Department of Veterans Affairs — As the number of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Traumatic Brain Injury (TBI) patients has grown, so has the need to track and monitor...
... Research Information Clinical Trials Resources and Publications Traumatic Brain Injury (TBI): Condition Information Skip sharing on social ... external force that affects the functioning of the brain. It can be caused by a bump or ...
management of adult, blunt-mechanism traumatic brain injury ( TBI ) patients and assess the overall mortality of this cohort at Grady...this study is to determine the current compliance with widely accepted guidelines for the management of severe traumatic brain injury ( TBI ) patients...AD_________________ Award Number: W81XWH-09-2-0145 Study Title: Traumatic Brain Injury ( TBI
Bigler, Erin D
Reviewed herein are contemporary neuroimaging methods that detect abnormalities associated with mild traumatic brain injury (mTBI). Despite advances in demonstrating underlying neuropathology in a subset of individuals who sustain mTBI, considerable disagreement persists in neuropsychology about mTBI outcome and metrics for evaluation. This review outlines a thesis for the select use of sensitive neuroimaging methods as potential biomarkers of brain injury recognizing that the majority of individuals who sustain an mTBI recover without neuroimaging signs or neuropsychological sequelae detected with methods currently applied. Magnetic resonance imaging (MRI) provides several measures that could serve as mTBI biomarkers including the detection of hemosiderin and white matter abnormalities, assessment of white matter integrity derived from diffusion tensor imaging (DTI), and quantitative measures that directly assess neuroanatomy. Improved prediction of neuropsychological outcomes in mTBI may be achieved with the use of targeted neuroimaging markers.
Johnson, Victoria E.; Stewart, William
Traumatic brain injury (TBI) is increasingly recognized as a risk factor for dementia. New data provide further support for this association and demonstrate the influence of age at injury and injury severity on dementia risk after TBI, revealing that even mild TBI increases dementia risk in those aged ≥65 years.
Kurowski, Brad; Martin, Lisa J; Wade, Shari L
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.
craniectomy for urgent evacuation of intracranial hemorrhage improves intracranial and cerebral perfusion pressures and overrides benefits of vasopressors in...for the management of CPP (cerebral perfusion pressure ) after TBI (traumatic brain injury) and support the continued investigation and use of AVP...and 12 patients received vasopressin (AVP). Those in the "no vasopressor" group were the least severely injured and had the best outcomes. Those in the
Trudel, Tina M.; Scherer, Marcia J.; Elias, Eileen
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,…
Dams-O'Connor, Kristen; Spielman, Lisa; Singh, Ayushi; Gordon, Wayne A; Lingsma, Hester F; Maas, Andrew I R; Manley, Geoffrey T; Mukherjee, Pratik; Okonkwo, David O; Puccio, Ava M; Schnyer, David M; Valadka, Alex B; Yue, John K; Yuh, Esther L
The idea that multiple traumatic brain injury (TBI) can have a cumulative detrimental effect on functioning is widely accepted. Most research supporting this idea comes from athlete samples, and it is not known whether remote history of previous TBI affects functioning after subsequent TBI in community-based samples. This study investigates whether a previous history of TBI with loss of consciousness (LOC) is associated with worse health and functioning in a sample of individuals who require emergency department care for current TBI. Twenty-three percent of the 586 individuals with current TBI in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study reported having sustained a previous TBI with LOC. Individuals with previous TBI were more likely to be unemployed (χ(2)=17.86; p=0.000), report a variety of chronic medical and psychiatric conditions (4.75≤χ(2)≥24.16; pTBI history. Those with a previous TBI had less-severe acute injuries, but experienced worse outcomes at 6-month follow-up. Results of a series of regression analyses controlling for demographics and acute injury severity indicated that individuals with previous TBI reported more mood symptoms, more postconcussive symptoms, lower life satisfaction, and had slower processing speed and poorer verbal learning, compared to those with no previous TBI history. These findings suggest that history of TBI with LOC may have important implications for health and psychological functioning after TBI in community-based samples.
Full Text Available The fact that injuries caused by accidents are the most common cause of death in children and adolescents in Germany gave rise to the study, which mainly deals with traffic accidents in this group. 200,221 records of emergency-service physicians in Bavaria which cover the period 1995-1999 were analysed with respect to the importance of traumatic brain injury (TBI in children and adolescents (n = 721 - representing 45.8% of traffic injuries in this age group. The highest incidence of TBI was in summer (34.3% and in the evening between 16.00 and 18.00 (23.7%. The time taken between accident and arrival of the emergency services was 8.8 ± 3.1 minutes. The preclinical phase lasted 19.3 ± 5.8 minutes. The probability of having an accident with TBI increases with age, the maximum being in the age-range 7 - 14 years (61.6%. Boys (63.2% were almost twice as susceptible to injury as girls. 36.8% of all cases had no noticeable neurological disorder, 71.1% resulted in a Glasgow Coma Scale (GCS score of 15. Only 6.3% had most severe neurological disorders, resulting in a GCS score of 3 - 5. Circulation parameters in the form of adapted hypotension were abnormal in only 3.4%, 21.9% of the children had a bradycardia and in 12.3% the blood oxygen saturation fell below 94%. The most frequent intervention was the laying of an i.v. line for infusions. 8.6% of the patients were intubated to allow for ventilation with oxygen. Analgesics were given in 16.7% of the cases. In 84.7% of all cases, the condition was stable and in only 3.3% was a severe deterioration to be observed. The assessments were made using both the National Advisory Committee for Aeronautics (NACA and Glasgow Coma Scales (GCS. Discrepancies occurred, as a NACA scale of I - III and a GCS score of < 9 was reported in 4.9% of cases. In contrast a NACA scale of IV - VI was reported with a GCS score of 15 in 30% of all cases. TBI symptoms in children are less obvious than in adults, which leads to an
Scherer, Marcia; Elias, Eileen; Weider, Katie
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…
Prasad, Kedar N; Bondy, Stephen C
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.
... Trials Resources and Publications What are common TBI symptoms? Skip sharing on social media links Share this: ... is not always a sign of severe TBI. Symptoms of Mild TBI A person with a mild ...
Wilde, Elisabeth A; McCauley, Stephen R; Kelly, Tara M; Weyand, Annie M; Pedroza, Claudia; Levin, Harvey S; Clifton, Guy L; Schnelle, Kathleen P; Shah, Monika V; Moretti, Paolo
The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) is a measure adapted from the National Institutes of Health Stroke Scale (NIHSS), and is intended to capture essential neurological deficits impacting individuals with traumatic brain injury (TBI) (see Wilde et al., 2010 ). In the present study we evaluate the measure's construct validity via comparison with a quantified neurological examination performed by a neurologist. Spearman rank-order correlation between the NOS-TBI and the neurological examination was rho = 0.76, p TBI compared favorably to the neurological examination items, with correlations ranging from 0.60 to 0.99 (all p TBI, and on the NOS-TBI neurological impairment was evident in all but one participant. This study documents the presence of measurable neurological sequelae in a sample of patients with TBI in a post-acute rehabilitation setting, underscoring the need for formal measurement of the frequency and severity of neurological deficits in this population. The results suggest that the NOS-TBI is a valid measure of neurological functioning in patients with TBI.
McCauley, Stephen R; Wilde, Elisabeth A; Kelly, Tara M; Weyand, Annie M; Yallampalli, Ragini; Waldron, Eric J; Pedroza, Claudia; Schnelle, Kathleen P; Boake, Corwin; Levin, Harvey S; Moretti, Paolo
A standardized measure of neurological dysfunction specifically designed for TBI currently does not exist and the lack of assessment of this domain represents a substantial gap. To address this, the Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) was developed for TBI outcomes research through the addition to and modification of items specifically relevant to patients with TBI, based on the National Institutes of Health Stroke Scale. In a sample of 50 participants (mean age = 33.3 years, SD = 12.9) TBI, internal consistency of the NOS-TBI was high (Cronbach's alpha = 0.942). Test-retest reliability also was high (rho = 0.97, p TBI total score was excellent (W = 0.995). Convergent validity was demonstrated through significant Spearman rank-order correlations between the NOS-TBI and the concurrently administered Disability Rating Scale (rho = 0.75, p TBI is a reliable and valid measure of neurological functioning in patients with moderate to severe TBI.
Implementation of post- TBI pain behavior measurements. 15. SUBJECT TERMS Traumatic brain injury, cortical spreading depression, seizure, post-traumatic...conventional recovery is complete. We test with video EEG monitoring for increased excitability, and use behavioral measures to test the pain response...months after CCI TBI (Brennan/Dudek, Months 18-36). Pending. Will be performed simultaneous with task 1.f. above. g. Perform nociception
Pain ( nociceptive ) sensitization was followed using the von Frey method. Those measures were continued until the resolution of sensitization. We...AWARD NUMBER: W81XWH-14-1-0579 TITLE: Targeting Epigenetic Mechanisms in Pain due to Trauma and Traumatic Brain Injury (TBI) PRINCIPAL...SUBTITLE Targeting Epigenetic Mechanisms in Pain due to Trauma and Traumatic Brain Injury (TBI) 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0579 5c
Full Text Available Traumatic brain injury (TBI is a major cause of disability (1, 2. Sleep disturbances, such as insomnia, are very common following traumatic brain injury and have been reported in frequencies from 40% (3 to as high as 84% (4. Sleep disruption can be related to the TBI itself but may also be secondary to neuropsychiatric (e.g., depression or neuromuscular (e.g., pain conditions associated with TBI or to the pharmacological management of the injury and its consequences. Post-TBI insomnia has been associated with numerous negative outcomes including daytime fatigue, tiredness, difficulty functioning: impaired performance at work, memory problems, mood problems, greater functional disability, reduced participation in activities of daily living, less social and recreational activity, less employment potential, increased caregiver burden, greater sexual dysfunction, and also lower ratings of health, poor subjective wellbeing. These negative consequences can hamper the person’s reintegration into the community, adjustment after injury, and overall QOL. (5 The connection between depression and insomnia has not been investigated within the post TBI population to a great extent. For the general population, clinically significant insomnia is often associated with the presence of an emotional disorder (6. Fichtenberg et al. (2002 (7, in his study established that the strongest relationship with the diagnosis of insomnia belonged to depression. Given the high prevalence of depression during the first 2 years following TBI (8, a link between depression and insomnia among TBI patients makes innate sense. The present study aims at assessing role of sertralline in post TBI insomnia associated with depression.
2013). Decreased connectivity in resting-state MEG may persist for years after mTBI ( Castellanos et al., 2011), but the abnormally reduced...of rehabilitation medicine, 36(0), 28-60.  Castellanos , N.P. (2011). Principles of recovery from traumatic brain injury: Reorganization of
Hernández, Theresa D; Brenner, Lisa A; Walter, Kristen H; Bormann, Jill E; Johansson, Birgitta
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.
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.
Inoue, Tomoo; Lin, Amity; Ma, Xiaokui; McKenna, Stephen L; Creasey, Graham H; Manley, Geoffrey T; Ferguson, Adam R; Bresnahan, Jacqueline C; Beattie, Michael S
A significant proportion (estimates range from 16 to 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 6weeks, 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 contralateral
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
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.
Ryan, Nicholas P; van Bijnen, Loeka; Catroppa, Cathy; Beauchamp, Miriam H; Crossley, Louise; Hearps, Stephen; Anderson, Vicki
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
Algattas, Hanna; Huang, Jason H
Traumatic brain injury (TBI) affects a growing portion of the population and continues to take national spotlight with advances in imaging technology and understanding of long-term effects. However, there is large variance in TBI treatment protocols due to injury variability and lack of both mechanistic understanding and strong treatment recommendations. Recent practice suggests three disparate treatment approaches, all which aim at promoting neuroprotection after TBI, show promise: immediate hypothermia, hyperbaric oxygen, and progesterone supplementation. The research is controversial at times, yet there are abundant opportunities to develop the technology behind hypothermia and hyperbaric oxygen treatments which would surely aid in aligning the current data. Additionally, while progesterone has already been packaged in nanoparticle form it may benefit from continued formulation and administration research. The treatments and the avenues for improvement are reviewed in the present paper.
Mitra, Jhimli; Shen, Kai-kai; Ghose, Soumya; Bourgeat, Pierrick; Fripp, Jurgen; Salvado, Olivier; Pannek, Kerstin; Taylor, D Jamie; Mathias, Jane L; Rose, Stephen
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.
Francis, Robert; Khan, Bilal; Alexandrakis, George; Florence, James; MacFarlane, Duncan
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.
Paul E. Rapp
Full Text Available 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 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 traumatic brain injury 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 traumatic brain injury, 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.
Thompson, Hilaire J; Vavilala, Monica S; Rivara, Frederick P
Despite increased attention to traumatic brain injury (TBI), there remains no specific treatment and available interventions focus rather on the prevention of secondary injury. One of the reasons posited for the lack of a successful therapy is the amalgamation of various types of injuries under the same severity category in clinical trials. Informatics approaches have been suggested as a means to develop an improved classification system for TBI. As a result of federal interagency efforts, common data elements (CDEs) for TBI have now been developed. Further, the Federal Interagency Traumatic Brain Injury Research Informatics System (FITBIR) has been created and is now available for TBI researchers to both add and retrieve data. This chapter will discuss the goals, development, and evolution of the CDEs and FITBIR and discuss how these tools can be used to support TBI research. A specific exemplar using the CDEs and lessons learned from working with the CDEs and FITBIR are included to aid future researchers.
Ganti, Latha; Daneshvar, Yasamin; Bodhit, Aakash; Ayala, Sarah; Patel, Pratik S; Lottenberg, Lawrence L; York, Donna; Counsell, Colleen; Peters, Keith R
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.
Harburg, Leah; McCormack, Erin; Kenney, Kimbra; Moore, Carol; Yang, Kelly; Vos, Pieter; Jacobs, Bram; Madden, Christopher J; Diaz-Arrastia, Ramon; Bogoslovsky, Tanya
BACKGROUND: Non-contrast head computer tomography (CT) is widely used to evaluate eligibility of patients after acute traumatic brain injury (TBI) for clinical trials. The NINDS Common Data Elements (CDEs) TBI were developed to standardize collection of CT variables. The objectives of this study wer
Ren, Zeguang; Iliff, Jeffrey J.; Yang, LiJun; Yang, Jiankai; Chen, Xiaolin; Chen, Michael J.; Giese, Rebecca N; Wang, Baozhi; Shi, Xuefang; Nedergaard, Maiken
Cerebral edema is a major contributor to morbidity associated with traumatic brain injury (TBI). The methods involved in most rodent models of TBI, including head fixation, opening of the skull, and prolonged anesthesia, likely alter TBI development and reduce secondary injury. We report the development of a closed-skull model of murine TBI, which minimizes time of anesthesia, allows the monitoring of intracranial pressure (ICP), and can be modulated to produce mild and moderate grade TBI. In...
Shenaq, Mohammed; Kassem, Hassan; Peng, Changya; Schafer, Steven; Ding, Jamie Y; Fredrickson, Vance; Guthikonda, Murali; Kreipke, Christian W; Rafols, José A; Ding, Yuchuan
The present study, using a rodent model of closed-head diffuse traumatic brain injury (TBI), investigated the role of dysregulated aquaporins (AQP) 4 and 9, as well as hypoxia inducible factor -1α(HIF-1α) on brain edema formation, neuronal injury, and functional deficits. TBI was induced in adult (400-425 g), male Sprague-Dawley rats using a modified Marmarou's head impact-acceleration device (450 g weight dropped from 2m height). Animals in each treatment group were administered intravenous anti-AQP4 or -AQP9 antibodies or 2-Methoxyestradiol (2ME2, an inhibitor of HIF-1α) 30 min after injury. At 24h post-TBI, animals (n=6 each group) were sacrificed to examine the extent of brain edema by water content, as well as protein expression of AQP and HIF-1α by Western immune-blotting. At 48-hours post-TBI, neuronal injury (n=8 each group) was assessed by FluoroJade (FJ) histochemistry. Spatial learning and memory deficits were evaluated by radial arm maze (n=8 each group) up to 21 days post-TBI. Compared to non-injured controls, significant (pTBI was associated with increases (p TBI animals, AQP or HIF-1α inhibition significantly (pTBI. Taken together, the present data supports a causal relation between HIF-AQP mediated cerebral edema, secondary neuronal injury, and tertiary behavioral deficits post-TBI. The data further suggests that upstream modulation of the molecular patho-trajectory effectively ameliorates both neuronal injury and behavioral deficits post-TBI.
Maas, Andrew I R; Menon, David K; Steyerberg, Ewout W
BACKGROUND: Current classification of traumatic brain injury (TBI) is suboptimal, and management is based on weak evidence, with little attempt to personalize treatment. A need exists for new precision medicine and stratified management approaches that incorporate emerging technologies. OBJECTIVE......: To improve characterization and classification of TBI and to identify best clinical care, using comparative effectiveness research approaches. METHODS: This multicenter, longitudinal, prospective, observational study in 22 countries across Europe and Israel will collect detailed data from 5400 consenting...... in process and clinical care. Results will be integrated with living systematic reviews in a process of knowledge transfer. The study initiation was from October to December 2014, and the recruitment period was for 18 to 24 months. EXPECTED OUTCOMES: Collaborative European NeuroTrauma Effectiveness Research...
Takahata, Keisuke; Tabuchi, Hajime; Mimura, Masaru
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.
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
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.
Li, Ningzhi; Chou, Yi-Yu; Shiee, Navid; Chan, Leighton; Pham, Dzung L.; Butman, John A.
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%).
Nichols, Jessica N; Deshane, Alok S; Niedzielko, Tracy L; Smith, Cory D; Floyd, Candace L
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.
Yuh, Esther L.; Cooper, Shelly R.; Mukherjee, Pratik; Yue, John K.; Lingsma, Hester F.; Gordon, Wayne A.; Valadka, Alex B.; Okonkwo, David O.; Schnyer, David M.; Vassar, Mary J.; Maas, Andrew I.R.; Casey, Scott S.; Cheong, Maxwell; Dams-O'Connor, Kristen; Hricik, Allison J.; Inoue, Tomoo; Menon, David K.; Morabito, Diane J.; Pacheco, Jennifer L.; Puccio, Ava M.; Sinha, Tuhin K.
Abstract We evaluated 3T diffusion tensor imaging (DTI) for white matter injury in 76 adult mild traumatic brain injury (mTBI) patients at the semiacute stage (11.2±3.3 days), employing both whole-brain voxel-wise and region-of-interest (ROI) approaches. The subgroup of 32 patients with any traumatic intracranial lesion on either day-of-injury computed tomography (CT) or semiacute magnetic resonance imaging (MRI) demonstrated reduced fractional anisotropy (FA) in numerous white matter tracts, compared to 50 control subjects. In contrast, 44 CT/MRI-negative mTBI patients demonstrated no significant difference in any DTI parameter, compared to controls. To determine the clinical relevance of DTI, we evaluated correlations between 3- and 6-month outcome and imaging, demographic/socioeconomic, and clinical predictors. Statistically significant univariable predictors of 3-month Glasgow Outcome Scale-Extended (GOS-E) included MRI evidence for contusion (odds ratio [OR] 4.9 per unit decrease in GOS-E; p=0.01), ≥1 ROI with severely reduced FA (OR, 3.9; p=0.005), neuropsychiatric history (OR, 3.3; p=0.02), age (OR, 1.07/year; p=0.002), and years of education (OR, 0.79/year; p=0.01). Significant predictors of 6-month GOS-E included ≥1 ROI with severely reduced FA (OR, 2.7; p=0.048), neuropsychiatric history (OR, 3.7; p=0.01), and years of education (OR, 0.82/year; p=0.03). For the subset of 37 patients lacking neuropsychiatric and substance abuse history, MRI surpassed all other predictors for both 3- and 6-month outcome prediction. This is the first study to compare DTI in individual mTBI patients to conventional imaging, clinical, and demographic/socioeconomic characteristics for outcome prediction. DTI demonstrated utility in an inclusive group of patients with heterogeneous backgrounds, as well as in a subset of patients without neuropsychiatric or substance abuse history. PMID:24742275
Yuh, Esther L; Cooper, Shelly R; Mukherjee, Pratik; Yue, John K; Lingsma, Hester F; Gordon, Wayne A; Valadka, Alex B; Okonkwo, David O; Schnyer, David M; Vassar, Mary J; Maas, Andrew I R; Manley, Geoffrey T
We evaluated 3T diffusion tensor imaging (DTI) for white matter injury in 76 adult mild traumatic brain injury (mTBI) patients at the semiacute stage (11.2±3.3 days), employing both whole-brain voxel-wise and region-of-interest (ROI) approaches. The subgroup of 32 patients with any traumatic intracranial lesion on either day-of-injury computed tomography (CT) or semiacute magnetic resonance imaging (MRI) demonstrated reduced fractional anisotropy (FA) in numerous white matter tracts, compared to 50 control subjects. In contrast, 44 CT/MRI-negative mTBI patients demonstrated no significant difference in any DTI parameter, compared to controls. To determine the clinical relevance of DTI, we evaluated correlations between 3- and 6-month outcome and imaging, demographic/socioeconomic, and clinical predictors. Statistically significant univariable predictors of 3-month Glasgow Outcome Scale-Extended (GOS-E) included MRI evidence for contusion (odds ratio [OR] 4.9 per unit decrease in GOS-E; p=0.01), ≥1 ROI with severely reduced FA (OR, 3.9; p=0.005), neuropsychiatric history (OR, 3.3; p=0.02), age (OR, 1.07/year; p=0.002), and years of education (OR, 0.79/year; p=0.01). Significant predictors of 6-month GOS-E included ≥1 ROI with severely reduced FA (OR, 2.7; p=0.048), neuropsychiatric history (OR, 3.7; p=0.01), and years of education (OR, 0.82/year; p=0.03). For the subset of 37 patients lacking neuropsychiatric and substance abuse history, MRI surpassed all other predictors for both 3- and 6-month outcome prediction. This is the first study to compare DTI in individual mTBI patients to conventional imaging, clinical, and demographic/socioeconomic characteristics for outcome prediction. DTI demonstrated utility in an inclusive group of patients with heterogeneous backgrounds, as well as in a subset of patients without neuropsychiatric or substance abuse history.
Dona, Olga; DeMatteo, Carol; Connolly, John F.
Background Conventional imaging techniques are unable to detect abnormalities in the brain following mild traumatic brain injury (mTBI). Yet patients with mTBI typically show delayed response on neuropsychological evaluation. Because fractal geometry represents complexity, we explored its utility in measuring temporal fluctuations of brain resting state blood oxygen level dependent (rs-BOLD) signal. We hypothesized that there could be a detectable difference in rs-BOLD signal complexity between healthy subjects and mTBI patients based on previous studies that associated reduction in signal complexity with disease. Methods Fifteen subjects (13.4 ± 2.3 y/o) and 56 age-matched (13.5 ± 2.34 y/o) healthy controls were scanned using a GE Discovery MR750 3T MRI and 32-channel RF-coil. Axial FSPGR-3D images were used to prescribe rs-BOLD (TE/TR = 35/2000ms), acquired over 6 minutes. Motion correction was performed and anatomical and functional images were aligned and spatially warped to the N27 standard atlas. Fractal analysis, performed on grey matter, was done by estimating the Hurst exponent using de-trended fluctuation analysis and signal summation conversion methods. Results and Conclusions Voxel-wise fractal dimension (FD) was calculated for every subject in the control group to generate mean and standard deviation maps for regional Z-score analysis. Voxel-wise validation of FD normality across controls was confirmed, and non-Gaussian voxels (3.05% over the brain) were eliminated from subsequent analysis. For each mTBI patient, regions where Z-score values were at least 2 standard deviations away from the mean (i.e. where |Z| > 2.0) were identified. In individual patients the frequently affected regions were amygdala (p = 0.02), vermis(p = 0.03), caudate head (p = 0.04), hippocampus(p = 0.03), and hypothalamus(p = 0.04), all previously reported as dysfunctional after mTBI, but based on group analysis. It is well known that the brain is best modeled as a complex
Ren, Zeguang; Iliff, Jeffrey J; Yang, Lijun; Yang, Jiankai; Chen, Xiaolin; Chen, Michael J; Giese, Rebecca N; Wang, Baozhi; Shi, Xuefang; Nedergaard, Maiken
Cerebral edema is a major contributor to morbidity associated with traumatic brain injury (TBI). The methods involved in most rodent models of TBI, including head fixation, opening of the skull, and prolonged anesthesia, likely alter TBI development and reduce secondary injury. We report the development of a closed-skull model of murine TBI, which minimizes time of anesthesia, allows the monitoring of intracranial pressure (ICP), and can be modulated to produce mild and moderate grade TBI. In this model, we characterized changes in aquaporin-4 (AQP4) expression and localization after mild and moderate TBI. We found that global AQP4 expression after TBI was generally increased; however, analysis of AQP4 localization revealed that the most prominent effect of TBI on AQP4 was the loss of polarized localization at endfoot processes of reactive astrocytes. This AQP4 dysregulation peaked at 7 days after injury and was largely indistinguishable between mild and moderate grade TBI for the first 2 weeks after injury. Within the same model, blood-brain barrieranalysis of variance permeability, cerebral edema, and ICP largely normalized within 7 days after moderate TBI. These findings suggest that changes in AQP4 expression and localization may not contribute to cerebral edema formation, but rather may represent a compensatory mechanism to facilitate its resolution.
HONDA, Mitsuru; ICHIBAYASHI, Ryo; YOKOMURO, Hiroki; YOSHIHARA, Katsunori; MASUDA, Hiroyuki; HAGA, Daisuke; SEIKI, Yoshikatsu; KUDOH, Chiaki; KISHI, Taichi
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
Honda, Mitsuru; Ichibayashi, Ryo; Yokomuro, Hiroki; Yoshihara, Katsunori; Masuda, Hiroyuki; Haga, Daisuke; Seiki, Yoshikatsu; Kudoh, Chiaki; Kishi, Taichi
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.
M.C. Cnossen; S. Polinder (Suzanne); Lingsma, H.F. (Hester F.); A.I.R. Maas (Andrew); D.K. Menon (David ); E.W. Steyerberg (Ewout); Adams, H. (Hadie); Alessandro, M. (Masala); J. Allanson (Judith); Amrein, K. (Krisztina); Andaluz, N. (Norberto); N. Andelic (Nada); Andrea, N. (Nanni); L. Andreassen (Lasse); Anke, A. (Audny); Antoni, A. (Anna); Ardon, H. (Hilko); G. Audibert (Gérard); Auslands, K. (Kaspars); Azouvi, P. (Philippe); Baciu, C. (Camelia); Bacon, A. (Andrew); Badenes, R. (Rafael); Baglin, T. (Trevor); Bartels, R. (Ronald); Barzó, P. (Pál); Bauerfeind, U. (Ursula); R. Beer (Ronny); Belda, F.J. (Francisco Javier); B.-M. Bellander (Bo-Michael); A. Belli (Antonio); Bellier, R. (Rémy); H. Benali (Habib); Benard, T. (Thierry); M. Berardino (Maurizio); Beretta, L. (Luigi); Beynon, C. (Christopher); Bilotta, F. (Federico); H. Binder (Harald); Biqiri, E. (Erta); Blaabjerg, M. (Morten); Borgen, L.S. (Lund Stine); Bouzat, P. (Pierre); Bragge, P. (Peter); A. Brazinova (Alexandra); F. Brehar (Felix); Brorsson, C. (Camilla); Buki, A. (Andras); M. Bullinger (Monika); Bučková, V. (Veronika); Calappi, E. (Emiliana); P. Cameron (Peter); Carbayo, L.G. (Lozano Guillermo); Carise, E. (Elsa); Carpenter, C.; Castaño-León, A.M. (Ana M.); Causin, F. (Francesco); Chevallard, G. (Giorgio); A. Chieregato (Arturo); G. Citerio (Giuseppe); M. Coburn (Mark); J.P. Coles (Jonathan P.); Cooper, J.D. (Jamie D.); Correia, M. (Marta); A. Covic (Amra); N. Curry (Nicola); E. Czeiter (Endre); M. Czosnyka (Marek); Dahyot-Fizelier, C. (Claire); F. Damas (François); P. Damas (Pierre); H. Dawes (Helen); De Keyser, V. (Véronique); F. Della Corte (Francesco); B. Depreitere (Bart); Ding, S. (Shenghao); D.W.J. Dippel (Diederik); K. Dizdarevic (Kemal); Dulière, G.-L. (Guy-Loup); Dzeko, A. (Adelaida); G. Eapen (George); Engemann, H. (Heiko); A. Ercole (Ari); P. Esser (Patrick); Ezer, E. (Erzsébet); M. Fabricius (Martin); V.L. Feigin (V.); Feng, J. (Junfeng); Foks, K. (Kelly); F. Fossi (Francesca); Francony, G. (Gilles); J. Frantzén (Janek); Freo, U. (Ulderico); S.K. Frisvold (Shirin Kordasti); Furmanov, A. (Alex); P. Gagliardo (Pablo); D. Galanaud (Damien); G. Gao (Guoyi); K. Geleijns (Karin); A. Ghuysen (Alexandre); Giraud, B. (Benoit); Glocker, B. (Ben); Gomez, P.A. (Pedro A.); Grossi, F. (Francesca); R.L. Gruen (Russell); Gupta, D. (Deepak); J.A. Haagsma (Juanita); E. Hadzic (Ermin); I. Haitsma (Iain); J.A. Hartings (Jed); R. Helbok (Raimund); E. Helseth (Eirik); Hertle, D. (Daniel); S. Hill (Sean); Hoedemaekers, A. (Astrid); S. Hoefer (Stefan); P.J. Hutchinson (Peter J.); Håberg, A.K. (Asta Kristine); B.C. Jacobs (Bart); Janciak, I. (Ivan); K. Janssens (Koen); J.-Y. Jiang (Ji-Yao); Jones, K. (Kelly); Kalala, J.-P. (Jean-Pierre); Kamnitsas, K. (Konstantinos); Karan, M. (Mladen); Karau, J. (Jana); A. Katila (Ari); M. Kaukonen (Maija); Keeling, D. (David); Kerforne, T. (Thomas); N. Ketharanathan (Naomi); J. Kettunen (Johannes); Kivisaari, R. (Riku); A.G. Kolias (Angelos G.); Kolumbán, B. (Bálint); E.J.O. Kompanje (Erwin); D. Kondziella (Daniel); L.-O. Koskinen (Lars-Owe); Kovács, N. (Noémi); F. Kalovits (Ferenc); A. Lagares (Alfonso); L. Lanyon (Linda); S. Laureys (Steven); Lauritzen, M. (Martin); F.E. Lecky (Fiona); C. Ledig (Christian); R. Lefering; V. Legrand (Valerie); Lei, J. (Jin); L. Levi (Leon); R. Lightfoot (Roger); H.F. Lingsma (Hester); D. Loeckx (Dirk); Lozano, A. (Angels); Luddington, R. (Roger); Luijten-Arts, C. (Chantal); A.I.R. Maas (Andrew I.R.); MacDonald, S. (Stephen); MacFayden, C. (Charles); M. Maegele; M. Majdan (Marek); Major, S. (Sebastian); A. Manara (Alex); Manhes, P. (Pauline); G. Manley (Geoffrey); Martin, D. (Didier); C. Martino (Costanza); Maruenda, A. (Armando); H. Maréchal (Hugues); Mastelova, D. (Dagmara); Mattern, J. (Julia); C. McMahon (Catherine); Melegh, B. (Béla); T. Menovsky (Tomas); C. Morganti-Kossmann (Cristina); Mulazzi, D. (Davide); Mutschler, M. (Manuel); H. Mühlan (Holger); Negru, A. (Ancuta); D. Nelson (David); E. Neugebauer (Eddy); V.F. Newcombe (Virginia F.); Noirhomme, Q. (Quentin); Nyirádi, J. (József); M. Oddo (Mauro); Oldenbeuving, A. (Annemarie); M. Oresic (Matej); Ortolano, F. (Fabrizio); A. Palotie (Aarno); P.M. Parizel; Patruno, A. (Adriana); J.-F. Payen (Jean-François); Perera, N. (Natascha); V. Perlbarg (Vincent); Persona, P. (Paolo); W.C. Peul (Wilco); N. Pichon (Nicolas); Piilgaard, H. (Henning); A. Piippo (Anna); Pili, F.S. (Floury Sébastien); M. Pirinen (Matti); H. Ples (Horia); Pomposo, I. (Inigo); M. Psota (Marek); P. Pullens (Pim); L. Puybasset (Louis); A. Ragauskas (Arminas); Raj, R. (Rahul); Rambadagalla, M. (Malinka); Rehorčíková, V. (Veronika); J.K.J. Rhodes (Jonathan K.J.); S. Richardson (Sylvia); S. Ripatti (Samuli); S. Rocka (Saulius); Rodier, N. (Nicolas); Roe, C. (Cecilie); Roise, O. (Olav); Roks, G. (Gerwin); Romegoux, P. (Pauline); J. Rosand (Jonathan); Rosenfeld, J. (Jeffrey); C. Rosenlund (Christina); G. Rosenthal (Guy); R. Rossaint (Rolf); S. Rossi (Sandra); Rostalski, T. (Tim); Rueckert, D.L. (Danie L.); Ruiz De Arcaute, F. (Felix); M. Rusnák (Martin); Sacchi, M. (Marco); Sahakian, B. (Barbara); J. Sahuquillo (Juan); O. Sakowitz (Oliver); Sala, F. (Francesca); Sanchez-Pena, P. (Paola); Sanchez-Porras, R. (Renan); Sandor, J. (Janos); Santos, E. (Edgar); N. Sasse (Nadine); Sasu, L. (Luminita); Savo, D. (Davide); I.B. Schipper (Inger); Schlößer, B. (Barbara); S. Schmidt (Silke); Schneider, A. (Annette); H. Schoechl (Herbert); G.G. Schoonman; R. Schou (Rico); E. Schwendenwein (Elisabeth); Schöll, M. (Michael); Sir, O. (Özcan); T. Skandsen (Toril); Smakman, L. (Lidwien); D. Smeets (Dirk); Smielewski, P. (Peter); Sorinola, A. (Abayomi); Stamatakis, E.L. (Emmanue L.); S. Stanworth (Simon); Stegemann, K. (Katrin); Steinbüchel, N. (Nicole); R. Stevens (Robert); W. Stewart (William); N. Stocchetti (Nino); Sundström, N. (Nina); Synnot, A. (Anneliese); J. Szabó (József); J. Söderberg (Jeannette); F.S. Taccone (Fabio); Tamás, V. (Viktória); Tanskanen, P. (Päivi); A. Tascu (Alexandru); Taylor, M.S. (Mark Steven); Te Ao, B. (Braden); O. Tenovuo (Olli); Teodorani, G. (Guido); A. Theadom (Alice); Thomas, M. (Matt); D. Tibboel (Dick); C.M. Tolias (Christos M.); Tshibanda, J.-F.L. (Jean-Flory Luaba); Tudora, C.M. (Cristina Maria); P. Vajkoczy (Peter); Valeinis, E. (Egils); W. van Hecke (Wim); D. Van Praag (Dominique); D. Van Roost (Dirk); Van Vlierberghe, E. (Eline); Vande Vyvere, T. (Thijs); Vanhaudenhuyse, A. (Audrey); A. Vargiolu (Alessia); E. Vega (Emmanuel); J. Verheyden (Jan); P.M. Vespa (Paul M.); A. Vik (Anne); R. Vilcinis (Rimantas); Vizzino, G. (Giacinta); C.L.A.M. Vleggeert-Lankamp (Carmen); V. Volovici (Victor); P. Vulekovic (Peter); Vámos, Z. (Zoltán); Wade, D. (Derick); Wang, K.K.W. (Kevin K.W.); Wang, L. (Lei); Wildschut, E. (Eno); G. Williams (Guy); Willumsen, L. (Lisette); Wilson, A. (Adam); L. Wilson (Lindsay); Winkler, M.K.L. (Maren K. L.); P. Ylén (Peter); Younsi, A. (Alexander); M. Zaaroor (Menashe); Zhang, Z. (Zhiqun); Zheng, Z. (Zelong); Zumbo, F. (Fabrizio); De Lange, S. (Stefanie); G.C.W. De Ruiter (Godard C.W.); Den Boogert, H. (Hugo); Van Dijck, J. (Jeroen); T.A. van Essen (T.); C.M. van Heugten (Caroline M.); M. van der Jagt (Mathieu); J. van der Naalt (Joukje)
textabstractIntroduction: 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
Lingsma, Hester F.; Yue, John K.; Maas, Andrew I.R.; Steyerberg, Ewout W.; Cooper, Shelly R.; Dams-O'Connor, Kristen; Gordon, Wayne A.; Menon, David K.; Mukherjee, Pratik; Okonkwo, David O.; Puccio, Ava M.; Schnyer, David M.; Valadka, Alex B.; Vassar, Mary J.; Yuh, Esther L.
Abstract Although the majority of patients with mild traumatic brain injury (mTBI) recover completely, some still suffer from disabling ailments at 3 or 6 months. We validated existing prognostic models for mTBI and explored predictors of poor outcome after mTBI. We selected patients with mTBI from TRACK-TBI Pilot, an unselected observational cohort of TBI patients from three centers in the United States. We validated two prognostic models for the Glasgow Outcome Scale Extended (GOS-E) at 6 months after injury. One model was based on the CRASH study data and another from Nijmegen, The Netherlands. Possible predictors of 3- and 6-month GOS-E were analyzed with univariate and multi-variable proportional odds regression models. Of the 386 of 485 patients included in the study (median age, 44 years; interquartile range, 27–58), 75% (n=290) presented with a Glasgow Coma Score (GCS) of 15. In this mTBI population, both previously developed models had a poor performance (area under the receiver operating characteristic curve, 0.49–0.56). In multivariable analyses, the strongest predictors of lower 3- and 6-month GOS-E were older age, pre-existing psychiatric conditions, and lower education. Injury caused by assault, extracranial injuries, and lower GCS were also predictive of lower GOS-E. Existing models for mTBI performed unsatisfactorily. Our study shows that, for mTBI, different predictors are relevant as for moderate and severe TBI. These include age, pre-existing psychiatric conditions, and lower education. Development of a valid prediction model for mTBI patients requires further research efforts. PMID:25025611
Lingsma, Hester F; Yue, John K; Maas, Andrew I R; Steyerberg, Ewout W; Manley, Geoffrey T
Although the majority of patients with mild traumatic brain injury (mTBI) recover completely, some still suffer from disabling ailments at 3 or 6 months. We validated existing prognostic models for mTBI and explored predictors of poor outcome after mTBI. We selected patients with mTBI from TRACK-TBI Pilot, an unselected observational cohort of TBI patients from three centers in the United States. We validated two prognostic models for the Glasgow Outcome Scale Extended (GOS-E) at 6 months after injury. One model was based on the CRASH study data and another from Nijmegen, The Netherlands. Possible predictors of 3- and 6-month GOS-E were analyzed with univariate and multi-variable proportional odds regression models. Of the 386 of 485 patients included in the study (median age, 44 years; interquartile range, 27-58), 75% (n=290) presented with a Glasgow Coma Score (GCS) of 15. In this mTBI population, both previously developed models had a poor performance (area under the receiver operating characteristic curve, 0.49-0.56). In multivariable analyses, the strongest predictors of lower 3- and 6-month GOS-E were older age, pre-existing psychiatric conditions, and lower education. Injury caused by assault, extracranial injuries, and lower GCS were also predictive of lower GOS-E. Existing models for mTBI performed unsatisfactorily. Our study shows that, for mTBI, different predictors are relevant as for moderate and severe TBI. These include age, pre-existing psychiatric conditions, and lower education. Development of a valid prediction model for mTBI patients requires further research efforts.
Allen, Daniel N; Stolberg, Paul C; Thaler, Nicholas S; Sutton, Griffin; Mayfield, Joan
Intelligence tests are commonly administered to children following moderate-to-severe traumatic brain injury (TBI). The Reynolds Intellectual Assessment Scales (RIAS) is a recently developed measure of intellectual ability that has a number of appealing features for assessing individuals with brain damage, but as yet has little validity information when applied to children with TBI or other forms of brain injury. It is therefore unclear whether RIAS scores are sensitive to brain injury and how they compare to older more well-established tests such as the Wechsler scales. The current article reports two studies that examine these matters in youth with TBI. The first study examined sensitivity of the RIAS to TBI in 110 children. Results indicated the TBI sample performed significantly worse compared with the standardization sample on all RIAS index scores. The second study included 102 children who were administered either the RIAS, Wechsler Intelligence Scale for Children-Third Edition (WISC-III), or WISC-Fourth Edition (WISC-IV; 34 children in each group). Comparisons among the RIAS, WISC-III, and WISC-IV groups indicated no significant differences among the measures on verbal, nonverbal, and Composite Index/Full-Scale IQs. Results provide support for the sensitivity of the RIAS to TBI in children and also suggest that IQs produced by the RIAS, WISC-III, and WISC-IV do not significantly vary from one test to the other, which is particularly true of the verbal and Composite Index/Full-Scale IQs.
memantine after TBI, in this case with a focus on pain metrics. Subtask 2. Perform nociception behavior experiments (mechanical and thermal thresholds...cortex is more susceptible to spreading depolarizations, consistent with prominent sensory and pain features after TBI; 5. the effects of TBI are... nociception behavior experiments (mechanical and thermal thresholds, rotarod) on animals 3 months after CCI TBI. We have experience with both
Ryan, Nicholas P; Anderson, Vicki; Godfrey, Celia; Eren, Senem; Rosema, Stefanie; Taylor, Kaitlyn; Catroppa, Cathy
Traumatic brain injury (TBI) is a common cause of childhood disability, and is associated with elevated risk for long-term social impairment. Though social (pragmatic) communication deficits may be among the most debilitating consequences of childhood TBI, few studies have examined very long-term communication outcomes as children with TBI make the transition to young adulthood. In addition, the extent to which reduced social function contributes to externalizing behaviors in survivors of childhood TBI remains poorly understood. The present study aimed to evaluate the extent of social communication difficulty among young adult survivors of childhood TBI (n=34, injury age: 1.0-7.0 years; M time since injury: 16.55 years) and examine relations among aspects of social function including emotion perception, social communication and externalizing behaviors rated by close-other proxies. Compared to controls the TBI group had significantly greater social communication difficulty, which was associated with more frequent externalizing behaviors and poorer emotion perception. Analyses demonstrated that reduced social communication mediated the association between poorer emotion perception and more frequent externalizing behaviors. Our findings indicate that socio-cognitive impairments may indirectly increase the risk for externalizing behaviors among young adult survivors of childhood TBI, and underscore the need for targeted social skills interventions delivered soon after injury, and into the very long-term.
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 ...
Roozenbeek, Bob; Chiu, Ya-Lin; Lingsma, Hester F; Gerber, Linda M; Steyerberg, Ewout W; Ghajar, Jamshid; Maas, Andrew I R
Prognostic models for outcome prediction in patients with traumatic brain injury (TBI) are important instruments in both clinical practice and research. To remain current a continuous process of model validation is necessary. We aimed to investigate the performance of the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) prognostic models in predicting mortality in a contemporary New York State TBI registry developed and maintained by the Brain Trauma Foundation. The Brain Trauma Foundation (BTF) TBI-trac® database contains data on 3125 patients who sustained severe TBI (Glasgow Coma Scale [GCS] score ≤ 8) in New York State between 2000 and 2009. The outcome measure was 14-day mortality. To predict 14-day mortality with admission data, we adapted the IMPACT Core and Extended models. Performance of the models was assessed by determining calibration (agreement between observed and predicted outcomes), and discrimination (separation of those patients who die from those who survive). Calibration was explored graphically with calibration plots. Discrimination was expressed by the area under the receiver operating characteristic (ROC) curve (AUC). A total of 2513 out of 3125 patients in the BTF database met the inclusion criteria. The 14-day mortality rate was 23%. The models showed excellent calibration. Mean predicted probabilities were 20% for the Core model and 24% for the Extended model. Both models showed good discrimination with AUCs of 0.79 (Core) and 0.83 (Extended). We conclude that the IMPACT models validly predict 14-day mortality in the BTF database, confirming generalizability of these models for outcome prediction in TBI patients.
Larrabee, Glenn J; Binder, Laurence M; Rohling, Martin L; Ploetz, Danielle M
Bigler et al. (2013, The Clinical Neuropsychologist) contend that weak methodology and poor quality of the studies comprising our recent meta-analysis led us to miss detecting a subgroup of mild traumatic brain injury (mTBI) characterized by persisting symptomatic complaint and positive biomarkers for neurological damage. Our computation of non-significant Q, tau(2), and I(2) statistics contradicts the existence of a subgroup of mTBI with poor outcome, or variation in effect size as a function of quality of research design. Consistent with this conclusion, the largest single contributor to our meta-analysis, Dikmen, Machamer, Winn, and Temkin (1995, Neuropsychology, 9, 80) yielded an effect size, -0.02, that was smaller than our overall effect size of -0.07 despite using the most liberal definition of mTBI: loss of consciousness less than 1 hour, with no exclusion of subjects who had positive CT scans. The evidence is weak for biomarkers of mTBI, such as diffusion tensor imaging and for demonstrable neuropathology in uncomplicated mTBI. Postconcussive symptoms, and reduced neuropsychological test scores are not specific to mTBI but can result from pre-existing psychosocial and psychiatric problems, expectancy effects and diagnosis threat. Moreover, neuropsychological impairment is seen in a variety of primary psychiatric disorders, which themselves are predictive of persistent complaints following mTBI. We urge use of prospective studies with orthopedic trauma controls in future investigations of mTBI to control for these confounding factors.
Asken, Breton Michael; DeKosky, Steven T; Clugston, James R; Jaffee, Michael S; Bauer, Russell M
This review seeks to summarize diffusion tensor imaging (DTI) studies that have evaluated structural changes attributed to the mechanisms of mild traumatic brain injury (mTBI) in adult civilian, military, and athlete populations. Articles from 2002 to 2016 were retrieved from PubMed/MEDLINE, EBSCOhost, and Google Scholar, using a Boolean search string containing the following terms: "diffusion tensor imaging", "diffusion imaging", "DTI", "white matter", "concussion", "mild traumatic brain injury", "mTBI", "traumatic brain injury", and "TBI". We added studies not identified by this method that were found via manually-searched reference lists. We identified 86 eligible studies from English-language journals using, adult, human samples. Studies were evaluated based on duration between injury and DTI assessment, categorized as acute, subacute/chronic, remote mTBI, and repetitive brain trauma considerations. Since changes in brain structure after mTBI can also be affected by other co-occurring medical and demographic factors, we also briefly review DTI studies that have addressed socioeconomic status factors (SES), major depressive disorder (MDD), and attention-deficit hyperactivity disorder (ADHD). The review describes population-specific risks and the complications of clinical versus pathophysiological outcomes of mTBI. We had anticipated that the distinct population groups (civilian, military, and athlete) would require separate consideration, and various aspects of the study characteristics supported this. In general, study results suggested widespread but inconsistent differences in white matter diffusion metrics (primarily fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], and axial diffusivity [AD]) following mTBI/concussion. Inspection of study designs and results revealed potential explanations for discrepant DTI findings, such as control group variability, analytic techniques, the manner in which regional differences were reported, and
Full Text Available Purpose: To describe the definition of quality of life (QoL and identify the most appropriate tool for QoL assessment used in patients with TBI.Method: Searching was conducted from PubMed, CINAHL, EBSCO, and ProQuest during 2000-2011. A total of 33 studies were analyzed for this review consisting of 9 review studies, 2 intervention studies, and 22 descriptive studies.Result: Two important definitions of QoL were used in studies related to TBI namely achievement and subjective well-being. Although varieties of generic measurements have been used to measure QoL in TBI patients, there was a lack of TBI-specific Health-related Quality of Life (HRQoL instrument. Despite the different approach and time measured either short or long outcomes, appropriate domains of QoL tool seem essential particularly among those with moderate and severe TBI.Conclusion: QoL is a wide concept which can be defined in several dimensions. The QOLIBRI as a new disease-specific QoL measurement in TBI seems a feasible and valid approach for the assessment of QoL in TBI. However, the application across cultural remains a challenge and needs a validation.
Rosenberg, H.; McDonald, S.; Dethier, M.; Kessels, R.P.C.; Westbrook, R.F.
Many individuals who sustain moderate-severe traumatic brain injuries (TBI) are poor at recognizing emotional expressions, with a greater impairment in recognizing negative (e.g., fear, disgust, sadness, and anger) than positive emotions (e.g., happiness and surprise). It has been questioned whether
High versus Low PTSD Symptom Severity. National Capital Area TBI Research Symposium. 2014. Bethesda, Maryland. 5. DeGraba M, Merrifield W...Localized Correlated Spectroscopy. Alzheimer Research and Therapy. (In Press) 12. APPENDICES Nothing to report.
Gollaher, K; High, W; Sherer, M; Bergloff, P; Boake, C; Young, M E; Ivanhoe, C
The current study investigated the relationship between age, education (EDUC), pre-injury productivity (PIP), Glasgow Coma Scale score, and a functional rating score at admittance and discharge from rehabilitation (Disability Rating Scale [DRS]) to employment status at one to three years following traumatic brain injury. EDUC, admit DRS, discharge DRS, and PIP all correlated significantly with follow-up employment status, 0.29, -0.32, -0.36, and 0.25 respectively. All possible combinations were then evaluated by Mallow's Cp statistic. The best fitting model was then used in a discriminant function analysis. The discriminant function correctly classified 84% of the employed subjects, 66% of the unemployed, and 75% across both groups. The current results compare favourably with those obtained in previous studies.
We investigated variability of responses to emotionally important auditory stimulation in different groups of TBI (Traumatic Brain Injury) in acute state or recovery. The patients sampling consisted of three different groups: patients in coma or vegetative state, patients with Severe and Moderate TBI in recovery period. Subjects were stimulated with auditory stimuli containing important physiological sounds (coughing, vomiting), emotional sounds (laughing, crying), nature sounds (bird song, barking), unpleasant household sounds (nails scratching the glass), natural sounds (sea, rain, fire) and neutral sounds (white noise). The background encephalographic activity was registered during at least 7 minutes. EEG was recorded while using portable device "Entsefalan". Significant differences of power of the rhythmic activity registered during the presentation of different types of stimuli were analyzed using Mathlab and Statistica 6.0. Results showed that EEG-response to the emotional stimuli differed depending on consciousness level, stimuli type, severity of TBI. Most valuable changes in EEG spectrum power for a patient with TBI were found for unpleasant auditory stimulation. Responsiveness to the pleasant stimulation could be registered in later stages of coming out of coma than to unpleasant stimulation. Alpha-activity is reducing in patients with TBI: the alpha rhythm depression is most evident in the control group, less in group after moderate TBI, and even less in group after severe TBI. Patients in coma or vegetative state didn't show any response in rhythmic power in the frequency of alpha rhythm.
type: Assault Peak ADC = 0.71 Peak FA = 0.45 GCS = 10 Injury type: MVC Peak ADC = 0.73 Peak FA = 0.42 GCS = 7 Injury type: Fall Peak ADC = 0.75 Peak FA...who demonstrated. negative conventional MRI/CT MCC = Motorcycle Collision, MVC = Motor Vehicle Collision. Standard T2*-GRE SWI 51y old male who...findings! GCS 5, MVC , 38y M Normal Patient Does normal DTI mean no injury? • Acutely post injury: – Increased FA – Reduced MD Possible cause: cytotoxic
Logan, Dustin M; Hill, Kyle R; Larson, Michael J
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.
Gatson, Joshua W; Stebbins, Cari; Mathews, Dana; Harris, Thomas S; Madden, Christopher; Batjer, Hunt; Diaz-Arrastia, Ramon; Minei, Joseph P
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
Patel Mayur B
the Extended Glasgow Outcome Scale and Quality of Life after Brain Injury scale. Safety parameters evaluated will include cardiac complications. Discussion The DASH After TBI Study is the first randomized, double-blinded, placebo-controlled trial powered to determine feasibility and investigate safety and outcomes associated with adrenergic blockade in patients with severe TBI. If the study results in positive trends, this could provide pilot evidence for a larger multicenter randomized clinical trial. If there is no effect of therapy, this trial would still provide a robust prospective description of sympathetic hyperactivity after TBI. Trial registration ClinicalTrials.gov NCT01322048
Karamouzis, Ioannis; Pagano, Loredana; Prodam, Flavia; Mele, Chiara; Zavattaro, Marco; Busti, Arianna; Marzullo, Paolo; Aimaretti, Gianluca
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.
Resting microglia Activated microglia Brain Injury Veliparib (_) APPENDIX B Oral Presentation to 2014 University of California Brain Trauma...TBI 1 mg/kg 9 mg/kg3 mg/kg Veliparib APPENDIX F Gene expression in lesioned cortex after CCI in the rat Effects of veliparib on gene expression at day 3 after CCI
Full Text Available Memory deficits and other cognitive symptoms frequently associated with mTBI are commonly thought to resolve within 7 to 10 days. This generalization is based principally on observations made in individuals who are in the unstressed environmental conditions typical to a clinic and so does not consider the impact of physiologic, environmental or psychological stress. Normobaric Hypoxia (NH stress can be generated by mixing normal mean sea level air (MSL containing 21% oxygen (O2 with nitrogen, which is biologically inert, so that the resultant mixed gas has a partial pressure of O2 approximating that of specified altitudes. This technique was used to generate NH equivalents of 8,000, 12,000 and 14,000 feet above MSL in a group of 36 volunteers with an mTBI history and an equal number of controls matched on the basis of age, gender, weight, etc. Short term visual memory was tested using Matching to Sample (M2S subtest of the BrainCheckers analogue of the Automated Neuropsychological Assessment Metrics (ANAM. Although there were no significant differences in M2S performance between the two groups of subjects at MSL, with increased altitude, performance deteriorated in the mTBI group as predicted to be significantly worse than that of the controls. When the subjects were returned to MSL, the difference disappeared. This finding suggests that the hypoxic challenge paradigm developed here has potential clinical utility for assessing the effects of mTBI in individuals who appear asymptomatic under normal conditions.
Full Text Available 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 (IL-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.
Salvador, Ellaine; Burek, Malgorzata; Förster, Carola Y
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.
Im, Brian; Schrer, Marcia J.; Gaeta, Raphael; Elias, Eileen
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…
Garcia, Patricia Gracia; Mielke, Michelle M.; Rosenberg, Paul; Bergey, Alyssa; Rao, Vani
Traumatic brain injury (TBI) is frequently complicated by alterations in mood and behaviour and changes in personality. We report mild personality changes post-TBI as a possible indicator of traumatic brain injury, but not of injury severity or psychiatric complications.
Adeoye, Opeolu; Lindsell, Christopher J.; Hart, Kimberly W.; Pancioli, Arthur; McMullan, Jason T.; Yue, John K.; Nishijima, Daniel K.; Gordon, Wayne A.; Valadka, Alex B.; Okonkwo, David O.; Lingsma, Hester F.; Maas, Andrew I.R.
Objective Mild traumatic brain injury (mTBI) patients are frequently admitted to high levels of care despite limited evidence suggesting benefit. Such decisions may contribute to the significant cost of caring for mTBI patients. Understanding the factors that drive disposition decision making and how disposition is associated with outcomes is necessary for developing an evidence-base supporting disposition decisions. We evaluated factors associated with emergency department triage of mTBI patients to 1 of 3 levels of care: home, inpatient floor, or intensive care unit (ICU). Methods This multicenter, prospective, cohort study included patients with isolated head trauma, a cranial computed tomography as part of routine care, and a Glasgow Coma Scale (GCS) score of 13 to 15. Data analysis was performed using multinomial logistic regression. Results Of the 304 patients included, 167 (55%) were discharged home, 76 (25%) were admitted to the inpatient floor, and 61 (20%) were admitted to the ICU. In the multivariable model, admission to the ICU, compared with floor admission, varied by study site, odds ratio (OR) 0.18 (95% confidence interval [CI], 0.06–0.57); antiplatelet/anticoagulation therapy, OR 7.46 (95% CI, 1.79–31.13); skull fracture, OR 7.60 (95% CI, 2.44–23.73); and lower GCS, OR 2.36 (95% CI, 1.05–5.30). No difference in outcome was observed between the 3 levels of care. Conclusion Clinical characteristics and local practice patterns contribute to mTBI disposition decisions. Level of care was not associated with outcomes. Intracranial hemorrhage, GCS 13 to 14, skull fracture, and current antiplatelet/anticoagulant therapy influenced disposition decisions. PMID:24857248
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.
Molina-Vicenty, Irma L; Santiago-Sánchez, Michelaldemar; Vélez-Miró, Iván; Motta-Valencia, Keryl
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.
Bellerose, Jenny; Bernier, Annie; Beaudoin, Cindy; Gravel, Jocelyn; Beauchamp, Miriam H
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.
traumatic brain injury TRAUMATIC BRAIN INJURY ( TBI ) is often dis-cussed as a common injury of the war in... Traumatic Brain Injury Screening 17 TABLE 1 Screening results∗ Injury status Injured with TBI 907 (22.8) Injured without TBI 385 (9.7) Not injured 2681...remember the injury 335 (36.9) Total with TBI 907 (100) ∗Values represent n (%). TBI indicates traumatic brain
Trudel, Tina M.; Scherer, Marcia J.; Elias, Eileen
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,…
ABSTRACT The overall subject of this project is blast- traumatic brain injury (blast- TBI ) and the role of the SUR1-regulated NCCa-ATP channel in blast- TBI ...project is blast- traumatic brain injury (blast- TBI ) and the role of the SUR1-regulated NCCa-ATP channel in secondary injury following blast- TBI . The...effective treatment for traumatic brain injury PRINCIPAL INVESTIGATOR: J. Marc Simard, M.D., Ph.D
Mannix, Rebekah C.; Whalen, Michael J
Recently, there has been growing interest in the association between traumatic brain injury (TBI) and Alzheimer's Disease (AD). TBI and AD share many pathologic features including chronic inflammation and the accumulation of beta amyloid (A\\(\\beta\\)). Data from both AD and TBI studies suggest that microglia play a central role in A\\(\\beta\\) accumulation after TBI. This paper focuses on the current research on the role of microglia response to A\\(\\beta\\) after TBI.
Klose, Marianne; Feldt-Rasmussen, Ulla
While hypopituitarism after traumatic brain injury (TBI) was previously considered rare, it is now thought to be a major cause of treatable morbidity among TBI survivors. Consequently, recommendations for assessment of pituitary function and replacement in TBI were recently introduced. Given...... the high incidence of TBI with more than 100 pr. 100,000 inhabitants, TBI would be by far the most common cause of hypopituitarism if the recently reported prevalence rates hold true. The disproportion between this proposed incidence and the occasional cases of post-TBI hypopituitarism in clinical practice...... justifies reflection as to whether hypopituitarism has been unrecognized in TBI patients or whether diagnostic testing designed for high risk populations such as patients with obvious pituitary pathology has overestimated the true risk and thereby the disease burden of hypopituitarism in TBI. The findings...
Deficits in Visual System Functional Connectivity after Blast-Related Mild TBI are Associated with Injury Severity and Executive Dysfunction Casey S...5Department of Ophthalmology & Visual Science, University of Iowa, Iowa City, Iowa 6Iowa City Veterans Affairs Health Care System, Iowa City, Iowa...Keywords blast TBI, executive function, functional connectivity, rest fMRI, TBI severity, traumatic brain injury, Visual Correspondence Casey S. Gilmore, PhD
traumatic brain injury ( TBI ) and posttraumatic stress disorder...stress disorder, TBI = traumatic brain injury . *Address all correspondence to Hilary J. Aralis, MS; Naval Health Research Center, Warfighter...both diagnoses. See Figure 1 for sampling details. Figure 1. Flow diagram outlining selection of final blast traumatic brain injury ( TBI ) and no TBI
创伤性脑损伤目前仍然是全世界死亡和致残的最主要原因之一，伤后的功能恢复仍是治疗面临的难题，神经干细胞移植为促进伤后神经功能恢复带来了光明的前景。%Traumatic brain injury (TBI) represents a major cause of neurological mortality and morbidity throughout the world. After the injury the functional recovery is still the dififcult problems in treatment. Neural stem cells therapy is a burgeoning ifeld of experimental treatment that has shown promise in the management of TBI.
Zagorchev, L.; McAllister, T.
Traumatic brain injury (TBI) represents an enormous public health challenge and is often associated with life long neurobehavioral sequelae in survivors. Several factors including higher percentages of individuals surviving TBI, as well as increasing concern about potential long term sequelae of ev
not be feasible without episodic representation to form a spatial environment map ( Eichenbaum , 1999). Moreover, current study is the first study to...and GABA(B) receptors in the regulation of the nucleus accumbens dopamine response to stress. Brain research. 1150, 62-8. Eichenbaum , H., 1999. The...and hyperactivity following cochlear damage. HearRes 147, 261-274. Sanderson, K.L., Raghupathi, R., Saatman, K.E., Martin , D., Miller, G., and
Odgaard, Lene; Poulsen, Ingrid; Kammersgaard, Lars Peter;
PURPOSE: To identify all hospitalized patients surviving severe traumatic brain injury (TBI) in Denmark and to compare these patients to TBI patients admitted to highly specialized rehabilitation (HS-rehabilitation). PATIENTS AND METHODS: Patients surviving severe TBI were identified from...... severe TBI were admitted to HS-rehabilitation. Female sex, older age, and non-working status pre-injury were independent predictors of no HS-rehabilitation among patients surviving severe TBI. CONCLUSION: The incidence rate of hospitalized patients surviving severe TBI was stable in Denmark...
Raghubar, Kimberly P; Barnes, Marcia A; Prasad, Mary; Johnson, Chad P; Ewing-Cobbs, Linda
This study compared mathematical outcomes in children with predominantly moderate to severe traumatic brain injury (TBI; n550) or orthopedic injury (OI; n547) at 2 and 24 months post-injury. Working memory and its contribution to math outcomes at 24 months post-injury was also examined. Participants were administered an experimental cognitive addition task and standardized measures of calculation, math fluency, and applied problems; as well as experimental measures of verbal and visual-spatial working memory. Although children with TBI did not have deficits in foundational math fact retrieval, they performed more poorly than OIs on standardized measures of math. In the TBI group, performance on standardized measures was predicted by age at injury, socioeconomic status, and the duration of impaired consciousness. Children with TBI showed impairments on verbal, but not visual working memory relative to children with OI. Verbal working memory mediated group differences on math calculations and applied problems at 24 months post-injury. Children with TBI have difficulties in mathematics, but do not have deficits in math fact retrieval, a signature deficit of math disabilities. Results are discussed with reference to models of mathematical cognition and disability and the role of working memory in math learning and performance for children with TBI.
Lucas, Matthew D.
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…
Marini, Andrea; Galetto, Valentina; Zampieri, Elisa; Vorano, Lorenza; Zettin, Marina; Carlomagno, Sergio
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…
W. Peeters (Wouter); R. van den Brande (Ruben); S. Polinder (Suzanne); A. Brazinova (Alexandra); E.W. Steyerberg (Ewout); H.F. Lingsma (Hester); A.I.R. Maas (Andrew)
textabstractBackground: Traumatic brain injury (TBI) is a critical public health and socio-economic problem throughout the world, making epidemiological monitoring of incidence, prevalence and outcome of TBI necessary. We aimed to describe the epidemiology of traumatic brain injury in Europe and to
Levin, Harvey S.; Robertson, Claudia S.
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 ...
Trudel, Tina M.; Halper, James; Pines, Hayley; Cancro, Lorraine
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…
traumatic brain injury ( TBI ). Neurons and astrocytes are susceptible to damage mechanisms arising from various...further developments may be pursued to unravel the key mechanical pathways potentially involved in TBI . 1. INTRODUCTION Traumatic brain injury ... injury mechanisms at the cellular level. This is especially important when studying traumatic brain injury ( TBI ). Neurons and astrocytes
Elias, Eileen; Weider, Katie; Mustafa, Ruman
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,…
public release; distribution unlimited Although blast-induced traumatic brain injury (BI- TBI ) is a significant cause of morbidity and behavioral...survival model of BI- TBI in swine. Traumatic Brain Injury , Swine, Blast, Model Development U U U 7 USAMRMC W81XWH-08-2-0082... Injury , TBI Scientific Advisor, Defense Center of Excellence for Psychological Health and Traumatic Brain Injury ) and Dr. Tamara Crowder at the DoD
Vermeij, Jan-Dirk; Aslami, Hamid; Fluiter, Kees; Roelofs, Joris J.; van den Bergh, Walter M.; Juffermans, Nicole P.; Schultz, Marcus J.; Van der Sluijs, Koen; van de Beek, Diederik; van Westerloo, David J.
Traumatic brain injury (TBI) is frequently complicated by acute lung injury, which is predictive for poor outcome. However, it is unclear whether lung injury develops independently or as a result of mechanical ventilation after TBI. Further, TBI is strongly associated with the development of pneumon
Full Text Available ABSTRACT Annually, 700,000 people are hospitalized with brain injury acquired after traumatic brain injury (TBI in Brazil. Objective: We aim to review the basic concepts related to TBI, and the most common Behavioral and Psychological Symptoms of Dementia (BPSD findings in moderate and severe TBI survivors. We also discussed our strategies used to manage such patients in the post-acute period. Methods: Fifteen TBI outpatients followed at the Center for Cognitive Rehabilitation Post-TBI of the Clinicas Hospital of the University of São Paulo were submitted to a neurological, neuropsychological, speech and occupational therapy evaluation, including the Mini-Mental State Examination. Rehabilitation strategies will then be developed, together with the interdisciplinary team, for each patient individually. Where necessary, the pharmacological approach will be adopted. Results: Our study will discuss options of pharmacologic treatment choices for cognitive, behavioral, or affective disorders following TBI, providing relevant information related to a structured cognitive rehabilitation service and certainly will offer an alternative for patients and families afflicted by TBI. Conclusion: Traumatic brain injury can cause a variety of potentially disabling psychiatric symptoms and syndromes. Combined behavioral and pharmacological strategies, in the treatment of a set of highly challenging behavioral problems, appears to be essential for good patient recovery.
Thompson, H; Pinto-Martin, J; Bullock, M.
Objectives: To determine the incidence of neurogenic fever (NF) in a population of patients in the acute phase following severe traumatic brain injury (TBI); to identify factors associated with the development of NF following severe TBI in adults.
Tournier, Charlène; CHARNAY, Pierrette; LUAUTE, Jacques; Hours, Martine
Introduction Few longitudinal studies investigated the long-term future of road accident victims. The ESPARR cohort has been followed for five years after the crash occurred. Objective To study the future of serious injured with TBI three years after their road accident. Methods The ESPARR cohort comprises 324 serious injured including 72 mild TBI (AIS2) and 70 moderate/severe TBI (AIS3+). 51 TBI2 and 49 TBI3+ responded to the questionnaire at three years. They are compared to 131 serious in...
Carlozzi, Noelle E; Kirsch, Ned L; Kisala, Pamela A; Tulsky, David S
This study examined the clinical utility of the Wechsler Adult Intelligence Scales-Fourth Edition (WAIS-IV) in individuals with complicated mild, moderate or severe TBI. One hundred individuals with TBI (n = 35 complicated mild or moderate TBI; n = 65 severe TBI) and 100 control participants matched on key demographic variables from the WAIS-IV normative dataset completed the WAIS-IV. Univariate analyses indicated that participants with severe TBI had poorer performance than matched controls on all index scores and subtests (except Matrix Reasoning). Individuals with complicated mild/moderate TBI performed more poorly than controls on the Working Memory Index (WMI), Processing Speed Index (PSI), and Full Scale IQ (FSIQ), and on four subtests: the two processing speed subtests (SS, CD), two working memory subtests (AR, LN), and a perceptual reasoning subtest (BD). Participants with severe TBI had significantly lower scores than the complicated mild/moderate TBI on PSI, and on three subtests: the two processing speed subtests (SS and CD), and the new visual puzzles test. Effect sizes for index and subtest scores were generally small-to-moderate for the group with complicated mild/moderate and moderate-to-large for the group with severe TBI. PSI also showed good sensitivity and specificity for classifying individuals with severe TBI versus controls. Findings provide support for the clinical utility of the WAIS-IV in individuals with complicated mild, moderate, and severe TBI.
Loane, David J; Kumar, Alok
As the major cellular component of the innate immune system in the central nervous system (CNS) and the first line of defense whenever injury or disease occurs, microglia play a critical role in neuroinflammation following a traumatic brain injury (TBI). In the injured brain microglia can produce neuroprotective factors, clear cellular debris and orchestrate neurorestorative processes that are beneficial for neurological recovery after TBI. However, microglia can also become dysregulated and can produce high levels of pro-inflammatory and cytotoxic mediators that hinder CNS repair and contribute to neuronal dysfunction and cell death. The dual role of microglial activation in promoting beneficial and detrimental effects on neurons may be accounted for by their polarization state and functional responses after injury. In this review article we discuss emerging research on microglial activation phenotypes in the context of acute brain injury, and the potential role of microglia in phenotype-specific neurorestorative processes such as neurogenesis, angiogenesis, oligodendrogenesis and regeneration. We also describe some of the known molecular mechanisms that regulate phenotype switching, and highlight new therapeutic approaches that alter microglial activation state balance to enhance long-term functional recovery after TBI. An improved understanding of the regulatory mechanisms that control microglial phenotypic shifts may advance our knowledge of post-injury recovery and repair, and provide opportunities for the development of novel therapeutic strategies for TBI.
Bhattacharya, Bishwajit; Maung, Adrian A
Traumatic brain injury (TBI) represents a wide spectrum of disease and disease severity. Because the primary brain injury occurs before the patient enters the health care system, medical interventions seek principally to prevent secondary injury. Anesthesia teams that provide care for patients with TBI both in and out of the operating room should be aware of the specific therapies and needs of this unique and complex patient population.
Boeing, Marianne; Barton, Barbara; Zinsmeister, Paula; Brouwers, Lynn; Trudel, Tina M.; Elias, Eileen; Weider, Katie
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.…
Fernandez-Rodriguez, Eva; Bernabeu, Ignacio; Castro, Ana I; Casanueva, Felipe F
The prevalence of hypopituitarism after traumatic brain (TBI) injury is widely variable in the literature; a meta-analysis determined a pooled prevalence of anterior hypopituitarism of 27.5%. Growth hormone deficiency is the most prevalent hormone insufficiency after TBI; however, the prevalence of each type of pituitary deficiency is influenced by the assays used for diagnosis, severity of head trauma, and time of evaluation. Recent studies have demonstrated improvement in cognitive function and cognitive quality of life with substitution therapy in GH-deficient patients after TBI.
Traumatic Brain Injury and Delayed Sequelae: A Review - Traumatic Brain Injury and Mild Traumatic Brain Injury (Concussion) are Precursors to Later-Onset Brain Disorders, Including Early-Onset Dementia
Kiraly, Michael A.; Kiraly, Stephen J.
Brain injuries are too common. Most people are unaware of the incidence of and horrendous consequences of traumatic brain injury (TBI) and mild traumatic brain injury (MTBI). Research and the advent of sophisticated imaging have led to progression in the understanding of brain pathophysiology following TBI. Seminal evidence from animal and human experiments demonstrate links between TBI and the subsequent onset of premature, psychiatric syndromes and neurodegenerative diseases, including Alzh...
Bigler, Erin D; Stern, Yaakov
The potential role of brain and cognitive reserve in traumatic brain injury (TBI) is reviewed. Brain reserve capacity (BRC) refers to preinjury quantitative measures such as brain size that relate to outcome. Higher BRC implies threshold differences when clinical deficits will become apparent after injury, where those individuals with higher BRC require more pathology to reach that threshold. Cognitive reserve (CR) refers to how flexibly and efficiently the individual makes use of available brain resources. The CR model suggests the brain actively attempts to cope with brain damage by using pre-existing cognitive processing approaches or by enlisting compensatory approaches. Standard proxies for CR include education and IQ although this has expanded to include literacy, occupational attainment, engagement in leisure activities, and the integrity of social networks. Most research on BRC and CR has taken place in aging and degenerative disease but these concepts likely apply to the effects of TBI, especially with regards to recovery. Since high rates of TBI occur in those under age 35, both CR and BRC factors likely relate to how the individual copes with TBI over the lifespan. These factors may be particularly relevant to the relationship of developing dementia in the individual who has sustained a TBI earlier in life.
Bansal, V; Ryu, SY; Lopez, N; Allexan, S; Krzyzaniak, M; Eliceiri, B; Baird, A.; Coimbra, R
Traumatic brain injury (TBI) releases a cascade of inflammatory cytokines. Vagal nerve stimulation (VNS) and ghrelin have known anti-inflammatory effects; furthermore, ghrelin release is stimulated by acetylcholine. We hypothesized VNS decreases post-TBI inflammation through a ghrelin-mediated mechanism. TBI was created in five groups of mice: sham, TBI, TBI/ghrelin, TBI/VNS, and TBI/VNS/ghrelin receptor antagonist (GRa). Serum and tissue ghrelin, and serum TNF-αwere measured. Ghrelin increas...
Greenberg, Mark S; Wood, Nellie E; Spring, Justin D; Gurvits, Tamara V; Nagurney, John T; Zafonte, Ross D; Pitman, Roger K
Neurological soft signs (NSSs) tap into a variety of perceptual, motor, and cognitive functions. The authors administered a battery of NSSs serially to a group of 14 pilot patients recruited from an emergency room after they experienced a mild traumatic brain injury. Patients were seen within 96 hours after injury, and again 30 and 90 days later. Measures of balance, mood, and postconcussive symptoms and impairment were also obtained. NSSs and balance improved across visits. Across visits, NSSs and balance were not significantly associated with any postconcussive outcome measures, although depressive symptoms were. Initial neurological impairment appeared to predict subsequent residual postconcussive symptoms and impairment, but this result requires replication.
Jiang, Hai-Hong; Kokiko-Cochran, Olga N; Li, Kevin; Balog, Brian; Lin, Ching-Yi; Damaser, Margot S.; Lin, Vernon; Cheng, Julian Yaoan; Lee, Yu-Shang
Although bladder dysfunction is common after traumatic brain injury (TBI), few studies have investigated resultant bladder changes and the detailed relationship between TBI and bladder dysfunction. The goal of this study was to characterize the effects of TBI on bladder function in an animal model. Fluid-percussion injury was used to create an animal model with moderate TBI. Female Sprague-Dawley rats underwent TBI, sham TBI or were not manipulated (naïve). All rats underwent filling cystomet...
Traumatic Brain Injury and Delayed Sequelae: A Review - Traumatic Brain Injury and Mild Traumatic Brain Injury (Concussion are Precursors to Later-Onset Brain Disorders, Including Early-Onset Dementia
Michael A. Kiraly
Full Text Available Brain injuries are too common. Most people are unaware of the incidence of and horrendous consequences of traumatic brain injury (TBI and mild traumatic brain injury (MTBI. Research and the advent of sophisticated imaging have led to progression in the understanding of brain pathophysiology following TBI. Seminal evidence from animal and human experiments demonstrate links between TBI and the subsequent onset of premature, psychiatric syndromes and neurodegenerative diseases, including Alzheimer's disease (AD and Parkinson's disease (PD. Objectives of this summary are, therefore, to instill appreciation regarding the importance of brain injury prevention, diagnosis, and treatment, and to increase awareness regarding the long-term delayed consequences following TBI.
Bigler, Erin D
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.
Erin D. Bigler
Full Text Available 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.
T.M.J.C. Andriessen; J. Horn; G. Franschman; J. van der Naalt; I. Haitsma; B. Jacobs; E.W. Steyerberg; P.E. Vos
Changes in the demographics, approach, and treatment of traumatic brain injury (TBI) patients require regular evaluation of epidemiological profiles, injury severity classification, and outcomes. This prospective multicenter study provides detailed information on TBI-related variables of 508 moderat
Andriessen, T.M.J.C.; Horn, J.; Franschman, G.; Naalt, J. van der; Haitsma, I.; Jacobs, B.; Steyerberg, E.W.; Vos, P.E.
Changes in the demographics, approach, and treatment of traumatic brain injury (TBI) patients require regular evaluation of epidemiological profiles, injury severity classification, and outcomes. This prospective multicenter study provides detailed information on TBI-related variables of 508 moderat
Andriessen, Teuntje M. J. C.; Horn, Janneke; Franschman, Gaby; van der Naalt, Joukje; Haitsma, Iain; Jacobs, Bram; Steyerberg, Ewout W.; Vos, Pieter E.
Changes in the demographics, approach, and treatment of traumatic brain injury (TBI) patients require regular evaluation of epidemiological profiles, injury severity classification, and outcomes. This prospective multicenter study provides detailed information on TBI-related variables of 508 moderat
The multiple pathological cascades activated after traumatic brain injury (TBI) and their extended nature offer the possibility for therapeutic interventions possibly affecting multiple injury mechanisms simultaneously. Mesenchymal stromal cell (MSC) therapy matches this need, being a bioreactor of a variety of molecules able to interact and modify the injured brain microenvironment. Compared to autologous MSCs, bank stored GMP-graded allogenic MSCs appear to be a realistic choice for TBI ...
Deidrick, Kathleen K. M.; Farmer, Janet E.
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…
Sánchez-Catasús, Carlos A; Vállez Garcia, David; Le Riverend Morales, Eloísa; Galvizu Sánchez, Reinaldo; Dierckx, Rudi; Dierckx, Rudi AJO; Otte, Andreas; de Vries, Erik FJ; van Waarde, Aren; Leenders, Klaus L
This chapter provides an up-to-date review of nuclear medicine neuroimaging in traumatic brain injury (TBI). 18F-FDG PET will remain a valuable tool in researching complex mechanisms associated with early metabolic dysfunction in TBI. Although evidence-based imaging studies are needed, 18F-FDG PET i
Sharma, Deepak; Vavilala, Monica S.
This article presents an overview of the management of traumatic brain injury (TBI) as relevant to the practicing anesthesiologist. Key concepts surrounding the pathophysiology, anesthetic principles are used to describe potential ways to reduce secondary insults and improve outcomes after TBI.
Curry, Parichat; Viernes, Darwin; Sharma, Deepak
Traumatic brain injury (TBI) is a major public health problem and the leading cause of death and disability worldwide. Despite the modern diagnosis and treatment, the prognosis for patients with TBI remains poor. While severity of primary injury is the major factor determining the outcomes, the secondary injury caused by physiological insults such as hypotension, hypoxemia, hypercarbia, hypocarbia, hyperglycemia and hypoglycemia, etc. that develop over time after the onset of the initial inju...
subjected to TBI via a controlled cortical impact (CCI) device. Animals were anesthetized with isoflurane (5% induction , 2% maintenance) and...BDNF mRNA expression in the rat hippocampus after traumatic brain injury. Molecular Neuroscience. 11(15): 3381-3384 Hamm, R.J., Temple , M.D...Factors. RR Donnelly Willard. Pg. 96-99 Marmigere, F., Givalois, L., Rage, F., Arancibia, S., Tapia-Arancibia, L. (2003). Rapid induction of
Reid, Matthew W; Velez, Carmen S
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'.
Full Text Available OBJECTIVE: To reveal the expression and possible roles of aquaporin 9 (AQP9 in rat brain, after severe traumatic brain injury (TBI. METHODS: Brain water content (BWC, tetrazolium chloride staining, Evans blue staining, immunohistochemistry (IHC, immunofluorescence (IF, western blot, and real-time polymerase chain reaction were used. RESULTS: The BWC reached the first and second (highest peaks at 6 and 72 hours, and the blood brain barrier (BBB was severely destroyed at six hours after the TBI. The worst brain ischemia occurred at 72 hours after TBI. Widespread AQP9-positive astrocytes and neurons in the hypothalamus were detected by means of IHC and IF after TBI. The abundance of AQP9 and its mRNA increased after TBI and reached two peaks at 6 and 72 hours, respectively, after TBI. CONCLUSIONS: Increased AQP9 might contribute to clearance of excess water and lactate in the early stage of TBI. Widespread AQP9-positive astrocytes might help lactate move into neurons and result in cellular brain edema in the later stage of TBI. AQP9-positive neurons suggest that AQP9 plays a role in energy balance after TBI.
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. ...
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
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.
Traumatic brain injury (TBI) is a major cause of mortality and morbidity. Various attempts have been made to replicate clinical TBI using animal models. The fluid-percussion model (FP) is one of the oldest and most commonly used models of experimentally induced TBI. Both central (CFP) and lateral (LFP) variations of the model have been used. Developed initially for use in larger species, the standard FP device was adapted more than 20 years ago to induce consistent degrees of brain injury in ...
Full Text Available 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.
Hart, Tessa; Kozlowski, Allan; Whyte, John
OBJECTIVE: To examine person, injury, and treatment characteristics associated with recovery trajectories of people with severe traumatic brain injury (TBI) during inpatient rehabilitation. DESIGN: Observational prospective longitudinal study. SETTING: Two specialized inpatient TBI rehabilitation...... functional levels received more treatment and more treatment was associated with slower recovery, presumably because treatment was allocated according to need. Thus, effects of treatment on outcome could not be disentangled from effects of case mix factors. CONCLUSIONS: FIM gain during inpatient recovery...
Bigler, Erin D; Maxwell, William L
Neuroimaging identified abnormalities associated with traumatic brain injury (TBI) are but gross indicators that reflect underlying trauma-induced neuropathology at the cellular level. This review examines how cellular pathology relates to neuroimaging findings with the objective of more closely relating how neuroimaging findings reveal underlying neuropathology. Throughout this review an attempt will be made to relate what is directly known from post-mortem microscopic and gross anatomical studies of TBI of all severity levels to the types of lesions and abnormalities observed in contemporary neuroimaging of TBI, with an emphasis on mild traumatic brain injury (mTBI). However, it is impossible to discuss the neuropathology of mTBI without discussing what occurs with more severe injury and viewing pathological changes on some continuum from the mildest to the most severe. Historical milestones in understanding the neuropathology of mTBI are reviewed along with implications for future directions in the examination of neuroimaging and neuropathological correlates of TBI.
van der Horn, Harm J.; Liemburg, Edith J.; Aleman, Andre; Spikman, Jacoba M.; van der Naalt, Joukje
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 deve
Kushner, David S; Alvarez, Gemayaret
Spinal cord injury (SCI) patients should be assessed for a co-occurring traumatic brain injury (TBI) on admission to a rehabilitation program. Incidence of a dual diagnosis may approach 60% with certain risk factors. Diagnosis of mild-moderate severity TBIs may be missed during acute care hospitalizations of SCI. Neuropsychological symptoms of a missed TBI diagnosis may be perceived during rehabilitation as noncompliance, inability to learn, maladaptive reactions to SCI, and poor motivation. There are life-threatening and quality-of-life-threatening complications of TBI that also may be missed if a dual diagnosis is not made.
notwithstanding any other provision of law , no person shall be subject to any penalty for failing to comply with a collection of information if it does...ruTSl • PC!f4:..()lf/OEP SoId.i~ \\\\ llb roTS) • SolJiern\\liKl hl’l\\’t" not 8e’n~ in OIP/OEF. If you CIUl hfip towurd tbi... gnul,p~ contAct the pre8t...Many thanks to the participants from the Minnesota National Guard B Company (BII- 194) and Utuversity of Minnesota’s Golden Gopher Battalion - AmlY
traumatic brain injury ( TBI ) can both result in lasting neurobehavioral abnormalities. Post- traumatic stress disorder and blast...factor on the battlefield INTRODUCTION Traumatic brain injury ( TBI ) is one of the leading causes of death and chronic disability worldwide (Bruns and...ulcer devel- opment. Brain Res. Bull. 25, 691–695. Jaffee, M. S., and Meyer, K. S. (2009). A brief overview of traumatic brain injury ( TBI ) and
Wang, Xiaoting; Gao, Xiang; Michalski, Stephanie; Zhao, Shu; Chen, Jinhui
Traumatic brain injury (TBI) has been proven to enhance neural stem cell (NSC) proliferation in the hippocampal dentate gyrus. However, various groups have reported contradictory results on whether TBI increases neurogenesis, partially due to a wide range in the severities of injuries seen with different TBI models. To address whether the severity of TBI affects neurogenesis in the injured brain, we assessed neurogenesis in mouse brains receiving different severities of controlled cortical impact (CCI) with the same injury device. The mice were subjected to mild, moderate, or severe TBI by a CCI device. The effects of TBI severity on neurogenesis were evaluated at three stages: NSC proliferation, immature neurons, and newly-generated mature neurons. The results showed that mild TBI did not affect neurogenesis at any of the three stages. Moderate TBI promoted NSC proliferation without increasing neurogenesis. Severe TBI increased neurogenesis at all three stages. Our data suggest that the severity of injury affects adult neurogenesis in the hippocampus, and thus it may partially explain the inconsistent results of different groups regarding neurogenesis following TBI. Further understanding the mechanism of TBI-induced neurogenesis may provide a potential approach for using endogenous NSCs to protect against neuronal loss after trauma.
Mishra, Vikas; Skotak, Maciej; Schuetz, Heather; Heller, Abi; Haorah, James; Chandra, Namas
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.
...-Competitive One-Year Extension Funds for Current Traumatic Brain Injury (TBI) State Implementation Partnership... Traumatic Brain Injury Act of 2008 (Pub. L. 110- 206). Under this authority, the HRSA TBI Program is charged... HUMAN SERVICES Health Resources and Services Administration Current Traumatic Brain Injury......
Ling, Geoffrey S. F.; Hawley, Jason; Grimes, Jamie; Macedonia, Christian; Hancock, James; Jaffee, Michael; Dombroski, Todd; Ecklund, James M.
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  and mild TBI/concussion  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.
Haddad Samir H; Arabi Yaseen M
Abstract Traumatic brain injury (TBI) is a major medical and socio-economic problem, and is the leading cause of death in children and young adults. The critical care management of severe TBI is largely derived from the "Guidelines for the Management of Severe Traumatic Brain Injury" that have been published by the Brain Trauma Foundation. The main objectives are prevention and treatment of intracranial hypertension and secondary brain insults, preservation of cerebral perfusion pressure (CPP...
Brouwer, WH; Withaar, FK; Tant, MLM; van Zomeren, AH
Background: Diffuse and focal traumatic brain injury (TBI) can result in perceptual, cognitive, and motor dysfunction possibly leading to activity limitations in driving. Characteristic dysfunctions for severe diffuse TBI are confronted with function requirements derived from the hierarchical task a
Harting, Matthew T.; jimenez, fernando; Adams, Sasha D.; Mercer, David W.; Cox, Charles S.
While cellular therapy has shown promise in the management of traumatic brain injury (TBI), microenvironment interactions between the intracerebral milieu and therapeutic stem cells are poorly understood. We sought to characterize the acute, regional inflammatory response after TBI.
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
The Erythropoietin in Traumatic Brain Injury (EPO-TBI) trial aims to determine whether the administration of erythropoietin to patients with moderate or severe traumatic brain injury improves patient-centred outcomes.
Chiu, Chong-Chi; Liao, Yi-En; Yang, Ling-Yu; Wang, Jing-Ya; Tweedie, David; Karnati, Hanuma K.; Greig, Nigel H.; Wang, Jia-Yi
Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. Neuroinflammation is prominent in the short and long-term consequences of neuronal injuries that occur after TBI. Neuroinflammation involves the activation of glia, including microglia and astrocytes, to release inflammatory mediators within the brain, and the subsequent recruitment of peripheral immune cells. Various animal models of TBI have been developed that have proved valuable to elucidate the pathophysiology of the disorder and to assess the safety and efficacy of novel therapies prior to clinical trials. These models provide an excellent platform to delineate key injury mechanisms that associate with types of injury (concussion, contusion, and penetration injuries) that occur clinically for the investigation of mild, moderate, and severe forms of TBI. Additionally, TBI modeling in genetically engineered mice, in particular, has aided the identification of key molecules and pathways for putative injury mechanisms, as targets for development of novel therapies for human TBI. This Review details the evidence showing that neuroinflammation, characterized by the activation of microglia and astrocytes and elevated production of inflammatory mediators, is a critical process occurring in various TBI animal models, provides a broad overview of commonly used animal models of TBI, and overviews representative techniques to quantify markers of the brain inflammatory process. A better understanding of neuroinflammation could open therapeutic avenues for abrogation of secondary cell death and behavioral symptoms that may mediate the progression of TBI. PMID:27382003
SUN Xiao-chuan; JIANG Yong
@@ Traumatic brain injury (TBI) is defined as an injury caused by a blow or jolt to the head or a penetrating head injury that disrupts the normal function of the brain. It is a common emergency and severe case in neurosurgery field. Nowadays, there are more and more evidences showing that TBI, which is apparently similar in pathology and severity in the acute stage, may have different outcomes.
Yeates, Keith Owen; Armstrong, Kira; Janusz, Jennifer; Taylor, H. Gerry; Wade, Shari; Stancin, Terry; Drotar, Dennis
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…
M. Königs (Marsh); W.D. Weeda (Wouter D.); L.W.E. Van Heurn (L.W. Ernest); R.J. Vermeulen (R. Jeroen); J.C. Goslings (Carel); J.S.K. Luitse (Jan S.K.); B.T. Poll-Thé (Bwee Tien); A. Beelen (Anita); M. Van Der Wees (Marleen); R.J.J.K. Kemps (Rachèl J.J.K.); C.E. Catsman-Berrevoets (Coriene); J. Oosterlaan (Jaap)
textabstractBackground 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
Hasan, Anwarul; Deeb, George; Rahal, Rahaf; Atwi, Khairallah; Mondello, Stefania; Marei, Hany Elsayed; Gali, Amr; Sleiman, Eliana
Traumatic brain injury (TBI) is characterized by a disruption in the normal function of the brain due to an injury following a trauma, which can potentially cause severe physical, cognitive, and emotional impairment. The primary insult to the brain initiates secondary injury cascades consisting of multiple complex biochemical responses of the brain that significantly influence the overall severity of the brain damage and clinical sequelae. The use of mesenchymal stem cells (MSCs) offers huge potential for application in the treatment of TBI. MSCs have immunosuppressive properties that reduce inflammation in injured tissue. As such, they could be used to modulate the secondary mechanisms of injury and halt the progression of the secondary insult in the brain after injury. Particularly, MSCs are capable of secreting growth factors that facilitate the regrowth of neurons in the brain. The relative abundance of harvest sources of MSCs also makes them particularly appealing. Recently, numerous studies have investigated the effects of infusion of MSCs into animal models of TBI. The results have shown significant improvement in the motor function of the damaged brain tissues. In this review, we summarize the recent advances in the application of MSCs in the treatment of TBI. The review starts with a brief introduction of the pathophysiology of TBI, followed by the biology of MSCs, and the application of MSCs in TBI treatment. The challenges associated with the application of MSCs in the treatment of TBI and strategies to address those challenges in the future have also been discussed.
Sturdivant, Nasya M.; Smith, Sean G.; Ali, Syed F.; Wolchok, Jeffrey C.; Balachandran, Kartik
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.
Enming Joe Su
Full Text Available 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 minutes after TBI and given twice daily for 5 days, significantly reduces BBB dysfunction. This is associated with significantly reduced lesion size 24 hours, 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 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.
Traumatic Brain Injury (TBI) afflicts more than 1.7 million people in the United States each year and even mild TBI can lead to persistent neurological impairments 1. Two pervasive and disabling symptoms experienced by TBI survivors, memory deficits and a reduction in seizure threshold, are thought to be mediated by TBI-induced hippocampal dysfunction 2,3. In order to demonstrate how altered hippocampal circuit function adversely affects behavior after TBI in mice, we employ lateral fluid per...
Due to its high incidence,high disability rate,and high mortality rate,traumatic brain injury (TBI) poses a serious threat to human health.This manuscript describes the urgent problems currently existing in China's TBI treatment and proposes a scheme of a nationwide collaboration platform for the treatment of TBI so as to improve the overall level of TBI treatment in China,and reduce disability and mortality rates in TBI patients.
Young, Lee Ann; Rule, Gregory T; Bocchieri, Robert T; Burns, Jennie M
Despite years of effort to prevent traumatic brain injuries (TBIs), the occurrence of TBI in the United States alone has reached epidemic proportions. When an external force is applied to the head, it is converted into stresses that must be absorbed into the brain or redirected by a helmet or other protective equipment. Complex interactions of the head, neck, and jaw kinematics result in strains in the brain. Even relatively mild mechanical trauma to these tissues can initiate a neurochemical cascade that leads to TBI. Civilians and warfighters can experience head injuries in both combat and noncombat situations from a variety of threats, including ballistic and blunt impact, acceleration, and blast. It is critical to understand the physics created by these threats to develop meaningful improvements to clinical care, injury prevention, and mitigation. Here the authors review the current state of understanding of the complex loading conditions that lead to TBI and characterize how these loads are transmitted through soft tissue, the skull and into the brain, resulting in TBI. In addition, gaps in knowledge and injury thresholds are reviewed, as these must be addressed to better design strategies that reduce TBI incidence and severity.
van der Horn, Harm J.; Liemburg, Edith J.; Scheenen, Myrthe E.; de Koning, Myrthe E.; Marsman, Jan-Bernard C.; Spikman, Jacoba M.; van der Naalt, Joukje
ObjectivesTo assess the role of brain networks in emotion regulation and post-traumatic complaints in the sub-acute phase after non-complicated mild traumatic brain injury (mTBI). Experimental designFifty-four patients with mTBI (34 with and 20 without complaints) and 20 healthy controls (group-matc
Research Program/ Stuart Hoffman (VA), Scientific Program Manager for the Brain Injury Portfolio 810 Vermont Avenue, NW, Washington, DC 20420... class of brain proteins that undergo TBI-induced citrullination (2). Development of Assays for TBI Biomarkers. Immunoassays will be developed for...hours) x x x Head CT scan or imaging completed x x x ? ? ? Negative x x Positive x x Acuity for testing (hearing/eye) x x x x Speak English or
Karelina, Kate; Sarac, Benjamin; Freeman, Lindsey M; Gaier, Kristopher R; Weil, Zachary M
Traumatic brain injury (TBI)-induced impairments in cerebral energy metabolism impede tissue repair and contribute to delayed functional recovery. Moreover, the transient alteration in brain glucose utilization corresponds to a period of increased vulnerability to the negative effects of a subsequent TBI. In order to better understand the factors contributing to TBI-induced central metabolic dysfunction, we examined the effect of single and repeated TBIs on brain insulin signalling. Here we show that TBI induced acute brain insulin resistance, which resolved within 7 days following a single injury but persisted until 28 days following repeated injuries. Obesity, which causes brain insulin resistance and neuroinflammation, exacerbated the consequences of TBI. Obese mice that underwent a TBI exhibited a prolonged reduction of Akt (also known as protein kinase B) signalling, exacerbated neuroinflammation (microglial activation), learning and memory deficits, and anxiety-like behaviours. Taken together, the transient changes in brain insulin sensitivity following TBI suggest a reduced capacity of the injured brain to respond to the neuroprotective and anti-inflammatory actions of insulin and Akt signalling, and thus may be a contributing factor for the damaging neuroinflammation and long-lasting deficits that occur following TBI.
... to Help Feel Better After a Mild Traumatic Brain Injury? Although most people recover after a concussion, how ... Potential Effects Prevention Severe TBI HEADS UP to Brain Injury Awareness Get Email Updates To receive email updates ...
Kampen, P.J. van; Martina, J.D.; Vos, P.E.; Hoedemaekers, C.W.E.; Hendricks, H.T.
BACKGROUND: Heterotopic ossification (HO) is a frequent complication after traumatic brain injury (TBI). The current preliminary study is intended to provide additional data on the potential roles that brain injury severity, concomitant orthopaedic trauma, and specific intensive care complicating ev
... and caregivers. Biausa.org. www.biausa.org/brain-injury-family-caregivers.htm#Manage the Home . Accessed December 8, 2016. ... Caregiver Alliance; National Center on Caregiving. Traumatic brain injury. ... www.caregiver.org/traumatic-brain-injury . Accessed ...
Dong, Hui; Ma, Yunfu; Ren, Zengxi; Xu, Bin; Zhang, Yunhe; Chen, Jing; Yang, Bo
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.
D.C. Engel (Doortje Caroline)
textabstractTraumatic brain injury (TBI) is defined as a microscopic or macroscopic injury to the brain caused by external physical forces. Road traffic accidents, falls, sports injuries (i.e. boxing), recreational accidents (i.e. parachute jumping), the use of firearms, assault, child abuse, and se
Biteghe-bi-Nzeng Alain; WANG Yun-jie
Traumatic brain injury(TBI)remains a complicated and urgent disease in our modernized cities. It becomes now a public health disease. We have got more and more patients in Neurosurgery Intensive Care Unit following motor vehicle accidents and others causes. TBI brings multiple disorders,from the primary injury to secondary injury. The body received the disturbances in the brain,in the hypothalamo-pituitary-adrenocortical(HPA)axis,in the gastric mucosa,in the immune and neuroendocrine systems.The mortality of TBI is more than 50 000 deaths/year, the third of the mortality of all iniuries. Cushing ulcer is one of the severe complications of TBI and its mortality rate is more than 50%. Many studies have improved the management of TBI and the associated complications to give patients a better outcome. Furthers studies need to be done based on the similar methodology to clarify the different steps of the HPA axis and the neuroendocrine change associated. The aim of the present review is to assess the clinical and endocrinal features of hypopituitarism and stress ulcer following TBI.
Hartings, Jed A; Bullock, M Ross; Okonkwo, David O
Pathological waves of spreading mass neuronal depolarisation arise repeatedly in injured, but potentially salvageable, grey matter in 50-60% of patients after traumatic brain injury (TBI). We aimed to ascertain whether spreading depolarisations are independently associated with unfavourable...
U.S. Department of Health & Human Services — The Federal Interagency Traumatic Brain Injury Research (FITBIR) informatics system is an extensible, scalable informatics platform for TBI relevant imaging,...
... Sign up Search: Defense Centers of Excellence For Psychological Health & Traumatic Brain Injury U.S. Department of Defense ... Reports Program Evaluation DoD/VA PH & TBI Registry Psychological Health About Psychological Health Psychological Health Resources About ...
Baldwin, Grant; Breiding, Matt; Sleet, David
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.
Full Text Available Abstract Traumatic brain injury (TBI is a result of an outside force causing immediate mechanical disruption of brain tissue and delayed pathogenic events. In order to examine injury processes associated with TBI, a number of rodent models to induce brain trauma have been described. However, none of these models covers the entire spectrum of events that might occur in TBI. Here we provide a thorough methodological description of a straightforward closed head weight drop mouse model to assess brain injuries close to the clinical conditions of human TBI.
Schmid, Kara E.; Frank C Tortella
The conflicts in Iraq and Afghanistan have placed an increased awareness on traumatic brain injury (TBI). Various publications have estimated the incidence of TBI for our deployed servicemen, however all have been based on extrapolations of data sets or subjective evaluations due to our current method of diagnosing a TBI. Therefore it has been difficult to get an accurate rate and severity of deployment related TBIs, or the incidence of multiple TBIs our service members are experiencing. As s...
Arroyos-Jurado, Elsa; Savage, Todd A.
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…
Bowen, Julie M.
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…
Vijay Krishnamoorthy; Deepak Sharma; Sumidtra Prathep; Vavilala, Monica S.
Traumatic brain injury (TBI) is a major public health issue and is a leading cause of death in North America. After a primary TBI, secondary brain insults can predispose patients to a worse outcome. One of the earliest secondary insults encountered during the perioperative period is hypotension, which has been directly linked to both mortality and poor disposition after TBI. Despite this, it has been shown that hypotension commonly occurs during surgery for TBI. We present a case of intraoper...
André Mendes Arent; Luiz Felipe de Souza; Roger Walz; Alcir Luiz Dafre
Traumatic brain injury (TBI) is frequently associated with abnormal blood-brain barrier function, resulting in the release of factors that can be used as molecular biomarkers of TBI, among them GFAP, UCH-L1, S100B, and NSE. Although many experimental studies have been conducted, clinical consolidation of these biomarkers is still needed to increase the predictive power and reduce the poor outcome of TBI. Interestingly, several of these TBI biomarkers are oxidatively modified to carbonyl group...
Karaca, Züleyha; Tanrıverdi, Fatih; Ünlühızarcı, Kürşad; Kelestimur, Fahrettin
Traumatic brain injury (TBI) is a crucially important public health problem around the world, which gives rise to increased mortality and is the leading cause of physical and psychological disability in young adults, in particular. Pituitary dysfunction due to TBI was first described 95 years ago. However, until recently, only a few papers have been published in the literature and for this reason, TBI-induced hypopituitarism has been neglected for a long time. Recent studies have revealed that TBI is one of the leading causes of hypopituitarism. TBI which causes hypopituitarism may be characterized by a single head injury such as from a traffic accident or by chronic repetitive head trauma as seen in combative sports including boxing, kickboxing, and football. Vascular damage, hypoxic insult, direct trauma, genetic predisposition, autoimmunity, and neuroinflammatory changes may have a role in the development of hypopituitarism after TBI. Because of the exceptional structure of the hypothalamo-pituitary vasculature and the special anatomic location of anterior pituitary cells, GH is the most commonly lost hormone after TBI, and the frequency of isolated GHD is considerably high. TBI-induced pituitary dysfunction remains undiagnosed and therefore untreated in most patients because of the nonspecific and subtle clinical manifestations of hypopituitarism. Treatment of TBI-induced hypopituitarism depends on the deficient anterior pituitary hormones. GH replacement therapy has some beneficial effects on metabolic parameters and neurocognitive dysfunction. Patients with TBI without neuroendocrine changes and those with TBI-induced hypopituitarism share the same clinical manifestations, such as attention deficits, impulsion impairment, depression, sleep abnormalities, and cognitive disorders. For this reason, TBI-induced hypopituitarism may be neglected in TBI victims and it would be expected that underlying hypopituitarism would aggravate the clinical picture of TBI
Award Number: W81XWH-08-2-0017 TITLE: " Kevlar Vest Protection Against Blast Overpressure Brain Injury: Systemic Contributions to Injury Etiology...TITLE AND SUBTITLE 5a. CONTRACT NUMBER “ Kevlar Vest Protection Against Blast Overpressure Brain Injury: Systemic Contributions to Injury Etiology...traumatic brain injury (bTBI) is largely undefined. Along with reducing mortality, in preliminary experiments Kevlar vests significantly protected
An estimated 60.25% of offenders have a history of traumatic brain injury (TBI). There is currently no established valid or reliable screening tool for identifying female prisoners with a TBI and associated cognitive impairment available in the UK. Using a cross-sectional design, this study aimed to investigate the retest reliability and construct validity of the Brain Injury Screening Index (BISI). Convergent validity was explored using self-report measures of mood and neurodisability, as we...
Durham, William J; Foreman, Jack P; Randolph, Kathleen M; Danesi, Christopher P; Spratt, Heidi; Masel, Brian D; Summons, Jennifer R; Singh, Charan K; Morrison, Melissa; Robles, Claudia; Wolfram, Cindy; Kreber, Lisa A; Urban, Randall J; Sheffield-Moore, Melinda; Masel, Brent E
Individuals with a history of traumatic brain injury (TBI) are at increased risk for a number of disorders, including Alzheimer's disease, Parkinson's disease, and chronic traumatic encephalopathy. However, mediators of the long-term morbidity are uncertain. We conducted a multi-site, prospective trial in chronic TBI patients (∼18 years post-TBI) living in long-term 24-h care environments and local controls without a history of head injury. Inability to give informed consent was exclusionary for participation. A total of 41 individuals (17 moderate-severe TBI, 24 controls) were studied before and after consumption of a standardized breakfast to determine if concentrations of amino acids, cytokines, C-reactive protein, and insulin are potential mediators of long-term TBI morbidity. Analyte concentrations were measured in serum drawn before (fasting) and 1 h after meal consumption. Mean ages were 44 ± 15 and 49 ± 11 years for controls and chronic TBI patients, respectively. Chronic TBI patients had significantly lower circulating concentrations of numerous individual amino acids, as well as essential amino acids (p = 0.03) and large neutral amino acids (p = 0.003) considered as groups, and displayed fundamentally altered cytokine-amino acid relationships. Many years after injury, TBI patients exhibit abnormal metabolic responses and altered relationships between circulating amino acids, cytokines, and hormones. This pattern is consistent with TBI, inducing a chronic disease state in patients. Understanding the mechanisms causing the chronic disease state could lead to new treatments for its prevention.
J Gordon Millichap
Full Text Available The Behavior Rating Inventory of Executive Function (BRIEF, a caregiver-report questionnaire, was used to measure changes in executive function in the first year after traumatic brain injury (TBI in a study of children, aged 5 to 15 years, at University of Minnesota, Minneapolis, and Johns Hopkins University School of Medicine, Baltimore, MD.
Fortin, Audrey; Lefebvre, Mathilde Beaulieu; Ptito, Maurice
PRIMARY OBJECTIVE: Olfactory functions are not systematically evaluated following traumatic brain injury (TBI). This study aimed at comparing two smell tests that are used in a clinical setting. RESEARCH DESIGN: The University of Pennsylvania Smell Identification Test (UPSIT) and the Alberta Smell...
Aggarwal, Neil Krishan; Ford, Elizabeth
Neuroethics and neurolaw are fields of study that involve the interface of neuroscience with clinical and legal decision-making. The past two decades have seen increasing attention being paid to both fields, in large part because of the advances in neuroimaging techniques and improved ability to visualize and measure brain structure and function. Traumatic brain injury (TBI), along with its acute and chronic sequelae, has emerged as a focus of neuroethical issues, such as informed consent for treatment and research, diagnostic and prognostic uncertainties, and the subjectivity of interpretation of data. The law has also more frequently considered TBI in criminal settings for exculpation, mitigation and sentencing purposes and in tort and administrative law for personal injury, disability and worker's compensation cases. This article provides an overview of these topics with an emphasis on the current challenges that the neuroscience of TBI faces in the medicolegal arena.
Caeyenberghs, K.; Wenderoth, N.; Smits-Engelsman, B.C.M.; Sunaert, S.; Swinnen, S.P.
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 control
ARAKI, Takashi; YOKOTA, Hiroyuki; MORITA, Akio
Traumatic brain injury (TBI) is the leading cause of death and disability in children. Pediatric TBI is associated with several distinctive characteristics that differ from adults and are attributable to age-related anatomical and physiological differences, pattern of injuries based on the physical ability of the child, and difficulty in neurological evaluation in children. Evidence suggests that children exhibit a specific pathological response to TBI with distinct accompanying neurological symptoms, and considerable efforts have been made to elucidate their pathophysiology. In addition, recent technical advances in diagnostic imaging of pediatric TBI has facilitated accurate diagnosis, appropriate treatment, prevention of complications, and helped predict long-term outcomes. Here a review of recent studies relevant to important issues in pediatric TBI is presented, and recent specific topics are also discussed. This review provides important updates on the pathophysiology, diagnosis, and age-appropriate acute management of pediatric TBI. PMID:28111406
Kammersgaard, Lars Peter; Linnemann, Mia; Tibæk, Maiken
To investigate timing and clinical predictors that might predict hydrocephalus emerging during rehabilitation until 1 year following severe traumatic brain injury (TBI).......To investigate timing and clinical predictors that might predict hydrocephalus emerging during rehabilitation until 1 year following severe traumatic brain injury (TBI)....
Martinez, Sarah; Davalos, Deana
Objective: Executive dysfunction in college students who have had an acute traumatic brain injury (TBI) was investigated. The cognitive, behavioral, and metacognitive effects on college students who endorsed experiencing a brain injury were specifically explored. Participants: Participants were 121 college students who endorsed a mild TBI, and 121…
Atkins, Coleen M.; Oliva, Anthony A.; Alonso, Ofelia F.; Pearse, Damien D.; Bramlett, Helen M; Dietrich, W. Dalton
Traumatic brain injury (TBI) results in both focal and diffuse brain pathologies that are exacerbated by the inflammatory response and progress from hours to days after the initial injury. Using a clinically relevant model of TBI, the parasagittal fluid-percussion brain injury (FPI) model, we found injury-induced impairments in the cyclic AMP (cAMP) signaling pathway. Levels of cAMP were depressed in the ipsilateral parietal cortex and hippocampus, as well as activation of its downstream targ...
Norup, Anne; Perrin, Paul B; Cuberos-Urbano, Gustavo
OBJECTIVE: The objective of this study was to explore differences by country in the importance of family needs after traumatic brain injury (TBI), as well as differences in met/unmet needs. METHOD: Two hundred and seventy-one family members of an individual with TBI in Mexico, Colombia, Spain......, Denmark, and Norway completed the Family Needs Questionnaire. RESULTS: Eight of the ten needs rated as most important globally were from the Health Information subscale. Importance ratings on the Health Information, Professional Support, and Involvement With Care subscales were similar across countries......, but Mexican family members rated Instrumental Support needs as less important than Colombian, Spanish, and Danish family members, and also rated their Community Support needs as less important than Danish and Spanish family members. Mexican family member's rated emotional support needs as less important than...
Full Text Available Kenya has a disproportionately high rate of road traffic accidents each year, many of them resulting in traumatic brain injuries (TBIs. A review of articles written on issues pertaining to the medical treatment of people with TBI in the past 15 years in Kenya indicates a significantly high incidence of TBIs and a high mortality rate. This article reviews the available literature as a first step in exploring the status of rehabilitation of Kenyans with cognitive impairments and other disabilities resulting from TBIs. From this preliminary review, it is apparent that despite TBI being a pervasive public health problem in Kenya, it has not received due attention in the public and private sectors as evidenced by a serious lack of post-acute rehabilitation services for people with TBIs. Implications for this lack of services are discussed and recommendations are made for potential approaches to this problem.
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.…
Lopez-Rodriguez, Ana Belen; Acaz-Fonseca, Estefania; Giatti, Silvia; Caruso, Donatella; Viveros, Maria-Paz; Melcangi, Roberto C; Garcia-Segura, Luis M
Traumatic brain injury (TBI) is an important cause of disability in humans. Neuroactive steroids, such as progesterone and dehydroepiandrosterone (DHEA), are neuroprotective in TBI models. However in order to design potential neuroprotective strategies based on neuroactive steroids it is important to determine whether its brain levels are altered by TBI. In this study we have used a weight-drop model of TBI in young adult female mice to determine the levels of neuroactive steroids in the brain and plasma at 24h, 72 h and 2 weeks after injury. We have also analyzed whether the levels of neuroactive steroids after TBI correlated with the neurological score of the animals. TBI caused neurological deficit detectable at 24 and 72 h, which recovered by 2 weeks after injury. Brain levels of progesterone, tetrahydroprogesterone (THP), isopregnanolone and 17β-estradiol were decreased 24h, 72 h and 2 weeks after TBI. DHEA and brain testosterone levels presented a transient decrease at 24h after lesion. Brain levels of progesterone and DHEA showed a positive correlation with neurological recovery. Plasma analyses showed that progesterone was decreased 72 h after lesion but, in contrast with brain progesterone, its levels did not correlate with neurological deficit. These findings indicate that TBI alters the levels of neuroactive steroids in the brain with independence of its plasma levels and suggest that the pharmacological increase in the brain of the levels of progesterone and DHEA may result in the improvement of neurological recovery after TBI.
Traumatic brain injury (TBI) is a common occurrence in the United States, with an estimated incidence exceeding 1 million injuries per year. Cognitive, emotional, behavioral, and physical impairments are common sequelae of TBI and may, in a significant minority of patients, persist well into the late period following injury. The etiology of these symptoms in individuals with mild TBI is controversial, with hypotheses of postconcussive symptom formation variously ascribing greater or lesser we...
Merlo, Lucia; Cimino, Francesco; Angileri, Filippo Flavio; La Torre, Domenico; Conti, Alfredo; Cardali, Salvatore Massimiliano; Saija, Antonella; Germanò, Antonino
Extensive research and scientific efforts have been focused on the elucidation of the pathobiology of cellular and axonal damage following traumatic brain injury (TBI). Conversely, few studies have specifically addressed the issue of synaptic dysfunction. Synaptic junction proteins may be involved in post-TBI alterations, leading to synaptic loss or disrupted plasticity. A Synapse Protein Database on synapse ontology identified 109 domains implicated in synaptic activities and over 5000 proteins, but few of these demonstrated to play a role in the synaptic dysfunction after TBI. These proteins are involved in neuroplasticity and neuromodulation and, most importantly, may be used as novel neuronal markers of TBI for specific intervention.
traumatic brain injury ( TBI ). The main limitation to these earlier results is that VNS treatment was initiated at either 2 hr or 24 hr after TBI ...the potential utility of VNS as a clinical treatment for human TBI . 15. SUBJECT TERMS Vagus nerve stimulation, recovery of function, brain injury ... TBI induced by Controlled Cortical Impact. A brain injury was induced over the left hemisphere at the following coordinates: Epicenter: Midpoint
Blennow, Kaj; Hardy, John; Zetterberg, Henrik
The acute and long-term consequences of traumatic brain injury (TBI) have received increased attention in recent years. In this Review, we discuss the neuropathology and neural mechanisms associated with TBI, drawing on findings from sports-induced TBI in athletes, in whom acute TBI damages axons and elicits both regenerative and degenerative tissue responses in the brain and in whom repeated concussions may initiate a long-term neurodegenerative process called dementia pugilistica or chronic traumatic encephalopathy (CTE). We also consider how the neuropathology and neurobiology of CTE in many ways resembles other neurodegenerative illnesses such as Alzheimer's disease, particularly with respect to mismetabolism and aggregation of tau, β-amyloid, and TDP-43. Finally, we explore how translational research in animal models of acceleration/deceleration types of injury relevant for concussion together with clinical studies employing imaging and biochemical markers may further elucidate the neurobiology of TBI and CTE.
Ling, Helen; Hardy, John; Zetterberg, Henrik
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
A.C. Scholten (Annemieke)
markdownabstractInjuries are among the leading causes of death and disability in the world, often imposing great personal suffering and economic costs. An important severe injury that often affects young people is a traumatic brain injury (TBI). Over the past decades, the number of survivors of se
Yin, Xiang-Jie; Chen, Zhen-Yan; Zhu, Xiao-Na; Hu, Jin-Jia
Traumatic brain injury (TBI) is a principal cause of death and disability worldwide, which is a major public health problem. Death caused by TBI accounts for a third of all damage related illnesses, which 75% TBI occurred in low and middle income countries. With the increasing use of motor vehicles, the incidence of TBI has been at a high level. The abnormal brain functions of TBI patients often show the acute and long-term neurological dysfunction, which mainly associated with the pathological process of malignant brain edema and neuroinflammation in the brain. Owing to the neuroinflammation lasts for months or even years after TBI, which is a pivotal causative factor that give rise to neurodegenerative disease at late stage of TBI. Studies have shown that platelet activating factor (PAF) inducing inflammatory reaction after TBI could not be ignored. The morphological and behavioral abnormalities after TBI in wild type mice are rescued by general knockout of PAFR gene that neuroinflammation responses and cognitive ability are improved. Our results thus define a key inflammatory molecule PAF that participates in the neuroinflammation and helps bring about cerebral dysfunction during the TBI acute phase. PMID:28094295
Full Text Available Traumatic brain injury (TBI occurs when a sudden trauma causes brain damage. Depending on the severity, outcome can be anything from complete recovery to permanent disability or death. Emergency medical services play a dominant role in provision of primary care at the site of injury. Since little can be done to reverse the initial brain damage due to trauma, attempts to prevent further brain damage and stabilize the patient before he can be brought to a specialized trauma care centre play a pivotal role in the final outcome. Recognition and early treatment of hypoten-sion, hypoxemia, and hypoglycemia, objective neurological assessment based on GCS and pupils, and safe transport to an optimal care centre are the key elements of prehospital care of a TBI patient.
being less competent (Sawchyn, Mateer, & Suffi eld, 2005 ). Mild TBI has also been associated with greater emotional distress ( Leininger , Kreutzer...brain injury . Brain Injury , 23 , 83 – 91 . Leininger , B.E. , Kreutzer , J.S. , & Hill , M.R . ( 1991 ). Comparison of minor and severe
Roth, Theodore L.; Nayak, Debasis; Atanasijevic, Tatjana; Koretsky, Alan P.; Latour, Lawrence L.; McGavern, Dorian B.
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.
Laursen, Bjarne; Helweg-Larsen, Karin
To estimate the health service use over 9 years after the injury year for patients with traumatic brain injury (TBI), spinal cord injury (SCI) and pelvic fracture (PF), and compare with non-injured.......To estimate the health service use over 9 years after the injury year for patients with traumatic brain injury (TBI), spinal cord injury (SCI) and pelvic fracture (PF), and compare with non-injured....
Epstein, Daniel J.; Legarreta, Margaret; Bueler, Elliot; King, Jace; McGlade, Erin; Yurgelun‐Todd, Deborah
Abstract Introduction Although mild traumatic brain injury (mTBI) comprises 80% of all TBI, the morphological examination of the orbitofrontal cortex (OFC) in relation to clinical symptoms such as aggression, anxiety and depression in a strictly mTBI sample has never before been performed. Objectives The primary objective of the study was to determine if mTBI patients would show morphological differences in the OFC and if the morphology of this region would relate to clinical symptoms. Method...
Kuo, Jinn-Rung; Cheng, Yi-Hsuan; Chen, Yi-Shion; Chio, Chung-Ching; Gean, Po-Wu
Traumatic brain injury (TBI) is the most common cause of death and acquired disability among children and young adults in the developed countries. In clinical studies, the incidence of depression is high after TBI, and the mechanisms behind TBI-induced depression remain unclear. In the present study, we subjected rats to a moderate fluid percussion into the closed cranial cavity to induce TBI. After 3 days of recovery, injured rats were given a forced swim test (FST) and novelty-suppressed fe...
Tanriverdi, F; Agha, A; Aimaretti, G
Traumatic brain injury (TBI)-induced hypopituitarism remains a relevant medical problem, because it may affect a significant proportion of the population. In the last decade important studies have been published investigating pituitary dysfunction after TBI. Recently, a group of experts gathered...... and revisited the topic of TBI-induced hypopituitarism. During the 2-day meeting, the main issues of this topic were presented and discussed, and current understanding and management of TBI-induced hypopituitarism are summarized here....
Traumatic brain injury (TBI)-induced hypopituitarism remains a relevant medical problem, because it may affect a significant proportion of the population. In the last decade important studies have been published investigating pituitary dysfunction after TBI. Recently, a group of experts gathered and revisited the topic of TBI-induced hypopituitarism. During the 2-day meeting, the main issues of this topic were presented and discussed, and current understanding and management of TBI-induced hypopituitarism are summarized here.
Moss, W C; King, M J; Blackman, E G
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.
Zheng Gang Zhang
Full Text Available Stroke and traumatic brain injury (TBI damage white and grey matter. Loss of oligodendrocytes and their myelin, impairs axonal function. Remyelination involves oligodendrogenesis during which new myelinating oligodendrocytes are generated by differentiated oligodendrocyte progenitor cells (OPCs. This article briefly reviews the processes of oligodendrogenesis in adult rodent brains, and promising experimental therapies targeting the neurovascular unit that reduce oligodendrocyte damage and amplify endogenous oligodendrogenesis after stroke and TBI.
Das, Mahasweta; Wang, Chunyan; Bedi, Raminder; Mohapatra, Shyam S; Mohapatra, Subhra
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.
Anjali eRaja Beharelle
Full Text Available Traumatic brain injury (TBI patients typically respond more slowly and with more variability than controls during tasks of attention requiring speeded reaction time. These behavioral changes are attributable, at least in part, to diffuse axonal injury (DAI, which affects integrated processing in distributed systems. Here we use a multivariate method sensitive to distributed neural activity to compare brain activity patterns of patients with chronic phase moderate-to-severe TBI to those of controls during performance on a visual feature-integration task assessing complex attentional processes that has previously shown sensitivity to TBI. The TBI patients were carefully screened to be free of large focal lesions that can affect performance and brain activation independently of DAI. The task required subjects to hold either one or three features of a target in mind while suppressing responses to distracting information. In controls, the multi-feature condition activated a distributed network including limbic, prefrontal, and medial temporal structures. TBI patients engaged this same network in the single-feature and baseline conditions. In multi-feature presentations, TBI patients alone activated additional frontal, parietal, and occipital regions. These results are consistent with neuroimaging studies using tasks assessing different cognitive domains, where increased spread of brain activity changes was associated with TBI. Our results also extend previous findings that brain activity for relatively moderate task demands in TBI patients is similar to that associated with of high task demands in controls.
... Videos mild Traumatic Brain Injury 94447 reads Please Log in You must be logged in to access ... Brain Injury (DCoE) to promote the processes of building resilience, facilitating recovery and supporting reintegration of returning ...
Alted López, Emilio; Aznárez, Susana Bermejo; Fernández, Mario Chico
Traumatic brain injury (TBI) is an important reason of morbidity-mortality all over the world, affecting young males more and generating Public Health problem. Unfortunately, the advances in the pathophysiology knowledge have not followed a similar development in therapeutic options, there currently not being any contrasted neuroprotectants. In this article, we have reviewed the epidemiology, pathophysiology and therapeutic measures used in the management of patient with severe TBI. The general measures as well as those aimed at controlling intracranial hypertension, the role of the surgery and some more innovative therapeutic options currently under evaluation in these patients are analyzed.
Choi, Woo June; Qin, Wan; Qi, Xiaoli; Wang, Ruikang K.
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.
Jared F Benge
Full Text Available Moderate to severe traumatic brain injury (TBI is one of the leading causes of acquired epilepsy. Prophylaxis for seizures is the standard of care for individuals with moderate to severe injuries at risk for developing seizures, though relatively limited comparative data is available to guide clinicians in their choice of agents. There have however been experimental studies which demonstrate potential neuroprotective qualities of levetiracetam after TBI, and in turn there is hope that eventually such agents may improve neurobehavioral outcomes post-TBI. This mini-review summarizes the available studies and suggests areas for future studies.
Meng, Qingying; Zhuang, Yumei; Ying, Zhe; Agrawal, Rahul; Yang, Xia; Gomez-Pinilla, Fernando
The complexity of the traumatic brain injury (TBI) pathology, particularly concussive injury, is a serious obstacle for diagnosis, treatment, and long-term prognosis. Here we utilize modern systems biology in a rodent model of concussive injury to gain a thorough view of the impact of TBI on fundamental aspects of gene regulation, which have the potential to drive or alter the course of the TBI pathology. TBI perturbed epigenomic programming, transcriptional activities (expression level and alternative splicing), and the organization of genes in networks centered around genes such as Anax2, Ogn, and Fmod. Transcriptomic signatures in the hippocampus are involved in neuronal signaling, metabolism, inflammation, and blood function, and they overlap with those in leukocytes from peripheral blood. The homology between genomic signatures from blood and brain elicited by TBI provides proof of concept information for development of biomarkers of TBI based on composite genomic patterns. By intersecting with human genome-wide association studies, many TBI signature genes and network regulators identified in our rodent model were causally associated with brain disorders with relevant link to TBI. The overall results show that concussive brain injury reprograms genes which could lead to predisposition to neurological and psychiatric disorders, and that genomic information from peripheral leukocytes has the potential to predict TBI pathogenesis in the brain.
Full Text Available The complexity of the traumatic brain injury (TBI pathology, particularly concussive injury, is a serious obstacle for diagnosis, treatment, and long-term prognosis. Here we utilize modern systems biology in a rodent model of concussive injury to gain a thorough view of the impact of TBI on fundamental aspects of gene regulation, which have the potential to drive or alter the course of the TBI pathology. TBI perturbed epigenomic programming, transcriptional activities (expression level and alternative splicing, and the organization of genes in networks centered around genes such as Anax2, Ogn, and Fmod. Transcriptomic signatures in the hippocampus are involved in neuronal signaling, metabolism, inflammation, and blood function, and they overlap with those in leukocytes from peripheral blood. The homology between genomic signatures from blood and brain elicited by TBI provides proof of concept information for development of biomarkers of TBI based on composite genomic patterns. By intersecting with human genome-wide association studies, many TBI signature genes and network regulators identified in our rodent model were causally associated with brain disorders with relevant link to TBI. The overall results show that concussive brain injury reprograms genes which could lead to predisposition to neurological and psychiatric disorders, and that genomic information from peripheral leukocytes has the potential to predict TBI pathogenesis in the brain.
Pitkänen, A; Immonen, R; Ndode-Ekane, X; Gröhn, O; Stöhr, T; Nissinen, J
In a subgroup of patients, traumatic brain injury (TBI) results in the occurrence of acute epileptic seizures or even status epilepticus, which are treated with antiepileptic drugs (AEDs). Recent experimental data, however, suggest that administration of AEDs at the early post-injury phase can compromise the recovery process. The present study was designed to assess the profile of a novel anticonvulsant, lacosamide (Vimpat) on post-TBI structural, motor and cognitive outcomes. Moderate TBI was induced by lateral fluid-percussion injury in adult rats. Treatment with 0.9% saline or lacosamide (30 mg/kg, i.p.) was started at 30 min post-injury and continued at 8h intervals for 3d (total daily dose 90 mg/kg/d). Rats were randomly assigned to 4 treatment groups: sham-operated controls treated with vehicle (Sham-Veh) or lacosamide (Sham-LCM) and injured animals treated with vehicle (TBI-Veh) or lacosamide (TBI-LCM). As functional outcomes we tested motor recovery with composite neuroscore and beam-walking at 2, 7, and 15 d post-injury. Cognitive recovery was tested with the Morris water-maze at 12-14 d post-TBI. To assess the structural outcome, animals underwent magnetic resonance imaging (MRI) at 2 d post-TBI. At 16d post-TBI, rats were perfused for histology to analyze cortical and hippocampal neurodegeneration and axonal damage. Our data show that at 2 d post-TBI, both the TBI-Veh and TBI-LCM groups were equally impaired in neuroscore. Thereafter, motor recovery occurred similarly during the first week. At 2 wk post-TBI, recovery of the TBI-LCM group lagged behind that in the TBI-VEH group (p<0.05). Performance in beam-walking did not differ between the TBI-Veh and TBI-LCM groups. Both TBI groups were similarly impaired in the Morris water-maze at 2 wk post-TBI. MRI and histology did not reveal any differences in the cortical or hippocampal damage between the TBI-Veh and TBI-LCM groups. Taken together, acute treatment with LCM had no protective effects on post-TBI
Sillesen, Martin; Johansson, Pär I; Rasmussen, Lars S
Traumatic brain injury (TBI) and hemorrhage are the leading causes of trauma-related mortality. Both TBI and hemorrhage are associated with coagulation disturbances, including platelet dysfunction. We hypothesized that platelet dysfunction could be detected early after injury, and that this dysfu...
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.
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…
Nizamutdinov, Damir; Shapiro, Lee A.
Traumatic brain injury (TBI) afflicts people of all ages and genders, and the severity of injury ranges from concussion/mild TBI to severe TBI. Across all spectrums, TBI has wide-ranging, and variable symptomology and outcomes. Treatment options are lacking for the early neuropathology associated with TBIs and for the chronic neuropathological and neurobehavioral deficits. Inflammation and neuroinflammation appear to be major mediators of TBI outcomes. These systems are being intensively studies using animal models and human translational studies, in the hopes of understanding the mechanisms of TBI, and developing therapeutic strategies to improve the outcomes of the millions of people impacted by TBIs each year. This manuscript provides an overview of the epidemiology and outcomes of TBI, and presents data obtained from animal and human studies focusing on an inflammatory and immunological context. Such a context is timely, as recent studies blur the traditional understanding of an “immune-privileged” central nervous system. In presenting the evidence for specific, adaptive immune response after TBI, it is hoped that future studies will be interpreted using a broader perspective that includes the contributions of the peripheral immune system, to central nervous system disorders, notably TBI and post-traumatic syndromes. PMID:28124982
Marshall, Kathryn R; Holland, Sherray L; Meyer, Kimberly S; Martin, Elisabeth Moy; Wilmore, Michael; Grimes, Jamie B
The majority of combat-related traumatic brain injury (TBI) within the U.S. Armed Forces is mild TBI (mTBI). This article focuses specifically on the screening, diagnosis, and treatment aspects of mTBI within the military community. Aggressive screening measures were instituted in 2006 to ensure that the mTBI population is identified and treated. Screenings occur in-theater, outside the contiguous United States, and in-garrison. We discuss specific screening procedures at each screening setting. Current diagnosis of mTBI is based upon self-report or through witnesses to the event. TBI severity is determined by specific Department of Defense criteria. Abundant clinician resources are available for mTBI in the military health care setting. Education resources for both the patient and the clinician are discussed in detail. An evidence-based clinical practice guideline for the care of mTBI was created through collaborative efforts of the DoD and the U.S. Department of Veterans Affairs. Although symptoms following mTBI generally resolve with time, active treatment is centered on symptom management, supervised rest, recovery, and patient education. Medical specialty care, ancillary services, and other therapeutic services may be required.
Lin, Yunpeng; Luo, Lan Lan; Sun, Jian; Gao, Weiwei; Tian, Ye; Park, Eugene; Baker, Andrew; Chen, Jieli; Jiang, Rongcai; Zhang, Jianning
To investigate the changes of circulating endothelial progenitor cells (EPCs) and stromal cell-derived factor-1α (SDF-1α)/CXCR4 expression in patients with mild traumatic brain injury (TBI) and the correlation between EPC level and the prognosis of mild TBI. 72 TBI patients (57 mild TBI, 15 moderate TBI patients) and 25 healthy subjects (control) were included. The number of circulating EPCs, CD34+, and CD133+ cells and the percentage of CXCR4+ cells in each cell population at 1,4,7,14,21 days after TBI were counted by flow cytometer. SDF-1α levels in serum were detected by ELISA assay. The patients were divided into poor and good prognosis groups based on Extended Glasgow Outcome Scale and Activity of Daily Living Scale at 3 months after TBI. Correlation analysis between each detected index and prognosis of mild TBI was performed. Moderate TBI patients have higher levels of SDF-1α and CXCR4 expression than mild TBI patients (P < 0.05). The percentage of CXCR4+ EPCs at day 7 post-TBI was significantly higher in mild TBI patients with poor prognosis than the ones with good prognosis (P < 0.05). HAMA and HAMD scores in mild TBI patients were significantly lower than moderate TBI patients (P < 0.05) in early term. The percentage of CXCR4+ EPCs at day 7 after TBI was significantly correlated with the prognosis outcome at 3 months. The mobilization of circulating EPCs can be induced in mild TBI. The expression of CXCR4+ in EPCs at 7 days after TBI reflects the short-term prognosis of brain injury, and could be a potential biological marker for prognosis prediction of mild TBI. PMID:28203485
Grundy, P L; Patel, N; Harbuz, M S; Lightman, S L; Sharples, P M
Nerve growth factor (NGF) expression in the rat hippocampus is increased after experimental traumatic brain injury (TBI) and is neuroprotective. Glucocorticoids are regulators of brain neurotrophin levels and are often prescribed following TBI. The effect of adrenalectomy (ADX) and corticosterone (CORT) replacement on the expression of NGF mRNA in the hippocampus after TBI has not been investigated to date. We used fluid percussion injury and in situ hybridisation to evaluate the expression of NGF mRNA in the hippocampus 4 h after TBI in adrenal-intact or adrenalectomised rats (with or without CORT replacement). TBI increased expression of NGF mRNA in sham-ADX rats, but not in ADX rats. Furthermore, CORT replacement in ADX rats restored the increase in NGF mRNA induced by TBI. These findings suggest that glucocorticoids have an important role in the induction of hippocampal NGF mRNA after TBI.
LU Yi; HUI Guo-zhen; WU Zhi-yuan; GUO Li-he; JI Xun-he; WU Xin
@@ Traumatic brain injury (TBI), which is an important reason of human mortality and morbidity in industrialized countries, still cannot be treated effectively. Since the self-repair capacity of brain is limited, cellular transplantation in TBI may be a therapeutic option.
Full Text Available Huiling Huang,1 Lin Chen,2,3 Hongyun Huang4–61Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin Neurosurgical Institute, Tianjin, People's Republic of China; 2Medical Center, Tsinghua University, Beijing, People's Republic of China; 3Tsinghua University Yuquan Hospital, Beijing, People's Republic of China; 4General Hospital of Chinese people's Armed Police Forces, 5Beijing Rehabilitation Hospital of Capital Medical University, Beijing, People's Republic of China; 6Beijing Hongtianji Neuroscience Academy, Beijing, People's Republic of ChinaAbstract: Traumatic brain injury (TBI is a leading cause of death and disability from trauma to the central nervous system. Besides the surgical interventions and symptomatic management, the conventional therapies for TBI and its sequelae are still limited. Recently emerging evidence suggests that some neurorestorative treatments appear to have a potential therapeutic role for TBI and improving the patient's quality of life. The current clinical neurorestorative strategies available in TBI include pharmacological treatments (recombinant human interleukin-1 receptor antagonist, amantadine, lithium, and valproate, the neuromodulation treatments (repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and low-level laser therapy, cell transplantation (bone marrow stromal cells and umbilical cord stromal cells, and combined neurorehabilitation. In this review, we summarize the recent clinical neurorestorative progress in the management of neurodegeneration as well as cognitive and motor deficits after TBI; indeed further clinical trials are required to provide more robust evidence.Keywords: brain trauma, neurorestorative treatment, cell transplantation, clinical study
Full Text Available 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.We report on the prevalence of adolescent TBI and its associations with energy drinks, alcohol and energy drink mixed in with alcohol consumption.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.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.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.TBI remains a disabling and common condition among adolescents and the consumption of alcohol, energy drinks, and alcohol
Knox, Lucy; Douglas, Jacinta
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…
Journal Article 3. DATES COVERED (From – To) Aug 2008 – Dec 2013 4. TITLE AND SUBTITLE The Effect of Hyperbaric Oxygen on Symptoms after Mild...absolute (ATA) hyperbaric oxygen (HBO2) on post-concussion symptoms in 50 military service members with at least one combat-related, mild traumatic brain...symptoms after mild TBI. 15. SUBJECT TERMS: hyperbaric oxygen, HBOT, HBO, HBO2, traumatic brain injury, TBI, mTBI, post-traumatic stress disorder, PTSD
Abstract Background Traumatic brain injury (TBI) evokes a systemic immune response including leukocyte migration into the brain and release of pro-inflammatory cytokines; however, the mechanisms underlying TBI pathogenesis and protection are poorly understood. Due to the high incidence of head trauma in the sports field, battlefield and automobile accidents identification of the molecular signals involved in TBI progression is critical for the development of novel therapeutics. Methods In thi...
Anderson, Vicki; Beauchamp, Miriam Helen; Yeates, Keith Owen; Crossley, Louise; Ryan, Nicholas Peter; Hearps, Stephen J C; Catroppa, Cathy
Children with traumatic brain injury (TBI) are at risk of social impairment, but research is yet to document the trajectory of these skills post-injury and factors that may predict social problems. The study addressed these gaps in knowledge, reporting on findings from a prospective, longitudinal follow-up study which investigated social outcomes post injury and explored factors contributing to these outcomes at 2 years post-injury. The sample included 113 children, 74 with TBI and 39 typically developing (TD) controls. TBI participants were recruited on presentation to hospital. Parents rated pre-injury function at that time and all children underwent magnetic resonance imaging (MRI) scan. Participants were followed up at 2 years post-injury. Outcomes were social adjustment, social participation, social relationships, and social cognition. Predictors of social outcomes examined included brain lesion characteristics, child cognition (6 months post-TBI) and behavior and environmental factors (pre-injury and 2 years). Reduced social adjustment (p=.011) and social participation (pchildren with TBI compared to TD controls. Poor social adjustment was predicted by externalizing behaviour problems and younger age at injury. Reduced social participation was linked to internalizing behavior problems. Greater lesion volume, lower socioeconomic status and family burden contributed to poorer social relationships, while age at injury predicted social cognition. Within the TBI group, 23% of children exhibited social impairment: younger age at injury, greater pre-injury and current behavior problems and family dysfunction, poorer IQ, processing speed, and empathy were linked to impairment. Further follow-up is required to track social recovery and the influences of cognition, brain, and environment over time.
Imam, Ayesha M; Jin, Guang; Sillesen, Martin
Combination of traumatic brain injury (TBI) and hemorrhagic shock (HS) can result in significant morbidity and mortality. We have previously shown that early administration of fresh frozen plasma (FFP) in a large animal model of TBI and HS reduces the size of the brain lesion as well as the assoc......Combination of traumatic brain injury (TBI) and hemorrhagic shock (HS) can result in significant morbidity and mortality. We have previously shown that early administration of fresh frozen plasma (FFP) in a large animal model of TBI and HS reduces the size of the brain lesion as well...
Grove, Michael J.
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…
Hartings, Jed A; Vidgeon, Steven; Strong, Anthony J;
OBJECT: Mass lesions from traumatic brain injury (TBI) often require surgical evacuation as a life-saving measure and to improve outcomes, but optimal timing and surgical technique, including decompressive craniectomy, have not been fully defined. The authors compared neurosurgical approaches...... enrolled in the Co-Operative Studies on Brain Injury Depolarizations (COSBID) at King's College Hospital (KCH, n = 27) and Virginia Commonwealth University (VCU, n = 24) from July 2004 to March 2010. Subdural electrode strips were placed at the time of surgery for subsequent electrocorticographic...
DU Ai-ling; JI Tai-ling; YANG Bin; CAO Jian-feng; ZHANG Xing-guang; LI Yu; PAN Shun
Background Traumatic brain injury (TBI) is a major cause of death and disability in children and young adults worldwide.Therefore,we investigated the role of AG490 in regulating brain oedema,expression of CD40 and neurological function after TBI.Methods Sprague Dawley rats (n=240) were randomly divided into a sham operation group,TBl+saline group and TBI+AG490 (JAK/STAT inhibitor) group.Members of each group were euthanized at 6,12,24 or 72 hours after injury.Neurological severity score (NSS) was used to evaluate the severity of neurological damage.Brain water was quantitated by wet/dry weight method.The expression of CD40 was assessed by flow cytometry.Results In both the TBl+saline group and the TBI+AG490 group,the brain water content was elevated after TBI,reached a peak at 24-hour and remained high for the rest of the period investigated; the expression of CD40 reached a peak 24hours after TBI; the NSS was elevated after TBI and then decreased after 6 hours.Elevations in the level of CD40,degree of brain edema and NSS after TBI were significantly reduced in TBI+AG490 group.Conclusion Inhibition of the JAK/STAT signalling pathway reduces brain oedema,decreases the expression of CD40 and exerts neuroprotective effects after TBI.
Full Text Available 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.
Aims\\ud Many patients experience physical, behavioural, cognitive and emotional problems following traumatic brain injury (TBI). They may require continuing care for many years, most of which is provided by informal caregivers, such as spouses, parents, or other family members. The caregiving role is associated with a range of adverse effects including anxiety, depression, poor physical health and lowered quality of life. This article explores issues around caregiver stress; highlighting inte...
Kramer, Daniel R.; Winer, Jesse L.; B. A. Matthew Pease; Arun P. Amar; Mack, William J.
Vasospasm following traumatic brain injury (TBI) may dramatically affect the neurological and functional recovery of a vulnerable patient population. While the reported incidence of traumatic vasospasm ranges from 19%–68%, the true incidence remains unknown due to variability in protocols for its detection. Only 3.9%–16.6% of patients exhibit clinical deficits. Compared to vasospasm resulting from aneurysmal SAH (aSAH), the onset occurs earlier and the duration is shorter. Overall, the clinic...
Traumatic brain injury ( TBI ) is a life-altering... TBI , traumatic brain injury anuary 2010Helmet-use data from the DCIPS fıle specifıed whether helmet was worn, not worn, or unknown during the...78.3 9.5) 12.2 78.0 9.6) 12.4 ation nd Tcessing System; TBI , traumatic brain injury www.ajpm-online.net p s d E r o r r g p m p s m p T a b c C
Rose Dawn Bharath
Full Text Available 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. 25 subjects with mild head injury were longitudinally evaluated within 36 hours, 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 three months, the majority of the ROI pairs had decreased connectivity in mTBI population, which increased and became comparable to healthy controls at 6 months. Initial imaging within 36 hours of injury revealed hyper connectivity predominantly involving the salience network and default mode network, which reduced at 3 months when lingual, inferior frontal and fronto-parietal networks revealed hyper connectivity. At six months all the evaluated networks revealed hyper connectivity and became comparable to the healthy controls. 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 3-6 months after injury. Hyper connectivity of several networks supported normal recovery in the first six months and it remains to be seen in future studies whether this can predict an early and efficient recovery of brain function.
Bigler, Erin D
The expectation for moderate to severe traumatic brain injury (TBI) is permanent damage and lasting deficits. However, in a multicenter investigation, Schneider et al.(1) show that by 1 year postinjury, one-fourth of patients with TBI achieve disability-free recovery (DFR), defined as a score of zero on the Disability Rating Scale. Of importance, cognitive reserve (CR) in the form of educational attainment was related to DFR.
Lei, Jin; Gao, Guo-Yi; Jiang, Ji-Yao
【Abstract】 Objective: To evaluate all the possible therapeutic measures concerning the acute management of traumatic brain injury (TBI) mentioned in Cochrane System-atic Reviews published in the Cochrane Database of Sys-tematic Reviews (CDSR). Methods: An exhausted literature search for all pub-lished Cochrane Systematic Reviews discussing therapeu-tic rather than prevention or rehabilitative interventions of TBI was conducted. We retrieved such databases as CDSR and Coch...
King, Nigel S
A number of controversies and debates have arisen over the years surrounding the dual diagnosis of post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI). Many of these have centred around the around the degree of protection provided by TBI against developing the disorder. The following is brief review of the literature in this area to help resolve some of these issues and to address a number of specific challenges which arise when working with this patient group.
Sillesen, Martin; Rasmussen, Lars Simon; Jin, Guang;
Traumatic brain injury (TBI) and hemorrhagic shock (HS) can be associated with coagulopathy and inflammation, but the mechanisms are poorly understood. We hypothesized that a combination of TBI and HS would disturb coagulation, damage the endothelium, and activate inflammatory and complement...
Cuisinier, Adrien; Maufrais, Claire; Payen, Jean-François; Nottin, Stephane; Walther, Guillaume; Bouzat, Pierre
Background The concept of brain-heart interaction has been described in several brain injuries. Traumatic brain injury (TBI) may also lead to cardiac dysfunction but evidences are mainly based upon experimental and clinical retrospective studies. Methods We conducted a prospective case-control study in a level I trauma center. Twenty consecutive adult patients with severe TBI were matched according to age and gender with 20 control patients. The control group included adult patients undergoin...
Huang, Xian-jian; Mao, Qing; Lin, Yong; Feng, Jun-Feng; Jiang, Ji-Yao
During the secondary injury period after traumatic brain injury (TBI), depolarization of neurons mediated by voltage-gated sodium channels (VGSCs) leads to cellular abnormalities and neurological dysfunction. Alterations in expression of different α subunits of VGSCs can affect early brain pathology following TBI. This study detected the expression of Nav1.3 mRNA and protein in the rat cortex post-TBI. Adult male Sprague–Dawley rats were randomly assigned to sham-TBI, mild-TBI (mTBI), or seve...
Teng, Sophie X; Katz, Paige S; Maxi, John K; Mayeux, Jacques P; Gilpin, Nicholas W; Molina, Patricia E
Traumatic brain injury (TBI) represents a leading cause of morbidity and mortality among young individuals. Alcohol abuse is a risk factor associated with increased TBI incidence. In addition, up to 26% of TBI patients engage in alcohol consumption after TBI. Limited preclinical studies have examined the impact of post-injury alcohol exposure on TBI recovery. The aim of this study was to determine the isolated and combined effects of TBI and alcohol on cognitive, behavioral, and physical recovery, as well as on associated neuroinflammatory changes. Male Sprague-Dawley rats (∼300g) were subjected to a mild focal TBI by lateral fluid percussion (∼30PSI, ∼25ms) under isoflurane anesthesia. On day 4 after TBI, animals were exposed to either sub-chronic intermittent alcohol vapor (95% ethanol 14h on/10h off; BAL∼200mg/dL) or room air for 10days. TBI induced neurological dysfunction reflected by an increased neurological severity score (NSS) showed progressive improvement in injured animals exposed to room air (TBI/air). In contrast, TBI animals exposed to alcohol vapor (TBI/alcohol) showed impaired NSS recovery throughout the 10-day period of alcohol exposure. Open-field exploration test revealed an increased anxiety-like behavior in TBI/alcohol group compared to TBI/air group. Additionally, alcohol-exposed animals showed decreased locomotion and impaired novel object recognition. Immunofluorescence showed enhanced reactive astrocytes, microglial activation, and HMGB1 expression localized to the injured cortex of TBI/alcohol as compared to TBI/air animals. The expression of neuroinflammatory markers showed significant positive correlation with NSS. These findings indicated a close relationship between accentuated neuroinflammation and impaired neurological recovery from post-TBI alcohol exposure. The clinical implications of long-term consequences in TBI patients exposed to alcohol during recovery warrant further investigation.
Taylor, Mary Ellen; Sanner, Jennifer E.
Sports-related concussion or traumatic brain injury (TBI) is a frequent occurrence among high school athletes. Long-term and short-term effects of TBI on the athlete's developing brain can be minimized if the athlete reports and is effectively treated for TBI symptoms. Knowledge of concussion symptoms and a school culture of support are critical…
Full Text Available Traumatic brain injury (TBI is a major cause of death and disability worldwide, especially in children and young adults. TBI is an example of a medical condition where there are still major lacks in diagnostics and outcome prediction. Here we apply comprehensive metabolic profiling of serum samples from TBI patients and controls in two independent cohorts. The discovery study included 144 TBI patients, with the samples taken at the time of hospitalization. The patients were diagnosed as severe (sTBI; n = 22, moderate (moTBI; n = 14 or mild TBI (mTBI; n = 108 according to Glasgow Coma Scale. The control group (n = 28 comprised of acute orthopedic non-brain injuries. The validation study included sTBI (n = 23, moTBI (n = 7, mTBI (n = 37 patients and controls (n = 27. We show that two medium-chain fatty acids (decanoic and octanoic acids and sugar derivatives including 2,3-bisphosphoglyceric acid are strongly associated with severity of TBI, and most of them are also detected at high concentrations in brain microdialysates of TBI patients. Based on metabolite concentrations from TBI patients at the time of hospitalization, an algorithm was developed that accurately predicted the patient outcomes (AUC = 0.84 in validation cohort. Addition of the metabolites to the established clinical model (CRASH, comprising clinical and computed tomography data, significantly improved prediction of patient outcomes. The identified ‘TBI metabotype’ in serum, that may be indicative of disrupted blood-brain barrier, of protective physiological response and altered metabolism due to head trauma, offers a new avenue for the development of diagnostic and prognostic markers of broad spectrum of TBIs.
Zhao, Jinbing; Chen, Zhi; Xi, Guohua; Keep, Richard F; Hua, Ya
Acute post-traumatic ventricular dilation and hydrocephalus are relatively frequent consequences of traumatic brain injury (TBI). Several recent studies have indicated that high iron levels in brain may relate to hydrocephalus development after intracranial hemorrhage. However, the role of iron in the development of post-traumatic hydrocephalus is still unclear. This study was to determine whether or not iron has a role in hydrocephalus development after TBI. TBI was induced by lateral fluid-percussion in male Sprague-Dawley rats. Some rats had intraventricular injection of iron. Acute hydrocephalus was measured by magnetic resonance T2-weighted imaging and brain hemorrhage was determined by T2* gradient-echo sequence imaging and brain hemoglobin levels. The effect of deferoxamine on TBI-induced hydrocephalus was examined. TBI resulted in acute hydrocephalus at 24 h (lateral ventricle volume: 24.1 ± 3.0 vs. 9.9 ± 0.2 mm(3) in sham group). Intraventricular injection of iron also caused hydrocephalus (25.7 ± 3.4 vs. 9.0 ± 0.6 mm(3) in saline group). Deferoxamine treatment attenuated TBI-induced hydrocephalus and heme oxygenase-1 upregulation. In conclusion, iron may contribute to acute hydrocephalus after TBI.
Full Text Available 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.
Dora Szymanowicz, OD, MS
Full Text Available Vergence dysfunction in individuals with mild traumatic brain injury (mTBI may have a negative effect on quality of life, functional abilities, and rehabilitative progress. In this study, we used a range of dynamic and static objective and subjective measures of vergence to assess 21 adult patients with mTBI and nearwork symptoms. The results were compared with 10 control adult subjects. With respect to dynamic parameters, responses in those with mTBI were slowed, variable, and delayed. With respect to static parameters, reduced near point of convergence and restricted near vergence ranges were found in those with mTBI. The present results provide evidence for the substantial adverse effect of mTBI on vergence function.
Traumatic brain injury (TBI) is frequently complicated by disinhibition and aggression. These often profound changes in personality, present obstacles to rehabilitative treatments and community reentry. Syndromal presentations may involve a loss of impulse control, spontaneous aggression, and dysphoric bipolar states. Common neuropathological findings of inferior frontal lobe dysfunction support both disinhibition and kindling models of TBI-induced aggression. Assessment of these highly disruptive symptoms requires detailed historical, clinical, and neuropsychological information to formulate appropriate strategies. Management of TBI-related aggression may involve pharmacological, environmental, and psychotherapeutic strategies that incorporate caregiver training and support.
Full Text Available Background Traumatic brain injury (TBI is a worldwide problem, especially in countries with high incidence of road traffic accidents such as Iran. Patients with a single occurrence of TBI have been shown to be at increased risk to sustain future TBI. Objectives The aim of this study was to present the incidence and characteristics of repeated TBI (RTBI in Iranian patients. Patients and Methods During one year, all admitted TBI patients with prior TBI history were enrolled into the study. In each patient, data such as age, gender, past medical history, injury cause, anatomic site of injury, TBI severity, clinical findings and CT scan findings were collected. Results RTBI comprised 2.5% of TBI cases (41 of 1629. The incidence of RTBI per 100,000 individuals per years was 9.7. The main cause of RTBI was road traffic accident (68.3%; 9.7 % of cases had preexisting seizure/epilepsy disorder; 36.6% of patients with RTBI had pervious ICU admission due to severe TBI. Ten patients had Glasgow coma scale (GCS ≤ 13 (24.4%. Seizure was seen in seven patients (17.1%. Thirty-nine percent of patients with RTBI had associated injuries. Eleven patients had abnormal CT scan findings (26.9%. Conclusions Considering the high incidence of trauma in developing countries, RTBI may also be more common compared with that of developed countries. This mandates a newer approach to preventive strategies, particularly in those with a previous experience of head injury.
Full Text Available 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.
Nathan, Dominic E; Bellgowan, Julie F; Oakes, Terrence R; French, Louis M; Nadar, Sreenivasan R; Sham, Elyssa B; Liu, Wei; Riedy, Gerard
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.
Full Text Available Secondary injuries especially extremity fractures may be seen concurrently with traumatic brain injury (TBI. Peripheral nerve damages may accompany to these fractures and may be missed out, especially in acute stage. In this case report; damage of radial, ulnar and median nerves which was developed secondarily to distal humerus fracture that could not be detected in acute stage, in a patient who had motor vehicle accident (MVA. 29-year-old male patient was admitted with weakness in the right upper extremity. 9 months ago, he had traumatic brain injury because of MVA, and fracture of distal humerus was detected in follow-ups. Upon the suspect of the peripheral nerve injury, the diagnosis was confirmed with ENMG. The patient responded well to the rehabilitation program treatment. In a TBI patient, it must be kept in mind that there might be a secondary trauma and therefore peripheral nerve lesions may accompany to TBI.
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
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.
Kane, Michael J; Pérez, Mariana Angoa; Briggs, Denise I.; Viano, David C.; Kreipke, Christian W.; Kuhn, Donald M.
A novel method for the study of repetitive mild traumatic brain injury (rmTBI) that models the most common form of head injury in humans is presented. Existing animal models of TBI impart focal, severe damage unlike that seen in repeated and mild concussive injuries, and few are configured for repetitive application. Our model is a modification of the Marmarou weight drop method and allows repeated head impacts to lightly anesthetized mice. A key facet of this method is the delivery of an imp...
Nicole M Wilson
Full Text Available 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 (cAMP, 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 hr and 6 hr after TBI. PDE4B2 and 4D2 were also significantly increased at 1, 6 and 24 hr after TBI. Additionally, phosphorylation of PDE4A was significantly increased at 6 and 24 hr 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 hr 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 LTP into long-lasting LTP. Overall, these results identify several possible PDE targets for reducing hippocampal synaptic plasticity deficits and improving cognitive dysfunction acutely after TBI.
Opara, J A; Małecka, E; Szczygiel, J
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.
Full Text Available Abstract 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
Yattoo, Gh; Tabish, Amin
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.
Hawryluk, Gregory W J; Bullock, M Ross
Traumatic brain injury (TBI) is the greatest cause of death and severe disability in young adults; its incidence is increasing in the elderly and in the developing world. Outcome from severe TBI has improved dramatically as a result of advancements in trauma systems and supportive critical care, however we remain without a therapeutic which acts directly to attenuate brain injury. Recognition of secondary injury and its molecular mediators has raised hopes for such targeted treatments. Unfortunately, over 30 late-phase clinical trials investigating promising agents have failed to translate a therapeutic for clinical use. Numerous explanations for this failure have been postulated and are reviewed here. With this historical context we review ongoing research and anticipated future trends which are armed with lessons from past trials, new scientific advances, as well as improved research infrastructure and funding. There is great hope that these new efforts will finally lead to an effective therapeutic for TBI as well as better clinical management strategies.
O'Connell, Karen M; Littleton-Kearney, Marguerite T
Traumatic brain injury (TBI) is a significant cause of death and disability in both the civilian and the military populations. The primary impact causes initial tissue damage, which initiates biochemical cascades, known as secondary injury, that expand the damage. Free radicals are implicated as major contributors to the secondary injury. Our review of recent rodent and human research reveals the prominent role of the free radicals superoxide anion, nitric oxide, and peroxynitrite in secondary brain injury. Much of our current knowledge is based on rodent studies, and the authors identified a gap in the translation of findings from rodent to human TBI. Rodent models are an effective method for elucidating specific mechanisms of free radical-induced injury at the cellular level in a well-controlled environment. However, human TBI does not occur in a vacuum, and variables controlled in the laboratory may affect the injury progression. Additionally, multiple experimental TBI models are accepted in rodent research, and no one model fully reproduces the heterogeneous injury seen in humans. Free radical levels are measured indirectly in human studies based on assumptions from the findings from rodent studies that use direct free radical measurements. Further study in humans should be directed toward large samples to validate the findings in rodent studies. Data obtained from these studies may lead to more targeted treatment to interrupt the secondary injury cascades.
Stevens, Michael C; Lovejoy, David; Kim, Jinsuh; Oakes, Howard; Kureshi, Inam; Witt, Suzanne T
Several reports show that traumatic brain injury (TBI) results in abnormalities in the coordinated activation among brain regions. Because most previous studies examined moderate/severe TBI, the extensiveness of functional connectivity abnormalities and their relationship to postconcussive complaints or white matter microstructural damage are unclear in mild TBI. This study characterized widespread injury effects on multiple integrated neural networks typically observed during a task-unconstrained "resting state" in mild TBI patients. Whole brain functional connectivity for twelve separate networks was identified using independent component analysis (ICA) of fMRI data collected from thirty mild TBI patients mostly free of macroscopic intracerebral injury and thirty demographically-matched healthy control participants. Voxelwise group comparisons found abnormal mild TBI functional connectivity in every brain network identified by ICA, including visual processing, motor, limbic, and numerous circuits believed to underlie executive cognition. Abnormalities not only included functional connectivity deficits, but also enhancements possibly reflecting compensatory neural processes. Postconcussive symptom severity was linked to abnormal regional connectivity within nearly every brain network identified, particularly anterior cingulate. A recently developed multivariate technique that identifies links between whole brain profiles of functional and anatomical connectivity identified several novel mild TBI abnormalities, and represents a potentially important new tool in the study of the complex neurobiological sequelae of TBI.
Robert L. Ruff
Full Text Available 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.
Pedersen, Martin Volmer; Helweg-Larsen, Rehannah Borup; Nielsen, Finn Cilius;
Cerebral responses to traumatic brain injury (TBI) include up- and downregulation of a vast number of proteins involved in endogenous inflammatory responses and defense mechanisms developing postinjury. The present study analyzed the global gene expression profile in response to cryo-induced TBI...... at various time-points postlesion (6 h, 1 day and 4 days). The effects of injury, treatment, and injury-treatment interaction were observed. TBI alone rendered a large number of genes affected. Analysis of lesion and treatment interactions resulted in a clear effect of the interaction between injury and FGL......-treatment compared to injury and placebo-treatment. Genes affected by TBI alone included inflammation markers, protein kinases, ion channel members and growth factors. Genes encoding regulators of apoptosis, signal transduction and metabolism were altered by the interaction between FGL-treatment and TBI. FGL...
incidence of post - traumatic stress disorder and suicide .112 Efforts to treat TBI in the field include avoiding hypotension and secondary brain injury...378-384. 19 Harhangi BS, Kompanje JO, Leebeek FWG, et al. Coagulation disorders after traumatic brain injury. Acta Neurochir. 2008;150;165-175...K, Xu X-M. MicroRNA in central nervous system trauma and degenerative disorders . Physiol Genomics. 2011;43:571-580. 37. Hoyt DB. Post hoc ergo
Pfister, Bryan J; Chickola, Larry; Smith, Douglas H
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.
Chun-Chuan Shih; Hsun-Hua Lee; Ta-Liang Chen; Chin-Chuan Tsai; Hsin-Long Lane; Wen-Ta Chiu; Chien-Chang Liao
Background. Little research exists on acupuncture treatment's effect on patients with traumatic brain injury (TBI). Methods. Using Taiwan's National Health Insurance Research Database, we conducted a cohort study to compare the use of emergency care and hospitalization in TBI patients with and without acupuncture treatment in the first year after TBI. The adjusted relative risks (RRs) and 95% confidence intervals (CIs) of high use of emergency care and hospitalization associated with acupunct...
Chien, Ding-Kuo; Hwang, Hei-Fen; Lin, Mau-Roung
This study compared the ability of five injury severity measures, namely the Abbreviated Injury Scale to the Head (AIS-H), Glasgow Coma Scale (GCS), Glasgow Outcome Scale (GOS), Extended Glasgow Outcome Scale (GOSE), and Injury Severity Score (ISS), to predict return-to-work after a traumatic brain injury (TBI). Furthermore, factors potentially associated with return-to-work were investigated. In total, 207 individuals aged ≤65 years newly diagnosed with a TBI and employed at the time of injury were recruited and followed-up for 1year by telephone every 3 months. A bivariate proportional hazards model analysis revealed that all five injury severity measures were significantly associated with return-to-work after a TBI. The AIS-H and non-head ISS explained 23.8% of the variation in the duration of returning to work from discharge after hospitalization for a TBI; similarly, the GCS, GOS, GOSE, and ISS respectively accounted for 4.7%, 21.4%, 12.9%, and 48.4% of the variation. A multivariable analysis revealed that individuals with higher injury severity as measured by the ISS (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.92-0.97), a lack of autonomy in transportation (HR, 2.55; 95% CI, 1.23-5.32), cognitive impairment (HR, 0.47; 95% CI, 0.28-0.79), and depression (HR, 0.97; 95% CI, 0.95-0.99) were significantly less likely to be employed after a TBI. In conclusion, of the five injury severity measures, the ISS may be the most capable measure of predicting return-to-work after a TBI. In addition to injury severity, autonomy in transportation, cognitive function, and the depressive status may also influence the employment status during the first year after a TBI.
Klose, M; Juul, A; Struck, J
To assess the prevalence of hypopituitarism following traumatic brain injury (TBI), describe the time-course and assess the association with trauma-related parameters and early post-traumatic hormone alterations.......To assess the prevalence of hypopituitarism following traumatic brain injury (TBI), describe the time-course and assess the association with trauma-related parameters and early post-traumatic hormone alterations....
Moth Wolffbrandt, Mia; Poulsen, Ingrid; Engberg, Aase W;
To investigate the occurrence and severity of agitation in patients after severe traumatic brain injury (TBI), to identify predictors of agitation and to study interrater reliability for a translated version of the Agitated Behavior Scale (ABS).......To investigate the occurrence and severity of agitation in patients after severe traumatic brain injury (TBI), to identify predictors of agitation and to study interrater reliability for a translated version of the Agitated Behavior Scale (ABS)....
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 manipulat...
induced mTBI has increased in recent years. Intracranial pressure monitoring is not always available in clinical care settings, and protocols need to... intracranial pressure , shear stress concentration, and relative motion between the brain and skull do indeed cause surface contusion, concussion, diffuse axonal injury, as well as acute subdural hematoma. ...civilian hospital for mild head injury. Follow-up 1-month post-injury, allowed for PCS evaluation. The analyses (odds ratios) suggest that elevated
Balaban, Tammy; Hyde, Nellemarie; Colantonio, Angela
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…
Brenner, Lisa A.; Betthauser, Lisa M.; Homaifar, Beeta Y.; Villarreal, Edgar; Harwood, Jeri E. F.; Staves, Pamela J.; Huggins, Joseph A.
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…
Jantz, Paul B.; Comerchero, Victoria A.; Canto, Angela I.; Pierson, Eric
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…
Davies, Susan C.; Ray, Ashlyn M.
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…
57 58 59 60 42 Running /Table of Contents title: Inhibition of EC Degradation Improves mTBI Outcomes Key Words: 2-AG, MAGL, TBI, neuroinflammation...sequelae of traumatic brain injury: relationship to neurochemical and biomechanical mechanisms. Lab Invest. 74(2):315-42. 15. Prow NA, Irani DN
Mioni, G.; Mattalia, G.; Stablum, F.
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…
Body, Richard; Parker, Mark
Topic repetitiveness is a common component of pragmatic impairment and a powerful contributor to social exclusion. Despite this, description, characterization and intervention remain underdeveloped. This article explores the nature of repetitiveness in traumatic brain injury (TBI). A case study of one individual after TBI provides the basis for a…
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,…
Wang, Y.T.; Kent, R.D.; Duffy, J.R.; Thomas, J.E.
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…
Vu, Jennifer A.; Babikian, Talin; Asarnow, Robert F .
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…
Scheenen, Myrthe; de Koning, Myrthe; van der Horn, Harm; van der Naalt, Joukje; Spikman, Jacoba
Objectives. To investigate the incidence of acute alcohol intoxication (AAI) at the time of sustaining mild traumatic brain injury (mTBI), describe the characteristics of this intoxicated subgroup, and evaluate recovery and outcome in comparison to sober mTBI patients. Methods. Multicenter cohort st
Jacobs, B.; Beems, T.; Vliet, T.M. van der; Vugt, A.B. van; Hoedemaekers, C.W.; Horn, J.; Franschman, G.; Haitsma, I.; Naalt, J. van der; Andriessen, T.M.J.C.; Borm, G.F.; Vos, P.E.
BACKGROUND: With this study we aimed to design validated outcome prediction models in moderate and severe traumatic brain injury (TBI) using demographic, clinical, and radiological parameters. METHODS: Seven hundred consecutive moderate or severe TBI patients were included in this observational pros
Jacobs, Bram; Beems, Tjemme; van der Vliet, Ton M.; van Vugt, Arie B.; Hoedemaekers, Cornelia; Horn, Janneke; Franschman, Gaby; Haitsma, Ian; van der Naalt, Joukje; Andriessen, Teuntje M. J. C.; Borm, George F.; Vos, Pieter E.
With this study we aimed to design validated outcome prediction models in moderate and severe traumatic brain injury (TBI) using demographic, clinical, and radiological parameters. Seven hundred consecutive moderate or severe TBI patients were included in this observational prospective cohort study.
Bosco, Francesca M.; Angeleri, Romina; Sacco, Katiuscia; Bara, Bruno G.
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…
Schutz, Larry E.; Rivers, Kenyatta O.; McNamara, Elizabeth; Schutz, Judith A.; Lobato, Emilio J.
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…
Allain, P.; Fasotti, L.; Roy, A.; Chauvire, V.; Etcharry-Bouyx, F.; Gall, D. le
The aim of the present study was to examine the syntactic and semantic dimensions of script representation in patients with structural damage within the cerebral cortex following a severe traumatic brain injury (TBI). Forty TBI patients and 38 healthy control subjects (HC) were asked to sort cards d
L. Valk-Kleibeuker (Linda); M.H. Heijenbrok-Kal (Majanka); G.M. Ribbers (Gerard)
textabstractObjective: To evaluate the course of mood and identify its determinants up to 3 years after moderate to severe traumatic brain injury (TBI). Design: Prospective cohort study. Patients: Patients hospitalised with moderate to severe TBI, who survived until hospital discharge. Methods: At 3
Andriessen, T.M.J.C.; Jacobs, B.; Vos, P.E.
Traumatic brain injury (TBI) is a frequent and clinically highly heterogeneous neurological disorder with large socioeconomic consequences. TBI severity classification, based on the hospital admission Glasgow Coma Scale (GCS) score, ranges from mild (GCS 13-15) and moderate (GCS 9-12) to severe (GCS
Andriessen, Teuntje M J C; Jacobs, Bram; Vos, Pieter E
Traumatic brain injury (TBI) is a frequent and clinically highly heterogeneous neurological disorder with large socioeconomic consequences. TBI severity classification, based on the hospital admission Glasgow Coma Scale (GCS) score, ranges from mild (GCS 13-15) and moderate (GCS 9-12) to severe (GCS
Capitani, Erminio; Rosci, Chiara; Saetti, Maria Cristina; Laiacona, Marcella
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…
Vos, P E; Jacobs, B; Andriessen, T M J C; Lamers, K J B; Borm, G F; Beems, T; Edwards, M; Rosmalen, C F; Vissers, J L M
BACKGROUND: Biomarker levels in blood after traumatic brain injury (TBI) may offer diagnostic and prognostic tools in addition to clinical indices. This study aims to validate glial fibrillary acidic protein (GFAP) and S100B concentrations in blood as outcome predictors of TBI using cutoff levels of
Li, Shuai; Li, Hang; He, Xiao-Fei; Li, Ge; Zhang, Qun; Liang, Feng-Ying; Jia, Huan-Huan; Li, Jiang-Chao; Huang, Ren; Pei, Zhong; Wang, Li-Jing; Zhang, Yu
Traumatic brain injury (TBI) is the leading cause of mortality and disability among male adolescents and young adults; and mild traumatic brain injury is the most common type of traumatic brain injury. The disruption of blood-brain barrier (BBB) plays an important role in brain trauma. Previously, we have found that slit2, a member of slit protein family, increases permeability of BBB. In the present study, we examined the role of slit2 in the pathogenesis of mild TBI in a mouse model of micro TBI. Rhodamine BandPI (PropidiumIodide) staining were used to detect the permeability of BBB and cell death, respectively. The leakage of Rhodamine B and cell death were significantly increased in Slit2-Tg mice than in C57 control mice after micro TBI. The present results suggest that over expression of slit2 plays a detrimental role in the pathophysiology of mild TBI.
Collins, Niamh C
The Phillips Report on traumatic brain injury (TBI) in Ireland found that injury was more frequent in men and that gender differences were present in childhood. This study determined when gender differences emerge and examined the effect of gender on the mechanism of injury, injury type and severity and outcome.
Dean, PJA; Sato, JR; Vieira, G.; McNamara, A; Sterr, A
Background: Persistent postconcussion syndrome (PCS) occurs in around 5– 10% of individuals after mild traumatic brain injury (mTBI), but research into the underlying biology of these ongoing symptoms is limited and inconsistent. One reason for this could be the heterogeneity inherent to mTBI, with individualized injury mechanisms and psychological factors. A multimodal imaging study may be able to characterize the injury better. Aim: To look at the relationship between functional (fMRI), str...
Full Text Available Background: The conflicts in Iraq and Afghanistan and the prominence of traumatic brain injury (TBI, mostly from improvised explosive devices, have focused attention on the effectiveness of combat helmets. Purpose: This paper examines the importance of TBI, the role and history of the development of combat helmets, current helmet designs and effectiveness, helmet design methodology, helmet sensors, future research and recommendations. Method: A literature review was conducted using search terms – combat helmets, traumatic brain injury, concussion, Iraq, Afghanistan and helmet sensors, searching PubMed, MEDLINE, ProQuest and Google Scholar. Conclusions: At present, no existing helmet is able to fully protect against all threats faced on the battlefield. The prominence of traumatic brain injury from improvised explosive devices in the current conflicts in Iraq and Afghanistan has highlighted the limitations in knowledge about blast and how to provide protection from it. As a result, considerable research is currently occurring in how to protect the head from blast over-pressure. Helmet sensors may provide valuable data. Some new combat helmets may be able to protect against rifle rounds, but may result in injuries occurring behind body armour. Optimal combat helmet design requires a balance between the need for protection from trauma and the comfort and practicality of the helmet for the user to ensure the best outcomes.
Jennifer H. Olson-Madden
Full Text Available Traumatic brain injury (TBI and substance use disorders (SUDs frequently co-occur. Individuals with histories of alcohol or other drug use are at greater risk for sustaining TBI, and individuals with TBI frequently misuse substances before and after injury. Further, a growing body of literature supports the relationship between comorbid histories of mild TBI (mTBI and SUDs and negative outcomes. Alcohol and other drug use are strongly associated with risk taking. Disinhibition, impaired executive function, and/or impulsivity as a result of mTBI also contribute to an individual’s proclivity towards risk-taking. Risk-taking behavior may therefore, be a direct result of SUD and/or history of mTBI, and risky behaviors may predispose individuals for subsequent injury or continued use of substances. Based on these findings, evaluation of risk-taking behavior associated with the co-occurrence of SUD and mTBI should be a standard clinical practice. Interventions aimed at reducing risky behavior among members of this population may assist in decreasing negative outcomes. A novel intervention (Substance Use and Traumatic Brain Injury Risk Reduction and Prevention (STRRP for reducing and preventing risky behaviors among individuals with co-occurring mTBI and SUD is presented. Areas for further research are discussed.
the value of this experimental platform to investigate the single bubble cavitation- induced damage in a biological tissue is illustrated with an...Lei Wu, Malisa Sarntinoranont, Huikai Xie1. Refractive index measurement of acute rat brain tissue slices using optical coherence tomography, Optics...b-TBI, i.e. what is “broken”, in the brain during exposure to shock loading is currently unknown. While blast waves are well known to have negative
Abou-Abbass, Hussein; Bahmad, Hisham; Ghandour, Hiba; Fares, Jawad; Wazzi-Mkahal, Rayyan; Yacoub, Basel; Darwish, Hala; Mondello, Stefania; Harati, Hayat; El Sayed, Mazen J.; Tamim, Hani; Kobeissy, Firas
Abstract Background: Traumatic brain injury (TBI) is a debilitating medical and emerging public health problem that is affecting people worldwide due to a multitude of factors including both domestic and war-related acts. The objective of this paper is to systematically review the status of TBI in Lebanon – a Middle Eastern country with a weak health system that was chartered by several wars and intermittent outbursts of violence - in order to identify the present gaps in knowledge, direct future research initiatives and to assist policy makers in planning progressive and rehabilitative policies. Methods: OVID/Medline, PubMed, Scopus databases and Google Scholar were lastly searched on April 15th, 2016 to identify all published research studies on TBI in Lebanon. Studies published in English, Arabic or French that assessed Lebanese patients afflicted by TBI in Lebanon were warranting inclusion in this review. Case reports, reviews, biographies and abstracts were excluded. Throughout the whole review process, reviewers worked independently and in duplicate during study selection, data abstraction and methodological assessment using the Downs and Black Checklist. Results: In total, 11 studies were recognized eligible as they assessed Lebanese patients afflicted by TBI on Lebanese soils. Considerable methodological variation was found among the identified studies. All studies, except for two that evaluated domestic causes such as falls, reported TBI due to war-related injuries. Age distribution of TBI victims revealed two peaks, young adults between 18 and 40 years, and older adults aged 60 years and above, where males constituted the majority. Only three studies reported rates of mild TBI. Mortality, rehabilitation and systemic injury rates were rarely reported and so were the complications involved; infections were an exception. Conclusion: Apparently, status of TBI in Lebanon suffers from several gaps which need to be bridged through implementing more basic
Diana G Hernadez-Ontiveros
Full Text Available 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.
Lanska, Douglas J
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
Robert A. Scranton
Full Text Available Pituitary dysfunction following traumatic brain injury (TBI is significant and rarely considered by clinicians. This topic has received much more attention in the last decade. The incidence of post TBI anterior pituitary dysfunction is around 30% acutely, and declines to around 20% by one year. Growth hormone and gonadotrophic hormones are the most common deficiencies seen after traumatic brain injury, but also the most likely to spontaneously recover. The majority of deficiencies present within the first year, but extreme delayed presentation has been reported. Information on posterior pituitary dysfunction is less reliable ranging from 3%–40% incidence but prospective data suggests a rate around 5%. The mechanism, risk factors, natural history, and long-term effect of treatment are poorly defined in the literature and limited by a lack of standardization. Post TBI pituitary dysfunction is an entity to recognize with significant clinical relevance. Secondary hypoadrenalism, hypothyroidism and central diabetes insipidus should be treated acutely while deficiencies in growth and gonadotrophic hormones should be initially observed.
John Thomas Weber
Full Text Available 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.
Jordan, Barry D
Acute and chronic sports-related traumatic brain injuries (TBIs) are a substantial public health concern. Various types of acute TBI can occur in sport, but detection and management of cerebral concussion is of greatest importance as mismanagement of this syndrome can lead to persistent or chronic postconcussion syndrome (CPCS) or diffuse cerebral swelling. Chronic TBI encompasses a spectrum of disorders that are associated with long-term consequences of brain injury, including chronic traumatic encephalopathy (CTE), dementia pugilistica, post-traumatic parkinsonism, post-traumatic dementia and CPCS. CTE is the prototype of chronic TBI, but can only be definitively diagnosed at autopsy as no reliable biomarkers of this disorder are available. Whether CTE shares neuropathological features with CPCS is unknown. Evidence suggests that participation in contact-collision sports may increase the risk of neurodegenerative disorders such as Alzheimer disease, but the data are conflicting. In this Review, the spectrum of acute and chronic sport-related TBI is discussed, highlighting how examination of athletes involved in high-impact sports has advanced our understanding of pathology of brain injury and enabled improvements in detection and diagnosis of sport-related TBI.
and whether s/he had ever received school help for conditions such as Attention Deficit / Hyperactivity Disorder or a learning disability. These... Deficit - Hyperactivity Disorder ; TBI=Traumatic Brain Injury; CES-D=Center for Epidemiologic Studies-Depression Scale; PCL=Posttraumatic Stress Disorder ...mTBI late effects from other similar disorders . Pre- vious studies have found that, in comparison with other injuries, a history of mTBI seems to
Grundy, P L; Patel, N; Harbuz, M S; Lightman, S L; Sharples, P M
Brain-derived neurotrophic factor (BDNF) expression in rat hippocampus is increased after experimental traumatic brain injury (TBI) and may be neuroprotective. Glucocorticoids are important regulators of brain neurotrophin levels and are often prescribed following TBI. The effect of adrenalectomy (ADX) on the expression of BDNF mRNA in the hippocampus after TBI has not been investigated to date. We used fluid percussion injury (FPI) and in situ hybridization to evaluate the expression of BDNF mRNA in the hippocampus 4 h after TBI in adrenal-intact or adrenalectomized rats (with or without corticosterone replacement). FPI and ADX independently increased expression of BDNF mRNA. In animals undergoing FPI, prior ADX caused further elevation of BDNF mRNA and this upregulation was prevented by corticosterone replacement in ADX rats. These findings suggest that glucocorticoids are involved in the modulation of the BDNF mRNA response to TBI.
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
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.
Goddeyne, Corey; Nichols, Joshua; Wu, Chen; Anderson, Trent
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.
Garcia, Jane Mertz; Sellers, Debra M.; Hilgendorf, Amy E.; Burnett, Debra L.
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…
J.T.M. van Baalen (Bianca)
textabstractThis thesis is based on the findings of the FuPro-TBI (Functional Prognosis in Traumatic Brain Injury) study, which was part of the national FuPro research programme which investigated the functional prognosis of four neurological disorders: multiple sclerosis (MS), stroke, amyotrofic l
Aldrich, Erin M.; Obrzut, John E.
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…
Bansal, Vishal; Costantini, Todd; Kroll, Lauren; Peterson, Carrie; Loomis, William; Eliceiri, Brian; Baird, Andrew; Wolf, Paul; Coimbra, Raul
Traumatic brain injury (TBI) can lead to several physiologic complications including gastrointestinal dysfunction. Specifically, TBI can induce an increase in intestinal permeability, which may lead to bacterial translocation, sepsis, and eventually multi-system organ failure. However, the exact mechanism of increased intestinal permeability following TBI is unknown. We hypothesized that expression of tight junction protein ZO-1 and occludin, responsible for intestinal architectural and functional integrity, will decrease following TBI and increase intestinal permeability. BALB/c mice underwent a weight drop TBI model following anesthesia. Brain injury was confirmed by a neurologic assessment and gross brain pathology. Six hours following injury, FITC-dextran (25 mg 4.4 kDa FITC-dextran) was injected into the intact lumen of the isolated ileum. Intestinal permeability was measured in plasma 30 min following injection, by using spectrophotometry to determine plasma FITC-dextran concentrations. Whole ileum extracts were used to measure expression of tight junction proteins ZO-1 and occludin by Western blot. TBI caused a significant increase in intestinal permeability (110.0 microg/mL +/-22.2) compared to sham animals (29.4 microg/mL +/- 9.7) 6 h after injury (p = 0.016). Expression of ZO-1 was decreased by 49% relative to sham animals (p intestinal permeability corresponds with decreased expression of tight junction proteins ZO-1 and occludin following TBI. Expression of intestinal tight junction proteins may be an important factor in gastrointestinal dysfunction following brain injury.
Dennis, Maureen; Simic, Nevena; Gerry Taylor, H; Bigler, Erin D; Rubin, Kenneth; Vannatta, Kathryn; Gerhardt, Cynthia A; Stancin, Terry; Roncadin, Caroline; Yeates, Keith Owen
Theory of mind (ToM) involves thinking about mental states and intentions to understand what other people know and to predict how they will act. We studied ToM in children with traumatic brain injury (TBI) and age- and gender-matched children with orthopedic injuries (OI), using a new three-frame Jack and Jill cartoon task that measures intentional thinking separate from contingent task demands. In the key ToM trials, which required intentional thinking, Jack switched a black ball from one hat to another of a different color, but Jill did not witness the switch; in the otherwise identical non-ToM trials, the switch was witnessed. Overall accuracy was higher in children with OI than in those with TBI. Children with severe TBI showed a larger decline in accuracy on ToM trials, suggesting a specific deficit in ToM among children with severe TBI. Accuracy was significantly higher on trials following errors than on trials following correct responses, suggesting that all groups monitored performance and responded to errors with increased vigilance. TBI is associated with poorer intentional processing in school-age children and adolescents relative to peers with OI; furthermore, children with TBI are challenged specifically by intentional demands, especially when their injury is severe. (JINS, 2012, 19, 1-9).
brain injury (TBI) is the leading cause of death in children and young adults globally. Malignant cerebral edema plays a major role in the...pathophysiology which evolves after severe TBI. Added to this is the significant morbidity and mortality from cerebral edema associated with acute stroke...hypoxic ischemic coma, neurological cancers and brain infection. Therapeutic strategies to prevent cerebral edema are limited and if brain swelling
Engberg, Aase Worså; Liebach, Annette; Nordenbo, Annette Mosbæk
OBJECTIVES: To present results from the first 3 years of centralized subacute rehabilitation after very severe traumatic brain injury (TBI), and to compare results of centralized versus decentralized rehabilitation. MATERIAL AND METHODS: Prospectively, the most severely injured group of adults from...... an uptake area of 2.4 million in Denmark were included at admission to a regional brain injury unit (BIU), on average 19 days after injury. Patients in the retrospective study used for comparison were randomly chosen from the national hospital register. RESULTS AND CONCLUSIONS: Out of 117 patients...... post-trauma was 0.29, and at 1 year 0.055 per 100,000 population. By comparison of 39 patients from the centralized unit injured in 2000-2003 with 21 patients injured in 1982, 1987 or 1992 and with similar PTA- and age distributions and male/female ratio, Glasgow Outcome Scale score at discharge...
Engberg, Aase Worså; Liebach, Annette; Nordenbo, Annette Mosbæk
post-trauma was 0.29, and at 1 year 0.055 per 100,000 population. By comparison of 39 patients from the centralized unit injured in 2000-2003 with 21 patients injured in 1982, 1987 or 1992 and with similar PTA- and age distributions and male/female ratio, Glasgow Outcome Scale score at discharge......OBJECTIVES: To present results from the first 3 years of centralized subacute rehabilitation after very severe traumatic brain injury (TBI), and to compare results of centralized versus decentralized rehabilitation. MATERIAL AND METHODS: Prospectively, the most severely injured group of adults from...... an uptake area of 2.4 million in Denmark were included at admission to a regional brain injury unit (BIU), on average 19 days after injury. Patients in the retrospective study used for comparison were randomly chosen from the national hospital register. RESULTS AND CONCLUSIONS: Out of 117 patients...
Full Text Available 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.
This podcast provides tips on how older adults can prevent falls and related injuries, such as traumatic brain injuries (TBI). Created: 3/5/2008 by National Center for Injury Prevention and Control (NCIPC). Date Released: 3/7/2008.
Wilde, Elisabeth A; Li, Xiaoqi; Hunter, Jill V; Narayana, Ponnada A; Hasan, Khader; Biekman, Brian; Swank, Paul; Robertson, Claudia; Miller, Emmy; McCauley, Stephen R; Chu, Zili David; Faber, Jessica; McCarthy, James; Levin, Harvey S
To study the relation of loss of consciousness (LOC) to white matter integrity after mild traumatic brain injury (mTBI), we acquired diffusion tensor imaging (DTI) at 3 Tesla in 79 participants with mTBI and normal computed tomography (age 18 to 50 years) whom we imaged after a mean post-injury interval of 25.9 h (standard deviation = 12.3) and at 3 months. For comparison, 64 participants with orthopedic injury (OI) underwent DTI at similar intervals. Quantitative tractography was used to measure fractional anisotropy (FA) and mean diffusivity (MD) in the left and right uncinate fasciculus (UF), left and right inferior frontal occipital fasciculus (IFOF), and the genu of the corpus callosum. Generalized estimating equation models assessed the association between LOC and both MD and FA across time after mTBI and compared their DTI metrics with the OI group. LOC was significantly related to MD in UF and IFOF (p values ranged from p < 0.0001 to 0.0270) and to FA in left UF (p = 0.0104) and right UF (p = 0.0404). Between-group differences in MD were significant for left UF, left and right IFOF, and the genu of the corpus callosum on initial DTI, but not at 3 months post-injury, and these differences were specific to the mTBI subgroup with LOC. Groups did not differ in FA at either occasion. Early DTI may provide a biomarker for mTBI with LOC, even in patients whose consciousness recovers by arrival in the emergency department. MD better differentiates mTBI from OI than FA on early DTI, but this is specific to mTBI with LOC. DTI findings support a continuum of white matter injury in early mTBI.
Mitra, Biswadev; Rau, Thomas F; Surendran, Nanda; Brennan, James H; Thaveenthiran, Prasanthan; Sorich, Edmond; Fitzgerald, Mark C; Rosenfeld, Jeffrey V; Patel, Sarjubhai A
Prediction of post-concussive syndrome after apparent mild traumatic brain injury (TBI) and subsequent cognitive recovery remains challenging, with substantial limitations of current methods of cognitive testing. This pilot study aimed to determine if levels of micro ribonucleic acids (RNAs) circulating in plasma are altered following TBI, and if changes to levels of such biomarkers over time could assist in determination of prognosis after TBI. Patients were enrolled after TBI on presentation to the Emergency Department and allocated to three groups: A - TBI (physical trauma to the head), witnessed loss of consciousness, amnesia, GCS=15, a normal CT Brain and a recorded first pass after post-traumatic amnesia (PTA) scale; B TBI, witnessed LOC, amnesia, GCS=15, a normal CT brain and a PTA scale test fail and: C - TBI and initial GCS RNA was then assayed using a custom miRNA PCR array. Two micro-RNAs, mir142-3p and mir423-3p demonstrated potential clinical utility differentiating patients after mild head injury into those at greater risk of developing amnesia and therefore, post-concussive syndromes. In addition, these miRNA demonstrated a decrease in expression over time, possibly indicative of brain healing after the injury. Further evaluation of these identified miRNA markers with larger patient cohorts, correlation with clinical symptoms and analysis over longer time periods are essential next steps in developing objective markers of severity of TBI.
Schober, Michelle Elena; Block, Benjamin; Requena, Daniela F; Hale, Merica A; Lane, Robert H
Pediatric traumatic brain injury (TBI) is a major cause of acquired cognitive dysfunction in children. Hippocampal Brain Derived Neurotrophic Factor (BDNF) is important for normal cognition. Little is known about the effects of TBI on BDNF levels in the developing hippocampus. We used controlled cortical impact (CCI) in the 17 day old rat pup to test the hypothesis that CCI would first increase rat hippocampal BDNF mRNA/protein levels relative to SHAM and Naïve rats by post injury day (PID) 2 and then decrease BDNF mRNA/protein by PID14. Relative to SHAM, CCI did not change BDNF mRNA/protein levels in the injured hippocampus in the first 2 days after injury but did decrease BDNF protein at PID14. Surprisingly, BDNF mRNA decreased at PID 1, 3, 7 and 14, and BDNF protein decreased at PID 2, in SHAM and CCI hippocampi relative to Naïve. In conclusion, TBI decreased BDNF protein in the injured rat pup hippocampus 14 days after injury. BDNF mRNA levels decreased in both CCI and SHAM hippocampi relative to Naïve, suggesting that certain aspects of the experimental paradigm (such as craniotomy, anesthesia, and/or maternal separation) may decrease the expression of BDNF in the developing hippocampus. While BDNF is important for normal cognition, no inferences can be made regarding the cognitive impact of any of these factors. Such findings, however, suggest that meticulous attention to the experimental paradigm, and possible inclusion of a Naïve group, is warranted in studies of BDNF expression in the developing brain after TBI.
Ekinci, Ozalp; Direk, Meltem Çobanoğullari; Ekinci, Nuran; Okuyaz, Cetin
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
Elder, Gregory A; Dorr, Nathan P.; De Gasperi, Rita; Gama Sosa, Miguel A.; Shaughness, Michael C.; Maudlin-Jeronimo, Eric; Hall, Aaron A; McCarron, Richard M.; Ahlers, Stephen T
Blast related traumatic brain injury (TBI) has been a major cause of injury in the wars in Iraq and Afghanistan. A striking feature of the mild TBI (mTBI) cases has been the prominent association with post-traumatic stress disorder (PTSD). However, because of the overlapping symptoms, distinction between the two disorders has been difficult. We studied a rat model of mTBI in which adult male rats were exposed to repetitive blast injury while under anesthesia. Blast exposure induced a variety ...
Singh, Kavita; Trivedi, Richa; Haridas, Seenu; Manda, Kailash; Khushu, Subash
Mild traumatic brain injury (mTBI) is the most common form of TBI (70-90%) with consequences of anxiety-like behavioral alterations in approximately 23% of mTBI cases. This study aimed to assess whether mTBI-induced anxiety-like behavior is a consequence of neurometabolic alterations. mTBI was induced using a weight drop model to simulate mild human brain injury in rodents. Based on injury induction and dosage of anesthesia, four animal groups were included in this study: (i) injury with anesthesia (IA); (ii) sham1 (injury only, IO); (iii) sham2 (only anesthesia, OA); and (iv) control rats. After mTBI, proton magnetic resonance spectroscopy ((1) H-MRS) and neurobehavioral analysis were performed in these groups. At day 5, reduced taurine (Tau)/total creatine (tCr, creatine and phosphocreatine) levels in cortex were observed in the IA and IO groups relative to the control. These groups showed mTBI-induced anxiety-like behavior with normal cognition at day 5 post-injury. An anxiogenic effect of repeated dosage of anesthesia in OA rats was observed with normal Tau/tCr levels in rat cortex, which requires further examination. In conclusion, this mTBI model closely mimics human concussion injury with anxiety-like behavior and normal cognition. Reduced cortical Tau levels may provide a putative neurometabolic basis of anxiety-like behavior following mTBI.
Simonsen, Louise Lau; Sonne-Holm, Stig; Krasheninnikoff, Michael;
The incidence of heterotopic ossification (HO) among patients with traumatic brain injury (TBI) varies in the literature from 11 to 73.3%. The aim of this study was to determine the incidence of HO among patients with very severe TBI treated in a new established intensive rehabilitation Brain...... Injury Unit and to list some of the risk-predicting features. The study comprised an approximately complete, consecutive series of 114 adult patients from a well-defined geographical area, and with a posttraumatic amnesia period of at least 28 days, i.e. very severe TBI. Demographic and functional data...
Washington, Patricia M; Villapol, Sonia; Burns, Mark P
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.
McBride, Devin W; Szu, Jenny I; Hale, Chris; Hsu, Mike S; Rodgers, Victor G J; Binder, Devin K
Traumatic brain injury (TBI) is significant, from a public health standpoint, because it is a major cause of the morbidity and mortality of young people. Cerebral edema after a TBI, if untreated, can lead to devastating damage of the remaining tissue. The current therapies of severe TBI (sTBI), as outlined by the Brain Trauma Foundation, are often ineffective, thus a new method for the treatment of sTBI is necessary. Herein, the reduction of cerebral edema, after TBI, using an osmotic transport device (OTD) was evaluated. Controlled cortical impact (CCI) was performed on adult female CD-1 mice, and cerebral edema was allowed to form for 3 h, followed by 2 h of treatment. The treatment groups were craniectomy only, craniectomy with a hydrogel, OTD without bovine serum albumin (BSA), and OTD. After CCI, brain water content was significantly higher for animals treated with a craniectomy only, craniectomy with a hydrogel, and OTD without BSA, compared to that of control animals. However, when TBI animals were treated with an OTD, brain water content was not significantly higher than that of controls. Further, brain water content of TBI animals treated with an OTD was significantly reduced, compared to that of untreated TBI animals, TBI animals treated with a craniectomy and a hydrogel, and TBI animals treated with an OTD without BSA. Here, we demonstrate the successful reduction of cerebral edema, as determined by brain water content, after TBI using an OTD. These results demonstrate proof of principle for direct water extraction from edematous brain tissue by direct osmotherapy using an OTD.
Reddy, Rajakumari Pampa; Rajeswaran, Jamuna; Devi, B. Indira; Kandavel, Thennarasu
Introduction: Traumatic brain injury (TBI) constitutes a significant burden on health care resources in India. TBI is a dynamic process which involves damage to the brain thus leading to behavior cognitive and emotional consequences. Aim: To study the cognitive profile, post-concussion symptoms (PCS), quality of life (QOL), and their correlation. Methods: A total of 60 patients with TBI were recruited and assessed for neuropsychological profile, PCS, and QOL, the correlation among the variables were analyzed. Results: The results suggest that TBI has series of consequences which is interrelated, and the study has implications for rehabilitation of TBI. Conclusion: The study highlights the deficits of cognition, and its correlation with PCS and QOL, emphasizing integrated rehabilitation approach for patients with TBI.
Eliane Correa Miotto
Full Text Available Traumatic brain injury (TBI is one of the most frequent causes of brain damage. Cognitive deficits reported in the literature after moderate to severe TBI include memory, language, executive functions, attention and information processing speed impairments. However, systematic studies on patients with mild TBI are scarce although neuropsychological changes are present. OBJECTIVE: To investigate the cognitive functioning of patients with mild to moderate TBI. METHOD: We evaluated 12 patients with mild to moderate TBI using a comprehensive protocol (PN01 of neuropsychological tests. RESULTS: There were significant deficits of episodic memory including immediate and delayed verbal memory recall, verbal recognition, immediate and delayed visual memory recall, naming, verbal fluency and information processing speed. CONCLUSION: These results emphasize the importance of comprehensive neuropsychological assessments even in cases of mild TBI in order to identify impaired and preserved functions providing adequate managing including rehabilitation programs for each case.
Thal, Serge C.; Clara Luh; Eva-Verena Schaible; Ralph Timaru-Kast; Jana Hedrich; Luhmann, Heiko J.; Kristin Engelhard; Zehendner, Christoph M.
Disruption of the blood-brain barrier (BBB) results in cerebral edema formation, which is a major cause for high mortalityrnafter traumatic brain injury (TBI). As anesthetic care is mandatory in patients suffering from severe TBI it may be importantrnto elucidate the effect of different anesthetics on cerebral edema formation. Tight junction proteins (TJ) such as zonularnoccludens-1 (ZO-1) and claudin-5 (cl5) play a central role for BBB stability. First, the influence of the volatile anesthet...
Sharma, Bhanu; Lawrence, David Wyndham
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
陈志刚; 卢亦成; 朱诚; 张光霁; 丁学华; 江基尧
Objective: To observe the effects of ganglioside GM1 on reduction of brain edema and amelioration of cerebral metabolism after traumatic brain injury (TBI).Methods: An acute experimental closed TBI model in rats was induced by a fluid-percussion brain injury model. At five and sixty minutes after TBI, the animals were intraperitoneally injected by ganglioside GM1 (30 mg/kg) or the same volume of saline. At the 6th hour after TBI, effects of ganglioside GM1 or saline on changes of mean arterial pressure (MAP), contents of water, lactic acid (LA) and lipid peroxidation (LPO) in the injured cerebral tissues were observed.Results: After TBI, MAP decreased and contents of water, LA and LPO increased in brain injury group; however, MAP was back to normal levels and contents of water, LA and LPO decreased in ganglioside GM1 treated group, compared with those in brain injury group (P0.05) was observed.Conclusions: Ganglioside GM1 does have obvious neuroprotective effect on early TBI.
Chico-Calero, Isabel; Shishkov, Milen; Welt, Jonathan; Blatter, Cedric; Vakoc, Benjamin J.
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.
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
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
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
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.
Sandra A Acosta
Full Text Available 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
Motzkin, Julian C; Koenigs, Michael R
Disentangling the effects of "organic" neurologic damage and psychological distress after a traumatic brain injury poses a significant challenge to researchers and clinicians. Establishing a link between traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) has been particularly contentious, reflecting difficulties in establishing a unique diagnosis for conditions with overlapping and sometimes contradictory symptom profiles. However, each disorder is linked to a variety of adverse health outcomes, underscoring the need to better understand how neurologic and psychiatric risk factors interact following trauma. Here, we present data showing that individuals with a TBI are more likely to develop PTSD, and that individuals with PTSD are more likely to develop persistent cognitive sequelae related to TBI. Further, we describe neurobiological models of PTSD, highlighting how patterns of neurologic damage typical in TBI may promote or protect against the development of PTSD in brain-injured populations. These data highlight the unique course of PTSD following a TBI and have important diagnostic, prognostic, and treatment implications for individuals with a dual diagnosis.
Full Text Available Objective: To study the dynamic changes of pituitary hormones in traumatic brain injury (TBI and to correlate the severity and neurological outcome. Patients and Methods: Dynamic changes in the pituitary hormones were evaluated in 164 patients with TBI on day-1, day-7, day-14, day-21, and day-28 post injury. Admission TBI severity and long-term outcome were assessed with Glasgow Coma Scale (GCS score and Glasgow Outcome Scale (GOS score. The pituitary hormonal changes were correlated with TBI severity and outcome. Results: Of the 164 patients included in the study, pituitary dysfunction was found in 84 patients and in the remaining 80 patients pituitary function was normal. Most of the pituitary hormone deficiencies observed resolved over time; however, a significant proportion of patients had pituitary dysfunction at one month post injury. The hormones associated with poor outcome included growth hormone, thyrotropic hormone, and gonadotropic hormone. Conclusion: Dynamic changes of pituitary hormones in patients with TBI may reflect the severity of injury and also determine the outcome. Deficiency of growth hormone, gonadotropic hormone, and thyrotropic hormone can adversely affect neurological outcome.
Michael E Hoffer
Full Text Available 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.
Glenn R Wylie
Full Text Available 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
Tomura, Satoshi; de Rivero Vaccari, Juan Pablo; Keane, Robert W; Bramlett, Helen M; Dietrich, W Dalton
Traumatic brain injury (TBI) activates the NALP1/NLRP1 inflammasome, which is an important component of the early innate inflammatory response to injury. We investigated the influence of therapeutic hypothermia on inflammasome activation after TBI. Adult male Sprague-Dawley rats were subjected to moderate fluid percussion brain injury. Temperature manipulation (33°C or 37°C) was initiated 30 minutes after TBI and maintained for 4 hours. At 4 or 24 hours after TBI, traumatized cortex and hippocampus were prepared for immunoblot or immunohistochemical analysis. In the normothermic groups, caspase-1, caspase-11 and expression of the purinergic receptor P2X7 increased at 24 hours after TBI. Posttraumatic hypothermia lead to decreased expression of these proteins at 24 hours compared with normothermic levels. Immunocytochemical studies showed that posttraumatic hypothermia also decreased caspase-1 staining in cerebral cortical neurons compared with normothermic TBI. Cultured cortical neurons subjected to stretch injury demonstrated significant secretion of caspase-1 into the culture medium and caspase-3 activation, both results reduced by hypothermic treatment. Posttraumatic hypothermia decreases inflammasome signaling in neurons and reduces the innate immune response to TBI at 24 hours after injury. Therapeutic hypothermia may protect the injured central nervous system by targeting the detrimental consequences of the innate immune response to injury.
Papadimitriou, Konstantinos I.; Wang, Chu; Rogers, Michelle L.; Gowers, Sally A. N.; Leong, Chi L.; Boutelle, Martyn G.; Drakakis, Emmanuel M.
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
Hansen, Trine S; Engberg, Aase W; Larsen, Klaus
OBJECTIVES: To investigate the status of functional oral intake for patients with severe traumatic brain injury (TBI) and time to return to unrestricted dieting; and to investigate whether severity of brain injury is a predictor for unrestricted dieting. DESIGN: Observational retrospective cohort...... planning rehabilitation, giving information to patients and relatives, and designing efficacy studies of facial oral tract therapy, which are highly recommended....
Yeates, Keith Owen
The vast majority of traumatic brain injuries (TBI) in children are of mild severity. Even if only a small proportion of children with mild TBI suffer negative outcomes, then mild TBI is a serious public health problem. This review summarizes the literature regarding the neurobehavioral outcomes associated with mild TBI in children and adolescents, focusing on the longstanding debate regarding postconcussive symptoms and attendant conceptual and methodological issues. The review also discusses future research directions, the long-term goal of which is to develop a comprehensive and integrated biopsychosocial model of outcomes that helps guide clinical management.
Full Text Available In recent years, the mortality rates after severe traumatic brain injury (TBI have decreased because of advances in emergency medicine. Despite these positive achievements, the disability due to TBI has not appreciably reduced. TBI results in impairment of neurological and cognitive functions leading to activity restriction of patients. The current focus is to rehabilitate them so that they can regain their premorbid functional status as much as possible. This paper would like to review the treatment mechanism, methods and clinical advantages of early rehabilitation therapy in patients with severe TBI. doi: 10.3969/j.issn.1672-6731.2014.06.017
Moss, William C; Blackman, Eric G
Traumatic brain injury [TBI] has become the signature injury of current military conflicts. The debilitating effects of TBI on society 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 mechanisms, including impacts caused by the blast, have been investigated, but blast-induced deformation of the skull has been neglected. Through the use of hydrodynamical numerical simulations, we have discovered that non-lethal blasts can induce sufficient flexure of the skull to generate potentially damaging loads in the brain, even if no impact occurs. This mechanism has implications for the diagnosis of TBI in soldiers and the design of protective equipment such as helmets.
Moss, W C; King, M J; Blackman, E G
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.
Gu, Xiaohuan; Wei, Zheng Zachory; Espinera, Alyssa; Lee, Jin Hwan; Ji, Xiaoya; Wei, Ling; Dix, Thomas A; Yu, Shan Ping
Neonatal brain trauma is linked to higher risks of mortality and neurological disability. The use of mild to moderate hypothermia has shown promising potential against brain injuries induced by stroke and traumatic brain injury (TBI) in various experimental models and in clinical trials. Conventional methods of physical cooling, however, are difficult to use in acute treatments and in induction of regulated hypothermia. In addition, general anesthesia is usually required to mitigate the negative effects of shivering during physical cooling. Our recent investigations demonstrate the potential therapeutic benefits of pharmacologically induced hypothermia (PIH) using the neurotensin receptor (NTR) agonist HPI201 (formerly known as ABS201) in stroke and TBI models of adult rodents. The present investigation explored the brain protective effects of HPI201 in a P14 rat pediatric model of TBI induced by controlled cortical impact. When administered via intraperitoneal (i.p.) injection, HPI201 induced dose-dependent reduction of body and brain temperature. A 6-h hypothermic treatment, providing an overall 2-3°C reduction of brain and body temperature, showed significant effect of attenuating the contusion volume versus TBI controls. Attenuation occurs whether hypothermia is initiated 15min or 2h after TBI. No shivering response was seen in HPI201-treated animals. HPI201 treatment also reduced TUNEL-positive and TUNEL/NeuN-colabeled cells in the contusion area and peri-injury regions. TBI-induced blood-brain barrier damage was attenuated by HPI201 treatment, evaluated using the Evans Blue assay. HPI201 significantly decreased MMP-9 levels and caspase-3 activation, both of which are pro-apototic, while it increased anti-apoptotic Bcl-2 gene expression in the peri-contusion region. In addition, HPI201 prevented the up-regulation of pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. In sensorimotor activity assessments, rats in the HPI201
Scholten, Annemieke C; Polinder, Suzanne; Panneman, Martien J M; van Beeck, Ed F; Haagsma, Juanita A
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
Jepsen, Cecilie Heerdegen; deMoya, Marc A; Perner, Anders;
BACKGROUND: In isolated traumatic brain injury (TBI), little is known about the endothelial response and the effects of endothelial glycocalyx shedding. We have previously shown that treatment with valproic acid (VPA) improves outcomes following TBI and hemorrhagic shock.In this model, we...... hypothesized that severe isolated TBI would cause shedding of the endothelial glycocalyx, as measured by serum syndecan-1 (sSDC-1) levels. We further hypothesized that VPA treatment would reduce this response and reduce lesion size volume. METHODS: Forty Sprague-Dawley rats were allocated to TBI + VPA (n = 8......), TBI + saline vehicle control infusion (n = 8), sham + saline vehicle control infusion (n = 6), or sham + VPA (n = 8). TBI animals were subjected to severe controlled cortical impact and killed 6 hours after injury. VPA 300 mg/kg was given as an intravenous bolus 30 minutes after injury. Serum samples...
Losoi, Heidi; Silverberg, Noah D; Wäljas, Minna; Turunen, Senni; Rosti-Otajärvi, Eija; Helminen, Mika; Luoto, Teemu Miikka Artturi; Julkunen, Juhani; Öhman, Juha; Iverson, Grant L
Resilient individuals manifest adaptive behavior and are better able to recover from adversity. The association between resilience and outcome from mild traumatic brain injury (mTBI) is examined, and the reliability and validity of the Resilience Scale and its short form in mTBI research is evaluated. Patients with mTBI (n=74) and orthopedic controls (n=39) completed the Resilience Scale at one, six, and 12 months after injury. Additionally, self-reported post-concussion symptoms, fatigue, insomnia, pain, post-traumatic stress, and depression, as well as quality of life, were evaluated. The internal consistency of the Resilience Scale and the short form ranged from 0.91 to 0.93 for the mTBI group and from 0.86 to 0.95 for controls. The test-retest reliability ranged from 0.70 to 0.82. Patients with mTBI and moderate-to-high resilience reported significantly fewer post-concussion symptoms, less fatigue, insomnia, traumatic stress, and depressive symptoms, and better quality of life, than the patients with low resilience. No association between resilience and time to return to work was found. Resilience was associated with self-reported outcome from mTBI, and based on this preliminary study, can be reliably evaluated with Resilience Scale and its short form in those with mTBIs.
Full Text Available 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.
Mathias, Jane L; Harman-Smith, Yasmin; Bowden, Stephen C; Rosenfeld, Jeffrey V; Bigler, Erin D
Clinical research into outcomes after traumatic brain injury (TBI) frequently combines injuries that have been sustained through different causes (e.g., car accidents, assaults, and falls), the effect of which is not well understood. This study examined the contribution of injury-related psychological trauma—which is more commonly associated with specific types of injuries—to outcomes after nonpenetrating TBI in order to determine whether it may be having a differential effect in samples containing mixed injuries. Data from three groups that were prospectively recruited for two larger studies were compared: one that sustained a TBI as a result of physical assaults (i.e., psychologically traumatizing) and another as a result of sporting injuries (i.e., nonpsychologically traumatizing), as well as an orthopedic control group (OC). Psychosocial and emotional (postconcussion symptoms, injury-related stress, and depression), cognitive (memory, abstract reasoning, problem solving, and verbal fluency), and functional (general outcome; resumption of home, social, and work roles) outcomes were all assessed. The TBI(assault) group reported significantly poorer psychosocial and emotional outcomes and higher rates of litigation (criminal rather than civil) than both the TBI(sport) and OC groups approximately 6 months postinjury, but there were no differences in the cognitive or functional outcomes of the three groups. The findings suggest that the cause of a TBI may assist in explaining some of the differences in outcomes of people who have seemingly comparable injuries. Involvement in litigation and the cause of an injury may also be confounded, which may lead to the erroneous conclusion that litigants have poorer outcomes.
Canto, Angela I.; Chesire, David J.; Buckley, Valerie A.; Andrews, Terrie W.; Roehrig, Alysia D.
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…
Ledig, Christian; Heckemann, Rolf A; Hammers, Alexander; Lopez, Juan Carlos; Newcombe, Virginia F J; Makropoulos, Antonios; Lötjönen, Jyrki; Menon, David K; Rueckert, Daniel
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
Wu, Chieh-Hsin; Tsai, Tai-Hsin; Zhang, Zi-Hao; Liu, Wei; Wu, Ming-Kung; Chang, Chih-Hui; Kuo, Keng-Liang
Whether traumatic brain injury (TBI) is causally related to substance related disorder (SRD) is still debatable, especially in persons with no history of mental disorders at the time of injury. This study analyzed data in the Taiwan National Health Insurance Research Database for 19,109 patients aged ≥18 years who had been diagnosed with TBI during 2000–2010. An additional 19,109 randomly selected age and gender matched patients without TBI (1 : 1 ratio) were enrolled in the control group. The relationship between TBI and SRD was estimated with Cox proportional hazard regression models. During the follow-up period, SRD developed in 340 patients in the TBI group and in 118 patients in the control group. After controlling for covariates, the overall incidence of SRD was 3.62-fold higher in the TBI group compared to the control group. Additionally, patients in the severe TBI subgroup were 9.01 times more likely to have SRD compared to controls. Notably, patients in the TBI group were prone to alcohol related disorders. The data in this study indicate that TBI is significantly associated with the subsequent risk of SRD. Physicians treating patients with TBI should be alert to this association to prevent the occurrence of adverse events.
Full Text Available Whether traumatic brain injury (TBI is causally related to substance related disorder (SRD is still debatable, especially in persons with no history of mental disorders at the time of injury. This study analyzed data in the Taiwan National Health Insurance Research Database for 19,109 patients aged ≥18 years who had been diagnosed with TBI during 2000–2010. An additional 19,109 randomly selected age and gender matched patients without TBI (1 : 1 ratio were enrolled in the control group. The relationship between TBI and SRD was estimated with Cox proportional hazard regression models. During the follow-up period, SRD developed in 340 patients in the TBI group and in 118 patients in the control group. After controlling for covariates, the overall incidence of SRD was 3.62-fold higher in the TBI group compared to the control group. Additionally, patients in the severe TBI subgroup were 9.01 times more likely to have SRD compared to controls. Notably, patients in the TBI group were prone to alcohol related disorders. The data in this study indicate that TBI is significantly associated with the subsequent risk of SRD. Physicians treating patients with TBI should be alert to this association to prevent the occurrence of adverse events.
WANG Lei; YUAN Ji-shan; ZHANG Hong-xi; DING Hua; TANG Xing-guo; WEI Yong-zhong
Objective: To observe serum and callus leptin expression within the setting of fracture and traumatic brain injury (TBI).Methods: Atotal of 64 male SD rats were randomized equally into 4 groups: nonoperated group, TBI group, fraeture group, and fracture+TBI group. Rats were sacrificed at 2, 4, 8 and 12 weeks after fracture+TBI. Serum leptin was detected using radioimmunoassay, and callus formation was measured radiologically. Callus leptin was analyzed by immunohistochemistry.Results: Serum ieptin levels in the fracture group, TBI group and combined fracture+TBI group were all significantly increased compared with control group at the 2 week time-point (P＜0.05). Serum leptin in the combined fracture +TBI group was significantly higher than that in the fracture and TBI groups at 4 and 8 weeks after injury (P＜0. 05).The percentage of leptin-positive cells in the fracture+TBI callus and callus volume were significantly higher than those in the fracture-only group (P＜0.01).Conclusions: We demonstrated elevated leptin expression within healing bone especially in the first 8 weeks in a rat model of fracture and TBI. A close association exists between leptin levels and the degree of callus formation in fractures.
Jantz, Paul B; Bigler, Erin D
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.
Mantua, Janna; Mahan, Keenan M; Henry, Owen S; Spencer, Rebecca M C
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.
Full Text Available 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-hrs later, following an interval awake or with overnight sleep. Young adult participants (18-22 yrs 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 yr post-injury. Sleep physiology was measured with polysomnography. Memory consolidation was assessed by comparing change in word-pair recall over 12-hr 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.
Hansen, T.S.; Engberg, Anders; Larsen, K.
OBJECTIVES: To investigate the status of functional oral intake for patients with severe traumatic brain injury (TBI) and time to return to unrestricted dieting; and to investigate whether severity of brain injury is a predictor for unrestricted dieting. DESIGN: Observational retrospective cohort...... study. SETTING: Subacute rehabilitation department, university hospital. PARTICIPANTS: Patients age 16 to 65 years (N=173) with severe TBI (posttraumatic amnesia from 7d to >6 mo) admitted over a 5-year period. Patients are transferred to the brain injury unit as soon as they ventilate spontaneously...... instrument (Wald chi(2)=44.40, PTBI admitted to a subacute rehabilitation department. For those who recovered during hospital rehabilitation...
Nielson, Jessica L.; Cooper, Shelly R.; Sorani, Marco D.; Inoue, Tomoo; Yuh, Esther L.; Mukherjee, Pratik; Petrossian, Tanya C.; Lum, Pek Y.; Lingsma, Hester F.; Gordon, Wayne A.; Okonkwo, David O.; Manley, Geoffrey T.
Background Traumatic brain injury (TBI) is a complex disorder that is traditionally stratified based on clinical signs and symptoms. Recent imaging and molecular biomarker innovations provide unprecedented opportunities for improved TBI precision medicine, incorporating patho-anatomical and molecular mechanisms. Complete integration of these diverse data for TBI diagnosis and patient stratification remains an unmet challenge. Methods and findings The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot multicenter study enrolled 586 acute TBI patients and collected diverse common data elements (TBI-CDEs) across the study population, including imaging, genetics, and clinical outcomes. We then applied topology-based data-driven discovery to identify natural subgroups of patients, based on the TBI-CDEs collected. Our hypothesis was two-fold: 1) A machine learning tool known as topological data analysis (TDA) would reveal data-driven patterns in patient outcomes to identify candidate biomarkers of recovery, and 2) TDA-identified biomarkers would significantly predict patient outcome recovery after TBI using more traditional methods of univariate statistical tests. TDA algorithms organized and mapped the data of TBI patients in multidimensional space, identifying a subset of mild TBI patients with a specific multivariate phenotype associated with unfavorable outcome at 3 and 6 months after injury. Further analyses revealed that this patient subset had high rates of post-traumatic stress disorder (PTSD), and enrichment in several distinct genetic polymorphisms associated with cellular responses to stress and DNA damage (PARP1), and in striatal dopamine processing (ANKK1, COMT, DRD2). Conclusions TDA identified a unique diagnostic subgroup of patients with unfavorable outcome after mild TBI that were significantly predicted by the presence of specific genetic polymorphisms. Machine learning methods such as TDA may provide a robust
Lu, Dunyue; Qu, Changsheng; Goussev, Anton; Jiang, Hao; Lu, Chang; Schallert, Timothy; Mahmood, Asim; Chen, Jieli; Li, Yi; Chopp, Michael
Traumatic brain injury (TBI) remains a major public health problem globally. Presently, there is no way to restore cognitive deficits caused by TBI. In this study, we seek to evaluate the effect of statins (simvastatin and atorvastatin) on the spatial learning and neurogenesis in rats subjected to controlled cortical impact. Rats were treated with atorvastatin and simvastatin 1 day after TBI and daily for 14 days. Morris water maze tests were performed during weeks 2 and 5 after TBI. Bromodeo...
Gregory L. Goodrich, PhD
Full Text Available 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.
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
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.
Chhor, Vibol; Moretti, Raffaella; Le Charpentier, Tifenn; Sigaut, Stephanie; Lebon, Sophie; Schwendimann, Leslie; Oré, Marie-Virginie; Zuiani, Chiara; Milan, Valentina; Josserand, Julien; Vontell, Regina; Pansiot, Julien; Degos, Vincent; Ikonomidou, Chrysanthy; Titomanlio, Luigi; Hagberg, Henrik; Gressens, Pierre; Fleiss, Bobbi
The cognitive and behavioural deficits caused by traumatic brain injury (TBI) to the immature brain are more severe and persistent than TBI in the mature brain. Understanding this developmental sensitivity is critical as children under four years of age sustain TBI more frequently than any other age group. Microglia (MG), resident immune cells of the brain that mediate neuroinflammation, are activated following TBI in the immature brain. However, the type and temporal profile of this activation and the consequences of altering it are still largely unknown. In a mouse model of closed head weight drop paediatric brain trauma, we characterized i) the temporal course of total cortical neuroinflammation and the phenotype of ex vivo isolated CD11B-positive microglia/macrophage (MG/MΦ) using a battery of 32 markers, and ii) neuropathological outcome 1 and 5days post-injury. We also assessed the effects of targeting MG/MΦ activation directly, using minocycline a prototypical microglial activation antagonist, on these processes and outcome. TBI induced a moderate increase in both pro- and anti-inflammatory cytokines/chemokines in the ipsilateral hemisphere. Isolated cortical MG/MΦ expressed increased levels of markers of endogenous reparatory/regenerative and immunomodulatory phenotypes compared with shams. Blocking MG/MΦ activation with minocycline at the time of injury and 1 and 2days post-injury had only transient protective effects, reducing ventricular dilatation and cell death 1day post-injury but having no effect on injury severity at 5days. This study demonstrates that, unlike in adults, the role of MG/MΦ in injury mechanisms following TBI in the immature brain may not be negative. An improved understanding of MG/MΦ function in paediatric TBI could support translational efforts to design therapeutic interventions.
Wheble, Joanna L C; Menon, D K
Each year, approximately 2.5 million people experience some form of traumatic brain injury (TBI) in Europe. One million of these are admitted to hospital and 75 000 will die. TBI represents a major cause of death and disability, particularly among those of working age. Substantial investments have been made in an effort to improve diagnosis, management and survival in TBI, but with little success. The Collaborative European Neuro-Trauma Effectiveness Research in TBI (CENTER-TBI) study promises to use the natural variability seen in the management of TBI across Europe with the application of Comparative Effectiveness Research (CER). It will generate repositories of baseline and comprehensive TBI patient data, neuroimaging, neurogenetics and biomarkers, which aim to improve the diagnosis, stratification, management and prognostication of patients with TBI.
Lippa, Sara M; Pastorek, Nicholas J; Benge, Jared F; Thornton, G Matthew
Blast injury is common in current warfare, but little is known about the effects of blast-related mild traumatic brain injury (mTBI). Profile analyses were conducted investigating differences in self-reported postconcussive (PC) symptoms in 339 veteran outpatients with mTBI histories reporting current symptoms based on mechanism of injury (blast only, nonblast only, or both blast and nonblast), number of blast injuries, and distance from the blast. Veterans with any blast-related mTBI history were younger and reported higher posttraumatic stress symptoms than veterans with nonblast-related mTBI histories, with a marginally significant difference in posttraumatic stress symptom report between veterans reporting blast-related mTBI only and those reporting nonblast-related mTBI. The groups did not differ in terms of PC symptom severity or PC symptom cluster profiles. Among veterans with blast-related mTBI histories, PC symptom report did not vary by number of blast-related mTBIs or proximity to blast. Overall, posttraumatic stress symptoms accounted for a substantial portion of variance in PC symptom report. In veteran outpatients with remote mTBI histories who have enduring symptom complaints related to the mTBI, mechanism of injury did not clearly contribute to differential PC symptom severity or PC symptom cluster profile. Proximal rather than distal factors may be important intervention targets in returning symptomatic veterans with mTBI histories.
Colin James Smith
Full Text Available More than 2.5 million Americans suffer a traumatic brain injury (TBI each year. Even mild to moderate traumatic brain injury 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.
Shackelford, Jo L.; Cappiccie, Amy
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.…
Chiu, Hsiao-Yean; Lin, En-Yuan; Wei, Li; Lin, Jiann-Her; Lee, Hsin-Chien; Fan, Yen-Chun; Tsai, Pei-Shan
This study was intended to determine whether the use of hypnotics is associated with dementia in traumatic-brain-injury (TBI) patients. Data retrieved from the Longitudinal Health Insurance Database 2000. TBI patients who received a diagnosis of insomnia at 2 or more independent examinations after the index date of TBI were included. The comparison cohort consisted of randomly selected TBI patients who were matched to insomnia cohort patients based on sex and age. The 2 cohorts of TBI patients were subsequently divided into the following 4 study groups: hypnotics users with insomnia (TBI-IH, N=599), insomniacs who did not use hypnotics (TBI-I, N=931), hypnotics users without insomnia (TBI-H, N=199), and people without insomnia who did not use hypnotics (TBI-C, N=4271). Cox proportional-hazards regression models were used to determine the difference in dementia-free survival among the 4 study groups, after adjusting for the propensity score. The adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of the TBI-IH and TBI-H groups showed that they had a higher risk of dementia (aHRs: 1.86 and 3.98; 95% CIs: 1.15-3.00 and 2.44-6.47, respectively), compared with that of the TBI-C group. However, the risk of dementia in the TBI-I group was not significantly different from that of the TBI-C group (aHR: 1.36; 95% CI: 0.85-2.19). This study suggests that the use of hypnotics is associated with an increased risk of dementia in TBI patients with or without insomnia, whereas insomnia alone is not.
Steven R Flanagan
Full Text Available Steven R Flanagan1, Joshua B Cantor2, Teresa A Ashman21New York University School of Medicine, The Rusk Institute of Rehabilitation, New York, NY, USA; 2Department of Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY, USAAbstract: Traumatic brain injury (TBI is widespread and leads to death and disability in millions of individuals around the world each year. Overall incidence and prevalence of TBI are likely to increase in absolute terms in the future. Tackling the problem of treating TBI successfully will require improvements in the understanding of normal cerebral anatomy, physiology, and function throughout the lifespan, as well as the pathological and recuperative responses that result from trauma. New treatment approaches and combinations will need to be targeted to the heterogeneous needs of TBI populations. This article explores and evaluates the research evidence in areas that will likely lead to a reduction in TBI-related morbidity and improved outcomes. These include emerging assessment instruments and techniques in areas of structural/chemical and functional neuroimaging and neuropsychology, advances in the realms of cell-based therapies and genetics, promising cognitive rehabilitation techniques including cognitive remediation and the use of electronic technologies including assistive devices and virtual reality, and the emerging field of complementary and alternative medicine.Keywords: traumatic brain injury, assessments, treatments
Traumatic brain injury (TBI) is a multifaceted disease with intrinsically complex heterogeneity and remains a significant clinical challenge to manage. TBI model systems have demonstrated many mechanisms that contribute to brain parenchymal cell death, including glutamate and calcium toxicity, oxidative stress, inflammation, and mitochondrial dysfunction. Mitochondria are critically regulated by uncoupling proteins (UCP), which allow protons to leak back into the matrix and thus r...
S S Dhandapani
Full Text Available Background: Age is a strong prognostic factor following traumatic brain injury (TBI, with discrepancies defining the critical prognostic age threshold. This study was undertaken to determine the impact of various age thresholds on outcome after TBI. Materials and Methods : The ages of patients admitted with TBI were prospectively studied in relation to mode of injury, Glasgow coma score (GCS, CT category and surgical intervention. Mortality was assessed at 1 month, and neurological outcome was assessed at 6 months. Appropriate statistical analyzes (details in article were performed. Results: Of the total 244 patients enrolled, 144 patients had severe, 38 patients had moderate and 62 patients had mild TBI, respectively. Age had significant association with grade of injury, CT category and surgical intervention (P 59 years respectively (P 40 years in all subgroups, based on GCS and surgical intervention (P < 0.05. Conclusions : In patients with TBI, age demonstrates independent association with unfavorable outcome at 6 months, in stepwise manner centered on a threshold of 40 years.
Hazeldine, Jon; Lord, Janet M; Belli, Antonio
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.
Max, Jeffrey E; Lopez, Aholibama; Wilde, Elisabeth A; Bigler, Erin D; Schachar, Russell J; Saunders, Ann; Ewing-Cobbs, Linda; Chapman, Sandra B; Yang, Tony T; Levin, Harvey S
The objective of this prospective longitudinal study was to assess the nature, rate, predictive variables, and neuroimaging characteristics of novel (new-onset) anxiety disorders (compared with no novel anxiety disorders) 6-12 months after pediatric traumatic brain injury (TBI). Psychiatric and psychosocial interviews were administered to children who sustained mild to severe TBI at baseline (soon after injury) and at the 12-month follow-up post-injury (n= 125). The psychiatric outcome of children 12-months post-injury revealed that novel anxiety disorders present in the second six months after TBI were heterogeneous and occurred in 13 (10.4%) participants. Novel anxiety disorder was significantly associated with concurrent novel depressive disorder and with novel personality change due to TBI. Novel anxiety disorder was marginally associated with younger age at injury and with pre-injury anxiety disorder in univariate analyses. Age at injury, pre-injury anxiety disorder, and personality change due to TBI were each significantly and independently related to novel anxiety disorder in a logistic regression analysis. There were no significant neuroimaging group differences. These findings suggest that the emergence of novel anxiety disorder after TBI might be related to a broader problem of affective dysregulation especially in younger children and those with a vulnerability even to pre-injury anxiety disorder.
Donahue, Deborah L; Beck, Julia; Fritz, Braxton; Davis, Patrick; Sandoval-Cooper, Mayra J; Thomas, Scott G; Yount, Robert A; Walsh, Mark; Ploplis, Victoria A; Castellino, Francis J
Acute coagulopathy is a serious complication of traumatic brain injury (TBI) and is of uncertain etiology because of the complex nature of TBI. However, recent work has shown a correlation between mortality and abnormal hemostasis resulting from early platelet dysfunction. The aim of the current study was to develop and characterize a rodent model of TBI that mimics the human coagulopathic condition so that mechanisms of the early acute coagulopathy in TBI can be more readily assessed. Studies utilizing a highly reproducible constrained blunt-force brain injury in rats demonstrate a strong correlation with important postinjury pathological changes that are observed in human TBI patients, namely, diminished platelet responses to agonists, especially adenosine diphosphate (ADP), and subarachnoid bleeding. Additionally, administration of a direct thrombin inhibitor, preinjury, recovers platelet functionality to ADP stimulation, indicating a direct role for excess thrombin production in TBI-induced early platelet dysfunction.
Simon, Dennis W; McGeachy, Mandy J; Bayır, Hülya; Clark, Robert S B; Loane, David J; Kochanek, Patrick M
The 'silent epidemic' of traumatic brain injury (TBI) has been placed in the spotlight as a result of clinical investigations and popular press coverage of athletes and veterans with single or repetitive head injuries. Neuroinflammation can cause acute secondary injury after TBI, and has been linked to chronic neurodegenerative diseases; however, anti-inflammatory agents have failed to improve TBI outcomes in clinical trials. In this Review, we therefore propose a new framework of targeted immunomodulation after TBI for future exploration. Our framework incorporates factors such as the time from injury, mechanism of injury, and secondary insults in considering potential treatment options. Structuring our discussion around the dynamics of the immune response to TBI - from initial triggers to chronic neuroinflammation - we consider the ability of soluble and cellular inflammatory mediators to promote repair and regeneration versus secondary injury and neurodegeneration. We summarize both animal model and human studies, with clinical data explicitly defined throughout this Review. Recent advances in neuroimmunology and TBI-responsive neuroinflammation are incorporated, including concepts of inflammasomes, mechanisms of microglial polarization, and glymphatic clearance. Moreover, we highlight findings that could offer novel therapeutic targets for translational and clinical research, assimilate evidence from other brain injury models, and identify outstanding questions in the field.
Shan, Rongzi; Thomasian, Nicole; Chodobski, Adam
The pathophysiological mechanisms underlying mild traumatic brain injury (mTBI) are not well understood, but likely involve neuroinflammation. Here the controlled cortical impact model of mTBI in rats was used to test this hypothesis. Mild TBI caused a rapid (within 6 h post-mTBI) upregulation of synthesis of TNF-α and IL-1β in the cerebral cortex and hippocampus, followed by an increase in production of neutrophil (CXCL1–3) and monocyte (CCL2) chemoattractants. While astrocytes were not a significant source of CXC chemokines, they highly expressed CCL2. An increase in production of CXC chemokines coincided with the influx of neutrophils into the injured brain. At 6 h post-mTBI, we observed a robust influx of CCL2-expressing neutrophils across pial microvessels into the subarachnoid space (SAS) near the injury site. Mild TBI was not accompanied by any significant influx of neutrophils into the brain parenchyma until 24 h after injury. This was associated with an early induction of expression of intercellular adhesion molecule 1 on the endothelium of the ipsilateral pial, but not intraparenchymal, microvessels. At 6 h post-mTBI, we also observed a robust influx of neutrophils into the ipsilateral cistern of velum interpositum (CVI), a slit-shaped cerebrospinal fluid space located above the 3rd ventricle with highly vascularized pia mater. From SAS and CVI, neutrophils appeared to move along the perivascular spaces to enter the brain parenchyma. The monocyte influx was not observed until 24 h post-mTBI, and these inflammatory cells predominantly entered the ipsilateral SAS and CVI, with a limited invasion of brain parenchyma. These observations indicate that the endothelium of pial microvessels responds to injury differently than that of intraparenchymal microvessels, which may be associated with the lack of astrocytic ensheathment of cerebrovascular endothelium in pial microvessels. These findings also suggest that neuroinflammation represents the potential
Schurman, Lesley D.; Lichtman, Aron H.
The endogenous cannabinoid (endocannabinoid) system regulates a diverse array of physiological processes and unsurprisingly possesses considerable potential targets for the potential treatment of numerous disease states, including two receptors (i.e., CB1 and CB2 receptors) and enzymes regulating their endogenous ligands N-arachidonoylethanolamine (anandamide) and 2-arachidonyl glycerol (2-AG). Increases in brain levels of endocannabinoids to pathogenic events suggest this system plays a role in compensatory repair mechanisms. Traumatic brain injury (TBI) pathology remains mostly refractory to currently available drugs, perhaps due to its heterogeneous nature in etiology, clinical presentation, and severity. Here, we review pre-clinical studies assessing the therapeutic potential of cannabinoids and manipulations of the endocannabinoid system to ameliorate TBI pathology. Specifically, manipulations of endocannabinoid degradative enzymes (e.g., fatty acid amide hydrolase, monoacylglycerol lipase, and α/β-hydrolase domain-6), CB1 and CB2 receptors, and their endogenous ligands have shown promise in modulating cellular and molecular hallmarks of TBI pathology such as; cell death, excitotoxicity, neuroinflammation, cerebrovascular breakdown, and cell structure and remodeling. TBI-induced behavioral deficits, such as learning and memory, neurological motor impairments, post-traumatic convulsions or seizures, and anxiety also respond to manipulations of the endocannabinoid system. As such, the endocannabinoid system possesses potential drugable receptor and enzyme targets for the treatment of diverse TBI pathology. Yet, full characterization of TBI-induced changes in endocannabinoid ligands, enzymes, and receptor populations will be important to understand that role this system plays in TBI pathology. Promising classes of compounds, such as the plant-derived phytocannabinoids, synthetic cannabinoids, and endocannabinoids, as well as their non-cannabinoid receptor
FELIPE F eCASANUEVA
Full Text Available Neuroendocrine dysfunction, long recognised as a consequence of traumatic brain injury (TBI, is a major cause of disability that includes physical and psychological involvement with long-term cognitive, behavioural and social changes.There is no standard procedure regarding at what time after trauma the diagnosis should be made. Also there is uncertainty on defining the best methods for diagnosis and testing and what types of patients should be selected for screening. Common criteria for evaluating these patients are required on account of the high prevalence of TBI worldwide and the potential new cases of hypopituitarism.
BATOOL F. KIRMANI
Full Text Available Traumatic brain injury (TBI can cause seizures and the development of epilepsy. The incidence of seizures varies from 21% in patients with severe brain injuries to 50% in patients with war-related penetrating TBI. In the acute and sub-acute periods following injury, seizures can lead to increased intracranial pressure and cerebral edema, further complicating TBI management. Anticonvulsants should be used for seizure prophylaxis and treatment. Phenytoin is the most widely prescribed anticonvulsant in these patients. Intravenous levetiracetam, made available in 2006, is now being considered as an alternative to phenytoin in acute care settings. When compared with phenytoin, levetiracetam has fewer side-effects and drug-drug interactions. In the following, the role of levetiracetam in TBI care and the supporting evidence is discussed.
Full Text Available The present review highlights critical issues related to cerebral metabolism following traumatic brain injury (TBI and the use of 13C labeled substrates and nuclear magnetic resonance (NMR spectroscopy to study these changes. First we address some pathophysiologic factors contributing to metabolic dysfunction following TBI. We then examine how 13C NMR spectroscopy strategies have been used to investigate energy metabolism, neurotransmission, the intracellular redox state, and neuroglial compartmentation following injury. 13C NMR spectroscopy studies of brain extracts from animal models of TBI have revealed enhanced glycolytic production of lactate, evidence of pentose phosphate pathway (PPP activation, and alterations in neuronal and astrocyte oxidative metabolism that are dependent on injury severity. Differential incorporation of label into glutamate and glutamine from 13C labeled glucose or acetate also suggest TBI-induced adaptations to the glutamate-glutamine cycle.
Simarjot K Dhaliwal
Full Text Available Background: Traumatic brain injury (TBI is a common cause of physical, psychological, and cognitive impairment, but many current treatments for TBI are ineffective or produce adverse side effects. Non-invasive methods of brain stimulation could help ameliorate some common trauma-induced symptoms.Objective: This review summarizes instances in which repetitive Transcranial Magnetic Stimulation (rTMS and transcranial Direct Current Stimulation (tDCS have been used to treat symptoms following a traumatic brain injury. A subsequent discussion attempts to determine the value of these methods in light of their potential risks.Methods: The research databases of PubMed/MEDLINE and PsycINFO were electronically searched using terms relevant to the use of rTMS and tDCS as a tool to decrease symptoms in the context of rehabilitation post-TBI.Results: Eight case-studies and four multi-subject reports using rTMS and six multi-subject studies using tDCS were found. Two instances of seizure are discussed. Conclusions: There is evidence that rTMS can be an effective treatment option for some post-TBI symptoms such as depression, tinnitus, and neglect. Although the safety of this method remains uncertain, the use of rTMS in cases of mild-TBI without obvious structural damage may be justified. Evidence on the effectiveness of tDCS is mixed, highlighting the need for additional
Blaya, Meghan O; Bramlett, Helen M; Naidoo, Jacinth; Pieper, Andrew A; Dietrich, W Dalton
Traumatic brain injury (TBI) is characterized by histopathological damage and long-term sensorimotor and cognitive dysfunction. Recent studies have reported the discovery of the P7C3 class of aminopropyl carbazole agents with potent neuroprotective properties for both newborn neural precursor cells in the adult hippocampus and mature neurons in other regions of the central nervous system. This study tested, for the first time, whether the highly active P7C3-A20 compound would be neuroprotective, promote hippocampal neurogenesis, and improve functional outcomes after experimental TBI. Sprague-Dawley rats subjected to moderate fluid percussion brain injury were evaluated for quantitative immunohistochemical and behavioral changes after trauma. P7C3-A20 (10 mg/kg) or vehicle was initiated intraperitoneally 30 min postsurgery and twice per day every day thereafter for 7 days. Administration of P7C3-A20 significantly reduced overall contusion volume, preserved vulnerable anti-neuronal nuclei (NeuN)-positive pericontusional cortical neurons, and improved sensorimotor function 1 week after trauma. P7C3-A20 treatment also significantly increased both bromodeoxyuridine (BrdU)- and doublecortin (DCX)-positive cells within the subgranular zone of the ipsilateral dentate gyrus 1 week after TBI. Five weeks after TBI, animals treated with P7C3-A20 showed significantly increased BrdU/NeuN double-labeled neurons and improved cognitive function in the Morris water maze, compared to TBI-control animals. These results suggest that P7C3-A20 is neuroprotective and promotes endogenous reparative strategies after TBI. We propose that the chemical scaffold represented by P7C3-A20 provides a basis for optimizing and advancing new pharmacological agents for protecting patients against the early and chronic consequences of TBI.
Full Text Available Traumatic brain injury (TBI is ubiquitous and effective treatments for it remain supportive largely due to uncertainty over how endogenous repair occurs. Recently, we demonstrated that hippocampal injury-induced neurogenesis is one mechanism underlying endogenous repair following TBI. Donepezil is associated with increased hippocampal neurogenesis and has long been known to improve certain aspects of cognition following many types of brain injury through unknown mechanisms. By coupling donepezil therapy with temporally regulated ablation of injury-induced neurogenesis using nestin-HSV transgenic mice, we investigated whether the pro-cognitive effects of donepezil following injury might occur through increasing neurogenesis. We demonstrate that donepezil itself enhances neurogenesis and improves cognitive function following TBI, even when injury-induced neurogenesis was inhibited. This suggests that the therapeutic effects of donepezil in TBI occur separately from its effects on neurogenesis.
Yu, Tzong-Shiue; Kim, Ahleum; Kernie, Steven G
Traumatic brain injury (TBI) is ubiquitous and effective treatments for it remain supportive largely due to uncertainty over how endogenous repair occurs. Recently, we demonstrated that hippocampal injury-induced neurogenesis is one mechanism underlying endogenous repair following TBI. Donepezil is associated with increased hippocampal neurogenesis and has long been known to improve certain aspects of cognition following many types of brain injury through unknown mechanisms. By coupling donepezil therapy with temporally regulated ablation of injury-induced neurogenesis using nestin-HSV transgenic mice, we investigated whether the pro-cognitive effects of donepezil following injury might occur through increasing neurogenesis. We demonstrate that donepezil itself enhances neurogenesis and improves cognitive function following TBI, even when injury-induced neurogenesis was inhibited. This suggests that the therapeutic effects of donepezil in TBI occur separately from its effects on neurogenesis.
Yong Jiang; Xiaochuan Sun
At present,much evidence indicates that TBI is similar in pathology and severity during the acute stage,yet may result in varied outcomes.Known prognostic factors,such as age and severity of injury and treatments,only partially explain this variability.In addition,it has been demonstrated that genetic polymorphisms may play an important role in TBI susceptibility,as well as outcome following TBI.
Jia, Feng; Yin, Yu Hua; Gao, Guo Yi; Wang, Yu; Cen, Lian; Jiang, Ji-Yao
The aim of this study was to evaluate the potential efficacy of SB-3CT, a matrix metallopeptidase 9 inhibitor, on behavioral and histological outcomes after traumatic brain injury (TBI) in rats. Adult male Sprague-Dawley rats were randomly divided into three groups (n=15/group): TBI with SB-3CT treatment, TBI with saline, and sham injury. The TBI model was induced by a fluid percussion TBI device. SB-3CT (50 mg/kg in 10% dimethyl sulfoxide) was administered intraperitoneally at 30 min, 6 h, and 12 h after the TBI. Motor function (beam-balance/beam-walk tests) and spatial learning/memory (Morris water maze) were assessed on post-operative Days 1-5 and 11-15, respectively. Fluoro-Jade staining, immunofluorescence, and cresyl violet-staining were carried out for histopathological evaluation at 24 h, 72 h, and 15 days after TBI, respectively. It was shown that TBI can result in significant behavioral deficit induced by acute neurodegeneration, increased expression of cleaved caspase-3, and long-term neuronal loss. SB-3CT intervention via the current regime provides robust behavioral protection and hippocampal neurons preservation from the deleterious effects of TBI. Hence, the efficacy of SB-3CT on TBI prognosis could be ascertained. It is believed that the current study adds to the growing literature in identifying SB-3CT as a potential therapy for human brain injury.
Guerrero, Arthur F; Alfonso, Abel
Recent civilian data obtained in those sustaining head injuries, has found a high prevalence of pituitary dysfunction. Currently, there is no data available in the military population. We reviewed the literature for traumatic brain injury (TBI)-related hypopituitarism and found that the prevalence of anterior hypopituitarism may be as high as 30-80% after 24-36 months. Since many of the symptoms of hypopituitarism are similar to those of TBI, it is important to make clinicians caring for combat veterans aware of its occurrence. Herein, we provide an overview of the literature and recommendations for hormonal testing when TBI-related hypopituitarism is suspected.
brain injury (TBI) and alcohol abuse/ dependence (AA/D). This group appears to use alcohol to self-treat fronto-limbic disinhibition, expressed... benzodiazepines may address similar symptoms, yet these drugs introduce addiction and tolerance issues and do not appear to address specific causes of...fronto-limbic disinhibition following the TBI. Alcohol abuse and/or dependence (AA/D) and mood disturbance often co-occur following TBI. (Corrigan
Traumatic brain injury (TBI) represents a huge global medical and public health problem across all ages and in all populations.In this review,we discussed the changing concepts and approaches.Globally,the incidence is increasing and in high income countries epidemiologic patterns are changing with consequences for prevention campaigns.TBI should not be viewed as an event,but as a progressive and chronic disease with lifetime consequences.In the clinical field,precision approaches to treatment are being developed,which require more accurate disease phenotyping.Recent advances in genomics,neuroimaging and biomarker development offer great opportunities to develop improved phenotyping and better disease characterization.In clinical research,randomized controlled clinical trials are being complemented by large data collections in broad TBI populations in comparative effectiveness designs.Global collaborations are being developed among funding agencies,research organizations and researchers.Only by combining efforts and collaboration will we be able to advance the field by providing long-needed evidence to support practice recommendations and to improve treatment.
... 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 ...
Plog, Benjamin A; Dashnaw, Matthew L; Hitomi, Emi; Peng, Weiguo; Liao, Yonghong; Lou, Nanhong; Deane, Rashid; Nedergaard, Maiken
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.
Yu, Chenggang; Boutté, Angela; Yu, Xueping; Dutta, Bhaskar; Feala, Jacob D; Schmid, Kara; Dave, Jitendra; Tawa, Gregory J; Wallqvist, Anders; Reifman, Jaques
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.
Hardcastle, Nina; Benzon, Hubert A.; Vavilala, Monica S.
Traumatic brain injury (TBI) is a significant contributor to death and disability in children. Considering the prevalence of pediatric TBI, it is important for the clinician to be aware of evidence-based recommendations for the care of these patients. The first edition of the Guidelines for the Acute Medical Management of Severe Traumatic Brain Injury in Infants, Children, and Adolescents was published in 2003. The Guidelines were updated in 2012, with significant changes in the recommendatio...
Full Text Available Marcelo Schwarzbold1, Alexandre Diaz1, Evandro Tostes Martins2, Armanda Rufino1, Lúcia Nazareth Amante1,3, Maria Emília Thais1, João Quevedo4, Alexandre Hohl1, Marcelo Neves Linhares1,5,6, Roger Walz1,61Núcleo de Pesquisas em Neurologia Clínica e Experimental (NUPNEC, Departamento de Clínica Médica, Hospital Universitário, UFSC, Florianópolis, SC, Brazil; 2Unidade de Terapia Intensiva, Hospital Governador Celso Ramos, Florianópolis, SC, Brazil; 3Departamento de Enfermagem, UFSC, Florianópolis, SC, Brazil; 4Laboratório de Neurociências, UNESC, Criciúma, SC, Brazil; 5Departamento de Cirurgia, Hospital Universitário, UFSC, Florianópolis, SC, Brazil; 6Centro de Cirurgia de Epilepsia de Santa Catarina (CEPESC, Hospital Governador Celso Ramos, Florianópolis, SC, BrazilAbstract: 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.Keywords: psychiatric disorders, traumatic brain injury, neuropsychiatry, diagnostic, epidemiology, pathophysiology
Michael D Cusimano
Full Text Available 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.
YANG Xiao-feng; LIU Wei-guo; SHEN Hong; GONG Jiang-biao; YU Jun; HU Wei-wei; L(U) Shi-ting; ZHENG Xiu-jue; FU Wei-ming
Objective: To study the correlation between brain edema, elevated intracranial pressure (ICP) and cell apoptosis in traumatic brain injury (TBI). Methods: In this study, totally 42 rabbits in 7 groups were studied. Six of the animals were identified as a control group, and the remaining 36 animals were equally divided into 6 TBI groups. TBI models were produced by the modified method of Feeney. After the impact, ICP of each subject was recorded continuously by an ICP monitor until the animal was sacrificed at scheduled time. The apoptotic brain cells were detected by an terminal deoxynucleotide-transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay. Cerebral water content (CWC) was measured with a drying method and calculated according to the Elliott formula. Then, an analysis was conducted to determine the correlation between the count of apoptotic cells and the clinical pathological changes of the brain. Results: Apoptotic cell count began to increase 2 h after the impact, and reached its maximum about 3 days after the impact. The peak value of CWC and ICP appeared 1 day and 3 days after the impact, respectively. Apoptotic cell count had a positive correlation with CWC and ICP. Conclusions: In TBI, occurrence of brain edema and ICP increase might lead to apoptosis of brain cells. Any therapy which can relieve brain edema and/or decrease ICP would be able to reduce neuron apoptosis, thereby to attenuate the secondary brain damage.
Heffernan, Meghan E; Huang, Wei; Sicard, Kenneth M; Bratane, Bernt T; Sikoglu, Elif M; Zhang, Nanyin; Fisher, Marc; King, Jean A
Use of novel approaches in imaging modalities is needed for enhancing diagnostic and therapeutic outcomes of persons with a traumatic brain injury (TBI). This study explored the feasibility of using functional magnetic resonance imaging (fMRI) in conjunction with behavioral measures to target dynamic changes in specific neural circuitries in an animal model of TBI. Wistar rats were randomly assigned to one of two groups (traumatic brain injury/sham operation). TBI rats were subjected to the closed head injury (CHI) model. Any observable motor deficits and cognitive deficits associated with the injury were measured using beam walk and Morris water maze tests, respectively. fMRI was performed to assess the underlying post-traumatic cerebral anatomy and function in acute (24 hours after the injury) and chronic (7 and 21 days after the injury) phases. Beam walk test results detected no significant differences in motor deficits between groups. The Morris water maze test indicated that cognitive deficits persisted for the first week after injury and, to a large extent, resolved thereafter. Resting state functional connectivity (rsFC) analysis detected initially diminished connectivity between cortical areas involved in cognition for the TBI group; however, the connectivity patterns normalized at 1 week and remained so at the 3 weeks post-injury time point. Taken together, we have demonstrated an objective in vivo marker for mapping functional brain changes correlated with injury-associated cognitive behavior deficits and offer an animal model for testing potential therapeutic interventions options.
Full Text Available Objective(s:Melatonin is known as an anti-inflammatory agent, and it has been proven to exert neuroprotection through inhibition of cell death (apoptosis in several models of brain injury.Secondary injury following the primary traumatic brain injury (TBI results in glial cells activation, especially astrocytes. In fact, astrocyte activation causes the production of pro-inflammatory cytokines that may lead to secondary injury. Since most TBI research studies have focused on injured neurons and paid little attention to glial cells, the aim of current study was to investigate the effects of melatonin against astrocytes activation (astrogliosis, as well as inhibition of apoptosis in brain tissue of male rats after TBI. Materials and Methods: The animals were randomly allocated into five groups: sham group, TBI+ vehicle group (1% ethanol in saline and TBI+ melatonin groups (5 mg/kg, 10 mg/kg and 20 mg/kg. All rats were intubated and then exposed to diffuse TBI, except for the sham group. Immunohistochemical methods were conducted using glial fibrillary acidic protein (GFAP marker and TUNEL assay to evaluate astrocyte reactivity and cell death, respectively. Results: The results showed that based on the number of GFAP positive astrocytes in brain cortex, astrogliosis was reduced significantly (P
Full Text Available 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.
Rabinowitz, Amanda R; Li, Xiaoqi; Levin, Harvey S
Mild traumatic brain injury (mTBI) has recently gained appreciation as a significant public health problem, which has highlighted just how little is known about its proximal and long-term effects. A major challenge in the study of mTBI is the heterogeneity of the condition. Research on mTBI has historically separated sport and nonsport etiologies, and the extent to which research from one of these samples translates to the other is unclear. This review examines the literature on mTBI, with a focus on comparing sport and nonsport etiologies with regard to the latest research on biomechanics, pathophysiology, neurocognitive effects, and neuroimaging. Issues of particular relevance to sports injuries, such as exercise, repetitive injuries, subconcussive blows, and chronic injury effects, are also reviewed.
Full Text Available Background. Apoptosis associates with secondary brain injury after traumatic brain injury (TBI. This study posits that serum leukocyte apoptosis levels in acute TBI are predictive of outcome. Methods. Two hundred and twenty-nine blood samples from 88 patients after acute TBI were obtained on admission and on Days 4 and 7. Serial apoptosis levels of different leukocyte subsets were examined in 88 TBI patients and 27 control subjects. Results. The leukocyte apoptosis was significantly higher in TBI patients than in controls. Brief unconsciousness (P=0.009, motor deficits (P≤0.001, GCS (P≤0.001, ISS (P=0.001, WBC count (P=0.015, late apoptosis in lymphocytes and monocytes on Day 1 (P=0.004 and P=0.022, resp., subdural hemorrhage on initial brain CT (P=0.002, neurosurgical intervention (P≤0.001, and acute posttraumatic seizure (P=0.046 were significant risk factors of outcome. Only motor deficits (P=0.033 and late apoptosis in monocytes on Day 1 (P=0.037 were independently associated with outcome. A cutoff value of 5.72% of late apoptosis in monocytes was associated with poor outcome in acute TBI patients. Conclusion. There are varying degrees of apoptosis in patients following TBI and in healthy individuals. Such differential expression suggests that apoptosis in different leukocyte subsets plays an important role in outcome following injury.
Nizamutdinov, Damir; DeMorrow, Sharon; McMillin, Matthew; Kain, Jessica; Mukherjee, Sanjib; Zeitouni, Suzanne; Frampton, Gabriel; Bricker, Paul Clint S.; Hurst, Jacob; Shapiro, Lee A.
Annually, there are over 2 million incidents of traumatic brain injury (TBI) and treatment options are non-existent. While many TBI studies have focused on the brain, peripheral contributions involving the digestive and immune systems are emerging as factors involved in the various symptomology associated with TBI. We hypothesized that TBI would alter hepatic function, including bile acid system machinery in the liver and brain. The results show activation of the hepatic acute phase response by 2 hours after TBI, hepatic inflammation by 6 hours after TBI and a decrease in hepatic transcription factors, Gli 1, Gli 2, Gli 3 at 2 and 24 hrs after TBI. Bile acid receptors and transporters were decreased as early as 2 hrs after TBI until at least 24 hrs after TBI. Quantification of bile acid transporter, ASBT-expressing neurons in the hypothalamus, revealed a significant decrease following TBI. These results are the first to show such changes following a TBI, and are compatible with previous studies of the bile acid system in stroke models. The data support the emerging idea of a systemic influence to neurological disorders and point to the need for future studies to better define specific mechanisms of action. PMID:28106051
Maruta, Jun; Heaton, Kristin J; Maule, Alexis L; Ghajar, Jamshid
We tested whether reduced cognitive function associated with mild traumatic brain injury (mTBI) and sleep deprivation can be detected and distinguished using indices of predictive visual tracking. A circular visual tracking test was given to 13 patients with acute mTBI (recruited within 2 weeks of injury), 127 normal control subjects, and 43 healthy subjects who were fatigued by 26-hour sleep deprivation. Eye movement was monitored with video-oculography. In the mTBI-related portion of the study, visual tracking performance of acute mTBI patients was significantly worse than normal subjects (p visual tracking performance (p visual tracking than sleep-deprived subjects that could also be identified with different visual tracking indices, indicating possible different neurophysiological mechanisms. Results suggest that cognitive impairment associated with mTBI and fatigue may be triaged with the aid of visual tracking measures.
Trudel, Tina M; Nidiffer, F Don; Barth, Jeffrey T
Traumatic brain injury (TBI) is a major health problem in civilian, military, and veteran populations. Individuals experiencing moderate to severe TBI require a continuum of care involving acute hospitalization and postacute rehabilitation, including community reintegration and, one would hope, a return home to function as a productive member of the community. In the military, the goal is to help individuals with TBI return to active duty or make an optimal return to civilian life if the extent of their injuries necessitates a "medical board" discharge. Whether civilian, military, or veteran with TBI, individuals who move beyond the need to live in a facility must be reintegrated back into the community. This article discusses four treatment models for community reintegration, reviews treatment standardization and outcome issues, and describes a manualized rehabilitation pilot program designed to provide community reintegration and return to duty/work for civilians, veterans, and military personnel with TBI.
Full Text Available 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.
Sinopoli, Katia J; Chen, Jen-Kai; Wells, Greg; Fait, Philippe; Ptito, Alain; Taha, Tim; Keightley, Michelle
Mild traumatic brain injury (mTBI) is a common cause of injury in youth athletes. Much of what is known about the sequelae of mTBI is yielded from the adult literature, and it appears that it is mainly those with persistent post-injury symptoms who have ongoing cognitive and neural abnormalities. However, most studies have employed single-task paradigms, which may not be challenging enough to uncover subtle deficits. We sought to examine the neural correlates of dual-task performance in male athletes aged 9-15 years using a functional neuroimaging protocol. Participants included 13 youths with a history of mTBI three to six months prior to testing and 14 typically-developing controls. All participants completed a working memory task in isolation (single-task) and while completing a concurrent motor task (dual-task); neural activity during performance was then compared between groups. Although working memory performance was similar during the single-task condition, increased working memory load resulted in an altered pattern of neural activation in key working memory areas (i.e., dorsolateral prefrontal and parietal cortices) in youth with mTBI relative to controls. During the dual-task condition, accuracy was similar between groups but injured youth performed slower than typically-developing controls, suggesting a speed-accuracy tradeoff in the mTBI group only. The injured youths also exhibited abnormal recruitment of brain structures involved in both working memory and dual-tasking. These data show that the dual-task paradigm can uncover functional impairments in youth with mTBI who are not highly symptomatic and who do not exhibit neuropsychological dysfunction. Moreover, neural recruitment abnormalities were noted in both task conditions, which we argue suggests mTBI-related disruptions in achieving efficient cognitive control and allocation of processing resources.
Pearn, Matthew L; Niesman, Ingrid R; Egawa, Junji; Sawada, Atsushi; Almenar-Queralt, Angels; Shah, Sameer B; Duckworth, Josh L; Head, Brian P
Traumatic brain injury (TBI) is one of the leading causes of death of young people in the developed world. In the United States alone, 1.7 million traumatic events occur annually accounting for 50,000 deaths. The etiology of TBI includes traffic accidents, falls, gunshot wounds, sports, and combat-related events. TBI severity ranges from mild to severe. TBI can induce subtle changes in molecular signaling, alterations in cellular structure and function, and/or primary tissue injury, such as contusion, hemorrhage, and diffuse axonal injury. TBI results in blood-brain barrier (BBB) damage and leakage, which allows for increased extravasation of immune cells (i.e., increased neuroinflammation). BBB dysfunction and impaired homeostasis contribute to secondary injury that occurs from hours to days to months after the initial trauma. This delayed nature of the secondary injury suggests a potential therapeutic window. The focus of this article is on the (1) pathophysiology of TBI and (2) potential therapies that include biologics (stem cells, gene therapy, peptides), pharmacological (anti-inflammatory, antiepileptic, progrowth), and noninvasive (exercise, transcranial magnetic stimulation). In final, the review briefly discusses membrane/lipid rafts (MLR) and the MLR-associated protein caveolin (Cav). Interventions that increase Cav-1, MLR formation, and MLR recruitment of growth-promoting signaling components may augment the efficacy of pharmacologic agents or already existing endogenous neurotransmitters and neurotrophins that converge upon progrowth signaling cascades resulting in improved neuronal function after injury.
Jin, Yichao; Lin, Yingying; Feng, Jun-feng; Jia, Feng; Gao, Guo-yi; Jiang, Ji-yao
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.
Shearer, Joseph; Boone, Deborah; Weisz, Harris; Jennings, Kristofer; Uchida, Tatsuo; Parsley, Margaret; DeWitt, Douglas; Prough, Donald; Hellmich, Helen
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.
Full Text Available Many studies of protein expression after traumatic brain injury (TBI have identified biomarkers for diagnosing or determining the prognosis of TBI. In this study, we searched for additional protein markers of TBI using a fluid perfusion impact device to model TBI in S-D rats. Two-dimensional gel electrophoresis and mass spectrometry were used to identify differentially expressed proteins. After proteomic analysis, we detected 405 and 371 protein spots within a pH range of 3-10 from sham-treated and contused brain cortex, respectively. Eighty protein spots were differentially expressed in the two groups and 20 of these proteins were identified. This study validated the established biomarkers of TBI and identified potential biomarkers that could be examined in future work.
Khalin, Igor; Alyautdin, Renad; Wong, Tin Wui; Gnanou, Justin; Kocherga, Ganna; Kreuter, Jörg
Currently, traumatic brain injury (TBI) is the leading cause of death or disabilities in young individuals worldwide. The multi-complexity of its pathogenesis as well as impermeability of the blood-brain barrier (BBB) makes the drug choice and delivery very challenging. The brain-derived neurotrophic factor (BDNF) regulates neuronal plasticity, neuronal cell growth, proliferation, cell survival and long-term memory. However, its short half-life and low BBB permeability are the main hurdles to be an effective therapeutic for TBI. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles coated by surfactant can enable the delivery of a variety of molecules across the BBB by receptor-mediated transcytosis. This study examines the ability of PLGA nanoparticles coated with poloxamer 188 (PX) to deliver BDNF into the brain and neuroprotective effects of BNDF in mice with TBI. C57bl/6 mice were subjected to weight-drop closed head injuries under anesthesia. Using enzyme-linked immunosorbent assay, we demonstrated that the intravenous (IV) injection of nanoparticle-bound BDNF coated by PX (NP-BDNF-PX) significantly increased BDNF levels in the brain of sham-operated mice (p brain in TBI mice compared to controls. This study also showed using the passive avoidance (PA) test, that IV injection of NP-BDNF-PX 3 h post-injury prolonged the latent time in mice with TBI thereby reversing cognitive deficits caused by brain trauma. Finally, neurological severity score test demonstrated that our compound efficiently reduced the scores at day 7 after the injury indicating the improvement of neurological deficit in animals with TBI. This study shows that PLGA nanoparticles coated with PX effectively delivered BDNF into the brain, and improved neurological and cognitive deficits in TBI mice, thereby providing a neuroprotective effect.
Ettenhofer, Mark L; Barry, David M
Mild traumatic brain injury (mild TBI) is often associated with postconcussive symptoms such as headache, memory problems, and irritability. However, high rates of similar symptoms in groups without a history of TBI raise questions about the clinical validity of the postconcussive syndrome. This study was conducted to address these issues through systematic examination of symptoms reported by those with and without a history of mild TBI or orthopedic injury. Responses to the Postconcussion Syndrome Checklist (PCSC), demographic information, and medical history were collected via online questionnaire from 3027 non-referred university students (2280 without a history of mild TBI or orthopedic injury, 491 with a history of orthopedic injury, and 256 with post-acute mild TBI). Although the mild TBI group reported higher mean levels of symptoms, confirmatory factor analyses demonstrated that symptoms clustered into parallel cognitive, somatic, affective, and sensory factors in all three groups. Despite modestly higher mean symptoms among those with a history of mild TBI, symptom clusters did not differ from non-TBI groups. These findings cast doubts about the clinical validity of the "postconcussive syndrome" and raise questions about pathways by which mild TBI and other factors may influence the expression of chronic symptoms.
... Tumors Brain Tumors Brain Disorders AVMs Radiosurgery Gamma Knife Linac Radiotherapy Overview Childhood Brain Tumors IMRT Radiation Therapy Radiation Injury Treatment Day Making a Decision Centers of Excellence Publications Definitions Q & ...
Silverberg, Noah D; Crane, Paul K; Dams-O'Connor, Kristen; Holdnack, James; Ivins, Brian J; Lange, Rael T; Manley, Geoffrey T; McCrea, Michael; Iverson, Grant L
Cognitive impairment is a core clinical feature of traumatic brain injury (TBI). After TBI, cognition is a key determinant of post-injury productivity, outcome, and quality of life. As a final common pathway of diverse molecular and microstructural TBI mechanisms, cognition is an ideal endpoint in clinical trials involving many candidate drugs and nonpharmacological interventions. Cognition can be reliably measured with performance-based neuropsychological tests that have greater granularity than crude rating scales, such as the Glasgow Outcome Scale-Extended, which remain the standard for clinical trials. Remarkably, however, there is no well-defined, widely accepted, and validated cognition endpoint for TBI clinical trials. A single cognition endpoint that has excellent measurement precision across a wide functional range and is sensitive to the detection of small improvements (and declines) in cognitive functioning would enhance the power and precision of TBI clinical trials and accelerate drug development research. We outline methodologies for deriving a cognition composite score and a research program for validation. Finally, we discuss regulatory issues and the limitations of a cognition endpoint.
Full Text Available Traumatic brain injury (TBI is a leading cause of death and disability in the United States. Despite more than 30 years of research, no pharmacological agents have been identified that improve neurological function following TBI. However, several lines of research described in this review provide support for further development of voltage gated calcium channel (VGCC antagonists as potential therapeutic agents. Following TBI, neurons and astrocytes experience a rapid and sometimes enduring increase in intracellular calcium ([Ca2+]i. These fluxes in [Ca2+]i drive not only apoptotic and necrotic cell death, but also can lead to long-term cell dysfunction in surviving cells. In a limited number of in vitro experiments, both L-type and N-type VGCC antagonists successfully reduced calcium loads as well as neuronal and astrocytic cell death following mechanical injury. In rodent models of TBI, administration of VGCC antagonists reduced cell death and improved cognitive function. It is clear that there is a critical need to find effective therapeutics and rational drug delivery strategies for the management and treatment of TBI, and we believe that further investigation of VGCC antagonists should be pursued before ruling out the possibility of successful translation to the clinic.
Klemenhagen, Kristen C; O'Brien, Scott P; Brody, David L
The debilitating effects of repetitive concussive traumatic brain injury (rcTBI) have been increasingly recognized in both military and civilian populations. rcTBI may result in significant neurological, cognitive, and affective sequelae, and is often followed by physical and/or psychological post-injury stressors that may exacerbate the effects of the injury and prolong the recovery period for injured patients. However, the consequences of post-injury stressors and their subsequent effects on social and emotional behavior in the context of rcTBI have been relatively little studied in animal models. Here, we use a mouse model of rcTBI with two closed-skull blunt impacts 24 hours apart and social and emotional behavior testing to examine the consequences of a stressor (foot shock fear conditioning) following brain injury (rcTBI). rcTBI alone did not affect cued or contextual fear conditioning or extinction compared to uninjured sham animals. In the sucrose preference test, rcTBI animals had decreased preference for sucrose, an anhedonia-like behavior, regardless of whether they experienced foot shock stress or were non-shocked controls. However, rcTBI and post-injury foot shock stress had synergistic effects in tests of social recognition and depression-like behavior. In the social recognition test, animals with both injury and shock were more impaired than either non-shocked injured mice or shocked but uninjured mice. In the tail suspension test, injured mice had increased depression-like behavior compared with uninjured mice, and shock stress worsened the depression-like behavior only in the injured mice with no effect in the uninjured mice. These results provide a model of subtle emotional behavioral deficits after combined concussive brain injury and stress, and may provide a platform for testing treatment and prevention strategies for social behavior deficits and mood disorders that are tailored to patients with traumatic brain injury.
Kristen C Klemenhagen
Full Text Available The debilitating effects of repetitive concussive traumatic brain injury (rcTBI have been increasingly recognized in both military and civilian populations. rcTBI may result in significant neurological, cognitive, and affective sequelae, and is often followed by physical and/or psychological post-injury stressors that may exacerbate the effects of the injury and prolong the recovery period for injured patients. However, the consequences of post-injury stressors and their subsequent effects on social and emotional behavior in the context of rcTBI have been relatively little studied in animal models. Here, we use a mouse model of rcTBI with two closed-skull blunt impacts 24 hours apart and social and emotional behavior testing to examine the consequences of a stressor (foot shock fear conditioning following brain injury (rcTBI. rcTBI alone did not affect cued or contextual fear conditioning or extinction compared to uninjured sham animals. In the sucrose preference test, rcTBI animals had decreased preference for sucrose, an anhedonia-like behavior, regardless of whether they experienced foot shock stress or were non-shocked controls. However, rcTBI and post-injury foot shock stress had synergistic effects in tests of social recognition and depression-like behavior. In the social recognition test, animals with both injury and shock were more impaired than either non-shocked injured mice or shocked but uninjured mice. In the tail suspension test, injured mice had increased depression-like behavior compared with uninjured mice, and shock stress worsened the depression-like behavior only in the injured mice with no effect in the uninjured mice. These results provide a model of subtle emotional behavioral deficits after combined concussive brain injury and stress, and may provide a platform for testing treatment and prevention strategies for social behavior deficits and mood disorders that are tailored to patients with traumatic brain injury.
Yan Zhao; Zheng-Guo Wang
Blast injury has become the major life-and function-threatening injuries in recent warfares.There is increased research interest in the mental disorders caused by blast-induced traumatic brain injury (bTBI),which has been proved as one of the "signature wounds" in modern battlefield.We reviewed the recent progresses in bTBl-related researches and concluded that the new era of blast injury research has shifted from the traditional physical impairments to cognitive dysfunctional/mental disorders that are proved to be more related to the outcome of combat casualty care.
Gilg Anne G
Full Text Available Abstract Background Traumatic brain injury (TBI induces primary and secondary damage in both the endothelium and the brain parenchyma, collectively termed the neurovascular unit. While neurons die quickly by necrosis, a vicious cycle of secondary injury in endothelial cells exacerbates the initial injury in the neurovascular unit following TBI. In activated endothelial cells, excessive superoxide reacts with nitric oxide (NO to form peroxynitrite. Peroxynitrite has been implicated in blood brain barrier (BBB leakage, altered metabolic function, and neurobehavioral impairment. S-nitrosoglutathione (GSNO, a nitrosylation-based signaling molecule, was reported not only to reduce brain levels of peroxynitrite and oxidative metabolites but also to improve neurological function in TBI, stroke, and spinal cord injury. Therefore, we investigated whether GSNO promotes the neurorepair process by reducing the levels of peroxynitrite and the degree of oxidative injury. Methods TBI was induced by controlled cortical impact (CCI in adult male rats. GSNO or 3-Morpholino-sydnonimine (SIN-1 (50 μg/kg body weight was administered orally two hours following CCI. The same dose was repeated daily until endpoints. GSNO-treated (GSNO group or SIN-1-treated (SIN-1 group injured animals were compared with vehicle-treated injured animals (TBI group and vehicle-treated sham-operated animals (Sham group in terms of peroxynitrite, NO, glutathione (GSH, lipid peroxidation, blood brain barrier (BBB leakage, edema, inflammation, tissue structure, axon/myelin integrity, and neurotrophic factors. Results SIN-1 treatment of TBI increased whereas GSNO treatment decreased peroxynitrite, lipid peroxides/aldehydes, BBB leakage, inflammation and edema in a short-term treatment (4-48 hours. GSNO also reduced brain infarctions and enhanced the levels of NO and GSH. In a long-term treatment (14 days, GSNO protected axonal integrity, maintained myelin levels, promoted synaptic plasticity
Heverly-Fitt, Sara; Wimsatt, Maureen A.; Menzer, Melissa M.; Rubin, Kenneth H.; Dennis, Maureen; Taylor, Gerry; Stancin, Terry; Gerhardt, Cynthia A.; Vannatta, Kathryn; Bigler, Erin D.; Yeates, Keith Owen
This study examined differences in friendship quality between children with traumatic brain injury (TBI) and orthopedic injury (OI) and behavioral outcomes for children from both groups. Participants were 41 children with TBI and 43 children with OI (M age = 10.4). Data were collected using peer- and teacher-reported measures of participants’ social adjustment and parent-reported measures of children’s post-injury behaviors. Participants and their mutually nominated best friends also completed a measure of the quality of their friendships. Children with TBI reported significantly more support and satisfaction in their friendships than children with OI. Children with TBI and their mutual best friend were more similar in their reports of friendship quality compared to children with OI and their mutual best friends. Additionally, for children with TBI who were rejected by peers, friendship support buffered against maladaptive psychosocial outcomes, and predicted skills related to social competence. Friendship satisfaction was related to higher teacher ratings of social skills for the TBI group only. Positive and supportive friendships play an important role for children with TBI, especially for those not accepted by peers. Such friendships may protect children with TBI who are rejected against maladaptive psychosocial outcomes, and promote skills related to social competence. PMID:24840021
Full Text Available Abstract Background Traumatic brain injury (TBI evokes a systemic immune response including leukocyte migration into the brain and release of pro-inflammatory cytokines; however, the mechanisms underlying TBI pathogenesis and protection are poorly understood. Due to the high incidence of head trauma in the sports field, battlefield and automobile accidents identification of the molecular signals involved in TBI progression is critical for the development of novel therapeutics. Methods In this report, we used a rat lateral fluid percussion impact (LFPI model of TBI to characterize neurodegeneration, apoptosis and alterations in pro-inflammatory mediators at two time points within the secondary injury phase. Brain histopathology was evaluated by fluoro-jade (FJ staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL assay, polymerase chain reaction (qRT PCR, enzyme linked immunosorbent assay (ELISA and immunohistochemistry were employed to evaluate the CCL20 gene expression in different tissues. Results Histological analysis of neurodegeneration by FJ staining showed mild injury in the cerebral cortex, hippocampus and thalamus. TUNEL staining confirmed the presence of apoptotic cells and CD11b+ microglia indicated initiation of an inflammatory reaction leading to secondary damage in these areas. Analysis of spleen mRNA by PCR microarray of an inflammation panel led to the identification of CCL20 as an important pro-inflammatory signal upregulated 24 h after TBI. Although, CCL20 expression was observed in spleen and thymus after 24h of TBI, it was not expressed in degenerating cortex or hippocampal neurons until 48 h after insult. Splenectomy partially but significantly decreased the CCL20 expression in brain tissues. Conclusion These results demonstrate that the systemic inflammatory reaction to TBI starts earlier than the local brain response and suggest that spleen- and/ or thymus-derived CCL20 might play a role in
HUANG, XIAN-JIAN; Li, Wei-Ping; Lin, Yong; Feng, Jun-Feng; Jia,Feng; Mao, Qing; Jiang, Ji-yao
Excessive active voltage-gated sodium channels are responsible for the cellular abnormalities associated with secondary brain injury following traumatic brain injury (TBI). We previously presented evidence that significant upregulation of Nav1.3 expression occurs in the rat cortex at 2 h and 12 h post-TBI and is correlated with TBI severity. In our current study, we tested the hypothesis that blocking upregulation of Nav1.3 expression in vivo in the acute stage post-TBI attenuates the seconda...
Elder, Gregory A
Traumatic brain injury (TBI) is a common cause of morbidity and mortality in military life. Interest in military TBI has increased recently due to the conflicts in Iraq and Afghanistan. Certain types of TBI are relatively unique to the military, the most prominent being blast-related TBI. Blast-related mild TBI has been of particular concern in veterans from the most recent conflicts although controversy remains concerning its separation from post-traumatic stress disorder. TBI is also a risk factor for the later development of neurodegenerative diseases in which cognitive impairment is prominent putting veterans at risk for disorders including Alzheimer's disease and chronic traumatic encephalopathy. Recent evidence associating TBI with chronic cognitive impairment is reviewed in the context of its relevance to military veterans.
Full Text Available All experimental models of traumatic brain injury (TBI result in a progressive loss of brain tissue. The extent of tissue loss reflects the injury severity and can be measured to evaluate the potential neuroprotective effect of experimental treatments. Quantitation of tissue volumes is commonly performed using evenly spaced brain sections stained using routine histochemical methods and digitally captured. The brain tissue areas are then measured and the corresponding volumes are calculated using the distance between the sections. Measurements of areas are usually performed using a general purpose image analysis software and the results are then transferred to another program for volume calculations. To facilitate the measurement of brain tissue loss we developed novel algorithms which automatically separate the areas of brain tissue from the surrounding image background and identify the ventricles. We implemented these new algorithms by creating a new computer program (SectionToVolume which also has functions for image organization, image adjustments and volume calculations. We analyzed brain sections from mice subjected to severe focal TBI using both SectionToVolume and ImageJ, a commonly used image analysis program. The volume measurements made by the two programs were highly correlated and analysis using SectionToVolume required considerably less time. The inter-rater reliability was high. Given the extensive use of brain tissue loss measurements in TBI research, SectionToVolume will likely be a useful tool for TBI research. We therefore provide both the source code and the program as attachments to this article.
Schmidt, Adam T.; Hanten, Gerri R.; Li, Xiaoqi; Orsten, Kimberley D.; Levin, Harvey S.
Children with closed head injuries often experience significant and persistent disruptions in their social and behavioral functioning. Studies with adults sustaining a traumatic brain injury (TBI) indicate deficits in emotion recognition and suggest that these difficulties may underlie some of the social deficits. The goal of the current study was…
Full Text Available Context: Coagulopathy frequently occurs following traumatic brain injury (TBI and usually occurs 6-72 hour post-trauma. The incidence and the probable risk factors for development of coagulopathy and poor outcome following TBI are largely unknown and vary considerably. Aims: To assess the incidence and probable risk factors for development of coagulopathy and to identify the risk factors for poor outcome in terms of median survival time following TBI. Materials and Methods: In this prospective study over two years, patients of isolated moderate and severe traumatic brain injury (GCS≤12 admitted to trauma center had coagulation profile (PT, APTT, thrombin time, fibrinogen and D-dimer, arterial lactate and ABG analysis done on day of admission and on day three. Coagulopathy was defined as prothrombin time (PT or/and activated partial thromboplastin time (APTT more than 1.5 times the normal control. Incidence of in-hospital mortality was assessed in all cases. Statistical Analysis: A stepwise logistic regression analysis was performed to identify risk factors for coagulopathy and mortality in these patients. Results: A total of 208 patients were enrolled in the study. The mean age was 32 ± 12 years and mean GCS was 7.1 ± 2.8. Coagulopathy was present in 46% ( n = 96 of patients. Risk factors for development of coagulopathy were found out to be severity of head injury (OR: 2.81, elevated D-dimer (OR: 3.43, low hemoglobin (OR: 3.13, and effaced cisterns in the CT scan (OR: 2.72. Presence of coagulopathy (OR: 2.97 and severity of head injury (OR: 5.70 strongly predicted poor outcome, and were associated with a decreased median survival time. Conclusions: There is a high incidence of coagulopathy following TBI. The presence of coagulopathy as well as of severity of TBI are strong predictors of in-hospital mortality in these patients.
Taylor, Paul Allen; Ford, Corey C. (University of New Mexico, Albuquerque, NM)
U.S. soldiers are surviving blast and impacts due to effective body armor, trauma evacuation and care. Blast injuries are the leading cause of traumatic brain injury (TBI) in military personnel returning from combat. Understanding of Primary Blast Injury may be needed to develop better means of blast mitigation strategies. The objective of this paper is to investigate the effects of blast direction and strength on the resulting mechanical stress and wave energy distributions generated in the brain.
Full Text Available We describe six psychomotor, language, and neuropsychological sequential developmental evaluations in a boy who sustained a severe bifrontal traumatic brain injury (TBI at 19 months of age. Visuospatial, drawing, and writing skills failed to develop normally. Gradually increasing difficulties were noted in language leading to reading and spontaneous speech difficulties. The last two evaluations showed executive deficits in inhibition, flexibility, and working memory. Those executive abnormalities seemed to be involved in the other impairments. In conclusion, early frontal brain injury disorganizes the development of cognitive functions, and interactions exist between executive function and other cognitive functions during development.
Alvis-Miranda, Hernando Raphael; Castellar-Leones, Sandra Milena; Moscote-Salazar, Luis Rafael
The patient with head trauma is a challenge for the emergency physician and for the neurosurgeon. Currently traumatic brain injury constitutes a public health problem. Knowledge of the various supportive therapeutic strategies in the pre-hospital and pre-operative stages is essential for optimal care. The immediate rapid infusion of large volumes of crystalloids to restore blood volume and blood pressure is now the standard treatment of patients with combined traumatic brain injury (TBI) and hemorrhagic shock (HS). The fluid in patients with brain trauma and especially in patients with brain injur y is a critical issue. In this context we present a review of the literature about the history, physiology of current fluid preparations, and a discussion regarding the use of fluid therapy in traumatic brain injury and decompressive craniectomy. PMID:27162857
Hernando Raphael Alvis-Miranda
Full Text Available The patient with head trauma is a challenge for the emergency physician and for the neurosurgeon. Currently traumatic brain injury constitutes a public health problem. Knowledge of the various supportive therapeutic strategies in the pre-hospital and pre-operative stages is essential for optimal care. The immediate rapid infusion of large volumes of crystalloids to restore blood volume and blood pressure is now the standard treatment of patients with combined traumatic brain injury (TBI and hemorrhagic shock (HS. The fluid in patients with brain trauma and especially in patients with brain injur y is a critical issue. In this context we present a review of the literature about the history, physiology of current fluid preparations, and a discussion regarding the use of fluid therapy in traumatic brain injury and decompressive craniectomy.
Hart, Tessa; Whyte, John; Poulsen, Ingrid;
OBJECTIVE: Determine effects of inpatient and outpatient treatment intensity on functional and emotional well-being outcomes at 1 year post severe traumatic brain injury (TBI). DESIGN: Prospective, quasi-experimental study comparing outcomes in a US TBI treatment center with those in a Denmark (DK......) center providing significantly greater intensity and duration of rehabilitation. SETTING: Inpatient and outpatient TBI rehabilitation. PARTICIPANTS: 274 persons with severe traumatic brain injury. INTERVENTIONS: Inpatient rehabilitation interventions were counted daily by discipline. Outpatient....... CONCLUSIONS: Contrary to expectation, DK patients who received significantly more rehabilitation services during the year following severe TBI did not differ in outcome from their less intensively treated US counterparts, after adjusting for initial severity. The negative association of functional treatment...
Costanzo, Michelle E; Chou, Yi-Yu; Leaman, Suzanne; Pham, Dzung L; Keyser, David; Nathan, Dominic E; Coughlin, Mary; Rapp, Paul; Roy, Michael J
Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) may share common symptom and neuropsychological profiles in military service members (SMs) following deployment; while a connection between the two conditions is plausible, the relationship between them has been difficult to discern. The intent of this report is to enhance our understanding of the relationship between findings on structural and functional brain imaging and symptoms of PTSD. Within a cohort of SMs who did not meet criteria for PTSD but were willing to complete a comprehensive assessment within 2 months of their return from combat deployment, we conducted a nested case-control analysis comparing those with combat-related mTBI to age/gender-matched controls with diffusion tensor imaging, resting state functional magnetic resonance imaging and a range of psychological measures. We report degraded white matter integrity in those with a history of combat mTBI, and a positive correlation between the white matter microstructure and default mode network (DMN) connectivity. Higher clinician-administered and self-reported subthreshold PTSD symptoms were reported in those with combat mTBI. Our findings offer a potential mechanism through which mTBI may alter brain function, and in turn, contribute to PTSD symptoms.
Robinson, Kristen E; Fountain-Zaragoza, Stephanie; Dennis, Maureen; Taylor, H Gerry; Bigler, Erin D; Rubin, Kenneth; Vannatta, Kathryn; Gerhardt, Cynthia A; Stancin, Terry; Yeates, Keith Owen
This study examined whether executive function and theory of mind mediate the effects of pediatric traumatic brain injury (TBI) on social adjustment, relative to children with orthopedic injury (OI). Participants included 19 children with severe TBI, 41 children with complicated mild/moderate TBI, and 57 children with OI. They completed measures of executive function, as well as cognitive, affective, and conative theory of mind. Parents provided ratings of children's social adjustment. Children with severe TBI performed more poorly than children with OI on executive function and theory of mind tasks and were rated by parents as having more behavioral symptoms and worse communication and social skills. Executive function and theory of mind were positively correlated with social skills and communication skills, and negatively correlated with behavioral symptoms. In multiple mediator models, theory of mind and executive function were not significant direct predictors of any measure of social adjustment, but mediated the association between injury and adjustment for children with severe TBI. Theory of mind was a significant independent mediator when predicting social skills, but executive function was not. TBI in children, particularly severe injury, is associated with poor social adjustment. The impact of TBI on children's social adjustment is likely mediated by its effects on executive function and theory of mind.
Fountain-Zaragoza, Stephanie; Dennis, Maureen; Taylor, H. Gerry; Bigler, Erin D.; Rubin, Kenneth; Vannatta, Kathryn; Gerhardt, Cynthia A.; Stancin, Terry; Yeates, Keith Owen
Abstract This study examined whether executive function and theory of mind mediate the effects of pediatric traumatic brain injury (TBI) on social adjustment, relative to children with orthopedic injury (OI). Participants included 19 children with severe TBI, 41 children with complicated mild/moderate TBI, and 57 children with OI. They completed measures of executive function, as well as cognitive, affective, and conative theory of mind. Parents provided ratings of children's social adjustment. Children with severe TBI performed more poorly than children with OI on executive function and theory of mind tasks and were rated by parents as having more behavioral symptoms and worse communication and social skills. Executive function and theory of mind were positively correlated with social skills and communication skills, and negatively correlated with behavioral symptoms. In multiple mediator models, theory of mind and executive function were not significant direct predictors of any measure of social adjustment, but mediated the association between injury and adjustment for children with severe TBI. Theory of mind was a significant independent mediator when predicting social skills, but executive function was not. TBI in children, particularly severe injury, is associated with poor social adjustment. The impact of TBI on children's social adjustment is likely mediated by its effects on executive function and theory of mind. PMID:25003478
Thompson, Hilaire J; Lifshitz, Jonathan; Marklund, Niklas; Grady, M Sean; Graham, David I; Hovda, David A; McIntosh, Tracy K
This article comprehensively reviews the lateral fluid percussion (LFP) model of traumatic brain injury (TBI) in small animal species with particular emphasis on its validity, clinical relevance and reliability. The LFP model, initially described in 1989, has become the most extensively utilized animal model of TBI (to date, 232 PubMed citations), producing both focal and diffuse (mixed) brain injury. Despite subtle variations in injury parameters between laboratories, universal findings are evident across studies, including histological, physiological, metabolic, and behavioral changes that serve to increase the reliability of the model. Moreover, demonstrable histological damage and severity-dependent behavioral deficits, which partially recover over time, validate LFP as a clinically-relevant model of human TBI. The LFP model, also has been used extensively to evaluate potential therapeutic interventions, including resuscitation, pharmacologic therapies, transplantation, and other neuroprotective and neuroregenerative strategies. Although a number of positive studies have identified promising therapies for moderate TBI, the predictive validity of the model may be compromised when findings are translated to severely injured patients. Recently, the clinical relevance of LFP has been enhanced by combining the injury with secondary insults, as well as broadening studies to incorporate issues of gender and age to better approximate the range of human TBI within study design. We conclude that the LFP brain injury model is an appropriate tool to study the cellular and mechanistic aspects of human TBI that cannot be addressed in the clinical setting, as well as for the development and characterization of novel therapeutic interventions. Continued translation of pre-clinical findings to human TBI will enhance the predictive validity of the LFP model, and allow novel neuroprotective and neuroregenerative treatment strategies developed in the laboratory to reach the
Janna eMantua; Keenan M Mahan; Owen S Henry; Rebecca M. C. Spencer
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 wor...
Vinay Kukreti; Hadi Mohseni-Bod; James Drake
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 man...
Roozenbeek, Bob; Perel, Pablo; Edwards, Phil; Roberts, Ian; Murray, Gordon; Maas, Andrew; Steyerberg, Ewout
textabstractIntroduction: In clinical trials, ordinal outcome measures are often dichotomized into two categories. In traumatic brain injury (TBI) the 5-point Glasgow outcome scale (GOS) is collapsed into unfavourable versus favourable outcome. Simulation studies have shown that exploiting the ordinal nature of the GOS increases chances of detecting treatment effects. The objective of this study is to quantify the benefits of ordinal analysis in the real-life situation of a large TBI trial.Me...
Full Text Available In a rat model of traumatic brain injury (TBI, we investigated changes in cognitive function and S100A6 expression in the hippocampus. TBI-associated changes in this protein have not previously been reported. Rat S100A6 was studied via immunohistochemical staining, Western blot, and reverse transcription-polymerase chain reaction (RT-PCR after either lateral head acceleration or sham. Reduced levels of S100A6 protein and mRNA were observed 1 h after TBI, followed by gradual increases over 6, 12, 24, and 72 h, and then a return to sham level at 14 day. Morris water maze (MWM test was used to evaluate animal spatial cognition. TBI- and sham-rats showed an apparent learning curve, expressed as escape latency. Although TBI-rats displayed a relatively poorer cognitive ability than sham-rats, the disparity was not significant early post-injury. Marked cognitive deficits in TBI-rats were observed at 72 h post-injury compared with sham animals. TBI-rats showed decreased times in platform crossing in the daily MWM test; the performance at 72 h post-injury was the worst. In conclusion, a reduction in S100A6 may be one of the early events that lead to secondary cognitive decline after TBI, and its subsequent elevation is tightly linked with cognitive improvement. S100A6 may play important roles in neuronal degeneration and regeneration in TBI.
Brady, Rhys D; Grills, Brian L; Church, Jarrod E; Walsh, Nicole C; McDonald, Aaron C; Agoston, Denes V; Sun, Mujun; O’Brien, Terence J; Shultz, Sandy R; McDonald, Stuart J
Concomitant traumatic brain injury (TBI) and long bone fracture are commonly observed in multitrauma and polytrauma. Despite clinical observations of enhanced bone healing in patients with TBI, the relationship between TBI and fracture healing remains poorly understood, with clinical data limited by the presence of several confounding variables. Here we developed a novel trauma model featuring closed-skull weight-drop TBI and concomitant tibial fracture in order to investigate the effect of TBI on fracture healing. Male mice were assigned into Fracture + Sham TBI (FX) or Fracture + TBI (MULTI) groups and sacrificed at 21 and 35 days post-injury for analysis of healing fractures by micro computed tomography (μCT) and histomorphometry. μCT analysis revealed calluses from MULTI mice had a greater bone and total tissue volume, and displayed higher mean polar moment of inertia when compared to calluses from FX mice at 21 days post-injury. Histomorphometric results demonstrated an increased amount of trabecular bone in MULTI calluses at 21 days post-injury. These findings indicate that closed head TBI results in calluses that are larger in size and have an increased bone volume, which is consistent with the notion that TBI induces the formation of a more robust callus. PMID:27682431
de Koning, M. E.; Gareb, Barzi; El Moumni, M.; Scheenen, M. E.; van der Horn, H. J.; Timmerman, M. E.; Spikman, J. M.; van der Naalt, J.
Objective: To identify the frequency, nature and profile of complaints for trauma patients with and without mild traumatic brain injury (mTBI), and to assess their relation to anxiety and depression. Methods: A prospective cohort study in a level-one trauma centre was conducted. Mild traumatic brain
Douglas, David B; Iv, Michael; Douglas, Pamela K; Anderson, Ariana; Vos, Sjoerd B; Bammer, Roland; Zeineh, Michael; Wintermark, Max
Neuroimaging plays a critical role in the setting in traumatic brain injury (TBI). Diffusion tensor imaging (DTI) is an advanced magnetic resonance imaging technique that is capable of providing rich information on the brain's neuroanatomic connectome. The purpose of this article is to systematically review the role of DTI and advanced diffusion techniques in the setting of TBI, including diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging, diffusion spectrum imaging, and q-ball imaging. We discuss clinical applications of DTI and review the DTI literature as it pertains to TBI. Despite the continued advancements in DTI and related diffusion techniques over the past 20 years, DTI techniques are sensitive for TBI at the group level only and there is insufficient evidence that DTI plays a role at the individual level. We conclude by discussing future directions in DTI research in TBI including the role of machine learning in the pattern classification of TBI.
Sabir, Meriem; Gaudreault, Pierre-Olivier; Freyburger, Marlène; Massart, Renaud; Blanchet-Cohen, Alexis; Jaber, Manar; Gosselin, Nadia; Mongrain, Valérie
Traumatic brain injury (TBI), including mild TBI (mTBI), is importantly associated with vigilance and sleep complaints. Because sleep is required for learning, plasticity and recovery, we here evaluated the bidirectional relationship between mTBI and sleep with two specific objectives: (1) Test that mTBI rapidly impairs sleep-wake architecture and the dynamics of the electrophysiological marker of sleep homeostasis (i.e., non-rapid eye movement sleep delta (1-4Hz) activity); (2) evaluate the impact of sleep loss following mTBI on the expression of plasticity markers that have been linked to sleep homeostasis and on genome-wide gene expression. A closed-head injury model was used to perform a 48h electrocorticographic (ECoG) recording in mice submitted to mTBI or Sham surgery. mTBI was found to immediately decrease the capacity to sustain long bouts of wakefulness as well as the amplitude of the time course of ECoG delta activity during wakefulness. Significant changes in ECoG spectral activity during wakefulness, non-rapid eye movement and rapid eye movement sleep were observed mainly on the second recorded day. A second experiment was performed to measure gene expression in the cerebral cortex and hippocampus after a mTBI followed either by two consecutive days of 6h sleep deprivation (SD) or of undisturbed behavior (quantitative PCR and next-generation sequencing). mTBI modified the expression of genes involved in immunity, inflammation and glial function (e.g., chemokines, glial markers) and SD changed that of genes linked to circadian rhythms, synaptic activity/neuronal plasticity, neuroprotection and cell death and survival. SD appeared to affect gene expression in the cerebral cortex more importantly after mTBI than Sham surgery including that of the astrocytic marker Gfap, which was proposed as a marker of clinical outcome after TBI. Interestingly, SD impacted the hippocampal expression of the plasticity elements Arc and EfnA3 only after mTBI. Overall, our
Full Text Available Traumatic brain injury (TBI is one of the major causes of death and disability worldwide. No effective treatment has been identified from clinical trials. Compelling evidence exists that treatment with mesenchymal stem cells (MSCs exerts a substantial therapeutic effect after experimental brain injury. In addition to their soluble factors, therapeutic effects of MSCs may be attributed to their generation and release of exosomes. Exosomes are endosomal origin small-membrane nano-sized vesicles generated by almost all cell types. Exosomes play a pivotal role in intercellular communication. Intravenous delivery of MSC-derived exosomes improves functional recovery and promotes neuroplasticity in rats after TBI. Therapeutic effects of exosomes derive from the exosome content, especially microRNAs (miRNAs. miRNAs are small non-coding regulatory RNAs and play an important role in posttranscriptional regulation of genes. Compared with their parent cells, exosomes are more stable and can cross the blood-brain barrier. They have reduced the safety risks inherent in administering viable cells such as the risk of occlusion in microvasculature or unregulated growth of transplanted cells. Developing a cell-free exosome-based therapy may open up a novel approach to enhancing multifaceted aspects of neuroplasticity and to amplifying neurological recovery, potentially for a variety of neural injuries and neurodegenerative diseases. This review discusses the most recent knowledge of exosome therapies for TBI, their associated challenges and opportunities.
Xiong, Ye; Mahmood, Asim; Chopp, Michael
Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide. No effective treatment has been identified from clinical trials. Compelling evidence exists that treatment with mesenchymal stem cells (MSCs) exerts a substantial therapeutic effect after experimental brain injury. In addition to their soluble factors, therapeutic effects of MSCs may be attributed to their generation and release of exosomes. Exosomes are endosomal origin small-membrane nano-sized vesicles generated by almost all cell types. Exosomes play a pivotal role in intercellular communication. Intravenous delivery of MSC-derived exosomes improves functional recovery and promotes neuroplasticity in rats after TBI. Therapeutic effects of exosomes derive from the exosome content, especially microRNAs (miRNAs). miRNAs are small non-coding regulatory RNAs and play an important role in posttranscriptional regulation of genes. Compared with their parent cells, exosomes are more stable and can cross the blood-brain barrier. They have reduced the safety risks inherent in administering viable cells such as the risk of occlusion in microvasculature or unregulated growth of transplanted cells. Developing a cell-free exosome-based therapy may open up a novel approach to enhancing multifaceted aspects of neuroplasticity and to amplifying neurological recovery, potentially for a variety of neural injuries and neurodegenerative diseases. This review discusses the most recent knowledge of exosome therapies for TBI, their associated challenges and opportunities.
Kesinger, Matthew R.; Kumar, Raj G.; Wagner, Amy K.; Puyana, Juan C.; Peitzman, Andrew P.; Billiar, Timothy R.; Sperry, Jason L.
Objectives Long-term outcomes following traumatic brain injury (TBI) correlate with initial head injury severity and other acute factors. Hospital-acquired pneumonia (HAP) is a common complication in TBI. Little information exists regarding the significance of infectious complications on long-term outcomes post-TBI. We sought to characterize risks associated with HAP on outcomes 5 years post-TBI. Methods Ddata from the merger of an institutional trauma registry and the TBI Model Systems outcome data. Individuals with severe head injuries (Abbreviated Injury Scale≥4), who survived to rehabilitation were analyzed. Primary outcome was Glasgow Outcome Scaled-Extended (GOSE) at 1, 2, and 5 years. GOSE was dichotomized into LOW (GOSEPneumonia TBI PMID:25757128
Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun
Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.
Full Text Available 【Abstract】Objective: To investigate the neuroprotective effects of glycyrrhizin (Gly as well as its effect on expression of high-mobility group box 1 (HMGB1 in rats after traumatic brain injury (TBI. Methods: Male Sprague-Dawley rats were randomly divided into three groups: sham group, TBI group, and TBI+Gly group (n=36 per group. Rat TBI model was made by using the modified Feeney’s method. In TBI+Gly group, Gly was administered intravenously at a dosage of 10 mg/kg 30 min after TBI. At 24 h after TBI, motor function and brain water content were evaluated. Meanwhile, HMGB1/HMGB1 receptors including toll-like receptor 4 (TLR4 and receptor for advanced glycation end products (RAGE/nuclear factor- κB(NF- κB signaling pathway and inflammatory cytokines in the injured brain tissues were detected using quantitative real-time polymerase chain reaction, western blot, electrophoretic mobility shift assay and enzyme-linked immunosorbent assay. Furthermore, HMGB1, RAGE and TLR4 immunohistochemistry and apoptosis were analyzed. Results: Beam walking performance impairment and brain edema were significantly reduced in TBI+Gly group compared with TBI group; meanwhile, the over-expressions of HMGB1/HMGB1 receptors (TLR4 and RAGE/NF-κB DNA-binding activity and inflammatory cytokines were inhibited. The percentages of HMGB1, RAGE and TLR4- positive cells and apoptotic cells were respectively 58.37%±5.06%, 54.15%±4.65%, 65.50%± 4.83%, 52.02%± 4.63% in TBI group and 39.99%±4.99%, 34.87%±5.02%, 43.33%±4.54%, 37.84%±5.16% in TBI+Gly group (all P<0.01 compared with TBI group. Conclusion: Gly can reduce secondary brain injury and improve outcomes in rat following TBI by down-regulation of HMGB1/HMGB1 receptors (TLR4 and RAGE/NF-κB - mediated inflammatory responses in the injured rat brain.
Gu Xiangjin; Xu Jin; Ma Banyou; Chen Gong; Gu Peiyuan; Wei Dong; Hu Weixing
Objective:To investigate the neuroprotective effects of glycyrrhizin (Gly) as well as its effect on expression of high-mobility group box 1 (HMGB 1) in rats after traumatic brain injury (TBI).Methods:Male Sprague-Dawley rats were randomly divided into three groups:sham group,TBI group,and TBI+Gly group (n=36 per group).Rat TBI model was made by using the modified Feeney's method.In TBI+Gly group,Gly was administered intravenously at a dosage of 10 mg/kg 30 min after TBI.At 24 h after TBI,motor function and brain water content were evaluated.Meanwhile,HMGB 1/HMGB 1 receptors including toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nuclear factor-κ B(NF-κ B) signaling pathway and inflammatory cytokines in the injured brain tissues were detected using quantitative real-time polymerase chain reaction,western blot,electrophoretic mobility shift assay and enzyme-linked immunosorbent assay.Furthermore,HMGB 1,RAGE and TLR4 immunohistochemistry and apoptosis were analyzed.Results:Beam walking performance impairment and brain edema were significantly reduced in TBI+Gly group compared with TBI group; meanwhile,the over-expressions of HMGB 1/HMGB 1 receptors (TLR4 and RAGE)/NF-κB DNA-binding activity and inflammatory cytokines were inhibited.The percentages of HMGB 1,RAGE and TLR4positive cells and apoptotic cells were respectively 58.37％±5.06％,54.15％±4.65％,65.50％± 4.83％,52.02％± 4.63％ in TBI group and 39.99％±4.99％,34.87％±5.02％,43.33％±4.54％,37.84％±5.16％ in TBI+Gly group (all P＜0.01 compared with TBI group).Conclusion:Gly can reduce secondary brain injury and improve outcomes in rat following TBI by down-regulation of HMGB 1/HMGB 1 receptors (TLR4 and RAGE)/NF-κ B-mediated inflammatory responses in the injured rat brain.
Harish, Gangadharappa; Mahadevan, Anita; Pruthi, Nupur; Sreenivasamurthy, Sreelakshmi K; Puttamallesh, Vinuth N; Keshava Prasad, Thottethodi Subrahmanya; Shankar, Susarla Krishna; Srinivas Bharath, Muchukunte Mukunda
Traumatic brain injury (TBI) contributes to fatalities and neurological disabilities worldwide. While primary injury causes immediate damage, secondary events contribute to long-term neurological defects. Contusions (Ct) are primary injuries correlated with poor clinical prognosis, and can expand leading to delayed neurological deterioration. Pericontusion (PC) (penumbra), the region surrounding Ct, can also expand with edema, increased intracranial pressure, ischemia, and poor clinical outcome. Analysis of Ct and PC can therefore assist in understanding the pathobiology of TBI and its management. This study on human TBI brains noted extensive neuronal, astroglial and inflammatory changes, alterations in mitochondrial, synaptic and oxidative markers, and associated proteomic profile, with distinct differences in Ct and PC. While Ct displayed petechial hemorrhages, thrombosis, inflammation, neuronal pyknosis, and astrogliosis, PC revealed edema, vacuolation of neuropil, axonal loss, and dystrophic changes. Proteomic analysis demonstrated altered immune response, synaptic, and mitochondrial dysfunction, among others, in Ct, while PC displayed altered regulation of neurogenesis and cytoskeletal architecture, among others. TBI brains displayed oxidative damage, glutathione depletion, mitochondrial dysfunction, and loss of synaptic proteins, with these changes being more profound in Ct. We suggest that analysis of markers specific to Ct and PC may be valuable in the evaluation of TBI pathobiology and therapeutics. We have characterized the primary injury in human traumatic brain injury (TBI). Contusions (Ct) - the injury core displayed hemorrhages, inflammation, and astrogliosis, while the surrounding pericontusion (PC) revealed edema, vacuolation, microglial activation, axonal loss, and dystrophy. Proteomic analysis demonstrated altered immune response, synaptic and mitochondrial dysfunction in Ct, and altered regulation of neurogenesis and cytoskeletal architecture in
Torrente, Daniel; Cabezas, Ricardo; Avila, Marco Fidel; García-Segura, Luis Miguel; Barreto, George E; Guedes, Rubem Carlos Araújo
Cortical spreading depression (CSD) is a presumably pathophysiological phenomenon that interrupts local cortical function for periods of minutes to hours. This phenomenon is important due to its association with different neurological disorders such as migraine, malignant stroke and traumatic brain injury (TBI). Glial cells, especially astrocytes, play an important role in the regulation of CSD and in the protection of neurons under brain trauma. The correlation of TBI with CSD and the astrocytic function under these conditions remain unclear. This review discusses the possible link of TBI and CSD and its implication for neuronal survival. Additionally, we highlight the importance of astrocytic function for brain protection, and suggest possible therapeutic strategies targeting astrocytes to improve the outcome following TBI-associated CSD.
Cope, Elise C; Morris, Deborah R; Gower-Winter, Shannon D; Brownstein, Naomi C; Levenson, Cathy W
There is great deal of debate about the possible role of adult-born hippocampal cells in the prevention of depression and related mood disorders. We first showed that zinc supplementation prevents the development of the depression-like behavior anhedonia associated with an animal model of traumatic brain injury (TBI). This work then examined the effect of zinc supplementation on the proliferation of new cells in the hippocampus that have the potential to participate in neurogenesis. Rats were fed a zinc adequate (ZA, 30ppm) or zinc supplemented (ZS, 180ppm) diet for 4wk followed by TBI using controlled cortical impact. Stereological counts of EdU-positive cells showed that TBI doubled the density of proliferating cells 24h post-injury (pzinc significantly increased this by an additional 2-fold (pzinc supplementation resulted in significant increases in the density of new doublecortin-positive neurons one week post-TBI that were maintained for 4wk after injury (pzinc supplementation on neuronal precursor cells in the hippocampus was robust, use of targeted irradiation to eliminate these cells after zinc supplementation and TBI revealed that these cells are not the sole mechanism through which zinc acts to prevent depression associated with brain injury, and suggest that other zinc dependent mechanisms are needed for the anti-depressant effect of zinc in this model of TBI.
Kawa, Lizan; Arborelius, Ulf P; Yoshitake, Takashi; Kehr, Jan; Hökfelt, Tomas; Risling, Mårten; Agoston, Denes
Exposure to improvised explosive devices can result in a unique form of traumatic brain injury--blast-induced traumatic brain injury (bTBI). At the mild end of the spectrum (mild bTBI [mbTBI]), there are cognitive and mood disturbances. Similar symptoms have been observed in post-traumatic stress disorder caused by exposure to extreme psychological stress without physical injury. A role of the monoaminergic system in mood regulation and stress is well established but its involvement in mbTBI is not well understood. To address this gap, we used a rodent model of mbTBI and detected a decrease in immobility behavior in the forced swim test at 1 d post-exposure, coupled with an increase in climbing behavior, but not after 14 d or later, possibly indicating a transient increase in anxiety-like behavior. Using in situ hybridization, we found elevated messenger ribonucleic acid levels of both tyrosine hydroxylase and tryptophan hydroxylase 2 in the locus coeruleus and the dorsal raphe nucleus, respectively, as early as 2 h post-exposure. High-performance liquid chromatography analysis 1 d post-exposure primarily showed elevated noradrenaline levels in several forebrain regions. Taken together, we report that exposure to mild blast results in transient changes in both anxiety-like behavior and brain region-specific molecular changes, implicating the monoaminergic system in the pathobiology of mbTBI.
Biederman, Joseph; Feinberg, Leah; Chan, James; Adeyemo, Bamidele O; Woodworth, K Yvonne; Panis, Walter; McGrath, Neal; Bhatnagar, Saurabha; Spencer, Thomas J; Uchida, Mai; Kenworthy, Tara; Grossman, Rebecca; Zafonte, Ross; Faraone, Stephen V
A recent meta-analysis documented a significant statistical association between mild traumatic brain injury (mTBI) and attention deficit hyperactivity disorder (ADHD) (Adeyemo et al., 2014), but the direction of this effect was unclear. In this study, we hypothesized that ADHD would be an antecedent risk factor for mTBI. Participants were student athletes ages 12 to 25 who had sustained a mTBI and Controls of similar age and sex selected from studies of youth with and without ADHD. Subjects were assessed for symptoms of ADHD, concussion severity, and cognitive function. mTBI subjects had a significantly higher rate of ADHD than Controls, and in all cases the age of onset of ADHD was before mTBI onset. mTBI+ADHD subjects also had more severe concussion symptoms (fatigue and poor concentration) than mTBI-ADHD subjects. These results support ADHD as an antecedent risk factor for mTBI in student athletes and that its presence complicates the course of mTBI.
Full Text Available Objective To explore the effects of low-dose methylprednisolone(MP treatment after traumatic brain injury(TBI in rats on the number of peripheral blood endothelial progenitor cells(EPCs and injury area of the brain.Methods One hundred and fifty-four adult male Wistar rats were involved in the present study,and they were randomly divided into normal control group(n=18,TBI control group(n=38,MP control group(n=30,MP+TBI group(n=30 and TBI+MP group(n=38.The TBI model was reproduced by fluid percussion injury(FPI.MP(5mg/kg was intraperitoneally administered once a day for 4 days.Peripheral venous blood samples were taken on day 1,3,7 and 14,and the counts of EPCs were determined by flow cytometry.The rats were sacrificed on day 1 and 3,brain edema was estimated by dry-wet weight method,and the blood-brain barrier(BBB permeability was determined by Evans-blue extravasation.Results The counts of peripheral blood EPCs were significantly higher in MP control group,MP+TBI group and TBI+MP group on day 1,3 and 7 than that in normal control and TBI control group,and it returned to the level of normal control group on day 14.The BBB permeability was improved and brain edema alleviated in MP+TBI and TBI+MP group on day 3.Conclusion The administration of low-dose MP may increase the count of peripheral blood EPCs in rats,decrease BBB damage,and alleviate brain edema.
Thomas F. Rau
Full Text Available Phenoxybenzamine (PBZ is an FDA approved α-1 adrenergic receptor antagonist that is currently used to treat symptoms of pheochromocytoma. However, it has not been studied as a neuroprotective agent for traumatic brain injury (TBI. While screening neuroprotective candidates, we found that phenoxybenzamine reduced neuronal death in rat hippocampal slice cultures following exposure to oxygen glucose deprivation (OGD. Using this system, we found that phenoxybenzamine reduced neuronal death over a broad dose range (0.1 µM–1 mM and provided efficacy when delivered up to 16 h post-OGD. We further tested phenoxybenzamine in the rat lateral fluid percussion model of TBI. When administered 8 h after TBI, phenoxybenzamine improved neurological severity scoring and foot fault assessments. At 25 days post injury, phenoxybenzamine treated TBI animals also showed a significant improvement in both learning and memory compared to saline treated controls. We further examined gene expression changes within the cortex following TBI. At 32 h post-TBI phenoxybenzamine treated animals had significantly lower expression of pro-inflammatory signaling proteins CCL2, IL1β, and MyD88, suggesting that phenoxybenzamine may exert a neuroprotective effect by reducing neuroinflammation after TBI. These data suggest that phenonxybenzamine may have application in the treatment of TBI.
Miszczuk, Diana; Dębski, Konrad J; Tanila, Heikki; Lukasiuk, Katarzyna; Pitkänen, Asla
To test the hypothesis that an amyloidogenic genetic background predisposes to worsening of post-TBI outcome, we investigated whether traumatic brain injury (TBI) in amyloid precursor protein (APP)/PS1 mice aggravates epileptogenesis and/or enhances somatomotor and cognitive impairment. To elaborate the mechanisms of worsening outcomes, we studied changes in the expression of genes involved in APP processing and Tau pathways in the perilesional cortex, ipsilateral thalamus, and ipsilateral hippocampus 16 weeks post-TBI. Mild (mTBI) or severe TBI (sTBI) was triggered using controlled cortical impact in 3-month-old APP/PS1 mice and wild-type (Wt) littermates. Morris water-maze revealed a genotype effect on spatial learning and memory as APP/PS1-sTBI mice performed more poorly than Wt-sTBI mice (p APP/PS1-sTBI mice had epilepsy compared to 11 % in Wt-sTBI (genotype effect p APP/PS1-sham groups (TBI effect p APP/PS1-sTBI mice compared to APP/PS1-sham (p APP/PS1-sTBI mice compared to APP/PS1-sham mice (p < 0.05). The present study provides the first comprehensive evidence of exacerbated epileptogenesis and its molecular mechanisms in Alzheimer's disease (AD)-related genetic background after TBI.
Full Text Available Traumatic brain injury (TBI is a widespread epidemic with severe cognitive, affective, and behavioral consequences. TBIs typically result in a relatively rapid inflammatory and neuroinflammatory response. A major component of the neuroinflammatory response is astrocytes, a type of glial cell in the brain. Astrocytes are important in maintaining the integrity of neuronal functioning, and it is possible that astrocyte hypertrophy after TBIs might contribute to pathogenesis. The hippocampus is a unique brain region, because neurogenesis persists in adults. Accumulating evidence supports the functional importance of these newborn neurons and their associated astrocytes. Alterations to either of these cell types can influence neuronal functioning. To determine if hypertrophied astrocytes might negatively influence immature neurons in the dentate gyrus, astrocyte and newborn neurons were analyzed at 30 days following a TBI in mice. The results demonstrate a loss of radial glial-like processes extending through the granule cell layer after TBI, as well as ectopic growth and migration of immature dentate neurons. The results further show newborn neurons in close association with hypertrophied astrocytes, suggesting a role for the astrocytes in aberrant neurogenesis. Future studies are needed to determine the functional significance of these alterations to the astrocyte/immature neurons after TBI.
Harman-Smith, Yasmin E; Mathias, Jane L; Bowden, Stephen C; Rosenfeld, Jeffrey V; Bigler, Erin D
Neuropsychological assessments of outcome after traumatic brain injury (TBI) are often unrelated to self-reported problems after TBI. The current study cluster-analyzed the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) subtest scores from mild, moderate, and severe TBI (n=220) and orthopedic injury control (n=95) groups, to determine whether specific cognitive profiles are related to people's perceived outcomes after TBI. A two-stage cluster analysis produced 4- and 6-cluster solutions, with the 6-cluster solution better capturing subtle variations in cognitive functioning. The 6 clusters differed in the levels and profiles of cognitive performance, self-reported recovery, and education and injury severity. The findings suggest that subtle cognitive impairments after TBI should be interpreted in conjunction with patient's self-reported problems.
Donders, Jacobus; Strong, Carrie-Ann H
The performance of 100 patients with traumatic brain injury (TBI) on the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) was compared with that of 100 demographically matched neurologically healthy controls. Processing Speed was the only WAIS-IV factor index that was able to discriminate between persons with moderate-severe TBI on the one hand and persons with either less severe TBI or neurologically healthy controls on the other hand. The Processing Speed index also had acceptable sensitivity and specificity when differentiating between patients with TBI who either did or did not have scores in the clinically significant range on the Trail Making Test. It is concluded that WAIS-IV Processing Speed has acceptable clinical utility in the evaluation of patients with moderate-severe TBI but that it should be supplemented with other measures to assure sufficient accuracy in the diagnostic process.
Kennedy, Jan E.; Cooper, Douglas B.; Reid, Matthew W.; Tate, David F.; Lange, Rael T.
Personality Assessment Inventory (PAI) profiles were examined in 160 U.S. service members (SMs) following mild–severe traumatic brain injury (TBI). Participants who sustained a mild TBI had significantly higher PAI scores than those with moderate–severe TBI on eight of the nine clinical scales examined. A two-step cluster analysis identified four PAI profiles, heuristically labeled “High Distress”, “Moderate Distress”, “Somatic Distress,” and “No Distress”. Postconcussive and posttraumatic stress symptom severity was highest for the High Distress group, followed by the Somatic and Moderate Distress groups, and the No Distress group. Profile groups differed in age, ethnicity, rank, and TBI severity. Findings indicate that meaningful patterns of behavioral and personality characteristics can be detected in active duty military SMs following TBI, which may prove useful in selecting the most efficacious rehabilitation strategies. PMID:25857403
Kennedy, Jan E; Cooper, Douglas B; Reid, Matthew W; Tate, David F; Lange, Rael T
Personality Assessment Inventory (PAI) profiles were examined in 160 U.S. service members (SMs) following mild-severe traumatic brain injury (TBI). Participants who sustained a mild TBI had significantly higher PAI scores than those with moderate-severe TBI on eight of the nine clinical scales examined. A two-step cluster analysis identified four PAI profiles, heuristically labeled "High Distress", "Moderate Distress", "Somatic Distress," and "No Distress". Postconcussive and posttraumatic stress symptom severity was highest for the High Distress group, followed by the Somatic and Moderate Distress groups, and the No Distress group. Profile groups differed in age, ethnicity, rank, and TBI severity. Findings indicate that meaningful patterns of behavioral and personality characteristics can be detected in active duty military SMs following TBI, which may prove useful in selecting the most efficacious rehabilitation strategies.
Ofek, Hadas; Defrin, Ruth
Central pain following traumatic brain injury (TBI) has not been studied in depth. Our purpose was to conduct a systematic study of patients with TBI suffering from chronic central pain, and to describe the characteristics of the central pain. Groups were TBI patients with (TBIP) and without central pain (TBINP) and healthy controls. TBI patients with other pain mechanisms were excluded from the study. Participants underwent quantitative somatosensory testing in the painful and pain-free body regions. Thresholds for warmth, cold, heat-pain, touch and graphesthesia were measured and pathologically evoked pain (allodynia, hyperpathia and wind-up pain) evaluated. Chronic pain was mapped and characterized. Chronic pain developed at a relatively late onset (6.6+/-9 months) was almost exclusively unilateral and reported as pricking, throbbing and burning. Although both TBIP and TBINP exhibited a significant reduction in thermal and tactile sensations compared to controls, thermal sensations in the painful regions of TBIP were significantly more impaired than pain-free regions in the same patients (p<0.01) and in TBINP (p<0.01). Painful regions also exhibited very high rates of allodynia, hyperpathia and exaggerated wind-up. The characteristics of the chronic pain resembled those of other central pain patients although TBIP displayed several unique features. The sensory profile indicated that damage to the pain and temperature systems is a necessary but not sufficient condition for the development of chronic central pain following TBI. Neuronal hyperexcitability may be a contributing factor to the chronic pain.
Full Text Available Background: Traumatic brain injury (TBI is a leading cause of secondary hypopituitarism in children and adults, and is responsible for impaired quality of life, disabilities and compromised development. Alterations of pituitary function can occur at any time after the traumatic event, presenting in various ways and evolving during time, so they require appropriate screening for early detection and treatment. Although the exact pathophysiology is unknown, several mechanisms have been hypothesized, including hypothalamic-pituitary autoimmunity (HP-A. The aim of this study was to systematically review literature on the association between HP-A and TBI-induced hypopituitarism. Major pitfalls related to the HP-A investigation were also discussed. Methods: The PubMed database was searched with a string developed for this purpose, without temporal or language limits, for original articles assessing the association of HP-A and TBI-induced hypopituitarism. Results: Three articles from the same group met the inclusion criteria. Anti-pituitary and anti-hypothalamic antibodies were detected using indirect immunofluorescence in a significant number of patients with acute and chronic TBI. Elevated antibody titer was associated with an increased risk of persistent hypopituitarism, especially somatotroph and gonadotroph deficiency, while no correlations were found with clinical parameters. Conclusion: HPA seems to contribute to TBI-induced pituitary damage, although major methodological issues need to be overcome and larger studies are warranted to confirm these preliminary data.
Geary, Elizabeth K; Kraus, Marilyn F; Rubin, Leah H; Pliskin, Neil H; Little, Deborah M
That learning and memory deficits persist many years following mild traumatic brain injury (mTBI) is controversial due to inconsistent objective evidence supporting subjective complaints. Our prior work demonstrated significant reductions in performance on the initial trial of a verbal learning task and overall slower rate of learning in well-motivated mTBI participants relative to demographically matched controls. In our previous work, we speculated that differences in strategy use could explain the differences in rate of learning. The current study serves to test this hypothesis by examining strategy use on the California Verbal Learning Test-Second Edition. Our present findings support the primary hypothesis that mTBI participants under-utilize semantic clustering strategies during list-learning relative to control participants. Despite achieving comparable total learning scores, we posit that the persisting learning and memory difficulties reported by some mTBI patients may be related to reduced usage of efficient internally driven strategies that facilitate learning. Given that strategy training has demonstrated improvements in learning and memory in educational and occupational settings, we offer that these findings have translational value in offering an additional approach in remediation of learning and memory complaints reported by some following mTBI.
Rochat, Lucien; Beni, Catia; Billieux, Joël; Azouvi, Philippe; Annoni, Jean-Marie; Van der Linden, Martial
The aim of the study was to develop and validate a short questionnaire assessing four dimensions of impulsivity (urgency, lack of premeditation, lack of perseverance, sensation seeking) in patients with traumatic brain injury (TBI). To this end, 82 patients with TBI and their caregivers completed a short questionnaire adapted from the UPPS Impulsive Behavior Scale designed to assess impulsivity changes after TBI. Confirmatory factor analyses (CFAs) performed on the version of the scale completed by the relatives revealed that a hierarchical model holding that lack of premeditation and lack of perseverance are facets of a higher order construct (lack of conscientiousness), with urgency and sensation seeking as separate correlated factors, fit the data best. Urgency, lack of premeditation, and lack of perseverance increased after the TBI, whereas sensation seeking decreased. CFA failed to reveal a satisfactory model in the version of the scale completed by the patients. The psychological processes related to these impulsivity changes and the discrepancy observed between self-report and informant-report are discussed. This short questionnaire opens up interesting prospects for better comprehension and assessment of behavioural symptoms of TBI.
Keri Linda Carpenter
Full Text Available In traumatic brain injury (TBI patients, elevation of the brain extracellular lactate concentration and the lactate/pyruvate ratio are well recognised, and are associated statistically with unfavourable clinical outcome. Brain extracellular lactate was conventionally regarded as a waste product of glucose, when glucose is metabolised via glycolysis (Embden-Meyerhof-Parnas pathway to pyruvate, followed by conversion to lactate by the action of lactate dehydrogenase, and export of lactate into the extracellular fluid. In TBI, glycolytic lactate is ascribed to hypoxia or mitochondrial dysfunction, although the precise nature of the latter is incompletely understood. Seemingly in contrast to lactate’s association with unfavourable outcome is a growing body of evidence that lactate can be beneficial. The idea that the brain can utilise lactate by feeding into the tricarboxylic acid (TCA cycle of neurons, first published two decades ago, has become known as the astrocyte-neuron lactate shuttle hypothesis. Direct evidence of brain utilisation of lactate was first obtained 5 years ago in a cerebral microdialysis study in TBI patients, where administration of 13C-labelled lactate via the microdialysis catheter and simultaneous collection of the emerging microdialysates, with 13C NMR analysis, revealed 13C labelling in glutamine consistent with lactate utilisation via the TCA cycle. This suggests that where neurons are too damaged to utilise the lactate produced from glucose by astrocytes, i.e. uncoupling of neuronal and glial metabolism, high extracellular levels of lactate would accumulate, explaining association between high lactate and poor outcome. An intravenous exogenous lactate supplementation study in TBI patients showed evidence for a beneficial effect judged by surrogate endpoints. Here we review current knowledge about glycolysis and lactate in TBI, how it can be measured in patients, and whether it can be modulated to achieve better
Powell, Janet M
Awareness of the incidence and consequences of traumatic brain injury (TBI) has increased in recent years, along with interest in knowing how best to treat this complex condition. This editorial provides an overview of the various factors that contribute to the complexity of TBI and introduces the six systematic reviews and one qualitative study included in this special issue of the American Journal of Occupational Therapy focusing on interventions for TBI from an occupational therapy perspective. Issues with the generation and interpretation of research evidence are discussed, along with the importance of valuing clinician expertise and client perspectives along with research findings in implementing evidence-based and evidence-informed practice.
Boddé, Tamar Roos Annemarie; Scheinberg, Adam; McKinlay, Audrey
Considerable confusion surrounds pediatric mild traumatic brain injury (mTBI) and its management. This study provides a comparison between mTBI management pamphlets distributed by Australasian hospitals and the Centers for Disease Control and Prevention (CDC) gold standard. Twenty-seven different pamphlets were collected from 96 hospitals in Australia and New Zealand and were assessed for readability, compliance with nine CDC criteria, and inclusion of confusing or incorrect information. None of the pamphlets completely complied with the CDC criteria and all included incorrect information. Findings demonstrate that mTBI management information in Australasia needs urgent revision, and evaluation in other countries is strongly advised.
... occupational therapy, speech/language therapy, physiatry (physical medicine), psychology/psychiatry, and social ... brain. TBI can result when the head suddenly and violently hits an object, or when an object pierces the skull and ...
Radouil Tzekov; Clint Dawson; Megan Orlando; Benoit Mouzon; Jon Reed; James Evans; Gogce Crynen; Michael Mullan; Fiona Crawford
Repetitive mild traumatic brain injury (r-mTBI) results in neuropathological and biochemical consequences in the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham) we assessed the effects on the retina and optic nerve using histology, immunohistochemistry, proteomic and lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC) number, while optic nerve tissue w...
Dennis, Maureen; Simic, Nevena; Bigler, Erin D; Abildskov, Tracy; Agostino, Alba; Taylor, H Gerry; Rubin, Kenneth; Vannatta, Kathryn; Gerhardt, Cynthia A; Stancin, Terry; Yeates, Keith Owen
We studied three forms of dyadic communication involving theory of mind (ToM) in 82 children with traumatic brain injury (TBI) and 61 children with orthopedic injury (OI): Cognitive (concerned with false belief), Affective (concerned with expressing socially deceptive facial expressions), and Conative (concerned with influencing another's thoughts or feelings). We analyzed the pattern of brain lesions in the TBI group and conducted voxel-based morphometry for all participants in five large-scale functional brain networks, and related lesion and volumetric data to ToM outcomes. Children with TBI exhibited difficulty with Cognitive, Affective, and Conative ToM. The perturbation threshold for Cognitive ToM is higher than that for Affective and Conative ToM, in that Severe TBI disturbs Cognitive ToM but even Mild-Moderate TBI disrupt Affective and Conative ToM. Childhood TBI was associated with damage to all five large-scale brain networks. Lesions in the Mirror Neuron Empathy network predicted lower Conative ToM involving ironic criticism and empathic praise. Conative ToM was significantly and positively related to the package of Default Mode, Central Executive, and Mirror Neuron Empathy networks and, more specifically, to two hubs of the Default Mode Network, the posterior cingulate/retrosplenial cortex and the hippocampal formation, including entorhinal cortex and parahippocampal cortex.
Dennis, Maureen; Simic, Nevena; Bigler, Erin D.; Abildskov, Tracy; Agostino, Alba; Taylor, H. Gerry; Rubin, Kenneth; Vannatta, Kathryn; Gerhardt, Cynthia A.; Stancin, Terry; Yeates, Keith Owen
We studied three forms of dyadic communication involving theory of mind (ToM) in 82 children with traumatic brain injury (TBI) and 61 children with orthopedic injury (OI): Cognitive (concerned with false belief), Affective (concerned with expressing socially deceptive facial expressions), and Conative (concerned with influencing another’s thoughts or feelings). We analyzed the pattern of brain lesions in the TBI group and conducted voxel-based morphometry for all participants in five large-scale functional brain networks, and related lesion and volumetric data to ToM outcomes. Children with TBI exhibited difficulty with Cognitive, Affective, and Conative ToM. The perturbation threshold for Cognitive ToM is higher than that for Affective and Conative ToM, in that Severe TBI disturbs Cognitive ToM but even Mild-Moderate TBI disrupt Affective and Conative ToM. Childhood TBI was associated with damage to all five large-scale brain networks. Lesions in the Mirror Neuron Empathy network predicted lower Conative ToM involving ironic criticism and empathic praise. Conative ToM was significantly and positively related to the package of Default Mode, Central Executive, and Mirror Neuron Empathy networks and, more specifically, to two hubs of the Default Mode network, the posterior cingulate/retrosplenial cortex and the hippocampal formation, including entorhinal cortex and parahippocampal cortex. PMID:23291312
Ling, Geoffrey S. F.; Grimes, Jamie; Ecklund, James M.
Traumatic brain injury (TBI) and Post Traumatic Stress Disorder (PTSD) are common conditions. In Iraq and Afghanistan, explosive blast related TBI became prominent among US service members but the vast majority of TBI was still due to typical causes such as falls and sporting events. PTS has long been a focus of the US military mental health providers. Combat Stress Teams have been integral to forward deployed units since the beginning of the Global War on Terror. Military medical management of disease and injury follows standard of care clinical practice guidelines (CPG) established by civilian counterparts. However, when civilian CPGs do not exist or are not applicable to the military environment, new practice standards are created. Such is the case for mild TBI. In 2009, the VA-DoD CPG for management of mild TBI/concussion was published and a system-wide clinical care program for mild TBI/concussion was introduced. This was the first large scale effort on an entire medical care system to address all severities of TBI in a comprehensive organized way. In 2010, the VA-DoD CPG for management of PTSD was published. Nevertheless, both TBI and PTS are still incompletely understood. Investment in terms of money and effort has been committed by the DoD to their study. 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 are prominent examples of this effort. These are just beginnings, a work in progress ready to leverage advances made scientifically and always striving to provide the very best care to its military beneficiaries.
Wofford, Kathryn L; Harris, James P; Browne, Kevin D; Brown, Daniel P; Grovola, Michael R; Mietus, Constance J; Wolf, John A; Duda, John E; Putt, Mary E; Spiller, Kara L; Cullen, D Kacy
Despite increasing appreciation of the critical role that neuroinflammatory pathways play in brain injury and neurodegeneration, little is known about acute microglial reactivity following diffuse traumatic brain injury (TBI) - the most common clinical presentation that includes all concussions. Therefore, we investigated acute microglial reactivity using a porcine model of closed-head rotational velocity/acceleration-induced TBI that closely mimics the biomechanical etiology of inertial TBI in humans. We observed rapid microglial reactivity within 15min of both mild and severe TBI. Strikingly, microglial activation was restrained to regions proximal to individual injured neurons - as denoted by trauma-induced plasma membrane disruption - which served as epicenters of acute reactivity. Single-cell quantitative analysis showed that in areas free of traumatically permeabilized neurons, microglial density and morphology were similar between sham or following mild or severe TBI. However, microglia density increased and morphology shifted to become more reactive in proximity to injured neurons. Microglial reactivity around injured neurons was exacerbated following repetitive TBI, suggesting further amplification of acute neuroinflammatory responses. These results indicate that neuronal trauma rapidly activates microglia in a highly localized manner, and suggest that activated microglia may rapidly influence neuronal stability and/or pathophysiology after diffuse TBI.
Sullivan, Karen A; Kempe, Chloe B; Edmed, Shannon L; Bonanno, George A
The relation between resilience and mild traumatic brain injury (TBI) outcome has been theorized but empirical studies have been scarce. This systematic review aimed to describe the research in this area. Electronic databases (Medline, CINAHL, PsychINFO, SPORTdiscus, and PILOTS) were searched from inception to August 2015 for studies in which resilience was measured following TBI. The search terms included 'TBI' 'concussion' 'postconcussion' 'resilience' and 'hardiness'. Inclusion criteria were peer reviewed original research reports published in English, human participants aged 18 years and over with brain injury, and an accepted definition of mild TBI. Hand searching of identified articles was also undertaken. Of the 71 studies identified, five studies were accepted for review. These studies were formally assessed for risk of bias by two independent reviewers. Each study carried a risk of bias, most commonly a detection bias, but none were excluded on this basis. A narrative interpretation of the findings was used because the studies reflected fundamental differences in the conceptualization of resilience. No studies employed a trajectory based approach to measure a resilient outcome. In most cases, the eligible studies assessed trait resilience with a scale and used it as a predictor of outcome (postconcussion symptoms). Three of these studies showed that greater trait resilience was associated with better mild TBI outcomes (fewer symptoms). Future research of the adult mild TBI response that predicts a resilient outcome is encouraged. These studies could yield empirical evidence for a resilient, and other possible mild TBI outcomes.
Carroll, Aine Dr.
Objective: Adverse cognitive, emotional and behavioural sequelae of Traumatic Brain Injury (TBI) are commonly noted by family members. These sequelae can adversely impact on marital and family relationships. The aim of this study is to examine marital and relationship satisfaction following a TBI amongst patients and partners. Design: A questionnaire based postal survey was used to investigate relationship and marital satisfaction. Participants: Thirty four participants (14 male; 20 female), ranging in age from 25-68 years ( = 44 years, SD 11 years), took part in this study. Sixteen had sustained a TBI and eighteen were partners of patients with TBI. Participants with TBI who were inpatients at the National Rehabilitation Hospital (NRH) and their partners were invited to participate in the study. Outcome Measures: The Marital Satisfaction Questionnaire (MSI-R) was used to examine marital and relationship satisfaction. Results: Both patients and partners reported relationship difficulties following brain injury (z = -3.078, p < .05 patients; z = 2.699, p < .05 partners). Conclusion: This study highlights the significant impact of TBI on relationships for both the TBI survivor and their partners. Implications for interventions in neuropsychological rehabilitation are discussed.
Full Text Available Background. Overall traumatic brain injury (TBI incidence and related death rates vary across different age groups. Objectives. To evaluate the incidence, causes, and outcome of TBI in adolescents and young adult population in Qatar. Method. This was a retrospective review of all TBIs admitted to the trauma center between January 2008 and December 2011. Demographics, mechanism of injury, morbidity, and mortality were analyzed in different age groups. Results. A total of 1665 patients with TBI were admitted; the majority were males (92% with a mean age of 28 ± 16 years. The common mechanism of injury was motor vehicle crashes and falls from height (51% and 35%, resp.. TBI was incidentally higher in young adults (34% and middle age group (21%. The most frequent injuries were contusion (40%, subarachnoid (25%, subdural (24%, and epidural hemorrhage (18%. The mortality rate was 11% among TBI patients. Mortality rates were 8% and 12% among adolescents and young adults, respectively. The highest mortality rate was observed in elderly patients (35%. Head AIS, ISS, and age were independent predictors for mortality. Conclusion. Adolescents and adults sustain significant portions of TBI, whereas mortality is much higher in the older group. Public awareness and injury prevention campaigns should target young population.
Spikman, Jacoba M.; Timmerman, Marieke E.; Milders, Maarten V.; Veenstra, Wencke S.; van der Naalt, Joukje
Impairments in social behavior are frequently found in moderate to severe traumatic brain injury (TBI) patients and are associated with an unfavorable outcome with regard to return to work and social reintegration. Neuropsychological tests measuring aspects of social cognition are thought to be sens
HE Min; LIU Wei-guo; WEN Liang; DU Hang-gen; YIN Li-chun; CHEN Li
To study the influence and mechanism of acute ethanol intoxication (AEI) on rat neuronal apoptosis after severe traumatic brain injury (TBI).Methods:Ninety-six Sprague-Dawley rats were randomly divided into four groups:normal control,AEI-only,TBI-only and TBI+AEI (n=24 for each).Severe TBI model was developed according to Feeney's method.Rats in TBI+AEI group were firstly subjected to AEI,and then suffered head trauma.In each group,animals were sacrificed at 6 h,24 h,72 h,and 168 h after TBI.The level of neuronal apoptosis and the expression of Bcl-2 protein were determined by TUNEL assay and immunohistochemical method,respectively.Results:Apoptotic cells mainly distributed in the cortex and white matter around the damaged area.Neuronal apoptosis significantly increased at 6 h after trauma and peaked at 72 h.Both the level of neuronal apoptosis and expression of Bcl-2 protein in TBI-only group and TBI+AEI group were higher than those in control group (P＜0.05).Compared with TBI-only group,the two indexes were much higher in TBI+AEI group at all time points (P＜0.05).Conclusion:Our findings suggest that AEI can increase neuronal apoptosis after severe TBI.
Glushakova, Olena Y; Johnson, Danny; Hayes, Ronald L
Traumatic brain injury (TBI) is a significant risk factor for chronic traumatic encephalopathy (CTE), Alzheimer's disease (AD), and Parkinson's disease (PD). Cerebral microbleeds, focal inflammation, and white matter damage are associated with many neurological and neurodegenerative disorders including CTE, AD, PD, vascular dementia, stroke, and TBI. This study evaluates microvascular abnormalities observed at acute and chronic stages following TBI in rats, and examines pathological processes associated with these abnormalities. TBI in adult rats was induced by controlled cortical impact (CCI) of two magnitudes. Brain pathology was assessed in white matter of the corpus callosum for 24 h to 3 months following injury using immunohistochemistry (IHC). TBI resulted in focal microbleeds that were related to the magnitude of injury. At the lower magnitude of injury, microbleeds gradually increased over the 3 month duration of the study. IHC revealed TBI-induced focal abnormalities including blood-brain barrier (BBB) damage (IgG), endothelial damage (intercellular adhesion molecule 1 [ICAM-1]), activation of reactive microglia (ionized calcium binding adaptor molecule 1 [Iba1]), gliosis (glial fibrillary acidic protein [GFAP]) and macrophage-mediated inflammation (cluster of differentiation 68 [CD68]), all showing different temporal profiles. At chronic stages (up to 3 months), apparent myelin loss (Luxol fast blue) and scattered deposition of microbleeds were observed. Microbleeds were surrounded by glial scars and co-localized with CD68 and IgG puncta stainings, suggesting that localized BBB breakdown and inflammation were associated with vascular damage. Our results indicate that evolving white matter degeneration following experimental TBI is associated with significantly delayed microvascular damage and focal microbleeds that are temporally and regionally associated with development of punctate BBB breakdown and progressive inflammatory responses. Increased
Full Text Available Although N-acetylcysteine (NAC has been shown to be neuroprotective for traumatic brain injury (TBI, the mechanisms for this beneficial effect are still poorly understood. Cerebral inflammation plays an important role in the pathogenesis of secondary brain injury after TBI. However, it has not been investigated whether NAC modulates TBI-induced cerebral inflammatory response. In this work, we investigated the effect of NAC administration on cortical expressions of nuclear factor kappa B (NF-κB and inflammatory proteins such as interleukin-1β (IL-1β, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, and intercellular adhesion molecule-1 (ICAM-1 after TBI. As a result, we found that NF-κB, proinflammatory cytokines, and ICAM-1 were increased in all injured animals. In animals given NAC post-TBI, NF-κB, IL-1β, TNF-α, and ICAM-1 were decreased in comparison to vehicle-treated animals. Measures of IL-6 showed no change after NAC treatment. NAC administration reduced brain edema, BBB permeability, and apoptotic index in the injured brain. The results suggest that post-TBI NAC administration may attenuate inflammatory response in the injured rat brain, and this may be one mechanism by which NAC ameliorates secondary brain damage following TBI.
Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Coleman, Lee; Ditchfield, Michael; Crossley, Louise; Beauchamp, Miriam H; Anderson, Vicki A
The purpose of the present investigation was to evaluate the contribution of age-at-insult and brain pathology on longitudinal outcome and recovery of pragmatic language in a sample of children and adolescents with traumatic brain injury (TBI). Children and adolescents with mild to severe TBI (n=112) were categorized according to timing of brain insult: (i) Middle Childhood (5-9 years; n=41); (ii) Late Childhood (10-11 years; n=39); and (iii) Adolescence (12-15 years; n=32) and group-matched for age, gender and socio-economic status (SES) to a typically developing (TD) control group (n=43). Participants underwent magnetic resonance imaging (MRI) including a susceptibility weighted imaging (SWI) sequence 2-8 weeks after injury and were assessed on measures of pragmatic language and behavioural functioning at 6- and 24-months after injury. Children and adolescents with TBI of all severity levels demonstrated impairments in these domains at 6-months injury before returning to age-expected levels at 2-years post-TBI. However, while adolescent TBI was associated with post-acute disruption to skills that preceded recovery to age-expected levels by 2-years post injury, the middle childhood TBI group demonstrated impairments at 6-months post-injury that were maintained at 2-year follow up. Reduced pragmatic communication was associated with frontal, temporal and corpus callosum lesions, as well as more frequent externalizing behaviour at 24-months post injury. Findings show that persisting pragmatic language impairment after pediatric TBI is related to younger age at brain insult, as well as microhemorrhagic pathology in brain regions that contribute to the anatomically distributed social brain network. Relationships between reduced pragmatic communication and more frequent externalizing behavior underscore the need for context-sensitive rehabilitation programs that aim to increase interpersonal effectiveness and reduce risk for maladaptive behavior trajectories into the
Irimia, Andrei; Chambers, Micah C; Alger, Jeffry R; Filippou, Maria; Prastawa, Marcel W; Wang, Bo; Hovda, David A; Gerig, Guido; Toga, Arthur W; Kikinis, Ron; Vespa, Paul M; Van Horn, John D
Although neuroimaging is essential for prompt and proper management of traumatic brain injury (TBI), there is a regrettable and acute lack of robust methods for the visualization and assessment of TBI pathophysiology, especially for of the purpose of improving clinical outcome metrics. Until now, the application of automatic segmentation algorithms to TBI in a clinical setting has remained an elusive goal because existing methods have, for the most part, been insufficiently robust to faithfully capture TBI-related changes in brain anatomy. This article introduces and illustrates the combined use of multimodal TBI segmentation and time point comparison using 3D Slicer, a widely-used software environment whose TBI data processing solutions are openly available. For three representative TBI cases, semi-automatic tissue classification and 3D model generation are performed to perform intra-patient time point comparison of TBI using multimodal volumetrics and clinical atrophy measures. Identification and quantitative assessment of extra- and intra-cortical bleeding, lesions, edema, and diffuse axonal injury are demonstrated. The proposed tools allow cross-correlation of multimodal metrics from structural imaging (e.g., structural volume, atrophy measurements) with clinical outcome variables and other potential factors predictive of recovery. In addition, the workflows described are suitable for TBI clinical practice and patient monitoring, particularly for assessing damage extent and for the measurement of neuroanatomical change over time. With knowledge of general location, extent, and degree of change, such metrics can be associated with clinical measures and subsequently used to suggest viable treatment options.
Full Text Available AbstractObjective(sGastric ulceration is induced by various forms of stress like surgery, ischemia and trauma. The female sex has more resistance to stress and the gastrointestinal lesions happen fewer than male sex. The purpose of this study was to evaluate the role of estradiol and progesterone on the gastric acid and pepsin levels following traumatic brain injury (TBI induction.Materials and MethodsDiffuse TBI was induced by Marmarou method in female rats. Rats randomly assigned into 9 groups: intact, OVX (ovarectomized rat, Sham+OVX, TBI (intact rats under TBI, TBI+OVX (ovarectomized rats under TBI and treated OVX rats with vehicle (sesame oil, E2 (estradiol, P4 (progesterone or E2+P4 combination. The acid content and pepsin levels of each gastric washout sample were measured 5 days after the TBI induction.ResultsThere was no significant difference in gastric acid output between groups either after TBI induction or after treatment with E2 or P4 or E2+P4. Gastric pepsin levels were increased in Sham+OVX, TBI (P< 0.001 and TBI+OVX (P< 0.05 compared to intact group. Gastric pepsin levels were significantly lower in E2 and E2+ P4 treated rats than vehicle treated group (P< 0.01. P4 treatment increased gastric pepsin level compared to TBI+OVX group (P< 0.05 and this increment was higher than rats that were treated with the E2 and E2+P4 (P< 0.01.ConclusionThese results suggest that protective effect of estradiol and E2+P4 combination against mucosal damage after TBI, might be mediated by inhibition of pepsin secretion.
Full Text Available BACKGROUND: Oxidative stress is known to play an important role in the pathology of traumatic brain injury. Mitochondria are thought to be the major source of the damaging reactive oxygen species (ROS following TBI. However, recent work has revealed that the membrane, via the enzyme NADPH oxidase can also generate the superoxide radical (O(2(-, and thereby potentially contribute to the oxidative stress following TBI. The current study thus addressed the potential role of NADPH oxidase in TBI. METHODOLOGY/PRINCIPAL FINDINGS: The results revealed that NADPH oxidase activity in the cerebral cortex and hippocampal CA1 region increases rapidly following controlled cortical impact in male mice, with an early peak at 1 h, followed by a secondary peak from 24-96 h after TBI. In situ localization using oxidized hydroethidine and the neuronal marker, NeuN, revealed that the O(2(- induction occurred in neurons at 1 h after TBI. Pre- or post-treatment with the NADPH oxidase inhibitor, apocynin markedly inhibited microglial activation and oxidative stress damage. Apocynin also attenuated TBI-induction of the Alzheimer's disease proteins β-amyloid and amyloid precursor protein. Finally, both pre- and post-treatment of apocynin was also shown to induce significant neuroprotection against TBI. In addition, a NOX2-specific inhibitor, gp91ds-tat was also shown to exert neuroprotection against TBI. CONCLUSIONS/SIGNIFICANCE: As a whole, the study demonstrates that NADPH oxidase activity and superoxide production exhibit a biphasic elevation in the hippocampus and cortex following TBI, which contributes significantly to the pathology of TBI via mediation of oxidative stress damage, microglial activation, and AD protein induction in the brain following TBI.
... 4 [top] Speech and Language Tests A speech-language pathologist completes a formal evaluation of speech and language skills, including an oral motor evaluation of the strength and coordination of the muscles ...
Full Text Available Traumatic brain injury (TBI can result in persistent cognitive, behavioral and emotional deficits. However, the vast majority of patients are not chronically hospitalized; rather they have to manage their disabilities once they are discharged to home. Promoting recovery to pre-injury level is important from a patient care as well as a societal perspective. Electrical neuromodulation is one approach that has shown promise in alleviating symptoms associated with neurological disorders such as in Parkinson’s disease and epilepsy. Consistent with this perspective, both animal and clinical studies have revealed that TBI alters physiological oscillatory rhythms. More recently several studies demonstrated that low frequency stimulation improves cognitive outcome in models of TBI. Specifically, stimulation of the septohippocampal circuit in the theta frequency entrained oscillations and improved spatial learning following traumatic brain injury. In order to evaluate the potential of electrical deep brain stimulation for clinical translation we review the basic neurophysiology of oscillations, their role in cognition and how they are changed post-TBI. Furthermore, we highlight several factors for future pre-clinical and clinical studies to consider, with the hope that it will promote a hypothesis driven approach to subsequent experimental designs and ultimately successful translation to improve outcome in patients with TBI.
Full Text Available Primary blast induced traumatic brain injury (bTBI is a prevalent battlefield injury in recent conflicts, yet biomechanical mechanisms of bTBI remain unclear. Elucidating specific biomechanical mechanisms is essential to developing animal models for testing candidate therapies and for improving protective equipment. Three hypothetical mechanisms of primary bTBI have received the most attention. Because translational and rotational head accelerations are primary contributors to TBI from non-penetrating blunt force head trauma, the acceleration hypothesis suggests that blast-induced head accelerations may cause bTBI. The hypothesis of direct cranial transmission suggests that a pressure transient traverses the skull into the brain and directly injures brain tissue. The thoracic hypothesis of bTBI suggests that some combination of a pressure transient reaching the brain via the thorax and a vagally mediated reflex result in bTBI. These three mechanisms may not be mutually exclusive, and quantifying exposure thresholds (for blasts of a given duration is essential for determining which mechanisms may be contributing for a level of blast exposure. Progress has been hindered by experimental designs which do not effectively expose animal models to a single mechanism and by over-reliance on poorly validated computational models. The path forward should be predictive validation of computational models by quantitative confirmation with blast experiments in animal models, human cadavers, and biofidelic human surrogates over a range of relevant blast magnitudes and durations coupled with experimental designs which isolate a single injury mechanism.
Silva, Paula P B; Bhatnagar, Saurabha; Herman, Seth D; Zafonte, Ross; Klibanski, Anne; Miller, Karen K; Tritos, Nicholas A
Hypopituitarism may often occur in association with traumatic brain injury (TBI). Identification of reliable predictors of pituitary dysfunction is of importance in order to establish a rational testing approach. We searched the records of patients with TBI, who underwent neuroendocrine evaluation in our institution between 2007 and 2013. One hundred sixty-six adults (70% men) with TBI (median age: 41.6 years; range: 18-76) were evaluated at a median interval of 40.4 months (0.2-430.4).Of these, 31% had ≥1 pituitary deficiency, including 29% of patients with mild TBI and 35% with moderate/severe TBI. Growth hormone deficiency was the most common deficiency (21%); when body mass index (BMI)-dependent cutpoints were used, this was reduced to 15%. Central hypoadrenalism occurred in10%, who were more likely to have suffered a motor vehicle accident (MVA, p = 0.04), experienced post-traumatic seizures (p = 0.04), demonstrated any intracranial hemorrhage (p = 0.05), petechial brain hemorrhages (p = 0.017), or focal cortical parenchymal contusions (p = 0.02). Central hypothyroidism occurred in 8% and central hypogonadism in 12%; the latter subgroup had higher BMI (p = 0.03), were less likely to be working after TBI (p = 0.002), and had lower Global Assessment of Functioning (GAF) scores (p = 0.03). Central diabetes insipidus (DI) occurred in 6%, who were more likely to have experienced MVA (p hypopituitarism.
DeLaRosa, Bambi L.; Didehbani, Nyaz; Hart, John; Kraut, Michael A
Abstract Persons who have had a traumatic brain injury (TBI) often have word retrieval deficits; however, the underlying neural mechanisms of such deficits are yet to be clarified. Previous studies in normal subjects have shown that during a word retrieval task, there is a 750 msec event-related potential (ERP) divergence detected at the left fronto-temporal region when subjects evaluate word pairs that facilitate retrieval compared with responses elicited by word pairs that do not facilitate retrieval. In this study, we investigated the neurophysiological correlates of word retrieval networks in 19 retired professional athletes with TBI and 19 healthy control (HC) subjects. We recorded electroencephalography (EEG) in the participants during a semantic object retrieval task. In this task, participants indicated whether presented word pairs did (retrieval) or did not (non-retrieval) facilitate the retrieval of an object name. There were no significant differences in accuracy or reaction time between the two groups. The EEG showed a significant group by condition interaction over the left fronto-temporal region. The HC group mean amplitudes were significantly different between conditions, but the TBI group data did not show this difference, suggesting neurophysiological effects of injury. These findings provide evidence that ERP amplitudes may be used as a marker of disrupted semantic retrieval circuits in persons with TBI even when those persons perform normally. PMID:27596052
Xiao-dong Qu; Resha Shrestha; Mao-de Wang
To investigate the independent risk factors of traumatic brain injury (TBI) prognosis.Methods A retrospective analysis was performed in 885 hospitalized TEl patients from January 1,2003 to January 1, 2010 in the First Affiliated Hospital of Medical College of Xi' an Jiaotong University. Single-factor and logistic regression analysis were conducted to evaluate the association of different variables with TBI outcome.Results The single-factor analysis revealed significant association between several variables and TEl outcome, including age (P=0.044 for the age group 40-60, P＜0.001 for the age group ≥60), complications (P＜0.001), cerebrospinal fluid leakage (P＜0.001), Glasgow Coma Scale (GCS) (P＜0.001), pupillary light reflex (P＜0.001), shock (P＜0.001), associated extra-cranial lesions (P=0.01), subdural hematoma (P＜0.001), cerebral contusion (P＜0.001), diffuse axonal injury (P＜0.001), and subarachnoid hemorrhage (P＜0.001), suggesting the influence of those factors on the prognosis of TBI. Furthermore, logistic regression analysis identified age, GCS score, pupillary light reflex, subdural hematoma, and subarachnoid hemorrhage as independent risk factors of TEl prognosis.Conclusion Age, GCS score, papillary light reflex, subdural hematoma, and subarachnoid hemorrhage may be risk factors influencing the prognosis of TEl. Paying attention to those factors might improve the outcome of TBI in clinical treatment.
Gaafar M Ishaq
Full Text Available Background: Traumatic brain injury (TBI is accompanied by substantial accumulation of biomarkers of oxidative stress and depletion of antioxidants reserve which initiate chain reactions that damage brain cells. The present study investigated the role of ascorbic acid and α-tocopherol on the severity and management of TBI in rats. Materials and Methods: Wistar rats were subjected to closed head injury using an accelerated impact device. Rats were administered 45 mg/kg and 60 mg/kg body weight of ascorbic acid, α-tocopherol or a combination of the two vitamins for 2 weeks pre- and post injury. Blood and brain tissue homogenates were analyzed for vitamin C, vitamin E, malondialdehyde, superoxide dismutase, and creatine kinase activities. Results: The results indicated that TBI caused significant (P < 0.05 decreased in vitamins C and E levels in the blood and brain tissue of TBI-untreated rats. The activities of superoxide dismutase in TBI rats were markedly reduced when compared with non traumatized control and showed a tendency to increased following supplementation with vitamins C and E. Supplementation of the vitamins significantly (P < 0.05 reduced malondialdehyde in the treatment groups compared with the TBI-untreated group. Conclusion: The study indicated that pre and post treatment with ascorbic acid and α-tocopherol reduced oxidative stress induced by brain injury and effectively reduced mortality rate in rats.
Traumatic brain injury (TBI) may be due to a bump, blow, or jolt to the head or a penetrating head injury that disrupts normal brain function; it presents an ever-growing, serious public health problem that causes a considerable number of fatalities and cases of permanent disability annually. Physical exercise restores the healthy homeostatic regulation of stress, affect and the regulation of hypothalamic-pituitary-adrenal axis. Physical activity attenuates or reverses the performance deficits observed in neurocognitive tasks. It induces anti-apoptotic effects and buttresses blood-brain barrier intactness. Exercise offers a unique non-pharmacologic, non-invasive intervention that incorporates different regimes, whether dynamic or static, endurance, or resistance. Exercise intervention protects against vascular risk factors that include hypertension, diabetes, cellular inflammation, and aortic rigidity. It induces direct changes in cerebrovasculature that produce beneficial changes in cerebral blood flow, angiogenesis and vascular disease improvement. The improvements induced by physical exercise regimes in brain plasticity and neurocognitive performance are evident both in healthy individuals and in those afflicted by TBI. The overlap and inter-relations between TBI effects on brain and cognition as related to physical exercise and cognition may provide lasting therapeutic benefits for recovery from TBI. It seems likely that some modification of the notion of scaffolding would postulate that physical exercise reinforces the adaptive processes of the brain that has undergone TBI thereby facilitating the development of existing networks, albeit possibly less efficient, that compensate for those lost through damage.
Full Text Available Objective(s:Estrogen (E2 has neuroprotective effects on blood-brain-barrier (BBB after traumatic brain injury (TBI. In order to investigate the roles of estrogen receptors (ERs in these effects, ER-α antagonist (MPP and, ER-β antagonist (PHTPP, or non-selective estrogen receptors antagonist (ICI 182780 were administered. Materials and Methods: Ovariectomized rats were divided into 10 groups, as follows: Sham, TBI, E2, oil, MPP+E2, PHTPP+E2, MPP+PHTPP+E2, ICI+E2, MPP, and DMSO. E2 (33.3 µg/Kg or oil were administered 30 min after TBI. 1 dose (150 µg/Kg of each of MPP, PHTPP, and (4 mg/kg ICI182780 was injected two times, 24 hr apart, before TBI and estrogen treatment. BBB disruption (Evans blue content and brain edema (brain water content evaluated 5 hr and 24 hr after the TBI were evaluated, respectively. Results: The results showed that E2 reduced brain edema after TBI compared to vehicle (P
Vas, Asha Kuppachi; Spence, Jeffrey; Chapman, Sandra Bond
Gist reasoning (abstracting meaning from complex information) was compared between adults with moderate-to-severe traumatic brain injury (TBI, n = 30) at least one year post injury and healthy adults (n = 40). The study also examined the contribution of executive functions (working memory, inhibition, and switching) and memory (immediate recall and memory for facts) to gist reasoning. The correspondence between gist reasoning and daily function was also examined in the TBI group. Results indicated that the TBI group performed significantly lower than the control group on gist reasoning, even after adjusting for executive functions and memory. Executive function composite was positively associated with gist reasoning (p reasoning significantly predicted daily function in the TBI group beyond the predictive ability of executive function alone (p = .011). Synthesizing and abstracting meaning(s) from information (i.e., gist reasoning) could provide an informative index into higher order cognition and daily functionality.