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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) DATABASE

    EPA Science Inventory

    The Traumatic Brain Injury National Data Center (TBINDC) at Kessler Medical Rehabilitation Research and Education Center is the coordinating center for the research and dissemination efforts of the Traumatic Brain Injury Model Systems (TBIMS) program funded by the National Instit...

  3. 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 ...

  4. 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 ...

  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. Traumatic Brain Injury (TBI): Moderate or Severe

    MedlinePlus

    ... know? There are two types of TBIs: Closed Head Injury Caused by a blow or jolt to the head that does not penetrate the skull Penetrating Head Injury Occurs when an object goes through the skull ...

  7. 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,…

  8. 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. PMID:25553619

  9. 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…

  10. 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 ...

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. TBI ADAPTER: traumatic brain injury assessment diagnosis advocacy prevention and treatment from the emergency room--a prospective observational study.

    PubMed

    Ganti, Latha; Daneshvar, Yasamin; Bodhit, Aakash; Ayala, Sarah; Patel, Pratik S; Lottenberg, Lawrence L; York, Donna; Counsell, Colleen; Peters, Keith R

    2015-04-01

    There is no standard treatment algorithm for patients who present to the emergency department (ED) with acute traumatic brain injury (TBI). This is in part because of the heterogeneity of the injury pattern and the patient profile, and the lack of evidence-based guidelines, especially for mild TBI in adults. As TBI is seen more and more frequently in the ED, a standardized assessment would be beneficial in terms of efficiency. The authors present their ED approach to mild TBI evaluation in the ED, along with results to date. These data represent a prospective observational cohort study, where each patient provided individual, written informed consent. PMID:25826342

  20. 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

  1. 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. PMID:26806403

  2. An evaluation of the strategic approach to the rehabilitation of traumatic brain injury (TBI) patients

    PubMed Central

    Tomaszewski, Wiesław; Mańko, Grzegorz

    2011-01-01

    Summary Background The objective of our study was to evaluate a goal-driven strategic plan for the step-by-step rehabilitation of traumatic brain injury (TBI) patients, with effectiveness measured in terms of quality of life, as compared to patients treated according to a standard, progressive rehabilitation program. Material/Methods We studied 40 patients after TBI awakened from a long-term coma. The patients were divided into two equal groups: a control group (n=20) involving patients treated before the introduction of the strategic approach, and an experimental group (n=20) involving patients rehabilitated under the strategic approach. In evaluating the effectiveness of rehabilitation we used a structured interview with clinical observation and a scale for assessing the quality of life of patients after TBI. Results The deterioration in the quality of life of TBI patients is mainly related to difficulties in satisfying physiological needs, self-care, reduced mobility and disorders of cognitive, regulatory, and social functions. In both groups, the feature most susceptible to rehabilitation related change was movement, while the least susceptible functions were associated with the use of different means of transport. This change is significantly greater in persons in the experimental group, as compared to controls. Conclusions We found that a rehabilitation program controlled by a strategic plan, with the cooperation of the patient, is more effective in improving the quality of life, as the patient is more self-motivated to individually designed objectives. PMID:21873948

  3. [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

  4. 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

  5. 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%).

  6. 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. PMID:23952719

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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,…

  12. Abnormal neurological exam findings in individuals with mild traumatic brain injury (mTBI) versus psychiatric and healthy controls.

    PubMed

    Silva, Marc A; Donnell, Alison J; Kim, Michelle S; Vanderploeg, Rodney D

    2012-01-01

    In those with a history of mild traumatic brain injury (mTBI), cognitive and emotional disturbances are often misattributed to that preexisting injury. However, causal determinations of current symptoms cannot be conclusively determined because symptoms are often nonspecific to etiology and offer virtually no differential diagnostic value in postacute or chronic phases. This population-based study examined whether the presence of abnormalities during neurological examination would distinguish between mTBI (in the chronic phase), healthy controls, and selected psychiatric conditions. Retrospective analysis of data from 4462 community-dwelling Army veterans was conducted. Diagnostically unique groups were compared on examination of cranial nerve function and other neurological signs. Results demonstrated that individuals with mTBI were no more likely than those with a major depressive disorder, generalized anxiety disorder, posttraumatic stress disorder, or somatoform disorder to show any abnormality. Thus, like self-reported cognitive and emotional symptoms, the presence of cranial nerve or other neurological abnormalities offers no differential diagnostic value. Clinical implications and study limitations are presented. PMID:23020281

  13. 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

  14. Evolving hypopituitarism as a consequence of traumatic brain injury (TBI) in childhood - call for attention.

    PubMed

    Medic-Stojanoska, Milica; Pekic, Sandra; Curic, Nikola; Djilas-Ivanovic, Dragana; Popovic, Vera

    2007-06-01

    Hypopituitarism is a common complication of TBI in long-term survivors, more frequent than previously realized. It may be partial or complete, sometimes very subtle without visible lesions in hypothalamo-pituitary region and is diagnosed only by biochemical means. Neuroendocrine abnormalities caused by TBI may have significant implications for the recovery and rehabilitation of these patients. The subjects at risk are those who have suffered moderate to severe trauma, although mild intensity trauma may precede hypopituitarism also. Particular attention should be paid to this problem in children and adolescents. We describe a patient with hypopituitarism thought to be idiopathic due to mild head trauma which caused diabetes insipidus in childhood, gradual failure of pituitary hormones during the period of growth and development, and metabolic (dyslipidemia), physical (obesity), and cognitive impairments in the adult period. PMID:17906374

  15. Synchronization between the anterior and posterior cortex determines consciousness level in patients with traumatic brain injury (TBI).

    PubMed

    Leon-Carrion, Jose; Leon-Dominguez, Umberto; Pollonini, Luca; Wu, Meng-Hung; Frye, Richard E; Dominguez-Morales, Maria Rosario; Zouridakis, George

    2012-10-01

    Survivors of traumatic brain injury (TBI) often suffer disorders of consciousness as a result of a breakdown in cortical connectivity. However, little is known about the neural discharges and cortical areas working in synchrony to generate consciousness in these patients. In this study, we analyzed cortical connectivity in patients with severe neurocognitive disorder (SND) and in the minimally conscious state (MCS). We found two synchronized networks subserving consciousness; one retrolandic (cognitive network) and the other frontal (executive control network). The synchrony between these networks is severely disrupted in patients in the MCS as compared to those with better levels of consciousness and a preserved state of alertness (SND). The executive control network could facilitate the synchronization and coherence of large populations of distant cortical neurons using high frequency oscillations on a precise temporal scale. Consciousness is altered or disappears after losing synchrony and coherence. We suggest that the synchrony between anterior and retrolandic regions is essential to awareness, and that a functioning frontal lobe is a surrogate marker for preserved consciousness. This article is part of a Special Issue entitled: Brain Integration. PMID:22534483

  16. 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 ...

  17. 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 ...

  18. 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

  19. 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

  20. Evidence of increased brain amyloid in severe TBI survivors at 1, 12, and 24 months after injury: report of 2 cases.

    PubMed

    Gatson, Joshua W; Stebbins, Cari; Mathews, Dana; Harris, Thomas S; Madden, Christopher; Batjer, Hunt; Diaz-Arrastia, Ramon; Minei, Joseph P

    2016-06-01

    Traumatic brain injury (TBI) is a major risk factor for Alzheimer's disease. With respect to amyloid deposition, there are no published serial data regarding the deposition rate of amyloid throughout the brain after TBI. The authors conducted serial (18)F-AV-45 (florbetapir F18) positron emission tomography (PET) imaging in 2 patients with severe TBI at 1, 12, and 24 months after injury. A total of 12 brain regions were surveyed for changes in amyloid levels. Case 1 involved a 50-year-old man who experienced a severe TBI. Compared with the 1-month time point, of the 12 brain regions that were surveyed, a decrease in amyloid (as indicated by standard uptake value ratios) was only observed in the hippocampus (-16%, left; -12%, right) and caudate nucleus (-18%, left; -18%, right), suggesting that initial amyloid accumulation in the brain was cleared between time points 1 and 12 months after injury. Compared to the scan at 1 year, a greater increase in amyloid (+15%) was observed in the right hippocampus at the 24-month time point. The patient in Case 2 was a 37-year-old man who suffered severe trauma to the head and a subsequent stroke; he had poor cognitive/functional outcomes and underwent 1.5 years of rehabilitation. Due to a large infarct area on the injured side of the brain (right side), the authors focused primarily on brain regions affected within the left hemisphere. Compared with the 1-month scan, they only found an increase in brain amyloid within the left anterior putamen (+11%) at 12 months after injury. In contrast, decreased amyloid burden was detected in the left caudate nucleus (-48%), occipital cortex (-21%), and precuneus (-19%) brain regions at the 12-month time point, which is indicative of early accumulation and subsequent clearance. In comparison with 12-month values, more clearance was observed, since a reduction in amyloid was found at 24 months after trauma within the left anterior putamen (-12%) and occipital cortex (-15%). Also, by 24

  1. Clinical and diagnostic approach to patients with hypopituitarism due to traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and ischemic stroke (IS).

    PubMed

    Karamouzis, Ioannis; Pagano, Loredana; Prodam, Flavia; Mele, Chiara; Zavattaro, Marco; Busti, Arianna; Marzullo, Paolo; Aimaretti, Gianluca

    2016-06-01

    The hypothalamic-pituitary dysfunction attributable to traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage (SAH), and ischemic stroke (IS) has been lately highlighted. The diagnosis of TBI-induced-hypopituitarism, defined as a deficient secretion of one or more pituitary hormones, is made similarly to the diagnosis of classical hypopituitarism because of hypothalamic/pituitary diseases. Hypopituitarism is believed to contribute to TBI-associated morbidity and to functional and cognitive final outcome, and quality-of-life impairment. Each pituitary hormone must be tested separately, since there is a variable pattern of hormone deficiency among patients with TBI-induced-hypopituitarism. Similarly, the SAH and IS may lead to pituitary dysfunction although the literature in this field is limited. The drive to diagnose hypopituitarism is the suspect that the secretion of one/more pituitary hormone may be subnormal. This suspicion can be based upon the knowledge that the patient has an appropriate clinical context in which hypopituitarism can be present, or a symptom known as caused by hypopituitarism. Hypopituitarism should be diagnosed as a combination of low peripheral and inappropriately normal/low pituitary hormones although their basal evaluation may be not distinctive due to pulsatile, circadian, or situational secretion of some hormones. Evaluation of the somatotroph and corticotroph axes require dynamic stimulation test (ITT for both axes, GHRH + arginine test for somatotroph axis) in order to clearly separate normal from deficient responses. PMID:26573924

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

    PubMed Central

    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

  3. 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

  4. 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

  5. Trigeminal neuroplasticity underlies allodynia in a preclinical model of mild closed head traumatic brain injury (cTBI).

    PubMed

    Mustafa, Golam; Hou, Jiamei; Tsuda, Shigeharu; Nelson, Rachel; Sinharoy, Ankita; Wilkie, Zachary; Pandey, Rahul; Caudle, Robert M; Neubert, John K; Thompson, Floyd J; Bose, Prodip

    2016-08-01

    Post-traumatic headache (PTH) following TBI is a common and often persisting pain disability. PTH is often associated with a multimodal central pain sensitization on the skin surface described as allodynia. However, the particular neurobiology underlying cTBI-induced pain disorders are not known. These studies were performed to assess trigeminal sensory sensitization and to determine if sensitization measured behaviorally correlated with detectable changes in portions of the trigeminal sensory system (TSS), particularly trigeminal nucleus, thalamus, and sensory cortex. Thermal stimulation is particularly well suited to evaluate sensitization and was used in these studies. Recent advances in the use of reward/conflict paradigms permit use of operant measures of behavior, versus reflex-driven response behaviors, for thermal sensitization studies. Thus, to quantitate facial thermal sensitization (allodynia) in the setting of acute TBI, the current study utilized an operant orofacial pain reward/conflict testing paradigm to assess facial thermal sensitivity in uninjured control animals compared with those two weeks after cTBI in a rodent model. Significant reductions in facial contact/lick behaviors were observed in the TBI animals using either cool or warm challenge temperatures compared with behaviors in the normal animals. These facial thermal sensitizations correlated with detectable changes in multiple levels of the TSS. The immunohistochemical (IHC) studies revealed significant alterations in the expression of the serotonin (5-HT), neurokinin 1 receptor (NK1R), norepinephrine (NE), and gamma-aminobutyric acid (GABA) in the caudal trigeminal nucleus, thalamic VPL/VPM nucleus, and sensory cortex of the orofacial pain pathways. There was a strong correlation between increased expression of certain IHC markers and increased behavioral markers for facial sensitization. The authors conclude that TBI-induced changes observed in the TSS are consistent with the expression

  6. 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

  7. 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…

  8. 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

  9. 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,…

  10. 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…

  11. 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

  12. Cerebral Vascular Injury in Traumatic Brain Injury.

    PubMed

    Kenney, Kimbra; Amyot, Franck; Haber, Margalit; Pronger, Angela; Bogoslovsky, Tanya; Moore, Carol; Diaz-Arrastia, Ramon

    2016-01-01

    Traumatic cerebral vascular injury (TCVI) is a very frequent, if not universal, feature after traumatic brain injury (TBI). It is likely responsible, at least in part, for functional deficits and TBI-related chronic disability. Because there are multiple pharmacologic and non-pharmacologic therapies that promote vascular health, TCVI is an attractive target for therapeutic intervention after TBI. The cerebral microvasculature is a component of the neurovascular unit (NVU) coupling neuronal metabolism with local cerebral blood flow. The NVU participates in the pathogenesis of TBI, either directly from physical trauma or as part of the cascade of secondary injury that occurs after TBI. Pathologically, there is extensive cerebral microvascular injury in humans and experimental animal, identified with either conventional light microscopy or ultrastructural examination. It is seen in acute and chronic TBI, and even described in chronic traumatic encephalopathy (CTE). Non-invasive, physiologic measures of cerebral microvascular function show dysfunction after TBI in humans and experimental animal models of TBI. These include imaging sequences (MRI-ASL), Transcranial Doppler (TCD), and Near InfraRed Spectroscopy (NIRS). Understanding the pathophysiology of TCVI, a relatively under-studied component of TBI, has promise for the development of novel therapies for TBI. PMID:26048614

  13. 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…

  14. Sleep in traumatic brain injury.

    PubMed

    Vermaelen, James; Greiffenstein, Patrick; deBoisblanc, Bennett P

    2015-07-01

    More than one-half million patients are hospitalized annually for traumatic brain injury (TBI). One-quarter demonstrate sleep-disordered breathing, up to 50% experience insomnia, and half have hypersomnia. Sleep disturbances after TBI may result from injury to sleep-regulating brain tissue, nonspecific neurohormonal responses to systemic injury, ICU environmental interference, and medication side effects. A diagnosis of sleep disturbances requires a high index of suspicion and appropriate testing. Treatment starts with a focus on making the ICU environment conducive to normal sleep. Treating sleep-disordered breathing likely has outcome benefits in TBI. The use of sleep promoting sedative-hypnotics and anxiolytics should be judicious. PMID:26118920

  15. 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,…

  16. 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

  17. 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.…

  18. 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…

  19. 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…

  20. Traumatic Brain Injury. Fact Sheet Number 18.

    ERIC Educational Resources Information Center

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

    This fact sheet describes traumatic brain injury (TBI), an injury of the brain caused by the head being hit by something or being shaken violently. It discusses the incidence of TBI, and describes its symptoms as changes in thinking and reasoning, understanding words, remembering things, paying attention, solving problems, thinking abstractly,…

  1. Resource Guide on Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Monfore, Dorothea

    2005-01-01

    The purpose of this resource guide on traumatic brain injury (TBI) is to provide assistance to educators, families, and professionals who may be striving to increase their knowledge and understanding of brain injury. This guide will hopefully become an initial resource. It provides: a glossary of TBI Terms; contact information for and brief…

  2. 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…

  3. 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…

  4. 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.…

  5. 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

  6. 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. PMID:25170668

  7. 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…

  8. 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

  9. Biomarkers in traumatic brain injury: a review.

    PubMed

    Toman, Emma; Harrisson, S; Belli, T

    2016-04-01

    Biomarkers allow physiological processes to be monitored, in both health and injury. Multiple attempts have been made to use biomarkers in traumatic brain injury (TBI). Identification of such biomarkers could allow improved understanding of the pathological processes involved in TBI, diagnosis, prognostication and development of novel therapies. This review article aims to cover both established and emerging TBI biomarkers along with their benefits and limitations. It then discusses the potential value of TBI biomarkers to military, civilian and sporting populations and the future hopes for developing a role for biomarkers in head injury management. PMID:26527607

  10. 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. PMID:22836523

  11. 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

  12. 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

  13. Post-injury administration of NAAG peptidase inhibitor prodrug, PGI-02776, in experimental TBI.

    PubMed

    Feng, Jun-Feng; Van, Ken C; Gurkoff, Gene G; Kopriva, Christina; Olszewski, Rafal T; Song, Minsoo; Sun, Shifeng; Xu, Man; Neale, Joseph H; Yuen, Po-Wai; Lowe, David A; Zhou, Jia; Lyeth, Bruce G

    2011-06-13

    Traumatic brain injury (TBI) leads to a rapid and excessive increase in glutamate concentration in the extracellular milieu, which is strongly associated with excitotoxicity and neuronal degeneration. N-acetylaspartylglutamate (NAAG), a prevalent peptide neurotransmitter in the vertebrate nervous system, is released along with glutamate and suppresses glutamate release by actions at pre-synaptic metabotropic glutamate autoreceptors. Extracellular NAAG is hydrolyzed to N-acetylaspartate and glutamate by peptidase activity. In the present study PGI-02776, a newly designed di-ester prodrug of the urea-based NAAG peptidase inhibitor ZJ-43, was tested for neuroprotective potential when administered intraperitoneally 30 min after lateral fluid percussion TBI in the rat. Stereological quantification of hippocampal CA2-3 degenerating neurons at 24 h post injury revealed that 10 mg/kg PGI-02776 significantly decreased the number of degenerating neurons (p<0.05). Both average latency analysis of Morris water maze performance and assessment of 24-hour memory retention revealed significant differences between sham-TBI and TBI-saline. In contrast, no significant difference was found between sham-TBI and PGI-02776 treated groups in either analysis indicating an improvement in cognitive performance with PGI-02776 treatment. Histological analysis on day 16 post-injury revealed significant cell death in injured animals regardless of treatment. In vitro NAAG peptidase inhibition studies demonstrated that the parent compound (ZJ-43) exhibited potent inhibitory activity while the mono-ester (PGI-02749) and di-ester (PGI-02776) prodrug compounds exhibited moderate and weak levels of inhibitory activity, respectively. Pharmacokinetic assays in uninjured animals found that the di-ester (PGI-02776) crossed the blood-brain barrier. PGI-02776 was also readily hydrolyzed to both the mono-ester (PGI-02749) and the parent compound (ZJ-43) in both blood and brain. Overall, these findings

  14. Kids' Mild Brain Injury Can Have Long-Term Effects

    MedlinePlus

    ... medlineplus.gov/news/fullstory_160606.html Kids' Mild Brain Injury Can Have Long-Term Effects Early head ... 000 Swedes who suffered at least one traumatic brain injury (TBI) before age 25 with their unaffected ...

  15. 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

  16. 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

  17. 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

  18. 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…

  19. 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…

  20. Psychiatric disorders and traumatic brain injury

    PubMed Central

    Schwarzbold, Marcelo; Diaz, Alexandre; Martins, Evandro Tostes; Rufino, Armanda; Amante, Lúcia Nazareth; Thais, Maria Emília; Quevedo, João; Hohl, Alexandre; Linhares, Marcelo Neves; Walz, Roger

    2008-01-01

    Psychiatric disorders after traumatic brain injury (TBI) are frequent. Researches in this area are important for the patients’ care and they may provide hints for the comprehension of primary psychiatric disorders. Here we approach epidemiology, diagnosis, associated factors and treatment of the main psychiatric disorders after TBI. Finally, the present situation of the knowledge in this field is discussed. PMID:19043523

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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'. PMID:25827093

  6. Depression After Brain Injury: A Guide for Patients and Their Caregivers

    MedlinePlus

    ... a> Consumer Summary – Apr. 13, 2011 Depression After Brain Injury: A Guide for Patients and Their Caregivers ... productID=658 . Understanding Your Condition What is traumatic brain injury? Traumatic brain injury (TBI) is the medical ...

  7. 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

  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. PMID:27070263

  10. Controversies in the Management of Traumatic Brain Injury.

    PubMed

    Jinadasa, Sayuri; Boone, M Dustin

    2016-09-01

    Traumatic brain injury (TBI) is a physical insult (a bump, jolt, or blow) to the brain that results in temporary or permanent impairment of normal brain function. TBI describes a heterogeneous group of disorders. The resulting secondary injury, namely brain swelling and its sequelae, is the reason why patients with these vastly different initial insults are homogenously treated. Much of the evidence for the management of TBI is poor or conflicting, and thus definitive guidelines are largely unavailable for clinicians at this time. A substantial portion of this article focuses on discussing the controversies in the management of TBI. PMID:27521198

  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. Evidence That the Blood Biomarker SNTF Predicts Brain Imaging Changes and Persistent Cognitive Dysfunction in Mild TBI Patients

    PubMed Central

    Siman, Robert; Giovannone, Nicholas; Hanten, Gerri; Wilde, Elisabeth A.; McCauley, Stephen R.; Hunter, Jill V.; Li, Xiaoqi; Levin, Harvey S.; Smith, Douglas H.

    2013-01-01

    Although mild traumatic brain injury (mTBI), or concussion, is not typically associated with abnormalities on computed tomography (CT), it nevertheless causes persistent cognitive dysfunction for many patients. Consequently, new prognostic methods for mTBI are needed to identify at risk cases, especially at an early and potentially treatable stage. Here, we quantified plasma levels of the neurodegeneration biomarker calpain-cleaved αII-spectrin N-terminal fragment (SNTF) from 38 participants with CT-negative mTBI, orthopedic injury (OI), and normal uninjured controls (UCs) (age range 12–30 years), and compared them with findings from diffusion tensor imaging (DTI) and long-term cognitive assessment. SNTF levels were at least twice the lower limit of detection in 7 of 17 mTBI cases and in 3 of 13 OI cases, but in none of the UCs. An elevation in plasma SNTF corresponded with significant differences in fractional anisotropy and the apparent diffusion coefficient in the corpus callosum and uncinate fasciculus measured by DTI. Furthermore, increased plasma SNTF on the day of injury correlated significantly with cognitive impairment that persisted for at least 3 months, both across all study participants and also among the mTBI cases by themselves. The elevation in plasma SNTF in the subset of OI cases, accompanied by corresponding white matter and cognitive abnormalities, raises the possibility of identifying undiagnosed cases of mTBI. These data suggest that the blood level of SNTF on the day of a CT-negative mTBI may identify a subset of patients at risk of white matter damage and persistent disability. SNTF could have prognostic and diagnostic utilities in the assessment and treatment of mTBI. PMID:24302918

  15. NONINVASIVE BRAIN STIMULATION IN TRAUMATIC BRAIN INJURY

    PubMed Central

    Demirtas-Tatlidede, Asli; Vahabzadeh-Hagh, Andrew M.; Bernabeu, Montserrat; Tormos, Jose M.; Pascual-Leone, Alvaro

    2012-01-01

    Brain stimulation techniques have evolved in the last few decades with more novel methods capable of painless, noninvasive brain stimulation. While the number of clinical trials employing noninvasive brain stimulation continues to increase in a variety of medication-resistant neurological and psychiatric diseases, studies evaluating their diagnostic and therapeutic potential in traumatic brain injury (TBI) are largely lacking. This review introduces different techniques of noninvasive brain stimulation, which may find potential use in TBI. We cover transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), low-level laser therapy (LLLT) and transcranial doppler sonography (TCD) techniques. We provide a brief overview of studies to date, discuss possible mechanisms of action, and raise a number of considerations when thinking about translating these methods to clinical use. PMID:21691215

  16. 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…

  17. 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

  18. 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

  19. 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

  20. 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. PMID:19333063

  1. Traumatic brain injury: a review of characteristics, molecular basis and management.

    PubMed

    Wang, Ke; Cui, Daming; Gao, Liang

    2016-01-01

    Traumatic brain injury (TBI) is a critical cause of hospitalization, disability, and death worldwide. The global increase in the incidence of TBI poses a significant socioeconomic burden. Guidelines for the management of acute TBI mostly pertain to emergency treatment. Comprehensive gene expression analysis is currently available for several animal models of TBI, along with enhanced understanding of the molecular mechanisms activated during injury and subsequent recovery. The current review focuses on the characteristics, molecular basis and management of TBI. PMID:27100477

  2. 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…

  3. 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

  4. Changing the Odds: A North Carolina Family's Search to Help Those with TBI

    MedlinePlus

    ... Brain Injury Changing the Odds A North Carolina family's search to help those with TBI Past Issues / ... with traumatic brain injury (TBI)—and changed his family's life forever. "Back then there were no roadmaps ...

  5. Changing the Odds A North Carolina family's search to help those with TBI

    MedlinePlus

    ... Brain Injury Changing the Odds A North Carolina family's search to help those with TBI Past Issues / ... with traumatic brain injury (TBI)—and changed his family's life forever. "Back then there were no roadmaps ...

  6. 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

  7. Thaliporphine derivative improves acute lung injury after traumatic brain injury.

    PubMed

    Chen, Gunng-Shinng; Huang, Kuo-Feng; Huang, Chien-Chu; Wang, Jia-Yi

    2015-01-01

    Acute lung injury (ALI) occurs frequently in patients with severe traumatic brain injury (TBI) and is associated with a poor clinical outcome. Aquaporins (AQPs), particularly AQP1 and AQP4, maintain water balances between the epithelial and microvascular domains of the lung. Since pulmonary edema (PE) usually occurs in the TBI-induced ALI patients, we investigated the effects of a thaliporphine derivative, TM-1, on the expression of AQPs and histological outcomes in the lung following TBI in rats. TM-1 administered (10 mg/kg, intraperitoneal injection) at 3 or 4 h after TBI significantly reduced the elevated mRNA expression and protein levels of AQP1 and AQP4 and diminished the wet/dry weight ratio, which reflects PE, in the lung at 8 and 24 h after TBI. Postinjury TM-1 administration also improved histopathological changes at 8 and 24 h after TBI. PE was accompanied with tissue pathological changes because a positive correlation between the lung injury score and the wet/dry weight ratio in the same animal was observed. Postinjury administration of TM-1 improved ALI and reduced PE at 8 and 24 h following TBI. The pulmonary-protective effect of TM-1 may be attributed to, at least in part, downregulation of AQP1 and AQP4 expression after TBI. PMID:25705683

  8. 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

  9. 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.

  10. 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

  11. Mapping the Connectome Following Traumatic Brain Injury.

    PubMed

    Hannawi, Yousef; Stevens, Robert D

    2016-05-01

    There is a paucity of accurate and reliable biomarkers to detect traumatic brain injury, grade its severity, and model post-traumatic brain injury (TBI) recovery. This gap could be addressed via advances in brain mapping which define injury signatures and enable tracking of post-injury trajectories at the individual level. Mapping of molecular and anatomical changes and of modifications in functional activation supports the conceptual paradigm of TBI as a disorder of large-scale neural connectivity. Imaging approaches with particular relevance are magnetic resonance techniques (diffusion weighted imaging, diffusion tensor imaging, susceptibility weighted imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, and positron emission tomographic methods including molecular neuroimaging). Inferences from mapping represent unique endophenotypes which have the potential to transform classification and treatment of patients with TBI. Limitations of these methods, as well as future research directions, are highlighted. PMID:27021773

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

    PubMed

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

    2012-09-01

    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

  13. 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…

  14. 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

  15. 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,…

  16. TBI Symptoms, Diagnosis, Treatment, Prevention

    MedlinePlus

    ... Issues Cover Story: Traumatic Brain Injury TBI Symptoms, Diagnosis, Treatment, Prevention Past Issues / Fall 2008 Table of ... of coordination, and increased confusion, restlessness or agitation. Diagnosis Imaging tests, including X-rays of the head ...

  17. 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

  18. Practice Update: What Professionals Who Are Not Brain Injury Specialists Need to Know About Intimate Partner Violence-Related Traumatic Brain Injury.

    PubMed

    Murray, Christine E; Lundgren, Kristine; Olson, Loreen N; Hunnicutt, Gwen

    2016-07-01

    There is growing recognition of the risk for traumatic brain injury (TBI) among victims and survivors of intimate partner violence (IPV). A wide range of physically abusive behaviors may lead to injuries to the head or neck and place an individual at risk for a TBI. The purpose of this article is to consolidate current research and present practical guidelines for professionals, who are not brain injury specialists, but work with clients who may have sustained a TBI in the context of IPV. Recommendations are provided for TBI risk screening, making appropriate referrals, and providing services in light of a potential TBI. PMID:25951838

  19. Traumatic Brain Injury

    MedlinePlus

    ... a wide range of changes affecting thinking, sensation, language, or emotions. TBI can be associated with post-traumatic stress disorder. People with severe injuries usually need rehabilitation. NIH: National Institute of Neurological Disorders and Stroke

  20. 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…

  1. 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…

  2. Pathophysiology of battlefield associated traumatic brain injury.

    PubMed

    Duckworth, Josh L; Grimes, Jamie; Ling, Geoffrey S F

    2013-02-01

    As more data is accumulated from Operation Iraqi Freedom and Operation Enduring Freedom (OEF in Afghanistan), it is becoming increasing evident that traumatic brain injury (TBI) is a serious and highly prevalent battle related injury. Although traditional TBIs such as closed head and penetrating occur in the modern battle space, the most common cause of modern battle related TBI is exposure to explosive blast. Many believe that explosive blast TBI is unique from the other forms of TBI. This is because the physical forces responsible for explosive blast TBI are different than those for closed head TBI and penetrating TBI. The unique force associated with explosive blast is the blast shock pressure wave. This shock wave occurs over a very short period, milliseconds, and has a specific profile known as the Freidlander curve. This pressure-time curve is characterized by an initial very rapid up-rise followed by a longer decay that reaches a negative inflection point before returning to baseline. This is important as the effect of this shock pressure on brain parenchyma is distinct. The diffuse interaction of the pressure wave with the brain leads to a complex cascade of events that affects neurons, axons, glia cells, and vasculature. It is only by properly studying this disease will meaningful therapies be realized. PMID:22703708

  3. Mild traumatic brain injury in a gymnast.

    PubMed

    Knight, Debra; Dewitt, Rachel; Moser, Sharon

    2016-07-01

    Primary care providers often are responsible for the initial evaluation and management plan of young patients with mild traumatic brain injury (mild TBI, also called concussion), and need to be familiar with new protocols and how to incorporate them into a patient's treatment plan. This article describes a patient who suffered a mild TBI and returned to sports too early, and discusses the appropriate protocols for managing concussion in children. PMID:27351644

  4. Psychotic disorder caused by traumatic brain injury.

    PubMed

    Fujii, Daryl E; Ahmed, Iqbal

    2014-03-01

    Psychosis is a rare and severe sequela of traumatic brain injury (TBI). This article assists clinicians in differential diagnosis by providing literature-based guidance with regard to use of the Diagnostic and Statistical Manual for Mental Disorders 5 criteria for this condition. This article also describes potential relationships between TBI and the development of a psychosis within the conceptualization of psychosis as a neurobehavioral syndrome. PMID:24529427

  5. 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

  6. 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

  7. 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

  8. Adenosine Neuromodulation and Traumatic Brain Injury

    PubMed Central

    Lusardi, T.A

    2009-01-01

    Adenosine is a ubiquitous signaling molecule, with widespread activity across all organ systems. There is evidence that adenosine regulation is a significant factor in traumatic brain injury (TBI) onset, recovery, and outcome, and a growing body of experimental work examining the therapeutic potential of adenosine neuromodulation in the treatment of TBI. In the central nervous system (CNS), adenosine (dys)regulation has been demonstrated following TBI, and correlated to several TBI pathologies, including impaired cerebral hemodynamics, anaerobic metabolism, and inflammation. In addition to acute pathologies, adenosine function has been implicated in TBI comorbidities, such as cognitive deficits, psychiatric function, and post-traumatic epilepsy. This review presents studies in TBI as well as adenosine-related mechanisms in co-morbidities of and unfavorable outcomes resulting from TBI. While the exact role of the adenosine system following TBI remains unclear, there is increasing evidence that a thorough understanding of adenosine signaling will be critical to the development of diagnostic and therapeutic tools for the treatment of TBI. PMID:20190964

  9. 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

  10. Hyperbaric oxygen therapy for traumatic brain injury

    PubMed Central

    2011-01-01

    Traumatic brain injury (TBI) is a major public health issue. The complexity of TBI has precluded the use of effective therapies. Hyperbaric oxygen therapy (HBOT) has been shown to be neuroprotective in multiple neurological disorders, but its efficacy in the management of TBI remains controversial. This review focuses on HBOT applications within the context of experimental and clinical TBI. We also discuss its potential neuroprotective mechanisms. Early or delayed multiple sessions of low atmospheric pressure HBOT can reduce intracranial pressure, improve mortality, as well as promote neurobehavioral recovery. The complimentary, synergistic actions of HBOT include improved tissue oxygenation and cellular metabolism, anti-apoptotic, and anti-inflammatory mechanisms. Thus HBOT may serve as a promising neuroprotective strategy that when combined with other therapeutic targets for TBI patients which could improve long-term outcomes. PMID:22146562

  11. 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

  12. 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

  13. 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

  14. Nutritional treatment for acute and chronic traumatic brain injury patients.

    PubMed

    Curtis, L; Epstein, P

    2014-09-01

    Proper nutrition is critical for recovery from traumatic brain injury (TBI). Prompt enteral feeding of moderate to severe TBI patients has been associated with significantly lower mortality and rates of infection. Probiotic supplementation has been associated with significantly lower rates of infection in TBI and other trauma patients. Human studies have suggested that supplementation with omega 3 fats, vitamin D, N-Acetylcysteine, branched chain amino acids, and zinc may be helpful for recovery from TBI. Animal TBI models have suggested that alpha-lipoic acid, magnesium, taurine, coenzyme Q10, and many phytonutrients (such as resveratrol) are also helpful. Unfortunately, recent human clinical trials with citicoline in TBI and stroke patients have produced disappointing results. Much more research is needed on multifaceted nutritional strategies to treat TBI patients in both the immediate post-injury phase and throughout the patients lifespan. PMID:24844176

  15. Neuropsychiatry of Pediatric Traumatic Brain Injury

    PubMed Central

    Max, Jeffrey E.

    2014-01-01

    Synopsis Pediatric traumatic brain injury (TBI) is a major public health problem. Psychiatric disorders with onset before the injury appear to be more common than population base rates. Novel (postinjury onset) psychiatric disorders (NPD) are also common and complicate child function after injury. Novel disorders include personality change due to TBI, secondary attention-deficit/hyperactivity disorder (SADHD), as well as other disruptive behavior disorders, and internalizing disorders. This article reviews preinjury psychiatric disorders as well as biopsychosocial risk factors and treatments for NPD. PMID:24529428

  16. Sigma-1 Receptor Modulates Neuroinflammation After Traumatic Brain Injury.

    PubMed

    Dong, Hui; Ma, Yunfu; Ren, Zengxi; Xu, Bin; Zhang, Yunhe; Chen, Jing; Yang, Bo

    2016-07-01

    Traumatic brain injury (TBI) remains a significant clinical problem and contributes to one-third of all injury-related deaths. Activated microglia-mediated inflammatory response is a distinct characteristic underlying pathophysiology of TBI. Here, we evaluated the effect and possible mechanisms of the selective Sigma-1 receptor agonist 2-(4-morpholinethyl)-1-phenylcyclohexanecarboxylate (PRE-084) in mice TBI model. A single intraperitoneal injection 10 μg/g PRE-084, given 15 min after TBI significantly reduced lesion volume, lessened brain edema, attenuated modified neurological severity score, increased the latency time in wire hang test, and accelerated body weight recovery. Moreover, immunohistochemical analysis with Iba1 staining showed that PRE-084 lessened microglia activation. Meanwhile, PRE-084 reduced nitrosative and oxidative stress to proteins. Thus, Sigma-1 receptors play a major role in inflammatory response after TBI and may serve as useful target for TBI treatment in the future. PMID:26228028

  17. 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)…

  18. Traumatic Brain Injury: A Guidebook for Idaho Educators.

    ERIC Educational Resources Information Center

    Carter, Susanne

    This guide is an introduction to head injury and to educational resources in the field. An introductory section describes traumatic brain injury (TBI) as a federally recognized disability category and provides its federal and Idaho definitions. The following section introduces the unique characteristics of students with brain injuries. A section…

  19. 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, ...

  20. 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

  1. 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

  2. Traumatic brain injury: pathophysiology for neurocritical care.

    PubMed

    Kinoshita, Kosaku

    2016-01-01

    Severe cases of traumatic brain injury (TBI) require neurocritical care, the goal being to stabilize hemodynamics and systemic oxygenation to prevent secondary brain injury. It is reported that approximately 45 % of dysoxygenation episodes during critical care have both extracranial and intracranial causes, such as intracranial hypertension and brain edema. For this reason, neurocritical care is incomplete if it only focuses on prevention of increased intracranial pressure (ICP) or decreased cerebral perfusion pressure (CPP). Arterial hypotension is a major risk factor for secondary brain injury, but hypertension with a loss of autoregulation response or excess hyperventilation to reduce ICP can also result in a critical condition in the brain and is associated with a poor outcome after TBI. Moreover, brain injury itself stimulates systemic inflammation, leading to increased permeability of the blood-brain barrier, exacerbated by secondary brain injury and resulting in increased ICP. Indeed, systemic inflammatory response syndrome after TBI reflects the extent of tissue damage at onset and predicts further tissue disruption, producing a worsening clinical condition and ultimately a poor outcome. Elevation of blood catecholamine levels after severe brain damage has been reported to contribute to the regulation of the cytokine network, but this phenomenon is a systemic protective response against systemic insults. Catecholamines are directly involved in the regulation of cytokines, and elevated levels appear to influence the immune system during stress. Medical complications are the leading cause of late morbidity and mortality in many types of brain damage. Neurocritical care after severe TBI has therefore been refined to focus not only on secondary brain injury but also on systemic organ damage after excitation of sympathetic nerves following a stress reaction. PMID:27123305

  3. Effects of traumatic brain injury on intestinal contractility

    PubMed Central

    OLSEN, A. B.; HETZ, R. A.; XUE, H.; AROOM, K. R.; BHATTARAI, D.; JOHNSON, E.; BEDI, S.; COX, C. S.; URAY, K.

    2014-01-01

    Background Patients with traumatic brain injury (TBI) often suffer from gastrointestinal dysfunction including intolerance to enteral feedings. However, it is unclear how TBI affects small intestinal contractile activity. The purpose of this study was to determine if TBI affects intestinal smooth muscle function. Methods Sprague–Dawley rats were subjected to controlled cortical impact injury (TBI). Sham animals underwent a similar surgery but no injury (SHAM). Animals were sacrificed 1, 3, and 7 days after TBI and intestinal smooth muscle tissue was collected for measurement of contractile activity and transit, NF-kB activity, and cytokine levels. Brains were collected after sacrifice to determine volume loss due to injury. Key Results Contractile activity decreased significantly in ileum, but not jejunum, in the TBI group 7 days after injury compared with SHAM. Brain volume loss increased significantly 7 days after injury compared with 3 days and correlated significantly with the contractile activity 1 day after injury. In the intestinal smooth muscle, NF-kB activity increased significantly in the TBI group 3 and 7 days after injury vs SHAM. Wet to dry weight ratio, indicating edema, also increased significantly in the TBI group. Interleukin- 1α, -1β, and -17 increased significantly in the TBI group compared with SHAM. Conclusions & Inferences Traumatic brain injury causes a delayed but significant decrease in intestinal contractile activity in the ileum leading to delayed transit. The decreased intestinal contractile activity is attributed to secondary inflammatory injury as evidenced by increased NF-kB activity, increased edema, and increased inflammatory cytokines in the intestinal smooth muscle. PMID:23551971

  4. 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…

  5. 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…

  6. 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…

  7. 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 95years 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 itself

  8. 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

  9. The Effects of Shilajit on Brain Edema, Intracranial Pressure and Neurologic Outcomes following the Traumatic Brain Injury in Rat

    PubMed Central

    Khaksari, Mohammad; Mahmmodi, Reza; Shahrokhi, Nader; Shabani, Mohammad; Joukar, Siavash; Aqapour, Mobin

    2013-01-01

    Objective(s): Brain edema is one of the most serious causes of death within the first few days after trauma brain injury (TBI). In this study we have investigated the role of Shilajit on brain edema, blood-brain barrier (BBB) permeability, intracranial pressure (ICP) and neurologic outcomes following brain trauma. Materials and Methods: Diffuse traumatic brain trauma was induced in rats by drop of a 250 g weight from a 2 m high (Marmarou’s methods). Animals were randomly divided into 5 groups including sham, TBI, TBI-vehicle, TBI-Shi150 group and TBI-Shi250 group. Rats were undergone intraperitoneal injection of Shilajit and vehicle at 1, 24, 48 and 72 hr after trauma. Brain water content, BBB permeability, ICP and neurologic outcomes were finally measured. Results: Brain water and Evans blue dye contents showed significant decrease in Shilajit-treated groups compared to the TBI-vehicle and TBI groups. Intracranial pressure at 24, 48 and 72 hr after trauma had significant reduction in Shilajit-treated groups as compared to TBI-vehicle and TBI groups (P<0.001). The rate of neurologic outcomes improvement at 4, 24, 48 and 72 hr after trauma showed significant increase in Shilajit-treated groups in comparison to theTBI- vehicle and TBI groups (P <0.001). Conclusion: The present results indicated that Shilajit may cause in improvement of neurologic outcomes through decreasing brain edema, disrupting of BBB, and ICP after the TBI. PMID:23997917

  10. 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…

  11. Misconceptions about traumatic brain injury among correctional health care professionals.

    PubMed

    Yuhasz, James E

    2013-04-01

    This study explored the prevalence of misconceptions of traumatic brain injury (TBI) among a sample of correctional health care professionals. Prior research has identified a high prevalence of TBI among criminal offenders, and misconceptions about TBI exist among laypersons and nonexpert professionals. Participants (N = 155) completed a 25-item survey about the sequelae of TBI. Results were compared with previous studies. This sample performed significantly better than laypersons and commensurable to other nonexpert professionals. Misconceptions were higher on items related to loss of consciousness, memory, and recovery. Gender, prior familiarity to someone with a history of TBI, and prior training in TBI accounted for statistically fewer misconceptions. The findings support the need for continued training and increased awareness about TBI among inmates. PMID:23446874

  12. Purines: forgotten mediators in traumatic brain injury.

    PubMed

    Jackson, Edwin K; Boison, Detlev; Schwarzschild, Michael A; Kochanek, Patrick M

    2016-04-01

    Recently, the topic of traumatic brain injury has gained attention in both the scientific community and lay press. Similarly, there have been exciting developments on multiple fronts in the area of neurochemistry specifically related to purine biology that are relevant to both neuroprotection and neurodegeneration. At the 2105 meeting of the National Neurotrauma Society, a session sponsored by the International Society for Neurochemistry featured three experts in the field of purine biology who discussed new developments that are germane to both the pathomechanisms of secondary injury and development of therapies for traumatic brain injury. This included presentations by Drs. Edwin Jackson on the novel 2',3'-cAMP pathway in neuroprotection, Detlev Boison on adenosine in post-traumatic seizures and epilepsy, and Michael Schwarzschild on the potential of urate to treat central nervous system injury. This mini review summarizes the important findings in these three areas and outlines future directions for the development of new purine-related therapies for traumatic brain injury and other forms of central nervous system injury. In this review, novel therapies based on three emerging areas of adenosine-related pathobiology in traumatic brain injury (TBI) were proposed, namely, therapies targeting 1) the 2',3'-cyclic adenosine monophosphate (cAMP) pathway, 2) adenosine deficiency after TBI, and 3) augmentation of urate after TBI. PMID:26809224

  13. 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…

  14. 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

  15. Traumatic brain injury: Does gender influence outcomes?

    PubMed Central

    Munivenkatappa, Ashok; Agrawal, Amit; Shukla, Dhaval P.; Kumaraswamy, Deepika; Devi, Bhagavatula Indira

    2016-01-01

    Background: Traumatic brain injury (TBI) is a major public health problem. Both genders are affected, but little is known about female TBI. The present study exclusively explores epidemiological, clinical, imaging, and death aspects of female TBI, and how it differs from males. Methods: It is a retrospective study. Data were documented from a tertiary institute during January 2010 to March 2010. All variables were documented on standard proforma. The data were analyzed using R statistics software. Age group was categorized into pediatric (<18 years), middle (19–60 years) and elderly (>61 years). Significance was tested using Chi-square test at the significance level of P < 0.05. Results: Data of 1627 TBI patients were recorded. Of the total, female TBIs contributed nearly 20%. Compared to males, female patients reported higher percentages in manifesting symptoms (84.3% vs. 82.6%), injuries due to fall (32.1% vs. 24.4%), and surgical interventions (11.6% vs. 10.4%). Female patients were significantly higher in mild head injury group (76.8% vs. 69.5%, P - 0.016) and mortality (3.4% vs. 1.6%, P - 0.048). Number of patients and deaths was more among females than males in pediatric and elderly age group. Severities of injuries were more among female patients than male patients in middle and elder age groups. Conclusion: The study results observe that female TBI group differ significantly in the severity of injury and mortality. PMID:27308254

  16. Acute blast injury reduces brain abeta in two rodent species.

    PubMed

    De Gasperi, Rita; Gama Sosa, Miguel A; Kim, Soong Ho; Steele, John W; Shaughness, Michael C; Maudlin-Jeronimo, Eric; Hall, Aaron A; Dekosky, Steven T; McCarron, Richard M; Nambiar, Madhusoodana P; Gandy, Sam; Ahlers, Stephen T; Elder, Gregory A

    2012-01-01

    Blast-induced traumatic brain injury (TBI) has been a major cause of morbidity and mortality in the conflicts in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. In particular, it is unclear whether blast injures the brain through mechanisms similar to those found in non-blast closed impact injuries (nbTBI). The β-amyloid (Aβ) peptide associated with the development of Alzheimer's disease is elevated acutely following TBI in humans as well as in experimental animal models of nbTBI. We examined levels of brain Aβ following experimental blast injury using enzyme-linked immunosorbent assays for Aβ 40 and 42. In both rat and mouse models of blast injury, rather than being increased, endogenous rodent brain Aβ levels were decreased acutely following injury. Levels of the amyloid precursor protein (APP) were increased following blast exposure although there was no evidence of axonal pathology based on APP immunohistochemical staining. Unlike the findings in nbTBI animal models, levels of the β-secretase, β-site APP cleaving enzyme 1, and the γ-secretase component presenilin-1 were unchanged following blast exposure. These studies have implications for understanding the nature of blast injury to the brain. They also suggest that strategies aimed at lowering Aβ production may not be effective for treating acute blast injury to the brain. PMID:23267342

  17. 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…

  18. 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…

  19. 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…

  20. 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

  1. 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

  2. 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.…

  3. 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

  4. Driving, brain injury and assistive technology.

    PubMed

    Lane, Amy K; Benoit, Dana

    2011-01-01

    Individuals with brain injury often present with cognitive, physical and emotional impairments which impact their ability to resume independence in activities of daily living. Of those activities, the resumption of driving privileges is cited as one of the greatest concerns by survivors of brain injury. The integration of driving fundamentals within the hierarchical model proposed by Keskinen represents the complexity of skills and behaviors necessary for driving. This paper provides a brief review of specific considerations concerning the driver with TBI and highlights current vehicle technology which has been developed by the automotive industry and by manufacturers of adaptive driving equipment that may facilitate the driving task. Adaptive equipment technology allows for compensation of a variety of operational deficits, whereas technological advances within the automotive industry provide drivers with improved safety and information systems. However, research has not yet supported the use of such intelligent transportation systems or advanced driving systems for drivers with brain injury. Although technologies are intended to improve the safety of drivers within the general population, the potential of negative consequences for drivers with brain injury must be considered. Ultimately, a comprehensive driving evaluation and training by a driving rehabilitation specialist is recommended for individuals with brain injury. An understanding of the potential impact of TBI on driving-related skills and knowledge of current adaptive equipment and technology is imperative to determine whether return-to-driving is a realistic and achievable goal for the individual with TBI. PMID:21558628

  5. Agmatine Attenuates Brain Edema and Apoptotic Cell Death after Traumatic Brain Injury.

    PubMed

    Kim, Jae Young; Lee, Yong Woo; Kim, Jae Hwan; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun

    2015-07-01

    Traumatic brain injury (TBI) is associated with poor neurological outcome, including necrosis and brain edema. In this study, we investigated whether agmatine treatment reduces edema and apoptotic cell death after TBI. TBI was produced by cold injury to the cerebral primary motor cortex of rats. Agmatine was administered 30 min after injury and once daily until the end of the experiment. Animals were sacrificed for analysis at 1, 2, or 7 days after the injury. Various neurological analyses were performed to investigate disruption of the blood-brain barrier (BBB) and neurological dysfunction after TBI. To examine the extent of brain edema after TBI, the expression of aquaporins (AQPs), phosphorylation of mitogen-activated protein kinases (MAPKs), and nuclear translocation of nuclear factor-κB (NF-κB) were investigated. Our findings demonstrated that agmatine treatment significantly reduces brain edema after TBI by suppressing the expression of AQP1, 4, and 9. In addition, agmatine treatment significantly reduced apoptotic cell death by suppressing the phosphorylation of MAPKs and by increasing the nuclear translocation of NF-κB after TBI. These results suggest that agmatine treatment may have therapeutic potential for brain edema and neural cell death in various central nervous system diseases. PMID:26130959

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Sexual changes associated with traumatic brain injury.

    PubMed

    Ponsford, Jennie

    2003-01-01

    Findings from numerous outcome studies have suggested that people with traumatic brain injuries (TBI) experience relationship difficulties and changes in sexuality. However, there have been few investigations of these problems. This paper reports the results of a study of sexuality following TBI, which aimed to identify changes in sexual behaviour, affect, self-esteem, and relationship quality, and their inter-relationships. Two hundred and eight participants with moderate-to-severe TBI (69% males) completed a questionnaire 1-5 years post-injury. Their responses were compared with those of 150 controls, matched for age, gender, and education. Of TBI participants 36-54% reported: (1) A decrease in the importance of sexuality, opportunities, and frequency of engaging in sexual activities; (2) reduced sex drive; (3) a decline in their ability to give their partner sexual satisfaction and to engage in sexual intercourse; and (4) decreased enjoyment of sexual activity and ability to stay aroused and to climax. The frequencies of such negative changes were significantly higher than those reported by controls and far outweighed the frequency of increases on these dimensions. A significant proportion of TBI participants also reported decreased self-confidence, sex appeal, higher levels of depression, and decreased communication levels and relationship quality with their sexual partner. Factors associated with sexual problems in the TBI group are explored and implications of all findings discussed. PMID:21854338

  12. 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

  13. Concussive brain injury from explosive blast

    PubMed Central

    de Lanerolle, Nihal C; Hamid, Hamada; Kulas, Joseph; Pan, Jullie W; Czlapinski, Rebecca; Rinaldi, Anthony; Ling, Geoffrey; Bandak, Faris A; Hetherington, Hoby P

    2014-01-01

    Objective Explosive blast mild traumatic brain injury (mTBI) is associated with a variety of symptoms including memory impairment and posttraumatic stress disorder (PTSD). Explosive shock waves can cause hippocampal injury in a large animal model. We recently reported a method for detecting brain injury in soldiers with explosive blast mTBI using magnetic resonance spectroscopic imaging (MRSI). This method is applied in the study of veterans exposed to blast. Methods The hippocampus of 25 veterans with explosive blast mTBI, 20 controls, and 12 subjects with PTSD but without exposure to explosive blast were studied using MRSI at 7 Tesla. Psychiatric and cognitive assessments were administered to characterize the neuropsychiatric deficits and compare with findings from MRSI. Results Significant reductions in the ratio of N-acetyl aspartate to choline (NAA/Ch) and N-acetyl aspartate to creatine (NAA/Cr) (P < 0.05) were found in the anterior portions of the hippocampus with explosive blast mTBI in comparison to control subjects and were more pronounced in the right hippocampus, which was 15% smaller in volume (P < 0.05). Decreased NAA/Ch and NAA/Cr were not influenced by comorbidities – PTSD, depression, or anxiety. Subjects with PTSD without blast had lesser injury, which tended to be in the posterior hippocampus. Explosive blast mTBI subjects had a reduction in visual memory compared to PTSD without blast. Interpretation The region of the hippocampus injured differentiates explosive blast mTBI from PTSD. MRSI is quite sensitive in detecting and localizing regions of neuronal injury from explosive blast associated with memory impairment. PMID:25493283

  14. 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.

  15. 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

  16. Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes

    PubMed Central

    2014-01-01

    Background Lysophosphatidic acid (LPA) is a bioactive phospholipid with a potentially causative role in neurotrauma. Blocking LPA signaling with the LPA-directed monoclonal antibody B3/Lpathomab is neuroprotective in the mouse spinal cord following injury. Findings Here we investigated the use of this agent in treatment of secondary brain damage consequent to traumatic brain injury (TBI). LPA was elevated in cerebrospinal fluid (CSF) of patients with TBI compared to controls. LPA levels were also elevated in a mouse controlled cortical impact (CCI) model of TBI and B3 significantly reduced lesion volume by both histological and MRI assessments. Diminished tissue damage coincided with lower brain IL-6 levels and improvement in functional outcomes. Conclusions This study presents a novel therapeutic approach for the treatment of TBI by blocking extracellular LPA signaling to minimize secondary brain damage and neurological dysfunction. PMID:24576351

  17. Factors associated with completing comprehensive traumatic brain injury evaluation.

    PubMed

    Maguen, Shira; Lau, Karen M; Madden, Erin; Seal, Karen

    2012-07-01

    This study examined factors associated with Iraq and Afghanistan Veterans following up with the Department of Veterans Affairs (VA) comprehensive traumatic brain injury (TBI) evaluation after a positive first-level VA TBI screen. Participants included 465 Iraq and Afghanistan Veterans at one VA Medical Center and its five affiliated community-based outpatient clinics, with a positive initial TBI screen between April 1, 2007 and June 1, 2010. We found that 75% of Veterans completed the comprehensive TBI evaluation. Women were three times less likely to complete the comprehensive TBI evaluation than men, and those who endorsed post-traumatic stress disorder avoidance symptoms were nearly two times less likely to complete the comprehensive TBI evaluation. In contrast, headaches, Hispanic ethnicity, and the season of the initial TBI screen (summer vs. winter) were positively associated with completing a comprehensive TBI evaluation. A substantial minority of Veterans who screen positive on the VA initial TBI screen fail to present for the comprehensive TBI evaluation. Addressing specific gender-related issues, avoidance, and the timing of referrals in the context of VA polytrauma programs may increase the likelihood that Veterans receive further assessment, education, and early intervention for TBI or other mental health problems to prevent chronic postdeployment disability. PMID:22808886

  18. [Mental disorders after mild traumatic brain injury].

    PubMed

    Gonschorek, A S; Schwenkreis, P; Guthke, T

    2016-05-01

    Mild traumatic brain injury (mTBI) is a frequent neurological disorder following a closed head injury. It is often accompanied by temporary changes of consciousness as well as cognitive, emotional and physical symptoms. These symptoms subside in the vast majority of affected persons within a few weeks; however, in recent years it has become increasingly more apparent that functionally significant long-term effects can remain after an initially diagnosed mTBI. In these cases mental disorders, such as impairment of cognitive and emotional functions as well as somatic disorders play an important role. This article presents the frequency, diagnosis, therapy and possible mechanisms of cognitive and emotional dysfunction after mTBI, including medicolegal aspects. PMID:27119532

  19. Aggression after Traumatic Brain Injury: Prevalence & Correlates

    PubMed Central

    Rao, Vani; Rosenberg, Paul; Bertrand, Melaine; Salehinia, Saeed; Spiro, Jennifer; Vaishnavi, Sandeep; Rastogi, Pramit; Noll, Kathy; Schretlen, David J; Brandt, Jason; Cornwell, Edward; Makley, Michael; Miles, Quincy Samus

    2010-01-01

    Aggression after traumatic brain injury (TBI) is common but not well defined. Sixty-seven participants with first-time TBI were seen within three months of injury and evaluated for aggression. The prevalence of aggression was found to be 28.4% and to be predominantly verbal aggression. Post-TBI aggression was associated with new-onset major depression (p=0.02), poorer social functioning (p=0.04), and increased dependency on activities of daily living (p=0.03), but not with a history of substance abuse or adult/childhood behavioral problems. Implications of the study include early screening for aggression, evaluation for depression, and consideration of psychosocial support in aggressive patients. PMID:19996251

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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

  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. INTERLEUKIN 6 MEDIATES NEUROINFLAMMATION AND MOTOR COORDINATION DEFICITS AFTER MILD TRAUMATIC BRAIN INJURY AND BRIEF HYPOXIA IN MICE

    PubMed Central

    Yang, Sung H.; Gangidine, Matt; Pritts, Timothy A.; Goodman, Michael D.; Lentsch, Alex B.

    2014-01-01

    Traumatic brain injury (TBI) is a leading cause of mortality and disability. Acute postinjury insults after TBI, such as hypoxia, contribute to secondary brain injury and worse clinical outcomes. The functional and neuroinflammatory effects of brief episodes of hypoxia experienced following TBI have not been evaluated. Our previous studies have identified interleukin 6 (IL-6) as a potential mediator of mild TBI–induced pathology. In the present study, we sought to determine the effects of brief hypoxia on mild TBI and whether IL-6 played a role in the neuroinflammatory and functional deficits after injury. A murine model of mild TBI was induced by a weight drop (500 g from 1.5 cm). After injury, mice were exposed to immediate hypoxia (Fio2 = 15.1%) or normoxia (Fio2 = 21%) for 30 min. Serum and brain samples were analyzed for inflammatory cytokines 24 h after TBI. Neuron-specific enolase was measured as a serum biomarker of brain injury. Evaluation of motor coordination was performed for 5 days after TBI using a rotarod device. In some animals, anti–IL-6 was administered following TBI and hypoxia to neutralize systemic IL-6. Mice undergoing TBI had significant increases in brain injury. Exposure to brief hypoxia after TBI resulted in a more than 5-fold increase in serum neuron-specific enolase. This increase was associated with increases in serum and brain cytokine expression, suggesting that brief hypoxia exacerbates systemic and brain inflammation. Neutralization of IL-6 suppressed postinjury neuroinflammation and neuronal injury. In addition, TBI and hypoxia induced significant motor coordination deficits that were completely abrogated by IL-6 blockade. Exposure to hypoxia after TBI induces neuroinflammation and brain injury. These changes can be mitigated by neutralization of systemic IL-6. Interleukin 6 blockade also corrected the TBI-induced deficit in motor coordination. These data suggest that systemic IL-6 modulates the degree of neuroinflammation and

  7. Brain injury - discharge

    MedlinePlus

    ... Rehabilitation Nurses. Care of the patient with mild traumatic brain injury. Available at: www.aann.org/pubs/content/guidelines. ... Stroud, NL, Zafonte R. Rehabilitation of patients with traumatic brain injury. In: Winn HR, ed. Youman's Neurological Surgery . 6th ...

  8. 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

  9. 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

  10. 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

  11. 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.

  12. Current status of fluid biomarkers in mild traumatic brain injury.

    PubMed

    Kulbe, Jacqueline R; Geddes, James W

    2016-01-01

    Mild traumatic brain injury (mTBI) affects millions of people annually and is difficult to diagnose. Mild injury is insensitive to conventional imaging techniques and diagnoses are often made using subjective criteria such as self-reported symptoms. Many people who sustain a mTBI develop persistent post-concussive symptoms. Athletes and military personnel are at great risk for repeat injury which can result in second impact syndrome or chronic traumatic encephalopathy. An objective and quantifiable measure, such as a serum biomarker, is needed to aid in mTBI diagnosis, prognosis, return to play/duty assessments, and would further elucidate mTBI pathophysiology. The majority of TBI biomarker research focuses on severe TBI with few studies specific to mild injury. Most studies use a hypothesis-driven approach, screening biofluids for markers known to be associated with TBI pathophysiology. This approach has yielded limited success in identifying markers that can be used clinically, additional candidate biomarkers are needed. Innovative and unbiased methods such as proteomics, microRNA arrays, urinary screens, autoantibody identification and phage display would complement more traditional approaches to aid in the discovery of novel mTBI biomarkers. PMID:25981889

  13. 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

  14. Simulated Aeromedical Evacuation Exacerbates Experimental Brain Injury.

    PubMed

    Skovira, Jacob W; Kabadi, Shruti V; Wu, Junfang; Zhao, Zaorui; DuBose, Joseph; Rosenthal, Robert; Fiskum, Gary; Faden, Alan I

    2016-07-15

    Aeromedical evacuation, an important component in the care of many patients with traumatic brain injury (TBI), particularly in war zones, exposes them to prolonged periods of hypobaria. The effects of such exposure on pathophysiological changes and outcome after TBI are largely unexplored. The objective of this study was to investigate whether prolonged hypobaria in rats subjected to TBI alters behavioral and histological outcomes. Adult male Sprague-Dawley rats underwent fluid percussion induced injury at 1.5-1.9 atmospheres of pressure. The effects of hypobaric exposure (6 h duration; equivalent to 0.75 atmospheres) at 6, 24, and 72 h, or 7 days after TBI were evaluated with regard to sensorimotor, cognitive, and histological changes. Additional groups were evaluated to determine the effects of two hypobaric exposures after TBI, representing primary simulated aeromedical evacuation (6 h duration at 24 h after injury) and secondary evacuation (10 h duration at 72 h after injury), as well as the effects of 100% inspired oxygen concentrations during simulated evacuation. Hypobaric exposure up to 7 days after injury significantly worsened cognitive deficits, hippocampal neuronal loss, and microglial/astrocyte activation in comparison with injured controls not exposed to hypobaria. Hyperoxia during hypobaric exposure or two exposures to prolonged hypobaric conditions further exacerbated spatial memory deficits. These findings indicate that exposure to prolonged hypobaria up to 7 days after TBI, even while maintaining physiological oxygen concentration, worsens long-term cognitive function and neuroinflammation. Multiple exposures or use of 100% oxygen further exacerbates these pathophysiological effects. PMID:26593382

  15. 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. PMID:25946383

  16. Clinical Outcomes after Traumatic Brain Injury.

    PubMed

    Sandsmark, Danielle K

    2016-06-01

    Traumatic brain injury (TBI) is a major cause of death and disability that often affects young people. After injury, the degree of recovery can be highly variable, with some people regaining near complete function while others remain severely disabled. Understanding what factors influence recovery is important for counseling patients and families in the acute period after injury and can help guide therapeutic decisions in the acute period following injury. In this review, prognostic algorithms useful for clinicians are discussed. Tools for grading patient outcomes, their role in clinical care and research studies, and their limitations are reviewed. Ongoing work focusing on the development of biomarkers to track TBI recovery and the refinement of clinical outcome metrics is summarized. PMID:27072952

  17. Simvastatin Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

    PubMed

    Mountney, Andrea; Bramlett, Helen M; Dixon, C Edward; Mondello, Stefania; Dietrich, W Dalton; Wang, Kevin K W; Caudle, Krista; Empey, Philip E; Poloyac, Samuel M; Hayes, Ronald L; Povlishock, John T; Tortella, Frank C; Kochanek, Patrick M; Shear, Deborah A

    2016-03-15

    Simvastatin, the fourth drug selected for testing by Operation Brain Trauma Therapy (OBTT), is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor used clinically to reduce serum cholesterol. In addition, simvastatin has demonstrated potent antineuroinflammatory and brain edema reducing effects and has shown promise in promoting functional recovery in pre-clinical models of traumatic brain injury (TBI). The purpose of this study was to assess the potential neuroprotective effects of oral administration of simvastatin on neurobehavioral, biomarker, and histopathological outcome measures compared across three pre-clinical TBI animal models. Adult male Sprague-Dawley rats were exposed to either moderate fluid percussion injury (FPI), controlled cortical impact injury (CCI), or penetrating ballistic-like brain injury (PBBI). Simvastatin (1 or 5 mg/kg) was delivered via oral gavage at 3 h post-injury and continued once daily out to 14 days post-injury. Results indicated an intermediate beneficial effect of simvastatin on motor performance on the gridwalk (FPI), balance beam (CCI), and rotarod tasks (PBBI). No significant therapeutic benefit was detected, however, on cognitive outcome across the OBTT TBI models. In fact, Morris water maze (MWM) performance was actually worsened by treatment in the FPI model and scored full negative points for low dose in the MWM latency and swim distance to locate the hidden platform. A detrimental effect on cortical tissue loss was also seen in the FPI model, and there were no benefits on histology across the other models. Simvastatin also produced negative effects on circulating glial fibrillary acidic protein biomarker outcomes that were evident in the FPI and PBBI models. Overall, the current findings do not support the beneficial effects of simvastatin administration over 2 weeks post-TBI using the oral route of administration and, as such, it will not be further pursued by OBTT. PMID:26541177

  18. 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

  19. Traumatic brain injury caused by laser-induced shock wave in rats: a novel laboratory model for studying blast-induced traumatic brain injury

    NASA Astrophysics Data System (ADS)

    Hatano, Ben; Matsumoto, Yoshihisa; Otani, Naoki; Saitoh, Daizoh; Tokuno, Shinichi; Satoh, Yasushi; Nawashiro, Hiroshi; Matsushita, Yoshitaro; Sato, Shunichi

    2011-03-01

    The detailed mechanism of blast-induced traumatic brain injury (bTBI) has not been revealed yet. Thus, reliable laboratory animal models for bTBI are needed to investigate the possible diagnosis and treatment for bTBI. In this study, we used laser-induced shock wave (LISW) to induce TBI in rats and investigated the histopathological similarities to actual bTBI. After craniotomy, the rat brain was exposed to a single shot of LISW with a diameter of 3 mm at various laser fluences. At 24 h after LISW exposure, perfusion fixation was performed and the extracted brain was sectioned; the sections were stained with hematoxylin-eosin. Evans blue (EB) staining was also used to evaluate disruption of the blood brain barrier. At certain laser fluence levels, neural cell injury and hemorrhagic lesions were observed in the cortex and subcortical region. However, injury was limited in the tissue region that interacted with the LISW. The severity of injury increased with increasing laser fluence and hence peak pressure of the LISW. Fluorescence originating from EB was diffusively observed in the injuries at high fluence levels. Due to the grade and spatial controllability of injuries and the histological observations similar to those in actual bTBI, brain injuries caused by LISWs would be useful models to study bTBI.

  20. 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…

  1. 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…

  2. Contribution of brain or biological reserve and cognitive or neural reserve to outcome after TBI: A meta-analysis (prior to 2015).

    PubMed

    Mathias, Jane L; Wheaton, Patricia

    2015-08-01

    Brain/biological (BR) and cognitive/neural reserve (CR) have increasingly been used to explain some of the variability that occurs as a consequence of normal ageing and neurological injuries or disease. However, research evaluating the impact of reserve on outcomes after adult traumatic brain injury (TBI) has yet to be quantitatively reviewed. This meta-analysis consolidated data from 90 studies (published prior to 2015) that either examined the relationship between measures of BR (genetics, age, sex) or CR (education, premorbid IQ) and outcomes after TBI or compared the outcomes of groups with high and low reserve. The evidence for genetic sources of reserve was limited and often contrary to prediction. APOE ∈4 status has been studied most, but did not have a consistent or sizeable impact on outcomes. The majority of studies found that younger age was associated with better outcomes, however most failed to adjust for normal age-related changes in cognitive performance that are independent of a TBI. This finding was reversed (older adults had better outcomes) in the small number of studies that provided age-adjusted scores; although it remains unclear whether differences in the cause and severity of injuries that are sustained by younger and older adults contributed to this finding. Despite being more likely to sustain a TBI, males have comparable outcomes to females. Overall, as is the case in the general population, higher levels of education and pre-morbid IQ are both associated with better outcomes. PMID:26054792

  3. 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

  4. Cerebral and extracerebral vulnerability to hypoxic insults after diffuse traumatic brain injury in rats.

    PubMed

    Mrozek, Ségolène; Luzi, Aymeric; Gonzalez, Leslie; Kerhuel, Lionel; Fourcade, Olivier; Geeraerts, Thomas

    2016-09-01

    The post-traumatic brain vulnerability suggests that after traumatic brain injury (TBI), the brain may be more susceptible to posttraumatic hypoxic insults. This concept could be extended to 'peripheral' organs, as non-neurologic organ failure is common after TBI. This study aims to characterize and quantify cerebral and extracerebral tissue hypoxia with pimonidazole resulting from a standardized hypoxia-hypotension (HH) phase occurring after a diffuse experimental TBI in rats. Rats were allocated to Sham (n=5), TBI (n=7), HH (n=7) and TBI+HH (n=7) groups. Then, pimonidazole was injected and brain, liver, heart and kidneys were analysed. In the cerebral cortex, post-treatment hypoxia was higher in TBI+HH group than Sham group (p=0.003), HH group (p=0.003) and TBI group (p=0.002). Large trends in thalamus, hippocampus and striatum for the TBI+HH group compared to the other groups were observed. For the heart and liver, the 4 groups were comparable. For the kidneys, post-treatment hypoxia was higher in the TBI group compared to the Sham and HH groups, but not more than TBI+HH group. This study reveals that a posttraumatic hypoxic insult occurring after a severe TBI has major hypoxic consequences on brain structures. However, TBI by itself appears to induce renal hypoxia that is not enhanced by posttraumatic hypoxic insult. PMID:27302136

  5. 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

  6. 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

  7. 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

  8. A Drosophila model of closed head traumatic brain injury

    PubMed Central

    Katzenberger, Rebeccah J.; Loewen, Carin A.; Wassarman, Douglas R.; Petersen, Andrew J.; Ganetzky, Barry; Wassarman, David A.

    2013-01-01

    Traumatic brain injury (TBI) is a substantial health issue worldwide, yet the mechanisms responsible for its complex spectrum of pathologies remains largely unknown. To investigate the mechanisms underlying TBI pathologies, we developed a model of TBI in Drosophila melanogaster. The model allows us to take advantage of the wealth of experimental tools available in flies. Closed head TBI was inflicted with a mechanical device that subjects flies to rapid acceleration and deceleration. Similar to humans with TBI, flies with TBI exhibited temporary incapacitation, ataxia, activation of the innate immune response, neurodegeneration, and death. Our data indicate that TBI results in death shortly after a primary injury only if the injury exceeds a certain threshold and that age and genetic background, but not sex, substantially affect this threshold. Furthermore, this threshold also appears to be dependent on the same cellular and molecular mechanisms that control normal longevity. This study demonstrates the potential of flies for providing key insights into human TBI that may ultimately provide unique opportunities for therapeutic intervention. PMID:24127584

  9. 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

  10. 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

  11. 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…

  12. Advances in neuroimaging of traumatic brain injury and posttraumatic stress disorder

    PubMed Central

    Van Boven, Robert W.; Harrington, Greg S.; Hackney, David B.; Ebel, Andreas; Gauger, Grant; Bremner, J. Douglas; D’Esposito, Mark; Detre, John A.; Haacke, E. Mark; Jack, Clifford R.; Jagust, William J.; Le Bihan, Denis; Mathis, Chester A.; Mueller, Susanne; Mukherjee, Pratik; Schuff, Norbert; Chen, Anthony; Weiner, Michael W.

    2011-01-01

    Improved diagnosis and treatment of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are needed for our military and veterans, their families, and society at large. Advances in brain imaging offer important biomarkers of structural, functional, and metabolic information concerning the brain. This article reviews the application of various imaging techniques to the clinical problems of TBI and PTSD. For TBI, we focus on findings and advances in neuroimaging that hold promise for better detection, characterization, and monitoring of objective brain changes in symptomatic patients with combat-related, closed-head brain injuries not readily apparent by standard computed tomography or conventional magnetic resonance imaging techniques. PMID:20104401

  13. 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

  14. Head injury - first aid

    MedlinePlus

    ... is shaken, is the most common type of traumatic brain injury. Scalp wounds. Skull fractures. Head injuries may cause ... of people who suffer head injuries are children. Traumatic brain injury (TBI) accounts for over 1 in 6 injury- ...

  15. 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…

  16. 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…

  17. 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 ...

  18. 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

  19. 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). PMID:23315947

  20. 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…

  1. Lateral fluid percussion: model of traumatic brain injury in mice.

    PubMed

    Alder, Janet; Fujioka, Wendy; Lifshitz, Jonathan; Crockett, David P; Thakker-Varia, Smita

    2011-01-01

    Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes (1,2). Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement (3,4). The resulting hematomas and lacerations cause a vascular response (3,5), and the morphological and functional damage of the white matter leads to diffuse axonal injury (6-8). Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure (9). Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals (10-12), which ultimately result in long-term neurological disabilities (13,14). Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration (1). The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue (1,15). Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure (16,17). The weight drop/impact model is characterized by the fall of a rod with a specific

  2. Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

    PubMed Central

    Alder, Janet; Fujioka, Wendy; Lifshitz, Jonathan; Crockett, David P.; Thakker-Varia, Smita

    2011-01-01

    Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes 1,2. Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement 3,4. The resulting hematomas and lacerations cause a vascular response 3,5, and the morphological and functional damage of the white matter leads to diffuse axonal injury 6-8. Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure 9. Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals 10-12, which ultimately result in long-term neurological disabilities 13,14. Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration 1. The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue 1,15. Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure 16,17. The weight drop/impact model is characterized by the fall of a rod with a specific mass on the closed

  3. Inhibitory Control after Traumatic Brain Injury in Children

    PubMed Central

    Sinopoli, Katia J.; Dennis, Maureen

    2011-01-01

    Inhibitory control describes a number of distinct processes. Effortless inhibition refers to acts of control that are automatic and reflexive. Effortful inhibition refers to voluntary, goal-directed acts of control such as response flexibility, interference control, cancellation inhibition, and restraint inhibition. Disruptions to a number of inhibitory control processes occur as a consequence of childhood traumatic brain injury (TBI). This paper reviews the current knowledge of inhibition deficits following childhood TBI, and includes an overview of the inhibition construct and a discussion of the specific deficits shown by children and adolescents with TBI and the factors that mediate the expression of these deficits, including injury-related variables and the expression of pre- and post-injury attention-deficit/hyperactivity disorder. The review illustrates that inhibitory control processes differ in terms of measurement, assessment, and neurological underpinnings, and also that childhood TBI may selectively disrupt particular forms of inhibition. PMID:22100363

  4. Traumatic brain injury induces neuroinflammation and neuronal degeneration that is associated with escalated alcohol self-administration in rats

    PubMed Central

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

    2014-01-01

    Background Traumatic brain injury (TBI) affects millions of people each year and is characterized by direct tissue injury followed by a neuroinflammatory response. The post-TBI recovery period can be associated with a negative emotional state characterized by alterations in affective behaviors implicated in the development of Alcohol Use Disorder in humans. The aim of this study was to test the hypothesis that post-TBI neuroinflammation is associated with behavioral dysfunction, including escalated alcohol intake. Methods Adult male Wistar rats were trained to self-administer alcohol prior to counterbalanced assignment into naïve, craniotomy, and TBI groups by baseline drinking. TBI was produced by lateral fluid percussion (LFP; >2 ATM; 25 ms). Alcohol drinking and neurobehavioral function were measured at baseline and following TBI in all experimental groups. Markers of neuroinflammation (GFAP & ED1) and neurodegeneration (FJC) were determined by fluorescence histochemistry in brains excised at sacrifice 19 days post-TBI. Results The cumulative increase in alcohol intake over the 15 days post-TBI was greater in TBI animals compared to naïve controls. A higher rate of pre-injury alcohol intake was associated with a greater increase in post-injury alcohol intake in both TBI and craniotomy animals. Immediately following TBI, both TBI and craniotomy animals exhibited greater neurobehavioral dysfunction compared to naïve animals. GFAP, IBA-1, ED1, and FJC immunoreactivity at 19 days post-TBI was significantly higher in brains from TBI animals compared to both craniotomy and naïve animals. Conclusions These results show an association between post-TBI escalation of alcohol drinking and marked localized neuroinflammation at the site of injury. Moreover, these results highlight the relevance of baseline alcohol preference in determining post-TBI alcohol drinking. Further investigation to determine the contribution of neuroinflammation to increased alcohol drinking

  5. 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

  6. 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

  7. 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

  8. 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 ...

  9. Language functioning and deficits following pediatric traumatic brain injury.

    PubMed

    Sullivan, Jeremy R; Riccio, Cynthia A

    2010-04-01

    The purpose of this article is to provide a current review of language functioning and deficits following traumatic brain injury (TBI), specifically among the pediatric population. This paper will: (a) outline the manner in which these deficits may impede functioning across environments; (b) review methods of assessing language functioning within this population; and (c) discuss empirically supported interventions to address noted language deficits as they present in pediatric TBI. PMID:20467948

  10. Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury.

    PubMed

    Shlosberg, Dan; Benifla, Mony; Kaufer, Daniela; Friedman, Alon

    2010-07-01

    Traumatic brain injury (TBI) is the leading cause of death in young adults and children. The treatment of TBI in the acute phase has improved substantially; however, the prevention and management of long-term complications remain a challenge. Blood-brain barrier (BBB) breakdown has often been documented in patients with TBI, but the role of such vascular pathology in neurological dysfunction has only recently been explored. Animal studies have demonstrated that BBB breakdown is involved in the initiation of transcriptional changes in the neurovascular network that ultimately lead to delayed neuronal dysfunction and degeneration. Brain imaging data have confirmed the high incidence of BBB breakdown in patients with TBI and suggest that such pathology could be used as a biomarker in the clinic and in drug trials. Here, we review the neurological consequences of TBI, focusing on the long-term complications of such injuries. We present the clinical evidence for involvement of BBB breakdown in TBI and examine the primary and secondary mechanisms that underlie such pathology. We go on to consider the consequences of BBB injury, before analyzing potential mechanisms linking vascular pathology to neuronal dysfunction and degeneration, and exploring possible targets for treatment. Finally, we highlight areas for future basic research and clinical studies into TBI. PMID:20551947

  11. Brain stimulation: Neuromodulation as a potential treatment for motor recovery following traumatic brain injury.

    PubMed

    Clayton, E; Kinley-Cooper, S K; Weber, R A; Adkins, D L

    2016-06-01

    There is growing evidence that electrical and magnetic brain stimulation can improve motor function and motor learning following brain damage. Rodent and primate studies have strongly demonstrated that combining cortical stimulation (CS) with skilled motor rehabilitative training enhances functional motor recovery following stroke. Brain stimulation following traumatic brain injury (TBI) is less well studied, but early pre-clinical and human pilot studies suggest that it is a promising treatment for TBI-induced motor impairments as well. This review will first discuss the evidence supporting brain stimulation efficacy derived from the stroke research field as proof of principle and then will review the few studies exploring neuromodulation in experimental TBI studies. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26855256

  12. 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

  13. 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

  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. Controlled Cortical Impact Model for Traumatic Brain Injury

    PubMed Central

    Romine, Jennifer; Gao, Xiang; Chen, Jinhui

    2014-01-01

    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. PMID:25145417

  16. Controlled cortical impact model for traumatic brain injury.

    PubMed

    Romine, Jennifer; Gao, Xiang; Chen, Jinhui

    2014-01-01

    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. PMID:25145417

  17. Affective modulation of the startle reflex following traumatic brain injury.

    PubMed

    Williams, Claire; Wood, Rodger L

    2012-01-01

    Diminished emotional recognition, expression, and responsivity are frequent legacies of traumatic brain injury (TBI) that can have an adverse impact on relationships and psychosocial recovery. However, assessment of emotion responsivity is often difficult because many patients lack insight into their altered personality. To overcome this obstacle, we used a physiological measure of emotion responsivity, the startle reflex, to examine how this can vary according to the affective valence of stimuli by comparing a TBI group with a matched control group. The study also examined whether weaknesses of attention and speed of information processing could account for differences in startle modulation across groups. Sixty-four TBI patients and controls completed the startle reflex procedure. Participants were presented with pictures that differed in affective valence, and measures were taken of eyeblink startle responses to an acoustic probe. Subjective ratings of affect and arousal for each picture were obtained, and TBI patients completed measures of attention and information processing. Results revealed that the TBI group did not show the pattern of startle modulation observed in the control group. Whilst pleasant pictures produced the usual attenuation of the startle response, startle responses to unpleasant pictures were significantly lower in the TBI group than in controls. No significant correlations emerged between startle responses and performance on neuropsychological measures in the TBI group. The TBI group also rated unpleasant pictures as significantly less arousing than did controls. The results provide partial support for a growing body of evidence that has proposed impaired emotion responsivity following TBI. PMID:22873359

  18. Erythropoietin and Its Derivates Modulate Mitochondrial Dysfunction after Diffuse Traumatic Brain Injury.

    PubMed

    Millet, Anne; Bouzat, Pierre; Trouve-Buisson, Thibaut; Batandier, Cécile; Pernet-Gallay, Karin; Gaide-Chevronnay, Lucie; Barbier, Emmanuel L; Debillon, Thierry; Fontaine, Eric; Payen, Jean-François

    2016-09-01

    Inhibiting the opening of mitochondrial permeability transition pore (mPTP), thereby maintaining the mitochondrial membrane potential and calcium homeostasis, could reduce the induction of cell death. Although recombinant human erythropoietin (rhEpo) and carbamylated erythropoietin (Cepo) were shown to prevent apoptosis after traumatic brain injury (TBI), their impact on mPTP is yet unknown. Thirty minutes after diffuse TBI (impact-acceleration model), rats were intravenously administered a saline solution (TBI-saline), 5000 UI/kg rhEpo (TBI-rhEpo) or 50 μg/kg Cepo (TBI-Cepo). A fourth group received no TBI insult (sham-operated) (n = 11 rats per group). Post-traumatic brain edema was measured using magnetic resonance imaging. A first series of experiments was conducted 2 h after TBI (or equivalent) to investigate the mitochondrial function with the determination of thresholds for mPTP opening and ultrastructural mitochondrial changes. In addition, the intramitochondrial calcium content [Caim] was measured. In a second series of experiments, brain cell apoptosis was assessed at 24 h post-injury. TBI-rhEpo and TBI-Cepo groups had a reduced brain edema compared with TBI-saline. They had higher threshold for mPTP opening with succinate as substrate: 120 (120-150) (median, interquartiles) and 100 (100-120) versus 80 (60-90) nmol calcium/mg protein in TBI-saline, respectively (p < 0.05). Similar findings were shown with glutamate-malate as substrate. TBI-rhEpo and Cepo groups had less morphological mitochondrial disruption in astrocytes. The elevation in [Caim] after TBI was not changed by rhEpo and Cepo treatment. Finally, rhEpo and Cepo reduced caspase-3 expression at 24 h post-injury. These results indicate that rhEpo and Cepo could modulate mitochondrial dysfunction after TBI. The mechanisms involved are discussed. PMID:26530102

  19. 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

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

    PubMed Central

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

    2014-01-01

    Acute post-traumatic ventricular dilation and hydrocephalus are relatively frequent consequences of traumatic brain injury (TBI). Several recent studies have indicated that high iron level 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 hours (lateral ventricle volume: 24.1±3.0 vs. 9.9±0.2 mm3 in sham group). Intraventricular injection of iron also caused hydrocephalus (25.7 ± 3.4 vs. 9.0 ± 0.6 mm3 in saline group). Deferoxamine treatment attenuated TBI-induced hydrocephalus and heme oxygenase-1 upregulation. In conclusion, iron may contribute to acute hydrocephalus after TBI. PMID:24935175

  1. 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

  2. Neuropsychology of Neuroendocrine Dysregulation after Traumatic Brain Injury

    PubMed Central

    Zihl, Josef; Almeida, Osborne F. X.

    2015-01-01

    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. PMID:26239465

  3. 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

  4. Traumatic brain injury: a risk factor for neurodegenerative diseases.

    PubMed

    Gupta, Rajaneesh; Sen, Nilkantha

    2016-01-01

    Traumatic brain injury (TBI), a major global health and socioeconomic problem, is now established as a chronic disease process with a broad spectrum of pathophysiological symptoms followed by long-term disabilities. It triggers multiple and multidirectional biochemical events that lead to neurodegeneration and cognitive impairment. Recent studies have presented strong evidence that patients with TBI history have a tendency to develop proteinopathy, which is the pathophysiological feature of neurodegenerative disorders such as Alzheimer disease (AD), chronic traumatic encephalopathy (CTE), and amyotrophic lateral sclerosis (ALS). This review mainly focuses on mechanisms related to AD, CTE, and ALS that are induced after TBI and their relevance to the advancement of these neurodegenerative diseases. This review encompasses acute effects and chronic neurodegenerative consequences after TBI for a better understanding of TBI-induced neuronal death and to design therapies that will effectively treat patients in the primary or secondary progressive stages. PMID:26352199

  5. Repeated mild traumatic brain injury results in long-term white-matter disruption

    PubMed Central

    Donovan, Virginia; Kim, Claudia; Anugerah, Ariana K; Coats, Jacqueline S; Oyoyo, Udochuwku; Pardo, Andrea C; Obenaus, Andre

    2014-01-01

    Mild traumatic brain injury (mTBI) is an increasing public health concern as repetitive injuries can exacerbate existing neuropathology and result in increased neurologic deficits. In contrast to other models of repeated mTBI (rmTBI), our study focused on long-term white-matter abnormalities after bilateral mTBIs induced 7 days apart. A controlled cortical impact (CCI) was used to induce an initial mTBI to the right cortex of Single and rmTBI Sprague Dawley rats, followed by a second injury to the left cortex of rmTBI animals. Shams received only a craniectomy. Ex vivo diffusion tensor imaging (DTI), transmission electron microscopy (TEM), and histology were performed on the anterior corpus callosum at 60 days after injury. The rmTBI animals showed a significant bilateral increase in radial diffusivity (myelin), while only modest changes in axial diffusivity (axonal) were seen between the groups. Further, the rmTBI group showed an increased g-ratio and axon caliber in addition to myelin sheath abnormalities using TEM. Our DTI results indicate ongoing myelin changes, while the TEM data show continuing axonal changes at 60 days after rmTBI. These data suggest that bilateral rmTBI induced 7 days apart leads to progressive alterations in white matter that are not observed after a single mTBI. PMID:24473478

  6. Ethical and regulatory considerations in the design of traumatic brain injury clinical studies.

    PubMed

    Hicks, Ramona

    2015-01-01

    Research is essential for improving outcomes after traumatic brain injury (TBI). However, the ubiquity, variability, and nature of TBI create many ethical issues and accompanying regulations for research. To capture the complexity and importance of designing and conducting TBI research within the framework of key ethical principles, a few highly relevant topics are highlighted. The selected topics are: (1) research conducted in emergency settings; (2) maintaining equipoise in TBI clinical trials; (3) TBI research on vulnerable populations; and (4) ethical considerations for sharing data. The topics aim to demonstrate the dynamic and multifaceted challenges of TBI research, and also to stress the value of addressing these challenges with the key ethical principles of respect, beneficence, and justice. Much has been accomplished to ensure that TBI research meets the highest ethical standards and has fair and enforceable regulations, but important challenges remain and continued efforts are needed by all members of the TBI research community. PMID:25701918

  7. Narrative language in traumatic brain injury.

    PubMed

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

    2011-08-01

    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<8) in the phase of neurological stability and 14 neurologically intact participants were recruited for the experiment. Their cognitive, linguistic and narrative skills were thoroughly assessed. The group of non-aphasic individuals with TBI had normal lexical and grammatical skills. However, they produced narratives with increased errors of cohesion and coherence due to the frequent interruption of ongoing utterances, derailments and extraneous utterances that made their discourse vague and ambiguous. They produced a normal amount of thematic units (i.e. concepts) in their narratives. However, this information was not correctly organized at micro- and macrolinguistic levels of processing. A Principal Component Analysis showed that a single factor accounted for the production of global coherence errors, and the reduction of both propositional density at the utterance level and proportion of words that conveyed information. It is hypothesized that the linguistic deficits observed in the participants with TBI may reflect a deficit at the interface between cognitive and linguistic processing rather than a specific linguistic disturbance. PMID:21723304

  8. [International multicenter studies of treatment of severe traumatic brain injury].

    PubMed

    Talypov, A E; Kordonsky, A Yu; Krylov, V V

    2016-01-01

    Despite the introduction of new diagnostic and therapeutic methods, traumatic brain injury (TBI) remains one of the leading cause of death and disability worldwide. Standards and recommendations on conservative and surgical treatment of TBI patients should be based on concepts and methods with proven efficacy. The authors present a review of studies of the treatment and surgery of severe TBI: DECRA, RESCUEicp, STITCH(TRAUMA), CRASH, CRASH-2, CAPTAIN, NABIS: H ll, Eurotherm 3235. Important recommendations of the international group IMPACT are considered. PMID:27045148

  9. 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

  10. 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. PMID:26956452

  11. Recovery of resting brain connectivity ensuing mild traumatic brain injury

    PubMed Central

    Bharath, Rose D.; Munivenkatappa, Ashok; Gohel, Suril; Panda, Rajanikant; Saini, Jitender; Rajeswaran, Jamuna; Shukla, Dhaval; Bhagavatula, Indira D.; Biswal, Bharat B.

    2015-01-01

    Brains reveal amplified plasticity as they recover from an injury. We aimed to define time dependent plasticity changes in patients recovering from mild traumatic brain injury (mTBI). Twenty-five subjects with mild head injury were longitudinally evaluated within 36 h, 3 and 6 months using resting state functional connectivity (RSFC). Region of interest (ROI) based connectivity differences over time within the patient group and in comparison with a healthy control group were analyzed at p < 0.005. We found 33 distinct ROI pairs that revealed significant changes in their connectivity strength with time. Within 3 months, the majority of the ROI pairs had decreased connectivity in mTBI population, which increased and became comparable to healthy controls at 6 months. Within this diffuse decreased connectivity in the first 3 months, there were also few regions with increased connections. This hyper connectivity involved the salience network and default mode network within 36 h, and lingual, inferior frontal and fronto-parietal networks at 3 months. Our findings in a fairly homogenous group of patients with mTBI evaluated during the 6 month window of recovery defines time varying brain connectivity changes as the brain recovers from an injury. A majority of these changes were seen in the frontal and parietal lobes between 3 and 6 months after injury. Hyper connectivity of several networks supported normal recovery in the first 6 months and it remains to be seen in future studies whether this can predict an early and efficient recovery of brain function. PMID:26441610

  12. 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

  13. 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. PMID:26668228

  14. Coated-Platelet Levels Increase with Number of Injuries in Patients with Mild Traumatic Brain Injury.

    PubMed

    Prodan, Calin I; Vincent, Andrea S; Dale, George L

    2016-05-01

    Coated-platelets are procoagulant platelets that are elevated in stroke and are associated with stroke recurrence. In a previous study, prompted by data showing an increased risk for stroke following traumatic brain injury (TBI), we found that coated-platelet levels are elevated in patients with combat-related mild TBI (mTBI) several years after the injury, compared with controls. We now investigate in an expanded patient population whether parameters commonly recorded in mTBI are related to increased coated-platelet potential. Coated-platelet levels were assayed in 120 mTBI patients at intervals ranging from 6 months to 10 years from the last injury. Correlations were calculated between coated-platelet levels and age, gender, race/ethnicity, loss of consciousness, alteration in consciousness, post-traumatic amnesia, number of injuries, mechanism of injury, time since first and last injury, smoking, medications that may influence coated-platelet levels, and pertinent comorbid conditions. Significant correlations were detected between coated-platelet levels and number of injuries (p = 0.026), gender (p = 0.01), and time since last injury (p = 0.04). A multi-variable linear model analysis, including these three parameters and an additional three parameters (race/ethnicity, smoking, and mechanism of injury) that reached a p value of <0.2, showed that the number of injuries were predictive of coated-platelet levels (p = 0.004). These results support a mechanistic link between increased coated-platelet levels and repeated injuries in mTBI. Long-term studies will be required to determine the impact of increased prothrombotic potential in mTBI patients. PMID:26414016

  15. 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

  16. 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

  17. Traumatic Brain Injury Upregulates Phosphodiesterase Expression in the Hippocampus

    PubMed Central

    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

  18. 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

  19. 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

  20. 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 ...

  1. Clinimetric measurement in traumatic brain injuries

    PubMed Central

    Opara, N; Małecka, I; Szczygiel, M

    2014-01-01

    Abstract 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. PMID:25408714

  2. Strategies for CNS repair following TBI.

    PubMed

    Aertker, Benjamin M; Bedi, Supinder; Cox, Charles S

    2016-01-01

    Traumatic brain injury (TBI) imparts a significant health burden in the United States, leaving many patients with chronic deficits. Improvement in clinical outcome following TBI has been hindered by a lack of treatments that have proven successful during phase III trials. Research remains active into a variety of non-pharmacologic, small molecule, endocrine and cell based therapies. Of particular focus in this review are the recent therapeutic avenues that have undergone clinical investigation and the mechanisms by which cell therapies may mediate recovery in severe TBI. Preclinical data show cell therapies to provide benefit when administered systemically or with transplantation to the site of injury. Increasingly, studies have shown that these cells are able to attenuate the inflammatory response to injury and stimulate production of neurotrophic factors. In animal models, beneficial effects on blood-brain barrier permeability, neuroprotection and neural repair through enhanced axonal remodeling have been observed. Clinical investigation with cell therapies for TBI remains ongoing. PMID:25637707

  3. 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

  4. 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

  5. Mild Traumatic Brain Injury among the Geriatric Population.

    PubMed

    Papa, Linda; Mendes, Matthew E; Braga, Carolina F

    2012-09-01

    Mild traumatic brain injury (TBI) is an unfortunately common occurrence in the elderly. With the growing population of older adults in the United States and globally, strategies that reduce the risk of becoming injured need to be developed, and diagnostic tools and treatments that may benefit this group need to be explored. Particular attention needs to be given to polypharmacy, drug interactions, the use of anticoagulants, safety issues in the living environment, elder abuse, and alcohol consumption. Low-mechanism falls should prompt health care providers to consider the possibility of head injury in elderly patients. Early and tailored management of our seniors following a mild TBI can provide them with the best possible quality of life. This review will discuss the current literature on mild TBI in the older adult, address gaps in research, and discuss the implications for future care of the older TBI patient. PMID:23589783

  6. 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

  7. 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

  8. Pituitary Dysfunction after Blast Traumatic Brain Injury: The UK BIOSAP Study

    PubMed Central

    Baxter, David; Sharp, David J; Feeney, Claire; Papadopoulou, Debbie; Ham, Timothy E; Jilka, Sagar; Hellyer, Peter J; Patel, Maneesh C; Bennett, Alexander N; Mistlin, Alan; McGilloway, Emer; Midwinter, Mark; Goldstone, Anthony P

    2013-01-01

    Objective Pituitary dysfunction is a recognized consequence of traumatic brain injury (TBI) that causes cognitive, psychological, and metabolic impairment. Hormone replacement offers a therapeutic opportunity. Blast TBI (bTBI) from improvised explosive devices is commonly seen in soldiers returning from recent conflicts. We investigated: (1) the prevalence and consequences of pituitary dysfunction following moderate to severe bTBI and (2) whether it is associated with particular patterns of brain injury. Methods Nineteen male soldiers with moderate to severe bTBI (median age = 28.3 years) and 39 male controls with moderate to severe nonblast TBI (nbTBI; median age = 32.3 years) underwent full dynamic endocrine assessment between 2 and 48 months after injury. In addition, soldiers had structural brain magnetic resonance imaging, including diffusion tensor imaging (DTI), and cognitive assessment. Results Six of 19 (32.0%) soldiers with bTBI, but only 1 of 39 (2.6%) nbTBI controls, had anterior pituitary dysfunction (p = 0.004). Two soldiers had hyperprolactinemia, 2 had growth hormone (GH) deficiency, 1 had adrenocorticotropic hormone (ACTH) deficiency, and 1 had combined GH/ACTH/gonadotrophin deficiency. DTI measures of white matter structure showed greater traumatic axonal injury in the cerebellum and corpus callosum in those soldiers with pituitary dysfunction than in those without. Soldiers with pituitary dysfunction after bTBI also had a higher prevalence of skull/facial fractures and worse cognitive function. Four soldiers (21.1%) commenced hormone replacement(s) for hypopituitarism. Interpretation We reveal a high prevalence of anterior pituitary dysfunction in soldiers suffering moderate to severe bTBI, which was more frequent than in a matched group of civilian moderate to severe nbTBI subjects. We recommend that all patients with moderate to severe bTBI should routinely have comprehensive assessment of endocrine function. Ann Neurol 2013;74:527–536 PMID

  9. Experimental Traumatic Brain Injury Alters Ethanol Consumption and Sensitivity

    PubMed Central

    Lowing, Jennifer L.; Susick, Laura L.; Caruso, James P.; Provenzano, Anthony M.; Raghupathi, Ramesh

    2014-01-01

    Abstract 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

  10. Nicotinamide Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

    PubMed

    Shear, Deborah A; Dixon, C Edward; Bramlett, Helen M; Mondello, Stefania; Dietrich, W Dalton; Deng-Bryant, Ying; Schmid, Kara E; Wang, Kevin K W; Hayes, Ronald L; Povlishock, John T; Kochanek, Patrick M; Tortella, Frank C

    2016-03-15

    Nicotinamide (vitamin B3) was the first drug selected for cross-model testing by the Operation Brain Trauma Therapy (OBTT) consortium based on a compelling record of positive results in pre-clinical models of traumatic brain injury (TBI). Adult male Sprague-Dawley rats were exposed to either moderate fluid percussion injury (FPI), controlled cortical impact injury (CCI), or penetrating ballistic-like brain injury (PBBI). Nicotinamide (50 or 500 mg/kg) was delivered intravenously at 15 min and 24 h after injury with subsequent behavioral, biomarker, and histopathological outcome assessments. There was an intermediate effect on balance beam performance with the high (500 mg/kg) dose in the CCI model, but no significant therapeutic benefit was detected on any other motor task across the OBTT TBI models. There was an intermediate benefit on working memory with the high dose in the FPI model. A negative effect of the low (50 mg/kg) dose, however, was observed on cognitive outcome in the CCI model, and no cognitive improvement was observed in the PBBI model. Lesion volume analysis showed no treatment effects after either FPI or PBBI, but the high dose of nicotinamide resulted in significant tissue sparing in the CCI model. Biomarker assessments included measurements of glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase-1 (UCH-L1) in blood at 4 or 24 h after injury. Negative effects (both doses) were detected on biomarker levels of GFAP after FPI and on biomarker levels of UCH-L1 after PBBI. The high dose of nicotinamide, however, reduced GFAP levels after both PBBI and CCI. Overall, our results showed a surprising lack of benefit from the low dose nicotinamide. In contrast, and partly in keeping with the literature, some benefit was achieved with the high dose. The marginal benefits achieved with nicotinamide, however, which appeared sporadically across the TBI models, has reduced enthusiasm for further investigation by the OBTT Consortium

  11. Wharton's jelly transplantation improves neurologic function in a rat model of traumatic brain injury

    PubMed Central

    Cheng, Tian; Yang, Bo; Li, Dongpeng; Ma, Shanshan; Tian, Yi; Qu, Ruina; Zhang, Wenjin; Zhang, Yanting; Hu, Kai; Guan, Fangxia; Wang, Jian

    2015-01-01

    Traumatic brain injury (TBI), which can lead to disability, dysfunction, and even death, is a prominent health problem worldwide. Effective therapy for this serious and debilitating condition is needed. Human umbilical cord matrix, known as Wharton's jelly (WJ), provides a natural, interface scaffold that is enriched in mesenchymal stem cells. In this study, we tested the efficacy of WJ tissue transplantation in a weight drop model of TBI in rats. WJ tissue was cultured and transplanted into the injury site 24h after TBI. The modified neurologic severity score, body weight, brain edema, and lesion volume were evaluated at various time points after TBI. Cognitive behavior was assessed by the novel object recognition test and the Morris water maze test. Expression of brain-derived neurotrophic factor (BDNF) in the perilesional brain area was measured at day 14 after TBI. We found that WJ tissue transplantation lessened TBI-induced brain edema (day 3), reduced lesion volume (day 28), improved neurologic function (days 21 to 28), and promoted memory and cognitive recovery. Additionally, expression of BDNF mRNA and protein was higher in WJ tissue-treated rats than in sham-operated or vehicle-treated rats. These data suggest that WJ tissue transplantation can reduce TBI-induced brain injury and may have therapeutic potential for the treatment of TBI. PMID:25638565

  12. Beneficial effects of hyperbaric oxygen on edema in rat hippocampus following traumatic brain injury.

    PubMed

    Liu, Su; Liu, Ying; Deng, Shukun; Guo, Aisong; Wang, Xiubing; Shen, Guangyu

    2015-12-01

    Hyperbaric oxygen (HBO) therapy helps alleviate secondary injury following brain trauma [traumatic brain injury (TBI)], although the mechanisms remain unclear. In this study, we assessed recovery of post-TBI spatial learning and memory in rats using the Morris water maze (MWM) and measured changes in apparent diffusion coefficient in the hippocampus by diffusion-weighted imaging (DWI) to evaluate possible therapeutic effects of HBO on TBI-associated brain edema. DWIs were obtained 8, 24, 48 h, 7 days, and 14 days post-TBI. Daily HBO therapy significantly improved post-TBI MWM performance and reduced edema in the ipsilateral hippocampus, suggesting that the therapeutic efficacy of HBO is mediated, at least in part, by a reduction in brain edema. PMID:26267487

  13. 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.

  14. Sleep disorders in patients with traumatic brain injury: a review.

    PubMed

    Castriotta, Richard J; Murthy, Jayasimha N

    2011-03-01

    Traumatic brain injury (TBI) is a global problem and causes long-term disability in millions of individuals. This is a major problem for both military- and civilian-related populations. The prevalence of sleep disorders in individuals with TBI is very high, yet mostly unrecognized. Approximately 46% of all chronic TBI patients have sleep disorders, which require nocturnal polysomnography and the Multiple Sleep Latency Test for diagnosis. These disorders include sleep apnoea (23% of all TBI patients), post-traumatic hypersomnia (11%), narcolepsy (6%) and periodic limb movements (7%). Over half of all TBI patients will have insomnia complaints, most often with less severe injury and after personal assault, and half of these may be related to a circadian rhythm disorder. Hypothalamic injury with decreased levels of wake-promoting neurotransmitters such as hypocretin (orexin) and histamine may be involved in the pathophysiology of excessive sleepiness associated with TBI. These sleep disorders result in additional neurocognitive deficits and functional impairment, which might be attributed to the original brain injury itself and thus be left without specific treatment. Most standard treatment regimens of sleep disorders appear to be effective in these patients, including continuous positive airway pressure for sleep apnoea, pramipexole for periodic limb movements and cognitive behavioural therapy for insomnia. The role of wake-promoting agents and CNS stimulants for TBI-associated narcolepsy, post-traumatic hypersomnia and excessive daytime sleepiness requires further study with larger numbers of patients to determine effectiveness and benefit in this population. Future research with multiple collaborating centres should attempt to delineate the pathophysiology of TBI-associated sleep disorders, including CNS-derived hypersomnia and circadian rhythm disturbances, and determine definitive, effective treatment for associated sleep disorders. PMID:21062105

  15. A Review of Magnetic Resonance Imaging and Diffusion Tensor Imaging Findings in Mild Traumatic Brain Injury

    PubMed Central

    Shenton, ME; Hamoda, HM; Schneiderman, JS; Bouix, S; Pasternak, O; Rathi, Y; M-A, Vu; Purohit, MP; Helmer, K; Koerte, I; Lin, AP; C-F, Westin; Kikinis, R; Kubicki, M; Stern, RA; Zafonte, R

    2013-01-01

    Mild traumatic brain injury (mTBI), also referred to as concussion, remains a controversial diagnosis because the brain often appears quite normal on conventional computed tomography (CT) and magnetic resonance imaging (MRI) scans. Such conventional tools, however, do not adequately depict brain injury in mTBI because they are not sensitive to detecting diffuse axonal injuries (DAI), also described as traumatic axonal injuries (TAI), the major brain injuries in mTBI. Furthermore, for the 15 to 30% of those diagnosed with mTBI on the basis of cognitive and clinical symptoms, i.e., the “miserable minority,” the cognitive and physical symptoms do not resolve following the first three months post-injury. Instead, they persist, and in some cases lead to long-term disability. The explanation given for these chronic symptoms, i.e., postconcussive syndrome, particularly in cases where there is no discernible radiological evidence for brain injury, has led some to posit a psychogenic origin. Such attributions are made all the easier since both post-traumatic stress disorder (PTSD) and depression are frequently co-morbid with mTBI. The challenge is thus to use neuroimaging tools that are sensitive to DAI/TAI, such as diffusion tensor imaging (DTI), in order to detect brain injuries in mTBI. Of note here, recent advances in neuroimaging techniques, such as DTI, make it possible to characterize better extant brain abnormalities in mTBI. These advances may lead to the development of biomarkers of injury, as well as to staging of reorganization and reversal of white matter changes following injury, and to the ability to track and to characterize changes in brain injury over time. Such tools will likely be used in future research to evaluate treatment efficacy, given their enhanced sensitivity to alterations in the brain. In this article we review the incidence of mTBI and the importance of characterizing this patient population using objective radiological measures. Evidence

  16. 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

  17. 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

  18. Management of raised intracranial pressure in children with traumatic brain injury

    PubMed Central

    Kukreti, Vinay; Mohseni-Bod, Hadi; Drake, James

    2014-01-01

    Increased intracranial pressure (ICP) is associated with worse outcome after traumatic brain injury (TBI). The current guidelines and management strategies are aimed at maintaining adequate cerebral perfusion pressure and treating elevated ICP. Despite controversies, ICP monitoring is important particularly after severe TBI to guide treatment and in developed countries is accepted as a standard of care. We provide a narrative review of the recent evidence for the use of ICP monitoring and management of ICP in pediatric TBI. PMID:25624921

  19. Severe and penetrating traumatic brain injury in the context of war.

    PubMed

    Meyer, Kimberly; Helmick, Kathy; Doncevic, Selina; Park, Rachel

    2008-01-01

    Our data suggests that traumatic brain injury (TBI) may account for up to one third of battle-related injuries in today's war. Although the majority of these injuries are classified as mild in severity, service members with severe or penetrating TBI can be faced with many challenges. Injuries sustained on the battlefield require a slightly different approach than the TBI care that is traditionally seen in a civilian setting. This article presents the range of care that occurs beginning on the battlefield and continuing to state-of-the-art rehabilitation within the Department of Defense and Veterans Affairs Polytrauma System of Care. PMID:19092508

  20. In Home Family Supports: What Families of Youngsters with Traumatic Brain Injury Really Need.

    ERIC Educational Resources Information Center

    Pieper, Betty

    This guide, based on a qualitative research study which identified primary stressors in families of children with traumatic brain injury (TBI), presents: (1) a summary of the needs of families affected by TBI; and (2) a proposed theoretical intervention model to meet those needs. The first section attempts to describe the present system of…

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. California Verbal Learning Test Indicators of Malingered Neurocognitive Dysfunction: Sensitivity and Specificity in Traumatic Brain Injury

    ERIC Educational Resources Information Center

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

    2006-01-01

    The present study used well-defined traumatic brain injury (TBI) and mixed neurological (other than TBI) and psychiatric samples to examine the specificity and sensitivity to Malingered Neurocognitive Dysfunction (MND) of four individual California Verbal Learning Test (CVLT) variables and eight composite CVLT malingering indicators. Participants…

  6. 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.…

  7. 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…

  8. 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…

  9. Future Concerns of Adult Siblings of Persons with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Degeneffe, Charles Edmund; Olney, Marjorie F.

    2008-01-01

    This study examined future concerns conveyed by adult siblings who provided regular caregiving support to their brothers and sisters with traumatic brain injury (TBI). The authors surveyed a national sample of 280 adult siblings of persons with TBI. Using a constant comparative approach to text analysis, the authors analyzed responses to the…

  10. Dysarthria Associated with Traumatic Brain Injury: Speaking Rate and Emphatic Stress

    ERIC Educational Resources Information Center

    Wang, Y.T.; Kent, R.D.; Duffy, J.R.; Thomas, J.E.

    2005-01-01

    Prosodic abnormality is common in the dysarthria associated with traumatic brain injury (TBI), and adjustments of speaking rate and emphatic stress are often used as steps in treating the speech disorder in patients with TBI-induced dysarthria. However, studies to date do not present a clear and detailed picture of how speaking rate and emphatic…

  11. Classroom Strategies to Use with Students Following Traumatic Brain Injuries: Reading, Math, Writing, and Behavior

    ERIC Educational Resources Information Center

    Spear, Andi

    2005-01-01

    A Traumatic Brain Injury (TBI) changes cognition and behavior in students. Their learning needs are different from students with other exceptionalities. General and special education teachers can use specific strategies based on learning style, along with certain resources, with students who have experienced a TBI to promote learning in reading,…

  12. 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…

  13. Myths and Misconceptions about Traumatic Brain Injury: Endorsements by School Psychologists

    ERIC Educational Resources Information Center

    Hooper, Stephen R.

    2006-01-01

    This study was conducted to assess the perceptions of school psychologists regarding myths and misconceptions pertaining to traumatic brain injury (TBI). A sample of 304 school psychologists in the state of North Carolina was surveyed on 11 common myths and misconceptions about TBI. Results indicated that this group performed significantly better…

  14. 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…

  15. 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…

  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. 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…

  19. 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…

  20. 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…

  1. 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…

  2. 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…

  3. 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…

  4. Stroke Incidence Following Traumatic Brain Injury in Older Adults

    PubMed Central

    Albrecht, Jennifer S.; Liu, Xinggang; Smith, Gordon S.; Baumgarten, Mona; Rattinger, Gail B.; Gambert, Steven R.; Langenberg, Patricia; Zuckerman, Ilene H.

    2015-01-01

    Objective Following traumatic brain injury (TBI), older adults are at increased risk of hemorrhagic and thromboembolic events, but it is unclear whether the increased risk continues after hospital discharge. We estimated incidence rates of hemorrhagic and ischemic stroke following hospital discharge for TBI among adults ≥65 and compared them with pre-TBI rates. Participants 16,936 Medicare beneficiaries aged ≥65 with a diagnosis of TBI in any position on an inpatient claim between 6/1/2006 and 12/31/2009 who survived to hospital discharge. Design Retrospective analysis of a random 5% sample of Medicare claims data Main Measures Hemorrhagic stroke was defined as ICD-9 codes 430.xx-432.xx. Ischemic stroke was defined as ICD-9 codes 433.xx-435.xx, 437.0x, and 437.1x. Results There was a six-fold increase in the rate of hemorrhagic stroke following TBI compared to the pre-TBI period (adjusted Rate Ratio (RR) 6.5; 95% Confidence Interval (CI) 5.3, 7.8), controlling for age and sex. A smaller increase in the rate of ischemic stroke was observed (adjusted RR 1.3; 95% CI 1.2, 1.4). Conclusion Future studies should investigate causes of increased stroke risk post-TBI as well as effective treatments to reduce stroke risk and improve outcomes post-TBI among older adults. PMID:24816156

  5. Methylene Blue Is Neuroprotective against Mild Traumatic Brain Injury

    PubMed Central

    Long, Justin Alexander; Chemello, Jonathan; Van Koughnet, Samantha; Fernandez, Angelica; Huang, Shiliang; Shen, Qiang

    2014-01-01

    Abstract Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Methylene blue (MB) has known energy-enhancing and antioxidant properties. This study tested the hypothesis that MB treatment reduces lesion volume and behavioral deficits in a rat model of mild TBI. In a randomized double-blinded design, animals received either MB (n=5) or vehicle (n=6) after TBI. Studies were performed on 0, 1, 2, 7, and 14 days following an impact to the primary forelimb somatosensory cortex. MRI lesion was not apparent 1 h after TBI, became apparent 3 h after TBI, and peaked at 2 days for both groups. The MB-treated animals showed significantly smaller MRI lesion volume than the vehicle-treated animals at all time points studied. The MB-treated animals exhibited significantly improved scores on forelimb placement asymmetry and foot fault tests than did the vehicle-treated animals at all time points studied. Smaller numbers of dark-stained Nissl cells and Fluoro-Jade® positive cells were observed in the MB-treated group than in vehicle-treated animals 14 days post-TBI. In conclusion, MB treatment minimized lesion volume, behavioral deficits, and neuronal degeneration following mild TBI. MB is already approved by the United States Food and Drug Administration (FDA) to treat a number of indications, likely expediting future clinical trials in TBI. PMID:24479842

  6. 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

  7. Evidence for Impaired Plasticity after Traumatic Brain Injury in the Developing Brain

    PubMed Central

    Li, Nan; Yang, Ya; Glover, David P.; Zhang, Jiangyang; Saraswati, Manda; Robertson, Courtney

    2014-01-01

    Abstract The robustness of plasticity mechanisms during brain development is essential for synaptic formation and has a beneficial outcome after sensory deprivation. However, the role of plasticity in recovery after acute brain injury in children has not been well defined. Traumatic brain injury (TBI) is the leading cause of death and disability among children, and long-term disability from pediatric TBI can be particularly devastating. We investigated the altered cortical plasticity 2–3 weeks after injury in a pediatric rat model of TBI. Significant decreases in neurophysiological responses across the depth of the noninjured, primary somatosensory cortex (S1) in TBI rats, compared to age-matched controls, were detected with electrophysiological measurements of multi-unit activity (86.4% decrease), local field potential (75.3% decrease), and functional magnetic resonance imaging (77.6% decrease). Because the corpus callosum is a clinically important white matter tract that was shown to be consistently involved in post-traumatic axonal injury, we investigated its anatomical and functional characteristics after TBI. Indeed, corpus callosum abnormalities in TBI rats were detected with diffusion tensor imaging (9.3% decrease in fractional anisotropy) and histopathological analysis (14% myelination volume decreases). Whole-cell patch clamp recordings further revealed that TBI results in significant decreases in spontaneous firing rate (57% decrease) and the potential to induce long-term potentiation in neurons located in layer V of the noninjured S1 by stimulation of the corpus callosum (82% decrease). The results suggest that post-TBI plasticity can translate into inappropriate neuronal connections and dramatic changes in the function of neuronal networks. PMID:24050267

  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. 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

  10. 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

  11. 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

  12. Microglia activation as a biomarker for traumatic brain injury.

    PubMed

    Hernandez-Ontiveros, Diana G; Tajiri, Naoki; Acosta, Sandra; Giunta, Brian; Tan, Jun; Borlongan, Cesar V

    2013-01-01

    Traumatic brain injury (TBI) has become the signature wound of wars in Afghanistan and Iraq. Injury may result from a mechanical force, a rapid acceleration-deceleration movement, or a blast wave. A cascade of secondary cell death events ensues after the initial injury. In particular, multiple inflammatory responses accompany TBI. A series of inflammatory cytokines and chemokines spreads to normal brain areas juxtaposed to the core impacted tissue. Among the repertoire of immune cells involved, microglia is a key player in propagating inflammation to tissues neighboring the core site of injury. Neuroprotective drug trials in TBI have failed, likely due to their sole focus on abrogating neuronal cell death and ignoring the microglia response despite these inflammatory cells' detrimental effects on the brain. Another relevant point to consider is the veracity of results of animal experiments due to deficiencies in experimental design, such as incomplete or inadequate method description, data misinterpretation, and reporting may introduce bias and give false-positive results. Thus, scientific publications should follow strict guidelines that include randomization, blinding, sample-size estimation, and accurate handling of all data (Landis et al., 2012). A prolonged state of inflammation after brain injury may linger for years and predispose patients to develop other neurological disorders, such as Alzheimer's disease. TBI patients display progressive and long-lasting impairments in their physical, cognitive, behavioral, and social performance. Here, we discuss inflammatory mechanisms that accompany TBI in an effort to increase our understanding of the dynamic pathological condition as the disease evolves over time and begin to translate these findings for defining new and existing inflammation-based biomarkers and treatments for TBI. PMID:23531681

  13. Microglia Activation as a Biomarker for Traumatic Brain Injury

    PubMed Central

    Hernandez-Ontiveros, Diana G.; Tajiri, Naoki; Acosta, Sandra; Giunta, Brian; Tan, Jun; Borlongan, Cesar V.

    2013-01-01

    Traumatic brain injury (TBI) has become the signature wound of wars in Afghanistan and Iraq. Injury may result from a mechanical force, a rapid acceleration-deceleration movement, or a blast wave. A cascade of secondary cell death events ensues after the initial injury. In particular, multiple inflammatory responses accompany TBI. A series of inflammatory cytokines and chemokines spreads to normal brain areas juxtaposed to the core impacted tissue. Among the repertoire of immune cells involved, microglia is a key player in propagating inflammation to tissues neighboring the core site of injury. Neuroprotective drug trials in TBI have failed, likely due to their sole focus on abrogating neuronal cell death and ignoring the microglia response despite these inflammatory cells’ detrimental effects on the brain. Another relevant point to consider is the veracity of results of animal experiments due to deficiencies in experimental design, such as incomplete or inadequate method description, data misinterpretation, and reporting may introduce bias and give false-positive results. Thus, scientific publications should follow strict guidelines that include randomization, blinding, sample-size estimation, and accurate handling of all data (Landis et al., 2012). A prolonged state of inflammation after brain injury may linger for years and predispose patients to develop other neurological disorders, such as Alzheimer’s disease. TBI patients display progressive and long-lasting impairments in their physical, cognitive, behavioral, and social performance. Here, we discuss inflammatory mechanisms that accompany TBI in an effort to increase our understanding of the dynamic pathological condition as the disease evolves over time and begin to translate these findings for defining new and existing inflammation-based biomarkers and treatments for TBI. PMID:23531681

  14. 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

  15. 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

  16. Altered Calcium Signaling Following Traumatic Brain Injury

    PubMed Central

    Weber, John T.

    2012-01-01

    Cell death and dysfunction after traumatic brain injury (TBI) is caused by a primary phase, related to direct mechanical disruption of the brain, and a secondary phase which consists of delayed events initiated at the time of the physical insult. Arguably, the calcium ion contributes greatly to the delayed cell damage and death after TBI. A large, sustained influx of calcium into cells can initiate cell death signaling cascades, through activation of several degradative enzymes, such as proteases and endonucleases. However, a sustained level of intracellular free calcium is not necessarily lethal, but the specific route of calcium entry may couple calcium directly to cell death pathways. Other sources of calcium, such as intracellular calcium stores, can also contribute to cell damage. In addition, calcium-mediated signal transduction pathways in neurons may be perturbed following injury. These latter types of alterations may contribute to abnormal physiology in neurons that do not necessarily die after a traumatic episode. This review provides an overview of experimental evidence that has led to our current understanding of the role of calcium signaling in death and dysfunction following TBI. PMID:22518104

  17. 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

  18. Cyclosporine Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

    PubMed

    Dixon, C Edward; Bramlett, Helen M; Dietrich, W Dalton; Shear, Deborah A; Yan, Hong Q; Deng-Bryant, Ying; Mondello, Stefania; Wang, Kevin K W; Hayes, Ronald L; Empey, Philip E; Povlishock, John T; Tortella, Frank C; Kochanek, Patrick M

    2016-03-15

    Operation Brain Trauma Therapy (OBTT) is a consortium of investigators using multiple pre-clinical models of traumatic brain injury (TBI) to bring acute therapies to clinical trials. To screen therapies, we used three rat models (parasagittal fluid percussion injury [FPI], controlled cortical impact [CCI], and penetrating ballistic-like brain injury [PBBI]). We report results of the third therapy (cyclosporin-A; cyclosporine; [CsA]) tested by OBTT. At each site, rats were randomized to treatment with an identical regimen (TBI + vehicle, TBI + CsA [10 mg/kg], or TBI + CsA [20 mg/kg] given intravenously at 15 min and 24 h after injury, and sham). We assessed motor and Morris water maze (MWM) tasks over 3 weeks after TBI and lesion volume and hemispheric tissue loss at 21 days. In FPI, CsA (10 mg/kg) produced histological protection, but 20 mg/kg worsened working memory. In CCI, CsA (20 mg/kg) impaired MWM performance; surprisingly, neither dose showed benefit on any outcome. After PBBI, neither dose produced benefit on any outcome, and mortality was increased (20 mg/kg) partly caused by the solvent vehicle. In OBTT, CsA produced complex effects with histological protection at the lowest dose in the least severe model (FPI), but only deleterious effects as model severity increased (CCI and 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 positive treatment effects were seen on biomarker levels in any of the models, whereas significant increases in 24 h UCH-L1 levels were seen with CsA (20 mg/kg) after CCI and 24 h GFAP levels in both CsA treated groups in the PBBI model. Lack of behavioral protection in any model, indicators of toxicity, and a narrow therapeutic index reduce enthusiasm for clinical translation. PMID:26671075

  19. Extracellular N-Acetylaspartate in Human Traumatic Brain Injury

    PubMed Central

    Shannon, Richard J.; Carter, Eleanor L.; Jalloh, Ibrahim; Menon, David K.; Hutchinson, Peter J.; Carpenter, Keri L.H.

    2016-01-01

    Abstract N-acetylaspartate (NAA) is an amino acid derivative primarily located in the neurons of the adult brain. The function of NAA is incompletely understood. Decrease in brain tissue NAA is presently considered symptomatic and a potential biomarker of acute and chronic neuropathological conditions. The aim of this study was to use microdialysis to investigate the behavior of extracellular NAA (eNAA) levels after traumatic brain injury (TBI). Sampling for this study was performed using cerebral microdialysis catheters (M Dialysis 71) perfused at 0.3 μL/min. Extracellular NAA was measured in microdialysates by high-performance liquid chromatography in 30 patients with severe TBI and for comparison, in radiographically “normal” areas of brain in six non-TBI neurosurgical patients. We established a detailed temporal eNAA profile in eight of the severe TBI patients. Microdialysate concentrations of glucose, lactate, pyruvate, glutamate, and glycerol were measured on an ISCUS clinical microdialysis analyzer. Here, we show that the temporal profile of microdialysate eNAA was characterized by highest levels in the earliest time-points post-injury, followed by a steady decline; beyond 70 h post-injury, average levels were 40% lower than those measured in non-TBI patients. There was a significant inverse correlation between concentrations of eNAA and pyruvate; eNAA showed significant positive correlations with glycerol and the lactate/pyruvate (L/P) ratio measured in microdialysates. The results of this on-going study suggest that changes in eNAA after TBI relate to the release of intracellular components, possibly due to neuronal death or injury, as well as to adverse brain energy metabolism. PMID:26159566

  20. 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

  1. 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. PMID:26613116

  2. 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.

  3. Traumatic Brain Injury in Young Children: Post-Acute Effects on Cognitive and School Readiness Skills

    PubMed Central

    Taylor, H. Gerry; Swartwout, Maegan; Yeates, Keith O.; Walz, Nicolay C.; Stancin, Terry; Wade, Shari L.

    2009-01-01

    Previous studies have documented weaknesses in cognitive ability and early academic readiness in young children with traumatic brain injury (TBI). However, few of these studies have rigorously controlled for demographic characteristics, examined the effects of TBI severity on a wide range of skills, or explored moderating influences of environmental factors on outcomes. To meet these objectives, each of three groups of children with TBI (20 with severe, 64 with moderate, and 15 with mild) were compared with a group of 117 children with orthopedic injuries (OI group). The children were hospitalized for their injuries between 3 and 6 years of age and were assessed an average of 1½ months post injury. Analysis revealed generalized weaknesses in cognitive and school readiness skills in the severe TBI group and suggested less pervasive effects of moderate and mild TBI. Indices of TBI severity predicted outcomes within the TBI sample and environmental factors moderated the effects of TBI on some measures. The findings document adverse effects of TBI in early childhood on post-acute cognitive and school readiness skills and indicate that residual deficits are related to both injury severity and the family environment. PMID:18764969

  4. Pharmacotherapy in rehabilitation of post-acute traumatic brain injury.

    PubMed

    Bhatnagar, Saurabha; Iaccarino, Mary Alexis; Zafonte, Ross

    2016-06-01

    There are nearly 1.8 million annual emergency room visits and over 289,000 annual hospitalizations related to traumatic brain injury (TBI). The goal of this review article is to highlight pharmacotherapies that we often use in the clinic that have been shown to benefit various sequelae of TBI. We have decided to focus on sequelae that we commonly encounter in our practice in the post-acute phase after a TBI. These symptoms are hyper-arousal, agitation, hypo-arousal, inattention, slow processing speed, memory impairment, sleep disturbance, depression, headaches, spasticity, and paroxysmal sympathetic hyperactivity. In this review article, the current literature for the pharmacological management of these symptoms are mentioned, including medications that have not had success and some ongoing trials. It is clear that the pharmacological management specific to those with TBI is often based on small studies and that often treatment is based on assumptions of how similar conditions are managed when not relating to TBI. As the body of the literature expands and targeted treatments start to emerge for TBI, the function of pharmacological management will need to be further defined. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26801831

  5. 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. PMID:26414955

  6. 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

  7. 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

  8. Traumatic Brain Injury: What the Teacher Needs To Know.

    ERIC Educational Resources Information Center

    Pieper, Betty

    Intended for use by the classroom teacher, this guide presents teaching suggestions as well as suggested resources for teaching children with traumatic brain injuries (TBI). Emphasis is placed on working with the injured family and the importance of planning for transition and re-entry into the classroom through a continuum of settings. Teachers…

  9. Working with Parents of Students with Traumatic Brain Injuries.

    ERIC Educational Resources Information Center

    Rhein, Barbara; And Others

    Intended for educators working with children who have suffered traumatic brain injuries (TBI), this brief paper addresses parent issues, administrative issues, and programmatic issues. Noted are the five stages of adjustment typically experienced by parents: shock, elation, reality, crisis, and mourning. Professionals are encouraged to be informed…

  10. 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…

  11. Communicative Impairment in Traumatic Brain Injury: A Complete Pragmatic Assessment

    ERIC Educational Resources Information Center

    Angeleri, R.; Bosco, F. M.; Zettin, M.; Sacco, K.; Colle, L.; Bara, B. G.

    2008-01-01

    The aim of the present study was to examine the communicative abilities of traumatic brain injury patients (TBI). We wish to provide a complete assessment of their communicative ability/disability using a new experimental protocol, the "Assessment Battery of Communication," ("ABaCo") comprising five scales--linguistic, extralinguistic,…

  12. Traumatic Brain Injury and Special Education: An Information Resource Guide.

    ERIC Educational Resources Information Center

    Stevens, Alice M.

    This resource guide of annotated references on traumatic brain injury (TBI) was created to help educators locate information from such disciplines as neurology, neuropsychology, rehabilitation, and pediatric medicine. Twenty-four resources published from 1990 to 1994 are listed, with annotations. The resources include research reports/reviews,…

  13. Integration of Neuropsychology in Educational Planning Following Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Stavinoha, Peter L.

    2005-01-01

    Traumatic brain injuries (TBIs) have the potential to significantly disrupt a student's cognitive, academic, social, emotional, behavioral, and physical functioning. It is important for educators to appreciate the array of difficulties students with TBI may experience in order to appropriately assess needs and create an educational plan that…

  14. Hemispheric Visual Attentional Imbalance in Patients with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Pavlovskaya, Marina; Groswasser, Zeev; Keren, Ofer; Mordvinov, Eugene; Hochstein, Shaul

    2007-01-01

    We find a spatially asymmetric allocation of attention in patients with traumatic brain injury (TBI) despite the lack of obvious asymmetry in neurological indicators. Identification performance was measured for simple spatial patterns presented briefly to a locus 5 degrees into the left or right hemifield, after precuing attention to the same…

  15. 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…

  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. Mild Traumatic Brain Injury Decreases Broadband Power in Area CA1.

    PubMed

    Paterno, Rosalia; Metheny, Hannah; Xiong, Guoxiang; Elkind, Jaclynn; Cohen, Akiva S

    2016-09-01

    Cognitive impairment caused by traumatic brain injury (TBI) can lead to devastating consequences for both patients and their families. The underlying neurological basis for TBI-induced cognitive dysfunction remains unknown. However, many lines of research have implicated the hippocampus in the pathophysiology of TBI. In particular, past research has found that theta oscillations, long thought to be the electrophysiological basis of learning and memory, are decreased in the hippocampus post-TBI. Here, we recorded in vivo electrophysiological activity in the hippocampi of 16 mice, 8 of which had previously undergone a TBI. Consistent with previous data, we found that theta power in the hippocampus was decreased in TBI animals compared to sham controls; however, this effect was driven by changes in broadband power and not theta oscillations. This result suggests that broadband fluctuations in the hippocampal local field potential can be used as an electrophysiological surrogate of abnormal neurological activity post-TBI. PMID:26529412

  18. 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

  19. 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.…

  20. 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

  1. Pituitary dysfunction after traumatic brain injury: a clinical and pathophysiological approach.

    PubMed

    Tanriverdi, Fatih; Schneider, Harald Jörn; Aimaretti, Gianluca; Masel, Brent E; Casanueva, Felipe F; Kelestimur, Fahrettin

    2015-06-01

    Traumatic brain injury (TBI) is a growing public health problem worldwide and is a leading cause of death and disability. The causes of TBI include motor vehicle accidents, which are the most common cause, falls, acts of violence, sports-related head traumas, and war accidents including blast-related brain injuries. Recently, pituitary dysfunction has also been described in boxers and kickboxers. Neuroendocrine dysfunction due to TBI was described for the first time in 1918. Only case reports and small case series were reported until 2000, but since then pituitary function in TBI victims has been investigated in more detail. The frequency of hypopituitarism after TBI varies widely among different studies (15-50% of the patients with TBI in most studies). The estimates of persistent hypopituitarism decrease to 12% if repeated testing is applied. GH is the most common hormone lost after TBI, followed by ACTH, gonadotropins (FSH and LH), and TSH. The underlying mechanisms responsible for pituitary dysfunction after TBI are not entirely clear; however, recent studies have shown that genetic predisposition and autoimmunity may have a role. Hypopituitarism after TBI may have a negative impact on the pace or degree of functional recovery and cognition. What is not clear is whether treatment of hypopituitarism has a beneficial effect on specific function. In this review, the current data related to anterior pituitary dysfunction after TBI in adult patients are updated, and guidelines for the diagnosis, follow-up strategies, and therapeutic approaches are reported. PMID:25950715

  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. 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. ...

  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. Neuroinflammatory responses to traumatic brain injury: etiology, clinical consequences, and therapeutic opportunities

    PubMed Central

    Lozano, Diego; Gonzales-Portillo, Gabriel S; Acosta, Sandra; de la Pena, Ike; Tajiri, Naoki; Kaneko, Yuji; Borlongan, Cesar V

    2015-01-01

    Traumatic brain injury (TBI) is a serious public health problem accounting for 1.4 million emergency room visits by US citizens each year. Although TBI has been traditionally considered an acute injury, chronic symptoms reminiscent of neurodegenerative disorders have now been recognized. These progressive neurodegenerative-like symptoms manifest as impaired motor and cognitive skills, as well as stress, anxiety, and mood affective behavioral alterations. TBI, characterized by external bumps or blows to the head exceeding the brain’s protective capacity, causes physical damage to the central nervous system with accompanying neurological dysfunctions. The primary impact results in direct neural cell loss predominantly exhibiting necrotic death, which is then followed by a wave of secondary injury cascades including excitotoxicity, oxidative stress, mitochondrial dysfunction, blood–brain barrier disruption, and inflammation. All these processes exacerbate the damage, worsen the clinical outcomes, and persist as an evolving pathological hallmark of what we now describe as chronic TBI. Neuroinflammation in the acute stage of TBI mobilizes immune cells, astrocytes, cytokines, and chemokines toward the site of injury to mount an antiinflammatory response against brain damage; however, in the chronic stage, excess activation of these inflammatory elements contributes to an “inflamed” brain microenvironment that principally contributes to secondary cell death in TBI. Modulating these inflammatory cells by changing their phenotype from proinflammatory to antiinflammatory would likely promote therapeutic effects on TBI. Because neuroinflammation occurs at acute and chronic stages after the primary insult in TBI, a treatment targeting neuroinflammation may have a wider therapeutic window for TBI. To this end, a better understanding of TBI etiology and clinical manifestations, especially the pathological presentation of chronic TBI with neuroinflammation as a major

  6. Traumatic Brain Injury and Aeromedical Evacuation: When is the Brain Fit to Fly?

    PubMed Central

    Goodman, Michael D.; Makley, Amy T.; Lentsch, Alex B.; Barnes, Stephen L.; Dorlac, Gina R.; Dorlac, Warren C.; Johannigman, Jay A.; Pritts, Timothy A.

    2015-01-01

    Background To review the inflammatory sequelae of traumatic brain injury (TBI) and altitude exposure and discuss the potential impact of aeromedical evacuation (AE) on this process. Methods Literature review and expert opinion regarding the inflammatory effects of TBI and AE. Results Traumatic brain injury has been called the signature injury of the current military conflict. As a result of the increasing incidence of blast injury, TBI is responsible for significant mortality and enduring morbidity in injured soldiers. Common secondary insults resulting from post-traumatic cerebral inflammation are recognized to adversely impact outcome. AE utilizing Critical Care Air Transport Teams has become a standard of care practice following battlefield injury, to quickly and safely transport critically injured soldiers to more sophisticated echelons of care. Exposure to the hypobaric conditions of the AE process may impose an additional physiologic risk on the TBI patient as well as a “second hit” inflammatory stimulus. Conclusions We review the known inflammatory effects of TBI and altitude exposure and propose that optimizing the post-traumatic inflammatory profile may assist in determining an ideal time to fly for head-injured soldiers. PMID:20006349

  7. 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

  8. 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

  9. Traumatic brain injury in children: acute care management.

    PubMed

    Geyer, Kristen; Meller, Karen; Kulpan, Carol; Mowery, Bernice D

    2013-01-01

    The care of the pediatric patient with a severe traumatic brain injury (TBI) is an all-encompassing nursing challenge. Nursing vigilance is required to maintain a physiological balance that protects the injured brain. From the time a child and family first enter the hospital, they are met with the risk of potential death and an uncertain future. The family is subjected to an influx of complex medical and nursing terminology and interventions. Nurses need to understand the complexities of TBI and the modalities of treatment, as well as provide patients and families with support throughout all phases of care. PMID:24640314

  10. Early ghrelin treatment attenuates disruption of the blood brain barrier and apoptosis after traumatic brain injury through a UCP-2 mechanism.

    PubMed

    Lopez, N E; Gaston, L; Lopez, K R; Coimbra, R C; Hageny, A; Putnam, J; Eliceiri, B; Coimbra, R; Bansal, V

    2012-12-13

    Ghrelin has been shown to be anti-inflammatory and neuroprotective in models of neurologic injury. We hypothesize that treatment with ghrelin will attenuate breakdown of the blood brain barrier (BBB) and apoptosis 24h following traumatic brain injury (TBI). We believe this protection is at least in part mediated by up-regulation of UCP-2, thereby stabilizing mitochondria and preventing up-regulation of caspase-3. A weight drop model was used to create severe TBI. Balb/c mice were divided into 3 groups. Sham: no TBI or ghrelin treatment; TBI: TBI only; TBI/ghrelin: 20μg (IP) ghrelin at the time of TBI. BBB permeability to 70kDa FITC-Dextran was measured 24h following injury and quantified in arbitrary integrated fluorescence (afu). Brain tissue was subjected to TUNEL staining and TUNEL positive cells were quantified. Immunohistochemistry was performed on injured tissue to reveal patterns of caspase-3 and UCP-2 expression. TBI increased cerebral vascular permeability by three-fold compared to sham. Ghrelin treatment restored vascular permeability to the level of shams. TUNEL staining showed that ghrelin mitigated the significant increase in apoptosis that follows TBI. TBI increased both caspase-3 compared to sham. Treatment with ghrelin significantly increased UCP-2 compared to TBI alone and this increase in UCP-2 expression was associated with a decrease in expression of caspase-3. Early ghrelin treatment prevents TBI induced BBB disruption and TBI mediated apoptosis 24h following injury. These results demonstrate the neuroprotective potential of ghrelin as a therapy in TBI. PMID:23099053

  11. 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

  12. 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

  13. CCR2 antagonism alters brain macrophage polarization and ameliorates cognitive dysfunction induced by traumatic brain injury.

    PubMed

    Morganti, Josh M; Jopson, Timothy D; Liu, Sharon; Riparip, Lara-Kirstie; Guandique, Cristian K; Gupta, Nalin; Ferguson, Adam R; Rosi, Susanna

    2015-01-14

    Traumatic brain injury (TBI) is a major risk factor for the development of multiple neurodegenerative diseases. With respect to the increasing prevalence of TBI, new therapeutic strategies are urgently needed that will prevent secondary damage to primarily unaffected tissue. Consistently, neuroinflammation has been implicated as a key mediator of secondary damage following the initial mechanical insult. Following injury, there is uncertainty regarding the role that accumulating CCR2(+) macrophages play in the injury-induced neuroinflammatory sequelae and cognitive dysfunction. Using CX3CR1(GFP/+)CCR2(RFP/+) reporter mice, we show that TBI initiated a temporally restricted accumulation of peripherally derived CCR2(+) macrophages, which were concentrated in the hippocampal formation, a region necessary for learning and memory. Multivariate analysis delineated CCR2(+) macrophages' neuroinflammatory response while identifying a novel therapeutic treatment window. As a proof of concept, targeting CCR2(+) macrophages with CCX872, a novel Phase I CCR2 selective antagonist, significantly reduced TBI-induced inflammatory macrophage accumulation. Concomitantly, there was a significant reduction in multiple proinflammatory and neurotoxic mediators with this treatment paradigm. Importantly, CCR2 antagonism resulted in a sparing of TBI-induced hippocampal-dependent cognitive dysfunction and reduced proinflammatory activation profile 1 month after injury. Thus, therapeutically targeting the CCR2(+) subset of monocytes/macrophages may provide a new avenue of clinical intervention following TBI. PMID:25589768

  14. CCR2 Antagonism Alters Brain Macrophage Polarization and Ameliorates Cognitive Dysfunction Induced by Traumatic Brain Injury

    PubMed Central

    Jopson, Timothy D.; Liu, Sharon; Riparip, Lara-Kirstie; Guandique, Cristian K.; Gupta, Nalin; Ferguson, Adam R.

    2015-01-01

    Traumatic brain injury (TBI) is a major risk factor for the development of multiple neurodegenerative diseases. With respect to the increasing prevalence of TBI, new therapeutic strategies are urgently needed that will prevent secondary damage to primarily unaffected tissue. Consistently, neuroinflammation has been implicated as a key mediator of secondary damage following the initial mechanical insult. Following injury, there is uncertainty regarding the role that accumulating CCR2+ macrophages play in the injury-induced neuroinflammatory sequelae and cognitive dysfunction. Using CX3CR1GFP/+CCR2RFP/+ reporter mice, we show that TBI initiated a temporally restricted accumulation of peripherally derived CCR2+ macrophages, which were concentrated in the hippocampal formation, a region necessary for learning and memory. Multivariate analysis delineated CCR2+ macrophages' neuroinflammatory response while identifying a novel therapeutic treatment window. As a proof of concept, targeting CCR2+ macrophages with CCX872, a novel Phase I CCR2 selective antagonist, significantly reduced TBI-induced inflammatory macrophage accumulation. Concomitantly, there was a significant reduction in multiple proinflammatory and neurotoxic mediators with this treatment paradigm. Importantly, CCR2 antagonism resulted in a sparing of TBI-induced hippocampal-dependent cognitive dysfunction and reduced proinflammatory activation profile 1 month after injury. Thus, therapeutically targeting the CCR2+ subset of monocytes/macrophages may provide a new avenue of clinical intervention following TBI. PMID:25589768

  15. 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

  16. Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should they be classified together as traumatic encephalopathy?

    PubMed

    Washington, Patricia M; Villapol, Sonia; Burns, Mark P

    2016-01-01

    Neuropathological studies of human traumatic brain injury (TBI) cases have described amyloid plaques acutely after a single severe TBI, and tau pathology after repeat mild TBI (mTBI). This has helped drive the hypothesis that a single moderate to severe TBI increases the risk of developing late-onset Alzheimer's disease (AD), while repeat mTBI increases the risk of developing chronic traumatic encephalopathy (CTE). In this review we critically assess this position-examining epidemiological and case control human studies, neuropathological evidence, and preclinical data. Epidemiological studies emphasize that TBI is associated with the increased risk of developing multiple types of dementia, not just AD-type dementia, and that TBI can also trigger other neurodegenerative conditions such as Parkinson's disease. Further, human post-mortem studies on both single TBI and repeat mTBI can show combinations of amyloid, tau, TDP-43, and Lewy body pathology indicating that the neuropathology of TBI is best described as a 'polypathology'. Preclinical studies confirm that multiple proteins associated with the development of neurodegenerative disease accumulate in the brain after TBI. The chronic sequelae of both single TBI and repeat mTBI share common neuropathological features and clinical symptoms of classically defined neurodegenerative disorders. However, while the spectrum of chronic cognitive and neurobehavioral disorders that occur following repeat mTBI is viewed as the symptoms of CTE, the spectrum of chronic cognitive and neurobehavioral symptoms that occur after a single TBI is considered to represent distinct neurodegenerative diseases such as AD. These data support the suggestion that the multiple manifestations of TBI-induced neurodegenerative disorders be classified together as traumatic encephalopathy or trauma-induced neurodegeneration, regardless of the nature or frequency of the precipitating TBI. PMID:26091850

  17. 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. PMID:26129873

  18. 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

  19. Top-Cited Articles in Traumatic Brain Injury

    PubMed Central

    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

  20. The pathophysiology of traumatic brain injury at a glance.

    PubMed

    Prins, Mayumi; Greco, Tiffany; Alexander, Daya; Giza, Christopher C

    2013-11-01

    Traumatic brain injury (TBI) is defined as an impact, penetration or rapid movement of the brain within the skull that results in altered mental state. TBI occurs more than any other disease, including breast cancer, AIDS, Parkinson's disease and multiple sclerosis, and affects all age groups and both genders. In the US and Europe, the magnitude of this epidemic has drawn national attention owing to the publicity received by injured athletes and military personnel. This increased public awareness has uncovered a number of unanswered questions concerning TBI, and we are increasingly aware of the lack of treatment options for a crisis that affects millions. Although each case of TBI is unique and affected individuals display different degrees of injury, different regional patterns of injury and different recovery profiles, this review and accompanying poster aim to illustrate some of the common underlying neurochemical and metabolic responses to TBI. Recognition of these recurrent features could allow elucidation of potential therapeutic targets for early intervention. PMID:24046353

  1. Neurobiological mechanisms associated with facial affect recognition deficits after traumatic brain injury.

    PubMed

    Neumann, Dawn; McDonald, Brenna C; West, John; Keiski, Michelle A; Wang, Yang

    2016-06-01

    The neurobiological mechanisms that underlie facial affect recognition deficits after traumatic brain injury (TBI) have not yet been identified. Using functional magnetic resonance imaging (fMRI), study aims were to 1) determine if there are differences in brain activation during facial affect processing in people with TBI who have facial affect recognition impairments (TBI-I) relative to people with TBI and healthy controls who do not have facial affect recognition impairments (TBI-N and HC, respectively); and 2) identify relationships between neural activity and facial affect recognition performance. A facial affect recognition screening task performed outside the scanner was used to determine group classification; TBI patients who performed greater than one standard deviation below normal performance scores were classified as TBI-I, while TBI patients with normal scores were classified as TBI-N. An fMRI facial recognition paradigm was then performed within the 3T environment. Results from 35 participants are reported (TBI-I = 11, TBI-N = 12, and HC = 12). For the fMRI task, TBI-I and TBI-N groups scored significantly lower than the HC group. Blood oxygenation level-dependent (BOLD) signals for facial affect recognition compared to a baseline condition of viewing a scrambled face, revealed lower neural activation in the right fusiform gyrus (FG) in the TBI-I group than the HC group. Right fusiform gyrus activity correlated with accuracy on the facial affect recognition tasks (both within and outside the scanner). Decreased FG activity suggests facial affect recognition deficits after TBI may be the result of impaired holistic face processing. Future directions and clinical implications are discussed. PMID:26040980

  2. Metabolic, enzymatic and gene involvement in cerebral glucose dysmetabolism after traumatic brain injury.

    PubMed

    Amorini, Angela Maria; Lazzarino, Giacomo; Di Pietro, Valentina; Signoretti, Stefano; Lazzarino, Giuseppe; Belli, Antonio; Tavazzi, Barbara

    2016-04-01

    In this study, the metabolic, enzymatic and gene changes causing cerebral glucose dysmetabolism following graded diffuse traumatic brain injury (TBI) were evaluated. TBI was induced in rats by dropping 450g from 1 (mild TBI; mTBI) or 2m height (severe TBI; sTBI). After 6, 12, 24, 48, and 120h gene expressions and enzymatic activities of glycolysis and pentose phosphate pathway (PPP) enzymes, and levels of lactate, ATP, ADP, ATP/ADP (indexing mitochondrial phosphorylating capacity), NADP(+), NADPH and GSH were determined in whole brain extracts (n=9 rats at each time for both TBI levels). Sham-operated animals (n=9) were used as controls. Results demonstrated that mTBI caused a late increase (48-120h post injury) of glycolytic gene expression and enzymatic activities, concomitantly with mitochondrial functional recovery (ATP and ATP/ADP normalization). No changes in lactate and PPP genes and enzymes, were accompanied by transient decrease in GSH, NADP(+), NADPH and NADPH/NADP(+). Animals following sTBI showed early increase (6-24h post injury) of glycolytic gene expression and enzymatic activities, occurring during mitochondrial malfunctioning (50% decrease in ATP and ATP/ADP). Higher lactate and lower GSH, NADP(+), NADPH, NADPH/NADP(+) than controls were recorded at anytime post injury (p<0.01). Both TBI levels caused metabolic and gene changes affecting glucose metabolism. Following mTBI, increased glucose flux through glycolysis is coupled to mitochondrial glucose oxidation. "True" hyperglycolysis occurs only after sTBI, where metabolic changes, caused by depressed mitochondrial phosphorylating capacity, act on genes causing net glycolytic flux increase uncoupled from mitochondrial glucose oxidation. PMID:26844378

  3. 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

  4. The HMGB1-RAGE axis mediates traumatic brain injury-induced pulmonary dysfunction in lung transplantation.

    PubMed

    Weber, Daniel J; Gracon, Adam S A; Ripsch, Matthew S; Fisher, Amanda J; Cheon, Bo M; Pandya, Pankita H; Vittal, Ragini; Capitano, Maegan L; Kim, Youngsong; Allette, Yohance M; Riley, Amanda A; McCarthy, Brian P; Territo, Paul R; Hutchins, Gary D; Broxmeyer, Hal E; Sandusky, George E; White, Fletcher A; Wilkes, David S

    2014-09-01

    Traumatic brain injury (TBI) results in systemic inflammatory responses that affect the lung. This is especially critical in the setting of lung transplantation, where more than half of donor allografts are obtained postmortem from individuals with TBI. The mechanism by which TBI causes pulmonary dysfunction remains unclear but may involve the interaction of high-mobility group box-1 (HMGB1) protein with the receptor for advanced glycation end products (RAGE). To investigate the role of HMGB1 and RAGE in TBI-induced lung dysfunction, RAGE-sufficient (wild-type) or RAGE-deficient (RAGE(-/-)) C57BL/6 mice were subjected to TBI through controlled cortical impact and studied for cardiopulmonary injury. Compared to control animals, TBI induced systemic hypoxia, acute lung injury, pulmonary neutrophilia, and decreased compliance (a measure of the lungs' ability to expand), all of which were attenuated in RAGE(-/-) mice. Neutralizing systemic HMGB1 induced by TBI reversed hypoxia and improved lung compliance. Compared to wild-type donors, lungs from RAGE(-/-) TBI donors did not develop acute lung injury after transplantation. In a study of clinical transplantation, elevated systemic HMGB1 in donors correlated with impaired systemic oxygenation of the donor lung before transplantation and predicted impaired oxygenation after transplantation. These data suggest that the HMGB1-RAGE axis plays a role in the mechanism by which TBI induces lung dysfunction and that targeting this pathway before transplant may improve recipient outcomes after lung transplantation. PMID:25186179

  5. Chronic Histopathological and Behavioral Outcomes of Experimental Traumatic Brain Injury in Adult Male Animals.

    PubMed

    Osier, Nicole D; Carlson, Shaun W; DeSana, Anthony; Dixon, C Edward

    2015-12-01

    The purpose of this review is to survey the use of experimental animal models for studying the chronic histopathological and behavioral consequences of traumatic brain injury (TBI). The strategies employed to study the long-term consequences of TBI are described, along with a summary of the evidence available to date from common experimental TBI models: fluid percussion injury; controlled cortical impact; blast TBI; and closed-head injury. For each model, evidence is organized according to outcome. Histopathological outcomes included are gross changes in morphology/histology, ventricular enlargement, gray/white matter shrinkage, axonal injury, cerebrovascular histopathology, inflammation, and neurogenesis. Behavioral outcomes included are overall neurological function, motor function, cognitive function, frontal lobe function, and stress-related outcomes. A brief discussion is provided comparing the most common experimental models of TBI and highlighting the utility of each model in understanding specific aspects of TBI pathology. The majority of experimental TBI studies collect data in the acute postinjury period, but few continue into the chronic period. Available evidence from long-term studies suggests that many of the experimental TBI models can lead to progressive changes in histopathology and behavior. The studies described in this review contribute to our understanding of chronic TBI pathology. PMID:25490251

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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

  11. Hypopituitarism in pediatric survivors of inflicted traumatic brain injury.

    PubMed

    Auble, Bethany A; Bollepalli, Sureka; Makoroff, Kathi; Weis, Tammy; Khoury, Jane; Colliers, Tracy; Rose, Susan R

    2014-02-15

    Endocrine dysfunction is common after accidental traumatic brain injury (TBI). Prevalence of endocrine dysfunction after inflicted traumatic brain injury (iTBI) is not known. The aim of this study was to examine endocrinopathy in children after moderate-to-severe iTBI. Children with previous iTBI (n=14) were evaluated for growth/endocrine dysfunction, including anthropometric measurements and hormonal evaluation (nocturnal growth hormone [GH], thyrotropin surge, morning and low-dose adrenocorticotropin stimulated cortisol, insulin-like growth factor 1, IGF-binding protein 3, free thyroxine, prolactin [PRL], and serum/urine osmolality). Analysis used Fisher's exact test and Wilcoxon's rank-sum test, as appropriate. Eighty-six percent of subjects had endocrine dysfunction with at least one abnormality, whereas 50% had two or more abnormalities, significantly increased compared to an estimated 2.5% with endocrine abnormality in the general population (p<0.001). Elevated prolactin was common (64%), followed by abnormal thyroid function (33%), short stature (29%), and low GH peak (17%). High prolactin was common in subjects with other endocrine abnormalities. Two were treated with thyroid hormone and 2 may require GH therapy. In conclusion, children with a history of iTBI show high risk for endocrine dysfunction, including elevated PRL and growth abnormalities. This effect of iTBI has not been well described in the literature. Larger, multi-center, prospective studies would provide more data to determine the extent of endocrine dysfunction in iTBI. We recommend that any child with a history of iTBI be followed closely for growth velocity and pubertal changes. If growth velocity is slow, PRL level and a full endocrine evaluation should be performed. PMID:24028400

  12. The impact of injury severity on long-term social outcome following paediatric traumatic brain injury.

    PubMed

    Muscara, Frank; Catroppa, Cathy; Eren, Senem; Anderson, Vicki

    2009-08-01

    Despite suggestions that paediatric traumatic brain injury (TBI) disrupts social skill development, few studies have investigated long-term social outcome following the transition into adulthood. The current study aimed to investigate long-term social outcome, in a sample of 36 survivors who suffered a mild, moderate or severe TBI between 8 and 12 years of age. At 7-10 years post-injury, the age of participants ranged between 16 and 22 years. Social outcome was assessed using a number of self-rated and parent-rated questionnaires, in order to obtain self- and other-rated accounts of the groups' current social functioning. Predictors of long-term social outcome were also explored, with findings suggesting that young people who suffered mild TBI during childhood tended to be functioning at a higher level on some measures of social functioning, compared to those that suffered a moderate and severe injury. Further, results suggested that pre-injury adaptive functioning and socio-economic status predicted long-term functioning for some measures of social outcome. Finally, social problem-solving skills predicted the success of social reintegration post-TBI. These preliminary findings indicate that there is a risk of social difficulties following paediatric TBI continuing into adulthood, and that a number of demographic, social, and neuropsychological variables continue to predict social outcome even at this late stage post-injury. PMID:18839384

  13. Executive Functioning of Combat Mild Traumatic Brain Injury.

    PubMed

    Gaines, Katy D; Soper, Henry V; Berenji, Gholam R

    2016-01-01

    This study investigates neuropsychological deficits in recently deployed veterans with mild traumatic brain injury (mTBI). Veterans discharged from 2007 to 2012 were recruited from Veterans Affairs clinics. Independent groups of participants with mTBI (n = 57) and those without TBI (n = 57) were administered the Beck Depression Inventory-II, Combat Exposure Scale, Word Memory Test, and the Self-Awareness of Deficits Interview. Neuropsychological instruments included the Rey-Osterrieth Complex Figure Test, Letter and Category Fluency, Trail-Making Test-Parts A and B, Christiansen H-abbreviated, Soper Neuropsychology Screen, Wechsler Memory Scale subtests Logical Memory I and II, and the Street Completion Test. The mTBI group performed significantly worse on all of the executive and nonexecutive measurements with the exception of Category Fluency, after controlling for age, depression effort, and combat exposure. Depression and combat exposure were greater for the mTBI group. The mTBI group scored poorer on effort, but only the Multiple Choice subtest was significant. The mTBI group had good awareness of their deficits. PMID:26496530

  14. 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

  15. 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

  16. Cognitive Improvement after Mild Traumatic Brain Injury Measured with Functional Neuroimaging during the Acute Period

    PubMed Central

    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

  17. 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

  18. 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

  19. 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

  20. 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

  1. Identification of Serum MicroRNA Signatures for Diagnosis of Mild Traumatic Brain Injury in a Closed Head Injury Model

    PubMed Central

    Barry, Erin S.; Bhomia, Manish; Hutchison, Mary Anne; Balakathiresan, Nagaraja S.; Grunberg, Neil E.; Maheshwari, Radha K.

    2014-01-01

    Wars in Iraq and Afghanistan have highlighted the problems of diagnosis and treatment of mild traumatic brain injury (mTBI). MTBI is a heterogeneous injury that may lead to the development of neurological and behavioral disorders. In the absence of specific diagnostic markers, mTBI is often unnoticed or misdiagnosed. In this study, mice were induced with increasing levels of mTBI and microRNA (miRNA) changes in the serum were determined. MTBI was induced by varying weight and fall height of the impactor rod resulting in four different severity grades of the mTBI. Injuries were characterized as mild by assessing with the neurobehavioral severity scale-revised (NSS-R) at day 1 post injury. Open field locomotion and acoustic startle response showed behavioral and sensory motor deficits in 3 of the 4 injury groups at day 1 post injury. All of the animals recovered after day 1 with no significant neurobehavioral alteration by day 30 post injury. Serum microRNA (miRNA) profiles clearly differentiated injured from uninjured animals. Overall, the number of miRNAs that were significantly modulated in injured animals over the sham controls increased with the severity of the injury. Thirteen miRNAs were found to identify mTBI regardless of its severity within the mild spectrum of injury. Bioinformatics analyses revealed that the more severe brain injuries were associated with a greater number of miRNAs involved in brain related functions. The evaluation of serum miRNA may help to identify the severity of brain injury and the risk of developing adverse effects after TBI. PMID:25379886

  2. 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... Services Administration (HRSA), Department of Health and Human Services (HHS). ACTION: Notice of Non-Competitive One-Year Extension Funds for Current Traumatic Brain Injury (TBI) State Implementation...

  3. 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.

  4. 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

  5. Neuropsychological differential diagnosis of mild traumatic brain injury.

    PubMed

    Larrabee, Glenn J; Rohling, Martin L

    2013-01-01

    The diagnosis and evaluation of mild traumatic brain injury (mTBI) is reviewed from the perspective of meta-analyses of neuropsychological outcome, showing full recovery from a single, uncomplicated mTBI by 90 days post-trauma. Persons with history of complicated mTBI characterized by day-of-injury computed tomography or magnetic resonance imaging abnormalities, and those who have suffered prior mTBIs may or may not show evidence of complete recovery similar to that experienced by persons suffering a single, uncomplicated mTBI. Persistent post-concussion syndrome (PCS) is considered as a somatoform presentation, influenced by the non-specificity of PCS symptoms which commonly occur in non-TBI samples and co-vary as a function of general life stress, and psychological factors including symptom expectation, depression and anxiety. A model is presented for forensic evaluation of the individual mTBI case, which involves open-ended interview, followed by structured interview, record review, and detailed neuropsychological testing. Differential diagnosis includes consideration of other neurologic and psychiatric disorders, symptom expectation, diagnosis threat, developmental disorders, and malingering. PMID:24105915

  6. Inosine improves functional recovery after experimental traumatic brain injury.

    PubMed

    Dachir, Shlomit; Shabashov, Dalia; Trembovler, Victoria; Alexandrovich, Alexander G; Benowitz, Larry I; Shohami, Esther

    2014-03-25

    Despite years of research, no effective therapy is yet available for the treatment of traumatic brain injury (TBI). The most prevalent and debilitating features in survivors of TBI are cognitive deficits and motor dysfunction. A potential therapeutic method for improving the function of patients following TBI would be to restore, at least in part, plasticity to the CNS in a controlled way that would allow for the formation of compensatory circuits. Inosine, a naturally occurring purine nucleoside, has been shown to promote axon collateral growth in the corticospinal tract (CST) following stroke and focal TBI. In the present study, we investigated the effects of inosine on motor and cognitive deficits, CST sprouting, and expression of synaptic proteins in an experimental model of closed head injury (CHI). Treatment with inosine (100 mg/kg i.p. at 1, 24 and 48 h following CHI) improved outcome after TBI, significantly decreasing the neurological severity score (NSS, p<0.04 vs. saline), an aggregate measure of performance on several tasks. It improved non-spatial cognitive performance (object recognition, p<0.016 vs. saline) but had little effect on sensorimotor coordination (rotarod) and spatial cognitive functions (Y-maze). Inosine did not affect CST sprouting in the lumbar spinal cord but did restore levels of the growth-associated protein GAP-43 in the hippocampus, though not in the cerebral cortex. Our results suggest that inosine may improve functional outcome after TBI. PMID:24502983

  7. “Studying Injured Minds” – The Vietnam Head Injury Study and 40 Years of Brain Injury Research

    PubMed Central

    Raymont, Vanessa; Salazar, Andres M.; Krueger, Frank; Grafman, Jordan

    2011-01-01

    The study of those who have sustained traumatic brain injuries (TBI) during military conflicts has greatly facilitated research in the fields of neuropsychology, neurosurgery, psychiatry, neurology, and neuroimaging. The Vietnam Head Injury Study (VHIS) is a prospective, long-term follow-up study of a cohort of 1,221 Vietnam veterans with mostly penetrating brain injuries, which has stretched over more than 40 years. The scope of this study, both in terms of the types of injury and fields of examination, has been extremely broad. It has been instrumental in extending the field of TBI research and in exposing pressing medical and social issues that affect those who suffer such injuries. This review summarizes the history of conflict-related TBI research and the VHIS to date, as well as the vast range of important findings the VHIS has established. PMID:21625624

  8. Gender Differences in Neurological Emergencies Part II: A Consensus Summary and Research Agenda on Traumatic Brain Injury

    PubMed Central

    Wright, David W.; Espinoza, Tamara R.; Merck, Lisa H.; Ratcliff, Jonathan J.; Backster, Anika; Stein, Donald G.

    2015-01-01

    Traumatic brain injury (TBI) is a major cause of death and disability worldwide. There is strong evidence that gender and sex play an important role across the spectrum of TBI, from pathophysiology to clinical care. In May 2014, Academic Emergency Medicine held a consensus conference “Gender-Specific Research in Emergency Care: Investigate, Understand, and Translate How Gender Affects Patient Outcomes.” A TBI working group was formed to explore what was known about the influence of sex and gender on TBI and to identify gaps for future research. The findings resulted in four major recommendations to guide the TBI research agenda. PMID:25420582

  9. Gender differences in neurological emergencies part II: a consensus summary and research agenda on traumatic brain injury.

    PubMed

    Wright, David W; Espinoza, Tamara R; Merck, Lisa H; Ratcliff, Jonathan J; Backster, Anika; Stein, Donald G

    2014-12-01

    Traumatic brain injury (TBI) is a major cause of death and disability worldwide. There is strong evidence that gender and sex play an important role across the spectrum of TBI, from pathophysiology to clinical care. In May 2014, Academic Emergency Medicine held a consensus conference "Gender-Specific Research in Emergency Care: Investigate, Understand, and Translate How Gender Affects Patient Outcomes." A TBI working group was formed to explore what was known about the influence of sex and gender on TBI and to identify gaps for future research. The findings resulted in four major recommendations to guide the TBI research agenda. PMID:25420582

  10. 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

  11. 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…

  12. Findings from Structural MR Imaging in Military Traumatic Brain Injury.

    PubMed

    Riedy, Gerard; Senseney, Justin S; Liu, Wei; Ollinger, John; Sham, Elyssa; Krapiva, Pavel; Patel, Jigar B; Smith, Alice; Yeh, Ping-Hong; Graner, John; Nathan, Dominic; Caban, Jesus; French, Louis M; Harper, Jamie; Eskay, Victoria; Morissette, John; Oakes, Terrence R

    2016-04-01

    Purpose To describe the initial neuroradiology findings in a cohort of military service members with primarily chronic mild traumatic brain injury (TBI) from blast by using an integrated magnetic resonance (MR) imaging protocol. Materials and Methods This study was approved by the Walter Reed National Military Medical Center institutional review board and is compliant with HIPAA guidelines. All participants were military service members or dependents recruited between August 2009 and August 2014. There were 834 participants with a history of TBI and 42 participants in a control group without TBI (not explicitly age- and sex-matched). MR examinations were performed at 3 T primarily with three-dimensional volume imaging at smaller than 1 mm(3) voxels for the structural portion of the examination. The structural portion of this examination, including T1-weighted, T2-weighted, before and after contrast agent administrtion T2 fluid attenuation inversion recovery, and susceptibility-weighted images, was evaluated by neuroradiologists by using a modified version of the neuroradiology TBI common data elements (CDEs). Incident odds ratios (ORs) between the TBI participants and a comparison group without TBI were calculated. Results The 834 participants were diagnosed with predominantly chronic (mean, 1381 days; median, 888 days after injury) and mild (92% [768 of 834]) TBI. Of these participants, 84.2% (688 of 817) reported one or more blast-related incident and 63.0% (515 of 817) reported loss of consciousness at the time of injury. The presence of white matter T2-weighted hyperintense areas was the most common pathologic finding, observed in 51.8% (432 of 834; OR, 1.75) of TBI participants. Cerebral microhemorrhages were observed in a small percentage of participants (7.2% [60 of 834]; OR, 6.64) and showed increased incidence with TBI severity (P < .001, moderate and severe vs mild). T2-weighted hyperintense areas and microhemorrhages did not collocate by visual

  13. Standardizing Data Collection in Traumatic Brain Injury

    PubMed Central

    Harrison-Felix, Cynthia L.; Menon, David; Adelson, P. David; Balkin, Tom; Bullock, Ross; Engel, Doortje C.; Gordon, Wayne; Langlois-Orman, Jean; Lew, Henry L.; Robertson, Claudia; Temkin, Nancy; Valadka, Alex; Verfaellie, Mieke; Wainwright, Mark; Wright, David W.; Schwab, Karen

    2011-01-01

    Abstract Collaboration among investigators, centers, countries, and disciplines is essential to advancing the care for traumatic brain injury (TBI). It is thus important that we “speak the same language.” Great variability, however, exists in data collection and coding of variables in TBI studies, confounding comparisons between and analysis across different studies. Randomized controlled trials can never address the many uncertainties concerning treatment approaches in TBI. Pooling data from different clinical studies and high-quality observational studies combined with comparative effectiveness research may provide excellent alternatives in a cost-efficient way. Standardization of data collection and coding is essential to this end. Common data elements (CDEs) are presented for demographics and clinical variables applicable across the broad spectrum of TBI. Most recommendations represent a consensus derived from clinical practice. Some recommendations concern novel approaches, for example assessment of the intensity of therapy in severely injured patients. Up to three levels of detail for coding data elements were developed: basic, intermediate, and advanced, with the greatest level of detail attained in the advanced version. More detailed codings can be collapsed into the basic version. Templates were produced to summarize coding formats, explanation of choices, and recommendations for procedures. Endorsement of the recommendations has been obtained from many authoritative organizations. The development of CDEs for TBI should be viewed as a continuing process; as more experience is gained, refinement and amendments will be required. This proposed process of standardization will facilitate comparative effectiveness research and encourage high-quality meta-analysis of individual patient data. PMID:21162610

  14. Brain injury in sports.

    PubMed

    Lloyd, John; Conidi, Frank

    2016-03-01

    OBJECT Helmets are used for sports, military, and transportation to protect against impact forces and associated injuries. The common belief among end users is that the helmet protects the whole head, including the brain. However, current consensus among biomechanists and sports neurologists indicates that helmets do not provide significant protection against concussion and brain injuries. In this paper the authors present existing scientific evidence on the mechanisms underlying traumatic head and brain injuries, along with a biomechanical evaluation of 21 current and retired football helmets. METHODS The National Operating Committee on Standards for Athletic Equipment (NOCSAE) standard test apparatus was modified and validated for impact testing of protective headwear to include the measurement of both linear and angular kinematics. From a drop height of 2.0 m onto a flat steel anvil, each football helmet was impacted 5 times in the occipital area. RESULTS Skull fracture risk was determined for each of the current varsity football helmets by calculating the percentage reduction in linear acceleration relative to a 140-g skull fracture threshold. Risk of subdural hematoma was determined by calculating the percentage reduction in angular acceleration relative to the bridging vein failure threshold, computed as a function of impact duration. Ranking the helmets according to their performance under these criteria, the authors determined that the Schutt Vengeance performed the best overall. CONCLUSIONS The study findings demonstrated that not all football helmets provide equal or adequate protection against either focal head injuries or traumatic brain injuries. In fact, some of the most popular helmets on the field ranked among the worst. While protection is improving, none of the current or retired varsity football helmets can provide absolute protection against brain injuries, including concussions and subdural hematomas. To maximize protection against head and

  15. Predictors of Driving Avoidance and Exposure Following Traumatic Brain Injury

    PubMed Central

    Labbe, Donald R.; Vance, David E.; Wadley, Virginia; Novack, Thomas A.

    2015-01-01

    Background An estimated 40–60% of individuals who experience a moderate to severe Traumatic Brain Injury (TBI) return to driving. However, little is known about driving behavior post-TBI and how this may be related to demographic, injury, and outcome factors. Methods A total of 184 participants who experienced moderate to severe TBI were included in this study. Participants completed a telephone survey regarding return to driving and current driving behavior. Structural Equation Modeling (SEM) was used to analyze predicted relationships between demographic and injury-related variables with driving exposure and avoidance within 5 years of injury. Results The model indicated that participants who were older and female tended to avoid a greater number of challenging everyday driving scenarios. Participants that had more severe injuries and those with poorer performance on cognitive measures at the time of rehabilitation discharge were likely to drive less frequently and over less distances at follow up, though they did not avoid challenging driving situations. Conclusions Young males and those with more severe injuries may require additional attention regarding their driving behavior following TBI. PMID:23474877

  16. Severe Traumatic Brain Injury: A Case Report

    PubMed Central

    Nelson, Clinton G.; Elta, Tara; Bannister, Jeanette; Dzandu, James; Mangram, Alicia; Zach, Victor

    2016-01-01

    Patient: Male, 28 Final Diagnosis: Closed head injury Symptoms: Bilateral mydriasis • coma Medication: — Clinical Procedure: Ventriculostomy and hemicraniectomy Specialty: Neurology Objective: Unusual clinical course Background: Traumatic brain injury remains a challenging and complicated disease process to care for, despite the advance of technology used to monitor and guide treatment. Currently, the mainstay of treatment is aimed at limiting secondary brain injury, with the help of multiple specialties in a critical care setting. Prognosis after TBI is often even more challenging than the treatment itself, although there are various exam and imaging findings that are associated with poor outcome. These findings are important because they can be used to guide families and loved ones when making decisions about goals of care. Case Report: In this case report, we demonstrate the unanticipated recovery of a 28-year-old male patient who presented with a severe traumatic brain injury after being in a motorcycle accident without wearing a helmet. He presented with several exam and imaging findings that are statistically associated with increased mortality and morbidity. Conclusions: The care of severe traumatic brain injuries is challenging and dynamic. This case highlights the unexpected recovery of a patient and serves as a reminder that there is variability among patients. PMID:27005826

  17. 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

  18. 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

  19. 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

  20. Altered sleep composition after traumatic brain injury does not affect declarative sleep-dependent memory consolidation.

    PubMed

    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

  1. 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

  2. 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

  3. Tensor-Based Morphometry Reveals Volumetric Deficits in Moderate=Severe Pediatric Traumatic Brain Injury.

    PubMed

    Dennis, Emily L; 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

    2016-05-01

    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

  4. Development of a mild traumatic brain injury-specific vision screening protocol: a Delphi study.

    PubMed

    Goodrich, Gregory L; Martinsen, Gary L; Flyg, Heidi M; Kirby, Jennine; Asch, Steven M; Brahm, Karen D; Brand, John M; Cajamarca, Diana; Cantrell, Jenette L; Chong, Theresa; Dziadul, John A; Hetrick, Barbara J; Huang, Michael A; Ihrig, Carolyn; Ingalla, Shanida P; Meltzer, Bradley R; Rakoczy, Chrystyna M; Rone, Ashley; Schwartz, Elliot; Shea, Jane E

    2013-01-01

    Although traumatic brain injury (TBI) can happen to anyone at any time, the wars in Iraq and Afghanistan have brought it renewed attention. Fortunately, most cases of TBI from the recent conflicts are mild TBI (mTBI). Still, many physical, psychological, and social problems are associated with mTBI. Among the difficulties encountered are oculomotor and vision problems, many of which can impede daily activities such as reading. Therefore, correct diagnosis and treatment of these mTBI-related vision problems is an important part of patient recovery. Numerous eye care providers in the Department of Veterans Affairs, in military settings, and in civilian practices specialize and are proficient in examining patients who have a history of TBI. However, many do not have this level of experience working with and treating patients with mTBI. Recognizing this, we used a modified Delphi method to derive expert opinions from a panel of 16 optometrists concerning visual examination of the patient with mTBI. This process resulted in a clinical tool containing 17 history questions and 7 examination procedures. This tool provides a set of clinical guidelines that can be used as desired by any eye care provider either as a screening tool or adjunct to a full eye examination when seeing a patient with a history of mTBI. The goal of this process was to provide optimal and uniform vision care for the patient with mTBI. PMID:24203539

  5. 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

  6. Arterial Spin Labeling Magnetic Resonance Perfusion for Traumatic Brain Injury: Technical Challenges and Potentials.

    PubMed

    Andre, Jalal B

    2015-10-01

    Traumatic brain injury (TBI), including concussion, is a public health concern, as it affects over 1.7 million persons in the United States per year. Yet, the diagnosis of TBI, particularly mild TBI (mTBI), can be controversial, as neuroimaging findings can be sparse on conventional magnetic resonance and computed tomography examinations, and when present, often poorly correlate with clinical signs and symptoms. Furthermore, the discussion of TBI, concussion, and head impact exposure is immediately complicated by the many differing opinions of what constitutes each, their respective severities, and how the underlying biomechanics of the inciting head impact might alter the distribution, severity, and prognosis of the underlying brain injury. Advanced imaging methodologies hold promise in improving the sensitivity and detectability of associated imaging biomarkers that might better correlate with patient outcome and prognostication, allowing for improved triage and therapeutic guidance in the setting of TBI, particularly in mTBI. This work will examine the defining symptom complex associated with mTBI and explore changes in cerebral blood flow measured by arterial spin labeling, as a potential imaging biomarker for TBI, and briefly correlate these observations with findings identified by single photon emission computed tomography and positron emission tomography imaging. PMID:26502309

  7. 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

  8. Neuroprotective Strategies for Traumatic Brain Injury: Improving Clinical Translation

    PubMed Central

    Kabadi, Shruti V.; Faden, Alan I.

    2014-01-01

    Traumatic brain injury (TBI) induces secondary biochemical changes that contribute to delayed neuroinflammation, neuronal cell death, and neurological dysfunction. Attenuating such secondary injury has provided the conceptual basis for neuroprotective treatments. Despite strong experimental data, more than 30 clinical trials of neuroprotection in TBI patients have failed. In part, these failures likely reflect methodological differences between the clinical and animal studies, as well as inadequate pre-clinical evaluation and/or trial design problems. However, recent changes in experimental approach and advances in clinical trial methodology have raised the potential for successful clinical translation. Here we critically analyze the current limitations and translational opportunities for developing successful neuroprotective therapies for TBI. PMID:24445258

  9. Ceruloplasmin and β-amyloid precursor protein confer neuroprotection in traumatic brain injury and lower neuronal iron.

    PubMed

    Ayton, Scott; Zhang, Moses; Roberts, Blaine R; Lam, Linh Q; Lind, Monica; McLean, Catriona; Bush, Ashley I; Frugier, Tony; Crack, Peter J; Duce, James A

    2014-04-01

    Traumatic brain injury (TBI) is in part complicated by pro-oxidant iron elevation independent of brain hemorrhage. Ceruloplasmin (CP) and β-amyloid protein precursor (APP) are known neuroprotective proteins that reduce oxidative damage through iron regulation. We surveyed iron, CP, and APP in brain tissue from control and TBI-affected patients who were stratified according to time of death following injury. We observed CP and APP induction after TBI accompanying iron accumulation. Elevated APP and CP expression was also observed in a mouse model of focal cortical contusion injury concomitant with iron elevation. To determine if changes in APP or CP were neuroprotective we employed the same TBI model on APP(-/-) and CP(-/-) mice and found that both exhibited exaggerated infarct volume and iron accumulation postinjury. Evidence supports a regulatory role of both proteins in defence against iron-induced oxidative damage after TBI, which presents as a tractable therapeutic target. PMID:24509156

  10. Inter-hemispheric wave propagation failures in traumatic brain injury are indicative of callosal damage.

    PubMed

    Spiegel, Daniel P; Laguë-Beauvais, Maude; Sharma, Gaurav; Farivar, Reza

    2015-04-01

    Approximately 3.2-5.3 million Americans live with the consequences of a traumatic brain injury (TBI), making TBI one of the most common causes of disability in the world. Visual deficits often accompany TBI but physiological and anatomical evidence for injury in mild TBI is lacking. Axons traversing the corpus callosum are particularly vulnerable to TBI. Hemifield representations of early visual areas are linked by bundles of fibers that together cross the corpus callosum while maintaining their topographic relations. Given the increased vulnerability of the long visual axons traversing the corpus callosum, we hypothesized that inter-hemispheric transmission for vision will be impaired following mild TBI. Using the travelling wave paradigm (Wilson, Blake, & Lee 2001), we measured inter-hemispheric transmission in terms of both speed and propagation failures in 14 mild TBI patients and 14 age-matched controls. We found that relative to intra-hemispheric waves, inter-hemispheric waves were faster and that the inter-hemispheric propagation failures were more common in TBI patients. Furthermore, the transmission failures were topographically distributed, with a bias towards greater failures for transmission across the upper visual field. We discuss the results in terms of increased local inhibition and topographically-selective axonal injury in mild TBI. PMID:25752746

  11. Neural correlates of verbal associative memory and mnemonic strategy use following childhood traumatic brain injury

    PubMed Central

    Kramer, Megan E.; Chiu, C.-Y. Peter; Shear, Paula K.; Wade, Shari L.

    2010-01-01

    Children with traumatic brain injury (TBI) often experience memory deficits, although the nature, functional implication, and recovery trajectory of such difficulties are poorly understood. The present fMRI study examined the neural activation patterns in a group of young children who sustained moderate TBI in early childhood (n = 7), and a group of healthy control children (n = 13) during a verbal paired associate learning (PAL) task that promoted the use of two mnemonic strategies differing in efficacy. The children with TBI demonstrated intact memory performance and were able to successfully utilize the mnemonic strategies. However, the TBI group also demonstrated altered brain activation patterns during the task compared to the control children. These findings suggest early childhood TBI may alter activation within the network of brain regions supporting associative memory even in children who show good behavioral performance. PMID:21188286

  12. 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

  13. Neuroprotective measures in children with traumatic brain injury

    PubMed Central

    Agrawal, Shruti; Branco, Ricardo Garcia

    2016-01-01

    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

  14. 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

  15. Predicting outcome after traumatic brain injury.

    PubMed

    Maas, Andrew I R; Lingsma, Hester F; Roozenbeek, Bob

    2015-01-01

    Developing insight into which factors determine prognosis after traumatic brain injury (TBI) is useful for clinical practice, research, and policy making. Several steps can be identified in prediction research: univariate analysis, multivariable analysis, and the development of prediction models. For each step, several methodological issues should be considered, such as selection/coding of predictors and dealing with missing data. "Traditional" predictors include demographic factors (age), type of injury, clinical severity, second insults, and the presence of structural abnormalities on neuroimaging. In combination, these predictors can explain approximately 35% of the variance in outcome in populations with severe and moderate TBI. Novel and emerging predictors include genetic constitution, biomarkers, and advanced magnetic resonance (MR) imaging. To estimate prognosis for individual patients reliably, multiple predictors need to be considered jointly in prognostic models. Two prognostic models for use in TBI, developed upon large patient numbers, have been extensively validated externally: the IMPACT and CRASH prediction models. Both models showed good performance in validations across a wide range of settings. Importantly, these models were developed not only for mortality but also for functional outcome. Prognostic models can be used for providing information to relatives of individual patients, for resource allocation, and to support decisions on treatment. At the group level, prognostic models aid in the characterization of patient populations, are important to clinical trial design and analysis, and importantly, can serve as benchmarks for assessing quality of care. Continued development, refinement, and validation of prognostic models for TBI is required and this should become an ongoing process. PMID:25701901

  16. Injury and Response: What Parents and Professional Providers Are Telling Us about Treating Children with Traumatic Brain Injury.

    ERIC Educational Resources Information Center

    Pieper, Betty

    This report addresses comments and recommendations of parents of children with traumatic brain injury (TBI) as well as those of professionals. The report is in two sections: (1) What Parents Say about the Time of Injury; and (2) What Emergency Personnel Should Know. The first section presents quotes from five parents about reactions and…

  17. 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

  18. Diffusion tensor imaging reveals white matter injury in a rat model of repetitive blast-induced traumatic brain injury.

    PubMed

    Calabrese, Evan; Du, Fu; Garman, Robert H; Johnson, G Allan; Riccio, Cory; Tong, Lawrence C; Long, Joseph B

    2014-05-15

    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

  19. 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

  20. 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

  1. Traumatic Brain Injury and Peripheral Immune Suppression: Primer and Prospectus

    PubMed Central

    Hazeldine, Jon; Lord, Janet M.; Belli, Antonio

    2015-01-01

    Nosocomial infections are a common occurrence in patients following traumatic brain injury (TBI) and are associated with an increased risk of mortality, longer length of hospital stay, and poor neurological outcome. Systemic immune suppression arising as a direct result of injury to the central nervous system (CNS) is considered to be primarily responsible for this increased incidence of infection, a view strengthened by recent studies that have reported novel changes in the composition and function of the innate and adaptive arms of the immune system post-TBI. However, our knowledge of the mechanisms that underlie TBI-induced immune suppression is equivocal at best. Here, after summarizing our current understanding of the impact of TBI on peripheral immunity and discussing CNS-mediated regulation of immune function, we propose roles for a series of novel mechanisms in driving the immune suppression that is observed post-TBI. These mechanisms, which have never been considered before in the context of TBI-induced immune paresis, include the CNS-driven emergence into the circulation of myeloid-derived suppressor cells and suppressive neutrophil subsets, and the release from injured tissue of nuclear and mitochondria-derived damage associated molecular patterns. Moreover, in an effort to further our understanding of the mechanisms that underlie TBI-induced changes in immunity, we pose throughout the review a series of questions, which if answered would address a number of key issues, such as establishing whether manipulating peripheral immune function has potential as a future therapeutic strategy by which to treat and/or prevent infections in the hospitalized TBI patient. PMID:26594196

  2. Traumatic Brain Injury-Induced Dysregulation of the Circadian Clock

    PubMed Central

    Boone, Deborah R.; Sell, Stacy L.; Micci, Maria-Adelaide; Crookshanks, Jeanna M.; Parsley, Margaret; Uchida, Tatsuo; Prough, Donald S.; DeWitt, Douglas S.; Hellmich, Helen L.

    2012-01-01

    Circadian rhythm disturbances are frequently reported in patients recovering from traumatic brain injury (TBI). Since circadian clock output is mediated by some of the same molecular signaling cascades that regulate memory formation (cAMP/MAPK/CREB), cognitive problems reported by TBI survivors may be related to injury-induced dysregulation of the circadian clock. In laboratory animals, aberrant circadian rhythms in the hippocampus have been linked to cognitive and memory dysfunction. Here, we addressed the hypothesis that circadian rhythm disruption after TBI is mediated by changes in expression of clock genes in the suprachiasmatic nuclei (SCN) and hippocampus. After fluid-percussion TBI or sham surgery, male Sprague-Dawley rats were euthanized at 4 h intervals, over a 48 h period for tissue collection. Expression of circadian clock genes was measured using quantitative real-time PCR in the SCN and hippocampus obtained by laser capture and manual microdissection respectively. Immunofluorescence and Western blot analysis were used to correlate TBI-induced changes in circadian gene expression with changes in protein expression. In separate groups of rats, locomotor activity was monitored for 48 h. TBI altered circadian gene expression patterns in both the SCN and the hippocampus. Dysregulated expression of key circadian clock genes, such as Bmal1 and Cry1, was detected, suggesting perturbation of transcriptional-translational feedback loops that are central to circadian timing. In fact, disruption of circadian locomotor activity rhythms in injured animals occurred concurrently. These results provide an explanation for how TBI causes disruption of circadian rhythms as well as a rationale for the consideration of drugs with chronobiotic properties as part of a treatment strategy for TBI. PMID:23056261

  3. Components of Traumatic Brain Injury Severity Indices

    PubMed Central

    Corrigan, John D.; Kreider, Scott; Cuthbert, Jeffrey; Whyte, John; Dams-O’Connor, Kristen; Faul, Mark; Harrison-Felix, Cynthia; Whiteneck, Gale; Pretz, Christopher R.

    2015-01-01

    The purpose of this study was to determine whether there are underlying dimensions common among traditional traumatic brain injury (TBI) severity indices and, if so, the extent to which they are interchangeable when predicting short-term outcomes. This study had an observational design, and took place in United States trauma centers reporting to the National Trauma Data Bank (NTDB). The sample consisted of 77,470 unweighted adult cases reported to the NTDB from 2007 to 2010, with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) TBI codes. There were no interventions. Severity indices used were the Emergency Department Glasgow Coma Scale (GCS) Total score and each of the subscales for eye opening (four levels), verbal response (five levels), and motor response (six levels); the worst Abbreviated Injury Scale (AIS) severity score for the head (six levels); and the worst Barell index type (three categories). Prediction models were computed for acute care length of stay (days), intensive care unit length of stay (days), hospital discharge status (alive or dead), and, if alive, discharge disposition (home versus institutional). Multiple correspondence analysis (MCA) indicated a two dimensional relationship among items of severity indexes. The primary dimension reflected overall injury severity. The second dimension seemed to capture volitional behavior without the capability for cogent responding. Together, they defined two vectors around which most of the items clustered. A scale that took advantage of the order of items along these vectors proved to be the most consistent index for predicting short-term health outcomes. MCA provided useful insight into the relationships among components of traditional TBI severity indices. The two vector pattern may reflect the impact of injury on different cortical and subcortical networks. Results are discussed in terms of score substitution and the ability to impute missing values. PMID

  4. 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

  5. 77 FR 30015 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-21

    ... the Short and Long Term Consequences of Traumatic Brain Injury (TBI) among Children in the United... Consequences of Traumatic Brain Injury (TBI) among Children in the United States, FOA CE12-004.''...

  6. 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

  7. What's New in Traumatic Brain Injury: Update on Tracking, Monitoring and Treatment.

    PubMed

    Reis, Cesar; Wang, Yuechun; Akyol, Onat; Ho, Wing Mann; Ii, Richard Applegate; 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

  8. 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.

  9. 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. PMID:24965838

  10. Radiation Injury to the Brain

    MedlinePlus

    ... Hits since January 2003 RADIATION INJURY TO THE BRAIN Radiation treatments affect all cells that are targeted. ... fractions, duration of therapy, and volume of [healthy brain] nervous tissue irradiated influence the likelihood of injury. ...

  11. 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

  12. 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

  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. 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

  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. Traumatic brain injury impairs small-world topology

    PubMed Central

    Pandit, Anand S.; Expert, Paul; Lambiotte, Renaud; Bonnelle, Valerie; Leech, Robert; Turkheimer, Federico E.

    2013-01-01

    Objective: We test the hypothesis that brain networks associated with cognitive function shift away from a “small-world” organization following traumatic brain injury (TBI). Methods: We investigated 20 TBI patients and 21 age-matched controls. Resting-state functional MRI was used to study functional connectivity. Graph theoretical analysis was then applied to partial correlation matrices derived from these data. The presence of white matter damage was quantified using diffusion tensor imaging. Results: Patients showed characteristic cognitive impairments as well as evidence of damage to white matter tracts. Compared to controls, the graph analysis showed reduced overall connectivity, longer average path lengths, and reduced network efficiency. A particular impact of TBI is seen on a major network hub, the posterior cingulate cortex. Taken together, these results confirm that a network critical to cognitive function shows a shift away from small-world characteristics. Conclusions: We provide evidence that key brain networks involved in supporting cognitive function become less small-world in their organization after TBI. This is likely to be the result of diffuse white matter damage, and may be an important factor in producing cognitive impairment after TBI. PMID:23596068

  17. Low level laser therapy for traumatic brain injury

    NASA Astrophysics Data System (ADS)

    Wu, Qiuhe; Huang, Ying-Ying; Dhital, Saphala; Sharma, Sulbha K.; Chen, Aaron C.-H.; Whalen, Michael J.; Hamblin, Michael R.

    2010-02-01

    Low level laser (or light) therapy (LLLT) has been clinically applied for many indications in medicine that require the following processes: protection from cell and tissue death, stimulation of healing and repair of injuries, and reduction of pain, swelling and inflammation. One area that is attracting growing interest is the use of transcranial LLLT to treat stroke and traumatic brain injury (TBI). The fact that near-infrared light can penetrate into the brain would allow non-invasive treatment to be carried out with a low likelihood of treatment-related adverse events. LLLT may have beneficial effects in the acute treatment of brain damage injury by increasing respiration in the mitochondria, causing activation of transcription factors, reducing key inflammatory mediators, and inhibiting apoptosis. We tested LLLT in a mouse model of TBI produced by a controlled weight drop onto the skull. Mice received a single treatment with 660-nm, 810-nm or 980-nm laser (36 J/cm2) four hours post-injury and were followed up by neurological performance testing for 4 weeks. Mice with moderate to severe TBI treated with 660- nm and 810-nm laser had a significant improvement in neurological score over the course of the follow-up and histological examination of the brains at sacrifice revealed less lesion area compared to untreated controls. Further studies are underway.

  18. Perceptual organization deficits in traumatic brain injury patients.

    PubMed

    Costa, Thiago L; Zaninotto, Ana Luiza C; Benute, Gláucia G; De Lúcia, Mara C S; Paiva, Wellingson S; Wagemans, Johan; Boggio, Paulo S

    2015-11-01

    Traumatic brain injury (TBI) is a prevalent condition and there is limited visual perception research with this population. Here, we investigated perceptual organization changes in a rather homogeneous sample of closed head TBI outpatients with diffuse axonal injury only and no other known comorbidities. Patients had normal or corrected visual acuity. Perceptual organization was measured with the Leuven Perceptual Organization Screening Test (L-POST), a coherent motion task (CM) and the Leuven Embedded Figures Test (L-EFT). These tests were chosen to screen for deficits in different aspects of perceptual organization (L-POST), to evaluate local and global processing (L-EFT) and grouping in a dynamic set of stimuli (CM). TBI patients were significantly impaired compared to controls in all measures for both response time and accuracy, except for CM thresholds and object recognition subtests. The TBI group was similarly affected in all aspects of the L-EFT. TBI was also similarly affected in all perceptual factors of the L-POST. No significant correlations were found between scores and time post-injury, except for CM thresholds (rs=-0.74), which might explain the lack of group-level differences. The only score significantly correlated to IQ was L-EFT response time (rs=-0.67). These findings demonstrate that perceptual organization is diffusely affected in TBI and this effect has no substantial correlations with IQ. As many of the neuropsychological tests used to measure different cognitive functions involve some level of visual discrimination and perceptual organization demands, these results must be taken into account in the general neuropsychological evaluation of TBI patients. PMID:26455804

  19. Acquired Brain Injury Program.

    ERIC Educational Resources Information Center

    Schwartz, Stacey Hunter

    This paper reviews the Acquired Brain Injury (ABI) Program at Coastline Community College (California). The ABI Program is a two-year, for-credit educational curriculum designed to provide structured cognitive retraining for adults who have sustained an ABI due to traumatic (such as motor vehicle accident or fall) or non-traumatic(such as…

  20. Advanced Neuroimaging in Traumatic Brain Injury

    PubMed Central

    Edlow, Brian L.; Wu, Ona

    2013-01-01

    Advances in structural and functional neuroimaging have occurred at a rapid pace over the past two decades. Novel techniques for measuring cerebral blood flow, metabolism, white matter connectivity, and neural network activation have great potential to improve the accuracy of diagnosis and prognosis for patients with traumatic brain injury (TBI), while also providing biomarkers to guide the development of new therapies. Several of these advanced imaging modalities are currently being implemented into clinical practice, whereas others require further development and validation. Ultimately, for advanced neuroimaging techniques to reach their full potential and improve clinical care for the many civilians and military personnel affected by TBI, it is critical for clinicians to understand the applications and methodological limitations of each technique. In this review, we examine recent advances in structural and functional neuroimaging and the potential applications of these techniques to the clinical care of patients with TBI. We also discuss pitfalls and confounders that should be considered when interpreting data from each technique. Finally, given the vast amounts of advanced imaging data that will soon be available to clinicians, we discuss strategies for optimizing data integration, visualization and interpretation. PMID:23361483

  1. Biomarkers of Traumatic Injury Are Transported from Brain to Blood via the Glymphatic System

    PubMed Central

    Plog, Benjamin A.; Dashnaw, Matthew L.; Hitomi, Emi; Peng, Weiguo; Liao, Yonghong; Lou, Nanhong; Deane, Rashid

    2015-01-01

    The nonspecific and variable presentation of traumatic brain injury (TBI) has motivated an intense search for blood-based biomarkers that can objectively predict the severity of injury. However, it is not known how cytosolic proteins released from traumatized brain tissue reach the peripheral blood. Here we show in a murine TBI model that CSF movement through the recently characterized glymphatic pathway transports biomarkers to blood via the cervical lymphatics. Clinically relevant manipulation of glymphatic activity, including sleep deprivation and cisternotomy, suppressed or eliminated TBI-induced increases in serum S100β, GFAP, and neuron specific enolase. We conclude that routine TBI patient management may limit the clinical utility of blood-based biomarkers because their brain-to-blood transport depends on glymphatic activity. PMID:25589747

  2. Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system.

    PubMed

    Plog, Benjamin A; Dashnaw, Matthew L; Hitomi, Emi; Peng, Weiguo; Liao, Yonghong; Lou, Nanhong; Deane, Rashid; Nedergaard, Maiken

    2015-01-14

    The nonspecific and variable presentation of traumatic brain injury (TBI) has motivated an intense search for blood-based biomarkers that can objectively predict the severity of injury. However, it is not known how cytosolic proteins released from traumatized brain tissue reach the peripheral blood. Here we show in a murine TBI model that CSF movement through the recently characterized glymphatic pathway transports biomarkers to blood via the cervical lymphatics. Clinically relevant manipulation of glymphatic activity, including sleep deprivation and cisternotomy, suppressed or eliminated TBI-induced increases in serum S100β, GFAP, and neuron specific enolase. We conclude that routine TBI patient management may limit the clinical utility of blood-based biomarkers because their brain-to-blood transport depends on glymphatic activity. PMID:25589747

  3. Brain Injury Association of America

    MedlinePlus

    ... Only) 1-800-444-6443 Welcome to the Brain Injury Association of America (BIAA) Brain injury is not an event or an outcome. ... misunderstood, under-funded neurological disease. People who sustain brain injuries must have timely access to expert trauma ...

  4. A systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury.

    PubMed

    Yu, Chenggang; Boutté, Angela; Yu, Xueping; Dutta, Bhaskar; Feala, Jacob D; Schmid, Kara; Dave, Jitendra; Tawa, Gregory J; Wallqvist, Anders; Reifman, Jaques

    2015-02-01

    The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI. PMID:25399920

  5. A systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury

    PubMed Central

    Yu, Chenggang; Boutté, Angela; Yu, Xueping; Dutta, Bhaskar; Feala, Jacob D; Schmid, Kara; Dave, Jitendra; Tawa, Gregory J; Wallqvist, Anders; Reifman, Jaques

    2015-01-01

    The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI. PMID:25399920

  6. Actual data on epidemiological evolution and prevention endeavours regarding traumatic brain injury

    PubMed Central

    Popescu, C; Anghelescu, A; Daia, C; Onose, G

    2015-01-01

    Background: Knowledge of the epidemiology of traumatic brain injury (TBI) is required both to prevent this disorder and to develop effective care and rehabilitation approaches for patients. Objective: The aim of this article is to find solutions to decrease the incidence of TBI and offer recommendations for their prevention. Material and methods: We analyzed epidemiological studies on TBI by performing a systematic review of literature, using information reported by different centers, collecting data on demographics, showing characteristics of TBI including incidence, identification of risk groups on differences in age, gender, geographical variation, severity and mortality. Results: Studies suggest that the incidence of TBI is between 18 and 250 per 100,000 persons per year. Men and people living in social and economical deprived areas, usually young adults and the elderly are high-risk groups for TBI. Discussion: Prevention remains the “key point” in medicine and especially for TBI, saving the patient from unnecessary often-harsh sufferance. Conclusions: Most public epidemiological data showed that TBI is a major cause of mortality and disability. The effort to understand TBI and the available strategies to treat this lesion, in order to improve clinical outcomes after TBI, may be based on an increase in research on the epidemiology of TBI. A coordinated strategy to evaluate this public health problem in Romania would first of all rely on a related advanced monitoring system, to provide precise information about the epidemiology, clinical and paraclinical data, but concerning the social and economic connected consequences, too. Abbreviations: CNS = central nervous system, ED = emergency department, EU = European Union, FTE = Full Time Employees, GCS = Glasgow Coma Scale, TBI = traumatic brain injury, US = United States, WHO = World Health Organization. PMID:26351526

  7. Trends in North American newspaper reporting of brain injury in ice hockey.

    PubMed

    Cusimano, Michael D; Sharma, Bhanu; Lawrence, David W; Ilie, Gabriela; Silverberg, Sarah; Jones, Rochelle

    2013-01-01

    The frequency and potential long-term effects of sport-related traumatic brain injuries (TBI) make it a major public health concern. The culture within contact sports, such as ice hockey, encourages aggression that puts youth at risk of TBI such as concussion. Newspaper reports play an important role in conveying and shaping the culture around health-related behaviors. We qualitatively studied reports about sport-related TBI in four major North American newspapers over the last quarter-century. We used the grounded-theory approach to identify major themes and then did a content analysis to compare the frequency of key themes between 1998-2000 and 2009-2011. The major themes were: perceptions of brain injury, aggression, equipment, rules and regulations, and youth hockey. Across the full study period, newspaper articles from Canada and America portrayed violence and aggression that leads to TBI both as integral to hockey and as an unavoidable risk associated with playing the game. They also condemned violence in ice hockey, criticized the administrative response to TBI, and recognized the significance of TBI. In Canada, aggression was reported more often recently and there was a distinctive shift in portraying protective equipment as a solution to TBI in earlier years to a potential contributing factor to TBI later in the study period. American newspapers gave a greater attention to 'perception of risks' and the role of protective equipment, and discussed TBI in a broader context in the recent time period. Newspapers from both countries showed similar recent trends in regards to a need for rule changes to curb youth sport-related TBI. This study provides a rich description of the reporting around TBI in contact sport. Understanding this reporting is important for evaluating whether the dangers of sport-related TBI are being appropriately communicated by the media. PMID:23613957

  8. Trends in North American Newspaper Reporting of Brain Injury in Ice Hockey

    PubMed Central

    Cusimano, Michael D.; Sharma, Bhanu; Lawrence, David W.; Ilie, Gabriela; Silverberg, Sarah; Jones, Rochelle

    2013-01-01

    The frequency and potential long-term effects of sport-related traumatic brain injuries (TBI) make it a major public health concern. The culture within contact sports, such as ice hockey, encourages aggression that puts youth at risk of TBI such as concussion. Newspaper reports play an important role in conveying and shaping the culture around health-related behaviors. We qualitatively studied reports about sport-related TBI in four major North American newspapers over the last quarter-century. We used the grounded-theory approach to identify major themes and then did a content analysis to compare the frequency of key themes between 1998–2000 and 2009–2011. The major themes were: perceptions of brain injury, aggression, equipment, rules and regulations, and youth hockey. Across the full study period, newspaper articles from Canada and America portrayed violence and aggression that leads to TBI both as integral to hockey and as an unavoidable risk associated with playing the game. They also condemned violence in ice hockey, criticized the administrative response to TBI, and recognized the significance of TBI. In Canada, aggression was reported more often recently and there was a distinctive shift in portraying protective equipment as a solution to TBI in earlier years to a potential contributing factor to TBI later in the study period. American newspapers gave a greater attention to ‘perception of risks’ and the role of protective equipment, and discussed TBI in a broader context in the recent time period. Newspapers from both countries showed similar recent trends in regards to a need for rule changes to curb youth sport-related TBI. This study provides a rich description of the reporting around TBI in contact sport. Understanding this reporting is important for evaluating whether the dangers of sport-related TBI are being appropriately communicated by the media. PMID:23613957

  9. WISC-IV Profiles in Children with Traumatic Brain Injury: Similarities to and Differences from the WISC-III

    ERIC Educational Resources Information Center

    Allen, Daniel N.; Thaler, Nicholas S.; Donohue, Brad; Mayfield, Joan

    2010-01-01

    The Wechsler Intelligence Scale for Children--Fourth Edition (WISC-IV; D. Wechsler, 2003a) is often utilized to assess children with traumatic brain injury (TBI), although little information is available regarding its psychometric properties in these children. The current study examined WISC-IV performance in a sample of 61 children with TBI. As…

  10. Predictors of Secondary Attention-Deficit/Hyperactivity Disorder in Children and Adolescents 6 to 24 Months after 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 from 6 to…

  11. Acute Alcohol Intoxication Prolongs Neuroinflammation without Exacerbating Neurobehavioral Dysfunction following Mild Traumatic Brain Injury

    PubMed Central

    Teng, Sophie X.

    2014-01-01

    Abstract Traumatic brain injury (TBI) represents a leading cause of death and disability among young persons with ∼1.7 million reported cases in the United States annually. Although acute alcohol intoxication (AAI) is frequently present at the time of TBI, conflicting animal and clinical reports have failed to establish whether AAI significantly impacts short-term outcomes after TBI. The objective of this study was to determine whether AAI at the time of TBI aggravates neurobehavioral outcomes and neuroinflammatory sequelae post-TBI. Adult male Sprague-Dawley rats were surgically instrumented with gastric and vascular catheters before a left lateral craniotomy. After recovery, rats received either a primed constant intragastric alcohol infusion (2.5 g/kg+0.3 g/kg/h for 15 h) or isocaloric/isovolumic dextrose infusion followed by a lateral fluid percussion TBI (∼1.4 J, ∼30 ms). TBI induced apnea and a delay in righting reflex. AAI at the time of injury increased the TBI induced delay in righting reflex without altering apnea duration. Neurological and behavioral dysfunction was observed at 6 h and 24 h post-TBI, and this was not exacerbated by AAI. TBI induced a transient upregulation of cortical interleukin (IL)-6 and monocyte chemotactic protein (MCP)-1 mRNA expression at 6 h, which was resolved at 24 h. AAI did not modulate the inflammatory response at 6 h but prevented resolution of inflammation (IL-1, IL-6, tumor necrosis factor-α, and MCP-1 expression) at 24 h post-TBI. AAI at the time of TBI did not delay the recovery of neurological and neurobehavioral function but prevented the resolution of neuroinflammation post-TBI. PMID:24050411

  12. Prevalence of Traumatic Brain Injury in Cocaine-Dependent Research Volunteers

    PubMed Central

    Ramesh, Divya; Keyser-Marcus, Lori A.; Ma, Liangsuo; Schmitz, Joy M.; Lane, Scott D.; Marwitz, Jennifer H.; Kreutzer, Jeffrey S.; Moeller, Frederick Gerard

    2015-01-01

    Background There is a high prevalence of traumatic brain injury (TBI) among those with substance dependence. However, TBI often remains undiagnosed in these individuals, due to lack of routine screening in substance use treatment settings or due to overlap in some of the cognitive sequelae (eg impulsivity, disinhibition) of TBI and cocaine dependence. Methods The prevalence of self-reported mild to moderate TBI in a group of cocaine-dependent (n = 95) and a group of healthy volunteers (n = 75) enrolled at the same facility was assessed. Additionally, the relationship between TBI and clinically relevant correlates, including impulsivity, cocaine use history, and treatment outcome in the cocaine-dependent group was also examined. Results A higher proportion of individuals with cocaine dependence (29.5%) reported having suffered a TBI in their lifetime compared to controls (8%) on a Closed Head Injury scale. Among cocaine users, the average age of sustaining TBI was significantly lower than the age of initiating cocaine use. Presence of TBI was not associated with higher impulsivity on the Barratt Impulsiveness Scale-11 or self-reported years of cocaine use. No differences were noted on treatment outcome for cocaine dependence as measured by treatment effectiveness scores (TES) between cocaine users with TBI and their non-TBI counterparts. Conclusions These results are the first to highlight the high prevalence of TBI among individuals with cocaine dependence. This study underscores the possible role of TBI history as a risk factor for onset of cocaine use, however, more research is needed to determine the impact of co-morbid TBI as a complicating factor in the substance abuse treatment setting. PMID:25662909

  13. The interplay between neuropathology and activity based rehabilitation after traumatic brain injury.

    PubMed

    Kreber, Lisa A; Griesbach, Grace S

    2016-06-01

    Exercise has been shown to facilitate the release of molecules that support neuroplasticity and to offer protection from brain damage. This article addresses the mechanisms behind exercise׳s beneficial effects within the context of traumatic brain injury (TBI). First, we describe how ongoing metabolic, neuroendocrine and inflammatory alterations after TBI interact with exercise. Given the dynamic nature of TBI-initiated pathophysiological processes, the timing, intensity and type of exercise need to be considered when implementing exercise. These factors have been shown to be important in determining whether exercise enhances or impedes neuroplasticity after TBI. In point of fact, intense exercise during the acute post-injury period has been associated with worsened cognitive performance. Similarly, exercise that is associated with a pronounced increase of stress hormones can inhibit the expression of brain derived neurotrophic factor that is usually increased with exercise. Second, we describe the clinical implications of these findings in returning to play following TBI. Finally, we address therapeutic exercise interventions in the context of rehabilitation following TBI. Exercise is likely to play an important role in improving cognitive and affective outcome during post-acute rehabilitation. It is important to take into account relevant patient, injury, and exercise variables when utilizing exercise as a therapeutic intervention to ensure that physical exercise programs promote adaptive neuroplasticity and hence recovery. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26776479

  14. Compensation through Functional Hyperconnectivity: A Longitudinal Connectome Assessment of Mild Traumatic Brain Injury

    PubMed Central

    Iraji, Armin; Chen, Hanbo; Wiseman, Natalie; Welch, Robert D.; O'Neil, Brian J.; Haacke, E. Mark; Liu, Tianming; Kou, Zhifeng

    2016-01-01

    Mild traumatic brain injury (mTBI) is a major public health concern. Functional MRI has reported alterations in several brain networks following mTBI. However, the connectome-scale brain network changes are still unknown. In this study, sixteen mTBI patients were prospectively recruited from an emergency department and followed up at 4–6 weeks after injury. Twenty-four healthy controls were also scanned twice with the same time interval. Three hundred fifty-eight brain landmarks that preserve structural and functional correspondence of brain networks across individuals were used to investigate longitudinal brain connectivity. Network-based statistic (NBS) analysis did not find significant difference in the group-by-time interaction and time effects. However, 258 functional pairs show group differences in which mTBI patients have higher functional connectivity. Meta-analysis showed that “Action” and “Cognition” are the most affected functional domains. Categorization of connectomic signatures using multiview group-wise cluster analysis identified two patterns of functional hyperconnectivity among mTBI patients: (I) between the posterior cingulate cortex and the association areas of the brain and (II) between the occipital and the frontal lobes of the brain. Our results demonstrate that brain concussion renders connectome-scale brain network connectivity changes, and the brain tends to be hyperactivated to compensate the pathophysiological disturbances. PMID:26819765

  15. Components of Myelin Damage and Repair in the Progression of White Matter Pathology After Mild Traumatic Brain Injury

    PubMed Central

    Mierzwa, Amanda J.; Marion, Christina M.; Sullivan, Genevieve M.; McDaniel, Dennis P.; Armstrong, Regina C.

    2015-01-01

    Abstract White matter tracts are highly vulnerable to damage from impact-acceleration forces of traumatic brain injury (TBI). Mild TBI is characterized by a low density of traumatic axonal injury, whereas associated myelin pathology is relatively unexplored. We examined the progression of white matter pathology in mice after mild TBI with traumatic axonal injury localized in the corpus callosum. Adult mice received a closed-skull impact and were analyzed from 3 days to 6 weeks post-TBI/sham surgery. At all times post-TBI, electron microscopy revealed degenerating axons distributed among intact fibers in the corpus callosum. Intact axons exhibited significant demyelination at 3 days followed by evidence of remyelination at 1 week. Accordingly, bromodeoxyuridine pulse-chase labeling demonstrated the generation of new oligodendrocytes, identified by myelin proteolipid protein messenger RNA expression, at 3 days post-TBI. Overall oligodendrocyte populations, identified by immunohistochemical staining for CC1 and/or glutathione S-transferase pi, were similar between TBI and sham mice by 2 weeks. Excessively long myelin figures, similar to redundant myelin sheaths, were a significant feature at all post-TBI time points. At 6 weeks post-TBI, microglial activation and astrogliosis were localized to areas of axon and myelin pathology. These studies show that demyelination, remyelination, and excessive myelin are components of white matter degeneration and recovery in mild TBI with traumatic axonal injury. PMID:25668562

  16. Quo Vadis 2010? – Carpe Diem: Challenges and Opportunities in Pediatric Traumatic Brain Injury

    PubMed Central

    Kochanek, Patrick M.; Bell, Michael J.; Bayır, Hülya

    2011-01-01

    Traumatic brain injury (TBI) in infants and children remains a public health problem of enormous magnitude. It is a complex and heterogeneous condition that presents many diagnostic, therapeutic and prognostic challenges. A number of investigative teams are studying pediatric TBI both in experimental models and in clinical studies at the bedside. This review builds on work presented in a prior supplement to Developmental Neuroscience that was published in 2006, and addresses several active areas of research on this topic, including (1) the application of novel imaging methods, (2) the use of serum and/or CSF biomarkers of injury, (3) advances in neuromonitoring, (4) the development and testing of novel therapies, (5) developments in modeling pediatric TBI, (6) the consideration of a new approach to classification of pediatric TBI, and (7) assessing the potential impact of the development of pediatric and neonatal neurocritical care services on the management and outcome of pediatric TBI. PMID:21252553

  17. Cognitive Impairment and Rehabilitation Strategies After Traumatic Brain Injury.

    PubMed

    Barman, Apurba; Chatterjee, Ahana; Bhide, Rohit

    2016-01-01

    Traumatic brain injury (TBI) is among the significant causes of morbidity and mortality in the present world. Around 1.6 million persons sustain TBI, whereas 200,000 die annually in India, thus highlighting the rising need for appropriate cognitive rehabilitation strategies. This literature review assesses the current knowledge of various cognitive rehabilitation training strategies. The entire spectrum of TBI severity; mild to severe, is associated with cognitive deficits of varying degree. Cognitive insufficiency is more prevalent and longer lasting in TBI persons than in the general population. A multidisciplinary approach with neuropsychiatric evaluation is warranted. Attention process training and tasks for attention deficits, compensatory strategies and errorless learning training for memory deficits, pragmatic language skills and social behavior guidance for cognitive-communication disorder, meta-cognitive strategy, and problem-solving training for executive disorder are the mainstay of therapy for cognitive deficits in persons with TBI. Cognitive impairments following TBI are common and vary widely. Different cognitive rehabilitation techniques and combinations in addition to pharmacotherapy are helpful in addressing various cognitive deficits. PMID:27335510

  18. Cognitive Impairment and Rehabilitation Strategies After Traumatic Brain Injury

    PubMed Central

    Barman, Apurba; Chatterjee, Ahana; Bhide, Rohit

    2016-01-01

    Traumatic brain injury (TBI) is among the significant causes of morbidity and mortality in the present world. Around 1.6 million persons sustain TBI, whereas 200,000 die annually in India, thus highlighting the rising need for appropriate cognitive rehabilitation strategies. This literature review assesses the current knowledge of various cognitive rehabilitation training strategies. The entire spectrum of TBI severity; mild to severe, is associated with cognitive deficits of varying degree. Cognitive insufficiency is more prevalent and longer lasting in TBI persons than in the general population. A multidisciplinary approach with neuropsychiatric evaluation is warranted. Attention process training and tasks for attention deficits, compensatory strategies and errorless learning training for memory deficits, pragmatic language skills and social behavior guidance for cognitive-communication disorder, meta-cognitive strategy, and problem-solving training for executive disorder are the mainstay of therapy for cognitive deficits in persons with TBI. Cognitive impairments following TBI are common and vary widely. Different cognitive rehabilitation techniques and combinations in addition to pharmacotherapy are helpful in addressing various cognitive deficits. PMID:27335510

  19. Association of traumatic brain injury with subsequent neurological and psychiatric disease: a meta-analysis.

    PubMed

    Perry, David C; Sturm, Virginia E; Peterson, Matthew J; Pieper, Carl F; Bullock, Thomas; Boeve, Bradley F; Miller, Bruce L; Guskiewicz, Kevin M; Berger, Mitchel S; Kramer, Joel H; Welsh-Bohmer, Kathleen A

    2016-02-01

    OBJECT Mild traumatic brain injury (TBI) has been proposed as a risk factor for the development of Alzheimer's disease, Parkinson's disease, depression, and other illnesses. This study's objective was to determine the association of prior mild TBI with the subsequent diagnosis (that is, at least 1 year postinjury) of neurological or psychiatric disease. METHODS All studies from January 1995 to February 2012 reporting TBI as a risk factor for diagnoses of interest were identified by searching PubMed, study references, and review articles. Reviewers abstracted the data and assessed study designs and characteristics. RESULTS Fifty-seven studies met the inclusion criteria. A random effects meta-analysis revealed a significant association of prior TBI with subsequent neurological and psychiatric diagnoses. The pooled odds ratio (OR) for the development of any illness subsequent to prior TBI was 1.67 (95% CI 1.44-1.93, p < 0.0001). Prior TBI was independently associated with both neurological (OR 1.55, 95% CI 1.31-1.83, p < 0.0001) and psychiatric (OR 2.00, 95% CI 1.50-2.66, p < 0.0001) outcomes. Analyses of individual diagnoses revealed higher odds of Alzheimer's disease, Parkinson's disease, mild cognitive impairment, depression, mixed affective disorders, and bipolar disorder in individuals with previous TBI as compared to those without TBI. This association was present when examining only studies of mild TBI and when considering the influence of study design and characteristics. Analysis of a subset of studies demonstrated no evidence that multiple TBIs were associated with higher odds of disease than a single TBI. CONCLUSIONS History of TBI, including mild TBI, is associated with the development of neurological and psychiatric illness. This finding indicates that either TBI is a risk factor for heterogeneous pathological processes or that TBI may contribute to a common pathological mechanism. PMID:26315003

  20. Sensory Cortex Underpinnings of Traumatic Brain Injury Deficits

    PubMed Central

    Alwis, Dasuni S.; Yan, Edwin B.; Morganti-Kossmann, Maria-Cristina; Rajan, Ramesh

    2012-01-01

    Traumatic brain injury (TBI) can result in persistent sensorimotor and cognitive deficits including long-term altered sensory processing. The few animal models of sensory cortical processing effects of TBI have been limited to examination of effects immediately after TBI and only in some layers of cortex. We have now used the rat whisker tactile system and the cortex processing whisker-derived input to provide a highly detailed description of TBI-induced long-term changes in neuronal responses across the entire columnar network in primary sensory cortex. Brain injury (n = 19) was induced using an impact acceleration method and sham controls received surgery only (n = 15). Animals were tested in a range of sensorimotor behaviour tasks prior to and up to 6 weeks post-injury when there were still significant sensorimotor behaviour deficits. At 8–10 weeks post-trauma, in terminal experiments, extracellular recordings were obtained from barrel cortex neurons in response to whisker motion, including motion that mimicked whisker motion observed in awake animals undertaking different tasks. In cortex, there were lamina-specific neuronal response alterations that appeared to reflect local circuit changes. Hyper-excitation was found only in supragranular layers involved in intra-areal processing and long-range integration, and only for stimulation with complex, naturalistic whisker motion patterns and not for stimulation with simple trapezoidal whisker motion. Thus TBI induces long-term directional changes in integrative sensory cortical layers that depend on the complexity of the incoming sensory information. The nature of these changes allow predictions as to what types of sensory processes may be affected in TBI and contribute to post-trauma sensorimotor deficits. PMID:23284921

  1. Post-Traumatic Seizures Exacerbate Histopathological Damage after Fluid-Percussion Brain Injury

    PubMed Central

    Bao, Ying-hui; Bramlett, Helen M.; Atkins, Coleen M.; Truettner, Jessie S.; Lotocki, George; Alonso, Ofelia F.

    2011-01-01

    Abstract The purpose of this study was to investigate the effects of an induced period of post-traumatic epilepsy (PTE) on the histopathological damage caused by traumatic brain injury (TBI). Male Sprague Dawley rats were given a moderate parasagittal fluid-percussion brain injury (1.9–2.1 atm) or sham surgery. At 2 weeks after surgery, seizures were induced by administration of a GABAA receptor antagonist, pentylenetetrazole (PTZ, 30 mg/kg). Seizures were then assessed over a 1-h period using the Racine clinical rating scale. To evaluate whether TBI-induced pathology was exacerbated by the seizures, contusion volume and cortical and hippocampal CA3 neuronal cell loss were measured 3 days after seizures. Nearly all TBI rats showed clinical signs of PTE following the decrease in inhibitory activity. In contrast, clinically evident seizures were not observed in TBI rats given saline or sham-operated rats given PTZ. Contusions in TBI-PTZ-treated rats were significantly increased compared to the TBI-saline-treated group (p < 0.001). In addition, the TBI-PTZ rats showed less NeuN-immunoreactive cells within the ipsilateral parietal cerebral cortex (p < 0.05) and there was a trend for decreased hippocampal CA3 neurons in TBI-PTZ rats compared with TBI-saline or sham-operated rats. These results demonstrate that an induced period of post-traumatic seizures significantly exacerbates the structural damage caused by TBI. These findings emphasize the need to control seizures after TBI to limit even further damage to the injured brain. PMID:20836615

  2. Brain injury tolerance limit based on computation of axonal strain.

    PubMed

    Sahoo, Debasis; Deck, Caroline; Willinger, Rémy

    2016-07-01

    Traumatic brain injury (TBI) is the leading cause of death and permanent impairment over the last decades. In both the severe and mild TBIs, diffuse axonal injury (DAI) is the most common pathology and leads to axonal degeneration. Computation of axonal strain by using finite element head model in numerical simulation can enlighten the DAI mechanism and help to establish advanced head injury criteria. The main objective of this study is to develop a brain injury criterion based on computation of axonal strain. To achieve the objective a state-of-the-art finite element head model with enhanced brain and skull material laws, was used for numerical computation of real world head trauma. The implementation of new medical imaging data such as, fractional anisotropy and axonal fiber orientation from Diffusion Tensor Imaging (DTI) of 12 healthy patients into the finite element brain model was performed to improve the brain constitutive material law with more efficient heterogeneous anisotropic visco hyper-elastic material law. The brain behavior has been validated in terms of brain deformation against Hardy et al. (2001), Hardy et al. (2007), and in terms of brain pressure against Nahum et al. (1977) and Trosseille et al. (1992) experiments. Verification of model stability has been conducted as well. Further, 109 well-documented TBI cases were simulated and axonal strain computed to derive brain injury tolerance curve. Based on an in-depth statistical analysis of different intra-cerebral parameters (brain axonal strain rate, axonal strain, first principal strain, Von Mises strain, first principal stress, Von Mises stress, CSDM (0.10), CSDM (0.15) and CSDM (0.25)), it was shown that axonal strain was the most appropriate candidate parameter to predict DAI. The proposed brain injury tolerance limit for a 50% risk of DAI has been established at 14.65% of axonal strain. This study provides a key step for a realistic novel injury metric for DAI. PMID:27038501

  3. cis p-tau: early driver of brain injury and tauopathy blocked by antibody

    PubMed Central

    Mannix, Rebekah; Qiu, Jianhua; Moncaster, Juliet; Chen, Chun-Hau; Yao, Yandan; Lin, Yu-Min; Driver, Jane A; Sun, Yan; Wei, Shuo; Luo, Man-Li; Albayram, Onder; Huang, Pengyu; Rotenberg, Alexander; Ryo, Akihide; Goldstein, Lee E; Pascual-Leone, Alvaro; McKee, Ann C.; Meehan, William; Zhou, Xiao Zhen; Lu, Kun Ping

    2015-01-01

    Traumatic brain injury (TBI), characterized by acute neurological dysfunction, is one of the best known environmental risk factors for chronic traumatic encephalopathy (CTE) and Alzheimer's disease (AD), whose defining pathologic features include tauopathy made of phosphorylated tau (p-tau). However, tauopathy has not been detected in early stages after TBI and how TBI leads to tauopathy is unknown. Here we find robust cis p-tau pathology after sport- and military-related TBI in humans and mice. Acutely after TBI in mice and stress in vitro, neurons prominently produce cis p-tau, which disrupts axonal microtubule network and mitochondrial transport, spreads to other neurons, and leads to apoptosis. This process, termed “cistauosis”, appears long before other tauopathy. Treating TBI mice with cis antibody blocks cistauosis, prevents tauopathy development and spread, and restores many TBI-related structural and functional sequelae. Thus, cis p-tau is a major early driver after TBI and leads to tauopathy in CTE and AD, and cis antibody may be further developed to detect and treat TBI, and prevent progressive neurodegeneration after injury. PMID:26176913

  4. Altered Amygdala Connectivity in Individuals with Chronic Traumatic Brain Injury and Comorbid Depressive Symptoms

    PubMed Central

    Han, Kihwan; Chapman, Sandra B.; Krawczyk, Daniel C.

    2015-01-01

    Depression is one of the most common psychiatric conditions in individuals with chronic traumatic brain injury (TBI). Though depression has detrimental effects in TBI and network dysfunction is a “hallmark” of TBI and depression, there have not been any prior investigations of connectivity-based neuroimaging biomarkers for comorbid depression in TBI. We utilized resting-state functional magnetic resonance imaging to identify altered amygdala connectivity in individuals with chronic TBI (8 years post-injury on average) exhibiting comorbid depressive symptoms (N = 31), relative to chronic TBI individuals having minimal depressive symptoms (N = 23). Connectivity analysis of these participant sub-groups revealed that the TBI-plus-depressive symptoms group showed relative increases in amygdala connectivity primarily in the regions that are part of the salience, somatomotor, dorsal attention, and visual networks (pvoxel < 0.01, pcluster < 0.025). Relative increases in amygdala connectivity in the TBI-plus-depressive symptoms group were also observed within areas of the limbic–cortical mood-regulating circuit (the left dorsomedial and right dorsolateral prefrontal cortices and thalamus) and the brainstem. Further analysis revealed that spatially dissociable patterns of correlation between amygdala connectivity and symptom severity according to subtypes (Cognitive and Affective) of depressive symptoms (pvoxel < 0.01, pcluster < 0.025). Taken together, these results suggest that amygdala connectivity may be a potentially effective neuroimaging biomarker for comorbid depressive symptoms in chronic TBI. PMID:26581959

  5. White Matter Injuries in Mild Traumatic Brain Injury and Posttraumatic Migraines: Diffusion Entropy Analysis.

    PubMed

    Delic, Joseph; Alhilali, Lea M; Hughes, Marion A; Gumus, Serter; Fakhran, Saeed

    2016-06-01

    Purpose To determine the performance of Shannon entropy (SE) as a diagnostic tool in patients with mild traumatic brain injury (mTBI) with posttraumatic migraines (PTMs) and those without PTMs on the basis of analysis of fractional anisotropy (FA) maps. Materials and Methods The institutional review board approved this retrospective study, with waiver of informed consent. FA maps were obtained and neurocognitive testing was performed in 74 patients with mTBI (57 with PTM, 17 without PTM). FA maps were obtained in 22 healthy control subjects and in 20 control patients with migraine headaches. Mean FA and SE were extracted from total brain FA histograms and were compared between patients with mTBI and control subjects and between patients with and those without PTM. Mean FA and SE were correlated with clinical variables and were used to determine the areas under the receiver operating characteristic curve (AUCs) and likelihood ratios for mTBI and development of PTM. Results Patients with mTBI had significantly lower SE (P < .001) and trended toward lower mean FA (P = .07) compared with control subjects. SE inversely correlated with time to recovery (TTR) (r = -0.272, P = .02). Patients with mTBI with PTM had significantly lower SE (P < .001) but not mean FA (P = .15) than did other patients with mTBI. SE provided better discrimination between patients with mTBI and control subjects than mean FA (AUC = 0.92; P = .01), as well as better discrimination between patients with mTBI with PTM and those without PTM (AUC = 0.85; P < .001). SE of less than 0.751 resulted in a 16.1 increased likelihood of having experienced mTBI and a 3.2 increased likelihood of developing PTM. Conclusion SE more accurately reveals mTBI than mean FA, more accurately reveals those patients with mTBI who develop PTM, and inversely correlates with TTR. (©) RSNA, 2016. PMID:26829524

  6. TBI: Our Teachers Are Not Prepared

    ERIC Educational Resources Information Center

    Bouldin, Kelly V.

    2005-01-01

    A graduate student preparing to teach, who suffered from traumatic brain injury (TBI) that resulted in partial amnesia and learning disabilities when she was a high school student, describes her experience. She illustrates the difficulties she faced in returning to school and recommends strategies educators could use to help similar student they…

  7. Moderate Hypothermia Significantly Decreases Hippocampal Cell Death Involving Autophagy Pathway after Moderate Traumatic Brain Injury

    PubMed Central

    Jin, Yichao; Lin, Yingying; Feng, Jun-feng; Jia, Feng; Gao, Guo-yi

    2015-01-01

    Abstract Here, we evaluated changes in autophagy after post-traumatic brain injury (TBI) followed by moderate hypothermia in rats. Adult male Sprague-Dawley rats were randomly divided into four groups: sham injury with normothermia group (37°C); sham injury with hypothermia group (32°C); TBI with normothermia group (TNG; 37°C); and TBI with hypothermia group (THG; 32°C). Injury was induced by a fluid percussion TBI device. Moderate hypothermia (32°C) was achieved by partial immersion in a water bath (0°C) under general anesthesia for 4 h. All rats were killed at 24 h after fluid percussion TBI. The ipsilateral hippocampus in all rats was analyzed with hematoxylin and eosin staining; terminal deoxynucleoitidyl transferase-mediated nick end labeling staining was used to determine cell death in ipsilateral hippocampus. Immunohistochemistry and western blotting of microtubule-associated protein light chain 3 (LC3), Beclin-1, as well as transmission electron microscopy performed to assess changes in autophagy. At 24 h after TBI, the cell death index was 27.90±2.36% in TNG and 14.90±1.52% in THG. Expression level of LC3 and Beclin-1 were significantly increased after TBI and were further up-regulated after post-TBI hypothermia. Further, ultrastructural observations showed that there was a marked increase of autophagosomes and autolysosomes in ipsilateral hippocampus after post-TBI hypothermia. Our data demonstrated that moderate hypothermia significantly attenuated cell death and increased autophagy in ipsilateral hippocampus after fluid percussion TBI. In conclusion, autophagy pathway may participate in the neuroprotective effect of post-TBI hypothermia. PMID:25942484

  8. Deployment Risk Factors and Postdeployment Health Profiles Associated With Traumatic Brain Injury in Heavy Drinking Veterans

    PubMed Central

    Williams, Joah L.; McDevitt-Murphy, Meghan E.; Murphy, James G.; Crouse, Ellen M.

    2014-01-01

    Along with post-traumatic stress disorder (PTSD), mild traumatic brain injury (mTBI) is considered one of the “signature wounds” of combat operations in Iraq (Operation Iraqi Freedom [OIF]) and Afghanistan (Operation Enduring Freedom [OEF]), but the role of mTBI in the clinical profiles of Veterans with other comorbid forms of postdeployment psychopathology is poorly understood. The current study explored the deployment risk and postdeployment health profiles of heavy drinking OIF and OEF Veterans as a function of mTBI. Sixty-nine heavy-drinking OIF/OEF Veterans were recruited through a Veterans’ Affairs Medical Center and completed questionnaires and structured interviews assessing war-zone experiences, postdeployment drinking patterns, and PTSD symptoms. Veterans with positive mTBI screens and confirmed mTBI diagnoses endorsed higher rates of combat experiences, including direct and indirect killing, and met criteria for PTSD at a higher rate than Veterans without a history of mTBI. Both PTSD and combat experiences independently predicted screening positive for mTBI, whereas only combat experiences predicted receiving a confirmed mTBI diagnosis. mTBI was not associated with any dimension of alcohol use. These results support a growing body of literature linking mTBI with PTSD. PMID:22808885

  9. In vivo functional photoacoustic tomography of traumatic brain injury in rats

    NASA Astrophysics Data System (ADS)

    Oh, Jung-Taek; Song, Kwang-Hyung; Li, Meng-Lin; Stoica, George; Wang, Lihong V.

    2006-02-01

    In this study, we demonstrate the potential of photoacoustic tomography for the study of traumatic brain injury (TBI) in rats in vivo. Based on spectroscopic photoacoustic tomography that can detect the absorption rates of oxy- and deoxy-hemoglobins, the blood oxygen saturation and total blood volume in TBI rat brains were visualized. Reproducible cerebral trauma was induced using a fluid percussion TBI device. The time courses of the hemodynamic response following the trauma initiation were imaged with multi-wavelength photoacoustic tomography with bandwidth-limited spatial resolution through the intact skin and skull. In the pilot set of experiments, trauma induced hematomas and blood oxygen saturation level changes were detected, a finding consistent with the known physiological responses to TBI. This new imaging method will be useful for future studies on TBI-related metabolic activities and the effects of therapeutic agents.

  10. Stochastic fluctuations in gene expression in aging hippocampal neurons could be exacerbated by traumatic brain injury.

    PubMed

    Shearer, Joseph; Boone, Deborah; Weisz, Harris; Jennings, Kristofer; Uchida, Tatsuo; Parsley, Margaret; DeWitt, Douglas; Prough, Donald; Hellmich, Helen

    2016-04-01

    Traumatic brain injury (TBI) is a risk factor for age-related dementia and development of neurodegenerative disorders such as Alzheimer's disease that are associated with cognitive decline. The exact mechanism for this risk is unknown but we hypothesized that TBI is exacerbating age-related changes in gene expression. Here, we present evidence in an animal model that experimental TBI increases age-related stochastic gene expression. We compared the variability in expression of several genes associated with cell survival or death, among three groups of laser capture microdissected hippocampal neurons from aging rat brains. TBI increased stochastic fluctuations in gene expression in both dying and surviving neurons compared to the naïve neurons. Increases in random, stochastic fluctuations in prosurvival or prodeath gene expression could potentially alter cell survival or cell death pathways in aging neurons after TBI which may lead to age-related cognitive decline. PMID:26140916

  11. Traumatic brain injury and subsequent glioblastoma development: Review of the literature and case reports

    PubMed Central

    Tyagi, Vineet; Theobald, Jason; Barger, James; Bustoros, Mark; Bayin, N. Sumru; Modrek, Aram S.; Kader, Michael; Anderer, Erich G.; Donahue, Bernadine; Fatterpekar, Girish; Placantonakis, Dimitris G

    2016-01-01

    Background: Previous reports have proposed an association between traumatic brain injury (TBI) and subsequent glioblastoma (GBM) formation. Methods: We used literature searches and radiographic evidence from two patients to assess the possibility of a link between TBI and GBM. Results: Epidemiological studies are equivocal on a possible link between brain trauma and increased risk of malignant glioma formation. We present two case reports of patients with GBM arising at the site of prior brain injury. Conclusion: The hypothesis that TBI may predispose to gliomagenesis is disputed by several large-scale epidemiological studies, but supported by some. Radiographic evidence from two cases presented here suggest that GBM formed at the site of brain injury. We propose a putative pathogenesis model that connects post-traumatic inflammation, stem and progenitor cell transformation, and gliomagenesis. PMID:27625888

  12. Functional MRI in the Investigation of Blast-Related Traumatic Brain Injury

    PubMed Central

    Graner, John; Oakes, Terrence R.; French, Louis M.; Riedy, Gerard

    2012-01-01

    This review focuses on the application of functional magnetic resonance imaging (fMRI) to the investigation of blast-related traumatic brain injury (bTBI). Relatively little is known about the exact mechanisms of neurophysiological injury and pathological and functional sequelae of bTBI. Furthermore, in mild bTBI, standard anatomical imaging techniques (MRI and computed tomography) generally fail to show focal lesions and most of the symptoms present as subjective clinical functional deficits. Therefore, an objective test of brain functionality has great potential to aid in patient diagnosis and provide a sensitive measurement to monitor disease progression and treatment. The goal of this review is to highlight the relevant body of blast-related TBI literature and present suggestions and considerations in the development of fMRI studies for the investigation of bTBI. The review begins with a summary of recent bTBI publications followed by discussions of various elements of blast-related injury. Brief reviews of some fMRI techniques that focus on mental processes commonly disrupted by bTBI, including working memory, selective attention, and emotional processing, are presented in addition to a short review of resting state fMRI. Potential strengths and weaknesses of these approaches as regards bTBI are discussed. Finally, this review presents considerations that must be made when designing fMRI studies for bTBI populations, given the heterogeneous nature of bTBI and its high rate of comorbidity with other physical and psychological injuries. PMID:23460082

  13. Reducing Traumatic Brain Injuries in Youth Sports: Youth Sports Traumatic Brain Injury State Laws, January 2009–December 2012

    PubMed Central

    2013-01-01

    Objectives. I sought to describe current state-wide youth sports traumatic brain injury (TBI) laws and their relationship to prevailing scientific understandings of youth sports TBIs, and to facilitate further research by creating an open-source data set of current laws. Methods. I used Westlaw and LexisNexis databases to create a 50-state data set of youth sports TBI laws enacted between January 2009 and December 2012. I collected and coded the text and citations of each law and developed a protocol and codebook to facilitate future research. Results. Forty-four states and Washington, DC, passed youth sports TBI laws between 2009 and 2012. No state’s youth sports TBI law focuses on primary prevention. Instead, such laws focus on (1) increasing coaches’ and parents’ ability to identify and respond to TBIs and (2) reducing the immediate risk of multiple TBIs. Conclusions. Existing youth sports TBI laws were not designed to reduce initial TBIs. Evaluation is required to assess their effectiveness in reducing the risk and consequences of multiple TBIs. Continued research and evaluation of existing laws will be needed to develop a more comprehensive youth TBI-reduction solution. PMID:23678903

  14. Concurrent Vision Dysfunctions in Convergence Insufficiency with Traumatic Brain Injury

    PubMed Central

    Alvarez, Tara L.; Kim, Eun H.; Vicci, Vincent R.; Dhar, Sunil K.; Biswal, Bharat B.; Barrett, A. M.

    2012-01-01

    Purpose This study assessed the prevalence of convergence insufficiency (CI) with and without simultaneous vision dysfunctions within the traumatic brain injury (TBI) sample population because although CI is commonly reported with TBI, the prevalence of concurrent visual dysfunctions with CI in TBI is unknown. Methods A retrospective analysis of 557 medical records from TBI civilian patients was conducted. Patients were all evaluated by a single optometrist. Visual acuity, oculomotor, binocular vision function, accommodation, visual fields, ocular health and vestibular function were assessed. Statistical comparisons between the CI and non-CI, as well as in-patient and out-patient subgroups, were conducted using chi-squared and Z-tests. Results Approximately 9% of the TBI sample had CI without the following simultaneous diagnoses: saccade or pursuit dysfunction; 3rd, 4th, or 6th nerve palsy; visual field deficit; visual spatial inattention/neglect; vestibular dysfunction or nystagmus. Photophobia with CI was observed in 16.3% (N=21/130) and vestibular dysfunction with CI was observed in 18.5% (N=24/130) of the CI subgroup. CI and cranial nerve palsies were common and yielded prevalence rates of 23.3% (N=130/557) and 26.9% (N=150/557), respectively, within the TBI sample. Accommodative dysfunction was common within the non-presbyopic TBI sample with a prevalence of 24.4% (N=76/314). Visual field deficits or unilateral visual spatial inattention/neglect were observed within 29.6% (N=80/270) of the TBI in-patient subgroup and were significantly more prevalent compared to the out-patient subgroup (p<0.001). Most TBI patients had visual acuities of 20/60 or better in the TBI sample (85%;N=473/557). Conclusions CI without simultaneous visual or vestibular dysfunctions was observed in about 9% of the visually symptomatic TBI civilian population studied. A thorough visual and vestibular examination is recommended for all TBI patients. PMID:23190716

  15. Updating memory after mild traumatic brain injury and orthopedic injuries.

    PubMed

    Hanten, Gerri; Li, Xiaoqi; Ibarra, Alyssa; Wilde, Elisabeth A; Barnes, Amanda; McCauley, Stephen R; McCarthy, James; Hoxhaj, Shkelzen; Mendez, Donna; Hunter, Jill V; Levin, Harvey S; Smith, Douglas H

    2013-04-15

    Few studies have examined the trajectory of recovery of executive function (EF) after mild TBI (mTBI). Therefore, consensus has not been reached on the incidence and extent of EF impairment after mTBI. The present study investigated trajectory of change in executive memory over 3 months after mTBI on 59 right-handed participants with mTBI, as defined by Centers for Disease Control criteria, ages 14-30 years, recruited within 96 hours post-injury and tested <1 week (baseline), 1 month, and 3 months after injury. Also included were 58 participants with orthopedic injury (OI) and 27 typically developing (TD) non-injured participants with similar age, socioeconomic status, sex, and ethnicity. MRI data were acquired at baseline and 3 months. Although criteria included a normal CT scan, lesions were detected by MRI in 19 mTBI patients. Participants completed the KeepTrack task, a verbal recall task placing demands on goal maintenance, semantic memory, and memory updating. Scores reflected items recalled and semantic categories maintained. The mTBI group was divided into two groups: high (score ≥12) or low (score <12) symptoms based on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ). Mixed model analyses revealed the trajectory of change in mTBI patients (high and low RPQ), OI patients, and TD subjects were similar over time (although the TD group differed from other groups at baseline), suggesting no recovery from mTBI up to 90 days. For categories maintained, differences in trajectory of recovery were discovered, with the OI comparison group surprisingly performing similar to those in the mTBI group with high RPQ symptoms, and different from low RPQ and the TD groups, bringing up questions about utility of OIs as a comparison group for mTBI. Patients with frontal lesions (on MRI) were also found to perform worse than those without lesions, a pattern that became more pronounced with time. PMID:23227898

  16. Moderate-to-Severe Traumatic Brain Injury in Children: Complications and Rehabilitation Strategies

    PubMed Central

    Popernack, Myra L.; Gray, Nicola; Reuter-Rice, Karin

    2015-01-01

    Traumatic brain injury (TBI) is the leading cause of death in children in the United States. Each year 37,200 children sustain a severe TBI, with up to 1.3 million life-years potentially adversely affected. Severe pediatric TBI is associated with significant mortality and morbidity. Of the children who survive their injury, more than 50% experience unfavorable outcomes 6 months after the injury. Although TBI-associated death rates decreased between 1997–2007, disabilities for TBI survivors continue to have both a direct and indirect impact on the economic and human integrity of our society. The degree of disability varies with the severity and mechanism of the injury, but a realm of physical and emotional deficits may be evident for years after the injury occurs. This article describes the pathophysiology of moderate to severe TBI, its associated complications, and opportunities to improve patient outcomes through use of acute management and rehabilitation strategies. To address the many challenges for TBI survivors and their families, including significant financial and emotional burdens, a collaborative effort is necessary to help affected children transition seamlessly from acute care through long-term rehabilitation. PMID:25449002

  17. Outcomes evaluation in TBI Rehabilitation. Part II: measurement tools for a nationwide data system.

    PubMed

    Hall, K M; Johnston, M V

    1994-12-01

    In Part II we address tools for describing general functional levels of clients in acute care, in traumatic brain injury (TBI) rehabilitation programs, and in the community. Tools must be brief, have proven reliability, and measure characteristics common to moderately and severely brain-injured individuals. Possible components of a uniform dataset dedicated to TBI are described. PMID:7993177

  18. Intracranial pressure monitoring and outcomes after traumatic brain injury

    PubMed Central

    Lane, Peter L.; Skoretz, Terry G.; Doig, Gordon; Girotti, Murray J.

    2000-01-01

    Objective Uncontrolled intracranial hypertension after traumatic brain injury (TBI) contributes significantly to the death rate and to poor functional outcome. There is no evidence that intracranial pressure (ICP) monitoring alters the outcome of TBI. The objective of this study was to test the hypothesis that insertion of ICP monitors in patients who have TBI is not associated with a decrease in the death rate. Design Study of case records. Methods The data files from the Ontario Trauma Registry from 1989 to 1995 were examined. Included were all cases with an Injury Severity Score (ISS) greater than 12 from the 14 trauma centres in Ontario. Cases identifying a Maximum Abbreviated Injury Scale score in the head region (MAIS head) greater than 3 were selected for further analysis. Logistic regression analyses were conducted to investigate the relationship between ICP and death. Results Of 9001 registered cases of TBI, an MAIS head greater than 3 was recorded in 5507. Of these patients, 541 (66.8% male, mean age 34.1 years) had an ICP monitor inserted. Their average ISS was 33.4 and 71.7% survived. There was wide variation among the institutions in the rate of insertion of ICP monitors in these patients (ranging from 0.4% to over 20%). Univariate logistic regression indicated that increased MAIS head, ISS, penetrating trauma and the insertion of an ICP monitor were each associated with an increased death rate. However, multivariate analyses controlling for MAIS head, ISS and injury mechanism indicated that ICP monitoring was associated with significantly improved survival (p < 0.015). Conclusions ICP monitor insertion rates vary widely in Ontario’s trauma hospitals. The insertion of an ICP monitor is associated with a statistically significant decrease in death rate among patients with severe TBI. This finding strongly supports the need for a prospective randomized trial of management protocols, including ICP monitoring, in patients with severe TBI. PMID:11129833

  19. Toward an international initiative for traumatic brain injury research.

    PubMed

    Tosetti, Patrizia; Hicks, Ramona R; Theriault, Elizabeth; Phillips, Anthony; Koroshetz, Walter; Draghia-Akli, Ruxandra

    2013-07-15

    The European Commission (EC) and the National Institutes of Health (NIH) jointly sponsored a workshop on October 18-20, 2011 in Brussels to discuss the feasibility and benefits of an international collaboration in the field of traumatic brain injury (TBI) research. The workshop brought together scientists, clinicians, patients, and industry representatives from around the globe as well as funding agencies from the EU, Spain, the United States, and Canada. Sessions tackled both the possible goals and governance of a future initiative and the scientific questions that would most benefit from an integrated international effort: how to optimize data collection and sharing; injury classification; outcome measures; clinical study design; and statistical analysis. There was a clear consensus that increased dialogue and coordination of research at an international level would be beneficial for advancing TBI research, treatment, and care. To this end, the EC, the NIH, and the Canadian Institutes of Health Research expressed interest in developing a framework for an international initiative for TBI Research (InTBIR). The workshop participants recommended that InTBIR initially focus on collecting, standardizing, and sharing clinical TBI data for comparative effectiveness research, which will ultimately result in better management and treatments for TBI. PMID:23731282

  20. Self-awareness and traumatic brain injury outcome

    PubMed Central

    Robertson, Kayela; Schmitter-Edgecombe, Maureen

    2016-01-01

    Primary Objective Impaired self-awareness following a traumatic brain injury (TBI) can reduce the effectiveness of rehabilitation, resulting in poorer outcomes. However, little is understood about how the multi-dimensional aspects of self-awareness may differentially change with recovery and impact outcome. Thus, we examined four self-awareness variables represented in the Dynamic Comprehensive Model of Awareness: metacognitive awareness, anticipatory awareness, error-monitoring, and self-regulation. Research Design We evaluated change of the self-awareness measures with recovery from TBI and whether the self-awareness measures predicted community reintegration at follow-up. Methods and Procedures Participants were 90 individuals with moderate to severe TBI who were tested acutely following injury and 90 age-matched controls. Forty-nine of the TBI participants and 49 controls were re-tested after 6 months. Main Outcome and Results Results revealed that the TBI group’s error-monitoring performance was significantly poorer than controls at both baseline and follow-up. Regression analyses revealed that the self-awareness variables at follow-up were predictive of community reintegration, with error-monitoring being a unique predictor. Conclusions Our results highlight the importance of error-monitoring and suggest that interventions targeted at improving error-monitoring may be particularly beneficial. Understanding the multi-dimensional nature of self-awareness will further improve rehabilitation efforts and understanding of the theoretical basis of self-awareness. PMID:25915097

  1. Caregiver burden at 1 year following severe traumatic brain injury.

    PubMed

    Marsh, N V; Kersel, D A; Havill, J H; Sleigh, J W

    1998-12-01

    Sixty-nine primary caregivers of adults with a severe traumatic brain injury (TBI) were assessed at 1-year post-injury. Caregivers completed questionnaires on the physical, cognitive, emotional, behavioural, and social functioning of the person with TBI. Caregiver objective burden, psychosocial functioning, and subjective burden were also assessed. Clinically significant levels of anxiety and depression were evident in over a third of the caregivers. Similarly, a quarter of the caregivers reported poor social adjustment. There was no consistent relationship between the prevalence of various types of objective burden and the level of subjective distress that resulted from these changes. The person with TBI's emotional difficulties, in particular their anger, apathy, and dependency, caused the greatest distress for caregivers. With regard to the impact that caregiving had on their own lives, caregivers were most distressed by the loss of personal free time. Results from a regression analysis indicated that the person with TBI's physical impairment, number of behavioural problems, and social isolation were the strongest predictors of caregiver burden. The impact that caring for a person with severe TBI can have on the extended family unit is discussed. PMID:9876864

  2. Toward an International Initiative for Traumatic Brain Injury Research

    PubMed Central

    Tosetti, Patrizia; Theriault, Elizabeth; Phillips, Anthony; Koroshetz, Walter; Draghia-Akli, Ruxandra

    2013-01-01

    Abstract The European Commission (EC) and the National Institutes of Health (NIH) jointly sponsored a workshop on October 18–20, 2011 in Brussels to discuss the feasibility and benefits of an international collaboration in the field of traumatic brain injury (TBI) research. The workshop brought together scientists, clinicians, patients, and industry representatives from around the globe as well as funding agencies from the EU, Spain, the United States, and Canada. Sessions tackled both the possible goals and governance of a future initiative and the scientific questions that would most benefit from an integrated international effort: how to optimize data collection and sharing; injury classification; outcome measures; clinical study design; and statistical analysis. There was a clear consensus that increased dialogue and coordination of research at an