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Sample records for brain injury model

  1. Opioid Abuse after Traumatic Brain Injury: Evaluation Using Rodent Models

    Science.gov (United States)

    2015-09-01

    craniotomy was cut with a trephine by hand over the right motor cortex . An injury cannula was fashioned from the hub of a female leur-lock 20g needle...ABSTRACT This project evaluated the effect of a moderate-level brain injury on risk for opioid abuse using preclinical models in rats . We assessed the...effect of brain injury on the rewarding effects of oxycodone in three rat self-administration procedures and found significant differences in the

  2. Longitudinal Examination of Resilience After Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study.

    Science.gov (United States)

    Marwitz, Jennifer H; Sima, Adam P; Kreutzer, Jeffrey S; Dreer, Laura E; Bergquist, Thomas F; Zafonte, Ross; Johnson-Greene, Douglas; Felix, Elizabeth R

    2018-02-01

    To evaluate (1) the trajectory of resilience during the first year after a moderate-severe traumatic brain injury (TBI); (2) factors associated with resilience at 3, 6, and 12 months postinjury; and (3) changing relationships over time between resilience and other factors. Longitudinal analysis of an observational cohort. Five inpatient rehabilitation centers. Patients with TBI (N=195) enrolled in the resilience module of the TBI Model Systems study with data collected at 3-, 6-, and 12-month follow-up. Not applicable. Connor-Davidson Resilience Scale. Initially, resilience levels appeared to be stable during the first year postinjury. Individual growth curve models were used to examine resilience over time in relation to demographic, psychosocial, and injury characteristics. After adjusting for these characteristics, resilience actually declined over time. Higher levels of resilience were related to nonminority status, absence of preinjury substance abuse, lower anxiety and disability level, and greater life satisfaction. Resilience is a construct that is relevant to understanding brain injury outcomes and has potential value in planning clinical interventions. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  3. Internet and Social Media Use After Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study.

    Science.gov (United States)

    Baker-Sparr, Christina; Hart, Tessa; Bergquist, Thomas; Bogner, Jennifer; Dreer, Laura; Juengst, Shannon; Mellick, David; OʼNeil-Pirozzi, Therese M; Sander, Angelle M; Whiteneck, Gale G

    To characterize Internet and social media use among adults with moderate to severe traumatic brain injury (TBI) and to compare demographic and socioeconomic factors associated with Internet use between those with and without TBI. Ten Traumatic Brain Injury Model Systems centers. Persons with moderate to severe TBI (N = 337) enrolled in the TBI Model Systems National Database and eligible for follow-up from April 1, 2014, to March 31, 2015. Prospective cross-sectional observational cohort study. Internet usage survey. The proportion of Internet users with TBI was high (74%) but significantly lower than those in the general population (84%). Smartphones were the most prevalent means of Internet access for persons with TBI. The majority of Internet users with TBI had a profile account on a social networking site (79%), with more than half of the sample reporting multiplatform use of 2 or more social networking sites. Despite the prevalence of Internet use among persons with TBI, technological disparities remain in comparison with the general population. The extent of social media use among persons with TBI demonstrates the potential of these platforms for social engagement and other purposes. However, further research examining the quality of online activities and identifying potential risk factors of problematic use is recommended.

  4. Fresh Frozen Plasma Modulates Brain Gene Expression in a Swine Model of Traumatic Brain Injury and Shock

    DEFF Research Database (Denmark)

    Sillesen, Martin; Bambakidis, Ted; Dekker, Simone E

    2017-01-01

    BACKGROUND: Resuscitation with fresh frozen plasma (FFP) decreases brain lesion size and swelling in a swine model of traumatic brain injury and hemorrhagic shock. We hypothesized that brain gene expression profiles after traumatic brain injury and hemorrhagic shock would be modulated by FFP resu...

  5. Cost prediction following traumatic brain injury: model development and validation.

    Science.gov (United States)

    Spitz, Gershon; McKenzie, Dean; Attwood, David; Ponsford, Jennie L

    2016-02-01

    The ability to predict costs following a traumatic brain injury (TBI) would assist in planning treatment and support services by healthcare providers, insurers and other agencies. The objective of the current study was to develop predictive models of hospital, medical, paramedical, and long-term care (LTC) costs for the first 10 years following a TBI. The sample comprised 798 participants with TBI, the majority of whom were male and aged between 15 and 34 at time of injury. Costing information was obtained for hospital, medical, paramedical, and LTC costs up to 10 years postinjury. Demographic and injury-severity variables were collected at the time of admission to the rehabilitation hospital. Duration of PTA was the most important single predictor for each cost type. The final models predicted 44% of hospital costs, 26% of medical costs, 23% of paramedical costs, and 34% of LTC costs. Greater costs were incurred, depending on cost type, for individuals with longer PTA duration, obtaining a limb or chest injury, a lower GCS score, older age at injury, not being married or defacto prior to injury, living in metropolitan areas, and those reporting premorbid excessive or problem alcohol use. This study has provided a comprehensive analysis of factors predicting various types of costs following TBI, with the combination of injury-related and demographic variables predicting 23-44% of costs. PTA duration was the strongest predictor across all cost categories. These factors may be used for the planning and case management of individuals following TBI. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  6. A preliminary model for posttraumatic brain injury depression.

    Science.gov (United States)

    Malec, James F; Brown, Allen W; Moessner, Anne M; Stump, Timothy E; Monahan, Patrick

    2010-07-01

    To develop, based on previous research, and evaluate a model for depression after traumatic brain injury (TBI). Cross-sectional structural equation modeling (SEM) of data from consecutively recruited patients. Acute hospital and inpatient rehabilitation units. Adult patients (N=158) after hospital admission for moderate to severe TBI. Not applicable. External appraisal of ability in participants was measured by the Mayo-Portland Adaptability Inventory (MPAI-4) Ability Index completed by a TBI clinical nurse specialist. Patient self-appraisal of post-TBI ability and depression were measured by the Awareness Questionnaire and Beck Depression Inventory-II. Functional outcome 1 year after injury was assessed with the MPAI-4 Participation Index. Successive SEM resulted in a parsimonious model with excellent fit. Consistent with prior research, a moderately strong association between self-appraisal of post-TBI ability and depression was found. Injury severity, as measured by the duration of posttraumatic amnesia (PTA), was not significantly associated with post-TBI depression. The 1-year functional outcome was associated with depression and TBI severity. The strong association between self-appraisal of post-TBI ability and depression is consistent with the cognitive-behavioral model of depression and recommends consideration and further study of cognitive-behavioral therapy for post-TBI depression. The lack of association between TBI severity and depression may represent the indirect and proxy nature of current measures of TBI severity such as PTA. Emerging neuroimaging techniques (eg, diffusion tensor imaging, magnetic resonance imaging spectroscopy) may provide the more direct measures of disruption of brain function after TBI that are needed to advance this line of research. Copyright 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  7. Resuscitation speed affects brain injury in a large animal model of traumatic brain injury and shock

    DEFF Research Database (Denmark)

    Sillesen, Martin; Jin, Guang; Johansson, Pär I

    2014-01-01

    as lesion size (3285.44¿±¿130.81 mm3 vs. 2509.41¿±¿297.44 mm3, p¿=¿0.04). This was also associated with decreased cardiac output (NS: 4.37¿±¿0.12 l/min vs. 6.35¿±¿0.10 l/min, p¿brain compared......BackgroundOptimal fluid resuscitation strategy following combined traumatic brain injury (TBI) and hemorrhagic shock (HS) remain controversial and the effect of resuscitation infusion speed on outcome is not well known. We have previously reported that bolus infusion of fresh frozen plasma (FFP......) protects the brain compared with bolus infusion of 0.9% normal saline (NS). We now hypothesize reducing resuscitation infusion speed through a stepwise infusion speed increment protocol using either FFP or NS would provide neuroprotection compared with a high speed resuscitation protocol.Methods23...

  8. Systematic review of prognostic models in traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Roberts Ian

    2006-11-01

    Full Text Available Abstract Background Traumatic brain injury (TBI is a leading cause of death and disability world-wide. The ability to accurately predict patient outcome after TBI has an important role in clinical practice and research. Prognostic models are statistical models that combine two or more items of patient data to predict clinical outcome. They may improve predictions in TBI patients. Multiple prognostic models for TBI have accumulated for decades but none of them is widely used in clinical practice. The objective of this systematic review is to critically assess existing prognostic models for TBI Methods Studies that combine at least two variables to predict any outcome in patients with TBI were searched in PUBMED and EMBASE. Two reviewers independently examined titles, abstracts and assessed whether each met the pre-defined inclusion criteria. Results A total of 53 reports including 102 models were identified. Almost half (47% were derived from adult patients. Three quarters of the models included less than 500 patients. Most of the models (93% were from high income countries populations. Logistic regression was the most common analytical strategy to derived models (47%. In relation to the quality of the derivation models (n:66, only 15% reported less than 10% pf loss to follow-up, 68% did not justify the rationale to include the predictors, 11% conducted an external validation and only 19% of the logistic models presented the results in a clinically user-friendly way Conclusion Prognostic models are frequently published but they are developed from small samples of patients, their methodological quality is poor and they are rarely validated on external populations. Furthermore, they are not clinically practical as they are not presented to physicians in a user-friendly way. Finally because only a few are developed using populations from low and middle income countries, where most of trauma occurs, the generalizability to these setting is limited.

  9. Establishment of a blunt impact-induced brain injury model in rabbits

    OpenAIRE

    LI Kui; CAO Yun-xing; YANG Yong-qiang; YIN Zhi-yong; ZHAO Hui; WANG Li-jun

    2012-01-01

    【Abstract】 Objective: To establish an animal model to replicate the blunt impact brain injury in forensic medicine. Methods: Twenty-four New Zealand white rabbits were randomly divided into control group (n=4), minor injury group (n=10) and severe injury group (n=10). Based on the BIM-Ⅱ Horizontal Bio-impact Machine, self-designed iron bar was used to produce blunt brain injury. Two rabbits from each injury group were randomly selected to monitor the change of in...

  10. Brain injuries from blast.

    Science.gov (United States)

    Bass, Cameron R; Panzer, Matthew B; Rafaels, Karen A; Wood, Garrett; Shridharani, Jay; Capehart, Bruce

    2012-01-01

    Traumatic brain injury (TBI) from blast produces a number of conundrums. This review focuses on five fundamental questions including: (1) What are the physical correlates for blast TBI in humans? (2) Why is there limited evidence of traditional pulmonary injury from blast in current military field epidemiology? (3) What are the primary blast brain injury mechanisms in humans? (4) If TBI can present with clinical symptoms similar to those of Post-Traumatic Stress Disorder (PTSD), how do we clinically differentiate blast TBI from PTSD and other psychiatric conditions? (5) How do we scale experimental animal models to human response? The preponderance of the evidence from a combination of clinical practice and experimental models suggests that blast TBI from direct blast exposure occurs on the modern battlefield. Progress has been made in establishing injury risk functions in terms of blast overpressure time histories, and there is strong experimental evidence in animal models that mild brain injuries occur at blast intensities that are similar to the pulmonary injury threshold. Enhanced thoracic protection from ballistic protective body armor likely plays a role in the occurrence of blast TBI by preventing lung injuries at blast intensities that could cause TBI. Principal areas of uncertainty include the need for a more comprehensive injury assessment for mild blast injuries in humans, an improved understanding of blast TBI pathophysiology of blast TBI in animal models and humans, the relationship between clinical manifestations of PTSD and mild TBI from blunt or blast trauma including possible synergistic effects, and scaling between animals models and human exposure to blasts in wartime and terrorist attacks. Experimental methodologies, including location of the animal model relative to the shock or blast source, should be carefully designed to provide a realistic blast experiment with conditions comparable to blasts on humans. If traditional blast scaling is

  11. Mild Traumatic Brain Injury

    Science.gov (United States)

    ... mild Traumatic Brain Injury Resilience Families with Kids Depression Families & Friendships Tobacco Life Stress Spirituality Anger Physical Injury Stigma Health & Wellness Work Adjustment Community Peer-2-Peer Forum ...

  12. Characteristics of Firearm Brain Injury Survivors in the Traumatic Brain Injury Model Systems (TBIMS) National Database: A Comparison of Assault and Self-Inflicted Injury Survivors.

    Science.gov (United States)

    Bertisch, Hilary; Krellman, Jason W; Bergquist, Thomas F; Dreer, Laura E; Ellois, Valerie; Bushnik, Tamara

    2017-11-01

    To characterize and compare subgroups of survivors with assault-related versus self-inflicted traumatic brain injuries (TBIs) via firearms at the time of inpatient rehabilitation and at 1-, 2-, and 5-year follow-up. Secondary analysis of data from the Traumatic Brain Injury Model Systems National Database (TBIMS NDB), a multicenter, longitudinal cohort study. Retrospective analyses of a subset of individuals enrolled in the TBIMS NDB. Individuals 16 years and older (N=399; 310 via assault, 89 via self-inflicted injury) with a primary diagnosis of TBI caused by firearm injury enrolled in the TBIMS NDB. Not applicable. Disability Rating Scale, Glasgow Outcome Scale-Extended, sociodemographic variables (sex, age, race, marital status), injury-related/acute care information (posttraumatic amnesia, loss of consciousness, time from injury to acute hospital discharge), and mental health variables (substance use history, psychiatric hospitalizations, suicide history, incarcerations). Individuals who survived TBI secondary to a firearm injury differed by injury mechanism (assault vs self-inflicted) on critical demographic, injury-related/acute care, and mental health variables at inpatient rehabilitation and across long-term recovery. Groups differed in terms of geographic area, age, ethnicity, education, marital status, admission Glasgow Coma Scale score, and alcohol abuse, suicide attempts, and psychiatric hospitalizations at various time points. These findings have implications for prevention (eg, mental health programming and access to firearms in targeted areas) and for rehabilitation planning (eg, by incorporating training with coping strategies and implementation of addictions-related services) for firearm-related TBI, based on subtype of injury. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  13. Brain injury - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000163.htm Brain injury - discharge To use the sharing features on ... know was in the hospital for a serious brain injury. At home, it will take time for ...

  14. Traumatic Brain Injury

    Science.gov (United States)

    ... brain injury Some traumatic brain injuries have lasting effects, and some do not. You may be left with disabilities. These can be physical, behavioral, communicative, and/or mental. Customized treatment helps you to have as full ...

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

    Science.gov (United States)

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

    2012-01-01

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

  16. Prognosis in moderate and severe traumatic brain injury: External validation of the IMPACT models and the role of extracranial injuries

    NARCIS (Netherlands)

    Lingsma, Hester; Andriessen, Teuntje M. J. C.; Haitsema, Iain; Horn, Janneke; van der Naalt, Joukje; Franschman, Gaby; Maas, Andrew I. R.; Vos, Pieter E.; Steyerberg, Ewout W.

    2013-01-01

    BACKGROUND: Several prognostic models to predict outcome in traumatic brain injury (TBI) have been developed, but few are externally validated. We aimed to validate the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) prognostic models in a recent unselected patient

  17. A new model for diffuse brain injury by rotational acceleration: I model, gross appearance, and astrocytosis.

    Science.gov (United States)

    Gutierrez, E; Huang, Y; Haglid, K; Bao, F; Hansson, H A; Hamberger, A; Viano, D

    2001-03-01

    Rapid head rotation is a major cause of brain damage in automobile crashes and falls. This report details a new model for rotational acceleration about the center of mass of the rabbit head. This allows the study of brain injury without translational acceleration of the head. Impact from a pneumatic cylinder was transferred to the skull surface to cause a half-sine peak acceleration of 2.1 x 10(5) rad/s2 and 0.96-ms pulse duration. Extensive subarachnoid hemorrhages and small focal bleedings were observed in the brain tissue. A pronounced reactive astrogliosis was found 8-14 days after trauma, both as networks around the focal hemorrhages and more diffusely in several brain regions. Astrocytosis was prominent in the gray matter of the cerebral cortex, layers II-V, and in the granule cell layer and around the axons of the pyramidal neurons in the hippocampus. The nuclei of cranial nerves, such as the hypoglossal and facial nerves, also showed intense astrocytosis. The new model allows study of brain injuries from head rotation in the absence of translational influences.

  18. Pathophysiological Responses in Rat and Mouse Models of Radiation-Induced Brain Injury.

    Science.gov (United States)

    Yang, Lianhong; Yang, Jianhua; Li, Guoqian; Li, Yi; Wu, Rong; Cheng, Jinping; Tang, Yamei

    2017-03-01

    The brain is the major dose-limiting organ in patients undergoing radiotherapy for assorted conditions. Radiation-induced brain injury is common and mainly occurs in patients receiving radiotherapy for malignant head and neck tumors, arteriovenous malformations, or lung cancer-derived brain metastases. Nevertheless, the underlying mechanisms of radiation-induced brain injury are largely unknown. Although many treatment strategies are employed for affected individuals, the effects remain suboptimal. Accordingly, animal models are extremely important for elucidating pathogenic radiation-associated mechanisms and for developing more efficacious therapies. So far, models employing various animal species with different radiation dosages and fractions have been introduced to investigate the prevention, mechanisms, early detection, and management of radiation-induced brain injury. However, these models all have limitations, and none are widely accepted. This review summarizes the animal models currently set forth for studies of radiation-induced brain injury, especially rat and mouse, as well as radiation dosages, dose fractionation, and secondary pathophysiological responses.

  19. A Blast Model of Traumatic Brain Injury in Swine

    Science.gov (United States)

    2011-02-01

    the smaller gun had a slower recovery, was extubated 14 minutes post injury, was given 100 mg carprofen IM one hour post injury because of the slow...at 80 psi was extubated 12 minutes post injury, showed signs of pain by excessively grinding teeth and was given 100 mg carprofen one hour post

  20. The application of a mathematical model linking structural and functional connectomes in severe brain injury

    Directory of Open Access Journals (Sweden)

    A. Kuceyeski

    2016-01-01

    Full Text Available Following severe injuries that result in disorders of consciousness, recovery can occur over many months or years post-injury. While post-injury synaptogenesis, axonal sprouting and functional reorganization are known to occur, the network-level processes underlying recovery are poorly understood. Here, we test a network-level functional rerouting hypothesis in recovery of patients with disorders of consciousness following severe brain injury. This hypothesis states that the brain recovers from injury by restoring normal functional connections via alternate structural pathways that circumvent impaired white matter connections. The so-called network diffusion model, which relates an individual's structural and functional connectomes by assuming that functional activation diffuses along structural pathways, is used here to capture this functional rerouting. We jointly examined functional and structural connectomes extracted from MRIs of 12 healthy and 16 brain-injured subjects. Connectome properties were quantified via graph theoretic measures and network diffusion model parameters. While a few graph metrics showed groupwise differences, they did not correlate with patients' level of consciousness as measured by the Coma Recovery Scale — Revised. There was, however, a strong and significant partial Pearson's correlation (accounting for age and years post-injury between level of consciousness and network diffusion model propagation time (r = 0.76, p < 0.05, corrected, i.e. the time functional activation spends traversing the structural network. We concluded that functional rerouting via alternate (and less efficient pathways leads to increases in network diffusion model propagation time. Simulations of injury and recovery in healthy connectomes confirmed these results. This work establishes the feasibility for using the network diffusion model to capture network-level mechanisms in recovery of consciousness after severe brain injury.

  1. Dendrimer Brain Uptake and Targeted Therapy for Brain Injury in a Large Animal Model of Hypothermic Circulatory Arrest

    Science.gov (United States)

    2015-01-01

    Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer–drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems. PMID:24499315

  2. Dendrimer brain uptake and targeted therapy for brain injury in a large animal model of hypothermic circulatory arrest.

    Science.gov (United States)

    Mishra, Manoj K; Beaty, Claude A; Lesniak, Wojciech G; Kambhampati, Siva P; Zhang, Fan; Wilson, Mary A; Blue, Mary E; Troncoso, Juan C; Kannan, Sujatha; Johnston, Michael V; Baumgartner, William A; Kannan, Rangaramanujam M

    2014-03-25

    Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer-drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems.

  3. Progesterone treatment shows benefit in a pediatric model of moderate to severe bilateral brain injury.

    Directory of Open Access Journals (Sweden)

    Rastafa I Geddes

    Full Text Available Controlled cortical impact (CCI models in adult and aged Sprague-Dawley (SD rats have been used extensively to study medial prefrontal cortex (mPFC injury and the effects of post-injury progesterone treatment, but the hormone's effects after traumatic brain injury (TBI in juvenile animals have not been determined. In the present proof-of-concept study we investigated whether progesterone had neuroprotective effects in a pediatric model of moderate to severe bilateral brain injury.Twenty-eight-day old (PND 28 male Sprague Dawley rats received sham (n = 24 or CCI (n = 47 injury and were given progesterone (4, 8, or 16 mg/kg per 100 g body weight or vehicle injections on post-injury days (PID 1-7, subjected to behavioral testing from PID 9-27, and analyzed for lesion size at PID 28.The 8 and 16 mg/kg doses of progesterone were observed to be most beneficial in reducing the effect of CCI on lesion size and behavior in PND 28 male SD rats.Our findings suggest that a midline CCI injury to the frontal cortex will reliably produce a moderate TBI comparable to what is seen in the adult male rat and that progesterone can ameliorate the injury-induced deficits.

  4. Brain injury and discrimination: Two competing models-perceptions of responsibility and dangerousness.

    Science.gov (United States)

    Foster, Lynette A; Leathem, Janet M; Humphries, Steve

    2016-01-01

    (1) To examine whether the willingness of people to socialize with adolescents with brain injury is influenced by gender, visibility of injury and/or knowing how to interact with people with brain injury; and (2) To consider two models: the responsibility model (attributions about the cause of a condition) and the danger appraisal model (perceptions of dangerousness due to anger/aggression) for their effect on willingness to socialize and to understand how these perceptions lead to avoidant behaviour. Participants were recruited either by personal approach or via Facebook advertising and completed a survey after reading a brief vignette and seeing a photo of an adolescent male or female, with or without a head scar. Vignettes for some participants were varied to represent perceptions of responsibility and dangerousness Main outcomes and results: ANOVAs and structural equation modelling revealed that participants were more willing to socialize with the adolescents with a scar than with no scar. Knowledge about how to interact with survivors impacted willingness to socialize, but familiarity did not. The full danger appraisal model was supported, but only some aspects of the responsibility model were supported. The results provide useful information for rehabilitation health professionals working with survivors of brain injury. The implications of these findings are discussed with regards to assisting adolescents' re-entry into society post-injury.

  5. Thymoquinone attenuates brain injury via an antioxidative pathway in a status epilepticus rat model

    Directory of Open Access Journals (Sweden)

    Shao Yi-ye

    2017-03-01

    Full Text Available Status epilepticus (SE results in the generation of reactive oxygen species (ROS, which contribute to seizure-induced brain injury. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE. Thymoquinone (TQ is a bioactive monomer extracted from black cumin (Nigella sativa seed oil that has anti-inflammatory, anti-cancer, and antioxidant activity in various diseases. This study evaluated the protective effects of TQ on brain injury in a lithium-pilocarpine rat model of SE and investigated the underlying mechanism related to antioxidative pathway.

  6. Opioid Abuse After Traumatic Brain Injury: Evaluation Using Rodet Models

    Science.gov (United States)

    2014-07-01

    pressing behavior was less likely to occur in brain-injured subjects following both exposure to oxycodone-associated cues as well as priming with a...pain medications. There is significant overlap in anatomical brain regions involved in reward pathways associated with addiction and the brain regions...commonly damaged in TBI which suggests that TBI could alter the reward circuitry, thereby increasing the likelihood of opioid abuse and addiction

  7. The Effects of Exercise on Cognitive Recovery after Acquired Brain Injury in Animal Models

    DEFF Research Database (Denmark)

    Wogensen, Elise; Rytter, Hana Malá; Mogensen, Jesper

    2015-01-01

    The objective of the present paper is to review the current status of exercise as a tool to promote cognitive rehabilitation after acquired brain injury (ABI) in animal model-based research. Searches were conducted on the PubMed, Scopus, and psycINFO databases in February 2014. Search strings used...

  8. Developing a Family-Centered Care Model for Critical Care After Pediatric Traumatic Brain Injury.

    Science.gov (United States)

    Moore, Megan; Robinson, Gabrielle; Mink, Richard; Hudson, Kimberly; Dotolo, Danae; Gooding, Tracy; Ramirez, Alma; Zatzick, Douglas; Giordano, Jessica; Crawley, Deborah; Vavilala, Monica S

    2015-10-01

    This study examined the family experience of critical care after pediatric traumatic brain injury in order to develop a model of specific factors associated with family-centered care. Qualitative methods with semi-structured interviews were used. Two level 1 trauma centers. Fifteen mothers of children who had an acute hospital stay after traumatic brain injury within the last 5 years were interviewed about their experience of critical care and discharge planning. Participants who were primarily English, Spanish, or Cantonese speaking were included. None. Content analysis was used to code the transcribed interviews and develop the family-centered care model. Three major themes emerged: 1) thorough, timely, compassionate communication, 2) capacity building for families, providers, and facilities, and 3) coordination of care transitions. Participants reported valuing detailed, frequent communication that set realistic expectations and prepared them for decision making and outcomes. Areas for capacity building included strategies to increase provider cultural humility, parent participation in care, and institutional flexibility. Coordinated care transitions, including continuity of information and maintenance of partnerships with families and care teams, were highlighted. Participants who were not primarily English speaking reported particular difficulty with communication, cultural understanding, and coordinated transitions. This study presents a family-centered traumatic brain injury care model based on family perspectives. In addition to communication and coordination strategies, the model offers methods to address cultural and structural barriers to meeting the needs of non-English-speaking families. Given the stress experienced by families of children with traumatic brain injury, careful consideration of the model themes identified here may assist in improving overall quality of care to families of hospitalized children with traumatic brain injury.

  9. Strain and rate-dependent neuronal injury in a 3D in vitro compression model of traumatic brain injury

    Science.gov (United States)

    Bar-Kochba, Eyal; Scimone, Mark T.; Estrada, Jonathan B.; Franck, Christian

    2016-01-01

    In the United States over 1.7 million cases of traumatic brain injury are reported yearly, but predictive correlation of cellular injury to impact tissue strain is still lacking, particularly for neuronal injury resulting from compression. Given the prevalence of compressive deformations in most blunt head trauma, this information is critically important for the development of future mitigation and diagnosis strategies. Using a 3D in vitro neuronal compression model, we investigated the role of impact strain and strain rate on neuronal lifetime, viability, and pathomorphology. We find that strain magnitude and rate have profound, yet distinctively different effects on the injury pathology. While strain magnitude affects the time of neuronal death, strain rate influences the pathomorphology and extent of population injury. Cellular injury is not initiated through localized deformation of the cytoskeleton but rather driven by excess strain on the entire cell. Furthermore we find that, mechanoporation, one of the key pathological trigger mechanisms in stretch and shear neuronal injuries, was not observed under compression. PMID:27480807

  10. Severe Traumatic Brain Injury

    Science.gov (United States)

    ... TBI Online Concussion Training Press Room Guide to Writing about TBI in News and Social Media Living with TBI HEADS UP to Brain Injury Awareness Get Email Updates To receive email updates about this topic, ...

  11. Relationship of mechanical impact magnitude to neurologic dysfunction severity in a rat traumatic brain injury model.

    Directory of Open Access Journals (Sweden)

    Tsung-Hsun Hsieh

    Full Text Available Traumatic brain injury (TBI is a major brain injury type commonly caused by traffic accidents, falls, violence, or sports injuries. To obtain mechanistic insights about TBI, experimental animal models such as weight-drop-induced TBI in rats have been developed to mimic closed-head injury in humans. However, the relationship between the mechanical impact level and neurological severity following weight-drop-induced TBI remains uncertain. In this study, we comprehensively investigated the relationship between physical impact and graded severity at various weight-drop heights.The acceleration, impact force, and displacement during the impact were accurately measured using an accelerometer, a pressure sensor, and a high-speed camera, respectively. In addition, the longitudinal changes in neurological deficits and balance function were investigated at 1, 4, and 7 days post TBI lesion. The inflammatory expression markers tested by Western blot analysis, including glial fibrillary acidic protein, beta-amyloid precursor protein, and bone marrow tyrosine kinase gene in chromosome X, in the frontal cortex, hippocampus, and corpus callosum were investigated at 1 and 7 days post-lesion.Gradations in impact pressure produced progressive degrees of injury severity in the neurological score and balance function. Western blot analysis demonstrated that all inflammatory expression markers were increased at 1 and 7 days post-impact injury when compared to the sham control rats. The severity of neurologic dysfunction and induction in inflammatory markers strongly correlated with the graded mechanical impact levels.We conclude that the weight-drop-induced TBI model can produce graded brain injury and induction of neurobehavioral deficits and may have translational relevance to developing therapeutic strategies for TBI.

  12. Pediatric acquired brain injury.

    Science.gov (United States)

    Bodack, Marie I

    2010-10-01

    Although pediatric patients are sometimes included in studies about visual problems in patients with acquired brain injury (ABI), few studies deal solely with children. Unlike studies dealing with adult patients, in which mechanisms of brain injury are divided into cerebral vascular accident (CVA) and traumatic brain injury (TBI), studies on pediatric patients deal almost exclusively with traumatic brain injury, specifically caused by accidents. Here we report on the vision problems of 4 pediatric patients, ages 3 to 18 years, who were examined in the ophthalmology/optometry clinic at a children's hospital. All patients had an internally caused brain injury and after the initial insult manifested problems in at least one of the following areas: acuity, binocularity, motility (tracking or saccades), accommodation, visual fields, and visual perceptual skills. Pediatric patients can suffer from a variety of oculo-visual problems after the onset of head injury. These patients may or may not be symptomatic and can benefit from optometric intervention. Copyright © 2010 American Optometric Association. Published by Elsevier Inc. All rights reserved.

  13. Is current brain injury rehabilitation enhancing the biopsychosocial model?

    DEFF Research Database (Denmark)

    Glintborg, Chalotte; Hansen, Tia G. B.; Thomsen, Ane Søndergaard

    2014-01-01

    original, peer-reviewed research published in English and other languages. References were also identified from the bibliographies of eligible articles. Study selection: Controlled trials and cohort and case-control studies were selected according to pre-defined criteria. Studies had to have a minimum...... symptom score, 95% confidence interval (CI) = 1.2–12.0), but no difference in general health outcome 6 months. The other was a RCT of the effectiveness of 6 days of bed rest on post-traumatic complaints 6 months post-injury, compared to no bed rest, and found no effect. Conclusions: Some evidence suggests...

  14. Neurocognitive Models of Medical Decision-Making Capacity in Traumatic Brain Injury Across Injury Severity.

    Science.gov (United States)

    Triebel, Kristen L; Novack, Thomas A; Kennedy, Richard; Martin, Roy C; Dreer, Laura E; Raman, Rema; Marson, Daniel C

    2016-01-01

    To identify neurocognitive predictors of medical decision-making capacity (MDC) in participants with mild and moderate/severe traumatic brain injury (TBI). Academic medical center. Sixty adult controls and 104 adults with TBI (49 mild, 55 moderate/severe) evaluated within 6 weeks of injury. Prospective cross-sectional study. Participants completed the Capacity to Consent to Treatment Instrument to assess MDC and a neuropsychological test battery. We used factor analysis to reduce the battery test measures into 4 cognitive composite scores (verbal memory, verbal fluency, academic skills, and processing speed/executive function). We identified cognitive predictors of the 3 most clinically relevant Capacity to Consent to Treatment Instrument consent standards (appreciation, reasoning, and understanding). In controls, academic skills (word reading, arithmetic) and verbal memory predicted understanding; verbal fluency predicted reasoning; and no predictors emerged for appreciation. In the mild TBI group, verbal memory predicted understanding and reasoning, whereas academic skills predicted appreciation. In the moderate/severe TBI group, verbal memory and academic skills predicted understanding; academic skills predicted reasoning; and academic skills and verbal fluency predicted appreciation. Verbal memory was a predictor of MDC in controls and persons with mild and moderate/severe TBI. In clinical practice, impaired verbal memory could serve as a "red flag" for diminished consent capacity in persons with recent TBI.

  15. Brain injury in sports.

    Science.gov (United States)

    Lloyd, John; Conidi, Frank

    2016-03-01

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

  16. Platelet activation and dysfunction in a large-animal model of traumatic brain injury and hemorrhage

    DEFF Research Database (Denmark)

    Sillesen, Martin; Johansson, Pär I; Rasmussen, Lars S

    2013-01-01

    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...

  17. Thymoquinone Attenuates Brain Injury via an Anti-oxidative Pathway in a Status Epilepticus Rat Model.

    Science.gov (United States)

    Shao, Yi-Ye; Li, Bing; Huang, Yong-Mei; Luo, Qiong; Xie, Yang-Mei; Chen, Ying-Hui

    2017-01-01

    Status epilepticus (SE) results in the generation of reactive oxygen species (ROS), which contribute to seizure-induced brain injury. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE). Thymoquinone (TQ) is a bioactive monomer extracted from black cumin (Nigella sativa) seed oil that has anti-inflammatory, anti-cancer, and antioxidant activity in various diseases. This study evaluated the protective effects of TQ on brain injury in a lithium-pilocarpine rat model of SE and investigated the underlying mechanism related to antioxidative pathway. Electroencephalogram and Racine scale were used to value seizure severity. Passive-avoidance test was used to determine learning and memory function. Moreover, anti-oxidative activity of TQ was observed using Western blot and super oxide dismutase (SOD) activity assay. Latency to SE increased in the TQ-pretreated group compared with rats in the model group, while the total power was significantly lower. Seizure severity measured on the Racine scale was significantly lower in the TQ group compared with the model group. Results of behavioral experiments suggest that TQ may also have a protective effect on learning and memory function. Investigation of the protective mechanism of TQ showed that TQ-pretreatment significantly increased the expression of Nrf2, HO-1 proteins and SOD in the hippocampus. These findings showed that TQ attenuated brain injury induced by SE via an anti-oxidative pathway.

  18. Human Recombinant Factor VIIa is Neuroprotective in a Model of Traumatic Brain Injury and Secondary Hypoxemia

    National Research Council Canada - National Science Library

    Bauman, R. A; Long, J. B; Ketchum, L. H; Macdonald, V. W

    2004-01-01

    .... In the untraumatized brain, TF is physically isolated from FVII. However, traumatic brain injury (TBI) frequently results in the disruption of the vascular endothelium and resultant exposure of FVII to subendothelial TF...

  19. Effect of pharmacologic resuscitation on the brain gene expression profiles in a swine model of traumatic brain injury and hemorrhage

    DEFF Research Database (Denmark)

    Dekker, Simone E; Bambakidis, Ted; Sillesen, Martin

    2014-01-01

    BACKGROUND: We have previously shown that addition of valproic acid (VPA; a histone deacetylase inhibitor) to hetastarch (Hextend [HEX]) resuscitation significantly decreases lesion size in a swine model of traumatic brain injury (TBI) and hemorrhagic shock (HS). However, the precise mechanisms...... have not been well defined. As VPA is a transcriptional modulator, the aim of this study was to investigate its effect on brain gene expression profiles. METHODS: Swine were subjected to controlled TBI and HS (40% blood volume), kept in shock for 2 hours, and resuscitated with HEX or HEX + VPA (n = 5...... per group). Following 6 hours of observation, brain RNA was isolated, and gene expression profiles were measured using a Porcine Gene ST 1.1 microarray (Affymetrix, Santa Clara, CA). Pathway analysis was done using network analysis tools Gene Ontology, Ingenuity Pathway Analysis, and Parametric Gene...

  20. A model to guide the rehabilitation of high-functioning employees after mild brain injury.

    Science.gov (United States)

    Dodson, Matthew B

    2010-01-01

    Impairment in executive functioning can occur after mild stroke, mild Traumatic Brain Injury, and neurodegenerative disease, and this can have deleterious effects on employment outcomes, occupational functioning, and general quality of life. What is not as well identified is the symbiotic relationship between executive functioning and other important psychosocial constructs inherent in successful employees ("Employee Performance Enablers"), and how various aspects of the employment environment can enable or inhibit the success of the employee with executive functioning deficits in meeting their essential job functions ("Workplace Ecology"). From an extensive review of the literature and the author's practice experience, a clinical model was developed to elucidate these two critical variables, as well as to provide guidance for organizing, planning, and implementing interventions that will address both employee enablers and workplace ecology to affect positive return to work outcomes for individuals with mild brain injury.

  1. Radiation Injury to the Brain

    Science.gov (United States)

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

  2. Differential effects of fresh frozen plasma and normal saline on secondary brain damage in a large animal model of polytrauma, hemorrhage and traumatic brain injury

    DEFF Research Database (Denmark)

    Hwabejire, John O; Imam, Ayesha M; Jin, Guang

    2013-01-01

    We have previously shown that the extent of traumatic brain injury (TBI) in large animal models can be reduced with early infusion of fresh frozen plasma (FFP), but the precise mechanisms remain unclear. In this study, we investigated whether resuscitation with FFP or normal saline differed in th...... in their effects on cerebral metabolism and excitotoxic secondary brain injury in a model of polytrauma, TBI, and hemorrhagic shock....

  3. Brain Injury Association of America

    Science.gov (United States)

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

  4. Epidemiology of Mild Traumatic Brain Injury with Intracranial Hemorrhage: Focusing Predictive Models for Neurosurgical Intervention.

    Science.gov (United States)

    Orlando, Alessandro; Levy, A Stewart; Carrick, Matthew M; Tanner, Allen; Mains, Charles W; Bar-Or, David

    2017-11-01

    To outline differences in neurosurgical intervention (NI) rates between intracranial hemorrhage (ICH) types in mild traumatic brain injuries and help identify which ICH types are most likely to benefit from creation of predictive models for NI. A multicenter retrospective study of adult patients spanning 3 years at 4 U.S. trauma centers was performed. Patients were included if they presented with mild traumatic brain injury (Glasgow Coma Scale score 13-15) with head CT scan positive for ICH. Patients were excluded for skull fractures, "unspecified hemorrhage," or coagulopathy. Primary outcome was NI. Stepwise multivariable logistic regression models were built to analyze the independent association between ICH variables and outcome measures. The study comprised 1876 patients. NI rate was 6.7%. There was a significant difference in rate of NI by ICH type. Subdural hematomas had the highest rate of NI (15.5%) and accounted for 78% of all NIs. Isolated subarachnoid hemorrhages had the lowest, nonzero, NI rate (0.19%). Logistic regression models identified ICH type as the most influential independent variable when examining NI. A model predicting NI for isolated subarachnoid hemorrhages would require 26,928 patients, but a model predicting NI for isolated subdural hematomas would require only 328 patients. This study highlighted disparate NI rates among ICH types in patients with mild traumatic brain injury and identified mild, isolated subdural hematomas as most appropriate for construction of predictive NI models. Increased health care efficiency will be driven by accurate understanding of risk, which can come only from accurate predictive models. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. A Novel Preclinical Model of Moderate Primary Blast-Induced Traumatic Brain Injury.

    Science.gov (United States)

    Divani, Afshin A; Murphy, Amanda J; Meints, Joyce; Sadeghi-Bazargani, Homayoun; Nordberg, Jessica; Monga, Manoj; Low, Walter C; Bhatia, Prerana M; Beilman, Greg J; SantaCruz, Karen S

    2015-07-15

    Blast-induced traumatic brain injury (bTBI) is the "signature" injury of the recent Iraq and Afghanistan wars. Here, we present a novel method to induce bTBI using shock wave (SW) lithotripsy. Using a lithotripsy machine, Wistar rats (N = 70; 408.3 ± 93 g) received five SW pulses to the right side of the frontal cortex at 24 kV and a frequency of 60 Hz. Animals were then randomly divided into three study endpoints: 24 h (n = 25), 72 h (n = 19) and 168 h (n = 26). Neurological and behavioral assessments (Garcia's test, beam walking, Rotarod, and elevated plus maze) were performed at the baseline, and further assessments followed at 3, 6, 24, 72, and 168 h post-injury, if applicable. We performed digital subtraction angiography (DSA) to assess presence of cerebral vasospasm due to induced bTBI. Damage to brain tissue was assessed by an overall histological severity (OHS) score based on depth of injury, area of hemorrhage, and extent of axonal injury. Except for beam walking, OHS was significantly correlated with the other three outcome measures with at least one of their assessments during the first 6 h after the experiment. OHS manifested the highest absolute correlation coefficients with anxiety at the baseline and 6 h post-injury (r(baseline) = -0.75, r(6hrs) = 0.85; p<0.05). Median hemispheric differences for contrast peak values (obtained from DSA studies) for 24, 72, and 168 h endpoints were 3.45%, 3.05% and 0.2%, respectively, with statistically significant differences at 1 versus 7 d (p<0.05) and 3 versus 7 d (p<0.01). In this study, we successfully established a preclinical rat model of bTBI with characteristics similar to those observed in clinical cases. This new method may be useful for future investigations aimed at understanding bTBI pathophysiology.

  6. Ethnographic analysis of traumatic brain injury patients in the national Model Systems database.

    Science.gov (United States)

    Burnett, Derek M; Kolakowsky-Hayner, Stephanie A; Slater, Dan; Stringer, Anthony; Bushnik, Tamara; Zafonte, Ross; Cifu, David X

    2003-02-01

    To compare demographics, injury characteristics, therapy service and intensity, and outcome in minority versus nonminority patients with traumatic brain injury (TBI). Retrospective analysis. Twenty medical centers. Two thousand twenty patients (men, n=1,518; women, n=502; nonminority, n=1,168; minority, n=852) with TBI enrolled in the Traumatic Brain Injury Model Systems database. Not applicable. Age, gender, marital status, education, employment status, injury severity (based on Glasgow Coma Scale [GCS] admission score, length of posttraumatic amnesia, duration of unconsciousness), intensity (hours) of therapy rendered, rehabilitation length of stay (LOS), rehabilitation charges, discharge disposition, postinjury employment status, FIM instrument change scores, and FIM efficiency scores. Independent sample t tests were used to analyze continuous variables; chi-square analyses were used to evaluate categorical data. overall, minorities were found to be mostly young men who were single, unemployed, and less well educated, with a longer work week if employed when injured. motor vehicle crashes (MVCs) predominated as the cause of injury for both groups; however, minorities were more likely to sustain injury from acts of violence and auto-versus-pedestrian crashes. Minorities also had higher GCS scores on admission and shorter LOS. Rehabilitation services: significant differences were found in the types and intensity of rehabilitation services provided; these included physical therapy, occupational therapy, and speech-language pathology, but not psychology. Minority patients who sustain TBI generally tend to be young men with less social responsibility. Although MVCs predominate as the primary etiology, acts of violence and auto-versus-pedestrian incidents are more common in the minority population. Minorities tend to have higher GCS scores at admission. Also, the type and intensity of rehabilitation services provided differed significantly for the various

  7. Exploration of the molecular basis of blast injury in a biofidelic model of traumatic brain injury

    Science.gov (United States)

    Thielen, P.; Mehoke, T.; Gleason, J.; Iwaskiw, A.; Paulson, J.; Merkle, A.; Wester, B.; Dymond, J.

    2018-01-01

    Biological response to blast overpressure is complex and results in various and potentially non-concomitant acute and long-term deficits to exposed individuals. Clinical links between blast severity and injury outcomes remain elusive and have yet to be fully described, resulting in a critical inability to develop associated protection and mitigation strategies. Further, experimental models frequently fail to reproduce observed physiological phenomena and/or introduce artifacts that confound analysis and reproducibility. New models are required that employ consistent mechanical inputs, scale with biological analogs and known clinical data, and permit high-throughput examination of biological responses for a range of environmental and battlefield- relevant exposures. Here we describe a novel, biofidelic headform capable of integrating complex biological samples for blast exposure studies. We additionally demonstrate its utility in detecting acute transcriptional responses in the model organism Caenorhabditis elegans after exposure to blast overpressure. This approach enables correlation between mechanical exposure and biological outcome, permitting both the enhancement of existing surrogate and computational models and the high-throughput biofidelic testing of current and future protection systems.

  8. Parallel Human and Animal Models of Blast- and Concussion-Induced Tinnitus and Related Traumatic Brain Injury (TBI)

    Science.gov (United States)

    2014-01-01

    Andersson G (2009) The role of anxiety sensitivity and behavioral avoidance in tinnitus disability. IntJAudiol 48:295-299. Hiller W, Goebel G (1999...Parallel Human and Animal Models of Blast- and Concussion-Induced Tinnitus and Related Traumatic Brain Injury (TBI) PRINCIPAL INVESTIGATOR...Induced Tinnitus and Related Traumatic Brain Injury (TBI) 5b. GRANT NUMBER W81XWH-11-2-0031 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

  9. Brain temperature profiles during epidural cooling with the ChillerPad in a monkey model of traumatic brain injury.

    Science.gov (United States)

    King, Christopher; Robinson, Timothy; Dixon, C Edward; Rao, Gutti R; Larnard, Donald; Nemoto, C Edwin M

    2010-10-01

    Therapeutic hypothermia remains a promising treatment for patients with severe traumatic brain injury (TBI). Multiple animal studies have suggested that hypothermia is neuroprotective after TBI, but clinical trials have been inconclusive. Systemic hypothermia, the method used in almost all major clinical trials, is limited by the time to target temperature, the depth of hypothermia, and complications, problems that may be solved by selective brain cooling. We evaluated the effects on brain temperature of a cooling device called the ChillerPad,™ which is applied to the dura in a non-human primate TBI model using controlled cortical impact (CCI). The cortical surface was rapidly cooled to approximately 15°C and maintained at that level for 24 h, followed by rewarming over about 10 h. Brain temperatures fell to 34-35°C at a depth of 15 mm at the cortical gray/white matter interface, and to 28-32°C at 10 mm deep. Intracranial pressure was mildly elevated (8-12 mm Hg) after cooling and rewarming, likely due to TBI. Other physiological variables were unchanged. Cooling was rapidly diminished at points distant from the cooling pad. The ChillerPad may be useful for highly localized cooling of the brain in circumstances in which a craniotomy is clinically indicated. However, because of the delay required by the craniotomy, other methods that are more readily available for inducing hypothermia may be used as a bridge between the time of injury to placement of the ChillerPad.

  10. Microwave and magnetic (M2 proteomics of a mouse model of mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Teresa M. Evans

    2014-06-01

    Full Text Available Short-term increases in oxidative stress and decreases in motor function, including debilitating effects on balance and motor control, can occur following primary mild traumatic brain injuries (mTBI. However, the long-term effects on motor unit impairment and integrity as well as the molecular mechanisms underlying secondary injuries are poorly understood. We hypothesized that changes in central nervous system-specific protein (CSP expression might correlate to these long-term effects. To test our hypothesis, we longitudinally assessed a closed-skull mTBI mouse model, vs. sham control, at 1, 7, 30, and 120 days post-injury. Motor impairment was determined by rotarod and grip strength performance measures, while motor unit integrity was determined using electromyography. Relative protein expression was determined by microwave and magnetic (M2 proteomics of ipsilateral brain tissue, as previously described. Isoprostane measurements were performed to confirm a primary oxidative stress response. Decoding the relative expression of 476 ± 56 top-ranked proteins for each specimen revealed statistically significant changes in the expression of two well-known CSPs at 1, 7 and 30 days post-injury: P < 0.001 for myelin basic protein (MBP and p < 0.05 for myelin associated glycoprotein (MAG. This was confirmed by Western blot. Moreover, MAG, αII-spectrin (SPNA2 and neurofilament light (NEFL expression at 30 days post-injury were directly related to grip strength (p < 0.05. While higher-powered studies of larger cohorts merit further investigation, this study supports the proof-of-concept that M2 proteomics is a rapid method to quantify putative protein biomarkers and therapeutic targets of mTBI and suggests the feasibility of CSP expression correlations to long-term effects on motor impairment.

  11. Modeling community integration in workers with delayed recovery from mild traumatic brain injury

    DEFF Research Database (Denmark)

    Mollayeva, T.; Shapiro, C. M.; Mollayeva, S.

    2015-01-01

    Background: Delayed recovery in persons after mild traumatic brain injury (mTBI) is poorly understood. Community integration (CI) is endorsed by persons with neurological disorders as an important outcome. We aimed to describe CI and its associated factors in insured Ontario workers with delayed...... assessments, and insurers' referral files. Community Integration Questionnaire (CIQ) scores were compared using analysis of variance or Spearman's correlation tests. Stepwise multivariable linear regression models were used to evaluate the associations with CI. Results: Ninety-four workers with mTBI (45...

  12. Moderate Traumatic Brain Injury: Clinical Characteristics and a Prognostic Model of 12-Month Outcome.

    Science.gov (United States)

    Einarsen, Cathrine Elisabeth; van der Naalt, Joukje; Jacobs, Bram; Follestad, Turid; Moen, Kent Gøran; Vik, Anne; Håberg, Asta Kristine; Skandsen, Toril

    2018-03-31

    Patients with moderate traumatic brain injury (TBI) often are studied together with patients with severe TBI, even though the expected outcome of the former is better. Therefore, we aimed to describe patient characteristics and 12-month outcomes, and to develop a prognostic model based on admission data, specifically for patients with moderate TBI. Patients with Glasgow Coma Scale scores of 9-13 and age ≥16 years were prospectively enrolled in 2 level I trauma centers in Europe. Glasgow Outcome Scale Extended (GOSE) score was assessed at 12 months. A prognostic model predicting moderate disability or worse (GOSE score ≤6), as opposed to a good recovery, was fitted by penalized regression. Model performance was evaluated by area under the curve of the receiver operating characteristics curves. Of the 395 enrolled patients, 81% had intracranial lesions on head computed tomography, and 71% were admitted to an intensive care unit. At 12 months, 44% were moderately disabled or worse (GOSE score ≤6), whereas 8% were severely disabled and 6% died (GOSE score ≤4). Older age, lower Glasgow Coma Scale score, no day-of-injury alcohol intoxication, presence of a subdural hematoma, occurrence of hypoxia and/or hypotension, and preinjury disability were significant predictors of GOSE score ≤6 (area under the curve = 0.80). Patients with moderate TBI exhibit characteristics of significant brain injury. Although few patients died or experienced severe disability, 44% did not experience good recovery, indicating that follow-up is needed. The model is a first step in development of prognostic models for moderate TBI that are valid across centers. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. Estimating Memory Deterioration Rates Following Neurodegeneration and Traumatic Brain Injuries in a Hopfield Network Model

    Directory of Open Access Journals (Sweden)

    Melanie Weber

    2017-11-01

    Full Text Available Neurodegenerative diseases and traumatic brain injuries (TBI are among the main causes of cognitive dysfunction in humans. At a neuronal network level, they both extensively exhibit focal axonal swellings (FAS, which in turn, compromise the information encoded in spike trains and lead to potentially severe functional deficits. There are currently no satisfactory quantitative predictors of decline in memory-encoding neuronal networks based on the impact and statistics of FAS. Some of the challenges of this translational approach include our inability to access small scale injuries with non-invasive methods, the overall complexity of neuronal pathologies, and our limited knowledge of how networks process biological signals. The purpose of this computational study is three-fold: (i to extend Hopfield's model for associative memory to account for the effects of FAS, (ii to calibrate FAS parameters from biophysical observations of their statistical distribution and size, and (iii to systematically evaluate deterioration rates for different memory-recall tasks as a function of FAS injury. We calculate deterioration rates for a face-recognition task to account for highly correlated memories and also for a discrimination task of random, uncorrelated memories with a size at the capacity limit of the Hopfield network. While it is expected that the performance of any injured network should decrease with injury, our results link, for the first time, the memory recall ability to observed FAS statistics. This allows for plausible estimates of cognitive decline for different stages of brain disorders within neuronal networks, bridging experimental observations following neurodegeneration and TBI with compromised memory recall. The work lends new insights to help close the gap between theory and experiment on how biological signals are processed in damaged, high-dimensional functional networks, and towards positing new diagnostic tools to measure cognitive

  14. Estimating Memory Deterioration Rates Following Neurodegeneration and Traumatic Brain Injuries in a Hopfield Network Model

    Science.gov (United States)

    Weber, Melanie; Maia, Pedro D.; Kutz, J. Nathan

    2017-01-01

    Neurodegenerative diseases and traumatic brain injuries (TBI) are among the main causes of cognitive dysfunction in humans. At a neuronal network level, they both extensively exhibit focal axonal swellings (FAS), which in turn, compromise the information encoded in spike trains and lead to potentially severe functional deficits. There are currently no satisfactory quantitative predictors of decline in memory-encoding neuronal networks based on the impact and statistics of FAS. Some of the challenges of this translational approach include our inability to access small scale injuries with non-invasive methods, the overall complexity of neuronal pathologies, and our limited knowledge of how networks process biological signals. The purpose of this computational study is three-fold: (i) to extend Hopfield's model for associative memory to account for the effects of FAS, (ii) to calibrate FAS parameters from biophysical observations of their statistical distribution and size, and (iii) to systematically evaluate deterioration rates for different memory-recall tasks as a function of FAS injury. We calculate deterioration rates for a face-recognition task to account for highly correlated memories and also for a discrimination task of random, uncorrelated memories with a size at the capacity limit of the Hopfield network. While it is expected that the performance of any injured network should decrease with injury, our results link, for the first time, the memory recall ability to observed FAS statistics. This allows for plausible estimates of cognitive decline for different stages of brain disorders within neuronal networks, bridging experimental observations following neurodegeneration and TBI with compromised memory recall. The work lends new insights to help close the gap between theory and experiment on how biological signals are processed in damaged, high-dimensional functional networks, and towards positing new diagnostic tools to measure cognitive deficits. PMID

  15. Cerebral Vascular Injury in Traumatic Brain Injury.

    Science.gov (United States)

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

    2016-01-01

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

  16. Integrating Traumatic Brain Injury Model Systems Data into the Federal InteragencyTraumatic Brain Injury Research Informatics Systems

    Science.gov (United States)

    2017-12-01

    strongest psychometric properties (NSI) was found to be too long for inclusion in TBIMS follow-up. For these reasons, all CDEs were rejected as...Revised Date: Forms: Last Reviewed Date: Introduction: The National Institute on Disability , Independent Living, and Rehabilitation Research... disabled pre-injury 4.8% Unemployed 0.8% Other 0.3% Unknown 2.2% Missing This CDE variable differs from the current TBIMS Primary

  17. Computational modeling of blast wave interaction with a human body and assessment of traumatic brain injury

    Science.gov (United States)

    Tan, X. G.; Przekwas, A. J.; Gupta, R. K.

    2017-11-01

    The modeling of human body biomechanics resulting from blast exposure poses great challenges because of the complex geometry and the substantial material heterogeneity. We developed a detailed human body finite element model representing both the geometry and the materials realistically. The model includes the detailed head (face, skull, brain and spinal cord), the neck, the skeleton, air cavities (lungs) and the tissues. Hence, it can be used to properly model the stress wave propagation in the human body subjected to blast loading. The blast loading on the human was generated from a simulated C4 explosion. We used the highly scalable solvers in the multi-physics code CoBi for both the blast simulation and the human body biomechanics. The meshes generated for these simulations are of good quality so that relatively large time-step sizes can be used without resorting to artificial time scaling treatments. The coupled gas dynamics and biomechanics solutions were validated against the shock tube test data. The human body models were used to conduct parametric simulations to find the biomechanical response and the brain injury mechanism due to blasts impacting the human body. Under the same blast loading condition, we showed the importance of inclusion of the whole body.

  18. Electroacupuncture improves neurobehavioral function and brain injury in rat model of intracerebral hemorrhage.

    Science.gov (United States)

    Zhu, Yan; Deng, Li; Tang, Huajun; Gao, Xiaoqing; Wang, Youhua; Guo, Kan; Kong, Jiming; Yang, Chaoxian

    2017-05-01

    Acupuncture has been widely used as a treatment for stroke in China for a long time. Recently, studies have demonstrated that electroacupuncture (EA) can accelerate intracerebral hemorrhage (ICH)-induced angiogenesis in rats. In the present study, we investigated the effect of EA on neurobehavioral function and brain injury in ICH rats. ICH was induced by stereotactic injection of collagenase type I and heparin into the right caudate putamen. Adult ICH rats were randomly divided into the following three groups: model control group (MC), EA at non-acupoint points group (non-acupoint EA) and EA at Baihui and Dazhui acupoints group (EA). The neurobehavioral deficits of ICH rats were assessed by modified neurological severity score (mNSS) and gait analysis. The hemorrhage volume and glucose metabolism of hemorrhagic foci were detected by PET/CT. The expression levels of MBP, NSE and S100-B proteins in serum were tested by ELISA. The histopathological features were examined by haematoxylin-eosin (H&E) staining. Apoptosis-associated proteins in the perihematomal region were observed by immunohistochemistry. EA treatment significantly promoted the recovery of neurobehavioral function in ICH rats. Hemorrhage volume reduced in EA group at day 14 when compared with MC and non-acupoint EA groups. ELISA showed that the levels of MBP, NSE and S100-B in serum were all down-regulated by EA treatment. The brain tissue of ICH rat in the EA group was more intact and compact than that in the MC and non-acupoint groups. In the perihematomal regions, the expression of Bcl-2 protein increased and expressions of Caspase-3 and Bax proteins decreased in the EA group vs MC and non-acupoint EA groups. Our data suggest that EA treatment can improve neurobehavioral function and brain injury, which were likely connected with the absorption of hematoma and regulation of apoptosis-related proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Modeling cognitive deficits following neurodegenerative diseases and traumatic brain injuries with deep convolutional neural networks.

    Science.gov (United States)

    Lusch, Bethany; Weholt, Jake; Maia, Pedro D; Kutz, J Nathan

    2018-06-01

    The accurate diagnosis and assessment of neurodegenerative disease and traumatic brain injuries (TBI) remain open challenges. Both cause cognitive and functional deficits due to focal axonal swellings (FAS), but it is difficult to deliver a prognosis due to our limited ability to assess damaged neurons at a cellular level in vivo. We simulate the effects of neurodegenerative disease and TBI using convolutional neural networks (CNNs) as our model of cognition. We utilize biophysically relevant statistical data on FAS to damage the connections in CNNs in a functionally relevant way. We incorporate energy constraints on the brain by pruning the CNNs to be less over-engineered. Qualitatively, we demonstrate that damage leads to human-like mistakes. Our experiments also provide quantitative assessments of how accuracy is affected by various types and levels of damage. The deficit resulting from a fixed amount of damage greatly depends on which connections are randomly injured, providing intuition for why it is difficult to predict impairments. There is a large degree of subjectivity when it comes to interpreting cognitive deficits from complex systems such as the human brain. However, we provide important insight and a quantitative framework for disorders in which FAS are implicated. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. HMGB1 a-Box Reverses Brain Edema and Deterioration of Neurological Function in a Traumatic Brain Injury Mouse Model

    Directory of Open Access Journals (Sweden)

    Lijun Yang

    2018-05-01

    Full Text Available Background/Aims: Traumatic brain injury (TBI is a complex neurological injury in young adults lacking effective treatment. Emerging evidences suggest that inflammation contributes to the secondary brain injury following TBI, including breakdown of the blood brain barrier (BBB, subsequent edema and neurological deterioration. High mobility group box-1 (HMGB1 has been identified as a key cytokine in the inflammation reaction following TBI. Here, we investigated the therapeutic efficacy of HMGB1 A-box fragment, an antagonist competing with full-length HMGB1 for receptor binding, against TBI. Methods: TBI was induced by controlled cortical impact (CCI in adult male mice. HMGB1 A-box fragment was given intravenously at 2 mg/kg/day for 3 days after CCI. HMGB1 A-box-treated CCI mice were compared with saline-treated CCI mice and sham mice in terms of BBB disruption evaluated by Evan’s blue extravasation, brain edema by brain water content, cell death by propidium iodide staining, inflammation by Western blot and ELISA assay for cytokine productions, as well as neurological functions by the modified Neurological Severity Score, wire grip and beam walking tests. Results: HMGB1 A-box reversed brain damages in the mice following TBI. It significantly reduced brain edema by protecting integrity of the BBB, ameliorated cell degeneration, and decreased expression of pro-inflammatory cytokines released in injured brain after TBI. These cellular and molecular effects were accompanied by improved behavioral performance in TBI mice. Notably, HMGB1 A-box blocked IL-1β-induced HMGB1 release, and preferentially attenuated TLR4, Myd88 and P65 in astrocyte cultures. Conclusion: Our data suggest that HMGB1 is involved in CCI-induced TBI, which can be inhibited by HMGB1 A-box fragment. Therefore, HMGB1 A-box fragment may have therapeutic potential for the secondary brain damages in TBI.

  1. HMGB1 a-Box Reverses Brain Edema and Deterioration of Neurological Function in a Traumatic Brain Injury Mouse Model.

    Science.gov (United States)

    Yang, Lijun; Wang, Feng; Yang, Liang; Yuan, Yunchao; Chen, Yan; Zhang, Gengshen; Fan, Zhenzeng

    2018-01-01

    Traumatic brain injury (TBI) is a complex neurological injury in young adults lacking effective treatment. Emerging evidences suggest that inflammation contributes to the secondary brain injury following TBI, including breakdown of the blood brain barrier (BBB), subsequent edema and neurological deterioration. High mobility group box-1 (HMGB1) has been identified as a key cytokine in the inflammation reaction following TBI. Here, we investigated the therapeutic efficacy of HMGB1 A-box fragment, an antagonist competing with full-length HMGB1 for receptor binding, against TBI. TBI was induced by controlled cortical impact (CCI) in adult male mice. HMGB1 A-box fragment was given intravenously at 2 mg/kg/day for 3 days after CCI. HMGB1 A-box-treated CCI mice were compared with saline-treated CCI mice and sham mice in terms of BBB disruption evaluated by Evan's blue extravasation, brain edema by brain water content, cell death by propidium iodide staining, inflammation by Western blot and ELISA assay for cytokine productions, as well as neurological functions by the modified Neurological Severity Score, wire grip and beam walking tests. HMGB1 A-box reversed brain damages in the mice following TBI. It significantly reduced brain edema by protecting integrity of the BBB, ameliorated cell degeneration, and decreased expression of pro-inflammatory cytokines released in injured brain after TBI. These cellular and molecular effects were accompanied by improved behavioral performance in TBI mice. Notably, HMGB1 A-box blocked IL-1β-induced HMGB1 release, and preferentially attenuated TLR4, Myd88 and P65 in astrocyte cultures. Our data suggest that HMGB1 is involved in CCI-induced TBI, which can be inhibited by HMGB1 A-box fragment. Therefore, HMGB1 A-box fragment may have therapeutic potential for the secondary brain damages in TBI. © 2018 The Author(s). Published by S. Karger AG, Basel.

  2. Neuroprotective effect of hyperbaric oxygen therapy in a juvenile rat model of repetitive mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Lei Huang

    2016-01-01

    Full Text Available Repetitive mild traumatic brain injury (rmTBI is an important medical concern for adolescent athletes that can lead to long-term disabilities. Multiple mild injuries may exacerbate tissue damage resulting in cumulative brain injury and poor functional recovery. In the present study, we investigated the increased brain vulnerability to rmTBI and the effect of hyperbaric oxygen treatment using a juvenile rat model of rmTBI. Two episodes of mild cortical controlled impact (3 days apart were induced in juvenile rats. Hyperbaric oxygen (HBO was applied 1 hour/day × 3 days at 2 atmosphere absolute consecutively, starting at 1 day after initial mild traumatic brain injury (mTBI. Neuropathology was assessed by multi-modal magnetic resonance imaging (MRI and tissue immunohistochemistry. After repetitive mTBI, there were increases in T2-weighted imaging-defined cortical lesions and susceptibility weighted imaging-defined cortical microhemorrhages, correlated with brain tissue gliosis at the site of impact. HBO treatment significantly decreased the MRI-identified abnormalities and tissue histopathology. Our findings suggest that HBO treatment improves the cumulative tissue damage in juvenile brain following rmTBI. Such therapy regimens could be considered in adolescent athletes at the risk of repeated concussions exposures.

  3. Evaluation after Traumatic Brain Injury

    Science.gov (United States)

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

    2010-01-01

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

  4. Early treatment with lyophilized plasma protects the brain in a large animal model of combined traumatic brain injury and hemorrhagic shock

    DEFF Research Database (Denmark)

    Imam, Ayesha M; Jin, Guang; Sillesen, Martin

    2013-01-01

    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...... as the associated edema. However, FFP is a perishable product that is not well suited for use in the austere prehospital settings. In this study, we tested whether a shelf-stable, low-volume, lyophilized plasma (LSP) product was as effective as FFP.......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...

  5. Systemic Inflammatory Effects of Traumatic Brain Injury, Femur Fracture, and Shock: An Experimental Murine Polytrauma Model

    Directory of Open Access Journals (Sweden)

    C. Probst

    2012-01-01

    Full Text Available Objective. Despite broad research in neurotrauma and shock, little is known on systemic inflammatory effects of the clinically most relevant combined polytrauma. Experimental investigation in an animal model may provide relevant insight for therapeutic strategies. We describe the effects of a combined injury with respect to lymphocyte population and cytokine activation. Methods. 45 male C57BL/6J mice (mean weight 27 g were anesthetized with ketamine/xylazine. Animals were subjected to a weight drop closed traumatic brain injury (WD-TBI, a femoral fracture and hemorrhagic shock (FX-SH. Animals were subdivided into WD-TBI, FX-SH and combined trauma (CO-TX groups. Subjects were sacrificed at 96 h. Blood was analysed for cytokines and by flow cytometry for lymphocyte populations. Results. Mortality was 8%, 13% and 47% for FX-SH, WD-TBI and CO-TX groups (P<0.05. TNFα (11/13/139 for FX-SH/WD-TBI/CO-TX; P<0.05, CCL2 (78/96/227; P<0.05 and IL-6 (16/48/281; P=0.05 showed significant increases in the CO-TX group. Lymphocyte populations results for FX-SH, WD-TBI and CO-TX were: CD-4 (31/21/22; P= n.s., CD-8 (7/28/34, P<0.05, CD-4-CD-8 (11/12/18; P= n.s., CD-56 (36/7/8; P<0.05. Conclusion. This study shows that a combination of closed TBI and femur-fracture/ shock results in an increase of the humoral inflammation. More attention to combined injury models in inflammation research is indicated.

  6. Fingolimod against endotoxin-induced fetal brain injury in a rat model.

    Science.gov (United States)

    Yavuz, And; Sezik, Mekin; Ozmen, Ozlem; Asci, Halil

    2017-11-01

    Fingolimod is a sphingosine-1-phosphate receptor modulator used for multiple sclerosis treatment and acts on cellular processes such as apoptosis, endothelial permeability, and inflammation. We hypothesized that fingolimod has a positive effect on alleviating preterm fetal brain injury. Sixteen pregnant rats were divided into four groups of four rats each. On gestational day 17, i.p. endotoxin was injected to induce fetal brain injury, followed by i.p. fingolimod (4 mg/kg maternal weight). Hysterotomy for preterm delivery was performed 6 h after fingolimod. The study groups included (i) vehicle controls (i.p. normal saline only); (ii) positive controls (endotoxin plus saline); (iii) saline plus fingolimod; and (iv) endotoxin plus fingolimod treatment. Brain tissues of the pups were dissected for evaluation of interleukin (IL)-6, caspase-3, and S100β on immunohistochemistry. Maternal fingolimod treatment attenuated endotoxin-related fetal brain injury and led to lower immunoreactions for IL-6, caspase-3, and S100β compared with endotoxin controls (P < 0.0001 for all comparisons). Antenatal maternal fingolimod therapy had fetal neuroprotective effects by alleviating preterm birth-related fetal brain injury with inhibitory effects on inflammation and apoptosis. © 2017 Japan Society of Obstetrics and Gynecology.

  7. Phenoxybenzamine Is Neuroprotective in a Rat Model of Severe Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Thomas F. Rau

    2014-01-01

    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.

  8. 77 FR 13578 - Disability and Rehabilitation Research Project; Traumatic Brain Injury Model Systems Centers

    Science.gov (United States)

    2012-03-07

    ... medical care, those seen only in private doctors' offices, or those treated in military or veteran health... Veterans Brain Injury Center, 2011b). Common disabilities resulting from TBI include problems with cognition, sensory processing, communication, and behavioral or mental health; and some TBI survivors...

  9. Impact of parental acquired brain injury on children: Review of the literature and conceptual model.

    Science.gov (United States)

    Tiar, Anna Maria Vitale; Dumas, Jean E

    2015-01-01

    Data on children's adjustment following parental acquired brain injury (ABI) are disparate and spare, and appear inconclusive. Nonetheless, they suggest that children's well-being is at risk, but often neglected. Indeed, lack of a unifying conceptual model makes it difficult to integrate available evidence, in order to circumscribe relevant factors and understand how these may influence children's outcomes in more or less favourable ways. The present review proposes the coping competence model as a theoretical framework apt to clarify these issues and organize the available evidence. In brief, the model states that impact of parental ABI on children reflects the extent of the challenges children face and their preponderant ways of coping with them, i.e. pro-socially, anti-socially or asocially. Evidence shows that children deal with some common socioaffective as well as achievement challenges. Further, it is consistent with the three main coping modalities supported by the model. Overall, children's outcomes appear variable, but clearly at risk and in need of special attention. This review summarizes these outcomes, raises conceptual as well as methodological questions to be addressed in future research and eventually presents relevant issues for support and clinical services.

  10. Docosahexaenoic Acid (DHA) Provides Neuroprotection in Traumatic Brain Injury Models via Activating Nrf2-ARE Signaling.

    Science.gov (United States)

    Zhu, Wei; Ding, Yuexia; Kong, Wei; Li, Tuo; Chen, Hongguang

    2018-04-16

    In this study, we explored the neuroprotective effects of docosahexaenoic acid (DHA) in traumatic brain injury (TBI) models. In this study, we first confirmed that DHA was neuroprotective against TBI via the NSS test and Morris water maze experiment. Western blot was conducted to identify the expression of Bax, caspase-3, and Bcl-2. And the cell apoptosis of the TBI models was validated by TUNEL staining. Relationships between nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) pathway-related genes and DHA were explored by RT-PCR and Western blot. Rats of the DHA group performed remarkably better than those of the TBI group in both NSS test and water maze experiment. DHA conspicuously promoted the expression of Bcl-2 and diminished that of cleaved caspase-3 and Bax, indicating the anti-apoptotic role of DHA. Superoxide dismutase (SOD) activity and cortical malondialdehyde content, glutathione peroxidase (GPx) activity were renovated in rats receiving DHA treatment, implying that the neuroprotective influence of DHA was derived from lightening the oxidative stress caused by TBI. Moreover, immunofluorescence and Western blot experiments revealed that DHA facilitated the translocation of Nrf2 to the nucleus. DHA administration also notably increased the expression of the downstream factors NAD(P)H:quinone oxidoreductase (NQO-1) and heme oxygenase 1(HO-1). DHA exerted neuroprotective influence on the TBI models, potentially through activating the Nrf2- ARE pathway.

  11. A Conceptual Model of Irritability Following Traumatic Brain Injury: A Qualitative, Participatory Research Study.

    Science.gov (United States)

    Hammond, Flora M; Davis, Christine; Cook, James R; Philbrick, Peggy; Hirsch, Mark A

    2016-01-01

    Individuals with a history of traumatic brain injury (TBI) may have chronic problems with irritability, which can negatively affect their lives. (1) To describe the experience (thoughts and feelings) of irritability from the perspectives of multiple people living with or affected by the problem, and (2) to develop a conceptual model of irritability. Qualitative, participatory research. Forty-four stakeholders (individuals with a history of TBI, family members, community professionals, healthcare providers, and researchers) divided into 5 focus groups. Each group met 10 times to discuss the experience of irritability following TBI. Data were coded using grounded theory to develop themes, metacodes, and theories. Not applicable. A conceptual model emerged in which irritability has 5 dimensions: affective (related to moods and feelings); behavioral (especially in areas of self-regulation, impulse control, and time management); cognitive-perceptual (self-talk and ways of seeing the world); relational issues (interpersonal and family dynamics); and environmental (including environmental stimuli, change, disruptions in routine, and cultural expectations). This multidimensional model provides a framework for assessment, treatment, and future research aimed at better understanding irritability, as well as the development of assessment tools and treatment interventions.

  12. Traumatic Brain Injury Registry (TBI)

    Data.gov (United States)

    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...

  13. Prospective memory after moderate-to-severe traumatic brain injury: a multinomial modeling approach.

    Science.gov (United States)

    Pavawalla, Shital P; Schmitter-Edgecombe, Maureen; Smith, Rebekah E

    2012-01-01

    Prospective memory (PM), which can be understood as the processes involved in realizing a delayed intention, is consistently found to be impaired after a traumatic brain injury (TBI). Although PM can be empirically dissociated from retrospective memory, it inherently involves both a prospective component (i.e., remembering that an action needs to be carried out) and retrospective components (i.e., remembering what action needs to be executed and when). This study utilized a multinomial processing tree model to disentangle the prospective (that) and retrospective recognition (when) components underlying PM after moderate-to-severe TBI. Seventeen participants with moderate to severe TBI and 17 age- and education-matched control participants completed an event-based PM task that was embedded within an ongoing computer-based color-matching task. The multinomial processing tree modeling approach revealed a significant group difference in the prospective component, indicating that the control participants allocated greater preparatory attentional resources to the PM task compared to the TBI participants. Participants in the TBI group were also found to be significantly more impaired than controls in the when aspect of the retrospective component. These findings indicated that the TBI participants had greater difficulty allocating the necessary preparatory attentional resources to the PM task and greater difficulty discriminating between PM targets and nontargets during task execution, despite demonstrating intact posttest recall and/or recognition of the PM tasks and targets.

  14. A pilot study on the operationalization of the Model of Occupational Self Efficacy: A model for the reintegration of persons with brain injuries to their worker roles.

    Science.gov (United States)

    Soeker, Shaheed

    2015-01-01

    Traumatic brain injury causes functional limitations that can cause people to struggle to reintegrate in the workplace despite participating in work rehabilitation programmes. The aim of the study was to explore, and describe the experiences of individuals with Traumatic Brain Injury regarding returning to work through the use of the model of occupational self-efficacy. In the study 10 individuals who were diagnosed with a mild to moderate brain injury participated in the study. The research study was positioned within the qualitative paradigm specifically utilizing case study methodology. In order to gather data from the participants, individual interviews and participant observation techniques were used. Two themes emerged from the findings of the study theme one reflected the barriers related to the use of the model (i.e. Theme one: Effective participation in the model is affected by financial assistance). The second theme related to the enabling factors related to the use of the model (i.e. Theme two: A sense of normality). The findings of this study indicated that the Model of Occupational Self Efficacy (MOS) is a useful model to use in retraining the work skills of individual's who sustained a traumatic brain injury. The participants in this study could maintain employment in the open labour market for a period of at least 12 months and it improved their ability to accept their brain injury as well as adapt to their worker roles. The MOS also provides a framework for facilitating community integration.

  15. A rat model of smoke inhalation injury: Influence of combustion smoke on gene expression in the brain

    International Nuclear Information System (INIS)

    Lee, Heung M.; Greeley, George H.; Herndon, David N.; Sinha, Mala; Luxon, Bruce A.; Englander, Ella W.

    2005-01-01

    Acute smoke inhalation causes death and injury in victims of home and industrial fires as well as victims of combat situations. The lethal factors in combustion smoke inhalation are toxic gases and oxygen deficiency, with carbon monoxide (CO) as a primary cause of death. In survivors, inhalation of smoke can result in severe immediate and delayed neuropathologies. To gain insight into the progression of molecular events contributing to smoke inhalation sequelae in the brain, we developed a smoke inhalation rat model and conducted a genome-wide analysis of gene expression. Microarray analysis revealed a modified brain transcriptome with changes peaking at 24 h and subsiding within 7 days post-smoke. Overall, smoke inhalation downregulated genes associated with synaptic function, neurotransmission, and neurotrophic support, and upregulated genes associated with stress responses, including nitric oxide synthesis, antioxidant defenses, proteolysis, inflammatory response, and glial activation. Notably, among the affected genes, many have been previously implicated in other types of brain injury, demonstrating the usefulness of microarrays for analysis of changes in gene expression in complex insults. In accord with previously described modulations of nitric oxide homeostasis in CO poisoning, microarray analysis revealed increased brain expression of nitric oxide synthase (NOS) and NOS ligand after inhalation of smoke. Furthermore, immunostaining showed significant elevations in perivascular NOS and in protein nitration, corroborating the involvement of nitric oxide perturbations in post-smoke sequelae in the brain. Thus, the new rat model, in combination with microarray analyses, affords insight into the complex molecular pathophysiology of smoke inhalation in the brain

  16. Intranasal insulin treatment of an experimental model of moderate traumatic brain injury.

    Science.gov (United States)

    Brabazon, Fiona; Wilson, Colin M; Jaiswal, Shalini; Reed, John; Frey, William H; Byrnes, Kimberly R

    2017-09-01

    Traumatic brain injury (TBI) results in learning and memory dysfunction. Cognitive deficits result from cellular and metabolic dysfunction after injury, including decreased cerebral glucose uptake and inflammation. This study assessed the ability of intranasal insulin to increase cerebral glucose uptake after injury, reduce lesion volume, improve memory and learning function and reduce inflammation. Adult male rats received a controlled cortical impact (CCI) injury followed by intranasal insulin or saline treatment daily for 14 days. PET imaging of [18F]-FDG uptake was performed at baseline and at 48 h and 10 days post-injury and MRI on days three and nine post injury. Motor function was tested with the beam walking test. Memory function was assessed with Morris water maze. Intranasal insulin after CCI significantly improved several outcomes compared to saline. Insulin-treated animals performed better on beam walk and demonstrated significantly improved memory. A significant increase in [18F]-FDG uptake was observed in the hippocampus. Intranasal insulin also resulted in a significant decrease in hippocampus lesion volume and significantly less microglial immunolabeling in the hippocampus. These data show that intranasal insulin improves memory, increases cerebral glucose uptake and decreases neuroinflammation and hippocampal lesion volume, and may therefore be a viable therapy for TBI.

  17. Using personality traits to construct linear growth models of mental health in family members of individuals with severe brain injury.

    Science.gov (United States)

    Trujillo, Michael; Perrin, Paul B; Doser, Karoline; Norup, Anne

    2016-11-01

    No studies have examined the impact of personality traits on mental health among caregivers of individuals with severe brain injury. Therefore, the purpose of the current study was to construct linear growth models to examine whether the personality traits of family members of individuals with severe brain injury could predict the trajectories of their own mental health-related quality of life (HRQoL), anxiety, and depression beginning in a neurointensive care unit through 1 year after injury. Danish family members of individuals with severe brain injury (n = 52) completed the Short Form-36 assessing mental HRQoL (vitality, social functioning, role limitations-emotional, mental health), anxiety, and depression across 5 time points during the 1st year after injury. The measure of personality was administered 3 months after the patients' discharge. All mental HRQoL, anxiety, and depression variables improved significantly over time. Caregivers who were less neurotic and less conscientious had higher vitality, social functioning, and mental health over time, whereas caregivers who were more agreeable had higher social functioning over time. Caregivers with lower neuroticism had lower anxiety and depression over time, as well as a more accelerated decrease in anxiety and depression. Caregivers' personality traits were strongly associated over time with mental HRQoL, anxiety, and depression, with neuroticism being especially important for trajectories of anxiety and depression. These results suggest that personality assessments for caregivers of individuals with severe brain injury could help identify those most at risk for poor mental health over the course of rehabilitation. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  18. Traumatic Brain Injury Inpatient Rehabilitation

    Science.gov (United States)

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

    2010-01-01

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

  19. Establishment of an ideal time window model in hypothermic-targeted temperature management after traumatic brain injury in rats.

    Science.gov (United States)

    Zhao, Wan-Yong; Chen, Shao-Bo; Wang, Jing-Jing; Xu, Chao; Zhao, Ming-Liang; Dong, Hua-Jiang; Liang, Hai-Qian; Li, Xiao-Hong; Tu, Yue; Zhang, Sai; Chen, Chong; Sun, Hong-Tao

    2017-08-15

    Although hypothermic-targeted temperature management (HTTM) holds great potential for the treatment of traumatic brain injury (TBI), translation of the efficacy of hypothermia from animal models to TBI patientshas no entire consistency. This study aimed to find an ideal time window model in experimental rats which was more in accordance with clinical practice through the delayed HTTM intervention. Sprague-Dawley rats were subjected to unilateral cortical contusion injury and received therapeutic hypothermia at 15mins, 2 h, 4 h respectively after TBI. The neurological function was evaluated with the modified neurological severity score and Morris water maze test. The brain edema and morphological changes were measured with the water content and H&E staining. Brain sections were immunostained with antibodies against DCX (a neuroblast marker) and GFAP (an astrocyte marker). The apoptosis levels in the ipsilateral hippocampi and cortex were examined with antibodies against the apoptotic proteins Bcl-2, Bax, and cleaved caspase-3 by the immunofluorescence and western blotting. The results indicated that each hypothermia therapy group could improve neurobehavioral and cognitive function, alleviate brain edema and reduce inflammation. Furthermore, we observed that therapeutic hypothermia increased DCX expression, decreased GFAP expression, upregulated Bcl-2 expression and downregulated Bax and cleaved Caspase-3 expression. The above results suggested that HTTM at 2h or even at 4h post-injury revealed beneficial brain protection similarly, despite the best effect at 15min post-injury. These findings may provide relatively ideal time window models, further making the following experimental results more credible and persuasive. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Mechanisms of dendritic spine remodeling in a rat model of traumatic brain injury.

    Science.gov (United States)

    Campbell, John N; Low, Brian; Kurz, Jonathan E; Patel, Sagar S; Young, Matt T; Churn, Severn B

    2012-01-20

    Traumatic brain injury (TBI), a leading cause of death and disability in the United States, causes potentially preventable damage in part through the dysregulation of neural calcium levels. Calcium dysregulation could affect the activity of the calcium-sensitive phosphatase calcineurin (CaN), with serious implications for neural function. The present study used both an in vitro enzymatic assay and Western blot analyses to characterize the effects of lateral fluid percussion injury on CaN activity and CaN-dependent signaling in the rat forebrain. TBI resulted in an acute alteration of CaN phosphatase activity and long-lasting alterations of its downstream effector, cofilin, an actin-depolymerizing protein. These changes occurred bilaterally in the neocortex and hippocampus, appeared to persist for hours after injury, and coincided with synapse degeneration, as suggested by a loss of the excitatory post-synaptic protein PSD-95. Interestingly, the effect of TBI on cofilin in some brain regions was blocked by a single bolus of the CaN inhibitor FK506, given 1 h post-TBI. Overall, these findings suggest a loss of synapse stability in both hemispheres of the laterally-injured brain, and offer evidence for region-specific, CaN-dependent mechanisms.

  1. Substance Use and Mild Traumatic Brain Injury Risk Reduction and Prevention: A Novel Model for Treatment

    Directory of Open Access Journals (Sweden)

    Jennifer H. Olson-Madden

    2012-01-01

    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.

  2. Modelling Ecological Cognitive Rehabilitation Therapies for Building Virtual Environments in Brain Injury.

    Science.gov (United States)

    Martínez-Moreno, J M; Sánchez-González, P; Luna, M; Roig, T; Tormos, J M; Gómez, E J

    2016-01-01

    Brain Injury (BI) has become one of the most common causes of neurological disability in developed countries. Cognitive disorders result in a loss of independence and patients' quality of life. Cognitive rehabilitation aims to promote patients' skills to achieve their highest degree of personal autonomy. New technologies such as virtual reality or interactive video allow developing rehabilitation therapies based on reproducible Activities of Daily Living (ADLs), increasing the ecological validity of the therapy. However, the lack of frameworks to formalize and represent the definition of this kind of therapies can be a barrier for widespread use of interactive virtual environments in clinical routine. To provide neuropsychologists with a methodology and an instrument to design and evaluate cognitive rehabilitation therapeutic interventions strategies based on ADLs performed in interactive virtual environments. The proposed methodology is used to model therapeutic interventions during virtual ADLs considering cognitive deficit, expected abnormal interactions and therapeutic hypotheses. It allows identifying abnormal behavioural patterns and designing interventions strategies in order to achieve errorless-based rehabilitation. An ADL case study ('buying bread') is defined according to the guidelines established by the ADL intervention model. This case study is developed, as a proof of principle, using interactive video technology and is used to assess the feasibility of the proposed methodology in the definition of therapeutic intervention procedures. The proposed methodology provides neuropsychologists with an instrument to design and evaluate ADL-based therapeutic intervention strategies, attending to solve actual limitation of virtual scenarios, to be use for ecological rehabilitation of cognitive deficit in daily clinical practice. The developed case study proves the potential of the methodology to design therapeutic interventions strategies; however our current

  3. The Effects of Chunghyul-Dan, an Agent of Korean Medicine, on a Mouse Model of Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Won-Woo Choi

    2017-01-01

    Full Text Available Chunghyul-Dan (CHD is the first choice agent for the prevention and treatment of stroke at the Kyung Hee Medical Hospital. To date, CHD has been reported to have beneficial effects on brain disease in animals and humans, along with antioxidative and anti-inflammatory effects. The aim of this study was to evaluate the pharmacological effects of CHD on a traumatic brain injury (TBI mouse model to explore the possibility of CHD use in patients with TBI. The TBI mouse model was induced using the controlled cortical impact method. CHD was orally administered twice a day for 5 d after TBI induction; mice were assessed for brain damage, brain edema, blood-brain barrier (BBB damage, motor deficits, and cognitive impairment. Treatment with CHD reduced brain damage seen on histological examination and improved motor and cognitive functions. However, CHD did not reduce brain edema and BBB damage. In conclusion, CHD could be a candidate agent in the treatment of patients with TBI. Further studies are needed to assess the exact mechanisms of the effects during the acute-subacute phase and pharmacological activity during the chronic-convalescent phase of TBI.

  4. Hypopituitarism after acute brain injury.

    Science.gov (United States)

    Urban, Randall J

    2006-07-01

    Acute brain injury has many causes, but the most common is trauma. There are 1.5-2.0 million traumatic brain injuries (TBI) in the United States yearly, with an associated cost exceeding 10 billion dollars. TBI is the most common cause of death and disability in young adults less than 35 years of age. The consequences of TBI can be severe, including disability in motor function, speech, cognition, and psychosocial and emotional skills. Recently, clinical studies have documented the occurrence of pituitary dysfunction after TBI and another cause of acute brain injury, subarachnoid hemorrhage (SAH). These studies have consistently demonstrated a 30-40% occurrence of pituitary dysfunction involving at least one anterior pituitary hormone following a moderate to severe TBI or SAH. Growth hormone (GH) deficiency is the most common pituitary hormone disorder, occurring in approximately 20% of patients when multiple tests of GH deficiency are used. Within 7-21 days of acute brain injury, adrenal insufficiency is the primary concern. Pituitary function can fluctuate over the first year after TBI, but it is well established by 1 year. Studies are ongoing to assess the effects of hormone replacement on motor function and cognition in TBI patients. Any subject with a moderate to severe acute brain injury should be screened for pituitary dysfunction.

  5. Factors affecting increased risk for substance use disorders following traumatic brain injury: What we can learn from animal models.

    Science.gov (United States)

    Merkel, Steven F; Cannella, Lee Anne; Razmpour, Roshanak; Lutton, Evan; Raghupathi, Ramesh; Rawls, Scott M; Ramirez, Servio H

    2017-06-01

    Recent studies have helped identify multiple factors affecting increased risk for substance use disorders (SUDs) following traumatic brain injury (TBI). These factors include age at the time of injury, repetitive injury and TBI severity, neurocircuits, neurotransmitter systems, neuroinflammation, and sex differences. This review will address each of these factors by discussing 1) the clinical and preclinical data identifying patient populations at greatest risk for SUDs post-TBI, 2) TBI-related neuropathology in discrete brain regions heavily implicated in SUDs, and 3) the effects of TBI on molecular mechanisms that may drive substance abuse behavior, like dopaminergic and glutamatergic transmission or neuroimmune signaling in mesolimbic regions of the brain. Although these studies have laid the groundwork for identifying factors that affect risk of SUDs post-TBI, additional studies are required. Notably, preclinical models have been shown to recapitulate many of the behavioral, cellular, and neurochemical features of SUDs and TBI. Therefore, these models are well suited for answering important questions that remain in future investigations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Missile injuries of the brain

    International Nuclear Information System (INIS)

    Kazmi, S.A.M.; Ashraf, A.T.; Qureshi, N.A.

    2001-01-01

    Data was analyzed relating to a consecutive series of 16 patients of penetrating brain injuries received at forward defense lines. Characteristics studied were the cause of injury, level of consciousness and various neurological deficits presented on initial examination, CT scan findings, the surgical procedures performed and the final outcome after one year of follow-up. One out of 16 patients, died due to severe associated injuries to abdominal viscera and major vessels. Meningitis occurred in one patient during the immediate postoperative period. All patients with motor weakness speech deficits and incontinence showed significant improvement. Hearing loss of one ear persisted in one patient. Two patients developed delayed onset seizures. It is concluded that, patients with penetrating brain injuries should be evacuated to the tertiary care neurosurgical centres as soon as possible. In operation only obviously necrotic brain and easily accessible metal and bone pieces should be removed. There is no need to explore the normal brain as it would only result in increased neurological deficits. The patients with such injuries should receive broad-spectrum antibiotics to prevent the infective complications. (author)

  7. Driving, brain injury and assistive technology.

    Science.gov (United States)

    Lane, Amy K; Benoit, Dana

    2011-01-01

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

  8. Perspectives on creating clinically relevant blast models for mild traumatic brain injury and post traumatic stress disorder symptoms

    Directory of Open Access Journals (Sweden)

    Lisa eBrenner

    2012-03-01

    Full Text Available Military personnel are returning from Iraq and Afghanistan and reporting non-specific physical (somatic, behavioral, psychological, and cognitive symptoms. Many of these symptoms are frequently associated with mild traumatic brain injury (mTBI and/or post traumatic stress disorder (PTSD. Despite significant attention and advances in assessment and intervention for these two conditions, challenges persist. To address this, clinically relevant blast models are essential in the full characterization of this type of injury, as well as in the testing and identification of potential treatment strategies. In this publication, existing diagnostic challenges and current treatment practices for mTBI and/or PTSD will be summarized, along with suggestions regarding how what has been learned from existing models of PTSD and traditional mechanism (e.g., non-blast TBI can be used to facilitate the development of clinically relevant blast models.

  9. Brain Injury Safety Tips and Prevention

    Science.gov (United States)

    ... submit" name="commit" type="submit" value="Submit" /> Brain Injury Safety Tips and Prevention Recommend on Facebook ... not grass or dirt. More HEADS UP Video: Brain Injury Safety and Prevention frame support disabled and/ ...

  10. Considerations for Experimental Animal Models of Concussion, Traumatic Brain Injury, and Chronic Traumatic Encephalopathy—These Matters Matter

    Directory of Open Access Journals (Sweden)

    Mark W. Wojnarowicz

    2017-06-01

    Full Text Available Animal models of concussion, traumatic brain injury (TBI, and chronic traumatic encephalopathy (CTE are widely available and routinely deployed in laboratories around the world. Effective animal modeling requires careful consideration of four basic principles. First, animal model use must be guided by clarity of definitions regarding the human disease or condition being modeled. Concussion, TBI, and CTE represent distinct clinical entities that require clear differentiation: concussion is a neurological syndrome, TBI is a neurological event, and CTE is a neurological disease. While these conditions are all associated with head injury, the pathophysiology, clinical course, and medical management of each are distinct. Investigators who use animal models of these conditions must take into account these clinical distinctions to avoid misinterpretation of results and category mistakes. Second, model selection must be grounded by clarity of purpose with respect to experimental questions and frame of reference of the investigation. Distinguishing injury context (“inputs” from injury consequences (“outputs” may be helpful during animal model selection, experimental design and execution, and interpretation of results. Vigilance is required to rout out, or rigorously control for, model artifacts with potential to interfere with primary endpoints. The widespread use of anesthetics in many animal models illustrates the many ways that model artifacts can confound preclinical results. Third, concordance between key features of the animal model and the human disease or condition being modeled is required to confirm model biofidelity. Fourth, experimental results observed in animals must be confirmed in human subjects for model validation. Adherence to these principles serves as a bulwark against flawed interpretation of results, study replication failure, and confusion in the field. Implementing these principles will advance basic science discovery and

  11. Fish oil improves motor function, limits blood-brain barrier disruption, and reduces Mmp9 gene expression in a rat model of juvenile traumatic brain injury.

    Science.gov (United States)

    Russell, K L; Berman, N E J; Gregg, P R A; Levant, B

    2014-01-01

    The effects of an oral fish oil treatment regimen on sensorimotor, blood-brain barrier, and biochemical outcomes of traumatic brain injury (TBI) were investigated in a juvenile rat model. Seventeen-day old Long-Evans rats were given a 15mL/kg fish oil (2.01g/kg EPA, 1.34g/kg DHA) or soybean oil dose via oral gavage 30min prior to being subjected to a controlled cortical impact injury or sham surgery, followed by daily doses for seven days. Fish oil treatment resulted in less severe hindlimb deficits after TBI as assessed with the beam walk test, decreased cerebral IgG infiltration, and decreased TBI-induced expression of the Mmp9 gene one day after injury. These results indicate that fish oil improved functional outcome after TBI resulting, at least in part from decreased disruption of the blood-brain barrier through a mechanism that includes attenuation of TBI-induced expression of Mmp9. © 2013 Elsevier Ltd. All rights reserved.

  12. Protective Effects of Salubrinal on Liver Injury in Rat Models of Brain Death

    Institute of Scientific and Technical Information of China (English)

    Tao Wang; Shui-Jun Zhang; Sheng-Li Cao; Wen-Zhi Guo; Bing Yan; Hong-Bo Fang

    2015-01-01

    Background:Previous studies have indicated that endoplasmic reticulum stress participates in and mediates liver injury and apoptosis in brain-dead (BD) rats.In this study,we observed the effect ofsalubrinal (Sal,Sigma,USA) on liver cells in BD rats and explored its relevant mechanisms.Methods:Thirty Sprague-Dawley rats were equally randomized into three groups:BD group,Sal group,and DMSO group.The BD models were established by increasing intracranial pressure in a modified,slow,and intermittent way.In the drug groups,Sal was administered l h before the induction of BD.After modeling was completed,the blood and liver samples were harvested.CHOP and Caspase-12 mRNA expression was detected using quantitative polymerase chain reaction.PKR-like ER kinase (PERK),P-eukaryotic translation initiation factor 2α (eIF2α),eIF2α,CHOP and caspase-12 expression was detected using western blotting (WB).CHOP and caspase-12 distribution and expression in liver tissues were determined using immunohistochemistry (IHC).Alanine aminotransferase and aspartate aminotransferase level were detected using an automatic biochemical analyzer.Hepatic cell apoptosis was detected using TUNEL.The results were analyzed using Quantity-one v4.62 software (Bio-Rad,USA).Results:CHOP and caspase-12 expression and PERK,eIF2α,and P-eIF2α protein expression showed no significant difference between BD group and DMSO group.Compared with BD group,Sal group had a significantly higher P-eIF2C level and a lower P-PERK level 2 h and 6 h after BD (P < 0.05).However,eIF2α expression showed no significant difference (P > 0.05).After the Sal treatment,CHOP and caspase-12 mRNA expression significantly decreased 4 h after BD (P < 0.05).WB and IHC indicated that CHOP and caspase-12 expression also significantly decreased after Sal treatment.Sal was associated with improved liver function and decreased hepatic cell apoptosis.Conclusions:Sal can significantly reduce apoptosis in hepatic cells of BD rats

  13. MRI of perinatal brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Rutherford, Mary; Allsop, Joanna [Imperial College, Robert Steiner MR Unit, Perinatal Imaging, MRC Clinical Sciences Centre, Hammersmith Hospital, London (United Kingdom); Martinez Biarge, Miriam [La Paz University Hospital, Dept of Neonatology, Madrid (Spain); Counsell, Serena [Imperial College, Robert Steiner MR Unit, Neonatal Medicine, MRC Clinical Sciences Centre, Hammersmith Hospital, London (United Kingdom); Cowan, Frances [Imperial College, Dept of Paediatrics, Hammersmith Hospital, London (United Kingdom)

    2010-06-15

    MRI is invaluable in assessing the neonatal brain following suspected perinatal injury. Good quality imaging requires adaptations to both the hardware and the sequences used for adults or older children. The perinatal and postnatal details often predict the pattern of lesions sustained and should be available to aid interpretation of the imaging findings. Perinatal lesions, the pattern of which can predict neurodevelopmental outcome, are at their most obvious on conventional imaging between 1 and 2 weeks from birth. Very early imaging during the first week may be useful to make management decisions in ventilated neonates but brain abnormalities may still be subtle using conventional sequences. Diffusion-weighted imaging (DWI) is very useful for the early identification of ischaemic tissue in the neonatal brain but may underestimate the final extent of injury, particularly basal ganglia and thalamic lesions. MR imaging is an excellent predictor of outcome following perinatal brain injury and can therefore be used as a biomarker in interventional trials designed to reduce injury and improve neurodevelopmental outcome. (orig.)

  14. MRI of perinatal brain injury

    International Nuclear Information System (INIS)

    Rutherford, Mary; Allsop, Joanna; Martinez Biarge, Miriam; Counsell, Serena; Cowan, Frances

    2010-01-01

    MRI is invaluable in assessing the neonatal brain following suspected perinatal injury. Good quality imaging requires adaptations to both the hardware and the sequences used for adults or older children. The perinatal and postnatal details often predict the pattern of lesions sustained and should be available to aid interpretation of the imaging findings. Perinatal lesions, the pattern of which can predict neurodevelopmental outcome, are at their most obvious on conventional imaging between 1 and 2 weeks from birth. Very early imaging during the first week may be useful to make management decisions in ventilated neonates but brain abnormalities may still be subtle using conventional sequences. Diffusion-weighted imaging (DWI) is very useful for the early identification of ischaemic tissue in the neonatal brain but may underestimate the final extent of injury, particularly basal ganglia and thalamic lesions. MR imaging is an excellent predictor of outcome following perinatal brain injury and can therefore be used as a biomarker in interventional trials designed to reduce injury and improve neurodevelopmental outcome. (orig.)

  15. Hypopituitarism in Traumatic Brain Injury

    DEFF Research Database (Denmark)

    Klose, Marianne; Feldt-Rasmussen, Ulla

    2015-01-01

    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...

  16. Family needs after brain injury

    DEFF Research Database (Denmark)

    Norup, Anne; Perrin, Paul B; Cuberos-Urbano, Gustavo

    2015-01-01

    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...

  17. Modeling and simulation of blast-induced, early-time intracranial wave physics leading to traumatic brain injury.

    Energy Technology Data Exchange (ETDEWEB)

    Ford, Corey C. (University of New Mexico, Albuquerque, NM); Taylor, Paul Allen

    2008-02-01

    The objective of this modeling and simulation study was to establish the role of stress wave interactions in the genesis of traumatic brain injury (TBI) from exposure to explosive blast. A high resolution (1 mm{sup 3} voxels), 5 material model of the human head was created by segmentation of color cryosections from the Visible Human Female dataset. Tissue material properties were assigned from literature values. The model was inserted into the shock physics wave code, CTH, and subjected to a simulated blast wave of 1.3 MPa (13 bars) peak pressure from anterior, posterior and lateral directions. Three dimensional plots of maximum pressure, volumetric tension, and deviatoric (shear) stress demonstrated significant differences related to the incident blast geometry. In particular, the calculations revealed focal brain regions of elevated pressure and deviatoric (shear) stress within the first 2 milliseconds of blast exposure. Calculated maximum levels of 15 KPa deviatoric, 3.3 MPa pressure, and 0.8 MPa volumetric tension were observed before the onset of significant head accelerations. Over a 2 msec time course, the head model moved only 1 mm in response to the blast loading. Doubling the blast strength changed the resulting intracranial stress magnitudes but not their distribution. We conclude that stress localization, due to early time wave interactions, may contribute to the development of multifocal axonal injury underlying TBI. We propose that a contribution to traumatic brain injury from blast exposure, and most likely blunt impact, can occur on a time scale shorter than previous model predictions and before the onset of linear or rotational accelerations traditionally associated with the development of TBI.

  18. Assessment of Students with Traumatic Brain Injury

    Science.gov (United States)

    Chesire, David J.; Buckley, Valerie A.; Canto, Angela I.

    2011-01-01

    The incidence of brain injuries, as well as their impact on individuals who sustain them, has received growing attention from American media in recent years. This attention is likely the result of high profile individuals suffering brain injuries. Greater public awareness of traumatic brain injuries (TBIs) has also been promoted by sources such as…

  19. Traumatic brain injury : from impact to rehabilitation

    NARCIS (Netherlands)

    Halliday, J.; Absalom, A. R.

    Traumatic brain injury is a significant cause of mortality and morbidity in our society, particularly among the young. This review discusses the pathophysiology of traumatic brain injury, and current management from the acute phase through to rehabilitation of the traumatic brain injury patient.

  20. Damage Control Resuscitation Supplemented with Vasopressin in a Severe Polytrauma Model with Traumatic Brain Injury and Uncontrolled Internal Hemorrhage.

    Science.gov (United States)

    Dickson, J Michael; Wang, Xu; St John, Alexander E; Lim, Esther B; Stern, Susan A; White, Nathan J

    2018-03-14

    Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of traumatic death worldwide and particularly on the battlefield. They are especially challenging when present simultaneously (polytrauma), and clear blood pressure end points during fluid resuscitation are not well described for this situation. The goal of this study is to evaluate for any benefit of increasing blood pressure using a vasopressor on brain blood flow during initial fluid resuscitation in a swine polytrauma model. We used a swine polytrauma model with simultaneous TBI, femur fracture, and HS with uncontrolled noncompressible internal bleeding from an aortic tear injury. Five animals were assigned to each of three experimental groups (hydroxyethyl starch only [HES], HES + 0.4 U/kg vasopressin, and no fluid resuscitation [No Fluids]). Fluids were given as two 10 mL/kg boluses according to tactical field care guidelines. Primary outcomes were mean arterial blood pressure (MAP) and brain blood flow at 60 min. Secondary outcomes were blood flows in the heart, intestine, and kidney; arterial blood lactate level; and survival at 6 hr. Organ blood flow was measured using injection of colored microspheres. Five animals were tested in each of the three groups. There was a statistically significant increase in MAP with vasopressin compared with other experimental groups, but no significant increase in brain blood flow during the first 60 min of resuscitation. The vasopressin group also exhibited greater total internal hemorrhage volume and rate. There was no difference in survival at 6 hours. In this experimental swine polytrauma model, increasing blood pressure with vasopressin did not improve brain perfusion, likely due to increased internal hemorrhage. Effective hemostasis should remain the top priority for field treatment of the polytrauma casualty with TBI.

  1. Functional recovery after injury of motor cortex in rats: effects of rehabilitation and stem cell transplantation in a traumatic brain injury model of cortical resection.

    Science.gov (United States)

    Lee, Do-Hun; Lee, Ji Yeoun; Oh, Byung-Mo; Phi, Ji Hoon; Kim, Seung-Ki; Bang, Moon Suk; Kim, Seung U; Wang, Kyu-Chang

    2013-03-01

    Experimental studies and clinical trials designed to help patients recover from various brain injuries, such as stroke or trauma, have been attempted. Rehabilitation has shown reliable, positive clinical outcome in patients with various brain injuries. Transplantation of exogenous neural stem cells (NSCs) to repair the injured brain is a potential tool to help patient recovery. This study aimed to evaluate the therapeutic efficacy of a combination therapy consisting of rehabilitation and NSC transplantation compared to using only one modality. A model of motor cortex resection in rats was used to create brain injury in order to obtain consistent and prolonged functional deficits. The therapeutic results were evaluated using three methods during an 8-week period with a behavioral test, motor-evoked potential (MEP) measurement, and measurement of the degree of endogenous NSC production. All three treatment groups showed the effects of treatment in the behavioral test, although the NSC transplantation alone group (CN) exhibited slightly worse results than the rehabilitation alone group (CR) or the combination therapy group (CNR). The latency on MEP was shortened to a similar extent in all three groups compared to the untreated group (CO). However, the enhancement of endogenous NSC proliferation was dramatically reduced in the CN group compared not only to the CR and CNR groups but also to the CO group. The CR and CNR groups seemed to prolong the duration of endogenous NSC proliferation compared to the untreated group. A combination of rehabilitation and NSC transplantation appears to induce treatment outcomes that are similar to rehabilitation alone. Further studies are needed to evaluate the electrophysiological outcome of recovery and the possible effect of prolonging endogenous NSC proliferation in response to NSC transplantation and rehabilitation.

  2. Relatives of patients with severe brain injury

    DEFF Research Database (Denmark)

    Norup, Anne; Petersen, Janne; Lykke Mortensen, Erik

    2015-01-01

    PRIMARY OBJECTIVE: To investigate trajectories and predictors of trajectories of anxiety and depression in relatives of patients with a severe brain injury during the first year after injury. RESEARCH DESIGN: A prospective longitudinal study with four repeated measurements. SUBJECTS: Ninety...... relatives of patients with severe brain injury. METHODS: The relatives were assessed on the anxiety and depression scales from the Symptom Checklist-90-Revised and latent variable growth curve models were used to model the trajectories. The effects of patient's age, patient's Glasgow Coma Score, level...... should focus not only on specific deficits in the patient, but also on how the emotional state and well-being of the relatives evolve, while trying to adjust and cope with a new life-situation....

  3. A novel inhibitor of p75-neurotrophin receptor improves functional outcomes in two models of traumatic brain injury.

    Science.gov (United States)

    Delbary-Gossart, Sandrine; Lee, Sangmi; Baroni, Marco; Lamarche, Isabelle; Arnone, Michele; Canolle, Benoit; Lin, Amity; Sacramento, Jeffrey; Salegio, Ernesto A; Castel, Marie-Noelle; Delesque-Touchard, Nathalie; Alam, Antoine; Laboudie, Patricia; Ferzaz, Badia; Savi, Pierre; Herbert, Jean-Marc; Manley, Geoffrey T; Ferguson, Adam R; Bresnahan, Jacqueline C; Bono, Françoise; Beattie, Michael S

    2016-06-01

    The p75 neurotrophin receptor is important in multiple physiological actions including neuronal survival and neurite outgrowth during development, and after central nervous system injury. We have discovered a novel piperazine-derived compound, EVT901, which interferes with p75 neurotrophin receptor oligomerization through direct interaction with the first cysteine-rich domain of the extracellular region. Using ligand binding assays with cysteine-rich domains-fused p75 neurotrophin receptor, we confirmed that EVT901 interferes with oligomerization of full-length p75 neurotrophin receptor in a dose-dependent manner. Here we report that EVT901 reduces binding of pro-nerve growth factor to p75 neurotrophin receptor, blocks pro-nerve growth factor induced apoptosis in cells expressing p75 neurotrophin receptor, and enhances neurite outgrowth in vitro Furthermore, we demonstrate that EVT901 abrogates p75 neurotrophin receptor signalling by other ligands, such as prion peptide and amyloid-β. To test the efficacy of EVT901 in vivo, we evaluated the outcome in two models of traumatic brain injury. We generated controlled cortical impacts in adult rats. Using unbiased stereological analysis, we found that EVT901 delivered intravenously daily for 1 week after injury, reduced lesion size, protected cortical neurons and oligodendrocytes, and had a positive effect on neurological function. After lateral fluid percussion injury in adult rats, oral treatment with EVT901 reduced neuronal death in the hippocampus and thalamus, reduced long-term cognitive deficits, and reduced the occurrence of post-traumatic seizure activity. Together, these studies provide a new reagent for altering p75 neurotrophin receptor actions after injury and suggest that EVT901 may be useful in treatment of central nervous system trauma and other neurological disorders where p75 neurotrophin receptor signalling is affected. © The Author (2016). Published by Oxford University Press on behalf of the

  4. The Evidence for Brain Injury in Whiplash Injuries

    Directory of Open Access Journals (Sweden)

    Michael P. Alexander

    2003-01-01

    Full Text Available The evidence that brain damage can occur in injuries that produce whiplash is reviewed. The clinical phenomena for the two injuries are the same. Pure whiplash injury implies no, or minimal head contact, but many patients also have head contact against a head rest or the steering wheel or windshield. The relative severity of the neck injury and the head injury distinguishes whiplash from mild closed head injury. If there is brain injury is some patients with whiplash, it, by definition, falls at the mildest end of the concussion spectrum. The relationship between these two injuries is examined.

  5. Neuroprotective Effects of Oleocanthal, A Compound in Virgin Olive Oil, in A Rat Model of Traumatic Brain Injury.

    Science.gov (United States)

    Mete, Mesut; Aydemir, Isıl; Unsal, Ulkun Unlu; Collu, Fatih; Vatandas, Gokhan; Gurcu, Beyhan; Duransoy, Yusuf Kurtulus; Taneli, Fatma; Tugrul, Mehmet Ibrahim; Selcuki, Mehmet

    2017-11-01

    TBI has two distinct phases: primary and secondary injury. Many agents have been used to prevent secondary injury. Oleocanthal (OC) has anti-inflammatory and antioxidant properties similar nonsteroidal anti-inflammatory drug. We evaluated the neuroprotective effects of OC in a rat model of TBI. Twenty-six adult male, Wistar albino rats were used. The rats were divided into 4 groups. group 1, sham (n = 5). group 2, trauma (n = 5): Rats were treated with 10 mg/kg saline intraperitoneally (IP) twice a day. Groups 3 and 4, rats were treated with 10 (group 3, n = 8) or 30 (group 4, n = 8) mg/kg OC IP twice a day. For each group brain samples were collected 72 h after injury. Brain samples and blood were evaluated with histopathological and biochemical methods. Histopathological evaluation revealed a significant difference between group 2 and group 4. Biochemical findings demonstrated that, oxidative stress index was the highest in group 2 and was the lowest in the group 4. Results indicated that OC has a protective effect on neural cells after TBI. This effect is achieved by reducing oxidative stress and apoptosis.

  6. SCI with Brain Injury: Bedside to Bench Modeling for Developing Treatment and Rehabilitation Strategies

    Science.gov (United States)

    2013-10-01

    INVOL  MOVEMENT  NEC 781 3,  8,  12,  14 APHASIA 784.3 8,  11,  12,  13 DYSPHAGIA 787.2 1,  4,  8,  9,  11,  12,  13 8...sensorimotor outcome in unilateral rat models of stroke, cortical ablation, Parkinsonism and spinal cord injury. Neuropharmacology 39, 777–787. Scheff

  7. Using Personality Traits to Construct Linear Growth Models of Mental Health in Family Members of Individuals With Severe Brain Injury

    DEFF Research Database (Denmark)

    Trujillo, Michael; Perrin, Paul B; Doser, Karoline

    2016-01-01

    Objective: No studies have examined the impact of personality traits on mental health among caregivers of individuals with severe brain injury. Therefore, the purpose of the current study was to construct linear growth models to examine whether the personality traits of family members...... neuroticism had lower anxiety and depression over time, as well as a more accelerated decrease in anxiety and depression. Conclusions: Caregivers' personality traits were strongly associated over time with mental HRQoL, anxiety, and depression, with neuroticism being especially important for trajectories...... the Short Form-36 assessing mental HRQoL (vitality, social functioning, role limitations-emotional, mental health), anxiety, and depression across 5 time points during the 1st year after injury. The measure of personality was administered 3 months after the patients' discharge. Results: All mental HRQo...

  8. Experimental model considerations for the study of protein-energy malnutrition co-existing with ischemic brain injury.

    Science.gov (United States)

    Prosser-Loose, Erin J; Smith, Shari E; Paterson, Phyllis G

    2011-05-01

    Protein-energy malnutrition (PEM) affects ~16% of patients at admission for stroke. We previously modeled this in a gerbil global cerebral ischemia model and found that PEM impairs functional outcome and influences mechanisms of ischemic brain injury and recovery. Since this model is no longer reliable, we investigated the utility of the rat 2-vessel occlusion (2-VO) with hypotension model of global ischemia for further study of this clinical problem. Male, Sprague-Dawley rats were exposed to either control diet (18% protein) or PEM induced by feeding a low protein diet (2% protein) for 7d prior to either global ischemia or sham surgery. PEM did not significantly alter the hippocampal CA1 neuron death (p = 0.195 by 2-factor ANOVA) or the increase in dendritic injury caused by exposure to global ischemia. Unexpectedly, however, a strong trend was evident for PEM to decrease the consistency of hippocampal damage, as shown by an increased incidence of unilateral or no hippocampal damage (p=0.069 by chi-square analysis). Although PEM caused significant changes to baseline arterial blood pH, pO(2), pCO(2), and fasting glucose (p0.269). Intra-ischemic tympanic temperature and blood pressure were strictly and equally controlled between ischemic groups. We conclude that co-existing PEM confounded the consistency of hippocampal injury in the 2-VO model. Although the mechanisms responsible were not identified, this model of brain ischemia should not be used for studying this co-morbidity factor. © 2011 Bentham Science Publishers Ltd.

  9. Anti-inflammatory and immunomodulatory mechanisms of atorvastatin in a murine model of traumatic brain injury.

    Science.gov (United States)

    Xu, Xin; Gao, Weiwei; Cheng, Shiqi; Yin, Dongpei; Li, Fei; Wu, Yingang; Sun, Dongdong; Zhou, Shuai; Wang, Dong; Zhang, Yongqiang; Jiang, Rongcai; Zhang, Jianning

    2017-08-23

    Neuroinflammation is an important secondary injury mechanism that has dual beneficial and detrimental roles in the pathophysiology of traumatic brain injury (TBI). Compelling data indicate that statins, a group of lipid-lowering drugs, also have extensive immunomodulatory and anti-inflammatory properties. Among statins, atorvastatin has been demonstrated as a neuroprotective agent in experimental TBI; however, there is a lack of evidence regarding its effects on neuroinflammation during the acute phase of TBI. The current study aimed to evaluate the effects of atorvastatin therapy on modulating the immune reaction, and to explore the possible involvement of peripheral leukocyte invasion and microglia/macrophage polarization in the acute period post-TBI. C57BL/6 mice were subjected to TBI using a controlled cortical impact (CCI) device. Either atorvastatin or vehicle saline was administered orally starting 1 h post-TBI for three consecutive days. Short-term neurological deficits were evaluated using the modified neurological severity score (mNSS) and Rota-rod. Brain-invading leukocyte subpopulations were analyzed by flow cytometry and immunohistochemistry. Pro- and anti-inflammatory cytokines and chemokines were examined using enzyme-linked immunosorbent assay (ELISA). Markers of classically activated (M1) and alternatively activated (M2) microglia/macrophages were then determined by quantitative real-time PCR (qRT-PCR) and flow cytometry. Neuronal apoptosis was identified by double staining of terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL) staining and immunofluorescence labeling for neuronal nuclei (NeuN). Acute treatment with atorvastatin at doses of 1 mg/kg/day significantly reduced neuronal apoptosis and improved behavioral deficits. Invasions of T cells, neutrophils and natural killer (NK) cells were attenuated profoundly after atorvastatin therapy, as was the production of pro-inflammatory cytokines (IFN-γ and IL-6) and chemokines

  10. Probabilistic Matching of Deidentified Data From a Trauma Registry and a Traumatic Brain Injury Model System Center: A Follow-up Validation Study.

    Science.gov (United States)

    Kumar, Raj G; Wang, Zhensheng; Kesinger, Matthew R; Newman, Mark; Huynh, Toan T; Niemeier, Janet P; Sperry, Jason L; Wagner, Amy K

    2018-04-01

    In a previous study, individuals from a single Traumatic Brain Injury Model Systems and trauma center were matched using a novel probabilistic matching algorithm. The Traumatic Brain Injury Model Systems is a multicenter prospective cohort study containing more than 14,000 participants with traumatic brain injury, following them from inpatient rehabilitation to the community over the remainder of their lifetime. The National Trauma Databank is the largest aggregation of trauma data in the United States, including more than 6 million records. Linking these two databases offers a broad range of opportunities to explore research questions not otherwise possible. Our objective was to refine and validate the previous protocol at another independent center. An algorithm generation and validation data set were created, and potential matches were blocked by age, sex, and year of injury; total probabilistic weight was calculated based on of 12 common data fields. Validity metrics were calculated using a minimum probabilistic weight of 3. The positive predictive value was 98.2% and 97.4% and sensitivity was 74.1% and 76.3%, in the algorithm generation and validation set, respectively. These metrics were similar to the previous study. Future work will apply the refined probabilistic matching algorithm to the Traumatic Brain Injury Model Systems and the National Trauma Databank to generate a merged data set for clinical traumatic brain injury research use.

  11. Interleukin-1 and acute brain injury

    Directory of Open Access Journals (Sweden)

    Katie N Murray

    2015-02-01

    Full Text Available Inflammation is the key host-defense response to infection and injury, yet also a major contributor to a diverse range of diseases, both peripheral and central in origin. Brain injury as a result of stroke or trauma is a leading cause of death and disability worldwide, yet there are no effective treatments, resulting in enormous social and economic costs. Increasing evidence, both preclinical and clinical, highlights inflammation as an important factor in stroke, both in determining outcome and as a contributor to risk. A number of inflammatory mediators have been proposed as key targets for intervention to reduce the burden of stroke, several reaching clinical trial, but as yet yielding no success. Many factors could explain these failures, including the lack of robust preclinical evidence and poorly designed clinical trials, in addition to the complex nature of the clinical condition. Lack of consideration in preclinical studies of associated co-morbidities prevalent in the clinical stroke population is now seen as an important omission in previous work. These co-morbidities (atherosclerosis, hypertension, diabetes, infection have a strong inflammatory component, supporting the need for greater understanding of how inflammation contributes to acute brain injury. Interleukin (IL-1 is the prototypical pro-inflammatory cytokine, first identified many years ago as the endogenous pyrogen. Research over the last 20 years or so reveals that IL-1 is an important mediator of neuronal injury and blocking the actions of IL-1 is beneficial in a number of experimental models of brain damage. Mechanisms underlying the actions of IL-1 in brain injury remain unclear, though increasing evidence indicates the cerebrovasculature as a key target. Recent literature supporting this and other aspects of how IL-1 and systemic inflammation in general contribute to acute brain injury are discussed in this review.

  12. Traumatic brain injury produced by exposure to blasts, a critical problem in current wars: biomarkers, clinical studies, and animal models

    Science.gov (United States)

    Dixon, C. Edward

    2011-06-01

    Traumatic brain injury (TBI) resulting from exposure to blast energy released by Improvised Explosive Devices (IEDs) has been recognized as the "signature injury" of Operation Iraqi Freedom and Operation Enduring Freedom. Repeated exposure to mild blasts may produce subtle deficits that are difficult to detect and quantify. Several techniques have been used to detect subtle brain dysfunction including neuropsychological assessments, computerized function testing and neuroimaging. Another approach is based on measurement of biologic substances (e.g. proteins) that are released into the body after a TBI. Recent studies measuring biomarkers in CSF and serum from patients with severe TBI have demonstrated the diagnostic, prognostic, and monitoring potential. Advancement of the field will require 1) biochemical mining for new biomarker candidates, 2) clinical validation of utility, 3) technical advances for more sensitive, portable detectors, 4) novel statistical approach to evaluate multiple biomarkers, and 5) commercialization. Animal models have been developed to simulate elements of blast-relevant TBI including gas-driven shock tubes to generate pressure waves similar to those produced by explosives. These models can reproduce hallmark clinical neuropathological responses such as neuronal degeneration and inflammation, as well as behavioral impairments. An important application of these models is to screen novel therapies and conduct proteomic, genomic, and lipodomic studies to mine for new biomarker candidates specific to blast relevant TBI.

  13. Neuropsychiatric Symptom Modeling in Male and Female C57BL/6J Mice after Experimental Traumatic Brain Injury

    Science.gov (United States)

    Tucker, Laura B.; Burke, John F.; Fu, Amanda H.

    2017-01-01

    Abstract Psychiatric symptoms such as anxiety and depression are frequent and persistent complaints following traumatic brain injury (TBI). Modeling these symptoms in animal models of TBI affords the opportunity to determine mechanisms underlying behavioral pathologies and to test potential therapeutic agents. However, testing these symptoms in animal models of TBI has yielded inconsistent results. The goal of the current study was to employ a battery of tests to measure multiple anxiety- and depressive-like symptoms following TBI in C57BL/6J mice, and to determine if male and female mice are differentially affected by the injury. Following controlled cortical impact (CCI) at a parietal location, neither male nor female mice showed depressive-like symptoms as measured by the Porsolt forced-swim test and sucrose preference test. Conclusions regarding anxiety-like behaviors were dependent upon the assay employed; CCI-induced thigmotaxis in the open field suggested an anxiogenic effect of the injury; however, results from the elevated zero maze, light-dark box, and marble-burying tests indicated that CCI reduced anxiety-like behaviors. Fewer anxiety-like behaviors were also associated with the female sex. Increased levels of activity were also measured in female mice and injured mice in these tests, and conclusions regarding anxiety should be taken with caution when experimental manipulations induce changes in baseline activity. These results underscore the irreconcilability of results from studies attempting to model TBI-induced neuropsychiatric symptoms. Changes in injury models or better attempts to replicate the clinical syndrome may improve the translational applicability of rodent models of TBI-induced anxiety and depression. PMID:27149139

  14. Lymphocytes Contribute to the Pathophysiology of Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Arshed Nazmi

    2018-03-01

    Full Text Available BackgroundPeriventricular leukomalacia (PVL is the most common form of preterm brain injury affecting the cerebral white matter. This type of injury involves a multiphase process and is induced by many factors, including hypoxia–ischemia (HI and infection. Previous studies have suggested that lymphocytes play a significant role in the pathogenesis of brain injury, and the aim of this study was to determine the contribution of lymphocyte subsets to preterm brain injury.MethodsImmunohistochemistry on brain sections from neonatal mice was performed to evaluate the extent of brain injury in wild-type and T cell and B cell-deficient neonatal mice (Rag1−/− mice using a mouse model of HI-induced preterm brain injury. Flow cytometry was performed to determine the presence of different types of immune cells in mouse brains following HI. In addition, immunostaining for CD3 T cells and CD20 B cells was performed on postmortem preterm human infant brains with PVL.ResultsMature lymphocyte-deficient Rag1−/− mice showed protection from white matter loss compared to wild type mice as indicated by myelin basic protein immunostaining of mouse brains. CD3+ T cells and CD20+ B cells were observed in the postmortem preterm infant brains with PVL. Flow cytometry analysis of mouse brains after HI-induced injury showed increased frequency of CD3+ T, αβT and B cells at 7 days after HI in the ipsilateral (injured hemisphere compared to the contralateral (control, uninjured hemisphere.ConclusionLymphocytes were found in the injured brain after injury in both mice and humans, and lack of mature lymphocytes protected neonatal mice from HI-induced brain white matter injury. This finding provides insight into the pathology of perinatal brain injury and suggests new avenues for the development of therapeutic strategies.

  15. Preclinical Models of Traumatic Brain Injury: Emerging Role of Glutamate in the Pathophysiology of Depression

    Directory of Open Access Journals (Sweden)

    Darik A. O’Neil

    2018-06-01

    Full Text Available More than 10 million people worldwide incur a traumatic brain injury (TBI each year, with two million cases occurring in the United States. TBI survivors exhibit long-lasting cognitive and affective sequelae that are associated with reduced quality of life and work productivity, as well as mental and emotional disturbances. While TBI-related disabilities often manifest physically and conspicuously, TBI has been linked with a “silent epidemic” of psychological disorders, including major depressive disorder (MDD. The prevalence of MDD post-insult is approximately 50% within the 1st year. Furthermore, given they are often under-reported when mild, TBIs could be a significant overall cause of MDD in the United States. The emergence of MDD post-TBI may be rooted in widespread disturbances in the modulatory role of glutamate, such that glutamatergic signaling becomes excessive and deleterious to neuronal integrity, as reported in both clinical and preclinical studies. Following this acute glutamatergic storm, regulators of glutamatergic function undergo various manipulations, which include, but are not limited to, alterations in glutamatergic subunit composition, release, and reuptake. This review will characterize the glutamatergic functional and signaling changes that emerge and persist following experimental TBI, utilizing evidence from clinical, molecular, and rodent behavioral investigations. Special care will be taken to speculate on how these manipulations may correlate with the development of MDD following injury in the clinic, as well as pharmacotherapies to date. Indisputably, TBI is a significant healthcare issue that warrants discovery and subsequent refinement of therapeutic strategies to improve neurobehavioral recovery and mental health.

  16. PET/CT imaging of striatal dopamine transporters in a newborn piglet model of hypoxic-ischemic brain injury

    International Nuclear Information System (INIS)

    Zhang Yanfen; Wang Xiaoming; Wang Xiaoyu; Cao Li; Guo Qiyong

    2013-01-01

    Objective: To investigate changes of striatal DAT following hypoxic ischemic (HI) brain injury in newborn piglets using 11 C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (CFT) PET/CT, and to evaluate the value of 11 C-CFT PET/CT in brain injury. Methods: Newborn piglets with HI brain injury (n=20) were taken as a model group,and five piglets were used as a control group. Radioligand 11 C-CFT (55.5-74.0 MBq) was injected through the jugular vein, and PET/CT imaging was performed to observe the changes of striatal DAT in newborn piglets. The ST/occipital lobe (OC) ratio was calculated. Model group was divided into 0-6 h, 20-24 h, 44-48 h and 68-72 h sub-groups after HI in accordance with the imaging time. The piglets were sacrificed immediately after 11 C-CFT PET/CT scanning, and then the brains were removed for pathological analysis. Data analysis was performed with one-way analysis of variance and Pearson linear correlation analysis. Results: After intravenous injection of 11 C-CFT, the radioactivity accumulation in cortical, striatum, and cerebellum was shown clearly in the control and model groups. The radioactivity accumulation was lower in the white matter. The radioactivity in cortical and cerebellum exhibited decreased with time, while the striatum was still clear. After HI, the ST/OC activity ratio in the striatum was initially increased, and the ratio of 0-6 h group (1.34 ± 0.04) was statistically significant compared with that of the control group (1.18 ± 0.06; F=4.658, P<0.05), followed by a gradual decrease. ST/OC ratios of other HI subgroups were 1.27 ±0.01, 1.27 ±0.10 and 1.18 ±0.05, respectively. There was a positive correlation between the number of DAT positive neurons ((13 ± 3), (13 ± 4), (8 ±3) and (4 ±4)/high power field) and 11 C-CFT ST/OC activity ratios (r=0.844, P<0.05). Conclusion: 11 C-CFT PET/CT study can accurately reflect the changes of DAT in the striatum, and the amount of DAT is related to the severity of the ischemic insult

  17. Neonatal erythropoietin mitigates impaired gait, social interaction and diffusion tensor imaging abnormalities in a rat model of prenatal brain injury.

    Science.gov (United States)

    Robinson, Shenandoah; Corbett, Christopher J; Winer, Jesse L; Chan, Lindsay A S; Maxwell, Jessie R; Anstine, Christopher V; Yellowhair, Tracylyn R; Andrews, Nicholas A; Yang, Yirong; Sillerud, Laurel O; Jantzie, Lauren L

    2018-04-01

    Children who are born preterm are at risk for encephalopathy of prematurity, a leading cause of cerebral palsy, cognitive delay and behavioral disorders. Current interventions are limited and none have been shown to reverse cognitive and behavioral impairments, a primary determinant of poor quality of life for these children. Moreover, the mechanisms of perinatal brain injury that result in functional deficits and imaging abnormalities in the mature brain are poorly defined, limiting the potential to target interventions to those who may benefit most. To determine whether impairments are reversible after a prenatal insult, we investigated a spectrum of functional deficits and diffusion tensor imaging (DTI) abnormalities in young adult animals. We hypothesized that prenatal transient systemic hypoxia-ischemia (TSHI) would induce multiple functional deficits concomitant with reduced microstructural white and gray matter integrity, and tested whether these abnormalities could be ameliorated using postnatal erythropoietin (EPO), an emerging neurorestorative intervention. On embryonic day 18 uterine arteries were transiently occluded for 60min via laparotomy. Shams underwent anesthesia and laparotomy for 60min. Pups were born and TSHI pups were randomized to receive EPO or vehicle via intraperitoneal injection on postnatal days 1 to 5. Gait, social interaction, olfaction and open field testing was performed from postnatal day 25-35 before brains underwent ex vivo DTI to measure fractional anisotropy, axial diffusivity and radial diffusivity. Prenatal TSHI injury causes hyperactivity, impaired gait and poor social interaction in young adult rats that mimic the spectrum of deficits observed in children born preterm. Collectively, these data show for the first time in a model of encephalopathy of prematurity that postnatal EPO treatment mitigates impairments in social interaction, in addition to gait deficits. EPO also normalizes TSHI-induced microstructural abnormalities

  18. Pharmacologic modulation of cerebral metabolic derangement and excitotoxicity in a porcine model of traumatic brain injury and hemorrhagic shock

    DEFF Research Database (Denmark)

    Hwabejire, John O; Jin, Guang; Imam, Ayesha M

    2013-01-01

    Cerebral metabolic derangement and excitotoxicity play critical roles in the evolution of traumatic brain injury (TBI). We have shown previously that treatment with large doses of valproic acid (VPA) decreases the size of brain lesion. The goal of this experiment was to determine whether...

  19. Another Look at the PART-O Using the Traumatic Brain Injury Model Systems National Database: Scoring to Optimize Psychometrics.

    Science.gov (United States)

    Malec, James F; Whiteneck, Gale G; Bogner, Jennifer A

    2016-02-01

    To integrate previous approaches to scoring the Participation Assessment with Recombined Tools-Objective (PART-O) in a unidimensional scale. Retrospective analysis of PART-O data from the Traumatic Brain Injury Model Systems. Community. Data from individuals (N=469) selected randomly from participants who completed 1-year follow-up in the Traumatic Brain Injury Model Systems were used in Rasch model development. The model was subsequently tested on data from additional random samples of similar size at 1-, 2-, 5-, 10-, and >15-year follow-ups. Not applicable. PART-O. After combining items for productivity and social interaction, the initial analysis at 1-year follow-up indicated relatively good fit to the Rasch model (person reliability=.80) but also suggested item misfit and that the 0-to-5 scale used for most items did not consistently show clear separation between rating levels. Reducing item rating scales to 3 levels (except combined and dichotomous items) resolved these issues and demonstrated good item level discrimination, fit, and person reliability (.81), with no evidence of multidimensionality. These results replicated in analyses at each additional follow-up period. Modifications to item scoring for the PART-O resulted in a unidimensional parametric equivalent measure that addresses previous concerns about competing item relations, and it fit the Rasch model consistently across follow-up periods. The person-item map shows a progression toward greater community participation from solitary and dyadic activities, such as leaving the house and having a friend through social and productivity activities, to group activities with others who share interests or beliefs. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  20. Prognostic models for predicting posttraumatic seizures during acute hospitalization, and at 1 and 2 years following traumatic brain injury.

    Science.gov (United States)

    Ritter, Anne C; Wagner, Amy K; Szaflarski, Jerzy P; Brooks, Maria M; Zafonte, Ross D; Pugh, Mary Jo V; Fabio, Anthony; Hammond, Flora M; Dreer, Laura E; Bushnik, Tamara; Walker, William C; Brown, Allen W; Johnson-Greene, Doug; Shea, Timothy; Krellman, Jason W; Rosenthal, Joseph A

    2016-09-01

    Posttraumatic seizures (PTS) are well-recognized acute and chronic complications of traumatic brain injury (TBI). Risk factors have been identified, but considerable variability in who develops PTS remains. Existing PTS prognostic models are not widely adopted for clinical use and do not reflect current trends in injury, diagnosis, or care. We aimed to develop and internally validate preliminary prognostic regression models to predict PTS during acute care hospitalization, and at year 1 and year 2 postinjury. Prognostic models predicting PTS during acute care hospitalization and year 1 and year 2 post-injury were developed using a recent (2011-2014) cohort from the TBI Model Systems National Database. Potential PTS predictors were selected based on previous literature and biologic plausibility. Bivariable logistic regression identified variables with a p-value models. Multivariable logistic regression modeling with backward-stepwise elimination was used to determine reduced prognostic models and to internally validate using 1,000 bootstrap samples. Fit statistics were calculated, correcting for overfitting (optimism). The prognostic models identified sex, craniotomy, contusion load, and pre-injury limitation in learning/remembering/concentrating as significant PTS predictors during acute hospitalization. Significant predictors of PTS at year 1 were subdural hematoma (SDH), contusion load, craniotomy, craniectomy, seizure during acute hospitalization, duration of posttraumatic amnesia, preinjury mental health treatment/psychiatric hospitalization, and preinjury incarceration. Year 2 significant predictors were similar to those of year 1: SDH, intraparenchymal fragment, craniotomy, craniectomy, seizure during acute hospitalization, and preinjury incarceration. Corrected concordance (C) statistics were 0.599, 0.747, and 0.716 for acute hospitalization, year 1, and year 2 models, respectively. The prognostic model for PTS during acute hospitalization did not

  1. Physiological complexity of acute traumatic brain injury in patients treated with a brain oxygen protocol: utility of symbolic regression in predictive modeling of a dynamical system.

    Science.gov (United States)

    Narotam, Pradeep K; Morrison, John F; Schmidt, Michael D; Nathoo, Narendra

    2014-04-01

    Predictive modeling of emergent behavior, inherent to complex physiological systems, requires the analysis of large complex clinical data streams currently being generated in the intensive care unit. Brain tissue oxygen protocols have yielded outcome benefits in traumatic brain injury (TBI), but the critical physiological thresholds for low brain oxygen have not been established for a dynamical patho-physiological system. High frequency, multi-modal clinical data sets from 29 patients with severe TBI who underwent multi-modality neuro-clinical care monitoring and treatment with a brain oxygen protocol were analyzed. The inter-relationship between acute physiological parameters was determined using symbolic regression (SR) as the computational framework. The mean patient age was 44.4±15 with a mean admission GCS of 6.6±3.9. Sixty-three percent sustained motor vehicle accidents and the most common pathology was intra-cerebral hemorrhage (50%). Hospital discharge mortality was 21%, poor outcome occurred in 24% of patients, and good outcome occurred in 56% of patients. Criticality for low brain oxygen was intracranial pressure (ICP) ≥22.8 mm Hg, for mortality at ICP≥37.1 mm Hg. The upper therapeutic threshold for cerebral perfusion pressure (CPP) was 75 mm Hg. Eubaric hyperoxia significantly impacted partial pressure of oxygen in brain tissue (PbtO2) at all ICP levels. Optimal brain temperature (Tbr) was 34-35°C, with an adverse effect when Tbr≥38°C. Survivors clustered at [Formula: see text] Hg vs. non-survivors [Formula: see text] 18 mm Hg. There were two mortality clusters for ICP: High ICP/low PbtO2 and low ICP/low PbtO2. Survivors maintained PbtO2 at all ranges of mean arterial pressure in contrast to non-survivors. The final SR equation for cerebral oxygenation is: [Formula: see text]. The SR-model of acute TBI advances new physiological thresholds or boundary conditions for acute TBI management: PbtO2≥25 mmHg; ICP≤22 mmHg; CPP≈60-75

  2. Comparison of Two Predictive Models for Short-Term Mortality in Patients after Severe Traumatic Brain Injury.

    Science.gov (United States)

    Kesmarky, Klara; Delhumeau, Cecile; Zenobi, Marie; Walder, Bernhard

    2017-07-15

    The Glasgow Coma Scale (GCS) and the Abbreviated Injury Score of the head region (HAIS) are validated prognostic factors in traumatic brain injury (TBI). The aim of this study was to compare the prognostic performance of an alternative predictive model including motor GCS, pupillary reactivity, age, HAIS, and presence of multi-trauma for short-term mortality with a reference predictive model including motor GCS, pupil reaction, and age (IMPACT core model). A secondary analysis of a prospective epidemiological cohort study in Switzerland including patients after severe TBI (HAIS >3) with the outcome death at 14 days was performed. Performance of prediction, accuracy of discrimination (area under the receiver operating characteristic curve [AUROC]), calibration, and validity of the two predictive models were investigated. The cohort included 808 patients (median age, 56; interquartile range, 33-71), median GCS at hospital admission 3 (3-14), abnormal pupil reaction 29%, with a death rate of 29.7% at 14 days. The alternative predictive model had a higher accuracy of discrimination to predict death at 14 days than the reference predictive model (AUROC 0.852, 95% confidence interval [CI] 0.824-0.880 vs. AUROC 0.826, 95% CI 0.795-0.857; p predictive model had an equivalent calibration, compared with the reference predictive model Hosmer-Lemeshow p values (Chi2 8.52, Hosmer-Lemeshow p = 0.345 vs. Chi2 8.66, Hosmer-Lemeshow p = 0.372). The optimism-corrected value of AUROC for the alternative predictive model was 0.845. After severe TBI, a higher performance of prediction for short-term mortality was observed with the alternative predictive model, compared with the reference predictive model.

  3. A modified beam-walking apparatus for assessment of anxiety in a rodent model of blast traumatic brain injury.

    Science.gov (United States)

    Sweis, Brian M; Bachour, Salam P; Brekke, Julia A; Gewirtz, Jonathan C; Sadeghi-Bazargani, Homayoun; Hevesi, Mario; Divani, Afshin A

    2016-01-01

    The elevated plus maze (EPM) is used to assess anxiety in rodents. Beam-walking tasks are used to assess vestibulomotor function. Brain injury in rodents can disrupt performance on both of these tasks. Developing novel paradigms that integrate tasks like these can reduce the need for multiple tests when attempting to assess multiple behaviors in the same animal. Using adult male rats, we evaluated the use of a modified beam-walking (MBW) apparatus as a surrogate indicator for anxiety. We used a model of blast-induced traumatic brain injury (bTBI). A total of 39 rats were assessed before and at 3, 6, 24, 72, and 168h either post- bTBI (n=33) or no-injury (n=6) using both EPM and MBW. A novel anxiety index was calculated that encompassed peeks and re-emergences on MBW. The proposed MBW anxiety index was compared with the standard anxiety index calculated from exploration into different sections of EPM. Post- bTBI, rats had an increased anxiety index when measured using EPM. Similarly, they peeked or fully emerged less out of the safe box on MBW. It was found that this novel MBW anxiety index captured similar aspects of behavior when compared to the standard anxiety index obtained from EPM. Further, these effects were dissociated from the effects of bTBI on motor function simultaneously measured on MBW. Over the course of 168h post-bTBI, rats gradually recovered on both EPM and MBW. The MBW apparatus succeeded at capturing and dissociating two separate facets of rat behavior, motor function and anxiety, simultaneously. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Influence of post-traumatic stress disorder on neuroinflammation and cell proliferation in a rat model of traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    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

  5. Influence of post-traumatic stress disorder on neuroinflammation and cell proliferation in a rat model of traumatic brain injury.

    Science.gov (United States)

    Acosta, Sandra A; Diamond, David M; Wolfe, Steven; Tajiri, Naoki; Shinozuka, Kazutaka; Ishikawa, Hiroto; Hernandez, Diana G; Sanberg, Paul R; Kaneko, Yuji; Borlongan, Cesar V

    2013-01-01

    Long-term consequences of traumatic brain injury (TBI) are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD), yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long-term inflammation and suppressed

  6. Influence of Post-Traumatic Stress Disorder on Neuroinflammation and Cell Proliferation in a Rat Model of Traumatic Brain Injury

    Science.gov (United States)

    Diamond, David M.; Shinozuka, Kazutaka; Ishikawa, Hiroto; Hernandez, Diana G.; Sanberg, Paul R.; Kaneko, Yuji; Borlongan, Cesar V.

    2013-01-01

    Long-term consequences of traumatic brain injury (TBI) are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD), yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long-term inflammation and suppressed

  7. Hypopituitarism after traumatic brain injury.

    Science.gov (United States)

    Fernandez-Rodriguez, Eva; Bernabeu, Ignacio; Castro, Ana I; Casanueva, Felipe F

    2015-03-01

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Traumatic Brain Injury (TBI) in Kids

    Science.gov (United States)

    ... Information Share Facebook Twitter Pinterest Email Print Traumatic Brain Injury (TBI): Condition Information What is TBI? TBI ... external force that affects the functioning of the brain. It can be caused by a bump or ...

  9. Quality of Life Following Brain Injury: Perspectives from Brain Injury Association of America State Affiliates

    Science.gov (United States)

    Degeneffe, Charles Edmund; Tucker, Mark

    2012-01-01

    Objective: to examine the perspectives of brain injury professionals concerning family members' feelings about the quality of life experienced by individuals with brain injuries. Participants: participating in the study were 28 individuals in leadership positions with the state affiliates of the Brain Injury Association of America (BIAA). Methods:…

  10. Chronic issues related to traumatic brain injury : traumatic brain injury is not an incident

    NARCIS (Netherlands)

    Grauwmeijer, Erik; van der Naalt, Joukje; ribbers, gerard

    2016-01-01

    Despite an increased awareness of the long-term consequences of traumatic brain injury, health care professionals often consider traumatic brain injury as an incident. However, patients with traumatic brain injury may experience long-term neurological, cognitive and behavioural problems. Due to the

  11. Clinical significance of changes of serum IL-6 and TNF-α levels in rat models of hypoxic-ischemia brain injury

    International Nuclear Information System (INIS)

    Niu Tingxian; Shi Zhiyong; Luo Jianjun

    2009-01-01

    Objective: To explore the clinical significance of changes of serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels in rat models of hypoxic-ischemia (HI) brain injury. Methods: Seventy five rat HI brain injury nodels were prepared with bilateral occlusion of common carotid artery for 24rs followed 2hrs later by hypoxia (breathing 8% oxygen) for 2hrs. One fifth of the animals were sacrificed at 4h, 8h, 12h, 24h and 48h later respectively, the serum and brain homogenate concentrations of IL-6 and TNF-α were determined with RIA and brain tissues were pathologically examined. Results: The concentrations of IL-6 and TNF-α were dynamically changed within 48h in serum and brain homogenate. Peak values occurred at 24h with serum and at 12h with brain homogenate. Meanwhile, levels of both cytokines were significantly higher in the models than those in controls (P<0.01 or P<0.05). Conclusion: The concentrations of IL-6 and TNF-α were dynamically(sham operation only, 15 animals) changed and might be regarded as the clinical markers of degree of HI brain injury. (authors)

  12. Rehabilitation after traumatic brain injury.

    Science.gov (United States)

    Barnes, M P

    1999-01-01

    Head injury is a common disabling condition but regrettably facilities for rehabilitation are sparse. There is now increasing evidence of the efficacy of a comprehensive multidisciplinary rehabilitation team compared to natural recovery following brain injury. This chapter outlines some basic concepts of rehabilitation and emphasises the importance of valid and reliable outcome measures. The evidence of the efficacy of a rehabilitation programme is discussed in some detail. A number of specific rehabilitation problems are outlined including the management of spasticity, nutrition, pressure sores and urinary continence. The increasingly important role of assistive technology is illustrated, particularly in terms of communication aids and environmental control equipment. However, the major long-term difficulties after head injury focus around the cognitive, intellectual, behavioural and emotional problems. The complex management of these disorders is briefly addressed and the evidence of the efficacy of some techniques discussed. The importance of recognition of the vegetative stage and avoidance of misdiagnosis is emphasised. Finally, the important, but often neglected, area of employment rehabilitation is covered.

  13. Intracranial Monitoring after Severe Traumatic Brain Injury

    OpenAIRE

    Donnelly, Joseph

    2018-01-01

    Intracranial monitoring after severe traumatic brain injury offers the possibility for early detection and amelioration of physiological insults. In this thesis, I explore cerebral insults due raised intracranial pressure, decreased cerebral perfusion pressure and impaired cerebral pressure reactivity after traumatic brain injury. In chapter 2, the importance of intracranial pressure, cerebral perfusion pressure and pressure reactivity in regulating the cerebral circulation is elucidated ...

  14. PET imaging of neuroinflammation in a rat traumatic brain injury model with radiolabeled TSPO ligand DPA-714

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yu [Medical School of Southeast University, Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Nanjing (China); National Institutes of Health - NIH, Laboratory of Molecular Imaging and Nanomedicine - LOMIN, National Institute of Biomedical Imaging and Bioengineering - NIBIB, Bethesda, MD (United States); Yue, Xuyi; Kiesewetter, Dale O.; Niu, Gang; Chen, Xiaoyuan [National Institutes of Health - NIH, Laboratory of Molecular Imaging and Nanomedicine - LOMIN, National Institute of Biomedical Imaging and Bioengineering - NIBIB, Bethesda, MD (United States); Teng, Gaojun [Medical School of Southeast University, Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Nanjing (China)

    2014-07-15

    The inflammatory response in injured brain parenchyma after traumatic brain injury (TBI) is crucial in the pathological process. In order to follow microglia activation and neuroinflammation after TBI, we performed PET imaging in a rat model of TBI using {sup 18}F-labeled DPA-714, a ligand of the 18-kDa translocator protein (TSPO). TBI was induced in male SD rats by a controlled cortical impact. The success of the TBI model was confirmed by MRI. [{sup 18}F]DPA-714 was synthesized using a slightly modified TRACERLab FX-FN module and an automated procedure. In vivo PET imaging was performed at different time points after surgery using an Inveon small-animal PET scanner. The specificity of [{sup 18}F]DPA-714 was confirmed by a displacement study with an unlabeled competitive TSPO ligand, PK11195. Ex vivo autoradiography as well as immunofluorescence staining was carried out to confirm the in vivo PET results. Both in vivo T{sub 2}-weighted MR images and ex vivo TTC staining results revealed successful establishment of the TBI model. Compared with the sham-treated group, [{sup 18}F]DPA-714 uptake was significantly higher in the injured brain area on PET images. Increased lesion-to-normal ratios of [{sup 18}F]DPA-714 were observed in the brain of TBI rats on day 2 after surgery. Ratios peaked around day 6 (2.65 ± 0.36) and then decreased gradually to nearly normal levels on day 28. The displacement study using PK11195 confirmed the specific binding of [{sup 18}F]DPA-714 to TSPO. The results of ex vivo autoradiography were consistent with in vivo PET results. Immunofluorescence staining showed the time course of TSPO expression after TBI and the temporal and the spatial distribution of microglia in the damaged brain area. TSPO-targeted PET using [{sup 18}F]DPA-714 as the imaging probe can be used to dynamically monitor the inflammatory response after TBI in a noninvasive manner. This method will not only facilitate a better understanding of the inflammatory process

  15. Effect of AVP on brain edema following traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    XU Miao; SU Wei; HUANG Wei-dong; LU Yuan-qiang; XU Qiu-ping; CHEN Zhao-jun

    2007-01-01

    Objective: To evaluate plasma arginine vasopressin (AVP) level in patients with traumatic brain injury and investigate the role of AVP in the process of brain edema. Methods: A total of 30 patients with traumatic brain injury were involved in our study. They were divided into two groups by Glasgow Coma Scale: severe traumatic brain injury group (STBI, GCS≤ 8) and moderate traumatic brain injury group (MTBI, GCS>8).Samples of venous blood were collected in the morning at rest from 15 healthy volunteers (control group)and within 24 h after traumatic brain injury from these patients for AVP determinations by radioimmunoassay. The severity and duration of the brain edema were estimated by head CT scan.Results: plasma AVP levels (ng/L) were (mean±SD): control, 3.06±1.49; MTBI, 38.12±7.25; and STBI, 66.61±17.10.The plasma level of AVP was significantly increased within 24 h after traumatic brain injury and followed by the reduction of GCS, suggesting the deterioration of cerebral injury (P<0.01). And the AVP level was correlated with the severity (STBI r=0.919, P<0.01; MTBI r=0.724, P<0.01) and the duration of brain edema (STBI r=0.790, P<0.01; MTBI r=0.712, P<0.01). Conclusions: The plasma AVP level is closely associated with the severity of traumatic brain injury. AVP may play an important role in pathogenesis of brain edema after traumatic brain injury.

  16. Characterization and Application of a Large Animal Model of Penetrating Ballistic Brain Injury (PBBI)

    Science.gov (United States)

    2012-03-01

    Jump, South American Track and Field Grand Prix. Cuenca, Ecuador , 2004. - Goodwill Ambassador, Ministry of Tourism of Ecuador . Quito, Ecuador , 2000...they only comprise 11.5% of all-cause injury deaths and have a case fatality rate (CFR) of less than 1% [33]. In contrast, penetrating TBIs due to...because many cases of mild closed TBI are not detected post-injury and because the bodily distribution of wounds for all combat casualties (e.g. Wounded In

  17. A novel rat model of blast-induced traumatic brain injury simulating different damage degree: implications for morphological, neurological, and biomarker changes

    Directory of Open Access Journals (Sweden)

    Mengdong eLiu

    2015-05-01

    Full Text Available In current military conflicts and civilian terrorism, blast-induced traumatic brain injury (bTBI is the primary cause of neurotrauma. However, the effects and mechanisms of bTBI are poorly understood. Although previous researchers have made significant contributions to establishing animal models for the simulation of bTBI, the precision and controllability of blast-induced injury in animal models must be improved. Therefore, we established a novel rat model to simulate blast-wave injury to the brain. To simulate different extents of bTBI injury, the animals were divided into moderate and severe injury groups. The miniature spherical explosives (PETN used in each group were of different sizes (2.5 mm diameter in the moderate injury group and 3.0 mm diameter in the severe injury group. A specially designed apparatus was able to precisely adjust the positions of the miniature explosives and create eight rats with bTBI simultaneously, using a single electric detonator. Neurological functions, gross pathologies, histopathological changes and the expression levels of various biomarkers were examined after the explosion. Compared with the moderate injury group, there were significantly more neurological dysfunctions, cortical contusions, intraparenchymal hemorrhages, cortical expression of S-100β, MBP, NSE, IL-8, IL-10, iNOS and HIF-1α in the severe injury group. These results demonstrate that we have created a reliable and reproducible bTBI model in rats. This model will be helpful for studying the mechanisms of bTBI and developing strategies for clinical bTBI treatment.

  18. Respiratory mechanics in brain injury: A review

    OpenAIRE

    Koutsoukou, Antonia; Katsiari, Maria; Orfanos, Stylianos E; Kotanidou, Anastasia; Daganou, Maria; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Rovina, Nikoletta

    2016-01-01

    Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients (BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case ...

  19. Traumatic Brain Injury in Kenya

    Directory of Open Access Journals (Sweden)

    Benson Kinyanjui

    2016-03-01

    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.

  20. Neuroprotective effects of ebselen in traumatic brain injury model: involvement of nitric oxide and p38 mitogen-activated protein kinase signalling pathway.

    Science.gov (United States)

    Wei, Liang; Zhang, Yanfei; Yang, Cheng; Wang, Qi; Zhuang, Zhongwei; Sun, Zhiyang

    2014-02-01

    Previous investigations have found that ebselen is able to treat neurodegenerative diseases caused by radical and acute total cerebral ischaemia. The aim of the present study was to investigate the neuroprotective effects of ebselen in a traumatic brain injury (TBI) model. Ninety Sprague-Dawley rats were randomly divided into five groups (n = 18 in each): (i) sham operation; (ii) an injury model group; (iii) low-dose (3 mg/kg) ebselen-treated group; (iv) a moderate-dose (10 mg/kg) ebselen-treated group; and (v) a high-dose (30 mg/kg) ebselen-treated group. The TBI model was created according using a modified weight-drop model. Neurological severity score (NSS), brain water content and histopathological deficits were assessed as parameters of injury severity. Expression of nitric oxide (NO), inducible NO synthase (iNOS) mRNA, Toll-like receptor (TLR) and phosphorylated (p-) p38 mitogen-activated protein kinase (MAPK) were examined by chemical colorimetry, quantitative polymerase chain reaction and western blotting 24 h after intragastric ebselen administration. Rats in the TBI model group exhibited markedly more severe neurological injury (higher NSS, more brain water content and more histopathological deficits) than those in the sham-operated group. Ebselen treatment significantly ameliorated the neurological injury of TBI rats in a dose-dependent manner. Moreover, ebselen significantly reduced the NO and iNOS mRNA levels and inhibited TLR4 and p-p38 MAPK expression, indicating the involvement of NO and p38 MAPK signalling pathways in the neuroprotection afforded by ebselen. In conclusion, ebselen ameliorated neurological injury, possibly by reducing NO levels and modulating the TLR4-mediated p38 MAPK signalling pathway. Therefore, ebselen may have potential to treat secondary injuries of TBI. © 2013 Wiley Publishing Asia Pty Ltd.

  1. Therapeutic Sleep for Traumatic Brain Injury

    Science.gov (United States)

    2017-06-01

    AWARD NUMBER: W81XWH-16-1-0166 TITLE: Therapeutic Sleep for Traumatic Brain Injury PRINCIPAL INVESTIGATOR: Ravi Allada CONTRACTING...1. REPORT DATE June 2017 2. REPORT TYPE Annual 3. DATES COVERED 1June2016 - 31May2017 4. TITLE AND SUBTITLE Therapeutic Sleep for Traumatic Brain ...proposal will test the hypothesis that correcting sleep disorders can have a therapeutic effect onTraumatic Brain Injury (TBI) The majority of TBI

  2. Synergistic effects of fresh frozen plasma and valproic acid treatment in a combined model of traumatic brain injury and hemorrhagic shock

    DEFF Research Database (Denmark)

    Imam, Ayesha M; Jin, Guang; Duggan, Michael

    2013-01-01

    Traumatic brain injury (TBI) and hemorrhagic shock (HS) are major causes of trauma-related deaths and are especially lethal as a combined insult. Previously, we showed that early administration of fresh frozen plasma (FFP) decreased the size of the brain lesion and associated swelling in a swine...... model of combined TBI+HS. We have also shown separately that addition of valproic acid (VPA) to the resuscitation protocol attenuates inflammatory markers in the brain as well as the degree of TBI. The current study was performed to determine whether a combined FFP+VPA treatment strategy would exert...

  3. Spreading depolarizations increase delayed brain injury in a rat model of subarachnoid hemorrhage

    NARCIS (Netherlands)

    Hamming, Arend M.; Wermer, Marieke J. H.; Rudrapatna, S. Umesh; Lanier, Christian; van Os, Hine J. A.; van den Bergh, Walter M.; Ferrari, Michel D.; van der Toorn, Annette; van den Maagdenberg, Arn M. J. M.; Stowe, Ann M.; Dijkhuizen, Rick M.

    Spreading depolarizations may contribute to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage, but the effect of spreading depolarizations on brain lesion progression after subarachnoid hemorrhage has not yet been assessed directly. Therefore, we tested the hypothesis that

  4. Mild closed head traumatic brain injury-induced changes in monoamine neurotransmitters in the trigeminal subnuclei of a rat model: mechanisms underlying orofacial allodynias and headache

    Directory of Open Access Journals (Sweden)

    Golam Mustafa

    2017-01-01

    Full Text Available Our recent findings have demonstrated that rodent models of closed head traumatic brain injury exhibit comprehensive evidence of progressive and enduring orofacial allodynias, a hypersensitive pain response induced by non-painful stimulation. These allodynias, tested using thermal hyperalgesia, correlated with changes in several known pain signaling receptors and molecules along the trigeminal pain pathway, especially in the trigeminal nucleus caudalis. This study focused to extend our previous work to investigate the changes in monoamine neurotransmitter immunoreactivity changes in spinal trigeminal nucleus oralis, pars interpolaris and nucleus tractus solitaries following mild to moderate closed head traumatic brain injury, which are related to tactile allodynia, touch-pressure sensitivity, and visceral pain. Our results exhibited significant alterations in the excitatory monoamine, serotonin, in spinal trigeminal nucleus oralis and pars interpolaris which usually modulate tactile and mechanical sensitivity in addition to the thermal sensitivity. Moreover, we also detected a robust alteration in the expression of serotonin, and inhibitory molecule norepinephrine in the nucleus tractus solitaries, which might indicate the possibility of an alteration in visceral pain, and existence of other morbidities related to solitary nucleus dysfunction in this rodent model of mild to moderate closed head traumatic brain injury. Collectively, widespread changes in monoamine neurotransmitter may be related to orofacial allodynhias and headache after traumatic brain injury.

  5. Fresh Frozen Plasma Resuscitation Provides Neuroprotection Compared to Normal Saline in a Large Animal Model of Traumatic Brain Injury and Polytrauma

    DEFF Research Database (Denmark)

    Imam, Ayesha; Jin, Guang; Sillesen, Martin

    2015-01-01

    Abstract We have previously shown that early treatment with fresh frozen plasma (FFP) is neuroprotective in a swine model of hemorrhagic shock (HS) and traumatic brain injury (TBI). However, it remains unknown whether this strategy would be beneficial in a more clinical polytrauma model. Yorkshire...... as well as cerebral perfusion pressures. Levels of cerebral eNOS were higher in the FFP-treated group (852.9 vs. 816.4 ng/mL; p=0.03), but no differences in brain levels of ET-1 were observed. Early administration of FFP is neuroprotective in a complex, large animal model of polytrauma, hemorrhage...

  6. Elevated lactate as an early marker of brain injury in inflicted traumatic brain injury

    International Nuclear Information System (INIS)

    Makoroff, Kathi L.; Cecil, Kim M.; Ball, William S.; Care, Marguerite

    2005-01-01

    Patients with inflicted traumatic brain injury and evidence of hypoxic-ischemic injury as indicated by elevated lactate on MRS tend to have worse early neurological status and early outcome scores. Lactate levels as sampled by MRS might predict early clinical outcome in inflicted traumatic brain injury. (orig.)

  7. Student perspectives of a Student-Led Groups Program model of professional practice education in a brain injury rehabilitation unit.

    Science.gov (United States)

    Patterson, Freyr; Fleming, Jennifer; Marshall, Kathryn; Ninness, Nadine

    2017-10-01

    Professional practice education is a core and essential component of occupational therapy training. With increasing numbers of education programmes and more students requiring professional practice placements, development of innovative models of professional practice education has emerged, but these require investigation. The aim of this study was to investigate student experiences and perceptions of the Student-Led Groups Program model of professional practice education in an inpatient brain injury rehabilitation unit. A qualitative approach, guided by phenomenological theory was used. Participants were 15 students who had completed a professional practice placement in the Student-Led Groups Program. Data were collected using in-depth semi-structured interviews and analysed thematically. Three over-arching themes emerged from the data; balance of support and freedom, development of clinical skills and missed opportunities. Students described how the structure of the placement facilitated independent learning and autonomy that was balanced with support from clinicians and student peers. Students perceived that they had developed a breadth of clinical skills and also had missed some learning opportunities in this professional practice placement structure. Overall student perceptions of the Student-Led Groups Program were positive, supporting the continued use of this model of professional practice education in this setting. The results highlight the value of structured and consistent approaches for supervision, including the use of formal approaches to peer supervision in the initial stages of learning. © 2017 Occupational Therapy Australia.

  8. Linking blast physics to biological outcomes in mild traumatic brain injury: Narrative review and preliminary report of an open-field blast model.

    Science.gov (United States)

    Song, Hailong; Cui, Jiankun; Simonyi, Agnes; Johnson, Catherine E; Hubler, Graham K; DePalma, Ralph G; Gu, Zezong

    2018-03-15

    Blast exposures are associated with traumatic brain injury (TBI) and blast-induced TBIs are common injuries affecting military personnel. Department of Defense and Veterans Administration (DoD/VA) reports for TBI indicated that the vast majority (82.3%) has been mild TBI (mTBI)/concussion. mTBI and associated posttraumatic stress disorders (PTSD) have been called "the invisible injury" of the current conflicts in Iraq and Afghanistan. These injuries induce varying degrees of neuropathological alterations and, in some cases, chronic cognitive, behavioral and neurological disorders. Appropriate animal models of blast-induced TBI will not only assist the understanding of physical characteristics of the blast, but also help to address the potential mechanisms. This report provides a brief overview of physical principles of blast, injury mechanisms related to blast exposure, current blast animal models, and the neurological behavioral and neuropathological findings related to blast injury in experimental settings. We describe relationships between blast peak pressures and the observed injuries. We also report preliminary use of a highly reproducible and intensity-graded blast murine model carried out in open-field with explosives, and describe physical and pathological findings in this experimental model. Our results indicate close relationships between blast intensities and neuropathology and behavioral deficits, particularly at low level blast intensities relevant to mTBI. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Development of brain injury criteria (BrIC).

    Science.gov (United States)

    Takhounts, Erik G; Craig, Matthew J; Moorhouse, Kevin; McFadden, Joe; Hasija, Vikas

    2013-11-01

    Rotational motion of the head as a mechanism for brain injury was proposed back in the 1940s. Since then a multitude of research studies by various institutions were conducted to confirm/reject this hypothesis. Most of the studies were conducted on animals and concluded that rotational kinematics experienced by the animal's head may cause axonal deformations large enough to induce their functional deficit. Other studies utilized physical and mathematical models of human and animal heads to derive brain injury criteria based on deformation/pressure histories computed from their models. This study differs from the previous research in the following ways: first, it uses two different detailed mathematical models of human head (SIMon and GHBMC), each validated against various human brain response datasets; then establishes physical (strain and stress based) injury criteria for various types of brain injury based on scaled animal injury data; and finally, uses Anthropomorphic Test Devices (ATDs) (Hybrid III 50th Male, Hybrid III 5th Female, THOR 50th Male, ES-2re, SID-IIs, WorldSID 50th Male, and WorldSID 5th Female) test data (NCAP, pendulum, and frontal offset tests) to establish a kinematically based brain injury criterion (BrIC) for all ATDs. Similar procedures were applied to college football data where thousands of head impacts were recorded using a six degrees of freedom (6 DOF) instrumented helmet system. Since animal injury data used in derivation of BrIC were predominantly for diffuse axonal injury (DAI) type, which is currently an AIS 4+ injury, cumulative strain damage measure (CSDM) and maximum principal strain (MPS) were used to derive risk curves for AIS 4+ anatomic brain injuries. The AIS 1+, 2+, 3+, and 5+ risk curves for CSDM and MPS were then computed using the ratios between corresponding risk curves for head injury criterion (HIC) at a 50% risk. The risk curves for BrIC were then obtained from CSDM and MPS risk curves using the linear relationship

  10. SCI with Brain Injury: Bedside to Bench Modeling for Developing Treatment and Rehabilitation Strategies

    Science.gov (United States)

    2013-10-01

    provide a new tool for studying the biological mechanisms involved, and to open new directions for therapeutics for combined injury. We initially...System (VAPAHCS). During the project, a teleconferencing system was established to facilitate communication among the study sites, and all... DYSPHAGIA 787.2 1, 4, 8, 9, 11, 12, 13 8 Patients were coded with a variety of ICD-9 codes, and individual patients were often coded with more than one

  11. Diffuse and Focal Brain Injury in a Large Animal Model of PTE: Mechanisms Underlying Epileptogenesis

    Science.gov (United States)

    2017-10-01

    nine months post injury, and blood biomarkers are being analyzed throughout in order to evaluate them as potential prognostic measures for the...pm en t o f P TE . •A im 2 : El uc id at e th e ci rc ui try a lte ra tio ns u nd er ly in g hy pe re xc ita bi lit y an d ep ile pt og en es

  12. Erythropoietin Restores Long-Term Neurocognitive Function Involving Mechanisms of Neuronal Plasticity in a Model of Hyperoxia-Induced Preterm Brain Injury

    Directory of Open Access Journals (Sweden)

    Daniela Hoeber

    2016-01-01

    Full Text Available Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules. A single dose of erythropoietin (20,000 IU/kg at the onset of hyperoxia (24 hours, 80% oxygen in 6-day-old Wistar rats improved long-lasting neurocognitive development up to the adolescent and adult stage. Analysis of white matter structures revealed a reduction of acute oligodendrocyte degeneration. However, erythropoietin did not influence hypomyelination occurring a few days after injury or long-term microstructural white matter abnormalities detected in adult animals. Erythropoietin administration reverted hyperoxia-induced reduction of neuronal plasticity-related mRNA expression up to four months after injury. Thus, our findings highlight the importance of erythropoietin as a neuroregenerative treatment option in neonatal brain injury, leading to improved memory function in adolescent and adult rats which may be linked to increased neuronal network connectivity.

  13. Modeling Pediatric Brain Trauma: Piglet Model of Controlled Cortical Impact.

    Science.gov (United States)

    Pareja, Jennifer C Munoz; Keeley, Kristen; Duhaime, Ann-Christine; Dodge, Carter P

    2016-01-01

    The brain has different responses to traumatic injury as a function of its developmental stage. As a model of injury to the immature brain, the piglet shares numerous similarities in regards to morphology and neurodevelopmental sequence compared to humans. This chapter describes a piglet scaled focal contusion model of traumatic brain injury that accounts for the changes in mass and morphology of the brain as it matures, facilitating the study of age-dependent differences in response to a comparable mechanical trauma.

  14. Evaluation of cerebral-cardiac syndrome using echocardiography in a canine model of acute traumatic brain injury.

    Science.gov (United States)

    Qian, Rong; Yang, Weizhong; Wang, Xiumei; Xu, Zhen; Liu, Xiaodong; Sun, Bing

    2015-01-01

    Previous studies have confirmed that traumatic brain injury (TBI) can induce general adaptation syndrome (GAS), which subsequently results in myocardial dysfunction and damage in some patients with acute TBI; this condition is also termed as cerebral-cardiac syndrome. However, most clinicians ignore the detection and treatment of myocardial dysfunction, and instead concentrate only on the serious neural damage that is observed in acute TBI, which is one of the most important fatal factors. Therefore, clarification is urgently needed regarding the relationship between TBI and myocardial dysfunction. In the present study, we evaluated 18 canine models of acute TBI, by using real-time myocardial contrast echocardiography and strain rate imaging to accurately evaluate myocardial function and regional microcirculation, including the strain rate of the different myocardial segments, time-amplitude curves, mean ascending slope of the curve, and local myocardial blood flow. Our results suggest that acute TBI often results in cerebral-cardiac syndrome, which rapidly progresses to the serious stage within 3 days. This study is the first to provide comprehensive ultrasonic characteristics of cerebral-cardiac syndrome in an animal model of TBI.

  15. Pharmacologic resuscitation for hemorrhagic shock combined with traumatic brain injury

    DEFF Research Database (Denmark)

    Jin, Guang; Duggan, Michael; Imam, Ayesha

    2012-01-01

    [Hex]) after traumatic brain injury (TBI) decreases brain swelling, without affecting size of the lesion. This study was performed to determine whether addition of VPA to Hex would decrease the lesion size in a clinically relevant large animal model of TBI + HS....

  16. Comprehensive Evaluation of Neuroprotection Achieved by Extended Selective Brain Cooling Therapy in a Rat Model of Penetrating Ballistic-Like Brain Injury

    Science.gov (United States)

    Shear, Deborah A.; Deng-Bryant, Ying; Leung, Lai Yee; Wei, Guo; Chen, Zhiyong; Tortella, Frank C.

    2016-01-01

    Brain hypothermia has been considered as a promising alternative to whole-body hypothermia in treating acute neurological disease, for example, traumatic brain injury. Previously, we demonstrated that 2-hours selective brain cooling (SBC) effectively mitigated acute (≤24 hours postinjury) neurophysiological dysfunction induced by a penetrating ballistic-like brain injury (PBBI) in rats. This study evaluated neuroprotective effects of extended SBC (4 or 8 hours in duration) on sub-acute secondary injuries between 3 and 21 days postinjury (DPI). SBC (34°C) was achieved via extraluminal cooling of rats' bilateral common carotid arteries (CCA). Depending on the experimental design, SBC was introduced either immediately or with a 2- or 4-hour delay after PBBI and maintained for 4 or 8 hours. Neuroprotective effects of SBC were evaluated by measuring brain lesion volume, axonal injury, neuroinflammation, motor and cognitive functions, and post-traumatic seizures. Compared to untreated PBBI animals, 4 or 8 hours SBC treatment initiated immediately following PBBI produced comparable neuroprotective benefits against PBBI-induced early histopathology at 3 DPI as evidenced by significant reductions in brain lesion volume, axonal pathology (beta-amyloid precursor protein staining), neuroinflammation (glial fibrillary acetic protein stained-activated astrocytes and rat major histocompatibility complex class I stained activated microglial cell), and post-traumatic nonconvulsive seizures. In the later phase of the injury (7–21 DPI), significant improvement on motor function (rotarod test) was observed under most SBC protocols, including the 2-hour delay in SBC initiation. However, SBC treatment failed to improve cognitive performance (Morris water maze test) measured 13–17 DPI. The protective effects of SBC on delayed axonal injury (silver staining) were evident out to 14 DPI. In conclusion, the CCA cooling method of SBC produced neuroprotection measured across multiple

  17. 45 CFR 1308.16 - Eligibility criteria: Traumatic brain injury.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Eligibility criteria: Traumatic brain injury. 1308... DISABILITIES Health Services Performance Standards § 1308.16 Eligibility criteria: Traumatic brain injury. A child is classified as having traumatic brain injury whose brain injuries are caused by an external...

  18. Fatigue in adults with traumatic brain injury

    DEFF Research Database (Denmark)

    Mollayeva, Tatyana; Kendzerska, Tetyana; Mollayeva, Shirin

    2013-01-01

    BACKGROUND: Despite strong indications that fatigue is the most common and debilitating symptom after traumatic brain injury, little is known about its frequency, natural history, or relation to other factors. The current protocol outlines a strategy for a systematic review that will identify......, assess, and critically appraise studies that assessed predictors for fatigue and the consequences of fatigue on at least two separate time points following traumatic brain injury. METHODS/DESIGN: MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, CINAHL, and PsycINFO will be systematically...... searched for relevant peer-reviewed studies. Reference lists of eligible papers will also be searched. All English language studies with a longitudinal design that focus on fatigue in adults with primary-impact traumatic brain injury will be included. Studies on fatigue following brain injury due...

  19. Traumatic Brain Injury (TBI) Data and Statistics

    Science.gov (United States)

    ... TBI Online Concussion Training Press Room Guide to Writing about TBI in News and Social Media Living with TBI HEADS UP to Brain Injury Awareness Get Email Updates To receive email updates about this topic, ...

  20. Traumatic Brain Injury service (TBI) Service

    Data.gov (United States)

    Department of Veterans Affairs — This Service provides access to Tramatic Brain injury patient data consult notes. The service also provides one write service method writeNote. The Service supports...

  1. Hypocretinergic and cholinergic contributions to sleep-wake disturbances in a mouse model of traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Hannah E. Thomasy

    2017-01-01

    Full Text Available Disorders of sleep and wakefulness occur in the majority of individuals who have experienced traumatic brain injury (TBI, with increased sleep need and excessive daytime sleepiness often reported. Behavioral and pharmacological therapies have limited efficacy, in part, because the etiology of post-TBI sleep disturbances is not well understood. Severity of injuries resulting from head trauma in humans is highly variable, and as a consequence so are their sequelae. Here, we use a controlled laboratory model to investigate the effects of TBI on sleep-wake behavior and on candidate neurotransmitter systems as potential mediators. We focus on hypocretin and melanin-concentrating hormone (MCH, hypothalamic neuropeptides important for regulating sleep and wakefulness, and two potential downstream effectors of hypocretin actions, histamine and acetylcholine. Adult male C57BL/6 mice (n=6–10/group were implanted with EEG recording electrodes and baseline recordings were obtained. After baseline recordings, controlled cortical impact was used to induce mild or moderate TBI. EEG recordings were obtained from the same animals at 7 and 15 days post-surgery. Separate groups of animals (n=6–8/group were used to determine effects of TBI on the numbers of hypocretin and MCH-producing neurons in the hypothalamus, histaminergic neurons in the tuberomammillary nucleus, and cholinergic neurons in the basal forebrain. At 15 days post-TBI, wakefulness was decreased and NREM sleep was increased during the dark period in moderately injured animals. There were no differences between groups in REM sleep time, nor were there differences between groups in sleep during the light period. TBI effects on hypocretin and cholinergic neurons were such that more severe injury resulted in fewer cells. Numbers of MCH neurons and histaminergic neurons were not altered under the conditions of this study. Thus, we conclude that moderate TBI in mice reduces wakefulness and increases

  2. Does preliminary optimisation of an anatomically correct skull-brain model using simple simulants produce clinically realistic ballistic injury fracture patterns?

    Science.gov (United States)

    Mahoney, P F; Carr, D J; Delaney, R J; Hunt, N; Harrison, S; Breeze, J; Gibb, I

    2017-07-01

    Ballistic head injury remains a significant threat to military personnel. Studying such injuries requires a model that can be used with a military helmet. This paper describes further work on a skull-brain model using skulls made from three different polyurethane plastics and a series of skull 'fills' to simulate brain (3, 5, 7 and 10% gelatine by mass and PermaGel™). The models were subjected to ballistic impact from 7.62 × 39 mm mild steel core bullets. The first part of the work compares the different polyurethanes (mean bullet muzzle velocity of 708 m/s), and the second part compares the different fills (mean bullet muzzle velocity of 680 m/s). The impact events were filmed using high speed cameras. The resulting fracture patterns in the skulls were reviewed and scored by five clinicians experienced in assessing penetrating head injury. In over half of the models, one or more assessors felt aspects of the fracture pattern were close to real injury. Limitations of the model include the skull being manufactured in two parts and the lack of a realistic skin layer. Further work is ongoing to address these.

  3. Spinal cord injury drives chronic brain changes

    Directory of Open Access Journals (Sweden)

    Ignacio Jure

    2017-01-01

    Full Text Available Only a few studies have considered changes in brain structures other than sensory and motor cortex after spinal cord injury, although cognitive impairments have been reported in these patients. Spinal cord injury results in chronic brain neuroinflammation with consequent neurodegeneration and cognitive decline in rodents. Regarding the hippocampus, neurogenesis is reduced and reactive gliosis increased. These long-term abnormalities could explain behavioral impairments exhibited in humans patients suffering from spinal cord trauma.

  4. Understanding Traumatic Brain Injury: An Introduction

    Science.gov (United States)

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

    2009-01-01

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

  5. Traumatic Brain Injury: Looking Back, Looking Forward

    Science.gov (United States)

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

    2011-01-01

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

  6. [Brain injury knowledge in family members of neurosurgical patients].

    Science.gov (United States)

    Navarro-Main, Blanca; Castaño-León, Ana M; Munarriz, Pablo M; Gómez, Pedro A; Rios-Lago, Marcos; Lagares, Alfonso

    Several studies have shown misconceptions about brain injury in different populations. The aim of this study was to assess the knowledge and perceptions about brain injury of family members of neurosurgical patients in our hospital. The participants (n=81) were relatives of patients admitted to the neurosurgery department between February and August 2016. They voluntarily completed a 19-item true-false format survey about brain injury based on a translation of other questionnaires used in previous studies from other countries (USA, Canada, UK, Ireland and New Zealand). Also, some sociodemographic data were collected (age, sex, education level and the patient's pathology). Data analysis was developed through graphical modelling with a regularisation parameter plotted on a network representing the association of the items of the questionnaire from the response pattern of participants. Data analysis showed two conceptual areas with a high rate of wrong answers: behaviour and management of patients, and expectations about acquired brain injury recovery. The results obtained in this study would enable us to objectify misconceptions about acquired brain injury in patients' relatives attended in the neurosurgery department. This lack of knowledge could be a great obstacle in patients' recovery process. Therefore, we suggest placing the emphasis on the provision of information on brain injury to patients' families, especially with regard to its symptoms and course of development. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Neuropsychological rehabilitation for traumatic brain injury patients

    Directory of Open Access Journals (Sweden)

    Marzena Chantsoulis

    2015-05-01

    Full Text Available The aim of this review is to discuss the basic forms of neuropsychological rehabilitation for patients with traumatic brain injury (TBI. More broadly, we discussed cognitive rehabilitation therapy (CRT which constitutes a fundamental component in therapeutic interaction at many centres worldwide. Equally presented is a comprehensive model of rehabilitation, the fundamental component of which is CRT. It should be noted that the principles of this approach first arose in Poland in the 1970s, in other words, several decades before their appearance in other programmemes. Taken into consideration are four factors conditioning the effectiveness of such a process: comprehensiveness, earlier interaction, universality and its individualized character. A comprehensive programmeme of rehabilitation covers: cognitive rehabilitation, individual and group rehabilitation with the application of a therapeutic environment, specialist vocational rehabilitation, as well as family psychotherapy. These training programmemes are conducted within the scope of the ‘Academy of Life,’ which provides support for the patients in their efforts and shows them the means by which they can overcome existing difficulties. Equally emphasized is the close cooperation of the whole team of specialists, as well as the active participation of the family as an essential condition for the effectiveness of rehabilitation and, in effect, a return of the patient to a relatively normal life. Also presented are newly developing neurothechnologies and the neuromarkers of brain injuries. This enables a correct diagnosis to be made and, as a result, the selection of appropriate methods for neuropsychological rehabilitation, including neurotherapy.

  8. Attenuated traumatic axonal injury and improved functional outcome after traumatic brain injury in mice lacking Sarm1.

    Science.gov (United States)

    Henninger, Nils; Bouley, James; Sikoglu, Elif M; An, Jiyan; Moore, Constance M; King, Jean A; Bowser, Robert; Freeman, Marc R; Brown, Robert H

    2016-04-01

    Axonal degeneration is a critical, early event in many acute and chronic neurological disorders. It has been consistently observed after traumatic brain injury, but whether axon degeneration is a driver of traumatic brain injury remains unclear. Molecular pathways underlying the pathology of traumatic brain injury have not been defined, and there is no efficacious treatment for traumatic brain injury. Here we show that mice lacking the mouse Toll receptor adaptor Sarm1 (sterile α/Armadillo/Toll-Interleukin receptor homology domain protein) gene, a key mediator of Wallerian degeneration, demonstrate multiple improved traumatic brain injury-associated phenotypes after injury in a closed-head mild traumatic brain injury model. Sarm1(-/-) mice developed fewer β-amyloid precursor protein aggregates in axons of the corpus callosum after traumatic brain injury as compared to Sarm1(+/+) mice. Furthermore, mice lacking Sarm1 had reduced plasma concentrations of the phophorylated axonal neurofilament subunit H, indicating that axonal integrity is maintained after traumatic brain injury. Strikingly, whereas wild-type mice exibited a number of behavioural deficits after traumatic brain injury, we observed a strong, early preservation of neurological function in Sarm1(-/-) animals. Finally, using in vivo proton magnetic resonance spectroscopy we found tissue signatures consistent with substantially preserved neuronal energy metabolism in Sarm1(-/-) mice compared to controls immediately following traumatic brain injury. Our results indicate that the SARM1-mediated prodegenerative pathway promotes pathogenesis in traumatic brain injury and suggest that anti-SARM1 therapeutics are a viable approach for preserving neurological function after traumatic brain injury. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. TRAUMATIC BRAIN INJURY CHILDREN: A LITERATURE REVIEW

    Directory of Open Access Journals (Sweden)

    Denismar Borges de Miranda

    2013-09-01

    Full Text Available Objective: to know the scientific literature on head injury in children. Method: this study is an integrative review of published articles in the database SciELO the period 2000-2010. Results: 10 articles were analyzed, from which emerged four categories: causes of traumatic brain child infant prognosis of traumatic brain child, treating children victims of child head injury and complications of therapy used for child victims of traumatic brain injury in children. Conclusions: there is consensus among the authors investigated the factors associated with better prognosis of traumatic brain child, remain vague and uncertain. They add that the success of this customer service related to the control of complications arising from cerebral trauma and mostly are treatable and / or preventable.

  10. Development of a human head FE model for the impact analysis using VOXEL approach and simulation for the assessment on the focal brain injury

    International Nuclear Information System (INIS)

    Watanabe, Dai; Yuge, Kohei; Nishimoto, Tetsuya; Murakami, Shigeyuki; Takao, Hiroyuki

    2008-01-01

    In this paper, a three-dimensional digital human-head model was developed and several dynamic analyses on the head trauma were conducted. This model was built up by the VOXEL approach using 433 slice CT images (512 x 512 pixels) and made of 1.22 million parallelepiped finite elements with 10 anatomical tissue properties such as scalp, cerebrospinal fluid (CSF), skull, brain, dura mater and so on. The numerical analyses were conducted using a finite element code the authors have developed. The main features of the code are it is based on the explicit time integration method and it uses the one point integration method to evaluate the equivalent nodal forces with the hourglass control proposed by Flanagan and Belythcko and it utilizes the parallel computation with the Massage Passing Interface (MPI). In order to verify the developed model, the head impact experiment for a cadaver by Nahum et al. was simulated. The calculated results showed good agreement with experimental ones. A front and rear impact analyses were also performed investigate the relation between the impact direction and the positions of the high measurement of pressure and stresses in brain. The obtained results represent that brain injury has a closer relation with the Mises equivalent stress rather than the pressure. At this time, the large deformation of a frontal cranial base was observed in both frontal and occipital impact analyses. We expect that it induces the brain injury in a frontal lobe regardless of the impact positions. (author)

  11. A Novel Closed-head Model of Mild Traumatic Brain Injury Caused by Primary Overpressure Blast to the Cranium Produces Sustained Emotional Deficits in Mice

    Directory of Open Access Journals (Sweden)

    Scott A Heldt

    2014-01-01

    Full Text Available Emotional disorders are a common outcome from mild traumatic brain injury (TBI in humans, but their pathophysiological basis is poorly understood. We have developed a mouse model of closed-head blast injury using an air pressure wave delivered to a small area on one side of the cranium, which we have used to create mild TBI. We found that 20-psi blasts in 3-month old C57BL/6 male mice yielded no obvious behavioral or histological evidence of brain injury, while 25-40 psi blasts produced transient anxiety in an open field arena but little histological evidence of brain damage. By contrast, 50-60 psi blasts resulted in anxiety-like behavior in an open field arena that became more evident with time after blast. In additional behavioral tests conducted 2-8 weeks after blast, 50-60 psi mice also demonstrated increased acoustic startle, perseverance of learned fear, and enhanced contextual fear, as well as depression-like behavior and diminished prepulse inhibition. We found no evident cerebral pathology, however, and only scattered axonal degeneration in brain sections from 50-60 psi mice 3-8 weeks after blast. Thus, the TBI caused by single 50-60 psi blasts in mice exhibits the minimal neuronal loss coupled to diffuse axonal injury characteristic of human mild TBI. A reduction in the abundance of a subpopulation of excitatory projection neurons in basolateral amygdala enriched in Thy1 was, however, observed. The reported link of this neuronal population to fear suppression suggests their damage by mild TBI may contribute to the heightened anxiety and fearfulness observed after blast in our mice. Our overpressure air blast model of concussion in mice will enable further studies of the mechanisms underlying the diverse emotional deficits seen after mild TBI.

  12. High Intensity Focused Ultrasound: A Novel Model of Mild Traumatic Brain Injury

    Science.gov (United States)

    2013-11-07

    and depression-related phenomena. Rationale. Changes in neurological functioning are measurable in humans using neuropsychological assessment... hunger , fear and rage. 20. Cernak I. 2005. Animal models of head trauma. NeuroRx 2:410-22 21. Chandran R, Sharma A, Barry ES, Balakathiresan NS...the Wechsler Test of Adult Reading (WTAR). Journal of Clinical and Experimental Neuropsychology 30:163-72 43. Grunberg NE. 1982. The effects of

  13. Intranasal epidermal growth factor treatment rescues neonatal brain injury

    Science.gov (United States)

    Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio

    2014-02-01

    There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

  14. SPECT brain perfusion imaging in mild traumatic brain injury

    International Nuclear Information System (INIS)

    Li Juan; Liu Baojun; Zhao Feng; He Lirong; Xia Yucheng

    2003-01-01

    Objective: To study the clinical value of SPECT brain perfusion imaging after mild traumatic brain injury and to evaluate the mechanism of brain blood flow changes in the brain traumatic symptoms. Methods: SPECT 99 Tc m -ethylene cysteinate dimer (ECD) brain perfusion imaging was performed on 39 patients with normal consciousness and normal computed tomography. The study was performed on 23 patients within 3 months after the accidental injury and on 16 patients at more than 3 months post-injury. The cerebellum was used as the reference site (100% maximum value). Any decrease in cerebral perfusion in cortex or basal ganglia to below 70%, or even to below 50% in the medial temporal lobe, compared to the cerebellar reference was considered abnormal. Results: The results of 23 patients (59%) were abnormal. Among them, 20 patients showed 74 focal lesions with an average of 3.7 per patient (15 studies performed within 3 months and 8 studies performed more than 3 months after injury). The remaining 3 showed diffuse hypoperfusion (two at the early stage and one at more than 3 months after the injury). The 13 abnormal studies performed at the early stage showed 58 lesions (average, 4.5 per patient), whereas there was a reduction to an average of 2.3 per patient in the 7 patients (total 16 lesions) at more than 3 months post-injury. In the 20 patients with focal lesions, mainly the following regions were involved: frontal lobes 43.2% (32/74), basal ganglia 24.3% (18/74) and temporal lobes 17.6% (13/74). Conclusions: 1) SPECT brain perfusion imaging is more sensitive than computed tomography in detecting brain lesions of mild traumatic brain injury. 2) SPECT brain perfusion imaging is more sensitive at early stage than at late stage after injury. 3) The most common complaints were headache, dizziness, memory deficit. The patients without loss of consciousness may present brain hypoperfusion, too. 4) The changes may explain a neurological component of the patient symptoms in

  15. Serial changes in metabolism and histology in the cold-injury trauma rat brain model. Proton magnetic resonance imaging and spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Kamada, Kyousuke; Houkin, Kiyohiro; Hida, Kazutoshi; Iwasaki, Yoshinobu; Abe, Hiroshi [Hokkaido Univ., Sapporo (Japan). School of Medicine

    1995-01-01

    The serial changes in metabolism and histology during the first 24 hours in the cold-injury trauma rat brain model were investigated by proton magnetic resonance (MR) imaging and high-resolution proton MR spectroscopy. Edema developed extensively via the corpus callosum in the ipsi- and contralateral hemispheres during observation as shown by gradually increased signal intensity on proton MR images. Proton MR spectroscopy showed increased levels of acetate (Ace), lactate (Lac), and glutamine (Glmi) 1 hour after lesion formation. The elevated Glmi level slightly decreased, the level of alanine (Ala) increased substantially, and that of N-acetyl-aspartate (NAA) decreased markedly after 24 hours. Increased Lac, Ace, and Ala might reflect anaerobic glycolysis associated with mitochondrial dysfunction, while decreased Glmi and NAA reveal brain tissue breakdown. The relationship between brain edema and tissue viability can be analyzed in detail using this simple traumatic model and MR techniques which will be useful in the development of therapeutic agents for brain injury. (author).

  16. Traumatic brain injuries in the construction industry.

    Science.gov (United States)

    Colantonio, Angela; McVittie, Doug; Lewko, John; Yin, Junlang

    2009-10-01

    This study analyses factors associated with work-related traumatic brain injury (TBI), specifically in the construction industry in Ontario, Canada. This cross-sectional study utilized data extracted from the Ontario Workplace Safety and Insurance Board (WSIB) records indicating concussion/intracranial injury that resulted in days off work in 2004-2005. Analyses of 218 TBI cases revealed that falls were the most common cause of injury, followed by being struck by or against an object. Mechanisms of injury and the temporal profile of injury also varied by age. For instance, a significantly higher proportion of injuries occurred in the mornings for young workers compared to older workers. The results of this study provide important information for prevention of TBI which suggest important age-specific strategies for workers in the construction industry.

  17. Controlled Low-Pressure Blast-Wave Exposure Causes Distinct Behavioral and Morphological Responses Modelling Mild Traumatic Brain Injury, Post-Traumatic Stress Disorder, and Comorbid Mild Traumatic Brain Injury-Post-Traumatic Stress Disorder.

    Science.gov (United States)

    Zuckerman, Amitai; Ram, Omri; Ifergane, Gal; Matar, Michael A; Sagi, Ram; Ostfeld, Ishay; Hoffman, Jay R; Kaplan, Zeev; Sadot, Oren; Cohen, Hagit

    2017-01-01

    The intense focus in the clinical literature on the mental and neurocognitive sequelae of explosive blast-wave exposure, especially when comorbid with post-traumatic stress-related disorders (PTSD) is justified, and warrants the design of translationally valid animal studies to provide valid complementary basic data. We employed a controlled experimental blast-wave paradigm in which unanesthetized animals were exposed to visual, auditory, olfactory, and tactile effects of an explosive blast-wave produced by exploding a thin copper wire. By combining cognitive-behavioral paradigms and ex vivo brain MRI to assess mild traumatic brain injury (mTBI) phenotype with a validated behavioral model for PTSD, complemented by morphological assessments, this study sought to examine our ability to evaluate the biobehavioral effects of low-intensity blast overpressure on rats, in a translationally valid manner. There were no significant differences between blast- and sham-exposed rats on motor coordination and strength, or sensory function. Whereas most male rats exposed to the blast-wave displayed normal behavioral and cognitive responses, 23.6% of the rats displayed a significant retardation of spatial learning acquisition, fulfilling criteria for mTBI-like responses. In addition, 5.4% of the blast-exposed animals displayed an extreme response in the behavioral tasks used to define PTSD-like criteria, whereas 10.9% of the rats developed both long-lasting and progressively worsening behavioral and cognitive "symptoms," suggesting comorbid PTSD-mTBI-like behavioral and cognitive response patterns. Neither group displayed changes on MRI. Exposure to experimental blast-wave elicited distinct behavioral and morphological responses modelling mTBI-like, PTSD-like, and comorbid mTBI-PTSD-like responses. This experimental animal model can be a useful tool for elucidating neurobiological mechanisms underlying the effects of blast-wave-induced mTBI and PTSD and comorbid mTBI-PTSD.

  18. Combined Effects of Primary and Tertiary Blast on Rat Brain: Characterization of a Model of Blast-induced Mild Traumatic Brain Injury

    Science.gov (United States)

    2013-03-01

    injury in U.S. military personnel. N Engl J Med 364, 2091–2100 (2011) 27. Lu J, Ng KC , Ling GS, Wu J, Poon JF, Kan EM, Tan MH, Wu YJ, Li P...Moochhala S, Yap E, Lee LK, Teo AL, Yeh IB, Ser- gio DM, Chua F, Kumar SD, Ling EA: Effect of blast exposure on the brain structure and cognition in the...12689448] 32. Henderson D, Bielefeld EC, Harris KC , Hu BH. The role of oxidative stress in noise-induced hearing loss. Ear Hear. 2006;27(1):1–19. [PMID

  19. Molecular Mechanisms of Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Claire Thornton

    2012-01-01

    Full Text Available Fetal/neonatal brain injury is an important cause of neurological disability. Hypoxia-ischemia and excitotoxicity are considered important insults, and, in spite of their acute nature, brain injury develops over a protracted time period during the primary, secondary, and tertiary phases. The concept that most of the injury develops with a delay after the insult makes it possible to provide effective neuroprotective treatment after the insult. Indeed, hypothermia applied within 6 hours after birth in neonatal encephalopathy reduces neurological disability in clinical trials. In order to develop the next generation of treatment, we need to know more about the pathophysiological mechanism during the secondary and tertiary phases of injury. We review some of the critical molecular events related to mitochondrial dysfunction and apoptosis during the secondary phase and report some recent evidence that intervention may be feasible also days-weeks after the insult.

  20. Minocycline Attenuates Iron-Induced Brain Injury.

    Science.gov (United States)

    Zhao, Fan; Xi, Guohua; Liu, Wenqaun; Keep, Richard F; Hua, Ya

    2016-01-01

    Iron plays an important role in brain injury after intracerebral hemorrhage (ICH). Our previous study found minocycline reduces iron overload after ICH. The present study examined the effects of minocycline on the subacute brain injury induced by iron. Rats had an intracaudate injection of 50 μl of saline, iron, or iron + minocycline. All the animals were euthanized at day 3. Rat brains were used for immunohistochemistry (n = 5-6 per each group) and Western blotting assay (n = 4). Brain swelling, blood-brain barrier (BBB) disruption, and iron-handling proteins were measured. We found that intracerebral injection of iron resulted in brain swelling, BBB disruption, and brain iron-handling protein upregulation (p minocycline with iron significantly reduced iron-induced brain swelling (n = 5, p Minocycline significantly decreased albumin protein levels in the ipsilateral basal ganglia (p minocycline co-injected animals. In conclusion, the present study suggests that minocycline attenuates brain swelling and BBB disruption via an iron-chelation mechanism.

  1. The Importance of Early Brain Injury after Subarachnoid Hemorrhage

    Science.gov (United States)

    Sehba, Fatima A.; Hou, Jack; Pluta, Ryszard M.; Zhang, John H.

    2012-01-01

    Aneurysmal subarachnoid hemorrhage (aSAH) is a medical emergency that accounts for 5% of all stroke cases. Individuals affected are typically in the prime of their lives (mean age 50 years). Approximately 12% of patients die before receiving medical attention, 33% within 48 hours and 50% within 30 days of aSAH. Of the survivors 50% suffer from permanent disability with an estimated lifetime cost more than double that of an ischemic stroke. Traditionally, spasm that develops in large cerebral arteries 3-7 days after aneurysm rupture is considered the most important determinant of brain injury and outcome after aSAH. However, recent studies show that prevention of delayed vasospasm does not improve outcome in aSAH patients. This finding has finally brought in focus the influence of early brain injury on outcome of aSAH. A substantial amount of evidence indicates that brain injury begins at the aneurysm rupture, evolves with time and plays an important role in patients’ outcome. In this manuscript we review early brain injury after aSAH. Due to the early nature, most of the information on this injury comes from animals and few only from autopsy of patients who died within days after aSAH. Consequently, we began with a review of animal models of early brain injury, next we review the mechanisms of brain injury according to the sequence of their temporal appearance and finally we discuss the failure of clinical translation of therapies successful in animal models of aSAH. PMID:22414893

  2. Virtual Reality for Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Elisa R. Zanier

    2018-05-01

    Full Text Available In this perspective, we discuss the potential of virtual reality (VR in the assessment and rehabilitation of traumatic brain injury, a silent epidemic of extremely high burden and no pharmacological therapy available. VR, endorsed by the mobile and gaming industries, is now available in more usable and cheaper tools allowing its therapeutic engagement both at the bedside and during the daily life at chronic stages after injury with terrific potential for a longitudinal disease modifying effect.

  3. Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats

    OpenAIRE

    McBride, Devin W.; Wang, Yuechun; Sherchan, Prativa; Tang, Jiping; Zhang, John H.

    2015-01-01

    Brain edema is a major contributor to poor outcome and reduced quality of life after surgical brain injury (SBI). Although SBI pathophysiology is well-known, the correlation between cerebral edema and neurological deficits has not been thoroughly examined in the rat model of SBI. Thus, the purpose of this study was to determine the correlation between brain edema and deficits in standard sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague-Dawley rats were subjected ...

  4. Neuropsychiatric aspects of severe brain injuries

    Directory of Open Access Journals (Sweden)

    O. S. Zaitsev

    2012-01-01

    Full Text Available The state-of-the-art of Russian neuropsychiatry and priority developments in different psychopathological syndromes in severe brain injuries are assessed. Many cognitive and emotional impairments are explained in terms of the idea on the organization of psychic activity over time. It is emphasized that to achieve the premorbid levels of an interhemispheric interaction and functional asymmetry of the cerebral hemispheres affords psychic activity recovery. The experience in investigating, classifying, and treating various mental disorders occurring after severe brain injuries is generalized. The basic principles of psychopharmacotherapy and rehabilitation of victims are stated.

  5. Relationship between changes of N-methyl-D-aspartate receptor activity and brain edema after brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the relationship between the changes of N-methyl-D-aspartate (NMDA) receptor activity and brain edema after injury in rats.   Methods: The brain injury models were made by using a free-falling body. The treatment model was induced by means of injecting AP5 into lateral ventricle before brain injury; water contents in brain cortex were measured with dry-wet method; and NMDA receptor activity was detected with a radio ligand binding assay.   Results: The water contents began to increase at 30 minutes and reached the peak at 6 hours after brain injury. The maximal binding (Bmax) of NMDA receptor increased significantly at 15 minutes and reached the peak at 30 minutes, then decreased gradually and had the lowest value 6 hours after brain injury. Followed the treatment with AP5, NMDA receptor activity in the injured brain showed a normal value; and the water contents were lower than that of AP5-free injury group 24 hours after brain injury.   Conclusions: It suggests that excessive activation of NMDA receptor may be one of the most important factors to induce the secondary cerebral impairments, and AP5 may protect the brain from edema after brain injury.

  6. Glibenclamide reduces secondary brain damage after experimental traumatic brain injury.

    Science.gov (United States)

    Zweckberger, K; Hackenberg, K; Jung, C S; Hertle, D N; Kiening, K L; Unterberg, A W; Sakowitz, O W

    2014-07-11

    Following traumatic brain injury (TBI) SUR1-regulated NCCa-ATP (SUR1/TRPM4) channels are transcriptionally up-regulated in ischemic astrocytes, neurons, and capillaries. ATP depletion results in depolarization and opening of the channel leading to cytotoxic edema. Glibenclamide is an inhibitor of SUR-1 and, thus, might prevent cytotoxic edema and secondary brain damage following TBI. Anesthetized adult Sprague-Dawley rats underwent parietal craniotomy and were subjected to controlled cortical impact injury (CCI). Glibenclamide was administered as a bolus injection 15min after CCI injury and continuously via osmotic pumps throughout 7days. In an acute trial (180min) mean arterial blood pressure, heart rate, intracranial pressure, encephalographic activity, and cerebral metabolism were monitored. Brain water content was assessed gravimetrically 24h after CCI injury and contusion volumes were measured by MRI scanning technique at 8h, 24h, 72h, and 7d post injury. Throughout the entire time of observation neurological function was quantified using the "beam-walking" test. Glibenclamide-treated animals showed a significant reduction in the development of brain tissue water content(80.47%±0.37% (glibenclamide) vs. 80.83%±0.44% (control); pbeam-walking test throughout 7days. In accordance to these results and the available literature, glibenclamide seems to have promising potency in the treatment of TBI. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Secondary injury in traumatic brain injury patients - A prospective ...

    African Journals Online (AJOL)

    Objective. Secondary insults of hypotension and hypoxia significantly impact on outcome in patients with traumatic brain injury (TBI). More than 4 hours' delay in evacuation of intracranial haematomas has been demonstrated to have an additional impact on outcome. The objective of this study was to document the ...

  8. secondary injury in traumatic brain injury patients - a prospective study

    African Journals Online (AJOL)

    Objective. Secondary insults of hypotension and hypoxia significantly impact on outcome in patients with traumatic brain injury (TBI). More than 4 hours' delay in evacuation of intracranial haematomas has been demonstrated to have an additional impact on outcome. The objective of this study was to document the ...

  9. Brain SPECT in severs traumatic head injury

    International Nuclear Information System (INIS)

    Beaulieu, F.; Eder, V.; Pottier, J.M.; Baulieu, J.L.; Fournier, P.; Legros, B.; Chiaroni, P.; Dalonneau, M.

    2000-01-01

    The aim of this work was to compare the results of the early brain scintigraphy in traumatic brain injury to the long term neuropsychological behavior. Twenty four patients had an ECD-Tc99m SPECT, within one month after the trauma; scintigraphic abnormalities were evaluated according to a semi-quantitative analysis. The neuropsychological clinical investigation was interpreted by a synthetic approach to evaluate abnormalities related to residual motor deficit, frontal behavior, memory and language disorders. Fourteen patients (58%) had sequela symptoms. SPECT revealed 80 abnormalities and CT scan only 31. Statistical analysis of uptake values showed significantly lower uptake in left basal ganglia and brain stem in patients with sequela memory disorders. We conclude that the brain perfusion scintigraphy is able to detect more lesions than CT and that it could really help to predict the neuropsychological behavior after severe head injury. Traumatology could become in the future a widely accepted indication of perfusion SPECT. (authors)

  10. Time dysperception perspective for acquired brain injury

    Directory of Open Access Journals (Sweden)

    Federica ePiras

    2014-01-01

    Full Text Available Distortions of time perception are presented by a number of neuropsychiatric disorders. Here we survey timing abilities in clinical populations with acquired brain injuries in key cerebral areas recently implicated in human studies of timing. We purposely analyzed the complex relationship between cognitive and contextual factors involved in time estimation, as to characterize the correlation between timed and other cognitive behaviors in each group. We assume that interval timing is a solid construct to study cognitive dysfunctions following brain injury, as timing performance is a sensitive metric of information processing, while temporal cognition has the potential of influencing a wide range of cognitive processes. Moreover, temporal performance is a sensitive assay of damage to the underlying neural substrate after a brain insult. Further research in neurological and psychiatric patients will definitively answer the question of whether time distortions are manifestations of cognitive and behavioral symptoms of brain damage and definitively clarify their mechanisms.

  11. Data on amyloid precursor protein accumulation, spontaneous physical activity, and motor learning after traumatic brain injury in the triple-transgenic mouse model of Alzheimer׳s disease

    Directory of Open Access Journals (Sweden)

    Yasushi Kishimoto

    2016-12-01

    Full Text Available This data article contains supporting information regarding the research article entitled “Traumatic brain injury accelerates amyloid-β deposition and impairs spatial learning in the triple-transgenic mouse model of Alzheimer׳s disease” (H. Shishido, Y. Kishimoto, N. Kawai, Y. Toyota, M. Ueno, T. Kubota, Y. Kirino, T. Tamiya, 2016 [1]. Triple-transgenic (3×Tg-Alzheimer׳s disease (AD model mice exhibited significantly poorer spatial learning than sham-treated 3×Tg-AD mice 28 days after traumatic brain injury (TBI. Correspondingly, amyloid-β (Aβ deposition within the hippocampus was significantly greater in 3×Tg-AD mice 28 days after TBI. However, data regarding the short-term and long-term influences of TBI on amyloid precursor protein (APP accumulation in AD model mice remain limited. Furthermore, there is little data showing whether physical activity and motor learning are affected by TBI in AD model mice. Here, we provide immunocytochemistry data confirming that TBI induces significant increases in APP accumulation in 3×Tg-AD mice at both 7 days and 28 days after TBI. Furthermore, 3×Tg-AD model mice exhibit a reduced ability to acquire conditioned responses (CRs during delay eyeblink conditioning compared to sham-treated 3×Tg-AD model mice 28 days after TBI. However, physical activity and motor performance are not significantly changed in TBI-treated 3×Tg-AD model mice.

  12. Mechanisms of Neuroprotection from Hypoxia-Ischemia (HI) Brain Injury by Up-regulation of Cytoglobin (CYGB) in a Neonatal Rat Model*

    Science.gov (United States)

    Tian, Shu-Feng; Yang, Han-Hua; Xiao, Dan-Ping; Huang, Yue-Jun; He, Gu-Yu; Ma, Hai-Ran; Xia, Fang; Shi, Xue-Chuan

    2013-01-01

    This study was designed to investigate the expression profile of CYGB, its potential neuroprotective function, and underlying molecular mechanisms using a model of neonatal hypoxia-ischemia (HI) brain injury. Cygb mRNA and protein expression were evaluated within the first 36 h after the HI model was induced using RT-PCR and Western blotting. Cygb mRNA expression was increased at 18 h in a time-dependent manner, and its level of protein expression increased progressively in 24 h. To verify the neuroprotective effect of CYGB, a gene transfection technique was employed. Cygb cDNA and shRNA delivery adenovirus systems were established (Cygb-cDNA-ADV and Cygb-shRNA-ADV, respectively) and injected into the brains of 3-day-old rats 4 days before they were induced with HI treatment. Rats from different groups were euthanized 24 h post-HI, and brain samples were harvested. 2,3,5-Triphenyltetrazolium chloride, TUNEL, and Nissl staining indicated that an up-regulation of CYGB resulted in reduced acute brain injury. The superoxide dismutase level was found to be dependent on expression of CYGB. The Morris water maze test in 28-day-old rats demonstrated that CYGB expression was associated with improvement of long term cognitive impairment. Studies also demonstrated that CYGB can up-regulate mRNA and protein levels of VEGF and increase both the density and diameter of the microvessels but inhibits activation of caspase-2 and -3. Thus, this is the first in vivo study focusing on the neuroprotective role of CYGB. The reduction of neonatal HI injury by CYGB may be due in part to antioxidant and antiapoptotic mechanisms and by promoting angiogenesis. PMID:23585565

  13. Nonlinear Dynamic Theory of Acute Cell Injuries and Brain Ischemia

    Science.gov (United States)

    Taha, Doaa; Anggraini, Fika; Degracia, Donald; Huang, Zhi-Feng

    2015-03-01

    Cerebral ischemia in the form of stroke and cardiac arrest brain damage affect over 1 million people per year in the USA alone. In spite of close to 200 clinical trials and decades of research, there are no treatments to stop post-ischemic neuron death. We have argued that a major weakness of current brain ischemia research is lack of a deductive theoretical framework of acute cell injury to guide empirical studies. A previously published autonomous model based on the concept of nonlinear dynamic network was shown to capture important facets of cell injury, linking the concept of therapeutic to bistable dynamics. Here we present an improved, non-autonomous formulation of the nonlinear dynamic model of cell injury that allows multiple acute injuries over time, thereby allowing simulations of both therapeutic treatment and preconditioning. Our results are connected to the experimental data of gene expression and proteomics of neuron cells. Importantly, this new model may be construed as a novel approach to pharmacodynamics of acute cell injury. The model makes explicit that any pro-survival therapy is always a form of sub-lethal injury. This insight is expected to widely influence treatment of acute injury conditions that have defied successful treatment to date. This work is supported by NIH NINDS (NS081347) and Wayne State University President's Research Enhancement Award.

  14. Increased Cortical Gamma-Aminobutyric Acid Precedes Incomplete Extinction of Conditioned Fear and Increased Hippocampal Excitatory Tone in a Mouse Model of Mild Traumatic Brain Injury.

    Science.gov (United States)

    Schneider, Brandy L; Ghoddoussi, Farhad; Charlton, Jennifer L; Kohler, Robert J; Galloway, Matthew P; Perrine, Shane A; Conti, Alana C

    2016-09-01

    Mild traumatic brain injury (mTBI) contributes to development of affective disorders, including post-traumatic stress disorder (PTSD). Psychiatric symptoms typically emerge in a tardive fashion post-TBI, with negative effects on recovery. Patients with PTSD, as well as rodent models of PTSD, demonstrate structural and functional changes in brain regions mediating fear learning, including prefrontal cortex (PFC), amygdala (AMYG), and hippocampus (HC). These changes may reflect loss of top-down control by which PFC normally exhibits inhibitory influence over AMYG reactivity to fearful stimuli, with HC contribution. Considering the susceptibility of these regions to injury, we examined fear conditioning (FC) in the delayed post-injury period, using a mouse model of mTBI. Mice with mTBI displayed enhanced acquisition and delayed extinction of FC. Using proton magnetic resonance spectroscopy ex vivo, we examined PFC, AMYG, and HC levels of gamma-aminobutyric acid (GABA) and glutamate as surrogate measures of inhibitory and excitatory neurotransmission, respectively. Eight days post-injury, GABA was increased in PFC, with no significant changes in AMYG. In animals receiving FC and mTBI, glutamate trended toward an increase and the GABA/glutamate ratio decreased in ventral HC at 25 days post-injury, whereas GABA decreased and GABA/glutamate decreased in dorsal HC. These neurochemical changes are consistent with early TBI-induced PFC hypoactivation facilitating the fear learning circuit and exacerbating behavioral fear responses. The latent emergence of overall increased excitatory tone in the HC, despite distinct plasticity in dorsal and ventral HC fields, may be associated with disordered memory function, manifested as incomplete extinction and enhanced FC recall.

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

    Directory of Open Access Journals (Sweden)

    Rose Dawn Bharath

    2015-09-01

    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.

  16. A model for mild traumatic brain injury that induces limited transient memory impairment and increased levels of axon related serum biomarkers

    Directory of Open Access Journals (Sweden)

    Elham eRostami

    2012-07-01

    Full Text Available Mild traumatic brain injury (mTBI is one of the most common neuronal insults and can lead to long-term disabilities. mTBI occurs when the head is exposed to a rapid acceleration-deceleration movement triggering axonal injuries. Our limited understanding of the underlying pathological changes makes it difficult to predict the outcome of mTBI. In this study we used a scalable rat model for rotational acceleration TBI, previously characterized for the threshold of axonal pathology. We have analyzed whether a TBI just above the defined threshold would induce any detectable behavioral changes and/or changes in serum biomarkers. The effect of injury on sensory motor functions, memory and anxiety were assessed by beam walking, radial arms maze and elevated plus maze at 3 to 7 days following TBI. The only behavioral deficits found were transient impairments in working and reference memory. Blood serum was analyzed at 1, 3 and 14 days after injury for changes in selected protein biomarkers. Serum levels of neurofilament heavy chain (NF-H and Tau, as well as S100B and myelin basic protein (MBP showed significant increases in the injured animals at all time points. No signs of macroscopic injuries such as intracerebral hematomas or contusions were found. Amyloid precursor protein (APP immunostaining indicated axonal injuries at all time points analyzed. In summary, this model mimics some of the key symptoms of mTBI, such as transient memory impairment, which is paralleled by an increase in serum biomarkers. Our findings suggest that serum biomarkers may be used to detect mTBI. The model provides a suitable foundation for further investigation of the underlying pathology of mTBI.

  17. The spectrum and outcome of paediatric traumatic brain injury in ...

    African Journals Online (AJOL)

    The spectrum and outcome of paediatric traumatic brain injury in ... to develop a comprehensive overview of traumatic brain injury (TBI) in children ... We reviewed the age, gender, outcomes, radiological findings and treatment of the patients.

  18. Short and Long Term Behavioral and Pathological Changes in a Novel Rodent Model of Repetitive Mild Traumatic Brain Injury.

    Directory of Open Access Journals (Sweden)

    Kelly M McAteer

    Full Text Available A history of concussion, particularly repeated injury, has been linked to an increased risk for the development of neurodegenerative diseases, particularly chronic traumatic encephalopathy (CTE. CTE is characterized by abnormal accumulation of hyperphosphorylated tau and deficits in learning and memory. As yet the mechanisms associated with the development of CTE are unknown. Accordingly, the aim of the current study was to develop and characterize a novel model of repetitive mTBI that accurately reproduces the key short and long-term functional and histopathological features seen clinically. Forty male Sprague-Dawley rats were randomly assigned to receive 0, 1 or 3x mTBI spaced five days apart using a modified version of the Marmarou impact-acceleration diffuse-TBI model to deliver 110G of linear force. Functional outcomes were assessed six and twelve weeks post-injury, with histopathology assessed twenty-four hours and twelve weeks post-injury. Repetitive mTBI resulted in mild spatial and recognition memory deficits as reflected by increased escape latency on the Barnes maze and decreased time spent in the novel arm of the Y maze. There was a trend towards increased anxiety-like behavior, with decreased time spent in the inner portion of the open field. At 24 hours and 12 weeks post injury, repetitive mTBI animals showed increased tau phosphorylation and microglial activation within the cortex. Increases in APP immunoreactivity were observed in repetitive mTBI animals at 12 weeks indicating long-term changes in axonal integrity. This novel model of repetitive mTBI with its persistent cognitive deficits, neuroinflammation, axonal injury and tau hyperphosphorylation, thus represents a clinically relevant experimental approach to further explore the underlying pathogenesis of CTE.

  19. Visual agnosia and focal brain injury.

    Science.gov (United States)

    Martinaud, O

    Visual agnosia encompasses all disorders of visual recognition within a selective visual modality not due to an impairment of elementary visual processing or other cognitive deficit. Based on a sequential dichotomy between the perceptual and memory systems, two different categories of visual object agnosia are usually considered: 'apperceptive agnosia' and 'associative agnosia'. Impaired visual recognition within a single category of stimuli is also reported in: (i) visual object agnosia of the ventral pathway, such as prosopagnosia (for faces), pure alexia (for words), or topographagnosia (for landmarks); (ii) visual spatial agnosia of the dorsal pathway, such as cerebral akinetopsia (for movement), or orientation agnosia (for the placement of objects in space). Focal brain injuries provide a unique opportunity to better understand regional brain function, particularly with the use of effective statistical approaches such as voxel-based lesion-symptom mapping (VLSM). The aim of the present work was twofold: (i) to review the various agnosia categories according to the traditional visual dual-pathway model; and (ii) to better assess the anatomical network underlying visual recognition through lesion-mapping studies correlating neuroanatomical and clinical outcomes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Optical coherence tomography imaging of cranial meninges post brain injury in vivo

    Institute of Scientific and Technical Information of China (English)

    Woo June Choi; Ruikang K.Wang

    2017-01-01

    We report a new application of optical coherence tomography (OCT) to investigate the cranial meninges in an animal model of brain injury in vivo.The injury is induced in a mouse due to skull thinning,in which the repeated and excessive drilling exerts mechanical stress on the mouse brain through the skull,resulting in acute and mild brain injury.Transcranial OCT imaging reveals an interesting virtual space between the cranial meningeal layers post skull thinning,which is gradually closed within hours.The finding suggests a promise of OCT as an effective tool to monitor the mechanical trauma in the small animal model of brain injury.

  1. Pattern of brain injury and depressed heart rate variability in newborns with hypoxic ischemic encephalopathy.

    Science.gov (United States)

    Metzler, Marina; Govindan, Rathinaswamy; Al-Shargabi, Tareq; Vezina, Gilbert; Andescavage, Nickie; Wang, Yunfei; du Plessis, Adre; Massaro, An N

    2017-09-01

    BackgroundDecreased heart rate variability (HRV) is a measure of autonomic dysfunction and brain injury in newborns with hypoxic ischemic encephalopathy (HIE). This study aimed to characterize the relationship between HRV and brain injury pattern using magnetic resonance imaging (MRI) in newborns with HIE undergoing therapeutic hypothermia.MethodsHRV metrics were quantified in the time domain (α S , α L , and root mean square at short (RMS S ) and long (RMS L ) timescales) and frequency domain (relative low-(LF) and high-frequency (HF) power) over 24-27 h of life. The brain injury pattern shown by MRI was classified as no injury, pure cortical/white matter injury, mixed watershed/mild basal ganglia injury, predominant basal ganglia or global injury, and death. HRV metrics were compared across brain injury pattern groups using a random-effects mixed model.ResultsData from 74 infants were analyzed. Brain injury pattern was significantly associated with the degree of HRV suppression. Specifically, negative associations were observed between the pattern of brain injury and RMS S (estimate -0.224, SE 0.082, P=0.006), RMS L (estimate -0.189, SE 0.082, P=0.021), and LF power (estimate -0.044, SE 0.016, P=0.006).ConclusionDegree of HRV depression is related to the pattern of brain injury. HRV monitoring may provide insights into the pattern of brain injury at the bedside.

  2. Traumatic Brain Injury and Personality Change

    Science.gov (United States)

    Fowler, Marc; McCabe, Paul C.

    2011-01-01

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

  3. Centralized rehabilitation after servere traumatic brain injury

    DEFF Research Database (Denmark)

    Engberg, Aase Worså; Liebach, Annette; Nordenbo, Annette Mosbæk

    2006-01-01

    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 fr...

  4. Fitness to drive after traumatic brain injury

    NARCIS (Netherlands)

    Brouwer, WH; Withaar, FK

    This paper deals with the issue of fitness to drive in patients suffering from traumatic brain injury (TBI). Guidelines for assessment are proposed and three types of studies are reviewed: studies about impairments of attention and information processing, studies of driving competence, and driver

  5. Working with Students with Traumatic Brain Injury

    Science.gov (United States)

    Lucas, Matthew D.

    2010-01-01

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

  6. Psychiatric sequelae of traumatic brain injury: Retrospective ...

    African Journals Online (AJOL)

    Objective: Traumatic brain injury (TBI) is a public health problem and is associated with many complications. However little is known about the psychiatric sequelae of TBI in Nigeria. This study described the pattern and determinants of psychiatric sequelae among subjects with TBI. Materials and Methods: The study is a ...

  7. Narrative Language in Traumatic Brain Injury

    Science.gov (United States)

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

    2011-01-01

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

  8. Traumatic Brain Injury: Nuclear Medicine Neuroimaging

    NARCIS (Netherlands)

    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

    2014-01-01

    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

  9. Beam diagnostics for traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Nikol`skiy Yu.E.

    2012-06-01

    Full Text Available

    The paper presents aliterature review of domestic and foreign sources of modern methods of diagnostics imaging for traumatic brain injury. Information of the magnetic resonance imaging and computed tomography in the of this disease

  10. Severe traumatic brain injury managed with decompressive ...

    African Journals Online (AJOL)

    2012-05-29

    May 29, 2012 ... Patients with severe taumatic brain injury may develop intractable raised ICP resulting in high mortality ... Glasgow coma score was 8/15 (E1V3M4) and he had left ... An emergency right fronto-temporo-parietal decompressive.

  11. New Antioxidant Drugs for Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Maria Luisa Tataranno

    2015-01-01

    Full Text Available The brain injury concept covers a lot of heterogeneity in terms of aetiology involving multiple factors, genetic, hemodynamic, metabolic, nutritional, endocrinological, toxic, and infectious mechanisms, acting in antenatal or postnatal period. Increased vulnerability of the immature brain to oxidative stress is documented because of the limited capacity of antioxidant enzymes and the high free radicals (FRs generation in rapidly growing tissue. FRs impair transmembrane enzyme Na+/K+-ATPase activity resulting in persistent membrane depolarization and excessive release of FR and excitatory aminoacid glutamate. Besides being neurotoxic, glutamate is also toxic to oligodendroglia, via FR effects. Neuronal cells die of oxidative stress. Excess of free iron and deficient iron/binding metabolising capacity are additional features favouring oxidative stress in newborn. Each step in the oxidative injury cascade has become a potential target for neuroprotective intervention. The administration of antioxidants for suspected or proven brain injury is still not accepted for clinical use due to uncertain beneficial effects when treatments are started after resuscitation of an asphyxiated newborn. The challenge for the future is the early identification of high-risk babies to target a safe and not toxic antioxidant therapy in combination with standard therapies to prevent brain injury and long-term neurodevelopmental impairment.

  12. ischemic brain injury in neonatal rats

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, ... Methods: Forty-eight rats (P7-pups) were randomly assigned to one of four groups: ... Keywords: Hypoxic–ischemic brain injury, α-Lipoic acid, Cerebral infarct area, Edema, Antioxidants, .... Of the 48 rats initially used in the current study, 5.

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

    Science.gov (United States)

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

    2016-09-01

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

  14. Perspective on Pediatric Traumatic Brain Injury | Igun | African ...

    African Journals Online (AJOL)

    Background: Traumatic brain injury is an important aspect of paediatric trauma because of its contribution to mortality ant post trauma seqeulae. Management of traumatic brain injury remains a challenge to surgeons, especially in developing countries. This study aims to determine the pattern of traumatic brain injury among ...

  15. Multi-scale mechanics of traumatic brain injury

    NARCIS (Netherlands)

    Cloots, R.J.H.

    2011-01-01

    Traumatic brain injury (TBI) can be caused by road traffic, sports-related or other types of accidents and often leads to permanent health issues or even death. For a good prevention or diagnosis of TBI, brain injury criteria are used to assess the probability of brain injury as a result of a

  16. Repetitive Hyperbaric Oxygenation Attenuates Reactive Astrogliosis and Suppresses Expression of Inflammatory Mediators in the Rat Model of Brain Injury

    Directory of Open Access Journals (Sweden)

    Irena Lavrnja

    2015-01-01

    Full Text Available The exact mechanisms by which treatment with hyperbaric oxygen (HBOT exerts its beneficial effects on recovery after brain injury are still unrevealed. Therefore, in this study we investigated the influence of repetitive HBOT on the reactive astrogliosis and expression of mediators of inflammation after cortical stab injury (CSI. CSI was performed on male Wistar rats, divided into control, sham, and lesioned groups with appropriate HBO. The HBOT protocol was as follows: 10 minutes of slow compression, 2.5 atmospheres absolute (ATA for 60 minutes, and 10 minutes of slow decompression, once a day for 10 consecutive days. Data obtained using real-time polymerase chain reaction, Western blot, and immunohistochemical and immunofluorescence analyses revealed that repetitive HBOT applied after the CSI attenuates reactive astrogliosis and glial scarring, and reduces expression of GFAP (glial fibrillary acidic protein, vimentin, and ICAM-1 (intercellular adhesion molecule-1 both at gene and tissue levels. In addition, HBOT prevents expression of CD40 and its ligand CD40L on microglia, neutrophils, cortical neurons, and reactive astrocytes. Accordingly, repetitive HBOT, by prevention of glial scarring and limiting of expression of inflammatory mediators, supports formation of more permissive environment for repair and regeneration.

  17. The WRAIR projectile concussive impact model of mild traumatic brain injury: re-design, testing and preclinical validation.

    Science.gov (United States)

    Leung, Lai Yee; Larimore, Zachary; Holmes, Larry; Cartagena, Casandra; Mountney, Andrea; Deng-Bryant, Ying; Schmid, Kara; Shear, Deborah; Tortella, Frank

    2014-08-01

    The WRAIR projectile concussive impact (PCI) model was developed for preclinical study of concussion. It represents a truly non-invasive closed-head injury caused by a blunt impact. The original design, however, has several drawbacks that limit the manipulation of injury parameters. The present study describes engineering advancements made to the PCI injury model including helmet material testing, projectile impact energy/head kinematics and impact location. Material testing indicated that among the tested materials, 'fiber-glass/carbon' had the lowest elastic modulus and yield stress for providing an relative high percentage of load transfer from the projectile impact, resulting in significant hippocampal astrocyte activation. Impact energy testing of small projectiles, ranging in shape and size, showed the steel sphere produced the highest impact energy and the most consistent impact characteristics. Additional tests confirmed the steel sphere produced linear and rotational motions on the rat's head while remaining within a range that meets the criteria for mTBI. Finally, impact location testing results showed that PCI targeted at the temporoparietal surface of the rat head produced the most prominent gait abnormalities. Using the parameters defined above, pilot studies were conducted to provide initial validation of the PCI model demonstrating quantifiable and significant increases in righting reflex recovery time, axonal damage and astrocyte activation following single and multiple concussions.

  18. Pretreatment with Shuanghe-Tang Extract Attenuates Postischemic Brain Injury and Edema in a Mouse Model of Stroke: An Analysis of Medicinal Herbs Listed in Dongui Bogam

    Directory of Open Access Journals (Sweden)

    Min Jae Kim

    2018-01-01

    Full Text Available Aim. Although stroke is among the leading causes of death and long-term disability, there are few effective treatments for limiting the severity of neurological sequelae. We evaluated the effects of 29 medicinal herbs listed in the Pung chapter of the 17th century Korean medical text Dongui Bogam on stroke symptoms in a mouse model of cerebral ischemia. Methods. Focal cerebral ischemia was induced via photothrombosis. Infarct volume, brain edema, and neurological deficits were evaluated. Immunofluorescence staining for tight junction proteins and aquaporin 4 (AQP4 was performed following ischemic injury. Results. Based on our initial findings, we examined the effects of two prescriptions in which the candidate herbs comprised more than 60% of the total formula: Shuanghe-tang and Zengsunsiwu-tang. Pretreatment with Shuanghe-tang significantly reduced infarct volume, decreased blood-brain barrier (BBB breakdown, attenuated edema, and improved neurological and motor functions in a dose-dependent manner (30, 100, and 300 mg/kg, while no such effects were observed in mice pretreated with Zengsunsiwu-tang. Immunohistochemical analysis revealed significant increases in ipsilateral occludin and zonula occludens 1 (ZO-1 expression in Shuanghe-tang-pretreated mice, as well as increased AQP4 immunofluorescence. Conclusions. These results indicate that Shuanghe-tang may protect against brain injury and promote recovery of neurological function following ischemia.

  19. Effect of mannose targeting of hydroxyl PAMAM dendrimers on cellular and organ biodistribution in a neonatal brain injury model.

    Science.gov (United States)

    Sharma, Anjali; Porterfield, Joshua E; Smith, Elizabeth; Sharma, Rishi; Kannan, Sujatha; Kannan, Rangaramanujam M

    2018-06-05

    Neurotherapeutics for the treatment of central nervous system (CNS) disorders must overcome challenges relating to the blood-brain barrier (BBB), brain tissue penetration, and the targeting of specific cells. Neuroinflammation mediated by activated microglia is a major hallmark of several neurological disorders, making these cells a desirable therapeutic target. Building on the promise of hydroxyl-terminated generation four polyamidoamine (PAMAM) dendrimers (D4-OH) for penetrating the injured BBB and targeting activated glia, we explored if conjugation of targeting ligands would enhance and modify brain and organ uptake. Since mannose receptors [cluster of differentiation (CD) 206] are typically over-expressed on injured microglia, we conjugated mannose to the surface of multifunctional D4-OH using highly efficient, atom-economical, and orthogonal Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click chemistry and evaluated the effect of mannose conjugation on the specific cell uptake of targeted and non-targeted dendrimers both in vitro and in vivo. In vitro results indicate that the conjugation of mannose as a targeting ligand significantly changes the mechanism of dendrimer internalization, giving mannosylated dendrimer a preference for mannose receptor-mediated endocytosis as opposed to non-specific fluid phase endocytosis. We further investigated the brain uptake and biodistribution of targeted and non-targeted fluorescently labeled dendrimers in a maternal intrauterine inflammation-induced cerebral palsy (CP) rabbit model using quantification methods based on fluorescence spectroscopy and confocal microscopy. We found that the conjugation of mannose modified the distribution of D4-OH throughout the body in this neonatal rabbit CP model without lowering the amount of dendrimer delivered to injured glia in the brain, even though significantly higher glial uptake was not observed in this model. Mannose conjugation to the dendrimer modifies the dendrimer

  20. Magnetic resonance imaging in diffuse brain injury

    International Nuclear Information System (INIS)

    Yokota, Hiroyuki; Yasuda, Kazuhiro; Mashiko, Kunihiro; Henmi, Hiroshi; Otsuka, Toshibumi; Kobayashi, Shiro; Nakazawa, Shozo

    1992-01-01

    Forty cases diagnosed as diffuse brain injury (DBI) were studied by magnetic resonance imaging (MRI) performed within 3 days after injury. These cases were divided into two groups, which were the concussion group and diffuse axonal injury (DAI) group established by Gennarelli. There were no findings on computerized tomography (CT) in the concussion group except for two cases which had a brain edema or subarachnoid hemorrhage. But on MRI, high intensity areas on T2 weighted imaging were demonstrated in the cerebral white matter in this group. Many lesions in this group were thought to be edemas of the cerebral white matter, because of the fact that on serial MRI, they were isointense. In mild types of DAI, the lesions on MRI were located only in the cerebral white matter, whereas, in the severe types of DAI, lesions were located in the basal ganglia, the corpus callosum, the dorsal part of the brain stem as well as in the cerebral white matter. As for CT findings, parenchymal lesions were not visualized especially in mild DAI. Our results suggested that the lesions in cerebral concussion were edemas in cerebral white matter. In mild DAI they were non-hemorrhagic contusion; and in severe DAI they were hemorrhagic contusions in the cerebral white matter, the basal ganglia, the corpus callosum or the dorsal part of the brain stem. (author)

  1. Evaluation of ultrasound techniques for brain injury detection

    Science.gov (United States)

    Mobley, Joel; Kasili, Paul M.; Norton, Stephen J.; Vo-Dinh, Tuan

    1998-05-01

    In this work, we examine the physics underlying wave propagation in the head to evaluate various ultrasonic transducers for use in a brian injury detection device. The results of measurements of the attenuation coefficient and phase velocity for ultrasonic propagation in samples of brain tissue and skull bone from sheep are presented. The material properties are then used to investigate the propagation of ultrasonic pressure fields in the head. The ultrasound fields for three different transducers are calculated for propagation in a simulated brain/skull model. The model is constructed using speed-of-sound and mass density values of the two tissue types. The impact of the attenuation on the ultrasound fields is then examined. Finally, the relevant points drawn from these discussions are summarized. We hope to minimize the confounding effects of the skull by using sub-MHz ultrasound while maintaining the necessary temporal and spatial resolution to successfully detect injury in the brain.

  2. Respiratory mechanics in brain injury: A review.

    Science.gov (United States)

    Koutsoukou, Antonia; Katsiari, Maria; Orfanos, Stylianos E; Kotanidou, Anastasia; Daganou, Maria; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Rovina, Nikoletta

    2016-02-04

    Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients (BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case that non lung protective ventilator settings are applied. Measurement of respiratory mechanics in BD patients, as well as assessment of their evolution during mechanical ventilation, may lead to preclinical lung injury detection early enough, allowing thus the selection of the appropriate ventilator settings to avoid ventilator-induced lung injury. The aim of this review is to explore the mechanical properties of the respiratory system in BD patients along with the underlying mechanisms, and to translate the evidence of animal and clinical studies into therapeutic implications regarding the mechanical ventilation of these critically ill patients.

  3. Modeling Cerebral Vascular Injury

    Science.gov (United States)

    2016-01-01

    epidural hematoma , 16% had a subdural hematoma , 11% had an intraventricular hemorrhage, and 14% had mixed hemorrhages (Armonda et al. 2006). In order... hematoma , 16% had a subdural hematoma , 11% had an intraventricular hemorrhage, and 14% had mixed hemorrhages (Armonda et al. 2006). Injuries such as...vasospasm and pseudoaneurysm can lead to further damage to the brain over time. Intracranial hemorrhages and hematomas can be life threatening and

  4. Therapeutic irradiation and brain injury

    International Nuclear Information System (INIS)

    Sheline, G.E.; Wara, W.M.; Smith, V.

    1980-01-01

    This is a review and reanalysis of the literature on adverse effects of therapeutic irradiation on the brain. Reactions have been grouped and considered according to time of appearance. The emphasis of the analysis is on delayed reactions, especially those that occur from a few months to several years after irradiation. All dose specifications were converted into equivalent megavoltage rads. The data were analyzed in terms of total dose, overall treatment time and number of treatment fractions. Also discussed were acute radiation reactions, early delayed radiation reactions, somnolence and leukoencephalopathy post-irradiation/chemotherapy and combined effects of radiation and chemotherapy

  5. Surviving severe traumatic brain injury in Denmark

    DEFF Research Database (Denmark)

    Odgaard, Lene; Poulsen, Ingrid; Kammersgaard, Lars Peter

    2015-01-01

    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...

  6. Inhaled nitric oxide improves short term memory and reduces the inflammatory reaction in a mouse model of mild traumatic brain injury.

    Science.gov (United States)

    Liu, Ping; Li, Yong-Sheng; Quartermain, David; Boutajangout, Allal; Ji, Yong

    2013-07-19

    Although the mechanisms underlying mild traumatic brain injury (mTBI) are becoming well understood, treatment options are still limited. In the present study, mTBI was induced by a weight drop model to produce a closed head injury to mice and the effect of inhaled nitric oxide (INO) was evaluated by a short term memory task (object recognition task) and immunohistochemical staining of glial fibrillary acidic protein (GFAP) and CD45 for the detection of reactive astrocytes and microglia. Results showed that mTBI model did not produce brain edema, skull fracture or sensorimotor coordination dysfunctions. Mice did however exhibit a significant deficit in short term memory (STM) and strong inflammatory reaction in the ipsilateral cortex and hippocampus compared to sham-injured controls 24h after mTBI. Additional groups of untreated mice tested 3 and 7 days later, demonstrated that recognition memory had recovered to normal levels by Day 3. Mice treated with 10ppm INO for 4 or 8h, beginning immediately after TBI demonstrated significantly improved STM at 24h when compared with room air controls (pshort durations of INO prevents this memory loss and also attenuates the inflammatory response. These findings may have relevance for the treatment of patients diagnosed with concussion. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Effects of Acanthopanax senticosus on Brain Injury Induced by Simulated Spatial Radiation in Mouse Model Based on Pharmacokinetics and Comparative Proteomics

    Directory of Open Access Journals (Sweden)

    Yingyu Zhou

    2018-01-01

    Full Text Available The active compounds in Acanthopanax senticosus (AS have different pharmacokinetic characteristics in mouse models. Cmax and AUC of Acanthopanax senticosus polysaccharides (ASPS were significantly reduced in radiation-injured mice, suggesting that the blood flow of mouse was blocked or slowed, due to the pathological state of ischemia and hypoxia, which are caused by radiation. In contrast, the ability of various metabolizing enzymes to inactivate, capacity of biofilm transport decrease, and lessening of renal blood flow accounts for radiation, resulting in the accumulation of syringin and eleutheroside E in the irradiated mouse. Therefore, there were higher pharmacokinetic parameters—AUC, MRT, and t1/2 of the two compounds in radiation-injured mouse, when compared with normal mouse. In order to investigate the intrinsic mechanism of AS on radiation injury, AS extract’s protective effects on brain, the main part of mouse that suffered from radiation, were explored. The function of AS extract in repressing expression changes of radiation response proteins in prefrontal cortex (PFC of mouse brain included tubulin protein family (α-, β-tubulin subunits, dihydropyrimidinase-related protein 2 (CRMP2, γ-actin, 14-3-3 protein family (14-3-3ζ, ε, heat shock protein 90β (HSP90β, and enolase 2. The results demonstrated the AS extract had positive effects on nerve cells’ structure, adhesion, locomotion, fission, and phagocytosis, through regulating various action pathways, such as Hippo, phagosome, PI3K/Akt (phosphatidylinositol 3 kinase/protein kinase B, Neurotrophin, Rap1 (Ras-related protein RAP-1A, gap junction glycolysis/gluconeogenesis, and HIF-1 (Hypoxia-inducible factor 1 signaling pathways to maintain normal mouse neurological activity. All of the results indicated that AS may be a promising alternative medicine for the treatment of radiation injury in mouse brain. It would be tested that whether the bioactive ingredients of AS could

  8. Monitoring in traumatic brain injury.

    Science.gov (United States)

    Matz, P G; Pitts, L

    1997-01-01

    In the past several years, improvements in technology have advanced the monitoring capabilities for patients with TBI. The primary goal of monitoring the patient with TBI is to prevent secondary insults to the brain, primarily cerebral ischemia. Cerebral ischemia may occur early and without clinical correlation and portends a poor outcome. Measurement of ICP is the cornerstone of monitoring in the patient with TBI. Monitoring of ICP provides a measurement of CPP and a rough estimation of CBF. However, with alterations in pressure autoregulation, measurement of CPP does not always allow for determination of CBF. To circumvent this problem, direct measurements of CBF can be performed using clearance techniques (133Xe, N2O, Xe-CT) or invasive monitoring techniques (LDF, TDF, NIRS). Although direct and quantitative, clearance techniques do not allow for continuous monitoring. Invasive CBF monitoring techniques are new, and artifactual results can be problematic. The techniques of jugular venous saturation monitoring and TCD are well established and are powerful adjuncts to ICP monitoring. They allow the clinician to monitor cerebral oxygen extraction and blood flow velocity, respectively, for any given CPP. Use of TCD may predict posttraumatic vasospasm before clinical sequelae. Jugular venous saturation monitoring may detect clinically occult episodes of cerebral ischemia and increased oxygen extraction. Jugular venous saturation monitoring optimizes the use of hyperventilation in the treatment of intracranial hypertension. Although PET and SPECT scanning allow direct measurement of CMRO2, these techniques have limited application currently. Similarly, microdialysis is in its infancy but has demonstrated great promise for metabolic monitoring. EEG and SEP are excellent adjuncts to the monitoring arsenal and provide immediate information on current brain function. With improvements in electronic telemetry, functional monitoring by EEG or SEP may become an important

  9. Inflammation, caffeine and adenosine in neonatal hypoxic ischemic brain injury

    OpenAIRE

    Winerdal, Max

    2014-01-01

    Background: Brain injury during the neonatal period has potentially lifelong consequences for a child. Perinatal infections and inflammation can induce preterm birth and unfavorable cognitive development, Thus inflammation has received enthusiastic interest for potential therapeutic approaches seeking to protect the newborn brain. Experimental evidence demonstrates that inflammation induces brain injury succeeding the initial insult. A key cytokine in brain injury is the tumor necrosis factor...

  10. Cooking breakfast after a brain injury

    OpenAIRE

    Tanguay, Annick N.; Davidson, Patrick S. R.; Guerrero Nuñez, Karla V.; Ferland, Mark B.

    2014-01-01

    Acquired brain injury (ABI) often compromises the ability to carry out instrumental activities of daily living such as cooking. ABI patients' difficulties with executive functions and memory result in less independent and efficient meal preparation. Accurately assessing safety and proficiency in cooking is essential for successful community reintegration following ABI, but in vivo assessment of cooking by clinicians is time-consuming, costly, and difficult to standardize. Accordingly, we exam...

  11. Cooking breakfast after a brain injury

    OpenAIRE

    Annick N. Tanguay; Patrick S. R. Davidson; Patrick S. R. Davidson; Patrick S. R. Davidson; K. Vanessa eGuerrero Nuñez; Mark B. Ferland; Mark B. Ferland; Mark B. Ferland

    2014-01-01

    Acquired brain injury (ABI) often compromises the ability to carry out instrumental activities of daily living such as cooking. ABI patients’ difficulties with executive functions and memory result in less independent and efficient meal preparation. Accurately assessing safety and proficiency in cooking is essential for successful community reintegration following ABI, but in vivo assessment of cooking by clinicians is time-consuming, costly, and difficult to standardize. Accordingly, we exa...

  12. Traumatic Brain Injury: Caregivers’ Problems and Needs

    OpenAIRE

    syed tajjudin syed hassan; WF Khaw; AR Rosna; J Husna

    2011-01-01

    Traumatic brain injury (TBI) is an increasingly major world health problem. This short review using the most pertinent articles on TBI caregiving problems and needs highlights the pressing issues. Articles focusing on both TBI-caregivers’ problems and needs are rarely found, especially for developing countries. Most TBI-caregiving is done by family members, whose altered lives portend burden and stresses which add to the overwhelming demand of caring for the TBI-survivor. Lack of information,...

  13. Cognitive Rehabilitation for Mild Traumatic Brain Injury

    Science.gov (United States)

    2009-06-08

    Cate Miller, Dr. Maria Mouratidis, Dr. George Prigatano, Dr. Carole Roth, LTC Michael Russell, LT Rick Schobitz, Dr. Joel Scholten, CAPT Edward Simmer...New York: The Guilford Press. Gordon W.A, Zafonte R., Cicerone, K., Cantor , J., Brown, M., Lombard, L., Goldsmith, R, & Chandna, T. (2006...Traumatic brain injury rehabilitation: State of the science. American Journal of Physical Medicine and Rehabilitation, 85, 343–82. Gordon, W.A., Cantor

  14. Radiation-induced brain injury: A review

    Directory of Open Access Journals (Sweden)

    Michael eRobbins

    2012-07-01

    Full Text Available Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (> 6 months to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses > 30 Gy; white matter necrosis occurs at fractionated doses > 60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain

  15. Defining the biomechanical and biological threshold of murine mild traumatic brain injury using CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration).

    Science.gov (United States)

    Namjoshi, Dhananjay R; Cheng, Wai Hang; Bashir, Asma; Wilkinson, Anna; Stukas, Sophie; Martens, Kris M; Whyte, Tom; Abebe, Zelalem A; McInnes, Kurt A; Cripton, Peter A; Wellington, Cheryl L

    2017-06-01

    CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) is a recently described animal model of traumatic brain injury (TBI) that primarily produces diffuse axonal injury (DAI) characterized by white matter inflammation and axonal damage. CHIMERA was specifically designed to reliably generate a variety of TBI severities using precise and quantifiable biomechanical inputs in a nonsurgical user-friendly platform. The objective of this study was to define the lower limit of single impact mild TBI (mTBI) using CHIMERA by characterizing the dose-response relationship between biomechanical input and neurological, behavioral, neuropathological and biochemical outcomes. Wild-type male mice were subjected to a single CHIMERA TBI using six impact energies ranging from 0.1 to 0.7J, and post-TBI outcomes were assessed over an acute period of 14days. Here we report that single TBI using CHIMERA induces injury dose- and time-dependent changes in behavioral and neurological deficits, axonal damage, white matter tract microgliosis and astrogliosis. Impact energies of 0.4J or below produced no significant phenotype (subthreshold), 0.5J led to significant changes for one or more phenotypes (threshold), and 0.6 and 0.7J resulted in significant changes in all outcomes assessed (mTBI). We further show that linear head kinematics are the most robust predictors of duration of unconsciousness, severity of neurological deficits, white matter injury, and microgliosis following single TBI. Our data extend the validation of CHIMERA as a biofidelic animal model of DAI and establish working parameters to guide future investigations of the mechanisms underlying axonal pathology and inflammation induced by mechanical trauma. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  16. Lateral automobile impacts and the risk of traumatic brain injury.

    Science.gov (United States)

    Bazarian, Jeffrey J; Fisher, Susan Gross; Flesher, William; Lillis, Robert; Knox, Kerry L; Pearson, Thomas A

    2004-08-01

    We determine the relative risk and severity of traumatic brain injury among occupants of lateral impacts compared with occupants of nonlateral impacts. This was a secondary analysis of the National Highway Traffic Safety Administration's National Automotive Sampling System, Crashworthiness Data Systems for 2000. Analysis was restricted to occupants of vehicles in which at least 1 person experienced an injury with Abbreviated Injury Scale score greater than 2. Traumatic brain injury was defined as an injury to the head or skull with an Abbreviated Injury Scale score greater than 2. Outcomes were analyzed using the chi2 test and multivariate logistic regression, with adjustment of variance to account for weighted probability sampling. Of the 1,115 occupants available for analysis, impact direction was lateral for 230 (18.42%) occupants and nonlateral for 885 (81.58%) occupants. One hundred eighty-seven (16.07%) occupants experienced a traumatic brain injury, 14.63% after lateral and 16.39% after nonlateral impact. The unadjusted relative risk of traumatic brain injury after lateral impact was 0.89 (95% confidence interval [CI] 0.51 to 1.56). After adjusting for several important crash-related variables, the relative risk of traumatic brain injury was 2.60 (95% CI 1.1 to 6.0). Traumatic brain injuries were more severe after lateral impact according to Abbreviated Injury Scale and Glasgow Coma Scale scores. The proportion of fatal or critical crash-related traumatic brain injuries attributable to lateral impact was 23.5%. Lateral impact is an important independent risk factor for the development of traumatic brain injury after a serious motor vehicle crash. Traumatic brain injuries incurred after lateral impact are more severe than those resulting from nonlateral impact. Vehicle modifications that increase head protection could reduce crash-related severe traumatic brain injuries by up to 61% and prevent up to 2,230 fatal or critical traumatic brain injuries each year

  17. The common antitussive agent dextromethorphan protects against hyperoxia-induced cell death in established in vivo and in vitro models of neonatal brain injury.

    Science.gov (United States)

    Posod, A; Pinzer, K; Urbanek, M; Wegleiter, K; Keller, M; Kiechl-Kohlendorfer, U; Griesmaier, E

    2014-08-22

    Preterm infants are prematurely subjected to relatively high oxygen concentrations, even when supplemental oxygen is not administered. There is increasing evidence to show that an excess of oxygen is toxic to the developing brain. Dextromethorphan (DM), a frequently used antitussive agent with pleiotropic mechanisms of action, has been shown to be neuroprotective in various models of central nervous system pathology. Due to its numerous beneficial properties, it might also be able to counteract detrimental effects of a neonatal oxygen insult. The aim of the current study was to evaluate its therapeutic potential in established cell culture and rodent models of hyperoxia-induced neonatal brain injury. For in vitro studies pre- and immature oligodendroglial (OLN-93) cells were subjected to hyperoxic conditions for 48 h after pre-treatment with increasing doses of DM. For in vivo studies 6-day-old Wistar rat pups received a single intraperitoneal injection of DM in two different dosages prior to being exposed to hyperoxia for 24h. Cell viability and caspase-3 activation were assessed as outcome parameters at the end of exposure. DM significantly increased cell viability in immature oligodendroglial cells subjected to hyperoxia. In pre-oligodendroglial cells cell viability was not significantly affected by DM treatment. In vivo caspase-3 activation induced by hyperoxic exposure was significantly lower after administration of DM in gray and white matter areas. In control animals kept under normoxic conditions DM did not significantly influence caspase-3-dependent apoptosis. The present results indicate that DM is a promising and safe treatment strategy for neonatal hyperoxia-induced brain injury that merits further investigation. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

    Directory of Open Access Journals (Sweden)

    Huang Yen

    2011-09-01

    Full Text Available Abstract Background Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE. Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE. Methods We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7 rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry. Results Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats. Conclusion These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.

  19. Injury Response of Resected Human Brain Tissue In Vitro

    NARCIS (Netherlands)

    Verwer, Ronald W. H.; Sluiter, Arja A.; Balesar, Rawien A.; Baaijen, Johannes C.; de Witt Hamer, Philip C.; Speijer, Dave; Li, Yichen; Swaab, Dick F.

    2015-01-01

    Brain injury affects a significant number of people each year. Organotypic cultures from resected normal neocortical tissue provide unique opportunities to study the cellular and neuropathological consequences of severe injury of adult human brain tissue in vitro. The in vitro injuries caused by

  20. Neonatal ischemic brain injury: what every radiologist needs to know

    International Nuclear Information System (INIS)

    Badve, Chaitra A.; Khanna, Paritosh C.; Ishak, Gisele E.

    2012-01-01

    We present a pictorial review of neonatal ischemic brain injury and look at its pathophysiology, imaging features and differential diagnoses from a radiologist's perspective. The concept of perinatal stroke is defined and its distinction from hypoxic-ischemic injury is emphasized. A brief review of recent imaging advances is included and a diagnostic approach to neonatal ischemic brain injury is suggested. (orig.)

  1. Secondary Damage after Traumatic Brain Injury: Epidemiology, Pathophysiology and Therapy

    NARCIS (Netherlands)

    D.C. Engel (Doortje Caroline)

    2008-01-01

    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,

  2. Patient Effort in Traumatic Brain Injury Inpatient Rehabilitation: Course and Associations With Age, Brain Injury Severity, and Time Postinjury

    Science.gov (United States)

    Seel, Ronald T.; Corrigan, John D.; Dijkers, Marcel P.; Barrett, Ryan S.; Bogner, Jennifer; Smout, Randall J.; Garmoe, William; Horn, Susan D.

    2016-01-01

    Objective To describe patients' level of effort in occupational, physical, and speech therapy sessions during traumatic brain injury (TBI) inpatient rehabilitation and to evaluate how age, injury severity, cognitive impairment, and time are associated with effort. Design Prospective, multicenter, longitudinal cohort study. Setting Acute TBI rehabilitation programs. Participants Patients (N=1946) receiving 138,555 therapy sessions. Interventions Not applicable. Main Outcome Measures Effort in rehabilitation sessions rated on the Rehabilitation Intensity of Therapy Scale, FIM, Comprehensive Severity Index brain injury severity score, posttraumatic amnesia (PTA), and Agitated Behavior Scale (ABS). Results The Rehabilitation Intensity of Therapy Scale effort ratings in individual therapy sessions closely conformed to a normative distribution for all 3 disciplines. Mean Rehabilitation Intensity of Therapy Scale ratings for patients' therapy sessions were higher in the discharge week than in the admission week (Prehabilitation, differences in effort ratings (Pcognitive scores and over time. In linear mixed-effects modeling, age and Comprehensive Severity Index brain injury severity score at admission, days from injury to rehabilitation admission, days from admission, and daily ratings of PTA and ABS score were predictors of level of effort (Prehabilitation setting using the Rehabilitation Intensity of Therapy Scale. Patients who sustain TBI show varying levels of effort in rehabilitation therapy sessions, with effort tending to increase over the stay. PTA and agitated behavior are primary risk factors that substantially reduce patient effort in therapies. PMID:26212400

  3. Reduced brain/serum glucose ratios predict cerebral metabolic distress and mortality after severe brain injury.

    Science.gov (United States)

    Kurtz, Pedro; Claassen, Jan; Schmidt, J Michael; Helbok, Raimund; Hanafy, Khalid A; Presciutti, Mary; Lantigua, Hector; Connolly, E Sander; Lee, Kiwon; Badjatia, Neeraj; Mayer, Stephan A

    2013-12-01

    The brain is dependent on glucose to meet its energy demands. We sought to evaluate the potential importance of impaired glucose transport by assessing the relationship between brain/serum glucose ratios, cerebral metabolic distress, and mortality after severe brain injury. We studied 46 consecutive comatose patients with subarachnoid or intracerebral hemorrhage, traumatic brain injury, or cardiac arrest who underwent cerebral microdialysis and intracranial pressure monitoring. Continuous insulin infusion was used to maintain target serum glucose levels of 80-120 mg/dL (4.4-6.7 mmol/L). General linear models of logistic function utilizing generalized estimating equations were used to relate predictors of cerebral metabolic distress (defined as a lactate/pyruvate ratio [LPR] ≥ 40) and mortality. A total of 5,187 neuromonitoring hours over 300 days were analyzed. Mean serum glucose was 133 mg/dL (7.4 mmol/L). The median brain/serum glucose ratio, calculated hourly, was substantially lower (0.12) than the expected normal ratio of 0.40 (brain 2.0 and serum 5.0 mmol/L). In addition to low cerebral perfusion pressure (P = 0.05) and baseline Glasgow Coma Scale score (P brain/serum glucose ratios below the median of 0.12 were independently associated with an increased risk of metabolic distress (adjusted OR = 1.4 [1.2-1.7], P brain/serum glucose ratios were also independently associated with in-hospital mortality (adjusted OR = 6.7 [1.2-38.9], P brain/serum glucose ratios, consistent with impaired glucose transport across the blood brain barrier, are associated with cerebral metabolic distress and increased mortality after severe brain injury.

  4. External Validation and Recalibration of Risk Prediction Models for Acute Traumatic Brain Injury among Critically Ill Adult Patients in the United Kingdom.

    Science.gov (United States)

    Harrison, David A; Griggs, Kathryn A; Prabhu, Gita; Gomes, Manuel; Lecky, Fiona E; Hutchinson, Peter J A; Menon, David K; Rowan, Kathryn M

    2015-10-01

    This study validates risk prediction models for acute traumatic brain injury (TBI) in critical care units in the United Kingdom and recalibrates the models to this population. The Risk Adjustment In Neurocritical care (RAIN) Study was a prospective, observational cohort study in 67 adult critical care units. Adult patients admitted to critical care following acute TBI with a last pre-sedation Glasgow Coma Scale score of less than 15 were recruited. The primary outcomes were mortality and unfavorable outcome (death or severe disability, assessed using the Extended Glasgow Outcome Scale) at six months following TBI. Of 3626 critical care unit admissions, 2975 were analyzed. Following imputation of missing outcomes, mortality at six months was 25.7% and unfavorable outcome 57.4%. Ten risk prediction models were validated from Hukkelhoven and colleagues, the Medical Research Council (MRC) Corticosteroid Randomisation After Significant Head Injury (CRASH) Trial Collaborators, and the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) group. The model with the best discrimination was the IMPACT "Lab" model (C index, 0.779 for mortality and 0.713 for unfavorable outcome). This model was well calibrated for mortality at six months but substantially under-predicted the risk of unfavorable outcome. Recalibration of the models resulted in small improvements in discrimination and excellent calibration for all models. The risk prediction models demonstrated sufficient statistical performance to support their use in research and audit but fell below the level required to guide individual patient decision-making. The published models for unfavorable outcome at six months had poor calibration in the UK critical care setting and the models recalibrated to this setting should be used in future research.

  5. The Effect Of Supraphysiologic Blood Pressure on Traumatic Brain Injury and Proximal Tissue Beds During Resuscitative Balloon Occlusion of the Aorta and Variable Aortic Control in a Porcine Model (Sus scrofa) of Polytrauma.

    Science.gov (United States)

    2017-04-27

    Control In A Porcine Model (Sus Scrofa) Of Polytrauma . PRINCIPAL INVESTIGATOR (PI) / TRAINING COORDINATOR (TC): Lt Col Timothy Williams DEPARTMENT...Mandatory) The Effect of REBOA, Partial Aortic Occlusion and Aggressive Blood Transfusion on Traumatic Brain Injury in a Swine Polytrauma Model

  6. Patterns of neonatal hypoxic-ischaemic brain injury

    International Nuclear Information System (INIS)

    Vries, Linda S. de; Groenendaal, Floris

    2010-01-01

    Enormous progress has been made in assessing the neonatal brain, using magnetic resonance imaging (MRI). In this review, we will describe the use of MRI and proton magnetic resonance spectroscopy in detecting different patterns of brain injury in (full-term) human neonates following hypoxic-ischaemic brain injury and indicate the relevance of these findings in predicting neurodevelopmental outcome. (orig.)

  7. Patterns of neonatal hypoxic-ischaemic brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Vries, Linda S. de [University Medical Centre, Department of Neonatology, Wilhelmina Children' s Hospital, Utrecht (Netherlands); Wilhelmina Children' s Hospital, University Medical Centre, Department of Neonatology, KE 04.123.1, P.O. Box 85090, Utrecht (Netherlands); Groenendaal, Floris [University Medical Centre, Department of Neonatology, Wilhelmina Children' s Hospital, Utrecht (Netherlands)

    2010-06-15

    Enormous progress has been made in assessing the neonatal brain, using magnetic resonance imaging (MRI). In this review, we will describe the use of MRI and proton magnetic resonance spectroscopy in detecting different patterns of brain injury in (full-term) human neonates following hypoxic-ischaemic brain injury and indicate the relevance of these findings in predicting neurodevelopmental outcome. (orig.)

  8. Acute cardiac support with intravenous milrinone promotes recovery from early brain injury in a murine model of severe subarachnoid haemorrhage.

    Science.gov (United States)

    Mutoh, Tomoko; Mutoh, Tatsushi; Nakamura, Kazuhiro; Yamamoto, Yukiko; Tsuru, Yoshiharu; Tsubone, Hirokazu; Ishikawa, Tatsuya; Taki, Yasuyuki

    2017-04-01

    Early brain injury/ischaemia (EBI) is a serious complication early after subarachnoid haemorrhage (SAH) that contributes to development of delayed cerebral ischaemia (DCI). This study aimed to determine the role of inotropic cardiac support using milrinone (MIL) on restoring acute cerebral hypoperfusion attributable to EBI and improving outcomes after experimental SAH. Forty-three male C57BL/6 mice were assigned to either sham surgery (SAH-sham), SAH induced by endovascular perforation plus postconditioning with 2% isoflurane (Control), or SAH plus isoflurane combined with MIL with and without hypoxia-inducible factor inhibitor (HIF-I) pretreatment. Cardiac output (CO) during intravenous MIL infusion (0.25-0.75 μg/kg/min) between 1.5 and 2.5 hours after SAH induction was monitored with Doppler echocardiography. Magnetic resonance imaging (MRI)-continuous arterial spin labelling was used for quantitative cerebral blood flow (CBF) measurements. Neurobehavioral function was assessed daily by neurological score and open field test. DCI was analyzed 3 days later by determining infarction on MRI. Mild reduction of cardiac output (CO) and global cerebral blood flow (CBF) depression were notable early after SAH. MIL increased CO in a dose-dependent manner (P<.001), which was accompanied by improved hypoperfusion, incidence of DCI and functional recovery than Control (P<.05). The neuroprotective effects afforded by MIL or Control were attenuated by hypoxia-inducible factor (HIF) inhibition (P<.05). These results suggest that MIL improves acute hypoperfusion by its inotropic effect, leading to neurobehavioral improvement in mice after severe SAH, in which HIF may be acting as a critical mediator. © 2017 John Wiley & Sons Australia, Ltd.

  9. Modelos animales de lesión y reparación del cerebro en desarrollo Animal models of injury and repair in developing brain

    Directory of Open Access Journals (Sweden)

    Eduardo Cuestas

    2007-04-01

    Full Text Available Gran parte de la morbilidad y mortalidad neonatal están determinadas por la lesión del cerebro en desarrollo. Un considerable número de los niños afectados presentarán secuelas neurológicas a largo plazo. A pesar de la importancia médica y social que presenta el problema, los avances alcanzados por la medicina neonatal no cuentan aún con una terapéutica eficaz para prevenir o aminorar las consecuencias de la lesión del cerebro en desarrollo. En la siguiente revisión nos proponemos actualizar las investigaciones más recientes en relación a los mecanismos de lesión y reparación del cerebro en desarrollo, basados en modelos animales que ilustran sobre los mecanismos plásticos de adaptación neuronal y funcional; el fin es un mejor conocimiento de los citados procesos que ayude al clínico en la práctica cotidiana de la neonatología.Brain injury is a major contributor to neonatal morbidity and mortality, a considerable group of these children will develop long term neurological sequels. Despite the great clinical and social significance and the advances in neonatal medicine, no therapy yet does exist that prevent or decrease detrimental effects in cases of neonatal brain injury. Our objective was to review recent research in relation to the hypothesis for repair mechanism in the developing brain, based in animal models that show developmental compensatory mechanisms that promote neural and functional plasticity. A better understanding of these adaptive mechanisms will help clinicians to apply knowledge derived from animals to human clinical situations.

  10. Imaging grafted cells with [18F]FHBG using an optimized HSV1-TK mammalian expression vector in a brain injury rodent model.

    Directory of Open Access Journals (Sweden)

    Anne-Sophie Salabert

    Full Text Available Cell transplantation is an innovative therapeutic approach after brain injury to compensate for tissue damage. To have real-time longitudinal monitoring of intracerebrally grafted cells, we explored the feasibility of a molecular imaging approach using thymidine kinase HSV1-TK gene encoding and [18F]FHBG as a reporter probe to image enzyme expression.A stable neuronal cell line expressing HSV1-TK was developed with an optimised mammalian expression vector to ensure long-term transgene expression. After [18F]FHBG incubation under defined parameters, calibration ranges from 1 X 104 to 3 X 106 Neuro2A-TK cells were analysed by gamma counter or by PET-camera. In parallel, grafting with different quantities of [18F]FHBG prelabelled Neuro2A-TK cells was carried out in a rat brain injury model induced by stereotaxic injection of malonate toxin. Image acquisition of the rats was then performed with PET/CT camera to study the [18F]FHBG signal of transplanted cells in vivo.Under the optimised incubation conditions, [18F]FHBG cell uptake rate was around 2.52%. In-vitro calibration range analysis shows a clear linear correlation between the number of cells and the signal intensity. The PET signal emitted into rat brain correlated well with the number of cells injected and the number of surviving grafted cells was recorded via the in-vitro calibration range. PET/CT acquisitions also allowed validation of the stereotaxic injection procedure. Technique sensitivity was evaluated under 5 X 104 grafted cells in vivo. No [18F]FHBG or [18F]metabolite release was observed showing a stable cell uptake even 2 h post-graft.The development of this kind of approach will allow grafting to be controlled and ensure longitudinal follow-up of cell viability and biodistribution after intracerebral injection.

  11. Measurement of Lactate Content and Amide Proton Transfer Values in the Basal Ganglia of a Neonatal Piglet Hypoxic-Ischemic Brain Injury Model Using MRI.

    Science.gov (United States)

    Zheng, Y; Wang, X-M

    2017-04-01

    As amide proton transfer imaging is sensitive to protein content and intracellular pH, it has been widely used in the nervous system, including brain tumors and stroke. This work aimed to measure the lactate content and amide proton transfer values in the basal ganglia of a neonatal piglet hypoxic-ischemic brain injury model by using MR spectroscopy and amide proton transfer imaging. From 58 healthy neonatal piglets (3-5 days after birth; weight, 1-1.5 kg) selected initially, 9 piglets remained in the control group and 43 piglets, in the hypoxic-ischemic brain injury group. Single-section amide proton transfer imaging was performed at the coronal level of the basal ganglia. Amide proton transfer values of the bilateral basal ganglia were measured in all piglets. The ROI of MR spectroscopy imaging was the right basal ganglia, and the postprocessing was completed with LCModel software. After hypoxic-ischemic insult, the amide proton transfer values immediately decreased, and at 0-2 hours, they remained at their lowest level. Thereafter, they gradually increased and finally exceeded those of the control group at 48-72 hours. After hypoxic-ischemic insult, the lactate content increased immediately, was maximal at 2-6 hours, and then gradually decreased to the level of the control group. The amide proton transfer values were negatively correlated with lactate content ( r = -0.79, P < .05). This observation suggests that after hypoxic-ischemic insult, the recovery of pH was faster than that of lactate homeostasis. © 2017 by American Journal of Neuroradiology.

  12. Mechanical injury induces brain endothelial-derived microvesicle release: Implications for cerebral vascular injury during traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Allison M. Andrews

    2016-02-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  14. Dissociation of brain edema induced by cold injury in rat model. MR imaging and perfusion studies with 14C-iodo-antipyrine

    International Nuclear Information System (INIS)

    Itabashi, Yoko; Prado, G.L.M.; Abo, Mitsuru; Miura, Hiroyuki; Abe, Yoshinao

    2001-01-01

    The purpose of this study is to confirm whether T2-weighted imaging and perfusion imaging, i.e. autoradiogram of 14 C-iodoantipyrine, on the course of brain edema correspond to each other or not. Cold injured rat brains were used as a model and were sequentially examined by both methods and compared with each other and with histological specimens. Special focus relies on the time changes in the lesions. High SI of T2-weighted images were observed and the percentages in the high SI area to the total brain area in the same slice were 4.7±0.31, 5.6±0.46 and 3.4±0.42 for 6, 24 and 48 hours, respectively. By contrast, low perfusion areas were indicated in the perfusion study and their percentages were 4.6±0.55, 5.6±0.86 and 2.4±0.35 for 6, 24 and 48 hours, respectively. At 48 hours after cold injury, low perfusion areas were smaller than high SI areas. Moreover, high accumulation areas consisting of macrophages were observed surrounding necrosis. It is concluded that there is dissociation between perfusion and T2-weighted MR imaging, where the collection of macrophages surrounding edema lesions and necrosis had the same appearance on MRI and different accumulations on perfusion studies. (author)

  15. Ethanolic extract of Astragali radix and Salviae radix prohibits oxidative brain injury by psycho-emotional stress in whisker removal rat model.

    Directory of Open Access Journals (Sweden)

    Hyeong-Geug Kim

    Full Text Available Myelophil, an ethanolic extract of Astragali Radix and Salviae Radix, has been clinically used to treat chronic fatigue and stress related disorders in South Korea. In this study, we investigated the protective effects of Myelophil on a whisker removal-induced psycho-emotional stress model. SD rats were subjected to whisker removal after oral administration of Myelophil or ascorbic acid for consecutive 4 days. Whisker removal considerably increased total reactive oxygen species in serum levels as well as cerebral cortex and hippocampal regions in brain tissues. Lipidperoxidation levels were also increased in the cerebral cortex, hippocampus regions, and brain tissue injuries as shown in histopathology and immunohistochemistry. However, Myelophil significantly ameliorated these alterations, and depletion of glutathione contents in both cerebral cortex and hippocampus regions respectively. Serum levels of corticosterone and adrenaline were notably altered after whisker removal stress, whereas these abnormalities were significantly normalized by pre-treatment with Myelophil. The NF-κB was notably activated in both cerebral cortex and hippocampus after whisker removal stress, while it was efficiently blocked by pre-treatment with Myelophil. Myelophil also significantly normalizes alterations of tumor necrosis factor-α, interleukin (IL-1β, IL-6 and interferon-γ in both gene expressions and protein levels. These results suggest that Myelophil has protective effects on brain damages in psycho-emotional stress, and the underlying mechanisms involve regulation of inflammatory proteins, especially NF-κB modulation.

  16. A factor analysis of Functional Independence and Functional Assessment Measure scores among focal and diffuse brain injury patients: The importance of bi-factor models.

    Science.gov (United States)

    Gunn, Sarah; Burgess, Gerald H; Maltby, John

    2018-04-28

    To explore the factor structure of the UK Functional Independence Measure and Functional Assessment Measure (FIM+FAM) among focal and diffuse acquired brain injury patients. Criterion standard. An NHS acute acquired brain injury inpatient rehabilitation hospital. Referred sample of 447 adults (835 cases after exclusions) admitted for inpatient treatment following an acquired brain injury significant enough to justify intensive inpatient neurorehabilitation. Not applicable. Functional Independence Measure and Functional Assessment Measure. Exploratory Factor Analysis suggested a two-factor structure to FIM+FAM scores, among both focal-proximate and diffuse-proximate acquired brain injury aetiologies. Confirmatory Factor Analysis suggested a three-factor bi-factor structure presented the best fit of the FIM+FAM score data across both aetiologies. However, across both analyses, a convergence was found towards a general factor, demonstrated by high correlations between factors in the Exploratory Factor Analysis, and by a general factor explaining the majority of the variance in scores on Confirmatory Factor Analysis. Our findings suggested that although factors describing specific functional domains can be derived from FIM+FAM item scores, there is a convergence towards a single factor describing overall functioning. This single factor informs the specific group factors (e.g. motor, psychosocial and communication function) following brain injury. Further research into the comparative value of the general and group factors as evaluative/prognostic measures is indicated. Copyright © 2018. Published by Elsevier Inc.

  17. Neurobehavioral, neuropathological and biochemical profiles in a novel mouse model of co-morbid post-traumatic stress disorder and mild traumatic brain injury

    Science.gov (United States)

    Ojo, Joseph O.; Greenberg, M. Banks; Leary, Paige; Mouzon, Benoit; Bachmeier, Corbin; Mullan, Michael; Diamond, David M.; Crawford, Fiona

    2014-01-01

    Co-morbid mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) has become the signature disorder for returning combat veterans. The clinical heterogeneity and overlapping symptomatology of mTBI and PTSD underscore the need to develop a preclinical model that will enable the characterization of unique and overlapping features and allow discrimination between both disorders. This study details the development and implementation of a novel experimental paradigm for PTSD and combined PTSD-mTBI. The PTSD paradigm involved exposure to a danger-related predator odor under repeated restraint over a 21 day period and a physical trauma (inescapable footshock). We administered this paradigm alone, or in combination with a previously established mTBI model. We report outcomes of behavioral, pathological and biochemical profiles at an acute timepoint. PTSD animals demonstrated recall of traumatic memories, anxiety and an impaired social behavior. In both mTBI and combination groups there was a pattern of disinhibitory like behavior. mTBI abrogated both contextual fear and impairments in social behavior seen in PTSD animals. No major impairment in spatial memory was observed in any group. Examination of neuroendocrine and neuroimmune responses in plasma revealed a trend toward increase in corticosterone in PTSD and combination groups, and an apparent increase in Th1 and Th17 proinflammatory cytokine(s) in the PTSD only and mTBI only groups respectively. In the brain there were no gross neuropathological changes in any groups. We observed that mTBI on a background of repeated trauma exposure resulted in an augmentation of axonal injury and inflammatory markers, neurofilament L and ICAM-1 respectively. Our observations thus far suggest that this novel stress-trauma-related paradigm may be a useful model for investigating further the overlapping and distinct spatio-temporal and behavioral/biochemical relationship between mTBI and PTSD experienced by combat

  18. Home environment, brain injury, & school performance in LBW survivors.

    Science.gov (United States)

    Mahoney, Ashley Darcy; Pinto-Martin, Jennifer; Hanlon, Alexandra

    2014-01-01

    There has been substantial research on low birthweight (LBW) as a predictor of adverse educational and cognitive outcomes. LBW infants perform worse on cognitive battery tests compared to children born at normal birthweight; however, children exposed to similar risks do not all share the same experiences. The complex, interrelated factors responsible for poor cognitive and achievement performance vary for different populations, but researchers hypothesize that the home environment may influence the infants' long-term health outcomes. Examine the home environment as a moderator in the causal pathway from neonatal brain injury to school performance in a secondary analysis of a prospectively studied, geographically defined cohort from the Neonatal Brain Hemorrhage Study. The secondary analysis sample included 543 infants with birthweights of 501 to 2,000 g who were born consecutively in three community hospitals in New Jersey between 1984 and 1986. School performance at age 9 was measured by the Woodcock-Johnson Tests of Achievement. The home environment variables were tested and analyzed using multistep hierarchical regression modeling. A moderating effect between the variable neighborhood observations and brain injury was demonstrated for the outcome math score. The moderating relationship was found in the category of children without brain injury (β = 1.76, p = .005). There were statistically significant and potentially clinical meaningful models when looking at the home environmental variables as they relate to reading and math scores. The findings suggest that at least one variable within a LBW child's socio-environmental milieu can moderate the effects of perinatal brain injury on school performance outcomes.

  19. Experimental Traumatic Brain Injury Induces Bone Loss in Rats.

    Science.gov (United States)

    Brady, Rhys D; Shultz, Sandy R; Sun, Mujun; Romano, Tania; van der Poel, Chris; Wright, David K; Wark, John D; O'Brien, Terence J; Grills, Brian L; McDonald, Stuart J

    2016-12-01

    Few studies have investigated the influence of traumatic brain injury (TBI) on bone homeostasis; however, pathophysiological mechanisms involved in TBI have potential to be detrimental to bone. The current study assessed the effect of experimental TBI in rats on the quantity and quality of two different weight-bearing bones, the femur and humerus. Rats were randomly assigned into either sham or lateral fluid percussion injury (FPI) groups. Open-field testing to assess locomotion was conducted at 1, 4, and 12 weeks post-injury, with the rats killed at 1 and 12 weeks post-injury. Bones were analyzed using peripheral quantitative computed tomography (pQCT), histomorphometric analysis, and three-point bending. pQCT analysis revealed that at 1 and 12 weeks post-injury, the distal metaphyseal region of femora from FPI rats had reduced cortical content (10% decrease at 1 week, 8% decrease at 12 weeks; p in trabecular bone volume ratio at 1 week post-injury and a 27% reduction at 12 weeks post-injury in FPI rats compared to sham (p in bone quantity and mechanical properties of the femoral midshaft between sham and TBI animals. There were no differences in locomotor outcomes, which suggested that post-TBI changes in bone were not attributed to immobility. Taken together, these findings indicate that this rat model of TBI was detrimental to bone and suggests a link between TBI and altered bone remodeling.

  20. Isolated traumatic brain injury and venous thromboembolism.

    Science.gov (United States)

    Van Gent, Jan-Michael; Bandle, Jesse; Calvo, Richard Y; Zander, Ashley L; Olson, Erik J; Shackford, Steven R; Peck, Kimberly A; Sise, C Beth; Sise, Michael J

    2014-08-01

    Traumatic brain injury (TBI) is considered an independent risk factor of venous thromboembolism (VTE). However, the role of TBI severity in VTE risk has not been determined. We hypothesized that increased severity of brain injury in patients with isolated TBI (iTBI) is associated with an increased incidence of VTE. The records of patients admitted from June 2006 to December 2011 were reviewed for injury data, VTE risk factors, results of lower extremity surveillance ultrasound, and severity of TBI. Patients were identified by DRG International Classification of Diseases-9th Rev. codes for TBI, and only those with a nonhead Abbreviated Injury Scale (AIS) score of 1 or lower, indicating minimal associated injury, were included. The association of iTBI and VTE was determined using a case-control design. Among iTBI patients, those diagnosed with VTE (cases) were matched for age, sex, and admission year to those without VTE (controls). Data were analyzed using conditional logistic regression. There were 345 iTBI patients: 41 cases (12%) and 304 controls (88%). A total of 151 controls could not be matched to an appropriate case and were excluded. Of the remaining 153 controls, 1 to 16 controls were matched to each of the 41 VTE cases. Compared with the controls, the cases had a higher mean head-AIS score (4.4 vs. 3.9, p = 0.001) and overall Injury Severity Score (20.4 vs. 16.8, p = 0.001). Following adjustment for all factors found to be associated with VTE (ventilator days, central line placement, operative time > 2 hours, chemoprophylaxis, history of VTE, and history of cancer), the cases were significantly more likely to have a greater head injury severity (head-AIS score ≥ 5; odds ratio, 5.25; 95% confidence interval, 1.59-17.30; p = 0.006). The incidence of VTE in iTBI patients was significantly associated with the severity of TBI. VTE surveillance protocols may be warranted in these high-risk patients, as early detection of VTE could guide subsequent therapy

  1. Addressing the challenges of obtaining functional outcomes in traumatic brain injury research: missing data patterns, timing of follow-up, and three prognostic models.

    Science.gov (United States)

    Zelnick, Leila R; Morrison, Laurie J; Devlin, Sean M; Bulger, Eileen M; Brasel, Karen J; Sheehan, Kellie; Minei, Joseph P; Kerby, Jeffrey D; Tisherman, Samuel A; Rizoli, Sandro; Karmy-Jones, Riyad; van Heest, Rardi; Newgard, Craig D

    2014-06-01

    Traumatic brain injury (TBI) is common and debilitating. Randomized trials of interventions for TBI ideally assess effectiveness by using long-term functional neurological outcomes, but such outcomes are difficult to obtain and costly. If there is little change between functional status at hospital discharge versus 6 months, then shorter-term outcomes may be adequate for use in future clinical trials. Using data from a previously published multi-center, randomized, placebo-controlled TBI clinical trial, we evaluated patterns of missing outcome data, changes in functional status between hospital discharge and 6 months, and three prognostic models to predict long-term functional outcome from covariates available at hospital discharge (functional measures, demographics, and injury characteristics). The Resuscitation Outcomes Consortium Hypertonic Saline trial enrolled 1282 TBI patients, obtaining the primary outcome of 6-month Glasgow Outcome Score Extended (GOSE) for 85% of patients, but missing the primary outcome for the remaining 15%. Patients with missing outcomes had less-severe injuries, higher neurological function at discharge (GOSE), and shorter hospital stays than patients whose GOSE was obtained. Of 1066 (83%) patients whose GOSE was obtained both at hospital discharge and at 6-months, 71% of patients had the same dichotomized functional status (severe disability/death vs. moderate/no disability) after 6 months as at discharge, 28% had an improved functional status, and 1% had worsened. Performance was excellent (C-statistic between 0.88 and 0.91) for all three prognostic models and calibration adequate for two models (p values, 0.22 and 0.85). Our results suggest that multiple imputation of the standard 6-month GOSE may be reasonable in TBI research when the primary outcome cannot be obtained through other means.

  2. 4: Rehabilitation after traumatic brain injury.

    Science.gov (United States)

    Khan, Fary; Baguley, Ian J; Cameron, Ian D

    2003-03-17

    Traumatic brain injury (TBI) commonly affects younger people and causes life-long impairments in physical, cognitive, behavioural and social function. The cognitive, behavioural and personality deficits are usually more disabling than the residual physical deficits. Recovery from TBI can continue for at least 5 years after injury. Rehabilitation is effective using an interdisciplinary approach, and close liaison with the patient, family and carers. The focus is on issues such as retraining in activities of daily living, pain management, cognitive and behavioural therapies, and pharmacological management. The social burden of TBI is significant, and therefore family education and counselling, and support of patient and carers, is important. General practitioners play an important role in providing ongoing support in the community, monitoring for medical complications, behavioural and personality issues, social reintegration, carer coping skills and return-to-work issues.

  3. Seizures and the Role of Anticonvulsants After Traumatic Brain Injury.

    Science.gov (United States)

    Zimmermann, Lara L; Diaz-Arrastia, Ramon; Vespa, Paul M

    2016-10-01

    Posttraumatic seizures are a common complication of traumatic brain injury. Posttraumatic epilepsy accounts for 20% of symptomatic epilepsy in the general population and 5% of all epilepsy. Early posttraumatic seizures occur in more than 20% of patients in the intensive care unit and are associated with secondary brain injury and worse patient outcomes. Most posttraumatic seizures are nonconvulsive and therefore continuous electroencephalography monitoring should be the standard of care for patients with moderate or severe brain injury. The literature shows that posttraumatic seizures result in secondary brain injury caused by increased intracranial pressure, cerebral edema and metabolic crisis. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Traumatic brain injury pharmacological treatment: recommendations

    Directory of Open Access Journals (Sweden)

    Renato Anghinah

    Full Text Available ABSTRACT This article presents the recommendations on the pharmacological treatment employed in traumatic brain injury (TBI at the outpatient clinic of the Cognitive Rehabilitation after TBI Service of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil. A systematic assessment of the consensus reached in other countries, and of articles on TBI available in the PUBMED and LILACS medical databases, was carried out. We offer recommendations of pharmacological treatments in patients after TBI with different symptoms.

  5. Centralized rehabilitation after servere traumatic brain injury

    DEFF Research Database (Denmark)

    Engberg, Aase Worså; Liebach, Annette; Nordenbo, Annette Mosbæk

    2006-01-01

    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...... 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...

  6. Radiation-induced brain injury: A review

    Energy Technology Data Exchange (ETDEWEB)

    Greene-Schloesser, Dana; Robbins, Mike E.; Peiffer, Ann M.; Shaw, Edward G. [Department of Radiation Oncology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Wheeler, Kenneth T. [Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Department of Radiology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Chan, Michael D., E-mail: mrobbins@wakehealth.edu [Department of Radiation Oncology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States)

    2012-07-19

    Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their

  7. Radiation-induced brain injury: A review

    International Nuclear Information System (INIS)

    Greene-Schloesser, Dana; Robbins, Mike E.; Peiffer, Ann M.; Shaw, Edward G.; Wheeler, Kenneth T.; Chan, Michael D.

    2012-01-01

    Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their

  8. Curcumin pretreatment attenuates brain lesion size and improves neurological function following traumatic brain injury in the rat.

    Science.gov (United States)

    Samini, Fariborz; Samarghandian, Saeed; Borji, Abasalt; Mohammadi, Gholamreza; bakaian, Mahdi

    2013-09-01

    Turmeric has been in use since ancient times as a condiment and due to its medicinal properties. Curcumin, the yellow coloring principle in turmeric, is a polyphenolic and a major active constituent. Besides anti-inflammatory, thrombolytic and anti-carcinogenic activities, curcumin also possesses strong antioxidant property. The neuroprotective effects of curcumin were evaluated in a weight drop model of cortical contusion trauma in rat. Male Wistar rats (350-400 g, n=9) were anesthetized with sodium pentobarbital (60 mg/kg i.p.) and subjected to head injury. Five days before injury, animals randomly received an i.p. bolus of either curcumin (50 and 100 mg/kg/day, n=9) or vehicle (n=9). Two weeks after the injury and drug treatment, animals were sacrificed and a series of brain sections, stained with hematoxylin and eosin (H&E) were evaluated for quantitative brain lesion volume. Two weeks after the injury, oxidative stress parameter (malondialdehyde) was also measured in the brain. Curcumin (100 mg/kg) significantly reduced the size of brain injury-induced lesions (Pcurcumin (100 mg/kg). Curcumin treatment significantly improved the neurological status evaluated during 2 weeks after brain injury. The study demonstrates the protective efficacy of curcumin in rat traumatic brain injury model. © 2013 Elsevier Inc. All rights reserved.

  9. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    HU Hua; YAO Hong-tian; ZHANG Wei-ping; ZHANG LEI; DING Wei; ZHANG Shi-hong; CHEN Zhong; WEI Er-qing

    2005-01-01

    Objective: To characterize the expression of aquaporin-4 (AQP4), one of the aquaporins (AQPs), in human brain specimens from patients with traumatic brain injury or brain tumors. Methods: Nineteen human brain specimens were obtained from the patients with traumatic brain injury, brain tumors, benign meningioma or early stage hemorrhagic stroke. MRI or CT imaging was used to assess brain edema. Hematoxylin and eosin staining were used to evaluate cell damage. Immunohistochemistry was used to detect the AQP4 expression. Results: AQP4 expression was increased from 15h to at least 8 d after injury. AQP4immunoreactivity was strong around astrocytomas, ganglioglioma and metastatic adenocarcinoma. However, AQP4 immunoreactivity was only found in the centers of astrocytomas and ganglioglioma, but not in metastatic adenocarcinoma derived from lung.Conclusion: AQP4 expression increases in human brains after traumatic brain injury, within brain-derived tumors, and around brain tumors.

  10. Brain injury with diabetes mellitus: evidence, mechanisms and treatment implications.

    Science.gov (United States)

    Hamed, Sherifa A

    2017-04-01

    Diabetes mellitus is a risk for brain injury. Brain injury is associated with acute and chronic hyperglycaemia, insulin resistance, hyperinsulinemia, diabetic ketoacidosis (DKA) and hypoglycaemic events in diabetic patients. Hyperglycemia is a cause of cognitive deterioration, low intelligent quotient, neurodegeneration, brain aging, brain atrophy and dementia. Areas covered: The current review highlights the experimental, clinical, neuroimaging and neuropathological evidence of brain injury induced by diabetes and its associated metabolic derangements. It also highlights the mechanisms of diabetes-induced brain injury. It seems that the pathogenesis of hyperglycemia-induced brain injury is complex and includes combination of vascular disease, oxidative stress, neuroinflammation, mitochondrial dysfunction, apoptosis, reduction of neurotrophic factors, acetylcholinesterase (AChE) activation, neurotransmitters' changes, impairment of brain repair processes, impairment of brain glymphatic system, accumulation of amyloid β and tau phosphorylation and neurodegeneration. The potentials for prevention and treatment are also discussed. Expert commentary: We summarize the risks and the possible mechanisms of DM-induced brain injury and recommend strategies for neuroprotection and neurorestoration. Recently, a number of drugs and substances [in addition to insulin and its mimics] have shown promising potentials against diabetes-induced brain injury. These include: antioxidants, neuroinflammation inhibitors, anti-apoptotics, neurotrophic factors, AChE inhibitors, mitochondrial function modifiers and cell based therapies.

  11. Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats.

    Science.gov (United States)

    McBride, Devin W; Wang, Yuechun; Sherchan, Prativa; Tang, Jiping; Zhang, John H

    2015-09-01

    Brain edema is a major contributor to poor outcome and reduced quality of life after surgical brain injury (SBI). Although SBI pathophysiology is well-known, the correlation between cerebral edema and neurological deficits has not been thoroughly examined in the rat model of SBI. Thus, the purpose of this study was to determine the correlation between brain edema and deficits in standard sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague-Dawley rats were subjected to either sham surgery or surgical brain injury via partial frontal lobectomy. All animals were tested for neurological deficits 24 post-SBI and fourteen were also tested 72 h after surgery using seven common behavior tests: modified Garcia neuroscore (Neuroscore), beam walking, corner turn test, forelimb placement test, adhesive removal test, beam balance test, and foot fault test. After assessing the functional outcome, animals were euthanized for brain water content measurement. Surgical brain injury resulted in significantly elevated frontal lobe brain water content 24 and 72 h after surgery compared to that of sham animals. In all behavior tests, significance was observed between sham and SBI animals. However, a correlation between brain water content and functional outcome was observed for all tests except Neuroscore. The selection of behavior tests is critical to determine the effectiveness of therapeutics. Based on this study's results, we recommend using beam walking, the corner turn test, the beam balance test, and the foot fault test since correlations with brain water content were observed at both 24 and 72 h post-SBI. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats

    Science.gov (United States)

    McBride, Devin W.; Wang, Yuechun; Sherchan, Prativa; Tang, Jiping; Zhang, John H.

    2015-01-01

    Brain edema is a major contributor to poor outcome and reduced quality of life after surgical brain injury (SBI). Although SBI pathophysiology is well-known, the correlation between cerebral edema and neurological deficits has not been thoroughly examined in the rat model of SBI. Thus, the purpose of this study was to determine the correlation between brain edema and deficits in standard sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague-Dawley rats were subjected to either sham surgery or surgical brain injury via partial frontal lobectomy. All animals were tested for neurological deficits 24 post-SBI and fourteen were also tested 72 hours after surgery using seven common behavior tests: modified Garcia neuroscore (Neuroscore), beam walking, corner turn test, forelimb placement test, adhesive removal test, beam balance test, and foot fault test. After assessing the functional outcome, animals were euthanized for brain water content measurement. Surgical brain injury resulted in a significantly elevated frontal lobe brain water content 24 and 72 hours after surgery compared to that of sham animals. In all behavior tests, significance was observed between sham and SBI animals. However, a correlation between brain water content and functional outcome was observed for all tests except Neuroscore. The selection of behavior tests is critical to determine the effectiveness of therapeutics. Based on this study’s results, we recommend using beam walking, the corner turn test, the beam balance test, and the foot fault test since correlations with brain water content were observed at both 24 and 72 hours post-SBI. PMID:25975171

  13. Facilitated assessment of tissue loss following traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Anders eHånell

    2012-03-01

    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.

  14. Environmental Enrichment Mitigates Deficits after Repetitive Mild Traumatic Brain Injury.

    Science.gov (United States)

    Liu, Xixia; Qiu, Jianhua; Alcon, Sasha; Hashim, Jumana; Meehan, William P; Mannix, Rebekah

    2017-08-15

    Although environmental enrichment has been shown to improve functional and histologic outcomes in pre-clinical moderate-to-severe traumatic brain injury (TBI), there are a paucity of pre-clinical data regarding enrichment strategies in the setting of repetitive mild traumatic brain injury (rmTBI). Given the vast numbers of athletes and those in the military who sustain rmTBI, the mounting evidence of the long-term and progressive sequelae of rmTBI, and the lack of targeted therapies to mitigate these sequelae, successful enrichment interventions in rmTBI could have large public health significance. Here, we evaluated enrichment strategies in an established pre-clinical rmTBI model. Seventy-one male C57BL/6 mice were randomized to two different housing conditions, environmental enrichment (EE) or normal condition (NC), then subjected to rmTBI injury (seven injuries in 9 days) or sham injury (anesthesia only). Functional outcomes in all four groups (NC-TBI, EE-TBI, NC-sham, and EE-sham) were assessed by motor, exploratory/anxiety, and mnemonic behavioral tests. At the synaptic level, N-methyl d-aspartate receptor (NMDAR) subunit expression of phosphorylated glutamate receptor 1 (GluR1), phosphorylated Ca 2+ /calmodulin-dependent protein kinase II (CaMKII), and calpain were evaluated by western blot. Compared to injured NC-TBI mice, EE-TBI mice had improved memory and decreased anxiety and exploratory activity post-injury. Treatment with enrichment also corresponded to normal NMDAR subunit expression, decreased GluR1 phosphorylation, decreased phosphorylated CaMKII, and normal calpain expression post-rmTBI. These data suggest that enrichment strategies may improve functional outcomes and mitigate synaptic changes post-rmTBI. Given that enrichment strategies are feasible in the clinical setting, particularly for athletes and soldiers for whom the risk of repetitive injury is greatest, these data suggest that clinical trials may be warranted.

  15. Dual Therapeutic Effects of C-10068, a Dextromethorphan Derivative, Against Post-Traumatic Nonconvulsive Seizures and Neuroinflammation in a Rat Model of Penetrating Ballistic-Like Brain Injury

    Science.gov (United States)

    Shear, Deborah A.; Graham, Philip B.; Bridson, Gary W.; Uttamsingh, Vinita; Chen, Zhiyong; Leung, Lai Yee; Tortella, Frank C.

    2015-01-01

    Abstract Post-traumatic seizures can exacerbate injurious outcomes of severe brain trauma, yet effective treatments are limited owing to the complexity of the pathology underlying the concomitant occurrence of both events. In this study, we tested C‐10068, a novel deuterium-containing analog of (+)-N-methyl-3-ethoxymorphinan, in a rat model of penetrating ballistic-like brain injury (PBBI) and evaluated the effects of C-10068 on PBBI-induced nonconvulsive seizures (NCS), acute neuroinflammation, and neurofunctional outcomes. NCS were detected by electroencephalographic monitoring. Neuroinflammation was evaluated by immunohistochemical markers, for example, glial fibrillary acidic protein and major histocompatibility complex class I, for activation of astrocytes and microglia, respectively. Neurofunction was tested using rotarod and Morris water maze tasks. Three infusion doses of C-10068 (1.0, 2.5, and 5.0 mg/kg/h×72 h) were tested in the antiseizure study. Neuroinflammation and neurofunction were evaluated in animals treated with 5.0 mg/kg/h×72 h C-10068. Compared to vehicle treatment, C-10068 dose dependently reduced PBBI-induced NCS incidence (40–50%), frequency (20–70%), and duration (30–82%). The most effective antiseizure dose of C-10068 (5.0 mg/kg/h×72 h) also significantly attenuated hippocampal astrocyte activation and perilesional microglial reactivity post-PBBI. Within C-10068-treated animals, a positive correlation was observed in reduction in NCS frequency and reduction in hippocampal astrocyte activation. Further, C-10068 treatment significantly attenuated astrocyte activation in seizure-free animals. However, C-10068 failed to improve PBBI-induced motor and cognitive functions with the dosing regimen used in this study. Overall, the results indicating that C-10068 exerts both potent antiseizure and antiinflammatory effects are promising and warrant further investigation. PMID:25794265

  16. Dual Therapeutic Effects of C-10068, a Dextromethorphan Derivative, Against Post-Traumatic Nonconvulsive Seizures and Neuroinflammation in a Rat Model of Penetrating Ballistic-Like Brain Injury.

    Science.gov (United States)

    Lu, Xi-Chun May; Shear, Deborah A; Graham, Philip B; Bridson, Gary W; Uttamsingh, Vinita; Chen, Zhiyong; Leung, Lai Yee; Tortella, Frank C

    2015-10-15

    Post-traumatic seizures can exacerbate injurious outcomes of severe brain trauma, yet effective treatments are limited owing to the complexity of the pathology underlying the concomitant occurrence of both events. In this study, we tested C-10068, a novel deuterium-containing analog of (+)-N-methyl-3-ethoxymorphinan, in a rat model of penetrating ballistic-like brain injury (PBBI) and evaluated the effects of C-10068 on PBBI-induced nonconvulsive seizures (NCS), acute neuroinflammation, and neurofunctional outcomes. NCS were detected by electroencephalographic monitoring. Neuroinflammation was evaluated by immunohistochemical markers, for example, glial fibrillary acidic protein and major histocompatibility complex class I, for activation of astrocytes and microglia, respectively. Neurofunction was tested using rotarod and Morris water maze tasks. Three infusion doses of C-10068 (1.0, 2.5, and 5.0 mg/kg/h × 72 h) were tested in the antiseizure study. Neuroinflammation and neurofunction were evaluated in animals treated with 5.0 mg/kg/h × 72 h C-10068. Compared to vehicle treatment, C-10068 dose dependently reduced PBBI-induced NCS incidence (40-50%), frequency (20-70%), and duration (30-82%). The most effective antiseizure dose of C-10068 (5.0 mg/kg/h × 72 h) also significantly attenuated hippocampal astrocyte activation and perilesional microglial reactivity post-PBBI. Within C-10068-treated animals, a positive correlation was observed in reduction in NCS frequency and reduction in hippocampal astrocyte activation. Further, C-10068 treatment significantly attenuated astrocyte activation in seizure-free animals. However, C-10068 failed to improve PBBI-induced motor and cognitive functions with the dosing regimen used in this study. Overall, the results indicating that C-10068 exerts both potent antiseizure and antiinflammatory effects are promising and warrant further investigation.

  17. Primary blast-induced traumatic brain injury: lessons from lithotripsy

    Science.gov (United States)

    Nakagawa, A.; Ohtani, K.; Armonda, R.; Tomita, H.; Sakuma, A.; Mugikura, S.; Takayama, K.; Kushimoto, S.; Tominaga, T.

    2017-11-01

    Traumatic injury caused by explosive or blast events is traditionally divided into four mechanisms: primary, secondary, tertiary, and quaternary blast injury. The mechanisms of blast-induced traumatic brain injury (bTBI) are biomechanically distinct and can be modeled in both in vivo and in vitro systems. The primary bTBI injury mechanism is associated with the response of brain tissue to the initial blast wave. Among the four mechanisms of bTBI, there is a remarkable lack of information regarding the mechanism of primary bTBI. On the other hand, 30 years of research on the medical application of shock waves (SWs) has given us insight into the mechanisms of tissue and cellular damage in bTBI, including both air-mediated and underwater SW sources. From a basic physics perspective, the typical blast wave consists of a lead SW followed by shock-accelerated flow. The resultant tissue injury includes several features observed in primary bTBI, such as hemorrhage, edema, pseudo-aneurysm formation, vasoconstriction, and induction of apoptosis. These are well-described pathological findings within the SW literature. Acoustic impedance mismatch, penetration of tissue by shock/bubble interaction, geometry of the skull, shear stress, tensile stress, and subsequent cavitation formation are all important factors in determining the extent of SW-induced tissue and cellular injury. In addition, neuropsychiatric aspects of blast events need to be taken into account, as evidenced by reports of comorbidity and of some similar symptoms between physical injury resulting in bTBI and the psychiatric sequelae of post-traumatic stress. Research into blast injury biophysics is important to elucidate specific pathophysiologic mechanisms of blast injury, which enable accurate differential diagnosis, as well as development of effective treatments. Herein we describe the requirements for an adequate experimental setup when investigating blast-induced tissue and cellular injury; review SW physics

  18. Traumatic Brain Injury: Caregivers’ Problems and Needs

    Directory of Open Access Journals (Sweden)

    syed tajjudin syed hassan

    2011-03-01

    Full Text Available Traumatic brain injury (TBI is an increasingly major world health problem. This short review using the most pertinent articles on TBI caregiving problems and needs highlights the pressing issues. Articles focusing on both TBI-caregivers’ problems and needs are rarely found, especially for developing countries. Most TBI-caregiving is done by family members, whose altered lives portend burden and stresses which add to the overwhelming demand of caring for the TBI-survivor. Lack of information, fi nancial inadequacy, anxiety, distress, coping defi cits, poor adaptability, inadequate knowledge and skills, and a poor support system comprise the major problems. Dysfunctional communication between caregivers and care-receivers has been little researched. The major needs are focused on health and rehabilitation information, fi nancial advice and assistance, emotional and social support, and positive psychological encouragement. In time, health information needs may be met, but not emotional support. Information on TBI caregiving problems and unmet needs is critical to all relevant healthcare stakeholders. Keywords: caregivers, rehabilitation, traumatic brain injury

  19. Impaired Pituitary Axes Following Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Robert A. Scranton

    2015-07-01

    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.

  20. Ischemic preconditioning protects against ischemic brain injury

    Directory of Open Access Journals (Sweden)

    Xiao-meng Ma

    2016-01-01

    Full Text Available In this study, we hypothesized that an increase in integrin αv ß 3 and its co-activator vascular endothelial growth factor play important neuroprotective roles in ischemic injury. We performed ischemic preconditioning with bilateral common carotid artery occlusion for 5 minutes in C57BL/6J mice. This was followed by ischemic injury with bilateral common carotid artery occlusion for 30 minutes. The time interval between ischemic preconditioning and lethal ischemia was 48 hours. Histopathological analysis showed that ischemic preconditioning substantially diminished damage to neurons in the hippocampus 7 days after ischemia. Evans Blue dye assay showed that ischemic preconditioning reduced damage to the blood-brain barrier 24 hours after ischemia. This demonstrates the neuroprotective effect of ischemic preconditioning. Western blot assay revealed a significant reduction in protein levels of integrin αv ß 3, vascular endothelial growth factor and its receptor in mice given ischemic preconditioning compared with mice not given ischemic preconditioning 24 hours after ischemia. These findings suggest that the neuroprotective effect of ischemic preconditioning is associated with lower integrin αv ß 3 and vascular endothelial growth factor levels in the brain following ischemia.

  1. Psychiatric disorders and traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Marcelo Schwarzbold

    2008-09-01

    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

  2. Twitter and traumatic brain injury: A content and sentiment analysis of tweets pertaining to sport-related brain injury.

    Science.gov (United States)

    Workewych, Adriana M; Ciuffetelli Muzzi, Madeline; Jing, Rowan; Zhang, Stanley; Topolovec-Vranic, Jane; Cusimano, Michael D

    2017-01-01

    Sport-related traumatic brain injuries are a significant public health burden, with hundreds of thousands sustained annually in North America. While sports offer numerous physical and social health benefits, traumatic brain injuries such as concussion can seriously impact a player's life, athletic career, and sport enjoyment. The culture in many sports encourages winning at all costs, placing athletes at risk for traumatic brain injuries. As social media has become a central part of everyday life, the content of users' messages often reflects the prevailing culture related to a particular event or health issue. We hypothesized that Twitter data might be useful for understanding public perceptions and misperceptions of sport-related traumatic brain injuries. We performed a content and sentiment analysis of 7483 Twitter ® tweets related to traumatic brain injuries in sports collected during June and July 2013. We identified five major themes. Users tweeted about personal traumatic brain injuries experiences, reported traumatic brain injuries in professional athletes, shared research about sport-related concussions, and discussed policy and safety in injury prevention, such as helmet use. We identified mixed perceptions of and sentiment toward traumatic brain injuries in sports: both an understanding that brain injuries are serious and disregard for activities that might reduce the public burden of traumatic brain injuries were prevalent in our Twitter analysis. While the scientific and medical community considers a concussion a form of traumatic brain injuries, our study demonstrates a misunderstanding of this fact among the public. In our current digital age, social media can provide useful insight into the culture around a health issue, facilitating implementation of prevention and treatment strategies.

  3. Evaluating paediatric brain injury services in NSW.

    Science.gov (United States)

    Badge, H; Hancock, J; Waugh, M-C

    2010-01-01

    Rehabilitation professionals strive to provide high-quality evidence-based services for children. Developing systems to measure and monitor the benefits of our services, and health outcomes for children is complex and challenging. The Community Outcome Project aims to introduce systematic outcome measurement across the network of paediatric community-based brain injury services within the New South Wales Brain Injury Rehabilitation Program (BIRP) to support clinical practice and service evaluation. A literature review informed the development of the evaluative framework and identified available paediatric outcome measures which may be appropriate. Extensive consultation with clinicians supported project planning and identified clinical priorities that the outcome measures needed to capture. Outcome measures were shortlisted by matching them to identified clinical priorities, and then trialled in clinical practice. Qualitative feedback regarding clinical utility and feasibility was obtained from clinical staff. The process has utilized change management strategies to ensure the success of the project and keep staff engaged. The process identified the three main clinical priorities for outcome measurement - family functioning, school performance and participation. Three outcome measures were chosen for the pilot project that is currently underway. They are Family Burden of Injury Interview, Academic Competence and Evaluation Scales and Child and Adolescent Scale of Participation. Plans for analyses of outcome data within the paediatric BIRP services are discussed. Extensive preparation is required to optimize staff engagement in a project that systematically introduces outcome measures that are useful to clinicians, clients and service providers. Managing the change required is a key focus of the project. Benefits and costs to clinicians and services will be discussed.

  4. Phosphorylation of Akt by SC79 Prevents Iron Accumulation and Ameliorates Early Brain Injury in a Model of Experimental Subarachnoid Hemorrhage

    Directory of Open Access Journals (Sweden)

    Shuangying Hao

    2016-03-01

    Full Text Available Previous studies have demonstrated that activation of Akt may alleviate early brain injury (EBI following subarachnoid hemorrhage (SAH. This study is undertaken to determine whether iron metabolism is involved in the beneficial effect of Akt activation after SAH. Therefore, we used a novel molecule, SC79, to activate Akt in an experimental Sprague–Dawley rat model of SAH. Rats were randomly divided into four groups as follows: sham, SAH, SAH + vehicle, SAH + SC79. The results confirmed that SC79 effectively enhanced the defense against oxidative stress and alleviated EBI in the temporal lobe after SAH. Interestingly, we found that phosphorylation of Akt by SC79 reduced cell surface transferrin receptor-mediated iron uptake and promoted ferroportin-mediated iron transport after SAH. As a result, SC79 administration diminished the iron content in the brain tissue. Moreover, the impaired Fe-S cluster biogenesis was recovered and loss of the activities of the Fe-S cluster-containing enzymes were regained, indicating that injured mitochondrial functions are restored to healthy levels. These findings suggest that disrupted iron homeostasis could contribute to EBI and Akt activation may regulate iron metabolism to relieve iron toxicity, further protecting neurons from EBI after SAH.

  5. Brain-Derived Neurotrophic Factor Increases Synaptic Protein Levels via the MAPK/Erk Signaling Pathway and Nrf2/Trx Axis Following the Transplantation of Neural Stem Cells in a Rat Model of Traumatic Brain Injury.

    Science.gov (United States)

    Chen, Tao; Wu, Yu; Wang, Yuzi; Zhu, Jigao; Chu, Haiying; Kong, Li; Yin, Liangwei; Ma, Haiying

    2017-11-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in promoting the growth, differentiation, survival and synaptic stability of neurons. Presently, the transplantation of neural stem cells (NSCs) is known to induce neural repair to some extent after injury or disease. In this study, to investigate whether NSCs genetically modified to encode the BDNF gene (BDNF/NSCs) would further enhance synaptogenesis, BDNF/NSCs or naive NSCs were directly engrafted into lesions in a rat model of traumatic brain injury (TBI). Immunohistochemistry, western blotting and RT-PCR were performed to detect synaptic proteins, BDNF-TrkB and its downstream signaling pathways, at 1, 2, 3 or 4 weeks after transplantation. Our results showed that BDNF significantly increased the expression levels of the TrkB receptor gene and the phosphorylation of the TrkB protein in the lesions. The expression levels of Ras, phosphorylated Erk1/2 and postsynaptic density protein-95 were elevated in the BDNF/NSCs-transplanted groups compared with those in the NSCs-transplanted groups throughout the experimental period. Moreover, the nuclear factor (erythroid-derived 2)-like 2/Thioredoxin (Nrf2/Trx) axis, which is a specific therapeutic target for the treatment of injury or cell death, was upregulated by BDNF overexpression. Therefore, we determined that the increased synaptic proteins level implicated in synaptogenesis might be associated with the activation of the MAPK/Erk1/2 signaling pathway and the upregulation of the antioxidant agent Trx modified by BDNF-TrkB following the BDNF/NSCs transplantation after TBI.

  6. Graph Analysis of Functional Brain Networks for Cognitive Control of Action in Traumatic Brain Injury

    Science.gov (United States)

    Caeyenberghs, Karen; Leemans, Alexander; Heitger, Marcus H.; Leunissen, Inge; Dhollander, Thijs; Sunaert, Stefan; Dupont, Patrick; Swinnen, Stephan P.

    2012-01-01

    Patients with traumatic brain injury show clear impairments in behavioural flexibility and inhibition that often persist beyond the time of injury, affecting independent living and psychosocial functioning. Functional magnetic resonance imaging studies have shown that patients with traumatic brain injury typically show increased and more broadly…

  7. Chronic Traumatic Brain Injury in Amateur Boxers

    Directory of Open Access Journals (Sweden)

    M. Rahmati

    2008-04-01

    Full Text Available Introduction & objective: Despite of young and adolescence intent to the boxing sport, because of dominant aggression and direct blows contact to head, face and central nervous system, it is continuously criticize by different groups. The groups of sporting and physician conventions are distinguished boxing with physical and neuropsychological disorders and some groups believe that side effects of this sport are not more than other sports. For this base the aim of this study was to determine the chronic traumatic brain injury in a group amateur boxers.Materials & Methods: In a case-control study, three groups of sport men were considered, each group contained 20 randomly selected cases. The first group were amateur boxers with 4 years minimal activity(directly has been presented to the head blows, second group were amateur soccer players with 4 years minimal activity(has been presented to the not very severe head blows, third group were non athlete subjects .The groups were matched in weight, height, age and education .To understand brain disorder interview by medicine method has been used, then Wiskancin, Bonardele, Bender geshtalt, Kim karad visual memory, Benton and wechler memory (Alef type tests has been performed and EEG has got in the same hour and condition.Results: The homogeneity of between group variances was gained by the statistical method. Also between structural–visual abilities neuropsychological aspect in groups, significant difference has been gained (p= 0.000. In Kim karad visual memory test at the mild and long term visual memory deficit, significant differences between three groups was observed (P= 0.000, P=0.009 that least score has been belonged to the boxers. Also in boxers 6 abnormal EEGs is observed.Conclusion: It can be said that of four years amateur boxing can affect on boxers visual and memory perception and their spatial orientation. Additionally our study have showed that amateur boxing has a significant

  8. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    HuaHu; Wei-PingZhang; LeiZhang; ZhongChen; Er-QingWei

    2004-01-01

    Aquaporin-4 (AQP4) is one of the aquaporins (AQPs), a water channel family. In the brain, AQP4 is expressed in astroeyte foot processes, and plays an important role in water homeostasis and in the formation of brain edema. In our study, AQP4 expression in human brain specimens from patients with traumatic brain injury or different brain tumors was detected

  9. Brain injury impairs working memory and prefrontal circuit function

    Directory of Open Access Journals (Sweden)

    Colin James Smith

    2015-11-01

    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.

  10. Effect of valproic acid and injury on lesion size and endothelial glycocalyx shedding in a rodent model of isolated traumatic brain injury

    DEFF Research Database (Denmark)

    Jepsen, Cecilie Heerdegen; deMoya, Marc A; Perner, Anders

    2014-01-01

    were analyzed for sSDC-1, and lesion size was determined on Nissl-stained cryosections. RESULTS: sSDC-1 was significantly elevated in injured compared with uninjured animals at 3 hours (p = 0.0009) and 6 hours (p = 0.0007) after injury. This effect was significantly more pronounced in the animals...

  11. Oxidative stress following traumatic brain injury: enhancement of ...

    African Journals Online (AJOL)

    neuronal loss following traumatic brain injury and presents experimental and clinical evidence of the role of exogenous antioxidants as neuroprotectants. Method: We reviewed published literature on reactive oxygen species and their role in experimental and clinical brain injuries in journals and the Internet using Yahoo ...

  12. White Matter Damage and Cognitive Impairment after Traumatic Brain Injury

    Science.gov (United States)

    Kinnunen, Kirsi Maria; Greenwood, Richard; Powell, Jane Hilary; Leech, Robert; Hawkins, Peter Charlie; Bonnelle, Valerie; Patel, Maneesh Chandrakant; Counsell, Serena Jane; Sharp, David James

    2011-01-01

    White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury…

  13. Traumatic Brain Injuries during Development: Implications for Alcohol Abuse

    Directory of Open Access Journals (Sweden)

    Zachary M. Weil

    2017-07-01

    Full Text Available Traumatic brain injuries are strongly related to alcohol intoxication as by some estimates half or more of all brain injuries involve at least one intoxicated individual. Additionally, there is mounting evidence that traumatic brain injuries can themselves serve as independent risk factors for the development of alcohol use disorders, particularly when injury occurs during juvenile or adolescent development. Here, we will review the epidemiological and experimental evidence for this phenomenon and discuss potential psychosocial mediators including attenuation of negative affect and impaired decision making as well as neurochemical mediators including disruption in the glutamatergic, GABAergic, and dopaminergic signaling pathways and increases in inflammation.

  14. Application of Ultrasonic Techniques for Brain Injury Diagnosis

    International Nuclear Information System (INIS)

    Kasili, P.M.; Mobley, J.; Norton, S.J.; Vo-Dinh, T.

    1999-01-01

    In this work, we evaluate methods for detecting brain injury using ultrasound. We have used simulations of ultrasonic fields in the head to model the phase distortion of the skull. In addition we present experimental data from the crania of large animals. The experimental data help us understand and evaluate the performance of different transducers in acquiring the backscatter data from the brain through the skull. Both the simulations and acquired data illustrate the superiority of lower-frequency (<= 1 MHz) ultrasonic fields for transcranial acquisition of signals from inside the brain. Additionally, the experimental work shows that the higher-frequency (5 MHz) ultrasound can also be useful in acquiring clean nearfield data to help detect the position of the inner boundary of the skull

  15. Antioxidant therapies in traumatic brain injury: a review

    Directory of Open Access Journals (Sweden)

    Romero-Rivera Hector Rolando

    2017-09-01

    Full Text Available Oxidative stress constitute one of the commonest mechanism of the secondary injury contributing to neuronal death in traumatic brain injury cases. The oxidative stress induced secondary injury blockade may be considered as to be a good alternative to improve the outcome of traumatic brain injury (TBI treatment. Due to absence of definitive therapy of traumatic brain injury has forced researcher to utilize unconventional therapies and its roles investigated in the improvement of management and outcome in recent year. Antioxidant therapies are proven effective in many preclinical studies and encouraging results and the role of antioxidant mediaction may act as further advancement in the traumatic brain injury management it may represent aonr of newer moadlaity in neurosurgical aramamentorium, this kind of therapy could be a good alternative or adjuct to the previously established neuroprotection agents in TBI.

  16. Neuroprotection by the histone deacetylase inhibitor trichostatin A in a model of lipopolysaccharide-sensitised neonatal hypoxic-ischaemic brain injury

    Directory of Open Access Journals (Sweden)

    Fleiss Bobbi

    2012-04-01

    Full Text Available Abstract Background Perinatal brain injury is complex and often associated with both inflammation and hypoxia-ischaemia (HI. In adult inflammatory brain injury models, therapies to increase acetylation are efficacious in reducing inflammation and cerebral injury. Our aim in the present study was to examine the neuropathological and functional effects of the histone deacetylase inhibitor (HDACi trichostatin A (TSA in a model of neonatal lipopolysaccharide (LPS-sensitised HI. We hypothesised that, by decreasing inflammation, TSA would improve injury and behavioural outcome. Furthermore, TSA’s effects on oligodendrocyte development, which is acetylation-dependent, were investigated. Methods On postnatal day 8 (P8, male and female mice were exposed to LPS together with or without TSA. On P9 (14 hours after LPS, mice were exposed to HI (50 minutes at 10% O2. Neuropathology was assessed at 24 hours, 5 days and 27 days post-LPS/HI via immunohistochemistry and/or Western blot analysis for markers of grey matter (microtubule-associated protein 2, white matter (myelin basic protein and cell death (activated caspase-3. Effects of TSA on LPS or LPS/HI-induced inflammation (cytokines and microglia number were assessed by Luminex assay and immunohistochemistry. Expression of acetylation-dependent oligodendrocyte maturational corepressors was assessed with quantitative PCR 6 hours after LPS and at 24 hours and 27 days post-LPS/HI. Animal behaviour was monitored with the open-field and trace fear-conditioning paradigms at 25 days post-LPS/HI to identify functional implications of changes in neuropathology associated with TSA treatment. Results TSA induced increased Ac-H4 in females only after LPS exposure. Also only in females, TSA reduced grey matter and white matter injury at 5 days post-LPS/HI. Treatment altered animal behaviour in the open field and improved learning in the fear-conditioning test in females compared with LPS/HI-only females at

  17. The potential of neural transplantation for brain repair and regeneration following traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Dong Sun

    2016-01-01

    Traumatic brain injury is a major health problem worldwide. Currently, there is no effective treatment to improve neural structural repair and functional recovery of patients in the clinic. Cell transplantation is a potential strategy to repair and regenerate the injured brain. This review article summarized recent de-velopment in cell transplantation studies for post-traumatic brain injury brain repair with varying types of cell sources. It also discussed the potential of neural transplantation to repair/promote recovery of the injured brain following traumatic brain injury.

  18. Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II: A Phase II Randomized Trial.

    Science.gov (United States)

    Okonkwo, David O; Shutter, Lori A; Moore, Carol; Temkin, Nancy R; Puccio, Ava M; Madden, Christopher J; Andaluz, Norberto; Chesnut, Randall M; Bullock, M Ross; Grant, Gerald A; McGregor, John; Weaver, Michael; Jallo, Jack; LeRoux, Peter D; Moberg, Dick; Barber, Jason; Lazaridis, Christos; Diaz-Arrastia, Ramon R

    2017-11-01

    A relationship between reduced brain tissue oxygenation and poor outcome following severe traumatic brain injury has been reported in observational studies. We designed a Phase II trial to assess whether a neurocritical care management protocol could improve brain tissue oxygenation levels in patients with severe traumatic brain injury and the feasibility of a Phase III efficacy study. Randomized prospective clinical trial. Ten ICUs in the United States. One hundred nineteen severe traumatic brain injury patients. Patients were randomized to treatment protocol based on intracranial pressure plus brain tissue oxygenation monitoring versus intracranial pressure monitoring alone. Brain tissue oxygenation data were recorded in the intracranial pressure -only group in blinded fashion. Tiered interventions in each arm were specified and impact on intracranial pressure and brain tissue oxygenation measured. Monitors were removed if values were normal for 48 hours consecutively, or after 5 days. Outcome was measured at 6 months using the Glasgow Outcome Scale-Extended. A management protocol based on brain tissue oxygenation and intracranial pressure monitoring reduced the proportion of time with brain tissue hypoxia after severe traumatic brain injury (0.45 in intracranial pressure-only group and 0.16 in intracranial pressure plus brain tissue oxygenation group; p injury after severe traumatic brain injury based on brain tissue oxygenation and intracranial pressure values was consistent with reduced mortality and increased proportions of patients with good recovery compared with intracranial pressure-only management; however, the study was not powered for clinical efficacy. Management of severe traumatic brain injury informed by multimodal intracranial pressure and brain tissue oxygenation monitoring reduced brain tissue hypoxia with a trend toward lower mortality and more favorable outcomes than intracranial pressure-only treatment. A Phase III randomized trial to assess

  19. Aetiology and treatment outcome of severe traumatic brain injuries ...

    African Journals Online (AJOL)

    Background: Severe traumatic brain injury (TBI) is a major challenge to the patient, the relatives, the care givers, and the society in general. The primary and secondary injuries, and the high metabolism are formidable stages of the injury, each capable of taking the life of the patient. The objectives were to determine the ...

  20. Pathological Fingerprints, Systems Biology and Biomarkers of Blast Brain Injury

    Science.gov (United States)

    2010-06-01

    changes after blast injury. J. Trauma 56, 393–403. Murthy, J.M., Chopra, J.S., and Gulati, D.R. (1979). Subdural hematoma in an adult following a blast...neuronal damage), diffuse brain injury, and subdural hemorrhage. It is still controversial whether primary blast forces directly damage the brain, and if...emboli, leading to infarction (Guy et al., 2000a; Guy et al., 2000b). The most common types of TBI are diffuse axonal injury, contusion, and subdural

  1. Neonatal ischemic brain injury: what every radiologist needs to know

    Energy Technology Data Exchange (ETDEWEB)

    Badve, Chaitra A.; Khanna, Paritosh C.; Ishak, Gisele E. [Seattle Children' s Hospital, University of Washington Medical Center, Department of Radiology, Seattle, WA (United States)

    2012-05-15

    We present a pictorial review of neonatal ischemic brain injury and look at its pathophysiology, imaging features and differential diagnoses from a radiologist's perspective. The concept of perinatal stroke is defined and its distinction from hypoxic-ischemic injury is emphasized. A brief review of recent imaging advances is included and a diagnostic approach to neonatal ischemic brain injury is suggested. (orig.)

  2. Caring for Patients with traumatic brain injury: a survey of nurses' perceptions.

    Science.gov (United States)

    Oyesanya, Tolu O; Brown, Roger L; Turkstra, Lyn S

    2017-06-01

    The purpose of this study was to determine nurses' perceptions about caring for patients with traumatic brain injury. Annually, it is estimated that over 10 million people sustain a traumatic brain injury around the world. Patients with traumatic brain injury and their families are often concerned with expectations about recovery and seek information from nurses. Nurses' perceptions of care might influence information provided to patients and families, particularly if inaccurate knowledge and perceptions are held. Thus, nurses must be knowledgeable about care of these patients. A cross-sectional survey, the Perceptions of Brain Injury Survey (PBIS), was completed electronically by 513 nurses between October and December 2014. Data were analysed with structural equation modelling, factor analysis, and pairwise comparisons. Using latent class analysis, authors were able to divide nurses into three homogeneous sub-groups based on perceived knowledge: low, moderate and high. Findings showed that nurses who care for patients with traumatic brain injury the most have the highest perceived confidence but the lowest perceived knowledge. Nurses also had significant variations in training. As there is limited literature on nurses' perceptions of caring for patients with traumatic brain injury, these findings have implications for training and educating nurses, including direction for development of nursing educational interventions. As the incidence of traumatic brain injury is growing, it is imperative that nurses be knowledgeable about care of patients with these injuries. The traumatic brain injury PBIS can be used to determine inaccurate perceptions about caring for patients with traumatic brain injury before educating and training nurses. © 2016 John Wiley & Sons Ltd.

  3. Sex differences in behavioral outcome following neonatal hypoxia ischemia: insights from a clinical meta-analysis and a rodent model of induced hypoxic ischemic brain injury.

    Science.gov (United States)

    Smith, Amanda L; Alexander, Michelle; Rosenkrantz, Ted S; Sadek, Mona Lisa; Fitch, R Holly

    2014-04-01

    Hypoxia ischemia (HI; reduced oxygen and/or blood flow to the brain) is one of the most common injuries among preterm infants and term infants with birth complications. Both populations show cognitive/behavioral deficits, including impairments in sensory, learning/memory, and attention domains. Clinical data suggests a sex difference in HI outcomes, with males exhibiting more severe cognitive/behavioral deficits relative to matched females. Our laboratory has also reported more severe behavioral deficits among male rats with induced HI relative to females with comparable injury (Hill et al., 2011a,b). The current study initially examined published clinical studies from the past 20years where long-term IQ outcome scores for matched groups of male and female premature infants were reported separately (IQ being the most common outcome measure). A meta-analysis revealed a female "advantage," as indicated by significantly better scores on performance and full scale IQ (but not verbal IQ) for premature females. We then utilized a rodent model of neonatal HI injury to assess sham and postnatal day 7 (P7) HI male and female rats on a battery of behavioral tasks. Results showed expected deficits in HI male rats, but also showed task-dependent sex differences, with HI males having significantly larger deficits than HI females on some tasks but equivalent deficits on other tasks. In contrast to behavioral results, post mortem neuropathology associated with HI was comparable across sex. These findings suggest: 1) neonatal female "protection" in some behavioral domains, as indexed by superior outcome following early injury relative to males; and 2) female protection may entail sex-specific plasticity or compensation, rather than a reduction in gross neuropathology. Further exploration of the mechanisms underlying this sex effect could aid in neuroprotection efforts for at-risk neonates in general, and males in particular. Moreover, our current report of comparable anatomical

  4. Plasticity in the Neonatal Brain following Hypoxic-Ischaemic Injury

    Directory of Open Access Journals (Sweden)

    Eridan Rocha-Ferreira

    2016-01-01

    Full Text Available Hypoxic-ischaemic damage to the developing brain is a leading cause of child death, with high mortality and morbidity, including cerebral palsy, epilepsy, and cognitive disabilities. The developmental stage of the brain and the severity of the insult influence the selective regional vulnerability and the subsequent clinical manifestations. The increased susceptibility to hypoxia-ischaemia (HI of periventricular white matter in preterm infants predisposes the immature brain to motor, cognitive, and sensory deficits, with cognitive impairment associated with earlier gestational age. In term infants HI causes selective damage to sensorimotor cortex, basal ganglia, thalamus, and brain stem. Even though the immature brain is more malleable to external stimuli compared to the adult one, a hypoxic-ischaemic event to the neonate interrupts the shaping of central motor pathways and can affect normal developmental plasticity through altering neurotransmission, changes in cellular signalling, neural connectivity and function, wrong targeted innervation, and interruption of developmental apoptosis. Models of neonatal HI demonstrate three morphologically different types of cell death, that is, apoptosis, necrosis, and autophagy, which crosstalk and can exist as a continuum in the same cell. In the present review we discuss the mechanisms of HI injury to the immature brain and the way they affect plasticity.

  5. Traumatic brain injury: caregivers' problems and needs.

    Science.gov (United States)

    Hassan, S T S; Khaw, W F; Rosna, A R; Husna, J

    2011-01-01

    Traumatic brain injury (TBI) is an increasingly major world health problem. This short review using the most pertinent articles on TBI caregiving problems and needs highlights the pressing issues. Articles focusing on both TBI-caregivers' problems and needs are rarely found, especially for developing countries. Most TBI-caregiving is done by family members, whose altered lives portend burden and stresses which add to the overwhelming demand of caring for the TBI-survivor. Lack of information, financial inadequacy, anxiety, distress, coping deficits, poor adaptability, inadequate knowledge and skills, and a poor support system comprise the major problems. Dysfunctional communication between caregivers and care-receivers has been little researched. The major needs are focused on health and rehabilitation information, financial advice and assistance, emotional and social support, and positive psychological encouragement. In time, health information needs may be met, but not emotional support. Information on TBI caregiving problems and unmet needs is critical to all relevant healthcare stakeholders.

  6. Monitoring Agitated Behavior After acquired Brain Injury

    DEFF Research Database (Denmark)

    Aadal, Lena; Mortensen, Jesper; Nielsen, Jørgen Feldbaek

    2016-01-01

    Purpose: To describe the onset, duration, intensity, and nursing shift variation of agitated behavior in patients with acquired brain injury (ABI) at a rehabilitation hospital. Design: Prospective descriptive study. Methods: A total of 11 patients with agitated behavior were included. Agitated...... behavior was registered with the Agitated Behavior Scale (ABS). The nurse or therapist allocated the individual patient assessed ABS during each shift. Intensity of agitated behavior was tested using exact test. A within-subject shift effect was analyzed with repeated-measure ANOVA. Findings: The onset...... of agitated behavior was at a median of 14 (1–28) days from admission. Seven patients remained agitated beyond 3 weeks from onset. Severe intensity of agitation was observed in 86 of 453 nursing shifts. Differences in agitated behavior between day, evening, and night shifts were found, F(2.20) = 7.90, p...

  7. Destination memory in traumatic brain injuries.

    Science.gov (United States)

    Wili Wilu, Amina; Coello, Yann; El Haj, Mohamad

    2018-06-01

    Destination memory, which is socially driven, refers to the ability to remember to whom one has sent information. Our study investigated destination memory in patients with traumatic brain injuries (TBIs). Patients and control participants were invited to tell proverbs (e.g., "the pen is mightier than the sword") to pictures of celebrities (e.g., Barack Obama). Then they were asked to indicate to which celebrity they had previously told the proverbs. Besides the assessment of destination memory, participants performed a binding task in which they were required to associate letters with their corresponding location. Analysis demonstrated less destination memory and binding in patients with TBIs than in controls. In both populations, significant correlations were observed between destination memory and performances on the binding task. These findings demonstrate difficulty in the ability to attribute information to its appropriate destination in TBI patients, perhaps owing to difficulties in binding separate information together to form a coherent representation of an event in memory.

  8. Brain injury in a forensic psychiatry population.

    Science.gov (United States)

    Colantonio, A; Stamenova, V; Abramowitz, C; Clarke, D; Christensen, B

    2007-12-01

    The prevalence and profile of adults with a history of traumatic brain injury (TBI) has not been studied in large North American forensic mental health populations. This study investigated how adults with a documented history of TBI differed with the non-TBI forensic population with respect to demographics, psychiatric diagnoses and history of offences. A retrospective chart review of all consecutive admissions to a forensic psychiatry programme in Toronto, Canada was conducted. Information on history of TBI, psychiatric diagnoses, living environments and types of criminal offences were obtained from medical records. History of TBI was ascertained in 23% of 394 eligible patient records. Compared to those without a documented history of TBI, persons with this history were less likely to be diagnosed with schizophrenia but more likely to have alcohol/substance abuse disorder. There were also differences observed with respect to offence profiles. This study provides evidence to support routine screening for a history of TBI in forensic psychiatry.

  9. Educational professionals' understanding of childhood traumatic brain injury.

    Science.gov (United States)

    Linden, Mark A; Braiden, Hannah-Jane; Miller, Sarah

    2013-01-01

    To determine the understanding of educational professionals around the topic of childhood brain injury and explore the factor structure of the Common Misconceptions about Traumatic Brain Injury Questionnaire (CM-TBI). Cross-sectional postal survey. The CM-TBI was posted to all educational establishments in one region of the UK. One representative from each school was asked to complete and return the questionnaire (n = 388). Differences were demonstrated between those participants who knew someone with a brain injury and those who did not, with a similar pattern being shown for those educators who had taught a child with brain injury. Participants who had taught a child with brain injury demonstrated greater knowledge in areas such as seatbelts/prevention, brain damage, brain injury sequelae, amnesia, recovery and rehabilitation. Principal components analysis suggested the existence of four factors and the discarding of half the original items of the questionnaire. In the first European study to explore this issue, it is highlighted that teachers are ill-prepared to cope with children who have sustained a brain injury. Given the importance of a supportive school environment in return to life following hospitalization, the lack of understanding demonstrated by teachers in this research may significantly impact on a successful return to school.

  10. Diabetes Insipidus after Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Cristina Capatina

    2015-07-01

    Full Text Available Traumatic brain injury (TBI is a significant cause of morbidity and mortality in many age groups. Neuroendocrine dysfunction has been recognized as a consequence of TBI and consists of both anterior and posterior pituitary insufficiency; water and electrolyte abnormalities (diabetes insipidus (DI and the syndrome of inappropriate antidiuretic hormone secretion (SIADH are amongst the most challenging sequelae. The acute head trauma can lead (directly or indirectly to dysfunction of the hypothalamic neurons secreting antidiuretic hormone (ADH or of the posterior pituitary gland causing post-traumatic DI (PTDI. PTDI is usually diagnosed in the first days after the trauma presenting with hypotonic polyuria. Frequently, the poor general status of most patients prevents adequate fluid intake to compensate the losses and severe dehydration and hypernatremia occur. Management consists of careful monitoring of fluid balance and hormonal replacement. PTDI is associated with high mortality, particularly when presenting very early following the injury. In many surviving patients, the PTDI is transient, lasting a few days to a few weeks and in a minority of cases, it is permanent requiring management similar to that offered to patients with non-traumatic central DI.

  11. Delayed radiation injury to the brain

    International Nuclear Information System (INIS)

    Takano, Shingo; Yoshii, Yoshihiko; Okazaki, Masao; Nose, Tadao; Aida, Shinsuke

    1989-01-01

    The authors report four cases of delayed radiation injury to the brain. One case was diagnosed histologically, and the other three cases, by means of serial CT scans and clinical symptoms. In all cases, a low-density area was observed 4-15 months after radiotherapy, then the contrast-enhanced area appeared within the low-density area about 4 months later. The enhanced area was distant from the original tumor, but within the field of radiotherapy. In the relationship between CT scans and superimposed dose distributions, the enhanced area and the low-density area were always observed within a zone of more than 80% of the total doses, and, as for the irradiated doses, there was no difference between the two areas. However, a distinct difference between these two areas was noted in the MRI scans and histopathology. The enhanced area was imaged as an area of a high signal by means of Gd-DTPA enhanced T 1 -weighted images in two cases. In the one histologically verified case, the fibrinoid necrosis of the blood vessel and demyelination appeared significantly higher in the enhanced area than in the low-density area. In conclusion, when a low-density area was observed by CT scan within the field of radiotherapy, we also suspected radiation injury and considered steroid or anticoagulant therapy in order to reverse it. However, if an enhanced area appeared within the injured lesion, the area seemed to have become irreversible and surgical therapy might also be needed. (author)

  12. Diabetes Insipidus after Traumatic Brain Injury

    Science.gov (United States)

    Capatina, Cristina; Paluzzi, Alessandro; Mitchell, Rosalid; Karavitaki, Niki

    2015-01-01

    Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in many age groups. Neuroendocrine dysfunction has been recognized as a consequence of TBI and consists of both anterior and posterior pituitary insufficiency; water and electrolyte abnormalities (diabetes insipidus (DI) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH)) are amongst the most challenging sequelae. The acute head trauma can lead (directly or indirectly) to dysfunction of the hypothalamic neurons secreting antidiuretic hormone (ADH) or of the posterior pituitary gland causing post-traumatic DI (PTDI). PTDI is usually diagnosed in the first days after the trauma presenting with hypotonic polyuria. Frequently, the poor general status of most patients prevents adequate fluid intake to compensate the losses and severe dehydration and hypernatremia occur. Management consists of careful monitoring of fluid balance and hormonal replacement. PTDI is associated with high mortality, particularly when presenting very early following the injury. In many surviving patients, the PTDI is transient, lasting a few days to a few weeks and in a minority of cases, it is permanent requiring management similar to that offered to patients with non-traumatic central DI. PMID:26239685

  13. Impact of perinatal systemic hypoxic-ischemic injury on the brain of male offspring rats: an improved model of neonatal hypoxic-ischemic encephalopathy in early preterm newborns.

    Directory of Open Access Journals (Sweden)

    Yuejun Huang

    Full Text Available In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

  14. Impact of Perinatal Systemic Hypoxic–Ischemic Injury on the Brain of Male Offspring Rats: An Improved Model of Neonatal Hypoxic–Ischemic Encephalopathy in Early Preterm Newborns

    Science.gov (United States)

    Xu, Hongwu; Wu, Weizhao; Lai, Xiulan; Ho, Guyu; Ma, Lian; Chen, Yunbin

    2013-01-01

    In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND) 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions. PMID:24324800

  15. Parallel Human and Animal Models of Blast- and Concussion-Induced Tinnitus and Related Traumatic Brain Injury (TBI)

    Science.gov (United States)

    2013-01-01

    emotionally valenced words in women with posttraumatic stress disorder related to early childhood sexual abuse. Biological psychiatry. 53, 879-89...and GABA(B) receptors in the regulation of the nucleus accumbens dopamine response to stress. Brain research. 1150, 62-8. Eichenbaum, H., 1999. The

  16. Dose-dependent neuroprotective effect of enoxaparin on cold-induced traumatic brain injury.

    Science.gov (United States)

    Keskin, Ilknur; Gunal, M Yalcin; Ayturk, Nilufer; Kilic, Ulkan; Ozansoy, Mehmet; Kilic, Ertugrul

    2017-05-01

    Recent evidence exists that enoxaparin can reduce brain injury because of its anticoagulant activity. To investigate the potential therapeutic effect of enoxaparin on cold-induced traumatic brain injury, at 20 minutes after modeling, male BALB/c mouse models of cold-induced traumatic brain injury were intraperitoneally administered 3 and 10 mg/kg enoxaparin or isotonic saline solution. Twenty-four hours later, enoxaparin at 10 mg/kg greatly reduced infarct volume, decreased cell apoptosis in the cortex and obviously increased serum level of total antioxidant status. By contrast, administration of enoxaparin at 3 mg/kg did not lead to these changes. These findings suggest that enoxaparin exhibits neuroprotective effect on cold-induced traumatic brain injury in a dose-dependent manner.

  17. Sports-related brain injuries: connecting pathology to diagnosis.

    Science.gov (United States)

    Pan, James; Connolly, Ian D; Dangelmajer, Sean; Kintzing, James; Ho, Allen L; Grant, Gerald

    2016-04-01

    Brain injuries are becoming increasingly common in athletes and represent an important diagnostic challenge. Early detection and management of brain injuries in sports are of utmost importance in preventing chronic neurological and psychiatric decline. These types of injuries incurred during sports are referred to as mild traumatic brain injuries, which represent a heterogeneous spectrum of disease. The most dramatic manifestation of chronic mild traumatic brain injuries is termed chronic traumatic encephalopathy, which is associated with profound neuropsychiatric deficits. Because chronic traumatic encephalopathy can only be diagnosed by postmortem examination, new diagnostic methodologies are needed for early detection and amelioration of disease burden. This review examines the pathology driving changes in athletes participating in high-impact sports and how this understanding can lead to innovations in neuroimaging and biomarker discovery.

  18. Brain functional connectivity and cognition in mild traumatic brain injury

    International Nuclear Information System (INIS)

    Xiong, K.L.; Zhang, Y.L.; Chen, H.; Zhang, J.N.; Zhang, Y.; Qiu, M.G.

    2016-01-01

    The aim of this study was to analyze brain functional connectivity and its relationship to cognition in patients with mild traumatic brain injury (mTBI). Twenty-five patients with mTBI and 25 healthy control subjects were studied using resting-state functional MRI (rs-fMRI). Amplitudes of low-frequency fluctuations (ALFFs) and functional connectivity (FC) were calculated and correlated with cognition. Compared with the normal control group, the mTBI patients showed a significant decrease in working memory index (WMI) and processing speed index (PSI), as well as significantly decreased ALFFs in the cingulate gyrus, the middle frontal gyrus and superior frontal gyrus. In contrast, the mTBI patients' ALFFs in the left middle occipital gyrus, the left precuneus, and lingual gyrus increased. Additionally, FC significantly decreased in the thalamus, caudate nucleus, and right hippocampus in the mTBI patients. Statistical analysis further showed a significant positive correlation between the ALFF in the cingulate gyrus and the WMI (R 2 = 0.423, P < 0.05) and a significant positive correlation between the FC in the left thalamus and left middle frontal gyrus and the WMI (R 2 = 0.381, P < 0.05). rs-fMRI can reveal the functional state of the brain in patients with mTBI. This finding differed from observations of the normal control group and was significantly associated with clinical cognitive dysfunction. Therefore, rs-fMRI offers an objective imaging modality for treatment planning and prognosis assessment in patients with mTBI. (orig.)

  19. Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species

    Science.gov (United States)

    Semple, Bridgette D.; Blomgren, Klas; Gimlin, Kayleen; Ferriero, Donna M.; Noble-Haeusslein, Linda J.

    2013-01-01

    Hypoxic-ischemic and traumatic brain injuries are leading causes of long-term mortality and disability in infants and children. Although several preclinical models using rodents of different ages have been developed, species differences in the timing of key brain maturation events can render comparisons of vulnerability and regenerative capacities difficult to interpret. Traditional models of developmental brain injury have utilized rodents at postnatal day 7–10 as being roughly equivalent to a term human infant, based historically on the measurement of post-mortem brain weights during the 1970s. Here we will examine fundamental brain development processes that occur in both rodents and humans, to delineate a comparable time course of postnatal brain development across species. We consider the timing of neurogenesis, synaptogenesis, gliogenesis, oligodendrocyte maturation and age-dependent behaviors that coincide with developmentally regulated molecular and biochemical changes. In general, while the time scale is considerably different, the sequence of key events in brain maturation is largely consistent between humans and rodents. Further, there are distinct parallels in regional vulnerability as well as functional consequences in response to brain injuries. With a focus on developmental hypoxicischemic encephalopathy and traumatic brain injury, this review offers guidelines for researchers when considering the most appropriate rodent age for the developmental stage or process of interest to approximate human brain development. PMID:23583307

  20. Brain protection by methylprednisolone in rats with spinal cord injury.

    Science.gov (United States)

    Chang, Chia-Mao; Lee, Ming-Hsueh; Wang, Ting-Chung; Weng, Hsu-Huei; Chung, Chiu-Yen; Yang, Jen-Tsung

    2009-07-01

    Traumatic spinal cord injury is clinically treated by high doses of methylprednisolone. However, the effect of methylprednisolone on the brain in spinal cord injury patients has been little investigated. This experimental study examined Bcl-2 and Bax protein expression and Nissl staining to evaluate an apoptosis-related intracellular signaling event and final neuron death, respectively. Spinal cord injury produced a significant apoptotic change and cell death not only in the spinal cord but also in the supraventricular cortex and hippocampal cornu ammonis 1 region in the rat brains. The treatment of methylprednisolone increased the Bcl-2/Bax ratio and prevented neuron death for 1-7 days after spinal cord injury. These findings suggest that rats with spinal cord injury show ascending brain injury that could be restricted through methylprednisolone management.

  1. Early predictors of outcome after mild traumatic brain injury (UPFRONT) : An observational cohort study

    NARCIS (Netherlands)

    van der Naalt, J.; Timmerman, M.E.; de Koning, M.E.; van der Horn, H.J.; Scheenen, M.E.; Jacobs, B.; Hageman, G.; Yilmaz, T.; Roks, G.; Spikman, J.M.

    Background: Mild traumatic brain injury (mTBI) accounts for most cases of TBI, and many patients show incomplete long-term functional recovery. We aimed to create a prognostic model for functional outcome by combining demographics, injury severity, and psychological factors to identify patients at

  2. Racial differences in employment outcomes after traumatic brain injury.

    Science.gov (United States)

    Arango-Lasprilla, Juan Carlos; Ketchum, Jessica M; Williams, Kelli; Kreutzer, Jeffrey S; Marquez de la Plata, Carlos D; O'Neil-Pirozzi, Therese M; Wehman, Paul

    2008-05-01

    To examine racial differences in employment status and occupational status 1 year after a traumatic brain injury (TBI). Retrospective study. Longitudinal dataset of the Traumatic Brain Injury Model Systems national database. Subjects with primarily moderate to severe TBI (3468 whites vs 1791 minorities) hospitalized between 1989 and 2005. Not applicable. Employment status (competitively employed or unemployed) and occupational status (professional/managerial, skilled, or manual labor) at 1 year postinjury. Race and/or ethnicity has a significant effect on employment status at 1 year postinjury (chi(1)(2)=58.23, Pstatus, sex, Disability Rating Scale at discharge, marital status, cause of injury, age, and education. The adjusted odds of being unemployed versus competitively employed are 2.17 times (95% confidence interval, 1.78-2.65) greater for minorities than for whites. Race and ethnicity does not have a significant effect on occupational status at 1 year postinjury. With this empirical evidence supporting racial differences in employment outcomes between minorities and whites at 1 year postinjury, priority should be given to tailoring interventions to maximize minority survivors' work-related productivity.

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

    Science.gov (United States)

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

    2016-09-01

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

  4. Brain Network Modelling

    DEFF Research Database (Denmark)

    Andersen, Kasper Winther

    Three main topics are presented in this thesis. The first and largest topic concerns network modelling of functional Magnetic Resonance Imaging (fMRI) and Diffusion Weighted Imaging (DWI). In particular nonparametric Bayesian methods are used to model brain networks derived from resting state f...... for their ability to reproduce node clustering and predict unseen data. Comparing the models on whole brain networks, BCD and IRM showed better reproducibility and predictability than IDM, suggesting that resting state networks exhibit community structure. This also points to the importance of using models, which...... allow for complex interactions between all pairs of clusters. In addition, it is demonstrated how the IRM can be used for segmenting brain structures into functionally coherent clusters. A new nonparametric Bayesian network model is presented. The model builds upon the IRM and can be used to infer...

  5. Position of probe determines prognostic information of brain tissue PO2 in severe traumatic brain injury.

    Science.gov (United States)

    Ponce, Lucido L; Pillai, Shibu; Cruz, Jovany; Li, Xiaoqi; Julia, H; Gopinath, Shankar; Robertson, Claudia S

    2012-06-01

    Monitoring brain tissue PO2 (PbtO2) is part of multimodality monitoring of patients with traumatic brain injury (TBI). However, PbtO2 measurement is a sampling of only a small area of tissue surrounding the sensor tip. To examine the effect of catheter location on the relationship between PbtO2 and neurological outcome. A total of 405 patients who had PbtO2 monitoring as part of standard management of severe traumatic brain injury were studied. The relationships between probe location and resulting PbtO2 and outcome were examined. When the probe was located in normal brain, PbtO2 averaged 30.8 ± 18.2 compared with 25.6 ± 14.8 mm Hg when placed in abnormal brain (P < .001). Factors related to neurological outcome in the best-fit logistic regression model were age, PbtO2 probe position, postresuscitation motor Glasgow Coma Scale score, and PbtO2 trend pattern. Although average PbtO2 was significantly related to outcome in univariate analyses, it was not significant in the final logistic model. However, the interaction between PbtO2 and probe position was statistically significant. When the PbtO2 probe was placed in abnormal brain, the average PbtO2 was higher in those with a favorable outcome, 28.8 ± 12.0 mm Hg, compared with those with an unfavorable outcome, 19.5 ± 13.7 mm Hg (P = .01). PbtO2 and outcome were not related when the probe was placed in normal-appearing brain. These results suggest that the location of the PbtO2 probe determines the PbtO2 values and the relationship of PbtO2 to neurological outcome.

  6. A review of the International Brain Research Foundation novel approach to mild traumatic brain injury presented at the International Conference on Behavioral Health and Traumatic Brain Injury.

    Science.gov (United States)

    Polito, Mary Zemyan; Thompson, James W G; DeFina, Philip A

    2010-09-01

    "The International Conference on Behavioral Health and Traumatic Brain Injury" held at St. Joseph's Regional Medical Center in Paterson, NJ., from October 12 to 15, 2008, included a presentation on the novel assessment and treatment approach to mild traumatic brain injury (mTBI) by Philip A. DeFina, PhD, of the International Brain Research Foundation (IBRF). Because of the urgent need to treat a large number of our troops who are diagnosed with mTBI and post-traumatic stress disorder (PTSD), the conference was held to create a report for Congress titled "Recommendations to Improve the Care of Wounded Warriors NOW. March 12, 2009." This article summarizes and adds greater detail to Dr. DeFina's presentation on the current standard and novel ways to approach assessment and treatment of mTBI and PTSD. Pilot data derived from collaborative studies through the IBRF have led to the development of clinical and research protocols utilizing currently accepted, valid, and reliable neuroimaging technologies combined in novel ways to develop "neuromarkers." These neuromarkers are being evaluated in the context of an "Integrity-Deficit Matrix" model to demonstrate their ability to improve diagnostic accuracy, guide treatment programs, and possibly predict outcomes for patients suffering from traumatic brain injury.

  7. Combined Effects of Primary and Tertiary Blast on Rat Brain: Characterization of a Model of Blast-induced Mild Traumatic Brain Injury

    Science.gov (United States)

    2015-03-01

    Prog Neurobiol. 2001;63:321-36. [34] Zador Z, Stiver S, Wang V, Manley GT. Role of aquaporin-4 in cerebral edema and stroke. Handb Exp Pharmacol. 2009...bullae were opened • Images were taken under microscope with a 20x magnification • Sham ( ll , 1R), 280Ps_S psi (2l, 2R), 2BOPs_12 psi (3l, 3R...8217 · ~~ lW . ll at 7 dafter double blast exposures (ID Effect of blast exposure on auditory cortex • Immunohistochemistry on brain sections • at 6 hand

  8. Brain injury and altered brain growth in preterm infants: predictors and prognosis.

    Science.gov (United States)

    Kidokoro, Hiroyuki; Anderson, Peter J; Doyle, Lex W; Woodward, Lianne J; Neil, Jeffrey J; Inder, Terrie E

    2014-08-01

    To define the nature and frequency of brain injury and brain growth impairment in very preterm (VPT) infants by using MRI at term-equivalent age and to relate these findings to perinatal risk factors and 2-year neurodevelopmental outcomes. MRI scans at term-equivalent age from 3 VPT cohorts (n = 325) were reviewed. The severity of brain injury, including periventricular leukomalacia and intraventricular and cerebellar hemorrhage, was graded. Brain growth was assessed by using measures of biparietal width (BPW) and interhemispheric distance. Neurodevelopmental outcome at age 2 years was assessed across all cohorts (n = 297) by using the Bayley Scales of Infant Development, Second Edition (BSID-II) or Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), and evaluation for cerebral palsy. Of 325 infants, 107 (33%) had some grade of brain injury and 33 (10%) had severe injury. Severe brain injury was more common in infants with lower Apgar scores, necrotizing enterocolitis, inotropic support, and patent ductus arteriosus. Severe brain injury was associated with delayed cognitive and motor development and cerebral palsy. Decreased BPW was related to lower gestational age, inotropic support, patent ductus arteriosus, necrotizing enterocolitis, prolonged parenteral nutrition, and oxygen at 36 weeks and was associated with delayed cognitive development. In contrast, increased interhemispheric distance was related to male gender, dexamethasone use, and severe brain injury. It was also associated with reduced cognitive development, independent of BPW. At term-equivalent age, VPT infants showed both brain injury and impaired brain growth on MRI. Severe brain injury and impaired brain growth patterns were independently associated with perinatal risk factors and delayed cognitive development. Copyright © 2014 by the American Academy of Pediatrics.

  9. Mathematical modelling of blood-brain barrier failure and edema

    Science.gov (United States)

    Waters, Sarah; Lang, Georgina; Vella, Dominic; Goriely, Alain

    2015-11-01

    Injuries such as traumatic brain injury and stroke can result in increased blood-brain barrier permeability. This increase may lead to water accumulation in the brain tissue resulting in vasogenic edema. Although the initial injury may be localised, the resulting edema causes mechanical damage and compression of the vasculature beyond the original injury site. We employ a biphasic mixture model to investigate the consequences of blood-brain barrier permeability changes within a region of brain tissue and the onset of vasogenic edema. We find that such localised changes can indeed result in brain tissue swelling and that the type of damage that results (stress damage or strain damage) depends on the ability of the brain to clear edema fluid.

  10. Ginsenoside Rg1 improves ischemic brain injury by balancing ...

    African Journals Online (AJOL)

    Ginsenoside Rg1 improves ischemic brain injury by balancing mitochondrial ... and autophagy-related proteins were determined by reat time-polymerase chain ... Treatment with autophagy inhibitors decreased the mitochondrial protective ...

  11. Loss of Financial Management Independence After Brain Injury: Survivors' Experiences.

    Science.gov (United States)

    Koller, Kathryn; Woods, Lindsay; Engel, Lisa; Bottari, Carolina; Dawson, Deirdre R; Nalder, Emily

    2016-01-01

    This pilot study explored the experiences of brain injury survivors after a change in financial management (FM) independence. Using a qualitative descriptive design, 6 participants with acquired brain injury were recruited from a community brain injury organization and participated in semistructured interviews. Data were analyzed using thematic analysis. Three themes emerged from the interviews: (1) trajectory of FM change, involving family members as key change agents; (2) current FM situation, involving FM strategies such as automatic deposits and restricted budgets; and (3) the struggle for control, in which survivors desired control while also accepting supports for FM. This study identifies some of the challenges brain injury survivors face in managing their finances and the adjustment associated with a loss of FM independence. Occupational therapists should be aware of clients' experiences when supporting them through a change in independence. Copyright © 2016 by the American Occupational Therapy Association, Inc.

  12. Spreading depolarisations and outcome after traumatic brain injury

    DEFF Research Database (Denmark)

    Hartings, Jed A; Bullock, M Ross; Okonkwo, David O

    2011-01-01

    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...

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

    Science.gov (United States)

    ... TBI Online Concussion Training Press Room Guide to Writing about TBI in News and Social Media Living with TBI HEADS UP to Brain Injury Awareness Get Email Updates To receive email updates about this topic, ...

  14. Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System

    Data.gov (United States)

    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,...

  15. Preliminary questions before studying mild traumatic brain injury outcome.

    Science.gov (United States)

    Fayol, P; Carrière, H; Habonimana, D; Dumond, J-J

    2009-07-01

    To point out from the literature the issues in mild traumatic brain injury outcome. METHODOLOGY-RESULTS: The literature review allows to point out several different factors involved in the difficulty to study mild traumatic brain injury: mild traumatic brain injury definition, postconcussional syndrome definition, diagnosis threshold, severity and functional symptoms outcome, neuropsychological tests, unspecific syndrome feature, individual factors, confounding factors and treatment interventions. The mild traumatic brain injury outcome study is complicated by the definitions issues and especially their practical use and by the multiplicity and the intricate interrelationships among involved factors. The individual outcome and social cost weight is widely emphasized for an event still considered as medically trivial. The well-ordered preventive interventions necessity and the targeted treatment programs need for the persisting postconcussive symptoms complete our critical review.

  16. Participation in leisure activities during brain injury rehabilitation.

    Science.gov (United States)

    Fleming, Jennifer; Braithwaite, Helen; Gustafsson, Louise; Griffin, Janelle; Collier, Ann Maree; Fletcher, Stephanie

    2011-01-01

    To describe and compare pre- and post-injury leisure activities of individuals receiving brain injury rehabilitation and explore levels of leisure participation and satisfaction. Cross-sectional descriptive study incorporating a survey of current and past leisure activities. Questionnaires were completed by 40 individuals with an acquired brain injury receiving inpatient or outpatient rehabilitation. Shortened Version of the Nottingham Leisure Questionnaire and Changes in Leisure Questionnaire (developed for this study). Leisure participation declined following injury, particularly in social leisure activities. Pre-injury activities with high rates of discontinued or decreased participation were driving, going to pubs and parties, do-it-yourself activities and attending sports events. Inpatient participants generally attributed decreased participation to the hospital environment, whereas outpatient participants reported this predominantly as a result of disability. Post-injury levels of perceived leisure satisfaction were significantly lower for the inpatient group compared to pre-injury, but not for the outpatient group. Uptake of some new leisure activities was reported post-injury, however not at the rate to which participation declined. Leisure participation decreases during brain injury rehabilitation compared to pre-injury levels. Re-engagement in relevant, age-appropriate leisure activities needs to be addressed during rehabilitation to improve participation in this domain.

  17. Cooking breakfast after a brain injury

    Directory of Open Access Journals (Sweden)

    Annick N. Tanguay

    2014-09-01

    Full Text Available Acquired brain injury (ABI often compromises the ability to carry out instrumental activities of daily living such as cooking. ABI patients’ difficulties with executive functions and memory result in less independent and efficient meal preparation. Accurately assessing safety and proficiency in cooking is essential for successful community reintegration following ABI, but in vivo assessment of cooking by clinicians is time-consuming, costly, and difficult to standardize. Accordingly, we examined the usefulness of a computerized meal preparation task (the Breakfast Task; Craik & Bialystok, 2006 as an indicator of real life meal preparation skills. Twenty-two ABI patients and 22 age-matched controls completed the Breakfast Task and the Rehabilitation Activities of Daily Living Survey (RADLS; Salmon, 2003. Patients also prepared actual meals, and were rated by members of the clinical team. As expected, the ABI patients had significant difficulty on all aspects of the Breakfast Task (failing to have all their foods ready at the same time, over- and under-cooking foods, setting fewer places at the table, and so on relative to controls. Surprisingly, however, patients’ Breakfast Task performance was not correlated with their in vivo meal preparation. These results indicate caution when endeavoring to replace traditional evaluation methods with computerized tasks for the sake of expediency.

  18. Visual problems associated with traumatic brain injury.

    Science.gov (United States)

    Armstrong, Richard A

    2018-02-28

    Traumatic brain injury (TBI) and its associated concussion are major causes of disability and death. All ages can be affected but children, young adults and the elderly are particularly susceptible. A decline in mortality has resulted in many more individuals living with a disability caused by TBI including those affecting vision. This review describes: (1) the major clinical and pathological features of TBI; (2) the visual signs and symptoms associated with the disorder; and (3) discusses the assessment of quality of life and visual rehabilitation of the patient. Defects in primary vision such as visual acuity and visual fields, eye movement including vergence, saccadic and smooth pursuit movements, and in more complex aspects of vision involving visual perception, motion vision ('akinopsia'), and visuo-spatial function have all been reported in TBI. Eye movement dysfunction may be an early sign of TBI. Hence, TBI can result in a variety of visual problems, many patients exhibiting multiple visual defects in combination with a decline in overall health. Patients with chronic dysfunction following TBI may require occupational, vestibular, cognitive and other forms of physical therapy. Such patients may also benefit from visual rehabilitation, including reading-related oculomotor training and the prescribing of spectacles with a variety of tints and prism combinations. © 2018 Optometry Australia.

  19. Investigations of primary blast-induced traumatic brain injury

    Science.gov (United States)

    Sawyer, T. W.; Josey, T.; Wang, Y.; Villanueva, M.; Ritzel, D. V.; Nelson, P.; Lee, J. J.

    2018-01-01

    The development of an advanced blast simulator (ABS) has enabled the reproducible generation of single-pulse shock waves that simulate free-field blast with high fidelity. Studies with rodents in the ABS demonstrated the necessity of head restraint during head-only exposures. When the head was not restrained, violent global head motion was induced by pressures that would not produce similar movement of a target the size and mass of a human head. This scaling artefact produced changes in brain function that were reminiscent of traumatic brain injury (TBI) due to impact-acceleration effects. Restraint of the rodent head eliminated these, but still produced subtle changes in brain biochemistry, showing that blast-induced pressure waves do cause brain deficits. Further experiments were carried out with rat brain cell aggregate cultures that enabled the conduct of studies without the gross movement encountered when using rodents. The suspension nature of this model was also exploited to minimize the boundary effects that complicate the interpretation of primary blast studies using surface cultures. Using this system, brain tissue was found not only to be sensitive to pressure changes, but also able to discriminate between the highly defined single-pulse shock waves produced by underwater blast and the complex pressure history exposures experienced by aggregates encased within a sphere and subjected to simulated air blast. The nature of blast-induced primary TBI requires a multidisciplinary research approach that addresses the fidelity of the blast insult, its accurate measurement and characterization, as well as the limitations of the biological models used.

  20. Cognitive functions in drivers with brain injury : Anticipation and adaption

    OpenAIRE

    Lundqvist, Anna

    2001-01-01

    The purpose of this thesis was to improve the understanding of what cognitive functions are important for driving performance, investigate the impact of impaired cognitive functions on drivers with brain injury, and study adaptation strategies relevant for driving performance after brain injury. Finally, the predictive value of a neuropsychological test battery was evaluated for driving performance. Main results can be summarized in the following conclusions: (a) Cognitive functions in terms ...

  1. Oculometric Screening for Traumatic Brain Injury in Veterans

    Science.gov (United States)

    2017-06-01

    intake physicals as a detection method for acute injury and for management of brain health in military and VA hospitals. An immersive evaluation of the...risk of traumatic brain injury following deployment. Journal of Head Trauma Rehabilitation, 31(1), 28–35. xviii THIS PAGE INTENTIONALLY LEFT BLANK...device in operational units, military treatment facilities, or VA hospitals. This question will be answered through an immersive qualitative

  2. Multi-modal MRI of mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Ponnada A. Narayana

    2015-01-01

    Full Text Available Multi-modal magnetic resonance imaging (MRI that included high resolution structural imaging, diffusion tensor imaging (DTI, magnetization transfer ratio (MTR imaging, and magnetic resonance spectroscopic imaging (MRSI were performed in mild traumatic brain injury (mTBI patients with negative computed tomographic scans and in an orthopedic-injured (OI group without concomitant injury to the brain. The OI group served as a comparison group for mTBI. MRI scans were performed both in the acute phase of injury (~24 h and at follow-up (~90 days. DTI data was analyzed using tract based spatial statistics (TBSS. Global and regional atrophies were calculated using tensor-based morphometry (TBM. MTR values were calculated using the standard method. MRSI was analyzed using LC Model. At the initial scan, the mean diffusivity (MD was significantly higher in the mTBI cohort relative to the comparison group in several white matter (WM regions that included internal capsule, external capsule, superior corona radiata, anterior corona radiata, posterior corona radiata, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, forceps major and forceps minor of the corpus callosum, superior longitudinal fasciculus, and corticospinal tract in the right hemisphere. TBSS analysis failed to detect significant differences in any DTI measures between the initial and follow-up scans either in the mTBI or OI group. No significant differences were found in MRSI, MTR or morphometry between the mTBI and OI cohorts either at the initial or follow-up scans with or without family wise error (FWE correction. Our study suggests that a number of WM tracts are affected in mTBI in the acute phase of injury and that these changes disappear by 90 days. This study also suggests that none of the MRI-modalities used in this study, with the exception of DTI, is sensitive in detecting changes in the acute phase of mTBI.

  3. Chronic traumatic encephalopathy-integration of canonical traumatic brain injury secondary injury mechanisms with tau pathology.

    Science.gov (United States)

    Kulbe, Jacqueline R; Hall, Edward D

    2017-11-01

    In recent years, a new neurodegenerative tauopathy labeled Chronic Traumatic Encephalopathy (CTE), has been identified that is believed to be primarily a sequela of repeated mild traumatic brain injury (TBI), often referred to as concussion, that occurs in athletes participating in contact sports (e.g. boxing, American football, Australian football, rugby, soccer, ice hockey) or in military combatants, especially after blast-induced injuries. Since the identification of CTE, and its neuropathological finding of deposits of hyperphosphorylated tau protein, mechanistic attention has been on lumping the disorder together with various other non-traumatic neurodegenerative tauopathies. Indeed, brains from suspected CTE cases that have come to autopsy have been confirmed to have deposits of hyperphosphorylated tau in locations that make its anatomical distribution distinct for other tauopathies. The fact that these individuals experienced repetitive TBI episodes during their athletic or military careers suggests that the secondary injury mechanisms that have been extensively characterized in acute TBI preclinical models, and in TBI patients, including glutamate excitotoxicity, intracellular calcium overload, mitochondrial dysfunction, free radical-induced oxidative damage and neuroinflammation, may contribute to the brain damage associated with CTE. Thus, the current review begins with an in depth analysis of what is known about the tau protein and its functions and dysfunctions followed by a discussion of the major TBI secondary injury mechanisms, and how the latter have been shown to contribute to tau pathology. The value of this review is that it might lead to improved neuroprotective strategies for either prophylactically attenuating the development of CTE or slowing its progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Psychometric properties of the college survey for students with brain injury: individuals with and without traumatic brain injury.

    Science.gov (United States)

    Kennedy, Mary R T; Krause, Miriam O; O'Brien, Katy H

    2014-01-01

    The psychometric properties of the college challenges sub-set from The College Survey for Students with Brain Injury (CSS-BI) were investigated with adults with and without traumatic brain injury (TBI). Adults with and without TBI completed the CSS-BI. A sub-set of participants with TBI were interviewed, intentional and convergent validity were investigated, and the internal structure of the college challenges was analysed with exploratory factor analysis/principle component analysis. Respondents with TBI understood the items describing college challenges with evidence of intentional validity. More individuals with TBI than controls endorsed eight of the 13 college challenges. Those who reported more health issues endorsed more college challenges, demonstrating preliminary convergent validity. Cronbach's alphas of >0.85 demonstrated acceptable internal reliability. Factor analysis revealed a four-factor model for those with TBI: studying and learning (Factor 1), time management and organization (Factor 2), social (Factor 3) and nervousness/anxiety (Factor 4). This model explained 72% and 69% of the variance for those with and without TBI, respectively. The college challenges sub-set from the CSS-BI identifies challenges that individuals with TBI face when going to college. Some challenges were related to two factors in the model, demonstrating the inter-connections of these experiences.

  5. A preclinical murine model for the early detection of radiation-induced brain injury using magnetic resonance imaging and behavioral tests for learning and memory: with applications for the evaluation of possible stem cell imaging agents and therapies.

    Science.gov (United States)

    Ngen, Ethel J; Wang, Lee; Gandhi, Nishant; Kato, Yoshinori; Armour, Michael; Zhu, Wenlian; Wong, John; Gabrielson, Kathleen L; Artemov, Dmitri

    2016-06-01

    Stem cell therapies are being developed for radiotherapy-induced brain injuries (RIBI). Magnetic resonance imaging (MRI) offers advantages for imaging transplanted stem cells. However, most MRI cell-tracking techniques employ superparamagnetic iron oxide particles (SPIOs), which are difficult to distinguish from hemorrhage. In current preclinical RIBI models, hemorrhage occurs concurrently with other injury markers. This makes the evaluation of the recruitment of transplanted SPIO-labeled stem cells to injury sites difficult. Here, we developed a RIBI model, with early injury markers reflective of hippocampal dysfunction, which can be detected noninvasively with MRI and behavioral tests. Lesions were generated by sub-hemispheric irradiation of mouse hippocampi with single X-ray beams of 80 Gy. Lesion formation was monitored with anatomical and contrast-enhanced MRI and changes in memory and learning were assessed with fear-conditioning tests. Early injury markers were detected 2 weeks after irradiation. These included an increase in the permeability of the blood-brain barrier, demonstrated by a 92 ± 20 % contrast enhancement of the irradiated versus the non-irradiated brain hemispheres, within 15 min of the administration of an MRI contrast agent. A change in short-term memory was also detected, as demonstrated by a 40.88 ± 5.03 % decrease in the freezing time measured during the short-term memory context test at this time point, compared to that before irradiation. SPIO-labeled stem cells transplanted contralateral to the lesion migrated toward the lesion at this time point. No hemorrhage was detected up to 10 weeks after irradiation. This model can be used to evaluate SPIO-based stem cell-tracking agents, short-term.

  6. Traumatic Brain Injury in the Accident and Emergency Department of ...

    African Journals Online (AJOL)

    Background: Traumatic brain injury is a major public health problem in Nigeria, as it could be associated with long term and life long deficits. Unlike other parts of the world, in our country, motorcycles are possibly the main cause of this injury. Unfortunately, we do not have a national epidemiological data base yet. This study ...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    Grove, Michael J.

    2013-01-01

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

  9. Severe blood-brain barrier disruption and surrounding tissue injury.

    Science.gov (United States)

    Chen, Bo; Friedman, Beth; Cheng, Qun; Tsai, Phil; Schim, Erica; Kleinfeld, David; Lyden, Patrick D

    2009-12-01

    Blood-brain barrier opening during ischemia follows a biphasic time course, may be partially reversible, and allows plasma constituents to enter brain and possibly damage cells. In contrast, severe vascular disruption after ischemia is unlikely to be reversible and allows even further extravasation of potentially harmful plasma constituents. We sought to use simple fluorescent tracers to allow wide-scale visualization of severely damaged vessels and determine whether such vascular disruption colocalized with regions of severe parenchymal injury. Severe vascular disruption and ischemic injury was produced in adult Sprague Dawley rats by transient occlusion of the middle cerebral artery for 1, 2, 4, or 8 hours, followed by 30 minutes of reperfusion. Fluorescein isothiocyanate-dextran (2 MDa) was injected intravenously before occlusion. After perfusion-fixation, brain sections were processed for ultrastructure or fluorescence imaging. We identified early evidence of tissue damage with Fluoro-Jade staining of dying cells. With increasing ischemia duration, greater quantities of high molecular weight dextran-fluorescein isothiocyanate invaded and marked ischemic regions in a characteristic pattern, appearing first in the medial striatum, spreading to the lateral striatum, and finally involving cortex; maximal injury was seen in the mid-parietal areas, consistent with the known ischemic zone in this model. The regional distribution of the severe vascular disruption correlated with the distribution of 24-hour 2,3,5-triphenyltetrazolium chloride pallor (r=0.75; P<0.05) and the cell death marker Fluoro-Jade (r=0.86; P<0.05). Ultrastructural examination showed significantly increased areas of swollen astrocytic foot process and swollen mitochondria in regions of high compared to low leakage, and compared to contralateral homologous regions (ANOVA P<0.01). Dextran extravasation into the basement membrane and surrounding tissue increased significantly from 2 to 8 hours of

  10. Melatonin reduces hypoxic-ischaemic (HI) induced autophagy and apoptosis: An in vivo and in vitro investigation in experimental models of neonatal HI brain injury.

    Science.gov (United States)

    Hu, Yingying; Wang, Zhouguang; Liu, Yanlong; Pan, Shulin; Zhang, Hao; Fang, Mingchu; Jiang, Huai; Yin, Jiayu; Zou, Shuangshuang; Li, Zhenmao; Zhang, Hongyu; Lin, Zhenlang; Xiao, Jian

    2017-07-13

    Melatonin has neuroprotective effects in many diseases, including neonatal hypoxic-ischaemic (HI) brain injury. The purpose of this study was to evaluate the neuroprotective effects of melatonin both in vivo and in vitro and associated molecular mechanisms behind these effects. Postnatal day 7 male and female rat pups were subjected to unilateral HI, melatonin was injected intraperitoneally 1h before HI and an additional six doses were administered at 24h intervals. The pups were sacrificed at 24h and 7 d after HI. Pre-treatment with melatonin significantly reduced brain damage at 7 d after HI, with 15mg/kg melatonin achieving over 30% recovery in tissue loss compared to vehicle-treated animals. Autophagy and apoptotic cell death as indicated by autophagy associated proteins, cleaved caspase 3 and Tunel staining, was significantly inhibited after melatonin treatment in vivo as well as in PC12 cells. Melatonin treatment also significantly increased the GAP43 in the cortex. In conclusion, melatonin treatment reduced neonatal rat brain injury after HI, and this appeared to be related to inhibiting autophagy as well as reducing apoptotic cell death. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Blast exposure causes early and persistent aberrant phospho- and cleaved-tau expression in a murine model of mild blast-induced traumatic brain injury.

    Science.gov (United States)

    Huber, Bertrand R; Meabon, James S; Martin, Tobin J; Mourad, Pierre D; Bennett, Raymond; Kraemer, Brian C; Cernak, Ibolja; Petrie, Eric C; Emery, Michael J; Swenson, Erik R; Mayer, Cynthia; Mehic, Edin; Peskind, Elaine R; Cook, David G

    2013-01-01

    Mild traumatic brain injury (mTBI) is considered the 'signature injury' of combat veterans that have served during the wars in Iraq and Afghanistan. This prevalence of mTBI is due in part to the common exposure to high explosive blasts in combat zones. In addition to the threats of blunt impact trauma caused by flying objects and the head itself being propelled against objects, the primary blast overpressure (BOP) generated by high explosives is capable of injuring the brain. Compared to other means of causing TBI, the pathophysiology of mild-to-moderate BOP is less well understood. To study the consequences of BOP exposure in mice, we employed a well-established approach using a compressed gas-driven shock tube that recapitulates battlefield-relevant open-field BOP. We found that 24 hours post-blast a single mild BOP provoked elevation of multiple phospho- and cleaved-tau species in neurons, as well as elevating manganese superoxide-dismutase (MnSOD or SOD2) levels, a cellular response to oxidative stress. In hippocampus, aberrant tau species persisted for at least 30 days post-exposure, while SOD2 levels returned to sham control levels. These findings suggest that elevated phospho- and cleaved-tau species may be among the initiating pathologic processes induced by mild blast exposure. These findings may have important implications for efforts to prevent blast-induced insults to the brain from progressing into long-term neurodegenerative disease processes.

  12. Statistical analysis plan for the Erythropoietin in Traumatic Brain Injury trial: a randomised controlled trial of erythropoietin versus placebo in moderate and severe traumatic brain injury.

    LENUS (Irish Health Repository)

    Presneill, Jeffrey

    2014-01-01

    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.

  13. Adding insult to brain injury: young adults' experiences of residing in nursing homes following acquired brain injury.

    Science.gov (United States)

    Dwyer, Aoife; Heary, Caroline; Ward, Marcia; MacNeela, Pádraig

    2017-08-28

    There is general consensus that adults under age 65 with acquired brain injury residing in nursing homes is inappropriate, however there is a limited evidence base on the issue. Previous research has relied heavily on third-party informants and qualitative studies have been of questionable methodological quality, with no known study adopting a phenomenological approach. This study explored the lived experiences of young adults with brain injury residing in aged care facilities. Interpretative phenomenological analysis was employed to collect and analyze data from six semi-structured interviews with participants regarding their experiences of living in nursing homes. Two themes were identified, including "Corporeal prison of acquired brain injury: broken selves" and "Existential prison of the nursing home: stagnated lives". Results illustrated that young adults with acquired brain injury can experience aged care as an existential prison in which their lives feel at a standstill. This experience was characterized by feelings of not belonging in a terminal environment, confinement, disempowerment, emptiness and hope for greater autonomy through rehabilitation. It is hoped that this study will provide relevant professionals, services and policy-makers with insight into the challenges and needs of young adults with brain injury facing these circumstances. Implications for rehabilitation This study supports the contention that more home-like and age-appropriate residential rehabilitation services for young adults with acquired brain injury are needed. As development of alternative accommodation is a lengthy process, the study findings suggest that the interim implementation of rehabilitative care in nursing homes should be considered. Taken together with existing research, it is proposed that nursing home staff may require training to deliver evidence-based rehabilitative interventions to those with brain injury. The present findings add support to the call for systemic

  14. [Traumatic brain injuries--forensic and expertise aspects].

    Science.gov (United States)

    Vuleković, Petar; Simić, Milan; Misić-Pavkov, Gordana; Cigić, Tomislav; Kojadinović, Zeljko; Dilvesi, Dula

    2008-01-01

    Traumatic brain injuries have major socio-economic importance due to their frequency, high mortality and serious consequences. According to their nature the consequences of these injuries may be classified as neurological, psychiatric and esthetic. Various lesions of brain structures cause neurological consequences such as disturbance of motor functions, sensibility, coordination or involuntary movements, speech disturbances and other deviations, as well as epilepsy. Psychiatric consequences include cognitive deficit, emotional disturbances and behavior disturbances. CRIMINAL-LEGAL ASPECT OF TRAUMATIC BRAIN INJURIES AND LITIGATION: Criminal-legal aspect of traumatic brain injuries expertise understands the qualification of these injuries as mild, serious and qualified serious body injuries as well as the expertise about the mechanisms of their occurrence. Litigation expertise includes the estimation of pain, fear, diminished, i.e. lost vital activity and disability, esthetic marring, and psychological suffer based on the diminished general vital activity and esthetic marring. Evaluation of consequences of traumatic brain injuries should be performed only when it can be positively confirmed that they are permanent, i.e. at least one year after the injury. Expertise of these injuries is interdisciplinary. Among clinical doctors the most competent medical expert is the one who is in charge for diagnostics and injury treatment, with the recommendation to avoid, if possible, the doctor who conducted treatment. For the estimation of general vital activity, the neurological consequences, pain and esthetic marring expertise, the most competent doctors are neurosurgeon and neurologist. Psychological psychiatric consequences and fear expertise have to be performed by the psychiatrist. Specialists of forensic medicine contribute with knowledge of criminal low and legal expertise.

  15. Treatment for delayed brain injury after pituitary irradiation

    International Nuclear Information System (INIS)

    Fujii, Takashi; Misumi, Shuzoh; Shibasaki, Takashi; Tamura, Masaru; Kunimine, Hideo; Hayakawa, Kazushige; Niibe, Hideo; Miyazaki, Mizuho; Miyagi, Osamu.

    1988-01-01

    Treatment for delayed brain injury after pituitary irradiation is discussed. Six cases with delayed brain injury were treated with a combination of dexamethasone or betamethasone, with heparin, glycerol, dextran 40 and some vasodilators. Two cases with temporal lobe syndrome were treated in the early stages of brain injury for a period of over 12 months were almost completely cured, another two cases with chiasma syndrome were treated in the relatively late stages, showed a partial improvement. One case which was irradiated 120 GY during 13 years did not improve. The final case treated with steroids for a short period also resulted in failure and the patient underwent an operation for the removal of the necrotic mass three years after the radiotherapy. Steroid therapy started in the early stages of brain injury after irradiation for over the 12 months is thought to be effective. Heparin therapy was also effective in one out of three cases, but in one of the cases subarachnoid hemorrhage from a traumatic aneurysm occurred during the therapy. In an acute phase, showing edematous change of the injured brain, the administration of glycerol is also thought to be useful. But the effectiveness of the other medicines containing some vasodilators was obscure or doubtful. We propose the following : (1) A meticulous observation is essential for the patients who received high doses of irradiation to diagnose brain injury in the early reversible stage. (2) Steroids should be given immediately in this reversible stage of brain injury before the irreversible ''necrosis'' occurs. (3) Steroids should be maintained for a long period over 12 months. (4) Heparin therapy is also thought to be effective, but careful precautions to avoid hemorrhagic complications before the therapy should be scheduled. This recommended plan may also be used for the treatment of brain injuries after cranial irradiation for other intracranial tumors. (author)

  16. Behavior Management for Children and Adolescents with Acquired Brain Injury

    Science.gov (United States)

    Slifer, Keith J.; Amari, Adrianna

    2009-01-01

    Behavioral problems such as disinhibition, irritability, restlessness, distractibility, and aggression are common after acquired brain injury (ABI). The persistence and severity of these problems impair the brain-injured individual's reintegration into family, school, and community life. Since the early 1980s, behavior analysis and therapy have…

  17. Amelioration of cold injury-induced cortical brain edema formation by selective endothelin ETB receptor antagonists in mice.

    Science.gov (United States)

    Michinaga, Shotaro; Nagase, Marina; Matsuyama, Emi; Yamanaka, Daisuke; Seno, Naoki; Fuka, Mayu; Yamamoto, Yui; Koyama, Yutaka

    2014-01-01

    Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs) are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice). Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV) administration of BQ788 (ETB antagonist), IRL-2500 (ETB antagonist), or FR139317 (ETA antagonist) prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults.

  18. Amelioration of cold injury-induced cortical brain edema formation by selective endothelin ETB receptor antagonists in mice.

    Directory of Open Access Journals (Sweden)

    Shotaro Michinaga

    Full Text Available Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice. Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV administration of BQ788 (ETB antagonist, IRL-2500 (ETB antagonist, or FR139317 (ETA antagonist prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults.

  19. Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury

    Science.gov (United States)

    Jolly, Amy; de Simoni, Sara; Bourke, Niall; Patel, Maneesh C; Scott, Gregory; Sharp, David J

    2018-01-01

    Abstract Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of MRI. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions; and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 patients with moderate-severe traumatic brain injury (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (1-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterized using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarized regionally and compared with clinical and neuropsychological measures. Patients with traumatic brain injury showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over 1 year was pronounced following traumatic brain injury. Patients with traumatic brain injury lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates were related to memory performance at the end of the

  20. Electrophysiological biomarkers of epileptogenicity after traumatic brain injury.

    Science.gov (United States)

    Perucca, Piero; Smith, Gregory; Santana-Gomez, Cesar; Bragin, Anatol; Staba, Richard

    2018-06-05

    Post-traumatic epilepsy is the architype of acquired epilepsies, wherein a brain insult initiates an epileptogenic process culminating in an unprovoked seizure after weeks, months or years. Identifying biomarkers of such process is a prerequisite for developing and implementing targeted therapies aimed at preventing the development of epilepsy. Currently, there are no validated electrophysiological biomarkers of post-traumatic epileptogenesis. Experimental EEG studies using the lateral fluid percussion injury model have identified three candidate biomarkers of post-traumatic epileptogenesis: pathological high-frequency oscillations (HFOs, 80-300 Hz); repetitive HFOs and spikes (rHFOSs); and reduction in sleep spindle duration and dominant frequency at the transition from stage III to rapid eye movement sleep. EEG studies in humans have yielded conflicting data; recent evidence suggests that epileptiform abnormalities detected acutely after traumatic brain injury carry a significantly increased risk of subsequent epilepsy. Well-designed studies are required to validate these promising findings, and ultimately establish whether there are post-traumatic electrophysiological features which can guide the development of 'antiepileptogenic' therapies. Copyright © 2017. Published by Elsevier Inc.

  1. Nasal application of HSV encoding human preproenkephalin blocks craniofacial pain in a rat model of traumatic brain injury

    DEFF Research Database (Denmark)

    Sørensen, Jens Christian Hedemann; Meidahl, Anders Christian Nørgaard; Tzabazis

    2017-01-01

    pain using nasal application of a herpes simplex virus (HSV)-based vector expressing human proenkephalin (SHPE) to target the trigeminal ganglia. Mild TBI was induced in rats by the use of a modified fluid percussion model. Two days after mild TBI, following the development of facial mechanical...... lasting at least 45 days. On the other hand, nasal SHPE application 2 days post-TBI attenuated facial allodynia, reaching significance by day 4–7 and maintaining this effect throughout the duration of the experiment. Immunohistochemical examination revealed strong expression of human proenkephalin...

  2. Medical Management of the Severe Traumatic Brain Injury Patient.

    Science.gov (United States)

    Marehbian, Jonathan; Muehlschlegel, Susanne; Edlow, Brian L; Hinson, Holly E; Hwang, David Y

    2017-12-01

    Severe traumatic brain injury (sTBI) is a major contributor to long-term disability and a leading cause of death worldwide. Medical management of the sTBI patient, beginning with prehospital triage, is aimed at preventing secondary brain injury. This review discusses prehospital and emergency department management of sTBI, as well as aspects of TBI management in the intensive care unit where advances have been made in the past decade. Areas of emphasis include intracranial pressure management, neuromonitoring, management of paroxysmal sympathetic hyperactivity, neuroprotective strategies, prognostication, and communication with families about goals of care. Where appropriate, differences between the third and fourth editions of the Brain Trauma Foundation guidelines for the management of severe traumatic brain injury are highlighted.

  3. Biomarkers of brain injury in the premature infant

    Directory of Open Access Journals (Sweden)

    Martha V. Douglas-Escobar

    2013-01-01

    Full Text Available The term encephalopathy of prematurity encompasses not only the acute brain injury (such as intraventricular hemorrhage but also complex disturbance on the infant’s subsequent brain development. In premature infants, the most frequent recognized source of brain injury is intraventricular hemorrhage (IVH and periventricular leukomalacia (PVL. Furthermore 20-25% infants with birth weigh less than 1,500 g will have IVH and that proportion increases to 45% if the birth weight is less than 500-750 g. In addition, nearly 60% of very low birth weight newborns will have hypoxic-ischemic injury. Therefore permanent lifetime neurodevelopmental disabilities are frequent in premature infants. Innovative approach to prevent or decrease brain injury in preterm infants requires discovery of biomarkers able to discriminate infants at risk for injury, monitor the progression of the injury and assess efficacy of neuroprotective clinical trials. In this article, we will review biomarkers studied in premature infants with IVH, Post-hemorrhagic ventricular dilation (PHVD and PVL including: S100b, Activin A, erythropoietin, chemokine CCL 18, GFAP and NFL will also be examined. Some of the most promising biomarkers for IVH are S100β and Activin. The concentrations of TGF-β1, MMP-9 and PAI-1 in cerebrospinal fluid could be used to discriminate patients that will require shunt after post-hemorrhagic ventricular dilation. Neonatal brain injury is frequent in premature infants admitted to the neonatal intensive care and we hope to contribute to the awareness and interest in clinical validation of established as well as novel neonatal brain injury biomarkers.

  4. Correlating learning and memory improvements to long-term potentiation in patients with brain injury

    Institute of Scientific and Technical Information of China (English)

    Xingfu Peng; Qian Yu

    2008-01-01

    BACKGROUND:Brain injury patients often exhibit learning and memory functional deficits.Long-term potentiation(LTP)is a representative index for studying learning and memory cellular models; the LTP index correlates to neural plasticity. OBJECTIVE:This study was designed to investigate correlations of learning and memory functions to LTP in brain injury patients,and to summarize the research advancements in mechanisms underlying brain functional improvements after rehabilitation intervention. RETRIEVAL STRATEGY:Using the terms "brain injuries,rehabilitation,learning and memory,long-term potentiation",manuscripts that were published from 2000-2007 were retrieved from the PubMed database.At the same time,manuscripts published from 2000-2007 were also retrieved from the Database of Chinese Scientific and Technical Periodicals with the same terms in the Chinese language.A total of 64 manuscripts were obtained and primarily screened.Inclusion criteria:studies on learning and memory,as well as LTP in brain injury patients,and studies focused on the effects of rehabilitation intervention on the two indices; studies that were recently published or in high-impact journals.Exclusion criteria:repetitive studies.LITERATURE EVALUATION:The included manuscripts primarily focused on correlations between learning and memory and LTP,the effects of brain injury on learning and memory,as well as LTP,and the effects of rehabilitation intervention on learning and memory after brain injury.The included 39 manuscripts were clinical,basic experimental,or review studies. DATA SYNTHESIS:Learning and memory closely correlates to LTP.The neurobiological basis of learning and memory is central nervous system plasticity,which involves neural networks,neural circuits,and synaptic connections,in particular,synaptic plasticity.LTP is considered to be an ideal model for studying synaptic plasticity,and it is also a classic model for studying neural plasticity of learning and memory.Brain injury

  5. Increased CD147 (EMMPRIN) expression in the rat brain following traumatic brain injury.

    Science.gov (United States)

    Wei, Ming; Li, Hong; Shang, Yanguo; Zhou, Ziwei; Zhang, Jianning

    2014-10-17

    The extracellular matrix metalloproteinase inducer (EMMPRIN), or CD147, has been known to play a key regulatory role in vascular permeability and leukocyte activation by inducing the expression of matrix metalloproteinases (MMPs). The effects of traumatic brain injury on the expression of EMMPRIN remain poorly understood. In this study, we investigated changes in EMMPRIN expression in a rat model of fluid percussion injury (FPI) and examined the potential association between EMMPRIN and MMP-9 expression. Adult male rats were subjected to FPI. EMMPRIN expression was markedly up-regulated in the brain tissue surrounding the injured region 6-48 h after TBI, as measured by immunoblot and immunohistochemistry. EMMPRIN expression was localized to inflammatory cells. The increase in EMMPRIN expression was temporally correlated with an increase in MMP-9 levels. These data demonstrate, for the first time, changes in CD147 and MMP-9 expression following TBI. These data also suggest that CD147 and MMP-9 may play a role in vascular injuries after TBI. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Tracheostomy risk factors and outcomes after severe traumatic brain injury.

    Science.gov (United States)

    Humble, Stephen S; Wilson, Laura D; McKenna, John W; Leath, Taylor C; Song, Yanna; Davidson, Mario A; Ehrenfeld, Jesse M; Guillamondegui, Oscar D; Pandharipande, Pratik P; Patel, Mayur B

    2016-01-01

    To determine risk factors associated with tracheostomy placement after severe traumatic brain injury (TBI) and subsequent outcomes among those who did and did not receive a tracheostomy. This retrospective cohort study compared adult trauma patients with severe TBI (n = 583) who did and did not receive tracheostomy. A multivariable logistic regression model assessed the associations between age, sex, race, insurance status, admission GCS, AIS (Head, Face, Chest) and tracheostomy placement. Ordinal logistic regression models assessed tracheostomy's influence on ventilator days and ICU LOS. To limit immortal time bias, Cox proportional hazards models assessed mortality at 1, 3 and 12-months. In this multivariable model, younger age and private insurance were associated with increased probability of tracheostomy. AIS, ISS, GCS, race and sex were not risk factors for tracheostomy placement. Age showed a non-linear relationship with tracheostomy placement; likelihood peaked in the fourth decade and declined with age. Compared to uninsured patients, privately insured patients had an increased probability of receiving a tracheostomy (OR = 1.89 [95% CI = 1.09-3.23]). Mortality was higher in those without tracheostomy placement (HR = 4.92 [95% CI = 3.49-6.93]). Abbreviated injury scale-Head was an independent factor for time to death (HR = 2.53 [95% CI = 2.00-3.19]), but age, gender and insurance were not. Age and insurance status are independently associated with tracheostomy placement, but not with mortality after severe TBI. Tracheostomy placement is associated with increased survival after severe TBI.

  7. Proton MR spectroscopy in mild traumatic brain injury

    International Nuclear Information System (INIS)

    Kubas, Bożena; Łebkowski, Wojciech; Łebkowska, Urszula; Kułak, Wojciech; Tarasow, Eugeniusz; Walecki, Jerzy

    2010-01-01

    To assess the role of 1H MRS in the detection of changes in cerebral metabolite levels in pyramidal tracts after mild traumatic brain injury (MTBI) and to compare metabolite alterations to the clinical status (Glasgow Coma Scale). Study group consisted of 25 patients after mild traumatic brain injury, with a score of 11 to 15 in GCS. The MR studies were performed with a 1.5 T scanner. The results of spectra approximation (presented as metabolite ratios: NAA/Cr, NAA/Cho, Cho/Cr, lac/Cr, lip/Cr, Glx/Cr) were subjected to statistical analysis. MR spectra were recorded from a normal-appearing brain region: internal capsules and cerebral peduncles. Spectra from traumatic patients were compared with a control group including 34 healthy volunteers recorded with the same techniques. The statistical analysis revealed significant differences between the data obtained from various brain regions of the same patients after an MTBI and between the study and the control group. Proton MR spectroscopy detects changes in cerebral metabolite levels in apparently normal regions. In pyramidal tracts (internal capsules, cerebral peduncles), we noticed a significant reduction of NAA /Cho, lip/Cr, lac/Cr and Glx/Cr. In patients with mild brain injury, we can detect some metabolite abnormalities in normal-appearing brain structures. Proton MRS is a very useful tool for evaluation of major changes in metabolite levels in pyramidal tracts after mild traumatic brain injury

  8. Traumatic Brain Injury Induces Genome-Wide Transcriptomic, Methylomic, and Network Perturbations in Brain and Blood Predicting Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Qingying Meng

    2017-02-01

    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.

  9. Sensory cortex underpinnings of traumatic brain injury deficits.

    Directory of Open Access Journals (Sweden)

    Dasuni S Alwis

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

  10. OCT imaging of acute vascular changes following mild traumatic brain injury in mice (Conference Presentation)

    Science.gov (United States)

    Chico-Calero, Isabel; Shishkov, Milen; Welt, Jonathan; Blatter, Cedric; Vakoc, Benjamin J.

    2016-03-01

    While most people recover completely from mild traumatic brain injuries (mTBIs) and concussions, a subset develop lasting neurological disorders. Understanding the complex pathophysiology of these injuries is critical to developing improved prognostic and therapeutic approaches. Multiple studies have shown that the structure and perfusion of brain vessels are altered after mTBI. It is possible that these vascular injuries contribute to or trigger neurodegeneration. Intravital microscopy and mouse models of TBI offer a powerful platform to study the vascular component of mTBI. Because optical coherence tomography based angiography is based on perfusion contrast and is not significantly degraded by vessel leakage or blood brain barrier disruption, it is uniquely suited to studies of brain perfusion in the setting of trauma. However, existing TBI imaging models require surgical exposure of the brain at the time of injury which conflates TBI-related vascular changes with those caused by surgery. In this work, we describe a modified cranial window preparation based on a flexible, transparent polyurethane membrane. Impact injuries were delivered directly through this membrane, and imaging was performed immediately after injury without the need for additional surgical procedures. Using this model, we demonstrate that mTBI induces a transient cessation of flow in the capillaries and smaller vessels near the injury point. Reperfusion is observed in all animals within 3 hours of injury. This work describes new insight into the transient vascular changes induced by mTBI, and demonstrates more broadly the utility of the OCT/polyurethane window model platform in preclinical studies of mTBI.

  11. Overuse Injury Assessment Model

    National Research Council Canada - National Science Library

    Stuhmiller, James H; Shen, Weixin; Sih, Bryant

    2005-01-01

    ... bone stresses and strains from kinematic and ground reaction force measures. We broaden the work to address not only the overuse injuries, but the performance enhancement and metabolic demands associated with training...

  12. Blunt splenic injury and severe brain injury: a decision analysis and implications for care

    Science.gov (United States)

    Alabbasi, Thamer; Nathens, Avery B.; Tien, Col Homer

    2015-01-01

    Background The initial nonoperative management (NOM) of blunt splenic injuries in hemodynamically stable patients is common. In soldiers who experience blunt splenic injuries with concomitant severe brain injury while on deployment, however, NOM may put the injured soldier at risk for secondary brain injury from prolonged hypotension. Methods We conducted a decision analysis using a Markov process to evaluate 2 strategies for managing hemodynamically stable patients with blunt splenic injuries and severe brain injury — immediate splenectomy and NOM — in the setting of a field hospital with surgical capability but no angiography capabilities. We considered the base case of a 40-year-old man with a life expectancy of 78 years who experienced blunt trauma resulting in a severe traumatic brain injury and an isolated splenic injury with an estimated failure rate of NOM of 19.6%. The primary outcome measured was life expectancy. We assumed that failure of NOM would occur in the setting of a prolonged casualty evacuation, where surgical capability was not present. Results Immediate splenectomy was the slightly more effective strategy, resulting in a very modest increase in overall survival compared with NOM. Immediate splenectomy yielded a survival benefit of only 0.4 years over NOM. Conclusion In terms of overall survival, we would not recommend splenectomy unless the estimated failure rate of NOM exceeded 20%, which corresponds to an American Association for the Surgery of Trauma grade III splenic injury. For military patients for whom angiography may not be available at the field hospital and who require prolonged evacuation, immediate splenectomy should be considered for grade III–V injuries in the presence of severe brain injury. PMID:26100770

  13. Extensive cortical rewiring after brain injury.

    Science.gov (United States)

    Dancause, Numa; Barbay, Scott; Frost, Shawn B; Plautz, Erik J; Chen, Daofen; Zoubina, Elena V; Stowe, Ann M; Nudo, Randolph J

    2005-11-02

    Previously, we showed that the ventral premotor cortex (PMv) underwent neurophysiological remodeling after injury to the primary motor cortex (M1). In the present study, we examined cortical connections of PMv after such lesions. The neuroanatomical tract tracer biotinylated dextran amine was injected into the PMv hand area at least 5 months after ischemic injury to the M1 hand area. Comparison of labeling patterns between experimental and control animals demonstrated extensive proliferation of novel PMv terminal fields and the appearance of retrogradely labeled cell bodies within area 1/2 of the primary somatosensory cortex after M1 injury. Furthermore, evidence was found for alterations in the trajectory of PMv intracortical axons near the site of the lesion. The results suggest that M1 injury results in axonal sprouting near the ischemic injury and the establishment of novel connections within a distant target. These results support the hypothesis that, after a cortical injury, such as occurs after stroke, cortical areas distant from the injury undergo major neuroanatomical reorganization. Our results reveal an extraordinary anatomical rewiring capacity in the adult CNS after injury that may potentially play a role in recovery.

  14. Injury timing alters metabolic, inflammatory and functional outcomes following repeated mild traumatic brain injury.

    Science.gov (United States)

    Weil, Zachary M; Gaier, Kristopher R; Karelina, Kate

    2014-10-01

    Repeated head injuries are a major public health concern both for athletes, and members of the police and armed forces. There is ample experimental and clinical evidence that there is a period of enhanced vulnerability to subsequent injury following head trauma. Injuries that occur close together in time produce greater cognitive, histological, and behavioral impairments than do injuries separated by a longer period. Traumatic brain injuries alter cerebral glucose metabolism and the resolution of altered glucose metabolism may signal the end of the period of greater vulnerability. Here, we injured mice either once or twice separated by three or 20days. Repeated injuries that were separated by three days were associated with greater axonal degeneration, enhanced inflammatory responses, and poorer performance in a spatial learning and memory task. A single injury induced a transient but marked increase in local cerebral glucose utilization in the injured hippocampus and sensorimotor cortex, whereas a second injury, three days after the first, failed to induce an increase in glucose utilization at the same time point. In contrast, when the second injury occurred substantially later (20days after the first injury), an increase in glucose utilization occurred that paralleled the increase observed following a single injury. The increased glucose utilization observed after a single injury appears to be an adaptive component of recovery, while mice with 2 injuries separated by three days were not able to mount this response, thus this second injury may have produced a significant energetic crisis such that energetic demands outstripped the ability of the damaged cells to utilize energy. These data strongly reinforce the idea that too rapid return to activity after a traumatic brain injury can induce permanent damage and disability, and that monitoring cerebral energy utilization may be a tool to determine when it is safe to return to the activity that caused the initial

  15. Role of Melatonin in Traumatic Brain Injury and Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Mehar Naseem

    2014-01-01

    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.

  16. Volumetric analysis of day of injury computed tomography is associated with rehabilitation outcomes after traumatic brain injury.

    Science.gov (United States)

    Majercik, Sarah; Bledsoe, Joseph; Ryser, David; Hopkins, Ramona O; Fair, Joseph E; Brock Frost, R; MacDonald, Joel; Barrett, Ryan; Horn, Susan; Pisani, David; Bigler, Erin D; Gardner, Scott; Stevens, Mark; Larson, Michael J

    2017-01-01

    Day-of-injury (DOI) brain lesion volumes in traumatic brain injury (TBI) patients are rarely used to predict long-term outcomes in the acute setting. The purpose of this study was to investigate the relationship between acute brain injury lesion volume and rehabilitation outcomes in patients with TBI at a level one trauma center. Patients with TBI who were admitted to our rehabilitation unit after the acute care trauma service from February 2009-July 2011 were eligible for the study. Demographic data and outcome variables including cognitive and motor Functional Independence Measure (FIM) scores, length of stay (LOS) in the rehabilitation unit, and ability to return to home were obtained. The DOI quantitative injury lesion volumes and degree of midline shift were obtained from DOI brain computed tomography scans. A multiple stepwise regression model including 13 independent variables was created. This model was used to predict postrehabilitation outcomes, including FIM scores and ability to return to home. A p value less than 0.05 was considered significant. Ninety-six patients were enrolled in the study. Mean age was 43 ± 21 years, admission Glasgow Coma Score was 8.4 ± 4.8, Injury Severity Score was 24.7 ± 9.9, and head Abbreviated Injury Scale score was 3.73 ± 0.97. Acute hospital LOS was 12.3 ± 8.9 days, and rehabilitation LOS was 15.9 ± 9.3 days. Day-of-injury TBI lesion volumes were inversely associated with cognitive FIM scores at rehabilitation admission (p = 0.004) and discharge (p = 0.004) and inversely associated with ability to be discharged to home after rehabilitation (p = 0.006). In a cohort of patients with moderate to severe TBI requiring a rehabilitation unit stay after the acute care hospital stay, DOI brain injury lesion volumes are associated with worse cognitive FIM scores at the time of rehabilitation admission and discharge. Smaller-injury volumes were associated with eventual discharge to home. Volumetric neuroimaging in the acute

  17. Volumetric analysis of day of injury computed tomography is associated with rehabilitation outcomes after traumatic brain injury

    Science.gov (United States)

    Majercik, Sarah; Bledsoe, Joseph; Ryser, David; Hopkins, Ramona O.; Fair, Joseph E.; Frost, R. Brock; MacDonald, Joel; Barrett, Ryan; Horn, Susan; Pisani, David; Bigler, Erin D.; Gardner, Scott; Stevens, Mark; Larson, Michael J.

    2016-01-01

    Introduction Day-of-injury (DOI) brain lesion volumes in traumatic brain injury (TBI) patients are rarely used to predict long-term outcomes in the acute setting. The purpose of this study was to investigate the relationship between acute brain injury lesion volume and rehabilitation outcomes in patients with TBI at a Level One Trauma Center. Methods Patients with TBI who were admitted to our rehabilitation unit after the acute care trauma service from February 2009-July 2011 were eligible for the study. Demographic data and outcome variables including cognitive and motor FIM scores, length of stay (LOS) in the rehabilitation unit, and ability to return to home were obtained. DOI quantitative injury lesion volumes and degree of midline shift were obtained from day-of-injury (DOI) brain computed tomography (CT) scans. A multiple step-wise regression model including 13 independent variables was created. This model was used to predict post-rehabilitation outcomes, including FIM scores and ability to return to home. PInjury Severity Score 24.7±9.9, and head Abbreviated Injury Scale score 3.73±0.97. Acute hospital length of stay (LOS) was 12.3±8.9 days and rehabilitation LOS was 15.9±9.3 days. Day-of-injury TBI lesion volumes were inversely associated with cognitive FIM scores at rehabilitation admission (p=0.004) and discharge (p=0.004) and inversely associated with ability to be discharged to home after rehabilitation (p=0.006). Conclusion In a cohort of patients with moderate to severe TBI requiring a rehabilitation unit stay after the acute care hospital stay, DOI brain injury lesion volumes are associated with worse cognitive FIM scores at the time of rehabilitation admission and discharge. Smaller injury volumes were associated with eventual discharge to home. Volumetric neuroimaging in the acute injury phase may improve surgeons’ ultimate outcome predictions in TBI patients. Level of Evidence/Study Type Level V, case series, Prognostic/Epidemiological PMID

  18. Functional brain imaging to investigate the higher brain dysfunction induced by diffuse brain injury

    International Nuclear Information System (INIS)

    Nariai, Tadashi; Inaji, Motoki; Ohno, Kikuo; Hiura, Mikio; Ishii, Kenji; Hosoda, Chihiro

    2011-01-01

    Higher brain dysfunction is the major problem of patients who recover from neurotrauma the prevents them from returning to their previous social life. Many such patients do not have focal brain damage detected with morphological imaging. We focused on studying the focal brain dysfunction that can be detected only with functional imaging with positron emission tomography (PET) in relation to the score of various cognition batteries. Patients who complain of higher brain dysfunction without apparent morphological cortical damage were recruited for this study. Thirteen patients with diffuse axonal injury (DAI) or cerebral concussion was included. They underwent a PET study to image glucose metabolism by 18 F-fluorodeoxyglucose (FDG), and central benodiazepine receptor (cBZD-R) (marker of neuronal body) by 11 C-flumazenil, together with cognition measurement by WAIS-R, WMS-R, and WCST etc. PET data were compared with age matched normal controls using statistical parametric mapping (SPM)2. DAI patients had a significant decrease in glucose matabolism and cBZD-R distribution in the cingulated cortex than normal controls. Patients diagnosed with concussion because of shorter consciousness disturbance also had abnormal FDG uptake and cBZD-R distribution. Cognition test scores were variable among patients. Degree of decreased glucose metabolism and cBZD-R distribution in the dominant hemishphere corresponded well to the severity of cognitive disturbance. PET molecular imaging was useful to depict focal cortical dysfunction of neurotrauma patients even when morphological change was not apparent. This method may be promising to clarify the pathophysiology of higher brain dysfunction of patients with diffuse axonal injury or chronic traumatic encephalopathy. (author)

  19. Epigenetic modulation of gene expression governs the brain's response to injury.

    Science.gov (United States)

    Simon, Roger P

    2016-06-20

    Mild stress from ischemia, seizure, hypothermia, or infection can produce a transient neuroprotected state in the brain. In the neuroprotected state, the brain responds differently to a severe stress and sustains less injury. At the genomic level, the response of the neuroprotected brain to a severe stress is characterized by widespread differential regulation of genes with diverse functions. This reprogramming of gene expression observed in the neuroprotected brain in response to a stress is consistent with an epigenetic model of regulation mediated by changes in DNA methylation and histone modification. Here, we summarize our evolving understanding of the molecular basis for endogenous neuroprotection and review recent findings that implicate DNA methylation and protein mediators of histone modification as epigenetic regulators of the brain's response to injury. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Brain injury and severe eating difficulties at admission

    DEFF Research Database (Denmark)

    Kjærsgaard, Annette; Kaae Kristensen, Hanne

    Objective: The objective of this pilot study was to explore and interpret the way that individuals with acquired brain injury, admitted to inpatient neurorehabilitation with severe eating difficulties, experienced eating nine to fifteen months after discharge. Methods: Four individuals with acqui......Objective: The objective of this pilot study was to explore and interpret the way that individuals with acquired brain injury, admitted to inpatient neurorehabilitation with severe eating difficulties, experienced eating nine to fifteen months after discharge. Methods: Four individuals...... with acquired brain injury were interviewed via qualitative semi-structured interviews. An explorative study was conducted to study eating difficulties. Qualitative content analysis was used. Results: Four main themes emerged from the analysis: personal values related to eating, swallowing difficulties, eating......-of-life. The preliminary findings provide knowledge regarding the patient perspective of adapting to and developing new strategies for activities related to eating, however, further prospective, longitudinal research in a larger scale and with repeated interviews is needed....

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

    Science.gov (United States)

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

    2016-04-01

    Traumatic brain injury (TBI)-induced impairments in cerebral energy metabolism impede tissue repair and contribute to delayed functional recovery. Moreover, the transient alteration in brain glucose utilization corresponds to a period of increased vulnerability to the negative effects of a subsequent TBI. In order to better understand the factors contributing to TBI-induced central metabolic dysfunction, we examined the effect of single and repeated TBIs on brain insulin signalling. Here we show that TBI induced acute brain insulin resistance, which resolved within 7 days following a single injury but persisted until 28 days following repeated injuries. Obesity, which causes brain insulin resistance and neuroinflammation, exacerbated the consequences of TBI. Obese mice that underwent a TBI exhibited a prolonged reduction of Akt (also known as protein kinase B) signalling, exacerbated neuroinflammation (microglial activation), learning and memory deficits, and anxiety-like behaviours. Taken together, the transient changes in brain insulin sensitivity following TBI suggest a reduced capacity of the injured brain to respond to the neuroprotective and anti-inflammatory actions of insulin and Akt signalling, and thus may be a contributing factor for the damaging neuroinflammation and long-lasting deficits that occur following TBI. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  2. Early inflammatory response in rat brain after peripheral thermal injury.

    Science.gov (United States)

    Reyes, Raul; Wu, Yimin; Lai, Qin; Mrizek, Michael; Berger, Jamie; Jimenez, David F; Barone, Constance M; Ding, Yuchuan

    2006-10-16

    Previous studies have shown that the cerebral complications associated with skin burn victims are correlated with brain damage. The aim of this study was to determine whether systemic thermal injury induces inflammatory responses in the brain. Sprague Dawley rats (n=28) were studied in thermal injury and control groups. Animals from the thermal injury (n=14) and control (n=14) group were anesthetized and submerged to the neck vertically in 85 degrees C water for 6 s producing a third degree burn affecting 60-70% of the animal body surface area. The controls were submerged in 37 degrees C water for 6 s. Early expression of tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL-1beta), and intracellular cell adhesion molecules (ICAM-1) protein levels in serum were determined at 3 (n=7) and 7 h (n=7) by enzyme-linked immunoabsorbent assay (ELISA). mRNA of TNF-alpha, IL-1beta, and ICAM-1 in the brain was measured at the same time points with a real-time reverse transcriptase-polymerase chain reaction (RT-PCR). An equal animal number was used for controls. Systemic inflammatory responses were demonstrated by dramatic up-regulations (5-50 fold) of TNF-alpha, IL-1beta, and ICAM-1 protein level in serum at 7 h after the thermal injury. However, as early as 3 h after peripheral thermal injury, a significant increase (3-15 fold) in mRNA expression of TNF-alpha, IL-1beta and ICAM-1 was observed in brain homogenates, with increased levels remaining at 7 h after injury. This study demonstrated an early inflammatory response in the brain after severe peripheral thermal injury. The cerebral inflammatory reaction was associated with expression of systemic cytokines and an adhesion molecule.

  3. [Scandinavian guidelines for prehospital management of severe traumatic brain injury

    DEFF Research Database (Denmark)

    Sollid, S.; Sundstrom, T.; Kock-Jensen, C.

    2008-01-01

    . Evidence-based guidelines already exist that focus on all steps in the process. In the present article members of the Scandinavian Neurotrauma Committee present recommendations on prehospital management of traumatic brain injury adapted to the infrastructure of the Nordic region Udgivelsesdato: 2008/6/26......Head trauma is the cause the death for many young persons. The number of fatalities can be reduced through systematic management. Prevention of secondary brain injury combined with the fastest possible transport to a neurosurgical unit, have been shown to effectively reduce mortality and morbidity...

  4. The emergence of artistic ability following traumatic brain injury

    OpenAIRE

    Midorikawa, Akira; Kawamura, Mitsuru

    2014-01-01

    In this study, the case of a patient who developed artistic ability following a traumatic brain injury is reported. The subject was a 49-year-old male who suffered brain injury at the age of 44 due to an accidental fall. At age 48, he began drawing with great enthusiasm and quickly developed a personal style with his own biomorphic iconography. At first, his drawing was restricted to realistic reproductions of photographs of buildings, but his style of drawing changed and became more personal...

  5. The emergence of artistic ability following traumatic brain injury.

    Science.gov (United States)

    Midorikawa, Akira; Kawamura, Mitsuru

    2015-02-01

    In this study, the case of a patient who developed artistic ability following a traumatic brain injury is reported. The subject was a 49-year-old male who suffered brain injury at the age of 44 due to an accidental fall. At age 48, he began drawing with great enthusiasm and quickly developed a personal style with his own biomorphic iconography. At first, his drawing was restricted to realistic reproductions of photographs of buildings, but his style of drawing changed and became more personal and expressionistic over the following 6 months.

  6. Glucose and oxygen metabolism after penetrating ballistic-like brain injury

    Science.gov (United States)

    Gajavelli, Shyam; Kentaro, Shimoda; Diaz, Julio; Yokobori, Shoji; Spurlock, Markus; Diaz, Daniel; Jackson, Clayton; Wick, Alexandra; Zhao, Weizhao; Leung, Lai Y; Shear, Deborah; Tortella, Frank; Bullock, M Ross

    2015-01-01

    Traumatic brain injury (TBI) is a major cause of death and disability in all age groups. Among TBI, penetrating traumatic brain injuries (PTBI) have the worst prognosis and represent the leading cause of TBI-related morbidity and death. However, there are no specific drugs/interventions due to unclear pathophysiology. To gain insights we looked at cerebral metabolism in a PTBI rat model: penetrating ballistic-like brain injury (PBBI). Early after injury, regional cerebral oxygen tension and consumption significantly decreased in the ipsilateral cortex in the PBBI group compared with the control group. At the same time point, glucose uptake was significantly reduced globally in the PBBI group compared with the control group. Examination of Fluorojade B-stained brain sections at 24 hours after PBBI revealed an incomplete overlap of metabolic impairment and neurodegeneration. As expected, the injury core had the most severe metabolic impairment and highest neurodegeneration. However, in the peri-lesional area, despite similar metabolic impairment, there was lesser neurodegeneration. Given our findings, the data suggest the presence of two distinct zones of primary injury, of which only one recovers. We anticipate the peri-lesional area encompassing the PBBI ischemic penumbra, could be salvaged by acute therapies. PMID:25669903

  7. Vitamins and nutrients as primary treatments in experimental brain injury: Clinical implications for nutraceutical therapies.

    Science.gov (United States)

    Vonder Haar, Cole; Peterson, Todd C; Martens, Kris M; Hoane, Michael R

    2016-06-01

    With the numerous failures of pharmaceuticals to treat traumatic brain injury in humans, more researchers have become interested in combination therapies. This is largely due to the multimodal nature of damage from injury, which causes excitotoxicity, oxidative stress, edema, neuroinflammation and cell death. Polydrug treatments have the potential to target multiple aspects of the secondary injury cascade, while many previous therapies focused on one particular aspect. Of specific note are vitamins, minerals and nutrients that can be utilized to supplement other therapies. Many of these have low toxicity, are already FDA approved and have minimal interactions with other drugs, making them attractive targets for therapeutics. Over the past 20 years, interest in supplementation and supraphysiologic dosing of nutrients for brain injury has increased and indeed many vitamins and nutrients now have a considerable body of the literature backing their use. Here, we review several of the prominent therapies in the category of nutraceutical treatment for brain injury in experimental models, including vitamins (B2, B3, B6, B9, C, D, E), herbs and traditional medicines (ginseng, Gingko biloba), flavonoids, and other nutrients (magnesium, zinc, carnitine, omega-3 fatty acids). While there is still much work to be done, several of these have strong potential for clinical therapies, particularly with regard to polydrug regimens. This article is part of a Special Issue entitled SI:Brain injury and recovery. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Blast-induced traumatic brain injury: a new trend of blast injury research.

    Science.gov (United States)

    Zhao, Yan; Wang, Zheng-Guo

    2015-01-01

    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 bTBI-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.

  9. Music interventions for acquired brain injury.

    Science.gov (United States)

    Magee, Wendy L; Clark, Imogen; Tamplin, Jeanette; Bradt, Joke

    2017-01-20

    Acquired brain injury (ABI) can result in impairments in motor function, language, cognition, and sensory processing, and in emotional disturbances, which can severely reduce a survivor's quality of life. Music interventions have been used in rehabilitation to stimulate brain functions involved in movement, cognition, speech, emotions, and sensory perceptions. An update of the systematic review published in 2010 was needed to gauge the efficacy of music interventions in rehabilitation for people with ABI. To assess the effects of music interventions for functional outcomes in people with ABI. We expanded the criteria of our existing review to: 1) examine the efficacy of music interventions in addressing recovery in people with ABI including gait, upper extremity function, communication, mood and emotions, cognitive functioning, social skills, pain, behavioural outcomes, activities of daily living, and adverse events; 2) compare the efficacy of music interventions and standard care with a) standard care alone, b) standard care and placebo treatments, or c) standard care and other therapies; 3) compare the efficacy of different types of music interventions (music therapy delivered by trained music therapists versus music interventions delivered by other professionals). We searched the Cochrane Stroke Group Trials Register (January 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 6), MEDLINE (1946 to June 2015), Embase (1980 to June 2015), CINAHL (1982 to June 2015), PsycINFO (1806 to June 2015), LILACS (1982 to January 2016), and AMED (1985 to June 2015). We handsearched music therapy journals and conference proceedings, searched dissertation and specialist music databases, trials and research registers, reference lists, and contacted relevant experts and music therapy associations to identify unpublished research. We imposed no language restriction. We performed the original search in 2009. We included all randomised controlled trials

  10. Neural Plasticity and Neurorehabilitation Following Traumatic Brain Injury

    Science.gov (United States)

    2011-04-01

    of Theresa Jones for sectioning and staining . To date, the brains have been sectioned and one set stained for Nissl . Using the Nissl stained ...three rehabilitations decreases contusion size compared to CCI-Yoked (#p=0.051). The remaining sets of brain sections have been stained with...optical densitometry, as appropriate, given staining patterns. Sample locations will be the remaining sensorimotor cortex around the injury, in the

  11. Oligodendrogenesis after Cerebral Ischaemia and Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Zheng Gang Zhang

    2013-08-01

    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.

  12. Brain-computer interface after nervous system injury.

    Science.gov (United States)

    Burns, Alexis; Adeli, Hojjat; Buford, John A

    2014-12-01

    Brain-computer interface (BCI) has proven to be a useful tool for providing alternative communication and mobility to patients suffering from nervous system injury. BCI has been and will continue to be implemented into rehabilitation practices for more interactive and speedy neurological recovery. The most exciting BCI technology is evolving to provide therapeutic benefits by inducing cortical reorganization via neuronal plasticity. This article presents a state-of-the-art review of BCI technology used after nervous system injuries, specifically: amyotrophic lateral sclerosis, Parkinson's disease, spinal cord injury, stroke, and disorders of consciousness. Also presented is transcending, innovative research involving new treatment of neurological disorders. © The Author(s) 2014.

  13. Interleukin-1 Receptor in Seizure Susceptibility after Traumatic Injury to the Pediatric Brain.

    Science.gov (United States)

    Semple, Bridgette D; O'Brien, Terence J; Gimlin, Kayleen; Wright, David K; Kim, Shi Eun; Casillas-Espinosa, Pablo M; Webster, Kyria M; Petrou, Steven; Noble-Haeusslein, Linda J

    2017-08-16

    Epilepsy after pediatric traumatic brain injury (TBI) is associated with poor quality of life. This study aimed to characterize post-traumatic epilepsy in a mouse model of pediatric brain injury, and to evaluate the role of interleukin-1 (IL-1) signaling as a target for pharmacological intervention. Male mice received a controlled cortical impact or sham surgery at postnatal day 21, approximating a toddler-aged child. Mice were treated acutely with an IL-1 receptor antagonist (IL-1Ra; 100 mg/kg, s.c.) or vehicle. Spontaneous and evoked seizures were evaluated from video-EEG recordings. Behavioral assays tested for functional outcomes, postmortem analyses assessed neuropathology, and brain atrophy was detected by ex vivo magnetic resonance imaging. At 2 weeks and 3 months post-injury, TBI mice showed an elevated seizure response to the convulsant pentylenetetrazol compared with sham mice, associated with abnormal hippocampal mossy fiber sprouting. A robust increase in IL-1β and IL-1 receptor were detected after TBI. IL-1Ra treatment reduced seizure susceptibility 2 weeks after TBI compared with vehicle, and a reduction in hippocampal astrogliosis. In a chronic study, IL-1Ra-TBI mice showed improved spatial memory at 4 months post-injury. At 5 months, most TBI mice exhibited spontaneous seizures during a 7 d video-EEG recording period. At 6 months, IL-1Ra-TBI mice had fewer evoked seizures compared with vehicle controls, coinciding with greater preservation of cortical tissue. Findings demonstrate this model's utility to delineate mechanisms underlying epileptogenesis after pediatric brain injury, and provide evidence of IL-1 signaling as a mediator of post-traumatic astrogliosis and seizure susceptibility. SIGNIFICANCE STATEMENT Epilepsy is a common cause of morbidity after traumatic brain injury in early childhood. However, a limited understanding of how epilepsy develops, particularly in the immature brain, likely contributes to the lack of efficacious treatments

  14. Behavioral Outcomes Differ Between Rotational Acceleration and Blast Mechanisms of Mild Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Brian D. Stemper

    2016-03-01

    Full Text Available Mild traumatic brain injury (mTBI can result from a number of mechanisms, including blunt impact, head rotational acceleration, exposure to blast, and penetration of projectiles. Mechanism is likely to influence the type, severity, and chronicity of outcomes. The objective of this study was to determine differences in the severity and time-course of behavioral outcomes following blast and rotational mTBI. The Medical College of Wisconsin (MCW Rotational Injury model and a shock tube model of primary blast injury were used to induce mTBI in rats and behavioral assessments were conducted within the first week, as well as 30 and 60 days following injury. Acute recovery time demonstrated similar increases over protocol-matched shams, indicating acute injury severity equivalence between the two mechanisms. Post-injury behavior in the elevated plus maze demonstrated differing trends, with rotationally injured rats acutely demonstrating greater activity, whereas blast-injured rats had decreased activity that developed at chronic time points. Similarly, blast-injured rats demonstrated trends associated with cognitive deficits that were not apparent following rotational injuries. These findings demonstrate that rotational and blast injury result in behavioral changes with different qualitative and temporal manifestations. Whereas rotational injury was characterized by a rapidly emerging phenotype consistent with behavioral disinhibition, blast injury was associated with emotional and cognitive differences that were not evident acutely, but developed later, with an anxiety-like phenotype still present in injured animals at our most chronic measurements.

  15. Neuroprotective effects of collagen matrix in rats after traumatic brain injury.

    Science.gov (United States)

    Shin, Samuel S; Grandhi, Ramesh; Henchir, Jeremy; Yan, Hong Q; Badylak, Stephen F; Dixon, C Edward

    2015-01-01

    In previous studies, collagen based matrices have been implanted into the site of lesion in different models of brain injury. We hypothesized that semisynthetic collagen matrix can have neuroprotective function in the setting of traumatic brain injury. Rats were subjected to sham injury or controlled cortical impact. They either received extracellular matrix graft (DuraGen) over the injury site or did not receive any graft and underwent beam balance/beam walking test at post injury days 1-5 and Morris water maze at post injury days 14-18. Animals were sacrificed at day 18 for tissue analysis. Collagen matrix implantation in injured rats did not affect motor function (beam balance test: p = 0.627, beam walking test: p = 0.921). However, injured group with collagen matrix had significantly better spatial memory acquisition (p < 0.05). There was a significant reduction in lesion volume, as well as neuronal loss in CA1 (p < 0.001) and CA3 (p < 0.05) regions of the hippocampus in injured group with collagen matrix (p < 0.05). Collagen matrix reduces contusional lesion volume, neuronal loss, and cognitive deficit after traumatic brain injury. Further studies are needed to demonstrate the mechanisms of neuroprotection by collagen matrix.

  16. Traumatic Brain Injury: Hope Through Research

    Science.gov (United States)

    ... fatigue or drowsiness; a lack of energy or motivation changes in sleep patterns (e.g., sleeping a ... nerve cells in the brain causing strange sensations, emotions, and behavior, or sometimes convulsions, muscle spasms, and ...

  17. [Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis].

    Science.gov (United States)

    Zhao, De-An; Bi, Ling-Yun; Huang, Qian; Zhang, Fang-Min; Han, Zi-Ming

    Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  18. Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis.

    Science.gov (United States)

    Zhao, De-An; Bi, Ling-Yun; Huang, Qian; Zhang, Fang-Min; Han, Zi-Ming

    Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  19. Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis

    Directory of Open Access Journals (Sweden)

    De-An Zhao

    Full Text Available Abstract Background and objectives: Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. Methods: A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Results: Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Conclusions: Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis.

  20. Neuroprotection from Brain Injury by Novel Estrogens

    Science.gov (United States)

    2001-08-01

    plate contained approxi- substituted estradlol. J. Steroid Blochem. 1988, 29, 657-664. mately 5000 cells as determined by a Neubauer hemacytometer (13...the brain was removed, and the base of the brain was photographed by a digital camera (Sony Preparation of animals MVC-FD5, Tokyo, Japan) for...chloride (TTC) in physiological saline at 37 0 C, and then fixed in 10% formalin. The stained slices were photographed by a digital camera (Sony MVC-FD5

  1. Voltage-Gated Calcium Channel Antagonists and Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Bruce Lyeth

    2013-06-01

    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.

  2. Minocycline Transiently Reduces Microglia/Macrophage Activation but Exacerbates Cognitive Deficits Following Repetitive Traumatic Brain Injury in the Neonatal Rat

    Science.gov (United States)

    Hanlon, Lauren A.; Huh, Jimmy W.

    2016-01-01

    Elevated microglial/macrophage-associated biomarkers in the cerebrospinal fluid of infant victims of abusive head trauma (AHT) suggest that these cells play a role in the pathophysiology of the injury. In a model of AHT in 11-day-old rats, 3 impacts (24 hours apart) resulted in spatial learning and memory deficits and increased brain microglial/macrophage reactivity, traumatic axonal injury, neuronal degeneration, and cortical and white-matter atrophy. The antibiotic minocycline has been effective in decreasing injury-induced microglial/macrophage activation while simultaneously attenuating cellular and functional deficits in models of neonatal hypoxic ischemia, but the potential for this compound to rescue deficits after impact-based trauma to the immature brain remains unexplored. Acute minocycline administration in this model of AHT decreased microglial/macrophage reactivity in the corpus callosum of brain-injured animals at 3 days postinjury, but this effect was lost by 7 days postinjury. Additionally, minocycline treatment had no effect on traumatic axonal injury, neurodegeneration, tissue atrophy, or spatial learning deficits. Interestingly, minocycline-treated animals demonstrated exacerbated injury-induced spatial memory deficits. These results contrast with previous findings in other models of brain injury and suggest that minocycline is ineffective in reducing microglial/macrophage activation and ameliorating injury-induced deficits following repetitive neonatal traumatic brain injury. PMID:26825312

  3. The effect of the diazepam to the free radical under the brain radiation injury

    International Nuclear Information System (INIS)

    Huo Hongmei; Wang Chen; Zhang Zhilin

    2007-01-01

    Objective: To study the effect of the diazepam on free radical under in the brain radiation injury in the early stage. Methods: A model of whole brain radiation injury in wakefulness was established in the Sprague-Dawley rat. Diazepam was given intraperitoneally 30 minutes before radiation. The brain tissue homogenate was prepared respectively while the rats were executed 6 hours, 1 day, 1 week, 1 month after irradiation. The contents of the superoxide dismutase (SOD) and the malondialdehyde (MDA) in the tissue homogenate were measured by chemical colorimetry. Results: Diazepam could increase the vigor of SOD and reduce the MDA contents after irradiated. Conclusions: Diazepam has certain neuroprotection effect on radiation injury and decreasing the level of the free radicals. (authors)

  4. Increased cerebral (R-[11C]PK11195 uptake and glutamate release in a rat model of traumatic brain injury: a longitudinal pilot study

    Directory of Open Access Journals (Sweden)

    Lammertsma Adriaan A

    2011-06-01

    Full Text Available Abstract Background The aim of the present study was to investigate microglia activation over time following traumatic brain injury (TBI and to relate these findings to glutamate release. Procedures Sequential dynamic (R-[11C]PK11195 PET scans were performed in rats 24 hours before (baseline, and one and ten days after TBI using controlled cortical impact, or a sham procedure. Extracellular fluid (ECF glutamate concentrations were measured using cerebral microdialysis. Brains were processed for histopathology and (immuno-histochemistry. Results Ten days after TBI, (R-[11C]PK11195 binding was significantly increased in TBI rats compared with both baseline values and sham controls (p -1 as compared with the sham procedure (6.4 ± 3.6 μmol·L-1. Significant differences were found between TBI and sham for ED-1, OX-6, GFAP, Perl's, and Fluoro-Jade B. Conclusions Increased cerebral uptake of (R-[11C]PK11195 ten days after TBI points to prolonged and ongoing activation of microglia. This activation followed a significant acute posttraumatic increase in ECF glutamate levels.

  5. Mechanical properties of brain tissue: characterisation and constitutive modelling

    NARCIS (Netherlands)

    Dommelen, van J.A.W.; Hrapko, M.; Peters, G.W.M.; Kamkin, A.; Kiseleva, I.

    2009-01-01

    The head is often considered as the most critical region of the human body for life-threatening injuries sustained in accidents. In order to develop effective protective measures, a better understanding of the process of injury development in the brain is required. Finite Element (FE) models are

  6. Reducing Secondary Insults in Traumatic Brain Injury

    Science.gov (United States)

    2015-03-01

    could more reliably document the frequency of these events and help us understand the causes. Understand- ing the causes wi ll allow us to design...hypoperfusion. J Trauma 2003; 54(2): 312-9. 12. Manley G, Knudson MM, Morabito D, Damron S, Erickson V, Pitts L: Hypotension , hypoxia, and head injury

  7. Treatment of surgical brain injury by immune tolerance induced by intrathymic and hepatic portal vein injection of brain antigens.

    Science.gov (United States)

    Yang, Weijian; Liu, Yong; Liu, Baolong; Tan, Huajun; Lu, Hao; Wang, Hong; Yan, Hua

    2016-08-24

    Surgical brain injury (SBI) defines complications induced by intracranial surgery, such as cerebral edema and other secondary injuries. In our study, intrathymic and hepatic portal vein injection of allogeneic myelin basic protein (MBP) or autogeneic brain cell suspensions were administered to a standard SBI model. Serum pro-inflammatory IL-2, anti-inflammatory IL-4 concentrations and the CD4(+)T/CD8(+)T ratio were measured at 1, 3, 7, 14 and 21 d after surgery to verify the establishment of immune tolerance. Furthermore, we confirmed neuroprotective effects by evaluating neurological scores at 1, 3, 7, 14 and 21 d after SBI. Anti-Fas ligand (FasL) immunohistochemistry and TUNEL assays of brain sections were tested at 21 d after surgery. Intrathymic injections of MBP or autogeneic brain cell suspensions functioned by both suppressing secondary inflammatory reactions and improving prognoses, whereas hepatic portal vein injections of autogeneic brain cell suspensions exerted a better effect than MBP. Intrathymic and hepatic portal vein injections of MBP had equal effects on reducing secondary inflammation and improving prognoses. Otherwise, hepatic portal vein injections of autogeneic brain cell suspensions had better outcomes than intrathymic injections of autogeneic brain cell suspensions. Moreover, the benefit of injecting antigens into the thymus was outweighed by hepatic portal vein injections.

  8. Increased Sleep Need and Reduction of Tuberomammillary Histamine Neurons after Rodent Traumatic Brain Injury.

    Science.gov (United States)

    Noain, Daniela; Büchele, Fabian; Schreglmann, Sebastian R; Valko, Philipp O; Gavrilov, Yuri V; Morawska, Marta M; Imbach, Lukas L; Baumann, Christian R

    2018-01-01

    Although sleep-wake disturbances are prevalent and well described after traumatic brain injury, their pathophysiology remains unclear, most likely because human traumatic brain injury is a highly heterogeneous entity that makes the systematic study of sleep-wake disturbances in relation to trauma-induced histological changes a challenging task. Despite increasing interest, specific and effective treatment strategies for post-traumatic sleep-wake disturbances are still missing. With the present work, therefore, we aimed at studying acute and chronic sleep-wake disturbances by electrophysiological means, and at assessing their histological correlates after closed diffuse traumatic brain injury in rats with the ultimate goal of generating a model of post-traumatic sleep-wake disturbances and associated histopathological findings that accurately represents the human condition. We assessed sleep-wake behavior by means of standard electrophysiological recordings before and 1, 7, and 28 days after sham or traumatic brain injury procedures. Sleep-wake findings were then correlated to immunohistochemically labeled and stereologically quantified neuronal arousal systems. Compared with control animals, we found that closed diffuse traumatic brain injury caused increased sleep need one month after trauma, and sleep was more consolidated. As histological correlate, we found a reduced number of histamine immunoreactive cells in the tuberomammillary nucleus, potentially related to increased neuroinflammation. Monoaminergic and hypocretinergic neurotransmitter systems in the hypothalamus and rostral brainstem were not affected, however. These results suggest that our rat traumatic brain injury model reflects human post-traumatic sleep-wake disturbances and associated histopathological findings very accurately, thus providing a study platform for novel treatment strategies for affected patients.

  9. Programmed Necrosis: A Prominent Mechanism of Cell Death following Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Raul Chavez-Valdez

    2012-01-01

    Full Text Available Despite the introduction of therapeutic hypothermia, neonatal hypoxic ischemic (HI brain injury remains a common cause of developmental disability. Development of rational adjuvant therapies to hypothermia requires understanding of the pathways of cell death and survival modulated by HI. The conceptualization of the apoptosis-necrosis “continuum” in neonatal brain injury predicts mechanistic interactions between cell death and hydrid forms of cell death such as programmed or regulated necrosis. Many of the components of the signaling pathway regulating programmed necrosis have been studied previously in models of neonatal HI. In some of these investigations, they participate as part of the apoptotic pathways demonstrating clear overlap of programmed death pathways. Receptor interacting protein (RIP-1 is at the crossroads between types of cellular death and survival and RIP-1 kinase activity triggers formation of the necrosome (in complex with RIP-3 leading to programmed necrosis. Neuroprotection afforded by the blockade of RIP-1 kinase following neonatal HI suggests a role for programmed necrosis in the HI injury to the developing brain. Here, we briefly review the state of the knowledge about the mechanisms behind programmed necrosis in neonatal brain injury recognizing that a significant proportion of these data derive from experiments in cultured cell and some from in vivo adult animal models. There are still more questions than answers, yet the fascinating new perspectives provided by the understanding of programmed necrosis in the developing brain may lay the foundation for new therapies for neonatal HI.

  10. Estrone is neuroprotective in rats after traumatic brain injury.

    Science.gov (United States)

    Gatson, Joshua W; Liu, Ming-Mei; Abdelfattah, Kareem; Wigginton, Jane G; Smith, Scott; Wolf, Steven; Simpkins, James W; Minei, Joseph P

    2012-08-10

    In various animal and human studies, early administration of 17β-estradiol, a strong antioxidant, anti-inflammatory, and anti-apoptotic agent, significantly decreases the severity of injury in the brain associated with cell death. Estrone, the predominant estrogen in postmenopausal women, has been shown to be a promising neuroprotective agent. The overall goal of this project was to determine if estrone mitigates secondary injury following traumatic brain injury (TBI) in rats. Male rats were given either placebo (corn oil) or estrone (0.5 mg/kg) at 30 min after severe TBI. Using a controlled cortical impact device in rats that underwent a craniotomy, the right parietal cortex was injured using the impactor tip. Non-injured control and sham animals were also included. At 72 h following injury, the animals were perfused intracardially with 0.9% saline followed by 10% phosphate-buffered formalin. The whole brain was removed, sliced, and stained for TUNEL-positive cells. Estrone decreased cortical lesion volume (pcerebral cortical levels of TUNEL-positive staining (pprotective pathways such as the ERK1/2 and BDNF pathways, decreases ischemic secondary injury, and decreases apoptotic-mediated cell death. These results suggest that estrone may afford protection to those suffering from TBI.

  11. A patients perspective on eating difficulties following brain injury

    DEFF Research Database (Denmark)

    Kjaersgaard, Annette; Kristensen, Hanne Kaae; Borg, Tove

    Purpose: The aim of this study is to explore and interpret how persons with acquired brain injury (ABI) experience and adapt to reduced abilities to swallowing and eating - and clinical implications. Method: Explorative multiple-case study with qualitative interviews of six persons following ABI ...

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

    Science.gov (United States)

    ... sleep habits Behavior or mood changes Trouble with memory, concentration, attention, or thinking Loss of consciousness lasting a few ... may have caused a TBI should seek medical attention. 4 ... Traumatic brain injury information page . Retrieved May 4, 2018, from https://www. ...

  13. Rehabilitation of discourse impairments after acquired brain injury

    Directory of Open Access Journals (Sweden)

    Gigiane Gindri

    Full Text Available ABSTRACT Language impairments in patients with acquired brain injury can have a negative impact on social life as well as on other cognitive domains. Discourse impairments are among the most commonly reported communication deficits among patients with acquired brain damage. Despite advances in the development of diagnostic tools for detecting such impairments, few studies have investigated interventions to rehabilitate patients presenting with these conditions. Objective: The aim of this study was to present a systematic review of the methods used in the rehabilitation of discourse following acquired brain injury. Methods: The PubMed database was searched for articles using the following keywords: "rehabilitation", "neurological injury", "communication" and "discursive abilities". Results: A total of 162 abstracts were found, but only seven of these met criteria for inclusion in the review. Four studies involved samples of individuals with aphasia whereas three studies recruited samples of individuals with traumatic brain injury. Conclusion: All but one article found that patient performance improved following participation in a discourse rehabilitation program.

  14. Effective protection of rabbits' explosive brain injury through blocking ...

    African Journals Online (AJOL)

    Background: The gap junction plays an important role in spreading of apoptotic and necrotic signals from injured and stressed cells to the neighboring viable cells. The present study was performed to investigate the important role of gap junction communication on rabbits' explosive brain injury. Methods: Explosion of paper ...

  15. Adolescents\\' experience of a parental traumatic brain injury | Harris ...

    African Journals Online (AJOL)

    The phenomenon of parental traumatic brain injury was characterised by denial, anger, grief, guilt, anxiety, over-protectiveness, social isolation, and change in many areas of the participants' lives. The adolescents coped using both approaches and avoidance styles of coping. Religion was a theme in the lives of all four ...

  16. Misconceptions about traumatic brain injuries among South African ...

    African Journals Online (AJOL)

    Objective. To investigate the incidence and type of misconceptions about traumatic brain injuries (TBIs) harboured by university students. Method. A convenience sample of 705 university students were recruited and data were collected using an electronic survey. The link to the survey was sent via e-mail to all registered ...

  17. Minor traumatic brain injuries – what is new? | Hollander ...

    African Journals Online (AJOL)

    Minor traumatic brain injuries – what is new? D Hollander, J Coventry, M Du Trevou. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors ...

  18. Traumatic Brain Injury: An Overview of School Re-Entry.

    Science.gov (United States)

    Tucker, Bonnie Foster; Colson, Steven E.

    1992-01-01

    This article presents a definition of traumatic brain injury (TBI); describes problem behavioral characteristics of students post-TBI and some possible solutions; examines academic, social, emotional, and cognitive factors; and outlines interventions to assist teachers in working constructively with TBI students. (JDD)

  19. Sex, Gender, and Traumatic Brain Injury: A Commentary.

    Science.gov (United States)

    Colantonio, Angela

    2016-02-01

    The goal of this supplemental issue is to address major knowledge, research, and clinical practice gaps regarding the limited focus on brain injury in girls and women as well as limited analysis of the effect of sex and gender in research on acquired brain injury. Integrating sex and gender in research is recognized as leading to better science and, ultimately, to better clinical practice. A sex and gender analytical approach to rehabilitation research is crucial to understanding traumatic brain injury and improving quality of life outcomes for survivors. Put another way, the lack of focus on sex and gender reduces the rigor of research design, the generalizability of study findings, and the effectiveness of clinical implementation and knowledge dissemination practices. The articles in this supplement examine sex and gender using a variety of methodological approaches and research contexts. Recommendations for future research on acquired brain injury that consciously incorporates sex and gender are made throughout this issue. This supplement is a product of the Girls and Women with ABI Task Force of the American Congress of Rehabilitation Medicine. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  20. Psychosocial consequences of mild traumatic brain injury in children

    DEFF Research Database (Denmark)

    Keightley, Michelle L; Côté, Pierre; Rumney, Peter

    2014-01-01

    OBJECTIVE: To synthesize the best available evidence regarding psychosocial consequences of mild traumatic brain injury (MTBI) in children. DATA SOURCES: MEDLINE, Embase, CINAHL, PsycINFO, and SPORTDiscus were searched (2001-2012). Inclusion criteria included published peer-reviewed reports...

  1. Investigating nystagmus in patients with traumatic brain injury: A ...

    African Journals Online (AJOL)

    Background. Traumatic brain injury (TBI) is a health and socioeconomic concern worldwide. In patients with TBI, post-traumatic balance problems are often the result of damage to the vestibular system. Nystagmus is common in these patients, and can provide insight into the damage that has resulted from the trauma.

  2. Traumatic Brain Injury and Its Effect on Students

    Science.gov (United States)

    Rosenthal, Stacy B.

    2012-01-01

    Over one million people suffer a traumatic brain injury every year, many of whom are students between the ages of 5 and 18. Using a qualitative case study approach, I wanted to discover the specific factors that both impede and help the school re-entry process for students in grades kindergarten through twelve so that these students can return to…

  3. School-Based Traumatic Brain Injury and Concussion Management Program

    Science.gov (United States)

    Davies, Susan C.

    2016-01-01

    Traumatic brain injuries (TBIs), including concussions, can result in a constellation of physical, cognitive, emotional, and behavioral symptoms that affect students' well-being and performance at school. Despite these effects, school personnel remain underprepared identify, educate, and assist this population of students. This article describes a…

  4. Traumatic brain injury in children | Coughlan | South African Family ...

    African Journals Online (AJOL)

    South African Family Practice. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 45, No 5 (2003) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Traumatic brain injury in children. M Coughlan, G Fieggen ...

  5. Traumatic brain injury in pediatric age group: Predictors of outcome ...

    African Journals Online (AJOL)

    Objective: To determine predictors for outcomes of traumatic brain injury (TBI) in infants and children younger than twelve years admitted to our pediatric intensive care units (PICU). Methods: This is a retrospective cohort study from 2004-5, done at the PICU of King Fahad Hofuf Hospital, Eastern Province, Saudi Arabia.

  6. Evaluation of a Health Education Programme about Traumatic Brain Injury

    Science.gov (United States)

    Garcia, Jane Mertz; Sellers, Debra M.; Hilgendorf, Amy E.; Burnett, Debra L.

    2014-01-01

    Objective: Our aim was to evaluate a health education programme (TBIoptions: Promoting Knowledge) designed to increase public awareness and understanding about traumatic brain injury (TBI) through in-person (classroom) and computer-based (electronic) learning environments. Design: We used a pre-post survey design with randomization of participants…

  7. Case Report - Severe traumatic brain injury managed with ...

    African Journals Online (AJOL)

    Patients with severe taumatic brain injury may develop intractable raised ICP resulting in high mortality and morbidity. This may be anticipated from the patient's clinical status and imaging findings even where intracranial monitoring is unavailable. Outcome may be improved by early and aggressive control of ICP and ...

  8. Traumatic brain injury, the hidden pandemic: A focused response to ...

    African Journals Online (AJOL)

    Introduction: Traumatic brain injury (TBI) has many potential cognitive, behavioural and psychological consequences, and contributes significantly to the national burden of disease and to ongoing violent behaviour. Few resources are available for the rehabilitation of patients with TBI in South Africa, and access to ...

  9. Demographic profile of severe traumatic brain injury admissions to ...

    African Journals Online (AJOL)

    Background. Paediatric traumatic brain injury (PTBI) is a major public health problem. However, recent epidemiological data for PTBI in South Africa (SA) are lacking. Objectives. To establish a demographic profile of severe PTBI admissions to the Red Cross War Memorial Children's Hospital (RCWMCH) over a 5-year ...

  10. Clinimetrics and functional outcome one year after traumatic brain injury

    NARCIS (Netherlands)

    J.T.M. van Baalen (Bianca)

    2008-01-01

    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

  11. Predictors of Outcome following Acquired Brain Injury in Children

    Science.gov (United States)

    Johnson, Abigail R.; DeMatt, Ellen; Salorio, Cynthia F.

    2009-01-01

    Acquired brain injury (ABI) in children and adolescents can result from multiple causes, including trauma, central nervous system infections, noninfectious disorders (epilepsy, hypoxia/ischemia, genetic/metabolic disorders), tumors, and vascular abnormalities. Prediction of outcomes is important, to target interventions, allocate resources,…

  12. Assisting Students with a Traumatic Brain Injury in School Interventions

    Science.gov (United States)

    Aldrich, Erin M.; Obrzut, John E.

    2012-01-01

    Traumatic brain injury (TBI) in children and adolescents can significantly affect their lives and educational needs. Deficits are often exhibited in areas such as attention, concentration, memory, executive function, emotional regulation, and behavioral functioning, but specific outcomes are not particular to any one child or adolescent with a…

  13. Issues of cultural diversity in acquired brain injury (ABI) rehabilitation.

    Science.gov (United States)

    Lequerica, Anthony; Krch, Denise

    2014-01-01

    With the general population in the United States becoming increasingly diverse, it is important for rehabilitation professionals to develop the capacity to provide culturally sensitive treatment. This is especially relevant when working with minority populations who have a higher risk for brain injury and poorer rehabilitation outcomes. This article presents a number of clinical vignettes to illustrate how cultural factors can influence behavior in patients recovering from brain injury, as well as rehabilitation staff. The main objectives are to raise awareness among clinicians and stimulate research ideas by highlighting some real world examples of situations where a specialized, patient-centered approach needs to consider factors of cultural diversity. Because one's own world view impacts the way we see the world and interpret behavior, it is important to understand one's own ethnocentrism when dealing with a diverse population of patients with brain injury where behavioral sequelae are often expected. Being able to see behavior after brain injury with an open mind and taking into account cultural and contextual factors is an important step in developing culturally competent rehabilitation practices.

  14. Mild traumatic brain injury: Impairment and disability assessment caveats.

    Science.gov (United States)

    Zasler, Nathan D; Martelli, Michael F

    2003-01-01

    Mild traumatic brain injury (MTBI) accounts for approximately 80% of all brain injuries, and persistent sequelae can impede physical, emotional, social, marital, vocational, and avocational functioning. Evaluation of impairment and disability following MTBI typically can involve such contexts as social security disability application, personal injury litigation, worker's compensation claims, disability insurance policy application, other health care insurance policy coverage issues, and the determination of vocational and occupational competencies and limitations. MTBI is still poorly understood and impairment and disability assessment in MTBI can present a significant diagnostic challenge. There are currently no ideal systems for rating impairment and disability for MTBI residua. As a result, medicolegal examiners and clinicians must necessarily familiarise themselves with the variety of disability and impairment evaluation protocols and understand their limitations. The current paper reviews recommended procedures and potential obstacles and confounding issues.

  15. Family Resiliency, Family Needs, and Community Reintegration in Persons with Brain Injury

    Science.gov (United States)

    Frain, Julianne; Dillahunt-Aspillaga, Tina; Frain, Michael; Ehkle, Sarah

    2014-01-01

    Purpose: The purpose of the study was to measure predictors of community reintegration and empirically test the resiliency model of family stress, adjustment, and adaptation in persons with traumatic brain injury (TBI). The study also aimed to measure family needs by surveying caregiving family members through the use of the Family Needs…

  16. Protective effect of grifolin against brain injury in an acute cerebral ...

    African Journals Online (AJOL)

    Purpose: To evaluate the protective effects of grifolin against brain injury in an acute cerebral ischemia rat model. Methods: Rats were assigned to five groups: control, negative control, and grifolin (50, 100, and 200 mg/kg, p.o.) treated groups, which received the drug for 2 weeks. All the animals were sacrificed at the end of ...

  17. Characteristics of brain injury induced by shock wave propagation in solids after underwater explosion in rats

    Directory of Open Access Journals (Sweden)

    Xin-ling LI

    2016-09-01

    Full Text Available Objective  To observe the characteristics of rat brain injury induced by shock wave propagation in solids resulting from underwater explosion and explore the related mechanism. Methods  Explosion source outside the simulated ship cabin underwater was detonated for establishing a model of brain injury in rats by shock wave propagation in solid; 72 male SD rats were randomly divided into normal control group (n=8, injury group 1 (600mg RDX paper particle explosion source, n=32, injury group 2 (800mg RDX paper particle explosion source, n=32. The each injury group was randomly divided into 4 subgroups (n=8, 3, 6, 24 and 72h groups. The division plate as a whole and the head of 8 rats in each injury group were measured for the peak value of the solid shock wave, its rising time and the duration time of shock wave propagation in solid. To observe the physiological changes of animals after injury, plasma samples were collected for determination of brain damage markers, NSE and S-100β. All the animals were sacrificed, the right hemisphere of the brain was taken in each group of animals, weighting after baking, and the brain water content was calculated. Pathological examination was performed for left cerebral hemisphere in 24-h group. The normal pyramidal cells in the hippocampal CA1 region were counted. Results  The peak value, rising time and duration time of shock wave propagation on the division plate and head were 1369.74±91.70g, 0.317±0.037ms and 24.85±2.53ms, 26.83±3.09g, 0.901±0.077ms and 104.21±6.26ms respectively in injury group 1, 1850.11±83.86g, 0.184±0.031ms and 35.61±2.66ms, 39.75±3.14g, 0.607±0.069ms and 132.44±7.17ms in injury group 2 (P<0.01. After the injury, there was no abnormality in the anatomy, and brain damage markers NSE, S-100β increased, reached the peak at 24 h, and they were highest in injury group 2 and lowest in control group with a statistically significant difference (P<0.05. The brain water content

  18. Penetrating Brain Injury after Suicide Attempt with Speargun

    Directory of Open Access Journals (Sweden)

    John Ross Williams

    2014-07-01

    Full Text Available Penetrating cranial injury by mechanisms other than are exceedingly rare, and so strategies and guidelines for the management of PBI are largely informed by data from higher-velocity penetrating injuries. Here we present a case of penetrating brain injury by the low velocity mechanism of a harpoon from an underwater fishing speargun in an attempted suicide by a 56-year-old Caucasian male. The case raised a number of interesting points in management of lower-velocity penetrating brain injury (LVPBI, including benefit in delaying foreign body removal to allow for tamponade; the importance of history taking in establishing the social/legal significance of the events surrounding the injury; the use of cerebral angiogram in all cases of PBI; advantages of using DECT to reduce artifact when available; and antibiotic prophylaxis in the context of idiosyncratic histories of usage of penetrating objects before coming in contact with the intracranial environment. We present here the management of the case in full along with an extended discussion and review of existing literature regarding key points in management of LVPBI vs. higher velocity forms of intracranial injury.

  19. Relationship between CT findings and prognosis in diffuse brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Akihito; Kuwana, Nobumasa; Mochimatsu, Yasuhiko; Fujino, Hideyo; Tokoro, Kazuhiko [Yokohama Minami Kyosai Hospital, Kanagawa (Japan)

    1984-12-01

    Types of diffuse brain injury (DBI) were classified based on a study of fifty patients with acute, severe head injuries. This study focused on findings of computed tomography (CT) and outcomes of the patients. The level of consciousness was estimated by the Glasgow Coma Scale; greater than 8 in 28 cases; 8 or less in 22 cases. The overall mortality rate was 28%, however the rate ranged from 8 to 67%, depending on the type of DBI. CT findings of DBI within 24 hours after head injury were classified into 5 type: diffuse cerebral swelling (DCS), isodense hemispheric swelling (IHS), deep-seated brain injury (DSI), subarachnoid hemorrhage (SAH) and normal findings. DSI demonstrated the highest mortality rate (67%), and IHS was the second (50%). However, there are many pediatric cases with excellent outcomes. Although both DCS and IHS occurred frequently in children, it was considered that these two conditions should be distinguished, because of the existence of some differences in the clinical course of the two. There were only 7 cases of SAH alone, but SAH was the most frequent associated finding in DBI, existing in 50% of 50 cases. SAH per se could not be regarded as a poor prognostic factor. It is the authors' impression that DBI without coup or contre-coup injuries can be readily diagnosed by CT scan and that DBI is an important clinical factor in the closed head injury cases.

  20. Astrocyte-targeted expression of IL-6 protects the CNS against a focal brain injury

    DEFF Research Database (Denmark)

    Penkowa, Milena; Giralt, Mercedes; Lago, Natalia

    2003-01-01

    significantly increased up to but not including 20 dpl in the GFAP-IL6 mice. Oxidative stress as well as apoptotic cell death was significantly decreased throughout the time period studied in the GFAP-IL6 mice compared to controls. This could be linked to the altered inflammatory response as well......The effect of CNS-targeted IL-6 gene expression has been thoroughly investigated in the otherwise nonperturbed brain but not following brain injury. Here we examined the impact of astrocyte-targeted IL-6 production in a traumatic brain injury (cryolesion) model using GFAP-IL6 transgenic mice...... as to the transgenic IL-6-induced increase of the antioxidant, neuroprotective proteins metallothionein-I + II. These results indicate that although in the brain the chronic astrocyte-targeted expression of IL-6 spontaneously induces an inflammatory response causing significant damage, during an acute...

  1. Top-cited articles in traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Bhanu eSharma

    2014-11-01

    Full Text Available 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, respectively, 1990 ± 14.9 years and 2003 ± 6.7 years. 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 TBI. 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 TBI

  2. Decompressive craniectomy following brain injury: factors important ...

    African Journals Online (AJOL)

    2010-01-07

    Jan 7, 2010 ... Background: Decompressive craniectomy (DC) is often performed as an empirical lifesaving measure to protect the injured brain from the damaging effects of propagating oedema and intracranial hypertension. However, there are no clearly defined indications or specified guidelines for patient selection for ...

  3. Microglial Inflammasome Activation in Penetrating Ballistic-Like Brain Injury.

    Science.gov (United States)

    Lee, Stephanie W; Gajavelli, Shyam; Spurlock, Markus S; Andreoni, Cody; de Rivero Vaccari, Juan Pablo; Bullock, M Ross; Keane, Robert W; Dietrich, W Dalton

    2018-04-02

    Penetrating traumatic brain injury (PTBI) is a significant cause of death and disability in the United States. Inflammasomes are one of the key regulators of the interleukin (IL)-1β mediated inflammatory responses after traumatic brain injury. However, the contribution of inflammasome signaling after PTBI has not been determined. In this study, adult male Sprague-Dawley rats were subjected to sham procedures or penetrating ballistic-like brain injury (PBBI) and sacrificed at various time-points. Tissues were assessed by immunoblot analysis for expression of IL-1β, IL-18, and components of the inflammasome: apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain (ASC), caspase-1, X-linked inhibitor of apoptosis protein (XIAP), nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3), and gasdermin-D (GSDMD). Specific cell types expressing inflammasome proteins also were evaluated immunohistochemically and assessed quantitatively. After PBBI, expression of IL-1β, IL-18, caspase-1, ASC, XIAP, and NLRP3 peaked around 48 h. Brain protein lysates from PTBI animals showed pyroptosome formation evidenced by ASC laddering, and also contained increased expression of GSDMD at 48 h after injury. ASC-positive immunoreactive neurons within the perilesional cortex were observed at 24 h. At 48 h, ASC expression was concentrated in morphologically activated cortical microglia. This expression of ASC in activated microglia persisted until 12 weeks following PBBI. This is the first report of inflammasome activation after PBBI. Our results demonstrate cell-specific patterns of inflammasome activation and pyroptosis predominantly in microglia, suggesting a sustained pro-inflammatory state following PBBI, thus offering a therapeutic target for this type of brain injury.

  4. Acute Respiratory Distress Syndrome in Severe Brain Injury

    Directory of Open Access Journals (Sweden)

    Yu. A. Churlyaev

    2009-01-01

    Full Text Available Objective: to study the development of acute respiratory distress syndrome (ARDS in victims with isolated severe brain injury (SBI. Subject and methods. 171 studies were performed in 16 victims with SBI. Their general condition was rated as very critical. The patients were divided into three groups: 1 non-ARDS; 2 Stage 1 ARDS; and 3 Stage 2 ARDS. The indicators of Stages 1 and 2 were assessed in accordance with the classification proposed by V. V. Moroz and A. M. Golubev. Intracranial pressure (ICP, extravascular lung water index, pulmonary vascular permeability, central hemodynamics, oxygenation index, lung anastomosis, the X-ray pattern of the lung and brain (computed tomography, and its function were monitored. Results. The hemispheric cortical level of injury of the brain with function compensation of its stem was predominantly determined in the controls; subcompensation and decompensation were ascertained in the ARDS groups. According to the proposed classification, these patients developed Stages 1 and 2 ARDS. When ARDS developed, there were rises in the level of extravascular lung fluid and pulmonary vascular permeability, a reduction in the oxygenation index (it was 6—12 hours later as compared with them, increases in a lung shunt and ICP; X-ray study revealed bilateral infiltrates in the absence of heart failure in Stage 2 ARDS. The correlation was positive between ICP and extravascular lung water index, and lung vascular permeability index (r>0.4;p<0.05. Conclusion. The studies have indicated that the classification proposed by V. V. Moroz and A. M. Golubev enables an early diagnosis of ARDS. One of its causes is severe brainstem injury that results in increased extravascular fluid in the lung due to its enhanced vascular permeability. The ICP value is a determinant in the diagnosis of secondary brain injuries. Key words: acute respiratory distress syndrome, extravascu-lar lung fluid, pulmonary vascular permeability, brain injury

  5. Triple Peripheral Nerve Injury Accompanying to Traumatic Brain Injury: A Case Report

    Directory of Open Access Journals (Sweden)

    Ižlknur Can

    2014-02-01

    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.

  6. Mechanisms of gender-linked ischemic brain injury

    Science.gov (United States)

    Liu, Mingyue; Dziennis, Suzan; Hurn, Patricia D.; Alkayed, Nabil J.

    2010-01-01

    Biological sex is an important determinant of stroke risk and outcome. Women are protected from cerebrovascular disease relative to men, an observation commonly attributed to the protective effect of female sex hormones, estrogen and progesterone. However, sex differences in brain injury persist well beyond the menopause and can be found in the pediatric population, suggesting that the effects of reproductive steroids may not completely explain sexual dimorphism in stroke. We review recent advances in our understanding of sex steroids (estradiol, progesterone and testosterone) in the context of ischemic cell death and neuroprotection. Understanding the molecular and cell-based mechanisms underlying sex differences in ischemic brain injury will lead to a better understanding of basic mechanisms of brain cell death and is an important step toward designing more effective therapeutic interventions in stroke. PMID:19531872

  7. Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury.

    Science.gov (United States)

    Cole, James H; Jolly, Amy; de Simoni, Sara; Bourke, Niall; Patel, Maneesh C; Scott, Gregory; Sharp, David J

    2018-01-04

    Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of MRI. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions; and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 patients with moderate-severe traumatic brain injury (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (1-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterized using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarized regionally and compared with clinical and neuropsychological measures. Patients with traumatic brain injury showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over 1 year was pronounced following traumatic brain injury. Patients with traumatic brain injury lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates were related to memory performance at the end of the follow

  8. CSF transthyretin neuroprotection in a mouse model of brain ischemia

    DEFF Research Database (Denmark)

    Santos, Sofia Duque; Lambertsen, Kate Lykke; Clausen, Bettina Hjelm

    2010-01-01

    Brain injury caused by ischemia is a major cause of human mortality and physical/cognitive disability worldwide. Experimentally, brain ischemia can be induced surgically by permanent middle cerebral artery occlusion. Using this model, we studied the influence of transthyretin in ischemic stroke. ...

  9. Changes in brain-behavior relationships following a 3-month pilot cognitive intervention program for adults with traumatic brain injury

    OpenAIRE

    S. Porter; I.J. Torres; W. Panenka; Z. Rajwani; D. Fawcett; A. Hyder; N. Virji-Babul

    2017-01-01

    Facilitating functional recovery following brain injury is a key goal of neurorehabilitation. Direct, objective measures of changes in the brain are critical to understanding how and when meaningful changes occur, however, assessing neuroplasticity using brain based results remains a significant challenge. Little is known about the underlying changes in functional brain networks that correlate with cognitive outcomes in traumatic brain injury (TBI). The purpose of this pilot study was to asse...

  10. Early CT signs of progressive hemorrhagic injury following acute traumatic brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Wu-song; Zheng, Ping; Xu, Jun-fa; Guo, Yi-jun; Zeng, Jing-song; Yang, Wen-jin; Li, Gao-yi; He, Bin; Yu, Hui [Pudong New Area People' s Hospital, Department of Neurosurgery, Shanghai (China)

    2011-05-15

    Since progressive hemorrhagic injury (PHI) was introduced in neurosurgical literatures, several studies have been performed, the results of which have influenced doctors but do not define guidelines for the best treatment of PHI. PHI may be confirmed by a serial computerized tomography (CT) scan, and it has been shown to be associated with a fivefold increase in the risk of clinical worsening and is a significant cause of morbidity and mortality as well. So, early detection of PHI is practically important in a clinical situation. To analyze the early CT signs of progressive hemorrhagic injury following acute traumatic brain injury (TBI) and explore their clinical significances, PHI was confirmed by comparing the first and repeated CT scans. Data were analyzed and compared including times from injury to the first CT and signs of the early CT scan. Logistic regression analysis was used to show the risk factors related to PHI. A cohort of 630 TBI patients was evaluated, and there were 189 (30%) patients who suffered from PHI. For patients with their first CT scan obtained as early as 2 h post-injury, there were 116 (77.25%) cases who suffered from PHI. The differences between PHIs and non-PHIs were significant in the initial CT scans showing fracture, subarachnoid hemorrhage (SAH), brain contusion, epidural hematoma (EDH), subdural hematoma (SDH), and multiple hematoma as well as the times from injury to the first CT scan (P < 0.01). Logistic regression analysis showed that early CT scans (EDH, SDH, SAH, fracture, and brain contusion) were predictors of PHI (P < 0.01). For patients with the first CT scan obtained as early as 2 h post-injury, a follow-up CT scan should be performed promptly. If the initial CT scan shows SAH, brain contusion, and primary hematoma with brain swelling, an earlier and dynamic CT scan should be performed for detection of PHI as early as possible and the medical intervention would be enforced in time. (orig.)

  11. Early CT signs of progressive hemorrhagic injury following acute traumatic brain injury

    International Nuclear Information System (INIS)

    Tong, Wu-song; Zheng, Ping; Xu, Jun-fa; Guo, Yi-jun; Zeng, Jing-song; Yang, Wen-jin; Li, Gao-yi; He, Bin; Yu, Hui

    2011-01-01

    Since progressive hemorrhagic injury (PHI) was introduced in neurosurgical literatures, several studies have been performed, the results of which have influenced doctors but do not define guidelines for the best treatment of PHI. PHI may be confirmed by a serial computerized tomography (CT) scan, and it has been shown to be associated with a fivefold increase in the risk of clinical worsening and is a significant cause of morbidity and mortality as well. So, early detection of PHI is practically important in a clinical situation. To analyze the early CT signs of progressive hemorrhagic injury following acute traumatic brain injury (TBI) and explore their clinical significances, PHI was confirmed by comparing the first and repeated CT scans. Data were analyzed and compared including times from injury to the first CT and signs of the early CT scan. Logistic regression analysis was used to show the risk factors related to PHI. A cohort of 630 TBI patients was evaluated, and there were 189 (30%) patients who suffered from PHI. For patients with their first CT scan obtained as early as 2 h post-injury, there were 116 (77.25%) cases who suffered from PHI. The differences between PHIs and non-PHIs were significant in the initial CT scans showing fracture, subarachnoid hemorrhage (SAH), brain contusion, epidural hematoma (EDH), subdural hematoma (SDH), and multiple hematoma as well as the times from injury to the first CT scan (P < 0.01). Logistic regression analysis showed that early CT scans (EDH, SDH, SAH, fracture, and brain contusion) were predictors of PHI (P < 0.01). For patients with the first CT scan obtained as early as 2 h post-injury, a follow-up CT scan should be performed promptly. If the initial CT scan shows SAH, brain contusion, and primary hematoma with brain swelling, an earlier and dynamic CT scan should be performed for detection of PHI as early as possible and the medical intervention would be enforced in time. (orig.)

  12. Characteristics of successful and unsuccessful completers of 3 postacute brain injury rehabilitation pathways.

    Science.gov (United States)

    Malec, James F; Degiorgio, Lisa

    2002-12-01

    To determine whether successful participants along different postacute brain injury rehabilitation pathways differ on demographic, injury-related, disability, and outcome variables. Secondary analysis of pre- and posttreatment, and 1-year follow-up data obtained in a previous study of specialized vocational services (SVS) for persons with brain injury. Outpatient brain injury rehabilitation clinic. One hundred fourteen persons with acquired brain injury. Participants in 3 distinct rehabilitation pathways were studied: SVS only; SVS and a 3-h/wk community reintegration outpatient group; and SVS and 6-h/d comprehensive day treatment (CDT). Mayo-Portland Adaptability Inventory (MPAI); Vocational Independence Scale; and "success," as defined by community-based employment (CBE) at 1-year follow-up. The percentage (77%-85%) of participants in CBE at 1-year follow-up did not differ among the 3 pathways. CDT participants had more limited educational backgrounds, were less recently injured, and showed greater disability and more impaired self-awareness than those receiving limited intervention (ie, SVS or community reintegration outpatient group). MPAI scores for limited-intervention participants who were unsuccessful were similar in level to successful participants in CDT. Logistic regression models were developed to predict the probability of success with limited intervention and CDT. Different rehabilitation pathways result in CBE for a large percentage of persons with brain injury if the intensity of service is appropriately matched to the severity of the disability, the time since injury, and other participant characteristics. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

  13. Changes of interleukin-1β, tumor necrosis factor α and interleukin-6 in brain and plasma after brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    朱涛; 姚智; 袁汉娜; 陆伯刚; 杨树源

    2004-01-01

    Objective: To study the changes of interleukin-1 β (IL-1β), tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) levels in brain and plasma after brain injury and to assess the relationship between the cytokine levels and injury severity in rats. Methods: A total of 51 male Wistar rats, weighing 280-340 g, were anesthetized with chloral hydrate (400 mg/kg body weight) through intraperitoneal injection and fixed on a stereotaxic instrument. Severe brain injury was created in 16 rats (severe injury group) and moderate brain injury in 18 rats (moderate injury group) by a fluid percussion model, and cytokine levels of IL-1β, TNFα and IL-6 were measured with biological assay. And sham operation was made on the other 17 rats (control group). Results: In the control group, the levels of IL-1β, TNFα and IL-6 were hardly detected in the cortex of the rats, but in the ipsilateral cortex of the rats in both injury groups, they increased obviously at 8 hours after injury. The increasing degree of these cytokines had no significant difference between the two injury groups. The levels of IL-6 in the plasma of all the rats increased slightly, whereas the levels of IL-1β and TNFα were undetectable. Conclusions: The increase of IL-1β, TNFα and IL-6 levels is closely related to brain injury. The increased cytokine levels in the central nervous system are not parallel to those in the peripheral blood. It suggests that inflammatory cytokines play important roles in the secondary neural damage after brain injury.

  14. Dabrafenib, an inhibitor of RIP3 kinase-dependent necroptosis, reduces ischemic brain injury

    Directory of Open Access Journals (Sweden)

    Shelly A Cruz

    2018-01-01

    Full Text Available Ischemic brain injury triggers neuronal cell death by apoptosis via caspase activation and by necroptosis through activation of the receptor-interacting protein kinases (RIPK associated with the tumor necrosis factor-alpha (TNF-α/death receptor. Recent evidence shows RIPK inhibitors are neuroprotective and alleviate ischemic brain injury in a number of animal models, however, most have not yet undergone clinical trials and safety in humans remains in question. Dabrafenib, originally identified as a B-raf inhibitor that is currently used to treat melanoma, was later revealed to be a potent RIPK3 inhibitor at micromolar concentrations. Here, we investigated whether Dabrafenib would show a similar neuroprotective effect in mice subjected to ischemic brain injury by photothrombosis. Dabrafenib administered intraperitoneally at 10 mg/kg one hour after photothrombosis-induced focal ischemic injury significantly reduced infarct lesion size in C57BL6 mice the following day, accompanied by a markedly attenuated upregulation of TNF-α. However, subsequent lower doses (5 mg/kg/day failed to sustain this neuroprotective effect after 4 days. Dabrafenib blocked lipopolysaccharides-induced activation of TNF-α in bone marrow-derived macrophages, suggesting that Dabrafenib may attenuate TNF-α-induced necroptotic pathway after ischemic brain injury. Since Dabrafenib is already in clinical use for the treatment of melanoma, it might be repurposed for stroke therapy.

  15. Traumatic Brain Injury Increases Cortical Glutamate Network Activity by Compromising GABAergic Control.

    Science.gov (United States)

    Cantu, David; Walker, Kendall; Andresen, Lauren; Taylor-Weiner, Amaro; Hampton, David; Tesco, Giuseppina; Dulla, Chris G

    2015-08-01

    Traumatic brain injury (TBI) is a major risk factor for developing pharmaco-resistant epilepsy. Although disruptions in brain circuitry are associated with TBI, the precise mechanisms by which brain injury leads to epileptiform network activity is unknown. Using controlled cortical impact (CCI) as a model of TBI, we examined how cortical excitability and glutamatergic signaling was altered following injury. We optically mapped cortical glutamate signaling using FRET-based glutamate biosensors, while simultaneously recording cortical field potentials in acute brain slices 2-4 weeks following CCI. Cortical electrical stimulation evoked polyphasic, epileptiform field potentials and disrupted the input-output relationship in deep layers of CCI-injured cortex. High-speed glutamate biosensor imaging showed that glutamate signaling was significantly increased in the injured cortex. Elevated glutamate responses correlated with epileptiform activity, were highest directly adjacent to the injury, and spread via deep cortical layers. Immunoreactivity for markers of GABAergic interneurons were significantly decreased throughout CCI cortex. Lastly, spontaneous inhibitory postsynaptic current frequency decreased and spontaneous excitatory postsynaptic current increased after CCI injury. Our results suggest that specific cortical neuronal microcircuits may initiate and facilitate the spread of epileptiform activity following TBI. Increased glutamatergic signaling due to loss of GABAergic control may provide a mechanism by which TBI can give rise to post-traumatic epilepsy. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Neutrophil depletion reduces edema formation and tissue loss following traumatic brain injury in mice

    Directory of Open Access Journals (Sweden)

    Kenne Ellinor

    2012-01-01

    Full Text Available Abstract Background Brain edema as a result of secondary injury following traumatic brain injury (TBI is a major clinical concern. Neutrophils are known to cause increased vascular permeability leading to edema formation in peripheral tissue, but their role in the pathology following TBI remains unclear. Methods In this study we used controlled cortical impact (CCI as a model for TBI and investigated the role of neutrophils in the response to injury. The outcome of mice that were depleted of neutrophils using an anti-Gr-1 antibody was compared to that in mice with intact neutrophil count. The effect of neutrophil depletion on blood-brain barrier function was assessed by Evan's blue dye extravasation, and analysis of brain water content was used as a measurement of brain edema formation (24 and 48 hours after CCI. Lesion volume was measured 7 and 14 days after CCI. Immunohistochemistry was used to assess cell death, using a marker for cleaved caspase-3 at 24 hours after injury, and microglial/macrophage activation 7 days after CCI. Data were analyzed using Mann-Whitney test for non-parametric data. Results Neutrophil depletion did not significantly affect Evan's blue extravasation at any time-point after CCI. However, neutrophil-depleted mice exhibited a decreased water content both at 24 and 48 hours after CCI indicating reduced edema formation. Furthermore, brain tissue loss was attenuated in neutropenic mice at 7 and 14 days after injury. Additionally, these mice had a significantly reduced number of activated microglia/macrophages 7 days after CCI, and of cleaved caspase-3 positive cells 24 h after injury. Conclusion Our results suggest that neutrophils are involved in the edema formation, but not the extravasation of large proteins, as well as contributing to cell death and tissue loss following TBI in mice.

  17. Experimental study on brain injury in Beagle dogs caused by adjacent cabin explosion in warship

    Directory of Open Access Journals (Sweden)

    Yan-teng LI

    2017-04-01

    Full Text Available Objective  Through the establishment of adjacent cabin blast injury model of Beagle dog, to investigate the pathophysiological changes in the experimental animals in this scenario, then speculate on the mechanisms of injury. Methods  Several adjacent cabins were built in the same size with the real warship. Seven Beagle dogs were subjected to injuries from the explosion, from whom one was selected randomly to implant intracranial pressure transducers before blast, the others were tested on the pathophysiological changes after blast. The dogs were mounted on the platform of a cabinet in the adjacent cabin, subjected to injury from 650g bare TNT explosive blast. The transducers recorded the value of space and intracranial shock wave pressure. Following blast treatment, the serum levels of IL -6, IL -8, neuron specific enolase (NSE, brain and chest CT and pathological changes of the brain tissue were observed. Results  Serum levels of IL-6, IL-8 and NSE were elevated to varying degrees after blast. All of them increased significantly at different time points after blast (P<0.05. Brain and chest CT examinations did not show any significant positive results. Pathological results showed that there was a little necrosis in the brain, some neurons had karyopycnosis, karyolysis or disappearance of the nucleoli, and the cell boundaries were blurred. The blast wave was blocked greatly by the scalp and skull (about 90%, but could still penetrate them and cause brain injuries. Conclusions  Explosion in the adjacent cabin causes mainly mild traumatic brain injuries. Blast wave can be blocked by the scalp and skull greatly. DOI: 10.11855/j.issn.0577-7402.2017.03.11

  18. Mild traumatic brain injury results in depressed cerebral glucose uptake: An (18)FDG PET study.

    Science.gov (United States)

    Selwyn, Reed; Hockenbury, Nicole; Jaiswal, Shalini; Mathur, Sanjeev; Armstrong, Regina C; Byrnes, Kimberly R

    2013-12-01

    Moderate to severe traumatic brain injury (TBI) in humans and rats induces measurable metabolic changes, including a sustained depression in cerebral glucose uptake. However, the effect of a mild TBI on brain glucose uptake is unclear, particularly in rodent models. This study aimed to determine the glucose uptake pattern in the brain after a mild lateral fluid percussion (LFP) TBI. Briefly, adult male rats were subjected to a mild LFP and positron emission tomography (PET) imaging with (18)F-fluorodeoxyglucose ((18)FDG), which was performed prior to injury and at 3 and 24 h and 5, 9, and 16 days post-injury. Locomotor function was assessed prior to injury and at 1, 3, 7, 14, and 21 days after injury using modified beam walk tasks to confirm injury severity. Histology was performed at either 10 or 21 days post-injury. Analysis of function revealed a transient impairment in locomotor ability, which corresponds to a mild TBI. Using reference region normalization, PET imaging revealed that mild LFP-induced TBI depresses glucose uptake in both the ipsilateral and contralateral hemispheres in comparison with sham-injured and naïve controls from 3 h to 5 days post-injury. Further, areas of depressed glucose uptake were associated with regions of glial activation and axonal damage, but no measurable change in neuronal loss or gross tissue damage was observed. In conclusion, we show that mild TBI, which is characterized by transient impairments in function, axonal damage, and glial activation, results in an observable depression in overall brain glucose uptake using (18)FDG-PET.

  19. Effect of ketamine on aquaporin-4 expression and neuronal apoptosis in brain tissues following brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Zangong Zhou; Xiangyu Ji; Li Song; Jianfang Song; Shiduan Wang; Yanwei Yin

    2006-01-01

    BACKGROUND: Aquaporin-4 (AQP-4) is closely related to the formation of brain edema. Neuronal apoptosis plays an important part in the conversion of swelled neuron following traumatic brain injury. At present, the studies on the protective effect of ketamine on brain have involved in its effect on aquaporin-4 expression and neuronal apoptosis in the brain tissues following brain injury in rats.OBJECTIVE: To observe the effect of ketamine on AQP-4 expression and neuronal apoptosis in the brain tissue following rat brain injury, and analyze the time-dependence of ketamine in the treatment of brain injury.DESIGN: Randomized grouping design, controlled animal trial.SETTING: Department of Anesthesiology, the Medical School Hospital of Qingdao University.MATERIALS: Totally 150 rats of clean grade, aged 3 months, were involved and randomized into control group and ketamine-treated group, with 75 rats in each. Each group was divided into 5 subgroups separately at 6,12, 24, 48 and 72 hours after injury, with 15 rats at each time point. Main instruments and reagents:homemade beat machine, ketamine hydrochloride (Hengrui Pharmaceutical Factory, Jiangsu), rabbit anti-rat AQP-4 polyclonal antibody, SABC immunohistochemical reagent kit and TUNEL reagent kit (Boster Co.,Ltd.,Wuhan).METHODS: This trial was carried out in the Institute of Cerebrovascular Disease, Medical College of Qingdao University during March 2005 to February 2006. A weight-dropping rat model of brain injury was created with Feeney method. The rats in the ketamine-treated group were intraperitoneally administered with 50 g/L ketamine (120 mg/kg) one hour after injury, but ketamine was replaced by normal saline in the control group. In each subgroup, the water content of cerebral hemisphere was measured in 5 rats chosen randomly. The left 10 rats in each subgroup were transcardiacally perfused with ketamine, then the brain tissue was made into paraffin sections and stained by haematoxylin and eosin. Neuronal

  20. Bidirectional brain-gut interactions and chronic pathological changes after traumatic brain injury in mice.

    Science.gov (United States)

    Ma, Elise L; Smith, Allen D; Desai, Neemesh; Cheung, Lumei; Hanscom, Marie; Stoica, Bogdan A; Loane, David J; Shea-Donohue, Terez; Faden, Alan I

    2017-11-01

    Traumatic brain injury (TBI) has complex effects on the gastrointestinal tract that are associated with TBI-related morbidity and mortality. We examined changes in mucosal barrier properties and enteric glial cell response in the gut after experimental TBI in mice, as well as effects of the enteric pathogen Citrobacter rodentium (Cr) on both gut and brain after injury. Moderate-level TBI was induced in C57BL/6mice by controlled cortical impact (CCI). Mucosal barrier function was assessed by transepithelial resistance, fluorescent-labelled dextran flux, and quantification of tight junction proteins. Enteric glial cell number and activation were measured by Sox10 expression and GFAP reactivity, respectively. Separate groups of mice were challenged with Cr infection during the chronic phase of TBI, and host immune response, barrier integrity, enteric glial cell reactivity, and progression of brain injury and inflammation were assessed. Chronic CCI induced changes in colon morphology, including increased mucosal depth and smooth muscle thickening. At day 28 post-CCI, increased paracellular permeability and decreased claudin-1 mRNA and protein expression were observed in the absence of inflammation in the colon. Colonic glial cell GFAP and Sox10 expression were significantly increased 28days after brain injury. Clearance of Cr and upregulation of Th1/Th17 cytokines in the colon were unaffected by CCI; however, colonic paracellular flux and enteric glial cell GFAP expression were significantly increased. Importantly, Cr infection in chronically-injured mice worsened the brain lesion injury and increased astrocyte- and microglial-mediated inflammation. These experimental studies demonstrate chronic and bidirectional brain-gut interactions after TBI, which may negatively impact late outcomes after brain injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury.

    Science.gov (United States)

    Moro, Nobuhiro; Ghavim, Sima; Harris, Neil G; Hovda, David A; Sutton, Richard L

    2013-10-16

    Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand. © 2013 Elsevier B.V. All rights reserved.

  2. Brain pathology after mild traumatic brain injury: an exploratory study by repeated magnetic resonance examination.

    Science.gov (United States)

    Lannsjö, Marianne; Raininko, Raili; Bustamante, Mariana; von Seth, Charlotta; Borg, Jörgen

    2013-09-01

    To explore brain pathology after mild traumatic brain injury by repeated magnetic resonance examination. A prospective follow-up study. Nineteen patients with mild traumatic brain injury presenting with Glasgow Coma Scale (GCS) 14-15. The patients were examined on day 2 or 3 and 3-7 months after the injury. The magnetic resonance protocol comprised conventional T1- and T2-weighted sequences including fluid attenuated inversion recovery (FLAIR), two susceptibility-weighted sequences to reveal haemorrhages, and diffusion-weighted sequences. Computer-aided volume comparison was performed. Clinical outcome was assessed by the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Hospital Anxiety and Depression Scale (HADS) and Glasgow Outcome Scale Extended (GOSE). At follow-up, 7 patients (37%) reported ≥  3 symptoms in RPQ, 5 reported some anxiety and 1 reported mild depression. Fifteen patients reported upper level of good recovery and 4 patients lower level of good recovery (GOSE 8 and 7, respectively). Magnetic resonance pathology was found in 1 patient at the first examination, but 4 patients (21%) showed volume loss at the second examination, at which 3 of them reported GOSE scores of 8. Loss of brain volume, demonstrated by computer-aided magnetic resonance imaging volumetry, may be a feasible marker of brain pathology after mild traumatic brain injury.

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

    Science.gov (United States)

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

    2015-07-01

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

  4. MICROGLIA ACTIVATION AS A BIOMARKER FOR TRAUMATIC BRAIN INJURY

    Directory of Open Access Journals (Sweden)

    Diana G Hernadez-Ontiveros

    2013-03-01

    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.

  5. Perinatal Hypoxic-Ischemic brain injury; MR findings

    International Nuclear Information System (INIS)

    Park, Dong Woo; Seo, Chang Hye

    1994-01-01

    To characterize the MR findings of hypoxic-ischemic brain injury and to assess the value of the MR imaging. SE T1-, T2-weighted, and IR brain MR images of 44 infants and children with the past history of perinatal hypoxic insults were reviewed. Abnormal brain MR findings of 8 patients with birth history of prematurity and 36 patients with birth history of full-term/posterm including 7 with severe anoxic insult history, were compared in regard to the location and the character of the lesions. MRI demonstrated the followings; (1)abnormal signal intensity lesions of subcortical and/or deep cerebral white matter, cortex, and deep gray matter, (2)atrophy of the cerebral white matter, cortex and corpus callosum, with/without ventriculomegaly, and (3)delay in myelination. Periventricular and deep white matter lesions were demonstrated in the prematurity, the deep white matter lesions and/ or subcortical white matter lesions in the term/post-term, and deep gray matter lesions in the 7 patients with severe anoxic insults history. MR imaging was useful in the diagnosis of the hypoxic-ischemic brain injury, and the white and gray matter lesions were correlated with the time of the injury and the severity of hypoxic insult

  6. Misconceptions about traumatic brain injuries among South African university students

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    Chrisma Pretorius

    2013-08-01

    Full Text Available Objective. To investigate the incidence and type of misconceptions about traumatic brain injuries (TBIs harboured by university students.  Method. A convenience sample of 705 university students were recruited and data were collected using an electronic survey. The link to the survey was sent via e-mail to all registered students at Stellenbosch University. The participants had to complete the Common Misconceptions about Traumatic Brain Injury (CM-TBI questionnaire.  Results. The findings of this study suggest that the students subscribe to misconceptions from each of the 7 categories of misconceptions about TBIs. The mean percentages of misconceptions about TBIs were calculated and the amnesia (mean 49.7% and unconsciousness (mean 46.1% categories were identified as the categories about which the respondents had the most misconceptions, while the mean percentages of misconceptions were lower for the categories of recovery (mean 27.6%, rehabilitation (mean 26.56%, prevention (mean 20.8%, brain injury sequelae (mean 18.7% and brain damage (mean 8.4%.  Conclusion. Generally, these findings appear to be in keeping with previous literature, which suggests that misconceptions about TBIs are common among the general population. This study’s identification of these misconceptions could help create awareness, provide a focus for information provision, and contribute to the development of educational intervention programmes tailored for the South African context.

  7. Systemic progesterone for modulating electrocautery-induced secondary brain injury.

    Science.gov (United States)

    Un, Ka Chun; Wang, Yue Chun; Wu, Wutian; Leung, Gilberto Ka Kit

    2013-09-01

    Bipolar electrocautery is an effective and commonly used haemostatic technique but it may also cause iatrogenic brain trauma due to thermal injury and secondary inflammatory reactions. Progesterone has anti-inflammatory and neuroprotective actions in traumatic brain injury. However, its potential use in preventing iatrogenic brain trauma has not been explored. We conducted a pilot animal study to investigate the effect of systemic progesterone on brain cellular responses to electrocautery-induced injury. Adult male Sprague-Dawley rats received standardized bipolar electrocautery (40 W for 2 seconds) over the right cerebral cortex. The treatment group received progesterone intraperitoneally 2 hours prior to surgery; the control group received the drug vehicle only. Immunohistochemical studies showed that progesterone could significantly reduce astrocytic hypertrophy on postoperative day 1, 3 and 7, as well as macrophage infiltration on day 3. The number of astrocytes, however, was unaffected. Our findings suggest that progesterone should be further explored as a neuroprotective agent against electrocautery-induced or other forms of iatrogenic trauma during routine neurosurgical procedures. Future studies may focus on different dosing regimens, neuronal survival, functional outcome, and to compare progesterone with other agents such as dexamethasone. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Cortical neurogenesis in adult rats after ischemic brain injury: most new neurons fail to mature

    Directory of Open Access Journals (Sweden)

    Qing-quan Li

    2015-01-01

    Full Text Available The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial fibrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identified using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromodeoxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial fibrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our findings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

  9. Diverging volumetric trajectories following pediatric traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Emily L. Dennis

    2017-01-01

    Full Text Available Traumatic brain injury (TBI is a significant public health concern, and can be especially disruptive in children, derailing on-going neuronal maturation in periods critical for cognitive development. There is considerable heterogeneity in post-injury outcomes, only partially explained by injury severity. Understanding the time course of recovery, and what factors may delay or promote recovery, will aid clinicians in decision-making and provide avenues for future mechanism-based therapeutics. We examined regional changes in brain volume in a pediatric/adolescent moderate-severe TBI (msTBI cohort, assessed at two time points. Children were first assessed 2–5 months post-injury, and again 12 months later. We used tensor-based morphometry (TBM to localize longitudinal volume expansion and reduction. We studied 21 msTBI patients (5 F, 8–18 years old and 26 well-matched healthy control children, also assessed twice over the same interval. In a prior paper, we identified a subgroup of msTBI patients, based on interhemispheric transfer time (IHTT, with significant structural disruption of the white matter (WM at 2–5 months post injury. We investigated how this subgroup (TBI-slow, N = 11 differed in longitudinal regional volume changes from msTBI patients (TBI-normal, N = 10 with normal WM structure and function. The TBI-slow group had longitudinal decreases in brain volume in several WM clusters, including the corpus callosum and hypothalamus, while the TBI-normal group showed increased volume in WM areas. Our results show prolonged atrophy of the WM over the first 18 months post-injury in the TBI-slow group. The TBI-normal group shows a different pattern that could indicate a return to a healthy trajectory.

  10. Family adaptation 18 months after traumatic brain injury in early childhood.

    Science.gov (United States)

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

    2010-05-01

    The purpose of this study was to examine family adaptation to a traumatic brain injury (TBI) in young children during the first 18-month postinjury, when compared with children who had an orthopedic injury. A concurrent cohort/prospective research design was used with repeated assessments of children aged 3 to 6 years with TBI or orthopedic injury requiring hospitalization and their families. Shortly after injury and at 6-, 12-, and 18-month postinjury, parents of 99 children with TBI (20 severe, 64 moderate, 15 mild) and 117 with orthopedic injury completed standardized assessments of family functioning, parental distress and coping, injury-related burden, and noninjury-related parent stressors and resources. Mixed models analyses examined group differences in parental burden and distress adjusted for race and social demographic factors. Both moderate and severe TBI were associated with higher levels of injury-related stress than orthopedic injury, with stress levels diminishing over time in all groups. Severe TBI was also associated with greater psychological distress on the Brief Symptom Inventory but not with more depressive symptoms. Family functioning and social resources moderated the relationship of TBI severity to injury-related burden and caregiver distress, respectively. Lower child adaptive skills were associated with poorer family outcome but group differences remained even when controlling for this effect. Severe TBI in young children has adverse consequences for parents and families during the first 18-month postinjury. The consequences lessen over time for many families and vary as a function of social resources.

  11. Every Newton Hertz: a macro to micro approach to investigating brain injury.

    Science.gov (United States)

    Duma, Stefan M; Rowson, Steven

    2009-01-01

    The high incidence of concussion in contact sports provides a unique opportunity to collect data to characterize mild traumatic brain injury. This paper outlines a macro to micro approach in which the organ level response of the head is analyzed through head acceleration data from human volunteers and the tissue level response is analyzed through finite element analysis of these data. The helmets of Virginia Tech football players are instrumented with multi-accelerometer measurement devices to record linear and rotational head accelerations for every impact during a game or practice. These impacts are then modeled using the Simulated Injury Monitor (SIMon) finite element head model. Cumulative strain damage measure was investigated for the impacts resulting in the high linear and rotational accelerations. The effect of head impacts on functional performance in football players is also investigated to identify any cognitive effects from repetitive sub-concussive impacts. A better understanding of the effects of head impacts and the mechanisms of brain injury will likely result in insight to future head injury prevention methods and cellular research on brain injury.

  12. Found in translation: understanding the biology and behavior of experimental traumatic brain injury

    Science.gov (United States)

    Bondi, Corina O.; Semple, Bridgette D.; Noble-Haeusslein, Linda J.; Osier, Nicole D.; Carlson, Shaun W.; Dixon, C. Edward; Giza, Christopher C.; Kline, Anthony E.

    2014-01-01

    BONDI, C.O., B.D. Semple, L.J. Noble-Haeusslein, N.D. Osier, S.W. Carlson, C.E. Dixon, C.C. Giza and A.E. Kline. Found in translation: understanding the biology and behavior of experimental traumatic brain injury. NEUROSCI BIOBEHAV REV. The aim of this review is to discuss in greater detail the topics covered in the recent symposium entitled “Traumatic brain injury: laboratory and clinical perspectives,” presented at the 2014 International Behavioral Neuroscience Society annual meeting. Herein we review contemporary laboratory models of traumatic brain injury (TBI) including common assays for sensorimotor and cognitive behavior. New modalities to evaluate social behavior after injury to the developing brain, as well as the attentional set-shifting test (AST) as a measure of executive function in TBI, will be highlighted. Environmental enrichment (EE) will be discussed as a preclinical model of neurorehabilitation, and finally, an evidence-based approach to sports-related concussion will be considered. The review consists predominantly of published data, but some discussion of ongoing or future directions is provided. PMID:25496906

  13. MW151 Inhibited IL-1β Levels after Traumatic Brain Injury with No Effect on Microglia Physiological Responses.

    Directory of Open Access Journals (Sweden)

    Adam D Bachstetter

    Full Text Available A prevailing neuroinflammation hypothesis is that increased production of proinflammatory cytokines contributes to progressive neuropathology, secondary to the primary damage caused by a traumatic brain injury (TBI. In support of the hypothesis, post-injury interventions that inhibit the proinflammatory cytokine surge can attenuate the progressive pathology. However, other post-injury neuroinflammatory responses are key to endogenous recovery responses. Therefore, it is critical that pharmacological attenuation of detrimental or dysregulated neuroinflammatory processes avoid pan-suppression of inflammation. MW151 is a CNS-penetrant, small molecule experimental therapeutic that restores injury- or disease-induced overproduction of proinflammatory cytokines towards homeostasis without immunosuppression. Post-injury administration of MW151 in a closed head injury model of mild TBI suppressed acute cytokine up-regulation and downstream cognitive impairment. Here, we report results from a diffuse brain injury model in mice using midline fluid percussion. Low dose (0.5-5.0 mg/kg administration of MW151 suppresses interleukin-1 beta (IL-1β levels in the cortex while sparing reactive microglia and astrocyte responses. To probe molecular mechanisms, we used live cell imaging of the BV-2 microglia cell line to demonstrate that MW151 does not affect proliferation, migration, or phagocytosis of the cells. Our results provide insight into the roles of glial responses to brain injury and indicate the feasibility of using appropriate dosing for selective therapeutic modulation of injurious IL-1β increases while sparing other glial responses to injury.

  14. Neutrophils in traumatic brain injury (TBI): friend or foe?

    Science.gov (United States)

    Liu, Yang-Wuyue; Li, Song; Dai, Shuang-Shuang

    2018-05-17

    Our knowledge of the pathophysiology about traumatic brain injury (TBI) is still limited. Neutrophils, as the most abundant leukocytes in circulation and the first-line transmigrated immune cells at the sites of injury, are highly involved in the initiation, development, and recovery of TBI. Nonetheless, our understanding about neutrophils in TBI is obsolete, and mounting evidences from recent studies have challenged the conventional views. This review summarizes what is known about the relationships between neutrophils and pathophysiology of TBI. In addition, discussions are made on the complex roles as well as the controversial views of neutrophils in TBI.

  15. Neurobehavioral Effects of Levetiracetam in Patients with Traumatic Brain Injury

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    Jared F Benge

    2013-12-01

    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.

  16. Surgical management of traumatic brain injury

    DEFF Research Database (Denmark)

    Hartings, Jed A; Vidgeon, Steven; Strong, Anthony J

    2014-01-01

    in the treatment of TBI at 2 academic medical centers to document variations in real-world practice and evaluate the efficacies of different approaches on postsurgical course and long-term outcome. METHODS: Patients 18 years of age or older who required neurosurgical lesion evacuation or decompression for TBI were...... monitoring of spreading depolarizations; injury characteristics, physiological monitoring data, and 6-month outcomes were collected prospectively. CT scans and medical records were reviewed retrospectively to determine lesion characteristics, surgical indications, and procedures performed. RESULTS: Patients......%-52%), signs of mass effect (midline shift ≥ 5 mm: 43%-52%), and preoperative intracranial pressure (ICP). At VCU, however, surgeries were performed earlier (median 0.51 vs 0.83 days posttrauma, p performed...

  17. MRI patterns in prolonged low response states following traumatic brain injury in children and adolescents.

    Science.gov (United States)

    Patrick, Peter D; Mabry, Jennifer L; Gurka, Matthew J; Buck, Marcia L; Boatwright, Evelyn; Blackman, James A

    2007-01-01

    To explore the relationship between location and pattern of brain injury identified on MRI and prolonged low response state in children post-traumatic brain injury (TBI). This observational study compared 15 children who spontaneously recovered within 30 days post-TBI to 17 who remained in a prolonged low response state. 92.9% of children with brain stem injury were in the low response group. The predicted probability was 0.81 for brain stem injury alone, increasing to 0.95 with a regional pattern of injury to the brain stem, basal ganglia, and thalamus. Low response state in children post-TBI is strongly correlated with two distinctive regions of injury: the brain stem alone, and an injury pattern to the brain stem, basal ganglia, and thalamus. This study demonstrates the need for large-scale clinical studies using MRI as a tool for outcome assessment in children and adolescents following severe TBI.

  18. Brain Cholinergic Function and Response to Rivastigmine in Patients With Chronic Sequels of Traumatic Brain Injury

    DEFF Research Database (Denmark)

    Östberg, Anna; Virta, Jere; Rinne, Juha O

    2018-01-01

    subjects for more than 1 year after at least moderate traumatic brain injury. Ten of the subjects were respondents and 7 nonrespondents to cholinergic medication. DESIGN:: Cholinergic function was assessed with [methyl-C] N-methylpiperidyl-4-acetate-PET (C-MP4A-PET), which reflects the activity...... was notably lower throughout the cortex in both respondents and nonrespondents, without significant differences between them. CONCLUSION:: Our study suggests that frontal cholinergic dysfunction is associated with the clinical response to cholinergic stimulation in patients with traumatic brain injury....

  19. A comparison of the Full Outline of UnResponsiveness (FOUR) score and Glasgow Coma Score (GCS) in predictive modelling in traumatic brain injury.

    Science.gov (United States)

    Kasprowicz, Magdalena; Burzynska, Malgorzata; Melcer, Tomasz; Kübler, Andrzej

    2016-01-01

    To compare the performance of multivariate predictive models incorporating either the Full Outline of UnResponsiveness (FOUR) score or Glasgow Coma Score (GCS) in order to test whether substituting GCS with the FOUR score in predictive models for outcome in patients after TBI is beneficial. A total of 162 TBI patients were prospectively enrolled in the study. Stepwise logistic regression analysis was conducted to compare the prediction of (1) in-ICU mortality and (2) unfavourable outcome at 3 months post-injury using as predictors either the FOUR score or GCS along with other factors that may affect patient outcome. The areas under the ROC curves (AUCs) were used to compare the discriminant ability and predictive power of the models. The internal validation was performed with bootstrap technique and expressed as accuracy rate (AcR). The FOUR score, age, the CT Rotterdam score, systolic ABP and being placed on ventilator within day one (model 1: AUC: 0.906 ± 0.024; AcR: 80.3 ± 4.8%) performed equally well in predicting in-ICU mortality as the combination of GCS with the same set of predictors plus pupil reactivity (model 2: AUC: 0.913 ± 0.022; AcR: 81.1 ± 4.8%). The CT Rotterdam score, age and either the FOUR score (model 3) or GCS (model 4) equally well predicted unfavourable outcome at 3 months post-injury (AUC: 0.852 ± 0.037 vs. 0.866 ± 0.034; AcR: 72.3 ± 6.6% vs. 71.9%±6.6%, respectively). Adding the FOUR score or GCS at discharge from ICU to predictive models for unfavourable outcome increased significantly their performances (AUC: 0.895 ± 0.029, p = 0.05; AcR: 76.1 ± 6.5%; p model 3; and AUC: 0.918 ± 0.025, p model 4), but there was no benefit from substituting GCS with the FOUR score. Results showed that FOUR score and GCS perform equally well in multivariate predictive modelling in TBI.

  20. Work Productivity Loss After Mild Traumatic Brain Injury.

    Science.gov (United States)

    Silverberg, Noah D; Panenka, William J; Iverson, Grant L

    2018-02-01

    To examine the completeness of return to work (RTW) and the degree of productivity loss in individuals who do achieve a complete RTW after mild traumatic brain injury (MTBI). Multisite prospective cohort. Outpatient concussion clinics. Patients (N=79; mean age, 41.5y; 55.7% women) who sustained an MTBI and were employed at the time of the injury. Participants were enrolled at their first clinic visit and assessed by telephone 6 to 8 months postinjury. Not applicable. Structured interview of RTW status, British Columbia Postconcussion Symptom Inventory (BC-PSI), Lam Employment Absence and Productivity Scale (LEAPS), Mini International Neuropsychiatric Interview, and brief pain questionnaire. Participants who endorsed symptoms from ≥3 categories with at least moderate severity on the BC-PSI were considered to meet International Classification of Diseases, 10th Revision criteria for postconcussional syndrome. RTW status was classified as complete if participants returned to their preinjury job with the same hours and responsibilities or to a new job that was at least as demanding. Of the 46 patients (58.2%) who achieved an RTW, 33 (71.7%) had a complete RTW. Participants with complete RTW had high rates of postconcussional syndrome (44.5%) and comorbid depression (18.2%), anxiety disorder (24.2%), and bodily pain (30.3%). They also reported productivity loss on the LEAPS, such as "getting less work done" (60.6%) and "making more mistakes" (42.4%). In a regression model, productivity loss was predicted by the presence of postconcussional syndrome and a comorbid psychiatric condition, but not bodily pain. Even in patients who RTW after MTBI, detailed assessment revealed underemployment and productivity loss associated with residual symptoms and psychiatric complications. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.