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Sample records for focal brain injury

  1. Visual agnosia and focal brain injury.

    PubMed

    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.

  2. Biomarkers of focal and diffuse traumatic brain injury.

    PubMed

    Vos, Pieter E

    2011-08-18

    Traumatic brain injury (TBI) is a pathologically heterogeneous disease affecting people of all ages. The highest incidence of TBI occurs in young people and the average age is 30 to 40 years. Injury grading may range from mild with a low frequency (1 per 100) of life-threatening intracranial hematoma that needs immediate neurosurgical operation and very low mortality (1 per 1,000) to severe with a high likelihood of life-threatening intracranial hematoma (up to 1 per 3), a 40% case fatality rate and a high disability rate (2 per 3) in survivors. Estimation of the prognosis in severe TBI is currently based on demographic and clinical predictors, including age, Glasgow Coma Scale, pupillary reactions, extracranial injury (hypotension and hypoxia) and computed tomography indices (brain swelling, focal mass lesions, subarachnoid hemorrhage). Biomarkers reflecting damage to neurons and astrocytes may add important complementary information to clinical predictors of outcome and provide insight into the pathophysiology of TBI.

  3. Focally perfused succinate potentiates brain metabolism in head injury patients.

    PubMed

    Jalloh, Ibrahim; Helmy, Adel; Howe, Duncan J; Shannon, Richard J; Grice, Peter; Mason, Andrew; Gallagher, Clare N; Stovell, Matthew G; van der Heide, Susan; Murphy, Michael P; Pickard, John D; Menon, David K; Carpenter, T Adrian; Hutchinson, Peter J; Carpenter, Keri Lh

    2016-01-01

    Following traumatic brain injury, complex cerebral energy perturbations occur. Correlating with unfavourable outcome, high brain extracellular lactate/pyruvate ratio suggests hypoxic metabolism and/or mitochondrial dysfunction. We investigated whether focal administration of succinate, a tricarboxylic acid cycle intermediate interacting directly with the mitochondrial electron transport chain, could improve cerebral metabolism. Microdialysis perfused disodium 2,3-(13)C2 succinate (12 mmol/L) for 24 h into nine sedated traumatic brain injury patients' brains, with simultaneous microdialysate collection for ISCUS analysis of energy metabolism biomarkers (nine patients) and nuclear magnetic resonance of (13)C-labelled metabolites (six patients). Metabolites 2,3-(13)C2 malate and 2,3-(13)C2 glutamine indicated tricarboxylic acid cycle metabolism, and 2,3-(13)C2 lactate suggested tricarboxylic acid cycle spinout of pyruvate (by malic enzyme or phosphoenolpyruvate carboxykinase and pyruvate kinase), then lactate dehydrogenase-mediated conversion to lactate. Versus baseline, succinate perfusion significantly decreased lactate/pyruvate ratio (p = 0.015), mean difference -12%, due to increased pyruvate concentration (+17%); lactate changed little (-3%); concentrations decreased for glutamate (-43%) (p = 0.018) and glucose (-15%) (p = 0.038). Lower lactate/pyruvate ratio suggests better redox status: cytosolic NADH recycled to NAD(+) by mitochondrial shuttles (malate-aspartate and/or glycerol 3-phosphate), diminishing lactate dehydrogenase-mediated pyruvate-to-lactate conversion, and lowering glutamate. Glucose decrease suggests improved utilisation. Direct tricarboxylic acid cycle supplementation with 2,3-(13)C2 succinate improved human traumatic brain injury brain chemistry, indicated by biomarkers and (13)C-labelling patterns in metabolites.

  4. Forebrain neurogenesis after focal Ischemic and traumatic brain injury.

    PubMed

    Kernie, Steven G; Parent, Jack M

    2010-02-01

    Neural stem cells persist in the adult mammalian forebrain and are a potential source of neurons for repair after brain injury. The two main areas of persistent neurogenesis, the subventricular zone (SVZ)-olfactory bulb pathway and hippocampal dentate gyrus, are stimulated by brain insults such as stroke or trauma. Here we focus on the effects of focal cerebral ischemia on SVZ neural progenitor cells in experimental stroke, and the influence of mechanical injury on adult hippocampal neurogenesis in models of traumatic brain injury (TBI). Stroke potently stimulates forebrain SVZ cell proliferation and neurogenesis. SVZ neuroblasts are induced to migrate to the injured striatum, and to a lesser extent to the peri-infarct cortex. Controversy exists as to the types of neurons that are generated in the injured striatum, and whether adult-born neurons contribute to functional restoration remains uncertain. Advances in understanding the regulation of SVZ neurogenesis in general, and stroke-induced neurogenesis in particular, may lead to improved integration and survival of adult-born neurons at sites of injury. Dentate gyrus cell proliferation and neurogenesis similarly increase after experimental TBI. However, pre-existing neuroblasts in the dentate gyrus are vulnerable to traumatic insults, which appear to stimulate neural stem cells in the SGZ to proliferate and replace them, leading to increased numbers of new granule cells. Interventions that stimulate hippocampal neurogenesis appear to improve cognitive recovery after experimental TBI. Transgenic methods to conditionally label or ablate neural stem cells are beginning to further address critical questions regarding underlying mechanisms and functional significance of neurogenesis after stroke or TBI. Future therapies should be aimed at directing appropriate neuronal replacement after ischemic or traumatic injury while suppressing aberrant integration that may contribute to co-morbidities such as epilepsy or

  5. [Neuropsychological development in children with focal brain injury].

    PubMed

    Masi, G; Marcheschi, M; Brovedani, P; Pfanner, P

    1993-06-01

    The study of children with focal brain injury has important implications from a clinical and theoretical perspective. Clinical data on children with congenital or early acquired lesions indicates that the cognitive sequelae are different from those resulting from similar damage sustained in adulthood. These differences depend in part on the differential effect that damage has on ongoing developmental process and in part on the different recovery capacity of the Central Nervous System of the child. From a theoretical perspective, focal lesion data is important for analyzing the issues of early neuropsychological functioning (especially in terms of early hemispheric specialization) and of plasticity and recovery of function of the CNS. This review analyzes the possible causes of this heterogeneity, that seems in part dependent on the interindividual variability of early neuropsychological organization and in part related to methodological factors such subject inclusion criteria and nature of neuropsychological measures. The review also discusses the role during development of the principal inter and intrahemispheric recovery mechanisms (special attention is given to intrahemispheric mechanisms which have been considered in the past as less determinant with respect to interhemispheric mechanisms). Furthermore, the role of lesion side as a prognostic parameter is discussed, specifically in terms of the evidence of a differential recovery capacity of left hemisphere with respect to the right. Various hypotheses have been put forward as possible interpretations of these data (maturational gradient, different neuropsychological organization of the two hemispheres), yet evidence is still controversial. If one considers the prognostic parameter--age of lesion onset--recent evidence does not confirm the hypothesis that the earlier the lesion, the greatest the recovery of function. Rather, it seems that relating age of lesion onset to other parameters, such as lesion side or

  6. CD38 Exacerbates Focal Cytokine Production, Postischemic Inflammation and Brain Injury after Focal Cerebral Ischemia

    PubMed Central

    Gelderblom, Mathias; Ludewig, Peter; Leypoldt, Frank; Koch-Nolte, Friedrich; Gerloff, Christian; Magnus, Tim

    2011-01-01

    Background Converging evidence suggests that inflammatory processes significantly influence brain injury and clinical impairment in ischemic stroke. Although early studies suggested a key role of lymphocytes, recent data has emphasized the orchestrating function of innate immunity, i.e., macrophages and microglia. The bifunctional receptor and ectoenzyme CD38 synthesizes calcium-mobilizing second messengers (e.g., cyclic ADP-ribose), which have been shown to be necessary for activation and migration of myeloid immune cells. Therefore, we investigated the dynamics of CD38 in stroke and the impact of CD38-deficiency on cytokine production, inflammation and cerebral damage in a mouse model of cerebral ischemia-reperfusion. Methodology/Principal Findings We show that the local expression of the chemokine MCP-1 was attenuated in CD38-deficient mice compared with wildtype mice after focal cerebral ischemia and reperfusion. In contrast, no significant induction of MCP-1 expression was observed in peripheral blood after 6 hours. Flow cytometry analysis revealed less infiltrating macrophages and lymphocytes in the ischemic hemisphere of CD38-deficient mice, whereas the amount of resident microglia was unaltered. An up-regulation of CD38 expression was observed in macrophages and CD8+ cells after focal cerebral ischemia in wildtype mice, whereas CD38 expression was unchanged in microglia. Finally, we demonstrate that CD38-deficiency decreases the cerebral ischemic injury and the persistent neurological deficit after three days of reperfusion in this murine temporary middle cerebral artery occlusion (tMCAO) model. Conclusion/Significance CD38 is differentially regulated following stroke and its deficiency attenuates the postischemic chemokine production, the immune cell infiltration and the cerebral injury after temporary ischemia and reperfusion. Therefore CD38 might prove a therapeutic target in ischemic stroke. PMID:21625615

  7. Mitochondrial bioenergetic alterations after focal traumatic brain injury in the immature brain.

    PubMed

    Kilbaugh, Todd J; Karlsson, Michael; Byro, Melissa; Bebee, Ashley; Ralston, Jill; Sullivan, Sarah; Duhaime, Ann-Christine; Hansson, Magnus J; Elmér, Eskil; Margulies, Susan S

    2015-09-01

    Traumatic brain injury (TBI) is one of the leading causes of death in children worldwide. Emerging evidence suggests that alterations in mitochondrial function are critical components of secondary injury cascade initiated by TBI that propogates neurodegeneration and limits neuroregeneration. Unfortunately, there is very little known about the cerebral mitochondrial bioenergetic response from the immature brain triggered by traumatic biomechanical forces. Therefore, the objective of this study was to perform a detailed evaluation of mitochondrial bioenergetics using high-resolution respirometry in a high-fidelity large animal model of focal controlled cortical impact injury (CCI) 24h post-injury. This novel approach is directed at analyzing dysfunction in electron transport, ADP phosphorylation and leak respiration to provide insight into potential mechanisms and possible interventions for mitochondrial dysfunction in the immature brain in focal TBI by delineating targets within the electron transport system (ETS). Development and application of these methodologies have several advantages, and adds to the interpretation of previously reported techniques, by having the added benefit that any toxins or neurometabolites present in the ex-vivo samples are not removed during the mitochondrial isolation process, and simulates the in situ tricarboxylic acid (TCA) cycle by maximizing key substrates for convergent flow of electrons through both complexes I and II. To investigate alterations in mitochondrial function after CCI, ipsilateral tissue near the focal impact site and tissue from the corresponding contralateral side were examined. Respiration per mg of tissue was also related to citrate synthase activity (CS) and calculated flux control ratios (FCR), as an attempt to control for variability in mitochondrial content. Our biochemical analysis of complex interdependent pathways of electron flow through the electron transport system, by most measures, reveals a bilateral

  8. Temporal and regional changes after focal traumatic brain injury.

    PubMed

    Lescot, Thomas; Fulla-Oller, Laurence; Fulla-Oller, Lawrence; Po, Chrystelle; Chen, Xiao Ru; Puybasset, Louis; Gillet, Brigitte; Plotkine, Michel; Meric, Philippe; Marchand-Leroux, Catherine

    2010-01-01

    Magnetic resonance imaging (MRI) is widely used to evaluate the consequences of traumatic brain injury (TBI) in both experimental and clinical studies. Improved assessment of experimental TBI using the same methods as those used in clinical investigations would help to translate laboratory research into clinical advances. Here our goal was to characterize lateral fluid percussion-induced TBI, with special emphasis on differentiating the contused cortex from the pericontusional subcortical tissue. We used both in vivo MRI and proton magnetic resonance spectroscopy ((1)H-MRS) to evaluate adult male Sprague-Dawley rats 24 h and 48 h and 7 days after TBI. T2 and apparent diffusion coefficient (ADC) maps were derived from T2-weighted and diffusion-weighted images, respectively. Ratios of N-acetylaspartate (NAA), choline compounds (Cho), and lactate (Lac) over creatine (Cr) were estimated by (1)H-MRS. T2 values were high in the contused cortex 24 h after TBI, suggesting edema development; ADC was low, consistent with cytotoxic edema. At the same site, NAA/Cr was decreased and Lac/Cr elevated during the first week after TBI. In the ipsilateral subcortical area, NAA/Cr was markedly decreased and Lac/Cr was elevated during the first week, although MRI showed no evidence of edema, suggesting that (1)H-MRS detected "invisible" damage. (1)H-MRS combined with MRI may improve the detection of brain injury. Extensive assessments of animal models may increase the chances of developing successful neuroprotective strategies.

  9. Brain Tissue Oxygenation and Cerebral Metabolic Patterns in Focal and Diffuse Traumatic Brain Injury

    PubMed Central

    Purins, Karlis; Lewén, Anders; Hillered, Lars; Howells, Tim; Enblad, Per

    2014-01-01

    Introduction: Neurointensive care of traumatic brain injury (TBI) patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted protocols. There are reasons to believe that knowledge of brain tissue oxygenation (BtipO2) would add information with the potential of improving patient outcome. The aim of this study was to examine BtipO2 and cerebral metabolism using the Neurovent-PTO probe and cerebral microdialysis (MD) in TBI patients. Methods: Twenty-three severe TBI patients with monitoring of physiological parameters, ICP, CPP, BtipO2, and MD for biomarkers of energy metabolism (glucose, lactate, and pyruvate) and cellular distress (glutamate, glycerol) were included. Patients were grouped according to injury type (focal/diffuse) and placement of the Neurovent-PTO probe and MD catheter (injured/non-injured hemisphere). Results: We observed different patterns in BtipO2 and MD biomarkers in diffuse and focal injury where placement of the probe also influenced the results (ipsilateral/contralateral). In all groups, despite fairly normal levels of ICP and CPP, increased MD levels of glutamate, glycerol, or the L/P ratio were observed at BtipO2 <5 mmHg, indicating increased vulnerability of the brain at this level. Conclusion: Monitoring of BtipO2 adds important information in addition to traditional ICP and CPP surveillance. Because of the different metabolic responses to very low BtipO2 in the individual patient groups we submit that brain tissue oximetry is a complementary tool rather than an alternative to MD monitoring. PMID:24817863

  10. Spontaneous gesture and spatial language: Evidence from focal brain injury

    PubMed Central

    Göksun, Tilbe; Lehet, Matthew; Malykhina, Katsiaryna; Chatterjee, Anjan

    2015-01-01

    People often use spontaneous gestures when communicating spatial information. We investigated focal brain-injured individuals to test the hypotheses that (1) naming motion event components of manner-path (represented by verbs-prepositions in English) are impaired selectively, (2) gestures compensate for impaired naming. Patients with left or right hemisphere damage (LHD or RHD) and elderly control participants were asked to describe motion events (e.g., running across) depicted in brief videos. Damage to the left posterior middle frontal gyrus, left inferior frontal gyrus, and left anterior superior temporal gyrus (aSTG) produced impairments in naming paths of motion; lesions to the left caudate and adjacent white matter produced impairments in naming manners of motion. While the frequency of spontaneous gestures were low, lesions to the left aSTG significantly correlated with greater production of path gestures. These suggest that producing prepositions-verbs can be separately impaired and gesture production compensates for naming impairments when damage involves left aSTG. PMID:26283001

  11. Mitochondrial bioenergetic alterations after focal traumatic brain injury in the immature brain☆

    PubMed Central

    Kilbaugh, Todd; Karlsson, Michael; Byro, Melissa; Bebee, Ashley; Ralston, Jill; Sullivan, Sarah; Duhaime, Ann-Christine; Hansson, Magnus J.; Elmer, Eskil; Margulies, Susan S.

    2015-01-01

    Traumatic brain injury (TBI) is one of the leading causes of death in children worldwide. Emerging evidence suggests that alterations in mitochondrial function are critical components of secondary injury cascade initiated by TBI that propogates neurodegeneration and limits neuroregeneration. Unfortunately, there is very little known about the cerebral mitochondrial bioenergetic response from the immature brain triggered by traumatic biomechanical forces. Therefore, the objective of this study was to perform a detailed evaluation of mitochondrial bioenergetics using high-resolution respirometry in a high-fidelity large animal model of focal controlled cortical impact injury (CCI) 24 h post-injury. This novel approach is directed at analyzing dysfunction in electron transport, ADP phosphorylation and leak respiration to provide insight into potential mechanisms and possible interventions for mitochondrial dysfunction in the immature brain in focal TBI by delineating targets within the electron transport system (ETS). Development and application of these methodologies have several advantages, and adds to the interpretation of previously reported techniques, by having the added benefit that any toxins or neurometabolites present in the ex-vivo samples are not removed during the mitochondrial is olation process, and simulates the in situ tricarboxylic acid (TCA) cycle by maximizing key substrates for convergent flow of electrons through both complexes I and II. To investigate alterations in mitochondrial function after CCI, ipsilateral tissue near the focal impact site and tissue from the corresponding contralateral side were examined. Respiration per mg of tissue was also related to citrate synthase activity (CS) and calculated flux control ratios (FCR), as an attempt to control for variability in mitochondrial content. Our biochemical analysis of complex interdependent pathways of electron flow through the electron transport system, by most measures, reveals a

  12. Pathophysiology and neuroprotection of global and focal perinatal brain injury: lessons from animal models

    PubMed Central

    Manganozzi, Lucilla; Moretti, Raffaella; Vexler, Zinaida S.; Gressens, Pierre

    2016-01-01

    BACKGROUND Arterial ischemic stroke occurs most frequently in term newborns than in the elderly, and brain immaturity affects mechanisms of ischemic injury and recovery. The susceptibility to injury of the brain was assumed to be lower in the perinatal period as compared to childhood. This concept was recently challenged by clinical studies showing marked motor disabilities after stroke in neonates, with the severity of motor and cortical sensory deficits similar in both perinatal and childhood ischemic stroke. The understanding of the triggers and the pathophysiological mechanisms of perinatal stroke has greatly improved in recent years, but many aspects remain still unclear. METHODS In this review, we will focus on the pathophysiology of perinatal stroke and on therapeutic strategies that can protect the immature brain from the consequences of stroke by targeting inflammation and brain microenvironment. RESULTS Studies in neonatal rodent models of cerebral ischemia have shown a potential role for soluble inflammatory molecules as important modulators of injury and recovery. A great effort has been made and is still in act to try neuroprotective molecules based on the new physiopatological acquisition. CONCLUSION In this review we aim to give a comprehensive view of new insights concerning pathophysiological mechanism of focal and global perinatal brain injury and its new therapeutic approaches. PMID:26002050

  13. Dynamics of rabbit brain edema in focal lesion and perilesion area after traumatic brain injury: a MRI study.

    PubMed

    Wei, Xiao-Er; Zhang, Yu-Zhen; Li, Yue-Hua; Li, Ming-Hua; Li, Wen-Bin

    2012-09-20

    To understand the dynamics of brain edema in different areas after traumatic brain injury (TBI) in rabbit, we used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) to monitor blood-brain barrier (BBB) permeability and cytotoxic brain edema after weight drop-induced TBI in rabbit. The dynamics of BBB permeability and brain edema were quantified using K(trans) and apparent diffusion coefficient (ADC) in the focal and perifocal lesion areas, as well as the area contralateral to the lesion. In the focal lesion area, K(trans) began to increase at 3 h post-TBI, peaked at 3 days, and decreased gradually while remaining higher than sham injury animals at 7 and 30 days. ADC was more variable, increased slightly at 3 h, decreased to its lowest value at 7 days, then increased to a peak at 30 days. In the perifocal lesion area, K(trans) began to increase at 1 day, peaked at 3-7 days, and returned to control level by 30 days. ADC showed a trend to increase at 1 day, followed by a continuous increase thereafter. In the contralateral area, no changes in K(trans) and ADC were observed at any time-point. These data demonstrate that different types of brain edema predominate in the focal and perifocal lesion areas. Specifically cytotoxic edema was predominant in the focal lesion area while vasogenic edema predominated in the perifocal area in acute phase. Furthermore, secondary opening of the BBB after TBI may appear if secondary injury is not controlled. BBB damage may be a driving force for cytotoxic brain edema and could be a new target for TBI intervention.

  14. Alterations in Daytime and Nighttime Activity in Piglets after Focal and Diffuse Brain Injury.

    PubMed

    Olson, Emily; Badder, Carlie; Sullivan, Sarah; Smith, Colin; Propert, Kathleen; Margulies, Susan S

    2016-04-15

    We have developed and implemented a noninvasive, objective neurofunctional assessment for evaluating the sustained effects of traumatic brain injury (TBI) in piglets with both diffuse and focal injury types. Derived from commercial actigraphy methods in humans, this assessment continuously monitors the day/night activity of piglets using close-fitting jackets equipped with tri-axial accelerometers to monitor movements of the thorax. Acceleration metrics were correlated (N = 7 naïve piglets) with video images to define values associated with a range of activities, from recumbancy (rest) to running. Both focal (N = 8) and diffuse brain injury (N = 9) produced alterations in activity that were significant 4 days post-TBI. Compared to shams (N = 6) who acclimated to the animal facility 4 days after an anesthesia experience by blurring the distinction between day and night activity, post-TBI time-matched animals had larger fractions of inactive periods during the daytime than nighttime, and larger fractions of active time in the night were spent in high activity (e.g., constant walking, intermittent running) than during the day. These persistent disturbances in rest and activity are similar to those observed in human adults and children post-TBI, establishing actigraphy as a translational metric, used in both humans and large animals, for assessment of injury severity, progressions, and intervention.

  15. Choosing upper limb muscles for focal intervention after traumatic brain injury.

    PubMed

    Mayer, Nathaniel H

    2004-01-01

    The upper motoneuron syndrome (UMNS) resulting from lesions of corticospinal pathways is an important source of disability after traumatic brain injury (TBI). Classic expressions of motor behavior in UMNS are of 2 kinds: (1) manifestation of muscle underactivity, termed negative signs, and (2) manifestation of a variety of forms of muscle overactivity, termed positive signs. Combinations of negative and positive signs give rise to clinical patterns of movement dysfunction such as the flexed elbow, the clenched fist, and the thumb-in-palm deformity. These clinical patterns can be viewed as reflecting a net balance of muscle forces acting across the joints of a limb. Individual muscles are amenable to a variety of focal interventions such as neurolysis, chemodenervation, or surgery. Since more than one muscle acts across most joints, choices among muscles for focal intervention are many. This article will focus on focal interventions of upper limb muscles of patients with TBI who have UMNS and will explore the theme of choosing upper limb muscles for focal interventions after TBI.

  16. Chronic nicotine exposure exacerbates transient focal cerebral ischemia-induced brain injury.

    PubMed

    Li, Chun; Sun, Hong; Arrick, Denise M; Mayhan, William G

    2016-02-01

    Tobacco smoking is a risk factor contributing to the development and progression of ischemic stroke. Among many chemicals in tobacco, nicotine may be a key contributor. We hypothesized that nicotine alters the balance between oxidant and antioxidant networks leading to an increase in brain injury following transient focal cerebral ischemia. Male Sprague-Dawley were treated with nicotine (2 or 4 mg·kg(-1)·day(-1)) for 4 wk via an implanted subcutaneous osmotic minipump and subjected to a 2-h middle cerebral artery occlusion (MCAO). Infarct size and neurological deficits were evaluated at 24 h of reperfusion. Superoxide levels were determined by lucigenin-enhanced chemiluminescence. Expression of oxidant and antioxidant proteins was measured using Western blot analysis. We found that chronic nicotine exposure significantly increased infarct size and worsened neurological deficits. In addition, nicotine significantly elevated superoxide levels of cerebral cortex under basal conditions. Transient focal cerebral ischemia produced an increase in superoxide levels of cerebral cortex in control group, but no further increase was found in the nicotine group. Furthermore, chronic nicotine exposure did not alter protein expression of NADPH oxidase but significantly decreased MnSOD and uncoupling protein-2 (UCP-2) in the cerebral cortex and cerebral arteries. Our findings suggest that nicotine-induced exacerbation in brain damage following transient focal cerebral ischemia may be related to a preexisting oxidative stress via decreasing of MnSOD and UCP-2. Copyright © 2016 the American Physiological Society.

  17. Clinical characteristics and pathophysiological mechanisms of focal and diffuse traumatic brain injury

    PubMed Central

    Andriessen, Teuntje M J C; Jacobs, Bram; Vos, Pieter E

    2010-01-01

    Abstract Traumatic brain injury (TBI) is a frequent and clinically highly heterogeneous neurological disorder with large socioeconomic consequences. TBI severity classification, based on the hospital admission Glasgow Coma Scale (GCS) score, ranges from mild (GCS 13–15) and moderate (GCS 9–12) to severe (GCS ≤ 8). The GCS reflects the risk of dying from TBI, which is low after mild (∼1%), intermediate after moderate (up to 15%) and high (up to 40%) after severe TBI. Intracranial damage can be focal, such as epidural and subdural haematomas and parenchymal contusions, or diffuse, for example traumatic axonal injury and diffuse cerebral oedema, although this distinction is somewhat arbitrary. Study of the cellular and molecular post-traumatic processes is essential for the understanding of TBI pathophysiology but even more to find therapeutic targets for the development of neuroprotective drugs to be eventually used in human beings. To date, studies in vitro and in vivo, mainly in animals but also in human beings, are unravelling the pathological TBI mechanisms at high pace. Nevertheless, TBI pathophysiology is all but completely elucidated. Neuroprotective treatment studies in human beings have been disappointing thus far and have not resulted in commonly accepted drugs. This review presents an overview on the clinical aspects and the pathophysiology of focal and diffuse TBI, and it highlights several acknowledged important events that occur on molecular and cellular level after TBI. PMID:20738443

  18. Clinical characteristics and pathophysiological mechanisms of focal and diffuse traumatic brain injury.

    PubMed

    Andriessen, Teuntje M J C; Jacobs, Bram; Vos, Pieter E

    2010-10-01

    Traumatic brain injury (TBI) is a frequent and clinically highly heterogeneous neurological disorder with large socioeconomic consequences. TBI severity classification, based on the hospital admission Glasgow Coma Scale (GCS) score, ranges from mild (GCS 13-15) and moderate (GCS 9-12) to severe (GCS ≤ 8). The GCS reflects the risk of dying from TBI, which is low after mild (∼1%), intermediate after moderate (up to 15%) and high (up to 40%) after severe TBI. Intracranial damage can be focal, such as epidural and subdural haematomas and parenchymal contusions, or diffuse, for example traumatic axonal injury and diffuse cerebral oedema, although this distinction is somewhat arbitrary. Study of the cellular and molecular post-traumatic processes is essential for the understanding of TBI pathophysiology but even more to find therapeutic targets for the development of neuroprotective drugs to be eventually used in human beings. To date, studies in vitro and in vivo, mainly in animals but also in human beings, are unravelling the pathological TBI mechanisms at high pace. Nevertheless, TBI pathophysiology is all but completely elucidated. Neuroprotective treatment studies in human beings have been disappointing thus far and have not resulted in commonly accepted drugs. This review presents an overview on the clinical aspects and the pathophysiology of focal and diffuse TBI, and it highlights several acknowledged important events that occur on molecular and cellular level after TBI.

  19. sAPPα rescues deficits in amyloid precursor protein knockout mice following focal traumatic brain injury.

    PubMed

    Corrigan, Frances; Vink, Robert; Blumbergs, Peter C; Masters, Colin L; Cappai, Roberto; van den Heuvel, Corinna

    2012-07-01

    The amyloid precursor protein (APP) is thought to be neuroprotective following traumatic brain injury (TBI), although definitive evidence at moderate to severe levels of injury is lacking. In the current study, we investigated histological and functional outcomes in APP-/- mice compared with APP+/+ mice following a moderate focal injury, and whether administration of sAPPα restored the outcomes in knockout animals back to the wildtype state. Following moderate controlled cortical impact injury, APP-/- mice demonstrated greater impairment in motor and cognitive outcome as determined by the ledged beam and Barnes Maze tests respectively (p < 0.05). This corresponded with the degree of neuronal damage, with APP-/- mice having significantly greater lesion volume (25.0 ± 1.6 vs. 20.3 ± 1.6%, p < 0.01) and hippocampal damage, with less remaining CA neurons (839 ± 245 vs. 1353 ± 142 and 1401 ± 263). This was also associated with an impaired neuroreparative response, with decreased GAP-43 immunoreactivity within the cortex around the lesion edge compared with APP+/+ mice. The deficits observed in the APP-/- mice related to a lack of sAPPα, as treatment with exogenously added sAPPα post-injury improved APP-/- mice histological and functional outcome to the point that they were no longer significantly different to APP+/+ mice (p < 0.05). This study shows that endogenous APP is potentially protective at moderate levels of TBI, and that this neuroprotective activity is related to the presence of sAPPα. Importantly, it indicates that the mechanism of action of exogenously added sAPPα is independent of the presence of endogenous APP.

  20. Neuroprotective effects of N-acetylcysteine amide on experimental focal penetrating brain injury in rats.

    PubMed

    Günther, Mattias; Davidsson, Johan; Plantman, Stefan; Norgren, Svante; Mathiesen, Tiit; Risling, Mårten

    2015-09-01

    We examined the effects of N-acetylcysteine amide (NACA) in the secondary inflammatory response following a novel method of focal penetrating traumatic brain injury (TBI) in rats. N-acetylcysteine (NAC) has limited but well-documented neuroprotective effects after experimental central nervous system ischemia and TBI, but its bioavailability is very low. We tested NACA, a modified form of NAC with higher membrane and blood-brain barrier permeability. Focal penetrating TBI was produced in male Sprague-Dawley rats randomly selected for NACA treatment (n=5) and no treatment (n=5). In addition, four animals were submitted to sham surgery. After 2 hours or 24 hours the brains were removed, fresh frozen, cut in 14 μm coronal sections and subjected to immunohistochemistry, immunofluorescence, Fluoro-Jade and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analyses. All treated animals were given 300 mg/kg NACA intraperitoneally (IP) 2 minutes post trauma. The 24 hour survival group was given an additional bolus of 300 mg/kg IP after 4 hours. NACA treatment decreased neuronal degeneration by Fluoro-Jade at 24 hours with a mean change of 35.0% (p<0.05) and decreased TUNEL staining indicative of apoptosis at 2 hours with a mean change of 38.7% (p<0.05). Manganese superoxide dismutase (MnSOD) increased in the NACA treatment group at 24 hours with a mean change of 35.9% (p<0.05). Levels of migrating macrophages and activated microglia (Ox-42/CD11b), nitric oxide-producing inflammatory enzyme iNOS, peroxynitrite marker 3-nitrotyrosine, NFκB translocated to the nuclei, cytochrome C and Bcl-2 were not affected. NACA treatment decreased neuronal degeneration and apoptosis and increased levels of antioxidative enzyme MnSOD. The antiapoptotic effect was likely regulated by pathways other than cytochrome C. Therefore, NACA prevents brain tissue damage after focal penetrating TBI, warranting further studies towards a clinical application.

  1. The effect of electric cortical stimulation after focal traumatic brain injury in rats.

    PubMed

    Yoon, Yong-Soon; Yu, Ki Pi; Kim, Hyojoon; Kim, Hyoung-Ihl; Kwak, Soo Hyun; Kim, Bong Ok

    2012-10-01

    To evaluate the effects of electric cortical stimulation in the experimentally induced focal traumatic brain injury (TBI) rat model on motor recovery and plasticity of the injured brain. Twenty male Sprague-Dawley rats were pre-trained on a single pellet reaching task (SPRT) and on a Rotarod task (RRT) for 14 days. Then, the TBI model was induced by a weight drop device (40 g in weight, 25 cm in height) on the dominant motor cortex, and the electrode was implanted over the perilesional cortical surface. All rats were divided into two groups as follows: Electrical stimulation (ES) group with anodal continuous stimulation (50 Hz and 194 µs duration) or Sham-operated control (SOC) group with no electrical stimulation. The rats were trained SPRT and RRT for 14 days for rehabilitation and measured Garcia's neurologic examination. Histopathological and immunostaining evaluations were performed after the experiment. There were no differences in the slice number in the histological analysis. Garcia's neurologic scores & SPRT were significantly increased in the ES group (p<0.05), yet, there was no difference in RRT in both groups. The ES group showed more expression of c-Fos around the brain injured area than the SOC group. Electric cortical stimulation with rehabilitation is considered to be one of the trial methods for motor recovery in TBI. However, more studies should be conducted for the TBI model in order to establish better stimulation methods.

  2. The Effect of Electric Cortical Stimulation after Focal Traumatic Brain Injury in Rats

    PubMed Central

    Yoon, Yong-Soon; Yu, Ki Pi; Kim, Hyojoon; Kim, Hyoung-ihl; Kim, Bong Ok

    2012-01-01

    Objective To evaluate the effects of electric cortical stimulation in the experimentally induced focal traumatic brain injury (TBI) rat model on motor recovery and plasticity of the injured brain. Method Twenty male Sprague-Dawley rats were pre-trained on a single pellet reaching task (SPRT) and on a Rotarod task (RRT) for 14 days. Then, the TBI model was induced by a weight drop device (40 g in weight, 25 cm in height) on the dominant motor cortex, and the electrode was implanted over the perilesional cortical surface. All rats were divided into two groups as follows: Electrical stimulation (ES) group with anodal continuous stimulation (50 Hz and 194 µs duration) or Sham-operated control (SOC) group with no electrical stimulation. The rats were trained SPRT and RRT for 14 days for rehabilitation and measured Garcia's neurologic examination. Histopathological and immunostaining evaluations were performed after the experiment. Results There were no differences in the slice number in the histological analysis. Garcia's neurologic scores & SPRT were significantly increased in the ES group (p<0.05), yet, there was no difference in RRT in both groups. The ES group showed more expression of c-Fos around the brain injured area than the SOC group. Conclusion Electric cortical stimulation with rehabilitation is considered to be one of the trial methods for motor recovery in TBI. However, more studies should be conducted for the TBI model in order to establish better stimulation methods. PMID:23185723

  3. Study the efficacy of neuroprotective drugs on brain physiological properties during focal head injury using optical spectroscopy data analysis

    NASA Astrophysics Data System (ADS)

    Abookasis, David; Shochat, Ariel

    2016-03-01

    We present a comparative evaluation of five different neuroprotective drugs in the early phase following focal traumatic brain injury (TBI) in mouse intact head. The effectiveness of these drugs in terms of changes in brain tissue morphology and hemodynamic properties was experimentally evaluated through analysis of the optical absorption coefficient and spectral reduced scattering parameters in the range of 650-1000 nm. Anesthetized male mice (n=50 and n=10 control) were subjected to weight drop model mimics real life focal head trauma. Monitoring the effect of injury and neuroprotective drugs was obtained by using a diffuse reflectance spectroscopy system utilizing independent source-detector separation and location. Result indicates that administration of minocycline improve hemodynamic and reduced the level of tissue injury at an early phase post-injury while hypertonic saline treatment decrease brain water content. These findings highlight the heterogeneity between neuroprotective drugs and the ongoing controversy among researchers regarding which drug therapy is preferred for treatment of TBI. On the other hand, our results show the capability of optical spectroscopy technique to noninvasively study brain function following injury and drug therapy.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-03-01

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

  6. Grammaticality Sensitivity in Children with Early Focal Brain Injury and Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Wulfeck, Beverly; Bates, Elizabeth; Krupa-Kwiatkowski, Magda; Saltzman, Danna

    2004-01-01

    Grammaticality judgments and processing times associated with violation detection were examined in typically developing children, children with focal brain lesions (FL) acquired early in life, and children with specific language impairment (SLI). Grammatical sensitivity in the FL group, while below typically developing children, was above levels…

  7. Focal Brain Injury Associated with a Model of Severe Hypoxic-Ischemic Encephalopathy in Nonhuman Primates.

    PubMed

    McAdams, Ryan M; McPherson, Ronald J; Kapur, Raj P; Juul, Sandra E

    2017-03-25

    Worldwide, hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal mortality and morbidity. To better understand the mechanisms contributing to brain injury and improve outcomes in neonates with HIE, better preclinical animal models that mimic the clinical situation following birth asphyxia in term newborns are needed. In an effort to achieve this goal, we modified our nonhuman primate model of HIE induced by in utero umbilical cord occlusion (UCO) to include postnatal hypoxic episodes, in order to simulate apneic events in human neonates with HIE. We describe a cohort of 4 near-term fetal Macaca nemestrina that underwent 18 min of in utero UCO, followed by cesarean section delivery, resuscitation, and subsequent postnatal mechanical ventilation, with exposure to intermittent daily hypoxia (3 min, 8% O2 3-8 times daily for 3 days). After delivery, all animals demonstrated severe metabolic acidosis (pH 7 ± 0.12; mean ± SD) and low APGAR scores (<5 at 10 min of age). Three of 4 animals had both electrographic and clinical seizures. Serial blood samples were collected and plasma metabolites were determined by 2-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOFMS). The 4 UCO animals and a single nonasphyxiated animal (delivered by cesarean section but without exposure to UCO or prolonged sedation) underwent brain magnetic resonance imaging (MRI) on day 8 of life. Thalamic injury was present on MRI in 3 UCO animals, but not in the control animal. Following necropsy on day 8, brain histopathology revealed neuronal injury/loss and gliosis in portions of the ventrolateral thalamus in all 4 UCO, with 2 animals also demonstrating putamen/globus pallidus involvement. In addition, all 4 UCO animals demonstrated brain stem gliosis, with neuronal loss present in the midbrain, pons, and lateral medulla in 3 of 4 animals. Transmission electron microscopy imaging of the brain tissues was performed, which demonstrated

  8. Role of Neutrophils in Exacerbation of Brain Injury After Focal Cerebral Ischemia in Hyperlipidemic Mice.

    PubMed

    Herz, Josephine; Sabellek, Pascal; Lane, Thomas E; Gunzer, Matthias; Hermann, Dirk M; Doeppner, Thorsten R

    2015-10-01

    Inflammation-related comorbidities contribute to stroke-induced immune responses and brain damage. We previously showed that hyperlipidemia exacerbates ischemic brain injury, which is associated with elevated peripheral and cerebral granulocyte numbers. Herein, we evaluate the contribution of neutrophils to the exacerbation of ischemic brain injury. Wild-type mice fed with a normal chow and ApoE knockout mice fed with a high cholesterol diet were exposed to middle cerebral artery occlusion. CXCR2 was blocked using the selective antagonist SB225002 (2 mg/kg) or neutralizing CXCR2 antiserum. Neutrophils were depleted using an anti-Ly6G antibody. At 72 hours post ischemia, immunohistochemistry, flow cytometry, and real-time polymerase chain reaction were performed to determine cerebral tissue injury and immunologic changes in the blood, bone marrow, and brain. Functional outcome was assessed by accelerated rota rod and tight rope tests at 4, 7, and 14 days post ischemia. CXCR2 antagonization reduced neurological deficits and infarct volumes that were exacerbated in hyperlipidemic ApoE-/- mice. This effect was mimicked by neutrophil depletion. Cerebral neutrophil infiltration and peripheral neutrophilia, which were increased on ischemia in hyperlipidemia, were attenuated by CXCR2 antagonization. This downscaling of neutrophil responses was associated with increased neutrophil apoptosis and reduced levels of CXCR2, inducible nitric oxide synthase, and NADPH oxidase 2 expression on bone marrow neutrophils. Our data demonstrate a role of neutrophils in the exacerbation of ischemic brain injury induced by hyperlipidemia. Accordingly, CXCR2 blockade, which prevents neutrophil recruitment into the brain, might be an effective option for stroke treatment in patients with hyperlipidemia. © 2015 American Heart Association, Inc.

  9. Docosahexaenoic acid improves behavior and attenuates blood-brain barrier injury induced by focal cerebral ischemia in rats.

    PubMed

    Hong, Sung-Ha; Khoutorova, Larissa; Bazan, Nicolas G; Belayev, Ludmila

    2015-01-01

    Ischemic brain injury disrupts the blood-brain barrier (BBB) and then triggers a cascade of events, leading to edema formation, secondary brain injury and poor neurological outcomes. Recently, we have shown that docosahexaenoic acid (DHA) improves functional and histological outcomes following experimental stroke. However, little is known about the effect of DHA on BBB dysfunction after cerebral ischemia-reperfusion injury. The present study was designed to determine whether DHA protects against BBB disruption after focal cerebral ischemia in rats. Physiologically-controlled SD rats received 2 h middle cerebral artery occlusion (MCAo). DHA (5 mg/kg) or vehicle (saline) was administered I.V. at 3 h after onset of MCAo. Fluorometric quantitation of Evans Blue dye (EB) was performed in eight brain regions at 6 h, 24 h or 72 h after MCAo. Fluorescein isothiocynate (FITC) - dextran leakage and histopathology was evaluated on day 3 after stroke. Physiological variables were stable and showed no significant differences between groups. DHA improved neurological deficits at 24 h, 48 h and 72 h and decreased EB extravasation in the ischemic hemisphere at 6 h (by 30%), 24 h (by 48%) and 72 h (by 38%). In addition, EB extravasation was decreased by DHA in the cortex and total hemisphere as well. FITC-dextran leakage was reduced by DHA treatment on day 3 by 68% compared to the saline group. DHA treatment attenuated cortical (by 50%) and total infarct volume (by 38%) compared to vehicle-treated rats on day 3 after stroke. DHA therapy diminishes BBB damage accompanied with the acceleration of behavioral recovery and attenuation of the infarct volume. It is reasonable to propose that DHA has the potential for treating focal ischemic stroke in the clinical setting.

  10. Volume of focal brain lesions and hippocampal formation in relation to memory function after closed head injury in children.

    PubMed

    Di Stefano, G; Bachevalier, J; Levin, H S; Song, J X; Scheibel, R S; Fletcher, J M

    2000-08-01

    (1) A study of verbal learning and memory in children who had sustained a closed head injury (CHI) at least 3 months earlier. (2) To relate memory function to focal brain lesion and hippocampal formation volumes using morphometric analysis of MRI. A group of 245 children who had been admitted to hospital for CHI graded by the Glasgow coma scale (GCS), including 161 patients with severe and 84 with mild CHI completed the California verbal learning test (CVLT) and underwent MRI which was analysed for focal brain lesion volume independently of memory test data. Brain MRI with 1.5 mm coronal slices obtained in subsets of 25 patients with severe and 25 patients with mild CHI were analysed for hippocampal formation volume. Interoperator reliability in morphometry was satisfactory. Severity of CHI and age at study significantly affected memory performance. Regression analysis showed that bifrontal, left frontal, and right frontal lesion volumes incremented prediction of various learning and memory indices after entering the GCS score and age into the model. Extrafrontal lesion volume did not contribute to predicting memory performance. Prefrontal lesions contribute to residual impairment of learning and memory after severe CHI in children. Although effects of CHI on hippocampal formation volume might be difficult to demonstrate in non-fatal paediatric CHI, further investigation using functional brain imaging could potentially demonstrate hippocampal dysfunction.

  11. Ischemic postconditioning may not influence early brain injury induced by focal cerebral ischemia/reperfusion in rats

    PubMed Central

    Kim, Yoo Kyung; Shin, Jin Woo; Joung, Kyoung Woon

    2010-01-01

    Background Experimental studies have shown that ischemic postconditioning can reduce neuronal injury in the setting of cerebral ischemia, but the mechanisms are not yet clearly elucidated. This study was conducted to determine whether ischemic postconditioning can alter expression of heat shock protein 70 and reduce acute phase neuronal injury in rats subjected to transient focal cerebral ischemia/reperfusion. Methods Focal cerebral ischemia was induced by intraluminal middle cerebral artery occlusion for 60 min in twenty male Sprague-Dawley rats (250-300 g). Rats were randomized into control group and an ischemic postconditioning group (10 rats per group). The animals of control group had no intervention either before or after MCA occlusion. Ischemic postconditioning was elicited by 3 cycles of 30 s reperfusion interspersed by 10 s ischemia immediately after onset of reperfusion. The infarct ratios, brain edema ratios and motor behavior deficits were analyzed 24 hrs after ischemic insult. Caspase-3 reactive cells and cells showing heat shock protein 70 activity were counted in the caudoputamen and frontoparietal cortex. Results Ischemic postconditiong did not reduce infarct size and brain edema ratios compared to control group. Neurologic scores were not significantly different between groups. The number of caspase-3 reactive cells in the ischemic postconditioning group was not significantly different than the value of the control group in the caudoputamen and frontoparietal cortex. The number of cells showing heat shock protein 70 activity was not significantly different than the control group, as well. Conclusions These results suggest that ischemic postconditioning may not influence the early brain damage induced by focal cerebral ischemia in rats. PMID:20498797

  12. Left hemisphere regions are critical for language in the face of early left focal brain injury.

    PubMed

    Raja Beharelle, Anjali; Dick, Anthony Steven; Josse, Goulven; Solodkin, Ana; Huttenlocher, Peter R; Levine, Susan C; Small, Steven L

    2010-06-01

    A predominant theory regarding early stroke and its effect on language development, is that early left hemisphere lesions trigger compensatory processes that allow the right hemisphere to assume dominant language functions, and this is thought to underlie the near normal language development observed after early stroke. To test this theory, we used functional magnetic resonance imaging to examine brain activity during category fluency in participants who had sustained pre- or perinatal left hemisphere stroke (n = 25) and in neurologically normal siblings (n = 27). In typically developing children, performance of a category fluency task elicits strong involvement of left frontal and lateral temporal regions and a lesser involvement of right hemisphere structures. In our cohort of atypically developing participants with early stroke, expressive and receptive language skills correlated with activity in the same left inferior frontal regions that support language processing in neurologically normal children. This was true independent of either the amount of brain injury or the extent that the injury was located in classical cortical language processing areas. Participants with bilateral activation in left and right superior temporal-inferior parietal regions had better language function than those with either predominantly left- or right-sided unilateral activation. The advantage conferred by left inferior frontal and bilateral temporal involvement demonstrated in our study supports a strong predisposition for typical neural language organization, despite an intervening injury, and argues against models suggesting that the right hemisphere fully accommodates language function following early injury.

  13. [Utility of diffusion-weighted magnetic resonance imaging in severe focal traumatic brain injuries].

    PubMed

    Prieto-Valderrey, F; Muñiz-Montes, J R; López-García, J A; Villegas-Del Ojo, J; Málaga-Gil, J; Galván-García, R

    2013-01-01

    To describe the apparent diffusion coefficient (ADC) in a series of severe traumatic brain injuries, their clinical and outcome features, and possible implications. A descriptive, observational case-series study was carried out. Patients with severe traumatic brain injuries (TBIs) admitted to the ICU were subjected to MRI study using a 1.5 T scanner. Diffusion-weighted images (DWMR) were obtained using the following echo-planar pulse sequence: TR 10000 ms, TE 126.9 ms, with b values 1000 s/mm2 in the three spatial dimensions. Combining the three sets of images, an isotropic image conforming a map of the mean ADCs was obtained. DWMR was performed in 23 patients with severe TBI admitted to the ICU between 2001 and 2004. In the MR images we selected 26 regions of interest (ROIs) where ADC was recorded. We observed a clear increase in diffusion in non-treated space-occupying lesions versus other types of injuries and the normal values. A poorer outcome was recorded in patients with lower ADC values. Mean ADC in the lesions was greater than the normal values and greater in contusions than in other types of injuries, as an expression of extracellular edema. ADCs were decreased in patients with a poor outcome, suggesting an association between ischemia and the patient prognosis. Copyright © 2011 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  14. Development of a Human Head FE Model and Impact Simulation on the Focal Brain Injury

    NASA Astrophysics Data System (ADS)

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

    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 (512×512 pixels) and made of 1.22 million parallelepiped finite elements with 10 anatomical tissue properties such as scalp, 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 1) it is based on the explicit time integration method and 2) it uses the one point integration method to evaluate the equivalent nodal forces with the hourglass control proposed by Flanagan and Belytschko(1) and 3) it utilizes the parallel computation system based on MPI. In order to verify the developed model, the head impact experiment for a cadaver by Nahum et al.(2) was simulated. The calculated results showed good agreement with the experimental ones. A front and rear impact analyses were also performed to discuss on the characteristic measure of the brain injury, in which the von-Mises stress was high in the frontal lobe in both of the analyses because of the large deformations of a frontal cranial base. This result suggests that the von-Mises stress can be a good measure of the brain injury since it is empirically well known that the frontal lobe tends to get injured regardless of the impact positions.

  15. The terminal pathway of the complement system is activated in focal penetrating but not in mild diffuse traumatic brain injury.

    PubMed

    Rostami, Elham; Davidsson, Johan; Gyorgy, Andrea; Agoston, Denes V; Risling, Mårten; Bellander, Bo-Michael

    2013-12-01

    The complement system plays an important role in the inflammatory response activated by many central nervous system disorders. However, its significance in traumatic diffuse traumatic axonal injury (TAI) is not fully known. Here we analyze the complement activity in two rat models of traumatic brain injury (TBI); a focal penetration injury (pen-TBI) and a rotational acceleration injury (rot-TBI) that leads to a mild TAI. We used in situ hybridization to examine the distribution of mRNA for C1q and C3 and immunohistochemistry to examine the presence of the C3 protein and C5b-9 complex at 1-5 days after injury. We found a time-dependent complement activity in both models. However, the responses caused by the two models were different. We detected C5b-9 surrounding the cavity in pen-TBI, but C5b-9 was not found in the rot-TBI. Our findings suggest that the terminal complement pathway is progressed to the formation of the C5b-9 membrane attack complex only in the penetrating TBI but not in isolated TAI model. This indicates that the complement activation does not lead to membrane-damaging effects and a subsequent secondary axotomy in TAI by the terminal complex C5b-9. The role of complement activation in TAI is unclear, but might indicate an alternative function following rot-TBI, such as opsonizing the synapses for elimination.

  16. [Cerebral activation during Stroop's test in a case of early focal brain injury].

    PubMed

    Salgado-Pineda, P; Román, F; Sánchez-Navarro, J P; López-Hernández, F; Bargalló, N; Falcón, C; Ramírez-Ruiz, B; Caldú-Ferrús, X; Martínez-Lage, J

    Functional magnetic resonance imaging (fMRI) offers an important advantage over other functional neuroimaging techniques used with children because of its harmlessness. Previous studies conducted with adults with alexia suggested two ways the brain can reorganise reading after a brain injury affecting the left hemisphere, one contralateral and the other ipsilateral. We describe a study carried out using fMRI of a 10 year old girl with an injury to the left hemisphere caused by a fishing harpoon when she was 6 years old. As a result of the accident the girl presented a right hemiparesia. The girl s parents and teachers also reported difficulties in the acquisition of reading writing and arithmetic, as well as a certain degree of attentional deficit. An fMRI exploration was performed while the girl was doing the Stroop test. The structural MR images showed left hemisphere cortical lesions in the orbital and angular gyrus regions, in addition to the caudate and putamen nuclei, and in the inferior longitudinal bundle. The fRMI revealed a strong overactivation of the right dorsolateral frontal cortex, in the evaluation of interference, and activations of the right angular and bilateral supramarginal gyri, in the evaluation of word reading. The functional study suggests the existence of a reorganisation of reading that is both intra and inter hemispheric.

  17. Repeated mild traumatic brain injury causes focal response in lateral septum and hippocampus

    PubMed Central

    Acabchuk, Rebecca; Briggs, Denise I; Angoa-Pérez, Mariana; Powers, Meghan; Wolferz, Richard; Soloway, Melanie; Stern, Mai; Talbot, Lillian R; Kuhn, Donald M; Conover, Joanne C

    2016-01-01

    Aim To advance our understanding of regional and temporal cellular responses to repeated mild traumatic brain injury (rmTBI), we used a mouse model of rmTBI that incorporated acceleration, deceleration and rotational forces. Materials & methods A modified weight-drop method was used to compare two inter-injury intervals, rmTBI-short (five hits delivered over 3 days) and rmTBI-long (five hits delivered over 15 days). Regional investigations of forebrain and midbrain histological alterations were performed at three post-injury time points (immediate, 2 weeks and 6 weeks). Results The rmTBI-short protocol generated an immediate, localized microglial and astroglial response in the dorsolateral septum and hippocampus, with the astroglial response persisting in the dorsolateral septum. The rmTBI-long protocol showed only a transitory astroglial response in the dorsolateral septum. Conclusion Our results indicate that the lateral septum and hippocampus are particularly vulnerable regions in rmTBI, possibly contributing to memory and emotional impairments associated with repeated concussions. PMID:28078102

  18. Nafamostat mesilate attenuates transient focal ischemia/reperfusion-induced brain injury via the inhibition of endoplasmic reticulum stress.

    PubMed

    Kwon, Sun Kwan; Ahn, Moonsang; Song, Hee-Jung; Kang, Shin Kwang; Jung, Saet-Byel; Harsha, Nagar; Jee, Sungju; Moon, Jae Young; Suh, Kwang-Sun; Lee, Sang Do; Jeon, Byeong Hwa; Kim, Dong Woon; Kim, Cuk-Seong

    2015-11-19

    Nafamostat mesilate (NM), a serine protease inhibitor, has a broad range of clinical applications that include use as an anticoagulant during hemodialysis in cerebral hemorrhage patients, as a hemoperfusion anticoagulant for patients with intravascular coagulation, hemorrhagic lesions, and hemorrhagic tendencies, and for the improvement of acute pancreatitis. However, the effects of NM on acute cerebral ischemia have yet to be investigated. Thus, the present study utilized a rat model in which transient middle cerebral artery occlusion (MCAO) was used to induce ischemic injury to investigate the effects of NM on infarct volume and histological and biological changes. NM (1mg/kg) was intravenously administered prior to and after the MCAO procedure. Compared to control rats, the administration of NM significantly decreased infarct size and the extent of brain edema after the induction of focal ischemia via MCAO. Additionally, NM treatment attenuated MCAO-induced neuronal degeneration and activation of microglia and astrocytes. NM treatment also inhibited the MCAO-induced expression levels of glucose-regulated protein 78 (GRP78), CATT/EBP homologous protein (CHOP), and p-eukaryotic initiation factor 2α (eIF2α), which are endoplasmic reticulum (ER) stress markers, in the cerebral cortex. The present findings demonstrate that NM exerts neuroprotective effects in the brain following focal ischemia via, at least in part, the inhibition of ER stress.

  19. YiQiFuMai powder injection ameliorates blood-brain barrier dysfunction and brain edema after focal cerebral ischemia-reperfusion injury in mice.

    PubMed

    Cao, Guosheng; Ye, Xinyi; Xu, Yingqiong; Yin, Mingzhu; Chen, Honglin; Kou, Junping; Yu, Boyang

    2016-01-01

    YiQiFuMai powder injection (YQFM) is a modern preparation derived from the traditional Chinese medicine Sheng-Mai-San. YQFM is widely used in clinical practice in the People's Republic of China, mainly for the treatment of microcirculatory disturbance-related diseases. However, little is known about its role in animals with ischemic stroke. The aim of this study was to examine the effect of YQFM on brain edema and blood-brain barrier (BBB) dysfunction induced by cerebral ischemia-reperfusion (I/R) injury. Male C57BL/6J mice underwent right middle cerebral artery occlusion for 1 hour with a subsequent 24-hour reperfusion to produce I/R injury. YQFM (three doses: 0.336, 0.671, and 1.342 g/kg) was then given intraperitoneally (IP). The results demonstrated that YQFM significantly decreased infarct size, improved neurological deficits, reduced brain water content, and increased cerebral blood flow after I/R injury. 18F-fluorodeoxyglucose micro-positron emission tomography imaging and hematoxylin and eosin staining results indicated that YQFM is able to ameliorate brain metabolism and histopathological damage after I/R. Moreover, YQFM administration reduced BBB leakage and upregulated the expression of zona occludens-1 (ZO-1) and occludin, which was confirmed by Evans Blue extravasation, Western blotting, and immunofluorescence assay. Our findings suggest that YQFM provides protection against focal cerebral I/R injury in mice, possibly by improving BBB dysfunction via upregulation of the expression of tight junction proteins.

  20. The effect of focal brain injury on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of Alzheimer's disease.

    PubMed

    Collins, Jessica M; King, Anna E; Woodhouse, Adele; Kirkcaldie, Matthew T K; Vickers, James C

    2015-05-01

    Traumatic brain injury is a risk factor for Alzheimer's disease (AD), however the effect of such neural damage on the onset and progression of beta-amyloid (Aβ) plaque pathology is not well understood. This study utilized an in vivo model of focal brain injury to examine how localized damage may acutely affect the onset and progression of Aβ plaque deposition as well as inflammatory and synaptic changes, in the APP/PS1 (APPSWE, PSEN1dE9) transgenic model of AD relative to wild-type (Wt) mice. Acute focal brain injury in 3- and 9-month-old APP/PS1 and Wt mice was induced by insertion of a needle into the somatosensory neocortex, as compared to sham surgery, and examined at 24h and 7d post-injury (PI). Focal brain injury did not induce thioflavine-S stained or (pan-Aβ antibody) MOAB-2-labeled plaques at either 24h or 7d PI in 3-month-old APP/PS1 mice or Wt mice. Nine-month-old APP/PS1 mice demonstrate cortical Aβ plaques but focal injury had no statistically significant (p>0.05) effect on thioflavine-S or MOAB-2 plaque load surrounding the injury site at 24h PI or 7d PI. There was a significant (p<0.001) increase in cross-sectional cortical area occupied by Iba-1 positive microglia in injured mice compared to sham animals, however this response did not differ between APP/PS1 and Wt mice (p>0.05). For both Wt and APP/PS1 mice alike, synaptophysin puncta near the injury site were significantly reduced 24h PI (compared to sites distant to the injury and the corresponding area in sham mice; p<0.01), but not after 7d PI (p>0.05). There was no significant effect of genotype on this response (p>0.05). These results indicate that focal brain injury and the associated microglial response do not acutely alter Aβ plaque deposition in the APP/PS1 mouse model. Furthermore the current study demonstrated that the brains of both Wt and APP/PS1 mice are capable of recovering lost synaptophysin immunoreactivity post-injury, the latter in the presence of Aβ plaque pathology that

  1. YiQiFuMai powder injection ameliorates blood–brain barrier dysfunction and brain edema after focal cerebral ischemia–reperfusion injury in mice

    PubMed Central

    Cao, Guosheng; Ye, Xinyi; Xu, Yingqiong; Yin, Mingzhu; Chen, Honglin; Kou, Junping; Yu, Boyang

    2016-01-01

    YiQiFuMai powder injection (YQFM) is a modern preparation derived from the traditional Chinese medicine Sheng-Mai-San. YQFM is widely used in clinical practice in the People’s Republic of China, mainly for the treatment of microcirculatory disturbance-related diseases. However, little is known about its role in animals with ischemic stroke. The aim of this study was to examine the effect of YQFM on brain edema and blood–brain barrier (BBB) dysfunction induced by cerebral ischemia–reperfusion (I/R) injury. Male C57BL/6J mice underwent right middle cerebral artery occlusion for 1 hour with a subsequent 24-hour reperfusion to produce I/R injury. YQFM (three doses: 0.336, 0.671, and 1.342 g/kg) was then given intraperitoneally (IP). The results demonstrated that YQFM significantly decreased infarct size, improved neurological deficits, reduced brain water content, and increased cerebral blood flow after I/R injury. 18F-fluorodeoxyglucose micro-positron emission tomography imaging and hematoxylin and eosin staining results indicated that YQFM is able to ameliorate brain metabolism and histopathological damage after I/R. Moreover, YQFM administration reduced BBB leakage and upregulated the expression of zona occludens-1 (ZO-1) and occludin, which was confirmed by Evans Blue extravasation, Western blotting, and immunofluorescence assay. Our findings suggest that YQFM provides protection against focal cerebral I/R injury in mice, possibly by improving BBB dysfunction via upregulation of the expression of tight junction proteins. PMID:26834461

  2. "Frog, Where Are You?" Narratives in Children with Specific Language Impairment, Early Focal Brain Injury, and Williams Syndrome

    ERIC Educational Resources Information Center

    Reilly, Judy; Losh, Molly; Bellugi, Ursula; Wulfeck, Beverly

    2004-01-01

    In this cross-population study, we use narratives as a context to investigate language development in children from 4 to 12 years of age from three experimental groups: children with early unilateral focal brain damage (FL; N=52); children with specific language impairment (SLI; N=44); children with Williams syndrome (WMS; N=36), and typically…

  3. Productive Use of the English Past Tense in Children with Focal Brain Injury and Specific Language Impairment

    ERIC Educational Resources Information Center

    Marchman, Virginia A.; Saccuman, Cristina; Wulfeck, Beverly

    2004-01-01

    In this study, 22 children with early left hemisphere (LHD) or right hemisphere (RHD) focal brain lesions (FL, n=14 LHD, n=8 RHD) were administered an English past tense elicitation test (M=6.5 years). Proportion correct and frequency of overregularization and zero-marking errors were compared to age-matched samples of children with specific…

  4. A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

    PubMed Central

    Guley, Natalie H.; Rogers, Joshua T.; Del Mar, Nobel A.; Deng, Yunping; Islam, Rafiqul M.; D'Surney, Lauren; Ferrell, Jessica; Deng, Bowei; Hines-Beard, Jessica; Bu, Wei; Ren, Huiling; Elberger, Andrea J.; Marchetta, Jeffrey G.; Rex, Tonia S.; Honig, Marcia G.

    2016-01-01

    Abstract Mild traumatic brain injury (TBI) from focal head impact is the most common form of TBI in humans. Animal models, however, typically use direct impact to the exposed dura or skull, or blast to the entire head. We present a detailed characterization of a novel overpressure blast system to create focal closed-head mild TBI in mice. A high-pressure air pulse limited to a 7.5 mm diameter area on the left side of the head overlying the forebrain is delivered to anesthetized mice. The mouse eyes and ears are shielded, and its head and body are cushioned to minimize movement. This approach creates mild TBI by a pressure wave that acts on the brain, with minimal accompanying head acceleration-deceleration. A single 20-psi blast yields no functional deficits or brain injury, while a single 25–40 psi blast yields only slight motor deficits and brain damage. By contrast, a single 50–60 psi blast produces significant visual, motor, and neuropsychiatric impairments and axonal damage and microglial activation in major fiber tracts, but no contusive brain injury. This model thus reproduces the widespread axonal injury and functional impairments characteristic of closed-head mild TBI, without the complications of systemic or ocular blast effects or head acceleration that typically occur in other blast or impact models of closed-skull mild TBI. Accordingly, our model provides a simple way to examine the biomechanics, pathophysiology, and functional deficits that result from TBI and can serve as a reliable platform for testing therapies that reduce brain pathology and deficits. PMID:26414413

  5. A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice.

    PubMed

    Guley, Natalie H; Rogers, Joshua T; Del Mar, Nobel A; Deng, Yunping; Islam, Rafiqul M; D'Surney, Lauren; Ferrell, Jessica; Deng, Bowei; Hines-Beard, Jessica; Bu, Wei; Ren, Huiling; Elberger, Andrea J; Marchetta, Jeffrey G; Rex, Tonia S; Honig, Marcia G; Reiner, Anton

    2016-02-15

    Mild traumatic brain injury (TBI) from focal head impact is the most common form of TBI in humans. Animal models, however, typically use direct impact to the exposed dura or skull, or blast to the entire head. We present a detailed characterization of a novel overpressure blast system to create focal closed-head mild TBI in mice. A high-pressure air pulse limited to a 7.5 mm diameter area on the left side of the head overlying the forebrain is delivered to anesthetized mice. The mouse eyes and ears are shielded, and its head and body are cushioned to minimize movement. This approach creates mild TBI by a pressure wave that acts on the brain, with minimal accompanying head acceleration-deceleration. A single 20-psi blast yields no functional deficits or brain injury, while a single 25-40 psi blast yields only slight motor deficits and brain damage. By contrast, a single 50-60 psi blast produces significant visual, motor, and neuropsychiatric impairments and axonal damage and microglial activation in major fiber tracts, but no contusive brain injury. This model thus reproduces the widespread axonal injury and functional impairments characteristic of closed-head mild TBI, without the complications of systemic or ocular blast effects or head acceleration that typically occur in other blast or impact models of closed-skull mild TBI. Accordingly, our model provides a simple way to examine the biomechanics, pathophysiology, and functional deficits that result from TBI and can serve as a reliable platform for testing therapies that reduce brain pathology and deficits.

  6. A Type-II Positive Allosteric Modulator of α7 nAChRs Reduces Brain Injury and Improves Neurological Function after Focal Cerebral Ischemia in Rats

    PubMed Central

    Sun, Fen; Jin, Kunlin; Uteshev, Victor V.

    2013-01-01

    In the absence of clinically-efficacious therapies for ischemic stroke there is a critical need for development of new therapeutic concepts and approaches for prevention of brain injury secondary to cerebral ischemia. This study tests the hypothesis that administration of PNU-120596, a type-II positive allosteric modulator (PAM-II) of α7 nicotinic acetylcholine receptors (nAChRs), as long as 6 hours after the onset of focal cerebral ischemia significantly reduces brain injury and neurological deficits in an animal model of ischemic stroke. Focal cerebral ischemia was induced by a transient (90 min) middle cerebral artery occlusion (MCAO). Animals were then subdivided into two groups and injected intravenously (i.v.) 6 hours post-MCAO with either 1 mg/kg PNU-120596 (treated group) or vehicle only (untreated group). Measurements of cerebral infarct volumes and neurological behavioral tests were performed 24 hrs post-MCAO. PNU-120596 significantly reduced cerebral infarct volume and improved neurological function as evidenced by the results of Bederson, rolling cylinder and ladder rung walking tests. These results forecast a high therapeutic potential for PAMs-II as effective recruiters and activators of endogenous α7 nAChR-dependent cholinergic pathways to reduce brain injury and improve neurological function after cerebral ischemic stroke. PMID:23951360

  7. Indices of impaired self-awareness in traumatic brain injury patients with focal frontal lesions and executive deficits: implications for outcome measurement.

    PubMed

    Spikman, Jacoba M; van der Naalt, Joukje

    2010-07-01

    In patients with moderate to severe traumatic brain injury (TBI), impairments of self-awareness are frequently found and associated with worse functional outcome and poor compliance with rehabilitation. The aim of this study was to investigate whether indications of impaired self-awareness could be found in TBI patients with frontal lesions and executive function deficits. Twenty-two TBI patients with focal frontal injuries were compared to 29 TBI patients without focal frontal injuries visible on neuroimaging. No differences were found on several outcome measures, including the Glasgow Outcome Scale-Extended (GOS-E), the Differential Outcome Scale (DOS), and return to work (RTW), although the frontal injury patients were more severely injured as indicated by the Glasgow Coma Scale (GCS) and duration of post-traumatic amnesia (PTA), and had impaired performance on a neuropsychological test of executive functioning. Even more so, the frontal injury group had a significantly lower score on the Sickness Impact Profile (SIP), indicating that they had fewer complaints than the patients without frontal injury, and scored significantly higher on the percentage of recovery (PoR) score, which expresses the extent of recovery as a percentage of their previous level of functioning. In contrast to the non-frontal-injury group, their PoR scores were not related to RTW, reflecting an erroneous perception of their actual working status. The positive results on these different outcome measures, which are partly or entirely self-reported, were seen as an indication of an impaired self-evaluative ability in the frontal injury patients. To determine outcome in a patient with frontal injuries and executive dysfunction, the judgment of several relevant other persons in the patient's life (e.g., partners, therapists, and employers) of the patient's daily life functioning should be sought.

  8. Differences in visual vs. verbal memory impairments as a result of focal temporal lobe damage in patients with traumatic brain injury.

    PubMed

    Ariza, Mar; Pueyo, Roser; Junqué, Carme; Mataró, María; Poca, María Antonia; Mena, Maria Pau; Sahuquillo, Juan

    2006-09-01

    The aim of the present study was to determine whether the type of lesion in a sample of moderate and severe traumatic brain injury (TBI) was related to material-specific memory impairment. Fifty-nine patients with TBI were classified into three groups according to whether the site of the lesion was right temporal, left temporal or diffuse. Six-months post-injury, visual (Warrington's Facial Recognition Memory Test and Rey's Complex Figure Test) and verbal (Rey's Auditory Verbal Learning Test) memories were assessed. Visual memory deficits assessed by facial memory were associated with right temporal lobe lesion, whereas verbal memory performance assessed with a list of words was related to left temporal lobe lesion. The group with diffuse injury showed both verbal and visual memory impairment. These results suggest a material-specific memory impairment in moderate and severe TBI after focal temporal lesions and a non-specific memory impairment after diffuse damage.

  9. Cilostazol attenuates ischemic brain injury and enhances neurogenesis in the subventricular zone of adult mice after transient focal cerebral ischemia.

    PubMed

    Tanaka, Y; Tanaka, R; Liu, M; Hattori, N; Urabe, T

    2010-12-29

    Evidence suggests that neurogenesis occurs in the adult mammalian brain, and that various stimuli, for example, ischemia/hypoxia, enhance the generation of neural progenitor cells in the subventricular zone (SVZ) and their migration into the olfactory bulb. In a mouse stroke model, focal ischemia results in activation of neural progenitor cells followed by their migration into the ischemic lesion. The present study assessed the in vivo effects of cilostazol, a type 3 phosphodiesterase inhibitor known to activate the cAMP-responsive element binding protein (CREB) signaling, on neurogenesis in the ipsilateral SVZ and peri-infarct area in a mouse model of transient middle cerebral artery occlusion. Mice were divided into sham operated (n=12), vehicle- (n=18) and cilostazol-treated (n=18) groups. Sections stained for 5-bromodeoxyuridine (BrdU) and several neuronal and a glial markers were analyzed at post-ischemia days 1, 3 and 7. Cilostazol reduced brain ischemic volume (P<0.05) and induced earlier recovery of neurologic deficit (P<0.05). Cilostazol significantly increased the density of BrdU-positive newly-formed cells in the SVZ compared with the vehicle group without ischemia. Increased density of doublecortin (DCX)-positive and BrdU/DCX-double positive neural progenitor cells was noted in the ipsilateral SVZ and peri-infarct area at 3 and 7 days after focal ischemia compared with the vehicle group (P<0.05). Cilostazol increased DCX-positive phosphorylated CREB (pCREB)-expressing neural progenitor cells, and increased brain derived neurotrophic factor (BDNF)-expressing astrocytes in the ipsilateral SVZ and peri-infarct area. The results indicated that cilostazol enhanced neural progenitor cell generation in both ipsilateral SVZ and peri-infarct area through CREB-mediated signaling pathway after focal ischemia.

  10. Effects of salidroside pretreatment on expression of tumor necrosis factor-alpha and permeability of blood brain barrier in rat model of focal cerebralischemia-reperfusion injury.

    PubMed

    Han, Tian

    2013-02-01

    To observe changes in expression of tumor necrosis factor (TNF)-alpha and permeability of blood brain barrier after salidroside pretreatment in rats with injury induced by focal cerebralischemia-reperfusion. Forty-five male SD rats were randomly divided into three groups (n=15): control group, ischemia-reperfusion (IR) model group, and salidroside pretreatment group. Before the IR model establishment, the rats in the salidroside pretreatment group were intraperitoneally administered with salidroside at a dose of 24 mg/(kg·d) for 7 d. After 30 min post the last administration, the IR model was induced by occlusion of middle cerebral artery with a filament. After 24 h post the operation, the water content and Evens blue content in the ischemia cerebral hemisphere were determined, and the level of TNF-alpha mRNA was detected by the semi-quantitative RT-PCR. Compared with the IR model group, the salidroside pretreatment group had significantly lower (P<0.05) water content and Evens blue content in the ischemia cerebral hemisphere and also had significantly lower (P<0.05) level of TNF-alpha in the ischemic cerebral cortex tissue. The salidroside pretreatment alleviated the focal cerebralischemia-reperfusion injury in the rat model, possibly by decreasing the permeability of blood brain barrier, attenuating brain edema and reducing TNF-alpha expression. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  11. Failure of intravenous or intracardiac delivery of mesenchymal stromal cells to improve outcomes after focal traumatic brain injury in the female rat.

    PubMed

    Turtzo, L Christine; Budde, Matthew D; Dean, Dana D; Gold, Eric M; Lewis, Bobbi K; Janes, Lindsay; Lescher, Jacob; Coppola, Tiziana; Yarnell, Angela; Grunberg, Neil E; Frank, Joseph A

    2015-01-01

    Mesenchymal stromal cells secrete a variety of anti-inflammatory factors and may provide a regenerative medicine option for the treatment of traumatic brain injury. The present study investigates the efficacy of multiple intravenous or intracardiac administrations of rat mesenchymal stromal cells or human mesenchymal stromal cells in female rats after controlled cortical impact by in vivo MRI, neurobehavior, and histopathology evaluation. Neither intravenous nor intracardiac administration of mesenchymal stromal cells derived from either rats or humans improved MRI measures of lesion volume or neurobehavioral outcome compared to saline treatment. Few mesenchymal stromal cells (<0.0005% of injected dose) were found within 3 days of last dosage at the site of injury after either delivery route, with no mesenchymal stromal cells being detectable in brain at 30 or 56 days post-injury. These findings suggest that non-autologous mesenchymal stromal cells therapy via intravenous or intracardiac administration is not a promising treatment after focal contusion traumatic brain injury in this female rodent model.

  12. [Changes of focal and brainstem neurologic signs in patients with traumatic brain injury and their dependence on the -675 4G/5G polymorphism in the PAI-1 gene].

    PubMed

    Potapov, O; Kmyta, O

    2014-09-01

    Regressive course of neurological signs and symptoms is an important factor of evaluating the clinical course and treatment efficacy of traumatic brain injury. This article presents changes evaluation of focal and brainstem symptoms in 200 patients with traumatic brain injury, and determines the association between these changes and the -675 4G/5G polymorphism in the PAI-1 gene. We have found a connection between 4G/4G and 4G/5G genotypes for the studied polymorphism and the changes of focal and brainstem symptoms in patients with traumatic brain injury. Thus, we have demonstrated that the clinical course of traumatic brain injury is influenced by the -675 4G/5G polymorphism in the PAI-1 gene.

  13. Mild Traumatic Brain Injury

    MedlinePlus

    ... Questions Glossary Contact Us Visitor Feedback mild Traumatic Brain Injury mild Traumatic Brain Injury VIDEO STORIES What is TBI Measuring Severity ... most common deployment injuries is a mild Traumatic Brain Injury (TBI). A mild TBI is an injury ...

  14. Antioxidant CR-6 protects against reperfusion injury after a transient episode of focal brain ischemia in rats

    PubMed Central

    Pérez-Asensio, Fernando J; de la Rosa, Xavier; Jiménez-Altayó, Francesc; Gorina, Roser; Martínez, Emili; Messeguer, Àngel; Vila, Elisabet; Chamorro, Àngel; Planas, Anna M

    2010-01-01

    Oxidative and nitrosative stress are targets for intervention after ischemia/reperfusion. The aim of this study was to explore the effect of CR-6, a vitamin-E analogue that is antioxidant and scavenger of nitrogen-reactive species. Sprague–Dawley rats had the middle cerebral artery (MCA) occluded either for 90 mins or permanently. Cortical perfusion was continuously monitored by laser–Doppler flowmetry. CR-6 (100 mg/kg) was administered orally either at 2 and 8 h after MCA occlusion, or at 2 h only. Infarct volume, neurological deficit, and signs of reperfusion injury were evaluated. CR-6 was detected in plasma and brain by HPLC. CR-6 reduced glutathione consumption in the ischemic brain and superoxide generation in the isolated MCA. CR-6 decreased infarct volume and attenuated the neurological deficit at 1 and 7 days after ischemia/reperfusion, but not after permanent ischemia. Immediately after reperfusion, cortical blood flow values returned to their baseline (±20%) in several animals, whereas others showed hyper-perfusion (>20% of baseline). Reactive hyperemia was associated with adverse events such as increased cortical BBB leakage, edema, protein nitrotyrosination, COX-2 expression, and neutrophil accumulation; and with a poorer outcome, and CR-6 attenuated these effects. In conclusion, oral CR-6 administration after transient ischemia protects the brain from reperfusion injury. PMID:19904289

  15. Functional and histological outcome after focal traumatic brain injury is not improved in conditional EphA4 knockout mice.

    PubMed

    Hånell, Anders; Clausen, Fredrik; Djupsjö, Anders; Vallstedt, Anna; Patra, Kalicharan; Israelsson, Charlotte; Larhammar, Martin; Björk, Maria; Paixão, Sónia; Kullander, Klas; Marklund, Niklas

    2012-11-20

    We investigated the role of the axon guidance molecule EphA4 following traumatic brain injury (TBI) in mice. Neutralization of EphA4 improved motor function and axonal regeneration following experimental spinal cord injury (SCI). We hypothesized that genetic absence of EphA4 could improve functional and histological outcome following TBI. Using qRT-PCR in wild-type (WT) mice, we evaluated the EphA4 mRNA levels following controlled cortical impact (CCI) TBI or sham injury and found it to be downregulated in the hippocampus (p<0.05) but not the cortex ipsilateral to the injury at 24 h post-injury. Next, we evaluated the behavioral and histological outcome following CCI using WT mice and Emx1-Cre-driven conditional knockout (cKO) mice. In cKO mice, EphA4 was completely absent in the hippocampus and markedly reduced in the cortical regions from embryonic day 16, which was confirmed using Western blot analysis. EphA4 cKO mice had similar learning and memory abilities at 3 weeks post-TBI compared to WT controls, although brain-injured animals performed worse than sham-injured controls (p<0.05). EphA4 cKO mice performed similarly to WT mice in the rotarod and cylinder tests of motor function up to 29 days post-injury. TBI increased cortical and hippocampal astrocytosis (GFAP immunohistochemistry, p<0.05) and hippocampal sprouting (Timm stain, p<0.05) and induced a marked loss of hemispheric tissue (p<0.05). EphA4 cKO did not alter the histological outcome. Although our results may argue against a beneficial role for EphA4 in the recovery process following TBI, further studies including post-injury pharmacological neutralization of EphA4 are needed to define the role for EphA4 following TBI.

  16. Attenuation of microglial activation with minocycline is not associated with changes in neurogenesis after focal traumatic brain injury in adult mice.

    PubMed

    Ng, Si Yun; Semple, Bridgette D; Morganti-Kossmann, M Cristina; Bye, Nicole

    2012-05-01

    Neurogenesis is stimulated following injury to the adult brain and could potentially contribute to tissue repair. However, evidence suggests that microglia activated in response to injury are detrimental to the survival of new neurons, thus limiting the neurogenic response. The aim of this study was to determine the effect of the anti-inflammatory drug minocycline on neurogenesis and functional recovery after a closed head injury model of focal traumatic brain injury (TBI). Beginning 30 min after trauma, minocycline was administered for up to 2 weeks and bromodeoxyuridine was given on days 1-4 to label proliferating cells. Neurological outcome and motor function were evaluated over 6 weeks using the Neurological Severity Score (NSS) and ledged beam task. Microglial activation was assessed in the pericontusional cortex and hippocampus at 1 week post-trauma, using immunohistochemistry to detect F4/80. Following immunolabeling of bromodeoxyuridine, double-cortin, and NeuN, cells undergoing distinct stages of neurogenesis, including proliferation, neuronal differentiation, neuroblast migration, and long-term survival, were quantified at 1 and 6 weeks in the hippocampal dentate gyrus, as well as in the subventricular zone of the lateral ventricles and the pericontusional cortex. Our results show that minocycline successfully reduced microglial activation and promoted early neurological recovery that was sustained over 6 weeks. We also show for the first time in the closed head injury model, that early stages of neurogenesis were stimulated in the hippocampus and subventricular zone; however, no increase in new mature neurons occurred. Contrary to our hypothesis, despite the attenuation of activated microglia, minocycline did not support neurogenesis in the hippocampus, lateral ventricles, or pericontusional cortex, with none of the neurogenic stages being affected by treatment. These data provide evidence that a general suppression of microglial activation is

  17. Musical anhedonia after focal brain damage.

    PubMed

    Belfi, Amy M; Evans, Erin; Heskje, Jonah; Bruss, Joel; Tranel, Daniel

    2017-03-01

    People listen to music because it is pleasurable. However, there are individual differences in the reward value of music. At the extreme low end of this continuum, individuals who derive no pleasure from music are said to have 'musical anhedonia.' Cases of acquired musical anhedonia following focal brain damage are rare, with only a handful having been reported in the scientific literature. Here, we surveyed a large sample of patients with focal brain damage to identify the frequency, specificity, and neural correlates of acquired musical anhedonia. Participants completed the Musical anhedonia Questionnaire and the Barcelona Music Reward Questionnaire (Mas-Herrero et al., 2013) to assess changes in musical enjoyment and reward following brain injury. Neuroanatomical data were analyzed with a proportional MAP-3 method to create voxelwise lesion proportion difference maps. No clear or consistent neuroanatomical correlates of musical anhedonia were identified. One patient with damage to the right-hemisphere putamen and internal capsule displayed specific and severe acquired musical anhedonia. These findings indicate that acquired musical anhedonia is very uncommon, a result which is consistent with the fact that only a small number of such cases have been reported in the literature. This rarity could have positive implications for the therapeutic potentialities of music in patients with severe neurological disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Focal brain inflammation and autism.

    PubMed

    Theoharides, Theoharis C; Asadi, Shahrzad; Patel, Arti B

    2013-04-09

    Increasing evidence indicates that brain inflammation is involved in the pathogenesis of neuropsychiatric diseases. Autism spectrum disorders (ASD) are characterized by social and learning disabilities that affect as many as 1/80 children in the USA. There is still no definitive pathogenesis or reliable biomarkers for ASD, thus significantly curtailing the development of effective therapies. Many children with ASD regress at about age 3 years, often after a specific event such as reaction to vaccination, infection, stress or trauma implying some epigenetic triggers, and may constitute a distinct phenotype. ASD children respond disproportionally to stress and are also affected by food and skin allergies. Corticotropin-releasing hormone (CRH) is secreted under stress and together with neurotensin (NT) stimulates mast cells and microglia resulting in focal brain inflammation and neurotoxicity. NT is significantly increased in serum of ASD children along with mitochondrial DNA (mtDNA). NT stimulates mast cell secretion of mtDNA that is misconstrued as an innate pathogen triggering an auto-inflammatory response. The phosphatase and tensin homolog (PTEN) gene mutation, associated with the higher risk of ASD, which leads to hyper-active mammalian target of rapamycin (mTOR) signalling that is crucial for cellular homeostasis. CRH, NT and environmental triggers could hyperstimulate the already activated mTOR, as well as stimulate mast cell and microglia activation and proliferation. The natural flavonoid luteolin inhibits mTOR, mast cells and microglia and could have a significant benefit in ASD.

  19. Brain injury in sports.

    PubMed

    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

  20. Traumatic Brain Injury

    MedlinePlus

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

  1. Time courses of post-injury mitochondrial oxidative damage and respiratory dysfunction and neuronal cytoskeletal degradation in a rat model of focal traumatic brain injury.

    PubMed

    Hill, Rachel L; Singh, Indrapal N; Wang, Juan A; Hall, Edward D

    2017-03-23

    Traumatic brain injury (TBI) results in rapid reactive oxygen species (ROS) production and oxidative damage to essential brain cellular components leading to neuronal dysfunction and cell death. It is increasingly appreciated that a major player in TBI-induced oxidative damage is the reactive nitrogen species (RNS) peroxynitrite (PN) which is produced in large part in injured brain mitochondria. Once formed, PN decomposes into highly reactive free radicals that trigger membrane lipid peroxidation (LP) of polyunsaturated fatty acids (e.g. arachidonic acid) and protein nitration (3-nitrotyrosine, 3-NT) in mitochondria and other cellular membranes causing various functional impairments to mitochondrial oxidative phosphorylation and calcium (Ca(2+)) buffering capacity. The LP also results in the formation of neurotoxic reactive aldehyde byproducts including 4-hydroxynonenal (4-HNE) and propenal (acrolein) which exacerbates ROS/RNS production and oxidative protein damage in the injured brain. Ultimately, this results in intracellular Ca(2+) overload that activates proteolytic degradation of α-spectrin, a neuronal cytoskeletal protein. Therefore, the aim of this study was to establish the temporal evolution of mitochondrial dysfunction, oxidative damage and cytoskeletal degradation in the brain following a severe controlled cortical impact (CCI) TBI in young male adult rats. In mitochondria isolated from an 8 mm diameter cortical punch including the 5 mm wide impact site and their respiratory function studied ex vivo, we observed an initial decrease in complex I and II mitochondrial bioenergetics within 3 h (h). For complex I bioenergetics, this partially recovered by 12-16 h, whereas for complex II respiration the recovery was complete by 12 h. During the first 24 h, there was no evidence of an injury-induced increase in LP or protein nitration in mitochondrial or cellular homogenates. However, beginning at 24 h, there was a gradual secondary decline in complex

  2. Traumatic brain injury-induced sleep disorders

    PubMed Central

    Viola-Saltzman, Mari; Musleh, Camelia

    2016-01-01

    Sleep disturbances are frequently identified following traumatic brain injury, affecting 30%–70% of persons, and often occur after mild head injury. Insomnia, fatigue, and sleepiness are the most frequent sleep complaints after traumatic brain injury. Sleep apnea, narcolepsy, periodic limb movement disorder, and parasomnias may also occur after a head injury. In addition, depression, anxiety, and pain are common brain injury comorbidities with significant influence on sleep quality. Two types of traumatic brain injury that may negatively impact sleep are acceleration/deceleration injuries causing generalized brain damage and contact injuries causing focal brain damage. Polysomnography, multiple sleep latency testing, and/or actigraphy may be utilized to diagnose sleep disorders after a head injury. Depending on the disorder, treatment may include the use of medications, positive airway pressure, and/or behavioral modifications. Unfortunately, the treatment of sleep disorders associated with traumatic brain injury may not improve neuropsychological function or sleepiness. PMID:26929626

  3. Magnetization transfer and T2 quantitation in normal appearing cortical gray matter and white matter adjacent to focal abnormality in patients with traumatic brain injury.

    PubMed

    Kumar, Rajesh; Gupta, Rakesh K; Rao, Sajja B; Chawla, Sanjeev; Husain, Mazhar; Rathore, Ram K S

    2003-10-01

    Traumatic brain injury (TBI) is one of the commonest causes of morbidity and mortality in the developed countries with posttraumatic epilepsy and functional disability being its major sequelae. The purpose of this study was to test the hypothesis whether the normal appearing adjacent gray and white matter regions on T2 and T1 weighted magnetization transfer (MT) weighted images show any abnormality on quantitative imaging in patients with TBI. A total of 51 patients with TBI and 10 normal subjects were included in this study. There were significant differences in T2 and MT ratio values of T2 weighted and T1 weighted MT normal appearing gray matter regions adjacent to focal image abnormality compared to normal gray matter regions in the normal individuals as corresponding contralateral regions of the TBI patient's group (p < 0.05). However the adjoining normal appearing white matter quantitative values did not show any significant change compared to the corresponding contralateral normal white matter values. We conclude that quantitative T2 and MT ratio values provide additional abnormality in patients with TBI that is not discernable on conventional T2 weighted and T1 weighted MT imaging especially in gray matter. This additional information may be of value in overall management of these patients with TBI.

  4. Focal neuronal damage in patients with neuropsychological impairment after diffuse traumatic brain injury: evaluation using ¹¹C-flumazenil positron emission tomography with statistical image analysis.

    PubMed

    Kawai, Nobuyuki; Maeda, Yukito; Kudomi, Nobuyuki; Yamamoto, Yuka; Nishiyama, Yoshihiro; Tamiya, Takashi

    2010-12-01

    This study was conducted to identify the regional neuronal damage occurring in patients with neuropsychological impairment following diffuse traumatic brain injury (TBI) compared with normal control subjects. In addition, measures of the neuropsychological tests were correlated with regional ¹¹C-flumazenil (FMZ) binding potential (BP) reductions to clarify the relationship between cognitive impairment and regional neuronal damage. We performed ¹¹C-flumazenil positron emission tomography (FMZ-PET) studies using three-dimensional stereotactic surface projection (3D-SSP) statistical image analysis in eight diffuse axonal injury (DAI) patients (mean age 29.1 ± 11.1 years, range 19-46 years). All patients underwent assessment with the Wechsler Adult Intellectual Scale-Third Edition (WAIS-III) to evaluate general intelligence. Twenty healthy control subjects (mean age 24.4 ± 2.8 years, range 22-30 years) were also studied to obtain a normal database for 3D-SSP. Group comparisons showed significant regional low FMZ uptake in the bilateral medial frontal gyri, the anterior cingulate gyri, and the thalamus. Individual analysis also showed decreased FMZ uptake in these regions; however, the distribution and extent of low FMZ uptake were different in each individual patient. Full-scale IQ (FIQ) and performance IQ (PIQ) negatively correlated with the degree of FMZ BP reduction (BZR index) in the right thalamus. FIQ, verbal IQ (VIQ), and PIQ also negatively correlated with the BZR index in the left medial frontal gyrus. DAI uniformly induced neuronal damage in the medial frontal cortex and the thalamus, which may be related to underlying cognitive impairments in diffuse TBI patients. Future studies to confirm a common area of focal neuronal damage and a direct correlation with neuropsychological testing may validate the use of FMZ-PET for the functional diagnosis of neuropsychological impairments after TBI.

  5. The neurophysiology of brain injury.

    PubMed

    Gaetz, Michael

    2004-01-01

    This article reviews the mechanisms and pathophysiology of traumatic brain injury (TBI). Research on the pathophysiology of diffuse and focal TBI is reviewed with an emphasis on damage that occurs at the cellular level. The mechanisms of injury are discussed in detail including the factors and time course associated with mild to severe diffuse injury as well as the pathophysiology of focal injuries. Examples of electrophysiologic procedures consistent with recent theory and research evidence are presented. Acceleration/deceleration (A/D) forces rarely cause shearing of nervous tissue, but instead, initiate a pathophysiologic process with a well defined temporal progression. The injury foci are considered to be diffuse trauma to white matter with damage occurring at the superficial layers of the brain, and extending inward as A/D forces increase. Focal injuries result in primary injuries to neurons and the surrounding cerebrovasculature, with secondary damage occurring due to ischemia and a cytotoxic cascade. A subset of electrophysiologic procedures consistent with current TBI research is briefly reviewed. The pathophysiology of TBI occurs over time, in a pattern consistent with the physics of injury. The development of electrophysiologic procedures designed to detect specific patterns of change related to TBI may be of most use to the neurophysiologist. This article provides an up-to-date review of the mechanisms and pathophysiology of TBI and attempts to address misconceptions in the existing literature.

  6. Nano-particle delivery of brain derived neurotrophic factor after focal cerebral ischemia reduces tissue injury and enhances behavioral recovery.

    PubMed

    Harris, Nia M; Ritzel, Rodney; Mancini, Nickolas S; Jiang, Yuhang; Yi, Xiang; Manickam, Devika S; Banks, William A; Kabanov, Alexander V; McCullough, Louise D; Verma, Rajkumar

    Low levels of brain-derived neurotrophic factor (BDNF) are linked to delayed neurological recovery, depression, and cognitive impairment following stroke. Supplementation with BDNF reverses these effects. Unfortunately, systemically administered BDNF in its native form has minimal therapeutic value due to its poor blood brain barrier permeability and short serum half-life. In this study, a novel nano-particle polyion complex formulation of BDNF (nano-BDNF) was administered to mice after experimental ischemic stroke. Male C57BL/6J (8-10weeks) mice were randomly assigned to receive nano-BDNF, native-BDNF, or saline treatment after being subjected to 60min of reversible middle cerebral artery occlusion (MCAo). Mice received the first dose at 3 (early treatment), 6 (intermediate treatment), or 12h (delayed treatment) following stroke onset; a second dose was given in all cohorts at 24h after stroke onset. Post-stroke outcome was evaluated by behavioral, histological, and molecular analysis for 15days after stroke. Early and intermediate nano-BDNF treatment led to a significant reduction in cerebral tissue loss. Delayed treatment led to improved memory/cognition, reduced post-stroke depressive phenotypes, and maintained myelin basic protein and brain BDNF levels, but had no effect on tissue atrophy. The results indicate that administration of a novel nano-particle formulation of BDNF leads to both neuroprotective and neuro-restorative effects after stroke. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. [Effect of ginsenoside Rb1 on cerebral infarction volume and IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion injury model rats].

    PubMed

    Liu, Jun-Wei; Ren, Ye-Long; Liu, Xu-Ling; Xia, Hong-Lian; Zhang, Hui-Ling; Jin, Shen-Hui; Dai, Qin-Xue; Wang, Jun-Lu

    2013-12-01

    To investigate the effect of ginsenoside Rb1 on cerebral infarction volume as well as IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion (I/R) injury model rats. The I/R rat model was established by using thread according to Zea-Longa. SD rats were randomly divided into five groups, i.e., the sham-operation group, the model group, the low dose ginsenoside Rb1 (20 mg/kg) group, the medium dose ginsenoside Rb1 group (40 mg/kg), and the high dose ginsenoside Rb1 group (80 mg/kg), 12 in each group. Rats in the sham-operation group only received middle cerebral artery occlusion (MCAO) but without thread insertion. The MCAO model was prepared in the rest 4 groups, followed by MCAO2 h later. Ginsenoside Rb1 at each dose was peritoneally administrated to rats in corresponding groups immediately after cerebral ischemia. Equal volume of normal saline was administered to rats in the sham-operation group. Rats' cerebral infarction volume, integrals of neurologic defect degree, expression of IL-1 beta content in the brain tissue and sera were observed 24 h after 2-h cerebral I/R. In the model group, integrals of neurologic defect degree were improved (P < 0.01), IL-1 beta positive cells in the brain tissue increased and serum IL-1 beta content elevated (P < 0.05), when compared with the sham-operation group. In comparison of the model group, integrals of neurologic defect degree were lowered in the medium dose and high dose ginsenoside Rb1 groups (P < 0.05, P < 0.01). The cerebral infarction volume was all shrunken in each ginsenoside Rb1 group, IL-1 beta positive cells in the brain tissue decreased, and IL-1 beta content in serum reduced (P < 0.01, P < 0.05). Compared with the low dose ginsenoside Rb1 group, integrals of neurologic defect degree decreased, the cerebral infarction volume shrunken, and IL-1 beta content in serum reduced in the high dose ginsenoside Rb1 group (P < 0.01, P < 0.05). Ginsenoside Rb1 (20, 40, 80 mg/kg) might effectively

  8. Effect of acute poly(ADP-ribose) polymerase inhibition by 3-AB on blood-brain barrier permeability and edema formation after focal traumatic brain injury in rats.

    PubMed

    Lescot, Thomas; Fulla-Oller, Laurence; Palmier, Bruno; Po, Christelle; Beziaud, Tiphaine; Puybasset, Louis; Plotkine, Michel; Gillet, Brigitte; Meric, Philippe; Marchand-Leroux, Catherine

    2010-06-01

    Recent evidence supports a crucial role for matrix metalloproteinase-9 (MMP-9) in blood-brain barrier (BBB) disruption and vasogenic edema formation after traumatic brain injury (TBI). Although the exact causes of MMP-9 upregulation after TBI are not fully understood, several arguments suggest a contribution of the enzyme poly(ADP-ribose)polymerase (PARP) in the neuroinflammatory response leading to MMP-9 activation. The objectives of this study were to evaluate the effect of PARP inhibition by 3-aminobenzamide (3-AB) (1) on MMP-9 upregulation and BBB integrity, (2) on edema formation as assessed by magnetic resonance imaging (MRI), (3) on neuron survival as assessed by (1)H magnetic resonance spectroscopy ((1)H-MRS), and (4) on neurological deficits at the acute phase of TBI. Western blots and zymograms showed blunting of MMP-9 upregulation 6 h after TBI. BBB permeability was decreased at the same time point in 3-AB-treated rats compared to vehicle-treated rats. Cerebral MRI showed less "free" water in 3-AB-treated than in vehicle-treated rats 6 h after TBI. MRI findings 24 h after TBI indicated predominant cytotoxic edema, and at this time point no significant differences were found between 3-AB- and vehicle-treated rats with regard to MMP-9 upregulation, BBB permeability, or MRI changes. At both 6 and 24 h, neurological function was better in the 3-AB-treated than in the vehicle-treated rats. These data suggest that PARP inhibition by 3-AB protected the BBB against hyperpermeability induced by MMP-9 upregulation, thereby decreasing vasogenic edema formation 6 h after TBI. Furthermore, our data confirm the neuroprotective effect of 3-AB at the very acute phase of TBI.

  9. Real-time monitoring of changes in brain extracellular sodium and potassium concentrations and intracranial pressure after selective vasopressin-1a receptor inhibition following focal traumatic brain injury in rats.

    PubMed

    Filippidis, Aristotelis S; Liang, Xiuyin; Wang, Weili; Parveen, Shanaaz; Baumgarten, Clive M; Marmarou, Christina R

    2014-07-15

    Brain swelling and increased intracranial pressure (ICP) following traumatic brain injury (TBI) contribute to poor outcome. Vasopressin-1a receptors (V1aR) and aquaporin-4 (AQP4) regulate water transport and brain edema formation, perhaps in part by modulating cation fluxes. After focal TBI, V1aR inhibitors diminish V1aR and AQP4, reduce astrocytic swelling and brain edema. We determined whether V1aR inhibition with SR49059 after lateral controlled-cortical-impact (CCI) injury affects extracellular Na(+) and K(+) concentrations ([Na(+)]e; [K(+)]e). Ion-selective Na(+) and K(+) electrodes (ISE) and an ICP probe were implanted in rat parietal cortex, and [Na(+)]e, [K(+)]e, and physiological parameters were monitored for 5 h post-CCI. Sham-vehicle-ISE, CCI-vehicle-ISE and CCI-SR49059-ISE groups were studied, and SR49059 was administered 5 min to 5 h post-injury. We found a significant injury-induced decrease in [Na(+)]e to 80.1 ± 15 and 87.9 ± 7.9 mM and increase in [K(+)]e to 20.9 ± 3.8 and 13.4 ± 3.4 mM at 5 min post-CCI in CCI-vehicle-ISE and CCI-SR49059-ISE groups, respectively (p<0.001 vs. baseline; ns between groups). Importantly, [Na(+)]e in CCI-SR49059-ISE was reduced 5-20 min post-injury and increased to baseline at 25 min, whereas recovery in CCI-vehicle-ISE required more than 1 hr, suggesting SR49059 accelerated [Na(+)]e recovery. In contrast, [K(+)]e recovery took 45 min in both groups. Further, ICP was lower in the CCI-SR49059-ISE group. Thus, selective V1aR inhibition allowed faster [Na(+)]e recovery and reduced ICP. By augmenting the [Na(+)]e recovery rate, SR49059 may reduce trauma-induced ionic imbalance, blunting cellular water influx and edema after TBI. These findings suggest SR49059 and V1aR inhibitors are potential tools for treating cellular edema post-TBI.

  10. Focal cerebral hyperemia after focal head injury in humans: a benign phenomenon?

    PubMed

    Sakas, D E; Bullock, M R; Patterson, J; Hadley, D; Wyper, D J; Teasdale, G M

    1995-08-01

    To assess the relationship between posttraumatic cerebral hyperemia and focal cerebral damage, the authors performed cerebral blood flow mapping studies by single-photon emission computerized tomography (SPECT) in 53 patients within 3 weeks of brain injury. Focal zones of hyperemia were present in 38% of patients. Hyperemia was correlated with clinical features and early computerized tomography (CT) and magnetic resonance (MR) imaging performed within 48 hours of the SPECT study and late CT and MR studies at 3 months. The hyperemia was observed primarily in structurally normal brain tissue (both gray and white matter), as revealed by CT and MR imaging, immediately adjacent to intraparenchymal or extracerebral focal lesions; it persisted for up to 10 days, but was never seen within the edematous pericontusional zones. The percentage of patients in the hyperemic group having brief (< 30 minutes) or no loss of consciousness was significantly higher than in the nonhyperemic group (twice as high, p < 0.05). Other clinical parameters were not significantly more common in the hyperemic group. The mortality of patients with focal hyperemia was lower than that of individuals without it, and the outcome of survivors with hyperemia was slightly better than patients without hyperemia. These results differ from the literature, which suggests that global post-traumatic hyperemia is primarily an acute, malignant phenomenon associated with increased intracranial pressure, profound unconsciousness, and poor outcome. The current results agree with more recent studies which show that posttraumatic hyperemia may occur across a wide spectrum of head injury severity and may be associated with favorable outcome.

  11. Experimental traumatic brain injury

    PubMed Central

    2010-01-01

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

  12. Longitudinal Assessments of Normal and Perilesional Tissues in Focal Brain Ischemia and Partial Optic Nerve Injury with Manganese-enhanced MRI

    PubMed Central

    Chan, Kevin C.; Zhou, Iris Y.; Liu, Stanley S.; van der Merwe, Yolandi; Fan, Shu-Juan; Hung, Victor K.; Chung, Sookja K.; Wu, Wu-tian; So, Kwok-fai; Wu, Ed X.

    2017-01-01

    Although manganese (Mn) can enhance brain tissues for improving magnetic resonance imaging (MRI) assessments, the underlying neural mechanisms of Mn detection remain unclear. In this study, we used Mn-enhanced MRI to test the hypothesis that different Mn entry routes and spatiotemporal Mn distributions can reflect different mechanisms of neural circuitry and neurodegeneration in normal and injured brains. Upon systemic administration, exogenous Mn exhibited varying transport rates and continuous redistribution across healthy rodent brain nuclei over a 2-week timeframe, whereas in rodents following photothrombotic cortical injury, transient middle cerebral artery occlusion, or neonatal hypoxic-ischemic brain injury, Mn preferentially accumulated in perilesional tissues expressing gliosis or oxidative stress within days. Intravitreal Mn administration to healthy rodents not only allowed tracing of primary visual pathways, but also enhanced the hippocampus and medial amygdala within a day, whereas partial transection of the optic nerve led to MRI detection of degrading anterograde Mn transport at the primary injury site and the perilesional tissues secondarily over 6 weeks. Taken together, our results indicate the different Mn transport dynamics across widespread projections in normal and diseased brains. Particularly, perilesional brain tissues may attract abnormal Mn accumulation and gradually reduce anterograde Mn transport via specific Mn entry routes. PMID:28230106

  13. Traumatic Brain Injury as a Cause of Behavior Disorders.

    ERIC Educational Resources Information Center

    Nordlund, Marcia R.

    There is increasing evidence that many children and adolescents who display behavior disorders have sustained a traumatic brain injury. Traumatic brain injury can take the following forms: closed head trauma in which the brain usually suffers diffuse damage; open head injury which usually results in specific focal damage; or internal trauma (e.g.,…

  14. Traumatic Brain Injury as a Cause of Behavior Disorders.

    ERIC Educational Resources Information Center

    Nordlund, Marcia R.

    There is increasing evidence that many children and adolescents who display behavior disorders have sustained a traumatic brain injury. Traumatic brain injury can take the following forms: closed head trauma in which the brain usually suffers diffuse damage; open head injury which usually results in specific focal damage; or internal trauma (e.g.,…

  15. The time course of vasogenic oedema after focal human head injury--evidence from SPECT mapping of blood brain barrier defects.

    PubMed

    Bullock, R; Statham, P; Patterson, J; Wyper, D; Hadley, D; Teasdale, E

    1990-01-01

    We have tomographically mapped changes in the blood brain barrier (BBB) (99 mTc Pertechnetate) in 20 patients with acute contusions, and four with acute subdural haematomas in situ. The changes were related to regional CBF, (99 mTc HMPAO SPECT) T2 weighted MRI scans, CT abnormalities and the clinical features. Seventy-five percent of contusions were accompanied by a BBB abnormality, usually a "halo" around the lesion, which was more common in scans made after the second day. All contusions demonstrated "oedema" as a zone of "T2" signal on MRI or a zone of lucency on CT, and all were accompanied by a focal zone of low CBF on SPECT. Early contusional oedema appears to be cytotoxic but in certain cases, delayed blood brain barrier lesions develop, suggesting a vasogenic component.

  16. Differential effects of rapamycin treatment on tonic and phasic GABAergic inhibition in dentate granule cells after focal brain injury in mice.

    PubMed

    Butler, Corwin R; Boychuk, Jeffery A; Smith, Bret N

    2016-06-01

    The cascade of events leading to post-traumatic epilepsy (PTE) after traumatic brain injury (TBI) remains unclear. Altered inhibition in the hippocampal formation and dentate gyrus is a hallmark of several neurological disorders, including TBI and PTE. Inhibitory synaptic signaling in the hippocampus is predominately driven by γ-aminobutyric acid (GABA) neurotransmission, and is prominently mediated by postsynaptic type A GABA receptors (GABAAR's). Subsets of these receptors involved in tonic inhibition of neuronal membranes serve a fundamental role in maintenance of inhibitory state, and GABAAR-mediated tonic inhibition is altered functionally in animal models of both TBI and epilepsy. In this study, we assessed the effect of mTOR inhibition on hippocampal hilar inhibitory interneuron loss and synaptic and tonic GABAergic inhibition of dentate gyrus granule cells (DGCs) after controlled cortical impact (CCI) to determine if mTOR activation after TBI modulates GABAAR function. Hilar inhibitory interneuron density was significantly reduced 72h after CCI injury in the dorsal two-thirds of the hemisphere ipsilateral to injury compared with the contralateral hemisphere and sham controls. Rapamycin treatment did not alter this reduction in cell density. Synaptic and tonic current measurements made in DGCs at both 1-2 and 8-13weeks post-injury indicated reduced synaptic inhibition and THIP-induced tonic current density in DGCs ipsilateral to CCI injury at both time points post-injury, with no change in resting tonic GABAAR-mediated currents. Rapamycin treatment did not alter the reduced synaptic inhibition observed in ipsilateral DGCs 1-2weeks post-CCI injury, but further reduced synaptic inhibition of ipsilateral DGCs at 8-13weeks post-injury. The reduction in THIP-induced tonic current after injury, however, was prevented by rapamycin treatment at both time points. Rapamycin treatment thus differentially modifies CCI-induced changes in synaptic and tonic GABAAR

  17. Brain injury - discharge

    MedlinePlus

    Head injury - discharge; Head trauma - discharge; Contusion - discharge; Shaken baby syndrome - discharge ... done to help them recover from the brain injury. The person may have stayed in a special ...

  18. Levo-tetrahydropalmatine attenuates mouse blood-brain barrier injury induced by focal cerebral ischemia and reperfusion: Involvement of Src kinase

    PubMed Central

    Mao, Xiao-Wei; Pan, Chun-Shui; Huang, Ping; Liu, Yu-Ying; Wang, Chuan-She; Yan, Li; Hu, Bai-He; Chang, Xin; He, Ke; Mu, Huan-Na; Li, Quan; Sun, Kai; Fan, Jing-Yu; Han, Jing-Yan

    2015-01-01

    The restoration of blood flow following thrombolytic therapy causes ischemia and reperfusion (I/R) injury leading to blood-brain barrier (BBB) disruption and subsequent brain edema in patients of ischemic stroke. Levo-tetrahydropalmatine (l-THP) occurs in Corydalis genus and some other plants. However, whether l-THP exerts protective role on BBB disrpution following cerebral I/R remains unclear. Male C57BL/6N mice (23 to 28 g) were subjected to 90 min middle cerebral artery occlusion, followed by reperfusion for 24 h. l-THP (10, 20, 40 mg/kg) was administrated by gavage 60 min before ischemia. We found I/R evoked Evans blue extravasation, albumin leakage, brain water content increase, cerebral blood flow decrease, cerebral infarction and neurological deficits, all of which were attenuated by l-THP treatment. Meanwhile, l-THP inhibited tight junction (TJ) proteins down-expression, Src kinase phosphorylation, matrix metalloproteinases-2/9 (MMP-2/9) and caveolin-1 activation. In addition, surface plasmon resonance revealed binding of l-THP to Src kinase with high affinity. Then we found Src kinase inhibitor PP2 could attenuate Evans blue dye extravasation and inhibit the caveolin-1, MMP-9 activation, occludin down-expression after I/R, respectively. In conclusion, l-THP attenuated BBB injury and brain edema, which were correlated with inhibiting the Src kinase phosphorylation. PMID:26059793

  19. [Sense of personal identity and focal brain lesions].

    PubMed

    Morin, Catherine

    2009-03-01

    The sense of personal identity is an element of the Jasperian definition of self-conscience. Each of us is convinced of being a unique and stable individual, different from other individuals. These properties - stability ad coherence - belong to an image of ourselves that was proposed to us by the Other's look during the mirror phase. Brain focal lesions may threaten this certitude in two ways: 1) brain lesions result in deficiency, disability or handicap, which are experienced as a narcissistic injury. The patient questions himself about the image he offers to the Other's look, and, as a result, his sense of personal identity is unsettled; 2) a variety of focal brain lesions or dysfunctions may alter the activity of areas which are necessary for maintaining a stable image of the patients' body or self. This may lead patients to experience depersonalisation, autoscopy, somatoparaphrenic "delusions" or disturbed agency. The sense of personal identity may be disturbed during brief paroxystic or psychologically traumatic phenomena. However, this is not observed in chronic sequelae of brain lesions (e.g. right hemisphere syndrome or amnesic syndrome), even though the patients may present a broken up image of themselves.

  20. Preconditioning for traumatic brain injury

    PubMed Central

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

    2016-01-01

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

  1. Preconditioning for traumatic brain injury.

    PubMed

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

    2013-02-01

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

  2. Traumatic Brain Injuries. Guidelines Paper.

    ERIC Educational Resources Information Center

    Colorado State Dept. of Education, Denver. Special Education Services Unit.

    This paper on traumatic brain injuries begins with statistics on the incidence of the disorder, especially as they relate to Colorado. Traumatic brain injury is then defined, and problems caused by traumatic brain injury are discussed. The components of effective programming for students with traumatic brain injuries are described, followed by the…

  3. [Traumatic brain injury].

    PubMed

    Hackenberg, K; Unterberg, A

    2016-02-01

    Since traumatic brain injury is the most common cause of long-term disability and death among young adults, it represents an enormous socio-economic and healthcare burden. As a consequence of the primary lesion, a perifocal brain edema develops causing an elevation of the intracranial pressure due to the limited intracranial space. This entails a reduction of the cerebral perfusion pressure and the cerebral blood flow. A cerebral perfusion deficit below the threshold for ischemia leads to further ischemic lesions and to a progression of the contusion. As the irreversible primary lesion can only be inhibited by primary prevention, the therapy of traumatic brain injury focuses on the secondary injuries. The treatment consists of surgical therapy evacuating the space-occupying intracranial lesion and conservative intensive medical care. Due to the complex pathophysiology the therapy of traumatic brain injury should be rapidly performed in a neurosurgical unit.

  4. Brain injuries from blast.

    PubMed

    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

  5. Traumatic Brain Injury and Sleep Disorders

    PubMed Central

    Viola-Saltzman, Mari; Watson, Nathaniel F.

    2012-01-01

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

  6. Brain polyphosphoinositide metabolism during focal ischemia in rat cortex

    SciTech Connect

    Lin, T.N.; Liu, T.H.; Xu, J.; Hsu, C.Y.; Sun, G.Y. )

    1991-04-01

    Using a rat model of stroke, we examined the effects of focal cerebral ischemia on the metabolism of polyphosphoinositides by injecting {sup 32}Pi into both the left and right cortices. After equilibration of the label for 2-3 hours, ischemia induced a significant decrease (p less than 0.001) in the concentrations of labeled phosphatidyl 4,5-bisphosphates (66-78%) and phosphatidylinositol 4-phosphate (64-67%) in the right middle cerebral artery cortex of four rats. The phospholipid labeling pattern in the left middle cerebral artery cortex, which sustained only mild ischemia and no permanent tissue damage, was not different from that of two sham-operated controls. However, when {sup 32}Pi was injected 1 hour after the ischemic insult, there was a significant decrease (p less than 0.01) in the incorporation of label into the phospholipids in both cortices of four ischemic rats compared with four sham-operated controls. Furthermore, differences in the phospholipid labeling pattern were observed in the left cortex compared with the sham-operated controls. The change in labeling pattern was attributed to the partial reduction in blood flow following ligation of the common carotid arteries. We provide a sensitive procedure for probing the effects of focal cerebral ischemia on the polyphosphoinositide signaling pathway in the brain, which may play an important role in the pathogenesis of tissue injury.

  7. Radiation Injury to the Brain

    MedlinePlus

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

  8. Acquired Brain Injury Program.

    ERIC Educational Resources Information Center

    Schwartz, Stacey Hunter

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

  9. Brain Injury Association of America

    MedlinePlus

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

  10. Glutamate transporter type 3 knockout reduces brain tolerance to focal brain ischemia in mice.

    PubMed

    Li, Liaoliao; Zuo, Zhiyi

    2011-05-01

    Excitatory amino-acid transporters (EAATs) transport glutamate into cells under physiologic conditions. Excitatory amino-acid transporter type 3 (EAAT3) is the major neuronal EAAT and also uptakes cysteine, the rate-limiting substrate for synthesis of glutathione. Thus, we hypothesize that EAAT3 contributes to providing brain ischemic tolerance. Male 8-week-old EAAT3 knockout mice on CD-1 mouse gene background and wild-type CD-1 mice were subjected to right middle cerebral artery occlusion for 90 minutes. Their brain infarct volumes, neurologic functions, and brain levels of glutathione, nitrotyrosine, and 4-hydroxy-2-nonenal (HNE) were evaluated. The EAAT3 knockout mice had bigger brain infarct volumes and worse neurologic deficit scores and motor coordination functions than did wild-type mice, no matter whether these neurologic outcome parameters were evaluated at 24 hours or at 4 weeks after brain ischemia. The EAAT3 knockout mice contained higher levels of HNE in the ischemic penumbral cortex and in the nonischemic cerebral cortex than did wild-type mice. Glutathione levels in the ischemic and nonischemic cortices of EAAT3 knockout mice tended to be lower than those of wild-type mice. Our results suggest that EAAT3 is important in limiting ischemic brain injury after focal brain ischemia. This effect may involve attenuating brain oxidative stress.

  11. Selective vasopressin-1a receptor antagonist prevents brain edema, reduces astrocytic cell swelling and GFAP, V1aR and AQP4 expression after focal traumatic brain injury.

    PubMed

    Marmarou, Christina R; Liang, Xiuyin; Abidi, Naqeeb H; Parveen, Shanaz; Taya, Keisuke; Henderson, Scott C; Young, Harold F; Filippidis, Aristotelis S; Baumgarten, Clive M

    2014-09-18

    A secondary and often lethal consequence of traumatic brain injury is cellular edema that we posit is due to astrocytic swelling caused by transmembrane water fluxes augmented by vasopressin-regulated aquaporin-4 (AQP4). We therefore tested whether vasopressin 1a receptor (V1aR) inhibition would suppress astrocyte AQP4, reduce astrocytic edema, and thereby diminish TBI-induced edematous changes. V1aR inhibition by SR49059 significantly reduced brain edema after cortical contusion injury (CCI) in rat 5h post-injury. Injured-hemisphere brain water content (n=6 animals/group) and astrocytic area (n=3/group) were significantly higher in CCI-vehicle (80.5±0.3%; 18.0±1.4 µm(2)) versus sham groups (78.3±0.1%; 9.5±0.9 µm(2)), and SR49059 blunted CCI-induced increases in brain edema (79.0±0.2%; 9.4±0.8µm(2)). CCI significantly up-regulated GFAP, V1aR and AQP4 protein levels and SR49059 suppressed injury induced up regulation (n=6/group). In CCI-vehicle, sham and CCI-SR49059 groups, GFAP was 1.58±0.04, 0.47±0.02, and 0.81±0.03, respectively; V1aR was 1.00±0.06, 0.45±0.05, and 0.46±0.09; and AQP4 was 2.03±0.34, 0.49±0.04, and 0.92±0.22. Confocal immunohistochemistry gave analogous results. In CCI-vehicle, sham and CCI-SR49059 groups, fluorescence intensity of GFAP was 349±38, 56±5, and 244±30, respectively, V1aR was 601±71, 117.8±14, and 390±76, and AQP4 was 818±117, 158±5, and 458±55 (n=3/group). The results support that edema was predominantly cellular following CCI and documented that V1aR inhibition with SR49059 suppressed injury-induced up regulation of GFAP, V1A and AQP4, blunting edematous changes. Our findings suggest V1aR inhibitors may be potential therapeutic tools to prevent cellular swelling and provide treatment for post-traumatic brain edema.

  12. Ameliorative effects of Gualou Guizhi decoction on inflammation in focal cerebral ischemic-reperfusion injury

    PubMed Central

    ZHANG, YUQIN; ZHANG, SHENGNAN; LI, HUANG; HUANG, MEI; XU, WEI; CHU, KEDAN; CHEN, LIDIAN; CHEN, XIANWEN

    2015-01-01

    Gualou Guizhi decoction (GLGZD) is a well-established Traditional Chinese Medicinal formulation which has long been used to treat stroke in a clinical setting in China. The present study investigated the ameliorative effects of GLGZD on inflammation in focal cerebral ischemic-reperfusion injury. A rat model of middle cerebral artery occlusion (MCAO) was employed. Rats were administrated GLGZD (7.2 and 14.4 g/kg per day) or saline as control 2 h after reperfusion and daily over the following seven days. Neurological deficit score and screen test were evaluated at 1, 3, 5 and 7 days after MCAO. Brain infarct size and brain histological changes were observed via 2,3,5-triphenyltetrazolium chloride staining and regular hematoxylin & eosin staining. Furthermore, inflammation mediators and nuclear factor-κB (NF-κB) were investigated using ELISA and immunohistochemistry. GLGZD treatment significantly improved neurological function, ameliorated histological changes to the brain and decreased infarct size in focal cerebral ischemic-reperfusion injury. GLGZD was found to significantly reduce interleukin (IL)-1, tumor necrosis factor-α and NF-κB levels, while increasing levels of IL-10. In conclusion, the present study suggested that GLGZD has a neuroprotective effect on focal cerebral ischemic-reperfusion injury and this effect is likely to be associated with the anti-inflammatory function of GLGZD. PMID:25815894

  13. PERSONALITY CHANGES IN BRAIN INJURY

    PubMed Central

    Garcia, Patricia Gracia; Mielke, Michelle M.; Rosenberg, Paul; Bergey, Alyssa; Rao, Vani

    2011-01-01

    Traumatic brain injury (TBI) is frequently complicated by alterations in mood and behaviour and changes in personality. We report mild personality changes post-TBI as a possible indicator of traumatic brain injury, but not of injury severity or psychiatric complications. PMID:21677207

  14. Traumatic brain injuries.

    PubMed

    Blennow, Kaj; Brody, David L; Kochanek, Patrick M; Levin, Harvey; McKee, Ann; Ribbers, Gerard M; Yaffe, Kristine; Zetterberg, Henrik

    2016-11-17

    Traumatic brain injuries (TBIs) are clinically grouped by severity: mild, moderate and severe. Mild TBI (the least severe form) is synonymous with concussion and is typically caused by blunt non-penetrating head trauma. The trauma causes stretching and tearing of axons, which leads to diffuse axonal injury - the best-studied pathogenetic mechanism of this disorder. However, mild TBI is defined on clinical grounds and no well-validated imaging or fluid biomarkers to determine the presence of neuronal damage in patients with mild TBI is available. Most patients with mild TBI will recover quickly, but others report persistent symptoms, called post-concussive syndrome, the underlying pathophysiology of which is largely unknown. Repeated concussive and subconcussive head injuries have been linked to the neurodegenerative condition chronic traumatic encephalopathy (CTE), which has been reported post-mortem in contact sports athletes and soldiers exposed to blasts. Insights from severe injuries and CTE plausibly shed light on the underlying cellular and molecular processes involved in mild TBI. MRI techniques and blood tests for axonal proteins to identify and grade axonal injury, in addition to PET for tau pathology, show promise as tools to explore CTE pathophysiology in longitudinal clinical studies, and might be developed into diagnostic tools for CTE. Given that CTE is attributed to repeated head trauma, prevention might be possible through rule changes by sports organizations and legislators.

  15. A simple method to induce focal brain hypothermia in rats.

    PubMed

    Clark, Darren L; Colbourne, Frederick

    2007-01-01

    Hypothermia reduces cell death and promotes recovery in models of cerebral ischemia, intracerebral hemorrhage and trauma. Clinical studies report significant benefit for treating cardiac arrest and studies are investigating hypothermia for stroke and related conditions. Both local (head) and generalized hypothermia have been used. However, selective brain cooling has fewer side effects than systemic cooling. In this study, we developed a method to induce local (hemispheric) brain hypothermia in rats. The method involves using a small metal coil implanted between the Temporalis muscle and adjacent skull. This coil is then cooled by flushing it with cold water. In our first experiment, we tested whether this method induces focal brain hypothermia in anesthetized rats. Brain temperature was assessed in the ipsilateral cortex and striatum, and contralateral striatum, while body temperature was kept normothermic. Focal, ipsilateral cooling was successfully produced, while the other locations remained normothermic. In the second experiment, we implanted the coil, and brain and body temperature telemetry probes. The coil was connected via overhead swivel to a cold-water source. Brain hypothermia was produced for 24 h, while body temperature remained normothermic. A third experiment measured brain and body temperature along with heart rate and blood pressure. Brain cooling was produced for 24 h without significant alterations in pressure, heart rate or body temperature. In summary, our simple method allows for focal brain hypothermia to be safely induced in anesthetized or conscious rats, and is, therefore, ideally suited to stroke and trauma studies.

  16. Subacute to chronic mild traumatic brain injury.

    PubMed

    Mott, Timothy F; McConnon, Michael L; Rieger, Brian P

    2012-12-01

    Although a universally accepted definition is lacking, mild traumatic brain injury and concussion are classified by transient loss of consciousness, amnesia, altered mental status, a Glasgow Coma Score of 13 to 15, and focal neurologic deficits following an acute closed head injury. Most patients recover quickly, with a predictable clinical course of recovery within the first one to two weeks following traumatic brain injury. Persistent physical, cognitive, or behavioral postconcussive symptoms may be noted in 5 to 20 percent of persons who have mild traumatic brain injury. Physical symptoms include headaches, dizziness, and nausea, and changes in coordination, balance, appetite, sleep, vision, and hearing. Cognitive and behavioral symptoms include fatigue, anxiety, depression, and irritability, and problems with memory, concentration and decision making. Women, older adults, less educated persons, and those with a previous mental health diagnosis are more likely to have persistent symptoms. The diagnostic workup for subacute to chronic mild traumatic brain injury focuses on the history and physical examination, with continuing observation for the development of red flags such as the progression of physical, cognitive, and behavioral symptoms, seizure, progressive vomiting, and altered mental status. Early patient and family education should include information on diagnosis and prognosis, symptoms, and further injury prevention. Symptom-specific treatment, gradual return to activity, and multidisciplinary coordination of care lead to the best outcomes. Psychiatric and medical comorbidities, psychosocial issues, and legal or compensatory incentives should be explored in patients resistant to treatment.

  17. Assessing connectivity related injury burden in diffuse traumatic brain injury.

    PubMed

    Solmaz, Berkan; Tunç, Birkan; Parker, Drew; Whyte, John; Hart, Tessa; Rabinowitz, Amanda; Rohrbach, Morgan; Kim, Junghoon; Verma, Ragini

    2017-03-15

    Many of the clinical and behavioral manifestations of traumatic brain injury (TBI) are thought to arise from disruption to the structural network of the brain due to diffuse axonal injury (DAI). However, a principled way of summarizing diffuse connectivity alterations to quantify injury burden is lacking. In this study, we developed a connectome injury score, Disruption Index of the Structural Connectome (DISC), which summarizes the cumulative effects of TBI-induced connectivity abnormalities across the entire brain. Forty patients with moderate-to-severe TBI examined at 3 months postinjury and 35 uninjured healthy controls underwent magnetic resonance imaging with diffusion tensor imaging, and completed behavioral assessment including global clinical outcome measures and neuropsychological tests. TBI patients were selected to maximize the likelihood of DAI in the absence of large focal brain lesions. We found that hub-like regions, with high betweenness centrality, were most likely to be impaired as a result of diffuse TBI. Clustering of participants revealed a subgroup of TBI patients with similar connectivity abnormality profiles who exhibited relatively poor cognitive performance. Among TBI patients, DISC was significantly correlated with post-traumatic amnesia, verbal learning, executive function, and processing speed. Our experiments jointly demonstrated that assessing structural connectivity alterations may be useful in development of patient-oriented diagnostic and prognostic tools. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

  18. VEGF reverts the cognitive impairment induced by a focal traumatic brain injury during the development of rats raised under environmental enrichment.

    PubMed

    Ortuzar, N; Rico-Barrio, I; Bengoetxea, H; Argandoña, E G; Lafuente, J V

    2013-06-01

    The role of VEGF in the nervous system is extensive; apart from its angiogenic effect, VEGF has been described as a neuroprotective, neurotrophic and neurogenic molecule. Similar effects have been described for enriched environment (EE). Moreover, both VEGF and EE have been related to improved spatial memory. Our aim was to investigate the neurovascular and cognitive effects of intracerebrally-administered VEGF and enriched environment during the critical period of the rat visual cortex development. Results showed that VEGF infusion as well as enriched environment induced neurovascular and cognitive effects in developing rats. VEGF administration produced an enhancement during the learning process of enriched animals and acted as an angiogenic factor both in primary visual cortex (V1) and dentate gyrus (DG) in order to counteract minipump implantation-induced damage. This fact revealed that DG vascularization is critical for normal learning. In contrast to this enriched environment acted on the neuronal density of the DG and V1 cortex, and results showed learning enhancement only in non-operated rats. In conclusion, VEGF administration only has effects if damage is observed due to injury. Once control values were reached, no further effects appeared, showing a ceiling effect. Our results strongly support that in addition to neurogenesis, vascularization plays a pivotal role for learning and memory.

  19. Animal models of focal brain ischemia

    PubMed Central

    2009-01-01

    Stroke is a leading cause of disability and death in many countries. Understanding the pathophysiology of ischemic injury and developing therapies is an important endeavor that requires much additional research. Animal stroke models provide an important mechanism for these activities. A large number of stroke models have been developed and are currently used in laboratories around the world. These models are overviewed as are approaches for measuring infarct size and functional outcome. PMID:20150985

  20. Early post-traumatic cerebral blood flow mapping: correlation with structural damage after focal injury.

    PubMed

    Bullock, R; Sakas, D; Patterson, J; Wyper, D; Hadley, D; Maxwell, W; Teasdale, G M

    1992-01-01

    Focal post traumatic mass lesions such as contusions and intracerebral haematomas are common, and often difficult for neurosurgeons to manage, because little is known of their pathophysiology. We have mapped cerebral blood flow, and studied small vessel ultrastructure at different time points within the first three weeks of head injury, in patients with these lesions. A zone of ischaemic brain is always present around these lesions, and persists for weeks or months. This accords with astrocyte swelling and microvascular compression seen on electron microscopy. Focal zones of hyperaemia were also present in 42% of patients, within the first two weeks of injury, and this appeared only within apparently normal tissue as judged by late MRI or CT.

  1. Traumatic brain injury

    PubMed Central

    Risdall, Jane E.; Menon, David K.

    2011-01-01

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

  2. NINDS Traumatic Brain Injury Information Page

    MedlinePlus

    ... Disparities Neural Interfaces Parkinson's Disease Spinal Cord Injury Stem Cells Traumatic Brain Injury Trans-Agency Activities Interagency Research ... Disparities Neural Interfaces Parkinson's Disease Spinal Cord Injury Stem Cells Traumatic Brain Injury Trans-Agency Activities Interagency Research ...

  3. Traumatic Brain Injury and Aggression.

    ERIC Educational Resources Information Center

    Miller, Laurence

    1994-01-01

    Persons who have suffered traumatic injury to the brain may subsequently display aggressive behavior. Three main syndromes of aggression following traumatic brain injury are described: (1) episodic dyscontrol; (2) frontal lobe disinhibition; and (3) exacerbation of premorbid antisociality. The neuropsychological substrates of these syndromes are…

  4. Evaluation after Traumatic Brain Injury

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  5. Evaluation after Traumatic Brain Injury

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  6. Brain Injury: A Manual For Educators.

    ERIC Educational Resources Information Center

    Connor, Karen; Dettmer, Judy; Dise-lewis, Jeanne E.; Murphy, Mary; Santistevan, Barbette; Seckinger, Barbara

    This manual provides Colorado educators with guidelines for serving students with brain injuries. Following an introductory chapter, chapter 2 provides basic information on the brain including definitions of brain injury and its severity, incidence of brain injury, and characteristics of students with brain injury. Chapter 3 considers…

  7. Endocrine response to brain injury.

    PubMed

    Chioléro, R; Berger, M

    1994-11-01

    The neuroendocrine response (NER) is an essential component of the adaptive process to trauma, brain injury, and major surgery. While receiving additive humoral and neural afferent inputs, the brain nuclei responsible for the NER act mainly by efferent pathways to the hypothalamic-pituitary-adrenal (HPA) axis and the sympathoadrenal system, the activations of which induce subsequent circulatory and metabolic responses. The NER to brain injury is similar to the response observed in patients with extracerebral injury, even if the response after brain injury is extremely variable. Generally, there is a biphasic pattern, with a sympathoadrenal storm associated with variable and altered stimulation of the HPA during the ebb phase. The first phase is followed by a decrease in both responses while other endocrine changes develop, involving mainly the counter-regulatory, gonadal, and thyroid hormones. The outcome after brain injury is closely correlated with the intensity of these changes, particularly with catecholamine plasma levels and the severity of the low triiodothyronine syndrome. Alterations of the thyroid hormones are largely related to a reduction in peripheral deiodination of thyroxin. Recent research shows that increased free-radical production and decreased selenium (an antioxidant) serum levels play an important role in thyroid metabolism. Two major issues remain unsolved: a) the precise definition of cerebral death, since endocrine brain function is not abolished in the state currently defined as brain death; and b) the question of whether substitutive hormone therapy should be applied in severe brain injury.

  8. Traumatic Brain Injury and Dystonia

    MedlinePlus

    ... Symptoms of dystonia associated with TBI may be chronic or occur in episodes. Dystonia symptoms associated with ... a multi- disciplinary team with experience treating traumatic brain injury and/or movement disorders. • Learn as much as ...

  9. The influence of focal brain cooling on neurophysiopathology: validation for clinical application.

    PubMed

    Oku, Takayuki; Fujii, Masami; Tanaka, Nobuhiro; Imoto, Hirochika; Uchiyama, Joji; Oka, Fumiaki; Kunitsugu, Ichiro; Fujioka, Hiroshi; Nomura, Sadahiro; Kajiwara, Koji; Fujisawa, Hirosuke; Kato, Shoichi; Saito, Takashi; Suzuki, Michiyasu

    2009-06-01

    induce any irreversible histological change or motor dysfunction. These results suggest that focal brain cooling above 0 degrees C has the potential to be a minimally invasive and valuable modality for the treatment of severe brain injury or to assist in the examination of brain function.

  10. Traumatic Brain Injury Inpatient Rehabilitation

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  11. Concussion and Traumatic Brain Injury

    MedlinePlus

    ... long stays in intensive care units. Read More "Concussion" Articles Sports and Concussion / NIH Research on Concussion and the Brain / Doug Flutie: "Be on the Safe Side." / Concussion and Traumatic Brain Injury Summer 2015 Issue: Volume 10 ... Viewers & Players Friends of the National Library of Medicine (FNLM)

  12. Traumatic Brain Injury Inpatient Rehabilitation

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  13. Traumatic brain injury is under-diagnosed in patients with spinal cord injury.

    PubMed

    Tolonen, Anu; Turkka, Jukka; Salonen, Oili; Ahoniemi, Eija; Alaranta, Hannu

    2007-10-01

    To investigate the occurrence and severity of traumatic brain injury in patients with traumatic spinal cord injury. Cross-sectional study with prospective neurological, neuropsychological and neuroradiological examinations and retrospective medical record review. Thirty-one consecutive, traumatic spinal cord injury patients on their first post-acute rehabilitation period in a national rehabilitation centre. The American Congress of Rehabilitation Medicine diagnostic criteria for mild traumatic brain injury were applied. Assessments were performed with neurological and neuropsychological examinations and magnetic resonance imaging 1.5T. Twenty-three of the 31 patients with spinal cord injury (74%) met the diagnostic criteria for traumatic brain injury. Nineteen patients had sustained a loss of consciousness or post-traumatic amnesia. Four patients had a focal neurological finding and 21 had neuropsychological findings apparently due to traumatic brain injury. Trauma-related magnetic resonance imaging abnormalities were detected in 10 patients. Traumatic brain injury was classified as moderate or severe in 17 patients and mild in 6 patients. The results suggest a high frequency of traumatic brain injury in patients with traumatic spinal cord injury, and stress a special diagnostic issue to be considered in this patient group.

  14. Dysautonomia after pediatric brain injury

    PubMed Central

    KIRK, KATHERINE A; SHOYKHET, MICHAEL; JEONG, JONG H; TYLER-KABARA, ELIZABETH C; HENDERSON, MARYANNE J; BELL, MICHAEL J; FINK, ERICKA L

    2012-01-01

    AIM Dysautonomia after brain injury is a diagnosis based on fever, tachypnea, hypertension, tachycardia, diaphoresis, and/or dystonia. It occurs in 8 to 33% of brain-injured adults and is associated with poor outcome. We hypothesized that brain-injured children with dysautonomia have worse outcomes and prolonged rehabilitation, and sought to determine the prevalence of dysautonomia in children and to characterize its clinical features. METHOD We developed a database of children (n=249, 154 males, 95 females; mean (SD) age 11y 10mo [5y 7mo]) with traumatic brain injury, cardiac arrest, stroke, infection of the central nervous system, or brain neoplasm admitted to The Children’s Institute of Pittsburgh for rehabilitation between 2002 and 2009. Dysautonomia diagnosis, injury type, clinical signs, length of stay, and Functional Independence Measure for Children (WeeFIM) testing were extracted from medical records, and analysed for differences between groups with and without dysautonomia. RESULTS Dysautonomia occurred in 13% of children with brain injury (95% confidence interval 9.3–18.0%), occurring in 10% after traumatic brain injury and 31% after cardiac arrest. The combination of hypertension, diaphoresis, and dystonia best predicted a diagnosis of dysautonomia (area under the curve=0.92). Children with dysautonomia had longer stays, worse WeeFIM scores, and improved less on the score’s motor component (all p≤0.001). INTERPRETATION Dysautonomia is common in children with brain injury and is associated with prolonged rehabilitation. Prospective study and standardized diagnostic approaches are needed to maximize outcomes. PMID:22712762

  15. NONINVASIVE BRAIN STIMULATION IN TRAUMATIC BRAIN INJURY

    PubMed Central

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

    2012-01-01

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

  16. Neurological consequences of traumatic brain injuries in sports.

    PubMed

    Ling, Helen; Hardy, John; Zetterberg, Henrik

    2015-05-01

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

  17. Dichotomous effects of chronic intermittent hypoxia on focal cerebral ischemic injury

    PubMed Central

    Jackman, Katherine A.; Zhou, Ping; Faraco, Giuseppe; Peixoto, Pablo M.; Coleman, Christal; Voss, Henning U.; Pickel, Virginia; Manfredi, Giovanni; Iadecola, Costantino

    2014-01-01

    Background and purpose Obstructive sleep apnea (OSA), a condition associated with chronic intermittent hypoxia (CIH), carries an increased risk of stroke. However, CIH has been reported to either increase or decrease brain injury in models of focal cerebral ischemia. The factors determining the differential effects of CIH on ischemic injury and their mechanisms remain unclear. Here, we tested the hypothesis that the intensity of the hypoxic challenge determines the protective or destructive nature of CIH by modulating mitochondrial resistance to injury. Methods Male C57Bl/6J mice were exposed to CIH with 10% or 6% O2 for up to 35 days and subjected to transient middle cerebral artery occlusion (MCAO). Motor deficits and infarct volume were assessed 3 days later. Intra-ischemic CBF was measured by laser-Doppler flowmetry and resting CBF by arterial spin labeling MRI. Ca2+-induced mitochondrial depolarization and reactive oxygen species (ROS) production were evaluated in isolated brain mitochondria. Results We found that 10% CIH is neuroprotective, while 6% CIH exacerbates tissue damage. No differences in resting or intra-ischemic CBF were observed between 6% and 10% CIH. However, 10% CIH reduced, while 6% CIH increases mitochondrial ROS production and susceptibility to Ca2+-induced depolarizations. Conclusions The influence of CIH on the ischemic brain is dichotomous and can be attributed in part to changes in the mitochondrial susceptibility to injury. The findings highlight a previously unappreciated complexity in the effect of CIH on the brain, which needs to be considered in evaluating the neurological impact of conditions associated with cyclic hypoxia. PMID:24713530

  18. Spreading depolarization monitoring in neurocritical care of acute brain injury.

    PubMed

    Hartings, Jed A

    2017-04-01

    Spreading depolarizations are unique in being discrete pathologic entities that are well characterized experimentally and also occur commonly in patients with substantial acute brain injury. Here, we review essential concepts in depolarization monitoring, highlighting its clinical significance, interpretation, and future potential. Cortical lesion development in diverse animal models is mediated by tissue waves of mass spreading depolarization that cause the toxic loss of ion homeostasis and limit energy substrate supply through associated vasoconstriction. The signatures of such deterioration are observed in electrocorticographic recordings from perilesional cortex of patients with acute stroke or brain trauma. Experimental work suggests that depolarizations are triggered by energy supply-demand mismatch in focal hotspots of the injury penumbra, and depolarizations are usually observed clinically when other monitoring variables are within recommended ranges. These results suggest that depolarizations are a sensitive measure of relative ischemia and ongoing secondary injury, and may serve as a clinical guide for personalized, mechanistically targeted therapy. Both existing and future candidate therapies offer hope to limit depolarization recurrence. Electrocorticographic monitoring of spreading depolarizations in patients with acute brain injury provides a sensitive measure of relative energy shortage in focal, vulnerable brains regions and indicates ongoing secondary damage. Depolarization monitoring holds potential for targeted clinical trial design and implementation of precision medicine approaches to acute brain injury therapy.

  19. Brain Injury Alters Volatile Metabolome.

    PubMed

    Kimball, Bruce A; Cohen, Akiva S; Gordon, Amy R; Opiekun, Maryanne; Martin, Talia; Elkind, Jaclynn; Lundström, Johan N; Beauchamp, Gary K

    2016-06-01

    Chemical signals arising from body secretions and excretions communicate information about health status as have been reported in a range of animal models of disease. A potential common pathway for diseases to alter chemical signals is via activation of immune function-which is known to be intimately involved in modulation of chemical signals in several species. Based on our prior findings that both immunization and inflammation alter volatile body odors, we hypothesized that injury accompanied by inflammation might correspondingly modify the volatile metabolome to create a signature endophenotype. In particular, we investigated alteration of the volatile metabolome as a result of traumatic brain injury. Here, we demonstrate that mice could be trained in a behavioral assay to discriminate mouse models subjected to lateral fluid percussion injury from appropriate surgical sham controls on the basis of volatile urinary metabolites. Chemical analyses of the urine samples similarly demonstrated that brain injury altered urine volatile profiles. Behavioral and chemical analyses further indicated that alteration of the volatile metabolome induced by brain injury and alteration resulting from lipopolysaccharide-associated inflammation were not synonymous. Monitoring of alterations in the volatile metabolome may be a useful tool for rapid brain trauma diagnosis and for monitoring recovery. Published by Oxford University Press on behalf of US Government 2016.

  20. Brain Injury Alters Volatile Metabolome

    PubMed Central

    Cohen, Akiva S.; Gordon, Amy R.; Opiekun, Maryanne; Martin, Talia; Elkind, Jaclynn; Lundström, Johan N.; Beauchamp, Gary K.

    2016-01-01

    Chemical signals arising from body secretions and excretions communicate information about health status as have been reported in a range of animal models of disease. A potential common pathway for diseases to alter chemical signals is via activation of immune function—which is known to be intimately involved in modulation of chemical signals in several species. Based on our prior findings that both immunization and inflammation alter volatile body odors, we hypothesized that injury accompanied by inflammation might correspondingly modify the volatile metabolome to create a signature endophenotype. In particular, we investigated alteration of the volatile metabolome as a result of traumatic brain injury. Here, we demonstrate that mice could be trained in a behavioral assay to discriminate mouse models subjected to lateral fluid percussion injury from appropriate surgical sham controls on the basis of volatile urinary metabolites. Chemical analyses of the urine samples similarly demonstrated that brain injury altered urine volatile profiles. Behavioral and chemical analyses further indicated that alteration of the volatile metabolome induced by brain injury and alteration resulting from lipopolysaccharide-associated inflammation were not synonymous. Monitoring of alterations in the volatile metabolome may be a useful tool for rapid brain trauma diagnosis and for monitoring recovery. PMID:26926034

  1. Microglial Activation in Traumatic Brain Injury

    PubMed Central

    Donat, Cornelius K.; Scott, Gregory; Gentleman, Steve M.; Sastre, Magdalena

    2017-01-01

    Microglia have a variety of functions in the brain, including synaptic pruning, CNS repair and mediating the immune response against peripheral infection. Microglia rapidly become activated in response to CNS damage. Depending on the nature of the stimulus, microglia can take a number of activation states, which correspond to altered microglia morphology, gene expression and function. It has been reported that early microglia activation following traumatic brain injury (TBI) may contribute to the restoration of homeostasis in the brain. On the other hand, if they remain chronically activated, such cells display a classically activated phenotype, releasing pro-inflammatory molecules, resulting in further tissue damage and contributing potentially to neurodegeneration. However, new evidence suggests that this classification is over-simplistic and the balance of activation states can vary at different points. In this article, we review the role of microglia in TBI, analyzing their distribution, morphology and functional phenotype over time in animal models and in humans. Animal studies have allowed genetic and pharmacological manipulations of microglia activation, in order to define their role. In addition, we describe investigations on the in vivo imaging of microglia using translocator protein (TSPO) PET and autoradiography, showing that microglial activation can occur in regions far remote from sites of focal injuries, in humans and animal models of TBI. Finally, we outline some novel potential therapeutic approaches that prime microglia/macrophages toward the beneficial restorative microglial phenotype after TBI. PMID:28701948

  2. Defense and Veterans Brain Injury Center

    MedlinePlus

    Skip to main content Search form Search Basket Contact Us DVBIC Defense and Veterans Brain Injury Center About DVBIC Leadership History Newsroom Contact Us FAQs About Traumatic Brain Injury TBI & the Military DoD Worldwide Numbers for TBI ...

  3. Traumatic Brain Injury (TBI) Data and Statistics

    MedlinePlus

    ... Cancel Submit Search The CDC Traumatic Brain Injury & Concussion Note: Javascript is disabled or is not supported ... this page: About CDC.gov . Traumatic Brain Injury & Concussion Basic Information Get the Facts Signs and Symptoms ...

  4. Prevention of Glutamate Accumulation and Upregulation of Phospho-Akt may Account for Neuroprotection Afforded by Bergamot Essential Oil against Brain Injury Induced by Focal Cerebral Ischemia in Rat.

    PubMed

    Amantea, Diana; Fratto, Vincenza; Maida, Simona; Rotiroti, Domenicantonio; Ragusa, Salvatore; Nappi, Giuseppe; Bagetta, Giacinto; Corasaniti, Maria Tiziana

    2009-01-01

    The effects of bergamot essential oil (BEO; Citrus bergamia, Risso) on brain damage caused by permanent focal cerebral ischemia in rat were investigated. Administration of BEO (0.1-0.5 ml/kg but not 1 ml/kg, given intraperitoneally 1 h before occlusion of the middle cerebral artery, MCAo) significantly reduced infarct size after 24 h permanent MCAo. The most effective dose (0.5 ml/kg) resulted in a significant reduction of infarct extension throughout the brain, especially in the medial striatum and the motor cortex as revealed by TTC staining of tissue slices. Microdialysis experiments show that BEO (0.5 ml/kg) did not affect basal amino acid levels, whereas it significantly reduced excitatory amino acid, namely aspartate and glutamate, efflux in the frontoparietal cortex typically observed following MCAo. Western blotting experiments demonstrated that these early effects were associated, 24 h after permanent MCAo, to a significant increase in the phosphorylation and activity of the prosurvival kinase, Akt. Indeed, BEO significantly enhanced the phosphorylation of the deleterious downstream kinase, GSK-3beta, whose activity is negatively regulated via phosphorylation by Akt.

  5. Hypersomnia Following Traumatic Brain Injury

    PubMed Central

    Watson, Nathaniel F; Dikmen, Sureyya; Machamer, Joan; Doherty, Michael; Temkin, Nancy

    2007-01-01

    Study Objectives: To evaluate the prevalence and natural history of sleepiness following traumatic brain injury. Methods: This prospective cohort study used the Sickness Impact Profile to evaluate sleepiness in 514 consecutive subjects with traumatic brain injury (TBI), 132 non-cranial trauma controls, and 102 trauma-free controls 1 month and 1 year after injury. Results: Fifty-five percent of TBI subjects, 41% of non-cranial trauma controls, and 3% of trauma-free controls endorsed 1 or more sleepiness items 1 month following injury (p < .001). One year following injury, 27% of TBI subjects, 23% of non-cranial trauma controls, and 1% of trauma-free controls endorsed 1 or more sleepiness items (p < .001). Patients with TBI were sleepier than non-cranial trauma controls at 1 month (p < .02) but not 1 year after injury. Brain-injured subjects were divided into injury-severity groups based on time to follow commands (TFC). At 1 month, the non-cranial trauma controls were less sleepy than the 1- to 6-day (p < .05), 7- to 13-day (p < .01), and 14-day or longer (p < .01) TFC groups. In addition, the ≤ 24-hour group was less sleepy then the 7- to 13-day and 14-day or longer groups (each p < .05). At 1 year, the non-cranial trauma control group (p < .05) and the ≤ 24-hour TFC group (p < .01) were less sleepy than the 14-day or longer TFC group. Sleepiness improved in 84% to 100% of subjects in the TBI TFC groups, as compared with 78% of the non-cranial trauma control group (p < .01). Conclusions: Sleepiness is common following traumatic injury, particularly TBI, with more severe injuries resulting in greater sleepiness. Sleepiness improves in many patients, particularly those with TBI. However, about a quarter of TBI subjects and non-cranial trauma control subjects remained sleepy 1 year after injury. Citation: Watson NF; Dikmen S; Machamer J et al. Hypersomnia following traumatic brain injury. J Clin Sleep Med 2007;3(4):363-368. PMID:17694724

  6. Traumatic Brain Injury (TBI) in Kids

    MedlinePlus

    ... head injury) or by an object penetrating the skull (called a penetrating injury). Some TBIs result in ... to) several types of injury to the brain: Skull fracture occurs when the skull cracks. Pieces of ...

  7. Cerebral Vascular Injury in Traumatic Brain Injury.

    PubMed

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

    2016-01-01

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

  8. Knowledge of Traumatic Brain Injury among Educators

    ERIC Educational Resources Information Center

    Ernst, William J.; Gallo, Adrienne B.; Sellers, Amanda L.; Mulrine, Jessica; MacNamara, Luciana; Abrahamson, Allison; Kneavel, Meredith

    2016-01-01

    The purpose of this study is to determine knowledge of traumatic brain injury among educators. Few studies have examined knowledge of traumatic brain injury in this population and fewer still have included a substantial proportion of general education teachers. Examining knowledge of traumatic brain injury in educators is important as the vast…

  9. Assessment of Students with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    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…

  10. Assessment of Students with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    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…

  11. Knowledge of Traumatic Brain Injury among Educators

    ERIC Educational Resources Information Center

    Ernst, William J.; Gallo, Adrienne B.; Sellers, Amanda L.; Mulrine, Jessica; MacNamara, Luciana; Abrahamson, Allison; Kneavel, Meredith

    2016-01-01

    The purpose of this study is to determine knowledge of traumatic brain injury among educators. Few studies have examined knowledge of traumatic brain injury in this population and fewer still have included a substantial proportion of general education teachers. Examining knowledge of traumatic brain injury in educators is important as the vast…

  12. Acute focal brain damage alters mitochondrial dynamics and autophagy in axotomized neurons.

    PubMed

    Cavallucci, V; Bisicchia, E; Cencioni, M T; Ferri, A; Latini, L; Nobili, A; Biamonte, F; Nazio, F; Fanelli, F; Moreno, S; Molinari, M; Viscomi, M T; D'Amelio, M

    2014-11-27

    Mitochondria are key organelles for the maintenance of life and death of the cell, and their morphology is controlled by continual and balanced fission and fusion dynamics. A balance between these events is mandatory for normal mitochondrial and neuronal function, and emerging evidence indicates that mitochondria undergo extensive fission at an early stage during programmed cell death in several neurodegenerative diseases. A pathway for selective degradation of damaged mitochondria by autophagy, known as mitophagy, has been described, and is of particular importance to sustain neuronal viability. In the present work, we analyzed the effect of autophagy stimulation on mitochondrial function and dynamics in a model of remote degeneration after focal cerebellar lesion. We provided evidence that lesion of a cerebellar hemisphere causes mitochondria depolarization in axotomized precerebellar neurons associated with PTEN-induced putative kinase 1 accumulation and Parkin translocation to mitochondria, block of mitochondrial fusion by Mfn1 degradation, increase of calcineurin activity and dynamin-related protein 1 translocation to mitochondria, and consequent mitochondrial fission. Here we suggest that the observed neuroprotective effect of rapamycin is the result of a dual role: (1) stimulation of autophagy leading to damaged mitochondria removal and (2) enhancement of mitochondria fission to allow their elimination by mitophagy. The involvement of mitochondrial dynamics and mitophagy in brain injury, especially in the context of remote degeneration after acute focal brain damage, has not yet been investigated, and these findings may offer new target for therapeutic intervention to improve functional outcomes following acute brain damage.

  13. Propofol post-conditioning protects the blood brain barrier by decreasing matrix metalloproteinase-9 and aquaporin-4 expression and improves the neurobehavioral outcome in a rat model of focal cerebral ischemia-reperfusion injury.

    PubMed

    Ji, Feng-Tao; Liang, Jian-Jun; Miao, Li-Ping; Wu, Qiang; Cao, Ming-Hui

    2015-08-01

    Propofol, an intravenous anesthetic, inhibits neuronal apoptosis induced by ischemic stroke, protects the brain from ischemia/reperfusion injury and improves neuronal function. However, whether propofol is able to protect the blood brain barrier (BBB) and the underlying mechanisms have remained to be elucidated. In the present study, a rat model of cerebral ischemia/reperfusion was established, using a thread embolism to achieve middle cerebral artery occlusion. Rats were treated with propofol (propofol post-conditioning) or physiological saline (control) administered by intravenous injection 30 min following reperfusion. Twenty-four hours following reperfusion, neurobehavioral manifestations were assessed. The levels of cephaloedema, damage to the BBB and expression levels of matrix metalloproteinase-9 (MMP-9), aquaporin-4 (AQP-4) and phosphorylated c-Jun N-terminal kinase (pJNK) were determined in order to evaluate the effects of propofol on the BBB. In comparison to the cerebral ischemia/reperfusion group, the levels of brain water content and Evans blue content, as well as the expression levels of MMP-9, AQP-4 and pJNK were significantly reduced in the propofol post-conditioning group. These results indicated that propofol post-conditioning improved the neurobehavioral manifestations and attenuated the BBB damage and cephaloedema induced following cerebral ischemia/reperfusion. This effect may be due to the inhibition of MMP-9 and AQP-4 expression, and the concurrent decrease in JNK phosphorylation.

  14. Neurostimulation for traumatic brain injury.

    PubMed

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

    2014-11-01

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

  15. Management of penetrating brain injury.

    PubMed

    Kazim, Syed Faraz; Shamim, Muhammad Shahzad; Tahir, Muhammad Zubair; Enam, Syed Ather; Waheed, Shahan

    2011-07-01

    Penetrating brain injury (PBI), though less prevalent than closed head trauma, carries a worse prognosis. The publication of Guidelines for the Management of Penetrating Brain Injury in 2001, attempted to standardize the management of PBI. This paper provides a precise and updated account of the medical and surgical management of these unique injuries which still present a significant challenge to practicing neurosurgeons worldwide. The management algorithms presented in this document are based on Guidelines for the Management of Penetrating Brain Injury and the recommendations are from literature published after 2001. Optimum management of PBI requires adequate comprehension of mechanism and pathophysiology of injury. Based on current evidence, we recommend computed tomography scanning as the neuroradiologic modality of choice for PBI patients. Cerebral angiography is recommended in patients with PBI, where there is a high suspicion of vascular injury. It is still debatable whether craniectomy or craniotomy is the best approach in PBI patients. The recent trend is toward a less aggressive debridement of deep-seated bone and missile fragments and a more aggressive antibiotic prophylaxis in an effort to improve outcomes. Cerebrospinal fluid (CSF) leaks are common in PBI patients and surgical correction is recommended for those which do not close spontaneously or are refractory to CSF diversion through a ventricular or lumbar drain. The risk of post-traumatic epilepsy after PBI is high, and therefore, the use of prophylactic anticonvulsants is recommended. Advanced age, suicide attempts, associated coagulopathy, Glasgow coma scale score of 3 with bilaterally fixed and dilated pupils, and high initial intracranial pressure have been correlated with worse outcomes in PBI patients.

  16. Management of penetrating brain injury

    PubMed Central

    Kazim, Syed Faraz; Shamim, Muhammad Shahzad; Tahir, Muhammad Zubair; Enam, Syed Ather; Waheed, Shahan

    2011-01-01

    Penetrating brain injury (PBI), though less prevalent than closed head trauma, carries a worse prognosis. The publication of Guidelines for the Management of Penetrating Brain Injury in 2001, attempted to standardize the management of PBI. This paper provides a precise and updated account of the medical and surgical management of these unique injuries which still present a significant challenge to practicing neurosurgeons worldwide. The management algorithms presented in this document are based on Guidelines for the Management of Penetrating Brain Injury and the recommendations are from literature published after 2001. Optimum management of PBI requires adequate comprehension of mechanism and pathophysiology of injury. Based on current evidence, we recommend computed tomography scanning as the neuroradiologic modality of choice for PBI patients. Cerebral angiography is recommended in patients with PBI, where there is a high suspicion of vascular injury. It is still debatable whether craniectomy or craniotomy is the best approach in PBI patients. The recent trend is toward a less aggressive debridement of deep-seated bone and missile fragments and a more aggressive antibiotic prophylaxis in an effort to improve outcomes. Cerebrospinal fluid (CSF) leaks are common in PBI patients and surgical correction is recommended for those which do not close spontaneously or are refractory to CSF diversion through a ventricular or lumbar drain. The risk of post-traumatic epilepsy after PBI is high, and therefore, the use of prophylactic anticonvulsants is recommended. Advanced age, suicide attempts, associated coagulopathy, Glasgow coma scale score of 3 with bilaterally fixed and dilated pupils, and high initial intracranial pressure have been correlated with worse outcomes in PBI patients. PMID:21887033

  17. Dehydroepiandrosterone sulfate is neuroprotective when administered either before or after injury in a focal cortical cold lesion model.

    PubMed

    Juhász-Vedres, Gabriella; Rózsa, Eva; Rákos, Gabriella; Dobszay, Márton B; Kis, Zsolt; Wölfling, János; Toldi, József; Párducz, Arpád; Farkas, Tamás

    2006-02-01

    Dehydroepiandrosterone and its sulfate (DHEAS) are sex hormone precursors that exert marked neurotrophic and/or neuroprotective activity in the central nervous system. The present study evaluated the effects of DHEAS and 17beta-estradiol (E2) in a focal cortical cold lesion model, in which DHEAS (50 mg/kg, sc) and E2 (35 mg/kg, sc) were administered either as pretreatment (two subsequent injections 1 d and 1 h before lesion induction) or posttreatment (immediately after lesion induction). The focal cortical cold lesion was induced in the primary motor cortex by means of a cooled copper cylinder placed directly onto the cortical surface. One hour later, the animals were killed, the brains cut into 0.4-mm-thick slices, and the sections stained with 1% triphenyltetrazolium chloride. The volume of the hemispheric lesion was calculated for each animal. The results demonstrated that the lesion area was significantly attenuated in both the DHEAS- and E2- pre- and posttreated groups and that in the presence of letrozole, a nonsteroidal aromatase inhibitor, no neuroprotection was observed, suggesting that the beneficial effect of DHEAS on the cold injury might depend on the conversion of DHEAS to E2 within the brain. It is concluded that even a single posttraumatic administration of DHEAS may be of substantial therapeutic benefit in the treatment of focal brain injury with vasogenic edema.

  18. Porphyrin-laser photodynamic induction of focal brain necrosis

    SciTech Connect

    Stroop, W.G.; Battles, E.J.; Townsend, J.J.; Schaefer, D.C.; Baringer, J.R.; Straight, R.C. )

    1989-09-01

    A noninvasive photodynamic method has been developed to produce focal brain necrosis using porphyrin activated in vivo with laser light. After peripheral injection of the photosensitive porphyrin derivative, Photofrin I, mice were irradiated on the posterior lateral aspect of the head through the intact depilated scalp with 632 nm argon-dye laser light. Animals were studied at one, two and seven days after irradiation. Blood-brain barrier damage was detected by the intravenous injection of Evans blue, horseradish peroxidase and heterologous immunoglobulins. At one and two days after irradiation, the lesions were characterized by extravasation of immunoglobulin and Evans blue, and by edema, ischemia and infiltration by monocytes. On the seventh day after irradiation, the lesion was smaller than it had been two days after irradiation, and had reactive changes at its edges and coagulative necrosis at its center. Extravasation of Evans blue and immunoglobulin was markedly reduced by the seventh day after irradiation, but uptake of horseradish peroxidase by macrophages located at the periphery of the lesion was evident.

  19. Sleep and Traumatic Brain Injury.

    PubMed

    Baumann, Christian R

    2016-03-01

    Post-traumatic sleep-wake disturbances are frequent and often chronic complications after traumatic brain injury. The most prevalent sleep-wake disturbances are insomnia, excessive daytime sleepiness, and pleiosomnia, (i.e., increased sleep need). These disturbances are probably of multifactorial origin, but direct traumatic damage to key brain structures in sleep-wake regulation is likely to contribute. Diagnosis and treatment consist of standard approaches, but because of misperception of sleep-wake behavior in trauma patients, subjective testing alone may not always suffice.

  20. TBI and Nonverbal Executive Functioning: Examination of a Modified Design Fluency Test's Psychometric Properties and Sensitivity to Focal Frontal Injury.

    PubMed

    Soble, Jason R; Donnell, Alison J; Belanger, Heather G

    2013-04-16

    The purpose of this study was to investigate a modified version of the Design Fluency Test (DFT; Jones-Gotman & Milner, 1977 ) to establish its psychometric properties and clinical sensitivity to frontal traumatic brain injury (TBI). Twenty-five participants with moderate-to-severe TBI and focal frontal injury confirmed on magnetic resonance imaging or computed tomography, and 25 participants with TBI and nonfrontal focal injury were administered a modified fixed version of the DFT (Russell & Starkey, 1993 ). Analyses revealed that this modified DFT demonstrated excellent interrater agreement and consistency. This measure also demonstrated modest convergent validity with established measures of executive function abilities and discriminant validity with measures of other cognitive domains. Lastly, participants with frontal TBI generated significantly fewer novel designs compared with participants with nonfrontal focal injury. However, no significant differences were detected with regard to the total number of errors committed. Collectively, these results suggest that this fixed version of the DFT is a reliable measure of nonverbal executive functioning sensitive to frontal TBI.

  1. Sedation in Traumatic Brain Injury

    PubMed Central

    Flower, Oliver; Hellings, Simon

    2012-01-01

    Several different classes of sedative agents are used in the management of patients with traumatic brain injury (TBI). These agents are used at induction of anaesthesia, to maintain sedation, to reduce elevated intracranial pressure, to terminate seizure activity and facilitate ventilation. The intent of their use is to prevent secondary brain injury by facilitating and optimising ventilation, reducing cerebral metabolic rate and reducing intracranial pressure. There is limited evidence available as to the best choice of sedative agents in TBI, with each agent having specific advantages and disadvantages. This review discusses these agents and offers evidence-based guidance as to the appropriate context in which each agent may be used. Propofol, benzodiazepines, narcotics, barbiturates, etomidate, ketamine, and dexmedetomidine are reviewed and compared. PMID:23050154

  2. Overexpression of Thioredoxin in Transgenic Mice Attenuates Focal Ischemic Brain Damage

    NASA Astrophysics Data System (ADS)

    Takagi, Yasushi; Mitsui, Akira; Nishiyama, Akira; Nozaki, Kazuhiko; Sono, Hiroshi; Gon, Yasuhiro; Hashimoto, Nobuo; Yodoi, Junji

    1999-03-01

    Thioredoxin (TRX) plays important biological roles both in intra- and extracellular compartments, including in regulation of various intracellular molecules via thiol redox control. We produced TRX overexpressing mice and confirmed that there were no anatomical and physiological differences between wild-type (WT) mice and TRX transgenic (Tg) mice. In the present study we subjected mice to focal brain ischemia to shed light on the role of TRX in brain ischemic injury. At 24 hr after middle cerebral artery occlusion, infarct areas and volume were significantly smaller in Tg mice than in WT mice. Moreover neurological deficit was ameliorated in Tg mice compared with WT mice. Protein carbonyl content, a marker of cellular protein oxidation, in Tg mice showed less increase than did that of WT mice after the ischemic insult. Furthermore, c-fos expression in Tg mice was stronger than in WT mice 1 hr after ischemia. Our results suggest that transgene expression of TRX decreased ischemic neuronal injury and that TRX and the redox state modified by TRX play a crucial role in brain damage during stroke.

  3. Brain injury requires lung protection

    PubMed Central

    Lopez-Aguilar, Josefina

    2015-01-01

    The paper entitled “The high-mobility group protein B1-Receptor for advanced glycation endproducts (HMGB1-RAGE) axis mediates traumatic brain injury (TBI)-induced pulmonary dysfunction in lung transplantation” published recently in Science Translational Medicine links lung failure after transplantation with alterations in the axis HMGB1-RAGE after TBI, opening a new field for exploring indicators for the early detection of patients at risk of developing acute lung injury (ALI). The lung is one of the organs most vulnerable to the inflammatory cascade triggered by TBI. HMGB1 is an alarm in that can be released from activated immune cells in response to tissue injury. Increased systemic HMGB1 concentration correlates with poor lung function before and after lung transplant, confirming its role in acute ALI after TBI. HMGB1 exerts its influence by interacting with several receptors, including the RAGE receptor. RAGE also plays an important role in the onset of innate immune inflammatory responses, and systemic levels of RAGE are strongly associated with ALI and clinical outcomes in ventilator-induced lung injury. RAGE ligation to HMGB1 triggers the amplification of the inflammatory cascade involving nuclear factor-κB (NF-κB) activation. Identifying early biomarkers that mediate pulmonary dysfunction will improve outcomes not only in lung transplantation, but also in other scenarios. These novel findings show that upregulation of the HMGB1-RAGE axis plays an important role in brain-lung crosstalk. PMID:26046092

  4. The validity of the Brain Injury Cognitive Screen (BICS) as a neuropsychological screening assessment for traumatic and non-traumatic brain injury.

    PubMed

    Vaughan, Frances L; Neal, Jo Anne; Mulla, Farzana Nizam; Edwards, Barbara; Coetzer, Rudi

    2017-04-01

    The Brain Injury Cognitive Screen (BICS) was developed as an in-service cognitive assessment battery for acquired brain injury patients entering community rehabilitation. The BICS focuses on domains that are particularly compromised following TBI, and provides a broader and more detailed assessment of executive function, attention and information processing than comparable screening assessments. The BICS also includes brief assessments of perception, naming, and construction, which were predicted to be more sensitive to impairments following non-traumatic brain injury. The studies reported here examine preliminary evidence for its validity in post-acute rehabilitation. In Study 1, TBI patients completed the BICS and were compared with matched controls. Patients with focal lesions and matched controls were compared in Study 2. Study 3 examined demographic effects in a sample of normative data. TBI and focal lesion patients obtained significantly lower composite memory, executive function and attention and information processing BICS scores than healthy controls. Injury severity effects were also obtained. Logistic regression analyses indicated that each group of BICS memory, executive function and attention measures reliably differentiated TBI and focal lesion participants from controls. Design Recall, Prospective Memory, Verbal Fluency, and Visual Search test scores showed significant independent regression effects. Other subtest measures showed evidence of sensitivity to brain injury. The study provides preliminary evidence of the BICS' sensitivity to cognitive impairment caused by acquired brain injury, and its potential clinical utility as a cognitive screen. Further validation based on a revised version of the BICS and more normative data are required.

  5. Traumatic brain injury among Indiana state prisoners.

    PubMed

    Ray, Bradley; Sapp, Dona; Kincaid, Ashley

    2014-09-01

    Research on traumatic brain injury among inmates has focused on comparing the rate of traumatic brain injury among offenders to the general population, but also how best to screen for traumatic brain injury among this population. This study administered the short version of the Ohio State University Traumatic Brain Injury Identification Method to all male inmates admitted into Indiana state prisons were screened for a month (N = 831). Results indicate that 35.7% of the inmates reported experiencing a traumatic brain injury during their lifetime and that these inmates were more likely to have a psychiatric disorder and a prior period of incarceration than those without. Logistic regression analysis finds that a traumatic brain injury predicts the likelihood of prior incarceration net of age, race, education, and psychiatric disorder. This study suggests that brief instruments can be successfully implemented into prison screenings to help divert inmates into needed treatment.

  6. How woodpecker avoids brain injury?

    NASA Astrophysics Data System (ADS)

    Wu, C. W.; Zhu, Z. D.; Zhang, W.

    2015-07-01

    It has long been recognized that woodpecker is an excellent anti-shock organism, as its head and brain can bear high deceleration up to 1500 g under fast pecking. To investigate the mechanism of brain protection of woodpecker, we built a finite element model of a whole woodpecker using computed topography scanning technique and geometry modeling. Numerical results show that the periodical changing Young's modulus around the skull affects the stress wave propagation in head and makes the stress lowest at the position of the brain. Modal analysis reveals the application of pre-tension force to the hyoid bone can increase the natural frequency of woodpecker's head. The large gap between the natural and working frequencies enable the woodpecker to effectively protect its brain from the resonance injury. Energy analyses indicate the majority of the impact energy (99.7%) is stored in the bulk of body and is utilized in the next pecking. There is only a small fraction of it enters into the head (0.3%). The whole body of the woodpecker gets involved in the energy conversion and forms an efficient anti-shock protection system for the brain.

  7. Pentoxifylline attenuates TNF-α protein levels and brain edema following temporary focal cerebral ischemia in rats.

    PubMed

    Vakili, Abedin; Mojarrad, Somye; Akhavan, Maziar Mohammad; Rashidy-Pour, Ali

    2011-03-04

    Cerebral edema is the most common cause of neurological deterioration and mortality during acute ischemic stroke. Despite the clinical importance of cerebral ischemia, the underlying mechanisms remain poorly understood. Recent studies suggest a role for TNF-α in the brain edema formation. To further investigate whether TNF-α would play a role in brain edema formation, we examined the effects of pentoxifylline (PTX, an inhibitor of TNF-α synthesis) on the brain edema and TNF-α levels in a model of transient focal cerebral ischemia. The right middle cerebral artery (MCA) of rats was occluded for 60 min using the intraluminal filament method. The animals received PTX (60 mg/kg) immediately, 1, 3, or 6h post-ischemic induction. Twenty-four hours after induction of ischemic injury, permeability of the blood-brain barrier (BBB) and brain edema were determined by in situ brain perfusion of Evans Blue (EB) and wet-to-dry weight ratio, respectively. TNF-α protein levels in ischemic cortex were also measured at 1, 4, and 24h after the beginning of an ischemic stroke by using an enzyme-linked immunosorbent assay method. The administration of PTX up to 6h after occlusion of the MCA significantly reduced the brain edema. Moreover, PTX significantly reduced the concentration of TNF-α in ischemic brain cortex up to 4h post-transient focal stroke (P<0.002). Finally, treatment by PTX led to a significant decrease in EB extravasations (P<0.001). Our data demonstrate that PTX administration up to 6h after ischemia can reduce brain edema in a model of transient focal cerebral ischemia. The beneficial effects of PTX may be mediated, at least in part, through a decline in TNF-α production and BBB breakdown.

  8. Brain plasticity and recovery from early cortical injury.

    PubMed

    Kolb, Bryan; Mychasiuk, Richelle; Williams, Preston; Gibb, Robbin

    2011-09-01

    Neocortical development represents more than a simple unfolding of a genetic blueprint: rather, it represents a complex dance of genetic and environmental events that interact to adapt the brain to fit a particular environmental context. Most cortical regions are sensitive to a wide range of experiential factors during development and later in life, but the injured cortex appears to be unusually sensitive to perinatal experiences. This paper reviews the factors that influence how normal and injured brains (both focal and ischemic injuries) develop and adapt into adulthood. Such factors include prenatal experiences in utero as well as postnatal experiences throughout life. Examples include the effects of sensory and motor stimulation, psychoactive drugs (including illicit and prescription drugs), maternal and postnatal stress, neurotrophic factors, and pre- and postnatal diet. All these factors influence cerebral development and influence recovery from brain injury during development.

  9. Hypopituitarism after traumatic brain injury.

    PubMed

    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.

  10. Topiramate reduces non-convulsive seizures after focal brain ischemia in the rat.

    PubMed

    Williams, Anthony J; Tortella, Frank C; Gryder, Divina; Hartings, Jed A

    2008-01-03

    Acute "silent" seizures after brain injury are associated with a worsening of patient outcome and are often refractory to anti-epileptic drug (AED) therapy. In the present study we evaluated topiramate (TPM, 1-30 mg/kg, i.v.) in a rodent model of spontaneous non-convulsive seizure (NCS) activity induced by focal cerebral ischemia. For seizure detection, electroencephalographic (EEG) activity was continuously recorded for 24h in male Sprague-Dawley rats subjected to permanent middle cerebral artery occlusion (MCAo). Infarct volume, neurological deficit, and NCS were evaluated by an experimenter blinded to the treatment group. All vehicle treated rats (7/7) exhibited NCS following MCAo. TPM treatment, delivered at 20 min post-occlusion and prior to onset of NCS activity, dose-dependently reduced the incidence of NCS (ED(50)=21.1mg/kg). The highest dose of TPM tested (30 mg/kg) exhibited maximal reductions of 76% in the number of NCS/rat (vehicle=22.1+/-5.3, TPM=4.4+/-3.2, P<0.05), 80% in the total time of NCS (vehicle=1259+/-337 s, TPM=253+/-220 s, P<0.05), 20% in core brain infarction (vehicle=45+/-1%, TPM=36+/-4%, percent of ipsilateral volume corrected for swelling, P<0.05), and 38% in neurological deficit score (vehicle=7.4+/-1.2, TPM=4.6+/-1.5, P<0.05). Despite efficacy as a pre-seizure treatment, TPM was not effective when delivered immediately following onset of the first NCS event (36+/-5 min post-MCAo). In conclusion, TPM exhibited significant efficacy for the prophylactic treatment of brain-injury induced NCS and represents a novel class of AED for treatment of this type of silent brain seizure.

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

    ERIC Educational Resources Information Center

    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:…

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

    ERIC Educational Resources Information Center

    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:…

  13. Brain Temperature: Physiology and Pathophysiology after Brain Injury

    PubMed Central

    Mrozek, Ségolène; Vardon, Fanny; Geeraerts, Thomas

    2012-01-01

    The regulation of brain temperature is largely dependent on the metabolic activity of brain tissue and remains complex. In intensive care clinical practice, the continuous monitoring of core temperature in patients with brain injury is currently highly recommended. After major brain injury, brain temperature is often higher than and can vary independently of systemic temperature. It has been shown that in cases of brain injury, the brain is extremely sensitive and vulnerable to small variations in temperature. The prevention of fever has been proposed as a therapeutic tool to limit neuronal injury. However, temperature control after traumatic brain injury, subarachnoid hemorrhage, or stroke can be challenging. Furthermore, fever may also have beneficial effects, especially in cases involving infections. While therapeutic hypothermia has shown beneficial effects in animal models, its use is still debated in clinical practice. This paper aims to describe the physiology and pathophysiology of changes in brain temperature after brain injury and to study the effects of controlling brain temperature after such injury. PMID:23326261

  14. A neuropsychiatric perspective on traumatic brain injury.

    PubMed

    Lux, Warren E

    2007-01-01

    Traumatic brain injury (TBI) due to closed mechanisms causes strain injuries to axons that increase in number and severity as injury severity increases. Axons that project up from the brain stem are vulnerable, even in milder concussive injuries, and include axons that participate in key monoaminergic pathways. Although called diffuse axonal injury, the supra-tentorial injury component typically shows an anterior preponderance in humans. As the injury forces increase, cerebral contusions may be superimposed on the axonal strain injuries, and these contusions show an anterior preponderance as well. The chronic neuropsychiatric manifestations of TBI reflect this injury distribution. In the cognitive sphere, these manifestations almost always include power function disturbances marked by difficulties with cognitive processing speed, multitasking, and cognitive endurance. These disturbances may then be followed by disturbances in executive function and self-awareness as injury severity increases. In the behavioral sphere, mood disturbances and disorders of behavioral control and regulation are particularly common.

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

    ERIC Educational Resources Information Center

    Bigler, Erin D.

    1996-01-01

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

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

    ERIC Educational Resources Information Center

    Bigler, Erin D.

    1996-01-01

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

  17. Surveillance of traumatic brain injuries in Utah.

    PubMed Central

    Thurman, D J; Jeppson, L; Burnett, C L; Beaudoin, D E; Rheinberger, M M; Sniezek, J E

    1996-01-01

    From 1990 through 1992 we conducted surveillance of cases requiring hospital admission and of fatal cases of traumatic brain injury among residents of Utah and found an annual incidence rate of 108.8 per 100,000 population. The greatest number of injuries occurred among men and persons aged 15 to 24 years. Motor vehicles were the leading cause of injury, followed by falls and assaults. The incidence rate we found is substantially lower than previously published rates of traumatic brain injury. This may be the result of a decrease in the incidence of these injuries in the decade since earlier studies were done, as well as changing hospital admission criteria that serve to exclude less severe cases of injury. Despite the apparent decline in rates, our findings indicate the continued importance of traumatic brain injury as a public health problem and the need to develop more effective prevention strategies that will address the major causes of these injuries. PMID:8987423

  18. ApoE and S-100 expression and its significance in the brain tissue of rats with focal contusion.

    PubMed

    Wang, Z L; Chai, R F; Yang, W S; Liu, Y; Qin, H; Wu, H; Zhu, X F; Wang, Y X; Dangmurenjiafu, G

    2015-12-29

    This study explored the effect of focal cerebral contusion on the expression of ApoE and S-100, and its significance in determining the time of brain injury. Based on a rat model of cerebral contusion, immunohistochemistry was used to analyze the expressions of S-100 and ApoE at different time points after injury. Thirty minutes following cerebral contusion, ApoE protein expression was significantly increased in cortex neurons (P < 0.01), and S-100 protein expression was significantly (P < 0.001) elevated 2 h after cerebral contusion. Over time, the number of ApoE and S-100 positively expressing cells gradually increased. Three days after injury, ApoE was widely distributed throughout the tissue and the number of ApoE-positive cells and staining intensity reached a peak. ApoE expression decreased after this time point. Five days after cerebral contusion, the number of S-100-positive cells reached a peak level of expression higher than that in the control group. Our data demonstrate that the expression of ApoE and S-100 correlated with the progression of focal cerebral contusion. This suggests that both proteins may serve as effective biomarkers of focal cerebral contusions.

  19. Support Network Responses to Acquired Brain Injury

    ERIC Educational Resources Information Center

    Chleboun, Steffany; Hux, Karen

    2011-01-01

    Acquired brain injury (ABI) affects social relationships; however, the ways social and support networks change and evolve as a result of brain injury is not well understood. This study explored ways in which survivors of ABI and members of their support networks perceive relationship changes as recovery extends into the long-term stage. Two…

  20. Behavioral Considerations Associated with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Mayfield, Joan; Homack, Susan

    2005-01-01

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

  1. Traumatic Brain Injury. Fact Sheet Number 18.

    ERIC Educational Resources Information Center

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

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

  2. Behavioral Considerations Associated with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Mayfield, Joan; Homack, Susan

    2005-01-01

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

  3. Resource Guide on Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Monfore, Dorothea

    2005-01-01

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

  4. Traumatic Brain Injury: A Challenge for Educators

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  5. Traumatic Brain Injury: A Challenge for Educators

    ERIC Educational Resources Information Center

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

    2005-01-01

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

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

    PubMed Central

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

    2011-01-01

    skull 18. Among the TBI models, LFP is the most established and commonly used model to evaluate mixed focal and diffuse brain injury 19. It is reproducible and is standardized to allow for the manipulation of injury parameters. LFP recapitulates injuries observed in humans, thus rendering it clinically relevant, and allows for exploration of novel therapeutics for clinical translation 20. We describe the detailed protocol to perform LFP procedure in mice. The injury inflicted is mild to moderate, with brain regions such as cortex, hippocampus and corpus callosum being most vulnerable. Hippocampal and motor learning tasks are explored following LFP. PMID:21876530

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

    PubMed

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

    2011-08-22

    mass on the closed skull (18). Among the TBI models, LFP is the most established and commonly used model to evaluate mixed focal and diffuse brain injury (19). It is reproducible and is standardized to allow for the manipulation of injury parameters. LFP recapitulates injuries observed in humans, thus rendering it clinically relevant, and allows for exploration of novel therapeutics for clinical translation (20). We describe the detailed protocol to perform LFP procedure in mice. The injury inflicted is mild to moderate, with brain regions such as cortex, hippocampus and corpus callosum being most vulnerable. Hippocampal and motor learning tasks are explored following LFP.

  8. Cost-appropriateness of whole body vs limited bone imaging for suspected focal sports injuries

    SciTech Connect

    Nagle, C.E.

    1986-07-01

    Bone imaging has been recognized as a useful diagnostic tool in detecting the presence of focal musculoskeletal injury when radiographs are normal. A retrospective review of bone images in a small number of amateur athletes indicates that secondary injuries were commonly detected at sites different from the site of musculoskeletal pain being evaluated for injury. While a larger study will be necessary to confirm the data, this review suggests that it is medically justified and cost-appropriate to perform imaging of the entire skeleton as opposed to imaging limited to the anatomic site of pain and suspected injury.

  9. Anesthesia for Patients with Traumatic Brain Injuries.

    PubMed

    Bhattacharya, Bishwajit; Maung, Adrian A

    2016-12-01

    Traumatic brain injury (TBI) represents a wide spectrum of disease and disease severity. Because the primary brain injury occurs before the patient enters the health care system, medical interventions seek principally to prevent secondary injury. Anesthesia teams that provide care for patients with TBI both in and out of the operating room should be aware of the specific therapies and needs of this unique and complex patient population.

  10. Animal models of traumatic brain injury: is there an optimal model to reproduce human brain injury in the laboratory?

    PubMed

    Morganti-Kossmann, M C; Yan, E; Bye, N

    2010-07-01

    Compared to other neurological diseases, the research surrounding traumatic brain injury (TBI) has a more recent history. The establishment and use of animal models of TBI remains vital to understand the pathophysiology of this highly complex disease. Such models share the ultimate goals of reproducing patterns of tissue damage observed in humans (thus rendering them clinically relevant), reproducible and highly standardised to allow for the manipulation of individual variables, and to finally explore novel therapeutics for clinical translation. There is no doubt that the similarity of cellular and molecular events observed in human and rodent TBI has reinforced the use of small animals for research. When confronted with the choice of the experimental model it becomes clear that the ideal animal model does not exist. This limitation derives from the fact that most models mimic either focal or diffuse brain injury, whereas the clinical reality suggests that each patient has an individual form of TBI characterised by various combinations of focal and diffuse patterns of tissue damage. This is additionally complicated by the occurrence of secondary insults such as hypotension, hypoxia, ischaemia, extracranial injuries, modalities of traumatic events, age, gender and heterogeneity of medical treatments and pre-existing conditions. This brief review will describe the variety of TBI models available for laboratory research beginning from the most widely used rodent models of focal brain trauma, to complex large species such as the pig. In addition, the models mimicking diffuse brain damage will be discussed in relation to the early primate studies until the use of most common rodent models to elucidate the intriguing and less understood pathology of axonal dysfunction. The most recent establishment of in vitro paradigms has complemented the in vivo modelling studies offering a further cellular and molecular insight of this pathology.

  11. Investigation of blast-induced traumatic brain injury

    PubMed Central

    Ludwigsen, John S.; Ford, Corey C.

    2014-01-01

    Objective Many troops deployed in Iraq and Afghanistan have sustained blast-related, closed-head injuries from being within non-lethal distance of detonated explosive devices. Little is known, however, about the mechanisms associated with blast exposure that give rise to traumatic brain injury (TBI). This study attempts to identify the precise conditions of focused stress wave energy within the brain, resulting from blast exposure, which will correlate with a threshold for persistent brain injury. Methods This study developed and validated a set of modelling tools to simulate blast loading to the human head. Using these tools, the blast-induced, early-time intracranial wave motions that lead to focal brain damage were simulated. Results The simulations predict the deposition of three distinct wave energy components, two of which can be related to injury-inducing mechanisms, namely cavitation and shear. Furthermore, the results suggest that the spatial distributions of these damaging energy components are independent of blast direction. Conclusions The predictions reported herein will simplify efforts to correlate simulation predictions with clinical measures of TBI and aid in the development of protective headwear. PMID:24766453

  12. Biomarkers in Silent Traumatic Brain Injury.

    PubMed

    Antonopoulos, Constantine N; Kadoglou, Nikolaos P E

    2016-01-01

    Traumatic brain injury (TBI) has been recognized among the leading causes of mortality and morbidity in young adults. Traditionally, the diagnosis of TBI has been based on neuroimaging. However, a significant portion of insulted patients appear to be apparently asymptomatic. As a result, more elaborate indices of silent TBI are required in order to immediately detect focal and diffuse asymptomatic TBI. Such valid indices will potentially increase the efficacy of therapeutic strategies in TBI patients. In this review of the literature, we present novel circulating biomolecules, as potential biomarkers of silent TBI, like neurofilaments, Cleaved-Tau (C-Tau), Microtubule-Associated Protein 2 (MAP2), Neuron-Specific Enolase, S100B and ferritin. In addition to this, assessment of white matter abnormalities and white matter integrity by diffusion tensor imaging (DTI) have emerged as promising sensitive neuroimaging methods of silent TBI. An integrated research is needed to fully understand the interplay between all the aforementioned indices and DTI. The potential diagnostic, therapeutic and prognostic values of the all aforementioned indices will be analyzed in the proposed review.

  13. Psychosis following traumatic brain injury.

    PubMed

    Arciniegas, David B; Harris, Susie N; Brousseau, Kristin M

    2003-11-01

    Psychosis is a relatively infrequent but potentially serious and debilitating consequence of traumatic brain injury (TBI), and one about which there is considerable scientific uncertainty and disagreement. There are several substantial clinical, epidemiological, and neurobiological differences between the post-traumatic psychoses and the primary psychotic disorders. The recognition of these differences may facilitate identification and treatment of patients whose psychosis is most appropriately regarded as post-traumatic. In the service of assisting psychiatrists and other mental health clinicians in the diagnosis and treatment of persons with post-traumatic psychoses, this article will review post-traumatic psychosis, including definitions relevant to describing the clinical syndrome, as well as epidemiologic, neurobiological, and neurogenetic factors attendant to it. An approach to evaluation and treatment will then be offered, emphasizing identification of the syndrome of post-traumatic psychosis, consideration of the differential diagnosis of this condition, and careful selection and administration of treatment interventions.

  14. T cell–derived interleukin (IL)-21 promotes brain injury following stroke in mice

    PubMed Central

    Clarkson, Benjamin D.S.; Ling, Changying; Shi, Yejie; Harris, Melissa G.; Rayasam, Aditya; Sun, Dandan; Salamat, M. Shahriar; Kuchroo, Vijay; Lambris, John D.; Sandor, Matyas

    2014-01-01

    T lymphocytes are key contributors to the acute phase of cerebral ischemia reperfusion injury, but the relevant T cell–derived mediators of tissue injury remain unknown. Using a mouse model of transient focal brain ischemia, we report that IL-21 is highly up-regulated in the injured mouse brain after cerebral ischemia. IL-21–deficient mice have smaller infarcts, improved neurological function, and reduced lymphocyte accumulation in the brain within 24 h of reperfusion. Intracellular cytokine staining and adoptive transfer experiments revealed that brain-infiltrating CD4+ T cells are the predominant IL-21 source. Mice treated with decoy IL-21 receptor Fc fusion protein are protected from reperfusion injury. In postmortem human brain tissue, IL-21 localized to perivascular CD4+ T cells in the area surrounding acute stroke lesions, suggesting that IL-21–mediated brain injury may be relevant to human stroke. PMID:24616379

  15. Evaluation of an Acute RNAi-Mediated Therapeutic for Visual Dysfunction Associated with Traumatic Brain Injury

    DTIC Science & Technology

    2013-10-01

    water from the brain to the blood and significantly impacts on brain swelling. We also show cognitive improvement in mice with focal cerebral...brain injury ( TBI ) is the leading cause of death in children and young adults globally. Malignant cerebral edema plays a major role in the...pathophysiology which evolves after severe TBI . Added to this is the significant morbidity and mortality from cerebral edema associated with acute stroke

  16. Hypopituitarism following traumatic brain injury.

    PubMed

    Popovic, V; Aimaretti, G; Casanueva, F F; Ghigo, E

    2005-06-01

    Recent studies have demonstrated that hypopituitarism, and in particular growth hormone (GH) deficiency, is common among survivors of traumatic brain injury (TBI) tested several months or years following head trauma. In addition, it has been shown that post-traumatic neuroendocrine abnormalities occur early and with high frequency. These findings may have significant implications for the recovery and rehabilitation of patients with TBI. Although data emerging after 2000 demonstrate the relevance of the problem, in general there is a lack of awareness in the medical community about the incidence and clinical repercussions of the pathology. Most, but not all, head trauma associated with hypopituitarism is the result of motor accidents. The subjects at risk are those who have suffered moderate-to severe head trauma although mild intensity trauma may precede hypopituitarism also. Particular attention should be paid to this problem in children and adolescents. Onset of pituitary deficits can evolve over years following injury. For the assessment of the GH-IGF axis in TBI patients, plasma IGF-I concentrations, plus dynamic GH testing is indicated. Some degree of hypopituitarism is found in 35-40% of TBI patients. Among multiple pituitary deficits, the most common ones were GHD and gonadotrophin deficiency. In most series 10-15% presented with severe GHD and 15% with partial GHD after stimulating GH secretion confirming that the most common isolated deficit is GHD. Psychometric evaluation together with neurocognitive testing shows variability of disability and the possibility that untreated TBI induced hypopituitarism contributes to the chronic neurobehavioral problems seen in many head-injured patients warrants consideration. Preliminary data, from small pilot, open-label studies show that subjects treated with GH experience significant improvements in concentration, memory, depression, anxiety and fatigue. In conclusion, pituitary failure can occur even in minor head

  17. Blast overpressure induces shear-related injuries in the brain of rats exposed to a mild traumatic brain injury.

    PubMed

    Sosa, Miguel A Gama; De Gasperi, Rita; Paulino, Alejandro J; Pricop, Paul E; Shaughness, Michael C; Maudlin-Jeronimo, Eric; Hall, Aaron A; Janssen, William G M; Yuk, Frank J; Dorr, Nathan P; Dickstein, Dara L; McCarron, Richard M; Chavko, Mikulas; Hof, Patrick R; Ahlers, Stephen T; Elder, Gregory A

    2013-08-14

    Blast-related traumatic brain injury (TBI) has been a significant cause of injury in the military operations of Iraq and Afghanistan, affecting as many as 10-20% of returning veterans. However, how blast waves affect the brain is poorly understood. To understand their effects, we analyzed the brains of rats exposed to single or multiple (three) 74.5 kPa blast exposures, conditions that mimic a mild TBI. Rats were sacrificed 24 hours or between 4 and 10 months after exposure. Intraventricular hemorrhages were commonly observed after 24 hrs. A screen for neuropathology did not reveal any generalized histopathology. However, focal lesions resembling rips or tears in the tissue were found in many brains. These lesions disrupted cortical organization resulting in some cases in unusual tissue realignments. The lesions frequently appeared to follow the lines of penetrating cortical vessels and microhemorrhages were found within some but not most acute lesions. These lesions likely represent a type of shear injury that is unique to blast trauma. The observation that lesions often appeared to follow penetrating cortical vessels suggests a vascular mechanism of injury and that blood vessels may represent the fault lines along which the most damaging effect of the blast pressure is transmitted.

  18. Blast overpressure induces shear-related injuries in the brain of rats exposed to a mild traumatic brain injury

    PubMed Central

    2013-01-01

    Background Blast-related traumatic brain injury (TBI) has been a significant cause of injury in the military operations of Iraq and Afghanistan, affecting as many as 10-20% of returning veterans. However, how blast waves affect the brain is poorly understood. To understand their effects, we analyzed the brains of rats exposed to single or multiple (three) 74.5 kPa blast exposures, conditions that mimic a mild TBI. Results Rats were sacrificed 24 hours or between 4 and 10 months after exposure. Intraventricular hemorrhages were commonly observed after 24 hrs. A screen for neuropathology did not reveal any generalized histopathology. However, focal lesions resembling rips or tears in the tissue were found in many brains. These lesions disrupted cortical organization resulting in some cases in unusual tissue realignments. The lesions frequently appeared to follow the lines of penetrating cortical vessels and microhemorrhages were found within some but not most acute lesions. Conclusions These lesions likely represent a type of shear injury that is unique to blast trauma. The observation that lesions often appeared to follow penetrating cortical vessels suggests a vascular mechanism of injury and that blood vessels may represent the fault lines along which the most damaging effect of the blast pressure is transmitted. PMID:24252601

  19. Acute Cortical Transhemispheric Diaschisis after Unilateral Traumatic Brain Injury.

    PubMed

    Le Prieult, Florie; Thal, Serge C; Engelhard, Kristin; Imbrosci, Barbara; Mittmann, Thomas

    2017-03-01

    Focal neocortical brain injuries lead to functional alterations, which can spread beyond lesion-neighboring brain areas. The undamaged hemisphere and its associated disturbances after a unilateral lesion, so-called transhemispheric diaschisis, have been progressively disclosed over the last decades; they are strongly involved in the pathophysiology and, potentially, recovery of brain injuries. Understanding the temporal dynamics of these transhemispheric functional changes is crucial to decipher the role of the undamaged cortex in the processes of functional reorganization at different stages post-lesion. In this regard, little is known about the acute-subacute processes after 24-48 h in the brain hemisphere contralateral to injury. In the present study, we performed a controlled cortical impact to produce a unilateral traumatic brain injury (TBI) in the motor and somatosensory cortex of mice. In vitro extracellular multi-unit recordings from large neuronal populations, together with single-cell patch-clamp recordings in the cortical network contralateral to the lesion, revealed a strong, but transient, neuronal hyperactivity as early as 24-48 h post-TBI. This abnormal excitable state in the intact hemisphere was not accompanied by alterations in neuronal intrinsic properties, but it was associated with an impairment of the phasic gamma aminobutyric acid (GABA)ergic transmission and an increased expression of GABAA receptor subunits related to tonic inhibition exclusively in the contralateral hemisphere. These data unravel a series of early transhemispheric functional alterations after diffuse unilateral cortical injury, which may compensate and stabilize the disrupted brain functions. Therefore, our findings support the hypothesis that the undamaged hemisphere could play a significant role in early functional reorganization processes after a TBI.

  20. Morphometric analysis of NADPH diaphorase reactive neurons in a rat model of focal excitotoxic striatal injury.

    PubMed

    Freire, Marco Aurelio M; Guimaraes, Joanilson S; Santos, Jose Ronaldo; Simplício, Hougelle; Gomes-Leal, Walace

    2016-12-01

    Excitotoxicity is the major component in neuropathological conditions, related to harmful action of imbalanced concentrations of glutamate and its agonists in the nervous tissue, ultimately resulting in cell death. In the present study, we evaluated the effects of an acute striatal lesion induced by a focal N-methyl-D-aspartate (NMDA) microinjection on the morphometry of NADPH diaphorase-reactive neurons (NADPH-d(+) ), a subset of cells which release nitric oxide (NO) in the brain and are known by its resistance in pathological conditions. Two hundred and forty NADPH-d neurons from NMDA-lesioned striatum and contralateral counterpart were tridimensionally reconstructed at 1, 3 and 7 post-lesion days (PLDs). Cell body and dendritic field areas, length of dendrites by order and fractal dimension were analyzed. There were no significant morphometric differences when NADPH-d(+) neurons from lesioned and control striatal regions were compared among PLDs evaluated. Conversely, a conspicuous pallor in striatal neuropil reactivity was evidenced, especially in latter survival time. In addition, we observed a noticeable inflammatory response induced by NMDA. Our results suggest that NADPH-d(+) neurons were spared from deleterious effects of acute NMDA excitotoxic damage in the striatum, reinforcing the notion that this cell group is selectively resistant to injury in the nervous system.

  1. Fluid markers of traumatic brain injury.

    PubMed

    Zetterberg, Henrik; Blennow, Kaj

    2015-05-01

    Traumatic brain injury (TBI) occurs when an external force traumatically injures the brain. Whereas severe TBI can be diagnosed using a combination of clinical signs and standard neuroimaging techniques, mild TBI (also called concussion) is more difficult to detect. This is where fluid markers of injury to different cell types and subcellular compartments in the central nervous system come into play. These markers are often proteins, peptides or other molecules with selective or high expression in the brain, which can be measured in the cerebrospinal fluid or blood as they leak out or get secreted in response to the injury. Here, we review the literature on fluid markers of neuronal, axonal and astroglial injury to diagnose mild TBI and to predict clinical outcome in patients with head trauma. We also discuss chronic traumatic encephalopathy, a progressive neurodegenerative disease in individuals with a history of multiple mild TBIs in a biomarker context. This article is part of a Special Issue entitled 'Traumatic Brain Injury'.

  2. Acquired Focal Brain Lesions in Childhood: Effects on Development and Reorganization of Language

    ERIC Educational Resources Information Center

    Chilosi, A. M.; Cipriani, P.; Pecini, C.; Brizzolara, D.; Biagi, L.; Montanaro, D.; Tosetti, M.; Cioni, G.

    2008-01-01

    In the present paper, we address brain-behaviour relationships in children with acquired aphasia, by reviewing some recent studies on the effects of focal brain lesions on language development. Timing of the lesion, in terms of its occurrence, before or after the onset of speech and language acquisition, may be a major factor determining language…

  3. Acquired Focal Brain Lesions in Childhood: Effects on Development and Reorganization of Language

    ERIC Educational Resources Information Center

    Chilosi, A. M.; Cipriani, P.; Pecini, C.; Brizzolara, D.; Biagi, L.; Montanaro, D.; Tosetti, M.; Cioni, G.

    2008-01-01

    In the present paper, we address brain-behaviour relationships in children with acquired aphasia, by reviewing some recent studies on the effects of focal brain lesions on language development. Timing of the lesion, in terms of its occurrence, before or after the onset of speech and language acquisition, may be a major factor determining language…

  4. The Role of Ghrelin in Neuroprotection after Ischemic Brain Injury

    PubMed Central

    Spencer, Sarah J.; Miller, Alyson A.; Andrews, Zane B.

    2013-01-01

    Ghrelin, a gastrointestinal peptide with a major role in regulating feeding and metabolism, has recently been investigated for its neuroprotective effects. In this review we discuss pre-clinical evidence suggesting ghrelin may be a useful therapeutic in protecting the brain against injury after ischemic stroke. Specifically, we will discuss evidence showing ghrelin administration can improve neuronal cell survival in animal models of focal cerebral ischemia, as well as rescue memory deficits. We will also discuss its proposed mechanisms of action, including anti-apoptotic and anti-inflammatory effects, and suggest ghrelin treatment may be a useful intervention after stroke in the clinic. PMID:24961317

  5. Diffuse optical systems and methods to image physiological changes of the brain in response to focal TBI (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Abookasis, David; Volkov, Boris; Kofman, Itamar

    2017-02-01

    During the last four decades, various optical techniques have been proposed and intensively used for biomedical diagnosis and therapy both in animal model and in human. These techniques have several advantages over the traditional existing methods: simplicity in structure, low-cost, easy to handle, portable, can be used repeatedly over time near the patient bedside for continues monitoring, and offer high spatiotemporal resolution. In this work, we demonstrate the use of two optical imaging modalities namely, spatially modulated illumination and dual-wavelength laser speckle to image the changes in brain tissue chromophores, morphology, and metabolic before, during, and after the onset of focal traumatic brain injury in intact mouse head (n=15). Injury was applied in anesthetized mice by weight-drop apparatus using 50gram metal rod striking the mouse's head. Following data analysis, we show a series of hemodynamic and structural changes over time including higher deoxyhemoglobin, reduction in oxygen saturation and blood flow, cell swelling, etc., in comparison with baseline measurements. In addition, to validate the monitoring of cerebral blood flow by the imaging system, measurements with laser Doppler flowmetry were also performed (n=5), which confirmed reduction in blood flow following injury. Overall, our result demonstrates the capability of diffuse optical modalities to monitor and map brain tissue optical and physiological properties following brain trauma.

  6. Penicillin-induced epileptiform activity elevates focal brain temperature in anesthetized rats.

    PubMed

    Tokiwa, Tatsuji; Inoue, Takao; Fujii, Masami; Ishizuka, Satoru; Aou, Shuji; Kida, Hiroyuki; Maruta, Yuichi; Yamakawa, Toshitaka; Nomura, Sadahiro; Suzuki, Michiyasu; Yamakawa, Takeshi

    2013-08-01

    To elucidate a relationship between changes in focal brain temperature and severity of abnormal brain activity, epileptiform discharges and behavioral seizures were induced by Penicillin G in anesthetized rats, and focal brain-temperature was measured. Penicillin G was injected into the right primary sensorimotor cortex (400IU/μl). After the injection, epileptiform discharges induced a temperature increase gradually by 0.65±0.24°C. Moreover, when behavioral seizures were induced by reducing the anesthesia level, the temperature was raised by 0.26±0.22°C. These results suggest that elevation of the focal brain temperature is associated with the severity of epileptic activity. Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  7. Childhood motocross truncal injuries: high-velocity, focal force to the chest and abdomen

    PubMed Central

    Kennedy, Raelene D; Potter, D Dean; Osborn, John B; Zietlow, Scott; Zarroug, Abdalla E; Moir, Christopher R; Ishitani, Michael B; McIntosh, Amy

    2012-01-01

    Objectives To review the need for operative intervention and critical care services for motocross truncal injuries in children. Design cohort Retrospective review of patients identified via the hospital trauma registry. Setting Our Level 1 Pediatric Trauma Center serves five motocross tracks. These patients require frequent medical care for injuries. Participants All patients ≤17 years of age with truncal injuries sustained during motocross activities, between 2000 and 2011, were identified through the trauma registry. Primary and secondary outcome measures Operative intervention, intensive care unit (ICU) admission, length of stay, morbidity and demographics were reviewed. Results Motocross injured 162 children. Thirty (18.5%) were thoracic or abdominal injuries. Operative intervention was required in eight (27%) patients. Mean injury severity score (ISS) was 11.8. ICU admission was required in 50% and average hospital length of stay was 4.1 days. The most common injuries include pulmonary contusion, pneumothorax, spleen and liver lacerations. 13% of subjects suffered truncal injury from motocross on more than one occasion. Conclusions Paediatric motocross-related truncal injuries are significant. Surgical intervention is required in 27% of patients. The lower ISS incurred from motocross combined with high surgical and ICU admission rates suggests focal high-impact injuries to the chest and abdomen. Despite significant injury, 13% of motocross patients suffer recurrent injuries. Parents and children need injury prevention education. PMID:23166134

  8. Childhood motocross truncal injuries: high-velocity, focal force to the chest and abdomen.

    PubMed

    Kennedy, Raelene D; Potter, D Dean; Osborn, John B; Zietlow, Scott; Zarroug, Abdalla E; Moir, Christopher R; Ishitani, Michael B; McIntosh, Amy

    2012-01-01

    To review the need for operative intervention and critical care services for motocross truncal injuries in children. DESIGN COHORT: Retrospective review of patients identified via the hospital trauma registry. Our Level 1 Pediatric Trauma Center serves five motocross tracks. These patients require frequent medical care for injuries. All patients ≤17 years of age with truncal injuries sustained during motocross activities, between 2000 and 2011, were identified through the trauma registry. Operative intervention, intensive care unit (ICU) admission, length of stay, morbidity and demographics were reviewed. Motocross injured 162 children. Thirty (18.5%) were thoracic or abdominal injuries. Operative intervention was required in eight (27%) patients. Mean injury severity score (ISS) was 11.8. ICU admission was required in 50% and average hospital length of stay was 4.1 days. The most common injuries include pulmonary contusion, pneumothorax, spleen and liver lacerations. 13% of subjects suffered truncal injury from motocross on more than one occasion. Paediatric motocross-related truncal injuries are significant. Surgical intervention is required in 27% of patients. The lower ISS incurred from motocross combined with high surgical and ICU admission rates suggests focal high-impact injuries to the chest and abdomen. Despite significant injury, 13% of motocross patients suffer recurrent injuries. Parents and children need injury prevention education.

  9. [Characteristics of structural injuries in pediatric patients with focal epilepsy in a Honduran hospital].

    PubMed

    Ramirez-Izcoa, A; Varela-Gonzalez, D; Fonseca, M I

    2017-08-01

    Epilepsy is the most commonly occurring neurological disorder in the world. The study of structural brain lesions is important to understand the secondary complications. In Honduras there is little information on this topic. To determine the characteristics and proportion of structural brain lesions in paediatric patients with focal epilepsy at the Hospital Escuela Universitario. A descriptive, cross-sectional, retrospective-prospective study. The study population consisted of 162 paediatric patients with focal epilepsy who were treated in the paediatric neurology outpatient department between January 2015 and June 2016. On applying the eligibility and exclusion criteria, the universe of study comprised 102 patients with focal epilepsy. 41% of the patients with focal epilepsy presented a structural lesion. The main locations of the structural lesions were the parietal lobe (12.8%), the occipital lobe (10.8%) and the frontal lobe (10.8%). An association was found between the presence of structural brain lesions and the presence of uncontrolled seizures, with statistical significance. The attributable risk was calculated and it was found that among patients with uncontrolled seizures, 67% had a structural lesion in the imaging study. The presence of uncontrolled seizures is associated to the presence of structural lesions in imaging studies, with a high attributable risk. Leukomalacia and cerebral ischaemia were the main findings that were reported. The predominant structural lesions in paediatric patients with focal epilepsy in the population studied are those related to events that take place during the peripartum period.

  10. [Assessment of neoplastic pancreatic focal injury by multidetector computed tomography].

    PubMed

    Ramírez Gaspar, Alberto Motta; Morató López Alberto, Emilio; Valenzuela Tamaris, Jorge; Castillo González, Federico Armando

    2012-01-01

    pancreatic focal neoplastic lesions (PFNL) should be characterized through image methods to differentiate from no neoplastic lesions, suggesting one or more probable diagnosis, and staging of malignant lesions, in order to help define the estrategy of medial or surgical management. The multidetector computed tomography (MDCT) offers multiple properties and advantages that enable adequate characterization of the PFNL. The objective of this study is to evaluate de usefulness of MDCT in characterizing PFNL. a descriptive, retrospective caseseries study has been conducted. It consisted of reviewing MDCT studies in which PFNL were found, over a period of 4 years 11 months from January 2006 to November 2010. we obtained 54 cases of PFNL which were characterized by MDCT; 75.9% for a specific diagnosis, and were categorized as indeterminate 24.1%, considering more than one possible diagnosis. The most frequent PFNL type was pancreatic ductal adenocarcinoma in 51.9%. Pancreatic cystic neoplasms accounted for 16.7%. MDCT is useful for identifying and characterizing LFNP, this means the possibility of establishing one or more diagnostic possibilities and guide medical management.

  11. Traumatic brain injury associated coagulopathy.

    PubMed

    de Oliveira Manoel, Airton Leonardo; Neto, Antonio Capone; Veigas, Precilla V; Rizoli, Sandro

    2015-02-01

    The presence of coagulopathy is common after severe trauma. The aim of this study was to identify whether isolated severe traumatic brain injury (TBI) is an independent risk factor for coagulopathy. Prospective observational cohort of adult patients admitted to a Level I Trauma Center within 6 h of injury. Patients were categorized according to the abbreviated injury scale (AIS): Group 1-isolated severe TBI (AIS head ≥ 3 + AIS non-head < 3); Group 2-severe multisystem trauma associated with severe TBI (AIS head ≥ 3 + AIS non-head ≥ 3); Group 3-severe multisystem trauma without TBI (AIS head < 3 + AIS non-head ≥ 3). Primary outcome was the development of coagulopathy. Secondary outcome was in-hospital mortality. Three hundred and forty five patients were included (Group 1 = 48 patients, Group 2 = 137, and Group 3 = 160). Group 1 patients had the lowest incidence of coagulopathy and disseminated intravascular coagulopathy, and in general presented with better coagulation profile measured by either classic coagulation tests, thromboelastography or clotting factors. Isolated severe TBI was not an independent risk factor for the development of coagulopathy (OR 1.06; 0.35-3.22 CI, p = 0.92), however, isolated severe TBI patients who developed coagulopathy had higher mortality rates than isolated severe TBI patients without coagulopathy (66 vs. 16.6 %, p < 0.05). The presence of coagulopathy (OR 5.61; 2.65-11.86 CI, p < 0.0001) and isolated severe TBI (OR 11.51; 3.9-34.2 CI, p < 0.0001) were independent risk factors for in-hospital mortality. Isolated severe TBI is not an independent risk factor for the development of coagulopathy. However, severe TBI patients who develop coagulopathy have extremely high mortality rates.

  12. Antiepileptic drug treatment of nonconvulsive seizures induced by experimental focal brain ischemia.

    PubMed

    Williams, A J; Tortella, F C; Lu, X M; Moreton, J E; Hartings, J A

    2004-10-01

    Nonconvulsive seizures (NCSs) after traumatic and ischemic brain injury are often refractory to antiepileptic drug therapy and are associated with a decline in patient outcome. We recently characterized an in vivo rat model of focal brain ischemia-induced NCS and here sought to evaluate potential pharmacological treatments. Electroencephalographic activity was recorded continuously for 24 h in freely behaving rats subjected to permanent middle cerebral artery occlusion (MCAo). Rats were treated with an antiepileptic drug from one of seven different drug classes at ED(50) and 2x ED(50) doses (as reported in other rat seizure models), delivered as a single i.v. injection 20 min post-MCAo. Vehicle-treated rats (n = 9) had an 89% incidence of NCS with an average number of NCS of 8.6 +/- 1.9. The latency to onset of NCS was 32.5 +/- 3.4 min post-MCAo with an average duration of 49.1 +/- 8.2 s/event. The high doses of ethosuximide, gabapentin, fos-phenytoin, and valproate significantly reduced the incidence of NCS (11, 14, 14, and 38%, respectively), whereas midazolam, phenobarbital, and dextromethorphan had no significant effect at either dose. Across treatment groups, there was a low but significant correlation between the number of NCS events per animal and volume of brain infarction (r = 0.352). Antiepileptic drug therapy that prevented the occurrence of NCS also reduced mortality from 26 to 7%. Based on combined effects on NCS, infarction, neurological recovery, and mortality, ethosuximide and gabapentin were identified as having the best therapeutic profile.

  13. Computational identification of conserved transcription factor binding sites upstream of genes induced in rat brain by transient focal ischemic stroke.

    PubMed

    Pulliam, John V K; Xu, Zhenfeng; Ford, Gregory D; Liu, Cuimei; Li, Yonggang; Stovall, Kyndra C; Cannon, Virginetta S; Tewolde, Teclemichael; Moreno, Carlos S; Ford, Byron D

    2013-02-07

    Microarray analysis has been used to understand how gene regulation plays a critical role in neuronal injury, survival and repair following ischemic stroke. To identify the transcriptional regulatory elements responsible for ischemia-induced gene expression, we examined gene expression profiles of rat brains following focal ischemia and performed computational analysis of consensus transcription factor binding sites (TFBS) in the genes of the dataset. In this study, rats were sacrificed 24 h after middle cerebral artery occlusion (MCAO) stroke and gene transcription in brain tissues following ischemia/reperfusion was examined using Affymetrix GeneChip technology. The CONserved transcription FACtor binding site (CONFAC) software package was used to identify over-represented TFBS in the upstream promoter regions of ischemia-induced genes compared to control datasets. CONFAC identified 12 TFBS that were statistically over-represented from our dataset of ischemia-induced genes, including three members of the Ets-1 family of transcription factors (TFs). Microarray results showed that mRNA for Ets-1 was increased following tMCAO but not pMCAO. Immunohistochemical analysis of Ets-1 protein in rat brains following MCAO showed that Ets-1 was highly expressed in neurons in the brain of sham control animals. Ets-1 protein expression was virtually abolished in injured neurons of the ischemic brain but was unchanged in peri-infarct brain areas. These data indicate that TFs, including Ets-1, may influence neuronal injury following ischemia. These findings could provide important insights into the mechanisms that lead to brain injury and could provide avenues for the development of novel therapies. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Traumatic brain injury and forensic neuropsychology.

    PubMed

    Bigler, Erin D; Brooks, Michael

    2009-01-01

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

  15. [The efficacy of botulinum toxin therapy in patients with upper limb spasticity due to traumatic brain injury].

    PubMed

    Akulov, M A; Hat'kova, S E; Mokienko, O A; Orlova, O R; Usachev, D Yu; Zakharov, V O; Orlova, A S; Tomskiy, A A

    Spasticity is a type of muscle hyperactivity that occurs in patients after focal lesions of the Central nervous system due to various diseases: stroke, traumatic brain injury or spinal cord injury, neurosurgical intervention, as well as multiple sclerosis and other diseases of the Central nervous system and is the most disability manifestation of the syndrome of upper motor neuron (UMNS). Focal spasticity of the upper limb requires a complex treatment. Botulinum toxin therapy is an effective treatment for focal/multifocal spasticity in reducing muscle tone and improving function with the highest level of evidence according to the latest American and European guidelines for treatment of spasticity. There are many publications devoted to BTA use in post-stroke patients. This article provides a review of the BTA use in patients with the upper limb spasticity due to severe traumatic brain injury. Some local data on the BTA efficacy in the cohort of patients with traumatic brain injury are also presented.

  16. Sleep in traumatic brain injury.

    PubMed

    Mazwi, Nicole L; Fusco, Heidi; Zafonte, Ross

    2015-01-01

    Sleep disturbances affect more than half of survivors of traumatic brain injury (TBI) and have the potential to undermine rehabilitation, recovery, and outcomes. Normal sleep architecture has been well-described and the neurophysiology of sleep is becoming better understood in recent years, though this complex process continues to be dissected for better appreciation. There are numerous types of sleep disorder, most of which fall under two categories: dyssomnias and parasomnias. In more challenging scenarios patients may be plagued with more than one dyssomnia and/or parasomnia simultaneously, complicating the diagnostic and therapeutic approach. Objective and subjective methods are used to evaluate sleep disorders and help distinguish them from psychiatric and environmental contributors to poor sleep. There are several pharmacologic and nonpharmacologic treatments options for sleep disturbances after TBI, many of which have been particularly helpful in restoring adequate quantity and quality of sleep for survivors. However, to date no consensus has been established regarding how to treat this entity, and it may be that a multimodal approach is ultimately best.

  17. Hypothermia for traumatic brain injury.

    PubMed

    Lewis, Sharon R; Evans, David Jw; Butler, Andrew R; Schofield-Robinson, Oliver J; Alderson, Phil

    2017-09-21

    Hypothermia has been used in the treatment of brain injury for many years. Encouraging results from small trials and laboratory studies led to renewed interest in the area and some larger trials. To determine the effect of mild hypothermia for traumatic brain injury (TBI) on mortality, long-term functional outcomes and complications. We ran and incorporated studies from database searches to 21 March 2016. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OvidSP), Embase Classic+Embase (OvidSP), PubMed, ISI Web of science (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH), clinical trials registers, and screened reference lists. We also re-ran these searches pre-publication in June 2017; the result from this search is presented in 'Studies awaiting classification'. We included randomised controlled trials of participants with closed TBI requiring hospitalisation who were treated with hypothermia to a maximum of 35 ºC for at least 12 consecutive hours. Treatment with hypothermia was compared to maintenance with normothermia (36.5 to 38 ºC). Two review authors assessed data on mortality, unfavourable outcomes according to the Glasgow Outcome Scale, and pneumonia. We included 37 eligible trials with a total of 3110 randomised participants; nine of these were new studies since the last update (2009) and five studies had been previously excluded but were re-assessed and included during the 2017 update. We identified two ongoing studies from searches of clinical trials registers and database searches and two studies await classification.Studies included both adults and children with TBI. Most studies commenced treatment immediately on admission to hospital or after craniotomies and all treatment was maintained for at least 24 hours. Thirty-three studies reported data for mortality, 31 studies reported data for unfavourable outcomes (death, vegetative state or severe disability

  18. Reducing Secondary Insults in Traumatic Brain Injury

    DTIC Science & Technology

    2013-04-01

    persons, and leaves 99,000 persons permanently disabled [1]. The total cost for treatment and rehabilitation of patients with brain injuries is...registry based or retrospective or include only secondary insults that occur in the intensive care unit ( ICU ) setting. Most prior investigations have...in the surgical and neurosurgical ICU diagnosed with a traumatic brain injury requiring a diagnostic procedure were eligible for the study. The study

  19. Modeling premature brain injury and recovery

    PubMed Central

    Scafidi, Joey; Fagel, Devon M.; Ment, Laura R.; Vaccarino, Flora M.

    2009-01-01

    Premature birth is a growing and significant public health problem because of the large number of infants that survive with neurodevelopmental sequelae from brain injury. Recent advances in neuroimaging have shown that although some neuroanatomical structures are altered, others improve over time. This review outlines recent insights into brain structure and function in these preterm infants at school age and relevant animal models. These animal models have provided scientists with an opportunity to explore in depth the molecular and cellular mechanisms of injury as well as the potential of the brain for recovery. The endogenous potential that the brain has for neurogenesis and gliogenesis, and how environment contributes to recovery, are also outlined. These preclinical models will provide important insights into the genetic and epigenetic mechanisms responsible for variable degrees of injury and recovery, permitting the exploration of targeted therapies to facilitate recovery in the developing preterm brain. PMID:19482072

  20. Traumatic Brain Injury: Looking Back, Looking Forward

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  1. Understanding Traumatic Brain Injury: An Introduction

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  2. Traumatic Brain Injury: Looking Back, Looking Forward

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  3. Understanding Traumatic Brain Injury: An Introduction

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  4. Neuronal and glial alterations due to focal cortical hypoxia induced by direct cobalt chloride (CoCl2) brain injection.

    PubMed

    Caltana, Laura; Merelli, Amalia; Lazarowski, Alberto; Brusco, Alicia

    2009-05-01

    Ischemic brain injury is a dynamic process that involves oxidative stress, inflammation, and cell death, as well as activation of endogenous adaptive and regenerative mechanisms depending on activation of transcription factors such as hypoxia inducible factor 1-alpha (HIF-1alpha). Because CoCl2 activates HIF-1alpha, we described a new focal-hypoxia model by direct intracerebral CoCl2 injection. Adult male Wistar rats were intracerebrally injected with CoCl2 (2 microl-50 mM), in frontoparietal cortex of right hemisphere, and saline (2 microl) in the contralateral hemisphere. In slides of fixed brains at 1, 6, 9, 24 h or 5 day after treatment, TTC, histochemistry (toluidine blue, Hoescht-33342, TUNEL), immunostaining (HIF-1alpha, GFAP), Lycopersicon esculentum lectin staining, and electron microscopy (EM) were performed. Immediately after 1 h post CoCl2 injection, HIF-1alpha stabilization and neuronal nuclear shrinkage and cromathin condensation were observed by immunostaining and EM, respectively. Neuronal apoptotic nuclear morphology and GFAP immunoreactivity and lectin maximal reactivity were detected during 6-9 h. Ultrastructural alterations of morphology included edematous perinuclear cytoplasm, organelles and endoplasmic reticulum (RE) enlargement, mitochondrial swelling with increased matrix density, and deposits of electron-dense material. Neurons showed particular nuclear indentations. Astrocytes and oligodendrocytes presented alterations in both nuclei and RE with dilated lumen and altered mitochondrias, and all these ultrastructural changes became detectable at day 5. CoCl2 cortical injection mimics focal brain ischemia, inducing neuronal death and glial activation. This model brings the opportunity to develop focal ischemia in selected brain areas to study their functional consequences and potential pharmacological therapies for in vivo models of stroke.

  5. [A man with severe traumatic brain injury].

    PubMed

    Oudeman, Eline A; Martins Jarnalo, Carine O; van Ouwerkerk, Willem J R

    2013-01-01

    We present a 41-year-old man with severe traumatic brain injury. Cranial imaging studies revealed cerebral contusion and a longitudinal fracture of the temporal bone. Several days later brain herniated into the left external auditory canal. Imaging studies showed the known skull fracture with a direct connection between the external acoustic meatus and the intracranial structures.

  6. Modeling Blast-Related Brain Injury

    DTIC Science & Technology

    2008-12-01

    02139 D. Moore Defense and Veterans Brain Injury Center (WRAMC) 6900 Georgia Ave. NW, Washington, DC 20307 L. Noels University of Liege Chemin des...chevreuils 1, B4000 Liege , Belgium ABSTRACT Recent military conflicts in Iraq and Afghanistan have highlighted the wartime effect of traumatic brain in

  7. [Effects of alcohol consumption on traumatic brain injury].

    PubMed

    Katada, Ryuichi

    2011-10-01

    It has been well known that alcohol consumption affects traumatic brain injury. The mechanism of detrimental effect of ethanol on traumatic brain injury has not been clarified. This review focused on the relationship among traumatic brain injury, ethanol and aquaporin-4. We have reported that ethanol increased brain edema after brain contusion and decreased survival rates in rats. It was suggested that increasing brain edema by ethanol after brain contusion may be caused by oxidative stress. Brain edema consists of cytotoxic brain edema, vasogenic brain edema, interstitial brain edema and osmotic edema. Ethanol mainly increases cytotoxic brain edema. Both alcohol consumption and brain contusion cause oxidative stress. Antioxidant treatment decreases cytotoxic brain edema. Aquaporin-4, an water channel, was increased by ethanol 24 hr after traumatic brain injury in rat. The aquaporin-4 inhibitor decreased brain edema after brain contusion and increased survival rates under ethanol consumption. Aquaporin-4 may have strict relation between ethanol and brain edema increasing after brain contusion.

  8. Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats: therapeutic time window and its mechanism.

    PubMed

    Jia, Jie; Zhang, Xi; Hu, Yong-Shan; Wu, Yi; Wang, Qing-Zhi; Li, Na-Na; Wu, Cai-Qin; Yu, Hui-Xian; Guo, Qing-Chuan

    2009-03-01

    Tetramethyl pyrazine has been considered an effective agent in treating neurons ischemia/reperfusion injury, but the mechanism of its therapeutic effect remains unclear. This study was to explore the therapeutic time window and mechanism of tetramethyl pyrazine on temporary focal cerebral ischemia/reperfusion injury. Middle cerebral artery occlusion was conducted in male Sprague-Dawley rats and 20 mg/kg of tetramethyl pyrazine was intraperitoneally injected at different time points. At 72 h after reperfusion, all animals' neurologic deficit scores were evaluated. Cerebrums were removed and cerebral infarction volume was measured. The expression of thioredoxin and thioredoxin reductase mRNA was determined at 6 and 24 h after reperfusion. Cerebral infarction volume and neurological deficit scores were significantly decreased in the group with tetramethyl pyrazine treatment. The expression of thioredoxin-1/thioredoxin-2 and thioredoxin reductase-1/thioredoxin reductase-2 was significantly decreased in rats with ischemia/reperfusion injury, while it was increased by tetramethyl pyrazine administration. Treatment with tetramethyl pyrazine, within 4 h after reperfusion, protects the brain from ischemic reperfusion injury in rats. The neuroprotective mechanism of tetramethyl pyrazine treatment is, in part, mediated through the upregulation of thioredoxin transcription.

  9. Using magnetic resonance imaging to predict new learning outcome at 5 years after childhood traumatic brain injury.

    PubMed

    Catroppa, Cathy; Anderson, Vicki; Ditchfield, Michael; Coleman, Lee

    2008-05-01

    Memory and learning entail the recruitment of a number of neural areas, including the medial temporal lobes, temporal association areas, and prefrontal cortices. This study examined the effects of injury severity on long-term memory function in 55 children who sustained traumatic brain injury 5 years earlier and compared this with 17 healthy controls. It also investigated cortical damage and diffuse axonal injury and their association to memory and learning outcomes 5 years after traumatic brain injury. Children were administered memory tests of increasing complexity. Results indicated that injury severity affected aspects of complex memory, with no significant influence on working memory; that focal cortical damage was not predictive of working or complex memory, whereas diffuse axonal injury predicted outcome on complex memory tasks. Findings suggest that the implementation of diffuse axonal injury as an index of injury may assist in predicting memory outcome after childhood traumatic brain injury.

  10. Further evidence for the neuroprotective role of oleanolic acid in a model of focal brain hypoxia in rats.

    PubMed

    Caltana, Laura; Rutolo, Damián; Nieto, María Luisa; Brusco, Alicia

    2014-12-01

    Ischemic brain injury is a dynamic process involving oxidative stress, inflammation, cell death and the activation of endogenous adaptive and regenerative mechanisms depending on the activation of transcription factors such as hypoxia-inducible factor 1-alpha. Accordingly, we have previously described a new focal hypoxia model by direct intracerebral cobalt chloride injection. In turn, oleanolic acid, a plant-derived triterpenoid, has been extensively used in Asian countries for its anti-inflammatory and anti-tumor properties. A variety of novel pharmacological effects have been attributed to this triterpenoid, including beneficial effects on neurodegenerative disorders--including experimental autoimmune encephalomyelitis--due to its immunomodulatory activities at systemic level, as well as within the central nervous system. In this context, we hypothesize that this triterpenoid may be capable of exerting neuroprotective effects in ischemic brain, suppressing glial activities that contribute to neurotoxicity while promoting those that support neuronal survival. In order to test this hypothesis, we used the intraperitoneal administration of oleanoic acid in adult rats for seven days previous to focal cortical hypoxia induced by cobalt chloride brain injection. We analyzed the neuroprotective effect of oleanoic acid from a morphological point of view, focusing on neuronal survival and glial reaction.

  11. Epileptogenesis following experimentally induced traumatic brain injury - a systematic review.

    PubMed

    Chandel, Shammy; Gupta, Sunil Kumar; Medhi, Bikash

    2016-04-01

    Traumatic brain injury (TBI) is a complex neurotrauma in civilian life and the battlefield with a broad spectrum of symptoms, long-term neuropsychological disability, as well as mortality worldwide. Posttraumatic epilepsy (PTE) is a common outcome of TBI with unknown mechanisms, followed by posttraumatic epileptogenesis. There are numerous rodent models of TBI available with varying pathomechanisms of head injury similar to human TBI, but there is no evidence for an adequate TBI model that can properly mimic all aspects of clinical TBI and the first successive spontaneous focal seizures follow a single episode of neurotrauma with respect to epileptogenesis. This review aims to provide current information regarding the various experimental animal models of TBI relevant to clinical TBI. Mossy fiber sprouting, loss of dentate hilar neurons along with recurrent seizures, and epileptic discharge similar to human PTE have been studied in fluid percussion injury, weight-drop injury, and cortical impact models, but further refinement of animal models and functional test is warranted to better understand the underlying pathophysiology of posttraumatic epileptogenesis. A multifaceted research approach in TBI model may lead to exploration of the potential treatment measures, which are a major challenge to the research community and drug developers. With respect to clinical setting, proper patient data collection, improved clinical trials with advancement in drug delivery strategies, blood-brain barrier permeability, and proper monitoring of level and effects of target drug are also important.

  12. Catecholamines and cognition after traumatic brain injury.

    PubMed

    Jenkins, Peter O; Mehta, Mitul A; Sharp, David J

    2016-09-01

    Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person's catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain 'networks' that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

  13. The Effects of Antecedent Exercise on Motor Function Recovery and Brain-derived Neurotrophic Factor Expression after Focal Cerebral Ischemia in Rats.

    PubMed

    Kim, Gyeyeop; Kim, Eunjung

    2013-05-01

    [Purpose] In the present study, we investigated the effect of antecedent exercise on functional recovery and brain-derived neurotrophic factor (BDNF) expression following focal cerebral ischemia injury. [Subjects] The rat middle cerebral artery occlusion (MCAO) model was employed. Adult male Sprague-Dawley rats were randomly divided into 4 groups. Group I included untreated normal rats (n=10); Group II included untreated rats with focal cerebral ischemia (n=10); Group III included rats that performed treadmill exercise (20 m/min) training after focal cerebral ischemia (n=10); and Group IV included rats that performed antecedent treadmill exercise (20 m/min) training before focal cerebral ischemia (n=10) as well as treadmill exercise after ischemia. At different time points (1, 7, 14, and 21 days) Garcia's score, and the hippocampal expressions level of BDNF were examined. [Results] In the antecedent exercise group, improvements in the motor behavior index (Garcia's score) were observed and hippocampal BDNF protein expression levels increased. [Conclusion] These results indicate that antecedent treadmill exercise, before permanent brain ischemia exerts a neuroprotective effect against ischemia brain injury by improving motor performance and increasing the level of BDNF expression. Furthermore, the antecedent treadmill exercise of appropriate intensity is critical for post-stroke rehabilitation.

  14. Purines: forgotten mediators in traumatic brain injury.

    PubMed

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

    2016-04-01

    Recently, the topic of traumatic brain injury has gained attention in both the scientific community and lay press. Similarly, there have been exciting developments on multiple fronts in the area of neurochemistry specifically related to purine biology that are relevant to both neuroprotection and neurodegeneration. At the 2105 meeting of the National Neurotrauma Society, a session sponsored by the International Society for Neurochemistry featured three experts in the field of purine biology who discussed new developments that are germane to both the pathomechanisms of secondary injury and development of therapies for traumatic brain injury. This included presentations by Drs. Edwin Jackson on the novel 2',3'-cAMP pathway in neuroprotection, Detlev Boison on adenosine in post-traumatic seizures and epilepsy, and Michael Schwarzschild on the potential of urate to treat central nervous system injury. This mini review summarizes the important findings in these three areas and outlines future directions for the development of new purine-related therapies for traumatic brain injury and other forms of central nervous system injury. In this review, novel therapies based on three emerging areas of adenosine-related pathobiology in traumatic brain injury (TBI) were proposed, namely, therapies targeting 1) the 2',3'-cyclic adenosine monophosphate (cAMP) pathway, 2) adenosine deficiency after TBI, and 3) augmentation of urate after TBI. © 2016 International Society for Neurochemistry.

  15. Stereotypic movement disorder after acquired brain injury.

    PubMed

    McGrath, Cynthia M; Kennedy, Richard E; Hoye, Wayne; Yablon, Stuart A

    2002-05-01

    Stereotypic movement disorder (SMD) consists of repetitive, non-functional motor behaviour that interferes with daily living or causes injury to the person. It is most often described in patients with mental retardation. However, recent evidence indicates that this condition is common among otherwise normal individuals. This case study describes a patient with new-onset SMD occurring after subdural haematoma and brain injury. SMD has rarely been reported after acquired brain injury, and none have documented successful treatment. The current psychiatric literature regarding neurochemistry, neuroanatomy, and treatment of SMD are reviewed with particular application to one patient. Treatment options include serotonin re-uptake inhibitors, opioid antagonists and dopamine antagonists. SMD has been under-appreciated in intellectually normal individuals, and may also be unrecognized after brain injury. Further investigation is needed in this area, which may benefit other individuals with SMD as well.

  16. Mapping the Connectome Following Traumatic Brain Injury.

    PubMed

    Hannawi, Yousef; Stevens, Robert D

    2016-05-01

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

  17. Cognitive outcome following traumatic brain injury.

    PubMed

    Dikmen, Sureyya S; Corrigan, John D; Levin, Harvey S; Machamer, Joan; Stiers, William; Weisskopf, Marc G

    2009-01-01

    To determine whether an association exists between traumatic brain injury (TBI) sustained in adulthood and cognitive impairment 6 months or longer after injury. Systematic review of the published, peer-reviewed literature. From 430 articles, we identified 11 primary and 22 secondary studies that examined cognitive impairment by using performance measures for adults who were at least 6 months post-TBI. There was clear evidence of an association between penetrating brain injury and impaired cognitive function. Factors that modified this association included preinjury intelligence, volume of brain tissue lost, and brain region injured. There was also suggestive evidence that penetrating brain injury may exacerbate the cognitive effects of normal aging. We found clear evidence for long-term cognitive deficits associated with severe TBI. There was suggestive evidence that moderately severe brain injuries are associated with cognitive impairments. There was inadequate/insufficient evidence to determine whether an association exists between a single, mild TBI and cognitive deficits 6 months or longer postinjury. In adults, penetrating, moderate, and severe TBIs are associated with cognitive deficits 6 months or longer postinjury. There is insufficient evidence to determine whether mild TBI is associated with cognitive deficits 6 months or longer postinjury.

  18. Increased segregation of brain networks in focal epilepsy: An fMRI graph theory finding

    PubMed Central

    Pedersen, Mangor; Omidvarnia, Amir H.; Walz, Jennifer M.; Jackson, Graeme D.

    2015-01-01

    Focal epilepsy is conceived of as activating local areas of the brain as well as engaging regional brain networks. Graph theory represents a powerful quantitative framework for investigation of brain networks. Here we investigate whether functional network changes are present in extratemporal focal epilepsy. Task-free functional magnetic resonance imaging data from 15 subjects with extratemporal epilepsy and 26 age and gender matched healthy controls were used for analysis. Local network properties were calculated using local efficiency, clustering coefficient and modularity metrics. Global network properties were assessed with global efficiency and betweenness centrality metrics. Cost-efficiency of the networks at both local and global levels was evaluated by estimating the physical distance between functionally connected nodes, in addition to the overall numbers of connections in the network. Clustering coefficient, local efficiency and modularity were significantly higher in individuals with focal epilepsy than healthy control subjects, while global efficiency and betweenness centrality were not significantly different between the two groups. Local network properties were also highly efficient, at low cost, in focal epilepsy subjects compared to healthy controls. Our results show that functional networks in focal epilepsy are altered in a way that the nodes of the network are more isolated. We postulate that network regularity, or segregation of the nodes of the networks, may be an adaptation that inhibits the conversion of the interictal state to seizures. It remains possible that this may be part of the epileptogenic process or an effect of medications. PMID:26110111

  19. Increased segregation of brain networks in focal epilepsy: An fMRI graph theory finding.

    PubMed

    Pedersen, Mangor; Omidvarnia, Amir H; Walz, Jennifer M; Jackson, Graeme D

    2015-01-01

    Focal epilepsy is conceived of as activating local areas of the brain as well as engaging regional brain networks. Graph theory represents a powerful quantitative framework for investigation of brain networks. Here we investigate whether functional network changes are present in extratemporal focal epilepsy. Task-free functional magnetic resonance imaging data from 15 subjects with extratemporal epilepsy and 26 age and gender matched healthy controls were used for analysis. Local network properties were calculated using local efficiency, clustering coefficient and modularity metrics. Global network properties were assessed with global efficiency and betweenness centrality metrics. Cost-efficiency of the networks at both local and global levels was evaluated by estimating the physical distance between functionally connected nodes, in addition to the overall numbers of connections in the network. Clustering coefficient, local efficiency and modularity were significantly higher in individuals with focal epilepsy than healthy control subjects, while global efficiency and betweenness centrality were not significantly different between the two groups. Local network properties were also highly efficient, at low cost, in focal epilepsy subjects compared to healthy controls. Our results show that functional networks in focal epilepsy are altered in a way that the nodes of the network are more isolated. We postulate that network regularity, or segregation of the nodes of the networks, may be an adaptation that inhibits the conversion of the interictal state to seizures. It remains possible that this may be part of the epileptogenic process or an effect of medications.

  20. Recovery after brain injury: mechanisms and principles

    PubMed Central

    Nudo, Randolph J.

    2013-01-01

    The past 20 years have represented an important period in the development of principles underlying neuroplasticity, especially as they apply to recovery from neurological injury. It is now generally accepted that acquired brain injuries, such as occur in stroke or trauma, initiate a cascade of regenerative events that last for at least several weeks, if not months. Many investigators have pointed out striking parallels between post-injury plasticity and the molecular and cellular events that take place during normal brain development. As evidence for the principles and mechanisms underlying post-injury neuroplasticity has been gleaned from both animal models and human populations, novel approaches to therapeutic intervention have been proposed. One important theme has persisted as the sophistication of clinicians and scientists in their knowledge of neuroplasticity mechanisms has grown: behavioral experience is the most potent modulator of brain plasticity. While there is substantial evidence for this principle in normal, healthy brains, the injured brain is particularly malleable. Based on the quantity and quality of motor experience, the brain can be reshaped after injury in either adaptive or maladaptive ways. This paper reviews selected studies that have demonstrated the neurophysiological and neuroanatomical changes that are triggered by motor experience, by injury, and the interaction of these processes. In addition, recent studies using new and elegant techniques are providing novel perspectives on the events that take place in the injured brain, providing a real-time window into post-injury plasticity. These new approaches are likely to accelerate the pace of basic research, and provide a wealth of opportunities to translate basic principles into therapeutic methodologies. PMID:24399951

  1. Network localization of neurological symptoms from focal brain lesions.

    PubMed

    Boes, Aaron D; Prasad, Sashank; Liu, Hesheng; Liu, Qi; Pascual-Leone, Alvaro; Caviness, Verne S; Fox, Michael D

    2015-10-01

    A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three-dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P < 10(-5)) and relative to other cortical regions (P < 0.01). Next, we tested for generalizability of our technique by applying it to three additional lesion syndromes: central post-stroke pain, auditory hallucinosis, and subcortical aphasia. In each syndrome, heterogeneous lesions that themselves had

  2. Traumatic brain injury, neuroimaging, and neurodegeneration

    PubMed Central

    Bigler, Erin D.

    2012-01-01

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

  3. Abnormal Brain Areas Common to the Focal Epilepsies: Multivariate Pattern Analysis of fMRI.

    PubMed

    Pedersen, Mangor; Curwood, Evan K; Vaughan, David N; Omidvarnia, Amir H; Jackson, Graeme D

    2016-04-01

    Individuals with focal epilepsy have heterogeneous sites of seizure origin. However, there may be brain regions that are common to most cases of intractable focal epilepsy. In this study, we aim to identify these using multivariate analysis of task-free functional MRI. Fourteen subjects with extratemporal focal epilepsy and 14 healthy controls were included in the study. Task-free functional MRI data were used to calculate voxel-wise regional connectivity with regional homogeneity (ReHo) and weighted degree centrality (DCw), in addition to regional activity using fraction of amplitude of low-frequency fluctuations (fALFF). Multivariate pattern analysis was applied to each of these metrics to discriminate brain areas that differed between focal epilepsy subjects and healthy controls. ReHo and DCw classified focal epilepsy subjects from healthy controls with high accuracy (89.3% and 75%, respectively). However, fALFF did not significantly classify patients from controls. Increased regional network activity in epilepsy subjects was seen in the ipsilateral piriform cortex, insula, and thalamus, in addition to the dorsal anterior cingulate cortex and lateral frontal cortices. Decreased regional connectivity was observed in the ventromedial prefrontal cortex, as well as lateral temporal cortices. Patients with extratemporal focal epilepsy have common areas of abnormality (ReHo and DCw measures), including the ipsilateral piriform cortex, temporal neocortex, and ventromedial prefrontal cortex. ReHo shows additional increase in the "salience network" that includes anterior insula and anterior cingulate cortex. DCw showed additional effects in the ipsilateral thalamus and striatum. These brain areas may represent key regional network properties underlying focal epilepsy.

  4. Network localization of neurological symptoms from focal brain lesions

    PubMed Central

    Prasad, Sashank; Liu, Hesheng; Liu, Qi; Pascual-Leone, Alvaro; Caviness, Verne S.; Fox, Michael D.

    2015-01-01

    A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three-dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P < 10−5) and relative to other cortical regions (P < 0.01). Next, we tested for generalizability of our technique by applying it to three additional lesion syndromes: central post-stroke pain, auditory hallucinosis, and subcortical aphasia. In each syndrome, heterogeneous lesions that themselves had

  5. Orally administered oleoylethanolamide protects mice from focal cerebral ischemic injury by activating peroxisome proliferator-activated receptor α.

    PubMed

    Zhou, Yu; Yang, Lichao; Ma, Ang; Zhang, Xuemei; Li, Weijie; Yang, Wushuang; Chen, Caixia; Jin, Xin

    2012-08-01

    Oleoylethanolamide (OEA) is a high-affinity agonist of peroxisome proliferator-activated receptor α (PPARα) which may act as an endogenous neuroprotective factor. However, it is not clear whether orally administered OEA is effective against ischemic brain injury. In our study, transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 90 min followed by reperfusion. To evaluate its preventive effects, OEA (10, 20 or 40 mg/kg, ig) was administered for 3 days before ischemia. To evaluate its therapeutic effects, OEA (40 mg/kg, ig) was administered at 0.5 or 1h before reperfusion or at 0 or 1h after reperfusion. In some experiments, the PPARα antagonist MK886 (10mg/kg, ig) was administered 0.5h before OEA. Neurological deficit score, infarct volume and brain edema degree were determined at 24h after reperfusion. Blood-brain barrier (BBB) disruption was evaluated by Evans blue (EB) leakage at 6h after reperfusion. Real-time RT-PCR and western blot were performed to detect PPARα mRNA and protein expression. Oral OEA pretreatment improved neurological dysfunction reduced infarct volume and alleviated brain edema in a dose-dependent manner; the most effective dose was 40 mg/kg. The therapeutic time is within 1h after reperfusion. OEA also increased PPARα mRNA and protein expression in the ischemic brain. The PPARα antagonist MK886 abolished the protective effects of OEA. In conclusion, our results indicate that orally administered OEA protects against acute cerebral ischemic injury in mice, at least in part by activating PPARα. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Disruption of Network Synchrony and Cognitive Dysfunction After Traumatic Brain Injury

    PubMed Central

    Wolf, John A.; Koch, Paul F.

    2016-01-01

    Traumatic brain injury (TBI) is a heterogeneous disorder with many factors contributing to a spectrum of severity, leading to cognitive dysfunction that may last for many years after injury. Injury to axons in the white matter, which are preferentially vulnerable to biomechanical forces, is prevalent in many TBIs. Unlike focal injury to a discrete brain region, axonal injury is fundamentally an injury to the substrate by which networks of the brain communicate with one another. The brain is envisioned as a series of dynamic, interconnected networks that communicate via long axonal conduits termed the “connectome”. Ensembles of neurons communicate via these pathways and encode information within and between brain regions in ways that are timing dependent. Our central hypothesis is that traumatic injury to axons may disrupt the exquisite timing of neuronal communication within and between brain networks, and that this may underlie aspects of post-TBI cognitive dysfunction. With a better understanding of how highly interconnected networks of neurons communicate with one another in important cognitive regions such as the limbic system, and how disruption of this communication occurs during injury, we can identify new therapeutic targets to restore lost function. This requires the tools of systems neuroscience, including electrophysiological analysis of ensemble neuronal activity and circuitry changes in awake animals after TBI, as well as computational modeling of the effects of TBI on these networks. As more is revealed about how inter-regional neuronal interactions are disrupted, treatments directly targeting these dysfunctional pathways using neuromodulation can be developed. PMID:27242454

  7. Catecholamines and cognition after traumatic brain injury

    PubMed Central

    Jenkins, Peter O.; Mehta, Mitul A.

    2016-01-01

    Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person’s catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain ‘networks’ that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner. PMID:27256296

  8. Driving, brain injury and assistive technology.

    PubMed

    Lane, Amy K; Benoit, Dana

    2011-01-01

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

  9. The neuropsychiatry of depression after brain injury.

    PubMed

    Fleminger, Simon; Oliver, Donna L; Williams, W Huw; Evans, Jonathan

    2003-01-01

    Biological aspects of depression after brain injury, in particular traumatic brain injury (TBI) and stroke, are reviewed. Symptoms of depression after brain injury are found to be rather non-specific with no good evidence of a clear pattern distinguishing it from depression in those without brain injury. Nevertheless symptoms of disturbances of interest and concentration are particularly prevalent, and guilt is less evident. Variabilitiy of mood is characteristic. The prevalence of depression is similar after both stroke and TBI with the order of 20-40% affected at any point in time in the first year, and about 50% of people experience depression at some stage. There is no good evidence for areas of specific vulnerability in terms of lesion location, and early suggestions of a specific association with injury to the left hemisphere have not been confirmed. Insight appears to be related to depressed mood with studies of TBI indicating that greater insight over time post-injury may be associated with greater depression. We consider that this relationship may be due to depression appearing as people gain more awareness of their disability, but also suggest that changes in mood may result in altered awareness. The risk of suicide after TBI is reviewed. There appears to be about a three to fourfold increased risk of suicide after TBI, although much of this increased risk may be due to pre-injury factors in terms of the characteristics of people who suffer TBI. About 1% of people who have suffered TBI will commit suicide over a 15-year follow-up. Drug management of depression is reviewed. There is little specific evidence to guide the choice of antidepressant medication and most psychiatrists would start with a selective serotonin reuptake inhibitor (SSRI). It is important that the drug management of depression after brain injury is part of a full package of care that can address biological as well as psychosocial factors in management.

  10. The neuropathology of traumatic brain injury.

    PubMed

    Mckee, Ann C; Daneshvar, Daniel H

    2015-01-01

    Traumatic brain injury, a leading cause of mortality and morbidity, is divided into three grades of severity: mild, moderate, and severe, based on the Glasgow Coma Scale, the loss of consciousness, and the development of post-traumatic amnesia. Although mild traumatic brain injury, including concussion and subconcussion, is by far the most common, it is also the most difficult to diagnose and the least well understood. Proper recognition, management, and treatment of acute concussion and mild traumatic brain injury are the fundamentals of an emerging clinical discipline. It is also becoming increasingly clear that some mild traumatic brain injuries have persistent, and sometimes progressive, long-term debilitating effects. Evidence indicates that a single traumatic brain injury can precipitate or accelerate multiple age-related neurodegenerations, increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease, and that repetitive mild traumatic brain injuries can provoke the development of a tauopathy, chronic traumatic encephalopathy. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus, septal abnormalities, and abnormal deposits of hyperphosphorylated tau (τ) as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy frequently occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including Alzheimer's disease, Lewy body disease, and motor neuron disease. Currently, chronic traumatic encephalopathy can be diagnosed only at

  11. CD38 facilitates recovery from traumatic brain injury.

    PubMed

    Levy, Ayelet; Bercovich-Kinori, Adi; Alexandrovich, Alexander G; Tsenter, Jeanna; Trembovler, Victoria; Lund, Frances E; Shohami, Esther; Stein, Reuven; Mayo, Lior

    2009-09-01

    Traumatic brain injury (TBI) is a major cause of death and disability worldwide. It causes progressive tissue atrophy and consequent neurological dysfunctions. TBI is accompanied by neuroinflammation, a process mediated largely by microglia. CD38 is an ectoenzyme that promotes transmembrane signaling via the synthesis of potent calcium mobilizing agents or via its receptor activity. CD38 is expressed in the brain in various cell types including microglia. In previous studies, we showed that CD38 regulates microglial activation and response to chemokines. In view of the important role of neuroinflammation in TBI and the effects of CD38 on microglial responses, the present study examines the role of CD38 in the recovery of mice from closed head injury (CHI), a model of focal TBI. For this purpose, CD38-deficient and wild-type (WT) mice were subjected to a similar severity of CHI and the effect of the injury on neurobehavioral and cognitive functions was assessed by the Neurological Severity Score (NSS) and the Object Recognition Test, at various time points post-injury. The results show that recovery after CHI (as indicated by the NSS) was significantly lower in CD38-deficient mice than in WT mice and that the object recognition performance after injury was significantly impaired in injured CD38-deficient mice than in WT mice. In addition, we also observed that the amount of activated microglia/macrophages at the injury site was significantly lower in CD38-deficient mice compared with WT mice. Taken together, our findings indicate that CD38 plays a beneficial role in the recovery of mice from CHI and that this effect is mediated, at least in part, via the effect of CD38 on microglia responses.

  12. MILD PASSIVE FOCAL COOLING PREVENTS EPILEPTIC SEIZURES AFTER HEAD INJURY IN RATS

    PubMed Central

    D’Ambrosio, Raimondo; Eastman, Clifford L.; Darvas, Felix; Fender, Jason S.; Verley, Derek R.; Farin, Federico M.; Wilkerson, Hui-Wen; Temkin, Nancy R.; Miller, John W.; Ojemann, Jeffrey; Rothman, Steven M.; Smyth, Matthew D.

    2013-01-01

    Objective Posttraumatic epilepsy is prevalent, often difficult to manage, and currently cannot be prevented. While cooling is broadly neuroprotective, cooling-induced prevention of chronic spontaneous recurrent seizures has never been demonstrated. We examined the effect of mild passive focal cooling of the perilesional neocortex on the development of neocortical epileptic seizures after head injury in the rat. Methods Rostral parasagittal fluid percussion injury in rats reliably induces a perilesional, neocortical epileptic focus within weeks after injury. Epileptic seizures were assessed by 5-electrode video-electrocorticography (ECoG) 2–16 weeks post-injury. Focal cooling was induced with ECoG headsets engineered for calibrated passive heat dissipation. Pathophysiology was assessed by GFAP immunostaining, cortical sclerosis, gene expression of inflammatory cytokines IL-1α and IL-1β, and ECoG spectral analysis. All animals were formally randomized to treatment groups and data were analyzed blind. Results Cooling by 0.5–2°C inhibited the onset of epileptic seizures in a dose dependent fashion. The treatment induced no additional pathology or inflammation, and normalized the power spectrum of stage N2 sleep. Cooling by 2°C for 5.5 weeks beginning 3 days after injury virtually abolished ictal activity. This effect persisted through the end of the study, over ten weeks after cessation of cooling. Rare remaining seizures were shorter than in controls. Interpretation These findings demonstrate potent and persistent prevention and modification of epileptic seizures after head injury with a cooling protocol that is neuroprotective, compatible with the care of head-injury patients, and conveniently implemented. The required cooling can be delivered passively without Peltier cells or electrical power. PMID:23225633

  13. Slope analysis of somatosensory evoked potentials in spinal cord injury for detecting contusion injury and focal demyelination.

    PubMed

    Agrawal, Gracee; Sherman, David; Maybhate, Anil; Gorelik, Michael; Kerr, Douglas A; Thakor, Nitish V; All, Angelo H

    2010-09-01

    In spinal cord injury (SCI) research there is a need for reliable measures to determine the extent of injury and assess progress due to natural recovery, drug therapy, surgical intervention or rehabilitation. Somatosensory evoked potentials (SEP) can be used to quantitatively examine the functionality of the ascending sensory pathways in the spinal cord. A reduction of more than 50% in peak amplitude or an increase of more than 10% in latency are threshold indicators of injury. However, in the context of injury, SEP peaks are often obscured by noise. We have developed a new technique to investigate the morphology of the SEP waveform, rather than focusing on a small number of peaks. In this study, we compare SEP signals before and after SCI using two rat models: a contusion injury model and a focal experimental autoimmune encephalomyelitis model. Based on mean slope changes over the signal, we were able to effectively differentiate pre-injury and post-injury SEP values with high levels of sensitivity (83.3%) and specificity (79.2%). Copyright 2010 Elsevier Ltd. All rights reserved.

  14. Treatments (12 and 48 h) with systemic and brain-selective hypothermia techniques after permanent focal cerebral ischemia in rat.

    PubMed

    Clark, Darren L; Penner, Mark; Wowk, Shannon; Orellana-Jordan, Ian; Colbourne, Frederick

    2009-12-01

    Mild hypothermia lessens brain injury when initiated after the onset of global or focal ischemia. The present study sought to determine whether cooling to approximately 33 degrees C provides enduring benefit when initiated 1 h after permanent middle cerebral artery occlusion (pMCAO, via electrocautery) in adult rats and whether protection depends upon treatment duration and cooling technique. In the first experiment, systemic cooling was induced in non-anesthetized rats through a whole-body exposure technique that used fans and water mist. In comparison to normothermic controls, 12- and 48-h bouts of hypothermia significantly lessened functional impairment, such as skilled reaching ability, and lesion volume out to a 1-month survival. In the second experiment, brain-selective cooling was induced in awake rats via a water-cooled metal strip implanted underneath the temporalis muscle overlying the ischemic territory. Use of a 48-h cooling treatment significantly mitigated injury and behavioral impairment whereas a 12-h treatment did not. These findings show that while systemic and focal techniques are effective when initiated after the onset of pMCAO, they differ in efficacy depending upon the treatment duration. A direct and uncomplicated comparison between methods is problematic, however, due to unknown gradients in brain temperature and the use of two separate experiments. In summary, prolonged cooling, even when delayed after onset of pMCAO, provides enduring behavioral and histological protection sufficient to suggest that it will be clinically effective. Nonetheless, further pre-clinical work is needed to improve treatment protocols, such as identifying the optimal depth of cooling, and how these factors interact with cooling method.

  15. Dual task performance after focal cerebral lesions and closed head injuries.

    PubMed

    Vilkki, J; Virtanen, S; Surma-Aho, O; Servo, A

    1996-11-01

    The aim of this study was to demonstrate that focal frontal lobe lesions and closed head injuries cause a deficit in the deliberate minimizing of dual task decrements that follow when two separate tasks should be done concurrently. In single tasks, subjects counted backwards and cancelled visual targets as quickly and accurately as possible on separate 1 min trials. In the dual task, they were required to do both tasks simultaneously, taking care that performance on neither task would be notably more impaired than on the other, as only the performance showing a larger percentage decrement from the corresponding single task performance was taken into account as the result of the test. Patients with acute closed head injury displayed more pronounced dual task decrement than the controls. This deficit was not secondary to inefficiency on the single tasks but was related to the depth of coma at admission, the acuteness of injury and age. Contrary to expectation, patients with focal frontal lobe lesions or patients with subacute closed head injury did not demonstrate abnormal dual task decrement.

  16. Focal arterial injuries of the proximal extremities: helical CT arteriography as the initial method of diagnosis.

    PubMed

    Soto, J A; Múnera, F; Morales, C; Lopera, J E; Holguín, D; Guarín, O; Castrillón, G; Sanabria, A; García, G

    2001-01-01

    To present our experience with helical computed tomographic (CT) arteriography as the initial diagnostic examination in patients suspected to have focal arterial injuries of the proximal extremities. During 19 months, 142 arterial segments in the proximal portions of the extremities of 139 patients with trauma were evaluated with helical CT arteriography. CT arteriograms were interpreted on site by the radiologist in charge of emergency procedures and retrospectively with consensus interpretation between two radiologists. CT study quality and the presence of arterial injuries were noted. CT arteriographic findings were compared with those of surgery, conventional arteriography, and/or clinical follow-up. Five (3.6%) patients had nondiagnostic studies and underwent conventional arteriography. In the remaining 137 arterial segments in 134 patients, helical CT arteriography demonstrated arterial injuries in 61 segments and normal arteries in 76 segments. These segments were treated initially with surgery (55 segments) or endovascular intervention (four segments) or were observed (78 segments); 77 of the 78 observed segments remained stable at 3-18 months (mean follow-up, 5.2 months). There were no differences between the on-site and consensus interpretations (kappa = 1.0). The sensitivity of CT arteriography was 95.1%, and the specificity was 98.7%. Helical CT arteriography can be performed as the initial diagnostic method in most patients suspected to have focal arterial injuries of the proximal portions of the extremities.

  17. Stem cell therapies for perinatal brain injuries.

    PubMed

    Vawda, Reaz; Woodbury, Jennifer; Covey, Matthew; Levison, Steven W; Mehmet, Huseyin

    2007-08-01

    This chapter reviews four groups of paediatric brain injury. The pathophysiology of these injuries is discussed to establish which cells are damaged and therefore which cells represent targets for cell replacement. Next, we review potential sources of cellular replacements, including embryonic stem cells, fetal and neonatal neural stem cells and a variety of mesenchymal stem cells. The advantages and disadvantages of each source are discussed. We review published studies to illustrate where stem cell therapies have been evaluated for therapeutic gain and discuss the hurdles that will need to be overcome to achieve therapeutic benefit. Overall, we conclude that children with paediatric brain injuries or inherited genetic disorders that affect the brain are worthy candidates for stem cell therapeutics.

  18. Public attitudes towards survivors of brain injury.

    PubMed

    Linden, M A; Rauch, R J; Crothers, I R

    2005-11-01

    To explore the effects of religious identity, gender and socioeconomic status (SES) on public attitudes towards survivors of brain injury. An independent groups design was used to compare the attitudes of Northern Irish participants. The participants were asked to complete a modified form of the Community Attitudes to Mental Illness scale. The new questionnaire replaced the original scales' emphasis on mental illness with that of brain injury. Complete data was available for 179 participants for the religious identity and gender analysis and 124 for gender and SES. Analyses of variance were conducted on these variables. Significant differences between male and female attitudes were found along with significant interactions between religious identity and gender and SES and gender. Religious, economic and gender-based divisions in society affect attitudes towards survivors of brain injury.

  19. Isolation of speech area from focal brain ischemia.

    PubMed

    Bogousslavsky, J; Regli, F; Assal, G

    1985-01-01

    A patient with atrial fibrillation and internal carotid artery occlusion developed mixed transcortical aphasia. The CT scan showed two recent distinct infarcts in the dominant hemisphere, one in the precentral artery area (pial artery infarct) and one in the borderzone area between the posterior and middle cerebral arteries territories (watershed infarct). The perisylvian speech areas were spared, but probably disconnected from other areas by the infarcts. The syndrome of isolation of speech area may be caused by vascular conditions which are able to produce simultaneous pial artery and watershed infarcts, and is not necessarily related to more extensive processes of the brain.

  20. Pediatric Rodent Models of Traumatic Brain Injury.

    PubMed

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

    2016-01-01

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

  1. Emergency Neurological Life Support: Traumatic Brain Injury.

    PubMed

    Garvin, Rachel; Venkatasubramanian, Chitra; Lumba-Brown, Angela; Miller, Chad M

    2015-12-01

    Traumatic Brain Injury (TBI) was chosen as an Emergency Neurological Life Support topic due to its frequency, the impact of early intervention on outcomes for patients with TBI, and the need for an organized approach to the care of such patients within the emergency setting. This protocol was designed to enumerate the practice steps that should be considered within the first critical hour of neurological injury.

  2. Managing traumatic brain injury secondary to explosions

    PubMed Central

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

    2010-01-01

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

  3. Brain Injury Risk from Primary Blast

    DTIC Science & Technology

    2012-02-29

    combined abdominal and thoracic protection that reduced blast levels to an order of magnitude below pulmonary injury threshold. The results were scaled to... contusions typically on or around the brainstem though there were no skull fractures for any blast intensity. Risk functions were developed that...primary blast exposure to the brain was found to be more than twice the pulmonary fatality injury risk. However, the blast level for 50% risk of mild

  4. Osmolar therapy in pediatric traumatic brain injury.

    PubMed

    Bennett, Tellen D; Statler, Kimberly D; Korgenski, E Kent; Bratton, Susan L

    2012-01-01

    To describe patterns of use for mannitol and hypertonic saline in children with traumatic brain injury, to evaluate any potential associations between hypertonic saline and mannitol use and patient demographic, injury, and treatment hospital characteristics, and to determine whether the 2003 guidelines for severe pediatric traumatic brain injury impacted clinical practice regarding osmolar therapy. Retrospective cohort study. Pediatric Health Information System database, January, 2001 to December, 2008. Children (age <18 yrs) with traumatic brain injury and head/neck Abbreviated Injury Scale score ≥ 3 who received mechanical ventilation and intensive care. : None. The primary outcome was hospital billing for parenteral hypertonic saline and mannitol use, by day of service. Overall, 33% (2,069 of 6,238) of the patients received hypertonic saline, and 40% (2,500 of 6,238) received mannitol. Of the 1,854 patients who received hypertonic saline or mannitol for ≥ 2 days in the first week of therapy, 29% did not have intracranial pressure monitoring. After adjustment for hospital-level variation, primary insurance payer, and overall injury severity, use of both drugs was independently associated with older patient age, intracranial hemorrhage (other than epidural), skull fracture, and higher head/neck injury severity. Hypertonic saline use increased and mannitol use decreased with publication of the 2003 guidelines, and these trends continued through 2008. Hypertonic saline and mannitol are used less in infants than in older children. The patient-level and hospital-level variation in osmolar therapy use and the substantial amount of sustained osmolar therapy without intracranial pressure monitoring suggest opportunities to improve the quality of pediatric traumatic brain injury care. With limited high-quality evidence available, published expert guidelines appear to significantly impact clinical practice in this area.

  5. MDCT imaging of traumatic brain injury

    PubMed Central

    Pezzullo, Martina; Delpierre, Isabelle; Sadeghi, Niloufar

    2016-01-01

    The aim of emergency imaging is to detect treatable lesions before secondary neurological damage occurs. CT plays a primary role in the acute setting of head trauma, allowing accurate detection of lesions requiring immediate neurosurgical treatment. CT is also accurate in detecting secondary injuries and is therefore essential in follow-up. This review discusses the main characteristics of primary and secondary brain injuries. PMID:26607650

  6. Paclitaxel improves outcome from traumatic brain injury

    PubMed Central

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

    2016-01-01

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

  7. Lateral (Parasagittal) Fluid Percussion Model of Traumatic Brain Injury.

    PubMed

    Van, Ken C; Lyeth, Bruce G

    2016-01-01

    Fluid percussion was first conceptualized in the 1940s and has evolved into one of the leading laboratory methods for studying experimental traumatic brain injury (TBI). Over the decades, fluid percussion has been used in numerous species and today is predominantly applied to the rat. The fluid percussion technique rapidly injects a small volume of fluid, such as isotonic saline, through a circular craniotomy onto the intact dura overlying the brain cortex. In brief, the methods involve surgical production of a circular craniotomy, attachment of a fluid-filled conduit between the dura overlying the cortex and the outlet port of the fluid percussion device. A fluid pulse is then generated by the free-fall of a pendulum striking a piston on the fluid-filled cylinder of the device. The fluid enters the cranium, producing a compression and displacement of the brain parenchyma resulting in a sharp, high magnitude elevation of intracranial pressure that is propagated diffusely through the brain. This results in an immediate and transient period of traumatic unconsciousness as well as a combination of focal and diffuse damage to the brain, which is evident upon histological and behavioral analysis. Numerous studies have demonstrated that the rat fluid percussion model reproduces a wide range of pathological features associated with human TBI.

  8. The prehospital management of traumatic brain injury.

    PubMed

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

    2015-01-01

    Traumatic brain injury (TBI) is an important cause of death and disability, particularly in younger populations. The prehospital evaluation and management of TBI is a vital link between insult and definitive care and can have dramatic implications for subsequent morbidity. Following a TBI the brain is at high risk for further ischemic injury, with prehospital interventions targeted at reducing this secondary injury while optimizing cerebral physiology. In the following chapter we discuss the prehospital assessment and management of the brain-injured patient. The initial evaluation and physical examination are discussed with a focus on interpretation of specific physical examination findings and interpretation of vital signs. We evaluate patient management strategies including indications for advanced airway management, oxygenation, ventilation, and fluid resuscitation, as well as prehospital strategies for the management of suspected or impending cerebral herniation including hyperventilation and brain-directed hyperosmolar therapy. Transport decisions including the role of triage models and trauma centers are discussed. Finally, future directions in the prehospital management of traumatic brain injury are explored. © 2015 Elsevier B.V. All rights reserved.

  9. Neurorestorative Treatments for Traumatic Brain Injury

    PubMed Central

    Xiong, Ye; Mahmood, Asim; Chopp, Michael

    2011-01-01

    Traumatic brain injury (TBI) remains a major cause of death and permanent disability worldwide, especially in children and young adults. A total of 1.5 million people experience head trauma each year in the United States, with an annual economic cost exceeding $56 billion. Unfortunately, almost all Phase III TBI clinical trials have yet to yield a safe and effective neuroprotective treatment, raising questions regarding the use of neuroprotective strategies as the primary therapy for acute brain injuries. Recent preclinical data suggest that neurorestorative strategies that promote angiogenesis (formation of new blood vessels from pre-existing endothelial cells), axonal remodeling (axonal sprouting and pruning), neurogenesis (generation of new neurons) and synaptogenesis (formation of new synapses) provide promising opportunities for the treatment of TBI. This review discusses select cell-based and pharmacological therapies that activate and amplify these endogenous restorative brain plasticity processes to promote both repair and regeneration of injured brain tissue and functional recovery after TBI. PMID:21122475

  10. Neuropsychiatry of Pediatric Traumatic Brain Injury

    PubMed Central

    Max, Jeffrey E.

    2014-01-01

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

  11. Minor traumatic brain injury in sports.

    PubMed

    Schleimer, Jonathan A

    2002-12-01

    Mild traumatic brain injury (MTBI) is an all-too-frequent occurrence among amateur and professional athletes alike. The increased attention it has received in recent literature may suggest that incidence of this injury has risen. The frequency of MTBI in general may be rising with the increased interest in so-called noncontact sports such as soccer, snowboarding, skateboarding, and motocross. Despite significant improvements made in the quality of protective equipment, head injury remains common in football, soccer, and amateur boxing. The management of athletes who suffer traumatic head injury remains problematic for coaches, trainers, team physicians, primary care physicians, and neurologic specialists. This article addresses guidelines, and diagnostic and treatment protocols to help with the management of athletes with concussion and traumatic head injuries.

  12. Targeted activation of CREB in reactive astrocytes is neuroprotective in focal acute cortical injury.

    PubMed

    Pardo, Luis; Schlüter, Agatha; Valor, Luis M; Barco, Angel; Giralt, Mercedes; Golbano, Arantxa; Hidalgo, Juan; Jia, Peilin; Zhao, Zhongming; Jové, Mariona; Portero-Otin, Manuel; Ruiz, Montserrat; Giménez-Llort, Lydia; Masgrau, Roser; Pujol, Aurora; Galea, Elena

    2016-05-01

    The clinical challenge in acute injury as in traumatic brain injury (TBI) is to halt the delayed neuronal loss that occurs hours and days after the insult. Here we report that the activation of CREB-dependent transcription in reactive astrocytes prevents secondary injury in cerebral cortex after experimental TBI. The study was performed in a novel bitransgenic mouse in which a constitutively active CREB, VP16-CREB, was targeted to astrocytes with the Tet-Off system. Using histochemistry, qPCR, and gene profiling we found less neuronal death and damage, reduced macrophage infiltration, preserved mitochondria, and rescued expression of genes related to mitochondrial metabolism in bitransgenic mice as compared to wild type littermates. Finally, with meta-analyses using publicly available databases we identified a core set of VP16-CREB candidate target genes that may account for the neuroprotective effect. Enhancing CREB activity in astrocytes thus emerges as a novel avenue in acute brain post-injury therapeutics.

  13. Advanced monitoring in traumatic brain injury: microdialysis.

    PubMed

    Carpenter, Keri L H; Young, Adam M H; Hutchinson, Peter J

    2017-04-01

    Here, we review the present state-of-the-art of microdialysis for monitoring patients with severe traumatic brain injury, highlighting the newest developments. Microdialysis has evolved in neurocritical care to become an established bedside monitoring modality that can reveal unique information on brain chemistry. A major advance is recent consensus guidelines for microdialysis use and interpretation. Other advances include insight obtained from microdialysis into the complex, interlinked traumatic brain injury disorders of electrophysiological changes, white matter injury, inflammation and metabolism. Microdialysis has matured into being a standard clinical monitoring modality that takes its place alongside intracranial pressure and brain tissue oxygen tension measurement in specialist neurocritical care centres, as well as being a research tool able to shed light on brain metabolism, inflammation, therapeutic approaches, blood-brain barrier transit and drug effects on downstream targets. Recent consensus on microdialysis monitoring is paving the way for improved neurocritical care protocols. Furthermore, there is scope for future improvements both in terms of the catheters and microdialysate analyser technology, which may further enhance its applicability.

  14. Interleukin-1 and acute brain injury

    PubMed Central

    Murray, Katie N.; Parry-Jones, Adrian R.; Allan, Stuart M.

    2015-01-01

    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. PMID:25705177

  15. Better Sleep May Signal Recovery from Brain Injury

    MedlinePlus

    ... 162672.html Better Sleep May Signal Recovery From Brain Injury New research suggests sleep-wake cycles are ... Dec. 21, 2016 (HealthDay News) -- Recovery from traumatic brain injury appears to go hand-in-hand with ...

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

    MedlinePlus

    ... Cancel Submit Search The CDC Traumatic Brain Injury & Concussion Note: Javascript is disabled or is not supported ... this page: About CDC.gov . Traumatic Brain Injury & Concussion Basic Information Get the Facts Signs and Symptoms ...

  17. Where are we in the modelling of traumatic brain injury? Models complicated by secondary brain insults.

    PubMed

    Wang, Hong-Cai; Sun, Cheng-Feng; Chen, Hai; Chen, Mao-Song; Shen, Gang; Ma, Yan-Bin; Wang, Bo-Ding

    2014-01-01

    Traumatic brain injury (TBI) contributes to a substantial number of deaths and cases of disability. Despite well-established experimental models and years of carefully conducted research, a clinical therapeutic breakthrough in TBI has lagged. This may be due, in part, to the discrepancies between commonly used experimental models and clinical scenarios. Secondary insults, such as hypotension and hypoxemia, have been well demonstrated as powerful determinants of outcomes from TBI. Despite the frequency of secondary insults in patients with TBI, they are rarely incorporated into most existing models of TBI. This review focuses on the combined injury models, especially coupled with systemic secondary insults, and aims to provide a new view to guiding future research endeavors in this field. A growing number of experimental models of TBI complicated by certain secondary insult have been gradually introduced and characterized. Correspondingly, the pathophysiological changes following combined injuries and the interactive effects of primary injury with secondary insults can be studied more in-depth. A more complete understanding of the interactions between the injured brain and secondary insults represents a potentially fruitful avenue that may increase the likelihood of developing effective therapies. Experimental models of TBI should not only attempt to model the focal or diffuse changes resulting from external forces, but also integrate, when appropriate, secondary insults reminiscent of human situations.

  18. Yawning induced by focal electrical stimulation in the human brain.

    PubMed

    Joshi, Sweta; Bayat, Arezou; Gagnon, Linda; Shields, Donald C; Koubeissi, Mohamad Z

    2017-01-01

    The primary function of yawning is not fully understood. We report a case in which electrical stimulation of the putamen in the human brain consistently elicited yawning. A 46-year-old woman with intractable epilepsy had invasive depth electrode monitoring and cortical stimulation mapping as part of her presurgical epilepsy evaluation. The first two contacts of a depth electrode that was intended to sample the left insula were in contact with the putamen. Stimulation of these contacts at 6mA and 8mA consistently elicited yawning on two separate days. Engagement in arithmetic and motor tasks during stimulation did not result in yawning. When considering the role of the putamen in motor control and its extensive connectivity to cortical and brainstem regions, our findings suggest that it plays a key role in the execution of motor movements necessitated by yawning. Furthermore, given the role of the anterior insula in attention and focused tasks, activation of this area while engaged in arithmetic and motor tasks could inhibit the putaminal processing necessary for yawning. Many have hypothesized the function of yawning; however, it remains debatable whether yawning serves a primarily physiological or communicative function or perhaps both. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. A mouse model of human repetitive mild traumatic brain injury

    PubMed Central

    Kane, Michael J.; Pérez, Mariana Angoa; Briggs, Denise I.; Viano, David C.; Kreipke, Christian W.; Kuhn, Donald M.

    2011-01-01

    A novel method for the study of repetitive mild traumatic brain injury (rmTBI) that models the most common form of head injury in humans is presented. Existing animal models of TBI impart focal, severe damage unlike that seen in repeated and mild concussive injuries, and few are configured for repetitive application. Our model is a modification of the Marmarou weight drop method and allows repeated head impacts to lightly anesthetized mice. A key facet of this method is the delivery of an impact to the cranium of an unrestrained subject allowing rapid acceleration of the free-moving head and torso, an essential characteristic known to be important for concussive injury in humans, and a factor that is missing from existing animal models of TBI. Our method does not require scalp incision, emplacement of protective skull helmets or surgery and the procedure can be completed in 1-2 minutes. Mice spontaneously recover the righting reflex and show no evidence of seizures, paralysis or impaired behavior. Skull fractures and intracranial bleeding are very rare. Minor deficits in motor coordination and locomotor hyperactivity recover over time. Histological analyses reveal mild astrocytic reactivity (increased expression of GFAP) and increased phospho-tau but a lack of blood-brain-barrier disruption, edema and microglial activation. This new animal model is simple and cost-effective and will facilitate characterization of the neurobiological and behavioral consequences of rmTBI. It is also ideal for high throughput screening of potential new therapies for mild concussive injuries as experienced by athletes and military personnel. PMID:21930157

  20. A mouse model of human repetitive mild traumatic brain injury.

    PubMed

    Kane, Michael J; Angoa-Pérez, Mariana; Briggs, Denise I; Viano, David C; Kreipke, Christian W; Kuhn, Donald M

    2012-01-15

    A novel method for the study of repetitive mild traumatic brain injury (rmTBI) that models the most common form of head injury in humans is presented. Existing animal models of TBI impart focal, severe damage unlike that seen in repeated and mild concussive injuries, and few are configured for repetitive application. Our model is a modification of the Marmarou weight drop method and allows repeated head impacts to lightly anesthetized mice. A key facet of this method is the delivery of an impact to the cranium of an unrestrained subject allowing rapid acceleration of the free-moving head and torso, an essential characteristic known to be important for concussive injury in humans, and a factor that is missing from existing animal models of TBI. Our method does not require scalp incision, emplacement of protective skull helmets or surgery and the procedure can be completed in 1-2 min. Mice spontaneously recover the righting reflex and show no evidence of seizures, paralysis or impaired behavior. Skull fractures and intracranial bleeding are very rare. Minor deficits in motor coordination and locomotor hyperactivity recover over time. Histological analyses reveal mild astrocytic reactivity (increased expression of GFAP) and increased phospho-tau but a lack of blood-brain-barrier disruption, edema and microglial activation. This new animal model is simple and cost-effective and will facilitate characterization of the neurobiological and behavioral consequences of rmTBI. It is also ideal for high throughput screening of potential new therapies for mild concussive injuries as experienced by athletes and military personnel.

  1. N-Acetylcysteine and Ceftriaxone as Preconditioning Strategies in Focal Brain Ischemia: Influence on Glutamate Transporters Expression.

    PubMed

    Krzyzanowska, Weronika; Pomierny, Bartosz; Budziszewska, Boguslawa; Filip, Malgorzata; Pera, Joanna

    2016-05-01

    Glutamate (Glu) plays a key role in excitotoxicity-related injury in cerebral ischemia. In the brain, Glu homeostasis depends on Glu transporters, including the excitatory amino acid transporters and the cysteine/Glu antiporter (xc-). We hypothesized that drugs acting on Glu transporters, such as ceftriaxone (CEF, 200 mg/kg, i.p.) and N-acetylcysteine (NAC, 150 mg/kg, i.p.), administered repeatedly for 5 days before focal cerebral ischemia in rats and induced by a 90-min middle cerebral artery occlusion (MCAO), may induce brain tolerance to ischemia. We compared the effects of these drugs on brain infarct volume, neurological deficits and the mRNA and protein expression of the Glu transporter-1 (GLT-1) and xc- with the effects of ischemic preconditioning and chemical preconditioning using 3-nitropropionic acid. Administration of CEF and NAC significantly reduced infarct size and neurological deficits caused by a 90-min MCAO. These beneficial effects were accompanied by changes in GLT-1 expression caused by a 90-min MCAO at both the mRNA and protein levels in the frontal cortex, hippocampus, and dorsal striatum. Thus, the results of this study suggest that the regulation of GLT-1 and xc- plays a role in the development of cerebral tolerance to ischemia and that this regulation may be a novel approach in the therapy of brain ischemia.

  2. Defective neuropeptide processing and ischemic brain injury: a study on proprotein convertase 2 and its substrate neuropeptide in ischemic brains

    PubMed Central

    Zhan, Shuqin; Zhao, Hongbo; White, Aaron J; Minami, Manabu; Pignataro, Giuseppe; Yang, Tao; Zhu, Xiaorong; Lan, Jingquan; Xiong, Zhigang; Steiner, Donald F; Simon, Roger P; Zhou, An

    2010-01-01

    Using a focal cerebral ischemia model in rats, brain ischemia-induced changes in expression levels of mRNA and protein, and activities of proprotein convertase 2 (PC2) in the cortex were examined. In situ hybridization analyses revealed a transient upregulation of the mRNA level for PC2 at an early reperfusion hour, at which the level of PC2 protein was also high as determined by immunocytochemistry and western blotting. When enzymatic activities of PC2 were analyzed using a synthetic substrate, a significant decrease was observed at early reperfusion hours at which levels of PC2 protein were still high. Also decreased at these reperfusion hours were tissue levels of dynorphin-A(1–8) (DYN-A(1–8)), a PC2 substrate, as determined by radioimmunoassay. Further examination of PC2 protein biosynthesis by metabolic labeling in cultured neuronal cells showed that in ischemic cells, the proteolytic processing of PC2 was greatly attenuated. Finally, in mice, an intracerebroventricular administration of synthetic DYN-A(1–8) significantly reduced the extent of ischemic brain injury. In mice those lack an active PC2, exacerbated brain injury was observed after an otherwise non-lethal focal ischemia. We conclude that brain ischemia attenuates PC2 and PC2-mediated neuropeptide processing. This attenuation may play a role in the pathology of ischemic brain injury. PMID:19142196

  3. Substantia nigra vulnerability after a single moderate diffuse brain injury in the rat

    PubMed Central

    van Bregt, Daniel R.; Thomas, Theresa Currier; Hinzman, Jason M.; Cao, Tuoxin; Liu, Mei; Bing, Guoying; Gerhardt, Greg A.; Pauly, James R.; Lifshitz, Jonathan

    2012-01-01

    Dementia and parkinsonism are late-onset symptoms associated with repetitive head injury, as documented in multiple contact-sport athletes. Clinical symptomatology is the likely phenotype of chronic degeneration and circuit disruption in the substantia nigra (SN). To investigate the initiating neuropathology, we hypothesize that a single diffuse brain injury is sufficient to initiate SN neuropathology including neuronal loss, vascular disruption and microglial activation, contributing to neurodegeneration and altered dopamine regulation. Adult, male Sprague-Dawley rats were subjected to sham or moderate midline fluid percussion brain injury. Stereological estimates indicated a significant 44% loss of the estimated total neuron number in the SN at 28-days post-injury, without atrophy of neuronal nuclear volumes, including 25% loss of tyrosine hydroxylase positive neurons by 28-days post-injury. Multi-focal vascular compromise occurred 1–2 days post-injury, with ensuing microglial activation (significant 40% increase at 4-days). Neurodegeneration (silver-stain technique) encompassed on average 21% of the SN by 7-days post-injury and increased to 29% by 28-days compared to sham (1%). Whole tissue SN, but not striatum, dopamine metabolism was altered at 28-days post-injury, without appreciable gene or protein changes in dopamine synthesis or regulation elements. Together, single moderate diffuse brain injury resulted in SN neurovascular pathology potentially associated with neuroinflammation or dopamine dysregulation. Compensatory mechanisms may preserve dopamine signaling acutely, but subsequent SN damage with aging or additional injury may expose clinical symptomatology of motor ataxias and dementia. PMID:22178300

  4. Increased calcineurin expression after pilocarpine-induced status epilepticus is associated with brain focal edema and astrogliosis.

    PubMed

    Liu, Jinzhi; Li, Xiaolin; Chen, Liguang; Xue, Ping; Yang, Qianqian; Wang, Aihua

    2015-07-28

    Calcineurin plays an important role in the development of neuronal excitability, modulation of receptor's function and induction of apoptosis in neurons. It has been established in kindling models that status epilepticus induces brain focal edema and astrocyte activation. However, the role of calcineurin in brain focal edema and astrocyte activation in status epilepticus has not been fully understood. In this study, we employed a model of lithium-pilocarpine-induced status epilepticus and detected calcineurin expression in hippocampus by immunoblotting, brain focal edema by non-invasive magnetic resonance imaging (MRI-7T) and astrocyte expression by immunohistochemistry. We found that the brain focal edema was seen at 24 h after status epilepticus, and astrocyte expression was obviously seen at 7 d after status epilepticus. Meanwhile, calcineurin expression was seen at24 h and retained to 7 d after status epilepticus. A FK506, a calcineurin inhibitor, remarkably suppressed the status epilepticus-induced brain focal edema and astrocyte expression. Our data suggested that calcineurin overexpression plays a very important role in brain focal edema and astrocyte expression. Therefore, calcineurin may be a novel candidate for brain focal edema occurring and intracellular trigger of astrogliosis in status epilepticus.

  5. Fyn in Neurodevelopment and Ischemic Brain Injury

    PubMed Central

    Knox, Renatta; Jiang, Xiangning

    2016-01-01

    The Src Family kinases (SFKs) are nonreceptor protein tyrosine kinases that are implicated in many normal and pathological processes in the nervous system. The SFKs Fyn, Src, Yes, Lyn and Lck are expressed in the brain. This review will focus on Fyn, as Fyn mutant mice have striking phenotypes in the brain and Fyn has been shown to be involved in ischemic brain injury in adult rodents, and with our work, in neonatal animals. An understanding of Fyn’s role in neurodevelopment and disease will allow researchers to target pathological pathways while preserving protective ones. PMID:25720756

  6. Group Treatment in Acquired Brain Injury Rehabilitation

    ERIC Educational Resources Information Center

    Bertisch, Hilary; Rath, Joseph F.; Langenbahn, Donna M.; Sherr, Rose Lynn; Diller, Leonard

    2011-01-01

    The current article describes critical issues in adapting traditional group-treatment methods for working with individuals with reduced cognitive capacity secondary to acquired brain injury. Using the classification system based on functional ability developed at the NYU Rusk Institute of Rehabilitation Medicine (RIRM), we delineate the cognitive…

  7. Narrative Language in Traumatic Brain Injury

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  8. Future directions in brain injury research.

    PubMed

    Gennarelli, Thomas A

    2014-01-01

    This paper reviews the potential future directions that are important for brain injury research, especially with regard to concussion. The avenues of proposed research are categorized according to current concepts of concussion, types of concussion, and a global schema for globally reducing the burden of concussion.

  9. Psychiatric disorders and traumatic brain injury

    PubMed Central

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

    2008-01-01

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

  10. School Reentry Following Traumatic Brain Injury

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  11. Academic Placement after Traumatic Brain Injury.

    ERIC Educational Resources Information Center

    Donders, Jacques

    The acadmic placement of 87 children (ages 6 to 16 years) who had sustained brain injuries was determined within 1 year after initial psychological assessment. Forty-five children had returned full time to regular academic programs, 21 children received special education support for less than half of their classes, and 21 children were enrolled in…

  12. Traumatic Brain Injury and Personality Change

    ERIC Educational Resources Information Center

    Fowler, Marc; McCabe, Paul C.

    2011-01-01

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

  13. Group Treatment in Acquired Brain Injury Rehabilitation

    ERIC Educational Resources Information Center

    Bertisch, Hilary; Rath, Joseph F.; Langenbahn, Donna M.; Sherr, Rose Lynn; Diller, Leonard

    2011-01-01

    The current article describes critical issues in adapting traditional group-treatment methods for working with individuals with reduced cognitive capacity secondary to acquired brain injury. Using the classification system based on functional ability developed at the NYU Rusk Institute of Rehabilitation Medicine (RIRM), we delineate the cognitive…

  14. Clinical review: ketones and brain injury.

    PubMed

    White, Hayden; Venkatesh, Balasubramanian

    2011-04-06

    Although much feared by clinicians, the ability to produce ketones has allowed humans to withstand prolonged periods of starvation. At such times, ketones can supply up to 50% of basal energy requirements. More interesting, however, is the fact that ketones can provide as much as 70% of the brain's energy needs, more efficiently than glucose. Studies suggest that during times of acute brain injury, cerebral uptake of ketones increases significantly. Researchers have thus attempted to attenuate the effects of cerebral injury by administering ketones exogenously. Hypertonic saline is commonly utilized for management of intracranial hypertension following cerebral injury. A solution containing both hypertonic saline and ketones may prove ideal for managing the dual problems of refractory intracranial hypertension and low cerebral energy levels. The purpose of the present review is to explore the physiology of ketone body utilization by the brain in health and in a variety of neurological conditions, and to discuss the potential for ketone supplementation as a therapeutic option in traumatic brain injury.

  15. Clinical review: Ketones and brain injury

    PubMed Central

    2011-01-01

    Although much feared by clinicians, the ability to produce ketones has allowed humans to withstand prolonged periods of starvation. At such times, ketones can supply up to 50% of basal energy requirements. More interesting, however, is the fact that ketones can provide as much as 70% of the brain's energy needs, more efficiently than glucose. Studies suggest that during times of acute brain injury, cerebral uptake of ketones increases significantly. Researchers have thus attempted to attenuate the effects of cerebral injury by administering ketones exogenously. Hypertonic saline is commonly utilized for management of intracranial hypertension following cerebral injury. A solution containing both hypertonic saline and ketones may prove ideal for managing the dual problems of refractory intracranial hypertension and low cerebral energy levels. The purpose of the present review is to explore the physiology of ketone body utilization by the brain in health and in a variety of neurological conditions, and to discuss the potential for ketone supplementation as a therapeutic option in traumatic brain injury. PMID:21489321

  16. Traumatic Brain Injury: A Guidebook for Educators.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Office for Special Education Services.

    This guidebook is designed to help New York school staff better understand the specialized needs of students with traumatic brain injury (TBI) and appropriately apply educational interventions to improve special and general education services for these students. It provides information on the following areas: (1) the causes, incidence, and…

  17. Traumatic Brain Injury. Quick Turn Around (QTA).

    ERIC Educational Resources Information Center

    Markowitz, Joy; Linehan, Patrice

    This brief paper summarizes information concerning use of the traumatic brain injury (TBI) disability classification by states and the nature of state-level activities related to the education of children and youth with TBI. It notes addition of the TBI disability category to the Individuals with Disabilities Education Act in 1990 and provides the…

  18. Traumatic Brain Injury and Vocational Rehabilitation.

    ERIC Educational Resources Information Center

    Corthell, David W., Ed.

    Intended to serve as a resource guide on traumatic brain injury for rehabilitation practitioners, the book's 10 chapters are grouped into sections which provide an introduction and examine aspects of evaluation, treatment and placement planning, and unresolved issues. Chapters have the following titles and authors: "Scope of the Problem" (Marilyn…

  19. Interviewing Children with Acquired Brain Injury (ABI)

    ERIC Educational Resources Information Center

    Boylan, Anne-Marie; Linden, Mark; Alderdice, Fiona

    2009-01-01

    Research into the lives of children with acquired brain injury (ABI) often neglects to incorporate children as participants, preferring to obtain the opinions of the adult carer (e.g. McKinlay et al., 2002). There has been a concerted attempt to move away from this position by those working in children's research with current etiquette…

  20. Narrative Language in Traumatic Brain Injury

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  1. Reality Lessons in Traumatic Brain Injury

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  2. Traumatic Brain Injury: Perspectives from Educational Professionals

    ERIC Educational Resources Information Center

    Mohr, J. Darrell; Bullock, Lyndal M.

    2005-01-01

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

  3. Working with Students with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Lucas, Matthew D.

    2010-01-01

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

  4. Traumatic Brain Injury: Empirical Family Assessment Techniques.

    ERIC Educational Resources Information Center

    Bishop, Duane S.; Miller, Ivan W.

    1988-01-01

    Methods are described for quantifying and formalizing assessment of traumatic brain injury patient families. The advantages and disadvantages of empirical and clinical assessment are outlined, and four family assessment methods are reviewed: self-report, interview, observation, and laboratory. Specific assessment instruments are noted along with…

  5. Traumatic Brain Injury and Personality Change

    ERIC Educational Resources Information Center

    Fowler, Marc; McCabe, Paul C.

    2011-01-01

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

  6. Seizures Following Traumatic Brain Injury in Childhood.

    ERIC Educational Resources Information Center

    Williams, Dennis

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

  7. Academic Placement after Traumatic Brain Injury.

    ERIC Educational Resources Information Center

    Donders, Jacques

    The acadmic placement of 87 children (ages 6 to 16 years) who had sustained brain injuries was determined within 1 year after initial psychological assessment. Forty-five children had returned full time to regular academic programs, 21 children received special education support for less than half of their classes, and 21 children were enrolled in…

  8. Working with Students with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Lucas, Matthew D.

    2010-01-01

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

  9. Traumatic Brain Injury: Perspectives from Educational Professionals

    ERIC Educational Resources Information Center

    Mohr, J. Darrell; Bullock, Lyndal M.

    2005-01-01

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

  10. Traumatic brain injury and posttraumatic stress disorder.

    PubMed

    Bahraini, Nazanin H; Breshears, Ryan E; Hernández, Theresa D; Schneider, Alexandra L; Forster, Jeri E; Brenner, Lisa A

    2014-03-01

    Given the upsurge of research in posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI), much of which has focused on military samples who served in Iraq and Afghanistan, the purpose of this article is to review the literature published after September 11th, 2001 that addresses the epidemiology, pathophysiology, evaluation, and treatment of PTSD in the context of TBI.

  11. Experimental models of repetitive brain injuries.

    PubMed

    Weber, John T

    2007-01-01

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

  12. Child and adolescent traumatic brain injury: correlates of injury severity.

    PubMed

    Max, J E; Lindgren, S D; Knutson, C; Pearson, C S; Ihrig, D; Welborn, A

    1998-01-01

    A record review focused on children and adolescents, with a history of traumatic brain injury, who were consecutively admitted to a brain injury clinic in which all new patients are psychiatrically evaluated. Significant correlates of severity of injury in the cognitive, education and communication domains of functioning included Performance IQ but not Verbal IQ nor standardized ratings of language or learning disability. Current organic personality syndrome (OPS) but not attention deficit hyperactivity disorder or oppositional defiant disorder/conduct disorder diagnostic status was significantly related to severity. In conclusion, the findings in this referred sample are similar to prospective studies indicating that Performance IQ appears sensitive in reflecting brain damage. The finding linking OPS to severity of injury is not surprising. This is because OPS is a diagnosis which is dependent on the clinician's judgment of the likelihood that the organic factor is etiologically related to a defined behavioural syndrome. The diagnosis therefore requires a clinical judgment that the threshold of severity of a presumed organic etiological factor has been reached.

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

    PubMed

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

    2016-09-01

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

  14. Traumatic Alterations in Consciousness: Traumatic Brain Injury

    PubMed Central

    Blyth, Brian J.; Bazarian, Jeffrey J.

    2010-01-01

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

  15. Discriminating military and civilian traumatic brain injuries.

    PubMed

    Reid, Matthew W; Velez, Carmen S

    2015-05-01

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

  16. Restoring Conscious Arousal During Focal Limbic Seizures with Deep Brain Stimulation.

    PubMed

    Kundishora, Adam J; Gummadavelli, Abhijeet; Ma, Chanthia; Liu, Mengran; McCafferty, Cian; Schiff, Nicholas D; Willie, Jon T; Gross, Robert E; Gerrard, Jason; Blumenfeld, Hal

    2016-03-03

    Impaired consciousness occurs suddenly and unpredictably in people with epilepsy, markedly worsening quality of life and increasing risk of mortality. Focal seizures with impaired consciousness are the most common form of epilepsy and are refractory to all current medical and surgical therapies in about one-sixth of cases. Restoring consciousness during and following seizures would be potentially transformative for these individuals. Here, we investigate deep brain stimulation to improve level of conscious arousal in a rat model of focal limbic seizures. We found that dual-site stimulation of the central lateral nucleus of the intralaminar thalamus (CL) and the pontine nucleus oralis (PnO) bilaterally during focal limbic seizures restored normal-appearing cortical electrophysiology and markedly improved behavioral arousal. In contrast, single-site bilateral stimulation of CL or PnO alone was insufficient to achieve the same result. These findings support the "network inhibition hypothesis" that focal limbic seizures impair consciousness through widespread inhibition of subcortical arousal. Driving subcortical arousal function would be a novel therapeutic approach to some forms of refractory epilepsy and may be compatible with devices already in use for responsive neurostimulation. Multisite deep brain stimulation of subcortical arousal structures may benefit not only patients with epilepsy but also those with other disorders of consciousness.

  17. Neuroprotection against Surgically-Induced Brain Injury

    PubMed Central

    Jadhav, Vikram; Solaroglu, Ihsan; Obenaus, Andre; Zhang, John H.

    2007-01-01

    Background Neurosurgical procedures are carried out routinely in health institutions across the world. A key issue to be considered during neurosurgical interventions is that there is always an element of inevitable brain injury that results from the procedure itself due to the unique nature of the nervous system. Brain tissue at the periphery of the operative site is at risk of injury by various means including incisions and direct trauma, electrocautery, hemorrhage, and retractor stretch. Methods/Results In the present review we will elaborate upon this surgically-induced brain injury and also present a novel animal model to study it. Additionally, we will summarize preliminary results obtained by pretreatment with PP1, a src tyrosine kinase inhibitor reported to have neuroprotective properties in in-vivo experimental studies. Any form of pretreatment to limit the damage to the susceptible functional brain tissue during neurosurgical procedures may have a significant impact on the patient recovery. Conclusion This brief review is intended to raise the question of ‘neuroprotection against surgically-induced brain injury’ in the neurosurgical scientific community and stimulate discussions. PMID:17210286

  18. Therapeutic effect of Korean red ginseng on inflammatory cytokines in rats with focal cerebral ischemia/reperfusion injury.

    PubMed

    Lee, Jong Seok; Choi, Han Sung; Kang, Sung Wook; Chung, Joo-Ho; Park, Hun Kuk; Ban, Ju Yeon; Kwon, Oh Young; Hong, Hoon Pyo; Ko, Young Gwan

    2011-01-01

    This study aims to identify the therapeutic effect of Korean red ginseng (KRG) on the expression of inflammatory cytokines in rats with focal cerebral ischemia/reperfusion injury. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (tMCAO) for two hours. They were fed KRG extract (100 mg/kg/day per orally) or saline after reperfusion. Tests for neurological deficits, using the modified neurologic severity score and the corner turn test, were performed before the ischemic event, and one, three, and seven days after tMCAO. Serum levels of cytokines were measured three and seven days after the operation, using enzyme-linked immunosorbent assays. The infarct volume was assessed after seven days by staining brain tissue with 2% 2, 3, 5-triphenyltetrazolium chloride. Oral administration of KRG significantly reduced the infarct volumes and rapidly improved neurological deficits. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6 were higher in tMCAO-operated rats than in the sham-operated rats. These changes were attenuated by daily KRG intake for seven days. Serum IL-10 levels were significantly increased in KRG-fed rats, as compared to sham-operated and saline-fed rats. Our results suggested that KRG provides neuroprotection for rats with focal cerebral ischemia/reperfusion injury. This neuroprotection may be due to raised IL-10 expression and a reduction in the serum levels of TNF-α, IL-1β, and IL-6.

  19. Synchrony in Normal and Focal Epileptic Brain: The Seizure Onset Zone is Functionally Disconnected

    PubMed Central

    Warren, Christopher P.; Hu, Sanqing; Stead, Matt; Brinkmann, Benjamin H.; Bower, Mark R.

    2010-01-01

    Synchronization of local and distributed neuronal assemblies is thought to underlie fundamental brain processes such as perception, learning, and cognition. In neurological disease, neuronal synchrony can be altered and in epilepsy may play an important role in the generation of seizures. Linear cross-correlation and mean phase coherence of local field potentials (LFPs) are commonly used measures of neuronal synchrony and have been studied extensively in epileptic brain. Multiple studies have reported that epileptic brain is characterized by increased neuronal synchrony except possibly prior to seizure onset when synchrony may decrease. Previous studies using intracranial electroencephalography (EEG), however, have been limited to patients with epilepsy. Here we investigate neuronal synchrony in epileptic and control brain using intracranial EEG recordings from patients with medically resistant partial epilepsy and control subjects with intractable facial pain. For both epilepsy and control patients, average LFP synchrony decreases with increasing interelectrode distance. Results in epilepsy patients show lower LFP synchrony between seizure-generating brain and other brain regions. This relative isolation of seizure-generating brain underlies the paradoxical finding that control patients without epilepsy have greater average LFP synchrony than patients with epilepsy. In conclusion, we show that in patients with focal epilepsy, the region of epileptic brain generating seizures is functionally isolated from surrounding brain regions. We further speculate that this functional isolation may contribute to spontaneous seizure generation and may represent a clinically useful electrophysiological signature for mapping epileptic brain. PMID:20926610

  20. Anti-inflammatory properties of lipoxin A4 protect against diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury

    PubMed Central

    Han, Jiang-quan; Liu, Cheng-ling; Wang, Zheng-yuan; Liu, Ling; Cheng, Ling; Fan, Ya-dan

    2016-01-01

    Lipoxin A4 can alleviate cerebral ischemia/reperfusion injury by reducing the inflammatory reaction, but it is currently unclear whether it has a protective effect on diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury. In this study, we established rat models of diabetes mellitus using an intraperitoneal injection of streptozotocin. We then induced focal cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours. After administration of lipoxin A4 via the lateral ventricle, infarction volume was reduced, the expression levels of pro-inflammatory factors tumor necrosis factor alpha and nuclear factor-kappa B in the cerebral cortex were decreased, and neurological functioning was improved. These findings suggest that lipoxin A4 has strong neuroprotective effects in diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury and that the underlying mechanism is related to the anti-inflammatory action of lipoxin A4. PMID:27212926

  1. P43/pro-EMAPII: A Potential Biomarker for Discriminating Traumatic Versus Ischemic Brain Injury

    PubMed Central

    Yao, Changping; Williams, Anthony J.; Ottens, Andrew K.; Lu, X.-C. May; Liu, Ming Cheng; Hayes, Ronald L.; Wang, Kevin K.; Tortella, Frank C.

    2009-01-01

    Abstract To gain additional insights into the pathogenic cellular and molecular mechanisms underlying different types of brain injury (e.g., trauma versus ischemia), recently attention has focused on the discovery and study of protein biomarkers. In previous studies, using a high-throughput immunoblotting (HTPI) technique, we reported changes in 29 out of 998 proteins following acute injuries to the rat brain (penetrating traumatic versus focal ischemic). Importantly, we discovered that one protein, endothelial monocyte-activating polypeptide II precursor (p43/pro-EMAPII), was differentially expressed between these two types of brain injury. Among other functions, p43/pro-EMAPII is a known pro-inflammatory cytokine involved in the progression of apoptotic cell death. Our current objective was to verify the changes in p43/pro-EMAPII expression, and to evaluate the potentially important implications that the differential regulation of this protein has on injury development. At multiple time points following either a penetrating ballistic-like brain injury (PBBI), or a transient middle cerebral artery occlusion (MCAo) brain injury, tissue samples (6–72 h), CSF samples (24 h), and blood samples (24 h) were collected from rats for analysis. Changes in protein expression were assessed by Western blot analysis and immunohistochemistry. Our results indicated that p43/pro-EMAPII was significantly increased in brain tissues, CSF, and plasma following PBBI, but decreased after MCAo injury compared to their respective sham control samples. This differential expression of p43/pro-EMAPII may be a useful injury-specific biomarker associated with the underlying pathologies of traumatic versus ischemic brain injury, and provide valuable information for directing injury-specific therapeutics. PMID:19317603

  2. Nicotinamide attenuates the decrease of astrocytic phosphoprotein PEA-15 in focal cerebral ischemic injury.

    PubMed

    Koh, Phil-Ok

    2012-03-01

    Nicotinamide exerts neuroprotective effects against focal cerebral ischemic injury. Phosphoprotein enriched in astrocytes 15 (PEA-15) is prominently expressed in astrocytes that exert broad anti-apoptotic functions. This study investigated whether nicotinamide modulates PEA-15 and levels of two phosphorylated PEA-15 (Serine 104 and 116) in an animal model of middle cerebral artery occlusion (MCAO)-induced injury. Adult male rats were treated with vehicle or nicotinamide (500 mg/kg) 2 hr after the onset of MCAO and cerebral cortices were collected at 24 hr after MCAO. In a proteomic approach, MCAO induced decreases of PEA-15 levels, while nicotinamide treatment attenuated the injury-induced decrease in PEA-15. The results of Western blot analysis suggest that nicotinamide prevented injury-induced reduction in phospho-PEA-15 (Serine 104) and phospho-PEA-15 (Serine 116) levels. The phosphorylation of PEA-15 exerts anti-apoptotic functions, and reduction of PEA-15 phosphorylation leads to apoptotic cell death. These results suggest that nicotinamide exerts a neuroprotective effect by attenuating the injury-induced decreases of PEA-15 and phospho-PEA-15 (Ser 104 and Ser 116) proteins.

  3. Attention and driving in traumatic brain injury: a question of coping with time-pressure.

    PubMed

    Brouwer, Wiebo H; Withaar, Frederiec K; Tant, Mark L M; van Zomeren, Adriaan H

    2002-02-01

    Diffuse and focal traumatic brain injury (TBI) can result in perceptual, cognitive, and motor dysfunction possibly leading to activity limitations in driving. Characteristic dysfunctions for severe diffuse TBI are confronted with function requirements derived from the hierarchical task analysis of driving skill. Specifically, we focus on slow information processing, divided attention, and the development of procedural knowledge. Also the effects of a combination of diffuse and focal dysfunctions, specifically homonymous hemianopia and the dysexecutive syndrome, are discussed. Finally, we turn to problems and challenges with regard to assessment and rehabilitation methods in the areas of driving and fitness to drive.

  4. Traumatic brain injury imaging research roadmap.

    PubMed

    Wintermark, M; Coombs, L; Druzgal, T J; Field, A S; Filippi, C G; Hicks, R; Horton, R; Lui, Y W; Law, M; Mukherjee, P; Norbash, A; Riedy, G; Sanelli, P C; Stone, J R; Sze, G; Tilkin, M; Whitlow, C T; Wilde, E A; York, G; Provenzale, J M

    2015-03-01

    The past decade has seen impressive advances in the types of neuroimaging information that can be acquired in patients with traumatic brain injury. However, despite this increase in information, understanding of the contribution of this information to prognostic accuracy and treatment pathways for patients is limited. Available techniques often allow us to infer the presence of microscopic changes indicative of alterations in physiology and function in brain tissue. However, because histologic confirmation is typically lacking, conclusions reached by using these techniques remain solely inferential in almost all cases. Hence, a need exists for validation of these techniques by using data from large population samples that are obtained in a uniform manner, analyzed according to well-accepted procedures, and correlated with closely monitored clinical outcomes. At present, many of these approaches remain confined to population-based research rather than diagnosis at an individual level, particularly with regard to traumatic brain injury that is mild or moderate in degree. A need and a priority exist for patient-centered tools that will allow advanced neuroimaging tools to be brought into clinical settings. One barrier to developing these tools is a lack of an age-, sex-, and comorbidities-stratified, sequence-specific, reference imaging data base that could provide a clear understanding of normal variations across populations. Such a data base would provide researchers and clinicians with the information necessary to develop computational tools for the patient-based interpretation of advanced neuroimaging studies in the clinical setting. The recent "Joint ASNR-ACR HII-ASFNR TBI Workshop: Bringing Advanced Neuroimaging for Traumatic Brain Injury into the Clinic" on May 23, 2014, in Montreal, Quebec, Canada, brought together neuroradiologists, neurologists, psychiatrists, neuropsychologists, neuroimaging scientists, members of the National Institute of Neurologic

  5. Brain tissue oxygen tension and its response to physiological manipulations: influence of distance from injury site in a swine model of traumatic brain injury.

    PubMed

    Hawryluk, Gregory W J; Phan, Nicolas; Ferguson, Adam R; Morabito, Diane; Derugin, Nikita; Stewart, Campbell L; Knudson, M Margaret; Manley, Geoffrey; Rosenthal, Guy

    2016-11-01

    OBJECTIVE The optimal site for placement of tissue oxygen probes following traumatic brain injury (TBI) remains unresolved. The authors used a previously described swine model of focal TBI and studied brain tissue oxygen tension (PbtO2) at the sites of contusion, proximal and distal to contusion, and in the contralateral hemisphere to determine the effect of probe location on PbtO2 and to assess the effects of physiological interventions on PbtO2 at these different sites. METHODS A controlled cortical impact device was used to generate a focal lesion in the right frontal lobe in 12 anesthetized swine. PbtO2 was measured using Licox brain tissue oxygen probes placed at the site of contusion, in pericontusional tissue (proximal probe), in the right parietal region (distal probe), and in the contralateral hemisphere. PbtO2 was measured during normoxia, hyperoxia, hypoventilation, and hyperventilation. RESULTS Physiological interventions led to expected changes, including a large increase in partial pressure of oxygen in arterial blood with hyperoxia, increased intracranial pressure (ICP) with hypoventilation, and decreased ICP with hyperventilation. Importantly, PbtO2 decreased substantially with proximity to the focal injury (contusion and proximal probes), and this difference was maintained at different levels of fraction of inspired oxygen and partial pressure of carbon dioxide in arterial blood. In the distal and contralateral probes, hypoventilation and hyperventilation were associated with expected increased and decreased PbtO2 values, respectively. However, in the contusion and proximal probes, these effects were diminished, consistent with loss of cerebrovascular CO2 reactivity at and near the injury site. Similarly, hyperoxia led to the expected rise in PbtO2 only in the distal and contralateral probes, with little or no effect in the proximal and contusion probes, respectively. CONCLUSIONS PbtO2 measurements are strongly influenced by the distance from the

  6. Traumatic Brain Injury - Multiple Languages

    MedlinePlus

    ... this page, please enable JavaScript. Hindi (हिन्दी) Japanese (日本語) Korean (한국어) Russian (Русский) Somali (Af-Soomaali ) ... हिन्दी (Hindi) Bilingual PDF Health Information Translations Japanese (日本語) Expand Section Brain Scan - 日本語 (Japanese) Bilingual ...

  7. Neuroprotective effects of focal brain cooling on photochemically-induced cerebral infarction in rats: analysis from a neurophysiological perspective.

    PubMed

    He, Yeting; Fujii, Masami; Inoue, Takao; Nomura, Sadahiro; Maruta, Yuichi; Oka, Fumiaki; Shirao, Satoshi; Owada, Yuji; Kida, Hiroyuki; Kunitsugu, Ichiro; Yamakawa, Toshitaka; Tokiwa, Tatsuji; Yamakawa, Takeshi; Suzuki, Michiyasu

    2013-02-25

    Although systemic hypothermia provides favorable outcomes in stroke patients, it has only been adopted in a limited number of patients because of fatal complications. To resolve these issues, focal brain cooling (FBC) has recently drawn attention as a less-invasive treatment for brain injuries. Therefore, we investigated whether FBC has a favorable effect on focal cerebral ischemia (FCI). Male-adult-Wistar rats were used. Under general anesthesia, a small burr hole was made and FCI was induced in the primary sensorimotor area (SI-MI) using photothrombosis. An additional craniotomy was made over the SI-MI and FBC was performed at a temperature of 15°C for 5h. Electrocorticograms (ECoG) were recorded on the border cortex of the ischemic focus. Thereafter, rats were sacrificed and the infarct area was measured. In another experiment, rats were allowed to recover for 5 days after cooling and neurobehavioral function was evaluated. FBC suppressed all ECoG frequency bands during and after cooling (p<0.05), except for the delta frequency band in the precooling versus rewarming periods. The injured areas in the cooling and non-cooling groups were 0.99±0.30 and 1.71±0.54 mm(2), respectively (p<0.03). The grip strength at 2 days after surgery was preserved in the cooling group (p<0.05). We report the novel finding that epileptiform discharges were suppressed in the ischemic border, the infarct area was reduced and neurobehaviour was preserved by FBC. These results indicate that FBC is neuroprotective in the ischemic brain and has demonstrated therapeutic potential for cerebral infarction. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Astrocyte roles in traumatic brain injury

    PubMed Central

    Burda, Joshua E.; Bernstein, Alexander M.; Sofroniew, Michael V.

    2015-01-01

    Astrocytes sense changes in neural activity and extracellular space composition. In response, they exert homeostatic mechanisms critical for maintaining neural circuit function, such as buffering neurotransmitters, modulating extracellular osmolarity and calibrating neurovascular coupling. In addition to upholding normal brain activities, astrocytes respond to diverse forms of brain injury with heterogeneous and progressive changes of gene expression, morphology, proliferative capacity and function that are collectively referred to as reactive astrogliosis. Traumatic brain injury (TBI) sets in motion complex events in which noxious mechanical forces cause tissue damage and disrupt central nervous system (CNS) homeostasis, which in turn trigger diverse multi-cellular responses that evolve over time and can lead either to neural repair or secondary cellular injury. In response to TBI, astrocytes in different cellular microenvironments tune their reactivity to varying degrees of axonal injury, vascular disruption, ischemia and inflammation. Here we review different forms of TBI-induced astrocyte reactivity and the functional consequences of these responses for TBI pathobiology. Evidence regarding astrocyte contribution to post-traumatic tissue repair and synaptic remodeling is examined, and the potential for targeting specific aspects of astrogliosis to ameliorate TBI sequelae is considered. PMID:25828533

  9. Traumatic Brain Injury-Associated Coagulopathy

    PubMed Central

    Zhang, Jianning; Jiang, Rongcai; Liu, Li; Watkins, Timothy; Zhang, Fangyi

    2012-01-01

    Abstract Traumatic injury is a common cause of coagulopathy, primarily due to blood loss and hemodilution secondary to fluid resuscitation. Traumatic injury-associated coagulopathy often follows a course of transition from hyper- to hypocoagulable state exemplified in disseminated intravascular coagulation. The incidence of coagulopathy is significantly higher in patients with traumatic brain injury (TBI), especially those with penetrating trauma compared to injury to the trunk and limbs. This occurs despite the fact that patients with isolated TBI bleed less and receive restricted volume load of fluids. TBI-associated coagulopathy is extensively documented to associate with poor clinical outcomes, but its pathophysiology remains poorly understood. Studies in the past have shown that brain tissue is highly enriched in key procoagulant molecules. This review focuses on the biochemical and cellular characteristics of these molecules and pathways that could make brain uniquely procoagulant and prone to coagulopathy. Understanding this unique procoagulant environment will help to identify new therapeutic targets that could reverse a state of coagulopathy with minimal impacts on hemostasis, a critical requirement for neurosurgical treatments of TBI. PMID:23020190

  10. Traumatic Brain Injury and Neuropsychiatric Complications.

    PubMed

    Ahmed, Saeed; Venigalla, Hema; Mekala, Hema Madhuri; Dar, Sara; Hassan, Mudasar; Ayub, Shahana

    2017-01-01

    Traumatic brain injury (TBI) occurs when a blow or jolt to the head or a penetrating injury results in damage to the brain. It is the most frequent cause of hospitalization in young people with a higher prevalence in men. TBI is the leading cause of disability and mortality between the ages 1 and 45. TBI can be caused either by the direct result of trauma or due to a complication of the primary injury. The most common etiological factors for TBI are falls, road traffic accidents, violent physical assaults, and injuries associated with athletic activities. Following TBI, significant neurologic complications may occur which include seizures, dementia, Alzheimer's disease, and cranial nerve injuries. In addition, people may suffer from various psychiatric complications such as depression, posttraumatic stress disorder, generalized anxiety disorder, obsessive-compulsive disorder, and other cognitive and behavioral sequel that might significantly increase the comorbidity of the victims. Considering all of the above complications, TBI is one of the significant public health burdens. Literature has shown that only about 25% of people achieve long-term functional independence following TBI. In this paper, we focused not only on the epidemiology but also the etiology, complications following TBI and understanding their underlying pathogenesis. Further, we focused on analyzing the options to improve the treatment and rehabilitation following TBI in future.

  11. The gut reaction to traumatic brain injury

    PubMed Central

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

    2015-01-01

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

  12. Substance P mediates reduced pneumonia rates after traumatic brain injury.

    PubMed

    Yang, Sung; Stepien, David; Hanseman, Dennis; Robinson, Bryce; Goodman, Michael D; Pritts, Timothy A; Caldwell, Charles C; Remick, Daniel G; Lentsch, Alex B

    2014-09-01

    Traumatic brain injury results in significant morbidity and mortality and is associated with infectious complications, particularly pneumonia. However, whether traumatic brain injury directly impacts the host response to pneumonia is unknown. The objective of this study was to determine the nature of the relationship between traumatic brain injury and the prevalence of pneumonia in trauma patients and investigate the mechanism of this relationship using a murine model of traumatic brain injury with pneumonia. Data from the National Trauma Data Bank and a murine model of traumatic brain injury with postinjury pneumonia. Academic medical centers in Cincinnati, OH, and Boston, MA. Trauma patients in the National Trauma Data Bank with a hospital length of stay greater than 2 days, age of at least 18 years at admission, and a blunt mechanism of injury. Subjects were female ICR mice 8-10 weeks old. Administration of a substance P receptor antagonist in mice. Pneumonia rates were measured in trauma patients before and after risk adjustment using propensity scoring. In addition, survival and pulmonary inflammation were measured in mice undergoing traumatic brain injury with or without pneumonia. After risk adjustment, we found that traumatic brain injury patients had significantly lower rates of pneumonia compared to blunt trauma patients without traumatic brain injury. A murine model of traumatic brain injury reproduced these clinical findings with mice subjected to traumatic brain injury demonstrating increased bacterial clearance and survival after induction of pneumonia. To determine the mechanisms responsible for this improvement, the substance P receptor was blocked in mice after traumatic brain injury. This treatment abrogated the traumatic brain injury-associated increases in bacterial clearance and survival. The data demonstrate that patients with traumatic brain injury have lower rates of pneumonia compared to non-head-injured trauma patients and suggest that the

  13. Military traumatic brain injury: a review.

    PubMed

    Chapman, Julie C; Diaz-Arrastia, Ramon

    2014-06-01

    Military mild traumatic brain injury (mTBI) differs from civilian injury in important ways. Although mTBI sustained in both military and civilian settings are likely to be underreported, the combat theater presents additional obstacles to reporting and accessing care. The impact of blast forces on the nervous system may differ from nonblast mechanisms, mTBI although studies comparing the neurologic and cognitive sequelae in mTBI survivors have not provided such evidence. However, emotional distress appears to figure prominently in symptoms following military mTBI. This review evaluates the extant literature with an eye towards future research directions.

  14. Kevlar Vest Protection Against Blast Overpressure Brain Injury: Systemic Contributions to Injury Etiology

    DTIC Science & Technology

    2014-11-01

    Award Number: W81XWH-08-2-0017 TITLE: " Kevlar Vest Protection Against Blast Overpressure Brain Injury: Systemic Contributions to Injury Etiology...TITLE AND SUBTITLE 5a. CONTRACT NUMBER “ Kevlar Vest Protection Against Blast Overpressure Brain Injury: Systemic Contributions to Injury Etiology...traumatic brain injury (bTBI) is largely undefined. Along with reducing mortality, in preliminary experiments Kevlar vests significantly protected

  15. Predictors of Hypopituitarism in Patients with Traumatic Brain Injury.

    PubMed

    Silva, Paula P B; Bhatnagar, Saurabha; Herman, Seth D; Zafonte, Ross; Klibanski, Anne; Miller, Karen K; Tritos, Nicholas A

    2015-11-15

    Hypopituitarism may often occur in association with traumatic brain injury (TBI). Identification of reliable predictors of pituitary dysfunction is of importance in order to establish a rational testing approach. We searched the records of patients with TBI, who underwent neuroendocrine evaluation in our institution between 2007 and 2013. One hundred sixty-six adults (70% men) with TBI (median age: 41.6 years; range: 18-76) were evaluated at a median interval of 40.4 months (0.2-430.4).Of these, 31% had ≥1 pituitary deficiency, including 29% of patients with mild TBI and 35% with moderate/severe TBI. Growth hormone deficiency was the most common deficiency (21%); when body mass index (BMI)-dependent cutpoints were used, this was reduced to 15%. Central hypoadrenalism occurred in10%, who were more likely to have suffered a motor vehicle accident (MVA, p = 0.04), experienced post-traumatic seizures (p = 0.04), demonstrated any intracranial hemorrhage (p = 0.05), petechial brain hemorrhages (p = 0.017), or focal cortical parenchymal contusions (p = 0.02). Central hypothyroidism occurred in 8% and central hypogonadism in 12%; the latter subgroup had higher BMI (p = 0.03), were less likely to be working after TBI (p = 0.002), and had lower Global Assessment of Functioning (GAF) scores (p = 0.03). Central diabetes insipidus (DI) occurred in 6%, who were more likely to have experienced MVA (p < 0.001) or sustained moderate/severe TBI (p < 0.001). Patients with MVA and those with post-traumatic seizures, intracranial hemorrhage, petechial brain hemorrhages, and/or focal cortical contusions are at particular risk for serious pituitary dysfunction, including adrenal insufficiency and DI, and should be referred for neuroendocrine testing. However, a substantial proportion of patients without these risk factors also developed hypopituitarism.

  16. Rapamycin alleviates brain edema after focal cerebral ischemia reperfusion in rats.

    PubMed

    Guo, Wei; Feng, Guoying; Miao, Yanying; Liu, Guixiang; Xu, Chunsheng

    2014-06-01

    Brain edema is a major consequence of cerebral ischemia reperfusion. However, few effective therapeutic options are available for retarding the brain edema progression after cerebral ischemia. Recently, rapamycin has been shown to produce neuroprotective effects in rats after cerebral ischemia reperfusion. Whether rapamycin could alleviate this brain edema injury is still unclear. In this study, the rat stroke model was induced by a 1-h left transient middle cerebral artery occlusion using an intraluminal filament, followed by 48 h of reperfusion. The effects of rapamycin (250 μg/kg body weight, intraperitoneal; i.p.) on brain edema progression were evaluated. The results showed that rapamycin treatment significantly reduced the infarct volume, the water content of the brain tissue and the Evans blue extravasation through the blood-brain barrier (BBB). Rapamycin treatment could improve histological appearance of the brain tissue, increased the capillary lumen space and maintain the integrity of BBB. Rapamycin also inhibited matrix metalloproteinase 9 (MMP9) and aquaporin 4 (AQP4) expression. These data imply that rapamycin could improve brain edema progression after reperfusion injury through maintaining BBB integrity and inhibiting MMP9 and AQP4 expression. The data of this study provide a new possible approach for improving brain edema after cerebral ischemia reperfusion by administration of rapamycin.

  17. Lung epithelial cell focal adhesion kinase signaling inhibits lung injury and fibrosis.

    PubMed

    Wheaton, Amanda K; Agarwal, Manisha; Jia, Shijing; Kim, Kevin K

    2017-05-01

    Progressive pulmonary fibrosis is a devastating consequence of many acute and chronic insults to the lung. Lung injury leads to alveolar epithelial cell (AEC) death, destruction of the basement membrane, and activation of transforming growth factor-β (TGF-β). There is subsequent resolution of the injury and a coordinated and concurrent initiation of fibrosis. Both of these processes may involve activation of similar intracellular signaling pathways regulated in part by dynamic changes to the extracellular matrix. Matrix signaling can augment the profibrotic fibroblast response to TGF-β. However, similar matrix/integrin signaling pathways may also be involved in the inhibition of ongoing TGF-β-induced AEC apoptosis. Focal adhesion kinase (FAK) is an integrin-associated signaling molecule expressed by many cell types. We used mice with AEC-specific FAK deletion to isolate the epithelial aspect of integrin signaling in the bleomycin model of lung injury and fibrosis. Mice with AEC-specific deletion of FAK did not exhibit spontaneous lung injury but did have significantly greater terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling-positive cells (18.6 vs. 7.1) per ×200 field, greater bronchoalveolar lavage protein (3.2 vs. 1.8 mg/ml), and significantly greater death (77 vs. 19%) after bleomycin injury compared with littermate control mice. Within primary AECs, activated FAK directly associates with caspase-8 and inhibits activation of the caspase cascade resulting in less apoptosis in response to TGF-β. Our studies support a model in which dynamic changes to the extracellular matrix after injury promote fibroblast activation and inhibition of epithelial cell apoptosis in response to TGF-β through FAK activation potentially complicating attempts to nonspecifically target this pathway for antifibrotic therapy. Copyright © 2017 the American Physiological Society.

  18. Focal Experimental Injury Leads to Widespread Gene Expression and Histologic Changes in Equine Flexor Tendons

    PubMed Central

    Jacobsen, Else; Dart, Andrew J.; Mondori, Takamitsu; Horadogoda, Neil; Jeffcott, Leo B.; Little, Christopher B.; Smith, Margaret M.

    2015-01-01

    It is not known how extensively a localised flexor tendon injury affects the entire tendon. This study examined the extent of and relationship between histopathologic and gene expression changes in equine superficial digital flexor tendon after a surgical injury. One forelimb tendon was hemi-transected in six horses, and in three other horses, one tendon underwent a sham operation. After euthanasia at six weeks, transected and control (sham and non-operated contralateral) tendons were regionally sampled (medial and lateral halves each divided into six 3cm regions) for histologic (scoring and immunohistochemistry) and gene expression (real time PCR) analysis of extracellular matrix changes. The histopathology score was significantly higher in transected tendons compared to control tendons in all regions except for the most distal (P ≤ 0.03) with no differences between overstressed (medial) and stress-deprived (lateral) tendon halves. Proteoglycan scores were increased by transection in all but the most proximal region (P < 0.02), with increased immunostaining for aggrecan, biglycan and versican. After correcting for location within the tendon, gene expression for aggrecan, versican, biglycan, lumican, collagen types I, II and III, MMP14 and TIMP1 was increased in transected tendons compared with control tendons (P < 0.02) and decreased for ADAMTS4, MMP3 and TIMP3 (P < 0.001). Aggrecan, biglycan, fibromodulin, and collagen types I and III expression positively correlated with all histopathology scores (P < 0.001), whereas lumican, ADAMTS4 and MMP14 expression positively correlated only with collagen fiber malalignment (P < 0.001). In summary, histologic and associated gene expression changes were significant and widespread six weeks after injury to the equine SDFT, suggesting rapid and active development of tendinopathy throughout the entire length of the tendon. These extensive changes distant to the focal injury may contribute to poor functional outcomes and re-injury

  19. Focal experimental injury leads to widespread gene expression and histologic changes in equine flexor tendons.

    PubMed

    Jacobson, Else; Jacobsen, Else; Dart, Andrew J; Mondori, Takamitsu; Horadogoda, Neil; Jeffcott, Leo B; Little, Christopher B; Smith, Margaret M

    2015-01-01

    It is not known how extensively a localised flexor tendon injury affects the entire tendon. This study examined the extent of and relationship between histopathologic and gene expression changes in equine superficial digital flexor tendon after a surgical injury. One forelimb tendon was hemi-transected in six horses, and in three other horses, one tendon underwent a sham operation. After euthanasia at six weeks, transected and control (sham and non-operated contralateral) tendons were regionally sampled (medial and lateral halves each divided into six 3 cm regions) for histologic (scoring and immunohistochemistry) and gene expression (real time PCR) analysis of extracellular matrix changes. The histopathology score was significantly higher in transected tendons compared to control tendons in all regions except for the most distal (P ≤ 0.03) with no differences between overstressed (medial) and stress-deprived (lateral) tendon halves. Proteoglycan scores were increased by transection in all but the most proximal region (P < 0.02), with increased immunostaining for aggrecan, biglycan and versican. After correcting for location within the tendon, gene expression for aggrecan, versican, biglycan, lumican, collagen types I, II and III, MMP14 and TIMP1 was increased in transected tendons compared with control tendons (P < 0.02) and decreased for ADAMTS4, MMP3 and TIMP3 (P < 0.001). Aggrecan, biglycan, fibromodulin, and collagen types I and III expression positively correlated with all histopathology scores (P < 0.001), whereas lumican, ADAMTS4 and MMP14 expression positively correlated only with collagen fiber malalignment (P < 0.001). In summary, histologic and associated gene expression changes were significant and widespread six weeks after injury to the equine SDFT, suggesting rapid and active development of tendinopathy throughout the entire length of the tendon. These extensive changes distant to the focal injury may contribute to poor functional outcomes and re-injury

  20. Brain SPECT with short focal-length cone-beam collimation

    SciTech Connect

    Park, Mi-Ae; Moore, Stephen C.; Kijewski, Marie Foley

    2005-07-15

    Single-photon emission-computed tomography (SPECT) imaging of deep brain structures is compromised by loss of photons due to attenuation. We have previously shown that a centrally peaked collimator sensitivity function can compensate for this phenomenon, increasing sensitivity over most of the brain. For dual-head instruments, parallel-hole collimators cannot provide variable sensitivity without simultaneously degrading spatial resolution near the center of the brain; this suggests the use of converging collimators. We have designed collimator pairs for dual-head SPECT systems to increase sensitivity, particularly in the center of the brain, and compared the new collimation approach to existing approaches on the basis of performance in estimating activity concentration of small structures at various locations in the brain. The collimator pairs we evaluated included a cone-beam collimator, for increased sensitivity, and a fan-beam collimator, for data sufficiency. We calculated projections of an ellipsoidal uniform background, with 0.9-cm-radius spherical lesions at several locations in the background. From these, we determined ideal signal-to-noise ratios (SNR{sub CRB}) for estimation of activity concentration within the spheres, based on the Cramer-Rao lower bound on variance. We also reconstructed, by an ordered-subset expectation-maximization (OS-EM) procedure, images of this phantom, as well as of the Zubal brain phantom, to allow visual assessment and to ensure that they were free of artifacts. The best of the collimator pairs evaluated comprised a cone-beam collimator with 20 cm focal length, for which the focal point is inside the brain, and a fan-beam collimator with 40 cm focal length. This pair yielded increased SNR{sub CRB}, compared to the parallel-parallel pair, throughout the imaging volume. The factor by which SNR{sub CRB} increased ranged from 1.1 at the most axially extreme location to 3.5 at the center. The gains in SNR{sub CRB} were relatively

  1. Optic radiation injury in a patient with traumatic brain injury.

    PubMed

    Yeo, Sang Seok; Kim, Seong Ho; Kim, Oh Lyong; Kim, Min-Su; Jang, Sung Ho

    2012-01-01

    This study reports on a patient who showed an optic radiation (OR) injury on diffusion tensor imaging (DTI) following head trauma. The patient, who had suffered a traffic accident, underwent conservative management for diffuse axonal injury and contusions in the left midbrain, temporal lobe and anterior to mid-portion of left OR. He complained of right homonymous hemianopsia from the onset of TBI and right bilateral homonymous hemianopsia was detected at the 6-month Humphrey visual field test. A 20 year-old man with traumatic brain injury (TBI) and eight age-matched normal subjects were recruited for this study. The left OR of the patient showed a discontinuation around the mid-portion. The FA (fractional anisotropy) values of the posterior portions of left OR decreased over two standard deviations of normal controls, but the ADC (apparent diffusion coefficient) values of these sites increased over two standard deviations of normal controls. Consequently, it was assumed that the main injury site of the left OR was located around the posterior portion of the left OR. This results suggest that DTI may be a useful technique for detection of an OR injury in patients with TBI.

  2. Progesterone for neuroprotection in pediatric traumatic brain injury.

    PubMed

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

    2015-03-01

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

  3. Electrocortical spectral analysis and fractal methods for assessing the effects of unilateral brain injury on rat cerebellum.

    PubMed

    Martac, L D; Sekulic, S; Cvijanovic, M

    2016-12-01

    We used electrocortical spectral analysis and fractal methods for assessing the effects of unilateral, single brain injury on cerebellum. Cerebellar electrocortical activity was recorded in control state (before the injury) and after a single brain injury of the cerebellar cortex in anesthetized rats. We noticed that the mean power in gamma high-frequency domain (32-128 Hz) of the cerebellum, was increased after the first brain injury, while after a two-week recovery, it was larger than before the injury. The unilateral brain injury induced a permanent increase of the mild gamma activity in both the left and the right side of cerebellum cortex, but there was no further increase after the lesion was repeated. Our recent electrophysiological study on the cerebellum (Culic et al., 2005) suggested that the mean power spectra of the cerebellar cortical activity in the gamma frequency range might be the indicator of acute single focal brain injury. However, there is insufficient information on the effects of the repeated brain injury on the cerebellar electrocortical activity and morphology. There was no significant difference between the absolute and the relative mean power of the left and the right paravermal cortical activity (before, as well as, after the injury), in each of the animals tested afterwards, but there were differences between the left and the right side of cerebellum in experimental animals. Repeated injury of the cerebellar cortical areas, is strengthened by morphological changes in the cerebellar hemisphere, and shows a decrease in delta and an increase in gamma range.

  4. Diagnosing pseudobulbar affect in traumatic brain injury

    PubMed Central

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

    2014-01-01

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

  5. Chronic Endocrinopathies in Traumatic Brain Injury Disease.

    PubMed

    Masel, Brent E; Urban, Randy

    2015-12-01

    The aim of this review was to explain the role played by pituitary hormonal deficiencies in the traumatic brain injury (TBI) disease process. Chronic dysfunction of the pituitary axis is observed in approximately 35% of individuals who sustain a moderate-to-severe TBI. The most common deficiency is that of growth hormone, followed by gonadotropin, cortisol, and thyroid. The medical, psychological, and psychiatric consequences of untreated hypopituitarism are extensive and can be devastating. Many of the consequences of a chronic symptomatic TBI have, in the past, been solely attributed to the brain injury per se. Analysis of the signs and symptoms of pituitary axis dysfunction suggests that many of these consequences can be attributed to post-traumatic hypopituitarism (PTH). PTH may well play a significant role in the progressive signs and symptoms that follow a chronic TBI.

  6. Traumatic Brain Injury in Sports: A Review

    PubMed Central

    Sahler, Christopher S.; Greenwald, Brian D.

    2012-01-01

    Traumatic brain injury (TBI) is a clinical diagnosis of neurological dysfunction following head trauma, typically presenting with acute symptoms of some degree of cognitive impairment. There are an estimated 1.7 to 3.8 million TBIs each year in the United States, approximately 10 percent of which are due to sports and recreational activities. Most brain injuries are self-limited with symptom resolution within one week, however, a growing amount of data is now establishing significant sequelae from even minor impacts such as headaches, prolonged cognitive impairments, or even death. Appropriate diagnosis and treatment according to standardized guidelines are crucial when treating athletes who may be subjected to future head trauma, possibly increasing their likelihood of long-term impairments. PMID:22848836

  7. [Diagnosis and treatment of traumatic brain injury].

    PubMed

    Rickels, E

    2009-02-01

    Traumatic brain injury (TBI) is still the major cause of death under 45 years of age and an important one for children under 15. Its incidence is 332/100,000 inhabitants. It results from an impact with the skull with/without lesion of the brain but at least a short-term neurological disorder. All other injuries to the skull should be called concussion. The duration of unconsciousness defines the severity of TBI. Patients with TBI should be admitted to a surgical ward. Those retaining consciousness and with GCS scores of 15 might be allowed to go home if under surveillance. With GCS of <15 or with risk factors, TBI requires a CT scan and in-hospital surveillance. Acutely life-threatening, i.e. space-occupying, bleeding must be operated on immediately. Epidural or subdural bleeding, especially in comatose patients, is still a vital risk and thus requires immediate surgery.

  8. The neuroethics and neurolaw of brain injury.

    PubMed

    Aggarwal, Neil Krishan; Ford, Elizabeth

    2013-01-01

    Neuroethics and neurolaw are fields of study that involve the interface of neuroscience with clinical and legal decision-making. The past two decades have seen increasing attention being paid to both fields, in large part because of the advances in neuroimaging techniques and improved ability to visualize and measure brain structure and function. Traumatic brain injury (TBI), along with its acute and chronic sequelae, has emerged as a focus of neuroethical issues, such as informed consent for treatment and research, diagnostic and prognostic uncertainties, and the subjectivity of interpretation of data. The law has also more frequently considered TBI in criminal settings for exculpation, mitigation and sentencing purposes and in tort and administrative law for personal injury, disability and worker's compensation cases. This article provides an overview of these topics with an emphasis on the current challenges that the neuroscience of TBI faces in the medicolegal arena.

  9. Ethanol-induced hyponatremia augments brain edema after traumatic brain injury.

    PubMed

    Katada, Ryuichi; Watanabe, Satoshi; Ishizaka, Atsushi; Mizuo, Keisuke; Okazaki, Shunichiro; Matsumoto, Hiroshi

    2012-04-01

    Alcohol consumption augments brain edema by expression of brain aquaporin-4 after traumatic brain injury. However, how ethanol induces brain aquaporin-4 expression remains unclear. Aquaporin-4 can operate with some of ion channels and transporters. Therefore, we hypothesized that ethanol may affect electrolytes through regulating ion channels, leading to express aquaporin-4. To clarify the hypothesis, we examined role of AQP4 expression in ethanol-induced brain edema and changes of electrolyte levels after traumatic brain injury in the rat. In the rat traumatic brain injury model, ethanol administration reduced sodium ion concentration in blood significantly 24 hr after injury. An aquaporin-4 inhibitor recovered sodium ion concentration in blood to normal. We observed low sodium ion concentration in blood and the increase of brain aquaporin-4 in cadaver with traumatic brain injury. Therefore, ethanol increases brain edema by the increase of aquaporin-4 expression with hyponatremia after traumatic brain injury.

  10. LOTUS overexpression accelerates neuronal plasticity after focal brain ischemia in mice.

    PubMed

    Takase, Hajime; Kurihara, Yuji; Yokoyama, Taka-Akira; Kawahara, Nobutaka; Takei, Kohtaro

    2017-01-01

    Nogo receptor-1 (NgR1) and its ligands inhibit neuronal plasticity and limit functional recovery after brain damage such as ischemic stroke. We have previously shown that lateral olfactory tract usher substance (LOTUS) antagonizes NgR1-mediated signaling. Here, we investigated whether LOTUS enhances neuronal plasticity and functional recovery after brain focal ischemia in adult mice. Focal ischemic infarcts were induced in wild-type and LOTUS-overexpressing transgenic mice via middle cerebral artery occlusion. Endogenous LOTUS expression was increased in brain and cervical spinal cord of the contralateral side of ischemia in the chronic phase after brain ischemia. LOTUS overexpression accelerated midline-crossing axonal sprouting from the contralateral side to the ipsilateral side of ischemia in the medullar reticular formation and gray matter of denervated cervical spinal cord. Importantly, LOTUS overexpression improved neurological score highly correlated with laterality ratio of corticoreticular fibers of the medulla oblongata, indicating that LOTUS overexpression may overcome the inhibitory environment induced by NgR1 signaling for damaged motor pathway reconstruction after ischemic stroke. Thus, our data suggest that LOTUS overexpression accelerates neuronal plasticity in the brainstem and cervical spinal cord after stroke and LOTUS administration is useful for future therapeutic strategies.

  11. Planning of spatially-oriented locomotion following focal brain damage in humans: A pilot study.

    PubMed

    Hicheur, Halim; Boujon, Carole; Wong, Cuebong; Pham, Quang-Cuong; Annoni, Jean-Marie; Bihl, Titus

    2016-03-15

    Motor impairments in human gait following stroke or focal brain damage are well documented. Here, we investigated whether stroke and/or focal brain damage also affect the navigational component of spatially oriented locomotion. Ten healthy adult participants and ten adult brain-damaged patients had to walk towards distant targets from different starting positions (with vision or blindfolded). No instructions as to which the path to follow were provided to them. We observed very similar geometrical forms of paths across the two groups of participants and across visual conditions. This spatial stereotypy of whole-body displacements was observed following brain damage, even in the most severely impaired (hemiparetic) patients. This contrasted with much more variability at the temporal level. In particular, healthy participants and non-hemiparetic patients varied their walking speed according to curvature changes along the path. On the contrary, the walking speed profiles were not stereotypical and were not systematically constrained by path geometry in hemiparetic patients where it was associated with different stepping behaviors. These observations confirm the dissociation between cognitive and motor aspects of gait recovery post-stroke. The impact of these findings on the understanding of the functional and anatomical organization of spatially-oriented locomotion and for rehabilitation purposes is discussed and contextualized in the light of recent advances in electrophysiological studies.

  12. Mild Traumatic Brain Injury in Translation

    PubMed Central

    Robertson, Claudia S.

    2013-01-01

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

  13. Blast-induced Mild Traumatic Brain Injury

    DTIC Science & Technology

    2010-01-01

    hemorrhagic lesions including intraparenchymal, subdural, and subarachnoid bleeding. Blast injury also induces a variety of histological effects...and microscopic intracerebral, subarachnoid and subdural hemorrhage , severity related to proximity of explosion to head Decreased rotarod and grip...tensor imaging study. J Neurosurg 2005;103:298-303. 66. Wilde EA, McCauley SR, Hunter JV, et al. Diffusion tensor imaging of acute mild traumatic brain

  14. Monitoring Brain Injury With TSALLIS Entropy

    DTIC Science & Technology

    2001-10-25

    significant but still remains to be studied. Literature has pointed to the role of q in the entropy computation for EEG studies [10]. In our study it is... EEG in the form of reduction during the bad physiological function outcome. The reduction level and recovery rate of TE are also consistent with...USA Abstract- Nonextensive entropy measure, Tsallis Entropy (TE), was undertaken to monitor the brain injury after cardiac arrest. EEG of human and

  15. Targeted suppression of claudin-5 decreases cerebral oedema and improves cognitive outcome following traumatic brain injury.

    PubMed

    Campbell, Matthew; Hanrahan, Finnian; Gobbo, Oliviero L; Kelly, Michael E; Kiang, Anna-Sophia; Humphries, Marian M; Nguyen, Anh T H; Ozaki, Ema; Keaney, James; Blau, Christoph W; Kerskens, Christian M; Cahalan, Stephen D; Callanan, John J; Wallace, Eugene; Grant, Gerald A; Doherty, Colin P; Humphries, Peter

    2012-05-22

    Traumatic brain injury is the leading cause of death in children and young adults globally. Malignant cerebral oedema has a major role in the pathophysiology that evolves after severe traumatic brain injury. Added to this is the significant morbidity and mortality from cerebral oedema associated with acute stroke, hypoxic ischemic coma, neurological cancers and brain infection. Therapeutic strategies to prevent cerebral oedema are limited and, if brain swelling persists, the risks of permanent brain damage or mortality are greatly exacerbated. Here we show that a temporary and size-selective modulation of the blood-brain barrier allows enhanced movement of water from the brain to the blood and significantly impacts on brain swelling. We also show cognitive improvement in mice with focal cerebral oedema following administration in these animals of short interfering RNA directed against claudin-5. These observations may have profound consequences for early intervention in cases of traumatic brain injury, or indeed any neurological condition where cerebral oedema is the hallmark pathology.

  16. Inflammatory neuroprotection following traumatic brain injury

    PubMed Central

    Russo, Matthew V.; McGavern, Dorian B.

    2017-01-01

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

  17. [Decompressive craniectomy in traumatic brain injury and malignant brain infarction].

    PubMed

    Greiner, Christoph

    2008-10-01

    High intracranial pressure (ICP) is the most frequent cause of death and disability after severe traumatic brain injury and malignant cerebral infarction. After failure of general therapeutic maneuvers and first line therapies, "second tier" therapies have to be considered. Decompressive craniectomy is an advanced treatment option for controlling intracranial pressure (ICP). In this review indications and techniques of decompressive craniectomy are described and current literature is discussed. The author concludes that decompressive craniectomy is no routine, but should be considered in individual cases.

  18. A recombinant inhibitory isoform of vascular endothelial growth factor164/165 aggravates ischemic brain damage in a mouse model of focal cerebral ischemia.

    PubMed

    Chaitanya, Ganta V; Cromer, Walter E; Parker, Courtney P; Couraud, Pierre O; Romero, Ignacio A; Weksler, Babette; Mathis, J Michael; Minagar, Alireza; Alexander, J Steven

    2013-09-01

    Vascular endothelial growth factors (VEGF) are a Janus-faced family of growth factors exerting both neuroprotective and maladaptive effects on the blood-brain barrier. For example, VEGFs are beneficial in promoting postischemic brain angiogenesis, but the newly formed vessels are leaky. We investigated the role of the naturally occurring murine inhibitory VEGF isoform VEGF165b in a mouse model of focal cerebral ischemia by middle cerebral artery occlusion and reperfusion (I/R) in male C57BL/6 mice. We investigated the roles of VEGF164/165 and VEGF165b in both brain and nonbrain endothelial barrier, angiogenesis, and neutrophil migration using oxygen glucose deprivation and reoxygenation as in vitro model. We investigated the role of VEGF165b in brain edema, neutrophil infiltration, ischemic brain damage, and neuronal death in vivo using an adenovirus encoding a recombinant VEGF164b isoform. Neither VEGF164/165 nor VEGF165b significantly altered brain endothelial barrier or angiogenesis in vitro. However, treatment of brain endothelial cells with VEGF165b increased neutrophil migration in vitro and exacerbated stroke injury by aggravating neutrophil infiltration and neurodegeneration in vivo. Our results indicate that alterations in the delicate balance in the relative levels of pro- and antiangiogenic VEGF isoforms can result in either adaptive or detrimental effects, depending on the VEGF isoform levels and on the duration and extent of injury.

  19. Chronic neurodegenerative consequences of traumatic brain injury.

    PubMed

    Chauhan, Neelima B

    2014-01-01

    Traumatic brain injury (TBI) is a serious public health concern and a major cause of death and disability worldwide. Each year, an estimated 1.7 million Americans sustain TBI of which ~52,000 people die, ~275,000 people are hospitalized and 1,365,000 people are treated as emergency outpatients. Currently there are ~5.3 million Americans living with TBI. TBI is more of a disease process than of an event that is associated with immediate and long-term sensomotor, psychological and cognitive impairments. TBI is the best known established epigenetic risk factor for later development of neurodegenerative diseases and dementia. People sustaining TBI are ~4 times more likely to develop dementia at a later stage than people without TBI. Single brain injury is linked to later development of symptoms resembling Alzheimer's disease while repetitive brain injuries are linked to later development of chronic traumatic encephalopathy (CTE) and/or Dementia Pugilistica (DP). Furthermore, genetic background of ß-amyloid precursor protein (APP), Apolipoprotein E (ApoE), presenilin (PS) and neprilysin (NEP) genes is associated with exacerbation of neurodegenerative process after TBI. This review encompasses acute effects and chronic neurodegenerative consequences after TBI.

  20. Treatment window for hypothermia in brain injury.

    PubMed

    Markgraf, C G; Clifton, G L; Moody, M R

    2001-12-01

    The goal of this study was to evaluate the therapeutic window for hypothermia treatment following experimental brain injury by measuring edema formation and functional outcome. Traumatic brain injury (TBI) was produced in anesthetized rats by using cortical impact injury. Edema was measured in the ipsilateral and contralateral hemispheres by subtracting dry weight from wet weight, and neurological function was assessed using a battery of behavioral tests 24 hours after TBI. In injured rats, it was found that brain water levels were elevated at I hour postinjury, compared with those in sham-injured control animals, and that edema peaked at 24 hours and remained elevated for 4 days. Hypothermia (3 hours at 30 degrees C) induced either immediately after TBI or 60 minutes after TBI significantly reduced early neurological deficits. Delay of treatment by 90 or 120 minutes postinjury did not result in this neurological protection. Immediate administration of hypothermia also significantly decreased the peak magnitude of edema at 24 hours and 48 hours postinjury, compared with that in normothermic injured control animals. When delayed by 90 minutes, hypothermia did not affect the pattern of edema formation. When hypothermia was administered immediately or 60 minutes after TBI, injured rats showed an improvement in functional outcome and a decrease in edema. Delayed hypothermia treatment had no effect on functional outcome or on edema.

  1. Traumatic brain injury in modern war

    NASA Astrophysics Data System (ADS)

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

    2013-05-01

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

  2. Spatial-temporal expression of NDRG2 in rat brain after focal cerebral ischemia and reperfusion.

    PubMed

    Li, Yan; Shen, Lan; Cai, Lei; Wang, Qiang; Hou, Wugang; Wang, Feng; Zeng, Yi; Zhao, Gang; Yao, Libo; Xiong, Lize

    2011-03-25

    N-myc downstream regulated gene 2 (NDRG2) was reported to be widely expressed in the nervous system. However, the expression and potential role of NDRG2 in focal cerebral ischemia brain remain unclear. Herein, we investigated spatial-temporal expression of NDRG2 in the rat brain following transient focal cerebral ischemia. Male Sprague-Dawley rats underwent a 120-min transient occlusion of middle cerebral artery. Rats were killed and brain samples were harvested at 4, 12, 24, and 72h after reperfusion. Expression of NDRG2 in the brain was determined by reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemical staining. Cellular apoptosis was assessed by TUNEL staining. The results showed that NDRG2 was expressed on cells with an astrocytes-like morphology in ischemic penumbra. NDRG2 mRNA and protein expression began to increase at 4h after reperfusion and peaked at 24h in the ischemic penumbra. By using immunofluorescence, NDRG2 signals were co-localized with GFAP-positive astrocytes, and NDRG2 expression in astrocytes translocated from a cytoplasm to a nuclear localization at 24h after reperfusion. Double immunofluorescent staining for TUNEL and NDRG2 showed that some NDRG2 signals co-localized with TUNEL-positive cells, and that the apoptotic cells increased with enhancement of NDRG2-positive signals. In conclusion, NDRG2 expression is up-regulated in ischemic penumbra following transient focal cerebral ischemia. NDRG2 expression in astrocytes may play important pathological roles in cell apoptosis after stroke. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Position statement: definition of traumatic brain injury.

    PubMed

    Menon, David K; Schwab, Karen; Wright, David W; Maas, Andrew I

    2010-11-01

    A clear, concise definition of traumatic brain injury (TBI) is fundamental for reporting, comparison, and interpretation of studies on TBI. Changing epidemiologic patterns, an increasing recognition of significance of mild TBI, and a better understanding of the subtler neurocognitive neuroaffective deficits that may result from these injuries make this need even more critical. The Demographics and Clinical Assessment Working Group of the International and Interagency Initiative toward Common Data Elements for Research on Traumatic Brain Injury and Psychological Health has therefore formed an expert group that proposes the following definition: In this article, we discuss criteria for considering or establishing a diagnosis of TBI, with a particular focus on the problems how a diagnosis of TBI can be made when patients present late after injury and how mild TBI may be differentiated from non-TBI causes with similar symptoms. Technologic advances in magnetic resonance imaging and the development of biomarkers offer potential for improving diagnostic accuracy in these situations. Copyright © 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  4. The molecular pathophysiology of concussive brain injury.

    PubMed

    Barkhoudarian, Garni; Hovda, David A; Giza, Christopher C

    2011-01-01

    Concussion or mild traumatic brain injury (mTBI) is a condition that affects hundreds of thousands of patients worldwide. Understanding the pathophysiology of this disorder can help manage its acute and chronic repercussions. Immediately following mTBI, there are several metabolic, hemodynamic, structural, and electric changes that alter normal cerebral function. These alterations can increase the brain's vulnerability to repeat injury and long-term disability. This review evaluates current studies from the bench to the bedside of mTBI. Acute and chronic effects of concussion are measured in both animal and clinical studies. Also, the effect of repeat concussions is analyzed. Concussion-induced pathophysiology with regards to glucose metabolism changes, mitochondrial dysfunction, axonal injury, and structural damage are evaluated. Translational studies such as functional magnetic resonance imaging, magnetic resonance spectroscopy and diffusion tensor imaging prove to be effective clinical tools for both prognostic and treatment parameters. Understanding the neurobiology of concussion will lead to development and validation of physiological biomarkers of this common injury. These biomarkers (eg, laboratory tests, imaging, electrophysiology) will then allow for improved detection, better functional assessment and evidence-based return to play recommendations. Published by Elsevier Inc.

  5. Emerging Therapies in Traumatic Brain Injury

    PubMed Central

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

    2015-01-01

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

  6. A form of motor cortical plasticity that correlates with recovery of function after brain injury

    PubMed Central

    Ramanathan, Dhakshin; Conner, James M.; H. Tuszynski, Mark

    2006-01-01

    To investigate functional mechanisms underlying cortical motor plasticity in the intact and injured brain, we used “behaviorally relevant,” long-duration intracortical microstimulation. We now report the existence of complex, multijoint movements revealed with a 500-msec duration intracortical stimulation in rat motor cortex. A consistent topographic distribution of these complex motor patterns is present across the motor cortex in naïve rats. We further document the plasticity of these complex movement patterns after focal cortical injury, with a significant expansion of specific complex movement representations in response to rehabilitative training after injury. Notably, the degree of functional recovery attained after cortical injury and rehabilitation correlates significantly with a specific feature of map reorganization, the ability to reexpress movement patterns disrupted by the initial injury. This evidence suggests the existence of complex movement representations in the rat motor cortex that exhibit plasticity after injury and rehabilitation, serving as a relevant predictor of functional recovery. PMID:16837575

  7. Stem Cells for Ischemic Brain Injury: A Critical Review

    PubMed Central

    Burns, Terry C.; Verfaillie, Catherine M.; Low, Walter C.

    2014-01-01

    No effective therapy is currently available to promote recovery following ischemic stroke. Stem cells have been proposed as a potential source of new cells to replace those lost due to central nervous system injury, as well as a source of trophic molecules to minimize damage and promote recovery. We undertook a detailed review of data from recent basic science and preclinical studies to investigate the potential application of endogenous and exogenous stem cell therapies for treatment of cerebral ischemia. To date, spontaneous endogenous neurogenesis has been observed in response to ischemic injury, and can be enhanced via infusion of appropriate cytokines. Exogenous stem cells from multiple sources can generate neural cells that survive and form synaptic connections after transplantation in the stroke-injured brain. Stem cells from multiple sources cells also exhibit neuroprotective properties that may ameliorate stroke deficits. In many cases, functional benefits observed are likely independent of neural differentiation, though exact mechanisms remain poorly understood. Future studies of neuroregeneration will require the demonstration of function in endogenously born neurons following focal ischemia. Further, methods are currently lacking to definitively demonstrate the therapeutic effect of newly introduced neural cells. Increased plasticity following stroke may facilitate the functional integration of new neurons, but the loss of appropriate guidance cues and supporting architecture in the infarct cavity will likely impede the restoration of lost circuitry. As such careful investigation of the mechanisms underlying trophic benefits will be essential. Evidence to date suggest that continued development of stem cell therapies may ultimately lead to viable treatment options for ischemic brain injury. PMID:19399885

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

    ERIC Educational Resources Information Center

    Carter, Susanne

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

  9. Large animal models of traumatic brain injury.

    PubMed

    Dai, Jun-Xi; Ma, Yan-Bin; Le, Nan-Yang; Cao, Jun; Wang, Yang

    2017-10-03

    Purpose/Aim: Animal models of traumatic brain injury (TBI) provide powerful tools to study TBI in a controlled, rigorous and cost-efficient manner. The mostly used animals in TBI studies so far are rodents. However, compared with rodents, large animals (e.g. swine, rabbit, sheep, ferret, etc.) show great advantages in modeling TBI due to the similarity of their brains to human brain. The aim of our review was to summarize the development and progress of common large animal TBI models in past 30 years. Mixed published articles and books associated with large animal models of TBI were researched and summarized. We majorly sumed up current common large animal models of TBI, including discussion on the available research methodologies in previous studies, several potential therapies in large animal trials of TBI as well as advantages and disadvantages of these models. Large animal models of TBI play crucial role in determining the underlying mechanisms and screening putative therapeutic targets of TBI.

  10. Recent advances in imaging preterm brain injury.

    PubMed

    Boardman, J P; Dyet, L E

    2007-08-01

    Survivors of preterm birth are at high risk of neurocognitive impairment in childhood, but the disturbances to brain growth and function that underlie impairment are not completely understood. Improvements in perinatal care have led to a reduction in the major destructive parenchymal brain lesions that are associated with motor impairment, such as cystic periventricular leucomalacia and haemorrhagic parenchymal infarction. However, with the application of advanced magnetic resonance (MR) imaging and processing techniques in the neonatal period, subtle alterations in brain development have become apparent. These changes occur with similar frequency to long-term neurocognitive impairment, and may therefore represent candidate neural substrates for this group of disorders. Here we review the range of lesions and associated outcomes that are seen in the current era of perinatal care, and discuss how state of the art MR imaging techniques have helped to define the neural systems affected by preterm birth, and have provided insights into understanding mechanisms of injury.

  11. Inflammation and Neuroprotection in Traumatic Brain Injury

    PubMed Central

    Corps, Kara N.; Roth, Theodore L.; McGavern, Dorian B.

    2016-01-01

    IMPORTANCE Traumatic brain injury (TBI) is a significant public health concern that affects individuals in all demographics. With increasing interest in the medical and public communities, understanding the inflammatory mechanisms that drive the pathologic and consequent cognitive outcomes can inform future research and clinical decisions for patients with TBI. OBJECTIVES To review known inflammatory mechanisms in TBI and to highlight clinical trials and neuroprotective therapeutic manipulations of pathologic and inflammatory mechanisms of TBI. EVIDENCE REVIEW We searched articles in PubMed published between 1960 and August 1, 2014, using the following keywords: traumatic brain injury, sterile injury, inflammation, astrocytes, microglia, monocytes, macrophages, neutrophils, T cells, reactive oxygen species, alarmins, danger-associated molecular patterns, purinergic receptors, neuroprotection, and clinical trials. Previous clinical trials or therapeutic studies that involved manipulation of the discussed mechanisms were considered for inclusion. The final list of selected studies was assembled based on novelty and direct relevance to the primary focus of this review. FINDINGS Traumatic brain injury is a diverse group of sterile injuries induced by primary and secondary mechanisms that give rise to cell death, inflammation, and neurologic dysfunction in patients of all demographics. Pathogenesis is driven by complex, interacting mechanisms that include reactive oxygen species, ion channel and gap junction signaling, purinergic receptor signaling, excitotoxic neurotransmitter signaling, perturbations in calcium homeostasis, and damage-associated molecular pattern molecules, among others. Central nervous system resident and peripherally derived inflammatory cells respond to TBI and can provide neuroprotection or participate in maladaptive secondary injury reactions. The exact contribution of inflammatory cells to a TBI lesion is dictated by their anatomical positioning

  12. Inflammation and neuroprotection in traumatic brain injury.

    PubMed

    Corps, Kara N; Roth, Theodore L; McGavern, Dorian B

    2015-03-01

    Traumatic brain injury (TBI) is a significant public health concern that affects individuals in all demographics. With increasing interest in the medical and public communities, understanding the inflammatory mechanisms that drive the pathologic and consequent cognitive outcomes can inform future research and clinical decisions for patients with TBI. To review known inflammatory mechanisms in TBI and to highlight clinical trials and neuroprotective therapeutic manipulations of pathologic and inflammatory mechanisms of TBI. We searched articles in PubMed published between 1960 and August 1, 2014, using the following keywords: traumatic brain injury, sterile injury, inflammation, astrocytes, microglia, monocytes, macrophages, neutrophils, T cells, reactive oxygen species, alarmins, danger-associated molecular patterns, purinergic receptors, neuroprotection, and clinical trials. Previous clinical trials or therapeutic studies that involved manipulation of the discussed mechanisms were considered for inclusion. The final list of selected studies was assembled based on novelty and direct relevance to the primary focus of this review. Traumatic brain injury is a diverse group of sterile injuries induced by primary and secondary mechanisms that give rise to cell death, inflammation, and neurologic dysfunction in patients of all demographics. Pathogenesis is driven by complex, interacting mechanisms that include reactive oxygen species, ion channel and gap junction signaling, purinergic receptor signaling, excitotoxic neurotransmitter signaling, perturbations in calcium homeostasis, and damage-associated molecular pattern molecules, among others. Central nervous system resident and peripherally derived inflammatory cells respond to TBI and can provide neuroprotection or participate in maladaptive secondary injury reactions. The exact contribution of inflammatory cells to a TBI lesion is dictated by their anatomical positioning as well as the local cues to which they are

  13. Perceived needs following traumatic brain injury.

    PubMed

    Corrigan, John D; Whiteneck, Gale; Mellick, Dave

    2004-01-01

    (1) Provide population-based estimates of perceived needs following traumatic brain injury (TBI) and the prevalence of unmet needs 1 year postinjury; (2) identify relations among needs that define unique clusters of individuals; and (3) identify risk factors for experiencing selected needs. Telephone survey 1 year after injury of a prospective cohort of all people hospitalized with TBI in the state of Colorado during 2000. Self-reported need for assistance in 13 areas of functioning. A total of 58.8% of persons hospitalized with TBI experienced at least 1 need during the year following injury; 40.2% will experience at least 1 unmet need 1 year after injury. Most frequently experienced needs were "improving your memory, solving problems better" (34.1%), "managing stress, emotional upsets" (27.9%), and "managing your money, paying bills" (23.3%). Cluster analysis revealed 8 distinctive groupings of subjects. If a need existed, those least likely to be met involved cognitive abilities, employment, and alcohol and/or drug use. Results were consistent with findings from previous assessments of need for services based on surveys of convenience samples; however, the prevalence of unmet needs 1 year after injury may be higher than previously suspected. More post-hospital services addressing cognitive and emotional problems appear needed. Risk factors for experiencing needs suggest potential avenues for clinical intervention.

  14. Cannabinoids: Well-Suited Candidates for the Treatment of Perinatal Brain Injury

    PubMed Central

    Fernández-López, David; Lizasoain, Ignacio; Moro, Maria Ángeles; Martínez-Orgado, José

    2013-01-01

    Perinatal brain injury can be induced by a number of different damaging events occurring during or shortly after birth, including neonatal asphyxia, neonatal hypoxia-ischemia and stroke-induced focal ischemia. Typical manifestations of these conditions are the presence of glutamate excitoxicity, neuroinflammation and oxidative stress, the combination of which can potentially result in apoptotic-necrotic cell death, generation of brain lesions and long-lasting functional impairment. In spite of the high incidence of perinatal brain injury, the number of clinical interventions available for the treatment of the affected newborn babies is extremely limited. Hence, there is a dramatic need to develop new effective therapies aimed to prevent acute brain damage and enhance the endogenous mechanisms of long-term brain repair. The endocannabinoid system is an endogenous neuromodulatory system involved in the control of multiple central and peripheral functions. An early responder to neuronal injury, the endocannabinoid system has been described as an endogenous neuroprotective system that once activated can prevent glutamate excitotoxicity, intracellular calcium accumulation, activation of cell death pathways, microglia activation, neurovascular reactivity and infiltration of circulating leukocytes across the blood-brain barrier. The modulation of the endocannabinoid system has proven to be an effective neuroprotective strategy to prevent and reduce neonatal brain injury in different animal models and species. Also, the beneficial role of the endocannabinoid system on the control of the endogenous repairing responses (neurogenesis and white matter restoration) to neonatal brain injury has been described in independent studies. This review addresses the particular effects of several drugs that modulate the activity of the endocannabinoid system on the progression of different manifestations of perinatal brain injury during both the acute and chronic recovery phases using

  15. Imaging assessment of traumatic brain injury.

    PubMed

    Currie, Stuart; Saleem, Nayyar; Straiton, John A; Macmullen-Price, Jeremy; Warren, Daniel J; Craven, Ian J

    2016-01-01

    Traumatic brain injury (TBI) constitutes injury that occurs to the brain as a result of trauma. It should be appreciated as a heterogeneous, dynamic pathophysiological process that starts from the moment of impact and continues over time with sequelae potentially seen many years after the initial event. Primary traumatic brain lesions that may occur at the moment of impact include contusions, haematomas, parenchymal fractures and diffuse axonal injury. The presence of extra-axial intracranial lesions such as epidural and subdural haematomas and subarachnoid haemorrhage must be anticipated as they may contribute greatly to secondary brain insult by provoking brain herniation syndromes, cranial nerve deficits, oedema and ischaemia and infarction. Imaging is fundamental to the management of patients with TBI. CT remains the imaging modality of choice for initial assessment due to its ease of access, rapid acquisition and for its sensitivity for detection of acute haemorrhagic lesions for surgical intervention. MRI is typically reserved for the detection of lesions that may explain clinical symptoms that remain unresolved despite initial CT. This is especially apparent in the setting of diffuse axonal injury, which is poorly discerned on CT. Use of particular MRI sequences may increase the sensitivity of detecting such lesions: diffusion-weighted imaging defining acute infarction, susceptibility-weighted imaging affording exquisite data on microhaemorrhage. Additional advanced MRI techniques such as diffusion tensor imaging and functional MRI may provide important information regarding coexistent structural and functional brain damage. Gaining robust prognostic information for patients following TBI remains a challenge. Advanced MRI sequences are showing potential for biomarkers of disease, but this largely remains at the research level. Various global collaborative research groups have been established in an effort to combine imaging data with clinical and

  16. Neuroprotective effects of vagus nerve stimulation on traumatic brain injury.

    PubMed

    Zhou, Long; Lin, Jinhuang; Lin, Junming; Kui, Guoju; Zhang, Jianhua; Yu, Yigang

    2014-09-01

    Previous studies have shown that vagus nerve stimulation can improve the prognosis of traumatic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain explosive injury received continuous stimulation (10 V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus nerve. Tumor necrosis factor-α, interleukin-1β and interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-α and interleukin-1β concentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-α, interleukin-1β and interleukin-10 in the serum and brain tissue.

  17. Neuroprotective effects of vagus nerve stimulation on traumatic brain injury

    PubMed Central

    Zhou, Long; Lin, Jinhuang; Lin, Junming; Kui, Guoju; Zhang, Jianhua; Yu, Yigang

    2014-01-01

    Previous studies have shown that vagus nerve stimulation can improve the prognosis of traumatic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain explosive injury received continuous stimulation (10 V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus nerve. Tumor necrosis factor-α, interleukin-1β and interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-α and interleukin-1β concentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-α, interleukin-1β and interleukin-10 in the serum and brain tissue. PMID:25368644

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

    ERIC Educational Resources Information Center

    Fiegenbaum, Ed, Ed.; And Others

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

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

    ERIC Educational Resources Information Center

    Fiegenbaum, Ed, Ed.; And Others

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

  20. The neuroprotective effects of xenon and helium in an in vitro model of traumatic brain injury.

    PubMed

    Coburn, Mark; Maze, Mervyn; Franks, Nicholas P

    2008-02-01

    The "inert" gas xenon has been shown to be an effective neuroprotectant in a variety of in vitro and in vivo models of neuronal injury. We examined its neuroprotective properties in an in vitro model of traumatic brain injury. Controlled laboratory study. Academic research laboratory. Organotypic hippocampal brain slices from mice pups. The cultured brain slices were subjected to a focal mechanical trauma, and injury was monitored in the presence and absence of inert gases at normal and elevated pressures and under both normothermic and hypothermic conditions. Neuronal injury was quantified using propidium iodide, which becomes fluorescent only when it enters injured cells. Low pressures of both helium and xenon were effective neuroprotectants when applied in addition to 1 atm of air. Moreover, both gases were effective at normal pressures when they replaced nitrogen in a gas mixture. The inert gases helium and xenon are effective neuroprotectants in a model for traumatic brain injury, and this novel treatment warrants further investigation. Xenon was particularly effective at reducing the secondary injury that developed following the initial trauma and could be administered at least 3 hrs postinjury with only a small reduction in efficacy.

  1. Mild Traumatic Brain Injury and Diffuse Axonal Injury in Swine

    PubMed Central

    Browne, Kevin D.; Chen, Xiao-Han; Meaney, David F.

    2011-01-01

    Abstract Until recently, mild traumatic brain injury (mTBI) or “concussion” was generally ignored as a major health issue. However, emerging evidence suggests that this injury is by no means mild, considering it induces persisting neurocognitive dysfunction in many individuals. Although little is known about the pathophysiological aspects of mTBI, there is growing opinion that diffuse axonal injury (DAI) may play a key role. To explore this possibility, we adapted a model of head rotational acceleration in swine to produce mTBI by scaling the mechanical loading conditions based on available biomechanical data on concussion thresholds in humans. Using these input parameters, head rotational acceleration was induced in either the axial plane (transverse to the brainstem; n=3), causing a 10- to 35-min loss of consciousness, or coronal plane (circumferential to the brainstem; n=2), which did not produce a sustained loss of consciousness. Seven days following injury, immunohistochemical analyses of the brains revealed that both planes of head rotation induced extensive axonal pathology throughout the white matter, characterized as swollen axonal bulbs or varicosities that were immunoreactive for accumulating neurofilament protein. However, the distribution of the axonal pathology was different between planes of head rotation. In particular, more swollen axonal profiles were observed in the brainstems of animals injured in the axial plane, suggesting an anatomic substrate for prolonged loss of consciousness in mTBI. Overall, these data support DAI as an important pathological feature of mTBI, and demonstrate that surprisingly overt axonal pathology may be present, even in cases without a sustained loss of consciousness. PMID:21740133

  2. Neuroprotective Role of a Brain-Enriched Tyrosine Phosphatase, STEP, in Focal Cerebral Ischemia

    PubMed Central

    Deb, Ishani; Manhas, Namratta; Poddar, Ranjana; Rajagopal, Sathyanarayanan; Allan, Andrea M.; Lombroso, Paul J.; Rosenberg, Gary A.; Candelario-Jalil, Eduardo

    2013-01-01

    The striatal-enriched phosphatase (STEP) is a component of the NMDA-receptor-mediated excitotoxic signaling pathway, which plays a key role in ischemic brain injury. Using neuronal cultures and a rat model of ischemic stroke, we show that STEP plays an initial role in neuroprotection, during the insult, by disrupting the p38 MAPK pathway. Degradation of active STEP during reperfusion precedes ischemic brain damage and is associated with secondary activation of p38 MAPK. Application of a cell-permeable STEP-derived peptide that is resistant to degradation and binds to p38 MAPK protects cultured neurons from hypoxia-reoxygenation injury and reduces ischemic brain damage when injected up to 6 h after the insult. Conversely, genetic deletion of STEP in mice leads to sustained p38 MAPK activation and exacerbates brain injury and neurological deficits after ischemia. Administration of the STEP-derived peptide at the onset of reperfusion not only prevents the sustained p38 MAPK activation but also reduces ischemic brain damage in STEP KO mice. The findings indicate a neuroprotective role of STEP and suggest a potential role of the STEP-derived peptide in stroke therapy. PMID:24198371

  3. The effect of concomitant peripheral injury on traumatic brain injury pathobiology and outcome.

    PubMed

    McDonald, Stuart J; Sun, Mujun; Agoston, Denes V; Shultz, Sandy R

    2016-04-26

    Traumatic injuries are physical insults to the body that are prevalent worldwide. Many individuals involved in accidents suffer injuries affecting a number of extremities and organs, otherwise known as multitrauma or polytrauma. Traumatic brain injury is one of the most serious forms of the trauma-induced injuries and is a leading cause of death and long-term disability. Despite over dozens of phase III clinical trials, there are currently no specific treatments known to improve traumatic brain injury outcomes. These failures are in part due to our still poor understanding of the heterogeneous and evolving pathophysiology of traumatic brain injury and how factors such as concomitant extracranial injuries can impact these processes. Here, we review the available clinical and pre-clinical studies that have investigated the possible impact of concomitant injuries on traumatic brain injury pathobiology and outcomes. We then list the pathophysiological processes that may interact and affect outcomes and discuss promising areas for future research. Taken together, many of the clinical multitrauma/polytrauma studies discussed in this review suggest that concomitant peripheral injuries may increase the risk of mortality and functional deficits following traumatic brain injury, particularly when severe extracranial injuries are combined with mild to moderate brain injury. In addition, recent animal studies have provided strong evidence that concomitant injuries may increase both peripheral and central inflammatory responses and that structural and functional deficits associated with traumatic brain injury may be exacerbated in multiply injured animals. The findings of this review suggest that concomitant extracranial injuries are capable of modifying the outcomes and pathobiology of traumatic brain injury, in particular neuroinflammation. Though additional studies are needed to further identify the factors and mechanisms involved in central and peripheral injury

  4. Concussive brain injury from explosive blast

    PubMed Central

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

    2014-01-01

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

  5. Concussive brain injury from explosive blast.

    PubMed

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

    2014-09-01

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

  6. Desflurane impairs outcome of organotypic hippocampal slices in an in vitro model of traumatic brain injury

    PubMed Central

    Krings, Matthias; Höllig, Anke; Liu, Jingjin; Grüsser, Linda; Rossaint, Rolf; Coburn, Mark

    2016-01-01

    Decreased mortality and disability after traumatic brain injury is a significant medical challenge. Desflurane, a widely used volatile anesthetic has proven to be neuroprotective in a variety of in vitro and in vivo models of ischemic brain injury. The aim of this study was to investigate whether desflurane exhibits neuroprotective properties in an in vitro model of traumatic brain injury. Organotypic hippocampal slice cultures were prepared from brains of 5–7-day-old C57/BL6 mouse pups. After 14 days of culture, the slices were subjected to a focal mechanical trauma and thereafter incubated with three different concentrations of desflurane (2, 4 and 6%) for 2, 24 and 72 hours. Cell injury was assessed with propodium iodide uptake. Our results showed that after 2 hours of desflurane exposure, no significant change in trauma intensity was observed. However, 2% and 4% desflurane could reduce the trauma intensity significantly in the no trauma group than in the no desflurane and trauma group. Incubation with 4% desflurane for 24 hours doubled the trauma intensity in comparison to the trauma control group and the trauma intensity further increased after 72 hours of incubation. Furthermore, a dose-dependent increase of trauma intensity after 24 hours exposure was observed. Our results suggest that a general neuroprotective attribute of desflurane in an in vitro model of traumatic brain injury was not observed. PMID:27826417

  7. Effect of Long-Term Treatment with Fimasartan on Transient Focal Ischemia in Rat Brain

    PubMed Central

    Kim, Chi Kyung; Yang, Xiu-Li; Kim, Young-Ju; Choi, In-Young; Jeong, Han-Gil; Park, Hong-Kyun; Kim, Dohoung; Kim, Tae Jung; Jang, Hyunduk; Ko, Sang-Bae; Yoon, Byung-Woo

    2015-01-01

    Fimasartan is a newly developed angiotensin receptor blocker, which may have protective effects during myocardial infarction or atherosclerosis. In this context, we investigated the effects of long-term treatment with low-dose fimasartan on focal ischemia in rat brain. We induced focal ischemia in brain by transient intraluminal occlusion of middle cerebral artery (MCA) and administered low-dose (0.5 mg/kg) or regular doses (1 or 3 mg/kg) of fimasartan via intravenous routes. After the administration of low-dose (0.5 mg/kg) fimasartan, blood pressure did not decrease compared to the phosphate-buffered saline- (PBS-) control with MCA occlusion (MCAO) group. The infarct volume and ischemic cell death were reduced in the low-dose fimasartan-treated group (46 ± 41 mm3 for 0.5 mg/kg and 153 ± 47 mm3 for PBS-control with MCAO; P < 0.01) but not in the regular-dose groups. Low-dose fimasartan treatment improved functional recovery after ischemia and significantly decreased mortality. In our study, fimasartan reduced the degradation of IκB and the formation of an inflammatory end-product, COX-2. As a result, the recruitment of inflammatory cells in the peri-infarct area decreased in fimasartan-treated group. We have demonstrated that long-term, low-dose fimasartan treatment improved outcomes after focal ischemia in the brain via a reduction of inflammation. PMID:26448932

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

    PubMed Central

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

    2016-01-01

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

  9. Role of Thalamus in Recovery of Traumatic Brain Injury

    PubMed Central

    Munivenkatappa, Ashok; Agrawal, Amit

    2016-01-01

    Degree of recovery after traumatic brain injury is highly variable that lasts for many weeks to months. The evidence of brain structures involved in recovery mechanisms is limited. This review highlights evidence of the brain structure particularly thalamus in neuroplasticity mechanism. Thalamus with its complex global networking has potential role in refining the cortical and other brain structures. Thalamic nuclei activation both naturally or by neurorehabilitation in injured brain can enhance and facilitate the improvement of posttraumatic symptoms. This review provides evidence from literature that thalamus plays a key role in recovery mechanism after injury. The study also emphasize that thalamus should be specifically targeted in neurorehabilitation following brain injury. PMID:28163509

  10. Pathological correlations between traumatic brain injury and chronic neurodegenerative diseases.

    PubMed

    Cruz-Haces, Marcela; Tang, Jonathan; Acosta, Glen; Fernandez, Joseph; Shi, Riyi

    2017-01-01

    Traumatic brain injury is among the most common causes of death and disability in youth and young adults. In addition to the acute risk of morbidity with moderate to severe injuries, traumatic brain injury is associated with a number of chronic neurological and neuropsychiatric sequelae including neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. However, despite the high incidence of traumatic brain injuries and the established clinical correlation with neurodegeneration, the causative factors linking these processes have not yet been fully elucidated. Apart from removal from activity, few, if any prophylactic treatments against post-traumatic brain injury neurodegeneration exist. Therefore, it is imperative to understand the pathophysiological mechanisms of traumatic brain injury and neurodegeneration in order to identify potential factors that initiate neurodegenerative processes. Oxidative stress, neuroinflammation, and glutamatergic excitotoxicity have previously been implicated in both secondary brain injury and neurodegeneration. In particular, reactive oxygen species appear to be key in mediating molecular insult in neuroinflammation and excitotoxicity. As such, it is likely that post injury oxidative stress is a key mechanism which links traumatic brain injury to increased risk of neurodegeneration. Consequently, reactive oxygen species and their subsequent byproducts may serve as novel fluid markers for identification and monitoring of cellular damage. Furthermore, these reactive species may further serve as a suitable therapeutic target to reduce the risk of post-injury neurodegeneration and provide long term quality of life improvements for those suffering from traumatic brain injury.

  11. Visual impairments in the first year after traumatic brain injury.

    PubMed

    Greenwald, Brian D; Kapoor, Neera; Singh, Adeepa D

    2012-01-01

    This article reviews literature regarding individuals with traumatic brain injury who have vision related impairments up to one year, post-injury. Such impairments may impact rehabilitation of activities of daily living and mobility since vision is integral in much of what one does on a daily basis. Search of Medline, Ovid, and PubMed was performed using terms including: traumatic brain injury, visual deficits after brain injury, vision and traumatic brain injury, and ADLs after brain injury. Eighteen studies were analyzed and reviewed. A range of visual and visual-motor impairments are seen across the severity of traumatic brain injury. Visual impairment negatively impacts independence in mobility and activities of daily living. Common sensorimotor visual symptoms reported by those with traumatic brain injury include blurred vision, reading problems, double vision or eyestrain, dizziness or disequilibrium in visually-crowded environments, visual field defects, light sensitivity, and color blindness. This review should alert the reader to common visual complaints and defects seen after traumatic brain injury. It is important to screen persons who have suffered traumatic brain injury for sensorimotor vision deficits early on in recovery so that these issues may be addressed and recovery of function and independence in the community are not delayed.

  12. Traumatic brain injury research priorities: the Conemaugh International Brain Injury Symposium.

    PubMed

    Zitnay, George A; Zitnay, Kevin M; Povlishock, John T; Hall, Edward D; Marion, Donald W; Trudel, Tina; Zafonte, Ross D; Zasler, Nathan; Nidiffer, F Don; DaVanzo, John; Barth, Jeffrey T

    2008-10-01

    In 2005, an international symposium was convened with over 100 neuroscientists from 13 countries and major research centers to review current research in traumatic brain injury (TBI) and develop a consensus document on research issues and priorities. Four levels of TBI research were the focus of the discussion: basic science, acute care, post-acute neurorehabilitation, and improving quality of life (QOL). Each working group or committee was charged with reviewing current research, discussion and prioritizing future research directions, identifying critical issues that impede research in brain injury, and establishing a research agenda that will drive research over the next five years, leading to significantly improved outcomes and QOL for individuals suffering brain injuries. This symposium was organized at the request of the Congressional Brain Injury Task Force, to follow up on the National Institutes of Health Consensus Conference on TBI as mandated by the TBI ACT of 1996. The goal was to review what progress had been made since the National Institutes of Health (NIH) Consensus Conference, and also to follow up on the 1990's Decade of the Brain Project. The major purpose of the symposium was to provide recommendations to the U.S. Congress on a priority basis for research, treatment, and training in TBI over the next five years.

  13. Ischemic brain injury in cerebral amyloid angiopathy

    PubMed Central

    van Veluw, Susanne J; Greenberg, Steven M

    2016-01-01

    Cerebral amyloid angiopathy (CAA) is a common form of cerebral small vessel disease and an important risk factor for intracerebral hemorrhage and cognitive impairment. While the majority of research has focused on the hemorrhagic manifestation of CAA, its ischemic manifestations appear to have substantial clinical relevance as well. Findings from imaging and pathologic studies indicate that ischemic lesions are common in CAA, including white-matter hyperintensities, microinfarcts, and microstructural tissue abnormalities as detected with diffusion tensor imaging. Furthermore, imaging markers of ischemic disease show a robust association with cognition, independent of age, hemorrhagic lesions, and traditional vascular risk factors. Widespread ischemic tissue injury may affect cognition by disrupting white-matter connectivity, thereby hampering communication between brain regions. Challenges are to identify imaging markers that are able to capture widespread microvascular lesion burden in vivo and to further unravel the etiology of ischemic tissue injury by linking structural magnetic resonance imaging (MRI) abnormalities to their underlying pathophysiology and histopathology. A better understanding of the underlying mechanisms of ischemic brain injury in CAA will be a key step toward new interventions to improve long-term cognitive outcomes for patients with CAA. PMID:25944592

  14. De novo artistic behaviour following brain injury.

    PubMed

    Pollak, Thomas A; Mulvenna, Catherine M; Lythgoe, Mark F

    2007-01-01

    The effect of brain injury and disease on the output of established artists is an object of much study and debate. The emergence of de novo artistic behaviour following such injury or disease, while very rare, has been recorded in cases of frontotemporal dementia, epilepsy, subarachnoid haemorrhage and Parkinson's disease. This may be an underdiagnosed phenomenon and may represent an opportunity to further understand the neural bases of creative thought and behaviour in man and those of cognitive change after brain injury. There is clearly an important role for hemispheric localization of pathology, which is usually within the temporal cortex, upon the medium of artistic expression, and a likely role for mild frontal cortical dysfunction in producing certain behavioural and cognitive characteristics that may be conducive to the production of art. Possible mechanisms of 'artistic drive' and 'creative idea generation' in these patients are also considered. The increased recognition and responsible nurturing of this behaviour in patients may serve as a source of great comfort to individuals and their families at an otherwise difficult time.

  15. Brain activation during a social attribution task in adolescents with moderate to severe traumatic brain injury.

    PubMed

    Scheibel, Randall S; Newsome, Mary R; Wilde, Elisabeth A; McClelland, Michelle M; Hanten, Gerri; Krawczyk, Daniel C; Cook, Lori G; Chu, Zili D; Vásquez, Ana C; Yallampalli, Ragini; Lin, Xiaodi; Hunter, Jill V; Levin, Harvey S

    2011-01-01

    The ability to make accurate judgments about the mental states of others, sometimes referred to as theory of mind (ToM), is often impaired following traumatic brain injury (TBI), and this deficit may contribute to problems with interpersonal relationships. The present study used an animated social attribution task (SAT) with functional magnetic resonance imaging (fMRI) to examine structures mediating ToM in adolescents with moderate to severe TBI. The study design also included a comparison group of matched, typically developing (TD) adolescents. The TD group exhibited activation within a number of areas that are thought to be relevant to ToM, including the medial prefrontal and anterior cingulate cortex, fusiform gyrus, and posterior temporal and parietal areas. The TBI subjects had significant activation within many of these same areas, but their activation was generally more intense and excluded the medial prefrontal cortex. Exploratory regression analyses indicated a negative relation between ToM-related activation and measures of white matter integrity derived from diffusion tensor imaging, while there was also a positive relation between activation and lesion volume. These findings are consistent with alterations in the level and pattern of brain activation that may be due to the combined influence of diffuse axonal injury and focal lesions.

  16. Brain activation during a social attribution task in adolescents with moderate to severe traumatic brain injury

    PubMed Central

    Scheibel, Randall S.; Newsome, Mary R.; Wilde, Elisabeth A.; McClelland, Michelle M.; Hanten, Gerri; Krawczyk, Daniel C.; Cook, Lori G.; Chu, Zili D.; Vásquez, Ana C.; Yallampalli, Ragini; Lin, Xiaodi; Hunter, Jill V.; Levin, Harvey S.

    2011-01-01

    The ability to make accurate judgments about the mental states of others, sometimes referred to as theory of mind (ToM), is often impaired following traumatic brain injury (TBI), and this deficit may contribute to problems with interpersonal relationships. The present study used an animated social attribution task (SAT) with functional magnetic resonance imaging (fMRI) to examine structures mediating ToM in adolescents with moderate to severe TBI. The study design also included a comparison group of matched, typically developing (TD) adolescents. The TD group exhibited activation within a number of areas that are thought to be relevant to ToM, including the medial prefrontal and anterior cingulate cortex, fusiform gyrus, and posterior temporal and parietal areas. The TBI subjects had significant activation within many of these same areas, but their activation was generally more intense and excluded the medial prefrontal cortex. Exploratory regression analyses indicated a negative relation between ToM-related activation and measures of white matter integrity derived from diffusion tensor imaging, while there was also a positive relation between activation and lesion volume. These findings are consistent with alterations in the level and pattern of brain activation that may be due to the combined influence of diffuse axonal injury and focal lesions. PMID:21777109

  17. Structural brain abnormalities in bipolar affective disorder. Ventricular enlargement and focal signal hyperintensities.

    PubMed

    Swayze, V W; Andreasen, N C; Alliger, R J; Ehrhardt, J C; Yuh, W T

    1990-11-01

    Structural brain abnormalities were examined in a sample of 48 patients with bipolar affective disorder who were compared with 54 schizophrenic patients and 47 normal controls. As in our previous work using computed tomographic scanning, lateral ventricular enlargement was due to a diagnostic effect. In this study, the effect was more prominent in the schizophrenic men, while a trend was seen in the bipolar men. Women in both groups did not differ significantly from normal subjects. This finding is possibly consistent with the fact that men have a higher frequency of birth anomalies such as hydrocephalus. Since one cause of such birth anomalies might be periventricular hemorrhage or infarction, we also evaluated all scans for the presence of small focal regions of signal hyperintensity. A significant increase in the number of focal signal hyperintensities was noted in the bipolar patients, in comparison with normal subjects, but not in the schizophrenics. The bipolar patients with focal signal hyperintensities had a trend toward larger ventricular size than those without. The pathophysiological significance of these findings is unclear.

  18. [Differentiated approach for determination of the patients treatment tactics in focal affection of brain, using stereotaxic methods].

    PubMed

    Tsymbaliuk, V I; Hlavats'kiĭ, O Ia; Zinkevych, Ia P; Kostiuk, K R; Medvedev, Iu M; Popov, A O; Malysheva, T A; Chernenko, O H

    2011-12-01

    There were analyzed the results of stereotaxic biopsy in 338 patients, using CRW stereotaxic system (Radionics, U.S.A.), performed with the objective for differential diagnosis and treatment conduction in the focal affection of brain (of tumoral and nontumoral etiology). In the recurrent cystic affection of brain there were determined diagnostic informativity and trustworthiness of the cysts stereotaxic aspirationance, the abscesses drainage and the Ommaya reservoir implantation. There was proved the important significance of stereotaxic methods in differential diagnosis and treatment of the brain focal affection.

  19. Inflammatory signalling associated with brain dead organ donation: from brain injury to brain stem death and posttransplant ischaemia reperfusion injury.

    PubMed

    Watts, Ryan P; Thom, Ogilvie; Fraser, John F

    2013-01-01

    Brain death is associated with dramatic and serious pathophysiologic changes that adversely affect both the quantity and quality of organs available for transplant. To fully optimise the donor pool necessitates a more complete understanding of the underlying pathophysiology of organ dysfunction associated with transplantation. These injurious processes are initially triggered by catastrophic brain injury and are further enhanced during both brain death and graft transplantation. The activated inflammatory systems then contribute to graft dysfunction in the recipient. Inflammatory mediators drive this process in concert with the innate and adaptive immune systems. Activation of deleterious immunological pathways in organ grafts occurs, priming them for further inflammation after engraftment. Finally, posttransplantation ischaemia reperfusion injury leads to further generation of inflammatory mediators and consequent activation of the recipient's immune system. Ongoing research has identified key mediators that contribute to the inflammatory milieu inherent in brain dead organ donation. This has seen the development of novel therapies that directly target the inflammatory cascade.

  20. Hemispheric visual atentional imbalance in patients with traumatic brain injury.

    PubMed

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

    2007-06-01

    We find a spatially asymmetric allocation of attention in patients with traumatic brain injury (TBI) despite the lack of obvious asymmetry in neurological indicators. Identification performance was measured for simple spatial patterns presented briefly to a locus 5 degrees into the left or right hemifield, after precuing attention to the same (ipsilateral) or opposite (cross-hemifield) side. Though the cue was non-predictive of target location overall, performance was significantly slower for cross than for ipsilateral trials in both patients and controls. We tested 21 TBI patients without overt focal brain damage and nine control subjects. Only patients demonstrated significantly worse performance for left side presentation in the ipsilateral condition. Furthermore, in the cross-hemifield condition, the left-right difference seen in TBI patients was significantly larger-reflecting a failure in producing a leftward attention shift. Again no significant difference was found in controls. These hemifield effects suggest an asymmetry in the ability of TBI patients in shifting attention to the left hemifield, whether from central fixation or from a cue in the contra-lateral hemifield. The results support basic hypotheses regarding visual attention: Attentional control may be asymmetric and attention may be a distributed, rather than localized cortical function.

  1. Traumatic Brain Injury: Are We Conducting Enough Resarch

    DTIC Science & Technology

    2017-04-17

    FROM: 59 MDW/SGVU SUBJECT: Professional Presentation Approval 7 APR 2017 1. Your paper, entitled Traumatic Brain Injury: Are We Conducting Enough...review and approval.) NA - Pubmed searches w ere the only source of data 6. TITLE OF MATERIAL TO BE PUBLISHED OR PRESENTED: Traumatic Brain Injury...Traumatic Brain Injury: Are We Conducting Enough Research? Capt Mariya Gusman MD, Lt Col Jonathan A Sosnov MD, Jeffrey T Howard PhD Background

  2. Baseline Establishment Using Virtual Environment Traumatic Brain Injury Screen (VETS)

    DTIC Science & Technology

    2015-06-01

    treating brain injuries is utilizing 16 an effective screening technique to target treatment for those individuals who need it most. Requirements for an...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS BASELINE ESTABLISHMENT USING VIRTUAL ENVIRONMENT TRAUMATIC BRAIN INJURY SCREEN (VETS) by Casey...ENVIRONMENT TRAUMATIC BRAIN INJURY SCREEN (VETS) 5. FUNDING NUMBERS 6. AUTHOR(S) Casey G. DeMunck 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES

  3. Hypersexuality or altered sexual preference following brain injury.

    PubMed Central

    Miller, B L; Cummings, J L; McIntyre, H; Ebers, G; Grode, M

    1986-01-01

    Eight patients are described in whom either hypersexuality (four cases) or change in sexual preference (four cases) occurred following brain injury. In this series disinhibition of sexual activity and hypersexuality followed medial basal-frontal or diencephalic injury. This contrasted with the patients demonstrating altered sexual preference whose injuries involved limbic system structures. In some patients altered sexual behaviour may be the presenting or dominant feature of brain injury. Images PMID:3746322

  4. Hypersexuality or altered sexual preference following brain injury.

    PubMed

    Miller, B L; Cummings, J L; McIntyre, H; Ebers, G; Grode, M

    1986-08-01

    Eight patients are described in whom either hypersexuality (four cases) or change in sexual preference (four cases) occurred following brain injury. In this series disinhibition of sexual activity and hypersexuality followed medial basal-frontal or diencephalic injury. This contrasted with the patients demonstrating altered sexual preference whose injuries involved limbic system structures. In some patients altered sexual behaviour may be the presenting or dominant feature of brain injury.

  5. Bromocriptine reduces lipid peroxidation and enhances spatial learning and hippocampal neuron survival in a rodent model of focal brain trauma.

    PubMed

    Kline, Anthony E; Massucci, Jaime L; Ma, Xiecheng; Zafonte, Ross D; Dixon, C Edward

    2004-12-01

    Oxidative stress is a significant contributor to the secondary sequelae of traumatic brain injury (TBI), and may mediate subsequent neurobehavioral deficits and histopathology. The present study examined the neuroprotective effects of bromocriptine (BRO), a dopamine D2 receptor agonist with significant antioxidant properties, on cognition, histopathology, and lipid peroxidation in a rodent model of focal brain trauma. BRO (5 mg/kg) or a comparable volume of vehicle (VEH) was administered intraperitoneally 15 min prior to cortical impact or sham injury. In experiment 1, spatial learning was assessed in an established water maze task on post-surgery days 14-18, followed by quantification of hippocampal cell survival and cortical lesion volume at 4 weeks. In experiment 2, rats were sacrificed 1 hr post-surgery, and malondialdehyde (MDA), the end product of lipid peroxidation, was measured in the frontal cortex, striatum, and substantia nigra using a thiobarbituric acid reactive substances assay. The TBI+BRO group was significantly more adept at locating a hidden platform in the water maze compared to the TBI+VEH group and also exhibited a greater percentage of surviving CA3 hippocampal neurons. TBI increased MDA in all examined regions of the VEH-treated, but not BRO-treated group versus SHAMs. MDA was significantly decreased in both the striatum (4.22 +/- 0.52 versus 5.60 +/- 0.44 nmol per mg/tissue +/- SEM) and substantia nigra (4.18 +/- 0.35 versus 7.76 +/- 2.05) of the TBI+BRO versus TBI+VEH groups, respectively, while only a trend toward decreased MDA was observed in the frontal cortex (5.44 +/- 0.44 versus 6.96 +/- 0.77). These findings suggest that TBI-induced oxidative stress is attenuated by acute BRO treatment, which may, in part, explain the benefit in cognitive and histological outcome.

  6. Psychiatric disorders after traumatic brain injury.

    PubMed

    van Reekum, R; Bolago, I; Finlayson, M A; Garner, S; Links, P S

    1996-05-01

    Substantial psychological and neurobehavioural evidence is available to support the hypothesis that traumatic brain injury (TBI) is a risk factor for subsequent psychiatric disorders. However, studies utilizing established psychiatric diagnostic schemes to study these outcomes after TBI are scarce, and no studies have included an assessment of personality disorders in addition to the major psychiatric disorders. This study utilizes structured psychiatric interviews to measure the prevalence of DSM-III(R) disorders in a sample of 18 subjects derived from a TBI rehabilitation programme. Results revealed high rates for major depression, bipolar affective disorder, generalized anxiety disorder, borderline and avoidant personality disorders. Co-morbidity was also high. A preliminary study of postulated predictive factors revealed possible roles for sex and for initial severity of injury. The study supports the association between TBI and psychiatric disorder, and suggests the need for monitoring, for prevention, and for treatment of psychiatric disorders after TBI.

  7. A clinical study on closing-in in focal brain-damaged individuals.

    PubMed

    De Lucia, Natascia; Grossi, Dario; Trojano, Luigi

    2016-04-15

    In visuo-constructional assessment, brain-damaged individuals may copy figures near to or superimposed on the model, showing the Closing-in (CI). CI has been largely investigated in dementia, and often ascribed to impairments of the attention/executive abilities ("Attraction hypothesis"). Only a few dated studies investigated frequency of CI in brain-damaged individuals, without clarifying the genesis of the phenomenon. We aimed at testing the "Attraction hypothesis" in 27 individuals with focal frontal cortical or sub-cortical brain lesions by a dual-task experimental paradigm. The participants underwent a neuropsychological battery and a copying task to be performed alone (single task condition), or concurrently with a simple or a complex verbal secondary task (dual-task conditions). CI was found in 66% of frontal-damaged individuals, who scored significantly lower than healthy adults on all neuropsychological measures; brain-damaged individuals showing CI performed worse than frontal-damaged individuals without CI on frontal and visuo-constructional measures. In the dual-task condition with the complex secondary task CI was significantly enhanced, with a weaker tendency to self-correction, in individuals with CI compared to individuals without CI. These findings would confirm that the CI in brain-damaged individuals is related to reduction of attentional resources, consistently with the "Attraction hypothesis".

  8. The Acute Phase of Mild Traumatic Brain Injury Is Characterized by a Distance-Dependent Neuronal Hypoactivity

    PubMed Central

    Johnstone, Victoria P.A.; Shultz, Sandy R.; Yan, Edwin B.; O'Brien, Terence J.

    2014-01-01

    Abstract The consequences of mild traumatic brain injury (TBI) on neuronal functionality are only now being elucidated. We have now examined the changes in sensory encoding in the whisker-recipient barrel cortex and the brain tissue damage in the acute phase (24 h) after induction of TBI (n=9), with sham controls receiving surgery only (n=5). Injury was induced using the lateral fluid percussion injury method, which causes a mixture of focal and diffuse brain injury. Both population and single cell neuronal responses evoked by both simple and complex whisker stimuli revealed a suppression of activity that decreased with distance from the locus of injury both within a hemisphere and across hemispheres, with a greater extent of hypoactivity in ipsilateral barrel cortex compared with contralateral cortex. This was coupled with an increase in spontaneous output in Layer 5a, but only ipsilateral to the injury site. There was also disruption of axonal integrity in various regions in the ipsilateral but not contralateral hemisphere. These results complement our previous findings after mild diffuse-only TBI induced by the weight-drop impact acceleration method where, in the same acute post-injury phase, we found a similar depth-dependent hypoactivity in sensory cortex. This suggests a common sequelae of events in both diffuse TBI and mixed focal/diffuse TBI in the immediate post-injury period that then evolve over time to produce different long-term functional outcomes. PMID:24927383

  9. The acute phase of mild traumatic brain injury is characterized by a distance-dependent neuronal hypoactivity.

    PubMed

    Johnstone, Victoria P A; Shultz, Sandy R; Yan, Edwin B; O'Brien, Terence J; Rajan, Ramesh

    2014-11-15

    The consequences of mild traumatic brain injury (TBI) on neuronal functionality are only now being elucidated. We have now examined the changes in sensory encoding in the whisker-recipient barrel cortex and the brain tissue damage in the acute phase (24 h) after induction of TBI (n=9), with sham controls receiving surgery only (n=5). Injury was induced using the lateral fluid percussion injury method, which causes a mixture of focal and diffuse brain injury. Both population and single cell neuronal responses evoked by both simple and complex whisker stimuli revealed a suppression of activity that decreased with distance from the locus of injury both within a hemisphere and across hemispheres, with a greater extent of hypoactivity in ipsilateral barrel cortex compared with contralateral cortex. This was coupled with an increase in spontaneous output in Layer 5a, but only ipsilateral to the injury site. There was also disruption of axonal integrity in various regions in the ipsilateral but not contralateral hemisphere. These results complement our previous findings after mild diffuse-only TBI induced by the weight-drop impact acceleration method where, in the same acute post-injury phase, we found a similar depth-dependent hypoactivity in sensory cortex. This suggests a common sequelae of events in both diffuse TBI and mixed focal/diffuse TBI in the immediate post-injury period that then evolve over time to produce different long-term functional outcomes.

  10. Housing conditions influence motor functions and exploratory behavior following focal damage of the rat brain.

    PubMed

    Gornicka-Pawlak, Elzbieta; Jabłońska, Anna; Chyliński, Andrzej; Domańska-Janik, Krystyna

    2009-01-01

    The present study investigated influence of housing conditions on motor functions recovery and exploratory behavior following ouabain focal brain lesion in the rat. During 30 days post-surgery period rats were housed individually in standard cages (IS) or in groups in enriched environment (EE) and behaviorally tested. The EE lesioned rats showed enhanced recovery from motor impairments in walking beam task, comparing with IS animals. Contrarily, in the open field IS rats (both lesioned and control) traveled a longer distance, showed less habituation and spent less time resting at the home base than the EE animals. Unlike the EE lesioned animals, the lesioned IS rats, presented a tendency to hyperactivity in postinjury period. Turning tendency was significantly affected by unilateral brain lesion only in the EE rats. We can conclude that housing conditions distinctly affected the rat's behavior in classical laboratory tests.

  11. Magnetic resonance volumetry reveals focal brain atrophy in transient epileptic amnesia.

    PubMed

    Butler, Christopher; van Erp, Willemijn; Bhaduri, Amit; Hammers, Alexander; Heckemann, Rolf; Zeman, Adam

    2013-09-01

    Transient epileptic amnesia (TEA) is a recently described epilepsy syndrome characterized by recurrent episodes of isolated memory loss. It is associated with two unusual forms of interictal memory impairment: accelerated long-term forgetting (ALF) and autobiographical amnesia. We investigated the neural basis of TEA using manual volumetry and automated multi-atlas-based segmentation of whole-brain magnetic resonance imaging data from 40 patients with TEA and 20 healthy controls. Both methods confirmed the presence of subtle, bilateral hippocampal atrophy. Additional atrophy was revealed in perirhinal and orbitofrontal cortices. The volumes of these regions correlated with anterograde memory performance. No structural correlates were found for ALF or autobiographical amnesia. The results support the hypothesis that TEA is a focal medial temporal lobe epilepsy syndrome but reveal additional pathology in connected brain regions. The unusual interictal memory deficits of TEA remain unexplained by structural pathology and may reflect physiological disruption of memory networks by subclinical epileptiform activity.

  12. Fear of falling after brain injury.

    PubMed

    Collicutt McGrath, Joanna

    2008-07-01

    To investigate the prevalence and nature of fear of falling in a sample of people with severe acquired brain injury. A descriptive study. A regional inpatient neurological rehabilitation unit. One hundred and five adults with acquired brain injury of mixed aetiology. All 105 participants were rated by observers who were asked to judge the degree to which fear behaviour interfered with rehabilitation therapy (activity limitation). Eighty-two participants also rated themselves. They were asked to report the degree of distress caused by fear. Both participants and observers were asked to describe the focus of any reported fear. Two stepwise logistic regression analyses were carried out to identify variables that predicted fear giving rise to significant activity limitation and fear giving rise to significant subjective distress. Self and observer rating scales designed and constructed specifically for the study. Raters reported significant fear-related activity limitation in 12-15% of participants. Significant fear-related subjective distress was reported by 40% of participants. Fear of falling, fear of physical harm and fear of not making sufficient rehabilitation progress dominated the reports of both observers and participants. The variables predicting significant activity limitation were premorbid alcohol misuse, low functional ability and the occurrence of a fall since onset. The variables predicting significant subjective distress were poor motor coordination and organization, and good verbal comprehension. Fear of falling is a clinically significant phenomenon in younger adults recovering from severe acquired brain injury. Fear sufficient to cause high degrees of subjective distress was often not evident to observers. Proactive questioning about fear of falling is therefore advisable when working clinically with this group.

  13. Brain Injury Vision Symptom Survey (BIVSS) Questionnaire.

    PubMed

    Laukkanen, Hannu; Scheiman, Mitchell; Hayes, John R

    2017-01-01

    Validation of the Brain Injury Vision Symptom Survey (BIVSS), a self-administered survey for vision symptoms related to traumatic brain injury (TBI). A 28-item vision symptom questionnaire was completed by 107 adult subjects (mean age 42.1, 16.2 SD, range 18-75) who self-reported as having sustained mild-to-moderate TBI and two groups of reference adult subjects (first-year optometry students: mean age 23.2, 2.8 SD, range 20-39; and 71 third-year optometry students: mean age 26.0, 2.9 SD, range 22-42) without TBI. Both a Likert-style method of analysis with factor analysis and a Rasch analysis were used. Logistic regression was used to determine sensitivity and specificity. At least 27 of 28 questions were completed by 93.5% of TBI subjects, and all 28 items were completed by all of the 157 reference subjects. BIVSS sensitivity was 82.2% for correctly predicting TBI and 90.4% for correctly predicting the optometry students. Factor analysis identified eight latent variables; six factors were positive in their risk for TBI. Other than dry eye and double vision, the TBI patients were significantly more symptomatic than either cohort of optometry students by at least one standard deviation (p < 0.001). Twenty-five of 28 questions were within limits for creating a single-dimension Rasch scale. Nearly all of the adult TBI subjects were able to self-complete the BIVSS, and there was significant mean score separation between TBI and non-TBI groups. The Rasch analysis revealed a single dimension associated with TBI. Using the Likert method with the BIVSS, it may be possible to identify different vision symptom profiles with TBI patients. The BIVSS seems to be a promising tool for better understanding the complex and diverse nature of vision symptoms that are associated with brain injury.

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

    PubMed

    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.

  15. Effects of crystalloid-colloid solutions on traumatic brain injury.

    PubMed

    Elliott, Melanie B; Jallo, Jack J; Gaughan, John P; Tuma, Ronald F

    2007-01-01

    The purpose of this study was to compare the effects of crystalloid and crystalloid-colloid solutions administered at different times after isolated traumatic brain injury. Male Sprague-Dawley rats were randomized to receive one of three intravenous treatments (4 mL/kg body weight) at 10 min or 6 h after moderate traumatic brain injury. Treatments included hypertonic saline, hypertonic albumin, and normal albumin. Moderate injuries were produced using the controlled cortical impact injury model set at 2.0 mm, 4.0 m/sec, and 130 msec. Tissue damage and cerebral edema were measured to evaluate the effect of treatments for traumatic brain injury. Blood brain barrier permeability was assessed at different time points after injury to identify a mechanism for treatment effectiveness. Injury volume was the smallest for animals treated with hypertonic albumin at 6 h after injury compared to all other treatments and administration times. Ipsilateral brain water content was significantly attenuated with immediate normal saline-albumin treatment. The presence of colloid in the infusion solutions was associated with an improvement in tissue damage and edema following isolated head injury while hypertonic saline alone, when given immediately after injury, worsened tissue damage and edema. When hypertonic saline was administered at 6 h after injury, tissue damage and edema were not worsened. In conclusion, the presence of colloid in solutions used to treat traumatic brain injury and the timing of treatment have a significant impact on tissue damage and edema.

  16. Sports-related traumatic brain injury.

    PubMed

    Phillips, Shawn; Woessner, Derek

    2015-06-01

    Concussions have garnered more attention in the medical literature, media, and social media. As such, in the nomenclature according to the Centers for Disease Control and Prevention, the term concussion has been supplanted by the term mild traumatic brain injury. Current numbers indicate that 1.7 million TBIs are documented annually, with estimates around 3 million annually (173,285 sports- and recreation-related TBIs among children and adolescents). The Sideline Concussion Assessment Tool 3 and the NFL Sideline Concussion Assessment Tool are commonly used sideline tools.

  17. Epidural focal brain cooling abolishes neocortical seizures in cats and non-human primates.

    PubMed

    Inoue, Takao; Fujii, Masami; Kida, Hiroyuki; Yamakawa, Toshitaka; Maruta, Yuichi; Tokiwa, Tatsuji; He, Yeting; Nomura, Sadahiro; Owada, Yuji; Yamakawa, Takeshi; Suzuki, Michiyasu

    2017-09-01

    Focal brain cooling (FBC) is under investigation in preclinical trials of intractable epilepsy (IE), including status epilepticus (SE). This method has been studied in rodents as a possible treatment for epileptic disorders, but more evidence from large animal studies is required. To provide evidence that FBC is a safe and effective therapy for IE, we investigated if FBC using a titanium cooling plate can reduce or terminate focal neocortical seizures without having a significant impact on brain tissue. Two cats and two macaque monkeys were chronically implanted with an epidural FBC device over the somatosensory and motor cortex. Penicillin G was delivered via the intracranial cannula for induction of local seizures. Repetitive FBC was performed using a cooling device implanted for a medium-term period (FBC for 30min at least twice every week; 3 months total) in three of the four animals. The animals exhibited seizures with repetitive epileptiform discharges (EDs) after administration of penicillin G, and these discharges decreased at less than 20°C cooling with no adverse histological effects. The results of this study suggest that epidural FBC is a safe and effective potential treatment for IE and SE. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  18. Severe Brain Injury in Massachusetts: Assessing the Continuum of Care.

    PubMed

    Lorenz, Laura; Katz, Gabrielle

    2015-12-10

    Acquired brain injury (ABI) is a major public health problem in Massachusetts (Hackman et al, 2014) and includes traumatic brain injury (TBI), stroke, ABI-related infectious diseases, metabolic disorders affecting the central nervous system (brain and spinal cord), and brain tumor. Advances in emergency medical care and neurosurgery mean that more people are surviving severe traumatic brain injury (Trexler et al, 2014). Yet many patients with severe TBI in particular, are not receiving inpatient services after initial treatment (Hackman et al, 2014; CDC, 2014) or later that are known to be effective (Malec & Kean, 2015; Lewis & Horn, 2015; BI Commission, 2011; Kolakowsky-Hayner et al, 2000; Interviews). These services include post-acute rehabilitation, case management, and brain injury-specific community programming (CDC, 2014; BI Commission, 2011; Interviews). Governance and data for decision-making are also major gaps in the continuum of care for severe brain injury in MA (Interviews; NASHIA, 2005). The last two decades saw a surge in interest in the brain, with advances in neuroscience, diagnosis and measurement of brain injury, rehabilitation services, and brain theory (Boyle, 2001). Severe brain injury however is the new "hidden epidemic" in our society. For many, an injury to the brain is not a short-term event that can be "cured" but the beginning of a life-long disability (CDC, 2014; Langlois et al, 2006). Fortunately, even after a severe brain injury, when the right rehabilitation is provided at the right time, the "rest of life" journey can be a positive one for many (Marquez de la Plata, 2015; Langlois et al, 2006). Severe brain injury can lead to a "new normal" as patients regain skills, find new meaning and in life, and take on new family, volunteer, and work roles. Throughout this brief, the term "severe brain injury" refers to "severe acquired brain injury," or any injury to the brain that occurs after birth. This definition does not include

  19. Astrocyte-derived interleukin-15 exacerbates ischemic brain injury via propagation of cellular immunity

    PubMed Central

    Li, Minshu; Li, Zhiguo; Yao, Yang; Jin, Wei-Na; Wood, Kristofer; Liu, Qiang; Shi, Fu-Dong; Hao, Junwei

    2017-01-01

    Astrocytes are believed to bridge interactions between infiltrating lymphocytes and neurons during brain ischemia, but the mechanisms for this action are poorly understood. Here we found that interleukin-15 (IL-15) is dramatically up-regulated in astrocytes of postmortem brain tissues from patients with ischemic stroke and in a mouse model of transient focal brain ischemia. We generated a glial fibrillary acidic protein (GFAP) promoter-controlled IL-15–expressing transgenic mouse (GFAP–IL-15tg) line and found enlarged brain infarcts, exacerbated neurodeficits after the induction of brain ischemia. In addition, knockdown of IL-15 in astrocytes attenuated ischemic brain injury. Interestingly, the accumulation of CD8+ T and natural killer (NK) cells was augmented in these GFAP–IL-15tg mice after brain ischemia. Of note, depletion of CD8+ T or NK cells attenuated ischemic brain injury in GFAP–IL-15tg mice. Furthermore, knockdown of the IL-15 receptor α or blockade of cell-to-cell contact diminished the activation and effector function of CD8+ T and NK cells in GFAP–IL-15tg mice, suggesting that astrocytic IL-15 is delivered in trans to target cells. Collectively, these findings indicate that astrocytic IL-15 could aggravate postischemic brain damage via propagation of CD8+ T and NK cell-mediated immunity. PMID:27994144

  20. Why Some Kids Take Longer to Recover from Brain Injury

    MedlinePlus

    ... Why Some Kids Take Longer to Recover From Brain Injury Scans reveal white-matter decline after some ... 15, 2017 WEDNESDAY, March 15, 2017 (HealthDay News) -- Brain scans may reveal which children will take longer ...

  1. Radiation-induced brain injury: A review

    PubMed Central

    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

  2. Early Systolic Dysfunction Following Traumatic Brain Injury: A Cohort Study.

    PubMed

    Krishnamoorthy, Vijay; Rowhani-Rahbar, Ali; Gibbons, Edward F; Rivara, Frederick P; Temkin, Nancy R; Pontius, Crystal; Luk, Kevin; Graves, Morgan; Lozier, Danielle; Chaikittisilpa, Nophanan; Kiatchai, Taniga; Vavilala, Monica S

    2017-06-01

    Prior studies have suggested that traumatic brain injury may affect cardiac function. Our study aims were to determine the frequency, longitudinal course, and admission risk factors for systolic dysfunction in patients with moderate-severe traumatic brain injury. Prospective cohort study. Level 1 trauma center. Transthoracic echocardiogram within 1 day and over the first week after moderate-severe traumatic brain injury; transthoracic echocardiogram within 1 day after mild traumatic brain injury (comparison group). Systolic function was assessed by transthoracic echocardiogram, and systolic dysfunction was defined as fractional shortening less than 25%. Multivariable Poisson regression models examined admission risk factors for systolic dysfunction. Systolic function in 32 patients with isolated moderate-severe traumatic brain injury and 32 patients with isolated mild traumatic brain injury (comparison group) was assessed with transthoracic echocardiogram. Seven (22%) moderate-severe traumatic brain injury and 0 (0%) mild traumatic brain injury patients had systolic dysfunction within the first day after injury (p < 0.01). All patients with early systolic dysfunction recovered in 1 week. Younger age (relative risk, 0.87; 95% CI, 0.79-0.94; for 1 yr increase in age) and lower admission Glasgow Coma Scale score (relative risk, 0.34; 95% CI, 0.20-0.58; for one unit increase in Glasgow Coma Scale) were independently associated with the development of systolic dysfunction among moderate-severe traumatic brain injury patients. Early systolic dysfunction can occur in previously healthy patients with moderate-severe traumatic brain injury, and it is reversible over the first week of hospitalization. Younger age and lower admission Glasgow Coma Scale score are independently associated with the development of systolic dysfunction after moderate-severe traumatic brain injury.

  3. Robust whole-brain segmentation: application to traumatic brain injury.

    PubMed

    Ledig, Christian; Heckemann, Rolf A; Hammers, Alexander; Lopez, Juan Carlos; Newcombe, Virginia F J; Makropoulos, Antonios; Lötjönen, Jyrki; Menon, David K; Rueckert, Daniel

    2015-04-01

    We propose a framework for the robust and fully-automatic segmentation of magnetic resonance (MR) brain images called "Multi-Atlas Label Propagation with Expectation-Maximisation based refinement" (MALP-EM). The presented approach is based on a robust registration approach (MAPER), highly performant label fusion (joint label fusion) and intensity-based label refinement using EM. We further adapt this framework to be applicable for the segmentation of brain images with gross changes in anatomy. We propose to account for consistent registration errors by relaxing anatomical priors obtained by multi-atlas propagation and a weighting scheme to locally combine anatomical atlas priors and intensity-refined posterior probabilities. The method is evaluated on a benchmark dataset used in a recent MICCAI segmentation challenge. In this context we show that MALP-EM is competitive for the segmentation of MR brain scans of healthy adults when compared to state-of-the-art automatic labelling techniques. To demonstrate the versatility of the proposed approach, we employed MALP-EM to segment 125 MR brain images into 134 regions from subjects who had sustained traumatic brain injury (TBI). We employ a protocol to assess segmentation quality if no manual reference labels are available. Based on this protocol, three independent, blinded raters confirmed on 13 MR brain scans with pathology that MALP-EM is superior to established label fusion techniques. We visually confirm the robustness of our segmentation approach on the full cohort and investigate the potential of derived symmetry-based imaging biomarkers that correlate with and predict clinically relevant variables in TBI such as the Marshall Classification (MC) or Glasgow Outcome Score (GOS). Specifically, we show that we are able to stratify TBI patients with favourable outcomes from non-favourable outcomes with 64.7% accuracy using acute-phase MR images and 66.8% accuracy using follow-up MR images. Furthermore, we are able to

  4. Blast-related mild traumatic brain injury: mechanisms of injury and impact on clinical care.

    PubMed

    Elder, Gregory A; Cristian, Adrian

    2009-04-01

    Mild traumatic brain injury has been called the signature injury of the wars in Iraq and Afghanistan. In both theaters of operation, traumatic brain injury has been a significant cause of mortality and morbidity, with blast-related injury the most common cause. Improvised explosive devices have been the major cause of blast injuries. It is estimated that 10% to 20% of veterans returning from these operations have suffered a traumatic brain injury, and there is concern that blast-related injury may produce adverse long-term health affects and affect the resilience and in-theater performance of troops. Blast-related injury occurs through several mechanisms related to the nature of the blast overpressure wave itself as well as secondary and tertiary injuries. Animal studies clearly show that blast overpressure waves are transmitted to the brain and can cause changes that neuropathologically are most similar to diffuse axonal injury. One striking feature of the mild traumatic brain injury cases being seen in veterans of the wars in Iraq and Afghanistan is the high association of mild traumatic brain injury with posttraumatic stress disorder. The overlap in symptoms between the disorders has made distinguishing them clinically challenging. The high rates of mild traumatic brain injury and posttraumatic stress disorder in the current operations are of significant concern for the long-term health of US veterans with associated economic implications.

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

    PubMed

    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.

  6. The new P2Y-like receptor G protein-coupled receptor 17 mediates acute neuronal injury and late microgliosis after focal cerebral ischemia in rats.

    PubMed

    Zhao, B; Zhao, C Z; Zhang, X Y; Huang, X Q; Shi, W Z; Fang, S H; Lu, Y B; Zhang, W P; Xia, Q; Wei, E Q

    2012-01-27

    G protein-coupled receptor 17 (GPR17), the new P2Y-like receptor, is phylogenetically related to the P2Y and cysteinyl leukotriene receptors, and responds to both uracil nucleotides and cysteinyl leukotrienes. GPR17 has been proposed to be a damage sensor in ischemic stroke; however, its role in brain inflammation needs further detailed investigation. Here, we extended previous studies on the spatiotemporal profiles of GPR17 expression and localization, and their implications for brain injury after focal cerebral ischemia. We found that in the ischemic core, GPR17 mRNA and protein levels were upregulated at both 12-24 h and 7-14 days, but in the boundary zone the levels increased 7-14 days after reperfusion. The spatiotemporal pattern of GPR17 expression well matched the acute and late (subacute/chronic) responses in the ischemic brain. According to previous findings, in the acute phase, after ischemia (24 h), upregulated GPR17 was localized in injured neurons in the ischemic core and in a few microglia in the ischemic core and boundary zone. In the late phase (14 days), it was localized in microglia, especially in activated (ED1-positive) microglia in the ischemic core, but weakly in most microglia in the boundary zone. No GPR17 was detectable in astrocytes. GPR17 knockdown by a small interfering RNA attenuated the neurological dysfunction, infarction, and neuron loss at 24 h, and brain atrophy, neuron loss, and microglial activation at 14 days after reperfusion. Thus, GPR17 might mediate acute neuronal injury and late microgliosis after focal cerebral ischemia.

  7. Identification and Functional Analysis of MicroRNAs in Mice following Focal Cerebral Ischemia Injury.

    PubMed

    Liu, Cuiying; Zhao, Lei; Han, Song; Li, Junfa; Li, Dongguo

    2015-10-14

    Numerous studies have demonstrated that genes, RNAs, and proteins are involved in the occurrence and development of stroke. In addition, previous studies concluded that microRNAs (miRNAs or miRs) are closely related to the pathological process of ischemic and hypoxic disease. Therefore, the aims of this study were to quantify the altered expression levels of miRNAs in the infarct region 6 h after middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in mice using a large-scale miRNAs microarray. Firstly, MCAO-induced cerebral ischemic injuries were investigated by observing the changes of neurological deficits, infarct volume and edema ratio. One hundred and eighteen differentially expressed miRNAs were identified in the infarct region of mice following the MCAOs compared with sham group (p<0.05 was considered as significant). Among these 118 significantly expressed microRNAs, we found that 12 miRNAs were up-regulated with fold changes lager than two, and 18 miRNAs were down-regulated with fold changes less than 0.5 in the infarct region of mice following the 6 h MCAOs, compared with the sham group. Then, these 30 miRNAs with expression in fold change larger than two or less than 0.5 was predicted, and the functions of the target genes of 30 miRNAs were analyzed using a bioinformatics method. Finally, the miRNA-gene network was established and the functional miRNA-mRNA pairs were identified, which provided insight into the roles of the specific miRNAs that regulated specified genes in the ischemic injuries. The miRNAs identified in this study may represent effective therapeutic targets for stroke, and further study of the role of these targets may increase our understanding of the mechanisms underlying ischemic injuries.

  8. Traumatic Brain Injury in the Workplace.

    PubMed

    Paci, Michael; Infante-Rivard, Claire; Marcoux, Judith

    2017-09-01

    Work-related traumatic brain injuries (TBIs) are not well documented in the literature. Published studies mostly rely on worker databases that fail to provide clinically relevant information. Our objective is to describe the characteristics of hospitalized patients and their work-related TBI. We used the Québec provincial trauma and TBI program databases to identify all patients with a diagnosis of work-related TBI admitted to the Montreal General Hospital, a level 1 trauma center, between 2000 and 2014. Data from their medical records were extracted using a predetermined information sheet. Simple descriptive statistics (means and percentages) were used to summarize the data. A total of 285 cases were analyzed. Workplace TBI patients were middle-aged (mean, 43.62 years), overwhelmingly male (male:female 18:1), mostly healthy, and had completed a high school level education. Most workers were from the construction industry; falling was the most common mechanism of injury. The majority of patients (76.8%) presented with a mild TBI; only a minority (14%) required neurosurgery. The most common finding on computed tomography was skull fracture. The median length of hospitalization was 7 days, after which most patients were discharged directly home. A total of 8.1% died of their injuries. Our study found that most hospitalized victims of work-related TBI had mild injury; however, some required neurosurgical intervention and a non-negligible proportion died of their injury. Improving fall prevention, accurately document helmet use and increasing the safety practice in the construction industry may help decrease work-related TBI burden.

  9. A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

    DTIC Science & Technology

    2012-09-01

    not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. REPORT...of function after brain damage using a neural prosthesis (Complete main body of manuscript is included in the appendix.) Authors: David J. Guggenmos...feasible for brain repair strategies. This paper tests the hypothesis that recovery after brain injury can be facilitated by a neural prosthesis serving as

  10. The neural basis of impaired self-awareness after traumatic brain injury

    PubMed Central

    Ham, Timothy E.; Bonnelle, Valerie; Hellyer, Peter; Jilka, Sagar; Robertson, Ian H.; Leech, Robert

    2014-01-01

    Self-awareness is commonly impaired after traumatic brain injury. This is an important clinical issue as awareness affects long-term outcome and limits attempts at rehabilitation. It can be investigated by studying how patients respond to their errors and monitor their performance on tasks. As awareness is thought to be an emergent property of network activity, we tested the hypothesis that impaired self-awareness is associated with abnormal brain network function. We investigated a group of subjects with traumatic brain injury (n = 63) split into low and high performance-monitoring groups based on their ability to recognize and correct their own errors. Brain network function was assessed using resting-state and event-related functional magnetic resonance imaging. This allowed us to investigate baseline network function, as well as the evoked response of networks to specific events including errors. The low performance-monitoring group underestimated their disability and showed broad attentional deficits. Neural activity within what has been termed the fronto-parietal control network was abnormal in patients with impaired self-awareness. The dorsal anterior cingulate cortex is a key part of this network that is involved in performance-monitoring. This region showed reduced functional connectivity to the rest of the fronto-parietal control network at ‘rest’. In addition, the anterior insulae, which are normally tightly linked to the dorsal anterior cingulate cortex, showed increased activity following errors in the impaired group. Interestingly, the traumatic brain injury patient group with normal performance-monitoring showed abnormally high activation of the right middle frontal gyrus, putamen and caudate in response to errors. The impairment of self-awareness was not explained either by the location of focal brain injury, or the amount of traumatic axonal injury as demonstrated by diffusion tensor imaging. The results suggest that impairments of self

  11. The neural basis of impaired self-awareness after traumatic brain injury.

    PubMed

    Ham, Timothy E; Bonnelle, Valerie; Hellyer, Peter; Jilka, Sagar; Robertson, Ian H; Leech, Robert; Sharp, David J

    2014-02-01

    Self-awareness is commonly impaired after traumatic brain injury. This is an important clinical issue as awareness affects long-term outcome and limits attempts at rehabilitation. It can be investigated by studying how patients respond to their errors and monitor their performance on tasks. As awareness is thought to be an emergent property of network activity, we tested the hypothesis that impaired self-awareness is associated with abnormal brain network function. We investigated a group of subjects with traumatic brain injury (n = 63) split into low and high performance-monitoring groups based on their ability to recognize and correct their own errors. Brain network function was assessed using resting-state and event-related functional magnetic resonance imaging. This allowed us to investigate baseline network function, as well as the evoked response of networks to specific events including errors. The low performance-monitoring group underestimated their disability and showed broad attentional deficits. Neural activity within what has been termed the fronto-parietal control network was abnormal in patients with impaired self-awareness. The dorsal anterior cingulate cortex is a key part of this network that is involved in performance-monitoring. This region showed reduced functional connectivity to the rest of the fronto-parietal control network at 'rest'. In addition, the anterior insulae, which are normally tightly linked to the dorsal anterior cingulate cortex, showed increased activity following errors in the impaired group. Interestingly, the traumatic brain injury patient group with normal performance-monitoring showed abnormally high activation of the right middle frontal gyrus, putamen and caudate in response to errors. The impairment of self-awareness was not explained either by the location of focal brain injury, or the amount of traumatic axonal injury as demonstrated by diffusion tensor imaging. The results suggest that impairments of self

  12. Quantifying Quadriceps Muscle Strength in Patients With ACL Injury, Focal Cartilage Lesions, and Degenerative Meniscus Tears

    PubMed Central

    Eitzen, Ingrid; Grindem, Hege; Nilstad, Agnethe; Moksnes, Håvard; Risberg, May Arna

    2016-01-01

    Background: Reduced quadriceps strength influences knee function and increases the risk of knee osteoarthritis. Thus, it is of significant clinical relevance to precisely quantify strength deficits in patients with knee injuries. Purpose: To evaluate isokinetic concentric quadriceps muscle strength torque values, assessed both from peak torque and at specific knee flexion joint angles, in patients with anterior cruciate ligament (ACL) injury, focal cartilage lesions, and degenerative meniscus tears. Study Design: Cohort study; Level of evidence, 3. Methods: Data were synthesized from patients included in 3 previously conducted research projects: 2 prospective cohort studies and 1 randomized controlled trial. At the time of inclusion, all patients were candidates for surgery. Isokinetic concentric quadriceps muscle strength measurements (60 deg/s) were performed at baseline (preoperative status) and after a period of progressive supervised exercise therapy (length of rehabilitation period: 5 weeks for ACL injury, 12 weeks for cartilage lesions and degenerative meniscus). Outcome measures were peak torque and torque at specific knee flexion joint angles from 20° to 70°. All patients had unilateral injuries, and side-to-side deficits were calculated. For comparisons between and within groups, we utilized 1-way analysis of variance and paired t tests, respectively. Results: In total, 250 patients were included. At baseline, cartilage patients had the most severe deficit (39.7% ± 24.3%; P < .001). Corresponding numbers for ACL and degenerative meniscus subjects were 21.7% (±13.2%) and 20.7% (±16.3%), respectively. At retest, there was significant improvement in all groups (P < .001), with remaining deficits of 24.7% (±18.5%) for cartilage, 16.8% (±13.9%) for ACL, and 3.3% (±17.8%) for degenerative meniscus. Peak torque was consistently measured at 60° of knee flexion, whereas the largest mean deficits were measured at 30° at baseline and 70° at retest for the

  13. The impact of acute hyponatraemia on severe traumatic brain injury in rats.

    PubMed

    Ke, C; Poon, W S; Ng, H K; Tang, N L; Chan, Y; Wang, J Y; Hsiang, J N

    2000-01-01

    The effect of experimental acute hyponatraemia on severe traumatic brain injury (TBI) was studied in a modified impact-acceleration model. The cortical contusional volume was quantified by image analysis on serial sections, injured axons were visualized and quantified by beta-Amyloid Precursor Protein (beta-APP) immunohistochemical staining. Regional brain water content was estimated by the wet-dry weight method. The experiment was conducted in Group I (injury only) and Group II (injury followed by acute hyponatraemia). Comparison between the two groups showed that acute hyponatraemia significantly increased contusional volume (3.24 +/- 0.70 mm3 vs. 1.80 +/- 0.65 mm3, P = 0.009) and the number of injured axons (128.7 +/- 44.3 vs. 41.7 +/- 50.1, P = 0.04) in the right thalamus & basal ganglia region. Water content of the brain stem region was also significantly increased by acute hyponatraemia (73.71 +/- 0.14% vs. 72.28 +/- 0.93%, P = 0.004). These results suggest that acute hyponatraemia potentiates secondary brain damage in severe TBI by augmentation of both focal contusion and diffuse axonal injury. The injured brain stem region is more susceptible to edema formation induced by experimental acute hyponatraemia.

  14. Detrimental consequences of brain injury on peripheral cells.

    PubMed

    Catania, Anna; Lonati, Caterina; Sordi, Andrea; Gatti, Stefano

    2009-10-01

    Acute brain injury and brain death exert detrimental effects on peripheral host cells. Brain-induced impairment of immune function makes patients more vulnerable to infections that are a major cause of morbidity and mortality after stroke, trauma, or subarachnoid hemorrhage (SAH). Systemic inflammation and organ dysfunction are other harmful consequences of CNS injury. Brain death, the most severe consequence of brain injury, causes inflammatory changes in peripheral organs that can contribute to the inferior outcome of organs transplanted from brain-dead donors. Understanding of the mechanisms underlying the detrimental effects of brain injury on peripheral organs remains incomplete. However, it appears that sympathetic nervous system (SNS)-activation contributes to elicit both inflammation and immunodepression. Indeed, norepinephrine (NE)-induced production of chemokines in liver and other organs likely participates in local and systemic inflammatory changes. Conversely, catecholamine-stimulated interleukin-10 (IL-10) production by blood monocytes exerts immunosuppressive effects. Activation of the hypothalamic-pituitary-adrenal axis (HPA) by increased inflammatory cytokines within the brain is a significant component in the CNS-induced immune function inhibition. Non-neurologic consequences of brain injury show impressive similarities regardless of the brain insult and appear to depend on altered neuroimmune circuits. Modulation of these circuits could reduce extra-brain damage and improve patient outcome in both vascular and traumatic brain injury.

  15. Impaired Pituitary Axes Following Traumatic Brain Injury

    PubMed Central

    Scranton, Robert A.; Baskin, David S.

    2015-01-01

    Pituitary dysfunction following traumatic brain injury (TBI) is significant and rarely considered by clinicians. This topic has received much more attention in the last decade. The incidence of post TBI anterior pituitary dysfunction is around 30% acutely, and declines to around 20% by one year. Growth hormone and gonadotrophic hormones are the most common deficiencies seen after traumatic brain injury, but also the most likely to spontaneously recover. The majority of deficiencies present within the first year, but extreme delayed presentation has been reported. Information on posterior pituitary dysfunction is less reliable ranging from 3%–40% incidence but prospective data suggests a rate around 5%. The mechanism, risk factors, natural history, and long-term effect of treatment are poorly defined in the literature and limited by a lack of standardization. Post TBI pituitary dysfunction is an entity to recognize with significant clinical relevance. Secondary hypoadrenalism, hypothyroidism and central diabetes insipidus should be treated acutely while deficiencies in growth and gonadotrophic hormones should be initially observed. PMID:26239686

  16. Update in mild traumatic brain injury.

    PubMed

    Freire-Aragón, María Dolores; Rodríguez-Rodríguez, Ana; Egea-Guerrero, Juan José

    2017-08-10

    There has been concern for many years regarding the identification of patients with mild traumatic brain injury (TBI) at high risk of developing an intracranial lesion (IL) that would require neurosurgical intervention. The small percentage of patients with these characteristics and the exceptional mortality associated with mild TBI with IL have led to the high use of resources such as computerised tomography (CT) being reconsidered. The various protocols developed for the management of mild TBI are based on the identification of risk factors for IL, which ultimately allows more selective indication or discarding both the CT application and the hospital stay for neurological monitoring. Finally, progress in the study of brain injury biomarkers with prognostic utility in different clinical categories of TBI has recently been incorporated by several clinical practice guidelines, which has allowed, together with clinical assessment, a more accurate prognostic approach for these patients to be established. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  17. Bridge Between Neuroimmunity and Traumatic Brain Injury

    PubMed Central

    Kelso, Matthew L.; Gendelman, Howard E.

    2014-01-01

    The pathophysiology of degenerative, infectious, inflammatory and traumatic diseases of the central nervous system includes a significant immune component. As to the latter, damage to the cerebral vasculature and neural cell bodies, caused by traumatic brain injury (TBI) activates innate immunity with concomitant infiltration of immunocytes into the damaged nervous system. This leads to pro-inflammatory cytokine and prostaglandin production and lost synaptic integrity and more generalized neurotoxicity. Engagement of adaptive immune responses follows including the production of antibodies and lymphocyte proliferation. These affect the tempo of disease along with tissue repair and as such provide a number of potential targets for pharmacological treatments for TBI. However, despite a large body of research, no such treatment intervention is currently available. In this review we will discuss the immune response initiated following brain injuries, drawing on knowledge gained from a broad array of experimental and clinical studies. Our discussion seeks to address potential therapeutic targets and propose ways in which the immune system can be controlled to promote neuroprotection. PMID:24025052

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

    PubMed Central

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

    2017-01-01

    Objectives: 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. Methods: 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. Results: 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. Conclusion: 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. PMID:28890783

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

    PubMed

    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.

  20. Haemostatic drugs for traumatic brain injury.

    PubMed

    Perel, Pablo; Roberts, Ian; Shakur, Haleema; Thinkhamrop, Bandit; Phuenpathom, Nakornchai; Yutthakasemsunt, Surakrant

    2010-01-20

    Traumatic brain injury (TBI) is a leading cause of death and disability. Intracranial bleeding is a common complication of TBI, and intracranial bleeding can develop or worsen after hospital admission. Haemostatic drugs may reduce the occurrence or size of intracranial bleeds and consequently lower the morbidity and mortality associated with TBI. To assess the effects of haemostatic drugs on mortality, disability and thrombotic complications in patients with traumatic brain injury. We searched the electronic databases: Cochrane Injuries Group Specialised Register (3 February 2009), CENTRAL (The Cochrane Library 2009, Issue 1), MEDLINE (1950 to Week 3 2009), PubMed (searched 3 February 2009 (last 180 days)), EMBASE (1980 to Week 4 2009), CINAHL (1982 to January 2009), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to January 2009), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to January 2009). We included published and unpublished randomised controlled trials comparing haemostatic drugs (antifibrinolytics: aprotinin, tranexamic acid (TXA), aminocaproic acid or recombined activated factor VIIa (rFVIIa)) with placebo, no treatment, or other treatment in patients with acute traumatic brain injury. Two review authors independently examined all electronic records, and extracted the data. We judged that there was clinical heterogeneity between trials so we did not attempt to pool the results of the included trials. The results are reported separately. We included two trials. One was a post-hoc analysis of 30 TBI patients from a randomised controlled trial of rFVIIa in blunt trauma patients. The risk ratio for mortality at 30 days was 0.64 (95% CI 0.25 to 1.63) for rFVIIa compared to placebo. This result should be considered with caution as the subgroup analysis was not pre-specified for the trial. The other trial evaluated the effect of rFVIIa in 97 TBI patients with evidence of intracerebral bleeding in a

  1. Haemostatic drugs for traumatic brain injury

    PubMed Central

    Perel, Pablo; Roberts, Ian; Shakur, Haleema; Thinkhamrop, Bandit; Phuenpathom, Nakornchai; Yutthakasemsunt, Surakrant

    2014-01-01

    Background Traumatic brain injury (TBI) is a leading cause of death and disability. Intracranial bleeding is a common complication of TBI, and intracranial bleeding can develop or worsen after hospital admission. Haemostatic drugs may reduce the occurrence or size of intracranial bleeds and consequently lower the morbidity and mortality associated with TBI. Objectives To assess the effects of haemostatic drugs on mortality, disability and thrombotic complications in patients with traumatic brain injury. Search methods We searched the electronic databases: Cochrane Injuries Group Specialised Register (3 February 2009), CENTRAL (The Cochrane Library 2009, Issue 1), MEDLINE (1950 to Week 3 2009), PubMed (searched 3 February 2009 (last 180 days)), EMBASE (1980 to Week 4 2009), CINAHL (1982 to January 2009), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to January 2009), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to January 2009). Selection criteria We included published and unpublished randomised controlled trials comparing haemostatic drugs (antifibrinolytics: aprotinin, tranexamic acid (TXA), aminocaproic acid or recombined activated factor VIIa (rFVIIa)) with placebo, no treatment, or other treatment in patients with acute traumatic brain injury. Data collection and analysis Two review authors independently examined all electronic records, and extracted the data. We judged that there was clinical heterogeneity between trials so we did not attempt to pool the results of the included trials. The results are reported separately. Main results We included two trials. One was a post-hoc analysis of 30 TBI patients from a randomised controlled trial of rFVIIa in blunt trauma patients. The risk ratio for mortality at 30 days was 0.64 (95% CI 0.25 to 1.63) for rFVIIa compared to placebo. This result should be considered with caution as the subgroup analysis was not pre-specified for the trial. The other trial

  2. Ethics of neuroimaging after serious brain injury

    PubMed Central

    2014-01-01

    Background Patient outcome after serious brain injury is highly variable. Following a period of coma, some patients recover while others progress into a vegetative state (unresponsive wakefulness syndrome) or minimally conscious state. In both cases, assessment is difficult and misdiagnosis may be as high as 43%. Recent advances in neuroimaging suggest a solution. Both functional magnetic resonance imaging and electroencephalography have been used to detect residual cognitive function in vegetative and minimally conscious patients. Neuroimaging may improve diagnosis and prognostication. These techniques are beginning to be applied to comatose patients soon after injury. Evidence of preserved cognitive function may predict recovery, and this information would help families and health providers. Complex ethical issues arise due to the vulnerability of patients and families, difficulties interpreting negative results, restriction of communication to “yes” or “no” answers, and cost. We seek to investigate ethical issues in the use of neuroimaging in behaviorally nonresponsive patients who have suffered serious brain injury. The objectives of this research are to: (1) create an approach to capacity assessment using neuroimaging; (2) develop an ethics of welfare framework to guide considerations of quality of life; (3) explore the impact of neuroimaging on families; and, (4) analyze the ethics of the use of neuroimaging in comatose patients. Methods/Design Our research program encompasses four projects and uses a mixed methods approach. Project 1 asks whether decision making capacity can be assessed in behaviorally nonresponsive patients. We will specify cognitive functions required for capacity and detail their assessment. Further, we will develop and pilot a series of scenarios and questions suitable for assessing capacity. Project 2 examines the ethics of welfare as a guide for neuroimaging. It grounds an obligation to explore patients’ interests, and we

  3. Ethics of neuroimaging after serious brain injury.

    PubMed

    Weijer, Charles; Peterson, Andrew; Webster, Fiona; Graham, Mackenzie; Cruse, Damian; Fernández-Espejo, Davinia; Gofton, Teneille; Gonzalez-Lara, Laura E; Lazosky, Andrea; Naci, Lorina; Norton, Loretta; Speechley, Kathy; Young, Bryan; Owen, Adrian M

    2014-05-20

    Patient outcome after serious brain injury is highly variable. Following a period of coma, some patients recover while others progress into a vegetative state (unresponsive wakefulness syndrome) or minimally conscious state. In both cases, assessment is difficult and misdiagnosis may be as high as 43%. Recent advances in neuroimaging suggest a solution. Both functional magnetic resonance imaging and electroencephalography have been used to detect residual cognitive function in vegetative and minimally conscious patients. Neuroimaging may improve diagnosis and prognostication. These techniques are beginning to be applied to comatose patients soon after injury. Evidence of preserved cognitive function may predict recovery, and this information would help families and health providers. Complex ethical issues arise due to the vulnerability of patients and families, difficulties interpreting negative results, restriction of communication to "yes" or "no" answers, and cost. We seek to investigate ethical issues in the use of neuroimaging in behaviorally nonresponsive patients who have suffered serious brain injury. The objectives of this research are to: (1) create an approach to capacity assessment using neuroimaging; (2) develop an ethics of welfare framework to guide considerations of quality of life; (3) explore the impact of neuroimaging on families; and, (4) analyze the ethics of the use of neuroimaging in comatose patients. Our research program encompasses four projects and uses a mixed methods approach. Project 1 asks whether decision making capacity can be assessed in behaviorally nonresponsive patients. We will specify cognitive functions required for capacity and detail their assessment. Further, we will develop and pilot a series of scenarios and questions suitable for assessing capacity. Project 2 examines the ethics of welfare as a guide for neuroimaging. It grounds an obligation to explore patients' interests, and we explore conceptual issues in the

  4. Mania secondary to focal brain lesions: implications for understanding the functional neuroanatomy of bipolar disorder.

    PubMed

    Satzer, David; Bond, David J

    2016-05-01

    Approximately 3.5 million Americans will experience a manic episode during their lifetimes. The most common causes are psychiatric illnesses such as bipolar I disorder and schizoaffective disorder, but mania can also occur secondary to neurological illnesses, brain injury, or neurosurgical procedures. For this narrative review, we searched Medline for articles on the association of mania with stroke, brain tumors, traumatic brain injury, multiple sclerosis, neurodegenerative disorders, epilepsy, and neurosurgical interventions. We discuss the epidemiology, features, and treatment of these cases. We also review the anatomy of the lesions, in light of what is known about the neurobiology of bipolar disorder. The prevalence of mania in patients with brain lesions varies widely by condition, from <2% in stroke to 31% in basal ganglia calcification. Mania occurs most commonly with lesions affecting frontal, temporal, and subcortical limbic brain areas. Right-sided lesions causing hypo-functionality or disconnection (e.g., stroke; neoplasms) and left-sided excitatory lesions (e.g., epileptogenic foci) are frequently observed. Secondary mania should be suspected in patients with neurological deficits, histories atypical for classic bipolar disorder, and first manic episodes after the age of 40 years. Treatment with antimanic medications, along with specific treatment for the underlying neurologic condition, is typically required. Typical lesion locations fit with current models of bipolar disorder, which implicate hyperactivity of left-hemisphere reward-processing brain areas and hypoactivity of bilateral prefrontal emotion-modulating regions. Lesion studies complement these models by suggesting that right-hemisphere limbic-brain hypoactivity, or a left/right imbalance, may be relevant to the pathophysiology of mania. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Male body image following acquired brain injury.

    PubMed

    Howes, Hannah; Edwards, Stephen; Benton, David

    2005-02-01

    The purpose of this study was to investigate body image concerns and psycho-emotional health in males with acquired brain injury (ABI). Using a between subjects study of 25 males with ABI and 25 matched controls, variables were analysed using correlations and 2 x 2 analyses of variance (ANOVAs) with head injury and injury type as independent variables. Body image and psycho-emotional health were evaluated using self-report questionnaires. Disability and cognitive impairment were measured using a mixture of self-report, cognitive testing and clinical notes. Results indicated that males with ABI had significantly lower self-esteem and body dissatisfaction on a number of items relating to physical and sexual functioning. There were significant differences in body image between stroke and TBI, but there was no corresponding relationship with psycho-emotional health. These body image differences might be explained by age. The finding that ABI has a negative effect on body image and that this relates to psycho-emotional health should be investigated further, perhaps being included in future rehabilitation strategies.

  6. Brain injury, neuroinflammation and Alzheimer's disease

    PubMed Central

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

    2013-01-01

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

  7. Brain injury, neuroinflammation and Alzheimer's disease.

    PubMed

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

    2013-01-01

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

  8. A pathophysiological role of TRPV1 in ischemic injury after transient focal cerebral ischemia in mice

    SciTech Connect

    Miyanohara, Jun; Shirakawa, Hisashi; Sanpei, Kazuaki; Nakagawa, Takayuki; Kaneko, Shuji

    2015-11-20

    Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel with high Ca{sup 2+} permeability, which functions as a polymodal nociceptor activated by heat, protons and several vanilloids, including capsaicin and anandamide. Although TRPV1 channels are widely distributed in the mammalian brain, their pathophysiological roles in the brain remain to be elucidated. In this study, we investigated whether TRPV1 is involved in cerebral ischemic injury using a middle cerebral artery (MCA) occlusion model in wild-type (WT) and TRPV1-knockout (KO) mice. For transient ischemia, the left MCA of C57BL/6 mice was occluded for 60 min and reperfused at 1 and 2 days after ischemia. We found that neurological and motor deficits, and infarct volumes in TRPV1-KO mice were lower than those of WT mice. Consistent with these results, intracerebroventricular injection of a TRPV1 antagonist, capsazepine (20 nmol), 30 min before the onset of ischemia attenuated neurological and motor deficits and improved infarct size without influencing cerebral blood flow in the occluded MCA territory. The protective effect of capsazepine on ischemic brain damage was not observed in TRPV1-KO mice. WT and TRPV1-KO mice did not show any differences with respect to the increased number of Iba1-positive microglia/macrophages, GFAP-positive astrocytes, and Gr1-positive neutrophils at 1 and 2 days after cerebral ischemia. Taken together, we conclude that brain TRPV1 channels are activated by ischemic stroke and cause neurological and motor deficits and infarction after brain ischemia. - Highlights: • We investigated whether TRPV1 is involved in transient ischemic brain damage in mice. • Neurological deficits and infarct volumes were lower in TRPV1-KO mice than in WT mice. • Injection of a TRPV1 antagonist, capsazepine, attenuated neurological deficits and improved infarct size. • No differences in astrocytic or microglial activation were observed between WT and TRPV1-KO mice.

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  11. Apolipoprotein E-Mimetic COG1410 Reduces Acute Vasogenic Edema following Traumatic Brain Injury.

    PubMed

    Cao, Fang; Jiang, Yong; Wu, Yue; Zhong, Jianjun; Liu, Jieshi; Qin, Xinghu; Chen, Ligang; Vitek, Michael P; Li, Fengqiao; Xu, Lu; Sun, Xiaochuan

    2016-01-15

    The degree of post-traumatic brain edema and dysfunction of the blood-brain barrier (BBB) influences the neurofunctional outcome after a traumatic brain injury (TBI). Previous studies have demonstrated that the administration of apolipoprotein E-mimetic peptide COG1410 reduces the brain water content after subarachnoid hemorrhage, intra-cerebral hemorrhage, and focal brain ischemia. However, the effects of COG1410 on vasogenic edema following TBI are not known. The current study evaluated the effects of 1 mg/kg daily COG1410 versus saline administered intravenously after a controlled cortical impact (CCI) injury on BBB dysfunction and vasogenic edema at an acute stage in mice. The results demonstrated that treatment with COG1410 suppressed the activity of matrix metalloproteinase-9, reduced the disruption of the BBB and Evans Blue dye extravasation, reduced the TBI lesion volume and vasogenic edema, and decreased the functional deficits compared with mice treated with vehicle, at an acute stage after CCI. These findings suggest that COG1410 is a promising preclinical therapeutic agent for the treatment of traumatic brain injury.

  12. Apolipoprotein E-Mimetic COG1410 Reduces Acute Vasogenic Edema following Traumatic Brain Injury

    PubMed Central

    Cao, Fang; Wu, Yue; Zhong, Jianjun; Liu, Jieshi; Qin, Xinghu; Chen, Ligang; Vitek, Michael P.; Li, Fengqiao; Xu, Lu

    2016-01-01

    Abstract The degree of post-traumatic brain edema and dysfunction of the blood–brain barrier (BBB) influences the neurofunctional outcome after a traumatic brain injury (TBI). Previous studies have demonstrated that the administration of apolipoprotein E-mimetic peptide COG1410 reduces the brain water content after subarachnoid hemorrhage, intra-cerebral hemorrhage, and focal brain ischemia. However, the effects of COG1410 on vasogenic edema following TBI are not known. The current study evaluated the effects of 1 mg/kg daily COG1410 versus saline administered intravenously after a controlled cortical impact (CCI) injury on BBB dysfunction and vasogenic edema at an acute stage in mice. The results demonstrated that treatment with COG1410 suppressed the activity of matrix metalloproteinase-9, reduced the disruption of the BBB and Evans Blue dye extravasation, reduced the TBI lesion volume and vasogenic edema, and decreased the functional deficits compared with mice treated with vehicle, at an acute stage after CCI. These findings suggest that COG1410 is a promising preclinical therapeutic agent for the treatment of traumatic brain injury. PMID:26192010

  13. 77 FR 34363 - Disability and Rehabilitation Research Projects and Centers Program; Traumatic Brain Injury Model...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-11

    ... Disability and Rehabilitation Research Projects and Centers Program; Traumatic Brain Injury Model Systems... Program--Disability Rehabilitation Research Project (DRRP)-- Traumatic Brain Injury Model Systems Centers... priority for Traumatic Brain Injury Model Systems (TBIMS) Centers. The Assistant Secretary may use...

  14. Temperature modulation of cerebral depolarization during focal cerebral ischemia in rats: correlation with ischemic injury.

    PubMed

    Chen, Q; Chopp, M; Bodzin, G; Chen, H

    1993-05-01

    The role of cerebral depolarizations in focal cerebral ischemia is unknown. We therefore measured the direct current (DC) electrical activity in the cortex of Wistar rats subjected to transient occlusion of the middle cerebral artery (MCA). Focal ischemia was induced for 90 min by insertion of an intraluminal filament to occlude the MCA. To modulate cell damage, we subjected the rats to hypothermic (30 degrees C, n = 4), normothermic (37 degrees C, n = 4), and hyperthermic (40 degrees C, n = 6) ischemia. Controlled temperatures were also maintained during 1 h of reperfusion. Continuous cortical DC potential changes were measured using two active Ag-AgCl electrodes placed in the cortical lesion. Animals were killed 1 week after ischemia. The brains were sectioned and stained with hematoxylin and eosin, for evaluation of neuronal damage, and calculation of infarct volume. All animals exhibited an initial depolarization within 30 min of ischemia, followed by a single depolarization event in hypothermic animals, and multiple periodic depolarization events in both normothermic and hyperthermic animals. Hyperthermic animals exhibited significantly more (p < 0.05) DC potential deflections (n = 6.17 +/- 0.67) than normothermic animals (n = 2.75 +/- 0.96). The ischemic infarct volume (% of hemisphere) was significantly different for the various groups; hypothermic animals exhibited no measurable infarct volume, while the ischemic infarct volume was 10.2 +/- 12.3% in normothermic animals and 36.5 +/- 3.4% in hyperthermic animals (p < 0.05). A significant correlation was detected between the volume of infarct and number of depolarization events (r = 0.90, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

  15. The neuroinflammatory response in humans after traumatic brain injury.

    PubMed

    Smith, C; Gentleman, S M; Leclercq, P D; Murray, L S; Griffin, W S T; Graham, D I; Nicoll, J A R

    2013-10-01

    Traumatic brain injury is a significant cause of morbidity and mortality worldwide. An epidemiological association between head injury and long-term cognitive decline has been described for many years and recent clinical studies have highlighted functional impairment within 12 months of a mild head injury. In addition chronic traumatic encephalopathy is a recently described condition in cases of repetitive head injury. There are shared mechanisms between traumatic brain injury and Alzheimer's disease, and it has been hypothesized that neuroinflammation, in the form of microglial activation, may be a mechanism underlying chronic neurodegenerative processes after traumatic brain injury. This study assessed the microglial reaction after head injury in a range of ages and survival periods, from <24-h survival through to 47-year survival. Immunohistochemistry for reactive microglia (CD68 and CR3/43) was performed on human autopsy brain tissue and assessed 'blind' by quantitative image analysis. Head injury cases were compared with age matched controls, and within the traumatic brain injury group cases with diffuse traumatic axonal injury were compared with cases without diffuse traumatic axonal injury. A major finding was a neuroinflammatory response that develops within the first week and persists for several months after traumatic brain injury, but has returned to control levels after several years. In cases with diffuse traumatic axonal injury the microglial reaction is particularly pronounced in the white matter. These results demonstrate that prolonged microglial activation is a feature of traumatic brain injury, but that the neuroinflammatory response returns to control levels after several years. © 2012 British Neuropathological Society.

  16. Students with Acquired Brain Injury. The School's Response.

    ERIC Educational Resources Information Center

    Glang, Ann, Ed.; Singer, George H. S., Ed.; Todis, Bonnie, Ed.

    Designed for educators, this book focuses on educational issues relating to students with acquired brain injury (ABI), and describes approaches that have been effective in improving the school experiences of students with brain injury. Section 1 provides an introduction to issues related to ABI in children and youth and includes: "An Overview of…

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

    ERIC Educational Resources Information Center

    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…

  18. Brain Injury among Children and Adolescents. Tip Cards.

    ERIC Educational Resources Information Center

    Lash, Marilyn; Savage, Ron; DePompei, Roberta; Blosser, Jean

    These eight brochures for parents provide practical information and suggestions regarding various aspects of managing a child with a brain injury. The brochures are: (1) "Back to School after a Mild Brain Injury or Concussion," which covers helping the student in the classroom and changes that occur in school and knowing when extra help is needed…

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

    ERIC Educational Resources Information Center

    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…

  20. The Pediatric Test of Brain Injury: Development and Interpretation

    ERIC Educational Resources Information Center

    Hotz, Gillian A.; Helm-Estabrooks, Nancy; Nelson, Nickola Wolf; Plante, Elena

    2009-01-01

    The Pediatric Test of Brain Injury (PTBI) is designed to assess neurocognitive, language, and literacy abilities that are relevant to the school curriculum of children and adolescents recovering from brain injury. The PTBI is intended to help clinicians establish baseline levels of cognitive-linguistic abilities in the acute stages of recovery,…

  1. Students with Acquired Brain Injury. The School's Response.

    ERIC Educational Resources Information Center

    Glang, Ann, Ed.; Singer, George H. S., Ed.; Todis, Bonnie, Ed.

    Designed for educators, this book focuses on educational issues relating to students with acquired brain injury (ABI), and describes approaches that have been effective in improving the school experiences of students with brain injury. Section 1 provides an introduction to issues related to ABI in children and youth and includes: "An Overview of…

  2. The Pediatric Test of Brain Injury: Development and Interpretation

    ERIC Educational Resources Information Center

    Hotz, Gillian A.; Helm-Estabrooks, Nancy; Nelson, Nickola Wolf; Plante, Elena

    2009-01-01

    The Pediatric Test of Brain Injury (PTBI) is designed to assess neurocognitive, language, and literacy abilities that are relevant to the school curriculum of children and adolescents recovering from brain injury. The PTBI is intended to help clinicians establish baseline levels of cognitive-linguistic abilities in the acute stages of recovery,…

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

    DTIC Science & Technology

    2009-06-01

    microglia as ’sensors’ of injury in the pineal gland of rats following a non-penetrative blast." Neurosci Res 27(4): 317-322. ...including blood brain barrier disruption, glia activation and neuronal alterations. 15. SUBJECT TERMS blast; brain injury; experimental models

  4. Telerehabilitation needs: a survey of persons with acquired brain injury.

    PubMed

    Ricker, Joseph H; Rosenthal, Mitchell; Garay, Edward; DeLuca, John; Germain, Anneliese; Abraham-Fuchs, Klaus; Schmidt, Kai-Uwe

    2002-06-01

    To survey individuals with acquired brain injury to assess multiple facets of interest, access, and familiarity necessary to implement new telerehabilitation technologies. Anonymous mail survey. Community. Seventy-one respondents to a survey. These individuals had experienced acquired brain injury (predominantly severe traumatic brain injury [TBI]) and were living in the community. Surveys were mailed by a state chapter of the Brain Injury Association to a random selection of members with acquired brain injury. Survey designed specifically for this investigation. The survey responses indicate that there is great interest in the possibility of accessing telerehabilitative services among individuals with acquired brain injury. In particular, there was strong interest expressed in services that could be used to assist with problems in memory, attention, problem-solving, and activities of daily living. Telemedicine, and more specifically telerehabilitation, holds great promise as an adjunct to traditional clinical service delivery. Little research in this area has been applied, however, to individuals with acquired brain injuries. Although on the surface, telerehabilitation seems to be an appropriate assessment and treatment modality for individuals with brain injury, it will only succeed if those individuals have the interest-and the access-necessary to use new and evolving technologies.

  5. Brain Injury among Children and Adolescents. Tip Cards.

    ERIC Educational Resources Information Center

    Lash, Marilyn; Savage, Ron; DePompei, Roberta; Blosser, Jean

    These eight brochures for parents provide practical information and suggestions regarding various aspects of managing a child with a brain injury. The brochures are: (1) "Back to School after a Mild Brain Injury or Concussion," which covers helping the student in the classroom and changes that occur in school and knowing when extra help is needed…

  6. Novel Nitroxide Resuscitation Strategies in Experimental Traumatic Brain Injury

    DTIC Science & Technology

    2010-03-01

    peroxidase activity after traumatic brain injury. J Neurotrauma 2003;20:437–445. 68. Mavelli I, Rigo A, Federico R, et al. Superoxide dismutase, glu... Engel , C.C., and Castro, C.A. (2008). Mild traumatic brain injury in U.S. soldiers returning from Iraq. N. Engl. J. Med. 358, 453–463. Ling, G., Bandak

  7. Barbiturates for acute traumatic brain injury.

    PubMed

    Roberts, I

    2000-01-01

    Raised intracranial pressure (ICP) is an important complication of severe brain injury, and is associated with a high mortality rate. Barbiturates are believed to reduce intracranial pressure by suppressing cerebral metabolism, thus reducing cerebral metabolic demands and cerebral blood volume. However, barbiturates also reduce blood pressure and therefore may adversely effect cerebral perfusion pressure. To assess the effects of barbiturates in reducing raised intracranial pressure, mortality and morbidity in people with acute traumatic brain injury. To quantify any side effects resulting from the use of barbiturates. The review draws largely on the search strategy developed for the Cochrane Injuries Group as a whole. However, in addition the Cochrane Library was searched in December 1996 using the text terms "barbiturate*," "pentobarb*," "phenobarb*," "head," and "brain." An updated search was done in April 1999. Randomised or quasi randomised trials of any one or more of the barbiturate class of drugs (amobarbital, barbital, hexobarbital, mephobarbital, methohexital, murexide, pentobarbital, phenobarbital, secobarbital, thiobarbiturate) where study participants had a clinically diagnosed acute traumatic brain injury of any severity. The reviewer extracted the data and assessed the quality of allocation concealment in the trials. The pooled relative risk for death (barbiturate vs no barbiturate) was 1.09 (95%CI 0.81 to 1.47). The pooled effect of barbiturates on adverse neurological outcome, measured using the Glasgow Outcome Scale (death, persistent vegetative state or severe disability) was 1.15 (95% 0.81 to 1.64). Two studies examined the effect of barbiturate therapy on intracranial pressure. In the study by Eisenberger et al, a smaller proportion of patients in the barbiturate group had uncontrolled ICP (68% vs 83%). The relative risk for uncontrolled ICP was 0.81 (95%CI 0.62 to 1.06). Similarly, in the study by Ward et al, mean ICP was lower in the

  8. Laser Doppler flowmetry of focal ischaemia and reperfusion in deep brain structures in rats.

    PubMed

    Reith, W; Forsting, M; Weber, J; Stingele, R; Hacke, W; Sartor, K

    1994-01-01

    Monitoring cerebral blood flow during focal ischaemia and reperfusion with established techniques such as hydrogen clearance and autoradiography is difficult. Laser Doppler flowmetry is a new technique, it allows one to continuously measure blood flow in small tissue samples. The objective of this study was to compare laser Doppler flowmetry with hydrogen clearance using a new single fiber probe to obtain measurements in deep brain structures and then to show the temporal profile of cerebral blood flow during focal ischaemia and after reperfusion. First, the single fiber laser Doppler method was compared with the hydrogen clearance method in ten Wistar rats. Second, focal cerebral ischaemia was induced in fifteen Wistar rats using a model of middle cerebral artery occlusion based on the intravascular insertion of a nylon suture; reperfusion occurred after withdrawal of the suture. The laser Doppler probe was placed in the lateral caudatoputamen, and local cerebral blood flow was measured continuously before and during occlusion as well as after reperfusion. The relative blood flow values obtained by the laser Doppler method and the hydrogen clearance method showed a good correlation (r = 0.76) and a linear relationship. A rapid decrease in laser Doppler flowmetry to 42 +/- 16% of former baseline values was seen with occlusion of the middle cerebral artery; during occlusion cerebral blood flow remained at this level. Reperfusion resulted in a heterogeneous pattern of cerebral blood flow as laser Doppler flowmetry values ranged from 25% to 134% of baseline values. The effects of middle cerebral artery occlusion and reperfusion on cerebral blood flow can be monitored on-line with laser Doppler flowmetry.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Repetitive mild traumatic brain injury in a mouse model produces learning and memory deficits accompanied by histological changes.

    PubMed

    Mouzon, Benoit; Chaytow, Helena; Crynen, Gogce; Bachmeier, Corbin; Stewart, Janice; Mullan, Michael; Stewart, William; Crawford, Fiona

    2012-12-10

    Concussion or mild traumatic brain injury (mTBI) represents the most common type of brain injury. However, in contrast with moderate or severe injury, there are currently few non-invasive experimental studies that investigate the cumulative effects of repetitive mTBI using rodent models. Here we describe and compare the behavioral and pathological consequences in a mouse model of single (s-mTBI) or repetitive injury (r-mTBI, five injuries given at 48 h intervals) administered by an electromagnetic controlled impactor. Our results reveal that a single mTBI is associated with transient motor and cognitive deficits as demonstrated by rotarod and the Barnes Maze respectively, whereas r-mTBI results in more significant deficits in both paradigms. Histology revealed no overt cell loss in the hippocampus, although a reactive gliosis did emerge in hippocampal sector CA1 and in the deeper cortical layers beneath the injury site in repetitively injured animals, where evidence of focal injury also was observed in the brainstem and cerebellum. Axonal injury, manifest as amyloid precursor protein immunoreactive axonal profiles, was present in the corpus callosum of both injury groups, though more evident in the r-mTBI animals. Our data demonstrate that this mouse model of mTBI is reproducible, simple, and noninvasive, with behavioral impairment after a single injury and increasing deficits after multiple injuries accompanied by increased focal and diffuse pathology. As such, this model may serve as a suitable platform with which to explore repetitive mTBI relevant to human brain injury.

  10. Surgical brain injury: prevention is better than cure.

    PubMed

    Jadhav, Vikram; Zhang, John H

    2008-05-01

    Neurosurgical procedures can cause inevitable brain damage resulting from the procedure itself. Unavoidable cortical and parenchymal incisions, intraoperative hemorrhage, brain lobe retraction and thermal injuries from electrocautery can cause brain injuries attributable exclusively to the neurosurgical operations and collectively referred to as surgical brain injury (SBI). This particular brain damage cannot be demarcated from the underlying brain pathology and has not been studied previously. Recently, we developed rat and mouse models to study SBI and the underlying cellular mechanisms. The animal modeling mimics a neurosurgical operation and causes commonly encountered postoperative complications such as brain edema following blood brain barrier (BBB) disruption, and neuronal cell death. Furthermore, the SBI animal model allows screening of known experimental neuroprotective agents and therapeutic agents being tried in clinical trials as possible pretreatments before neurosurgical procedures. In the present review, we elaborate on SBI and its clinical impact, the SBI animal models and their clinical relevance, and the importance of blanket neuroprotection before neurosurgical procedures.

  11. A vascular injury model using focal heat-induced activation of endothelial cells

    PubMed Central

    Sylman, J.L.; Artzer, D.T.; Rana, K.; Neeves, K.B.

    2015-01-01

    Endothelial cells (EC) both inhibit and promote platelet function depending on their activation state. Quiescent EC inhibit platelet activation by constitutive secretion of platelet inhibitors. Activated EC promote platelet adhesion by secretion of von Willebrand factor (vWF). EC also secrete an extracellular matrix that support platelet adhesion when exposed following vascular injury. Previous studies of EC-platelet interactions under flow activate entire monolayers of cells by chemical activation. In this study, EC cultured in microfluidic channels were focally activated by heat from an underlying microelectrode. Based on finite element modeling, microelectrodes induced peak temperature increases of 10–40 °C above 37 °C after applying 5–9 V for 30 s resulting in three zones: (1) A quiescent zone corresponded to peak temperatures of less than 15 °C characterized by no EC activation or platelet accumulation. (2) An activation zone corresponding to an increase of 16–22 °C yielded EC that were viable, secreted elevated levels of vWF, and were P-selectin positive. Platelets accumulated in the retracted spaces between EC in the activation zone at a wall shear rate of 150 s−1. Experiments with blocking antibodies show that platelets adhere via GPIbα-vWF and α6β1-laminin interactions. (3) A kill zone corresponded to peak temperatures of greater than 23 °C where EC were not viable and did not support platelet adhesion. These data define heating conditions for the activation of EC, causing the secretion of vWF and the exposure of a subendothelial matrix that support platelet adhesion and aggregation. This model provides for spatially defined zones of EC activation that could be a useful tool for measuring the relative roles of anti- and prothrombotic roles of EC at the site of vascular injury. PMID:26087748

  12. Protective effect of focal adhesion kinase against skeletal muscle reperfusion injury after acute limb ischemia.

    PubMed

    Flück, M; von Allmen, R S; Ferrié, C; Tevaearai, H; Dick, F

    2015-03-01

    In cardiac muscle, ischemia reperfusion (IR) injury is attenuated by mitochondrial function, which may be upregulated by focal adhesion kinase (FAK). The aim of this study was to determine whether increased FAK levels reduced rhabdomyolysis in skeletal muscle too. In a translational in vivo experiment, rat lower limbs were subjected to 4 hours of ischemia followed by 24 or 72 hours of reperfusion. FAK expression was stimulated 7 days before (via somatic transfection with pCMV-driven FAK expression plasmid) and outcomes were measured against non-transfected and empty transfected controls. Slow oxidative (i.e., mitochondria-rich) and fast glycolytic (i.e., mitochondria-poor) type muscles were analyzed separately regarding rhabdomyolysis, apoptosis, and inflammation. Severity of IR injury was assessed using paired non-ischemic controls. After 24 hours of reperfusion, marked rhabdomyolysis was found in non-transfected and empty plasmid-transfected fast-type glycolytic muscle, tibialis anterior. Prior transfection enhanced FAK concentration significantly (p = 0.01). Concomitantly, levels of BAX, promoting mitochondrial transition pores, were reduced sixfold (p = 0.02) together with a blunted inflammation (p = 0.01) and reduced rhabdomyolysis (p = 0.003). Slow oxidative muscle, m. soleus, reacted differently: although apoptosis was detectable after IR, rhabdomyolysis did not appear before 72 hours of reperfusion; and FAK levels were not enhanced in ischemic muscle despite transfection (p = 0.66). IR-induced skeletal muscle rhabdomyolysis is a fiber type-specific phenomenon that appears to be modulated by mitochondria reserves. Stimulation of FAK may exploit these reserves constituting a potential therapeutic approach to reduce tissue loss following acute limb IR in fast-type muscle. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Training to Optimize Learning after Traumatic Brain Injury

    PubMed Central

    Skidmore, Elizabeth R.

    2015-01-01

    One of the major foci of rehabilitation after traumatic brain injury is the design and implementation of interventions to train individuals to learn new knowledge and skills or new ways to access and execute previously acquired knowledge and skills. To optimize these interventions, rehabilitation professionals require a clear understanding of how traumatic brain injury impacts learning, and how specific approaches may enhance learning after traumatic brain injury. This brief conceptual review provides an overview of learning, the impact of traumatic brain injury on explicit and implicit learning, and the current state of the science examining selected training approaches designed to advance learning after traumatic brain injury. Potential directions for future scientific inquiry are discussed throughout the review. PMID:26217546

  14. Missed diagnosis of traumatic brain injury in patients with traumatic spinal cord injury.

    PubMed

    Sharma, Bhanu; Bradbury, Cheryl; Mikulis, David; Green, Robin

    2014-04-01

    To determine the frequency of missed acute care traumatic brain injury diagnoses in patients with traumatic spinal cord injury, and to examine risk factors for missed traumatic brain injury diagnosis. Prospective magnetic resonance imaging and neuro-psychological assessment plus retrospective medical record review, including computed tomography. Ninety-two adults with traumatic spinal cord injury recruited from a large, tertiary spinal cord injury program, initially referred from urban teaching hospitals with neurotrauma facilities. Diagnosis of traumatic brain injury made with clinical neurological indices (i.e., Glasgow Coma Scale, post-traumatic amnesia, and loss of consciousness), neuroimaging (computed tomography and structural magnetic resonance imaging), and neuropsychological tests of attention and speed of processing, memory, and executive function; all measures were validated on a case-by-case basis to rule out confounds. Missed traumatic brain injury diagnoses were made via acute care medical record review and were corroborated by patient/family report where possible. The frequency of missed traumatic brain injury diagnoses in our sample was 58.5%. Missed traumatic brain injury diagnoses were more frequent in injuries sustained outside of a motor vehicle collision (MVC), with 75.0% of acute care traumatic brain injury diagnoses missed in non-MVC patients vs. 42.9% missed in MVC patients. Among patients with non-MVC injuries, a comparable percentage of missed traumatic brain injury diagnoses were observed in patients with cervical (79%) and sub-cervical injuries (80%). In more than half of the traumatic spinal cord injury patients referred for in-patient rehabilitation, acute care diagnoses of traumatic brain injury were missed. A risk factor for missed diagnosis was an injury caused by a mechanism other than an MVC (e.g., falls, assaults), perhaps due to reduced expectations of traumatic brain injury in non-MVC patients. In our research study, we

  15. [Effects of combined ischemic postconditioning, remote ischemic postconditioning and naloxone postconditioning on focal cerebral ischemia-reperfusion injury in rats].

    PubMed

    Liu, Yi; Liao, Xu; Xue, Fu-shan; Xu, Ya-chao; Xiong, Jun; Yuan, Yu-jing; Wang, Qiang; Liu, Jian-hua; Zhao, Jia-xun

    2011-06-07

    To assess the effects of ischemic postconditioning, remote ischemic postconditioning and naloxone postconditioning on focal cerebral ischemia-reperfusion injury in rats. A total of 110 adult SD rats were randomly divided into 5 groups (n = 22 each). The focal cerebral ischemia-reperfusion injury was induced by a 90-minute occlusion of right middle cerebral artery (MCA) and a 24-hour reperfusion sequentially. Group 1 was of ischemia-reperfusion control; Group 2 ischemic postconditioning induced by three 30-second cycles of MCA occlusion followed by a 30-second reperfusion; Group 3 remote ischemic postconditioning performed via a transient occlusion of right femoral artery at 5 min before the initiation of reperfusion; Group 4 naloxone postconditioning with naloxone 10 mg/kg intraperitoneally injected at the initiation of reperfusion; Group 5 combined ischemic, remote ischemic & naloxone postconditioning performed simultaneously in accordance with the methods used in Groups 2, 3 & 4. The neurologic deficit scores (NDS) were obtained at 2 h & 24 h post-reperfusion. At 24 h post-reperfusion, the anesthetized rat was sacrificed by decapitation and the brain rapidly extracted to assess the size of cerebral infarct (n = 10), detect the cerebral expression of microtubule-associated protein-2 (MAP2) (n = 6), measure the plasma volume of cerebral tissues and quantify the diameter and segment length of cerebral microvessel (n = 6). There were no significant differences in the heart rate (HR) and mean arterial pressure (MAP) among the above five groups at all observed time points (P > 0.05). At 24 h post-reperfusion, the percentage of ischemic cerebral infarct size was 43% ± 6%, 31% ± 4%, 32% ± 5%, 28% ± 6% & 21% ± 7% in ipsilateral hemisphere area (i.e., cerebral infarct severity) in Groups 1-5 respectively. Compared with Group 1, the levels of NDS and cerebral infarct severity significantly decreased at ischemic side in Groups 2-5 (P < 0.05). And the cerebral expression

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

    PubMed Central

    Sun, Dong

    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 development 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. PMID:26981070

  17. Pediatric Traumatic Brain Injury. Special Topic Report #3.

    ERIC Educational Resources Information Center

    Waaland, Pamela K.; Cockrell, Janice L.

    This brief report summarizes what is known about pediatric traumatic brain injury, including the following: risk factors (e.g., males especially those ages 5 to 25, youth with preexisting problems including previous head injury victims, and children receiving inadequate supervision); life after injury; physical and neurological consequences (e.g.,…

  18. The enigma of "hidden" traumatic brain injury.

    PubMed

    Gordon, W A; Brown, M; Sliwinski, M; Hibbard, M R; Patti, N; Weiss, M J; Kalinsky, R; Sheerer, M

    1998-12-01

    To examine individuals with "hidden" traumatic brain injury (TBI), defined in this study as those who sustained a blow to the head, with altered mental status, and experienced a substantial number of the cognitive, behavioral, and emotional sequelae typically associated with brain injury but did not make the causal connection between the injury and its consequences. Comparison of four groups of individuals matched for age, gender, years of education, and duration of loss of consciousness. This study of hidden TBI followed the identification of 143 individuals who, within a larger study of people with TBI who live in the community, identified themselves as "nondisabled" (they were to be part of the comparison sample) but who had experienced a blow to the head that left them at minimum dazed and confused. 21 of these 143 individuals also reported large numbers of symptoms (eg, headaches, memory problems) associated with TBI. This group (Hidden TBI-High Symptoms group) was compared to three other matched samples: one with known TBI (Known Mild TBI group) and one with no disability (No Disability group) (both of which were drawn from the larger study), and one group of individuals who identified themselves as having no disability but who had experienced a blow to the head that resulted in a few symptoms (Head Trauma-Low Symptoms group). All study participants were administered an interview that incorporated several existing instruments documenting levels of reported symptoms, emotional well-being/distress, and vocational/social handicaps. The Hidden TBI-High Symptoms group was found to be similar to the Known Mild TBI group in terms of the number and types of symptoms experienced, whereas the Head Trauma-Low Symptoms group was similar in this respect to the No Disability group. The two former groups also evidenced high levels of emotional distress, whereas the two latter groups did not. However, on measures of handicap, the Hidden TBI-High Symptoms and Head Trauma

  19. Noninvasive Imaging of the High Frequency Brain Activity in Focal Epilepsy Patients

    PubMed Central

    Lu, Yunfeng; Worrell, Gregory A.; Zhang, Huishi Clara; Yang, Lin; Brinkmann, Benjamin; Nelson, Cindy

    2014-01-01

    High frequency (HF) activity represents a potential biomarker of the epileptogenic zone in epilepsy patients, the removal of which is considered to be crucial for seizure-free surgical outcome. We proposed a high frequency source imaging (HFSI) approach to noninvasively image the brain sources of scalp recorded high frequency EEG activity. Both computer simulation and clinical patient data analysis were performed to investigate the feasibility of using the HFSI approach to image the sources of HF activity from noninvasive scalp EEG recordings. The HF activity was identified from high-density scalp recordings after high-pass filtering the EEG data and the EEG segments with HF activity were concatenated together to form repetitive HF activity. Independent component analysis was utilized to extract the components corresponding to the HF activity. Noninvasive EEG source imaging using realistic geometric boundary element head modeling was then applied to image the sources of the pathological HF brain activity. Five medically intractable focal epilepsy patients were studied and the estimated sources were found to be concordant with the surgical resection or intracranial recordings of the patients. The present study demonstrates, for the first time, that source imaging from the scalp HF activity could help to localize the seizure onset zone (SOZ) and provide a novel noninvasive way of studying the epileptic brain in humans. This study also indicates the potential application of studying HF activity in the pre-surgical planning of medically intractable epilepsy patients. PMID:24845275

  20. A pathophysiological role of TRPV1 in ischemic injury after transient focal cerebral ischemia in mice.

    PubMed

    Miyanohara, Jun; Shirakawa, Hisashi; Sanpei, Kazuaki; Nakagawa, Takayuki; Kaneko, Shuji

    2015-11-20

    Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel with high Ca(2+) permeability, which functions as a polymodal nociceptor activated by heat, protons and several vanilloids, including capsaicin and anandamide. Although TRPV1 channels are widely distributed in the mammalian brain, their pathophysiological roles in the brain remain to be elucidated. In this study, we investigated whether TRPV1 is involved in cerebral ischemic injury using a middle cerebral artery (MCA) occlusion model in wild-type (WT) and TRPV1-knockout (KO) mice. For transient ischemia, the left MCA of C57BL/6 mice was occluded for 60 min and reperfused at 1 and 2 days after ischemia. We found that neurological and motor deficits, and infarct volumes in TRPV1-KO mice were lower than those of WT mice. Consistent with these results, intracerebroventricular injection of a TRPV1 antagonist, capsazepine (20 nmol), 30 min before the onset of ischemia attenuated neurological and motor deficits and improved infarct size without influencing cerebral blood flow in the occluded MCA territory. The protective effect of capsazepine on ischemic brain damage was not observed in TRPV1-KO mice. WT and TRPV1-KO mice did not show any differences with respect to the increased number of Iba1-positive microglia/macrophages, GFAP-positive astrocytes, and Gr1-positive neutrophils at 1 and 2 days after cerebral ischemia. Taken together, we conclude that brain TRPV1 channels are activated by ischemic stroke and cause neurological and motor deficits and infarction after brain ischemia.

  1. Levetiracetam Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

    PubMed

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

    2016-03-15

    Levetiracetam (LEV) is an antiepileptic agent targeting novel pathways. Coupled with a favorable safety profile and increasing empirical clinical use, it was the fifth drug tested by Operation Brain Trauma Therapy (OBTT). We assessed the efficacy of a single 15 min post-injury intravenous (IV) dose (54 or 170 mg/kg) on behavioral, histopathological, and biomarker outcomes after parasagittal fluid percussion brain injury (FPI), controlled cortical impact (CCI), and penetrating ballistic-like brain injury (PBBI) in rats. In FPI, there was no benefit on motor function, but on Morris water maze (MWM), both doses improved latencies and path lengths versus vehicle (p < 0.05). On probe trial, the vehicle group was impaired versus sham, but both LEV treated groups did not differ versus sham, and the 54 mg/kg group was improved versus vehicle (p < 0.05). No histological benefit was seen. In CCI, there was a benefit on beam balance at 170 mg/kg (p < 0.05 vs. vehicle). On MWM, the 54 mg/kg dose was improved and not different from sham. Probe trial did not differ between groups for either dose. There was a reduction in hemispheric tissue loss (p < 0.05 vs. vehicle) with 170 mg/kg. In PBBI, there was no motor, cognitive, or histological benefit from either dose. Regarding biomarkers, in CCI, 24 h glial fibrillary acidic protein (GFAP) blood levels were lower in the 170 mg/kg group versus vehicle (p < 0.05). In PBBI, GFAP blood levels were increased in vehicle and 170 mg/kg groups versus sham (p < 0.05) but not in the 54 mg/kg group. No treatment effects were seen for ubiquitin C-terminal hydrolase-L1 across models. Early single IV LEV produced multiple benefits in CCI and FPI and reduced GFAP levels in PBBI. LEV achieved 10 points at each dose, is the most promising drug tested thus far by OBTT, and the only drug to improve cognitive outcome in any model. LEV has been advanced to testing in the micropig model in OBTT.

  2. Dysbiosis in Crohn's disease - Joint action of stochastic injuries and focal inflammation in the gut

    PubMed Central

    Buttó, Ludovica F.; Haller, Dirk

    2017-01-01

    ABSTRACT Gut homeostasis involves interrelated biological networks that include the immune system, specialized cells of the epithelium, such as Paneth and goblet cells, as well as triggers derived from the microbiota. Disruption of these homeostatic interactions may lead to the pathogenesis of inflammatory bowel diseases (IBD). To develop more targeted and individual treatments in Crohn's disease and ulcerative colitis, it becomes more and more important to link key mechanisms of the disease pathogenesis to distinct IBD subsets. For the first time, our laboratory demonstrated a causal role of the microbiota for the development of Crohn's disease (CD)-like ileitis, supporting the hypothesis that a non-infectious, dysbiotic microbial ecosystem harbors aggressive traits relevant for the induction of chronic inflammation in the disease-susceptible host (i.e. TNFΔARE mouse model). Despite a growing body of evidence claiming a primary role for Paneth cells in the pathogenesis of ileal CD, we showed in the TNFΔARE mouse model that Paneth cell failure or exhaustion is a secondary event to inflammation. Therefore, additional mechanisms may act synergistically to initialize the development of CD-like pathology. Hereby, we propose a novel hypothesis suggesting that individual development of dysbiotic communities is based on stochastic injury and focal inflammation of the epithelial lining that propagate radially, finally leading to an aggressive microbial milieu. PMID:28102757

  3. Graph analysis of functional brain networks for cognitive control of action in traumatic brain injury.

    PubMed

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

    2012-04-01

    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 dispersed frontal and parietal activity during performance of cognitive control tasks. We constructed binary and weighted functional networks and calculated their topological properties using a graph theoretical approach. Twenty-three adults with traumatic brain injury and 26 age-matched controls were instructed to switch between coordination modes while making spatially and temporally coupled circular motions with joysticks during event-related functional magnetic resonance imaging. Results demonstrated that switching performance was significantly lower in patients with traumatic brain injury compared with control subjects. Furthermore, although brain networks of both groups exhibited economical small-world topology, altered functional connectivity was demonstrated in patients with traumatic brain injury. In particular, compared with controls, patients with traumatic brain injury showed increased connectivity degree and strength, and higher values of local efficiency, suggesting adaptive mechanisms in this group. Finally, the degree of increased connectivity was significantly correlated with poorer switching task performance and more severe brain injury. We conclude that analysing the functional brain network connectivity provides new insights into understanding cognitive control changes following brain injury.

  4. Quercetin attenuates cell apoptosis in focal cerebral ischemia rat brain via activation of BDNF-TrkB-PI3K/Akt signaling pathway.

    PubMed

    Yao, Rui-Qin; Qi, Da-Shi; Yu, Hong-Li; Liu, Jing; Yang, Li-Hua; Wu, Xiu-Xiang

    2012-12-01

    Many studies have demonstrated that apoptosis play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Neuroprotective effect of quercetin has been shown in a variety of brain injury models including ischemia/reperfusion. It is not clear whether BDNF-TrkB-PI3K/Akt signaling pathway mediates the neuroprotection of quercetin, though there has been some reports on the quercetin increased brain-derived neurotrophic factor (BDNF) level in brain injury models. We therefore first examined the neurological function, infarct volume and cell apoptosis in quercetin treated middle cerebral artery occlusion (MCAO) rats. Then the protein expression of BDNF, cleaved caspase-3 and p-Akt were evaluated in either the absence or presence of PI3K inhibitor (LY294002) or tropomyosin receptor kinase B (TrkB) receptor antagonist (K252a) by immunohistochemistry staining and western blotting. Quercetin significantly improved neurological function, while it decreased the infarct volume and the number of TdT mediated dUTP nick end labeling positive cells in MCAO rats. The protein expression of BDNF, TrkB and p-Akt also increased in the quercetin treated rats. However, treatment with LY294002 or K252a reversed the quercetin-induced increase of BDNF and p-Akt proteins and decrease of cleaved caspase-3 protein in focal cerebral ischemia rats. These results demonstrate that quercetin can decrease cell apoptosis in the focal cerebral ischemia rat brain and the mechanism may be related to the activation of BDNF-TrkB-PI3K/Akt signaling pathway.

  5. 78 FR 12334 - Proposed Collection; Comment Request: Federal Interagency Traumatic Brain Injury Research (FITBIR...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-22

    ... Traumatic Brain Injury Research (FITBIR) Informatics System Data Access Request SUMMARY: In compliance with.... Proposed Collection: Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System...

  6. Assessing the dosimetric accuracy of MR-generated synthetic CT images for focal brain VMAT radiotherapy

    PubMed Central

    Paradis, Eric; Cao, Yue; Lawrence, Theodore S.; Tsien, Christina; Vineberg, Karen; Balter, James M.

    2015-01-01

    Purpose To assess the dosimetric accuracy of synthetic CT volumes generated from MRI data for focal brain radiotherapy. Methods A study was conducted on 12 patients with gliomas who underwent both MR and CT imaging as part of their simulation for external beam treatment planning. Synthetic CT (MRCT) volumes were generated from the MR images. The patients’ clinical treatment planning directives were used to create 12 individual Volumetric Modulated Arc Therapy (VMAT) plans, which were then optimized 10 times on each of their respective CT and MRCT-derived electron density maps. Dose metrics derived from optimization criteria, as well as monitor units and gamma analyses, were evaluated to quantify differences between the imaging modalities. Results Mean differences between Planning Target Volume (PTV) doses on MRCT and CT plans across all patients were 0.0% (range −0.1 to 0.2%) for D95%, 0.0% (−0.7 to 0.6%) for D5%, and −0.2% (−1.0 to 0.2%) for Dmax. MRCT plans showed no significant change in monitor units (−0.4%) compared to CT plans. Organs at risk (OARs) had an average Dmax difference of 0.0 Gy (−2.2 to 1.9 Gy) over 85 structures across all 12 patients, with no significant differences when calculated doses approached planning constraints. Conclusions Focal brain VMAT plans optimized on MRCT images show excellent dosimetric agreement with standard CT-optimized plans. PTVs show equivalent coverage, and OARs do not show any overdose. These results indicate that MRI-derived synthetic CT volumes can be used to support treatment planning of most patients treated for intracranial lesions. PMID:26581151

  7. Real-time magnetic resonance-guided laser thermal therapy for focal metastatic brain tumors.

    PubMed

    Carpentier, Alexandre; McNichols, Roger J; Stafford, R Jason; Itzcovitz, Julian; Guichard, Jean-Pierre; Reizine, Daniel; Delaloge, Suzette; Vicaut, Eric; Payen, Didier; Gowda, Ashok; George, Bernard

    2008-07-01

    We report the initial results of a pilot clinical trial exploring the safety and feasibility of the first real-time magnetic resonance-guided laser-induced thermal therapy of treatment-resistant focal metastatic intracranial tumors. Patients with resistant metastatic intracranial tumors who had previously undergone chemotherapy, whole-brain radiation therapy, and radiosurgery and who were recused from surgery were eligible for this trial. Under local anesthesia, a Leksell stereotactic head frame was used to insert a water-cooled interstitial fiberoptic laser applicator inside the cranium. In the bore of a magnetic resonance imaging (MRI) scanner, laser energy was delivered to heat the tumor while continuous MRI was performed. A computer workstation extracted temperature-sensitive information to display images of laser heating and computed estimates of the thermal damage zone. Posttreatment MRI scans were used to confirm the zone of thermal necrosis, and follow-up was performed at 7, 15, 30, and 90 days after treatment. In all cases, the procedure was well tolerated without secondary effect, and patients were discharged to home within 14 hours after the procedure. Follow-up imaging showed an acute increase in apparent lesion volume followed by a gradual and steady decrease. No tumor recurrence within thermal ablation zones was noted. In this ongoing trial, a total of four patients have had six metastatic tumors treated with laser thermal ablations. Magnetic resonance-guided laser-induced thermal therapy appears to provide a new, efficient treatment for recurrent focal metastatic brain disease. This therapy is a prelude to the future development of closed-head interventional MRI techniques in neurosurgery.

  8. Fluoxetine and sertraline attenuate postischemic brain injury in mice.

    PubMed

    Shin, Tae Kyeong; Kang, Mi Sun; Lee, Ho Youn; Seo, Moo Sang; Kim, Si Geun; Kim, Chi Dae; Lee, Won Suk

    2009-06-01

    This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1alpha (HIF-1alpha) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1alpha proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

  9. Rehabilitation of persons with traumatic brain injury.

    PubMed

    The objective of this NIH Consensus Statement is to inform the biomedical research and clinical practice communities of the results of the NIH Consensus Development Conference on Rehabilitation of Persons with Traumatic Brain Injury. The statement provides state-of-the-art information regarding effective rehabilitation measures for persons who have suffered a traumatic brain injury (TBI) and presents the conclusions and recommendations of the consensus panel regarding these issues. In addition, the statement identifies those areas that deserve further investigation. Upon completion of this educational activity, the reader should possess a clear working clinical knowledge of the state of the art regarding this topic. The target audience for this statement includes, but is not limited to, pediatricians, family practitioners, internists, neurologists, physiatrists, psychologists, and behavioral medicine specialists. Participants were a non-Federal, nonadvocate, 16-member panel representing the fields of neuropsychology, neurology, psychiatry, behavioral medicine, family medicine, pediatrics, physical medicine and rehabilitation, speech and hearing, occupational therapy, nursing, epidemiology, biostatistics and the public. In addition, 23 experts from these same fields presented data to the panel and a conference audience of 883. The literature was searched through Medline and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. A compendium of evidence was prepared by the panel which included a contribution from a patient with TBI, a report from an Evidence Based Practice Center of the Agency for Health Care Policy and Research, and a report from the National Center for Injury Prevention and Control at the Centers for Disease Control and Prevention. Scientific evidence was given precedence over clinical anecdotal experience. The panel, answering predefined

  10. Critical care management of traumatic brain injury.

    PubMed

    Menon, D K; Ercole, A

    2017-01-01

    Traumatic brain injury (TBI) is a growing global problem, which is responsible for a substantial burden of disability and death, and which generates substantial healthcare costs. High-quality intensive care can save lives and improve the quality of outcome. TBI is extremely heterogeneous in terms of clinical presentation, pathophysiology, and outcome. Current approaches to the critical care management of TBI are not underpinned by high-quality evidence, and many of the current therapies in use have not shown benefit in randomized control trials. However, observational studies have informed the development of authoritative international guidelines, and the use of multimodality monitoring may facilitate rational approaches to optimizing acute physiology, allowing clinicians to optimize the balance between benefit and risk from these interventions in individual patients. Such approaches, along with the emerging impact of advanced neuroimaging, genomics, and protein biomarkers, could lead to the development of precision medicine approaches to the intensive care management of TBI.

  11. Animal models of traumatic brain injury

    PubMed Central

    Xiong, Ye; Mahmood, Asim; Chopp, Michael

    2014-01-01

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

  12. Hippocampal head atrophy after traumatic brain injury.

    PubMed

    Ariza, Mar; Serra-Grabulosa, Josep M; Junqué, Carme; Ramírez, Blanca; Mataró, Maria; Poca, Antonia; Bargalló, Nuria; Sahuquillo, Juan

    2006-01-01

    Traumatic brain injury (TBI) causes hippocampal damage. The hippocampus can be macroscopically divided into the head, body and tail, which differ in terms of their sensitivity to excitability and also in terms of their cortical connections. We investigated whether damage also varies according to the hippocampal area involved, and studied the relationship of hippocampal reductions with memory performance. Twenty TBI patients and matched controls were examined. MRI measurements were performed separately for the hippocampal head, body and tail. Memory outcome was measured by Rey's auditory verbal learning test, Rey's complex figure test and a modified version of Warrington's facial recognition memory test. Group comparison showed that patients had bilateral hippocampal atrophy, mainly involving the hippocampal head. Moreover, TBI subjects showed verbal memory deficits which presented slight correlations with left hippocampal head atrophy.

  13. Normobaric hyperoxia retards the evolution of ischemic brain tissue toward infarction in a rat model of transient focal cerebral ischemia.

    PubMed

    Xu, Ji; Zhang, Yuan; Liang, Zhouyuan; Wang, Ting; Li, Weiping; Ren, Lijie; Huang, Shaonong; Liu, Wenlan

    2016-01-01

    Oxygen therapy has been long considered a logical therapy for ischemic stroke. Our previous studies showed that normobaric hyperoxia (normobaric hyperoxia (NBO), 95% O2 with 5% CO2) treatment during ischemia reduced ischemic neuronal death and cerebromicrovascular injury in animal stroke models. In this study, we studied the effects of NBO on the evolution of ischemic brain tissue to infarction in a rat model of transient focal cerebral ischemia. Male Sprague-Dawley rats were given NBO (95% O2) or normoxia (21% O2) during 90-min filament occlusion of the middle cerebral artery (MCAO), followed by 3 or 22.5 h of reperfusion. 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to evaluate the longitudinal evolution of tissue infarction. Results: In normoxic rats, MCA-supplied cortical and striatal tissue was infarcted after 90-min MCAO with 22.5 h of reperfusion. NBO-treated rats showed a 61.4% reduction in infarct size and tissue infarction mainly occurred in the ischemic striatum. When infarction was assessed at an earlier time point, i.e. at 3 h of reperfusion, normoxic rats showed significantly smaller but mature infarction (no TTC staining, white color), with the infarction mainly occurring in the striatum. Unexpectedly, NBO-treated rats only showed immature lesion (partially stained by TTC, light white color) in the ischemic striatum, indicating that NBO treatment also retarded the process of neuronal death in the ischemic core. Of note, NBO-preserved striatal tissue underwent infarction after prolonged reperfusion. Conclusions: Our results demonstrate that NBO treatment given during cerebral ischemia retards the evolution of ischemic brain tissue toward infarction and NBO-preserved cortical tissue survives better than NBO-preserved striatal tissue during the phase of reperfusion.

  14. Expression of TNF and TNF receptors (p55 and p75) in the rat brain after focal cerebral ischemia.

    PubMed Central

    Botchkina, G. I.; Meistrell, M. E.; Botchkina, I. L.; Tracey, K. J.

    1997-01-01

    Cerebral ischemia induces a rapid and dramatic up-regulation of tumor necrosis factor (TNF) protein and mRNA, but the cellular sources of TNF in the ischemic brain have not been defined. The diverse activities of TNF are mediated via ligand interaction with two distinct receptors, p55 and p75, which activate separate intracellular signal transduction pathways, leading to distinct biological effects. Since the effects of cerebral ischemia on TNF receptor (TNFR) expression are unknown, we examined the cellular localization and protein expression of TNF and its two receptors in the rat cerebral cortex in response to permanent middle cerebral artery (MCA) occlusion. The results indicate that focal. cerebral ischemia up-regulates expression of TNF and both TNFRs within the ischemic cortex. The most abundant type of TNF immunoreactivity (IR) was a punctate and filamentous pattern of transected cellular processes; however, cell bodies of neurons, astrocytes, and microglia, as well as infiltrating polymorphonuclear (PMN) leukocytes also showed TNF IR. Brain vasculature displayed TNF IR not only within endothelial cells but also in the perivascular space. MCA occlusion induced significant up-regulation of TNF receptors, with p55 IR appearing within 6 hr, significantly before the appearance of p75 IR at 24 hr after the onset of ischemia. Since p55 has been implicated in transducing cytotoxic signalling of TNF, these results support the proposed injurious role of excessive TNF produced during the acute response to cerebral ischemia. Images FIG. 7 FIG. 3 FIG. 1 FIG. 2 FIG. 4 FIG. 5 FIG. 6 FIG. 8 FIG. 9 PMID:9407552

  15. Pontine axonal injury after brain trauma and nontraumatic hypoxic-ischemic brain damage.

    PubMed

    Oehmichen, M; Meissner, C; Schmidt, V; Pedal, I; König, H G

    1999-01-01

    Experimental studies have shown that diffuse axonal injury is usually induced by positive or negative acceleration mechanisms. In order to determine the reliability of axonal injury (AI) as a marker of this type of traumatic insult, we compared cases of trauma-induced focal cortical hemorrhage without dural involvement (n = 67) with cases of trauma-induced subdural bleeding without cortical hemorrhage (n = 26). Both groups exhibited a wide range of post-traumatic survival times. The injuries in the first group were caused mainly by direct impact to the head, those in the second by acceleration/deceleration mechanisms. The investigations were based primarily on immunohistochemical demonstration of antibodies targeted to beta-amyloid precursor protein (beta-APP) in the pons as a marker of AI and the results were assessed semiquantitatively. No significant differences were found between the two groups. In both groups AI was detected in 80-100% of cases with survival times of more than 3 h and two thirds of all positive cases showed pronounced positivity. Additional comparison of cases of brain death due to mechanical trauma (n = 14) with cases of brain death due to non-mechanical trauma (n = 18) also disclosed no significant intergroup differences. Finally, investigations of the pons in cases of non-traumatic death due to cerebral hypoxia/ischemia (n = 51) demonstrated AI with the same frequency as in the other groups, although the expression tended to be less pronounced. Our results confirm that beta-APP expression in the pons is a reliable indicator of AI but does not discriminate between injuries caused by traumatic strain or shearing mechanisms and secondary damage due to cerebral hypoxia/ischemia or edema. In the large majority of cases with prolonged post-traumatic survival, it can therefor