavioral outcomes. If these outcomes are significant, family members and the individual who has sustained the TBI may struggle with accepting the effects of these deficits. They may grieve over disrupted family relationships, roles, and routines…

  13. Traumatic Brain Injury: The Efficacy of a Half-Day Training for School Psychologists

    ERIC Educational Resources Information Center

    Davies, Susan C.; Ray, Ashlyn M.

    2014-01-01

    The incidence rates of traumatic brain injuries (TBI) are increasing, yet educators continue to be inadequately trained in assessing and serving students with TBIs. This study examined the efficacy of a half-day TBI training program for school psychologists designed to improve their knowledge and skills. Results of quantitative and qualitative…

  14. Response to Intervention: The Functional Assessment of Children Returning to School with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Dykeman, Bruce F.

    2009-01-01

    Children with Traumatic Brain Injury (TBI) face many demands when completing their rehabilitation and returning to school. Although the prognosis can be favorable for many children, the course of recovery poses unique challenges for children and staff alike. To this end, a functional assessment of TBI children within a Response-to-Intervention…

  15. Topic Repetitiveness after Traumatic Brain Injury: An Emergent, Jointly Managed Behaviour

    ERIC Educational Resources Information Center

    Body, Richard; Parker, Mark

    2005-01-01

    Topic repetitiveness is a common component of pragmatic impairment and a powerful contributor to social exclusion. Despite this, description, characterization and intervention remain underdeveloped. This article explores the nature of repetitiveness in traumatic brain injury (TBI). A case study of one individual after TBI provides the basis for a…

  16. The Effects of Traumatic Brain Injury during Adolescence on Career Plans and Outcomes

    ERIC Educational Resources Information Center

    Balaban, Tammy; Hyde, Nellemarie; Colantonio, Angela

    2009-01-01

    Traumatic brain injury (TBI) often occurs during the years when individuals are aiming for vocational goals and acquiring skills needed to achieve vocational success. This exploratory study aimed to describe the perceived long-term impact on career outcomes for individuals who were hospitalized with a TBI during adolescence. This study used a…

  17. Explaining Pragmatic Performance in Traumatic Brain Injury: A Process Perspective on Communicative Errors

    ERIC Educational Resources Information Center

    Bosco, Francesca M.; Angeleri, Romina; Sacco, Katiuscia; Bara, Bruno G.

    2015-01-01

    Background: The purpose of this study is to investigate the pragmatic abilities of individuals with traumatic brain injury (TBI). Several studies in the literature have previously reported communicative deficits in individuals with TBI, however such research has focused principally on communicative deficits in general, without providing an…

  18. Time Perception in Severe Traumatic Brain Injury Patients: A Study Comparing Different Methodologies

    ERIC Educational Resources Information Center

    Mioni, G.; Mattalia, G.; Stablum, F.

    2013-01-01

    In this study, we investigated time perception in patients with traumatic brain injury (TBI). Fifteen TBI patients and 15 matched healthy controls participated in the study. Participants were tested with durations above and below 1s on three different temporal tasks that involved time reproduction, production, and discrimination tasks. Data…

  19. Sisters and Brothers, Brothers and Sisters in the Family Affected by Traumatic Brain Injury.

    ERIC Educational Resources Information Center

    Pieper, Betty

    This report is based on a qualitative research study which utilized a nominal group process to identify major life stressors for parents of children with traumatic brain injuries (TBI). It focuses first on effects of TBI on siblings and then on effective interventions. The first section uses quotes from participating parents to identify their…

  20. Transgenic over-expression of slit2 enhances disruption of blood-brain barrier and increases cell death after traumatic brain injury in mice.

    PubMed

    Li, Shuai; Li, Hang; He, Xiao-Fei; Li, Ge; Zhang, Qun; Liang, Feng-Ying; Jia, Huan-Huan; Li, Jiang-Chao; Huang, Ren; Pei, Zhong; Wang, Li-Jing; Zhang, Yu

    2016-09-19

    Traumatic brain injury (TBI) is the leading cause of mortality and disability among male adolescents and young adults; and mild traumatic brain injury is the most common type of traumatic brain injury. The disruption of blood-brain barrier (BBB) plays an important role in brain trauma. Previously, we have found that slit2, a member of slit protein family, increases permeability of BBB. In the present study, we examined the role of slit2 in the pathogenesis of mild TBI in a mouse model of micro TBI. Rhodamine BandPI (PropidiumIodide) staining were used to detect the permeability of BBB and cell death, respectively. The leakage of Rhodamine B and cell death were significantly increased in Slit2-Tg mice than in C57 control mice after micro TBI. The present results suggest that over expression of slit2 plays a detrimental role in the pathophysiology of mild TBI.

  1. Predicting outcome in traumatic brain injury: Sharing experience of pilot traumatic brain injury registry

    PubMed Central

    Pal, Ranabir; Munivenkatappa, Ashok; Agrawal, Amit; Menon, Geetha R.; Galwankar, Sagar; Mohan, P. Rama; Kumar, S. Satish; Subrahmanyam, B. V.

    2016-01-01

    Background: A reliable prediction of outcome for the victims of traumatic brain injury (TBI) on admission is possible from concurrent data analysis from any systematic real-time registry. Objective: To determine the clinical relevance of the findings from our TBI registry to develop prognostic futuristic models with readily available traditional and novel predictors. Materials and Methods: Prospectively collected data using predesigned pro forma were analyzed from the first phase of a trauma registry from a South Indian Trauma Centre, compatible with computerized management system at electronic data entry and web data entry interface on demographics, clinical, management, and discharge status. Statistical Analysis: On univariate analysis, the variables with P < 0.15 were chosen for binary logistic model. On regression model, variables were selected with test of coefficient 0.001 and with Nagelkerke R2 with alpha error of 5%. Results: From 337 cases, predominantly males from rural areas in their productive age, road traffic injuries accounted for two-thirds cases, one-fourths occurred during postmonsoon while two-wheeler was the most common prerequisite. Fifty percent of patients had moderate to severe brain injury; the most common finding was unconsciousness followed by vomiting, ear bleed, seizures, and traumatic amnesia. Fifteen percent required intracranial surgery. Patients with severe Glasgow coma scale score were 4.5 times likely to have the fatal outcome (P = 0.003). Other important clinical variables accountable for fatal outcomes were oral bleeds and cervical spine injury while imperative socio-demographic risk correlates were age and seasons. Conclusion: TBI registry helped us finding predictors of clinical relevance for the outcomes in victims of TBI in search of prognostic futuristic models in TBI victims. PMID:27722114

  2. Sleep and wake disturbances following traumatic brain injury.

    PubMed

    Duclos, C; Dumont, M; Wiseman-Hakes, C; Arbour, C; Mongrain, V; Gaudreault, P-O; Khoury, S; Lavigne, G; Desautels, A; Gosselin, N

    2014-10-01

    Traumatic brain injury (TBI) is a major health concern in industrialised countries. Sleep and wake disturbances are among the most persistent and disabling sequelae after TBI. Yet, despite the widespread complaints of post-TBI sleep and wake disturbances, studies on their etiology, pathophysiology, and treatments remain inconclusive. This narrative review aims to summarise the current state of knowledge regarding the nature of sleep and wake disturbances following TBI, both subjective and objective, spanning all levels of severity and phases post-injury. A second goal is to outline the various causes of post-TBI sleep-wake disturbances. Globally, although sleep-wake complaints are reported in all studies and across all levels of severity, consensus regarding the objective nature of these disturbances is not unanimous and varies widely across studies. In order to optimise recovery in TBI survivors, further studies are required to shed light on the complexity and heterogeneity of post-TBI sleep and wake disturbances, and to fully grasp the best timing and approach for intervention.

  3. Cardiac reactive oxygen species after traumatic brain injury

    PubMed Central

    Larson, Brett E; Stockwell, David W.; Boas, Stefan; Andrews, Trevor; Wellman, George C.; Lockette, Warren; Freeman, Kalev

    2011-01-01

    Background Cardiovascular complications after traumatic brain injury (TBI) contribute to morbidity and mortality and may provide a target for therapy. We examined blood pressure and left ventricle contractility after TBI, and tested the hypothesis that beta-adrenergic blockade would decrease oxidative stress after TBI. Material and Methods Rodents received fluid-percussion injury or sham surgery, confirmed with magnetic resonance imaging (MRI) and histopathology. We followed recovery with sensorimotor coordination testing and blood pressure measurements. We assessed left ventricular ejection fraction using ECG-gated cardiac MRI and measured myocardial reactive oxygen species (ROS) with dihydroethidium. We randomized additional TBI and sham animals to post-operative treatment with propranolol or control, for measurement of ROS. Results Blood pressure and cardiac contractility were elevated 48 hours after TBI. Myocardial tissue sections showed increased ROS. Treatment with propranolol diminished ROS levels following TBI. Conclusions TBI is associated with increased cardiac contractility and myocardial ROS; decreased myocardial ROS after beta-blockade suggests that sympathetic stimulation is a mechanism of oxidative stress. PMID:22172132

  4. Chaperone-Mediated Autophagy after Traumatic Brain Injury

    PubMed Central

    Park, Yujung; Liu, Chunli; Luo, Tianfei; Dietrich, W. Dalton; Bramlett, Helen

    2015-01-01

    Abstract Chaperone-mediated autophagy (CMA) and the ubiquitin-proteasomal system (UPS) are two major protein degradation systems responsible for maintaining cellular homeostasis, but how these two systems are regulated after traumatic brain injury (TBI) remains unknown. TBI produces primary mechanical damage that must be repaired to maintain neuronal homeostasis. The level of lysosomal-associated membrane protein type 2A (LAMP2A) is the hallmark of CMA activity. The level of polyubiquitinated proteins (ubi-proteins) reflects UPS activity. This study utilized a moderate fluid percussion injury model in rats to investigate the changes in CMA and the UPS after TBI. Induction of CMA was manifested by significant upregulation of LAMP2A and secondary lysosomes during the periods of 1–15 days of recovery after TBI. In comparison, the levels of ubi-proteins were increased only moderately after TBI. The increases in the levels of LAMP2A and 70 kDa heat-shock protein for CMA after TBI were seen mainly in the secondary lysosome-containing fractions. Confocal and electron microscopy further showed that increased LAMP2A or lysosomes were found mainly in neurons and proliferated microglia. Because CMA and the UPS are two major routes for elimination of different types of cellular aberrant proteins, the consecutive activation of these two pathways may serve as a protective mechanism for maintaining cellular homeostasis after TBI. PMID:25891649

  5. Sleep and wake disturbances following traumatic brain injury.

    PubMed

    Duclos, C; Dumont, M; Wiseman-Hakes, C; Arbour, C; Mongrain, V; Gaudreault, P-O; Khoury, S; Lavigne, G; Desautels, A; Gosselin, N

    2014-10-01

    Traumatic brain injury (TBI) is a major health concern in industrialised countries. Sleep and wake disturbances are among the most persistent and disabling sequelae after TBI. Yet, despite the widespread complaints of post-TBI sleep and wake disturbances, studies on their etiology, pathophysiology, and treatments remain inconclusive. This narrative review aims to summarise the current state of knowledge regarding the nature of sleep and wake disturbances following TBI, both subjective and objective, spanning all levels of severity and phases post-injury. A second goal is to outline the various causes of post-TBI sleep-wake disturbances. Globally, although sleep-wake complaints are reported in all studies and across all levels of severity, consensus regarding the objective nature of these disturbances is not unanimous and varies widely across studies. In order to optimise recovery in TBI survivors, further studies are required to shed light on the complexity and heterogeneity of post-TBI sleep and wake disturbances, and to fully grasp the best timing and approach for intervention. PMID:25110283

  6. BDNF Polymorphism Predicts General Intelligence after Penetrating Traumatic Brain Injury

    PubMed Central

    Rostami, Elham; Krueger, Frank; Zoubak, Serguei; Dal Monte, Olga; Raymont, Vanessa; Pardini, Matteo; Hodgkinson, Colin A.; Goldman, David; Risling, Mårten; Grafman, Jordan

    2011-01-01

    Neuronal plasticity is a fundamental factor in cognitive outcome following traumatic brain injury. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays an important role in this process. While there are many ways to measure cognitive outcome, general cognitive intelligence is a strong predictor of everyday decision-making, occupational attainment, social mobility and job performance. Thus it is an excellent measure of cognitive outcome following traumatic brain injury (TBI). Although the importance of the single-nucleotide polymorphisms polymorphism on cognitive function has been previously addressed, its role in recovery of general intelligence following TBI is unknown. We genotyped male Caucasian Vietnam combat veterans with focal penetrating TBI (pTBI) (n = 109) and non-head injured controls (n = 38) for 7 BDNF single-nucleotide polymorphisms. Subjects were administrated the Armed Forces Qualification Test (AFQT) at three different time periods: pre-injury on induction into the military, Phase II (10–15 years post-injury, and Phase III (30–35 years post-injury). Two single-nucleotide polymorphisms, rs7124442 and rs1519480, were significantly associated with post-injury recovery of general cognitive intelligence with the most pronounced effect at the Phase II time point, indicating lesion-induced plasticity. The genotypes accounted for 5% of the variance of the AFQT scores, independently of other significant predictors such as pre-injury intelligence and percentage of brain volume loss. These data indicate that genetic variations in BDNF play a significant role in lesion-induced recovery following pTBI. Identifying the underlying mechanism of this brain-derived neurotrophic factor effect could provide insight into an important aspect of post-traumatic cognitive recovery. PMID:22087305

  7. Traumatic Brain Injury and the Effect on the Brain-Gut Axis.

    PubMed

    Kharrazian, Datis

    2015-08-01

    Traumatic brain injury (TBI) is a leading cause of disability worldwide. One commonly overlooked effect of TBI is the disruption of the brain-gut axis, leading to gastrointestinal dysfunction. The brain-gut axis consists of the cortical areas of the insular cortex, cingulate, and hypothalamus that have bidirectional communication with the visceral enteric nervous system through afferent and efferent projections into the pontine vagal complex and nucleus tractus solitarius. Communication with the brain also occurs through messenger signals from the gut's microbiota, involving gut peptides, cytokines, and lipopolysaccharides. Disruption of the brain-gut axis from TBI can lead to a chronic, inflammatory, vicious sequela, involving both the brain and the gastrointestinal system, with both neuroregulatory and neuroimmunological loops. PMID:26348611

  8. Intelligence after traumatic brain injury: meta-analysis of outcomes and prognosis.

    PubMed

    Königs, M; Engenhorst, P J; Oosterlaan, J

    2016-01-01

    Worldwide, 54-60 million individuals sustain traumatic brain injury (TBI) each year. This meta-analysis aimed to quantify intelligence impairments after TBI and to determine the value of age and injury severity in the prognosis of TBI. An electronic database search identified 81 relevant peer-reviewed articles encompassing 3890 patients. Full-scale IQ (FSIQ), performance IQ (PIQ) and verbal IQ (VIQ) impairments were quantified (Cohen's d) for patients with mild, moderate and severe TBI in the subacute phase of recovery and the chronic phase. Meta-regressions explored prognostic values of age and injury severity measures for intelligence impairments. The results showed that, in the subacute phase, FSIQ impairments were absent for patients with mild TBI, medium-sized for patients with moderate TBI (d = -0.61, P < 0.001) and large for patients with severe TBI (d = -1.09, P < 0.001). In the chronic phase, FSIQ impairments were small for patients with mild or moderate TBI (d = -0.37 and -0.19, P ≤ 0.008) and large for patients with severe TBI (d = -0.80, P < 0.001). Adults with mild TBI had larger PIQ and VIQ impairments in the chronic phase than children (both Q ≥ 5.21, P ≤ 0.02), whilst children with severe TBI had larger FSIQ and VIQ impairments than adults (both Q ≥ 4.40, P ≤ 0.04). Glasgow Coma Scale score, duration of loss of consciousness and post-traumatic amnesia duration moderately to strongly predicted FSIQ, PIQ and VIQ impairments (0.41 ≤ r ≤ 0.82, P ≤ 0.02), but no differences in predictive value were observed. In conclusion, TBI causes persisting intelligence impairments, where children may have better recovery from mild TBI and poorer recovery from severe TBI than adults. Injury severity measures predict intelligence impairments and do not outperform one another. PMID:25919757

  9. Intelligence after traumatic brain injury: meta-analysis of outcomes and prognosis.

    PubMed

    Königs, M; Engenhorst, P J; Oosterlaan, J

    2016-01-01

    Worldwide, 54-60 million individuals sustain traumatic brain injury (TBI) each year. This meta-analysis aimed to quantify intelligence impairments after TBI and to determine the value of age and injury severity in the prognosis of TBI. An electronic database search identified 81 relevant peer-reviewed articles encompassing 3890 patients. Full-scale IQ (FSIQ), performance IQ (PIQ) and verbal IQ (VIQ) impairments were quantified (Cohen's d) for patients with mild, moderate and severe TBI in the subacute phase of recovery and the chronic phase. Meta-regressions explored prognostic values of age and injury severity measures for intelligence impairments. The results showed that, in the subacute phase, FSIQ impairments were absent for patients with mild TBI, medium-sized for patients with moderate TBI (d = -0.61, P < 0.001) and large for patients with severe TBI (d = -1.09, P < 0.001). In the chronic phase, FSIQ impairments were small for patients with mild or moderate TBI (d = -0.37 and -0.19, P ≤ 0.008) and large for patients with severe TBI (d = -0.80, P < 0.001). Adults with mild TBI had larger PIQ and VIQ impairments in the chronic phase than children (both Q ≥ 5.21, P ≤ 0.02), whilst children with severe TBI had larger FSIQ and VIQ impairments than adults (both Q ≥ 4.40, P ≤ 0.04). Glasgow Coma Scale score, duration of loss of consciousness and post-traumatic amnesia duration moderately to strongly predicted FSIQ, PIQ and VIQ impairments (0.41 ≤ r ≤ 0.82, P ≤ 0.02), but no differences in predictive value were observed. In conclusion, TBI causes persisting intelligence impairments, where children may have better recovery from mild TBI and poorer recovery from severe TBI than adults. Injury severity measures predict intelligence impairments and do not outperform one another.

  10. Traumatic brain injury in mice and pentadecapeptide BPC 157 effect.

    PubMed

    Tudor, Mario; Jandric, Ivan; Marovic, Anton; Gjurasin, Miroslav; Perovic, Darko; Radic, Bozo; Blagaic, Alenka Boban; Kolenc, Danijela; Brcic, Luka; Zarkovic, Kamelija; Seiwerth, Sven; Sikiric, Predrag

    2010-02-25

    Gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, an anti-ulcer peptide, efficient in inflammatory bowel disease trials (PL 14736), no toxicity reported, improved muscle crush injury. After an induced traumatic brain injury (TBI) in mice by a falling weight, BPC 157 regimens (10.0microg, 10.0ng/kgi.p.) demonstrated a marked attenuation of damage with an improved early outcome and a minimal postponed mortality throughout a 24h post-injury period. Ultimately, the traumatic lesions (subarachnoidal and intraventricular haemorrhage, brain laceration, haemorrhagic laceration) were less intense and consecutive brain edema had considerably improved. Given prophylactically (30 min before TBI) the improved conscious/unconscious/death ratio in TBI-mice was after force impulses of 0.068 Ns, 0.093 Ns, 0.113 Ns, 0.130 Ns, 0.145 Ns, and 0.159 Ns. Counteraction (with a reduction of unconsciousness, lower mortality) with both microg- and ng-regimens included the force impulses of 0.068-0.145 Ns. A higher regimen presented effectiveness also against the maximal force impulse (0.159 Ns). Furthermore, BPC 157 application immediately prior to injury was beneficial in mice subjected to force impulses of 0.093 Ns-TBI. For a more severe force impulse (0.130 Ns, 0.145 Ns, or 0159 Ns), the time-relation to improve the conscious/unconscious/death ratio was: 5 min (0.130 Ns-TBI), 20 min (0.145 Ns-TBI) or 30 min (0.159 Ns-TBI). PMID:19931318

  11. Rodent Models of Traumatic Brain Injury: Methods and Challenges.

    PubMed

    Marklund, Niklas

    2016-01-01

    Traumatic brain injury (TBI) has been named the most complex disease in the most complex organ of the body. It is the most common cause of death and disability in the Western world in people <40 years old and survivors commonly suffer from persisting cognitive deficits, impaired motor function, depression and personality changes. TBI may vary in severity from uniformly fatal to mild injuries with rapidly resolving symptoms and without doubt, it is a markedly heterogeneous disease. Its different subtypes differs in their pathophysiology, treatment options and long-term consequences and to date, there are no pharmacological treatments with proven clinical benefit available to TBI patients. To enable development of novel treatment options for TBI, clinically relevant animal models are needed. Due to their availability and low costs, numerous rodent models have been developed which have substantially contributed to our current understanding of the pathophysiology of TBI. The most common animal models used in laboratories worldwide are likely the controlled cortical impact (CCI) model, the central and lateral fluid percussion injury (FPI) models, and weight drop/impact acceleration (I/A) models. Each of these models has inherent advantages and disadvantages; these need to be thoroughly considered when selecting the rodent TBI model according to the hypothesis and design of the study. Since TBI is not one disease, refined animal models must take into account the clinical features and complexity of human TBI. To enhance the possibility of establishing preclinical efficacy of a novel treatment, the preclinical use of several different experimental models is encouraged as well as varying the species, gender, and age of the animal. In this chapter, the methods, limitations, and challenges of the CCI and FPI models of TBI used in rodents are described. PMID:27604711

  12. Functional neuroimaging of traumatic brain injury: advances and clinical utility

    PubMed Central

    Irimia, Andrei; Van Horn, John Darrell

    2015-01-01

    Functional deficits due to traumatic brain injury (TBI) can have significant and enduring consequences upon patients’ life quality and expectancy. Although functional neuroimaging is essential for understanding TBI pathophysiology, an insufficient amount of effort has been dedicated to the task of translating functional neuroimaging findings into information with clinical utility. The purpose of this review is to summarize the use of functional neuroimaging techniques – especially functional magnetic resonance imaging, diffusion tensor imaging, positron emission tomography, magnetic resonance spectroscopy, and electroencephalography – for advancing current knowledge of TBI-related brain dysfunction and for improving the rehabilitation of TBI patients. We focus on seven core areas of functional deficits, namely consciousness, motor function, attention, memory, higher cognition, personality, and affect, and, for each of these, we summarize recent findings from neuroimaging studies which have provided substantial insight into brain function changes due to TBI. Recommendations are also provided to aid in setting the direction of future neuroimaging research and for understanding brain function changes after TBI. PMID:26396520

  13. Traumatic Brain Injury as a Risk Factor for Alzheimer's Disease: Is Inflammatory Signaling a Key Player?

    PubMed

    Djordjevic, Jelena; Sabbir, Mohammad Golam; Albensi, Benedict C

    2016-01-01

    Traumatic brain injury (TBI) has become a significant medical and social concern within the last 30 years. TBI has acute devastating effects, and in many cases, seems to initiate long-term neurodegeneration. With advances in medical technology, many people are now surviving severe brain injuries and their long term consequences. Post trauma effects include communication problems, sensory deficits, emotional and behavioral problems, physical complications and pain, increased suicide risk, dementia, and an increased risk for chronic CNS diseases, such as Alzheimer's disease (AD). In this review, we provide an introduction to TBI and hypothesize how it may lead to neurodegenerative disease in general and AD in particular. In addition, we discuss the evidence that supports the hypothesis that TBI may lead to AD. In particular, we focus on inflammatory responses as key processes in TBI-induced secondary injury, with emphasis on nuclear factor kappa B (NF-κB) signaling. PMID:26899581

  14. Neuroplasticity following non-penetrating traumatic brain injury.

    PubMed

    Levin, Harvey S

    2003-08-01

    The primary objective of this review is to examine the methodology and evidence for neuroplasticity operating in recovery from traumatic brain injury (TBI), as compared with previous findings in patients sustaining perinatal and infantile focal vascular lesions. The evidence to date indicates that the traditional view of enhanced reorganization of function after early focal brain lesions might apply to early focal brain lesions, but does not conform with studies of early severe diffuse brain injury. In contrast to early focal vascular lesions, young age confers no advantage in the outcome of severe diffuse brain injury. Disruption of myelination could potentially alter connectivity, a suggestion which could be confirmed through diffusion tensor imaging (DTI). Initial reports of DTI in TBI patients support the possibility that this technique can demonstrate alterations in white matter connections which are not seen on conventional magnetic resonance imaging (MRI) and might change over time or with interventions. Preliminary functional MRI studies of TBI patients indicate alterations in the pattern of brain activation, suggesting recruitment of more extensive cortical regions to perform tasks which stress computational resources. Functional MRI, coupled with DTI and possibly other imaging modalities holds the promise of elucidating mechanisms of neuroplasticity and repair following TBI. PMID:12850951

  15. Traumatic Brain Injury Studies in Britain during World War II.

    PubMed

    Lanska, Douglas J

    2016-01-01

    As a result of the wartime urgency to understand, prevent, and treat patients with traumatic brain injury (TBI) during World War II (WWII), clinicians and basic scientists in Great Britain collaborated on research projects that included accident investigations, epidemiologic studies, and development of animal and physical models. Very quickly, investigators from different disciplines shared information and ideas that not only led to new insights into the mechanisms of TBI but also provided very practical approaches for preventing or ameliorating at least some forms of TBI. Neurosurgeon Hugh Cairns (1896-1952) conducted a series of influential studies on the prevention and treatment of head injuries that led to recognition of a high rate of fatal TBI among motorcycle riders and subsequently to demonstrations of the utility of helmets in lowering head injury incidence and case fatality. Neurologists Derek Denny-Brown (1901-1981) and (William) Ritchie Russell (1903-1980) developed an animal model of TBI that demonstrated the fundamental importance of sudden acceleration (i.e., jerking) of the head in causing concussion and forced a distinction between head injury associated with sudden acceleration/deceleration and that associated with crush or compression. Physicist A.H.S. Holbourn (1907-1962) used theoretical arguments and simple physical models to illustrate the importance of shear stress in TBI. The work of these British neurological clinicians and scientists during WWII had a strong influence on subsequent clinical and experimental studies of TBI and also eventually resulted in effective (albeit controversial) public health campaigns and legislation in several countries to prevent head injuries among motorcycle riders and others through the use of protective helmets. Collectively, these studies accelerated our understanding of TBI and had subsequent important implications for both military and civilian populations. As a result of the wartime urgency to understand

  16. Traumatic Brain Injury Studies in Britain during World War II.

    PubMed

    Lanska, Douglas J

    2016-01-01

    As a result of the wartime urgency to understand, prevent, and treat patients with traumatic brain injury (TBI) during World War II (WWII), clinicians and basic scientists in Great Britain collaborated on research projects that included accident investigations, epidemiologic studies, and development of animal and physical models. Very quickly, investigators from different disciplines shared information and ideas that not only led to new insights into the mechanisms of TBI but also provided very practical approaches for preventing or ameliorating at least some forms of TBI. Neurosurgeon Hugh Cairns (1896-1952) conducted a series of influential studies on the prevention and treatment of head injuries that led to recognition of a high rate of fatal TBI among motorcycle riders and subsequently to demonstrations of the utility of helmets in lowering head injury incidence and case fatality. Neurologists Derek Denny-Brown (1901-1981) and (William) Ritchie Russell (1903-1980) developed an animal model of TBI that demonstrated the fundamental importance of sudden acceleration (i.e., jerking) of the head in causing concussion and forced a distinction between head injury associated with sudden acceleration/deceleration and that associated with crush or compression. Physicist A.H.S. Holbourn (1907-1962) used theoretical arguments and simple physical models to illustrate the importance of shear stress in TBI. The work of these British neurological clinicians and scientists during WWII had a strong influence on subsequent clinical and experimental studies of TBI and also eventually resulted in effective (albeit controversial) public health campaigns and legislation in several countries to prevent head injuries among motorcycle riders and others through the use of protective helmets. Collectively, these studies accelerated our understanding of TBI and had subsequent important implications for both military and civilian populations. As a result of the wartime urgency to understand

  17. A Novel Mouse Model of Penetrating Brain Injury

    PubMed Central

    Cernak, Ibolja; Wing, Ian D.; Davidsson, Johan; Plantman, Stefan

    2014-01-01

    Penetrating traumatic brain injury (pTBI) has been difficult to model in small laboratory animals, such as rats or mice. Previously, we have established a non-fatal, rat model for pTBI using a modified air-rifle that accelerates a pellet, which hits a small probe that then penetrates the experimental animal’s brain. Knockout and transgenic strains of mice offer attractive tools to study biological reactions induced by TBI. Hence, in the present study, we adapted and modified our model to be used with mice. The technical characterization of the impact device included depth and speed of impact, as well as dimensions of the temporary cavity formed in a brain surrogate material after impact. Biologically, we have focused on three distinct levels of severity (mild, moderate, and severe), and characterized the acute phase response to injury in terms of tissue destruction, neural degeneration, and gliosis. Functional outcome was assessed by measuring bodyweight and motor performance on rotarod. The results showed that this model is capable of reproducing major morphological and neurological changes of pTBI; as such, we recommend its utilization in research studies aiming to unravel the biological events underlying injury and regeneration after pTBI. PMID:25374559

  18. ANTIOXIDANT THERAPIES FOR TRAUMATIC BRAIN INJURY

    PubMed Central

    Hall, Edward D.; Vaishnav, Radhika A.; Mustafa, Ayman G.

    2010-01-01

    Free radical-induced oxidative damage reactions, and membrane lipid peroxidation (LP) in particular, are one of the best validated secondary injury mechanisms in preclinical traumatic brain injury models. In addition to the disruption of the membrane phospholipid architecture, LP results in the formation of cytotoxic aldehyde-containing products that bind to cellular proteins and impair their normal functions. This article reviews the progress over the past three decades in regards to the preclinical discovery and attempted clinical development of antioxidant drugs designed to inhibit free radical-induced LP and its neurotoxic consequences via different mechanisms including the O2•- scavenger superoxide dismutase (SOD) and the lipid peroxidation inhibitor tirilazad. In addition, various other antioxidant agents that have been shown to have efficacy in preclinical TBI models are briefly presented such as the LP inhibitors U83836E, resveratrol, curcumin, OPC-14177 and lipoic acid; the iron chelator deferoxamine and the nitroxide-containing antioxidants such as α-phenyl-tert-butyl nitrone and tempol. A relatively new antioxidant mechanistic strategy for acute TBI is aimed at the scavenging of aldehydic LP by-products that are highly neurotoxic with “carbonyl scavenging” compounds. Finally, it is proposed that the most effective approach to interrupt posttraumatic oxidative brain damage after TBI might involve the combined treatment with mechanistically-complementary antioxidants that simultaneously scavenge LP-initiating free radicals, inhibit LP propagation and lastly remove neurotoxic LP byproducts. PMID:20129497

  19. Impaired Pituitary Axes Following Traumatic Brain Injury

    PubMed Central

    Scranton, Robert A.; Baskin, David S.

    2015-01-01

    Pituitary dysfunction following traumatic brain injury (TBI) is significant and rarely considered by clinicians. This topic has received much more attention in the last decade. The incidence of post TBI anterior pituitary dysfunction is around 30% acutely, and declines to around 20% by one year. Growth hormone and gonadotrophic hormones are the most common deficiencies seen after traumatic brain injury, but also the most likely to spontaneously recover. The majority of deficiencies present within the first year, but extreme delayed presentation has been reported. Information on posterior pituitary dysfunction is less reliable ranging from 3%–40% incidence but prospective data suggests a rate around 5%. The mechanism, risk factors, natural history, and long-term effect of treatment are poorly defined in the literature and limited by a lack of standardization. Post TBI pituitary dysfunction is an entity to recognize with significant clinical relevance. Secondary hypoadrenalism, hypothyroidism and central diabetes insipidus should be treated acutely while deficiencies in growth and gonadotrophic hormones should be initially observed. PMID:26239686

  20. Disability evaluation following traumatic brain injury.

    PubMed

    McPeak, L A; Stiers, W M; Cope, D N

    2001-08-01

    Accurate disability evaluation of a patient with TBI is a very difficult and detailed process. It requires an excellent background concerning the evaluation of all the physical, cognitive, behavioral, and functional abnormalities associated with TBI. Texts that highlight all these abnormalities include Medical Rehabilitation of Traumatic Brain Injury by Horn and Zasler and Rehabilitation of the Adult and Child with Traumatic Brain Injury by Rosenthal et al. In addition, appropriate disability rating can only be performed by a physician with expert skills in obtaining accurate historical information and completing a detailed physical examination. Often, the historical information must be obtained from many sources because the patient may supply inaccurate information because of his or her cognitive deficits. Interviews with family members, caregivers, therapists, friends, and employers are sometimes necessary to obtain an accurate historical picture. Premorbid functioning, behavior, and personality are important because previous abnormalities are often exaggerated after the TBI. The physical examination should be tailored to provide detailed objective information concerning all deficits identified through the history. If cognitive and behavioral problems are identified through either the history or examination, a neuropsychologic assessment is necessary. All this information should be available before the disability or impairment rating. Only with detailed information can a clinician provide an accurate rating.

  1. The Power of Cross-Disciplinary Teams for Developing First Responder Training in TBI

    ERIC Educational Resources Information Center

    Shackelford, Jo L.; Cappiccie, Amy

    2016-01-01

    Misunderstanding of the symptoms of traumatic brain injury (TBI) often leaves first responders ill-equipped to handle encounters involving subjects with brain injury. This paper details a cross-disciplinary project to develop and disseminate a training curriculum designed to increase first responders' knowledge of and skills with TBI survivors.…

  2. Understanding the pathology and treatment of traumatic brain injury and posttraumatic stress disorder: a therapeutic role for hyperbaric oxygen therapy.

    PubMed

    Guedes, Vivian A; Song, Shuojing; Provenzano, Martina; Borlongan, Cesario V

    2016-01-01

    Traumatic brain injury (TBI) is an intracranial injury caused by external trauma leading to different degrees of brain damage. TBI can cause a wide array of symptoms and range in severity from concussion to coma and death. The link between TBI and posttraumatic stress disorder (PTSD) has received increasing attention due to the high incidence of these conditions in soldiers returning from recent conflicts. TBI has been associated with an increased risk of PTSD. Additionally, TBI and PTSD often demonstrate overlapping symptoms. In this article, we discuss the different forms of TBI and their links to PTSD. We also discuss current therapies for TBI and PTSD, in particular detailing the therapeutic potential of hyperbaric oxygen therapy in the management of these conditions.

  3. Erythropoietin Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

    PubMed

    Bramlett, Helen M; Dietrich, W Dalton; Dixon, C Edward; Shear, Deborah A; Schmid, Kara E; Mondello, Stefania; Wang, Kevin K W; Hayes, Ronald L; Povlishock, John T; Tortella, Frank C; Kochanek, Patrick M

    2016-03-15

    Experimental studies targeting traumatic brain injury (TBI) have reported that erythropoietin (EPO) is an endogenous neuroprotectant in multiple models. In addition to its neuroprotective effects, it has also been shown to enhance reparative processes including angiogenesis and neurogenesis. Based on compelling pre-clinical data, EPO was tested by the Operation Brain Trauma Therapy (OBTT) consortium to evaluate therapeutic potential in multiple TBI models along with biomarker assessments. Based on the pre-clinical TBI literature, two doses of EPO (5000 and 10,000 IU/kg) were tested given at 15 min after moderate fluid percussion brain injury (FPI), controlled cortical impact (CCI), or penetrating ballistic-like brain injury (PBBI) with subsequent behavioral, histopathological, and biomarker outcome assessments. There was a significant benefit on beam walk with the 5000 IU dose in CCI, but no benefit on any other motor task across models in OBTT. Also, no benefit of EPO treatment across the three TBI models was noted using the Morris water maze to assess cognitive deficits. Lesion volume analysis showed no treatment effects after either FPI or CCI; however, with the 5000 IU/kg dose of EPO, a paradoxical increase in lesion volume and percent hemispheric tissue loss was seen after PBBI. Biomarker assessments included measurements of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) in blood at 4 or 24 h after injury. No treatment effects were seen on biomarker levels after FPI, whereas treatment at either dose exacerbated the increase in GFAP at 24 h in PBBI but attenuated 24-4 h delta UCH-L1 levels at high dose in CCI. Our data indicate a surprising lack of efficacy of EPO across three established TBI models in terms of behavioral, histopathological, and biomarker assessments. Although we cannot rule out the possibility that other doses or more prolonged treatment could show different effects, the lack of efficacy of EPO reduced

  4. Erythropoietin Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

    PubMed

    Bramlett, Helen M; Dietrich, W Dalton; Dixon, C Edward; Shear, Deborah A; Schmid, Kara E; Mondello, Stefania; Wang, Kevin K W; Hayes, Ronald L; Povlishock, John T; Tortella, Frank C; Kochanek, Patrick M

    2016-03-15

    Experimental studies targeting traumatic brain injury (TBI) have reported that erythropoietin (EPO) is an endogenous neuroprotectant in multiple models. In addition to its neuroprotective effects, it has also been shown to enhance reparative processes including angiogenesis and neurogenesis. Based on compelling pre-clinical data, EPO was tested by the Operation Brain Trauma Therapy (OBTT) consortium to evaluate therapeutic potential in multiple TBI models along with biomarker assessments. Based on the pre-clinical TBI literature, two doses of EPO (5000 and 10,000 IU/kg) were tested given at 15 min after moderate fluid percussion brain injury (FPI), controlled cortical impact (CCI), or penetrating ballistic-like brain injury (PBBI) with subsequent behavioral, histopathological, and biomarker outcome assessments. There was a significant benefit on beam walk with the 5000 IU dose in CCI, but no benefit on any other motor task across models in OBTT. Also, no benefit of EPO treatment across the three TBI models was noted using the Morris water maze to assess cognitive deficits. Lesion volume analysis showed no treatment effects after either FPI or CCI; however, with the 5000 IU/kg dose of EPO, a paradoxical increase in lesion volume and percent hemispheric tissue loss was seen after PBBI. Biomarker assessments included measurements of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) in blood at 4 or 24 h after injury. No treatment effects were seen on biomarker levels after FPI, whereas treatment at either dose exacerbated the increase in GFAP at 24 h in PBBI but attenuated 24-4 h delta UCH-L1 levels at high dose in CCI. Our data indicate a surprising lack of efficacy of EPO across three established TBI models in terms of behavioral, histopathological, and biomarker assessments. Although we cannot rule out the possibility that other doses or more prolonged treatment could show different effects, the lack of efficacy of EPO reduced

  5. Characterization of T2 hyperintensity lesions in patients with mild traumatic brain injury

    NASA Astrophysics Data System (ADS)

    Caban, Jesus J.; Green, Savannah A.; Riedy, Gerard

    2013-03-01

    Mild traumatic brain injury (TBI) is often an invisible injury that is poorly understood and its sequelae can be difficult to diagnose. Recent neuroimaging studies on patients diagnosed with mild TBI (mTBI) have demonstrated an increase in hyperintense brain lesions on T2-weighted MR images. This paper presents an in-depth analysis of the multi-modal and morphological properties of T2 hyperintensity lesions among service members diagnosed with mTBI. A total of 790 punctuate T2 hyperintensity lesions from 89 mTBI subjects were analyzed and used to characterize the lesions based on different quantitative measurements. Morphological analysis shows that on average, T2 hyperintensity lesions have volumes of 23mm3 (+/-24.75), a roundness measure of 0.83 (+/-0.08) and an elongation of 7.90 (+/-2.49). The frontal lobe lesions demonstrated significantly more elongated lesions when compared to other areas of the brain.

  6. Glucocorticoids modulate BDNF mRNA expression in the rat hippocampus after traumatic brain injury.

    PubMed

    Grundy, P L; Patel, N; Harbuz, M S; Lightman, S L; Sharples, P M

    2000-10-20

    Brain-derived neurotrophic factor (BDNF) expression in rat hippocampus is increased after experimental traumatic brain injury (TBI) and may be neuroprotective. Glucocorticoids are important regulators of brain neurotrophin levels and are often prescribed following TBI. The effect of adrenalectomy (ADX) on the expression of BDNF mRNA in the hippocampus after TBI has not been investigated to date. We used fluid percussion injury (FPI) and in situ hybridization to evaluate the expression of BDNF mRNA in the hippocampus 4 h after TBI in adrenal-intact or adrenalectomized rats (with or without corticosterone replacement). FPI and ADX independently increased expression of BDNF mRNA. In animals undergoing FPI, prior ADX caused further elevation of BDNF mRNA and this upregulation was prevented by corticosterone replacement in ADX rats. These findings suggest that glucocorticoids are involved in the modulation of the BDNF mRNA response to TBI.

  7. Repetitive mild traumatic brain injury induces ventriculomegaly and cortical thinning in juvenile rats.

    PubMed

    Goddeyne, Corey; Nichols, Joshua; Wu, Chen; Anderson, Trent

    2015-05-01

    Traumatic brain injury (TBI) most frequently occurs in pediatric patients and remains a leading cause of childhood death and disability. Mild TBI (mTBI) accounts for nearly 75% of all TBI cases, yet its neuropathophysiology is still poorly understood. While even a single mTBI injury can lead to persistent deficits, repeat injuries increase the severity and duration of both acute symptoms and long-term deficits. In this study, to model pediatric repetitive mTBI (rmTBI) we subjected unrestrained juvenile animals (postnatal day 20) to repeat weight-drop impacts. Animals were anesthetized and subjected to sham injury or rmTBI once per day for 5 days. Magnetic resonance imaging (MRI) performed 14 days after injury revealed marked cortical atrophy and ventriculomegaly in rmTBI animals. Specifically, beneath the impact zone the thickness of the cortex was reduced by up to 46% and the area of the ventricles increased by up to 970%. Immunostaining with the neuron-specific marker NeuN revealed an overall loss of neurons within the motor cortex but no change in neuronal density. Examination of intrinsic and synaptic properties of layer II/III pyramidal neurons revealed no significant difference between sham-injured and rmTBI animals at rest or under convulsant challenge with the potassium channel blocker 4-aminopyridine. Overall, our findings indicate that the neuropathological changes reported after pediatric rmTBI can be effectively modeled by repeat weight drop in juvenile animals. Developing a better understanding of how rmTBI alters the pediatric brain may help improve patient care and direct "return to game" decision making in adolescents.

  8. Altered Neuroinflammation and Behavior after Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease.

    PubMed

    Kokiko-Cochran, Olga; Ransohoff, Lena; Veenstra, Mike; Lee, Sungho; Saber, Maha; Sikora, Matt; Teknipp, Ryan; Xu, Guixiang; Bemiller, Shane; Wilson, Gina; Crish, Samuel; Bhaskar, Kiran; Lee, Yu-Shang; Ransohoff, Richard M; Lamb, Bruce T

    2016-04-01

    Traumatic brain injury (TBI) has acute and chronic sequelae, including an increased risk for the development of Alzheimer's disease (AD). TBI-associated neuroinflammation is characterized by activation of brain-resident microglia and infiltration of monocytes; however, recent studies have implicated beta-amyloid as a major manipulator of the inflammatory response. To examine neuroinflammation after TBI and development of AD-like features, these studies examined the effects of TBI in the presence and absence of beta-amyloid. The R1.40 mouse model of cerebral amyloidosis was used, with a focus on time points well before robust AD pathologies. Unexpectedly, in R1.40 mice, the acute neuroinflammatory response to TBI was strikingly muted, with reduced numbers of CNS myeloid cells acquiring a macrophage phenotype and decreased expression of inflammatory cytokines. At chronic time points, macrophage activation substantially declined in non-Tg TBI mice; however, it was relatively unchanged in R1.40 TBI mice. The persistent inflammatory response coincided with significant tissue loss between 3 and 120 days post-injury in R1.40 TBI mice, which was not observed in non-Tg TBI mice. Surprisingly, inflammatory cytokine expression was enhanced in R1.40 mice compared with non-Tg mice, regardless of injury group. Although R1.40 TBI mice demonstrated task-specific deficits in cognition, overall functional recovery was similar to non-Tg TBI mice. These findings suggest that accumulating beta-amyloid leads to an altered post-injury macrophage response at acute and chronic time points. Together, these studies emphasize the role of post-injury neuroinflammation in regulating long-term sequelae after TBI and also support recent studies implicating beta-amyloid as an immunomodulator.

  9. Repetitive mild traumatic brain injury induces ventriculomegaly and cortical thinning in juvenile rats

    PubMed Central

    Goddeyne, Corey; Nichols, Joshua; Wu, Chen

    2015-01-01

    Traumatic brain injury (TBI) most frequently occurs in pediatric patients and remains a leading cause of childhood death and disability. Mild TBI (mTBI) accounts for nearly 75% of all TBI cases, yet its neuropathophysiology is still poorly understood. While even a single mTBI injury can lead to persistent deficits, repeat injuries increase the severity and duration of both acute symptoms and long-term deficits. In this study, to model pediatric repetitive mTBI (rmTBI) we subjected unrestrained juvenile animals (postnatal day 20) to repeat weight-drop impacts. Animals were anesthetized and subjected to sham injury or rmTBI once per day for 5 days. Magnetic resonance imaging (MRI) performed 14 days after injury revealed marked cortical atrophy and ventriculomegaly in rmTBI animals. Specifically, beneath the impact zone the thickness of the cortex was reduced by up to 46% and the area of the ventricles increased by up to 970%. Immunostaining with the neuron-specific marker NeuN revealed an overall loss of neurons within the motor cortex but no change in neuronal density. Examination of intrinsic and synaptic properties of layer II/III pyramidal neurons revealed no significant difference between sham-injured and rmTBI animals at rest or under convulsant challenge with the potassium channel blocker 4-aminopyridine. Overall, our findings indicate that the neuropathological changes reported after pediatric rmTBI can be effectively modeled by repeat weight drop in juvenile animals. Developing a better understanding of how rmTBI alters the pediatric brain may help improve patient care and direct “return to game” decision making in adolescents. PMID:25695652

  10. Dementia Resulting From Traumatic Brain Injury

    PubMed Central

    Shively, Sharon; Scher, Ann I.; Perl, Daniel P.; Diaz-Arrastia, Ramon

    2013-01-01

    Traumatic brain injury (TBI) is among the earliest illnesses described in human history and remains a major source of morbidity and mortality in the modern era. It is estimated that 2% of the US population lives with long-term disabilities due to a prior TBI, and incidence and prevalence rates are even higher in developing countries. One of the most feared long-term consequences of TBIs is dementia, as multiple epidemiologic studies show that experiencing a TBI in early or midlife is associated with an increased risk of dementia in late life. The best data indicate that moderate and severe TBIs increase risk of dementia between 2-and 4-fold. It is less clear whether mild TBIs such as brief concussions result in increased dementia risk, in part because mild head injuries are often not well documented and retrospective studies have recall bias. However, it has been observed for many years that multiple mild TBIs as experienced by professional boxers are associated with a high risk of chronic traumatic encephalopathy (CTE), a type of dementia with distinctive clinical and pathologic features. The recent recognition that CTE is common in retired professional football and hockey players has rekindled interest in this condition, as has the recognition that military personnel also experience high rates of mild TBIs and may have a similar syndrome. It is presently unknown whether dementia in TBI survivors is pathophysiologically similar to Alzheimer disease, CTE, or some other entity. Such information is critical for developing preventive and treatment strategies for a common cause of acquired dementia. Herein, we will review the epidemiologic data linking TBI and dementia, existing clinical and pathologic data, and will identify areas where future research is needed. PMID:22776913

  11. Traumatic Brain Injury – Modeling Neuropsychiatric Symptoms in Rodents

    PubMed Central

    Malkesman, Oz; Tucker, Laura B.; Ozl, Jessica; McCabe, Joseph T.

    2013-01-01

    Each year in the US, ∼1.5 million people sustain a traumatic brain injury (TBI). Victims of TBI can suffer from chronic post-TBI symptoms, such as sensory and motor deficits, cognitive impairments including problems with memory, learning, and attention, and neuropsychiatric symptoms such as depression, anxiety, irritability, aggression, and suicidal rumination. Although partially associated with the site and severity of injury, the biological mechanisms associated with many of these symptoms – and why some patients experience differing assortments of persistent maladies – are largely unknown. The use of animal models is a promising strategy for elucidation of the mechanisms of impairment and treatment, and learning, memory, sensory, and motor tests have widespread utility in rodent models of TBI and psychopharmacology. Comparatively, behavioral tests for the evaluation of neuropsychiatric symptomatology are rarely employed in animal models of TBI and, as determined in this review, the results have been inconsistent. Animal behavioral studies contribute to the understanding of the biological mechanisms by which TBI is associated with neurobehavioral symptoms and offer a powerful means for pre-clinical treatment validation. Therefore, further exploration of the utility of animal behavioral tests for the study of injury mechanisms and therapeutic strategies for the alleviation of emotional symptoms are relevant and essential. PMID:24109476

  12. Paediatric traumatic brain injury: a review of pertinent issues.

    PubMed

    Savage, Ronald C; DePompei, Roberta; Tyler, Janet; Lash, Marilyn

    2005-01-01

    Children with traumatic brain injury (TBI), regardless of the severity of the injury, often face challenges when living in home, school and community. Their needs are often overlooked and recognition of the long-term consequences is not always central to the management of the child in the school or community. This article provides references to pertinent literature and suggestions for intervention from the clinical experiences of four individuals with extensive experience of the family stresses, educational, cognitive-communicative and behavioural challenges that occur after TBI in children. It provides information regarding these issues, particularly educational situations, and suggests methods that may be useful for service providers and family members. PMID:16089249

  13. Evaluation of a Health Education Programme about Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Garcia, Jane Mertz; Sellers, Debra M.; Hilgendorf, Amy E.; Burnett, Debra L.

    2014-01-01

    Objective: Our aim was to evaluate a health education programme (TBIoptions: Promoting Knowledge) designed to increase public awareness and understanding about traumatic brain injury (TBI) through in-person (classroom) and computer-based (electronic) learning environments. Design: We used a pre-post survey design with randomization of participants…

  14. Predictors of Neuropsychological Test Performance After Pediatric Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Donders, Jacobus; Nesbit-Greene, Kelly

    2004-01-01

    The influence of neurological and demographic variables on neuropsychological test performance was examined in 100 9- to 16-year-old children with traumatic brain injury (TBI). Regression analyses were conducted to determine the relative contributions of coma, neuroimaging findings, ethnicity, socioeconomic status, and gender to variance in…

  15. Collaborative Intervention in Schools after Traumatic Brain Injury.

    ERIC Educational Resources Information Center

    Szekeres, Shirley F.; Meserve, Nancy F.

    1994-01-01

    This article discusses principles and procedures of collaborative intervention in delivering educational services for children with traumatic brain injury (TBI). The article presents examples of metacognitive-communicative intervention that can be carried out through collaboration across the school day and describes episodes of collaborative…

  16. Assisting Students with a Traumatic Brain Injury in School Interventions

    ERIC Educational Resources Information Center

    Aldrich, Erin M.; Obrzut, John E.

    2012-01-01

    Traumatic brain injury (TBI) in children and adolescents can significantly affect their lives and educational needs. Deficits are often exhibited in areas such as attention, concentration, memory, executive function, emotional regulation, and behavioral functioning, but specific outcomes are not particular to any one child or adolescent with a…

  17. Early Childhood Traumatic Brain Injuries: Effects on Development and Interventions.

    ERIC Educational Resources Information Center

    Lowenthal, Barbara

    1998-01-01

    Describes the variety of possible effects of traumatic brain injuries (TBI) on early childhood development in the cognitive, language, social-emotional, motor, and adaptive domains. Suggests interventions which can assist young survivors and their families. Suggests that more long-term, intensive studies be conducted on the short- and long-term…

  18. Imaging assessment of traumatic brain injury.

    PubMed

    Currie, Stuart; Saleem, Nayyar; Straiton, John A; Macmullen-Price, Jeremy; Warren, Daniel J; Craven, Ian J

    2016-01-01

    Traumatic brain injury (TBI) constitutes injury that occurs to the brain as a result of trauma. It should be appreciated as a heterogeneous, dynamic pathophysiological process that starts from the moment of impact and continues over time with sequelae potentially seen many years after the initial event. Primary traumatic brain lesions that may occur at the moment of impact include contusions, haematomas, parenchymal fractures and diffuse axonal injury. The presence of extra-axial intracranial lesions such as epidural and subdural haematomas and subarachnoid haemorrhage must be anticipated as they may contribute greatly to secondary brain insult by provoking brain herniation syndromes, cranial nerve deficits, oedema and ischaemia and infarction. Imaging is fundamental to the management of patients with TBI. CT remains the imaging modality of choice for initial assessment due to its ease of access, rapid acquisition and for its sensitivity for detection of acute haemorrhagic lesions for surgical intervention. MRI is typically reserved for the detection of lesions that may explain clinical symptoms that remain unresolved despite initial CT. This is especially apparent in the setting of diffuse axonal injury, which is poorly discerned on CT. Use of particular MRI sequences may increase the sensitivity of detecting such lesions: diffusion-weighted imaging defining acute infarction, susceptibility-weighted imaging affording exquisite data on microhaemorrhage. Additional advanced MRI techniques such as diffusion tensor imaging and functional MRI may provide important information regarding coexistent structural and functional brain damage. Gaining robust prognostic information for patients following TBI remains a challenge. Advanced MRI sequences are showing potential for biomarkers of disease, but this largely remains at the research level. Various global collaborative research groups have been established in an effort to combine imaging data with clinical and

  19. Imaging assessment of traumatic brain injury.

    PubMed

    Currie, Stuart; Saleem, Nayyar; Straiton, John A; Macmullen-Price, Jeremy; Warren, Daniel J; Craven, Ian J

    2016-01-01

    Traumatic brain injury (TBI) constitutes injury that occurs to the brain as a result of trauma. It should be appreciated as a heterogeneous, dynamic pathophysiological process that starts from the moment of impact and continues over time with sequelae potentially seen many years after the initial event. Primary traumatic brain lesions that may occur at the moment of impact include contusions, haematomas, parenchymal fractures and diffuse axonal injury. The presence of extra-axial intracranial lesions such as epidural and subdural haematomas and subarachnoid haemorrhage must be anticipated as they may contribute greatly to secondary brain insult by provoking brain herniation syndromes, cranial nerve deficits, oedema and ischaemia and infarction. Imaging is fundamental to the management of patients with TBI. CT remains the imaging modality of choice for initial assessment due to its ease of access, rapid acquisition and for its sensitivity for detection of acute haemorrhagic lesions for surgical intervention. MRI is typically reserved for the detection of lesions that may explain clinical symptoms that remain unresolved despite initial CT. This is especially apparent in the setting of diffuse axonal injury, which is poorly discerned on CT. Use of particular MRI sequences may increase the sensitivity of detecting such lesions: diffusion-weighted imaging defining acute infarction, susceptibility-weighted imaging affording exquisite data on microhaemorrhage. Additional advanced MRI techniques such as diffusion tensor imaging and functional MRI may provide important information regarding coexistent structural and functional brain damage. Gaining robust prognostic information for patients following TBI remains a challenge. Advanced MRI sequences are showing potential for biomarkers of disease, but this largely remains at the research level. Various global collaborative research groups have been established in an effort to combine imaging data with clinical and

  20. Manic Symptoms Due to Methylphenidate Use in an Adolescent with Traumatic Brain Injury.

    PubMed

    Ekinci, Ozalp; Direk, Meltem Çobanoğullari; Ekinci, Nuran; Okuyaz, Cetin

    2016-08-31

    Almost one-fifth of children who sustain a traumatic brain injury (TBI) are under the risk of attention problems after injury. The efficacy and tolerability of methylphenidate (MPH) in children with a history of TBI have not been completely identified. In this case report, MPH-induced manic symptoms in an adolescent with TBI will be summarized. A male patient aged 17 years was admitted with the complaints of attention difficulties on schoolwork and forgetfullness which became evident after TBI. Long-acting MPH was administered with the dose of 18 mg/day for attention problems. After one week, patient presented with the complaints of talking to himself, delusional thoughts, irritability and sleeplessness. This case highlights the fact that therapeutic dose of MPH may cause mania-like symptoms in children with TBI. Close monitarization and slow dose titration are crucial when considering MPH in children with TBI. PMID:27489389

  1. Manic Symptoms Due to Methylphenidate Use in an Adolescent with Traumatic Brain Injury

    PubMed Central

    Ekinci, Ozalp; Direk, Meltem Çobanoğullari; Ekinci, Nuran; Okuyaz, Cetin

    2016-01-01

    Almost one-fifth of children who sustain a traumatic brain injury (TBI) are under the risk of attention problems after injury. The efficacy and tolerability of methylphenidate (MPH) in children with a history of TBI have not been completely identified. In this case report, MPH-induced manic symptoms in an adolescent with TBI will be summarized. A male patient aged 17 years was admitted with the complaints of attention difficulties on schoolwork and forgetfullness which became evident after TBI. Long-acting MPH was administered with the dose of 18 mg/day for attention problems. After one week, patient presented with the complaints of talking to himself, delusional thoughts, irritability and sleeplessness. This case highlights the fact that therapeutic dose of MPH may cause mania-like symptoms in children with TBI. Close monitarization and slow dose titration are crucial when considering MPH in children with TBI. PMID:27489389

  2. Role of Melatonin in Traumatic Brain Injury and Spinal Cord Injury

    PubMed Central

    Naseem, Mehar; Parvez, Suhel

    2014-01-01

    Brain and spinal cord are implicated in incidences of two of the most severe injuries of central nervous system (CNS). Traumatic brain injury (TBI) is a devastating neurological deficit involving primary and secondary injury cascades. The primary and secondary mechanisms include complex consequences of activation of proinflammatory cytokines, cerebral edema, upregulation of NF-κβ, disruption of blood-brain barrier (BBB), and oxidative stress. Spinal cord injury (SCI) includes primary and secondary injury cascades. Primary injury leads to secondary injury in which generation of free radicals and oxidative or nitrative damage play an important pathophysiological role. The indoleamine melatonin is a hormone secreted or synthesized by pineal gland in the brain which helps to regulate sleep and wake cycle. Melatonin has been shown to be a versatile hormone having antioxidative, antiapoptotic, neuroprotective, and anti-inflammatory properties. It has a special characteristic of crossing BBB. Melatonin has neuroprotective role in the injured part of the CNS after TBI and SCI. A number of studies have successfully shown its therapeutic value as a neuroprotective agent in the treatment of neurodegenerative diseases. Here in this review we have compiled the literature supporting consequences of CNS injuries, TBI and SCI, and the protective role of melatonin in it. PMID:25587567

  3. Injury biomechanics, neuropathology, and simplified physics of explosive blast and impact mild traumatic brain injury.

    PubMed

    Bandak, F A; Ling, G; Bandak, A; De Lanerolle, N C

    2015-01-01

    Explosive blast shock waves and blunt impact to the head are two types of loading shown to result in mild traumatic brain injury (mTBI). While mTBI from these two causes shares some common features behaviorally, there are distinct differences in the pathophysiology of the underlying injury mechanisms. Various elucidations have been offered in the literature to explain the organic damage associated with mTBI resulting from both types of loading. The current state of understanding in this field is somewhat limited by the degree of appreciation of the physics and biomechanics governing the effects of explosive blast shock waves and blunt impact on the head, which has resulted in the various approaches to the investigation of the operative brain injury "wounding mechanisms". In this chapter we provide a simplified description of terminology associated with forces on the head from explosive blast shock waves and blunt impact, to assist readers in the field in evaluating interpretations of brain injury "wounding" processes. Remarkably, mTBI from either loading is shown generally to result in only a small loss of neurons, with hippocampal neurons appearing to be particularly vulnerable to explosive blast shock waves. Explosive blast studies in large animal models show a unique pattern of periventricular injury, which is different from the classic diffuse axonal injury. Both astrocyte and microglial activation are also seen in explosive blast as well as impact trauma, but this may be a general secondary brain injury response, nonspecific to explosive blast or blunt trauma. Additionally, while moderate to severe impact closed head injuries sometimes result in petechial hemorrhages or hematomas, they do not appear to be associated with explosive blast mTBI even with repeated exposure to blasts.

  4. Injury biomechanics, neuropathology, and simplified physics of explosive blast and impact mild traumatic brain injury.

    PubMed

    Bandak, F A; Ling, G; Bandak, A; De Lanerolle, N C

    2015-01-01

    Explosive blast shock waves and blunt impact to the head are two types of loading shown to result in mild traumatic brain injury (mTBI). While mTBI from these two causes shares some common features behaviorally, there are distinct differences in the pathophysiology of the underlying injury mechanisms. Various elucidations have been offered in the literature to explain the organic damage associated with mTBI resulting from both types of loading. The current state of understanding in this field is somewhat limited by the degree of appreciation of the physics and biomechanics governing the effects of explosive blast shock waves and blunt impact on the head, which has resulted in the various approaches to the investigation of the operative brain injury "wounding mechanisms". In this chapter we provide a simplified description of terminology associated with forces on the head from explosive blast shock waves and blunt impact, to assist readers in the field in evaluating interpretations of brain injury "wounding" processes. Remarkably, mTBI from either loading is shown generally to result in only a small loss of neurons, with hippocampal neurons appearing to be particularly vulnerable to explosive blast shock waves. Explosive blast studies in large animal models show a unique pattern of periventricular injury, which is different from the classic diffuse axonal injury. Both astrocyte and microglial activation are also seen in explosive blast as well as impact trauma, but this may be a general secondary brain injury response, nonspecific to explosive blast or blunt trauma. Additionally, while moderate to severe impact closed head injuries sometimes result in petechial hemorrhages or hematomas, they do not appear to be associated with explosive blast mTBI even with repeated exposure to blasts. PMID:25702211

  5. Traumatic Brain Injury

    MedlinePlus

    ... disabilities include problems with cognition (thinking, memory, and reasoning), sensory processing (sight, hearing, touch, taste, and smell), ... barrier. NIH Patient Recruitment for Traumatic Brain Injury Clinical Trials At NIH Clinical Center Throughout the U.S. ...

  6. [Traumatic brain injury].

    PubMed

    Hackenberg, K; Unterberg, A

    2016-02-01

    Since traumatic brain injury is the most common cause of long-term disability and death among young adults, it represents an enormous socio-economic and healthcare burden. As a consequence of the primary lesion, a perifocal brain edema develops causing an elevation of the intracranial pressure due to the limited intracranial space. This entails a reduction of the cerebral perfusion pressure and the cerebral blood flow. A cerebral perfusion deficit below the threshold for ischemia leads to further ischemic lesions and to a progression of the contusion. As the irreversible primary lesion can only be inhibited by primary prevention, the therapy of traumatic brain injury focuses on the secondary injuries. The treatment consists of surgical therapy evacuating the space-occupying intracranial lesion and conservative intensive medical care. Due to the complex pathophysiology the therapy of traumatic brain injury should be rapidly performed in a neurosurgical unit. PMID:26810405

  7. Multi-modal MRI of mild traumatic brain injury

    PubMed Central

    Narayana, Ponnada A.; Yu, Xintian; Hasan, Khader M.; Wilde, Elisabeth A.; Levin, Harvey S.; Hunter, Jill V.; Miller, Emmy R.; Patel, Vipul Kumar S.; Robertson, Claudia S.; McCarthy, James J.

    2014-01-01

    Multi-modal magnetic resonance imaging (MRI) that included high resolution structural imaging, diffusion tensor imaging (DTI), magnetization transfer ratio (MTR) imaging, and magnetic resonance spectroscopic imaging (MRSI) were performed in mild traumatic brain injury (mTBI) patients with negative computed tomographic scans and in an orthopedic-injured (OI) group without concomitant injury to the brain. The OI group served as a comparison group for mTBI. MRI scans were performed both in the acute phase of injury (~24 h) and at follow-up (~90 days). DTI data was analyzed using tract based spatial statistics (TBSS). Global and regional atrophies were calculated using tensor-based morphometry (TBM). MTR values were calculated using the standard method. MRSI was analyzed using LC Model. At the initial scan, the mean diffusivity (MD) was significantly higher in the mTBI cohort relative to the comparison group in several white matter (WM) regions that included internal capsule, external capsule, superior corona radiata, anterior corona radiata, posterior corona radiata, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, forceps major and forceps minor of the corpus callosum, superior longitudinal fasciculus, and corticospinal tract in the right hemisphere. TBSS analysis failed to detect significant differences in any DTI measures between the initial and follow-up scans either in the mTBI or OI group. No significant differences were found in MRSI, MTR or morphometry between the mTBI and OI cohorts either at the initial or follow-up scans with or without family wise error (FWE) correction. Our study suggests that a number of WM tracts are affected in mTBI in the acute phase of injury and that these changes disappear by 90 days. This study also suggests that none of the MRI-modalities used in this study, with the exception of DTI, is sensitive in detecting changes in the acute phase of mTBI. PMID:25610770

  8. Multi-modal MRI of mild traumatic brain injury.

    PubMed

    Narayana, Ponnada A; Yu, Xintian; Hasan, Khader M; Wilde, Elisabeth A; Levin, Harvey S; Hunter, Jill V; Miller, Emmy R; Patel, Vipul Kumar S; Robertson, Claudia S; McCarthy, James J

    2015-01-01

    Multi-modal magnetic resonance imaging (MRI) that included high resolution structural imaging, diffusion tensor imaging (DTI), magnetization transfer ratio (MTR) imaging, and magnetic resonance spectroscopic imaging (MRSI) were performed in mild traumatic brain injury (mTBI) patients with negative computed tomographic scans and in an orthopedic-injured (OI) group without concomitant injury to the brain. The OI group served as a comparison group for mTBI. MRI scans were performed both in the acute phase of injury (~24 h) and at follow-up (~90 days). DTI data was analyzed using tract based spatial statistics (TBSS). Global and regional atrophies were calculated using tensor-based morphometry (TBM). MTR values were calculated using the standard method. MRSI was analyzed using LC Model. At the initial scan, the mean diffusivity (MD) was significantly higher in the mTBI cohort relative to the comparison group in several white matter (WM) regions that included internal capsule, external capsule, superior corona radiata, anterior corona radiata, posterior corona radiata, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, forceps major and forceps minor of the corpus callosum, superior longitudinal fasciculus, and corticospinal tract in the right hemisphere. TBSS analysis failed to detect significant differences in any DTI measures between the initial and follow-up scans either in the mTBI or OI group. No significant differences were found in MRSI, MTR or morphometry between the mTBI and OI cohorts either at the initial or follow-up scans with or without family wise error (FWE) correction. Our study suggests that a number of WM tracts are affected in mTBI in the acute phase of injury and that these changes disappear by 90 days. This study also suggests that none of the MRI-modalities used in this study, with the exception of DTI, is sensitive in detecting changes in the acute phase of mTBI.

  9. Charting a course for erythropoietin in traumatic brain injury

    PubMed Central

    Maiese, Kenneth

    2016-01-01

    Traumatic brain injury (TBI) is a severe public health problem that impacts more than four million individuals in the United States alone and is increasing in incidence on a global scale. Importantly, TBI can result in acute as well as chronic impairments for the nervous system leaving individuals with chronic disability and in instances of severe trauma, death becomes the ultimate outcome. In light of the significant negative health consequences of TBI, multiple therapeutic strategies are under investigation, but those focusing upon the cytokine and growth factor erythropoietin (EPO) have generated a great degree of enthusiasm. EPO can control cell death pathways tied to apoptosis and autophagy as well oversees processes that affect cellular longevity and aging. In vitro studies and experimental animal models of TBI have shown that EPO can restore axonal integrity, promote cellular proliferation, reduce brain edema, and preserve cellular energy homeostasis and mitochondrial function. Clinical studies for neurodegenerative disorders that involve loss of cognition or developmental brain injury support a positive role for EPO to prevent or reduce injury in the nervous system. However, recent clinical trials with EPO and TBI have not produced such clear conclusions. Further clinical studies are warranted to address the potential efficacy of EPO during TBI, the concerns with the onset, extent, and duration of EPO therapeutic strategies, and to focus upon the specific downstream pathways controlled by EPO such as protein kinase B (Akt), mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), sirtuins, wingless pathways, and forkhead transcription factors for improved precision against the detrimental effects of TBI. PMID:27081573

  10. Educating students with TBI: themes and recommendations.

    PubMed

    Ylvisaker, M; Todis, B; Glang, A; Urbanczyk, B; Franklin, C; DePompei, R; Feeney, T; Maxwell, N M; Pearson, S; Tyler, J S

    2001-02-01

    Ten educational consultants and researchers, each with extensive experience working with children with traumatic brain injury (TBI) in school settings, identified seven themes related to serving this population in public schools. These themes are discussed under the headings (1) incidence of TBI and prevalence of persistent educational disability, (2) diversity and central tendencies within the population, (3) assessment, (4) intervention and support in school settings, (5) training and support for educators, (6) intervention and support for families, and (7) systems change and flexibility. For each theme, a set of recommendations is provided, forming an educational research and policy agenda for pediatric TBI.

  11. [Evidence-based intensive care treatment of intracranial hypertension after traumatic brain injury].

    PubMed

    Pannen, B H J; Loop, T

    2005-02-01

    Traumatic brain injury (TBI) occurs frequently and is associated with a poor prognosis. Severe TBI results in substantial disability or death in more than 40% of cases. The major aim of treatment of these patients is to minimize secondary brain injury and in this respect, the prevention of intracranial hypertension plays a key role. In addition to surgical approaches, various conservative treatment options exist, such as the use of osmodiuretics, barbiturates, or corticosteroids, hyperventilation as well as induced therapeutic hypothermia. This review analyzes these treatment options and the therapeutic goals of lowering intracranial pressure (ICP) in patients after TBI using evidence-based criteria, and provides recommendations for clinical practice.

  12. Reduction of cerebral edema after traumatic brain injury using an osmotic transport device.

    PubMed

    McBride, Devin W; Szu, Jenny I; Hale, Chris; Hsu, Mike S; Rodgers, Victor G J; Binder, Devin K

    2014-12-01

    Traumatic brain injury (TBI) is significant, from a public health standpoint, because it is a major cause of the morbidity and mortality of young people. Cerebral edema after a TBI, if untreated, can lead to devastating damage of the remaining tissue. The current therapies of severe TBI (sTBI), as outlined by the Brain Trauma Foundation, are often ineffective, thus a new method for the treatment of sTBI is necessary. Herein, the reduction of cerebral edema, after TBI, using an osmotic transport device (OTD) was evaluated. Controlled cortical impact (CCI) was performed on adult female CD-1 mice, and cerebral edema was allowed to form for 3 h, followed by 2 h of treatment. The treatment groups were craniectomy only, craniectomy with a hydrogel, OTD without bovine serum albumin (BSA), and OTD. After CCI, brain water content was significantly higher for animals treated with a craniectomy only, craniectomy with a hydrogel, and OTD without BSA, compared to that of control animals. However, when TBI animals were treated with an OTD, brain water content was not significantly higher than that of controls. Further, brain water content of TBI animals treated with an OTD was significantly reduced, compared to that of untreated TBI animals, TBI animals treated with a craniectomy and a hydrogel, and TBI animals treated with an OTD without BSA. Here, we demonstrate the successful reduction of cerebral edema, as determined by brain water content, after TBI using an OTD. These results demonstrate proof of principle for direct water extraction from edematous brain tissue by direct osmotherapy using an OTD.

  13. Mental Trauma Experienced by Caregivers of patients with Diffuse Axonal Injury or Severe Traumatic Brain Injury

    PubMed Central

    Syed Hassan, Syed Tajuddin; Jamaludin, Husna; Abd Raman, Rosna; Mohd Riji, Haliza; Wan Fei, Khaw

    2013-01-01

    Context As with care giving and rehabilitation in chronic illnesses, the concern with traumatic brain injury (TBI), particularly with diffuse axonal injury (DAI), is that the caregivers are so overwhelmingly involved in caring and rehabilitation of the victim that in the process they become traumatized themselves. This review intends to shed light on the hidden and silent trauma sustained by the caregivers of severe brain injury survivors. Motor vehicle accident (MVA) is the highest contributor of TBI or DAI. The essence of trauma is the infliction of pain and suffering and having to bear the pain (i.e. by the TBI survivor) and the burden of having to take care and manage and rehabilitate the TBI survivor (i.e. by the TBI caregiver). Moreover many caregivers are not trained for their care giving task, thus compounding the stress of care giving and rehabilitating patients. Most research on TBI including DAI, focus on the survivors and not on the caregivers. TBI injury and its effects and impacts remain the core question of most studies, which are largely based on the quantitative approach. Evidence Acquisition Qualitative research can better assess human sufferings such as in the case of DAI trauma. While quantitative research can measure many psychometric parameters to assess some aspects of trauma conditions, qualitative research is able to fully reveal the meaning, ramification and experience of TBI trauma. Both care giving and rehabilitation are overwhelmingly demanding; hence , they may complicate the caregivers’ stress. However, some positive outcomes also exist. Results Caregivers involved in caring and rehabilitation of TBI victims may become mentally traumatized. Posttraumatic recovery of the TBI survivor can enhance the entire family’s closeness and bonding as well as improve the mental status of the caregiver. Conclusions A long-term longitudinal study encompassing integrated research is needed to fully understand the traumatic experiences of

  14. Hippocampal Neurophysiologic Changes after Mild Traumatic Brain Injury and Potential Neuromodulation Treatment Approaches

    PubMed Central

    Girgis, Fady; Pace, Jonathan; Sweet, Jennifer; Miller, Jonathan P.

    2016-01-01

    Traumatic brain injury (TBI) is the leading cause of death and disability in individuals below age 45, and five million Americans live with chronic disability as a result. Mild TBI (mTBI), defined as TBI in the absence of major imaging or histopathological defects, is responsible for a majority of cases. Despite the lack of overt morphological defects, victims of mTBI frequently suffer lasting cognitive deficits, memory difficulties, and behavioral disturbances. There is increasing evidence that cognitive and memory dysfunction is related to subtle physiological changes that occur in the hippocampus, and these impact both the phenotype of deficits observed and subsequent recovery. Therapeutic modulation of physiological activity by means of medications commonly used for other indications or brain stimulation may represent novel treatment approaches. This review summarizes the present body of knowledge regarding neurophysiologic changes that occur in the hippocampus after mTBI, as well as potential targets for therapeutic modulation of neurologic activity. PMID:26903824

  15. Traumatic Brain Injury and Olfaction: A Systematic Review

    PubMed Central

    Schofield, Peter William; Moore, Tammie Maree; Gardner, Andrew

    2014-01-01

    Traumatic brain injury (TBI) is a common condition that is often complicated by neuropsychiatric sequelae that can have major impacts on function and quality of life. An alteration in the sense of smell is recognized as a relatively common complication of TBI; however in clinical practice, this complication may not be sought or adequately characterized. We conducted a systematic review of studies concerned with olfactory functioning following TBI. Our predetermined criteria led to the identification of 25 studies published in English, which we examined in detail. We have tabulated the data from these studies in eight separate tables, beginning with Table 1, which highlights each study’s key findings, and we provide a summary/synthesis of the findings in the accompanying results and discussion sections. Despite widely differing methodologies, the studies attest to a high frequency of post-TBI olfactory dysfunction and indicate that its presence can serve as a potential marker of additional structural or functional morbidities. PMID:24478752

  16. Effect of Preferred Music on Agitation After Traumatic Brain Injury.

    PubMed

    Park, Soohyun; Williams, Reg Arthur; Lee, Donghyun

    2016-04-01

    Agitation is a common behavioral problem after traumatic brain injury (TBI), which threatens the safety of patients and caregivers and disrupts the rehabilitation process. This study aimed to evaluate the effects of a preferred music intervention on the reduction of agitation in TBI patients and to compare the effects of preferred music with those of classical "relaxation" music. A single group, within-subjects, randomized crossover trial design was formed, consisting of 14 agitated patients with cognitive impairment after severe TBI. Patients listened to preferred music and classical "relaxation" music, with a wash-out period in between. Patients listening to the preferred music reported a significantly greater reduction in agitation compared with the effect seen during the classical "relaxation" music intervention (p = .046). These findings provide preliminary evidence that the preferred music intervention may be effective as an environmental therapeutic approach for reducing agitation after TBI.

  17. Hydroxysafflor yellow A exerts antioxidant effects in a rat model of traumatic brain injury.

    PubMed

    Wang, Yang; Zhang, Chunhu; Peng, Weijun; Xia, Zian; Gan, Pingping; Huang, Wei; Shi, Yafei; Fan, Rong

    2016-10-01

    Free radical-induced oxidative damage occurs rapidly and is of primary importance during the secondary pathophysiological cascades of traumatic brain injury (TBI). Hydroxysafflor yellow A (HSYA) is a constituent of the flower petals of Carthamus tinctorius (safflower) and may represent a potential therapeutic strategy to improve outcomes following TBI. The present study aimed to identify HSYA in the brain tissues of rats exposed to TBI to determine its absorption and to investigate the underlying effects of HSYA on antioxidant enzymes in the brain tissues of TBI rats. To determine the absorption of HSYA for the investigation of the underlying antioxidant effects of HSYA in TBI, the presence of HSYA in the brain tissues of the TBI rats was identified using an ultra performance liquid chromatography‑tandem mass spectrometry method. Subsequently, the state of oxidative stress in the TBI rat model following the administration of HSYA was investigated by determining the levels of antioxidant enzymes, including superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT), and the ratio of glutathione (GSH)/glutathione disulfide (GSSG). The data obtained demonstrated that HSYA was absorbed in the brain tissues of the TBI rats. HSYA increased the activities of SOD and CAT, the level of GSH and the GSH/GSSG ratio. However, HSYA concomitantly decreased the levels of MDA and GSSG. These preliminary data suggest that HSYA has the potential to be utilized as a neuroprotective drug in cases of TBI. PMID:27599591

  18. Hydroxysafflor yellow A exerts antioxidant effects in a rat model of traumatic brain injury

    PubMed Central

    Wang, Yang; Zhang, Chunhu; Peng, Weijun; Xia, Zian; Gan, Pingping; Huang, Wei; Shi, Yafei; Fan, Rong

    2016-01-01

    Free radical-induced oxidative damage occurs rapidly and is of primary importance during the secondary pathophysiological cascades of traumatic brain injury (TBI). Hydroxysafflor yellow A (HSYA) is a constituent of the flower petals of Carthamus tinctorius (safflower) and may represent a potential therapeutic strategy to improve outcomes following TBI. The present study aimed to identify HSYA in the brain tissues of rats exposed to TBI to determine its absorption and to investigate the underlying effects of HSYA on antioxidant enzymes in the brain tissues of TBI rats. To determine the absorption of HSYA for the investigation of the underlying antioxidant effects of HSYA in TBI, the presence of HSYA in the brain tissues of the TBI rats was identified using an ultra performance liquid chromatography-tandem mass spectrometry method. Subsequently, the state of oxidative stress in the TBI rat model following the administration of HSYA was investigated by determining the levels of antioxidant enzymes, including superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT), and the ratio of glutathione (GSH)/glutathione disulfide (GSSG). The data obtained demonstrated that HSYA was absorbed in the brain tissues of the TBI rats. HSYA increased the activities of SOD and CAT, the level of GSH and the GSH/GSSG ratio. However, HSYA concomitantly decreased the levels of MDA and GSSG. These preliminary data suggest that HSYA has the potential to be utilized as a neuroprotective drug in cases of TBI. PMID:27599591

  19. Pediatric Traumatic Brain Injury.

    PubMed

    Schaller, Alexandra L; Lakhani, Saquib A; Hsu, Benson S

    2015-10-01

    The purpose of this article is to provide a better understanding of pediatric traumatic brain injury and its management. Within the pediatric age group, ages 1 to 19, injuries are the number one cause of death with traumatic brain injury being involved in almost 50 percent of these cases. This, along with the fact that the medical system spends over $1 billion annually on pediatric traumatic brain injury, makes this issue both timely and relevant to health care providers. Over the course of this article the epidemiology, physiology, pathophysiology, and treatment of pediatric traumatic brain injury will be explored. Emphasis will be placed on the role of the early responder and the immediate interventions that should be considered and/or performed. The management discussed in this article follows the most recent recommendations from the 2012 edition of the Guidelines for the Acute Medical Management of Severe Traumatic Brain Injury in Infants, Children, and Adolescents. Despite the focus of this article, it is important not to lose sight of the fact that an ounce of prevention is worth a pound--or, to be more precise and use the average human's brain measurements, just above three pounds--of cure. PMID:26630835

  20. Top-cited articles in traumatic brain injury.

    PubMed

    Sharma, Bhanu; Lawrence, David Wyndham

    2014-01-01

    A review of the top-cited articles in a scientific discipline can identify areas of research that are well established and those in need of further development, and may, as a result, inform and direct future research efforts. Our objective was to identify and characterize the top-cited articles in traumatic brain injury (TBI). We used publically available software to identify the 50 TBI articles with the most lifetime citations, and the 50 TBI articles with the highest annual citation rates. A total of 73 articles were included in this review, with 27 of the 50 papers with the highest annual citation rates common to the cohort of 50 articles with the most lifetime citations. All papers were categorized by their primary topic or focus, namely: predictor of outcome, pathology/natural history, treatment, guidelines and consensus statements, epidemiology, assessment measures, or experimental model of TBI. The mean year of publication of the articles with the most lifetime citations and highest annual citation rates was 1990 ± 14.9 years and 2003 ± 6.7 years, respectively. The 50 articles with the most lifetime citations typically studied predictors of outcome (34.0%, 17/50) and were specific to severe TBI (38.0%, 19/50). In contrast, the most common subject of papers with the highest annual citation rates was treatment of brain injury (22.0%, 11/50), and these papers most frequently investigated mild TBI (36.0%, 18/50). These findings suggest an intensified focus on mild TBI, which is perhaps a response to the dedicated attention these injuries are currently receiving in the context of sports and war, and because of their increasing incidence in developing nations. Our findings also indicate increased focus on treatment of TBI, possibly due to the limited efficacy of current interventions for brain injury. This review provides a cross-sectional summary of some of the most influential articles in TBI, and a bibliometric examination of the current status of

  1. Influence of Post-Traumatic Stress Disorder on Neuroinflammation and Cell Proliferation in a Rat Model of Traumatic Brain Injury

    PubMed Central

    Diamond, David M.; Shinozuka, Kazutaka; Ishikawa, Hiroto; Hernandez, Diana G.; Sanberg, Paul R.; Kaneko, Yuji; Borlongan, Cesar V.

    2013-01-01

    Long-term consequences of traumatic brain injury (TBI) are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD), yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long-term inflammation and suppressed

  2. The Family Environment as a Moderator of Psychosocial Outcomes Following Traumatic Brain Injury in Young Children

    PubMed Central

    Yeates, Keith Owen; Taylor, H. Gerry; Walz, Nicolay Chertkoff; Stancin, Terry; Wade, Shari L.

    2010-01-01

    Objective This study sought to determine whether the family environment moderates psychosocial outcomes after traumatic brain injury (TBI) in young children. Method Participants were recruited prospectively from consecutive hospital admissions of 3-6 year old children, and included 19 with severe TBI, 56 with complicated mild/moderate TBI, and 99 with orthopedic injuries (OI). They completed four assessments across the first 18 months post-injury. The initial assessment included measures of parenting style, family functioning, and the quality of the home. Children’s behavioral adjustment, adaptive functioning, and social competence were assessed at each occasion. Mixed model analyses examined the relationship of the family environment to psychosocial outcomes across time. Results The OI and TBI groups differed significantly in social competence, but the family environment did not moderate the group difference, which was of medium magnitude. In contrast, group differences in behavioral adjustment became more pronounced across time at high levels of authoritarian and permissive parenting; among children with severe TBI, however, even those with low levels of permissive parenting showed increases in behavioral problems. For adaptive functioning, better home environments provided some protection following TBI, but not over time for the severe TBI group. These three-way interactions of group, family environment, and time post injury were all of medium magnitude. Conclusions The findings indicate that the family environment moderates the psychosocial outcomes of TBI in young children, but the moderating influence may wane with time among children with severe TBI. PMID:20438212

  3. OCT imaging of acute vascular changes following mild traumatic brain injury in mice (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Chico-Calero, Isabel; Shishkov, Milen; Welt, Jonathan; Blatter, Cedric; Vakoc, Benjamin J.

    2016-03-01

    While most people recover completely from mild traumatic brain injuries (mTBIs) and concussions, a subset develop lasting neurological disorders. Understanding the complex pathophysiology of these injuries is critical to developing improved prognostic and therapeutic approaches. Multiple studies have shown that the structure and perfusion of brain vessels are altered after mTBI. It is possible that these vascular injuries contribute to or trigger neurodegeneration. Intravital microscopy and mouse models of TBI offer a powerful platform to study the vascular component of mTBI. Because optical coherence tomography based angiography is based on perfusion contrast and is not significantly degraded by vessel leakage or blood brain barrier disruption, it is uniquely suited to studies of brain perfusion in the setting of trauma. However, existing TBI imaging models require surgical exposure of the brain at the time of injury which conflates TBI-related vascular changes with those caused by surgery. In this work, we describe a modified cranial window preparation based on a flexible, transparent polyurethane membrane. Impact injuries were delivered directly through this membrane, and imaging was performed immediately after injury without the need for additional surgical procedures. Using this model, we demonstrate that mTBI induces a transient cessation of flow in the capillaries and smaller vessels near the injury point. Reperfusion is observed in all animals within 3 hours of injury. This work describes new insight into the transient vascular changes induced by mTBI, and demonstrates more broadly the utility of the OCT/polyurethane window model platform in preclinical studies of mTBI.

  4. Post-traumatic stress disorder and traumatic brain injury.

    PubMed

    Motzkin, Julian C; Koenigs, Michael R

    2015-01-01

    Disentangling the effects of "organic" neurologic damage and psychological distress after a traumatic brain injury poses a significant challenge to researchers and clinicians. Establishing a link between traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) has been particularly contentious, reflecting difficulties in establishing a unique diagnosis for conditions with overlapping and sometimes contradictory symptom profiles. However, each disorder is linked to a variety of adverse health outcomes, underscoring the need to better understand how neurologic and psychiatric risk factors interact following trauma. Here, we present data showing that individuals with a TBI are more likely to develop PTSD, and that individuals with PTSD are more likely to develop persistent cognitive sequelae related to TBI. Further, we describe neurobiological models of PTSD, highlighting how patterns of neurologic damage typical in TBI may promote or protect against the development of PTSD in brain-injured populations. These data highlight the unique course of PTSD following a TBI and have important diagnostic, prognostic, and treatment implications for individuals with a dual diagnosis.

  5. Advances in imaging explosive blast mild traumatic brain injury.

    PubMed

    Hetherington, H; Bandak, A; Ling, G; Bandak, F A

    2015-01-01

    In the past, direct physical evidence of mild traumatic brain injury (mTBI) from explosive blast has been difficult to obtain through conventional imaging modalities such as T1- and T2-weighted magnetic resonance imaging (MRI) and computed tomography (CT). Here, we review current progress in detecting evidence of brain injury from explosive blast using advanced imaging, including diffusion tensor imaging (DTI), functional MRI (fMRI), and the metabolic imaging methods such as positron emission tomography (PET) and magnetic resonance spectroscopic imaging (MRSI), where each targets different aspects of the pathology involved in mTBI. DTI provides a highly sensitive measure to detect primary changes in the microstructure of white matter tracts. fMRI enables the measurement of changes in brain activity in response to different stimuli or tasks. Remarkably, all three of these paradigms have found significant success in conventional mTBI where conventional clinical imaging frequently fails to provide definitive differences. Additionally, although used less frequently for conventional mTBI, PET has the potential to characterize a variety of neurotransmitter systems using target agents and will undoubtedly play a larger role, once the basic mechanisms of injury are better understood and techniques to identify the injury are more common. Finally, our MRSI imaging studies, although acquired at much lower spatial resolution, have demonstrated selectivity to different metabolic and physiologic processes, uncovering some of the most profound differences on an individual by individual basis, suggesting the potential for utility in the management of individual patients.

  6. Assessing limb apraxia in traumatic brain injury and spinal cord injury

    PubMed Central

    McKenna, Cristin; Thakur, Uma; Marcus, Bradley; Barrett, Anna Mariya

    2013-01-01

    People with traumatic brain injury (TBI) may demonstrate action planning disorders and limb apraxia. Many patients, who sustain a spinal cord injury (SCI), sustain a co-occurring TBI (11-29 percent of people with SCI) and therefore are at risk for limb apraxia. People with SCI and TBI (SCI/TBI) rely on powered assistive devices which amplify movement. Their ability to learn complex motor compensatory strategies, that is, limb praxis, is critical to function. We wished to identify methods of screening for apraxia in patients with SCI/TBI. We reviewed instruments available for limb praxis assessment, presenting information on psychometric development, patient groups tested, commercial/clinical availability, and appropriateness for administration to people with motor weakness. Our review revealed that insufficient normative information exists for apraxia assessment in populations comparable to SCI/TBI patients who are typically young adults at the time of injury. There are few apraxia assessment instruments which do not require a motor response. Non-motoric apraxia assessments would be optimal for patients with an underlying motor weakness. PMID:23277082

  7. Neurosensory Symptom Complexes after Acute Mild Traumatic Brain Injury

    PubMed Central

    Szczupak, Mikhaylo; Kiderman, Alexander; Crawford, James; Murphy, Sara; Marshall, Kathryn; Pelusso, Constanza

    2016-01-01

    Mild Traumatic Brain Injury (mTBI) is a prominent public health issue. To date, subjective symptom complaints primarily dictate diagnostic and treatment approaches. As such, the description and qualification of these symptoms in the mTBI patient population is of great value. This manuscript describes the symptoms of mTBI patients as compared to controls in a larger study designed to examine the use of vestibular testing to diagnose mTBI. Five symptom clusters were identified: Post-Traumatic Headache/Migraine, Nausea, Emotional/Affective, Fatigue/Malaise, and Dizziness/Mild Cognitive Impairment. Our analysis indicates that individuals with mTBI have headache, dizziness, and cognitive dysfunction far out of proportion to those without mTBI. In addition, sleep disorders and emotional issues were significantly more common amongst mTBI patients than non-injured individuals. A simple set of questions inquiring about dizziness, headache, and cognitive issues may provide diagnostic accuracy. The consideration of other symptoms may be critical for providing prognostic value and treatment for best short-term outcomes or prevention of long-term complications. PMID:26727256

  8. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    NASA Astrophysics Data System (ADS)

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-06-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.

  9. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    PubMed Central

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-01-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries. PMID:27351915

  10. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries.

    PubMed

    Mann, Aman P; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J; Ruoslahti, Erkki

    2016-01-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries. PMID:27351915

  11. An update on traumatic brain injuries.

    PubMed

    Timmons, S D

    2012-09-01

    Severe traumatic brain injury (TBI) represents a major cause of neurological mortality and morbidity throughout the world. Several challenges have been faced in the conduct of clinical research in TBI in past decades, including inclusion of a broad heterogeneity of injuries, difficulties with standardization and consistency of complex medical management, and lack of sophisticated outcomes measures to sufficiently detect differences in outcomes. Consequently, evidence-based guidelines for targeted therapeutic approaches remain for the most part at the level of Class II or III evidence. Harnessing the power of computing is paramount to our understanding of different prognostic groups in order to devise treatments of the future. Multimodality bedside monitoring of various physiological parameters and events can be deployed in the intensive care unit (ICU) but better data repositories and analytics are required. Recent developments in neuroimaging and definition of potential genetic and biological markers in TBI are also aiding in the sub-categorization of patients into finer diagnostic and prognostic groups. Using mathematical prediction models incorporating the plethora of data gathered, future research will provide means of tailoring therapies to individuals based upon best evidence in populations similar to them, and according to their own biological and physiological situation.

  12. Blood biomarkers for brain injury: What are we measuring?

    PubMed Central

    Kawata, Keisuke; Liu, Charles Y.; Merkel, Steven F.; Ramirez, Servio H.; Tierney, Ryan T.; Langford, Dianne

    2016-01-01

    Accurate diagnosis for mild traumatic brain injury (mTBI) remains challenging, as prognosis and return-to-play/work decisions are based largely on patient reports. Numerous investigations have identified and characterized cellular factors in the blood as potential biomarkers for TBI, in the hope that these factors may be used to gauge the severity of brain injury. None of these potential biomarkers have advanced to use in the clinical setting. Some of the most extensively studied blood biomarkers for TBI include S100β, neuron-specific enolase, glial fibrillary acidic protein, and Tau. Understanding the biological function of each of these factors may be imperative to achieve progress in the field. We address the basic question: what are we measuring? This review will discuss blood biomarkers in terms of cellular origin, normal and pathological function, and possible reasons for increased blood levels. Considerations in the selection, evaluation, and validation of potential biomarkers will also be addressed, along with mechanisms that allow brain-derived proteins to enter the bloodstream after TBI. Lastly, we will highlight perspectives and implications for repetitive neurotrauma in the field of blood biomarkers for brain injury. PMID:27181909

  13. Blood biomarkers for brain injury: What are we measuring?

    PubMed

    Kawata, Keisuke; Liu, Charles Y; Merkel, Steven F; Ramirez, Servio H; Tierney, Ryan T; Langford, Dianne

    2016-09-01

    Accurate diagnosis for mild traumatic brain injury (mTBI) remains challenging, as prognosis and return-to-play/work decisions are based largely on patient reports. Numerous investigations have identified and characterized cellular factors in the blood as potential biomarkers for TBI, in the hope that these factors may be used to gauge the severity of brain injury. None of these potential biomarkers have advanced to use in the clinical setting. Some of the most extensively studied blood biomarkers for TBI include S100β, neuron-specific enolase, glial fibrillary acidic protein, and Tau. Understanding the biological function of each of these factors may be imperative to achieve progress in the field. We address the basic question: what are we measuring? This review will discuss blood biomarkers in terms of cellular origin, normal and pathological function, and possible reasons for increased blood levels. Considerations in the selection, evaluation, and validation of potential biomarkers will also be addressed, along with mechanisms that allow brain-derived proteins to enter the bloodstream after TBI. Lastly, we will highlight perspectives and implications for repetitive neurotrauma in the field of blood biomarkers for brain injury.

  14. Cognitive Improvement after Mild Traumatic Brain Injury Measured with Functional Neuroimaging during the Acute Period.

    PubMed

    Wylie, Glenn R; Freeman, Kalev; Thomas, Alex; Shpaner, Marina; OKeefe, Michael; Watts, Richard; Naylor, Magdalena R

    2015-01-01

    Functional neuroimaging studies in mild traumatic brain injury (mTBI) have been largely limited to patients with persistent post-concussive symptoms, utilizing images obtained months to years after the actual head trauma. We sought to distinguish acute and delayed effects of mild traumatic brain injury on working memory functional brain activation patterns < 72 hours after mild traumatic brain injury (mTBI) and again one-week later. We hypothesized that clinical and fMRI measures of working memory would be abnormal in symptomatic mTBI patients assessed < 72 hours after injury, with most patients showing clinical recovery (i.e., improvement in these measures) within 1 week after the initial assessment. We also hypothesized that increased memory workload at 1 week following injury would expose different cortical activation patterns in mTBI patients with persistent post-concussive symptoms, compared to those with full clinical recovery. We performed a prospective, cohort study of working memory in emergency department patients with isolated head injury and clinical diagnosis of concussion, compared to control subjects (both uninjured volunteers and emergency department patients with extremity injuries and no head trauma). The primary outcome of cognitive recovery was defined as resolution of reported cognitive impairment and quantified by scoring the subject's reported cognitive post-concussive symptoms at 1 week. Secondary outcomes included additional post-concussive symptoms and neurocognitive testing results. We enrolled 46 subjects: 27 with mild TBI and 19 controls. The time of initial neuroimaging was 48 (+22 S.D.) hours after injury (time 1). At follow up (8.7, + 1.2 S.D., days after injury, time 2), 18 of mTBI subjects (64%) reported moderate to complete cognitive recovery, 8 of whom fully recovered between initial and follow-up imaging. fMRI changes from time 1 to time 2 showed an increase in posterior cingulate activation in the mTBI subjects compared to

  15. High-Performance Bioinstrumentation for Real-Time Neuroelectrochemical Traumatic Brain Injury Monitoring

    PubMed Central

    Papadimitriou, Konstantinos I.; Wang, Chu; Rogers, Michelle L.; Gowers, Sally A. N.; Leong, Chi L.; Boutelle, Martyn G.; Drakakis, Emmanuel M.

    2016-01-01

    Traumatic brain injury (TBI) has been identified as an important cause of death and severe disability in all age groups and particularly in children and young adults. Central to TBIs devastation is a delayed secondary injury that occurs in 30–40% of TBI patients each year, while they are in the hospital Intensive Care Unit (ICU). Secondary injuries reduce survival rate after TBI and usually occur within 7 days post-injury. State-of-art monitoring of secondary brain injuries benefits from the acquisition of high-quality and time-aligned electrical data i.e., ElectroCorticoGraphy (ECoG) recorded by means of strip electrodes placed on the brains surface, and neurochemical data obtained via rapid sampling microdialysis and microfluidics-based biosensors measuring brain tissue levels of glucose, lactate and potassium. This article progresses the field of multi-modal monitoring of the injured human brain by presenting the design and realization of a new, compact, medical-grade amperometry, potentiometry and ECoG recording bioinstrumentation. Our combined TBI instrument enables the high-precision, real-time neuroelectrochemical monitoring of TBI patients, who have undergone craniotomy neurosurgery and are treated sedated in the ICU. Electrical and neurochemical test measurements are presented, confirming the high-performance of the reported TBI bioinstrumentation. PMID:27242477

  16. High-Performance Bioinstrumentation for Real-Time Neuroelectrochemical Traumatic Brain Injury Monitoring.

    PubMed

    Papadimitriou, Konstantinos I; Wang, Chu; Rogers, Michelle L; Gowers, Sally A N; Leong, Chi L; Boutelle, Martyn G; Drakakis, Emmanuel M

    2016-01-01

    Traumatic brain injury (TBI) has been identified as an important cause of death and severe disability in all age groups and particularly in children and young adults. Central to TBIs devastation is a delayed secondary injury that occurs in 30-40% of TBI patients each year, while they are in the hospital Intensive Care Unit (ICU). Secondary injuries reduce survival rate after TBI and usually occur within 7 days post-injury. State-of-art monitoring of secondary brain injuries benefits from the acquisition of high-quality and time-aligned electrical data i.e., ElectroCorticoGraphy (ECoG) recorded by means of strip electrodes placed on the brains surface, and neurochemical data obtained via rapid sampling microdialysis and microfluidics-based biosensors measuring brain tissue levels of glucose, lactate and potassium. This article progresses the field of multi-modal monitoring of the injured human brain by presenting the design and realization of a new, compact, medical-grade amperometry, potentiometry and ECoG recording bioinstrumentation. Our combined TBI instrument enables the high-precision, real-time neuroelectrochemical monitoring of TBI patients, who have undergone craniotomy neurosurgery and are treated sedated in the ICU. Electrical and neurochemical test measurements are presented, confirming the high-performance of the reported TBI bioinstrumentation. PMID:27242477

  17. Skull flexure from blast waves: a mechanism for brain injury with implications for helmet design

    SciTech Connect

    Moss, W C; King, M J; Blackman, E G

    2009-04-14

    Traumatic brain injury [TBI] has become a signature injury of current military conflicts. The debilitating effects of TBI are long-lasting and costly. Although the mechanisms by which impacts cause TBI have been well researched, the mechanisms by which blasts cause TBI are not understood. Various possibilities have been investigated, but blast-induced deformation of the skull has been neglected. From numerical hydrodynamic simulations, we have discovered that nonlethal blasts can induce sufficient flexure of the skull to generate potentially damaging loads in the brain, even if no impact occurs. The possibility that this mechanism may contribute to TBI has implications for the diagnosis of soldiers and the design of protective equipment such as helmets.

  18. Traumatic Brain Injury-Induced Ependymal Ciliary Loss Decreases Cerebral Spinal Fluid Flow

    PubMed Central

    Xiong, Guoxiang; Elkind, Jaclynn A.; Kundu, Suhali; Smith, Colin J.; Antunes, Marcelo B.; Tamashiro, Edwin; Kofonow, Jennifer M.; Mitala, Christina. M.; Stein, Sherman C.; Grady, M. Sean; Einhorn, Eugene; Cohen, Noam A.

    2014-01-01

    Abstract Traumatic brain injury (TBI) afflicts up to 2 million people annually in the United States and is the primary cause of death and disability in young adults and children. Previous TBI studies have focused predominantly on the morphological, biochemical, and functional alterations of gray matter structures, such as the hippocampus. However, little attention has been given to the brain ventricular system, despite the fact that altered ventricular function is known to occur in brain pathologies. In the present study, we investigated anatomical and functional alterations to mouse ventricular cilia that result from mild TBI. We demonstrate that TBI causes a dramatic decrease in cilia. Further, using a particle tracking technique, we demonstrate that cerebrospinal fluid flow is diminished, thus potentially negatively affecting waste and nutrient exchange. Interestingly, injury-induced ventricular system pathology resolves completely by 30 days after injury as ependymal cell ciliogenesis restores cilia density to uninjured levels in the affected lateral ventricle. PMID:24749541

  19. Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats.

    PubMed

    Gu, Xiaohuan; Wei, Zheng Zachory; Espinera, Alyssa; Lee, Jin Hwan; Ji, Xiaoya; Wei, Ling; Dix, Thomas A; Yu, Shan Ping

    2015-05-01

    Neonatal brain trauma is linked to higher risks of mortality and neurological disability. The use of mild to moderate hypothermia has shown promising potential against brain injuries induced by stroke and traumatic brain injury (TBI) in various experimental models and in clinical trials. Conventional methods of physical cooling, however, are difficult to use in acute treatments and in induction of regulated hypothermia. In addition, general anesthesia is usually required to mitigate the negative effects of shivering during physical cooling. Our recent investigations demonstrate the potential therapeutic benefits of pharmacologically induced hypothermia (PIH) using the neurotensin receptor (NTR) agonist HPI201 (formerly known as ABS201) in stroke and TBI models of adult rodents. The present investigation explored the brain protective effects of HPI201 in a P14 rat pediatric model of TBI induced by controlled cortical impact. When administered via intraperitoneal (i.p.) injection, HPI201 induced dose-dependent reduction of body and brain temperature. A 6-h hypothermic treatment, providing an overall 2-3°C reduction of brain and body temperature, showed significant effect of attenuating the contusion volume versus TBI controls. Attenuation occurs whether hypothermia is initiated 15min or 2h after TBI. No shivering response was seen in HPI201-treated animals. HPI201 treatment also reduced TUNEL-positive and TUNEL/NeuN-colabeled cells in the contusion area and peri-injury regions. TBI-induced blood-brain barrier damage was attenuated by HPI201 treatment, evaluated using the Evans Blue assay. HPI201 significantly decreased MMP-9 levels and caspase-3 activation, both of which are pro-apototic, while it increased anti-apoptotic Bcl-2 gene expression in the peri-contusion region. In addition, HPI201 prevented the up-regulation of pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. In sensorimotor activity assessments, rats in the HPI201

  20. Pharmacologically Induced Hypothermia Attenuates Traumatic Brain Injury in Neonatal Rats

    PubMed Central

    Espinera, Alyssa; Lee, Jin Hwan; Ji, Xiaoya; Wei, Ling; Dix, Thomas A.; Yu, Shan Ping

    2015-01-01

    Neonatal brain trauma is linked to higher risks of mortality and neurological disability. The use of mild to moderate hypothermia has shown promising potential against brain injuries induced by stroke and traumatic brain injury (TBI) in various experimental models and in clinical trials. Conventional methods of physical cooling, however, are difficult to use in acute treatments and in induction of regulated hypothermia. In addition, general anesthesia is usually required to mitigate the negative effects of shivering during physical cooling. Our recent investigations demonstrate the potential therapeutic benefits of pharmacologically induced hypothermia (PIH) using the neurotensin receptor (NTR) agonist HPI201 (formerly known as ABS201) in stroke and TBI models of adult rodents. The present investigation explored the brain protective effects of HPI201 in a P14 rat pediatric model of TBI induced by controlled cortical impact. When administered via intraperitoneal (i.p.) injection, HPI201 induced dose-dependent reduction of body and brain temperature. A six-hour hypothermic treatment, providing an overall 2-3°C reduction of brain and body temperature, showed significant effect of attenuating the contusion volume versus TBI controls. Attenuation occurs whether hypothermia is initiated 15 min or 2 hr after TBI. No shivering response was seen in HPI201-treated animals. HPI201 treatment also reduced TUNEL-positive and TUNEL/NeuN-colabeled cells in the contusion area and peri-injury regions. TBI-induced blood brain barrier damage was attenuated by HPI201 treatment, evaluated using the Evans Blue assay. HPI201 significantly decreased MMP-9 levels and Caspase-3 activation, both of which are pro-apototic, while it increased anti-apoptotic Bcl-2 gene expression in the peri-contusion region. In addition, HPI201 prevented the up-regulation of pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. In sensorimotor activity assessments, rats in the

  1. Long-term ability to interpret facial expression after traumatic brain injury and its relation to social integration.

    PubMed

    Knox, Lucy; Douglas, Jacinta

    2009-03-01

    There is considerable evidence that individuals with traumatic brain injury (TBI) experience problems interpreting the emotional state of others. However, the functional implications of these changes have not been fully investigated. A study of 13 individuals with severe TBI and an equal number of matched controls found that TBI participants had significantly more difficulty interpreting facial expression and matching emotions to social situations. A significant relationship was also established between social integration and ability to interpret facial expression for TBI participants. These results support the inclusion of therapy targeting this area within rehabilitation programs for individuals with TBI.

  2. Incidence and costs of bicycle-related traumatic brain injuries in the Netherlands.

    PubMed

    Scholten, Annemieke C; Polinder, Suzanne; Panneman, Martien J M; van Beeck, Ed F; Haagsma, Juanita A

    2015-08-01

    The main cause of death and serious disability in bicycle accidents is traumatic brain injury (TBI). The aim of this population-based study was to assess the incidence and costs of bicycle-related TBI across various age groups, and in comparison to all bicycle-related injuries, to identify main risk groups for the development of preventive strategies. Data from the National Injury Surveillance System and National Medical Registration were used for all patients with bicycle-related injuries and TBI who visited a Dutch emergency department (ED) between 1998 and 2012. Demographics and national, weighted estimates of injury mechanism, injury severity and costs were analysed per age group. Direct healthcare costs and indirect costs were determined using the incidence-based Dutch Burden of Injury Model. Between 1998 and 2012, the incidence of ED treatments due to bicycle-related TBI strongly increased with 54%, to 43 per 100,000 persons in 2012. However, the incidence of all bicycle-related injuries remained stable, from 444 in 1998 to 456/100,000 in 2012. Incidence of hospital admission increased in both TBI (92%) and all injuries from cycling (71%). Highest increase in incidence of both ED treatments and hospital admissions was seen in adults aged 55+. The injury rate of TBI per kilometre travelled increased (44%) except in children, but decreased (-4%) for all injuries, showing a strong decrease in children (-36%) but an increase in men aged 25+, and women aged 15+. Total costs of bicycle-related TBI were €74.5 million annually. Although bicycle-related TBI accounted for 9% of the incidence of all ED treatments due to cycling, it accounted for 18% of the total costs due to all bicycle-related injuries (€410.7 million). Children and adolescents (aged 0-24) had highest incidence of ED treatments due to bicycle-related injuries. Men in the working population (aged 15-64) had highest indirect costs following injuries from cycling, including TBI. Older cyclists (aged

  3. Incidence and costs of bicycle-related traumatic brain injuries in the Netherlands.

    PubMed

    Scholten, Annemieke C; Polinder, Suzanne; Panneman, Martien J M; van Beeck, Ed F; Haagsma, Juanita A

    2015-08-01

    The main cause of death and serious disability in bicycle accidents is traumatic brain injury (TBI). The aim of this population-based study was to assess the incidence and costs of bicycle-related TBI across various age groups, and in comparison to all bicycle-related injuries, to identify main risk groups for the development of preventive strategies. Data from the National Injury Surveillance System and National Medical Registration were used for all patients with bicycle-related injuries and TBI who visited a Dutch emergency department (ED) between 1998 and 2012. Demographics and national, weighted estimates of injury mechanism, injury severity and costs were analysed per age group. Direct healthcare costs and indirect costs were determined using the incidence-based Dutch Burden of Injury Model. Between 1998 and 2012, the incidence of ED treatments due to bicycle-related TBI strongly increased with 54%, to 43 per 100,000 persons in 2012. However, the incidence of all bicycle-related injuries remained stable, from 444 in 1998 to 456/100,000 in 2012. Incidence of hospital admission increased in both TBI (92%) and all injuries from cycling (71%). Highest increase in incidence of both ED treatments and hospital admissions was seen in adults aged 55+. The injury rate of TBI per kilometre travelled increased (44%) except in children, but decreased (-4%) for all injuries, showing a strong decrease in children (-36%) but an increase in men aged 25+, and women aged 15+. Total costs of bicycle-related TBI were €74.5 million annually. Although bicycle-related TBI accounted for 9% of the incidence of all ED treatments due to cycling, it accounted for 18% of the total costs due to all bicycle-related injuries (€410.7 million). Children and adolescents (aged 0-24) had highest incidence of ED treatments due to bicycle-related injuries. Men in the working population (aged 15-64) had highest indirect costs following injuries from cycling, including TBI. Older cyclists (aged

  4. The burden of traumatic brain injury among adolescent and young adult workers in Washington State

    PubMed Central

    Graves, Janessa M.; Sears, Jeanne M.; Vavilala, Monica S.; Rivara, Frederick P.

    2012-01-01

    Objective This study describes injury characteristics and costs of work-related traumatic brain injury (WRTBI) among 16–24 year olds in Washington State between 1998 and 2008. Methods WRTBIs were identified in the Washington Trauma Registry (WTR) and linked to workers’ compensation (WC) claims data. Medical and time-loss compensation costs were compared between workers with isolated TBI and TBI with other trauma. Results Of 273 WRTBI cases identified, most (61.5%) were TBI with other trauma. One-third of WRTBI did not link to a WC claim. Medical costs averaged $88,307 (median $16,426) for isolated TBI cases, compared to $73,669 (median $41,167) for TBI with other trauma. Conclusions Results highlight the financial impact of WRTBI among young workers. Multiple data sources provided a more comprehensive picture than a single data source alone. This linked-data approach holds great potential for future traumatic occupational injury research. PMID:23710080

  5. Endogenous Repair Signaling after Brain Injury and Complementary Bioengineering Approaches to Enhance Neural Regeneration

    PubMed Central

    Addington, Caroline P; Roussas, Adam; Dutta, Dipankar; Stabenfeldt, Sarah E

    2015-01-01

    Traumatic brain injury (TBI) affects 5.3 million Americans annually. Despite the many long-term deficits associated with TBI, there currently are no clinically available therapies that directly address the underlying pathologies contributing to these deficits. Preclinical studies have investigated various therapeutic approaches for TBI: two such approaches are stem cell transplantation and delivery of bioactive factors to mitigate the biochemical insult affiliated with TBI. However, success with either of these approaches has been limited largely due to the complexity of the injury microenvironment. As such, this review outlines the many factors of the injury microenvironment that mediate endogenous neural regeneration after TBI and the corresponding bioengineering approaches that harness these inherent signaling mechanisms to further amplify regenerative efforts. PMID:25983552

  6. Contribution of psychological trauma to outcomes after traumatic brain injury: assaults versus sporting injuries.

    PubMed

    Mathias, Jane L; Harman-Smith, Yasmin; Bowden, Stephen C; Rosenfeld, Jeffrey V; Bigler, Erin D

    2014-04-01

    Clinical research into outcomes after traumatic brain injury (TBI) frequently combines injuries that have been sustained through different causes (e.g., car accidents, assaults, and falls), the effect of which is not well understood. This study examined the contribution of injury-related psychological trauma—which is more commonly associated with specific types of injuries—to outcomes after nonpenetrating TBI in order to determine whether it may be having a differential effect in samples containing mixed injuries. Data from three groups that were prospectively recruited for two larger studies were compared: one that sustained a TBI as a result of physical assaults (i.e., psychologically traumatizing) and another as a result of sporting injuries (i.e., nonpsychologically traumatizing), as well as an orthopedic control group (OC). Psychosocial and emotional (postconcussion symptoms, injury-related stress, and depression), cognitive (memory, abstract reasoning, problem solving, and verbal fluency), and functional (general outcome; resumption of home, social, and work roles) outcomes were all assessed. The TBI(assault) group reported significantly poorer psychosocial and emotional outcomes and higher rates of litigation (criminal rather than civil) than both the TBI(sport) and OC groups approximately 6 months postinjury, but there were no differences in the cognitive or functional outcomes of the three groups. The findings suggest that the cause of a TBI may assist in explaining some of the differences in outcomes of people who have seemingly comparable injuries. Involvement in litigation and the cause of an injury may also be confounded, which may lead to the erroneous conclusion that litigants have poorer outcomes.

  7. Barriers to Meeting the Needs of Students with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Canto, Angela I.; Chesire, David J.; Buckley, Valerie A.; Andrews, Terrie W.; Roehrig, Alysia D.

    2014-01-01

    Many students with traumatic brain injury (TBI) are identified by the medical community each year and many more experience head injuries that are not examined by medical personnel. School psychologists and allied consultants have important liaison roles to identify and assist these students post-injury. In this study, 75 school psychologists (the…

  8. Traumatic Brain Injury and Substance Related Disorder: A 10-Year Nationwide Cohort Study in Taiwan

    PubMed Central

    Wu, Chieh-Hsin; Tsai, Tai-Hsin; Zhang, Zi-Hao; Liu, Wei; Wu, Ming-Kung; Chang, Chih-Hui; Kuo, Keng-Liang

    2016-01-01

    Whether traumatic brain injury (TBI) is causally related to substance related disorder (SRD) is still debatable, especially in persons with no history of mental disorders at the time of injury. This study analyzed data in the Taiwan National Health Insurance Research Database for 19,109 patients aged ≥18 years who had been diagnosed with TBI during 2000–2010. An additional 19,109 randomly selected age and gender matched patients without TBI (1 : 1 ratio) were enrolled in the control group. The relationship between TBI and SRD was estimated with Cox proportional hazard regression models. During the follow-up period, SRD developed in 340 patients in the TBI group and in 118 patients in the control group. After controlling for covariates, the overall incidence of SRD was 3.62-fold higher in the TBI group compared to the control group. Additionally, patients in the severe TBI subgroup were 9.01 times more likely to have SRD compared to controls. Notably, patients in the TBI group were prone to alcohol related disorders. The data in this study indicate that TBI is significantly associated with the subsequent risk of SRD. Physicians treating patients with TBI should be alert to this association to prevent the occurrence of adverse events. PMID:27774322

  9. Altered sleep composition after traumatic brain injury does not affect declarative sleep-dependent memory consolidation

    PubMed Central

    Mantua, Janna; Mahan, Keenan M.; Henry, Owen S.; Spencer, Rebecca M. C.

    2015-01-01

    Individuals with a history of traumatic brain injury (TBI) often report sleep disturbances, which may be caused by changes in sleep architecture or reduced sleep quality (greater time awake after sleep onset, poorer sleep efficiency, and sleep stage proportion alterations). Sleep is beneficial for memory formation, and herein we examine whether altered sleep physiology following TBI has deleterious effects on sleep-dependent declarative memory consolidation. Participants learned a list of word pairs in the morning or evening, and recall was assessed 12-h later, following an interval awake or with overnight sleep. Young adult participants (18–22 years) were assigned to one of four experimental groups: TBI Sleep (n = 14), TBI Wake (n = 12), non-TBI Sleep (n = 15), non-TBI Wake (n = 15). Each TBI participant was >1 year post-injury. Sleep physiology was measured with polysomnography. Memory consolidation was assessed by comparing change in word-pair recall over 12-h intersession intervals. The TBI group spent a significantly greater proportion of the night in SWS than the non-TBI group at the expense of NREM1. The TBI group also had marginally lower EEG delta power during SWS in the central region. Intersession changes in recall were greater for intervals with sleep than without sleep in both groups. However, despite abnormal sleep stage proportions for individuals with a TBI history, there was no difference in the intersession change in recall following sleep for the TBI and non-TBI groups. In both Sleep groups combined, there was a positive correlation between Intersession Change and the proportion of the night in NREM2 + SWS. Overall, sleep composition is altered following TBI but such deficits do not yield insufficiencies in sleep-dependent memory consolidation. PMID:26097451

  10. Glibenclamide reduces secondary brain damage after experimental traumatic brain injury.

    PubMed

    Zweckberger, K; Hackenberg, K; Jung, C S; Hertle, D N; Kiening, K L; Unterberg, A W; Sakowitz, O W

    2014-07-11

    Following traumatic brain injury (TBI) SUR1-regulated NCCa-ATP (SUR1/TRPM4) channels are transcriptionally up-regulated in ischemic astrocytes, neurons, and capillaries. ATP depletion results in depolarization and opening of the channel leading to cytotoxic edema. Glibenclamide is an inhibitor of SUR-1 and, thus, might prevent cytotoxic edema and secondary brain damage following TBI. Anesthetized adult Sprague-Dawley rats underwent parietal craniotomy and were subjected to controlled cortical impact injury (CCI). Glibenclamide was administered as a bolus injection 15min after CCI injury and continuously via osmotic pumps throughout 7days. In an acute trial (180min) mean arterial blood pressure, heart rate, intracranial pressure, encephalographic activity, and cerebral metabolism were monitored. Brain water content was assessed gravimetrically 24h after CCI injury and contusion volumes were measured by MRI scanning technique at 8h, 24h, 72h, and 7d post injury. Throughout the entire time of observation neurological function was quantified using the "beam-walking" test. Glibenclamide-treated animals showed a significant reduction in the development of brain tissue water content(80.47%±0.37% (glibenclamide) vs. 80.83%±0.44% (control); p<0.05; n=14). Contusion sizes increased continuously within 72h following CCI injury, but glibenclamide-treated animals had significantly smaller volumes at any time-points, like 172.53±38.74mm(3) (glibenclamide) vs. 299.20±64.02mm(3) (control) (p<0.01; n=10; 24h) or 211.10±41.03mm(3) (glibenclamide) vs. 309.76±19.45mm(3) (control) (p<0.05; n=10; 72h), respectively. An effect on acute parameters, however, could not be detected, most likely because of the up-regulation of the channel within 3-6h after injury. Furthermore, there was no significant effect on motor function assessed by the beam-walking test throughout 7days. In accordance to these results and the available literature, glibenclamide seems to have promising potency in

  11. Neuroimaging and the school-based assessment of traumatic brain injury.

    PubMed

    Jantz, Paul B; Bigler, Erin D

    2014-01-01

    Advanced neuroimaging contributes to a greater understanding of brain pathology following a traumatic brain injury (TBI) and has the ability to guide neurorehabilitation decisions. When integrated with the school-based psychoeducational assessment of a child with a TBI, neuroimaging can provide a different perspective when interpreting educational and behavioral variables relevant to school-based neurorehabilitation. School psychologists conducting traditional psychoeducational assessments of children with TBI seldom obtain and integrate neuroimaging, despite its availability. This article presents contextual information on the medical assessment of TBI, major types of neuroimaging, and networks of the brain. A case study illustrates the value of incorporating neuroimaging into the standard school-based psychoeducational evaluations of children with traumatic brain injury. PMID:24473251

  12. Neuroimaging and the school-based assessment of traumatic brain injury.

    PubMed

    Jantz, Paul B; Bigler, Erin D

    2014-01-01

    Advanced neuroimaging contributes to a greater understanding of brain pathology following a traumatic brain injury (TBI) and has the ability to guide neurorehabilitation decisions. When integrated with the school-based psychoeducational assessment of a child with a TBI, neuroimaging can provide a different perspective when interpreting educational and behavioral variables relevant to school-based neurorehabilitation. School psychologists conducting traditional psychoeducational assessments of children with TBI seldom obtain and integrate neuroimaging, despite its availability. This article presents contextual information on the medical assessment of TBI, major types of neuroimaging, and networks of the brain. A case study illustrates the value of incorporating neuroimaging into the standard school-based psychoeducational evaluations of children with traumatic brain injury.

  13. Longitudinal neuropsychological outcome in infants and preschoolers with traumatic brain injury.

    PubMed

    Ewing-Cobbs, L; Fletcher, J M; Levin, H S; Francis, D J; Davidson, K; Miner, M E

    1997-11-01

    Neuropsychological outcome was evaluated in a prospective, longitudinal follow-up study of children age 4 months to 7 years at injury with either mild-to-moderate (N = 35) or severe (N = 44) traumatic brain injury (TBI). Age-appropriate tests were administered at baseline, 6 months, 12 months, and 24 months after the injury. Performance was compared on (1) Composite IQ and motor, (2) Receptive and expressive language, and (3) Verbal and Perceptual-Performance IQ scores. In comparison to mild-to-moderate TBI, severe TBI in infants and preschoolers produced deficits in all areas. Interactions between task and severity of injury were obtained. Motor scores were lower than IQ scores, particularly after severe TBI. Both receptive and expressive scores were reduced following severe TBI. Expressive language scores were lower than receptive language scores for children sustaining mild-to-moderate TBI. While severe TBI lowered both Verbal and Perceptual-Performance IQ scores, Verbal IQ scores were significantly lower than Perceptual-Performance IQ scores after mild-to-moderate TBI. Mild injuries may produce subtle linguistic changes adversely impacting estimates of Verbal IQ and expressive language. Within the limited age range evaluated within this study, age at injury was unrelated to test scores: The impact of TBI was comparable in children ages 4 to 41 months versus 42 to 72 months at the time of injury. All neuropsychological scores improved significantly from baseline to the 6-month follow-up. However, no further change in scores was observed from 6 to 24 months after the injury. The persistent deficits and lack of catch-up over time suggest a reduction in the rate of acquisition of new skills after severe TBI. Methodological issues in longitudinal studies of young children were discussed. PMID:9448371

  14. Robust whole-brain segmentation: application to traumatic brain injury.

    PubMed

    Ledig, Christian; Heckemann, Rolf A; Hammers, Alexander; Lopez, Juan Carlos; Newcombe, Virginia F J; Makropoulos, Antonios; Lötjönen, Jyrki; Menon, David K; Rueckert, Daniel

    2015-04-01

    We propose a framework for the robust and fully-automatic segmentation of magnetic resonance (MR) brain images called "Multi-Atlas Label Propagation with Expectation-Maximisation based refinement" (MALP-EM). The presented approach is based on a robust registration approach (MAPER), highly performant label fusion (joint label fusion) and intensity-based label refinement using EM. We further adapt this framework to be applicable for the segmentation of brain images with gross changes in anatomy. We propose to account for consistent registration errors by relaxing anatomical priors obtained by multi-atlas propagation and a weighting scheme to locally combine anatomical atlas priors and intensity-refined posterior probabilities. The method is evaluated on a benchmark dataset used in a recent MICCAI segmentation challenge. In this context we show that MALP-EM is competitive for the segmentation of MR brain scans of healthy adults when compared to state-of-the-art automatic labelling techniques. To demonstrate the versatility of the proposed approach, we employed MALP-EM to segment 125 MR brain images into 134 regions from subjects who had sustained traumatic brain injury (TBI). We employ a protocol to assess segmentation quality if no manual reference labels are available. Based on this protocol, three independent, blinded raters confirmed on 13 MR brain scans with pathology that MALP-EM is superior to established label fusion techniques. We visually confirm the robustness of our segmentation approach on the full cohort and investigate the potential of derived symmetry-based imaging biomarkers that correlate with and predict clinically relevant variables in TBI such as the Marshall Classification (MC) or Glasgow Outcome Score (GOS). Specifically, we show that we are able to stratify TBI patients with favourable outcomes from non-favourable outcomes with 64.7% accuracy using acute-phase MR images and 66.8% accuracy using follow-up MR images. Furthermore, we are able to

  15. Socio Economic Status and Traumatic Brain Injury amongst Pediatric Populations: A Spatial Analysis in Greater Vancouver

    PubMed Central

    Amram, Ofer; Schuurman, Nadine; Pike, Ian; Yanchar, Natalie L; Friger, Michael; McBeth, Paul B.; Griesdale, Donald

    2015-01-01

    Introduction: Within Canada, injuries are the leading cause of death amongst children fourteen years of age and younger, and also one of the leading causes of morbidity. Low Socio Economic Status (SES) seems to be a strong indicator of a higher prevalence of injuries. This study aims to identify hotspots for pediatric Traumatic Brain Injury (TBI) and examines the relationship between SES and pediatric TBI rates in greater Vancouver, British Columbia (BC), Canada. Methods: Pediatric TBI data from the BC Trauma Registry (BCTR) was used to identify all pediatric TBI patients admitted to BC hospitals between the years 2000 and 2013. Spatial analysis was used to identify hotspots for pediatric TBI. Multivariate analysis was used to distinguish census variables that were correlated with rates of injury. Results: Six hundred and fifty three severe pediatric TBI injuries occurred within the BC Lower Mainland between 2000 and 2013. High rates of injury were concentrated in the East, while low rate clusters were most common in the West of the region (more affluent neighborhoods). A low level of education was the main predictor of a high rate of injury (OR = 1.13, 95% CI = 1.03–1.23, p-Value 0.009). Conclusion: While there was a clear relationship between different SES indicators and pediatric TBI rates in greater Vancouver, income-based SES indicators did not serve as good predictors within this region. PMID:26670241

  16. Phosphodiesterase Inhibition Rescues Chronic Cognitive Deficits Induced by Traumatic Brain Injury

    PubMed Central

    Titus, David J.; Sakurai, Atsushi; Kang, Yuan; Furones, Concepcion; Jergova, Stanislava; Santos, Rosmery; Sick, Thomas J.; Atkins, Coleen M.

    2013-01-01

    Traumatic brain injury (TBI) modulates several cell signaling pathways in the hippocampus critical for memory formation. Previous studies have found that the cAMP-protein kinase A signaling pathway is downregulated after TBI and that treatment with a phosphodiesterase (PDE) 4 inhibitor rolipram rescues the decrease in cAMP. In the present study, we examined the effect of rolipram on TBI-induced cognitive impairments. At 2 weeks after moderate fluid-percussion brain injury or sham surgery, adult male Sprague Dawley rats received vehicle or rolipram (0.03 mg/kg) 30 min before water maze acquisition or cue and contextual fear conditioning. TBI animals treated with rolipram showed a significant improvement in water maze acquisition and retention of both cue and contextual fear conditioning compared with vehicle-treated TBI animals. Cue and contextual fear conditioning significantly increased phosphorylated CREB levels in the hippocampus of sham animals, but not in TBI animals. This deficit in CREB activation during learning was rescued in TBI animals treated with rolipram. Hippocampal long-term potentiation was reduced in TBI animals, and this was also rescued with rolipram treatment. These results indicate that the PDE4 inhibitor rolipram rescues cognitive impairments after TBI, and this may be mediated through increased CREB activation during learning. PMID:23516287

  17. Tensor-Based Morphometry Reveals Volumetric Deficits in Moderate=Severe Pediatric Traumatic Brain Injury

    PubMed Central

    Hua, Xue; Villalon-Reina, Julio; Moran, Lisa M.; Kernan, Claudia; Babikian, Talin; Mink, Richard; Babbitt, Christopher; Johnson, Jeffrey; Giza, Christopher C.; Thompson, Paul M.; Asarnow, Robert F.

    2016-01-01

    Abstract Traumatic brain injury (TBI) can cause widespread and prolonged brain degeneration. TBI can affect cognitive function and brain integrity for many years after injury, often with lasting effects in children, whose brains are still immature. Although TBI varies in how it affects different individuals, image analysis methods such as tensor-based morphometry (TBM) can reveal common areas of brain atrophy on magnetic resonance imaging (MRI), secondary effects of the initial injury, which will differ between subjects. Here we studied 36 pediatric moderate to severe TBI (msTBI) participants in the post-acute phase (1–6 months post-injury) and 18 msTBI participants who returned for their chronic assessment, along with well-matched controls at both time-points. Participants completed a battery of cognitive tests that we used to create a global cognitive performance score. Using TBM, we created three-dimensional (3D) maps of individual and group differences in regional brain volumes. At both the post-acute and chronic time-points, the greatest group differences were expansion of the lateral ventricles and reduction of the lingual gyrus in the TBI group. We found a number of smaller clusters of volume reduction in the cingulate gyrus, thalamus, and fusiform gyrus, and throughout the frontal, temporal, and parietal cortices. Additionally, we found extensive associations between our cognitive performance measure and regional brain volume. Our results indicate a pattern of atrophy still detectable 1-year post-injury, which may partially underlie the cognitive deficits frequently found in TBI. PMID:26393494

  18. Clinical utility of brain stimulation modalities following traumatic brain injury: current evidence

    PubMed Central

    Li, Shasha; Zaninotto, Ana Luiza; Neville, Iuri Santana; Paiva, Wellingson Silva; Nunn, Danuza; Fregni, Felipe

    2015-01-01

    Traumatic brain injury (TBI) remains the main cause of disability and a major public health problem worldwide. This review focuses on the neurophysiology of TBI, and the rationale and current state of evidence of clinical application of brain stimulation to promote TBI recovery, particularly on consciousness, cognitive function, motor impairments, and psychiatric conditions. We discuss the mechanisms of different brain stimulation techniques including major noninvasive and invasive stimulations. Thus far, most noninvasive brain stimulation interventions have been nontargeted and focused on the chronic phase of recovery after TBI. In the acute stages, there is limited available evidence of the efficacy and safety of brain stimulation to improve functional outcomes. Comparing the studies across different techniques, transcranial direct current stimulation is the intervention that currently has the higher number of properly designed clinical trials, though total number is still small. We recognize the need for larger studies with target neuroplasticity modulation to fully explore the benefits of brain stimulation to effect TBI recovery during different stages of recovery. PMID:26170670

  19. A model of personality change after traumatic brain injury and the development of the Brain Injury Personality Scales

    PubMed Central

    Obonsawin, M C; Jefferis, S; Lowe, R; Crawford, J R; Fernandes, J; Holland, L; Woldt, K; Worthington, E; Bowie, G

    2007-01-01

    Objective The aims of this study were to develop models of personality change after traumatic brain injury (TBI) based on information provided by the TBI survivor and a significant other (SO), and to compare the models generated from the two different sources of information. Methods Individuals with and without TBI and an SO were interviewed separately about their current personality. The SOs were also interviewed about the personality of the TBI survivor before the injury. A subset of TBI survivors and their SOs were interviewed twice to assess test–retest reliability. Items which were not associated with personality change after TBI, which could not be measured reliably or which did not contribute to the model, were excluded. Results Of the 123 original items, 29 items from the interview with the survivor and 31 items from the interview with the SO were retained to form the Brain Injury Personality Scales. Separate factor analyses of ratings from each interview (survivor and SO) resulted in seven first order factors. The second order factor analyses for each interview resulted in four factors. Concordance between the information obtained from the two interviews was low. Conclusions The information obtained from the interviews with the TBI survivors and the SOs produced two models with a similar structure: three superordinate factors of personality items (affective regulation, behavioural regulation and engagement) and one superordinate factor of items relevant to mental state (restlessness and range of thought). Despite the similarity in structure, the content of the information obtained from the two interviews was different. PMID:17259352

  20. Structural Neuroimaging Findings in Mild Traumatic Brain Injury.

    PubMed

    Bigler, Erin D; Abildskov, Tracy J; Goodrich-Hunsaker, Naomi J; Black, Garrett; Christensen, Zachary P; Huff, Trevor; Wood, Dawn-Marie G; Hesselink, John R; Wilde, Elisabeth A; Max, Jeffrey E

    2016-09-01

    Common neuroimaging findings in mild traumatic brain injury (mTBI), including sport-related concussion (SRC), are reviewed based on computed tomography and magnetic resonance imaging (MRI). Common abnormalities radiologically identified on the day of injury, typically a computed tomographic scan, are in the form of contusions, small subarachnoid or intraparenchymal hemorrhages as well as subdural and epidural collections, edema, and skull fractures. Common follow-up neuroimaging findings with MRI include white matter hyperintensities, hypointense signal abnormalities that reflect prior hemorrhage, focal encephalomalacia, presence of atrophy and/or dilated Virchow-Robins perivascular space. The MRI findings from a large pediatric mTBI study show low frequency of positive MRI findings at 6 months postinjury. The review concludes with an examination of some of the advanced MRI-based image analysis methods that can be performed in the patient who has sustained an mTBI. PMID:27482782

  1. Structural Neuroimaging Findings in Mild Traumatic Brain Injury.

    PubMed

    Bigler, Erin D; Abildskov, Tracy J; Goodrich-Hunsaker, Naomi J; Black, Garrett; Christensen, Zachary P; Huff, Trevor; Wood, Dawn-Marie G; Hesselink, John R; Wilde, Elisabeth A; Max, Jeffrey E

    2016-09-01

    Common neuroimaging findings in mild traumatic brain injury (mTBI), including sport-related concussion (SRC), are reviewed based on computed tomography and magnetic resonance imaging (MRI). Common abnormalities radiologically identified on the day of injury, typically a computed tomographic scan, are in the form of contusions, small subarachnoid or intraparenchymal hemorrhages as well as subdural and epidural collections, edema, and skull fractures. Common follow-up neuroimaging findings with MRI include white matter hyperintensities, hypointense signal abnormalities that reflect prior hemorrhage, focal encephalomalacia, presence of atrophy and/or dilated Virchow-Robins perivascular space. The MRI findings from a large pediatric mTBI study show low frequency of positive MRI findings at 6 months postinjury. The review concludes with an examination of some of the advanced MRI-based image analysis methods that can be performed in the patient who has sustained an mTBI.

  2. Hypnotics use but not insomnia increased the risk of dementia in traumatic brain injury patients.

    PubMed

    Chiu, Hsiao-Yean; Lin, En-Yuan; Wei, Li; Lin, Jiann-Her; Lee, Hsin-Chien; Fan, Yen-Chun; Tsai, Pei-Shan

    2015-12-01

    This study was intended to determine whether the use of hypnotics is associated with dementia in traumatic-brain-injury (TBI) patients. Data retrieved from the Longitudinal Health Insurance Database 2000. TBI patients who received a diagnosis of insomnia at 2 or more independent examinations after the index date of TBI were included. The comparison cohort consisted of randomly selected TBI patients who were matched to insomnia cohort patients based on sex and age. The 2 cohorts of TBI patients were subsequently divided into the following 4 study groups: hypnotics users with insomnia (TBI-IH, N=599), insomniacs who did not use hypnotics (TBI-I, N=931), hypnotics users without insomnia (TBI-H, N=199), and people without insomnia who did not use hypnotics (TBI-C, N=4271). Cox proportional-hazards regression models were used to determine the difference in dementia-free survival among the 4 study groups, after adjusting for the propensity score. The adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of the TBI-IH and TBI-H groups showed that they had a higher risk of dementia (aHRs: 1.86 and 3.98; 95% CIs: 1.15-3.00 and 2.44-6.47, respectively), compared with that of the TBI-C group. However, the risk of dementia in the TBI-I group was not significantly different from that of the TBI-C group (aHR: 1.36; 95% CI: 0.85-2.19). This study suggests that the use of hypnotics is associated with an increased risk of dementia in TBI patients with or without insomnia, whereas insomnia alone is not.

  3. Methamphetamine potentiates behavioral and electrochemical responses after mild traumatic brain injury in mice.

    PubMed

    Shen, Hui; Harvey, Brandon K; Chiang, Yung-Hsiao; Pick, Chaim G; Wang, Yun

    2011-01-12

    We previously demonstrated that high doses of methamphetamine (MA) exacerbate damage induced by severe brain trauma. The purpose of the present study was to examine if MA, at low dosage, affected abnormalities in locomotor activity and dopamine turnover in a mouse model of mild traumatic brain injury (mTBI). Adult male CD1 mice were treated with MA (5 mg/kgi.p.) or vehicle 30-min prior to mTBI, conducted by dropping a 30 g metal weight onto the temporal skull, anterior the right ear. At 15 min after mTBI, animals were put into locomotor activity chambers for up to 72 h. During the first 3 h, mTBI alone, compared with vehicle control, did not alter total distance travelled. Treatment with MA significantly increased locomotor activity in the control animals during the first 3 h; mTBI reduced MA-induced hyperactivity. In contrast, at 2 and 3 days after injury, mTBI or MA alone reduced locomotor activity. Co-treatment with MA and mTBI further reduced this activity, suggesting a differential and temporal behavioral interaction between MA and mTBI during acute and subacute phases after injury. Dopamine and DOPAC levels in striatal tissue were analyzed using HPLC-ECD. At 1h after mTBI or injection, DA was not altered but DOPAC level and DOPAC/DA turnover ratios were significantly reduced. Co-treatment with MA further reduced the DOPAC/DA ratio. At 36 h after injury, mTBI increased tissue DA levels, but reduced DOPAC levels and DOPAC/DA ratios. Co-treatment with MA further reduced DOPAC/DA ratios in striatum. In conclusion, our data suggest that low dosage of MA worsens the suppression of locomotor responses and striatal dopamine turnover after mTBI.

  4. Brain Injury Impairs Working Memory and Prefrontal Circuit Function

    PubMed Central

    Smith, Colin J.; Xiong, Guoxiang; Elkind, Jaclynn A.; Putnam, Brendan; Cohen, Akiva S.

    2015-01-01

    More than 2.5 million Americans suffer a traumatic brain injury (TBI) each year. Even mild to moderate TBI causes long-lasting neurological effects. Despite its prevalence, no therapy currently exists to treat the underlying cause of cognitive impairment suffered by TBI patients. Following lateral fluid percussion injury (LFPI), the most widely used experimental model of TBI, we investigated alterations in working memory and excitatory/inhibitory synaptic balance in the prefrontal cortex. LFPI impaired working memory as assessed with a T-maze behavioral task. Field excitatory postsynaptic potentials recorded in the prefrontal cortex were reduced in slices derived from brain-injured mice. Spontaneous and miniature excitatory postsynaptic currents onto layer 2/3 neurons were more frequent in slices derived from LFPI mice, while inhibitory currents onto layer 2/3 neurons were smaller after LFPI. Additionally, an increase in action potential threshold and concomitant decrease in firing rate was observed in layer 2/3 neurons in slices from injured animals. Conversely, no differences in excitatory or inhibitory synaptic transmission onto layer 5 neurons were observed; however, layer 5 neurons demonstrated a decrease in input resistance and action potential duration after LFPI. These results demonstrate synaptic and intrinsic alterations in prefrontal circuitry that may underlie working memory impairment caused by TBI. PMID:26617569

  5. Cognitive and psychopathological sequelae of pediatric traumatic brain injury.

    PubMed

    Beauchamp, M H; Anderson, V

    2013-01-01

    Childhood traumatic brain injury (TBI) is a frequent cause of acquired disability in childhood and can have a serious impact on development across the lifespan. The consequences of early TBI vary according to injury severity, with severe injuries usually resulting in more serious physical, cognitive and behavioral sequelae. Both clinical and research reports document residual deficits in a range of skills, including intellectual function, attention, memory, learning, and executive function. In addition, recent investigations suggest that early brain injury also affects psychological and social development and that problems in these domains may increase in the long term postinjury. Together, these deficits affect children's ability to function effectively at school, in the home, and in their social environment, resulting in impaired acquisition of knowledge, psychological and social problems, and overall reduced quality of life. Ultimately, recovery from childhood TBI depends on a range of complex biological, developmental, and psychosocial factors making prognosis difficult to predict. This chapter will detail the cognitive (intellectual, attentional, mnesic, executive, educational, and vocational) and psychopathological (behavioral, adaptive, psychological, social) sequelae of childhood TBI with a particular focus on postinjury recovery patterns in the acute, short-, and long-term phases, as well as into adulthood. PMID:23622301

  6. Neuroprotective measures in children with traumatic brain injury.

    PubMed

    Agrawal, Shruti; Branco, Ricardo Garcia

    2016-02-01

    Traumatic brain injury (TBI) is a major cause of death and disability in children. Severe TBI is a leading cause of death and often leads to life changing disabilities in survivors. The modern management of severe TBI in children on intensive care unit focuses on preventing secondary brain injury to improve outcome. Standard neuroprotective measures are based on management of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) to optimize the cerebral blood flow and oxygenation, with the intention to avoid and minimise secondary brain injury. In this article, we review the current trends in management of severe TBI in children, detailing the general and specific measures followed to achieve the desired ICP and CPP goals. We discuss the often limited evidence for these therapeutic interventions in children, extrapolation of data from adults, and current recommendation from paediatric guidelines. We also review the recent advances in understanding the intracranial physiology and neuroprotective therapies, the current research focus on advanced and multi-modal neuromonitoring, and potential new therapeutic and prognostic targets. PMID:26855892

  7. Injury of the Arcuate Fasciculus in the Dominant Hemisphere in Patients With Mild Traumatic Brain Injury

    PubMed Central

    Jang, Sung Ho; Lee, Ah Young; Shin, So Min

    2016-01-01

    Abstract Little is known about injury of the arcuate fasciculus (AF) in patients with mild traumatic brain injury (TBI). We investigated injury of the AF in the dominant hemisphere in patients with mild TBI, using diffusion tensor tractography (DTT). We recruited 25 patients with injury of the left AF among 64 right-handed consecutive patients with mild TBI and 20 normal control subjects. DTTs of the left AF were reconstructed, and fractional anisotropy (FA), apparent diffusion coefficient (ADC), and fiber number of the AF were measured. Among 64 consecutive patients, 25 (39%) patients showed injury of the left AF. The patient group showed lower FA value and fiber number with higher ADC value than the control group (P < 0.05). On K-WAB evaluation, aphasia quotient and language quotient were 95.9 ± 4.1 (range 85–100) and 95.0 ± 5.4 (range 80–100), respectively. However, 23 (92.0%) of 25 patients complained of language-related symptoms after TBI; paraphasia in 12 (48.0%) patients, deficits of comprehension in 4 (16.0%) patients, deficits of speech production in 1 (4.0%) patient, and >2 language symptoms in 6 (24.0%) patients. We found that a significant number (39%) of patients with mild TBI had injury of the AF in the dominant hemisphere and these patients had mild language deficit. These results suggest that DTT could provide useful information in detecting injury of the AF and evaluation of the AF using DTT would be necessary even in the case of a patient with mild TBI who complains of mild language deficit. PMID:26945425

  8. Visual performance and the ocular surface in traumatic brain injury.

    PubMed

    Cockerham, Glenn C; Lemke, Sonne; Glynn-Milley, Catherine; Zumhagen, Lars; Cockerham, Kimberly P

    2013-01-01

    The pathophysiology of neurotrauma is reviewed and an original study investigating the prevalence of dry eye disease in a sample of veterans with traumatic brain injury (TBI) is presented. Fifty-three veterans with TBI were evaluated by history of injury, past ocular history, and medication use. Ocular Disease Surface Index (OSDI), ocular examination, cranial nerve evaluation, tear osmolarity, tear film break-up time (TFBUT), ocular surface staining and tear production testing were performed. A matched comparison group underwent similar testing. TBI causes were blast (44) or non-blast (9). TBI subjects scored significantly worse on the OSDI (P<.001), and ocular surface staining by Oxford scale (P<.001) than non-TBI subjects. Scores for tear film breakup (P=.6), basal tear production less than 3 mm (P=.13), and tear osmolarity greater than 314 mOsm/L (P=.15) were all higher in TBI subjects; significantly more TBI subjects had at least one abnormal dry eye measure than comparisons (P<.001). The OSDI related to presence of dry eye symptoms (P<.01). These effects were present in both blast and non-blast TBI. Seventy percent of TBI subjects were taking at least one medication in the following classes: antidepressant, atypical antipsychotic, anticonvulsant, or h1-antihistamine. There was no association between any medication class and the OSDI or dry eye measures. Reduced corneal sensation in 21 TBI subjects was not associated with OSDI, tear production, or TFBUT, but did correlate with reduced tear osmolarity (P=.05). History of refractive surgery, previous contact lens wear, facial nerve weakness, or meibomian gland dysfunction was not associated with DED. In summary, we found a higher prevalence of DED in subjects with TBI, both subjectively and objectively. This effect is unrelated to medication use, and it may persist for months to years. We recommend that patients with TBI from any cause be evaluated for DED using a battery of standard testing methods described in

  9. Diffusion Tensor Imaging Reveals White Matter Injury in a Rat Model of Repetitive Blast-Induced Traumatic Brain Injury

    PubMed Central

    Calabrese, Evan; Du, Fu; Garman, Robert H.; Johnson, G. Allan; Riccio, Cory; Tong, Lawrence C.

    2014-01-01

    Abstract Blast-induced traumatic brain injury (bTBI) is one of the most common combat-related injuries seen in U.S. military personnel, yet relatively little is known about the underlying mechanisms of injury. In particular, the effects of the primary blast pressure wave are poorly understood. Animal models have proven invaluable for the study of primary bTBI, because it rarely occurs in isolation in human subjects. Even less is known about the effects of repeated primary blast wave exposure, but existing data suggest cumulative increases in brain damage with a second blast. MRI and, in particular, diffusion tensor imaging (DTI), have become important tools for assessing bTBI in both clinical and preclinical settings. Computational statistical methods such as voxelwise analysis have shown promise in localizing and quantifying bTBI throughout the brain. In this study, we use voxelwise analysis of DTI to quantify white matter injury in a rat model of repetitive primary blast exposure. Our results show a significant increase in microstructural damage with a second blast exposure, suggesting that primary bTBI may sensitize the brain to subsequent injury. PMID:24392843

  10. Traumatic Brain Injury Detection Using Electrophysiological Methods

    PubMed Central

    Rapp, Paul E.; Keyser, David O.; Albano, Alfonso; Hernandez, Rene; Gibson, Douglas B.; Zambon, Robert A.; Hairston, W. David; Hughes, John D.; Krystal, Andrew; Nichols, Andrew S.

    2015-01-01

    Measuring neuronal activity with electrophysiological methods may be useful in detecting neurological dysfunctions, such as mild traumatic brain injury (mTBI). This approach may be particularly valuable for rapid detection in at-risk populations including military service members and athletes. Electrophysiological methods, such as quantitative electroencephalography (qEEG) and recording event-related potentials (ERPs) may be promising; however, the field is nascent and significant controversy exists on the efficacy and accuracy of the approaches as diagnostic tools. For example, the specific measures derived from an electroencephalogram (EEG) that are most suitable as markers of dysfunction have not been clearly established. A study was conducted to summarize and evaluate the statistical rigor of evidence on the overall utility of qEEG as an mTBI detection tool. The analysis evaluated qEEG measures/parameters that may be most suitable as fieldable diagnostic tools, identified other types of EEG measures and analysis methods of promise, recommended specific measures and analysis methods for further development as mTBI detection tools, identified research gaps in the field, and recommended future research and development thrust areas. The qEEG study group formed the following conclusions: (1) Individual qEEG measures provide limited diagnostic utility for mTBI. However, many measures can be important features of qEEG discriminant functions, which do show significant promise as mTBI detection tools. (2) ERPs offer utility in mTBI detection. In fact, evidence indicates that ERPs can identify abnormalities in cases where EEGs alone are non-disclosing. (3) The standard mathematical procedures used in the characterization of mTBI EEGs should be expanded to incorporate newer methods of analysis including non-linear dynamical analysis, complexity measures, analysis of causal interactions, graph theory, and information dynamics. (4) Reports of high specificity in q

  11. Effect of marijuana use on outcomes in traumatic brain injury.

    PubMed

    Nguyen, Brian M; Kim, Dennis; Bricker, Scott; Bongard, Fred; Neville, Angela; Putnam, Brant; Smith, Jennifer; Plurad, David

    2014-10-01

    Traumatic brain injury (TBI) is associated with significant morbidity and mortality. Several studies have demonstrated neuroprotective effects of cannabinoids. The objective of this study was to establish a relationship between the presence of a positive toxicology screen for tetrahydrocannabinol (THC) and mortality after TBI. A 3-year retrospective review of registry data at a Level I center of patients sustaining TBI having a toxicology screen was performed. Pediatric patients (younger than 15 years) and patients with a suspected nonsurvivable injury were excluded. The THC(+) group was compared with the THC(-) group with respect to injury mechanism, severity, disposition, and mortality. Logistic regression was used to determine independent associations with mortality. There were 446 cases meeting all inclusion criteria. The incidence of a positive THC screen was 18.4 per cent (82). Overall mortality was 9.9 per cent (44); however, mortality in the THC(+) group (2.4% [two]) was significantly decreased compared with the THC(-) group (11.5% [42]; P = 0.012). After adjusting for differences between the study cohorts on logistic regression, a THC(+) screen was independently associated with survival after TBI (odds ratio, 0.224; 95% confidence interval, 0.051 to 0.991; P = 0.049). A positive THC screen is associated with decreased mortality in adult patients sustaining TBI. PMID:25264643

  12. Transcranial magnetic stimulation facilitates neurorehabilitation after pediatric traumatic brain injury

    PubMed Central

    Lu, Hongyang; Kobilo, Tali; Robertson, Courtney; Tong, Shanbao; Celnik, Pablo; Pelled, Galit

    2015-01-01

    Traumatic brain injury (TBI) is the leading cause of death and disability among children in the United States. Affected children will often suffer from emotional, cognitive and neurological impairments throughout life. In the controlled cortical impact (CCI) animal model of pediatric TBI (postnatal day 16–17) it was demonstrated that injury results in abnormal neuronal hypoactivity in the non-injured primary somatosensory cortex (S1). It materializes that reshaping the abnormal post-injury neuronal activity may provide a suitable strategy to augment rehabilitation. We tested whether high-frequency, non-invasive transcranial magnetic stimulation (TMS) delivered twice a week over a four-week period can rescue the neuronal activity and improve the long-term functional neurophysiological and behavioral outcome in the pediatric CCI model. The results show that TBI rats subjected to TMS therapy showed significant increases in the evoked-fMRI cortical responses (189%), evoked synaptic activity (46%), evoked neuronal firing (200%) and increases expression of cellular markers of neuroplasticity in the non-injured S1 compared to TBI rats that did not receive therapy. Notably, these rats showed less hyperactivity in behavioral tests. These results implicate TMS as a promising approach for reversing the adverse neuronal mechanisms activated post-TBI. Importantly, this intervention could readily be translated to human studies. PMID:26440604

  13. Irony and empathy in children with traumatic brain injury.

    PubMed

    Dennis, Maureen; Simic, Nevena; Agostino, Alba; Taylor, H Gerry; Bigler, Erin D; Rubin, Kenneth; Vannatta, Kathryn; Gerhardt, Cynthia A; Stancin, Terry; Yeates, Keith Owen

    2013-03-01

    Social communication involves influencing what other people think and feel about themselves. We use the term conative theory of mind (ToM) to refer to communicative interactions involving one person trying to influence the mental and emotional state of another, paradigmatic examples of which are irony and empathy. This study reports how children with traumatic brain injury (TBI) understand ironic criticism and empathic praise, on a task requiring them to identify speaker belief and intention for direct conative speech acts involving literal truth, and indirect speech acts involving either ironic criticism or empathic praise. Participants were 71 children in the chronic state of a single TBI and 57 age- and gender-matched children with orthopedic injuries (OI). Group differences emerged on indirect speech acts involving conation (i.e., irony and empathy), but not on structurally and linguistically identical direct speech acts, suggesting specific deficits in this aspect of social cognition in school-age children with TBI. Deficits in children with mild-moderate TBI were less widespread and more selective than those of children with more severe injuries. Deficits in understanding the social, conative function of indirect speech acts like irony and empathy have widespread and deep implications for social function in children with TBI.

  14. Hysteria following brain injury.

    PubMed Central

    Eames, P

    1992-01-01

    Of 167 patients referred to a unit treating severe behaviour disorders after brain injury, 54 showed clinical features closely resembling those of gross hysteria as described by Charcot. Close correlation was found with very diffuse insults (hypoxia and hypoglycaemia), but not with severity of injury or with family or personal history of hysterical or other psychiatric disorder. The findings may have implications for the understanding of the nature of hysteria. PMID:1469401

  15. Traumatic brain injury: a disease process, not an event.

    PubMed

    Masel, Brent E; DeWitt, Douglas S

    2010-08-01

    Traumatic brain injury (TBI) is seen by the insurance industry and many health care providers as an "event." Once treated and provided with a brief period of rehabilitation, the perception exists that patients with a TBI require little further treatment and face no lasting effects on the central nervous system or other organ systems. In fact, TBI is a chronic disease process, one that fits the World Health Organization definition as having one or more of the following characteristics: it is permanent, caused by non-reversible pathological alterations, requires special training of the patient for rehabilitation, and/or may require a long period of observation, supervision, or care. TBI increases long-term mortality and reduces life expectancy. It is associated with increased incidences of seizures, sleep disorders, neurodegenerative diseases, neuroendocrine dysregulation, and psychiatric diseases, as well as non-neurological disorders such as sexual dysfunction, bladder and bowel incontinence, and systemic metabolic dysregulation that may arise and/or persist for months to years post-injury. The purpose of this article is to encourage the classification of TBI as the beginning of an ongoing, perhaps lifelong process, that impacts multiple organ systems and may be disease causative and accelerative. Our intent is not to discourage patients with TBI or their families and caregivers, but rather to emphasize that TBI should be managed as a chronic disease and defined as such by health care and insurance providers. Furthermore, if the chronic nature of TBI is recognized by government and private funding agencies, research can be directed at discovering therapies that may interrupt the disease processes months or even years after the initiating event. PMID:20504161

  16. Impulsive Pressurization of Neuronal Cells for Traumatic Brain Injury Study

    PubMed Central

    Feng, Ruqiang; Lim, Jung Yul

    2011-01-01

    A novel impulsive cell pressurization experiment has been developed using a Kolsky bar device to investigate blast-induced traumatic brain injury (TBI). We demonstrate in this video article how blast TBI-relevant impulsive pressurization is applied to the neuronal cells in vitro. This is achieved by using well-controlled pressure pulse created by a specialized Kolsky bar device, with complete pressure history within the cell pressurization chamber recorded. Pressurized neuronal cells are inspected immediately after pressurization, or further incubated to examine the long-term effects of impulsive pressurization on neurite/axonal outgrowth, neuronal gene expression, apoptosis, etc. We observed that impulsive pressurization at about 2 MPa induces distinct neurite loss relative to unpressurized cells. Our technique provides a novel method to investigate the molecular/cellular mechanisms of blast TBI, via impulsive pressurization of brain cells at well-controlled pressure magnitude and duration. PMID:22005926

  17. The UCLA Longitudinal Study of Neurocognitive Outcomes Following Mild Pediatric Traumatic Brain Injury

    PubMed Central

    Babikian, Talin; Satz, Paul; Zaucha, Ken; Light, Roger; Lewis, Richard S.; Asarnow, Robert F.

    2015-01-01

    Comprehensive reviews of neurocognitive outcomes following mild, uncomplicated traumatic brain injury (TBI) in children have shown minimal effects on neurocognition, especially in methodologically rigorous studies. In this study, we report longitudinal (1, 6, and 12 months post injury) results in four domains of neurocognitive functioning in a large sample of children with mild TBI (n = 124, ages 8–17 at injury) relative to two demographically matched control groups (other injury: n = 94 and non-injury: n = 106). After accounting for age and parental education, significant main effects of group were observed on 7 of the 10 neurocognitive tests. However, these differences were not unique to the TBI sample but were found between both the TBI and other injury groups relative to the non-injured group, suggesting a general injury effect. Effects were primarily within the domains measuring memory, psychomotor processing speed, and language. This is the largest longitudinal study to date of neurocognitive outcomes at discrete time points in pediatric mild TBI. When controlling for pre-injury factors, there is no evidence of long-term neurocognitive impairment in this group relative to another injury control group. The importance of longitudinal analyses and use of appropriate control groups are discussed in the context of evaluating the effects of mild TBI on cognition. PMID:21813031

  18. Anxiety disorders in children and adolescents in the second six months after traumatic brain injury.

    PubMed

    Max, Jeffrey E; Lopez, Aholibama; Wilde, Elisabeth A; Bigler, Erin D; Schachar, Russell J; Saunders, Ann; Ewing-Cobbs, Linda; Chapman, Sandra B; Yang, Tony T; Levin, Harvey S

    2015-01-01

    The objective of this prospective longitudinal study was to assess the nature, rate, predictive variables, and neuroimaging characteristics of novel (new-onset) anxiety disorders (compared with no novel anxiety disorders) 6-12 months after pediatric traumatic brain injury (TBI). Psychiatric and psychosocial interviews were administered to children who sustained mild to severe TBI at baseline (soon after injury) and at the 12-month follow-up post-injury (n= 125). The psychiatric outcome of children 12-months post-injury revealed that novel anxiety disorders present in the second six months after TBI were heterogeneous and occurred in 13 (10.4%) participants. Novel anxiety disorder was significantly associated with concurrent novel depressive disorder and with novel personality change due to TBI. Novel anxiety disorder was marginally associated with younger age at injury and with pre-injury anxiety disorder in univariate analyses. Age at injury, pre-injury anxiety disorder, and personality change due to TBI were each significantly and independently related to novel anxiety disorder in a logistic regression analysis. There were no significant neuroimaging group differences. These findings suggest that the emergence of novel anxiety disorder after TBI might be related to a broader problem of affective dysregulation especially in younger children and those with a vulnerability even to pre-injury anxiety disorder.

  19. Stroke, mTBI, infection, antibiotics and beta blockade: Connecting the dots.

    PubMed

    Griffin, Gerald Dieter

    2015-08-01

    Several themes supported by a robust literature are addressed in this clinical translational review and research paper: (1) the inadequate standard of care for minimal traumatic brain injury (mTBI)/concussion when compared to stroke because diagnosis and care for mTBI/concussion are based primarily on a symptom only framework; (2) the treatment of stroke (brain injury) infection with select antibiotics; (3) the use of beta blockade in stroke (brain injury). The various etiologies of brain injury appear to coalesce to common endpoints: potential neuronal demise, cognitive and functional losses, immune suppression and infection. The use of principles patterned after 'Koch's Postulates' (show/prove the presence of infection/illness/disease, treat until resolved, and prove objectively that the disease/illness is gone/healed/cured) appears to be marginalized in establishing a diagnosis and recovery from mTBI/TBI. The pathways of immune system interactions in stroke (brain injury) and infection are briefly discussed. The suggestion of combined specific antibiotic and beta blockade for ischemic stroke (brain injury) and mTBI is advanced for treatment and expeditious further study. Stroke is considered a brain injury in this paper. Stroke is also considered and recommended as a study model for mTBI therapy because of their common end points from brain damage. It is suggested that potential transfer or translation of therapy for stroke may be useful in mTBI.

  20. microRNA-22 attenuates neuronal cell apoptosis in a cell model of traumatic brain injury

    PubMed Central

    Ma, Ji; Shui, Shaofeng; Han, Xinwei; Guo, Dong; Li, Tengfei; Yan, Lei

    2016-01-01

    Traumatic brain injury (TBI) is a major cause of injury-related deaths, and the mechanism of TBI has become a research focus, but little is known about the mechanism of microRNAs in TBI. The aim of this study is the role of microRNA-22 (miR-22) in TBI-induced neuronal cell apoptosis. Rat cortical neurons were cultured and the TBI model was induced by scratch injury in vitro, before which miR-22 level was altered by transfection of agomir or antagomir. Lactate dehydrogenase (LDH) release and TUNEL assays were performed to examine neuronal cell injury and apoptosis. The activity of caspase 3 (CASP3) and level changes of several apoptosis factors including B-cell lymphoma 2 (BCL2), BCL2-associated X protein (BAX), phosphatase and tensin homolog (PTEN) and v-AKT murine thymoma viral oncogene homolog 1 (AKT1) were detected. Results showed that TBI model cells possessed a downregulated miR-22 level (P < 0.001) and more LDH release and apoptotic cells indicating the aggravated neuronal cell injury and apoptosis induced by TBI. miR-22 agomir attenuated neuronal cell injury and apoptosis of the TBI model. It also caused the corresponding changes in CASP3 activity and other apoptosis factors, with cleaved CASP3, BAX and PTEN inhibited and BCL2 and phosphorylated AKT1 promoted, while miR-22 antagomir had the opposite effects. So miR-22 has neuroprotective roles of attenuating neuronal cell injury and apoptosis induced by TBI, which may be associated with its regulation on apoptosis factors. This study reveals miR-22 as a potential approach to TBI treatment and detailed mechanism remains to be uncovered. PMID:27186313

  1. What’s New in Traumatic Brain Injury: Update on Tracking, Monitoring and Treatment

    PubMed Central

    Reis, Cesar; Wang, Yuechun; Akyol, Onat; Ho, Wing Mann; Applegate II, Richard; Stier, Gary; Martin, Robert; Zhang, John H.

    2015-01-01

    Traumatic brain injury (TBI), defined as an alteration in brain functions caused by an external force, is responsible for high morbidity and mortality around the world. It is important to identify and treat TBI victims as early as possible. Tracking and monitoring TBI with neuroimaging technologies, including functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), positron emission tomography (PET), and high definition fiber tracking (HDFT) show increasing sensitivity and specificity. Classical electrophysiological monitoring, together with newly established brain-on-chip, cerebral microdialysis techniques, both benefit TBI. First generation molecular biomarkers, based on genomic and proteomic changes following TBI, have proven effective and economical. It is conceivable that TBI-specific biomarkers will be developed with the combination of systems biology and bioinformation strategies. Advances in treatment of TBI include stem cell-based and nanotechnology-based therapy, physical and pharmaceutical interventions and also new use in TBI for approved drugs which all present favorable promise in preventing and reversing TBI. PMID:26016501

  2. Simulation of traumatic brain injury symptoms on the Personality Assessment Inventory: an analogue study.

    PubMed

    Keiski, Michelle A; Shore, Douglas L; Hamilton, Joanna M; Malec, James F

    2015-04-01

    The purpose of this study was to characterize the operating characteristics of the Personality Assessment Inventory (PAI) validity scales in distinguishing simulators feigning symptoms of traumatic brain injury (TBI) while completing the PAI (n = 84) from a clinical sample of patients with TBI who achieved adequate scores on performance validity tests (n = 112). The simulators were divided into two groups: (a) Specific Simulators feigning cognitive and somatic symptoms only or (b) Global Simulators feigning cognitive, somatic, and psychiatric symptoms. The PAI overreporting scales were indeed sensitive to the simulation of TBI symptoms in this analogue design. However, these scales were less sensitive to the feigning of somatic and cognitive TBI symptoms than the feigning of a broad range of cognitive, somatic, and emotional symptoms often associated with TBI. The relationships of TBI simulation to consistency and underreporting scales are also explored.

  3. Functional reorganisation of memory after traumatic brain injury: a study with H2150 positron emission tomography

    PubMed Central

    Levine, B; Cabeza, R; McIntosh, A; Black, S; Grady, C; Stuss, D

    2002-01-01

    Objective: To study the effects of moderate to severe traumatic brain injury (TBI) on the functional neuroanatomy supporting memory retrieval. Methods: Subjects were six patients who had sustained a moderate to severe TBI about four years before scanning and had since made a good recovery. Eleven healthy young adults matched to the patients for age and education served as controls. An established H2150 positron emission tomography paradigm was used to elicit brain activations in response to memory retrieval. TBI patients' patterns of brain activation were compared statistically with those of control subjects. Both group and individual case data were analysed. Results: Both TBI patients and controls engaged frontal, temporal, and parietal regions known to be involved in memory retrieval, yet the TBI patients showed relative increases in frontal, anterior cingulate, and occipital activity. The hemispheric asymmetry characteristic of controls was attenuated in patients with TBI. Reduced activation was noted in the right dorsomedial thalamus. Although local aspects of this pattern were affected by the presence of focal lesions and performance differences, the overall pattern was reliable across patients and comparable to functional neuroimaging results reported for normal aging, Alzheimer's disease, and other patients with TBI. Conclusions: The TBI patients performed memory tasks using altered functional neuroanatomical networks. These changes are probably the result of diffuse axonal injury and may reflect either cortical disinhibition attributable to disconnection or compensation for inefficient mnemonic processes. PMID:12122177

  4. Delayed and disorganised brain activation detected with magnetoencephalography after mild traumatic brain injury

    PubMed Central

    da Costa, Leodante; Robertson, Amanda; Bethune, Allison; MacDonald, Matt J; Shek, Pang N; Taylor, Margot J; Pang, Elizabeth W

    2015-01-01

    Background Awareness to neurocognitive issues after mild traumatic brain injury (mTBI) is increasing, but currently no imaging markers are available for mTBI. Advanced structural imaging recently showed microstructural tissue changes and axonal injury, mild but likely sufficient to lead to functional deficits. Magnetoencephalography (MEG) has high temporal and spatial resolution, combining structural and electrophysiological information, and can be used to examine brain activation patterns of regions involved with specific tasks. Methods 16 adults with mTBI and 16 matched controls were submitted to neuropsychological testing (Wechsler Abbreviated Scale of Intelligence (WASI); Conners; Alcohol Use Disorders Identification Test (AUDIT); Generalised Anxiety Disorder Seven-item Scale (GAD-7); Patient Health Questionnaire (PHQ-9); Symptom Checklist and Symptom Severity Score (SCAT2)) and MEG while tested for mental flexibility (Intra-Extra Dimensional set-shifting tasks). Three-dimensional maps were generated using synthetic aperture magnetometry beamforming analyses to identify differences in regional activation and activation times. Reaction times and accuracy between groups were compared using 2×2 mixed analysis of variance. Findings While accuracy was similar, patients with mTBI reaction time was delayed and sequence of activation of brain regions disorganised, with involvement of extra regions such as the occipital lobes, not used by controls. Examination of activation time showed significant delays in the right insula and left posterior parietal cortex in patients with mTBI. Conclusions Patients with mTBI showed significant delays in the activation of important areas involved in executive function. Also, more regions of the brain are involved in an apparent compensatory effort. Our study suggests that MEG can detect subtle neural changes associated with cognitive dysfunction and thus, may eventually be useful for capturing and tracking the onset and course of

  5. Priming the Inflammatory Pump of the CNS after Traumatic Brain Injury

    PubMed Central

    Witcher, Kristina G.; Eiferman, Daniel S.; Godbout, Jonathan P.

    2015-01-01

    Traumatic brain injury (TBI) can lead to secondary neuropsychiatric problems that develop and persist years after injury. Mounting evidence indicates that neuroinflammatory processes progress after the initial head injury and worsen with time. Microglia contribute to this inflammation by maintaining a primed profile long after the acute effects of the injury have dissipated. This may set the stage for glial dysfunction and hyperactivity to challenges including subsequent head injury, stress, or induction of a peripheral immune response. The purpose of this review is to discuss the evidence that microglia become primed following TBI and how this corresponds with vulnerability to a “second hit” and subsequent neuropsychiatric and neurodegenerative complications. PMID:26442695

  6. Finite Element Analysis of Brain Injury due to Head Impact

    NASA Astrophysics Data System (ADS)

    Suh, Chang Min; Kim, Sung Ho; Goldsmith, Werner

    Traumatic Brain Injury (TBI) due to head impact by external impactor was analyzed using Finite Element Method (FEM). Two-dimensiona modeling was performed according to Magnetic Resonance Imaging (MRI) data of Mongolian subject. Pressure variation in a cranium due to external impact was analyzed in order to simulate Nahum et al.'s cadaver test.6 And, analyzed results were compared with Nahum et al.'s experimental data.6 As results, stress and strain behaviors of the brain during impact were accorded with experimental data qualitatively even though there were some differences in quantitative values. In addition, they were accorded with other references about brain injury as well.

  7. In-vitro approaches for studying blast-induced traumatic brain injury.

    PubMed

    Chen, Yung Chia; Smith, Douglas H; Meaney, David F

    2009-06-01

    Traumatic brain injury caused by explosive or blast events is currently divided into four phases: primary, secondary, tertiary, and quaternary blast injury. These phases of blast-induced traumatic brain injury (bTBI) are biomechanically distinct, and can be modeled in both in-vivo and in-vitro systems. The purpose of this review is to consider the mechanical phases of bTBI, how these phases are reproduced with in-vitro models, and to review findings from these models to assess how each phase of bTBI can be examined in more detail. Highlighted are some important gaps in the literature that may be addressed in the future to better identify the exact contributing mechanisms for bTBI. These in-vitro models, viewed in combination with in-vivo models and clinical studies, can be used to assess both the mechanisms and possible treatments for this type of trauma.

  8. Insights into the metabolic response to traumatic brain injury as revealed by 13C NMR spectroscopy

    PubMed Central

    Bartnik-Olson, Brenda L.; Harris, Neil G.; Shijo, Katsunori; Sutton, Richard L.

    2013-01-01

    The present review highlights critical issues related to cerebral metabolism following traumatic brain injury (TBI) and the use of 13C labeled substrates and nuclear magnetic resonance (NMR) spectroscopy to study these changes. First we address some pathophysiologic factors contributing to metabolic dysfunction following TBI. We then examine how 13C NMR spectroscopy strategies have been used to investigate energy metabolism, neurotransmission, the intracellular redox state, and neuroglial compartmentation following injury. 13C NMR spectroscopy studies of brain extracts from animal models of TBI have revealed enhanced glycolytic production of lactate, evidence of pentose phosphate pathway (PPP) activation, and alterations in neuronal and astrocyte oxidative metabolism that are dependent on injury severity. Differential incorporation of label into glutamate and glutamine from 13C labeled glucose or acetate also suggest TBI-induced adaptations to the glutamate-glutamine cycle. PMID:24109452

  9. In-Vitro Approaches for Studying Blast-Induced Traumatic Brain Injury

    PubMed Central

    Chen, Yung Chia; Smith, Douglas H.

    2009-01-01

    Abstract Traumatic brain injury caused by explosive or blast events is currently divided into four phases: primary, secondary, tertiary, and quaternary blast injury. These phases of blast-induced traumatic brain injury (bTBI) are biomechanically distinct, and can be modeled in both in-vivo and in-vitro systems. The purpose of this review is to consider the mechanical phases of bTBI, how these phases are reproduced with in-vitro models, and to review findings from these models to assess how each phase of bTBI can be examined in more detail. Highlighted are some important gaps in the literature that may be addressed in the future to better identify the exact contributing mechanisms for bTBI. These in-vitro models, viewed in combination with in-vivo models and clinical studies, can be used to assess both the mechanisms and possible treatments for this type of trauma. PMID:19397424

  10. MMP-9 Inhibitor SB-3CT Attenuates Behavioral Impairments and Hippocampal Loss after Traumatic Brain Injury in Rat

    PubMed Central

    Jia, Feng; Yin, Yu Hua; Gao, Guo Yi; Wang, Yu

    2014-01-01

    Abstract The aim of this study was to evaluate the potential efficacy of SB-3CT, a matrix metallopeptidase 9 inhibitor, on behavioral and histological outcomes after traumatic brain injury (TBI) in rats. Adult male Sprague-Dawley rats were randomly divided into three groups (n=15/group): TBI with SB-3CT treatment, TBI with saline, and sham injury. The TBI model was induced by a fluid percussion TBI device. SB-3CT (50 mg/kg in 10% dimethyl sulfoxide) was administered intraperitoneally at 30 min, 6 h, and 12 h after the TBI. Motor function (beam-balance/beam-walk tests) and spatial learning/memory (Morris water maze) were assessed on post-operative Days 1−5 and 11–15, respectively. Fluoro-Jade staining, immunofluorescence, and cresyl violet-staining were carried out for histopathological evaluation at 24 h, 72 h, and 15 days after TBI, respectively. It was shown that TBI can result in significant behavioral deficit induced by acute neurodegeneration, increased expression of cleaved caspase-3, and long-term neuronal loss. SB-3CT intervention via the current regime provides robust behavioral protection and hippocampal neurons preservation from the deleterious effects of TBI. Hence, the efficacy of SB-3CT on TBI prognosis could be ascertained. It is believed that the current study adds to the growing literature in identifying SB-3CT as a potential therapy for human brain injury. PMID:24661104

  11. MMP-9 inhibitor SB-3CT attenuates behavioral impairments and hippocampal loss after traumatic brain injury in rat.

    PubMed

    Jia, Feng; Yin, Yu Hua; Gao, Guo Yi; Wang, Yu; Cen, Lian; Jiang, Ji-Yao

    2014-07-01

    The aim of this study was to evaluate the potential efficacy of SB-3CT, a matrix metallopeptidase 9 inhibitor, on behavioral and histological outcomes after traumatic brain injury (TBI) in rats. Adult male Sprague-Dawley rats were randomly divided into three groups (n=15/group): TBI with SB-3CT treatment, TBI with saline, and sham injury. The TBI model was induced by a fluid percussion TBI device. SB-3CT (50 mg/kg in 10% dimethyl sulfoxide) was administered intraperitoneally at 30 min, 6 h, and 12 h after the TBI. Motor function (beam-balance/beam-walk tests) and spatial learning/memory (Morris water maze) were assessed on post-operative Days 1-5 and 11-15, respectively. Fluoro-Jade staining, immunofluorescence, and cresyl violet-staining were carried out for histopathological evaluation at 24 h, 72 h, and 15 days after TBI, respectively. It was shown that TBI can result in significant behavioral deficit induced by acute neurodegeneration, increased expression of cleaved caspase-3, and long-term neuronal loss. SB-3CT intervention via the current regime provides robust behavioral protection and hippocampal neurons preservation from the deleterious effects of TBI. Hence, the efficacy of SB-3CT on TBI prognosis could be ascertained. It is believed that the current study adds to the growing literature in identifying SB-3CT as a potential therapy for human brain injury. PMID:24661104

  12. Disruption of Network Synchrony and Cognitive Dysfunction After Traumatic Brain Injury

    PubMed Central

    Wolf, John A.; Koch, Paul F.

    2016-01-01

    Traumatic brain injury (TBI) is a heterogeneous disorder with many factors contributing to a spectrum of severity, leading to cognitive dysfunction that may last for many years after injury. Injury to axons in the white matter, which are preferentially vulnerable to biomechanical forces, is prevalent in many TBIs. Unlike focal injury to a discrete brain region, axonal injury is fundamentally an injury to the substrate by which networks of the brain communicate with one another. The brain is envisioned as a series of dynamic, interconnected networks that communicate via long axonal conduits termed the “connectome”. Ensembles of neurons communicate via these pathways and encode information within and between brain regions in ways that are timing dependent. Our central hypothesis is that traumatic injury to axons may disrupt the exquisite timing of neuronal communication within and between brain networks, and that this may underlie aspects of post-TBI cognitive dysfunction. With a better understanding of how highly interconnected networks of neurons communicate with one another in important cognitive regions such as the limbic system, and how disruption of this communication occurs during injury, we can identify new therapeutic targets to restore lost function. This requires the tools of systems neuroscience, including electrophysiological analysis of ensemble neuronal activity and circuitry changes in awake animals after TBI, as well as computational modeling of the effects of TBI on these networks. As more is revealed about how inter-regional neuronal interactions are disrupted, treatments directly targeting these dysfunctional pathways using neuromodulation can be developed. PMID:27242454

  13. Brain Networks Subserving Emotion Regulation and Adaptation after Mild Traumatic Brain Injury.

    PubMed

    van der Horn, Harm J; Liemburg, Edith J; Aleman, André; Spikman, Jacoba M; van der Naalt, Joukje

    2016-01-01

    The majority of patients with traumatic brain injury (TBI) sustain a mild injury (mTBI). One out of 4 patients experiences persistent complaints, despite their often normal neuropsychological test results and the absence of structural brain damage on conventional neuroimaging. Susceptibility to develop persistent complaints is thought to be affected by interindividual differences in adaptation, which can also be influenced by preinjury psychological factors. Coping is a key construct of adaptation and refers to strategies to deal with new situations and serious life events. An important element of coping is the ability to regulate emotions and stress. The prefrontal cortex is a crucial area in this regulation process, given that it exerts a top-down influence on the amygdala and other subcortical structures involved in emotion processing. However, little is known about the role of the prefrontal cortex and associated brain networks in emotion regulation and adaptation post-mTBI. Especially, the influence of prefrontal dysfunction on development of persistent postconcussive complaints is poorly understood. In this article, we aim to integrate findings from functional and structural MRI studies on this topic. Alterations within the default mode, executive and salience network have been found in relation to complaints post-mTBI. Dysfunction of the medial prefrontal cortex may impair network dynamics for emotion regulation and adaptation post-mTBI, resulting in persistent post-concussive complaints. PMID:25962860

  14. Neuroprotective efficacy of a proneurogenic compound after traumatic brain injury.

    PubMed

    Blaya, Meghan O; Bramlett, Helen M; Naidoo, Jacinth; Pieper, Andrew A; Dietrich, W Dalton

    2014-03-01

    Traumatic brain injury (TBI) is characterized by histopathological damage and long-term sensorimotor and cognitive dysfunction. Recent studies have reported the discovery of the P7C3 class of aminopropyl carbazole agents with potent neuroprotective properties for both newborn neural precursor cells in the adult hippocampus and mature neurons in other regions of the central nervous system. This study tested, for the first time, whether the highly active P7C3-A20 compound would be neuroprotective, promote hippocampal neurogenesis, and improve functional outcomes after experimental TBI. Sprague-Dawley rats subjected to moderate fluid percussion brain injury were evaluated for quantitative immunohistochemical and behavioral changes after trauma. P7C3-A20 (10 mg/kg) or vehicle was initiated intraperitoneally 30 min postsurgery and twice per day every day thereafter for 7 days. Administration of P7C3-A20 significantly reduced overall contusion volume, preserved vulnerable anti-neuronal nuclei (NeuN)-positive pericontusional cortical neurons, and improved sensorimotor function 1 week after trauma. P7C3-A20 treatment also significantly increased both bromodeoxyuridine (BrdU)- and doublecortin (DCX)-positive cells within the subgranular zone of the ipsilateral dentate gyrus 1 week after TBI. Five weeks after TBI, animals treated with P7C3-A20 showed significantly increased BrdU/NeuN double-labeled neurons and improved cognitive function in the Morris water maze, compared to TBI-control animals. These results suggest that P7C3-A20 is neuroprotective and promotes endogenous reparative strategies after TBI. We propose that the chemical scaffold represented by P7C3-A20 provides a basis for optimizing and advancing new pharmacological agents for protecting patients against the early and chronic consequences of TBI. PMID:24070637

  15. Activation of Alpha 7 Cholinergic Nicotinic Receptors Reduce Blood–Brain Barrier Permeability following Experimental Traumatic Brain Injury

    PubMed Central

    Zhao, Jing; Kobori, Nobuhide; Redell, John B.; Hylin, Michael J.; Hood, Kimberly N.; Moore, Anthony N.

    2016-01-01

    Traumatic brain injury (TBI) is a major human health concern that has the greatest impact on young men and women. The breakdown of the blood–brain barrier (BBB) is an important pathological consequence of TBI that initiates secondary processes, including infiltration of inflammatory cells, which can exacerbate brain inflammation and contribute to poor outcome. While the role of inflammation within the injured brain has been examined in some detail, the contribution of peripheral/systemic inflammation to TBI pathophysiology is largely unknown. Recent studies have implicated vagus nerve regulation of splenic cholinergic nicotinic acetylcholine receptor α7 (nAChRa7) signaling in the regulation of systemic inflammation. However, it is not known whether this mechanism plays a role in TBI-triggered inflammation and BBB breakdown. Following TBI, we observed that plasma TNF-α and IL-1β levels, as well as BBB permeability, were significantly increased in nAChRa7 null mice (Chrna7−/−) relative to wild-type mice. The administration of exogenous IL-1β and TNF-α to brain-injured animals worsened Evans Blue dye extravasation, suggesting that systemic inflammation contributes to TBI-triggered BBB permeability. Systemic administration of the nAChRa7 agonist PNU-282987 or the positive allosteric modulator PNU-120596 significantly attenuated TBI-triggered BBB compromise. Supporting a role for splenic nAChRa7 receptors, we demonstrate that splenic injection of the nicotinic receptor blocker α-bungarotoxin increased BBB permeability in brain-injured rats, while PNU-282987 injection decreased such permeability. These effects were not seen when α-bungarotoxin or PNU-282987 were administered to splenectomized, brain-injured rats. Together, these findings support the short-term use of nAChRa7-activating agents as a strategy to reduce TBI-triggered BBB permeability. SIGNIFICANCE STATEMENT Breakdown of the blood–brain barrier (BBB) in response to traumatic brain injury (TBI

  16. Identification of Hematomas in Mild Traumatic Brain Injury Using an Index of Quantitative Brain Electrical Activity

    PubMed Central

    Naunheim, Rosanne; Bazarian, Jeffrey; Mould, W. Andrew; Hanley, Daniel

    2015-01-01

    Abstract Rapid identification of traumatic intracranial hematomas following closed head injury represents a significant health care need because of the potentially life-threatening risk they present. This study demonstrates the clinical utility of an index of brain electrical activity used to identify intracranial hematomas in traumatic brain injury (TBI) presenting to the emergency department (ED). Brain electrical activity was recorded from a limited montage located on the forehead of 394 closed head injured patients who were referred for CT scans as part of their standard ED assessment. A total of 116 of these patients were found to be CT positive (CT+), of which 46 patients with traumatic intracranial hematomas (CT+) were identified for study. A total of 278 patients were found to be CT negative (CT−) and were used as controls. CT scans were subjected to quanitative measurements of volume of blood and distance of bleed from recording electrodes by blinded independent experts, implementing a validated method for hematoma measurement. Using an algorithm based on brain electrical activity developed on a large independent cohort of TBI patients and controls (TBI-Index), patients were classified as either positive or negative for structural brain injury. Sensitivity to hematomas was found to be 95.7% (95% CI=85.2, 99.5), specificity was 43.9% (95% CI=38.0, 49.9). There was no significant relationship between the TBI-Index and distance of the bleed from recording sites (F=0.044, p=0.833), or volume of blood measured F=0.179, p=0.674). Results of this study are a validation and extension of previously published retrospective findings in an independent population, and provide evidence that a TBI-Index for structural brain injury is a highly sensitive measure for the detection of potentially life-threatening traumatic intracranial hematomas, and could contribute to the rapid, quantitative evaluation and treatment of such patients. PMID:25054838

  17. Donepezil rescues spatial learning and memory deficits following traumatic brain injury independent of its effects on neurogenesis.

    PubMed

    Yu, Tzong-Shiue; Kim, Ahleum; Kernie, Steven G

    2015-01-01

    Traumatic brain injury (TBI) is ubiquitous and effective treatments for it remain supportive largely due to uncertainty over how endogenous repair occurs. Recently, we demonstrated that hippocampal injury-induced neurogenesis is one mechanism underlying endogenous repair following TBI. Donepezil is associated with increased hippocampal neurogenesis and has long been known to improve certain aspects of cognition following many types of brain injury through unknown mechanisms. By coupling donepezil therapy with temporally regulated ablation of injury-induced neurogenesis using nestin-HSV transgenic mice, we investigated whether the pro-cognitive effects of donepezil following injury might occur through increasing neurogenesis. We demonstrate that donepezil itself enhances neurogenesis and improves cognitive function following TBI, even when injury-induced neurogenesis was inhibited. This suggests that the therapeutic effects of donepezil in TBI occur separately from its effects on neurogenesis.