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Sample records for acute brain slices

  1. Targeting neurotransmitter receptors with nanoparticles in vivo allows single-molecule tracking in acute brain slices

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    Varela, Juan A.; Dupuis, Julien P.; Etchepare, Laetitia; Espana, Agnès; Cognet, Laurent; Groc, Laurent

    2016-03-01

    Single-molecule imaging has changed the way we understand many biological mechanisms, particularly in neurobiology, by shedding light on intricate molecular events down to the nanoscale. However, current single-molecule studies in neuroscience have been limited to cultured neurons or organotypic slices, leaving as an open question the existence of fast receptor diffusion in intact brain tissue. Here, for the first time, we targeted dopamine receptors in vivo with functionalized quantum dots and were able to perform single-molecule tracking in acute rat brain slices. We propose a novel delocalized and non-inflammatory way of delivering nanoparticles (NPs) in vivo to the brain, which allowed us to label and track genetically engineered surface dopamine receptors in neocortical neurons, revealing inherent behaviour and receptor activity regulations. We thus propose a NP-based platform for single-molecule studies in the living brain, opening new avenues of research in physiological and pathological animal models.

  2. GnRH neuron firing and response to GABA in vitro depend on acute brain slice thickness and orientation.

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    Constantin, Stephanie; Piet, Richard; Iremonger, Karl; Hwa Yeo, Shel; Clarkson, Jenny; Porteous, Robert; Herbison, Allan E

    2012-08-01

    The GnRH neurons exhibit long dendrites and project to the median eminence. The aim of the present study was to generate an acute brain slice preparation that enabled recordings to be undertaken from GnRH neurons maintaining the full extent of their dendrites or axons. A thick, horizontal brain slice was developed, in which it was possible to record from the horizontally oriented GnRH neurons located in the anterior hypothalamic area (AHA). In vivo studies showed that the majority of AHA GnRH neurons projected outside the blood-brain barrier and expressed c-Fos at the time of the GnRH surge. On-cell recordings compared AHA GnRH neurons in the horizontal slice (AHAh) with AHA and preoptic area (POA) GnRH neurons in coronal slices [POA coronal (POAc) and AHA coronal (AHAc), respectively]. AHAh GnRH neurons exhibited tighter burst firing compared with other slice orientations. Although α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) excited GnRH neurons in all preparations, γ-aminobutyric acid (GABA) was excitatory in AHAc and POAc but inhibitory in AHAh slices. GABA(A) receptor postsynaptic currents were the same in AHAh and AHAc slices. Intriguingly, direct activation of GABA(A) or GABA(B) receptors respectively stimulated and inhibited GnRH neurons regardless of slice orientation. Subsequent experiments indicated that net GABA effects were determined by differences in the ratio of GABA(A) and GABA(B) receptor-mediated effects in "long" and "short" dendrites of GnRH neurons in the different slice orientations. These studies document a new brain slice preparation for recording from GnRH neurons with their extensive dendrites/axons and highlight the importance of GnRH neuron orientation relative to the angle of brain slicing in studying these neurons in vitro.

  3. Effects of normobaric versus hyperbaric oxygen on cell injury induced by oxygen and glucose deprivation in acute brain slices.

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    Chazalviel, Laurent; Blatteau, Jean-Eric; Vallée, Nicolas; Risso, Jean-Jacques; Besnard, Stéphane; Abraini, Jacques H

    2016-01-01

    Normobaric oxygen (NBO) and hyperbaric oxygen (HBO) are emerging as a possible co-treatment of acute ischemic stroke. Both have been shown to reduce infarct volume, to improve neurologic outcome, to promote endogenous tissue plasminogen activator-induced thrombolysis and cerebral blood flow, and to improve tissue oxygenation through oxygen diffusion in the ischemic areas, thereby questioning the interest of HBO compared to NBO. In the present study, in order to investigate and compare the oxygen diffusion effects of NBO and HBO on acute ischemic stroke independently of their effects at the vascular level, we used acute brain slices exposed to oxygen and glucose deprivation, an ex vivo model of brain ischemia that allows investigating the acute effects of NBO (partial pressure of oxygen (pO2) = 1 atmospheres absolute (ATA) = 0.1 MPa) and HBO (pO2 = 2.5 ATA = 0.25 MPa) through tissue oxygenation on ischemia-induced cell injury as measured by the release of lactate dehydrogenase. We found that HBO, but not NBO, reduced oxygen and glucose deprivation-induced cell injury, indicating that passive tissue oxygenation (i.e. without vascular support) of the brain parenchyma requires oxygen partial pressure higher than 1 ATA.

  4. Analysis of acute brain slices by electron microscopy: a correlative light-electron microscopy workflow based on Tokuyasu cryo-sectioning.

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    Loussert Fonta, Celine; Leis, Andrew; Mathisen, Cliff; Bouvier, David S; Blanchard, Willy; Volterra, Andrea; Lich, Ben; Humbel, Bruno M

    2015-01-01

    Acute brain slices are slices of brain tissue that are kept vital in vitro for further recordings and analyses. This tool is of major importance in neurobiology and allows the study of brain cells such as microglia, astrocytes, neurons and their inter/intracellular communications via ion channels or transporters. In combination with light/fluorescence microscopies, acute brain slices enable the ex vivo analysis of specific cells or groups of cells inside the slice, e.g. astrocytes. To bridge ex vivo knowledge of a cell with its ultrastructure, we developed a correlative microscopy approach for acute brain slices. The workflow begins with sampling of the tissue and precise trimming of a region of interest, which contains GFP-tagged astrocytes that can be visualised by fluorescence microscopy of ultrathin sections. The astrocytes and their surroundings are then analysed by high resolution scanning transmission electron microscopy (STEM). An important aspect of this workflow is the modification of a commercial cryo-ultramicrotome to observe the fluorescent GFP signal during the trimming process. It ensured that sections contained at least one GFP astrocyte. After cryo-sectioning, a map of the GFP-expressing astrocytes is established and transferred to correlation software installed on a focused ion beam scanning electron microscope equipped with a STEM detector. Next, the areas displaying fluorescence are selected for high resolution STEM imaging. An overview area (e.g. a whole mesh of the grid) is imaged with an automated tiling and stitching process. In the final stitched image, the local organisation of the brain tissue can be surveyed or areas of interest can be magnified to observe fine details, e.g. vesicles or gold labels on specific proteins. The robustness of this workflow is contingent on the quality of sample preparation, based on Tokuyasu's protocol. This method results in a reasonable compromise between preservation of morphology and maintenance of

  5. Brain perfusion CT for acute stroke using a 256-slice CT: improvement of diagnostic information by large volume coverage

    Energy Technology Data Exchange (ETDEWEB)

    Dorn, F. [Technical University, Department of Radiology, Klinikum rechts der Isar, Munich (Germany); Institut fuer Radiologie, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Muenchen (Germany); Muenzel, D.; Meier, R.; Rummeny, E.J.; Huber, A. [Technical University, Department of Radiology, Klinikum rechts der Isar, Munich (Germany); Poppert, H. [Technical University, Department of Neurology, Klinikum rechts der Isar, Munich (Germany)

    2011-09-15

    To compare a 256-slice CT with a simulated standard CT for brain CT perfusion (CTP). CTP was obtained in 51 patients using a 256-slice CT (128 detector rows, flying z-focus, 8-cm detector width, 80 kV, 120mAs, 20 measurements, 1 CT image/2.5 s). Signal-to-noise ratios (SNR) were compared in grey and white matter. Perfusion maps were evaluated for cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) in hypoperfused areas and corresponding contralateral regions. Two reconstructed 10-mm slices for simulation of a standard CT (SDCT) were compared with the complete data sets (large-volume CT, LVCT). Adequate image quality was achieved in 50/51 cases. SNR were significantly different in grey and white matter. A perfusion deficit was present in 27 data sets. Differences between the hypoperfusions and the control regions were significant for MTT and CBF, but not for CBV. Three lesions were missed by SDCT but detected by LVCT; 24 lesions were covered incompletely by SDCT, and 6 by LVCT. 21 lesions were detected completely by LVCT, but none by SDCT. CTP imaging of the brain using an increased detector width can detect additional ischaemic lesions and cover most ischaemic lesions completely. (orig.)

  6. Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation

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    Tamar ePashut

    2014-06-01

    Full Text Available Although transcranial magnetic stimulation (TMS is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

  7. Organotypic slice culture of embryonic brain tissue.

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    Daza, Ray A M; Englund, Chris; Hevner, Robert F

    2007-12-01

    INTRODUCTIONThis protocol describes how to dissect, assemble, and cultivate mouse embryonic (E) brain tissue from age E11.5 to E18.5 (days) for organotypic slice culture. These preparations can be used for a variety of assays and studies including coculture of different brain regions, cell migration assays, axon guidance assays, and DNA electroporation experiments. During electroporation, an electric current is applied to the surface of a specific target area of the brain slice in order to open holes in the plasma membrane and introduce a plasmid of coding DNA. The floating slice-on-membrane construct helps to preserve the structural integrity of the brain slices, while maintaining easy experimental access and optimal viability. Experiments can be monitored in living slices (e.g., with confocal imaging), and further studies can be completed using slices that have been fixed and cryosectioned at the end of the experiment. Any region of embryonic brain or spinal tissue can be used in this protocol.

  8. Image reconstruction for brain CT slices

    Institute of Scientific and Technical Information of China (English)

    吴建明; 施鹏飞

    2004-01-01

    Different modalities in biomedical images, like CT, MRI and PET scanners, provide detailed cross-sectional views of human anatomy. This paper introduces three-dimensional brain reconstruction based on CT slices. It contains filtering, fuzzy segmentation, matching method of contours, cell array structure and image animation. Experimental results have shown its validity. The innovation is matching method of contours and fuzzy segmentation algorithm of CT slices.

  9. Neuroprotection against diisopropylfluorophosphate in acute hippocampal slices

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    Ferchmin, P. A.; Pérez, Dinely; Cuadrado, Brenda L.; Carrasco, Marimée; Martins, Antonio H.; Eterović, Vesna A.

    2015-01-01

    Diisopropylfluorophosphate (DFP) is an irreversible inhibitor of acetylcholine esterase (AChE) and a surrogate of the organophosphorus (OP) nerve agent sarin. The neurotoxicity of DFP was assessed as a reduction of population spike (PS) area elicited by synaptic stimulation in acute hippocampal slices. Two classical antidotes, atropine, and pralidoxime, and two novel antidotes, 4R-cembranotriene-diol (4R) and a caspase 9 inhibitor, were tested. Atropine, pralidoxime, and 4R significantly protected when applied 30 min after DFP. The caspase inhibitor was neuroprotective when applied 5–10 min before or after DFP, suggesting that early synaptic apoptosis is responsible for the loss of PSs. It is likely that apoptosis starts at the synapses and, if antidotes are not applied, descends to the cell bodies, causing death. The acute slice is a reliable tool for mechanistic studies, and the assessment of neurotoxicity and neuroprotection with PS areas is, in general, pharmacologically congruent with in vivo results and predicts the effect of drugs in vivo. 4R was first found to be neuroprotective in slices and later we demonstrated that 4R is neuroprotective in vivo. The mechanism of neurotoxicity of OPs is not well understood, and there is a need for novel antidotes that could be discovered using acute slices. PMID:26438150

  10. Preserving GABAergic interneurons in acute brain slices of mice using the N-methyl-D-glucamine-based artificial cerebrospinal fluid method.

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    Pan, Geng; Li, Yue; Geng, Hong-Yan; Yang, Jian-Ming; Li, Ke-Xin; Li, Xiao-Ming

    2015-04-01

    Defects in the function and development of GABAergic interneurons have been linked to psychiatric disorders, so preservation of these interneurons in brain slices is important for successful electrophysiological recording in various ex vivo methods. However, it is difficult to maintain the activity and morphology of neurons in slices from mice of >30 days old. Here we evaluated the N-methyl-D-glucamine (NMDG)-based artificial cerebrospinal fluid (aCSF) method for the preservation of interneurons in slices from mice of up to ∼6 months old and discussed the steps that may affect their quality during slicing. We found that the NMDG-aCSF method rescued more cells than sucrose-aCSF and successfully preserved different types of interneurons including parvalbumin- and somatostatin-positive interneurons. In addition, both the chemical and electrical synaptic signaling of interneurons were maintained. These results demonstrate that the NMDG-aCSF method is suitable for the preservation of interneurons, especially in studies of gap junctions.

  11. Long-term brain slice culturing in a microfluidic platform

    DEFF Research Database (Denmark)

    Vedarethinam, Indumathi; Avaliani, N.; Tønnesen, J.;

    2011-01-01

    In this work, we present the development of a transparent poly(methyl methacrylate) (PMMA) based microfluidic culture system for handling long-term brain slice cultures independent of an incubator. The different stages of system development have been validated by culturing GFP producing brain...... brain slice culturing for 16 days....

  12. Preliminary Study of Realistic Blast Impact on Cultured Brain Slices

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    2015-04-01

    hippocampal slice samples to better understand blast-induced brain damage. 15. SUBJECT TERMS RDX spheres , organotypic cultures of hippocampus, small...Preliminary Study of Realistic Blast Impact on Cultured Brain Slices by Thuvan Piehler, Rohan Banton, Lars Piehler, Richard Benjamin, Ray...Aberdeen Proving Ground, MD 21005-5066 ARL-TR-7197 April 2015 Preliminary Study of Realistic Blast Impact on Cultured Brain Slices Thuvan

  13. Anti-inflammatory efficacy of dexamethasone and Nrf2 activators in the CNS using brain slices as a model of acute injury.

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    Graber, David J; Hickey, William F; Stommel, Elijah W; Harris, Brent T

    2012-03-01

    Limiting excessive production of inflammatory mediators is an effective therapeutic strategy for many diseases. It's also a promising remedy for neurodegenerative diseases and central nervous system (CNS) injuries. Glucocorticoids are valuable anti-inflammatory agents, but their use is constrained by adverse side-effects. Activators of NF-E2-related factor-2 (Nrf2) signaling represent an attractive anti-inflammatory alternative. In this study, dexamethasone, a synthetic glucocorticoid, and several molecular activators of Nrf2 were evaluated for efficacy in slices of cerebral cortex derived from adult SJL/J mice. Cortical explants increased expression of IL-1β and TNF-α mRNAs in culture within 5 h of sectioning. This expression was inhibited with dexamethasone in the explant medium or injected systemically in mice before sectioning. Semi-synthetic triterpenoid (SST) derivatives, potent activators of the Nrf2 pathway, demonstrated fast-acting anti-inflammatory activity in microglia cultures, but not in the cortical slice system. Quercetin, luteolin, and dimethyl fumarate were also evaluated as molecular activators of Nrf2. While expression of inflammatory mediators in microglia cultures was inhibited, these compounds did not demonstrate anti-inflammatory efficacy in cortical slices. In conclusion, brain slices were amenable to pharmacological modification as demonstrated by anti-inflammatory activity with dexamethasone. The utilization of Nrf2 activators to limit inflammatory mediators within the CNS requires further investigation. Inactivity in CNS tissue, however, suggests their safe use without neurological side-effects in treating non-CNS disorders. Short-term CNS explants may provide a more accurate model of in vivo conditions than microglia cultures since the complex tissue microenvironment is maintained.

  14. Acute and Long-Term Effects of Noise Exposure on the Neuronal Spontaneous Activity in Cochlear Nucleus and Inferior Colliculus Brain Slices

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    Moritz Gröschel

    2014-01-01

    Full Text Available Noise exposure leads to an immediate hearing loss and is followed by a long-lasting permanent threshold shift, accompanied by changes of cellular properties within the central auditory pathway. Electrophysiological recordings have demonstrated an upregulation of spontaneous neuronal activity. It is still discussed if the observed effects are related to changes of peripheral input or evoked within the central auditory system. The present study should describe the intrinsic temporal patterns of single-unit activity upon noise-induced hearing loss of the dorsal and ventral cochlear nucleus (DCN and VCN and the inferior colliculus (IC in adult mouse brain slices. Recordings showed a slight, but significant, elevation in spontaneous firing rates in DCN and VCN immediately after noise trauma, whereas no differences were found in IC. One week postexposure, neuronal responses remained unchanged compared to controls. At 14 days after noise trauma, intrinsic long-term hyperactivity in brain slices of the DCN and the IC was detected for the first time. Therefore, increase in spontaneous activity seems to develop within the period of two weeks, but not before day 7. The results give insight into the complex temporal neurophysiological alterations after noise trauma, leading to a better understanding of central mechanisms in noise-induced hearing loss.

  15. Acute and long-term effects of noise exposure on the neuronal spontaneous activity in cochlear nucleus and inferior colliculus brain slices.

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    Gröschel, Moritz; Ryll, Jana; Götze, Romy; Ernst, Arne; Basta, Dietmar

    2014-01-01

    Noise exposure leads to an immediate hearing loss and is followed by a long-lasting permanent threshold shift, accompanied by changes of cellular properties within the central auditory pathway. Electrophysiological recordings have demonstrated an upregulation of spontaneous neuronal activity. It is still discussed if the observed effects are related to changes of peripheral input or evoked within the central auditory system. The present study should describe the intrinsic temporal patterns of single-unit activity upon noise-induced hearing loss of the dorsal and ventral cochlear nucleus (DCN and VCN) and the inferior colliculus (IC) in adult mouse brain slices. Recordings showed a slight, but significant, elevation in spontaneous firing rates in DCN and VCN immediately after noise trauma, whereas no differences were found in IC. One week postexposure, neuronal responses remained unchanged compared to controls. At 14 days after noise trauma, intrinsic long-term hyperactivity in brain slices of the DCN and the IC was detected for the first time. Therefore, increase in spontaneous activity seems to develop within the period of two weeks, but not before day 7. The results give insight into the complex temporal neurophysiological alterations after noise trauma, leading to a better understanding of central mechanisms in noise-induced hearing loss.

  16. Acute hypercapnic hyperoxia stimulates reactive species production in the caudal solitary complex of rat brain slices but does not induce oxidative stress.

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    Ciarlone, Geoffrey E; Dean, Jay B

    2016-12-01

    Central CO2 chemoreceptive neurons in the caudal solitary complex (cSC) are stimulated by hyperoxia via a free radical mechanism. Hyperoxia has been shown to increase superoxide and nitric oxide in the cSC, but it remains unknown how changes in Pco2 during hyperoxia affect the production of O2-dependent reactive oxygen and nitrogen species (RONS) downstream that can lead to increased levels of oxidative and nitrosative stress, cellular excitability, and, potentially, dysfunction. We used real-time fluorescence microscopy in rat brain slices to determine how hyperoxia and hypercapnic acidosis (HA) modulate one another in the production of key RONS, as well as colorimetric assays to measure levels of oxidized and nitrated lipids and proteins. We also examined the effects of CO2 narcosis and hypoxia before euthanasia and brain slice harvesting, as these neurons are CO2 sensitive and hypothesized to employ CO2/H(+) mechanisms that exacerbate RONS production and potentially oxidative stress. Our findings show that hyperoxia ± HA increases the production of peroxynitrite and its derivatives, whereas increases in Fenton chemistry are most prominent during hyperoxia + HA. Using CO2 narcosis before euthanasia modulates cellular sensitivity to HA postmortem and enhances the magnitude of the peroxynitrite pathway, but blunts the activity of Fenton chemistry. Overall, hyperoxia and HA do not result in increased production of markers of oxidative and nitrosative stress as expected. We postulate this is due to antioxidant and proteosomal removal of damaged lipids and proteins to maintain cell viability and avoid death during protracted hyperoxia.

  17. Localized gene transfer into organotypic hippocampal slice cultures and acute hippocampal slices

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    Casaccia-Bonnefil, P; Benedikz, Eirikur; Shen, H;

    1993-01-01

    Viral vectors derived from herpes simplex virus, type-1 (HSV), can transfer and express genes into fully differentiated, post-mitotic neurons. These vectors also transduce cells effectively in organotypic hippocampal slice cultures. Nanoliter quantities of a virus stock of HSVlac, an HSV vector...... or hippocampal slices. The rapid expression of beta-gal by HSVlac allowed efficient transduction of acute hippocampal slices. Many genes have been transduced and expressed using HSV vectors; therefore, this microapplication method can be applied to many neurobiological questions....

  18. An aerator for brain slice experiments in individual cell culture plate wells.

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    Dorris, David M; Hauser, Caitlin A; Minnehan, Caitlin E; Meitzen, John

    2014-12-30

    Ex vivo acute living brain slices are a broadly employed and powerful experimental preparation. Most new technology regarding this tissue has involved the chamber used when performing electrophysiological experiments. Alternatively we instead focus on the creation of a simple, versatile aerator designed to allow maintenance and manipulation of acute brain slices and potentially other tissue in a multi-well cell culture plate. Here we present an easily manufactured aerator designed to fit into a 24-well cell culture plate. It features a nylon mesh and a single microhole to enable gas delivery without compromising tissue stability. The aerator is designed to be individually controlled, allowing both high throughput and single well experiments. The aerator was validated by testing material leach, dissolved oxygen delivery, brain slice viability and neuronal electrophysiology. Example experiments are also presented, including a test of whether β1-adrenergic receptor activation regulates gene expression in ex vivo dorsal striatum using qPCR. Key differences include enhanced control over gas delivery to individual wells containing brain slices, decreased necessary volume, a sample restraint to reduce movement artifacts, the potential to be sterilized, the avoidance of materials that absorb water and small biological molecules, minimal production costs, and increased experimental throughput. This new aerator is of high utility and will be useful for experiments involving brain slices and other potentially tissue samples in 24-well cell culture plates. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Altered regulation of brain-derived neurotrophic factor protein in hippocampus following slice preparation.

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    Danzer, S C; Pan, E; Nef, S; Parada, L F; McNamara, J O

    2004-01-01

    Brain-derived neurotrophic factor (BDNF) and its cognate receptor tyrosine kinase B (TrkB) play important roles in regulating survival, structure, and function of CNS neurons. One method of studying the functions of these molecules has utilized in vitro hippocampal slice preparations. An important caveat to using slices, however, is that slice preparation itself might alter the expression of BDNF, thereby confounding experimental results. To address this concern, BDNF immunoreactivity was examined in rodent slices using two different methods of slice preparation. Rapid and anatomically selective regulation of BDNF content followed slice preparation using both methodologies; however, different patterns of altered BDNF immunoreactivity were observed. First, in cultured slices, BDNF content decreased in the dentate molecular layer and increased in the CA3 pyramidal cell layer and the mossy fiber pathway of the hippocampus after 30 min. Furthermore, an initially "punctate" pattern of BDNF labeling observed in the mossy fiber pathway of control sections changed to homogenous labeling of the pathway in vitro. In contrast to these findings, slices prepared as for acute slice physiology exhibited no change in BDNF content in the molecular layer and mossy fiber pathway 30 min after slicing, but exhibited significant increases in the dentate granule and CA3 pyramidal cell layers. These findings demonstrate that BDNF protein content is altered following slice preparation, that different methods of slice preparation produce different patterns of BDNF regulation, and raise the possibility that BDNF release and TrkB activation may also be regulated. These consequences of hippocampal slice preparation may confound analyses of exogenous or endogenous BDNF on hippocampal neuronal structure or function.

  20. Precise spatial and temporal control of oxygen within in vitro brain slices via microfluidic gas channels.

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    Gerardo Mauleon

    Full Text Available The acute brain slice preparation is an excellent model for studying the details of how neurons and neuronal tissue respond to a variety of different physiological conditions. But open slice chambers ideal for electrophysiological and imaging access have not allowed the precise spatiotemporal control of oxygen in a way that might realistically model stroke conditions. To address this problem, we have developed a microfluidic add-on to a commercially available perfusion chamber that diffuses oxygen throughout a thin membrane and directly to the brain slice. A microchannel enables rapid and efficient control of oxygen and can be modified to allow different regions of the slice to experience different oxygen conditions. Using this novel device, we show that we can obtain a stable and homogeneous oxygen environment throughout the brain slice and rapidly alter the oxygen tension in a hippocampal slice. We also show that we can impose different oxygen tensions on different regions of the slice preparation and measure two independent responses, which is not easily obtainable with current techniques.

  1. Cavitation Induced Structural and Neural Damage in Live Brain Tissue Slices: Relevance to TBI

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    2014-09-29

    the value of this experimental platform to investigate the single bubble cavitation- induced damage in a biological tissue is illustrated with an...Lei Wu, Malisa Sarntinoranont, Huikai Xie1. Refractive index measurement of acute rat brain tissue slices using optical coherence tomography, Optics...b-TBI, i.e. what is “broken”, in the brain during exposure to shock loading is currently unknown. While blast waves are well known to have negative

  2. Brain slices as models for neurodegenerative disease and screening platforms to identify novel therapeutics.

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    Cho, Seongeun; Wood, Andrew; Bowlby, Mark R

    2007-03-01

    Recent improvements in brain slice technology have made this biological preparation increasingly useful for examining pathophysiology of brain diseases in a tissue context. Brain slices maintain many aspects of in vivo biology, including functional local synaptic circuitry with preserved brain architecture, while allowing good experimental access and precise control of the extracellular environment, making them ideal platforms for dissection of molecular pathways underlying neuronal dysfunction. Importantly, these ex vivo systems permit direct treatment with pharmacological agents modulating these responses and thus provide surrogate therapeutic screening systems without recourse to whole animal studies. Virus or particle mediated transgenic expression can also be accomplished relatively easily to study the function of novel genes in a normal or injured brain tissue context.In this review we will discuss acute brain injury models in organotypic hippocampal and co-culture systems and the effects of pharmacological modulation on neurodegeneration. The review will also cover the evidence of developmental plasticity in these ex vivo models, demonstrating emergence of injury-stimulated neuronal progenitor cells, and neurite sprouting and axonal regeneration following pathway lesioning. Neuro-and axo-genesis are emerging as significant factors contributing to brain repair following many acute and chronic neurodegenerative disorders. Therefore brain slice models may provide a critical contextual experimental system to explore regenerative mechanisms in vitro.

  3. Novel culturing platform for brain slices and neuronal cells

    DEFF Research Database (Denmark)

    Svendsen, Winnie Edith; Al Atraktchi, Fatima Al-Zahraa; Bakmand, Tanya

    2015-01-01

    In this paper we demonstrate a novel culturing system for brain slices and neuronal cells, which can control the concentration of nutrients and the waste removal from the culture by adjusting the fluid flow within the device. The entire system can be placed in an incubator. The system has been te...... tested successfully with brain slices and PC12 cells. The culture substrate can be modified using metal electrodes and/or nanostructures for conducting electrical measurements while culturing and for better mimicking the in vivo conditions.......In this paper we demonstrate a novel culturing system for brain slices and neuronal cells, which can control the concentration of nutrients and the waste removal from the culture by adjusting the fluid flow within the device. The entire system can be placed in an incubator. The system has been...

  4. Whole brain CT perfusion on a 320-slice CT scanner

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    Jai Jai Shiva Shankar

    2011-01-01

    Full Text Available Computed tomography perfusion (CTP has been criticized for limited brain coverage. This may result in inadequate coverage of the lesion, inadequate arterial input function, or omission of the lesion within the target perfusion volume. The availability of 320-slice CT scanners offers whole brain coverage. This minimizes the chances of misregistration of lesions regardless of location, and makes the selection of the arterial input function easy. We present different clinical scenarios in which whole brain CTP is especially useful.

  5. 5-HT4-receptors modulate induction of long-term depression but not potentiation at hippocampal output synapses in acute rat brain slices.

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    Matthias Wawra

    Full Text Available The subiculum is the principal target of CA1 pyramidal cells and mediates hippocampal output to various cortical and subcortical regions of the brain. The majority of subicular pyramidal cells are burst-spiking neurons. Previous studies indicated that high frequency stimulation in subicular burst-spiking cells causes presynaptic NMDA-receptor dependent long-term potentiation (LTP whereas low frequency stimulation induces postsynaptic NMDA-receptor-dependent long-term depression (LTD. In the present study, we investigate the effect of 5-hydroxytryptamine type 4 (5-HT4 receptor activation and blockade on both forms of synaptic plasticity in burst-spiking cells. We demonstrate that neither activation nor block of 5-HT4 receptors modulate the induction or expression of LTP. In contrast, activation of 5-HT4 receptors facilitates expression of LTD, and block of the 5-HT4 receptor prevents induction of short-term depression and LTD. As 5-HT4 receptors are positively coupled to adenylate cyclase 1 (AC1, 5-HT4 receptors might modulate PKA activity through AC1. Since LTD is blocked in the presence of 5-HT4 receptor antagonists, our data are consistent with 5-HT4 receptor activation by ambient serotonin or intrinsically active 5-HT4 receptors. Our findings provide new insight into aminergic modulation of hippocampal output.

  6. The energy demand of fast neuronal network oscillations: insights from brain slice preparations

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    Oliver eKann

    2012-01-01

    Full Text Available Fast neuronal network oscillations in the gamma range (30-100 Hz in the cerebral cortex have been implicated in higher cognitive functions such as sensual perception, working memory, and, perhaps, consciousness. However, little is known about the energy demand of gamma oscillations. This is mainly caused by technical limitations that are associated with simultaneous recordings of neuronal activity and energy metabolism in small neuronal networks and at the level of mitochondria in vivo. Thus recent studies have focused on brain slice preparations to address the energy demand of gamma oscillations in vitro. Here, reports will be summarized and discussed that combined electrophysiological recordings, oxygen sensor microelectrodes and live-cell fluorescence imaging in acutely prepared slices and organotypic slice cultures of the hippocampus from both, mouse and rat. These reports consistently show that gamma oscillations can be reliably induced in hippocampal slice preparations by different pharmacological tools. They suggest that gamma oscillations are associated with high energy demand, requiring both rapid adaptation of oxidative energy metabolism and sufficient supply with oxygen and nutrients. These findings might help to explain the exceptional vulnerability of higher cognitive functions during pathological processes of the brain, such as circulatory disturbances, genetic mitochondrial diseases, and neurodegeneration.

  7. Human brain slices for epilepsy research: Pitfalls, solutions and future challenges.

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    Jones, Roland S G; da Silva, Anderson Brito; Whittaker, Roger G; Woodhall, Gavin L; Cunningham, Mark O

    2016-02-15

    Increasingly, neuroscientists are taking the opportunity to use live human tissue obtained from elective neurosurgical procedures for electrophysiological studies in vitro. Access to this valuable resource permits unique studies into the network dynamics that contribute to the generation of pathological electrical activity in the human epileptic brain. Whilst this approach has provided insights into the mechanistic features of electrophysiological patterns associated with human epilepsy, it is not without technical and methodological challenges. This review outlines the main difficulties associated with working with epileptic human brain slices from the point of collection, through the stages of preparation, storage and recording. Moreover, it outlines the limitations, in terms of the nature of epileptic activity that can be observed in such tissue, in particular, the rarity of spontaneous ictal discharges, we discuss manipulations that can be utilised to induce such activity. In addition to discussing conventional electrophysiological techniques that are routinely employed in epileptic human brain slices, we review how imaging and multielectrode array recordings could provide novel insights into the network dynamics of human epileptogenesis. Acute studies in human brain slices are ultimately limited by the lifetime of the tissue so overcoming this issue provides increased opportunity for information gain. We review the literature with respect to organotypic culture techniques that may hold the key to prolonging the viability of this material. A combination of long-term culture techniques, viral transduction approaches and electrophysiology in human brain slices promotes the possibility of large scale monitoring and manipulation of neuronal activity in epileptic microcircuits. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Differential Conditioning of Associative Synaptic Enhancement in Hippocampal Brain Slices

    Science.gov (United States)

    Kelso, Stephen R.; Brown, Thomas H.

    1986-04-01

    An electrophysiological stimulation paradigm similar to one that produces Pavlovian conditioning was applied to synaptic inputs to pyramidal neurons of hippocampal brain slices. Persistent synaptic enhancement was induced in one of two weak synaptic inputs by pairing high-frequency electrical stimulation of the weak input with stimulation of a third, stronger input to the same region. Forward (temporally overlapping) but not backward (temporally separate) pairings caused this enhancement. Thus hippocampal synapses in vitro can undergo the conditional and selective type of associative modification that could provide the substrate for some of the mnemonic functions in which the hippocampus is thought to participate.

  9. Fluorescence imaging of changes in intracellular chloride in living brain slices.

    Science.gov (United States)

    Inglefield, J R; Schwartz-Bloom, R D

    1999-06-01

    In brain slice preparations, chloride movements across the cell membrane of living cells are measured traditionally with 36Cl- tracer methods, Cl--selective microelectrodes, or whole-cell recording using patch clamp analysis. We have developed an alternative, noninvasive technique that uses the fluorescent Cl- ion indicator, 6-methoxy-N-ethylquinolinium iodide (MEQ), to study changes in intracellular Cl- by epifluorescence or UV laser scanning confocal microscopy. In brain slices taken from rodents younger than 22 days of age, excellent cellular loading is achieved with the membrane-permeable form of the dye, dihydro-MEQ. Subsequent intracellular oxidation of dihydro-MEQ to the Cl--sensitive MEQ traps the polar form of the dye inside the neurons. Because MEQ is a single-excitation and single-emission dye, changes in intracellular Cl- concentrations can be calibrated from the Stern-Volmer relationship, determined in separate experiments. Using MEQ as the fluorescent indicator for Cl-, Cl- flux through the gamma-aminobutyric acid (GABA)-gated Cl- channel (GABAA receptor) can be studied by dynamic video imaging and either nonconfocal (epifluorescence) or confocal microscopy in the acute brain slice preparation. Increases in intracellular Cl- quench MEQ fluorescence, thereby reflecting GABAA receptor activation. GABAA receptor functional activity can be measured in discrete cells located in neuroanatomically defined populations within areas such as the neocortex and hippocampus. Changes in intracellular Cl- can also be studied under various conditions such as oxygen/glucose deprivation ("in vitro ischemia") and excitotoxicity. In such cases, changes in cell volume may also occur due to the dependence of cell volume regulation on Na+, K+, and Cl- flux. Because changes in cell volume can affect optical fluorescence measurements, we assess cell volume changes in the brain slice using the fluorescent indicator calcein-AM. Determination of changes in MEQ fluorescence versus

  10. Fluidic system for long-term in vitro culturing and monitoring of organotypic brain slices

    DEFF Research Database (Denmark)

    Bakmand, Tanya; Troels-Smith, Ane R.; Dimaki, Maria

    2015-01-01

    Brain slice preparations cultured in vitro have long been used as a simplified model for studying brain development, electrophysiology, neurodegeneration and neuroprotection. In this paper an open fluidic system developed for improved long term culturing of organotypic brain slices is presented. ...

  11. A novel carbon fiber bundle microelectrode and modified brain slice chamber for recording long-term multiunit activity from brain slices.

    Science.gov (United States)

    Tcheng, T K; Gillette, M U

    1996-11-01

    The fabrication and characteristics of a novel multiunit recording electrode and modified brain slice chamber suitable for long-term recording from brain slices are described. The electrode consisted of an electrolyte-filled glass micropipette with a 20-50 microns thick wax-coated bundle of 5-micron diameter carbon fibers extending 2.5 cm from the tapered end and an AgCl-coated silver wire inserted into the open end and connected to a preamplifier. Both ends of the electrode were sealed with wax to prevent evaporation of the electrolyte. The brain slice was maintained over this extended period in an interface-type brain slice chamber modified to completely surround the slice with medium. Using this electrode, regular 24-h oscillations of spontaneous multiunit activity were recorded for 3 days from a single location in a 500 microns thick rat suprachiasmatic nucleus brain slice. Preliminary data suggest that this novel carbon fiber bundle electrode will be a favorable alternative to traditional metal electrodes for long-term recording of multiunit activity from brain slices.

  12. Slices

    KAUST Repository

    McCrae, James

    2011-01-01

    Minimalist object representations or shape-proxies that spark and inspire human perception of shape remain an incompletely understood, yet powerful aspect of visual communication. We explore the use of planar sections, i.e., the contours of intersection of planes with a 3D object, for creating shape abstractions, motivated by their popularity in art and engineering. We first perform a user study to show that humans do define consistent and similar planar section proxies for common objects. Interestingly, we observe a strong correlation between user-defined planes and geometric features of objects. Further we show that the problem of finding the minimum set of planes that capture a set of 3D geometric shape features is both NP-hard and not always the proxy a user would pick. Guided by the principles inferred from our user study, we present an algorithm that progressively selects planes to maximize feature coverage, which in turn influence the selection of subsequent planes. The algorithmic framework easily incorporates various shape features, while their relative importance values are computed and validated from the user study data. We use our algorithm to compute planar slices for various objects, validate their utility towards object abstraction using a second user study, and conclude showing the potential applications of the extracted planar slice shape proxies. © 2011 ACM.

  13. Profile analysis of hepatic porcine and murine brain tissue slices obtained with a vibratome.

    Science.gov (United States)

    Mattei, G; Cristiani, I; Magliaro, C; Ahluwalia, A

    2015-01-01

    This study is aimed at characterizing soft tissue slices using a vibratome. In particular, the effect of two sectioning parameters (i.e., step size and sectioning speed) on resultant slice thickness was investigated for fresh porcine liver as well as for paraformaldehyde-fixed (PFA-fixed) and fresh murine brain. A simple framework for embedding, sectioning and imaging the slices was established to derive their thickness, which was evaluated through a purposely developed graphical user interface. Sectioning speed and step size had little effect on the thickness of fresh liver slices. Conversely, the thickness of PFA-fixed murine brain slices was found to be dependent on the step size, but not on the sectioning speed. In view of these results, fresh brain tissue was sliced varying the step size only, which was found to have a significant effect on resultant slice thickness. Although precision-cut slices (i.e., with regular thickness) were obtained for all the tissues, slice accuracy (defined as the match between the nominal step size chosen and the actual slice thickness obtained) was found to increase with tissue stiffness from fresh liver to PFA-fixed brain. This quantitative investigation can be very helpful for establishing the most suitable slicing setup for a given tissue.

  14. Fast whole-brain optical tomography capable of automated slice-collection (Conference Presentation)

    Science.gov (United States)

    Yuan, Jing; Jiang, Tao; Deng, Lei; Long, Beng; Peng, Jie; Luo, Qingming; Gong, Hui

    2016-03-01

    Acquiring brain-wide composite information of neuroanatomical and molecular phenotyping is crucial to understand brain functions. However, current whole-brain imaging methods based on mechnical sectioning haven't achieved brain-wide acquisition of both neuroanatomical and molecular phenotyping due to the lack of appropriate whole-brain immunostaining of embedded samples. Here, we present a novel strategy of acquiring brain-wide structural and molecular maps in the same brain, combining whole-brain imaging and subsequent immunostaining of automated-collected slices. We developed a whole-brain imaging system capable of automatically imaging and then collecting imaged tissue slices in order. The system contains three parts: structured illumination microscopy for high-throughput optical sectioning, vibratome for high-precision sectioning and slice-collection device for automated collecting of tissue slices. Through our system, we could acquire a whole-brain dataset of agarose-embedded mouse brain at lateral resolution of 0.33 µm with z-interval sampling of 100 µm in 9 h, and automatically collect the imaged slices in sequence. Subsequently, we performed immunohistochemistry of the collected slices in the routine way. We acquired mouse whole-brain imaging datasets of multiple specific types of neurons, proteins and gene expression profiles. We believe our method could accelerate systematic analysis of brain anatomical structure with specific proteins or genes expression information and understanding how the brain processes information and generates behavior.

  15. Label-free dopamine imaging in live rat brain slices.

    Science.gov (United States)

    Sarkar, Bidyut; Banerjee, Arkarup; Das, Anand Kant; Nag, Suman; Kaushalya, Sanjeev Kumar; Tripathy, Umakanta; Shameem, Mohammad; Shukla, Shubha; Maiti, Sudipta

    2014-05-21

    Dopaminergic neurotransmission has been investigated extensively, yet direct optical probing of dopamine has not been possible in live cells. Here we image intracellular dopamine with sub-micrometer three-dimensional resolution by harnessing its intrinsic mid-ultraviolet (UV) autofluorescence. Two-photon excitation with visible light (540 nm) in conjunction with a non-epifluorescent detection scheme is used to circumvent the UV toxicity and the UV transmission problems. The method is established by imaging dopamine in a dopaminergic cell line and in control cells (glia), and is validated by mass spectrometry. We further show that individual dopamine vesicles/vesicular clusters can be imaged in cultured rat brain slices, thereby providing a direct visualization of the intracellular events preceding dopamine release induced by depolarization or amphetamine exposure. Our technique opens up a previously inaccessible mid-ultraviolet spectral regime (excitation ~270 nm, emission free imaging of native molecules in live tissue.

  16. Biocompatibility of silicon-based arrays of electrodes coupled to organotypic hippocampal brain slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne Winther; Noraberg, J; Thiébaud, P

    2001-01-01

    In this study we examined the passive biocompatibility of a three-dimensional microelectrode array (MEA), designed to be coupled to organotypic brain slice cultures for multisite recording of electrophysiological signals. Hippocampal (and corticostriatal) brain slices from 1-week-old (and newborn...

  17. Influence of Thin Slice Reconstruction on CT Brain Perfusion Analysis

    NARCIS (Netherlands)

    Bennink, Edwin; Oosterbroek, Jaap; Horsch, Alexander D.; Dankbaar, Jan Willem; Velthuis, BK; Viergever, Max A.; de Jong, Hugo W. A. M.

    2015-01-01

    Objectives Although CT scanners generally allow dynamic acquisition of thin slices (1 mm), thick slice (>= 5 mm) reconstruction is commonly used for stroke imaging to reduce data, processing time, and noise level. Thin slice CT perfusion (CTP) reconstruction may suffer less from partial volume effec

  18. Ex Vivo Optogenetic Dissection of Fear Circuits in Brain Slices.

    Science.gov (United States)

    Bosch, Daniel; Asede, Douglas; Ehrlich, Ingrid

    2016-04-05

    Optogenetic approaches are now widely used to study the function of neural populations and circuits by combining targeted expression of light-activated proteins and subsequent manipulation of neural activity by light. Channelrhodopsins (ChRs) are light-gated cation-channels and when fused to a fluorescent protein their expression allows for visualization and concurrent activation of specific cell types and their axonal projections in defined areas of the brain. Via stereotactic injection of viral vectors, ChR fusion proteins can be constitutively or conditionally expressed in specific cells of a defined brain region, and their axonal projections can subsequently be studied anatomically and functionally via ex vivo optogenetic activation in brain slices. This is of particular importance when aiming to understand synaptic properties of connections that could not be addressed with conventional electrical stimulation approaches, or in identifying novel afferent and efferent connectivity that was previously poorly understood. Here, a few examples illustrate how this technique can be applied to investigate these questions to elucidating fear-related circuits in the amygdala. The amygdala is a key region for acquisition and expression of fear, and storage of fear and emotional memories. Many lines of evidence suggest that the medial prefrontal cortex (mPFC) participates in different aspects of fear acquisition and extinction, but its precise connectivity with the amygdala is just starting to be understood. First, it is shown how ex vivo optogenetic activation can be used to study aspects of synaptic communication between mPFC afferents and target cells in the basolateral amygdala (BLA). Furthermore, it is illustrated how this ex vivo optogenetic approach can be applied to assess novel connectivity patterns using a group of GABAergic neurons in the amygdala, the paracapsular intercalated cell cluster (mpITC), as an example.

  19. Influence of Thin Slice Reconstruction on CT Brain Perfusion Analysis.

    Directory of Open Access Journals (Sweden)

    Edwin Bennink

    Full Text Available Although CT scanners generally allow dynamic acquisition of thin slices (1 mm, thick slice (≥5 mm reconstruction is commonly used for stroke imaging to reduce data, processing time, and noise level. Thin slice CT perfusion (CTP reconstruction may suffer less from partial volume effects, and thus yield more accurate quantitative results with increased resolution. Before thin slice protocols are to be introduced clinically, it needs to be ensured that this does not affect overall CTP constancy. We studied the influence of thin slice reconstruction on average perfusion values by comparing it with standard thick slice reconstruction.From 50 patient studies, absolute and relative hemisphere averaged estimates of cerebral blood volume (CBV, cerebral blood flow (CBF, mean transit time (MTT, and permeability-surface area product (PS were analyzed using 0.8, 2.4, 4.8, and 9.6 mm slice reconstructions. Specifically, the influence of Gaussian and bilateral filtering, the arterial input function (AIF, and motion correction on the perfusion values was investigated.Bilateral filtering gave noise levels comparable to isotropic Gaussian filtering, with less partial volume effects. Absolute CBF, CBV and PS were 22%, 14% and 46% lower with 0.8 mm than with 4.8 mm slices. If the AIF and motion correction were based on thin slices prior to reconstruction of thicker slices, these differences reduced to 3%, 4% and 3%. The effect of slice thickness on relative values was very small.This study shows that thin slice reconstruction for CTP with unaltered acquisition protocol gives relative perfusion values without clinically relevant bias. It does however affect absolute perfusion values, of which CBF and CBV are most sensitive. Partial volume effects in large arteries and veins lead to overestimation of these values. The effects of reconstruction slice thickness should be taken into account when absolute perfusion values are used for clinical decision making.

  20. Acute brain hemorrhage in dengue

    Institute of Scientific and Technical Information of China (English)

    Somsri Wiwanitkit; Viroj Wiwanitkit

    2014-01-01

    Dengue is a tropical arboviral infection that can have severe hemorrhagic complication.Acute brain hemorrhage in dengue is rare and is a big challenge in neurosurgery.To perform surgery for management of acute brain hemorrhage in dengue is a controversial issue.Here, the authors try to summarize the previous reports on this topic and compare neurosurgery versus conservative management.

  1. Optimized Protocol of Methanol Treatment for Immunofluorescent Staining in Fixed Brain Slices

    Science.gov (United States)

    Yuan, Feng; Cohen, Noam A.; Cohen, Akiva S.

    2017-01-01

    We optimized methanol treatment in paraformaldehyde-fixed slices for immunofluorescent staining of ependymal basal bodies in brain ventricles. As 100% methanol induced severe deformations to the slices (including rolling and folding over), we tried to decrease methanol concentration. We found that 33.3% to 75% methanol could result in ideal immunostaining of basal bodies without inducing obvious deformations. Instead of treating slices at −20°C (without proper cryoprotection measurements) as suggested in previous studies, we carried out methanol treatment at room temperature. Our modified protocol can not only raise immunostaining efficiency in tissue slices, it may also prevent potential freezing damages to the samples. PMID:26509907

  2. Using laser confocal scanning microscope to study ischemia-hypoxia injury in rat brain slice

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The level of lipid peroxidation and cellular necrosis in rat living brain slices during brain ischemia-hypoxia injury have been observed using a laser confocal scanning microscope (LCSM) with double labeling of fluorescent probes D-399 (2,7-dichlorofluorescin diacetate) and propidium iodide (PI).The hypoxia and/or reoxygenation injury in rat brain slices is markedly decreased by pretreatment with L-NG-nitro-arginine (L-NNA) and N-acetylcysteine (NAC),showing that the nitric oxide (NO) and other free radicals play an important role in brain ischemia-hypoxia injury.

  3. Three-dimensional electrode array for brain slice culture

    DEFF Research Database (Denmark)

    Vazquez Rodriguez, Patricia

    Multielektroder arrays (MEA) er rækker af elektroder mest i mikrometer størrelse, som er blevet brugt i stor omfang til at stimulere og måle elektrisk aktivitet fra neuronale netværker. Brug af disse for at analysere hjerne slices (hjerneskiver) kan give indsigt i interaktioner mellem neuroner...

  4. Monitoring axonal and somatodendritic dopamine release using fast-scan cyclic voltammetry in brain slices.

    Science.gov (United States)

    Patel, Jyoti C; Rice, Margaret E

    2013-01-01

    Brain dopamine pathways serve wide-ranging functions including the control of movement, reward, cognition, learning, and mood. Consequently, dysfunction of dopamine transmission has been implicated in clinical conditions such as Parkinson's disease, schizophrenia, addiction, and depression. Establishing factors that regulate dopamine release can provide novel insights into dopaminergic communication under normal conditions, as well as in animal models of disease in the brain. Here we describe methods for the study of somatodendritic and axonal dopamine release in brain slice preparations. Topics covered include preparation and calibration of carbon-fiber microelectrodes for use with fast-scan cyclic voltammetry, preparation of midbrain and forebrain slices, and procedures of eliciting and recording electrically evoked dopamine release from in vitro brain slices.

  5. Coupling of organotypic brain slice cultures to silicon-based arrays of electrodes

    DEFF Research Database (Denmark)

    Jahnsen, Henrik; Kristensen, Bjarne Winther; Thiébaud, P

    1999-01-01

    Fetal or early postnatal brain tissue can be cultured in viable and healthy condition for several weeks with development and preservation of the basic cellular and connective organization as so-called organotypic brain slice cultures. Here we demonstrate and describe how it is possible to establi...

  6. Binding of mescaline with subcellular fractions upon incubation of brain cortex slices with [14C] mescaline.

    Science.gov (United States)

    Datta, R K; Antopol, W; Ghosh, J J

    1977-01-01

    Incubation of brain cortex slices in the presence of glucose resulted in the permeation of about 65% of [14C] mescaline into slices. Of this, about one-third radioactivity was bound with nuclei, mitochondria, microsomes, and ribosomes. Dialysis of subcellular fractions did not markedly reduce the amounts of radioactivity bound to the fractions. The permeation into slices and the binding of mescaline to subcellular fractions were fairly time-dependent, but were inhibited by the presence of potassium cyanide, or by the absence of glucose and by heating to 80 degrees C for 1 min.

  7. Acute death of astrocytes in blast-exposed rat organotypic hippocampal slice cultures

    Science.gov (United States)

    Miller, Anna P.; Shah, Alok S.; Aperi, Brandy V.; Kurpad, Shekar N.; Stemper, Brian D.; Glavaski-Joksimovic, Aleksandra

    2017-01-01

    Blast traumatic brain injury (bTBI) affects civilians, soldiers, and veterans worldwide and presents significant health concerns. The mechanisms of neurodegeneration following bTBI remain elusive and current therapies are largely ineffective. It is important to better characterize blast-evoked cellular changes and underlying mechanisms in order to develop more effective therapies. In the present study, our group utilized rat organotypic hippocampal slice cultures (OHCs) as an in vitro system to model bTBI. OHCs were exposed to either 138 ± 22 kPa (low) or 273 ± 23 kPa (high) overpressures using an open-ended helium-driven shock tube, or were assigned to sham control group. At 2 hours (h) following injury, we have characterized the astrocytic response to a blast overpressure. Immunostaining against the astrocytic marker glial fibrillary acidic protein (GFAP) revealed acute shearing and morphological changes in astrocytes, including clasmatodendrosis. Moreover, overlap of GFAP immunostaining and propidium iodide (PI) indicated astrocytic death. Quantification of the number of dead astrocytes per counting area in the hippocampal cornu Ammonis 1 region (CA1), demonstrated a significant increase in dead astrocytes in the low- and high-blast, compared to sham control OHCs. However only a small number of GFAP-expressing astrocytes were co-labeled with the apoptotic marker Annexin V, suggesting necrosis as the primary type of cell death in the acute phase following blast exposure. Moreover, western blot analyses revealed calpain mediated breakdown of GFAP. The dextran exclusion additionally indicated membrane disruption as a potential mechanism of acute astrocytic death. Furthermore, although blast exposure did not evoke significant changes in glutamate transporter 1 (GLT-1) expression, loss of GLT-1-expressing astrocytes suggests dysregulation of glutamate uptake following injury. Our data illustrate the profound effect of blast overpressure on astrocytes in OHCs at 2 h

  8. Ultra-fast MRI of the human brain with simultaneous multi-slice imaging

    Science.gov (United States)

    Feinberg, David A.; Setsompop, Kawin

    2013-04-01

    The recent advancement of simultaneous multi-slice imaging using multiband excitation has dramatically reduced the scan time of the brain. The evolution of this parallel imaging technique began over a decade ago and through recent sequence improvements has reduced the acquisition time of multi-slice EPI by over ten fold. This technique has recently become extremely useful for (i) functional MRI studies improving the statistical definition of neuronal networks, and (ii) diffusion based fiber tractography to visualize structural connections in the human brain. Several applications and evaluations are underway which show promise for this family of fast imaging sequences.

  9. Effects of ketamine, midazolam, thiopental, and propofol on brain ischemia injury in rat cerebral cortical slices

    Institute of Scientific and Technical Information of China (English)

    Qing-shengXUE; Bu-weiYU; Ze-jianWANG; Hong-zhuanCHEN

    2004-01-01

    AIM: To compare the effects of ketamine, midazolam, thiopental, and propofol on brain ischemia by the model of oxygen-glucose deprivation (OGD) in rat cerebral cortical slices. METHODS: Cerebral cortical slices were incu-bated in 2 % 2,3,5-triphenyltetrazolium chloride (TTC) solution after OGD, the damages and effects of ketamine,midazolam, thiopental, and propofol were quantitativlye evaluated by ELISA reader of absorbance (A) at 490 nm,which indicated the red formazan extracted from slices, lactic dehydrogenase (LDH) releases in the incubated supernate were also measured. RESULTS: Progressive prolongation of OGD resulted in decreases of TTC staining.The percentage of tissue injury had a positive correlation with LDH releases, r=0.9609, P<0.01. Two hours of reincubation aggravated the decrease of TTC staining compared with those slices stained immediately after OGD(P<0.01). These four anesthetics had no effects on the TTC staining of slices. Ketamine completely inhibited thedecrease of A value induced by 10 min of OGD injury. High concentrations of midazolam (10 μmol/L) and thiopental (400μmol/L) partly attenuated this decrease. Propofol at high concentration (100 μmol/L) enhanced the decrease of A value induced by 10 min of OGD injury (P<0.01). CONCLUSION; Ketamine, high concentration of midazolam and thiopental have neuroprotective effects against OGD injury in rat cerebral cortical slices, while high concentration of propofol augments OGD injury in rat cerebral cortical slices.

  10. Astrocytes, but not neurons, exhibit constitutive activation of P2X7 receptors in mouse acute cortical slices under non-stimulated resting conditions.

    Science.gov (United States)

    Kamatsuka, Yosuke; Fukagawa, Manami; Furuta, Takahiro; Ohishi, Akihiro; Nishida, Kentaro; Nagasawa, Kazuki

    2014-01-01

    We previously demonstrated that the P2X7 receptor (P2X7R), a purinergic receptor, expressed by mouse cultured cortical astrocytes is constitutively activated without any exogenous stimulus, differing from the case of neurons. It is well known that astrocytic morphology differs between in vitro and in vivo situations, implying different functionalities. Brain acute slices are widely accepted as an in vitro experimental system that reflects in vivo cell conditions better than in vitro cell culture ones. We examined whether astrocytic P2X7Rs exhibited constitutive activation in mouse cortical slices. In acute cortical slices, P2X7R-immunoreactivity was detected in both glial fibrillary acidic protein-immunopositive astrocytes and microtubule-associated protein 2-immunopositive neurons. Astrocytic, but not neuronal, spontaneous uptake of propidium iodide, an indicator of P2X7R channel/pore activity, was inhibited by representative antagonists of P2X7R, but they had no effect on the uptake by astrocytes in membrane-permeabilized fixed slices. These findings indicate that astrocytes, but not neurons, in acute cortical slices exhibit constitutive activation of P2X7Rs under non-stimulated resting conditions as in the case of cell culture systems.

  11. Dose-response testing of peptides by hippocampal brain slice recording.

    Science.gov (United States)

    Phillips, M I; Palovcik, R A

    1989-01-01

    The brain slice chamber described offers a method of studying, with intracellular electrodes, the relationship of response to dose of peptides. By raising the level of the slices 1 mm above the level of flowing perfusion medium, we can test substances in known concentrations, free from artifacts, during long duration, stable intracellular recordings. Manipulation of Ca2+/Mg2+ ratios in the medium can help to define synaptic and second messenger mediation of the responses. The addition of substances to the perfusion medium in this system could be combined with iontophoresis and/or micropressure techniques. Pathways in the slices may also be stimulated electrically and analyzed for the involvement of various synaptic transmitters. The results with the method so far show distinct differences among the peptides studied. Thus, there are several advantages to this method in establishing the physiological role of peptides in the brain.

  12. Dibucaine mitigates spreading depolarization in human neocortical slices and prevents acute dendritic injury in the ischemic rodent neocortex.

    Directory of Open Access Journals (Sweden)

    W Christopher Risher

    Full Text Available Spreading depolarizations that occur in patients with malignant stroke, subarachnoid/intracranial hemorrhage, and traumatic brain injury are known to facilitate neuronal damage in metabolically compromised brain tissue. The dramatic failure of brain ion homeostasis caused by propagating spreading depolarizations results in neuronal and astroglial swelling. In essence, swelling is the initial response and a sign of the acute neuronal injury that follows if energy deprivation is maintained. Choosing spreading depolarizations as a target for therapeutic intervention, we have used human brain slices and in vivo real-time two-photon laser scanning microscopy in the mouse neocortex to study potentially useful therapeutics against spreading depolarization-induced injury.We have shown that anoxic or terminal depolarization, a spreading depolarization wave ignited in the ischemic core where neurons cannot repolarize, can be evoked in human slices from pediatric brains during simulated ischemia induced by oxygen/glucose deprivation or by exposure to ouabain. Changes in light transmittance (LT tracked terminal depolarization in time and space. Though spreading depolarizations are notoriously difficult to block, terminal depolarization onset was delayed by dibucaine, a local amide anesthetic and sodium channel blocker. Remarkably, the occurrence of ouabain-induced terminal depolarization was delayed at a concentration of 1 µM that preserves synaptic function. Moreover, in vivo two-photon imaging in the penumbra revealed that, though spreading depolarizations did still occur, spreading depolarization-induced dendritic injury was inhibited by dibucaine administered intravenously at 2.5 mg/kg in a mouse stroke model.Dibucaine mitigated the effects of spreading depolarization at a concentration that could be well-tolerated therapeutically. Hence, dibucaine is a promising candidate to protect the brain from ischemic injury with an approach that does not rely on

  13. Mini-ruby is rapidly taken up by neurons and astrocytes in organotypic brain slices.

    Science.gov (United States)

    Ullrich, Celine; Humpel, Christian

    2011-10-01

    Cholinergic neurons are intensively studied, because they degenerate in Alzheimer's disease. Although neurotracer techniques are widely used to study axonal transport, guidance, regeneration or sprouting it is not clear if cholinergic neurons can be stained by tracer techniques and studied in brain slices. The aim of the present study was to evaluate the characteristics of the neurotracer Mini-ruby in organotypic brain slices of the basal nucleus of Meynert (nBM), focusing on cholinergic neurons. Mini-ruby is a biotinylated dextran amine and is taken up very fast by a variety of cells. When 2-week old nerve growth factor-incubated brain slices of the nBM were treated with Mini-ruby crystals for 1 h, only a few (2-3%) cholinergic neurons were clearly labeled as shown by co-localization with choline acetyltransferase. The staining was found in neuN-positive neurons and microtubule associated protein-2 (MAP-2)-positive nerve fibers. A very rapid dynamic change was observed in these labeled varicosities within seconds. However, Mini-ruby was taken up also by many glutamine synthethase-positive astrocytes. At the site of Mini-ruby application an intense CD11b-positive microglial staining was evident. In conclusion, neurons and astrocytes in organotypic brain slices can be labeled very fast with the fluorescent dye Mini-ruby which undergoes dynamic processes.

  14. 3D Data Mapping and Real-Time Experiment Control and Visualization in Brain Slices.

    Science.gov (United States)

    Navarro, Marco A; Hibbard, Jaime V K; Miller, Michael E; Nivin, Tyler W; Milescu, Lorin S

    2015-10-20

    Here, we propose two basic concepts that can streamline electrophysiology and imaging experiments in brain slices and enhance data collection and analysis. The first idea is to interface the experiment with a software environment that provides a 3D scene viewer in which the experimental rig, the brain slice, and the recorded data are represented to scale. Within the 3D scene viewer, the user can visualize a live image of the sample and 3D renderings of the recording electrodes with real-time position feedback. Furthermore, the user can control the instruments and visualize their status in real time. The second idea is to integrate multiple types of experimental data into a spatial and temporal map of the brain slice. These data may include low-magnification maps of the entire brain slice, for spatial context, or any other type of high-resolution structural and functional image, together with time-resolved electrical and optical signals. The entire data collection can be visualized within the 3D scene viewer. These concepts can be applied to any other type of experiment in which high-resolution data are recorded within a larger sample at different spatial and temporal coordinates.

  15. Electrical coupling between hippocampal astrocytes in rat brain slices.

    Science.gov (United States)

    Meme, William; Vandecasteele, Marie; Giaume, Christian; Venance, Laurent

    2009-04-01

    Gap junctions in astrocytes play a crucial role in intercellular communication by supporting both biochemical and electrical coupling between adjacent cells. Despite the critical role of electrical coupling in the network organization of these glial cells, the electrophysiological properties of gap junctions have been characterized in cultures while no direct evidence has been sought in situ. In the present study, gap-junctional currents were investigated using simultaneous dual whole-cell patch-clamp recordings between astrocytes from rat hippocampal slices. Bidirectional electrotonic coupling was observed in 82% of the cell pairs with an average coupling coefficient of 5.1%. Double patch-clamp analysis indicated that junctional currents were independent of the transjunctional voltage over a range from -100 to +110 mV. Interestingly, astrocytic electrical coupling displayed weak low-pass filtering properties compared to neuronal electrical synapses. Finally, during uncoupling processes triggered by either the gap-junction inhibitor carbenoxolone or endothelin-1, an increase in the input resistance in the injected cell paralleled the decrease in the coupling coefficient. Altogether, these results demonstrate that hippocampal astrocytes are electrically coupled through gap-junction channels characterized by properties that are distinct from those of electrical synapses between neurons. In addition, gap-junctional communication is efficiently regulated by endogenous compounds. This is taken to represent a mode of communication that may have important implications for the functional role of astrocyte networks in situ.

  16. Functional imaging of single synapses in brain slices.

    Science.gov (United States)

    Oertner, Thomas G

    2002-11-01

    The strength of synaptic connections in the brain is not fixed, but can be modulated by numerous mechanisms. Traditionally, electrophysiology has been used to characterize connections between neurons. Electrophysiology typically reports the activity of populations of synapses, while most mechanisms of plasticity are thought to operate at the level of single synapses. Recently, two-photon laser scanning microscopy has enabled us to perform optical quantal analysis of individual synapses in intact brain tissue. Here we introduce the basic principle of the two-photon microscope and discuss its main differences compared to the confocal microscope. Using calcium imaging in dendritic spines as an example, we explain the advantages of simultaneous dual-dye imaging for quantitative calcium measurements and address two common problems, dye saturation and background fluorescence subtraction.

  17. Dopaminergic differentiation of human neural stem cells mediated by co-cultured rat striatal brain slices

    DEFF Research Database (Denmark)

    Anwar, Mohammad Raffaqat; Andreasen, Christian Maaløv; Lippert, Solvej Kølvraa

    2008-01-01

    Properly committed neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. To establish a setting for identification of secreted neural compounds promoting dopaminergic...... differentiation, we co-cultured cells from a human neural forebrain-derived stem cell line (hNS1) with rat striatal brain slices. In brief, coronal slices of neonatal rat striatum were cultured on semiporous membrane inserts placed in six-well trays overlying monolayers of hNS1 cells. After 12 days of co......-culture, large numbers of tyrosine hydroxylase (TH)-immunoreactive, catecholaminergic cells could be found underneath individual striatal slices. Cell counting revealed that up to 25.3% (average 16.1%) of the total number of cells in these areas were TH-positive, contrasting a few TH-positive cells (

  18. Hyperexcitability in combined entorhinal/hippocampal slices of adult rat after exposure to brain-derived neurotrophic factor.

    Science.gov (United States)

    Scharfman, H E

    1997-08-01

    Effects of brain-derived neurotrophic factor (BDNF) in area CA3, the dentate gyrus, and medial entorhinal cortex were examined electrophysiologically by bath application of BDNF in slices containing the hippocampus and entorhinal cortex. Bath application of 25-100 ng/ml BDNF for 30-90 min increased responses to single afferent stimuli in selective pathways in the majority of slices. In area CA3, responses to mossy fiber stimulation increased in 73% of slices and entorhinal cortex responses to white matter stimulation increased in 64% of slices. After exposure to BDNF, these areas also demonstrated evidence of hyperexcitability, because responses to repetitive stimulation (1-Hz paired pulses for several s) produced multiple population spikes in response to mossy fiber stimulation in CA3 or multiple field potentials in response to white matter stimulation in the entorhinal cortex. Repetitive field potentials persisted after repetitive stimulation ended and usually were followed by spreading depression. Enhancement of responses to single stimuli and hyperexcitability were never evoked in untreated slices or after bath application of boiled BDNF or cytochrome C. The tyrosine kinase antagonist K252a (2 microM) blocked the effects of BDNF. In area CA3, both the potentiation of responses to single stimuli and hyperexcitability showed afferent specificity, because responses to mossy fiber stimulation were affected but responses to fimbria or Schaffer collateral stimulation were not. In addition, regional specificity was demonstrated in that the dentate gyrus was much less affected. The effects of BDNF in area CA3 were similar to those produced by bath application of low doses of kainic acid, which is thought to modulate glutamate release from mossy fiber terminals by a presynaptic action. These results suggest that BDNF has acute effects on excitability in different areas of the hippocampal-entorhinal circuit. These effects appear to be greatest in areas that are highly

  19. Does brain slices from pentylenetetrazole-kindled mice provide a more predictive screening model for antiepileptic drugs?

    Science.gov (United States)

    Hansen, Suzanne L; Sterjev, Zoran; Werngreen, Marie; Simonsen, Bodil J; Knudsen, Katrine E; Nielsen, Ane H; Pedersen, Mikael E; Badolo, Lassiana; Kristiansen, Uffe; Vestergaard, Henrik T

    2012-05-05

    The cortical wedge is a commonly applied model for in vitro screening of new antiepileptic drugs (AEDs) and has been extensively used in characterization of well-known AEDs. However, the predictive validity of this model as a screening model has been questioned as, e.g., carbamazepine has been reported to lack effect in this model. The neuroplastic changes induced in acute and chronic animal models of epilepsy are known to affect the pharmacological profile of AEDs in vivo. Hence, we investigated whether brain slices from pentylenetetrazole (PTZ)-kindled animals could provide a more predictive screening model for AEDs. To this end, we compared the in vitro and in vivo pharmacological profile of several selected AEDs (phenobarbital, phenytoin, tiagabine, fosphenytoin, valproate, and carbamazepine) along with citalopram using the PTZ-kindled model and brain slices from naïve, saline-injected and PTZ-kindled mice. Our data suggest that the use of slices from PTZ-kindled mice in the cortical wedge does not increase the predictive validity of the model as an in vitro screening model for AEDs. Traditionally, the incidence of certain seizure types is widely used as a measure to characterize drug action in animal models of epilepsy. In our study, the anticonvulsant effect of the AEDs was investigated in vivo using several observational parameters (i.e., incidence and duration of convulsions, latency to clonic convulsions, and severity of convulsions). We found that including the observational parameter "severity" offered important additional information about the drug profile that would otherwise be lost if only a single parameter as "incidence" was used.

  20. Organotypic brain slice cultures of adult transgenic P301S mice--a model for tauopathy studies.

    Directory of Open Access Journals (Sweden)

    Agneta Mewes

    Full Text Available BACKGROUND: Organotypic brain slice cultures represent an excellent compromise between single cell cultures and complete animal studies, in this way replacing and reducing the number of animal experiments. Organotypic brain slices are widely applied to model neuronal development and regeneration as well as neuronal pathology concerning stroke, epilepsy and Alzheimer's disease (AD. AD is characterized by two protein alterations, namely tau hyperphosphorylation and excessive amyloid β deposition, both causing microglia and astrocyte activation. Deposits of hyperphosphorylated tau, called neurofibrillary tangles (NFTs, surrounded by activated glia are modeled in transgenic mice, e.g. the tauopathy model P301S. METHODOLOGY/PRINCIPAL FINDINGS: In this study we explore the benefits and limitations of organotypic brain slice cultures made of mature adult transgenic mice as a potential model system for the multifactorial phenotype of AD. First, neonatal (P1 and adult organotypic brain slice cultures from 7- to 10-month-old transgenic P301S mice have been compared with regard to vitality, which was monitored with the lactate dehydrogenase (LDH- and the MTT (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assays over 15 days. Neonatal slices displayed a constant high vitality level, while the vitality of adult slice cultures decreased significantly upon cultivation. Various preparation and cultivation conditions were tested to augment the vitality of adult slices and improvements were achieved with a reduced slice thickness, a mild hypothermic cultivation temperature and a cultivation CO(2 concentration of 5%. Furthermore, we present a substantial immunohistochemical characterization analyzing the morphology of neurons, astrocytes and microglia in comparison to neonatal tissue. CONCLUSION/SIGNIFICANCE: Until now only adolescent animals with a maximum age of two months have been used to prepare organotypic brain slices. The current study

  1. Intersection-based registration of slice stacks to form 3D images of the human fetal brain

    DEFF Research Database (Denmark)

    Kim, Kio; Hansen, Mads Fogtmann; Habas, Piotr;

    2008-01-01

    Clinical fetal MR imaging of the brain commonly makes use of fast 2D acquisitions of multiple sets of approximately orthogonal 2D slices. We and others have previously proposed an iterative slice-to-volume registration process to recover a geometrically consistent 3D image. However, these approac...

  2. Automatic brain cropping and atlas slice matching using a PCNN and a generalized invariant Hough transform

    Science.gov (United States)

    Swathanthira Kumar, M. M.; Sullivan, John M., Jr.

    2007-03-01

    Medical research is dominated by animal models, especially rats and mice. Within a species most laboratory subjects exhibit little variation in brain anatomy. This uniformity of features is used to crop regions of interest based upon a known, cropped brain atlas. For any study involving N subjects, image registration or alignment to an atlas is required to construct a composite result. A highly resolved stack of T2 weighted MRI anatomy images of a Sprague-Dawley rat was registered and cropped to a known segmented atlas. This registered MRI volume was used as the reference atlas. A Pulse Coupled Neural Network (PCNN) was used to separate brain tissue from surrounding structures, such as cranium and muscle. Each iteration of the PCNN produces binary images of increasing area as the intensity spectrum is increased. A rapid filtering algorithm is applied that breaks narrow passages connecting larger segmented areas. A Generalized Invariant Hough Transform is applied subsequently to each PCNN segmented area to identify which segmented reference slice it matches. This process is repeated for multiple slices within each subject. Since we have apriori knowledge of the image ordering and fields of view this information provides initial estimates for subsequent registration codes. This process of subject slice extraction to PCNN mask creations and GIHT matching with known atlas locations is fully automatic.

  3. Effects of the pyrethroid insecticide, deltamethrin, on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice

    DEFF Research Database (Denmark)

    Rekling, J C; Theophilidis, G

    1995-01-01

    We have studied the action of deltamethrin on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice. Deltamethrin depolarized the hypoglossal motoneurons, increased the background synaptic noise and reduced the frequency and amplitude of current elicited action...

  4. A Unified Approach to Diffusion Direction Sensitive Slice Registration and 3-D DTI Reconstruction From Moving Fetal Brain Anatomy

    DEFF Research Database (Denmark)

    Hansen, Mads Fogtmann; Seshamani, Sharmishtaa; Kroenke, Christopher

    2014-01-01

    This paper presents an approach to 3-D diffusion tensor image (DTI) reconstruction from multi-slice diffusion weighted (DW) magnetic resonance imaging acquisitions of the moving fetal brain. Motion scatters the slice measurements in the spatial and spherical diffusion domain with respect...... to the underlying anatomy. Previous image registration techniques have been described to estimate the between slice fetal head motion, allowing the reconstruction of 3D a diffusion estimate on a regular grid using interpolation. We propose Approach to Unified Diffusion Sensitive Slice Alignment and Reconstruction...... (AUDiSSAR) that explicitly formulates a process for diffusion direction sensitive DW-slice-to-DTI-volume alignment. This also incorporates image resolution modeling to iteratively deconvolve the effects of the imaging point spread function using the multiple views provided by thick slices acquired...

  5. Parkia biglobosa Improves Mitochondrial Functioning and Protects against Neurotoxic Agents in Rat Brain Hippocampal Slices

    Directory of Open Access Journals (Sweden)

    Kayode Komolafe

    2014-01-01

    Full Text Available Objective. Methanolic leaf extracts of Parkia biglobosa, PBE, and one of its major polyphenolic constituents, catechin, were investigated for their protective effects against neurotoxicity induced by different agents on rat brain hippocampal slices and isolated mitochondria. Methods. Hippocampal slices were preincubated with PBE (25, 50, 100, or 200 µg/mL or catechin (1, 5, or 10 µg/mL for 30 min followed by further incubation with 300 µM H2O2, 300 µM SNP, or 200 µM PbCl2 for 1 h. Effects of PBE and catechin on SNP- or CaCl2-induced brain mitochondrial ROS formation and mitochondrial membrane potential (ΔΨm were also determined. Results. PBE and catechin decreased basal ROS generation in slices and blunted the prooxidant effects of neurotoxicants on membrane lipid peroxidation and nonprotein thiol contents. PBE rescued hippocampal cellular viability from SNP damage and caused a significant boost in hippocampus Na+, K+-ATPase activity but with no effect on the acetylcholinesterase activity. Both PBE and catechin also mitigated SNP- or CaCl2-dependent mitochondrial ROS generation. Measurement by safranine fluorescence however showed that the mild depolarization of the ΔΨm by PBE was independent of catechin. Conclusion. The results suggest that the neuroprotective effect of PBE is dependent on its constituent antioxidants and mild mitochondrial depolarization propensity.

  6. Coronary ostial involvement in acute aortic dissection: detection with 64-slice cardiac CT.

    LENUS (Irish Health Repository)

    Ryan, E Ronan

    2012-02-01

    A 41-year-old man collapsed after lifting weights at a gym. Following admission to the emergency department, a 64-slice cardiac computed tomography (CT) revealed a Stanford Type A aortic dissection arising from a previous coarctation repair. Multiphasic reconstructions demonstrated an unstable, highly mobile aortic dissection flap that extended proximally to involve the right coronary artery ostium. Our case is an example of the application of electrocardiogram-gated cardiac CT in directly visualizing involvement of the coronary ostia in acute aortic dissection, which may influence surgical management.

  7. Minimum conditions for the induction of cortical spreading depression in brain slices

    Science.gov (United States)

    Tang, Yujie T.; Mendez, Jorge M.; Theriot, Jeremy J.; Sawant, Punam M.; López-Valdés, Héctor E.; Ju, Y. Sungtaek

    2014-01-01

    Cortical spreading depression (CSD) occurs during various forms of brain injury such as stroke, subarachnoid hemorrhage, and brain trauma, but it is also thought to be the mechanism of the migraine aura. It is therefore expected to occur over a range of conditions including the awake behaving state. Yet it is unclear how such a massive depolarization could occur under relatively benign conditions. Using a microfluidic device with focal stimulation capability in a mouse brain slice model, we varied extracellular potassium concentration as well as the area exposed to increased extracellular potassium to determine the minimum conditions necessary to elicit CSD. Importantly, we focused on potassium levels that are physiologically plausible (≤145 mM; the intracellular potassium concentration). We found a strong correlation between the threshold concentration and the slice area exposed to increased extracellular potassium: minimum area of exposure was needed with the highest potassium concentration, while larger areas were needed at lower concentrations. We also found that moderate elevations of extracellular potassium were able to elicit CSD in relatively small estimated tissue volumes that might be activated under noninjury conditions. Our results thus show that CSD may be inducible under the conditions that expected in migraine aura as well as those related to brain trauma. PMID:25122714

  8. Organotypic hippocampal slice cultures for studies of brain damage, neuroprotection and neurorepair

    DEFF Research Database (Denmark)

    Noraberg, Jens; Poulsen, Frantz Rom; Blaabjerg, Morten

    2005-01-01

    ), Alzheimer's disease (AD) and epilepsia. Studies of non-excitotoxic neurotoxic compounds and the experimental use of slice cultures in studies of HIV neurotoxicity, traumatic brain injury (TBI) and neurogenesis are included. For cerebral ischemia, experimental models with oxygen-glucose deprivation (OGD......) and exposure to glutamate receptor agonists (excitotoxins) are reviewed. For epilepsia, focus is on induction of seizures with effects on neuronal loss, axonal sprouting and neurogenesis. For Alzheimer's disease, the review centers on the use of beta-amyloid (Abeta) in different models, while the section...... on repair is focused on neurogenesis and cell migration. The culturing techniques, set-up of models, and analytical tools, including markers for neurodegeneration, like the fluorescent dye propidium iodide (PI), are reviewed and discussed. Comparisons are made between hippocampal slice cultures and other...

  9. Rapid imaging of mammalian brain slices with a compact light sheet fluorescent microscope

    Science.gov (United States)

    Yang, Zhengyi; Haslehurst, Peter; Scott, Suzanne; Emptage, Nigel; Dholakia, Kishan

    2017-02-01

    Light sheet fluorescent microscopy is able to provide high acquisition speed and high contrast images, as well as the low photo-bleaching and photo-damage brought to the sample. Here we describe a compact setup design optimized for applications in neuroscience, in particular fast imaging of sub-neuronal structures in mammalian brain slices. We report this prototype instrument is capable of rapid imaging wide area of the dendritic or axonal arbor of a dye-filled neuron in hippocampal slice. We also show several applications of this compact light sheet fluorescent microscope, to demonstrate that our approach offers a powerful functionality to the neuroscience community that is not achievable with traditional imaging methods.

  10. Coculture system with an organotypic brain slice and 3D spheroid of carcinoma cells.

    Science.gov (United States)

    Chuang, Han-Ning; Lohaus, Raphaela; Hanisch, Uwe-Karsten; Binder, Claudia; Dehghani, Faramarz; Pukrop, Tobias

    2013-10-09

    Patients with cerebral metastasis of carcinomas have a poor prognosis. However, the process at the metastatic site has barely been investigated, in particular the role of the resident (stromal) cells. Studies in primary carcinomas demonstrate the influence of the microenvironment on metastasis, even on prognosis(1,2). Especially the tumor associated macrophages (TAM) support migration, invasion and proliferation(3). Interestingly, the major target sites of metastasis possess tissue-specific macrophages, such as Kupffer cells in the liver or microglia in the CNS. Moreover, the metastatic sites also possess other tissue-specific cells, like astrocytes. Recently, astrocytes were demonstrated to foster proliferation and persistence of cancer cells(4,5). Therefore, functions of these tissue-specific cell types seem to be very important in the process of brain metastasis(6,7). Despite these observations, however, up to now there is no suitable in vivo/in vitro model available to directly visualize glial reactions during cerebral metastasis formation, in particular by bright field microscopy. Recent in vivo live imaging of carcinoma cells demonstrated their cerebral colonization behavior(8). However, this method is very laborious, costly and technically complex. In addition, these kinds of animal experiments are restricted to small series and come with a substantial stress for the animals (by implantation of the glass plate, injection of tumor cells, repetitive anaesthesia and long-term fixation). Furthermore, in vivo imaging is thus far limited to the visualization of the carcinoma cells, whereas interactions with resident cells have not yet been illustrated. Finally, investigations of human carcinoma cells within immunocompetent animals are impossible(8). For these reasons, we established a coculture system consisting of an organotypic mouse brain slice and epithelial cells embedded in matrigel (3D cell sphere). The 3D carcinoma cell spheres were placed directly next to

  11. Oligodendrocyte transcription factor 1 mRNA and protein expression in organotypic rat brain slices

    Institute of Scientific and Technical Information of China (English)

    Hong Cui; Lijun Yang; Dezhuang Huang; Wandong Zhang; Weijuan Han; Yanqing Yao; Wenxing Jiang

    2010-01-01

    Numerous studies have confirmed that oligodendrocyte transcription factor 1 (Olig-1) is vital for myelin repair. However, the effects of hypoxia and ischemia on Olig-1 expression remain unknown.In this study, Olig-1 mRNA and protein expressions were analyzed by in situ hybridization and immunohistochemistry, to determine the expression profile of Olig-1 in rat brain slices exposed to hypoxia and ischemia. Brains were obtained from 2-day-old Sprague-Dawley rats, and sections were randomly assigned to control and hypoxia/ischemia groups. Hematoxylin-eosin staining revealed karyorrhexis and karyopyknosis in cells from the hypoxia/ischemia group. Under electron microscopy, mitochondria swelling and neuropil edema were observed in the hypoxia/ischemia group. Olig-1 mRNA and protein expressions were increased at 1 day after hypoxia and ischemia treatment. These results suggest that in situ hybridization and immunohistochemistry could be used simultaneously to detect mRNA and protein expression in brain slices.

  12. Ethyl-eicosapentaenoate modulates changes in neurochemistry and brain lipids induced by parkinsonian neurotoxin 1-methyl-4-phenylpyridinium in mouse brain slices.

    Science.gov (United States)

    Meng, QingJia; Luchtman, Dirk W; El Bahh, Bouchaib; Zidichouski, Jeffrey A; Yang, Jun; Song, Cai

    2010-12-15

    Evidence suggests a link between Parkinson's disease and the dietary intake of omega (n)-3 and n-6 polyunsaturated fatty acids (PUFAs). Presently, we investigated whether an acute dose of parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) affects brain n-3 and n-6 PUFA content and expression of fatty acid metabolic enzymes cytosolic phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX-2) in brain slices from C57Bl/6 mice. Furthermore, we investigated whether feeding a diet of n-3 PUFA ethyl-eicosapentaenoate (E-EPA) to these mice can attenuate the MPP(+) induced changes in brain PUFA content and expression of cPLA2 and COX-2, and attenuate MPP(+) induced changes in neurotransmitters and metabolites and apoptotic markers, bax, bcl-2 and caspase-3. MPP(+) increased brain content of n-6 PUFAs linoleic acid and arachidonic acid, and increased the mRNA expression of cPLA2. MPP(+) also depleted striatal dopamine levels and increased dopamine turnover, and depleted noradrenaline levels in the frontal cortex. The neurotoxin induced increases in bax, bcl-2 and caspase-3 mRNA expression that approached significance. E-EPA by itself increased brain n-3 content, including EPA and docosapentaenoic acid (C22:5, n-3), and increased cortical dopamine. More importantly, E-EPA attenuated the MPP(+) induced increase in n-6 fatty acids content, partially attenuated the striatal dopaminergic turnover, and prevented the increases of pro-apoptotic bax and caspase-3 mRNAs. In conclusion, increases in n-6 PUFAs in the acute stage of exposure to parkinsonian neurotoxins may promote pro-inflammatory conditions. EPA may provide modest beneficial effects in Parkinson's disease, but further investigation is warranted.

  13. Inhibitory effects of matrine on electrical signals and amino acid neurotransmitters in hippocampal brain slices

    Institute of Scientific and Technical Information of China (English)

    Xuping Wang; Jiping Chen; Guizhi Zhao; Dan Shou; Xuezhi Hong; Jianmin Zhang

    2009-01-01

    BACKGROUND: Studies on electrical signals of hippocampal brain slices in vivo have shown that matrine inhibits benzylpenicillin sodium-induced activation of neuronal signal transduction.OBJECTIVE: To verify the inhibition effect of matrine on activation of electrical signals in rat brain slices and the role matrine plays in hippocampal amino acid transmitter release.DESIGN, TIME AND SETTING: The in vitro, neurophysiological, controlled experiment was performed in the Zhejiang Province Key Laboratory of Cardio-cerebrovascular Disease and Nerve System Drugs Appraisement and Chinese Traditional Medicine Screening and Research between July 2003 and May 2004. The in vivo, neuronal, biochemical experiment was performed in the Zhejiang Province Key Laboratory of Chinese Traditional Medicine Quality Standardization from July 2005 to December 2006.MATERIALS: Forty healthy, Sprague Dawley rats, 7-8 weeks old, and 120 healthy, ICR mice, 5-6weeks old, were included in this study, irrespective of gender. Matrine powder was provided by the National Institute for the Control of Pharmaceutical and Biological Products, China. Matrine injection was purchased from Zhuhai Biochemical Pharmaceutical Factory, China. Penicillin was bought from Shijiazhuang Pharmaceutical Group Co., Ltd., China.METHODS: (1) Rats were randomly assigned to four groups: control, penicillin model, and matrine high-dose and low-dose, with 10 rats in each group. The control group was perfused with artificial cerebrospinal fluid, in the remaining three groups, hippocampal brain slices were perfused with normal artificial cerebrospinal fluid containing 1x106 U/L penicillin for the first 10 minutes. The penicillin model group received artificial cerebrospinal fluid for an additional 30 minutes, while the matrine high-dose and low-dose groups received 0.1 g/L and 0.05 g/L matdne, respectively, for an additional 30 minutes. (2) Mice were randomly assigned to four groups (n=30). The matrine high-,medium-, and low

  14. Microelectrode array recordings of excitability of low Mg2+-induced acute hippocampal slices

    Institute of Scientific and Technical Information of China (English)

    Fan Yang; Xinwei Gong; Haiqing Gong; Puming Zhang; Peiji Liang; Qinchi LU

    2010-01-01

    Neuronal connections can be detected by neuronal network discharges in hippocampal neurons cultured on multi-electrodes.However,the multi-electrode-array(MEA)has not been widely used in hippocampal slice culture studies focused on epilepsy.The present study induced spontaneous synchronous epileptiform activity using low Mg2+artificial cerebrospinal fluid on acute hippocampal slices to record hippocampal discharges with MEA.Results showed that burst duration and average number of spikes in a burst were significantly greater in the CA3 compared with dentate gyrus and CA1 areas.In Schaffer cut-off group,CA1 area discharges disappeared,but synchronous discharges remained in the CA3 area.Moreover,synchronous discharge frequency in the Schaffer cut-off group was similar to control.However,burst duration and average number of spikes in a burst were significantly decreased compared with control(P < 0.05).Results demonstrated that highest neuronal excitability occurred in the CA3 area,and synchronous discharges induced by low Mg2+originated from the CA3 region.

  15. Glucose-stimulated calcium dynamics in islets of Langerhans in acute mouse pancreas tissue slices.

    Directory of Open Access Journals (Sweden)

    Andraž Stožer

    Full Text Available In endocrine cells within islets of Langerhans calcium ions couple cell stimulation to hormone secretion. Since the advent of modern fluorimetry, numerous in vitro studies employing primarily isolated mouse islets have investigated the effects of various secretagogues on cytoplasmic calcium, predominantly in insulin-secreting beta cells. Due to technical limitations, insights of these studies are inherently limited to a rather small subpopulation of outermost cells. The results also seem to depend on various factors, like culture conditions and duration, and are not always easily reconcilable with findings in vivo. The main controversies regard the types of calcium oscillations, presence of calcium waves, and the level of synchronized activity. Here, we set out to combine the in situ acute mouse pancreas tissue slice preparation with noninvasive fluorescent calcium labeling and subsequent confocal laser scanning microscopy to shed new light on the existing controversies utilizing an innovative approach enabling the characterization of responses in many cells from all layers of islets. Our experiments reproducibly showed stable fast calcium oscillations on a sustained plateau rather than slow oscillations as the predominant type of response in acute tissue slices, and that calcium waves are the mechanistic substrate for synchronization of oscillations. We also found indirect evidence that even a large amplitude calcium signal was not sufficient and that metabolic activation was necessary to ensure cell synchronization upon stimulation with glucose. Our novel method helped resolve existing controversies and showed the potential to help answer important physiological questions, making it one of the methods of choice for the foreseeable future.

  16. Examining the complex regulation and drug-induced plasticity of dopamine release and uptake using voltammetry in brain slices.

    Science.gov (United States)

    Ferris, Mark J; Calipari, Erin S; Yorgason, Jordan T; Jones, Sara R

    2013-05-15

    Fast scan cyclic voltammetry in brain slices (slice voltammetry) has been used over the last several decades to increase substantially our understanding of the complex local regulation of dopamine release and uptake in the striatum. This technique is routinely used for the study of changes that occur in the dopamine system associated with various disease states and pharmacological treatments, and to study mechanisms of local circuitry regulation of dopamine terminal function. In the context of this Review, we compare the relative advantages of voltammetry using striatal slice preparations versus in vivo preparations, and highlight recent advances in our understanding of dopamine release and uptake in the striatum specifically from studies that use slice voltammetry in drug-naïve animals and animals with a history of psychostimulant self-administration.

  17. Epileptiform synchronization and high-frequency oscillations in brain slices comprising piriform and entorhinal cortices.

    Science.gov (United States)

    Hamidi, S; Lévesque, M; Avoli, M

    2014-12-05

    We employed field potential recordings in extended in vitro brain slices form Sprague-Dawley rats containing the piriform and entorhinal cortices (PC and EC, respectively) to identify the characteristics of epileptiform discharges and concomitant high-frequency oscillations (HFOs, ripples: 80-200Hz, fast ripples: 250-500Hz) during bath application of 4-aminopyridine (4AP, 50μM). Ictal-like discharges occurred in PC and EC either synchronously or independently of each other; synchronous ictal discharges always emerged from a synchronous "fast" interictal background whereas asynchronous ictal discharges were preceded by a "slow" interictal event. In addition, asynchronous ictal discharges had longer duration and interval of occurrence than synchronous ictal discharges, and contained a higher proportion of ripples and fast ripples. Cutting the connections between PC and EC made synchronicity disappear and increased ictal discharges duration in the EC but failed in changing HFO occurrence in both areas. Finally, antagonizing ionotropic glutamatergic receptors abolished ictal activity in all experiments, increased the duration and rate of occurrence of interictal discharges occurring in PC-EC interconnected slices while it did not influence the slow asynchronous interictal discharges in both areas. Our results identify some novel in vitro interactions between olfactory (PC) and limbic (EC) structures that presumably contribute to in vivo ictogenesis as well.

  18. Histamine H1 and endothelin ETB receptors mediate phospholipase D stimulation in rat brain hippocampal slices.

    Science.gov (United States)

    Sarri, E; Picatoste, F; Claro, E

    1995-08-01

    Different neurotransmitter receptor agonists [carbachol, serotonin, noradrenaline, histamine, endothelin-1, and trans-(1S,3R)-aminocyclopentyl-1,3-dicarboxylic acid (trans-ACPD)], known as stimuli of phospholipase C in brain tissue, were tested for phospholipase D stimulation in [32P]Pi-prelabeled rat brain cortical and hippocampal slices. The accumulation of [32P]phosphatidylethanol was measured as an index of phospholipase D-catalyzed transphosphatidylation in the presence of ethanol. Among the six neurotransmitter receptor agonists tested, only noradrenaline, histamine, endothelin-1, and trans-ACPD stimulated phospholipase D in hippocampus and cortex, an effect that was strictly dependent of the presence of millimolar extracellular calcium concentrations. The effect of histamine (EC50 18 microM) was inhibited by the H1 receptor antagonist mepyramine with a Ki constant of 0.7 nM and was resistant to H2 and H3 receptor antagonists (ranitidine and tioperamide, respectively). Endothelin-1-stimulated phospholipase D (EC50 44 nM) was not blocked by BQ-123, a specific antagonist of the ETA receptor. Endothelin-3 and the specific ETB receptor agonist safarotoxin 6c were also able to stimulate phospholipase D with efficacies similar to that of endothelin-1, and EC50 values of 16 and 3 nM, respectively. These results show that histamine and endothelin-1 stimulate phospholipase D in rat brain through H1 and ETB receptors, respectively.

  19. Effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices

    Directory of Open Access Journals (Sweden)

    Torres I.L.S.

    2001-01-01

    Full Text Available It has been suggested that glucocorticoids released during stress might impair neuronal function by decreasing glucose uptake by hippocampal neurons. Previous work has demonstrated that glucose uptake is reduced in hippocampal and cerebral cortex slices 24 h after exposure to acute stress, while no effect was observed after repeated stress. Here, we report the effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices and on plasma glucose and corticosterone levels. Male adult Wistar rats were exposed to restraint 1 h/day for 50 days in the chronic model. In the acute model there was a single exposure. Immediately or 24 h after stress, the animals were sacrificed and the hippocampus and cerebral cortex were dissected, sliced, and incubated with Krebs buffer, pH 7.4, containing 5 mM glucose and 0.2 µCi D-[U-14C] glucose. CO2 production from glucose was estimated. Trunk blood was also collected, and both corticosterone and glucose were measured. The results showed that corticosterone levels after exposure to acute restraint were increased, but the increase was smaller when the animals were submitted to repeated stress. Blood glucose levels increased after both acute and repeated stress. However, glucose utilization, measured as CO2 production in hippocampal and cerebral cortex slices, was the same in stressed and control groups under conditions of both acute and chronic stress. We conclude that, although stress may induce a decrease in glucose uptake, this effect is not sufficient to affect the energy metabolism of these cells.

  20. Mechanistic studies of antibody mediated clearance of tau aggregates using an ex vivo brain slice model

    Directory of Open Access Journals (Sweden)

    Pavan eKrishnamurthy

    2011-10-01

    Full Text Available Recent studies have shown that immunotherapy clears amyloid beta (A plaques and reduces A levels in mouse models of Alzheimer’s disease (AD, as well as in AD patients. Tangle pathology is also relevant for the neurodegeneration in AD, and our studies have shown that active immunization with an AD related phospho-tau peptide reduces aggregated tau within the brain and slows the progression of tauopathy-induced behavioural impairments. Thus, clearance of neurofibrillary tangles and/or their precursors may reduce synaptic and neuronal loss associated with AD and other tauopathies. So far the mechanisms involved in antibody-mediated clearance of tau pathology are yet to be elucidated. In this study we have used a mouse brain slice model to examine the uptake and localization of FITC labeled anti-tau antibodies. Confocal microscopy analysis showed that the FITC labelled anti-tau antibody co-stained with phosphorylated tau, had a perinuclear appearance and co-localised with markers of the endosomal/lysosomal pathway. Additionally, tau and FITC IgG were found together in an enriched lysosome fraction. In summary, antibody-mediated clearance of intracellular tau aggregates appears to occur via the lysosomal pathway.

  1. Investigation of acute lower gastrointestinal bleeding with 16- and 64-slice multidetector CT.

    Science.gov (United States)

    Lee, S; Welman, C J; Ramsay, D

    2009-02-01

    We evaluated the usefulness of 16- and 64-slice multidetector CT (MDCT) in the detection of a bleeding site in acute lower gastrointestinal tract (GIT) haemorrhage by conducting a retrospective study of cases of presumed acute lower GIT haemorrhage imaged with CT in two teaching hospitals in an 11-month period. The patients underwent contrast enhanced CT using either a 16 or 64 MDCT. No oral contrast was used. One hundred milliliters of non-ionic intravenous contrast agent was injected at 4.5 mL/s, followed by a 60 mL saline flush at 4 mL/s through a dual head injector. Images were acquired in arterial phase with or without non-contrast and portal phase imaging with 16 x 1.5 mm or 64 x 0.625 mm collimation. Active bleeding was diagnosed by the presence of iodinated contrast extravasation into the bowel lumen on arterial phase images with attenuation greater than and distinct from the normal mucosal enhancement or focal pooling of increased attenuation contrast material within a bowel segment on portal-venous images. Further management and final diagnosis was recorded. Fourteen patients and 15 studies were reviewed. CT detected and localized a presumed bleeding site or potential causative pathology in 12 (80%) of the patients. Seven of these were supported by other investigations or surgery, while five were not demonstrated by other modalities. Eight patients had mesenteric angiography, of which only four corroborated the site of bleeding. CT did not detect the bleeding site in three patients, of which two required further investigation and definitive treatment. We propose that MDCT serves a useful role as the initial rapid investigation to triage patients presenting with lower GIT bleeding for further investigation and management.

  2. Organotypic slice cultures from rat brain tissue: a new approach for Naegleria fowleri CNS infection in vitro.

    Science.gov (United States)

    Gianinazzi, C; Schild, M; Müller, N; Leib, S L; Simon, F; Nuñez, S; Joss, P; Gottstein, B

    2005-12-01

    The free-living amoeba Naegleria fowleri is the aetiological agent of primary amoebic meningoencephalitis (PAM), a disease leading to death in the vast majority of cases. In patients suffering from PAM, and in corresponding animal models, the brain undergoes a massive inflammatory response, followed by haemorrhage and severe tissue necrosis. Both, in vivo and in vitro models are currently being used to study PAM infection. However, animal models may pose ethical issues, are dependent upon availability of specific infrastructural facilities, and are time-consuming and costly. Conversely, cell cultures lack the complex organ-specific morphology found in vivo, and thus, findings obtained in vitro do not necessarily reflect the situation in vivo. The present study reports infection of organotypic slice cultures from rat brain with N. fowleri and compares the findings in this culture system with in vivo infection in a rat model of PAM, that proved complementary to that of mice. We found that brain morphology, as present in vivo, is well retained in organotypic slice cultures, and that infection time-course including tissue damage parallels the observations in vivo in the rat. Therefore, organotypic slice cultures from rat brain offer a new in vitro approach to study N. fowleri infection in the context of PAM.

  3. Inhibitory effect of morphine on excitatory synaptic transmission via presynaptic mechanism in rat SON neurons in brain slices

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-bin; HU San-jue; JU Gong

    2001-01-01

    To observe the effects of morphine on the excitatory postsynaptic currents (EPSCs) and miniature EPSCs (mEPSCs) in rat supraoptic nucleus (SON) neurons and to explore its synaptic mechanism. Methods: Using whole-cell voltage-clamp recording technique in the brain slices, the EPSCS and mEPSCs of rat SON neurons were recorded, respectively. Results: Morphine (20 μmol/L) decreased the frequency of EPSCs and mEPSCs (by 65% for EPSCS and by 45% for mEPSCs), and reduced the amplitude of EPSCs by 44% in all SON neurons, but the amplitude distribution ofmEPSCs was not affected. Conclusion: Morphine inhibits the excitatory transmissions via presynaptic mechanisms in SON neurons from rat brain slices.

  4. Metabolic Characterization of Acutely Isolated Hippocampal and Cerebral Cortical Slices Using [U-(13)C]Glucose and [1,2-(13)C]Acetate as Substrates

    DEFF Research Database (Denmark)

    McNair, Laura F; Kornfelt, Rasmus; Walls, Anne B

    2017-01-01

    Brain slice preparations from rats, mice and guinea pigs have served as important tools for studies of neurotransmission and metabolism. While hippocampal slices routinely have been used for electrophysiology studies, metabolic processes have mostly been studied in cerebral cortical slices. Few...... to incubation, slices were extracted and extracts analyzed for (13)C-labeling (%) and total amino acid contents (µmol/mg protein) using gas chromatography-mass spectrometry and high performance liquid chromatography, respectively. Release of lactate from the slices was quantified by analysis of the incubation...... media. Based on the measured (13)C-labeling (%), total amino acid contents and relative activity of metabolic enzymes/pathways, we conclude that the slice preparations in the current incubation apparatus exhibited a high degree of metabolic integrity. Comparison of (13)C-labeling observed with [U-(13)C...

  5. Acute hyperammonemia and systemic inflammation is associated with increased extracellular brain adenosine in rats

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Dale, Nicholas; Larsen, Fin Stolze

    2015-01-01

    Acute liver failure (ALF) can lead to brain edema, cerebral hyperperfusion and intracranial hypertension. These complications are thought to be mediated by hyperammonemia and inflammation leading to altered brain metabolism. As increased levels of adenosine degradation products have been found...... in brain tissue of patients with ALF we investigated whether hyperammonemia could induce adenosine release in brain tissue. Since adenosine is a potent vasodilator and modulator of cerebral metabolism we furthermore studied the effect of adenosine receptor ligands on intracranial pressure (ICP......) and cerebral blood flow (CBF). We measured the adenosine concentration with biosensors in rat brain slices exposed to ammonia and in a rat model with hyperammonemia and systemic inflammation. Exposure to ammonia in concentrations from 0.15-10 mM led to increases in the cortical adenosine concentration up to 18...

  6. Multi-slice spiral CT three-dimensional imaging and perfusion imaging in acute brain injury of dynamic application%多层螺旋CT三维图像重建和脑灌注成像在急性颅脑损伤动态变化中应用

    Institute of Scientific and Technical Information of China (English)

    杨小秦; 柳少光; 王治民; 王学斌; 张可; 魏晓东; 张冬志

    2012-01-01

    Objective Discussion of ultrathin multilayer spiral CT 3D image reconstruction,skull and brain perfusion imaging in acute brain injury to dynamic changes in the clinical value.Methods 2009December to 2011 October were collected in our hospital in 245 patients with acute traumatic brain injury patients check information,both in the 3-6 h after injury within conventional multislice spiral CT,thin multilayer spiral CT and three-dimensional image reconstruction of skull and brain CT perfusion imaging examination,all the cases in 2 to 7 days after injury dynamic review of conventional MSCT and ultrathin multilayer spiral CT,the data were retrospectively analyzed,using the chi-squared test evaluation.Results Super thin multilayer spiral CT in cerebral contusion and laceration,intracerebral hematoma in TBI with mixed diagnosis has statistics difference is better than the conventional MSCT.CTP in acute traumatic brain injury diagnosis was superior to conventional MSCT except diffuse axonal injury.CTP in cerebral contusion and laceration,subdural hematoma and intracerebral hematoma associated with intracerebral hematoma in the diagnosis with statistical difference,better than the ultrathin multilayer spiral CT (P < 0.05).The 3D image reconstruction of skull fracture demonstrated great advantages in the treatment of skull fracture,which include cranial suture separation and basal skull fracture.Conclusion combined Super thin multilayer spiral CT 3D image reconstruction skull and brain CT perfusion imaging for acute craniocerebral injury early diagnosis and minimal injury diagnosis is superior to conventional multislice spiral CT,The rate of misdiagnosis can be decreased.which provide Reliable basis for early diagnosis and Prognosis of TBI.%目的 探讨超薄多层螺旋CT、颅骨三维图像重建和脑灌注成像在急性颅脑外伤动态变化中的临床应用价值.方法 收集2009年12月至2011年10月我院收治的245例急性颅脑外

  7. Biocompatibility of silicon-based arrays of electrodes coupled to organotypic hippocampal brain slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne Winther; Noraberg, J; Thiébaud, P

    2001-01-01

    ) rats were grown for 4-8 weeks on the perforated silicon chips with silicon nitride surfaces and 40 microm sized holes and compared with corresponding tissue slices grown on conventional semiporous membranes. In terms of preservation of the basic cellular and connective organization, as visualized...... around the upper recording part of the 47-microm-high platinum-tip electrodes. Slice cultures grown on a separate set of chips with platinum instead of silicon nitride surfaces also displayed normal MAP2 and GFAP immunostaining. The width of the GFAP-rich zone (glia limitans) at the bottom surface...... of the slice cultures was the same ( approximately 20 microm) in cultures grown on chips with silicon nitride and platinum surfaces and on conventional insert membranes. The slice cultures grown on chips maintained a normal, subfield differentiated susceptibility to the glutamate receptor agonist N...

  8. Therapeutic hypothermia for acute brain injuries.

    Science.gov (United States)

    Andresen, Max; Gazmuri, Jose Tomás; Marín, Arnaldo; Regueira, Tomas; Rovegno, Maximiliano

    2015-06-05

    Therapeutic hypothermia, recently termed target temperature management (TTM), is the cornerstone of neuroprotective strategy. Dating to the pioneer works of Fay, nearly 75 years of basic and clinical evidence support its therapeutic value. Although hypothermia decreases the metabolic rate to restore the supply and demand of O₂, it has other tissue-specific effects, such as decreasing excitotoxicity, limiting inflammation, preventing ATP depletion, reducing free radical production and also intracellular calcium overload to avoid apoptosis. Currently, mild hypothermia (33°C) has become a standard in post-resuscitative care and perinatal asphyxia. However, evidence indicates that hypothermia could be useful in neurologic injuries, such as stroke, subarachnoid hemorrhage and traumatic brain injury. In this review, we discuss the basic and clinical evidence supporting the use of TTM in critical care for acute brain injury that extends beyond care after cardiac arrest, such as for ischemic and hemorrhagic strokes, subarachnoid hemorrhage, and traumatic brain injury. We review the historical perspectives of TTM, provide an overview of the techniques and protocols and the pathophysiologic consequences of hypothermia. In addition, we include our experience of managing patients with acute brain injuries treated using endovascular hypothermia.

  9. Long-term GnRH-induced gonadotropin secretion in a novel hypothalamo-pituitary slice culture from tilapia brain.

    Science.gov (United States)

    Bloch, Corinne L; Kedar, Noa; Golan, Matan; Gutnick, Michael J; Fleidervish, Ilya A; Levavi-Sivan, Berta

    2014-10-01

    Organotypic cultures, prepared from hypothalamo-pituitary slices of tilapia, were developed to enable long-term study of secretory cells in the pituitary of a teleost. Values of membrane potential at rest were similar to those recorded from acute slices, and cells presented similar spontaneous spikes and spikelets. Some cells also exhibited slow spontaneous oscillations in membrane potential, which may be network-driven. Long-term (6days) continuous exposure to GnRH induced increases in LH and FSH secretion. FSH levels reached the highest levels after 24h of exposure to GnRH, and the highest secretion of LH was observed in days 4 and 5 of the experiment. Since slices were viable for several weeks in culture, maintaining the original cytoarchitecture, electrical membrane properties and the ability to secrete hormones in response to exogenous GnRH, this technique is ideal for studying the mechanisms regulating cell-to-cell communication under conditions resembling the in vivo tissue organization.

  10. Interleukin-1 and acute brain injury.

    Science.gov (United States)

    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.

  11. Interleukin-1 and acute brain injury

    Directory of Open Access Journals (Sweden)

    Katie N Murray

    2015-02-01

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

  12. Excitatory amino acid neurotoxicity and modulation of glutamate receptor expression in organotypic brain slice cultures

    DEFF Research Database (Denmark)

    Zimmer, J; Kristensen, Bjarne Winther; Jakobsen, B

    2000-01-01

    Using organotypic slice cultures of hippocampus and cortex-striatum from newborn to 7 day old rats, we are currently studying the excitotoxic effects of kainic acid (KA), AMPA and NMDA and the neuroprotective effects of glutamate receptor blockers, like NBQX. For detection and quantitation of the...

  13. [Differentiated treatment of acute diffuse brain injuries].

    Science.gov (United States)

    Pedachenko, E G; Dziak, L A; Sirko, A G

    2012-01-01

    Diagnosis and treatment results of 57 patients with acute diffuse brain injury have been analyzed. Patients were divided into two groups: first study period 2000-2005; second study period 2006-2010. The main differences between the first and the second study periods were in health condition and brain functions monitoring parameters, therapy approaches and goals. Increasing of axial and lateral dislocation symptoms during progression from the first type of diffuse injury to the fourth one is related to intracranial hypertension (ICH) occurrence rate and significance it's significance. During the second study period, ICH was found in 25% patients with the second type of injury, 57% patients with the third type of injury, and 80%, with the fourth type of injury. Mean ICP in the group of patients with the second type of diffuse injury comprised 14.4 +/- 6.6 mmHg; with the third type of injury, 30 +/- 20.6 mmHg; with the fourth type of injuty, 37.6 +/- 14.1 mmHg. Introduction of differentiated approach to conservative or surgical treatment method application to acute diffuse brain injuries patients based on ICP monitoring data led to 13.8% reduction in mortality in the second study period compared with the first study period.

  14. Protective effect of bone marrow-derived mesenchymal stem cells on dopaminergic neurons against 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in rat brain slices

    Institute of Scientific and Technical Information of China (English)

    Lirong Jin; Zhen Hong; Chunjiu Zhong; Yang Wang

    2009-01-01

    BACKGROUND: To date, the use of bone marrow-derived mesenchymal stem cells (MSCs) for the treatment of Parkinson's disease have solely focused on in vivo animal models. Because of the number of influencing factors, it has been difficult to determine a consistent outcome. OBJECTIVE: To establish an injury model in brain slices of substantia nigra and striatum using 1-methyl-4-phenylpytidinium ion (MPP+), and to investigate the effect of MSCs on dopaminergic neurons following MPP+ induced damage.DESIGN, TIME AND SETTING: An in vitro, randomized, controlled, animal experiment using immunohistochemistry was performed at the Laboratory of the Department of Anatomy, Fudan University between January 2004 and December 2006.MATERIALS: Primary MSC cultures were obtained from femurs and tibias of adult Sprague Dawley rats. Organotypic brain slices were isolated from substantia nigra and striatum of 1-day-old Sprague Dawley rat pups. Monoclonal antibodies for tyrosine hydroxylase (TH, 1:5 000) were from Santa Cruz (USA); goat anti-rabbit IgG antibodies labeled with FITC were from Boster Company (China).METHODS: Organotypic brain slices were cultured for 5 days in whole culture medium supplemented with 50% DMEM, 25% equine serum, and 25% Tyrode's balanced salt solution. The medium was supplemented with 5 μg/mL Ara-C, and the culture was continued for an additional 5 days. The undergrowth of brain slices was discarded at day 10. Eugonic brain slices were cultured with basal media for an additional 7 days. The brain slices were divided into three groups: control, MPP+ exposure, and co-culture. For the MPP+ group, MPP+ (30 μmol/L) was added to the media at day 17 and brain slices were cultured for 4 days, followed by control media. For the co-culture group, the MPP+ injured brain slices were placed over MSCs in the well and were further cultured for 7 days.MAIN OUTCOME MEASURES: After 28 days in culture, neurite outgrowth was examined in the brain slices under phase

  15. Acute subarachnoid hemorrhage: using 64-slice multidetector CT angiography to ''triage'' patients' treatment

    Energy Technology Data Exchange (ETDEWEB)

    Agid, R.; Lee, S.K.; Willinsky, R.A.; Farb, R.I.; TerBrugge, K.G. [Toronto Western Hospital, Division of Neuroradiology, Department of Medical Imaging, Toronto, Ontario (Canada)

    2006-11-15

    To evaluate the clinical role of CT angiography (CTA) in patients with acute subarachnoid hemorrhage (SAH) for treatment decision-making. Consecutive patients with acute SAH had CTA using a 64-slice scanner for initial clinical decision-making. Image processing included multiplanar volume reformatted (MPVR) maximum intensity projections (MIP) and 3D volume-rendered reconstructions. CTAs were used for (1) evaluating the cause of SAH, and (2) triaging aneurysm-bearing patients to the more appropriate management, either surgical clipping or endovascular coiling. CTA findings were confirmed by neurosurgical exploration or catheter angiography (digital subtraction angiography, DSA). Successful coiling provided evidence that triaging to endovascular treatment was correct. Included in the study were 73 patients. CTA findings were confirmed by DSA or neurosurgical operation in 65 patients, and of these 65, 47 had aneurysmal SAH, 3 had vasculitis, 1 had arterial dissection and 14 had no underlying arterial abnormality. The cause of SAH was detected with CTA in 62 out of the 65 patients (95.4%, sensitivity 94%, specificity 100%). CTA revealed the aneurysm in 46 of 47 patients (98%, sensitivity 98%, specificity 100%, positive predictive value 100%, negative predictive value 82.3%), 1 of 3 vasculitides and 1 of 1 dissection. Of the 46 patients with aneurysm, 44 (95.7%) were referred for treatment based on CTA. In 2 patients (2 of 46, 4.4%) CTA was not informative enough to choose treatment requiring DSA. Of the 44 patients, 27 (61.4%) were referred to endovascular treatment and successful coiling was achieved in 25 (25 of 27, 92.6%). CTA using a 64-slice scanner is an accurate tool for detecting and characterizing aneurysms in acute SAH. CTA is useful in the decision process whether to coil or clip an aneurysm. (orig.)

  16. Impact of 64-slice coronary CT on the management of patients presenting with acute chest pain: results of a prospective two-centre study

    Energy Technology Data Exchange (ETDEWEB)

    Christiaens, Luc [Departement d' imagerie Cardiovasculaire, Assistance Publique- Hopitaux de Paris, Hopital Lariboisiere, Paris (France); CHU de Poitiers, Departement de Cardiologie, Poitiers (France); Duchat, Florent; Boudiaf, Mourad; Fargeaudou, Yann; Ledref, Olivier; Soyer, Philippe [Departement d' imagerie Cardiovasculaire, Assistance Publique- Hopitaux de Paris, Hopital Lariboisiere, Paris (France); Tasu, Jean-Pierre [CHU de Poitiers, Departement de Radiologie, Poitiers (France); Sirol, Marc [Departement d' imagerie Cardiovasculaire, Assistance Publique- Hopitaux de Paris, Hopital Lariboisiere, Paris (France); INSERM UFR U942, Insuffisance Cardiaque et Biomarqueurs, Universite Paris 7 - Denis Diderot, Hopital Lariboisiere, Paris (France); Universite Paris VII - Denis Diderot, Assistance Publique - Hopitaux de Paris, Service de Radiologie Vasculaire, Hopital Lariboisiere, Paris (France)

    2012-05-15

    Our two-centre prospective study evaluates the usefulness of 64-slice coronary computed tomography (CCT) to rule out significant coronary artery stenosis in patients admitted in emergency departments (ED) for acute coronary syndromes (ACS) with low-to-intermediate risk score. Patients (175) admitted for acute chest pain (ACP), unmodified electrocardiogram and first troponin measurement within normal ranges were included. A second troponin measurement and a 64-slice CCT within 24 h were performed. Major adverse cardiac events (MACE) were recorded during follow-up (6 months {+-} 2). 64-slice CCT was either normal or showed non-significant coronary stenosis in the majority of patients (78%). 64-slice CCT depicted significant stenosis (>50% diameter) in 22% of patient whereas initial clinical and biological evaluation was reassuring. For negative CCTs, elevated troponin at second measurement did not modify the strategy or treatment of patients. No MACEs were noted during follow up. In 12% of patients CCT identified unsuspected non-coronary abnormalities. Our study confirms 64-slice CCT utility to rule out significant coronary artery stenosis in 8/10 patients admitted in ED with ACP or ACS with low-to-intermediate risk score. Early discharge with a negative 64-slice CCT is associated with very low risk of cardiac events at 6 months. (orig.)

  17. Normobaric hyperoxia stimulates superoxide and nitric oxide production in the caudal solitary complex of rat brain slices.

    Science.gov (United States)

    Ciarlone, Geoffrey E; Dean, Jay B

    2016-12-01

    Central CO2-chemosensitive neurons in the caudal solitary complex (cSC) are stimulated not only by hypercapnic acidosis, but by hyperoxia as well. While a cellular mechanism for the CO2 response has yet to be isolated, previous data show that a redox-sensitive mechanism underlies neuronal excitability to hyperoxia. However, it remains unknown how changes in Po2 affect the production of reactive oxygen and nitrogen species (RONS) in the cSC that can lead to increased cellular excitability and, with larger doses, to cellular dysfunction and death. To this end, we used fluorescence microscopy in real time to determine how normobaric hyperoxia increases the production of key RONS in the cSC. Because neurons in the region are CO2 sensitive, we also examined the potential effects of CO2 narcosis, used during euthanasia before brain slice harvesting, on RONS production. Our findings show that normobaric hyperoxia (0.4 → 0.95 atmospheres absolute O2) increases the fluorescence rates of fluorogenic dyes specific to both superoxide and nitric oxide. Interestingly, different results were seen for superoxide fluorescence when CO2 narcosis was used during euthanasia, suggesting long-lasting changes in superoxide production and/or antioxidant activity subsequent to CO2 narcosis before brain slicing. Further research needs to distinguish whether the increased levels of RONS reported here are merely increases in oxidative and nitrosative signaling or, alternatively, evidence of redox and nitrosative stress.

  18. A combined long-term recording system for single-unit activity and neurotransmitter efflux of a brain slice

    Science.gov (United States)

    Sheu, Y. H.; Young, M. S.

    1998-04-01

    A combined long-term measurement and recording system for neurotransmission research of brain slices is presented in this study. This system, based on the IBM PC or compatible computer, is capable of simultaneously measuring and recording both single-unit neural electropotential signals and the electrochemical signals of neurotransmitter efflux from the same neuron in a brain slice for long periods of time (time limited largely by hard disk capacity, 100 h or more not being unreasonable with contemporary hardware) using a single carbon microelectrode for both measurements. The combined long-term recording system uses a simple switching circuit to switch periodically the single microelectrode between two data acquisition subsystems, one for electrochemical data and one for electrophysiological data. The simple switching circuit separates the electrophysiological signals and electrochemical signals, overcoming the traditional interference problem caused by the two different measuring techniques. Software designed for the proposed system allows easy reconstruction of the full time course of the compressed measured data and easy, simultaneous display of both types of signals on the same time scale. On-line and recorded displays are available. Test results of a practical implementation of the proposed system verify that the combined long-term recording system meets actual requirements for electrophysiological and neurochemical research.

  19. Conductor compounds of phenylpentane in Mycoleptodonoides aitchisonii mycelium enhance the release of dopamine from rat brain striatum slices.

    Science.gov (United States)

    Okuyama, Satoshi; Sawasaki, Emi; Yokogoshi, Hidehiko

    2004-04-01

    Monoterpene compound is a major component of essential oils in various aromatic species. Previous reports about the monoterpene compound linalool and its effect on the brain neurotransmitters glutamic acid, GABA and acetylcholine, but not catecholamines, have been reported. In this study, we investigated the effect of linalool or conductor compounds of phenylpentane, including 1-phenyl-3-pentanol and 1-phenyl-3-pentanone, on dopamine release using rat striatal slices. The edible mushroom Mycoleptodonoides aitchisonii belongs to the Climacodontaceae family, and its cultivate medium or mycelium contains derivatives of the fragrant conductor compound, phenylpentane. Compared to basal levels, 2.5 microg linalool increased dopamine from striatal slices 3-fold. A 4-fold increase in dopamine release resulted from 2.5 microg 1-phenyl-3-pentanol administration, while a half dose of this compound induced a 2.5-fold increase. A greater than 2-fold increase resulted with 2.5 microg 1-phenyl-3-pentanone. These data indicate that striatum has sensitivity for these fragrant compounds and different releasing effects result with differ structures. These actions may affect other neurotransmitters and influence brain function.

  20. Acute stent thrombosis after bifurcation stenting with the crush technique visualized with 64-slice computed tomography

    DEFF Research Database (Denmark)

    Kristensen, T.S.; Engstrom, T.; Kofoed, Klaus Fuglsang

    2008-01-01

    Acute stent thrombosis remains a potential complication after stent implantation. With the introduction of electrocardiographic gated multidetector row computed tomography (MDCT), a new nonnvasive imaging modality has become available that may contribute to the detection of complications after...

  1. Comparison of bNOS and chat immunohistochemistry in the laterodorsal tegmentum (LDT) and the pedunculopontine tegmentum (PPT) of the mouse from brain slices prepared for electrophysiology

    DEFF Research Database (Denmark)

    Veleanu, Maxime; Axen, Tina E; Kristensen, Morten P

    2016-01-01

    maintains that antibody staining for enzymes involved in synthesis or transport, of acetylcholine would be a more definitive marker and hence, preferable. NEW METHOD: Colocalization of bNOS and CHAT in the LDT/PPT, and presence of parvalbumin (PV), was examined in non-ideally prepared mouse brain slices......BACKGROUND: Identification of cell phenotype from brain slices upon which in vitro electrophysiological recordings have been performed often relies on conducting post hoc immunohistochemistry on tissue that necessarily has not been ideally prepared for immunohistochemical procedures...

  2. Multi-slice CT for visualization of acute pulmonary embolism: single breath-hold subtraction technique

    Energy Technology Data Exchange (ETDEWEB)

    Wildberger, J.E.; Mahnken, A.H.; Spuentrup, E.; Guenther, R.W. [Dept. of Diagnostic Radiology, Univ. of Technology, Aachen (Germany); Klotz, E.; Ditt, H. [Siemens Medical Solutions, Computed Tomography, Forchheim (Germany)

    2005-01-01

    Purpose: the purpose of our preliminary animal study was to evaluate the feasibility of a new subtraction technique for visualization of perfusion defects within the lung parenchyma in segmental and subsegmental pulmonary embolism (PE). Materials and methods: in three healthy pigs, PE were artificially induced by fresh human clot material. Within a single breath-hold, CT angiography (CTA) was performed on a 16-slice multi-slice CT scanner (SOMATOM Sensation 16; Siemens, Forchheim, Germany) before and after intravenous application of 80 mL of contrast-medium, followed by a saline chaser. Scan parameters were 120 kV and 100 mAs{sub eff.}, using a collimation of 16 x 1.5 mm and a table speed/rot. of 36 mm (pitch: 1.5; rotation time: 0.5 s). A new 3D subtraction technique was developed, which is based on automated segmentation, non-linear spatial filtering and non-rigid registration. Data were analysed using a color-encoded ''compound view'' of parenchymal enhancement and CTA information displayed in axial, coronal and sagittal orientation. Results: subtraction was technically feasible in all three data sets. The mean scan time for each series was 4.7 s, interscan delay was 14.7 s, respectively. Therefore, an average breath-hold of approximately 24 s was required for the overall scanning procedure. Downstream of occluded segmental and subsegmental arteries, perfusion defects were clearly assessable, showing lower or missing enhancement compared to normally perfused lung parenchyma. In all pigs, additional peripheral areas with triangular shaped perfusion defects were delineated, considered typical for PE. Conclusions: our initial results from the animal model studied slow that perfusion imaging of PE is feasible within a single breath-hold. It allows a comprehensive assessment of perfusion deficits as the direct proof of a pulmonary embolus, can be combined with an indirect visual quantification of the density changes in the adjacent lung tissue

  3. S100b Counteracts Neurodegeneration of Rat Cholinergic Neurons in Brain Slices after Oxygen-Glucose Deprivation

    Directory of Open Access Journals (Sweden)

    Daniela Serbinek

    2010-01-01

    Full Text Available Alzheimer's disease is a severe chronic neurodegenerative disorder characterized by beta-amyloid plaques, tau pathology, cerebrovascular damage, inflammation, reactive gliosis, and cell death of cholinergic neurons. The aim of the present study is to test whether the glia-derived molecule S100b can counteract neurodegeneration of cholinergic neurons after oxygen-glucose deprivation (OGD in organotypic brain slices of basal nucleus of Meynert. Our data showed that 3 days of OGD induced a marked decrease of cholinergic neurons (60% of control, which could be counteracted by 50 μg/mL recombinant S100b. The effect was dose and time dependent. Application of nerve growth factor or fibroblast growth factor-2 was less protective. C-fos-like immunoreactivity was enhanced 3 hours after OGD indicating metabolic stress. We conclude that S100b is a potent neuroprotective factor for cholinergic neurons during ischemic events.

  4. Neuroprotection afforded by diazepam against oxygen/glucose deprivation-induced injury in rat cortical brain slices.

    Science.gov (United States)

    Ricci, Lorenzo; Valoti, Massimo; Sgaragli, Giampietro; Frosini, Maria

    2007-04-30

    The aim of the present investigation was to assess neuroprotection exerted by diazepam (0.1-25 microM) in rat cortical brain slices subjected to oxygen-glucose deprivation and reoxygenation. Neuronal injury and neuroprotection were assessed by measuring the release of glutamate and lactate dehydrogenase and tissue water content. Results demonstrate that diazepam exerted neuroprotective effects according to a "U-shaped", hormetic-like, concentration-response curve, with an efficacy window of 0.5-5 microM concentration. Flumazenil (20 microM) fully antagonised neuroprotection afforded by 5 microM diazepam. In conclusion, the hormetic response of diazepam should be taken into consideration when designing experiments aimed at assessing diazepam neuroprotection against ischemia/reoxygenation injury.

  5. Tamoxifen mediated estrogen receptor activation protects against early impairment of hippocampal neuron excitability in an oxygen/glucose deprivation brain slice ischemia model

    OpenAIRE

    Zhang, Huaqiu; Xie, Minjie; Gary P. Schools; Feustel, Paul F.; Wang, Wei; Lei, Ting; Kimelberg, Harold K.; Zhou, Min

    2008-01-01

    Pretreatment of ovarectomized rats with estrogen shows long-term protection via activation of the estrogen receptor (ER). However, it remains unknown whether activation of the ER can provide protection against early neuronal damage when given acutely, we simulated ischemic conditions by applying oxygen and glucose deprived (OGD) solution to acute male rat hippocampal slices and examined the neuronal electrophysiological changes. Pyramidal neurons and interneurons showed a time-dependent membr...

  6. Depolarizing and calcium-mobilizing stimuli fail to enhance synthesis and release of endocannabinoids from rat brain cerebral cortex slices.

    Science.gov (United States)

    Sarmad, Sarir; Alexander, Stephen P H; Barrett, David A; Marsden, Charles A; Kendall, David A

    2011-05-01

    The concentrations of the endocannabinoids 2-arachidonoylglycerol (2-AG) and N-arachidonylethanolamine (anandamide) were examined in rat brain cerebral cortex slices and surrounding medium. Basal concentrations of endocannabinoids were similar to those identified previously in rat brain, with anandamide content being much lower (19 pmol/g) than that of 2-AG (7300 pmol/g). In contrast, basal concentrations in the surrounding medium were proportionally much lower for 2-arachidonoylglycerol (16 pmol/mL) compared to anandamide (0.6 pmol/mL). Incubation of slices with glutamate receptor agonists, depolarizing concentrations of KCl, or ionomycin failed to alter tissue concentrations of endocannabinoids, while endocannabinoids in the medium were unaltered by elevated KCl. Cyclohexyl carbamic acid 3'-carbamoyl-biphenyl-3-yl ester, an inhibitor of fatty acid amide hydrolase, significantly enhanced tissue concentrations of anandamide (and related N-acylethanolamines), without altering 2-AG, while evoking proportional elevations of anandamide in the medium. Removal of extracellular calcium ions failed to alter tissue concentrations of anandamide, but significantly reduced 2-AG in the tissue by 90% and levels in the medium to below the detection limit. Supplementation of the medium with 50 μM N-oleoylethanolamine only raised tissue concentrations of N-oleoylethanolamine in the presence of cyclohexyl carbamic acid 3'-carbamoyl-biphenyl-3-yl ester and failed to alter either tissue or medium anandamide or 2-AG concentrations. These results highlight the ongoing turnover of endocannabinoids, and the importance of calcium ions in maintaining 2-AG concentrations in this tissue.

  7. A LED-based method for monitoring NAD(P)H and FAD fluorescence in cell cultures and brain slices.

    Science.gov (United States)

    Rösner, Jörg; Liotta, Agustin; Schmitz, Dietmar; Heinemann, Uwe; Kovács, Richard

    2013-01-30

    Nicotinamide- and flavine-adenine-dinucleotides (NAD(P)H and FADH₂) are electron carriers involved in cellular energy metabolism and in a multitude of enzymatic processes. As reduced NAD(P)H and oxidised FAD molecules are fluorescent, changes in tissue auto-fluorescence provide valuable information on the cellular redox state and energy metabolism. Since fluorescence excitation, by mercury arc lamps (HBO) is inherently coupled to photo-bleaching and photo-toxicity, microfluorimetric monitoring of energy metabolism might benefit from the replacement of HBO lamps by light emitting diodes (LEDs). Here we describe a LED-based custom-built setup for monitoring NAD(P)H and FAD fluorescence at the level of single cells (HEK293) and of brain slices. We compared NAD(P)H bleaching characteristics with two light sources (HBO lamp and LED) as well as sensitivity and signal to noise ratio of three different detector types (multi-pixel photon counter (MPPC), photomultiplier tube (PMT) and photodiode). LED excitation resulted in reduced photo-bleaching at the same fluorescence output in comparison to excitation with the HBO lamp. Transiently increasing LED power resulted in reversible bleaching of NAD(P)H fluorescence. Recovery kinetics were dependent on metabolic substrates indicating coupling of NAD(P)H fluorescence to metabolism. Electrical stimulation of brain slices induced biphasic redox changes, as indicated by NAD(P)H/FAD fluorescence transients. Increasing the gain of PMT and decreasing the LED power resulted in similar sensitivity as obtained with the MPPC and the photodiode, without worsening the signal to noise ratio. In conclusion, replacement of HBO lamp with LED might improve conventional PMT based microfluorimetry of tissue auto-fluorescence.

  8. Cytoprotective effect of hydroxytyrosyl alkyl ether derivatives after oral administration to rats in a model of glucose-oxygen deprivation in brain slices.

    Science.gov (United States)

    Muñoz-Marín, Javier; De La Cruz, José Pedro; Guerrero, Ana; López-Leiva, Inmaculada; López-Villodres, Juan Antonio; Reyes, José Julio; Espartero, José Luis; Madrona, Andrés; Labajos, María Teresa; González-Correa, José Antonio

    2012-08-08

    This study was designed to determine whether the oral administration of hydroxytyrosol (HT) alkyl ether derivatives has a neuroprotective effect in rats. The animals were treated for 7 days with HT or ethyl, butyl, hexyl, octyl, and dodecyl HT ether. A method of in vitro hypoxia-reoxygenation in brain slices was used. Hexyl, octyl, and dodecyl HT derivatives reduced brain cell death (LDH efflux). Lipid peroxidation and nitrite concentrations were inhibited most by hexyl, octyl, and dodecyl derivatives. Concentrations of 3-nitrotyrosine were reduced by HT butyl, hexyl, octyl, and dodecyl ether derivatives. Interleukin-1β was significantly reduced in brain slices from rats treated with all HT ether derivatives. LDH efflux showed a linear correlation with brain concentrations of lipid peroxides, nitrites plus nitrates, and interleukin 1β. The reduction in oxidative and nitrosative stress and decreased production of pro-inflammatory interleukins may be the basis for the observed neuroprotective effects.

  9. Defining acute ischemic stroke tissue pathophysiology with whole brain CT perfusion.

    Science.gov (United States)

    Bivard, A; Levi, C; Krishnamurthy, V; Hislop-Jambrich, J; Salazar, P; Jackson, B; Davis, S; Parsons, M

    2014-12-01

    This study aimed to identify and validate whole brain perfusion computed tomography (CTP) thresholds for ischemic core and salvageable penumbra in acute stroke patients and develop a probability based model to increase the accuracy of tissue pathophysiology measurements. One hundred and eighty-three patients underwent multimodal stroke CT using a 320-slice scanner within 6hours of acute stroke onset, followed by 24hour MRI that included diffusion weighted imaging (DWI) and dynamic susceptibility weighted perfusion imaging (PWI). Coregistered acute CTP and 24hour DWI was used to identify the optimum single perfusion parameter thresholds to define penumbra (in patients without reperfusion), and ischemic core (in patients with reperfusion), using a pixel based receiver operator curve analysis. Then, these results were used to develop a sigma curve fitted probability based model incorporating multiple perfusion parameter thresholds. For single perfusion thresholds, a time to peak (TTP) of +5seconds best defined the penumbra (area under the curve, AUC 0.79 CI 0.74-0.83) while a cerebral blood flow (CBF) of acute ischemic core (AUC 0.73, CI 0.69-0.77). The probability model was more accurate at detecting the ischemic core (AUC 0.80 SD 0.75-0.83) and penumbra (0.85 SD 0.83-0.87) and was significantly closer in volume to the corresponding reference DWI (P=0.031). Whole brain CTP can accurately identify penumbra and ischemic core using similar thresholds to previously validated 16 or 64 slice CTP. Additionally, a novel probability based model was closer to defining the ischemic core and penumbra than single thresholds. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  10. Actions of brain-derived neurotrophic factor in slices from rats with spontaneous seizures and mossy fiber sprouting in the dentate gyrus.

    Science.gov (United States)

    Scharfman, H E; Goodman, J H; Sollas, A L

    1999-07-01

    This study examined the acute actions of brain-derived neurotrophic factor (BDNF) in the rat dentate gyrus after seizures, because previous studies have shown that BDNF has acute effects on dentate granule cell synaptic transmission, and other studies have demonstrated that BDNF expression increases in granule cells after seizures. Pilocarpine-treated rats were studied because they not only have seizures and increased BDNF expression in granule cells, but they also have reorganization of granule cell "mossy fiber" axons. This reorganization, referred to as "sprouting," involves collaterals that grow into novel areas, i.e., the inner molecular layer, where granule cell and interneuron dendrites are located. Thus, this animal model allowed us to address the effects of BDNF in the dentate gyrus after seizures, as well as the actions of BDNF on mossy fiber transmission after reorganization. In slices with sprouting, BDNF bath application enhanced responses recorded in the inner molecular layer to mossy fiber stimulation. Spontaneous bursts of granule cells occurred, and these were apparently generated at the site of the sprouted axon plexus. These effects were not accompanied by major changes in perforant path-evoked responses or paired-pulse inhibition, occurred only after prolonged (30-60 min) exposure to BDNF, and were blocked by K252a. The results suggest a preferential action of BDNF at mossy fiber synapses, even after substantial changes in the dentate gyrus network. Moreover, the results suggest that activation of trkB receptors could contribute to the hyperexcitability observed in animals with sprouting. Because human granule cells also express increased BDNF mRNA after seizures, and sprouting can occur in temporal lobe epileptics, the results may have implications for understanding temporal lobe epilepsy.

  11. GABA, taurine and learning: release of amino acids from slices of chick brain following filial imprinting.

    Science.gov (United States)

    McCabe, B J; Horn, G; Kendrick, K M

    2001-01-01

    The intermediate and medial hyperstriatum ventrale (IMHV) is a forebrain region in the domestic chick that is a site of information storage for the learning process of imprinting. We enquired whether imprinting is associated with learning-related increases in calcium-dependent, potassium-stimulated release of neurotransmitter amino acids from the IMHV. Chicks were hatched and reared in darkness until 15-30 h after hatching. They then either remained in darkness or were trained for 2 h by exposure to an imprinting stimulus. One hour later, the chicks were given a preference test and a preference score was calculated from the results of this test, as a measure of imprinting. Chicks were killed 2 h after training. Slices from the left and right IMHV of trained and untrained chicks were superfused with Krebs' solution either with or without calcium and the superfusate assayed for arginine, aspartate, citrulline, GABA, glutamate, glycine and taurine using high-performance liquid chromatography. For calcium-containing superfusates from the left IMHV, preference score was significantly correlated with potassium-stimulated release of (i) GABA (r=0.51, 23 d.f., P=0.008) and (ii) taurine (r=0.77, 23 d.f., Pimprinting is associated with increases in releasable pools of GABA and taurine and/or membrane excitability in the left IMHV.

  12. Cytosolic NADH-NAD+ Redox Visualized in Brain Slices by Two-Photon Fluorescence Lifetime Biosensor Imaging

    Science.gov (United States)

    Mongeon, Rebecca; Venkatachalam, Veena

    2016-01-01

    Abstract Aim: Cytosolic NADH-NAD+ redox state is central to cellular metabolism and a valuable indicator of glucose and lactate metabolism in living cells. Here we sought to quantitatively determine NADH-NAD+ redox in live cells and brain tissue using a fluorescence lifetime imaging of the genetically-encoded single-fluorophore biosensor Peredox. Results: We show that Peredox exhibits a substantial change in its fluorescence lifetime over its sensing range of NADH-NAD+ ratio. This allows changes in cytosolic NADH redox to be visualized in living cells using a two-photon scanning microscope with fluorescence lifetime imaging capabilities (2p-FLIM), using time-correlated single photon counting. Innovation: Because the lifetime readout is absolutely calibrated (in nanoseconds) and is independent of sensor concentration, we demonstrate that quantitative assessment of NADH redox is possible using a single fluorophore biosensor. Conclusion: Imaging of the sensor in mouse hippocampal brain slices reveals that astrocytes are typically much more reduced (with higher NADH:NAD+ ratio) than neurons under basal conditions, consistent with the hypothesis that astrocytes are more glycolytic than neurons. Antioxid. Redox Signal. 25, 553–563. PMID:26857245

  13. Direct Visualization of Neurotransmitters in Rat Brain Slices by Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI - MS)

    Science.gov (United States)

    Fernandes, Anna Maria A. P.; Vendramini, Pedro H.; Galaverna, Renan; Schwab, Nicolas V.; Alberici, Luciane C.; Augusti, Rodinei; Castilho, Roger F.; Eberlin, Marcos N.

    2016-12-01

    Mass spectrometry imaging (MSI) of neurotransmitters has so far been mainly performed by matrix-assisted laser desorption/ionization (MALDI) where derivatization reagents, deuterated matrix and/or high resolution, or tandem MS have been applied to circumvent problems with interfering ion peaks from matrix and from isobaric species. We herein describe the application of desorption electrospray ionization mass spectrometry imaging (DESI)-MSI in rat brain coronal and sagittal slices for direct spatial monitoring of neurotransmitters and choline with no need of derivatization reagents and/or deuterated materials. The amino acids γ-aminobutyric (GABA), glutamate, aspartate, serine, as well as acetylcholine, dopamine, and choline were successfully imaged using a commercial DESI source coupled to a hybrid quadrupole-Orbitrap mass spectrometer. The spatial distribution of the analyzed compounds in different brain regions was determined. We conclude that the ambient matrix-free DESI-MSI is suitable for neurotransmitter imaging and could be applied in studies that involve evaluation of imbalances in neurotransmitters levels.

  14. Investigation of inter-slice magnetization transfer effects as a new method for MTR imaging of the human brain.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Barker

    Full Text Available We present a new method for magnetization transfer (MT ratio imaging in the brain that requires no separate saturation pulse. Interslice MT effects that are inherent to multi-slice balanced steady-state free precession (bSSFP imaging were controlled via an interslice delay time to generate MT-weighted (0 s delay and reference images (5-8 s delay for MT ratio (MTR imaging of the brain. The effects of varying flip angle and phase encoding (PE order were investigated experimentally in normal, healthy subjects. Values of up to ∼50% and ∼40% were observed for white and gray matter MTR. Centric PE showed larger MTR, higher SNR, and better contrast between white and gray matter than linear PE. Simulations of a two-pool model of MT agreed well with in vivo MTR values. Simulations were also used to investigate the effects of varying acquisition parameters, and the effects of varying flip angle, PE steps, and interslice delay are discussed. Lastly, we demonstrated reduced banding with a non-balanced SSFP-FID sequence and showed preliminary results of interslice MTR imaging of meningioma.

  15. Direct Visualization of Neurotransmitters in Rat Brain Slices by Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI - MS)

    Science.gov (United States)

    Fernandes, Anna Maria A. P.; Vendramini, Pedro H.; Galaverna, Renan; Schwab, Nicolas V.; Alberici, Luciane C.; Augusti, Rodinei; Castilho, Roger F.; Eberlin, Marcos N.

    2016-10-01

    Mass spectrometry imaging (MSI) of neurotransmitters has so far been mainly performed by matrix-assisted laser desorption/ionization (MALDI) where derivatization reagents, deuterated matrix and/or high resolution, or tandem MS have been applied to circumvent problems with interfering ion peaks from matrix and from isobaric species. We herein describe the application of desorption electrospray ionization mass spectrometry imaging (DESI)-MSI in rat brain coronal and sagittal slices for direct spatial monitoring of neurotransmitters and choline with no need of derivatization reagents and/or deuterated materials. The amino acids γ-aminobutyric (GABA), glutamate, aspartate, serine, as well as acetylcholine, dopamine, and choline were successfully imaged using a commercial DESI source coupled to a hybrid quadrupole-Orbitrap mass spectrometer. The spatial distribution of the analyzed compounds in different brain regions was determined. We conclude that the ambient matrix-free DESI-MSI is suitable for neurotransmitter imaging and could be applied in studies that involve evaluation of imbalances in neurotransmitters levels.

  16. Abnormal whole-brain functional networks in homogeneous acute mild traumatic brain injury.

    NARCIS (Netherlands)

    Shumskaya, E.; Andriessen, T.; Norris, D.G.; Vos, P.E.

    2012-01-01

    Objectives: To evaluate the whole-brain resting-state networks in a homogeneous group of patients with acute mild traumatic brain injury (MTBI) and to identify alterations in functional connectivity induced by MTBI. Methods: Thirty-five patients with acute MTBI and 35 healthy control subjects, mat

  17. Abnormal whole-brain functional networks in homogeneous acute mild traumatic brain injury.

    NARCIS (Netherlands)

    Shumskaya, A.N.; Andriessen, T.M.J.C.; Norris, D.G.; Vos, P.E.

    2012-01-01

    OBJECTIVES: To evaluate the whole-brain resting-state networks in a homogeneous group of patients with acute mild traumatic brain injury (MTBI) and to identify alterations in functional connectivity induced by MTBI. METHODS: Thirty-five patients with acute MTBI and 35 healthy control subjects, match

  18. A visual thalamocortical slice.

    Science.gov (United States)

    MacLean, Jason N; Fenstermaker, Vivian; Watson, Brendon O; Yuste, Rafael

    2006-02-01

    We describe a thalamocortical slice preparation in which connectivity between the mouse lateral geniculate nucleus (LGN) and primary visual cortex (V1) is preserved. Through DiI injections in fixed brains we traced and created a three-dimensional model of the mouse visual pathways. From this computer model we designed a slice preparation that contains a projection from LGN to V1. We prepared brain slices with these predicted coordinates and demonstrated anatomical LGN-V1 connectivity in these slices after LGN tracer injections. We also revealed functional LGN-V1 connectivity by stimulating LGN electrically and detecting responses in layer 4 of V1 using calcium imaging, field potential recordings and whole-cell recordings. We also identified layer-4 neurons that receive direct thalamocortical input. Finally, we compared cortical activity after LGN stimulation with spontaneous cortical activity and found significant overlap of the spatiotemporal dynamics generated by both types of events.

  19. Expression of hypoxia-inducible factor 1 alpha and oligodendrocyte lineage gene-1 in cultured brain slices after oxygen-glucose deprivation

    Institute of Scientific and Technical Information of China (English)

    Hong Cui; Weijuan Han; Lijun Yang; Yanzhong Chang

    2013-01-01

    Oligodendrocyte lineage gene-1 expressed in oligodendrocytes may trigger the repair of neuronal myelin impairment, and play a crucial role in myelin repair. Hypoxia-inducible factor 1α, a transcription factor, is of great significance in premature infants with hypoxic-ischemic brain damage. There is little evidence of direct regulatory effects of hypoxia-inducible factor 1α on oligodendrocyte lineage gene-1. In this study, brain slices of Sprague-Dawley rats were cultured and subjected to oxygen-glucose deprivation. Then, slices were transfected with hypoxia-inducible factor 1α or oligodendrocyte lineage gene-1. The expression levels of hypoxia-inducible factor 1α and oligodendrocyte lineage gene-1 were significantly up-regulated in rat brains prior to transfection, as detected by immunohistochemical staining. Eight hours after transfection of slices with hypoxia-inducible factor 1α, oligodendrocyte lineage gene-1 expression was upregulated, and reached a peak 24 hours after transfection. Oligodendrocyte lineage gene-1 transfection induced no significant differences in hypoxia-inducible factor 1α levels in rat brain tissues with oxygen-glucose deprivation. These experimental findings indicate that hypoxia-inducible factor 1α can regulate oligodendrocyte lineage gene-1 expression in hypoxic brain tissue, thus repairing the neural impairment.

  20. Presynaptically mediated effects of cholecystokinin-8 on the excitability of area postrema neurons in rat brain slices.

    Science.gov (United States)

    Sugeta, Shingo; Hirai, Yoshiyuki; Maezawa, Hitoshi; Inoue, Nobuo; Yamazaki, Yutaka; Funahashi, Makoto

    2015-08-27

    Cholecystokinin (CCK) is a well-known gut hormone that shows anorexigenic effects via action at peripheral and central receptors. CCK is also widely distributed throughout the mammalian brain and appears to function as a neurotransmitter and neuromodulator. The area postrema is one of the circumventricular organs, located on the dorsal surface of the medulla oblongata at the caudal end of the fourth ventricle. Blood vessels in the area postrema lack a blood brain barrier, offering specific central neural elements unique access to circulating substances. Immunohistochemical studies show CCK-A receptors in the area postrema, and we reported CCK-sensitive area postrema neurons. However, the receptive mechanism of CCK in area postrema neurons still remains unexplained. We investigated the responses of area postrema neurons to agonists and antagonists of CCK receptors using whole cell and perforated patch-clamp recordings in rat brain slices. The application of CCK-8 elicited excitatory responses, such as increases in the frequency of mEPSCs (miniature excitatory postsynaptic currents), a shift toward larger amplitude mEPSCs, and increases in the frequency of action potentials. These changes were found mostly in cells not displaying the hyperpolarization-activated cation current (Ih), except for small excitatory changes in a minority of Ih-positive neurons. Tonic inward currents or an inhibitory response to CCK-8 were never seen. Analysis of the amplitude of mEPSCs before and after the administration of CCK-8 indicated the responses mediated via the presynaptic receptors. The effect of CCK-8 was abolished in the presence of CNQX (AMPA type glutamate receptor antagonist). In the presence of lorglumide (a selective CCK-A receptor antagonist), CCK-8-induced excitatory responses were inhibited. No cells responded to the administration of non-sulfated CCK-8 (CCK-8NS, a selective CCK-B receptor agonist). We conclude that CCK-8 exerts its action via presynaptic CCK-A receptors

  1. Microglial Kv1.3 Channels and P2Y12 Receptors Differentially Regulate Cytokine and Chemokine Release from Brain Slices of Young Adult and Aged Mice.

    Directory of Open Access Journals (Sweden)

    Nicoletta Charolidi

    Full Text Available Brain tissue damage following stroke or traumatic brain injury is accompanied by neuroinflammatory processes, while microglia play a central role in causing and regulating neuroinflammation via production of proinflammatory substances, including cytokines and chemokines. Here, we used brain slices, an established in situ brain injury model, from young adult and aged mice to investigate cytokine and chemokine production with particular focus on the role of microglia. Twenty four hours after slice preparation, higher concentrations of proinflammatory cytokines, i.e. TNF-α and IL-6, and chemokines, i.e. CCL2 and CXCL1, were released from brain slices of aged mice than from slices of young adult mice. However, maximal microglial stimulation with LPS for 24 h did not reveal age-dependent differences in the amounts of released cytokines and chemokines. Mechanisms underlying microglial cytokine and chemokine production appear to be similar in young adult and aged mice. Inhibition of microglial Kv1.3 channels with margatoxin reduced release of IL-6, but not release of CCL2 and CXCL1. In contrast, blockade of microglial P2Y12 receptors with PSB0739 inhibited release of CCL2 and CXCL1, whereas release of IL-6 remained unaffected. Cytokine and chemokine production was not reduced by inhibitors of Kir2.1 K+ channels or adenosine receptors. In summary, our data suggest that brain tissue damage-induced production of cytokines and chemokines is age-dependent, and differentially regulated by microglial Kv1.3 channels and P2Y12 receptors.

  2. Dual activities of the anti-cancer drug candidate PBI-05204 provide neuroprotection in brain slice models for neurodegenerative diseases and stroke.

    Science.gov (United States)

    Van Kanegan, Michael J; Dunn, Denise E; Kaltenbach, Linda S; Shah, Bijal; He, Dong Ning; McCoy, Daniel D; Yang, Peiying; Peng, Jiangnan; Shen, Li; Du, Lin; Cichewicz, Robert H; Newman, Robert A; Lo, Donald C

    2016-05-12

    We previously reported neuroprotective activity of the botanical anti-cancer drug candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, in brain slice and in vivo models of ischemic stroke. We showed that one component of this neuroprotective activity is mediated through its principal cardiac glycoside constituent, oleandrin, via induction of the potent neurotrophic factor brain-derived neurotrophic factor (BDNF). However, we also noted that the concentration-relation for PBI-05204 in the brain slice oxygen-glucose deprivation (OGD) model is considerably broader than that for oleandrin as a single agent. We thus surmised that PBI-05204 contains an additional neuroprotective component(s), distinct from oleandrin. We report here that neuroprotective activity is also provided by the triterpenoid constituents of PBI-05204, notably oleanolic acid. We demonstrate that a sub-fraction of PBI-05204 (Fraction 0-4) containing oleanolic and other triterpenoids, but without cardiac glycosides, induces the expression of cellular antioxidant gene transcription programs regulated through antioxidant transcriptional response elements (AREs). Finally, we show that Fraction 0-4 provides broad neuroprotection in organotypic brain slice models for neurodegeneration driven by amyloid precursor protein (APP) and tau implicated in Alzheimer's disease and frontotemporal dementias, respectively, in addition to ischemic injury modeled by OGD.

  3. Antioxidant effects of 1,4-dihydropyridine and nitroso aryl derivatives on the Fe+3/ascorbate-stimulated lipid peroxidation in rat brain slices.

    Science.gov (United States)

    Díaz-Araya, G; Godoy, L; Naranjo, L; Squella, J A; Letelier, M E; Núñez-Vergara, L J

    1998-09-01

    1. Lipid peroxidation in rat brain slices was induced by Fe+3/ascorbate. 2. Brain lipid peroxidation, as measured by malondialdehyde formation, was inhibited by all the tested nitro aryl 1,4-dihydropyridine derivatives over a wide range of concentrations. The time-course antioxidant effects of the most representative agents were assessed. On the basis of both time-course and IC50 experiments the tentative order of antioxidant activity on rat brain slices could be: nicardipine>nisoldipine> (R,S/S,R)-furnidipine > (R,R/S,S)-furnidipine>nitrendipine>nimodipine> nifedipine. 3. 1,4-Dihydropyridine derivatives that lack of a nitro group in the molecule (isradipine, amlodipine) also inhibited lipid peroxidation in rat brain slices but at higher concentrations than that of nitro-substituted derivatives. 4. All the tested nitroso aryl derivatives [2,6-dimethyl-4-(2-nitrosophenyl)-3,5-pyridinedicar. boxylic acid dimethyl ester (NTP), nitrosotoluene, nitrosobenzene] were more potent inhibitors of lipid peroxidation than were the parent nitro compounds. In conclusion, on the basis of the IC50 values determined, the rank order of antioxidant potency for these derivatives can be established as: ortho-nitrosotoluene>NTP>nitrosobenzene.

  4. Mathematical Identification of a Neuronal Network Consisting of GABA and DA in Striatal Slices of the Rat Brain

    Directory of Open Access Journals (Sweden)

    L. Ramrath

    2009-01-01

    Full Text Available High frequency stimulation (HFS has been used to treat various neurological and psychiatric diseases. Although further disorders are under investigation to extend the clinical application of HFS, the complex effect of HFS within a neuronal network is still unknown. Thus, it would be desirable to find a theoretical model that allows an estimation of the expected effect of applied HFS. Based on the neurochemical analysis of effects of the γ-aminobutyric acid (GABAA receptor antagonist bicuculline, the D2-like receptor antagonist sulpiride and the D1-like receptor antagonist SCH-23390 on HFS evoked GABA and dopamine (DA release from striatal slices of the rat brain, a mathematical network model is proposed including the neurotransmitters GABA, DA and glutamate (GLU. The model reflects inhibitory and excitatory interactions of the neurotransmitters outflow in the presence of HFS. Under the assumption of linear interactions and static measurements, the model is expressed analytically. Numerical identification of inhibition and excitation is performed on a basis of real outflow levels of GABA and DA in the rat striatum. Results validate the nature of the proposed model. Therefore, this leads to an analytical model of the interactions within distinct neural network components of the rat striatum.

  5. Effect of. cap alpha. -,. beta. -adrenergic receptor agonists and antagonists of the efflux of /sup 22/Na and uptake of /sup 42/K by rat brain cortical slices

    Energy Technology Data Exchange (ETDEWEB)

    Phillis, J.W.; Wu, P.H.; Thierry, D.L.

    1982-03-18

    The effects of norepinephrine on ion fluxes in rat brain cortical slices have now been ascertained. /sup 22/Na efflux and /sup 42/K influx are enhanced by norepinephrine. The increase in ion fluxes can be blocked by ouabain, phentolamine and propranolol, suggesting that the catecholamine activates a membrane sodium pump by a receptor-mediated step. The facilitation of /sup 22/Na efflux is stereospecific as demonstrated by the very weak action of D-norepinephrine at 10/sup -5/ M concentration. Various ..cap alpha..-adrenergic and ..beta..-adrenergic receptor agonists, including oxymetazoline, naphazoline, clonidine, tramazoline, methoxamine, phenylephrine, L-isoproterenol and methoxyphenamine are potent stimulants of the sodium pump as demonstrated by their enhancement of ion fluxes in rat brain cortical slices. The results are consistent with the hypothesis that norepinephrine hyperpolarizes central neurons by activating an ouabain-sensitive, receptor-mediated sodium pump.

  6. Brain-derived neurotrophic factor, but not neurotrophin-3, prevents ischaemia-induced neuronal cell death in organotypic rat hippocampal slice cultures.

    Science.gov (United States)

    Pringle, A K; Sundstrom, L E; Wilde, G J; Williams, L R; Iannotti, F

    1996-06-28

    We have investigated the neuroprotective actions of neurotrophins in a model of ischaemia using slice cultures. Ischaemia was induced in organotypic hippocampal cultures by simultaneous oxygen and glucose deprivation. Cell death was assessed 24 h later by propidium iodide fluorescence. Pre- but not post-ischaemic addition of brain-derived neurotrophic factor (BDNF) produced a concentration-dependent reduction in neuronal damage. Neurotrophin-3 was not neuroprotective. These data suggest that BDNF may form part of an endogenous neuroprotective mechanism.

  7. Whole-brain CT perfusion and CT angiography assessment of Moyamoya disease before and after surgical revascularization: preliminary study with 256-slice CT.

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    Full Text Available BACKGROUND/AIMS: The 256-slice CT enables the entire brain to be scanned in a single examination. We evaluated the application of 256-slice whole-brain CT perfusion (CTP in determining graft patency as well as investigating cerebral hemodynamic changes in Moyamoya disease before and after surgical revascularization. METHODS: Thirty-nine cases of Moyamoya disease were evaluated before and after surgical revascularization with 256-slice CT. Whole-brain perfusion images and dynamic 3D CT angiographic images generated from perfusion source data were obtained in all patients. Cerebral blood flow (CBF, cerebral blood volume (CBV, time to peak (TTP and mean transit time (MTT of one hemisphere in the region of middle cerebral artery (MCA distribution and contralateral mirroring areas were measured. Relative CTP values (rCBF, rCBV, rTTP, rMTT were also obtained. Differences in pre- and post- operation perfusion CT values were assessed with paired t test or matched-pairs signed-ranks test. RESULTS: Preoperative CBF, MTT and TTP of potential surgical side were significantly different from those of contralateral side (P<0.01 for all. All graft patencies were displayed using the 3D-CTA images. Postoperative CBF, rCBF and rCBV values of surgical side in the region of MCA were significantly higher than those before operation (P<0.01 for all. Postoperative MTT, TTP, rMTT and rTTP values of the surgical side in the region of MCA were significantly lower than those before operation (P<0.05 for all. CONCLUSION: The 256-slice whole-brain CTP can be used to evaluate cerebral hemodynamic changes in Moyamoya disease before and after surgery and the 3D-CTA is useful for assessing the abnormalities of intracranial arteries and graft patencies.

  8. β-Adrenoceptor activation depresses brain inflammation and is neuroprotective in lipopolysaccharide-induced sensitization to oxygen-glucose deprivation in organotypic hippocampal slices

    Directory of Open Access Journals (Sweden)

    Cilio Corrado

    2010-12-01

    Full Text Available Abstract Background Inflammation acting in synergy with brain ischemia aggravates perinatal ischemic brain damage. The sensitizing effect of pro-inflammatory exposure prior to hypoxia is dependent on signaling by TNF-α through TNF receptor (TNFR 1. Adrenoceptor (AR activation is known to modulate the immune response and synaptic transmission. The possible protective effect of α˜ and β˜AR activation against neuronal damage caused by tissue ischemia and inflammation, acting in concert, was evaluated in murine hippocampal organotypic slices treated with lipopolysaccharide (LPS and subsequently subjected to oxygen-glucose deprivation (OGD. Method Hippocampal slices from mice were obtained at P6, and were grown in vitro for 9 days on nitrocellulose membranes. Slices were treated with β1(dobutamine-, β2(terbutaline-, α1(phenylephrine- and α2(clonidine-AR agonists (5 and 50 μM, respectively during LPS (1 μg/mL, 24 h -exposure followed by exposure to OGD (15 min in a hypoxic chamber. Cell death in the slice CA1 region was assessed by propidium iodide staining of dead cells. Results Exposure to LPS + OGD caused extensive cell death from 4 up to 48 h after reoxygenation. Co-incubation with β1-agonist (50 μM during LPS exposure before OGD conferred complete protection from cell death (P -/- and TNFR2-/- slices exposed to LPS followed by OGD. Conclusions Our data demonstrate that activation of both β1- and β2-receptors is neuroprotective and may offer mechanistic insights valuable for development of neuro-protective strategies in neonates.

  9. The Appetite-Inducing Peptide, Ghrelin, Induces Intracellular Store-Mediated Rises in Calcium in Addiction and Arousal-Related Laterodorsal Tegmental Neurons in Mouse Brain Slices

    DEFF Research Database (Denmark)

    Hauberg, Katrine; Kohlmeier, Kristi Anne

    2015-01-01

    Ghrelin, a gut and brain peptide, has recently been shown to be involved in motivated behavior and regulation of the sleep and wakefulness cycle. The laterodorsal tegmental nucleus (LDT) is involved in appetitive behavior and control of the arousal state of an organism, and accordingly, behavioral...... this peptide has been shown in other cell types to lead to rises in calcium via release of calcium from intracellular stores. To determine whether ghrelin induced intracellular calcium rises in mouse LDT neurons, we conducted calcium imaging studies in LDT brain slices loaded with the calcium binding dye, Fura...

  10. Whole brain CT perfusion in acute anterior circulation ischemia: coverage size matters

    Energy Technology Data Exchange (ETDEWEB)

    Emmer, B.J. [Erasmus Medical Centre, Department of Radiology, Postbus 2040, Rotterdam (Netherlands); Rijkee, M.; Walderveen, M.A.A. van [Leiden University Medical Centre, Department of Radiology, Leiden (Netherlands); Niesten, J.M.; Velthuis, B.K. [University Medical Centre Utrecht, Department of Radiology, Utrecht (Netherlands); Wermer, M.J.H. [Leiden University Medical Centre, Department of Neurology, Leiden (Netherlands)

    2014-12-15

    Our aim was to compare infarct core volume on whole brain CT perfusion (CTP) with several limited coverage sizes (i.e., 3, 4, 6, and 8 cm), as currently used in routine clinical practice. In total, 40 acute ischemic stroke patients with non-contrast CT (NCCT) and CTP imaging of anterior circulation ischemia were included. Imaging was performed using a 320-multislice CT. Average volumes of infarct core of all simulated partial coverage sizes were calculated. Infarct core volume of each partial brain coverage was compared with infarct core volume of whole brain coverage and expressed using a percentage. To determine the optimal starting position for each simulated CTP coverage, the percentage of infarct coverage was calculated for every possible starting position of the simulated partial coverage in relation to Alberta Stroke Program Early CT Score in Acute Stroke Triage (ASPECTS 1) level. Whole brain CTP coverage further increased the percentage of infarct core volume depicted by 10 % as compared to the 8-cm coverage when the bottom slice was positioned at the ASPECTS 1 level. Optimization of the position of the region of interest (ROI) in 3 cm, 4 cm, and 8 cm improved the percentage of infarct depicted by 4 % for the 8-cm, 7 % for the 4-cm, and 13 % for the 3-cm coverage size. This study shows that whole brain CTP is the optimal coverage for CTP with a substantial improvement in accuracy in quantifying infarct core size. In addition, our results suggest that the optimal position of the ROI in limited coverage depends on the size of the coverage. (orig.)

  11. Cerebrospinal fluid enzymes in acute brain injury

    NARCIS (Netherlands)

    A.I.R. Maas (Andrew)

    1977-01-01

    textabstractSevere brain injury is a major cause of death, especially in young men. In 1972, over 20% of all deaths occurring in England and Wales in men aged 15-25 years were due to head injury (Field, 1976). The mortality rate after severe brain injuries is higb. Jennett et al. (1977) reporting on

  12. Properties of gamma-frequency oscillations initiated by propagating population bursts in retrohippocampal regions of rat brain slices.

    Science.gov (United States)

    Funahashi, M; Stewart, M

    1998-07-01

    1. In the hippocampal formation in vivo, brief periods of gamma-frequency activity follow population bursts called sharp waves. The approximately 200 Hz activity of the sharp wave itself may serve to enhance synaptic connections and the approximately 40 Hz gamma activity has been offered as a mechanism for solving the 'binding' problem. We describe epochs of gamma-frequency activity which follow population spikes evoked by low frequency repetitive extracellular stimuli in retrohippocampal neurons of horizontal rat brain slices. 2. gamma-Frequency activity recorded intracellularly from deep layer neurons of entorhinal cortex, presubiculum and parasubiculum consisted of one action potential correlated with each of the three to five gamma cycles recorded with a proximate field potential electrode. A minority of cells exhibited only sub-threshold gamma-frequency membrane potential oscillations (ranging from 5 to 10 mV). No cells fired more than one spike per gamma cycle under any conditions. 3. The range of synchrony varied from individual cells which showed gamma-frequency firing without corresponding oscillations in close field recordings to field potential recordings of oscillations which were well correlated across regions. The lead or lag between any two retrohippocampal regions was in the direction of the conduction delay for the primary population spike, but typically was less, and approached zero milliseconds for some cycles in most cells. The level of synchrony was stable for particular stimulating conditions (intensity, stimulation rate, stimulus location). 4. The duration of the period of gamma activity had the duration of a slow depolarizing potential which was mediated by NMDA receptor activation. NMDA receptor antagonists or low concentrations of AMPA receptor antagonists reduced the duration of, or completely abolished the slow potential, thereby eliminating the gamma portion of the evoked response. 5. gamma-Frequency firing was eliminated by the GABAA

  13. Acute Blast Injury Reduces Brain Abeta in Two Rodent Species

    Directory of Open Access Journals (Sweden)

    Rita eDe Gasperi

    2012-12-01

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

  14. Comparison of bNOS and chat immunohistochemistry in the laterodorsal tegmentum (LDT) and the pedunculopontine tegmentum (PPT) of the mouse from brain slices prepared for electrophysiology.

    Science.gov (United States)

    Veleanu, Maxime; Axen, Tina E; Kristensen, Morten P; Kohlmeier, Kristi A

    2016-04-01

    Identification of cell phenotype from brain slices upon which in vitro electrophysiological recordings have been performed often relies on conducting post hoc immunohistochemistry on tissue that necessarily has not been ideally prepared for immunohistochemical procedures. In such studies, antibody labeling against neuronal nitric oxide synthase (bNOS) has been used to identify cholinergic neurons of the laterodorsal tegmental nucleus (LDT) and the pedunculopontine tegmental nuclei (PPT), two brainstem nuclei importantly involved in arousal. However, a widespread perception maintains that antibody staining for enzymes involved in synthesis or transport, of acetylcholine would be a more definitive marker and hence, preferable. Colocalization of bNOS and CHAT in the LDT/PPT, and presence of parvalbumin (PV), was examined in non-ideally prepared mouse brain slices using currently available antibodies. Using fluorescent-based immunohistochemistry in LDT/PPT slices prepared for in vitro recordings, a near 100% colocalization of bNOS and CHAT was observed. We confirm in the mouse, findings of near 100% colocalization of bNOS and CHAT in the LDT/PPT, and we expand upon data from rat studies using optimally prepared tissue, that for dendritic visualization, bNOS staining exceeded the quality of CHAT staining for visualization of a higher degree of detail of fine processes. PV is not highly present in the mouse LDT/PPT. CHAT and bNOS are equally useful target proteins for immunofluorescent identification of cholinergic LDT/PPT cells in mouse brain slices prepared for in vitro recordings, however, antibody targeting of bNOS allows for a superior appreciation of structural detail. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Comparison of iterative model, hybrid iterative, and filtered back projection reconstruction techniques in low-dose brain CT: impact of thin-slice imaging

    Energy Technology Data Exchange (ETDEWEB)

    Nakaura, Takeshi; Iyama, Yuji; Kidoh, Masafumi; Yokoyama, Koichi [Amakusa Medical Center, Diagnostic Radiology, Amakusa, Kumamoto (Japan); Kumamoto University, Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto (Japan); Oda, Seitaro; Yamashita, Yasuyuki [Kumamoto University, Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto (Japan); Tokuyasu, Shinichi [Philips Electronics, Kumamoto (Japan); Harada, Kazunori [Amakusa Medical Center, Department of Surgery, Kumamoto (Japan)

    2016-03-15

    The purpose of this study was to evaluate the utility of iterative model reconstruction (IMR) in brain CT especially with thin-slice images. This prospective study received institutional review board approval, and prior informed consent to participate was obtained from all patients. We enrolled 34 patients who underwent brain CT and reconstructed axial images with filtered back projection (FBP), hybrid iterative reconstruction (HIR) and IMR with 1 and 5 mm slice thicknesses. The CT number, image noise, contrast, and contrast noise ratio (CNR) between the thalamus and internal capsule, and the rate of increase of image noise in 1 and 5 mm thickness images between the reconstruction methods, were assessed. Two independent radiologists assessed image contrast, image noise, image sharpness, and overall image quality on a 4-point scale. The CNRs in 1 and 5 mm slice thickness were significantly higher with IMR (1.2 ± 0.6 and 2.2 ± 0.8, respectively) than with FBP (0.4 ± 0.3 and 1.0 ± 0.4, respectively) and HIR (0.5 ± 0.3 and 1.2 ± 0.4, respectively) (p < 0.01). The mean rate of increasing noise from 5 to 1 mm thickness images was significantly lower with IMR (1.7 ± 0.3) than with FBP (2.3 ± 0.3) and HIR (2.3 ± 0.4) (p < 0.01). There were no significant differences in qualitative analysis of unfamiliar image texture between the reconstruction techniques. IMR offers significant noise reduction and higher contrast and CNR in brain CT, especially for thin-slice images, when compared to FBP and HIR. (orig.)

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

    Science.gov (United States)

    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.

  17. Estrogen receptor beta and 2-arachydonoylglycerol mediate the suppressive effects of estradiol on frequency of postsynaptic currents in gonadotropin-releasing hormone neurons of metestrous mice: an acute slice electrophysiological study

    Directory of Open Access Journals (Sweden)

    Flóra eBálint

    2016-03-01

    Full Text Available Gonadotropin-releasing hormone (GnRH neurons are controlled by 17β-estradiol (E2 contributing to the steroid feedback regulation of the reproductive axis. In rodents, E2 exerts a negative feedback effect upon GnRH neurons throughout the estrus-diestrus phase of the ovarian cycle. The present study was undertaken to reveal the role of estrogen receptor subtypes in the mediation of the E2 signal and elucidate the downstream molecular machinery of suppression. The effect of E2 administration at low physiological concentration (10 pM on GnRH neurons in acute brain slices obtained from metestrous GnRH-GFP mice was studied under paradigms of blocking or activating estrogen receptor subtypes and interfering with retrograde 2-arachydonoylglycerol (2-AG signaling. Whole-cell patch clamp recordings revealed that E2 significantly diminished the frequency of spontaneous postsynaptic currents (sPSCs in GnRH neurons (49. 62±7.6% which effect was abolished by application of the ERα/β blocker Faslodex (1 µM. Pretreatment of the brain slices with cannabinoid receptor type 1 (CB1 inverse agonist AM251 (1 µM and intracellularly applied endocannabinoid synthesis blocker THL (10 µM significantly attenuated the effect of E2 on the sPSCs. E2 remained effective in the presence of TTX indicating a direct action of E2 on GnRH cells. The ERβ specific agonist DPN (10 pM also significantly decreased the frequency of miniature postsynaptic currents (mPSCs in GnRH neurons. In addition, the suppressive effect of E2 was completely blocked by the selective ERβ antagonist PHTPP (1 µM indicating that ERβ is required for the observed rapid effect of the E2. In contrast, the ERα agonist PPT (10 pM or the membrane-associated G protein-coupled estrogen receptor (GPR30 agonist G1 (10 pM had no significant effect on the frequency of mPSCs in these neurons. AM251 and THL significantly abolished the effect of E2 whereas AM251 eliminated the action of DPN on the mPSCs. These

  18. Multi-slice spiral CT in routine diagnosis of suspected acute left-sided colonic diverticulitis: a prospective study of 120 patients

    Energy Technology Data Exchange (ETDEWEB)

    Werner, A.; Diehl, S.J.; Dueber, C. [Institut fuer Klinische Radiologie, Universitaetsklinikum Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim (Germany); Farag-Soliman, M. [Chirurgische Klinik, Universitaetsklinikum Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim (Germany)

    2003-12-01

    This prospective study evaluated the use of multi-slice CT (MSCT) for detection of clinically suspected left-sided colonic diverticulitis with regard to diagnosis, complications and alternative diagnoses. One hundred twenty patients with clinically suspected acute left-colonic diverticulitis underwent MSCT of the lower abdomen with IV contrast after rectal application of iodic contrast. The MSCT results were compared with histopathological and intraoperative findings or other radiological or endoscopic methods and clinical outcome. Acute diverticulitis was proven in 67 of the 120 (55.8%) patients, which was detected by MSCT with an accuracy of 98% (sensitivity 97%, specificity 98%). Contained perforation or abscess formation were detected with an accuracy of 96% (sensitivity 100%, specificity 91%) and 98% (sensitivity 100%, specificity 97%), respectively. In 31 of 120 (25.8%) patients diagnoses other than diverticulitis caused abdominal pain, which was correctly diagnosed by MSCT in 71%. The MSCT as well as other concurrently performed diagnostic methods showed normal findings and no causes for the patients symptoms in 22 of the 120 (18.4%) patients. Multi-slice CT is reliable in detecting diverticulitis, including extracolic complications, and often reveals other diagnoses; therefore, MSCT is recommended as standard diagnostic procedure in suspected acute diverticulitis. (orig.)

  19. Interleukin-1 as a pharmacological target in acute brain injury.

    Science.gov (United States)

    Brough, David; Rothwell, Nancy J; Allan, Stuart M

    2015-12-01

    What is the topic of this review? This review discusses the latest findings on the contribution of inflammation to brain injury, how inflammation is a therapeutic target, and details of recent and forthcoming clinical studies. What advances does it highlight? Here we highlight recent advances on the role and regulation of inflammasomes, and the latest clinical progress in targeting inflammation. Acute brain injury is one of the leading causes of mortality and disability worldwide. Despite this, treatments for acute brain injuries are limited, and there remains a massive unmet clinical need. Inflammation has emerged as a major contributor to non-communicable diseases, and there is now substantial and growing evidence that inflammation, driven by the cytokine interleukin-1 (IL-1), worsens acute brain injury. Interleukin-1 is regulated by large, multimolecular complexes called inflammasomes. Here, we discuss the latest research on the regulation of inflammasomes and IL-1 in the brain, preclinical efforts to establish the IL-1 system as a therapeutic target, and the promise of recent and future clinical studies on blocking the action of IL-1 for the treatment of brain injury. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

  20. Architectural slicing

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Hansen, Klaus Marius

    2013-01-01

    a system and a slicing criterion, architectural slicing produces an architectural prototype that contain the elements in the architecture that are dependent on the ele- ments in the slicing criterion. Furthermore, we present an initial design and implementation of an architectural slicer for Java.......Architectural prototyping is a widely used practice, con- cerned with taking architectural decisions through experiments with light- weight implementations. However, many architectural decisions are only taken when systems are already (partially) implemented. This is prob- lematic in the context...... of architectural prototyping since experiments with full systems are complex and expensive and thus architectural learn- ing is hindered. In this paper, we propose a novel technique for harvest- ing architectural prototypes from existing systems, \\architectural slic- ing", based on dynamic program slicing. Given...

  1. Slice Sampling

    CERN Document Server

    Neal, R M

    2000-01-01

    Markov chain sampling methods that automatically adapt to characteristics of the distribution being sampled can be constructed by exploiting the principle that one can sample from a distribution by sampling uniformly from the region under the plot of its density function. A Markov chain that converges to this uniform distribution can be constructed by alternating uniform sampling in the vertical direction with uniform sampling from the horizontal `slice' defined by the current vertical position, or more generally, with some update that leaves the uniform distribution over this slice invariant. Variations on such `slice sampling' methods are easily implemented for univariate distributions, and can be used to sample from a multivariate distribution by updating each variable in turn. This approach is often easier to implement than Gibbs sampling, and more efficient than simple Metropolis updates, due to the ability of slice sampling to adaptively choose the magnitude of changes made. It is therefore attractive f...

  2. Architectural Slicing

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Hansen, Klaus Marius

    2013-01-01

    a system and a slicing criterion, architectural slicing produces an architectural prototype that contain the elements in the architecture that are dependent on the ele- ments in the slicing criterion. Furthermore, we present an initial design and implementation of an architectural slicer for Java.......Architectural prototyping is a widely used practice, con- cerned with taking architectural decisions through experiments with light- weight implementations. However, many architectural decisions are only taken when systems are already (partially) implemented. This is prob- lematic in the context...... of architectural prototyping since experiments with full systems are complex and expensive and thus architectural learn- ing is hindered. In this paper, we propose a novel technique for harvest- ing architectural prototypes from existing systems, \\architectural slic- ing", based on dynamic program slicing. Given...

  3. An associative Brain-Computer-Interface for acute stroke patients

    DEFF Research Database (Denmark)

    Mrachacz-Kersting, Natalie; Stevenson, Andrew James Thomas; Aliakbaryhosseinabadi, Susan

    2016-01-01

    An efficient innovative Brain-Computer-Interface system that empowers chronic stroke patients to control an artificial activation of their lower limb muscle through task specific motor intent has been tested in the past. In the current study it was applied to acute stroke patients. The system...

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

    Science.gov (United States)

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

    2014-10-01

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

  5. Reversible acute methotrexate leukoencephalopathy: atypical brain MR imaging features

    Energy Technology Data Exchange (ETDEWEB)

    Ziereisen, France; Damry, Nash; Christophe, Catherine [Queen Fabiola Children' s University Hospital, Department of Radiology, Brussels (Belgium); Dan, Bernard [Queen Fabiola Children' s University Hospital, Department of Neurology, Brussels (Belgium); Azzi, Nadira; Ferster, Alina [Queen Fabiola Children' s University Hospital, Department of Paediatrics, Brussels (Belgium)

    2006-03-15

    Unusual acute symptomatic and reversible early-delayed leukoencephalopathy has been reported to be induced by methotrexate (MTX). We aimed to identify the occurrence of such atypical MTX neurotoxicity in children and document its MR presentation. We retrospectively reviewed the clinical findings and brain MRI obtained in 90 children treated with MTX for acute lymphoblastic leukaemia or non-B malignant non-Hodgkin lymphoma. All 90 patients had normal brain imaging before treatment. In these patients, brain imaging was performed after treatment completion and/or relapse and/or occurrence of neurological symptoms. Of the 90 patients, 15 (16.7%) showed signs of MTX neurotoxicity on brain MRI, 9 (10%) were asymptomatic, and 6 (6.7%) showed signs of acute leukoencephalopathy. On the routine brain MRI performed at the end of treatment, all asymptomatic patients had classical MR findings of reversible MTX neurotoxicity, such as abnormal high-intensity areas localized in the deep periventricular white matter on T2-weighted images. In contrast, the six symptomatic patients had atypical brain MRI characterized by T2 high-intensity areas in the supratentorial cortex and subcortical white matter (n=6), cerebellar cortex and white matter (n=4), deep periventricular white matter (n=2) and thalamus (n=1). MR normalization occurred later than clinical recovery in these six patients. In addition to mostly asymptomatic classical MTX neurotoxicity, MTX may induce severe but reversible unusual leukoencephalopathy. It is important to recognize this clinicoradiological presentation in the differential diagnosis of acute neurological deterioration in children treated with MTX. (orig.)

  6. Barbiturates for acute traumatic brain injury.

    OpenAIRE

    Roberts, I.; Sydenham, E

    2012-01-01

    BACKGROUND: Raised intracranial pressure (ICP) is an important complication of severe brain injury, and is associated with high mortality. Barbiturates are believed to reduce ICP by suppressing cerebral metabolism, thus reducing cerebral metabolic demands and cerebral blood volume. However, barbiturates also reduce blood pressure and may, therefore, adversely effect cerebral perfusion pressure. OBJECTIVES: To assess the effects of barbiturates in reducing mortality, disability and raised ICP ...

  7. Fast scan cyclic voltammetry as a novel method for detection of real-time gonadotropin-releasing hormone release in mouse brain slices.

    Science.gov (United States)

    Glanowska, Katarzyna M; Venton, B Jill; Moenter, Suzanne M

    2012-10-17

    Pulsatile gonadotropin-releasing hormone (GnRH) release is critical for the central regulation of fertility. There is no method allowing real-time GnRH detection in brain slices. We developed fast-scan cyclic voltammetry (FSCV) using carbon-fiber microelectrodes (CFME) to detect GnRH release and validated it using a biologically relevant system. FSCV parameters (holding potential, switching potential, and scan rate) were determined for stable GnRH detection in vitro, then optimized for GnRH detection in mouse brain slices. Placement of CFMEs in the median eminence (ME) near GnRH terminals allowed detection of both KCl-evoked and spontaneous GnRH release. GnRH release was also detected from GnRH fibers passing near GnRH soma and near fiber-fiber appositions in the preoptic area. No GnRH signal was detected from CFMEs in the ME of hpg mice, which lack GnRH, or in regions not containing GnRH neurons in wild-type mice; application of exogenous GnRH produced a signal similar to that observed for spontaneous/evoked endogenous GnRH release. Using an established mouse model that produces diurnal variations in GnRH neuron activity, we demonstrated corresponding changes in spontaneous GnRH release in the median eminence. These results validate FSCV to detect GnRH in brain slices and provide new information on the sites and amounts of GnRH release, providing insight into its neuromodulatory functions.

  8. GTP effects in rat brain slices support the non-interconvertability of M/sub 1/ and M/sub 2/ muscarinic acetylcholine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Spencer, D.G. Jr.; Horvath, E.; Traber, J.; Van Rooijen, L.A.A.

    1988-01-01

    GTP (guanosine-5'-triphosphate) markedly reduced high-affinity /sup 3/H-oxotremorine-M binding to M/sub 2/ receptors on brain slices in autoradiographic experiments while /sup 3/H-pirenzepine binding to M/sub 1/ receptors was largely unaffected. The distribution of M/sub 1/ receptors so labelled was also not altered by GTP to include former M/sub 2/-rich regions, thus indicating that GTP could not, by itself, interconvert high agonist-affinity M/sub 2/ receptors to M/sub 1/ receptors. 18 references, 1 figure.

  9. Effects of the blood components on the AMPA and NMDA synaptic responses in brain slices in the onset of hemorrhagic stroke.

    Science.gov (United States)

    Mokrushin, Anatoly A; Pavlinova, Larisa I

    2013-12-01

    Blood-borne events play a major role in post bleeding disturbances of the neuronal network. However, very little is known about the early effects of blood plasma, leucocytes, and the red blood cells on the AMPA and NMDA-mediated synaptic responses in the onset of experimental intracranial hemorrhage (ICH). In this study, we used the technique of on-line monitoring of electrophysiological parameters referred to synaptic activity in piriform cortex of SHR rat slice. We exposed the olfactory cortex slices to diluted autologous blood or its components and compared with effects of ferric chloride. Whole blood exerted a total inhibition of synaptic activity in piriform cortex within first 5 min. Dilution of blood induced prolonged epileptic synaptic activation of NMDA receptors. Blood plasma and fraction of leucocytes induced hyperactivation of neurons transforming to epileptiform discharges. Fraction of red blood cells acted biphasic, an initial sharp activity of AMPA- and NMDA-mediated receptors replaced by a following total depression. Our slice-based models of experimental stroke revealed the mechanism of the earliest pathophysiologic events occur in brain tissue during bleeding that may be relevant to the human ICH.

  10. Microcutting of living brain slices by a pulsed ultrafine water jet which allows simultaneous electrophysiological recordings (micromingotome).

    Science.gov (United States)

    Speckmann, E J; Köhling, R; Lücke, A; Straub, H; Wittkowski, W; Elger, C E; Wiemann, M; Bingmann, D

    1998-07-01

    Up to now microsurgical dissections in living nervous tissue (e.g. in slices or cell cultures) are performed either by micro-scalpels or by laser beams. As an alternative technique, a device for cutting with an ultrafine pulsed water jet was developed to allow precise, visually controled dissections in neuronal circuits even during electrophysiological recordings. Water is ejected by pressure (20-30 bar) from patch pipettes with tip diameters of 10-12 microm. By means of a piezo-element the pipette and the water jet are forced to oscillate vertically with a frequency of 200-400 Hz with an adjustable amplitude. These oscillations facilitate the transsection of neuronal connections even in thick slice preparations. Best results were obtained when the tip of the pipette was about 500 microm above the surface of the submerged slice tissue. This micromingotome offers the following advantages: (i) histological studies show that the water jet cleans the cutting surface, thus avoiding debris and its uncontrolable effects on cells underneath; (ii) the arrangement enables ongoing electrophysiological recordings from hippocampal slices during the cutting procedure and thus facilitates studies of the functions of neuronal connections; (iii) the device allows even disconnection in cultured nervous tissue overgrowing polyamid grids with 50 microm wide meshes.

  11. Autophagy in acute brain injury: feast, famine, or folly?

    Science.gov (United States)

    Smith, Craig M; Chen, Yaming; Sullivan, Mara L; Kochanek, Patrick M; Clark, Robert S B

    2011-07-01

    In the central nervous system, increased autophagy has now been reported after traumatic brain and spinal cord injury, cerebral ischemia, intracerebral hemorrhage, and seizures. This increase in autophagy could be physiologic, converting damaged or dysfunctional proteins, lipids, and/or organelles to their amino acid and fatty acid components for recycling. On the other hand, this increase in autophagy could be supraphysiologic, perhaps consuming and eliminating functional proteins, lipids, and/or organelles as well. Whether an increase in autophagy is beneficial (feast) or detrimental (famine) in brain likely depends on both the burden of intracellular substrate targeted for autophagy and the capacity of the cell's autophagic machinery. Of course, increased autophagy observed after brain injury could also simply be an epiphenomenon (folly). These divergent possibilities have clear ramifications for designing therapeutic strategies targeting autophagy after acute brain injury and are the subject of this review. This article is part of a Special Issue entitled "Autophagy and protein degradation in neurological diseases."

  12. N-Acetylaspartate distribution in rat brain striatum during acute brain ischemia

    DEFF Research Database (Denmark)

    Sager, T.N.; Laursen, H; Fink-Jensen, A

    1999-01-01

    Brain N-acetylaspartate (NAA) can be quantified by in vivo proton magnetic resonance spectroscopy (1H-MRS) and is used in clinical settings as a marker of neuronal density. It is, however, uncertain whether the change in brain NAA content in acute stroke is reliably measured by 1H-MRS and how NAA......]e increased linearly to 4 mmol/L after 3 hours and this level was maintained for the next 4 h. From the change in in vivo recovery of the interstitial space volume marker [14C]mannitol, the relative amount of NAA distributed in the interstitial space was calculated to be 0.2% of the total brain NAA during...... normal conditions and only 2 to 6% during ischemia. It was concluded that the majority of brain NAA is intracellularly located during ischemia despite large increases of interstitial [NAA]. Thus, MR quantification of NAA during acute ischemia reflects primarily changes in intracellular levels of NAA...

  13. Role of Interleukin-10 in Acute Brain Injuries

    Directory of Open Access Journals (Sweden)

    Joshua M. Garcia

    2017-06-01

    Full Text Available Interleukin-10 (IL-10 is an important anti-inflammatory cytokine expressed in response to brain injury, where it facilitates the resolution of inflammatory cascades, which if prolonged causes secondary brain damage. Here, we comprehensively review the current knowledge regarding the role of IL-10 in modulating outcomes following acute brain injury, including traumatic brain injury (TBI and the various stroke subtypes. The vascular endothelium is closely tied to the pathophysiology of these neurological disorders and research has demonstrated clear vascular endothelial protective properties for IL-10. In vitro and in vivo models of ischemic stroke have convincingly directly and indirectly shown IL-10-mediated neuroprotection; although clinically, the role of IL-10 in predicting risk and outcomes is less clear. Comparatively, conclusive studies investigating the contribution of IL-10 in subarachnoid hemorrhage are lacking. Weak indirect evidence supporting the protective role of IL-10 in preclinical models of intracerebral hemorrhage exists; however, in the limited number of clinical studies, higher IL-10 levels seen post-ictus have been associated with worse outcomes. Similarly, preclinical TBI models have suggested a neuroprotective role for IL-10; although, controversy exists among the several clinical studies. In summary, while IL-10 is consistently elevated following acute brain injury, the effect of IL-10 appears to be pathology dependent, and preclinical and clinical studies often paradoxically yield opposite results. The pronounced and potent effects of IL-10 in the resolution of inflammation and inconsistency in the literature regarding the contribution of IL-10 in the setting of acute brain injury warrant further rigorously controlled and targeted investigation.

  14. Monitorization of Acute Brain Dysfunction in Critical Illness

    Directory of Open Access Journals (Sweden)

    Günseli Orhun

    2016-08-01

    Full Text Available Acute brain dysfunction is a clinical condition which is commonly observed in intensive care units and exhibits neurological changes ranging from delirium to coma. Typically observed during sepsis in critical patients, this syndrome is also named as “sepsis-associated encephalopathy” and this situation is of significance since it is related to mortality, increase of morbidity and long-term cognitive impairment. Monitorization of brain functions in critically ill patients should be commenced with detailed neurological examination and effects of sedative drugs, which can alter neurological responses during evaluation, should be taken into consideration. On the other hand, brain imaging methods and electrophysiological examinations are diagnostic procedures which complement neurological examination. While computed tomography enables diagnosis of structural intracerebral lesions, magnetic resonance imaging provides important information on primary pathological mechanisms of sepsis-associated encephalopathy and structural alterations developing in the brain. Evidence of diagnosis and prognosis of acute brain dysfunction can be acquired through use of electroencephalography for. Although it was believed that neurological biomarkers can be useful in determination of diagnosis and prognosis, further studies are needed in this subject.

  15. Quantitation of dopamine, serotonin and adenosine content in a tissue punch from a brain slice using capillary electrophoresis with fast-scan cyclic voltammetry detection.

    Science.gov (United States)

    Fang, Huaifang; Pajski, Megan L; Ross, Ashley E; Venton, B Jill

    2013-01-01

    Methods to determine neurochemical concentrations in small samples of tissue are needed to map interactions among neurotransmitters. In particular, correlating physiological measurements of neurotransmitter release and the tissue content in a small region would be valuable. HPLC is the standard method for tissue content analysis but it requires microliter samples and the detector often varies by the class of compound being quantified; thus detecting molecules from different classes can be difficult. In this paper, we develop capillary electrophoresis with fast-scan cyclic voltammetry detection (CE-FSCV) for analysis of dopamine, serotonin, and adenosine content in tissue punches from rat brain slices. Using field-amplified sample stacking, the limit of detection was 5 nM for dopamine, 10 nM for serotonin, and 50 nM for adenosine. Neurotransmitters could be measured from a tissue punch as small as 7 µg (7 nL) of tissue, three orders of magnitude smaller than a typical HPLC sample. Tissue content analysis of punches in successive slices through the striatum revealed higher dopamine but lower adenosine content in the anterior striatum. Stimulated dopamine release was measured in a brain slice, then a tissue punch collected from the recording region. Dopamine content and release had a correlation coefficient of 0.71, which indicates much of the variance in stimulated release is due to variance in tissue content. CE-FSCV should facilitate measurements of tissue content in nanoliter samples, leading to a better understanding of how diseases or drugs affect dopamine, serotonin, and adenosine content.

  16. Is management of acute traumatic brain injury effective?

    OpenAIRE

    Lei, Jin; Gao, Guo-Yi; Jiang, Ji-Yao

    2012-01-01

    【Abstract】 Objective: To evaluate all the possible therapeutic measures concerning the acute management of traumatic brain injury (TBI) mentioned in Cochrane System-atic Reviews published in the Cochrane Database of Sys-tematic Reviews (CDSR). Methods: An exhausted literature search for all pub-lished Cochrane Systematic Reviews discussing therapeu-tic rather than prevention or rehabilitative interventions of TBI was conducted. We retrieved such databases as CDSR and Coch...

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

    Science.gov (United States)

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

    2015-03-01

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

  18. Biomarkers and acute brain injuries: interest and limits.

    Science.gov (United States)

    Mrozek, Ségolène; Dumurgier, Julien; Citerio, Giuseppe; Mebazaa, Alexandre; Geeraerts, Thomas

    2014-04-24

    For patients presenting with acute brain injury (such as traumatic brain injury, subarachnoid haemorrhage and stroke), the diagnosis and identification of intracerebral lesions and evaluation of the severity, prognosis and treatment efficacy can be challenging. The complexity and heterogeneity of lesions after brain injury are most probably responsible for this difficulty. Patients with apparently comparable brain lesions on imaging may have different neurological outcomes or responses to therapy. In recent years, plasmatic and cerebrospinal fluid biomarkers have emerged as possible tools to distinguish between the different pathophysiological processes. This review aims to summarise the plasmatic and cerebrospinal fluid biomarkers evaluated in subarachnoid haemorrhage, traumatic brain injury and stroke, and to clarify their related interests and limits for diagnosis and prognosis. For subarachnoid haemorrhage, particular interest has been focused on the biomarkers used to predict vasospasm and cerebral ischaemia. The efficacy of biomarkers in predicting the severity and outcome of traumatic brain injury has been stressed. The very early diagnostic performance of biomarkers and their ability to discriminate ischaemic from haemorrhagic stroke were studied.

  19. MR-visible brain water content in human acute stroke

    DEFF Research Database (Denmark)

    Gideon, P; Rosenbaum, S; Sperling, B

    1999-01-01

    Quantification of metabolite concentrations by proton magnetic resonance spectroscopy (1H-MRS) in the human brain using water as an internal standard is based on the assumption that water content does not change significantly in pathologic brain tissue. To test this, we used 1H-MRS to estimate...... brain water content during the course of cerebral infarction. Measurements were performed serially in the acute, subacute, and chronic phase of infarction. Fourteen patients with acute cerebral infarction were examined as well as 9 healthy controls. To correlate with regional cerebral blood flow (r......CBF from Day 0-3 to Day 4-7 (p = 0.050) and from Day 0-3 to Day 8-21 (p = 0.028). No correlation between rCBF and water content was found. Water content in ischemic brain tissue increased significantly between Day 4-7 after stroke. This should be considered when performing quantitative 1H-MRS using water...

  20. MR-visible brain water content in human acute stroke

    DEFF Research Database (Denmark)

    Gideon, P; Rosenbaum, S; Sperling, B;

    1999-01-01

    Quantification of metabolite concentrations by proton magnetic resonance spectroscopy (1H-MRS) in the human brain using water as an internal standard is based on the assumption that water content does not change significantly in pathologic brain tissue. To test this, we used 1H-MRS to estimate...... brain water content during the course of cerebral infarction. Measurements were performed serially in the acute, subacute, and chronic phase of infarction. Fourteen patients with acute cerebral infarction were examined as well as 9 healthy controls. To correlate with regional cerebral blood flow (r......CBF from Day 0-3 to Day 4-7 (p = 0.050) and from Day 0-3 to Day 8-21 (p = 0.028). No correlation between rCBF and water content was found. Water content in ischemic brain tissue increased significantly between Day 4-7 after stroke. This should be considered when performing quantitative 1H-MRS using water...

  1. Effect of pre-ischaemic conditioning on hypoxic depolarization of dopamine efflux in the rat caudate brain slice measured in real-time with fast cyclic voltammetry.

    Science.gov (United States)

    Davidson, Colin; Coomber, Ben; Gibson, Claire L; Young, Andrew M J

    2011-10-01

    Fast cyclic voltammetry can be used to measure dopamine release after oxygen and glucose deprivation (OGD) induced anoxic depolarization in vitro. Here we measure dopamine efflux with 1s time resolution, which is appropriate to measure OGD-evoked dopamine efflux accurately. In the present study, we examined whether OGD-evoked dopamine efflux could be used to show pre-ischaemic conditioning in the rat caudate brain slice. Caudate slices were exposed to 0, 2, or 10 min OGD pre-ischaemic conditioning, then 60 min later exposed to a second OGD event of 15 min duration. We measured the OGD-evoked dopamine efflux using fast cyclic voltammetry and in some experiments caudate dopamine and DOPAC tissue levels were measured using HPLC and 20 μm cryostat sections were Nissl stained to indicate neuronal loss. We found that 10 but not 2 min OGD pre-ischaemic conditioning resulted in a longer time to onset of OGD-evoked dopamine efflux on the main OGD event (475 ± 31 and 287 ± 30 s for 10 Vs 0 min pre-ischaemic conditioning respectively). Further, 10 min OGD pre-ischaemic conditioning resulted in less dopamine efflux on the second OGD event (4.23 ± 1.12 and 8.14 ± 0.82 μM for 10 Vs 0 min pre-ischaemic conditioning respectively), despite these slices having similar tissue dopamine content and DOPAC/DA ratio, and the rate of dopamine release was slower in the main OGD event (21 ± 5 and 74 ± 8 nM/s for 10 Vs 0 min pre-ischaemic conditioning respectively). These data suggest that 10 min OGD pre-ischaemic conditioning can evoke tolerance to a second OGD event and that voltammetric recording of OGD-evoked dopamine efflux is a useful model of pre-ischaemic conditioning in neuronal tissue.

  2. Murine precision-cut lung slices exhibit acute responses following exposure to gasoline direct injection engine emissions.

    Science.gov (United States)

    Maikawa, Caitlin L; Zimmerman, Naomi; Rais, Khaled; Shah, Mittal; Hawley, Brie; Pant, Pallavi; Jeong, Cheol-Heon; Delgado-Saborit, Juana Maria; Volckens, John; Evans, Greg; Wallace, James S; Godri Pollitt, Krystal J

    2016-10-15

    Gasoline direct injection (GDI) engines are increasingly prevalent in the global vehicle fleet. Particulate matter emissions from GDI engines are elevated compared to conventional gasoline engines. The pulmonary effects of these higher particulate emissions are unclear. This study investigated the pulmonary responses induced by GDI engine exhaust using an ex vivo model. The physiochemical properties of GDI engine exhaust were assessed. Precision cut lung slices were prepared using Balb/c mice to evaluate the pulmonary response induced by one-hour exposure to engine-out exhaust from a laboratory GDI engine operated at conditions equivalent to vehicle highway cruise conditions. Lung slices were exposed at an air-liquid interface using an electrostatic aerosol in vitro exposure system. Particulate and gaseous exhaust was fractionated to contrast mRNA production related to polycyclic aromatic hydrocarbon (PAH) metabolism and oxidative stress. Exposure to GDI engine exhaust upregulated genes involved in PAH metabolism, including Cyp1a1 (2.71, SE=0.22), and Cyp1b1 (3.24, SE=0.12) compared to HEPA filtered air (pengine exhaust further increased Cyp1b1 expression compared to filtered GDI engine exhaust (i.e., gas fraction only), suggesting this response was associated with the particulate fraction. Exhaust particulate was dominated by high molecular weight PAHs. Hmox1, an oxidative stress marker, exhibited increased expression after exposure to GDI (1.63, SE=0.03) and filtered GDI (1.55, SE=0.04) engine exhaust compared to HEPA filtered air (pengine exhaust contributes to upregulation of genes related to the metabolism of PAHs and oxidative stress.

  3. Acute respiratory distress syndrome assessment after traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Shahrooz Kazemi

    2016-01-01

    Full Text Available Background: Acute respiratory distress syndrome (ARDS is one of the most important complications associated with traumatic brain injury (TBI. ARDS is caused by inflammation of the lungs and hypoxic damage with lung physiology abnormalities associated with acute respiratory distress syndrome. Aim of this study is to determine the epidemiology of ARDS and the prevalence of risk factors. Methods: This prospective study performed on patients with acute traumatic head injury hospitalization in the intensive care unit of the Shohaday-e Haftom-e-Tir Hospital (September 2012 to September 2013 done. About 12 months, the data were evaluated. Information including age, sex, education, employment, drug and alcohol addiction, were collected and analyzed. The inclusion criteria were head traumatic patients and exclusion was the patients with chest trauma. Questionnaire was designed with doctors supervision of neurosurgery. Then the collected data were analysis. Results: In this study, the incidence of ARDS was 23.8% and prevalence of metabolic acidosis was 31.4%. Most injury with metabolic acidosis was Subarachnoid hemorrhage (SAH 48 (60% and Subdural hemorrhage (SDH was Next Level with 39 (48% Correlation between Glasgow Coma Scale (GCS and Respiratory Distress Syndrome (ARDS were significantly decreased (P< 0.0001. The level of consciousness in patients with skull fractures significantly lower than those without fractures (P= 0.009 [(2.3±4.6 vs (4.02±7.07]. Prevalence of metabolic acidosis during hospitalization was 80 patients (31.4%. Conclusion: Acute respiratory distress syndrome is a common complication of traumatic brain injury. Management and treatment is essential to reduce the mortality. In this study it was found the age of patients with ARDS was higher than patients without complications. ARDS risk factor for high blood pressure was higher in men. Most victims were pedestrians. The most common injury associated with ARDS was SDH. Our analysis

  4. Central diabetes insipidus in children with acute brain insult.

    Science.gov (United States)

    Yang, Yun-Hsuan; Lin, Jainn-Jim; Hsia, Shao-Hsuan; Wu, Chang-Teng; Wang, Huei-Shyong; Hung, Po-Cheng; Chou, Min-Liang; Hsieh, Meng-Ying; Lin, Kuang-Lin

    2011-12-01

    Central diabetes insipidus occurs in patients with overwhelming central nervous system injuries, and may be associated with brain death. The clinical picture of children with acquired central diabetes insipidus after acute brain insult is seldom reported. We retrospectively reviewed cases dating from January 2000-February 2008 at a tertiary pediatric intensive care unit. Fifty-four patients (28 girls, 26 boys), aged 3 months to 18 years, were enrolled. Etiologies included severe central nervous system infection (35.2%), hypoxic-ischemic events (31.5%), head injury (18.5%), and vascular lesions (14.8%). In 39 (72.2%) patients, diabetes insipidus was diagnosed during the first 2 days after acute central nervous system injury, and 40 (74.0%) developed maximum serum sodium concentrations of >160 mEq/L. In 16, sequential cerebral salt wasting syndrome developed after their initial diabetes insipidus presentation. Overall mortality at 2 months after admission was 77.8%. Our results demonstrate that patients who develop central diabetes insipidus after acute central nervous system injury manifest high mortality. Development of central diabetes insipidus within the first 2 days and a maximum plasma sodium >160 mEq/L were significant predictors of outcomes.

  5. Reproducibility of perfusion CT derived CBV and rCBV measurements with different slice thickness in patients with brain neoplasms%脑瘤灌注CT不同层厚CBV与rCBV测量的可重复性研究

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective: To assess inter-and intraobserver reproducibility for measuring perfusion CT derived cerebral blood volume(CBV)and relative cerebral blood volume(rCBV)with different slice thickness in patients with brain neoplasms.Methods: Three independent observers who were blinded to the histopathologic diagnosis performed perfusion derived CBV and rCBV measurements with 5 mm and 10 mm slice thickness in 52 patients with various cerebral neoplasms.The results of the measurements with different slice thickness were compared.Calculation of coefficient of variation(CV), and relative paired difference of the measurements were used to determine the levels of inter-and intraobserver reproducibility.Results: The differences of CBV and rCBV measurements between different slice thickness groups were statistically significant(P<0.05)respectively in observer 2, and were not significant in the other two observers(P>0.05).For the same slice thickness, both the difference of CBV and rCBV measurements among the three observers were not statistically significant.Interobserver CV and relative paired difference of the measurements with 10 mm slice thickness group were slightly lower than those of 5 mm slice thickness group.Interobserver CV and relative paired difference of CBV group were slightly lower than those of rCBV group.The intraobserver differences of CBV and rCBV in 10 mm slice thickness group were statistically significant for observer 2 respectively.No other intraobserver differences of measurements were statistically significant.CV and relative paired difference of intraobserver CBV and rCBV measurements for observer 2 were significantly higher than for the other two observers.Conclusion: High reproducibility of CBV and rCBV measurements was acquired with the two different slice thickness.Suitable training may be helpful to maintain a high level of consistency for measurements.

  6. Acute moderate exercise enhances compensatory brain activation in older adults.

    Science.gov (United States)

    Hyodo, Kazuki; Dan, Ippeita; Suwabe, Kazuya; Kyutoku, Yasushi; Yamada, Yuhki; Akahori, Mitsuya; Byun, Kyeongho; Kato, Morimasa; Soya, Hideaki

    2012-11-01

    A growing number of reports state that regular exercise enhances brain function in older adults. Recently a functional near-infrared spectroscopy (fNIRS) study revealed that an acute bout of moderate exercise enhanced activation of the left dorsolateral prefrontal cortex (L-DLPFC) associated with Stroop interference in young adults. Whether this acute effect is also applicable to older adults was examined. Sixteen older adults performed a color-word matching Stroop task before and after 10 minutes of exercise on a cycle ergometer at a moderate intensity. Cortical hemodynamics of the prefrontal area was monitored with a fNIRS during the Stroop task. We analyzed Stroop interference (incongruent-neutral) as Stroop performance. Though activation for Stroop interference was found in the bilateral prefrontal area before the acute bout of exercise, activation of the right frontopolar area (R-FPA) was enhanced after exercise. In the majority of participants, this coincided with improved performance reflected in Stroop interference results. Thus, an acute bout of moderate exercise improved Stroop performance in older adults, and this was associated with contralateral compensatory activation.

  7. Clinical application of magnetic resonance in acute traumatic brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Morais, Dionei F.; Gaia, Felipe F.P. [Hospital de Base de Sao Jose do Rio Preto, SP (Brazil). Servico de Neurocirurgia]. E-mail: centro@cerebroecoluna.com.br; Spotti, Antonio R.; Tognola, Waldir A. [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil). Dept. de Ciencias Neurologicas; Andrade, Almir F. [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Dept. de Neurocirurgia da Emergencia

    2008-07-01

    Purpose: To evaluate the clinical applications of magnetic resonance imaging (MRI) in patients with acute traumatic brain injury (TBI): to identify the type, quantity, severity; and improvement clinical-radiological correlation. Method: Assessment of 55 patients who were imaged using CT and MRI, 34 (61.8%) males and 21 (38.2%) females, with acute (0 to 5 days) and closed TBI. Results: Statistical significant differences (McNemar test): occurred fractures were detected by CT in 29.1% and by MRI in 3.6% of the patients; subdural hematoma by CT in 10.9% and MRI in 36.4 %; diffuse axonal injury (DAI) by CT in 1.8% and MRI in 50.9%; cortical contusions by CT in 9.1% and MRI in 41.8%; subarachnoid hemorrhage by CT in 18.2% and MRI in 41.8%. Conclusion: MRI was superior to the CT in the identification of DAI, subarachnoid hemorrhage, cortical contusions, and acute subdural hematoma; however it was inferior in diagnosing fractures. The detection of DAI was associated with the severity of acute TBI. (author)

  8. Massive splenic infarction and splenic venous thrombosis observed in a patient with acute splenic syndrome of sickle cell traits on contrast-enhanced thin-slice computed tomography.

    Science.gov (United States)

    Hayashi, Takana Yamakawa; Matsuda, Izuru; Hagiwara, Kazuchika; Takayanagi, Tomoko; Hagiwara, Akifumi

    2016-09-01

    We report a case of splenic infarction in a patient with sickle cell traits (SCT), focusing on the computed tomography (CT) findings. The patient was an African-American man in his twenties with no past medical history who experienced sudden left upper quadrant pain while climbing a mountain (over 3000 m above sea level). Dynamic contrast-enhanced CT revealed massive non-segmental splenic infarction accompanied with nodule-like preserved splenic tissue. The region of splenic infarction did not coincide with the arterial vascular territory and differed from the features of infarction caused by large arterial embolism. In addition, thrombotic occlusion of the distal splenic vein was depicted on plain and contrast-enhanced thin-slice CT images. Early-phase contrast-enhanced images also showed inhomogeneous enhancement of the hepatic parenchyma. The patient's symptoms improved with conservative therapy. A hemoglobin electrophoresis test confirmed the diagnosis of SCT. SCT is usually asymptomatic, but hypoxic environments may induce acute splenic syndrome, which is commonly manifested as splenic infarction. We observed splenic venous thrombosis and inhomogeneous hepatic parenchymal enhancement in addition to a huge splenic infarction in our patient. To the best of our knowledge, this is the first report describing the specific imaging findings, particularly splenic venous thrombosis and inhomogeneous hepatic parenchymal enhancement, of acute splenic syndrome in a patient with previously undiagnosed SCT. These findings demonstrate the pathophysiology of SCT, and may help with the diagnosis of this disease.

  9. Hyponatremia in acute brain disease: the cerebral salt wasting syndrome.

    Science.gov (United States)

    Betjes, Michiel G.H.

    2002-02-01

    Hyponatremia in acute brain disease is a common occurrence, especially after an aneurysmal subarachnoid hemorrhage. Originally, excessive natriuresis, called cerebral salt wasting, and later the syndrome of inappropriate antidiuretic hormone secretion (SIADH), were considered to be the causes of hyponatremia. In recent years, it has become clear that most of these patients are volume-depleted and have a negative sodium balance, consistent with the original description of cerebral salt wasting. Elevated plasma concentrations of atrial or brain natriuretic peptide have been identified as the putative natriuretic factor. Hyponatremia and volume depletion may aggravate neurological symptoms, and timely treatment with adequate replacement of water and NaCl is essential. The use of fludrocortisone to increase sodium reabsorption by the renal tubules may be an alternative approach.

  10. A brain slice culture model for studies of endogenous and exogenous precursor cell migration in the rostral migratory stream

    DEFF Research Database (Denmark)

    Tanvig, Mette; Blaabjerg, Morten; Andersen, Rikke K

    2009-01-01

    The rostral migratory stream (RMS) is the main pathway by which newly born subventricular zone (SVZ) cells reach the olfactory bulb (OB) in rodents. This migration has been well studied in vivo, but an organotypic in vitro model would facilitate more experimental investigations. Here we introduce...... a slice culture preparation of the rat forebrain including en suite the rostral part of the lateral ventricle, the RMS and the OB. The preparation was validated with regard to endogenous cell proliferation and migration by tracking bromodeoxyuridine (BrdU)-labelled cells in newly established and 3 and 6...... week old cultures. For testing the migratory abilities of exogenous precursor cells, rat SVZ neurospheres and human neural (HNS1 cells) and mesenchymal (hMSC-TERT) stem cell lines were micrografted to the rostral SVZ of 1 and 7 day old cultures. Two weeks later graft derivatives were identified...

  11. The value of brain CT findings in acute methanol toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Taheri, Morteza Sanei [Department of Radiology, Shohada Hospital, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Poison Control Center, Loghman-Hakim Poison Hospital, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of)], E-mail: saneim@yahoo.com; Moghaddam, Hossein Hassanian [Poison Control Center, Loghman-Hakim Poison Hospital, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Moharamzad, Yashar; Dadgari, Shahrzad [Department of Radiology, Shohada Hospital, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Nahvi, Vahideh [Poison Control Center, Loghman-Hakim Poison Hospital, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2010-02-15

    Objective: Due to depressant effects of methanol on the central nervous system, brain computed tomography (CT) scan has been introduced as a diagnostic device in methanol intoxication. The authors aimed to present brain CT findings in patients with acute methanol intoxication and to determine signs associated with death. Materials and methods: This cohort study involved 42 consecutive patients with acute methanol intoxication. Inclusion criteria were consisted of characteristic clinical presentation of methanol poisoning, and metabolic acidosis with increased anion and osmolar gaps. Brain CT scans without contrast medium were obtained. To determine the association between the CT findings and death, the chi-square test or the Fisher's exact test, odds ratio (OR) and its 95% confidence interval (95% CI) were calculated. Results: Twenty-eight patients (66.6%) had a total of 55 abnormal findings on brain CT, in which bilateral putaminal hypodense lesions was the most common manifestation (27 cases, 96.4%). Putaminal hemorrhage with varying degrees was observed in 7 patients (25%). Six patients (21.4%) had low attenuation lesions in the subcortical white matter of the insula. A significant association was observed between putaminal hemorrhage (OR = 8, 95% CI = 1.187-53.93, P = 0.018) and subcortical necrosis of the insula (OR = 11, 95% CI = 1.504-80.426, P = 0.007) with death. Conclusion: In addition to clinical and laboratory findings, presence of putaminal hemorrhage and insular subcortex white matter necrosis are associated with a poor clinical outcome in patients with methanol poisoning.

  12. Acute glucocorticoid deficiency and diabetes insipidus are common after acute traumatic brain injury and predict mortality.

    Science.gov (United States)

    Hannon, M J; Crowley, R K; Behan, L A; O'Sullivan, E P; O'Brien, M M C; Sherlock, M; Rawluk, D; O'Dwyer, R; Tormey, W; Thompson, C J

    2013-08-01

    Published data demonstrates that hypopituitarism is common after traumatic brain injury (TBI). Hormone deficiencies are transient in many, but the natural history of the acute changes after TBI has not been documented. In addition, it is not clear whether there are any early parameters that accurately predict the development of permanent hypopituitarism. There were 3 main objectives of this study: 1) to describe the natural history of plasma cortisol (PC) changes and sodium balance after TBI; 2) to identify whether acute hypocortisolemia or cranial diabetes insipidus (CDI) predict mortality; and 3) to identify whether the acute pituitary dysfunction predicts the development of chronic anterior hypopituitarism. Each TBI patient underwent sequential measurement of PC, plasma sodium, urine osmolality, and fluid balance after TBI. All other anterior pituitary hormones were measured on day 10 after TBI. The results from 15 surgical comparisons defined a PC less than 300 nmol/L as inappropriately low for an acutely ill patient. CDI was diagnosed according to standard criteria. Surviving TBI patients underwent dynamic anterior pituitary testing at least 6 months after TBI. The patients were recruited from the Irish National Neurosurgery Centre. One hundred sequential TBI patients were recruited. Fifteen patients admitted to Intensive Therapy Unit (ITU) after major surgery were recruited as comparison patients. PC in TBI patients was compared with that of comparison patients. The mortality rate was compared between TBI patients with and without acute hypocortisolemia. Results of follow-up dynamic pituitary testing were compared between those with and without acute hypocortisolemia. Most of the TBI patients (78%) developed inappropriately low PC after TBI. Low PC and CDI were predictive of mortality. Thirty-nine percent of the patients who had follow-up testing had at least 1 pituitary hormone deficit, all of whom had had previous acute hypocortisolemia or CDI. Acute

  13. Apoptosis and Acute Brain Ischemia in Ischemic Stroke.

    Science.gov (United States)

    Radak, Djordje; Katsiki, Niki; Resanovic, Ivana; Jovanovic, Aleksandra; Sudar-Milovanovic, Emina; Zafirovic, Sonja; Mousad, Shaker A; Isenovic, Esma R

    2017-01-01

    Apoptosis may contribute to a significant proportion of neuron death following acute brain ischemia (ABI), but the underlying mechanisms are still not fully understood. Brain ischemia may lead to stroke, which is one of the main causes of long-term morbidity and mortality in both developed and developing countries. Therefore, stroke prevention and treatment is clinically important. There are two important separate areas of the brain during ABI: the ischemic core and the ischemic penumbra. The ischemic core of the brain experiences a sudden reduction of blood flow, just minutes after ischemic attack with irreversible injury and subsequent cell death. On the other hand, apoptosis within the ischemic penumbra may occur after several hours or days, while necrosis starts in the first hours after the onset of ABI in the ischemic core. ABI is characterized by key molecular events that initiate apoptosis in many cells, such as overproduction of free radicals, Ca2+ overload and excitotoxicity. These changes in cellular homeostasis may trigger either necrosis or apoptosis, which often depends on cell type, cell age, and location in the brain. Apoptosis results in DNA fragmentation, degradation of cytoskeletal and nuclear proteins, cross-linking of proteins, formation of apoptotic bodies, expression of ligands for phagocytic cell receptors and finally uptake by phagocytic cells. This review focuses on recent findings based on animal and human studies regarding the apoptotic mechanisms of neuronal death following ABI and the development of potential neuroprotective agents that reduce morbidity. The effects of statins on stroke prevention and treatment as well as on apoptotic mediators are also considered. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Effects of aspirin plus alpha-tocopherol on brain slices damage after hypoxia-reoxygenation in rats with type 1-like diabetes mellitus.

    Science.gov (United States)

    González-Correa, J A; Arrebola, M M; Cansino, A L; Muñoz-Marín, J; Guerrero, A; Sánchez de la Cuesta, F; De la Cruz, J P

    2006-06-12

    Diabetes mellitus is a risk factor for cerebrovascular ischemic disease. Aspirin (acetylsalicylic acid) is the most widely used drug for the secondary prevention of thrombotic phenomena. It has been also recently demonstrated that alpha-tocopherol influenced in vitro the antiplatelet effect of aspirin. The aim of the present study is to evaluate the effects aspirin plus alpha-tocopherol on cerebral oxidative stress, prostaglandin production and the nitric oxide pathway in a model of hypoxia-reoxygenation in rat brain slices. Our results show an imbalance in brain oxidative status (reflected mainly as the increase in lipid peroxides) as a result of diabetes itself rather than a failure of the glutathione-based antioxidant system. Moreover, our results also show a higher concentration of prostaglandins in the brain of diabetic animals and a higher nitric oxide concentration, mainly through a high iNOS activity. After 180 min of post-hypoxia reoxygenation, LDH activity was 40.6% higher in animals with diabetes, in comparison to non-diabetic animals. The increase of the LDH efflux observed in non-treated rats was reduced by 31.2% with aspirin, by 34.7% with alpha-tocopherol and by 69.8% with the association aspirin-alpha-tocopherol. The accumulation of prostaglandin E2 observed in diabetic non-treated rats was reduced statistically after the treatment with aspirin (34.2% inhibition), alpha-tocopherol (19.3% inhibition) or the association aspirin-alpha-tocopherol (54.4% inhibition). Nitric oxide production after 180 min reoxygenation was significantly reduced in aspirin (36.4%), alpha-tocopherol (22.7%) and aspirin-alpha-tocopherol (77.8%) treated rats with respect to diabetic non-treated animals; this was related mainly with a reduction in iNOS activity. The association between aspirin and alpha tocopherol could protects against brain ischemic-reperfusion damage with a better profile than aspirin alone.

  15. Time-lapse Confocal Imaging of Migrating Neurons in Organotypic Slice Culture of Embryonic Mouse Brain Using In Utero Electroporation.

    Science.gov (United States)

    Wiegreffe, Christoph; Feldmann, Svenja; Gaessler, Simeon; Britsch, Stefan

    2017-07-25

    In utero electroporation is a rapid and powerful approach to study the process of radial migration in the cerebral cortex of developing mouse embryos. It has helped to describe the different steps of radial migration and characterize the molecular mechanisms controlling this process. To directly and dynamically analyze migrating neurons they have to be traced over time. This protocol describes a workflow that combines in utero electroporation with organotypic slice culture and time-lapse confocal imaging, which allows for a direct examination and dynamic analysis of radially migrating cortical neurons. Furthermore, detailed characterization of migrating neurons, such as migration speed, speed profiles, as well as radial orientation changes, is possible. The method can easily be adapted to perform functional analyses of genes of interest in radially migrating cortical neurons by loss and gain of function as well as rescue experiments. Time-lapse imaging of migrating neurons is a state-of-the-art technique that once established is a potent tool to study the development of the cerebral cortex in mouse models of neuronal migration disorders.

  16. Culturing of PC12 Cells, Neuronal Cells, Astrocytes Cultures and Brain Slices in an Open Microfluidic System

    DEFF Research Database (Denmark)

    Al Atraktchi, Fatima Al-Zahraa; Bakmand, Tanya; Rømer Sørensen, Ane

    The brain is the center of the nervous system, where serious neurodegenerative diseases such as Parkinson’s, Alzheimer’s and Huntington’s are products of functional loss in the neural cells (1). Typical techniques used to investigate these diseases lack precise control of the cellular surroundings...

  17. The inflammatory molecules IL-1β and HMGB1 can rapidly enhance focal seizure generation in a brain slice model of temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Angela eChiavegato

    2014-06-01

    Full Text Available Epilepsy is a neurological disorder characterized by a hyperexcitable brain tissue and unpredictable seizures, i.e., aberrant firing discharges in large neuronal populations. It is well established that proinflammatory cytokines, in addition to their canonical involvement in the immune response, have a crucial role in the mechanism of seizure generation. The purpose of the present study was to investigate the role of interleukin-1β (IL-1β and high mobility group B1 (HMGB1 in the generation of seizure-like discharges using two models of focal epilepsy in a rat entorhinal cortex slice preparation. Seizure like-discharges were evoked by either slice perfusion with low Mg2+ and picrotoxin or with a double NMDA local stimulation in the presence of the proconvulsant 4-amino-pyridine. The effects of IL-1β or HMGB1 were evaluated by monitoring seizure discharge generation through laser scanning microscope imaging of Ca2+ signals from neurons and astrocytes. In the picrotoxin model, we revealed that both cytokines increased the mean frequency of spontaneous ictal-like discharges, whereas only IL-1β reduced the latency and prolonged the duration of the first ictal-like event. In the second model, a single NMDA pulse, per se ineffective, became successful when it was performed after IL-β or HMGB1 local applications. These findings demonstrate that both IL-1β and HMGB1 can rapidly lower focal ictal event threshold and strengthen the possibility that targeting these inflammatory pathways may represent an effective therapeutic strategy to prevent seizures.

  18. Evaluation of Mitochondrial Function in the CNS of Rodent Models of Alzheimer's Disease - High Resolution Respirometry Applied to Acute Hippocampal Slices.

    Science.gov (United States)

    Dias, Candida; Barbosa, Rui M; Laranjinha, Joao; Ledo, Ana

    2014-10-01

    Alzheimer's disease (AD) is a multifactorial disease characterized by extracellular deposits of amyloid plaques and intracellular neurofibrillary tangles. These hallmark alterations are preceded by synaptic deterioration, changes in neuromolecular plasticity phenomena, mitochondrial dysfunction, increase in oxidative damage to cellular constituents and decreased energy metabolism. The hippocampus is a structure of the temporal medial lobe implicated in specific forms of memory processes. It is also one of the first and most affected regions of the CNS in AD. Here we present a novel approach to the study if mitochondrial function/disfunction in 2 rodent models of AD: an acute rat model obtained by intracerebroventricular injection of the toxin streptozotocin (STZ) and a progressive triple transgenic mouse model (3TgAD) harboring PS1M146V, APPSwe, and tauP301L transgenes. Mitochondrial dysfunction has classically been assessed in such models by isolating mitochondria, synaptossoms or working with cell cultures. Anyone of these approaches destroys the intricate intercellular connectivity and cytoarchitecture of neuronal tissue. We used acute hippocampal slices obtained from the 2 models of AD and evaluated changes in mitochondrial function as a function of disease and/or age. Mitochondrial stress test were performed on the high resolution respirometry (Oroboros 2K Oxymeter). Upon analysis of oxygen consumption rates (OCR) we observed significant decreases in basal OCR, maximal respiratory capacity, ATP turnover and a tendency for decrease in sparing capacity in the STZ rat model compared to shame injected animals. Regarding the 3TgAD model we observed an age-dependent decrease in all parameters evaluated in the mitochondrial stress test, in both 3TgAD and NTg animals. However, although a tendency towards decreased OCR was observed when comparing 3TgAD and age-matched NTg animals, no statistically significant difference was observed. Copyright © 2014. Published by

  19. Quantitative evaluation of benign meningioma and hemangiopericytoma with peritumoral brain edema by 64-slice CT perfusion imaging

    Institute of Scientific and Technical Information of China (English)

    REN Guang; CHEN Shuang; WANG Yin; ZHU Rui-jiang; GENG Dao-ying; FENG Xiao-yuan

    2010-01-01

    Background Hemangiopericytomas (HPCs) have a relentless tendency for local recurrence and metastases,differentiating between benign meningiomas and HPCs before surgery is important for both treatment planning and the prognosis appraisal.The purpose of this study was to evaluate the correlations between CT perfusion parameters and microvessel density (MVD) in extra-axial tumors and the possible role of CT perfusion imaging in preoperatively differentiating benign meningiomas and HPCs.Methods Seventeen patients with benign meningiomas and peritumoral edema, 12 patients with HPCs and peritumoral edema underwent 64-slice CT perfusion imaging pre-operation.Perfusion was calculated using the Patlak method.The quantitative parameters, include cerebral blood volume (CBV), permeability surface (PS) of parenchyma, peritumoral edema among benign meningiomas and HPCs were compared respectively.CBV and PS in parenchyma, peritumoral edema of benign meningiomas and HPCs were also compared to that of the contrallateral normal white matter respectively.The correlations between CBV, PS of tumoral parenchyma and MVD were examined.Results The value of CBV and PS in parenchyma of HPCs were significantly higher than that of benign meningiomas (P<0.05), while the values of CBV and PS in peritumoral edema of benign meningiomas and HPCs were not significantly different (P >0.05).MVD in parenchyma of HPCs were significantly higher than that of benign meningiomas (P<0.05).There were positive correlations between CBV and MVD (r=0.648, P<0.05), PS and MVD (r=0.541, P<0.05) respectively.Furthermore, the value of CBV and PS in parenchyma of benign meningiomas and HPCs were significantly higher than that of contrallateral normal white matter (P<0.05), the value of CBV in peritumoral edema of benign meningiomas and HPCs were significantly lower than that of contrallateral normal white matter (P<0.05), while the value of PS in peritumoral edema of benign meningiomas and HPCs were not

  20. Evaluation of 2D multiband EPI imaging for high-resolution, whole-brain, task-based fMRI studies at 3T: Sensitivity and slice leakage artifacts.

    Science.gov (United States)

    Todd, Nick; Moeller, Steen; Auerbach, Edward J; Yacoub, Essa; Flandin, Guillaume; Weiskopf, Nikolaus

    2016-01-01

    Functional magnetic resonance imaging (fMRI) studies that require high-resolution whole-brain coverage have long scan times that are primarily driven by the large number of thin slices acquired. Two-dimensional multiband echo-planar imaging (EPI) sequences accelerate the data acquisition along the slice direction and therefore represent an attractive approach to such studies by improving the temporal resolution without sacrificing spatial resolution. In this work, a 2D multiband EPI sequence was optimized for 1.5mm isotropic whole-brain acquisitions at 3T with 10 healthy volunteers imaged while performing simultaneous visual and motor tasks. The performance of the sequence was evaluated in terms of BOLD sensitivity and false-positive activation at multiband (MB) factors of 1, 2, 4, and 6, combined with in-plane GRAPPA acceleration of 2× (GRAPPA 2), and the two reconstruction approaches of Slice-GRAPPA and Split Slice-GRAPPA. Sensitivity results demonstrate significant gains in temporal signal-to-noise ratio (tSNR) and t-score statistics for MB 2, 4, and 6 compared to MB 1. The MB factor for optimal sensitivity varied depending on anatomical location and reconstruction method. When using Slice-GRAPPA reconstruction, evidence of false-positive activation due to signal leakage between simultaneously excited slices was seen in one instance, 35 instances, and 70 instances over the ten volunteers for the respective accelerations of MB 2×GRAPPA 2, MB 4×GRAPPA 2, and MB 6×GRAPPA 2. The use of Split Slice-GRAPPA reconstruction suppressed the prevalence of false positives significantly, to 1 instance, 5 instances, and 5 instances for the same respective acceleration factors. Imaging protocols using an acceleration factor of MB 2×GRAPPA 2 can be confidently used for high-resolution whole-brain imaging to improve BOLD sensitivity with very low probability for false-positive activation due to slice leakage. Imaging protocols using higher acceleration factors (MB 3 or MB 4

  1. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    Science.gov (United States)

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-06-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.

  2. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    Science.gov (United States)

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-01-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries. PMID:27351915

  3. Tamoxifen mediated estrogen receptor activation protects against early impairment of hippocampal neuron excitability in an oxygen/glucose deprivation brain slice ischemia model.

    Science.gov (United States)

    Zhang, Huaqiu; Xie, Minjie; Schools, Gary P; Feustel, Paul F; Wang, Wei; Lei, Ting; Kimelberg, Harold K; Zhou, Min

    2009-01-09

    Pretreatment of ovarectomized rats with estrogen shows long-term protection via activation of the estrogen receptor (ER). However, it remains unknown whether activation of the ER can provide protection against early neuronal damage when given acutely. We simulated ischemic conditions by applying oxygen and glucose deprived (OGD) solution to acute male rat hippocampal slices and examined the neuronal electrophysiological changes. Pyramidal neurons and interneurons showed a time-dependent membrane potential depolarization and reduction in evoked action potential frequency and amplitude over a 10 to 15 min OGD exposure. These changes were largely suppressed by 10 microM TAM. The TAM effect was neuron-specific as the OGD-induced astrocytic membrane potential depolarization was not altered. The TAM effect was mediated through ER activation because it could be simulated by 17beta-estradiol and was completely inhibited by the ER inhibitor ICI 182, 780, and is therefore an example of TAM's selective estrogen receptor modulator (SERM) action. We further show that TAM's effects on OGD-induced impairment of neuronal excitability was largely due to activation of neuroprotective BK channels, as the TAM effect was markedly attenuated by the BK channel inhibitor paxilline at 10 microM. TAM also significantly reduced the frequency and amplitude of AMPA receptor mediated spontaneous excitatory postsynaptic currents (sEPSCs) in pyramidal neurons which is an early consequence of OGD. Altogether, this study demonstrates that both 17beta-estradiol and TAM attenuate neuronal excitability impairment early on in a simulated ischemia model via ER activation mediated potentiation of BK K(+) channels and reduction in enhanced neuronal AMPA/NMDA receptor-mediated excitotoxicity.

  4. Brain expression of the water channels Aquaporin-1 and -4 in mice with acute liver injury, hyperammonemia and brain edema

    DEFF Research Database (Denmark)

    Eefsen, Martin; Jelnes, Peter; Schmidt, Lars E;

    2010-01-01

    Cerebral edema is a feared complication to acute liver failure (ALF), but the pathogenesis is still poorly understood. The water channels Aquaporin-1 (Aqp1) and -4 (Aqp4) has been associated with brain edema formation in several neuropathological conditions, indicating a possible role of Aqp1 and....../or Aqp4 in ALF mediated brain edema. We induced acute liver injury and hyperammonemia in mice, to evaluate brain edema formation and the parallel expression of Aqp1 and Aqp4 in ALF. Liver injury and hyperammonemia were induced by +D-galactosamine (GLN) plus lipopolysaccharide (LPS) intraperitoneally......(6266) (p edema in mice with ALF....

  5. Involvement of striatal lipid peroxidation and inhibition of calcium influx into brain slices in neurobehavioral alterations in a rat model of short-term oral exposure to manganese.

    Science.gov (United States)

    Avila, Daiana Silva; Gubert, Priscila; Fachinetto, Roselei; Wagner, Caroline; Aschner, Michael; Rocha, João Batista Teixeira; Soares, Félix Alexandre Antunes

    2008-11-01

    Manganese is an essential element for biological systems, nevertheless occupational exposure to high levels of Mn can lead to neurodegenerative disorder, characterized by excessive Mn accumulation, especially in astrocytes of basal ganglia and symptoms closely resembling idiopathic Parkinson's disease (PD). The purpose of this study was to evaluate behavioral and biochemical alterations in adult rats exposed for 30 days to 10 and 25mg/mL of MnCl(2) in their drinking water. MnCl(2) intoxicated rats showed impaired locomotor activity in comparison to control animals. Furthermore, lipid peroxidation were increased, delta-aminolevulinate dehydratase (delta-ALA-D, an enzyme sensitive to pro-oxidant situations) activity was inhibited and (45)Ca(2+) influx into striatal slices was decreased in rats exposed to 25mg/mL of Mn, indicating that this brain region was markedly affected by short-term Mn exposure. In contrast, Mn exposure was not associated with characteristic extrapyramidal effects and did not modify protein oxidation, suggesting that the striatal damage represents early stages of Mn-induced damage. In addition, treatment with Mn was associated with reduced body weight gain, but there were no discernible alterations in liver and kidney function. In conclusion, Mn caused increased oxidative stress and decreased (45)Ca(2+) influx into the striatum, which are likely linked to impaired locomotor activity, but not with the occurrence of orofacial dyskinesia.

  6. N-Methyl-d-aspartate Modulation of Nucleus Accumbens Dopamine Release by Metabotropic Glutamate Receptors: Fast Cyclic Voltammetry Studies in Rat Brain Slices in Vitro.

    Science.gov (United States)

    Yavas, Ersin; Young, Andrew M J

    2017-02-15

    The N-methyl-d-aspartate (NMDA) receptor antagonist, phencyclidine, induces behavioral changes in rodents mimicking symptoms of schizophrenia, possibly mediated through dysregulation of glutamatergic control of mesolimbic dopamine release. We tested the hypothesis that NMDA receptor activation modulates accumbens dopamine release, and that phencyclidine pretreatment altered this modulation. NMDA caused a receptor-specific, dose-dependent decrease in electrically stimulated dopamine release in nucleus accumbens brain slices. This decrease was unaffected by picrotoxin, making it unlikely to be mediated through GABAergic neurones, but was decreased by the metabotropic glutamate receptor antagonist, (RS)-α-methyl-4-sulfonophenylglycine, indicating that NMDA activates mechanisms controlled by these receptors to decrease stimulated dopamine release. The effect of NMDA was unchanged by in vivo pretreatment with phencyclidine (twice daily for 5 days), with a washout period of at least 7 days before experimentation, which supports the hypothesis that there is no enduring direct effect of PCP at NMDA receptors after this pretreatment procedure. We propose that NMDA depression of accumbal dopamine release is mediated by metabotropic glutamate receptors located pre- or perisynaptically, and suggest that NMDA evoked increased extrasynaptic spillover of glutamate is sufficient to activate these receptors that, in turn, inhibit dopamine release. Furthermore, we suggest that enduring functional changes brought about by subchronic phencyclidine pretreatment, modeling deficits in schizophrenia, are downstream effects consequent on chronic blockade of NMDA receptors, rather than direct effects on NMDA receptors themselves.

  7. Brain stem slice conditioned medium contains endogenous BDNF and GDNF that affect neural crest boundary cap cells in co-culture.

    Science.gov (United States)

    Kaiser, Andreas; Kale, Ajay; Novozhilova, Ekaterina; Siratirakun, Piyaporn; Aquino, Jorge B; Thonabulsombat, Charoensri; Ernfors, Patrik; Olivius, Petri

    2014-05-30

    Conditioned medium (CM), made by collecting medium after a few days in cell culture and then re-using it to further stimulate other cells, is a known experimental concept since the 1950s. Our group has explored this technique to stimulate the performance of cells in culture in general, and to evaluate stem- and progenitor cell aptitude for auditory nerve repair enhancement in particular. As compared to other mediums, all primary endpoints in our published experimental settings have weighed in favor of conditioned culture medium, where we have shown that conditioned culture medium has a stimulatory effect on cell survival. In order to explore the reasons for this improved survival we set out to analyze the conditioned culture medium. We utilized ELISA kits to investigate whether brain stem (BS) slice CM contains any significant amounts of brain-derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF). We further looked for a donor cell with progenitor characteristics that would be receptive to BDNF and GDNF. We chose the well-documented boundary cap (BC) progenitor cells to be tested in our in vitro co-culture setting together with cochlear nucleus (CN) of the BS. The results show that BS CM contains BDNF and GDNF and that survival of BC cells, as well as BC cell differentiation into neurons, were enhanced when BS CM were used. Altogether, we conclude that BC cells transplanted into a BDNF and GDNF rich environment could be suitable for treatment of a traumatized or degenerated auditory nerve. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Stimulant mechanisms of cathinones - effects of mephedrone and other cathinones on basal and electrically evoked dopamine efflux in rat accumbens brain slices.

    Science.gov (United States)

    Opacka-Juffry, Jolanta; Pinnell, Thomas; Patel, Nisha; Bevan, Melissa; Meintel, Meghan; Davidson, Colin

    2014-10-01

    Mephedrone, an erstwhile "legal high", and some non-abused cathinones (ethcathinone, diethylpropion and bupropion) were tested for stimulant effects in vitro, through assessing their abilities to increase basal and electrically evoked dopamine efflux in rat accumbens brain slices, and compared with cocaine and amphetamine. We also tested mephedrone against cocaine in a dopamine transporter binding study. Dopamine efflux was electrically evoked and recorded using voltammetry in the rat accumbens core. We constructed concentration response curves for these cathinones for effects on basal dopamine levels; peak efflux after local electrical stimulation and the time-constant of the dopamine decay phase, an index of dopamine reuptake. We also examined competition between mephedrone or cocaine and [(125)I]RTI121 at the dopamine transporter. Mephedrone was less potent than cocaine at displacing [(125)I]RTI121. Mephedrone and amphetamine increased basal levels of dopamine in the absence of electrical stimulation. Cocaine, bupropion, diethylpropion and ethcathinone all increased the peak dopamine efflux after electrical stimulation and slowed dopamine reuptake. Cocaine was more potent than bupropion and ethcathinone, while diethylpropion was least potent. Notably, cocaine had the fastest onset of action. These data suggest that, with respect to dopamine efflux, mephedrone is more similar to amphetamine than cocaine. These findings also show that cocaine was more potent than bupropion and ethcathinone while diethylpropion was least potent. Mephedrone's binding to the dopamine transporter is consistent with stimulant effects but its potency was lower than that of cocaine. These findings confirm and further characterize stimulant properties of mephedrone and other cathinones in adolescent rat brain.

  9. 31P-saturation-transfer nuclear-magnetic-resonance measurements of phosphocreatine turnover in guinea-pig brain slices.

    Science.gov (United States)

    Morris, P G; Feeney, J; Cox, D W; Bachelard, H S

    1985-05-01

    The technique of 31P saturation-transfer n.m.r. was used to determine the forward and the reverse rate constants of creatine phosphotransferase in superfused guinea-pig cerebral tissues in vitro. The calculated forward rate constant of 0.22 +/- 0.03s-1 compared well with a previously reported value for rat brain in vivo [Shoubridge, Briggs & Radda (1982) FEBS Lett. 140, 288-292]. The reverse rate constant was found to be 0.55 +/- 0.10s-1. 3. By using concentrations of ATP and phosphocreatine estimated previously for this superfused preparation [Cox, Morris, Feeney & Bachelard (1983) Biochem. J. 212, 365-370], forward and reverse flux rates were calculated to be 0.68 and 0.72 mumol X s-1 X g-1 respectively. The concordance of forward and reverse fluxes contrasts with the situation observed in vitro in other tissues, and suggests that the creatine phosphotransferase reaction is at equilibrium under the conditions used here. 4. Lowering the concentration of glucose in the superfusing medium from 10mM to 0.5mM had no significant effect on phosphocreatine concentration or on the forward (ATP-generating) flux through creatine phosphotransferase. The results indicate that a normal phosphocreatine content in the presence of lowered glucose availability is reflected by an unchanged turnover rate.

  10. Central Administration of Lipopolysaccharide Induces Depressive-like Behavior in Vivo and Activates Brain Indoleamine 2,3 Dioxygenase In Murine Organotypic Hippocampal Slice Cultures

    Directory of Open Access Journals (Sweden)

    Kavelaars Annemieke

    2010-08-01

    Full Text Available Abstract Background Transient stimulation of the innate immune system by an intraperitoneal injection of lipopolysaccharide (LPS activates peripheral and central expression of the tryptophan degrading enzyme indoleamine 2,3 dioxygenase (IDO which mediates depressive-like behavior. It is unknown whether direct activation of the brain with LPS is sufficient to activate IDO and induce depressive-like behavior. Methods Sickness and depressive-like behavior in C57BL/6J mice were assessed by social exploration and the forced swim test, respectively. Expression of cytokines and IDO mRNA was measured by real-time RT-PCR and cytokine protein was measured by enzyme-linked immunosorbent assays (ELISAs. Enzymatic activity of IDO was estimated as the amount of kynurenine produced from tryptophan as determined by high pressure liquid chromatography (HPLC with electrochemical detection. Results Intracerebroventricular (i.c.v. administration of LPS (100 ng increased steady-state transcripts of TNFα, IL-6 and the inducible isoform of nitric oxide synthase (iNOS in the hippocampus in the absence of any change in IFNγ mRNA. LPS also increased IDO expression and induced depressive-like behavior, as measured by increased duration of immobility in the forced swim test. The regulation of IDO expression was investigated using in situ organotypic hippocampal slice cultures (OHSCs derived from brains of newborn C57BL/6J mice. In accordance with the in vivo data, addition of LPS (10 ng/ml to the medium of OHSCs induced steady-state expression of mRNA transcripts for IDO that peaked at 6 h and translated into increased IDO enzymatic activity within 8 h post-LPS. This activation of IDO by direct application of LPS was preceded by synthesis and secretion of TNFα and IL-6 protein and activation of iNOS while IFNγ expression was undetectable. Conclusion These data establish that activation of the innate immune system in the brain is sufficient to activate IDO and induce

  11. Voltage-sensitive dye recording from axons, dendrites and dendritic spines of individual neurons in brain slices.

    Science.gov (United States)

    Popovic, Marko; Gao, Xin; Zecevic, Dejan

    2012-11-29

    Understanding the biophysical properties and functional organization of single neurons and how they process information is fundamental for understanding how the brain works. The primary function of any nerve cell is to process electrical signals, usually from multiple sources. Electrical properties of neuronal processes are extraordinarily complex, dynamic, and, in the general case, impossible to predict in the absence of detailed measurements. To obtain such a measurement one would, ideally, like to be able to monitor, at multiple sites, subthreshold events as they travel from the sites of origin on neuronal processes and summate at particular locations to influence action potential initiation. This goal has not been achieved in any neuron due to technical limitations of measurements that employ electrodes. To overcome this drawback, it is highly desirable to complement the patch-electrode approach with imaging techniques that permit extensive parallel recordings from all parts of a neuron. Here, we describe such a technique - optical recording of membrane potential transients with organic voltage-sensitive dyes (V(m)-imaging) - characterized by sub-millisecond and sub-micrometer resolution. Our method is based on pioneering work on voltage-sensitive molecular probes (2). Many aspects of the initial technology have been continuously improved over several decades (3, 5, 11). Additionally, previous work documented two essential characteristics of V(m)-imaging. Firstly, fluorescence signals are linearly proportional to membrane potential over the entire physiological range (-100 mV to +100 mV; (10, 14, 16)). Secondly, loading neurons with the voltage-sensitive dye used here (JPW 3028) does not have detectable pharmacological effects. The recorded broadening of the spike during dye loading is completely reversible (4, 7). Additionally, experimental evidence shows that it is possible to obtain a significant number (up to hundreds) of recordings prior to any detectable

  12. Outcome of 2 284 cases with acute traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To analyze the prognosis of 2 284 cases with acute traumatic brain injury and discuss possible methods to improve the outcome of head injuries.   Methods: The relationship between trauma cause, trauma severity and management and patients outcome was retrospectively analyzed.   Results: Good recovery was achieved in 60.20%, moderate disability was 13.22%, severe disability 15.24%, vegetative status 0.31% and mortality 11.03%. The mortality was 1.07% in cases with GCS 15-13, 2.47% in cases with GCS 12-9, 13.29% in cases with GCS 8-6, and 57.4% in cases with GCS 5-3.   Conclusions: To prevent hypoxia, remove intracranial hematoma as soon as possible, use standard large traumatic craniotomy and apply mild hypothermia may be useful means for improving the outcome of severely head injured patients.

  13. Acute, regional inflammatory response after traumatic brain injury: Implications for cellular therapy

    OpenAIRE

    Harting, Matthew T.; jimenez, fernando; Adams, Sasha D.; Mercer, David W.; Cox, Charles S.

    2008-01-01

    While cellular therapy has shown promise in the management of traumatic brain injury (TBI), microenvironment interactions between the intracerebral milieu and therapeutic stem cells are poorly understood. We sought to characterize the acute, regional inflammatory response after TBI.

  14. A Simulation-based Approach for Improving Utilization of Thrombolysis in Acute Brain Infarction

    NARCIS (Netherlands)

    Lahr, M. M. H.; van der Zee, D. J.; Luijckx, G. J.; Vroomen, Patrick; Buskens, E.

    2013-01-01

    BACKGROUND: Treatment with tissue plasminogen activator (tPA) is the most effective treatment in acute brain infarction. However, estimated worldwide treatment rates are <10%, with many barriers hampering broad implementation. Organization and resource-intense randomized controlled trials cannot

  15. Protective effect of grifolin against brain injury in an acute cerebral ...

    African Journals Online (AJOL)

    Protective effect of grifolin against brain injury in an acute ... Sent for review: 24 January 2017 ... levels in tissue homogenates of the cerebral ischemic rats compared with those in the negative ... Stroke is a major cause of death worldwide [1].

  16. Tumor necrosis factor α antibody prevents brain damage of rats with acute necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Yan-Ling Yang; Ji-Peng Li; Kai-Zong Li; Ke-Feng Dou

    2004-01-01

    AIM: To study the protective effects of tumor necrosis factor á (TNFα) antibody on pancreatic encephalopathy in rats.METHODS:One hundred and twenty SD rats were randomly divided into normal control group,acute necrotizing pancreatitis group and TNFα antibody treated group.Acute hemorrhage necrotizing pancreatitis model in rats was induced by retrograde injection of 50 g/L sodium taurocholate into the pancreatobiliary duct.Serum TNFα was detected and animals were killed 12 h after drug administration.Changes in content of brain water,MDA and SOD as well as leucocyte adhesion of brain microvessels were measured.RESULTS:In TNFα antibody treated group,serum TNFálevel was decreased.Content of brain water,MDA and SOD as well as leucocyte adhesion were decreased significantly in comparison with those of acute necrotizing pancreatitis group (P<0.05).CONCLUSION:TNFα antibody can alleviate the brain damage of rats with acute hemorrhage necrotizing pancreatitis.

  17. GLP-1R Signaling Directly Activates Arcuate Nucleus Kisspeptin Action in Brain Slices but Does not Rescue Luteinizing Hormone Inhibition in Ovariectomized Mice During Negative Energy Balance

    Science.gov (United States)

    Heppner, Kristy M.; Baquero, Arian F.; True, Cadence; Grove, Kevin L.

    2017-01-01

    Abstract Kisspeptin (Kiss1) neurons in the hypothalamic arcuate nucleus (ARC) are key components of the hypothalamic-pituitary-gonadal axis, as they regulate the basal pulsatile release of gonadotropin releasing hormone (GnRH). ARC Kiss1 action is dependent on energy status, and unmasking metabolic factors responsible for modulating ARC Kiss1 neurons is of great importance. One possible factor is glucagon-like peptide 1 (GLP-1), an anorexigenic neuropeptide produced by brainstem preproglucagon neurons. Because GLP fiber projections and the GLP-1 receptor (GLP-1R) are abundant in the ARC, we hypothesized that GLP-1R signaling could modulate ARC Kiss1 action. Using ovariectomized mice, we found that GLP-producing fibers come in close apposition with ARC Kiss1 neurons; these neurons also contain Glp1r mRNA. Electrophysiological recordings revealed that liraglutide (a long-acting GLP-1R agonist) increased action potential firing and caused a direct membrane depolarization of ARC Kiss1 cells in brain slices. We determined that brainstem preproglucagon mRNA is decreased after a 48-h fast in mice, a negative energy state in which ARC Kiss1 expression and downstream GnRH/luteinizing hormone (LH) release are potently suppressed. However, activation of GLP-1R signaling in fasted mice with liraglutide was not sufficient to prevent LH inhibition. Furthermore, chronic central infusions of the GLP-1R antagonist, exendin(9–39), in ad libitum–fed mice did not alter ARC Kiss1 mRNA or plasma LH. As a whole, these data identify a novel interaction of the GLP-1 system with ARC Kiss1 neurons but indicate that CNS GLP-1R signaling alone is not critical for the maintenance of LH during fasting or normal feeding. PMID:28144621

  18. GLP-1R Signaling Directly Activates Arcuate Nucleus Kisspeptin Action in Brain Slices but Does not Rescue Luteinizing Hormone Inhibition in Ovariectomized Mice During Negative Energy Balance.

    Science.gov (United States)

    Heppner, Kristy M; Baquero, Arian F; Bennett, Camdin M; Lindsley, Sarah R; Kirigiti, Melissa A; Bennett, Baylin; Bosch, Martha A; Mercer, Aaron J; Rønnekleiv, Oline K; True, Cadence; Grove, Kevin L; Smith, M Susan

    2017-01-01

    Kisspeptin (Kiss1) neurons in the hypothalamic arcuate nucleus (ARC) are key components of the hypothalamic-pituitary-gonadal axis, as they regulate the basal pulsatile release of gonadotropin releasing hormone (GnRH). ARC Kiss1 action is dependent on energy status, and unmasking metabolic factors responsible for modulating ARC Kiss1 neurons is of great importance. One possible factor is glucagon-like peptide 1 (GLP-1), an anorexigenic neuropeptide produced by brainstem preproglucagon neurons. Because GLP fiber projections and the GLP-1 receptor (GLP-1R) are abundant in the ARC, we hypothesized that GLP-1R signaling could modulate ARC Kiss1 action. Using ovariectomized mice, we found that GLP-producing fibers come in close apposition with ARC Kiss1 neurons; these neurons also contain Glp1r mRNA. Electrophysiological recordings revealed that liraglutide (a long-acting GLP-1R agonist) increased action potential firing and caused a direct membrane depolarization of ARC Kiss1 cells in brain slices. We determined that brainstem preproglucagon mRNA is decreased after a 48-h fast in mice, a negative energy state in which ARC Kiss1 expression and downstream GnRH/luteinizing hormone (LH) release are potently suppressed. However, activation of GLP-1R signaling in fasted mice with liraglutide was not sufficient to prevent LH inhibition. Furthermore, chronic central infusions of the GLP-1R antagonist, exendin(9-39), in ad libitum-fed mice did not alter ARC Kiss1 mRNA or plasma LH. As a whole, these data identify a novel interaction of the GLP-1 system with ARC Kiss1 neurons but indicate that CNS GLP-1R signaling alone is not critical for the maintenance of LH during fasting or normal feeding.

  19. Effective range of electrical stimulation in brain silica preparation; No slice hyohon ni okeru denki shigeki koka han`i no kento

    Energy Technology Data Exchange (ETDEWEB)

    Takimori, T.; Ogawa, T.; Nishida, M. [Akita University, Akita (Japan)

    1997-08-20

    In order to examine the confines of electrical stimulation in layer 2/3 of visual cortex in the brain slice preparation, we estimated the effective range of the stimulation based on the excitatory postsynaptic potential (EPSP) evoked in layer V neuron which receives input from layer 2/3. For this purpose, we recorded and compared EPSPs amplitudes evoked by stimulations at directly over site of recording electrode and lateral site in layer 2/3. Since the EPSP increased linearly with stimulus intensity before the saturation, it was considered that the EPSP correlates with the number of projecting neurons in area directly excited with the stimulation. Then we formed the region model by which we can get the ratios between the neuron numbers in areas excited by different sites stimulations against the stimulus effective ranges. And in the stimulus intensity for action potential threshold of layer 5 neuron, we evaluated the effective range for the relative values of EPSPs to be produced with the stimulations of 250{mu}m lateral site and directory over site. In the model, the ratio increased monotonically with the effective range and in the case of 250{mu}m for the effective range, the ratio between those EPSPs was less than the value in the model. These results led the conclusion that the effective range of the intensity for layer 5 neuron to generate the output is confined within 250{mu}m from directly over site, that is, within layer 2/3. 7 refs., 11 figs., 1 tab.

  20. Diagnosis of acute mesenteric ischemia with multi-slice spiral CT%急性肠系膜缺血的MSCT诊断

    Institute of Scientific and Technical Information of China (English)

    贾乾君; 梁长虹; 张水兴; 刘再毅

    2011-01-01

    目的:探讨MSCT对急性肠系膜缺血的诊断价值.方法:回顾性分析经手术或介入治疗证实的36例急性肠系膜缺血患者的CT表现.所有患者均行CT检查,包括平扫、增强扫描动脉期、增强扫描门脉期并进行血管重建.后处理采用容积显示技术(VRT)、多平面重组(MPR)和薄层最大密度投影(MIP)进行动脉和门脉成像.结果:肠系膜上动脉栓塞5例,肠系膜上动脉狭窄6例,肠系膜上静脉血栓形成25例.CT直接征象为血管内充盈缺损(30例)或狭窄(6例).间接征象包括:肠管扩张、肠腔内积液积气(22例),肠壁增厚(14例),肠壁薄纸样改变(3例),肠壁积气(3例).肠系膜脂肪水肿及渗出(4例).结论:MSCT与其三维重组技术相结合是诊断急性肠系膜缺血的一种有效且无创的影像检查方法,可以明确阻塞动脉的部位及范围,对手术有较高的指导价值.%Objective : To study the clinical value of multi-slice spiral CT(MSCT) in the diagnosis of acute mesenteric ischemia. Methods:The CT features of 36 patients with surgery/interventional therapy proved acute mesenteric ischemia were reviewed retrospectively. All patients underwent MSCT scanning,including plain scan, arterial phase and portal vein phase scanning after contrast administration. Post-processing techniques including volume rendering, multi-planar reformation and thin-section maximum intensity projection were performed to assess the mesenteric artery and vein, as well as the portal vein. Results:There were 5 cases of superior mesenteric artery embolism,6 cases of superior mesenteric artery stenosis and 25 cases of superior mesenteric vein thrombosis. The direct CT signs were filling defect (n=30) or stenosis (n=6)of mesenteric vessels. The indirect CT signs includcd: dilatation of bowel loops with air-fluid levels (n=22) , bowel wall thickening ( n= 14) , paper-like thin wall sign ( n= 3) , pneumatosis of bowel wall ( n= 3) , edema and exudation of mesenteric

  1. Thick Slice and Thin Slice Teaching Evaluations

    Science.gov (United States)

    Tom, Gail; Tong, Stephanie Tom; Hesse, Charles

    2010-01-01

    Student-based teaching evaluations are an integral component to institutions of higher education. Previous work on student-based teaching evaluations suggest that evaluations of instructors based upon "thin slice" 30-s video clips of them in the classroom correlate strongly with their end of the term "thick slice" student evaluations. This study's…

  2. Quantitative multivoxel H-1 MR spectroscopy of the brain in children with acute liver failure

    NARCIS (Netherlands)

    Sijens, Paul E.; Alkefaji, Heyder; Lunsing, Roelineke J.; van Spronsen, Francjan J.; Meiners, Linda C.; Oudkerk, Matthijs; Verkade, Henkjan J.

    2008-01-01

    Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx) an

  3. Prevention and management of brain edema in patients with acute liver failure

    DEFF Research Database (Denmark)

    Wendon, J.; Larsen, Finn Stolze

    2008-01-01

    1. Intracranial pressure is the pressure exerted by the cranial contents on the dural envelope and consists of the partial pressures of the brain, blood, and cerebrospinal fluid. 2. Severe cases of acute liver failure are frequently complicated by brain edema (due to cytotoxic edema...

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

    Science.gov (United States)

    Martinez, Sarah; Davalos, Deana

    2016-01-01

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

  5. The electrocardiographic changes in acute brain injury patients

    Institute of Scientific and Technical Information of China (English)

    FAN Xin; DU Feng-he; TIAN Jun-ping

    2012-01-01

    Background Electrocardiographic (ECG) changes occurring during the course of acute brain injury (ABI) have been described frequently,but their significances remain uncertain.The present study was designed to investigate the relation of ECG abnormalities to outcome in the patients with ABI.Methods We performed a retrospective,observational study on the ABI patients admitted to the Department of Neurosurgery of the Beijing Tiantan Hospital between December 2005 and December 2007.All the patients accepted 12-lead electrocardiographic examination within 24 hours after injury,then divided into three groups according to the Glasgow coma score (GCS).In-hospital mortality and one-month outcome assessed by the Glasgow outcome score (GOS) were investigated.Results Of 335 ABI patients (mean ages 32.4 years),246 patients (73.4%) had abnormal ECGs.The most common abnormality was ST-T changes (41.5%),followed by sinus tachycardia (23.6%).ECG changes had a significant association with the severity and outcome.Logistic regression analysis showed the presence of ST-T changes (OR 2.587,95%C/1.009 to 6.629,P=0.048) and QT dispersion prolongation (OR 4.656,95%C/1.956 to 11.082,P=0.001)significantly associated with short outcomes.Conclusions ABI can lead to myocardial damage and ECG changes had a significant association with the severity.ST-T changes and QT dispersion prolongation were the independent prognosis factors for the negative outcome of ABI oatients.

  6. Acute supramaximal exercise increases the brain oxygenation in relation to cognitive workload

    OpenAIRE

    Cem Seref Bediz; Adile eOniz; Cagdas eGuducu; Enise eUral Demirci; Hilmi eOgut; Erkan eGunay; Caner eCetinkaya; Murat eOzgoren

    2016-01-01

    Single bout of exercise can improve the performance on cognitive tasks. However, cognitive responses may be controversial due to different type, intensity, and duration of exercise. In addition, the mechanism of the effect of acute exercise on brain is still unclear. This study was aimed to investigate the effects of supramaximal exercise on cognitive tasks by means of brain oxygenation monitoring. The brain oxygenation of Prefrontal cortex (PFC) was measured on 35 healthy male volunteers via...

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

    Science.gov (United States)

    2013-10-01

    brain injury (TBI) is the leading cause of death in children and young adults globally. Malignant cerebral edema plays a major role in the...pathophysiology which evolves after severe TBI. Added to this is the significant morbidity and mortality from cerebral edema associated with acute stroke...hypoxic ischemic coma, neurological cancers and brain infection. Therapeutic strategies to prevent cerebral edema are limited and if brain swelling

  8. Pattern of Brain Injury in the Acute Setting of Human Septic Shock

    OpenAIRE

    Polito, Andrea; Eischwald, Frédéric; Maho, Anne-Laure,; Polito, Angelo; Azabou, Eric; annane, djillali; Chrétien, Fabrice; Stevens, Robert; Carlier, Robert; Sharshar, Tarek

    2013-01-01

    International audience; BackgroundSepsis-associated brain dysfunction has been linked to white matter lesions (leukoencephalopathy) and ischemic stroke. Our objective was to assess the prevalence of brain lesions in septic shock patients requiring magnetic resonance imaging (MRI) for an acute neurologic change.Method71 septic shock patients were included in a prospective observational study. Patients underwent daily neurological examination. Brain MRI was obtained in patients who developed fo...

  9. Protective Effects of Chlorogenic Acid and its Metabolites on Hydrogen Peroxide-Induced Alterations in Rat Brain Slices: A Comparative Study with Resveratrol.

    Science.gov (United States)

    Gul, Zulfiye; Demircan, Celaleddin; Bagdas, Deniz; Buyukuysal, Rifat Levent

    2016-08-01

    The effectiveness of chlorogenic acid and its main metabolites, caffeic and quinic acids, against oxidative stress was investigated. Resveratrol, another natural phenolic compound, was also tested for comparison. Rat cortical slices were incubated with 200 μM H2O2 for 1 h, and alterations in oxidative stress parameters, such as 2, 3, 5-triphenyltetrazolium chloride (TTC) staining and the production of both malondialdehyde (MDA) and reactive oxygen species (ROS), were assayed in the absence or presence of phenolic compounds. Additionally, the effectiveness of chlorogenic acid and other compounds on H2O2-induced increases in fluorescence intensities were also compared in slice-free incubation medium. Although quinic acid failed, chlorogenic and caffeic acids significantly ameliorated the H2O2-induced decline in TTC staining intensities. Although resveratrol also caused an increase in staining intensity, its effect was not dose-dependent; the high concentrations of resveratrol tested in the present study (10 and 100 μM) further lessened the staining of the slices. Additionally, all phenolic compounds significantly attenuated the H2O2-induced increases in MDA and ROS levels in cortical slices. When the IC50 values were compared to H2O2-induced alterations, chlorogenic acid was more potent than either its metabolites or resveratrol for all parameters studied under these experimental conditions. In slice-free experimental conditions, on the other hand, chlorogenic and caffeic acids significantly attenuated the fluorescence emission enhanced by H2O2 with a similar order of potency to that obtained in slice-containing physiological medium. These results indicate that chlorogenic acid is a more potent phenolic compound than resveratrol and its main metabolites caffeic and quinic acids against H2O2-induced alterations in oxidative stress parameters in rat cortical slices.

  10. Fluid Intake Related to Brain Edema in Acute Middle Cerebral Artery Infarction.

    Science.gov (United States)

    Dharmasaroja, Pornpatr A

    2016-02-01

    Evidence of the appropriate amount of fluid intake during the first few days after acute stroke was scarce. Concerns were raised in patients with acute malignant middle cerebral infarction, who tended to have malignant brain edema later. The purpose of the study was to evaluate the effect of fluid intake on the occurrence of malignant brain edema in patients with acute middle cerebral artery infarction. Patients with acute middle cerebral artery infarction who had National Institute of Health Stroke Scale (NIHSS) score of at least 15 were included. Baseline characteristics and amount of fluid intake during the first few days were compared in patients with and without malignant brain edema. One hundred ninety-three patients were studied. Mean NIHSS score was 20. Malignant brain edema occurred in 69 patients (36%). Higher amount of fluid intake (>1650 ml or >28 ml/kg/day or >93% of daily maintenance fluid) showed a significant association with malignant brain edema (OR = 13.86, 95% CI 5.11-37.60, p value edema, 39 patients (39/65, 60%) died and only 11% (7/65 patients) had favorable outcome. High amount of fluid intake in the first few days of acute middle cerebral infarction was related to the occurrence of malignant brain edema.

  11. A novel role for PHT1 in the disposition of l-histidine in brain: In vitro slice and in vivo pharmacokinetic studies in wildtype and Pht1 null mice.

    Science.gov (United States)

    Wang, Xiao-Xing; Hu, Yongjun; Keep, Richard F; Toyama-Sorimachi, Noriko; Smith, David E

    2017-01-15

    PHT1 (SLC15A4) is responsible for translocating l-histidine (l-His), di/tripeptides and peptide-like drugs across biological membranes. Previous studies have indicated that PHT1 is located in brain parenchyma, however, its role and significance in brain along with effect on the biodistribution of substrates is unknown. In this study, adult gender-matched Pht1-competent (wildtype) and Pht1-deficient (null) mice were used to investigate the effect of PHT1 on l-His brain disposition via in vitro slice and in vivo pharmacokinetic approaches. We also evaluated the serum clinical chemistry and expression levels of select transporters and enzymes in the two genotypes. No significant differences were observed between genotypes in serum chemistry, body weight, viability and fertility. PCR analyses indicated that Pept2 had a compensatory up-regulation in Pht1 null mice (about 2-fold) as compared to wildtype animals, which was consistent in different brain regions and confirmed by immunoblots. The uptake of l-His was reduced in brain slices by 50% during PHT1 ablation. The l-amino acid transporters accounted for 30% of the uptake, and passive (other) pathways for 20% of the uptake. During the in vivo pharmacokinetic studies, plasma concentration-time profiles of l-His were comparable between the two genotypes after intravenous administration. Still, biodistribution studies revealed that, when sampled 5min after dosing, l-His values were 28-48% lower in Pht1 null mice, as compared to wildtype animals, in brain parenchyma but not cerebrospinal fluid. These findings suggest that PHT1 may play an important role in histidine transport in brain, and resultant effects on histidine/histamine homeostasis and neuropeptide regulation.

  12. Acute Psychosis Associated with Subcortical Stroke: Comparison between Basal Ganglia and Mid-Brain Lesions

    Directory of Open Access Journals (Sweden)

    Aaron McMurtray

    2014-01-01

    Full Text Available Acute onset of psychosis in an older or elderly individual without history of previous psychiatric disorders should prompt a thorough workup for neurologic causes of psychiatric symptoms. This report compares and contrasts clinical features of new onset of psychotic symptoms between two patients, one with an acute basal ganglia hemorrhagic stroke and another with an acute mid-brain ischemic stroke. Delusions and hallucinations due to basal ganglia lesions are theorized to develop as a result of frontal lobe dysfunction causing impairment of reality checking pathways in the brain, while visual hallucinations due to mid-brain lesions are theorized to develop due to dysregulation of inhibitory control of the ponto-geniculate-occipital system. Psychotic symptoms occurring due to stroke demonstrate varied clinical characteristics that depend on the location of the stroke within the brain. Treatment with antipsychotic medications may provide symptomatic relief.

  13. Proteomic profiling in incubation medium of mouse, rat and human precision-cut liver slices for biomarker detection regarding acute drug-induced liver injury

    NARCIS (Netherlands)

    van Swelm, Rachel P. L.; Hadi, Mackenzie; Laarakkers, Coby M. M.; Masereeuw, Rosalinde; Groothuis, Geny M. M.; Russel, Frans G. M.

    2014-01-01

    Drug-induced liver injury is one of the leading causes of drug withdrawal from the market. In this study, we investigated the applicability of protein profiling of the incubation medium of human, mouse and rat precision-cut liver slices (PCLS) exposed to liver injury-inducing drugs for biomarker ide

  14. siRNA Treatment: “A Sword-in-the-Stone” for Acute Brain Injuries

    Directory of Open Access Journals (Sweden)

    Jerome Badaut

    2013-09-01

    Full Text Available Ever since the discovery of small interfering ribonucleic acid (siRNA a little over a decade ago, it has been highly sought after for its potential as a therapeutic agent for many diseases. In this review, we discuss the promising possibility of siRNA to be used as a drug to treat acute brain injuries such as stroke and traumatic brain injury. First, we will give a brief and basic overview of the principle of RNA interference as an effective mechanism to decrease specific protein expression. Then, we will review recent in vivo studies describing siRNA research experiments/treatment options for acute brain diseases. Lastly, we will discuss the future of siRNA as a clinical therapeutic strategy against brain diseases and injuries, while addressing the current obstacles to effective brain delivery.

  15. Microdialysis study of cefotaxime cerebral distribution in patients with acute brain injury.

    Science.gov (United States)

    Dahyot-Fizelier, Claire; Frasca, Denis; Grégoire, Nicolas; Adier, Christophe; Mimoz, Olivier; Debaene, Bertrand; Couet, William; Marchand, Sandrine

    2013-06-01

    Central nervous system (CNS) antibiotic distribution was described mainly from cerebrospinal fluid data, and only few data exist on brain extracellular fluid concentrations. The aim of this study was to describe brain distribution of cefotaxime (2 g/8 h) by microdialysis in patients with acute brain injury who were treated for a lung infection. Microdialysis probes were inserted into healthy brain tissue of five critical care patients. Plasma and unbound brain concentrations were determined at steady state by high-performance liquid chromatography. In vivo recoveries were determined individually using retrodialysis by drug. Noncompartmental and compartmental pharmacokinetic analyses were performed. Unbound cefotaxime brain concentrations were much lower than corresponding plasma concentrations, with a mean cefotaxime unbound brain-to-plasma area under the curve ratio equal to 26.1 ± 12.1%. This result was in accordance with the brain input-to-brain output clearances ratio (CL(in,brain)/CL(out,brain)). Unbound brain concentrations were then simulated at two dosing regimens (4 g every 6 h or 8 h), and the time over the MICs (T>MIC) was estimated for breakpoints of susceptible and resistant Streptococcus pneumoniae strains. T>MIC was higher than 90% of the dosing interval for both dosing regimens for susceptible strains and only for 4 g every 6 h for resistant ones. In conclusion, brain distribution of cefotaxime was well described by microdialysis in patients and was limited.

  16. Volumetric Integral Phase-shift Spectroscopy for Noninvasive Detection of Hemispheric Bioimpedance Asymmetry in Acute Brain Pathology

    Science.gov (United States)

    2017-07-20

    Stroke; Stroke, Acute; Ischemic Stroke; Hemorrhage; Clot (Blood); Brain; Subarachnoid Hemorrhage; Cerebral Infarction; Cerebral Hemorrhage; Cerebral Stroke; Intracerebral Hemorrhage; Intracerebral Injury

  17. Acute promyelocytic leukemia after whole brain irradiation of primary brain lymphomainan HIV-infected patient

    Directory of Open Access Journals (Sweden)

    Boban A

    2009-01-01

    Full Text Available Abstract The occurrence of acute promyelocytic leukemia (APL in HIV-infected patients has been reported in only five cases. Due to a very small number of reported HIV/APL patients who have been treated with different therapies with the variable outcome, the prognosis of APL in the setting of the HIV-infection is unclear. Here, we report a case of an HIV-patient who developed APL and upon treatment entered a complete remission. A 25-years old male patient was diagnosed with HIV-infection in 1996, but remained untreated. In 2004, the patient was diagnosed with primary central nervous system lymphoma. We treated the patient with antiretroviral therapy and whole-brain irradiation, resulting in complete remission of the lymphoma. In 2006, prompted by a sudden neutropenia, we carried out a set of diagnostic procedures, revealing APL. Induction therapy consisted of standard treatment with all-trans-retinoic-acid (ATRA and idarubicin. Subsequent cytological and molecular analysis of bone marrow demonstrated complete hematological and molecular remission. Due to the poor general condition, consolidation treatment with ATRA was given in March and April 2007. The last follow-up 14 months later, showed sustained molecular APL remission. In conclusion, we demonstrated that a complete molecular APL remission in an HIV-patient was achieved by using reduced-intensity treatment.

  18. Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress

    Institute of Scientific and Technical Information of China (English)

    De-guo Jiang; Shi-li Jin; Gong-ying Li; Qing-qing Li; Zhi-ruo Li; Hong-xia Ma; Chuan-jun Zhuo; Rong-huan Jiang; Min-jie Ye

    2016-01-01

    Previous studies suggest that serotonin (5-HT) might interact with brain-derived neurotrophic factor (BDNF) during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry andin situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no signiifcant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our ifndings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress.

  19. Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress

    Directory of Open Access Journals (Sweden)

    De-guo Jiang

    2016-01-01

    Full Text Available Previous studies suggest that serotonin (5-HT might interact with brain-derived neurotrophic factor (BDNF during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry and in situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no significant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our findings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress.

  20. Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress.

    Science.gov (United States)

    Jiang, De-Guo; Jin, Shi-Li; Li, Gong-Ying; Li, Qing-Qing; Li, Zhi-Ruo; Ma, Hong-Xia; Zhuo, Chuan-Jun; Jiang, Rong-Huan; Ye, Min-Jie

    2016-09-01

    Previous studies suggest that serotonin (5-HT) might interact with brain-derived neurotrophic factor (BDNF) during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry and in situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no significant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our findings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress.

  1. 64排螺旋CT重建技术在急性阑尾炎诊断中的应用价值%application of 64-Slice Spiral CT Reconstruction Technique in diagnosis of acute appendicitis

    Institute of Scientific and Technical Information of China (English)

    任春慧; 冯华; 梁爽; 曲世巍

    2013-01-01

    Objective To investigate the effectiveness of 64-slice spiral CT reconstruction technique in diagnosis of acute appendicitis. Methods Retrospective analysis of 64-slice spiral CT scan images was performed on 60 patients who underwent abdominal 64-slice spiral CT scans and were confirmed through clinical pathology as acute appendicitis sufferers. After multi-planar and curve reconstruction of all the images in the workstation, observation and analysis of appendicitis were made on the size, morphology and surrounding changes. Results Among 60 patients with acute appendicitis, 21 cases were found acute simple appendicitis, 32 superlative appendicitis, 5 appendiceal abscess, 2 appendiceal perforation. Two kinds of features - direct and indirect features could be gained from 64-slice spiral CT findings. Direct features include thickened and enlarged appendicitis(diameter> 6 mm), thickened wall of the appendicitis, appendicitis calculus. Indirect features included inflammation, abscess or inflammatory mass around the appendicitis, free intraperitoneal gas and swelling local lymph nodes. Conclusion Acute appendicitis had typical features in its CT iamges. Application of 64-slice spiral CT reconstruction techniques could have a better reveal of appendicitis and its surrounding circumstances, which significantly improved the diagnosis of appendicitis and was of great application value.%  目的探讨64排螺旋CT重建技术在急性阑尾炎诊断中的应用价值。方法对60例经临床病理证实的急性阑尾炎患者的64排螺旋CT扫描资料进行回顾性分析,所有患者行全腹部64排螺旋平扫,所得图像在工作站进行多平面及曲面重建,对阑尾的大小、形态及周围改变进行观察分析。结果60例资料中,急性单纯性阑尾炎21例、化脓性阑尾炎32例、阑尾脓肿5例、阑尾穿孔2例。64排螺旋CT直接征象为阑尾增粗、增大(直径>6 mm),阑尾壁增厚,阑尾结石;间接征象

  2. Phospholipase A2 changes and its significance on brain tissue of rat in severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Yao Xuan; Chen Xi; Ji Zongzheng

    2007-01-01

    Objective To survey changes and the significance of phospholipase A2(PLA2) on brain tissue of SD rat in acute pancreatitis. Methods With retrograde injection of 3% taurocholate sodium into pancreatic and biliary duct, rat model of severe acute pancreatitis (SAP) was made,and it included four groups: the control group, the sham-operation group, the SAP group and the PLA2 inhibitor-treated group of SAP. Serum amylases, PLA2 and PLA2 in brain tissue were measured and the brain tissue changes were observed. Results There were no significant difference in serum amylases, PLA2 and PLA2 in brain tissue between the sham-operation and the control groups; the levels of serum amylases, PLA2 and PLA2 in brain tissue in the SAP group were higher than those in the control. In the SAP group expansion and hemorrhage of meninges, intracephalic arteriolar hyperemia, in meninges and cephalic-parenchyma infiltration of inflammatory cells and interval broaden were observed, significant differences were found between two groups.Compared with the SAP group, the level of serum amylase, PLA2 and PLA2 in brain tissue were reduced significantly in the treatment group of SAP. Pathological damages in the treatment group were significantly reduced when compared with the SAP group. Conclusion PLA2 might play an important role in brain tissue damages in severe acute pancreatitis.

  3. Clinical and Echocardiographic Characteristics of Acute Cardiac Dysfunction Associated With Acute Brain Hemorrhage - Difference From Takotsubo Cardiomyopathy.

    Science.gov (United States)

    Lee, Mirae; Oh, Ju Hyeon; Lee, Kyung Been; Kang, Gu Hyun; Park, Yong Hwan; Jang, Woo Jin; Chun, Woo Jung; Lee, Sang Hyuk; Lee, In Chang

    2016-08-25

    Cardiac dysfunction (CD) associated with brain hemorrhage is similar to that with takotsubo cardiomyopathy but still not well understood. We aimed to investigate the clinical and echocardiographic findings of acute CD (ACD) related to brain hemorrhage. Between 2013 and 2014, consecutive patients diagnosed with spontaneous and traumatic brain hemorrhage were prospectively enrolled. Electrocardiography, cardiac enzymes, and echocardiography were performed. Left ventricular (LV) systolic dysfunction on echocardiography was defined as ACD related to brain hemorrhage when all the following conditions were satisfied: abnormal ECG and cardiac troponin level, LV wall motion abnormality or decreased LV systolic function on echocardiography, and no previous history of cardiac disease. Otherwise, LV dysfunction was considered to be other CD unrelated to brain hemorrhage. In a total of 208 patients, 15 (7.2%) showed ACD. Of them, 8 patients were men and 8 showed apex-sparing LV hypokinesia and 9 died in hospital. Other cardiac abnormalities observed in the study patients were NT-proBNP elevation (n=123), QT interval prolongation (n=95), LV hypertrophy (n=89), and troponin I elevation (n=47). There were 36 in-hospital deaths (17.3%). Glasgow coma score and ACD were independently associated with in-hospital death. ACD was observed in patients with various brain hemorrhages. Unlike takotsubo cardiomyopathy, high proportions of male sex, apex-sparing LV dysfunction, and in-hospital death were observed for ACD associated with brain hemorrhage. (Circ J 2016; 80: 2026-2032).

  4. Acute chest pain in emergency room. Preliminary findings with 40-64-slice CT ECG-gated of the whole chest.

    Science.gov (United States)

    Coche, E

    2007-01-01

    ECG-gated MDCT of the entire chest represents the latest technical advance in the diagnostic work-up of atypical chest pain. The authors report their preliminary experience with the use of 40 and 64-slice CT in the emergency room and recommend to study only patients with moderate likelihood of coronary artery disease. ECG-gated MDCT of the entire chest will be preferentially performed on 64-slice MDCT rather than 40-slice MDCT because it enable to reduce the scan time (18 seconds versus 28 seconds acquisition time), the volume of contrast medium (82 mL + 15 mL versus 97 mL + 15 mL of highly concentrated contrast agent for a patient of 70 kgs) and radiation exposure (17 mSv versus 19 mSv). Approximately 1500 to 2000 of images are produced and need to be analysed on a dedicated workstation by a radiologist expert in cardiac and thoracic disorders. At the present time, only a few studies exist in the literature showing some promising results but further large clinical studies are needed before to implement such sophisticated protocol in emergency room.

  5. The impact of acute brain dysfunction in the outcomes of mechanically ventilated cancer patients.

    Directory of Open Access Journals (Sweden)

    Isabel C T Almeida

    Full Text Available INTRODUCTION: Delirium and coma are a frequent source of morbidity for ICU patients. Several factors are associated with the prognosis of mechanically ventilated (MV cancer patients, but no studies evaluated delirium and coma (acute brain dysfunction. The present study evaluated the frequency and impact of acute brain dysfunction on mortality. METHODS: The study was performed at National Cancer Institute, Rio de Janeiro, Brazil. We prospectively enrolled patients ventilated >48 h with a diagnosis of cancer. Acute brain dysfunction was assessed during the first 14 days of ICU using RASS/CAM-ICU. Patients were followed until hospital discharge. Univariate and multivariable analysis were performed to evaluate factors associated with hospital mortality. RESULTS: 170 patients were included. 73% had solid tumors, age 65 [53-72 (median, IQR 25%-75%] years. SAPS II score was 54[46-63] points and SOFA score was (7 [6-9] points. Median duration of MV was 13 (6-21 days and ICU stay was 14 (7.5-22 days. ICU mortality was 54% and hospital mortality was 66%. Acute brain dysfunction was diagnosed in 161 patients (95%. Survivors had more delirium/coma-free days [4(1,5-6 vs 1(0-2, p<0.001]. In multivariable analysis the number of days of delirium/coma-free days were associated with better outcomes as they were independent predictors of lower hospital mortality [0.771 (0.681 to 0.873, p<0.001]. CONCLUSIONS: Acute brain dysfunction in MV cancer patients is frequent and independently associated with increased hospital mortality. Future studies should investigate means of preventing or mitigating acute brain dysfunction as they may have a significant impact on clinical outcomes.

  6. A Case of Acute Motor Axonal Neuropathy Mimicking Brain Death and Review of the Literature.

    Science.gov (United States)

    Ravikumar, Sandhya; Poysophon, Poysophon; Poblete, Roy; Kim-Tenser, May

    2016-01-01

    We describe a case report of fulminant Guillain-Barré syndrome (GBS) mimicking brain death. A previously healthy 60-year-old male was admitted to the neurointensive care unit after developing rapidly progressive weakness and respiratory failure. On presentation, the patient was found to have absent brainstem and spinal cord reflexes resembling that of brain death. Acute motor axonal neuropathy, a subtype of GBS, was diagnosed by cerebrospinal fluid and nerve conduction velocity testing. An electroencephalogram showed that the patient had normal, appropriately reactive brain function. Transcranial Doppler (TCD) ultrasound showed appropriate blood flow to the brain. GBS rarely presents with weakness so severe as to mimic brain death. This article provides a review of similar literature. This case demonstrates the importance of performing a proper brain death examination, which includes evaluation for irreversible cerebral injury, exclusion of any confounding conditions, and performance of tests such as electroencephalography and TCDs when uncertainty exists about the reliability of the clinical exam.

  7. A comparative autoradiography study in post mortem whole hemisphere human brain slices taken from Alzheimer patients and age-matched controls using two radiolabelled DAA1106 analogues with high affinity to the peripheral benzodiazepine receptor (PBR) system.

    Science.gov (United States)

    Gulyás, Balázs; Makkai, Boglárka; Kása, Péter; Gulya, Károly; Bakota, Lidia; Várszegi, Szilvia; Beliczai, Zsuzsa; Andersson, Jan; Csiba, László; Thiele, Andrea; Dyrks, Thomas; Suhara, Tetsua; Suzuki, Kazutoshi; Higuchi, Makato; Halldin, Christer

    2009-01-01

    The binding of two radiolabelled analogues (N-(5-[125I]Iodo-2-phenoxyphenyl)-N-(2,5-dimethoxybenzyl)acetamide ([125I]desfluoro-DAA1106) and N-(5-[125I]Fluoro-2-phenoxyphenyl)-N-(2-[125I]Iodo-5-methoxybenzyl)acetamide ([125I]desmethoxy-DAA1106) of the peripheral benzodiazepine receptor (PBR) (or TSPO, 18kDa translocator protein) ligand DAA1106 was examined by in vitro autoradiography on human post mortem whole hemisphere brain slices obtained from Alzheimer's disease (AD) patients and age-matched controls. Both [(125)I]desfluoro-IDAA1106 and [(125)I]desmethoxy-IDAA1106 were effectively binding to various brain structures. The binding could be blocked by the unlabelled ligand as well as by other PBR specific ligands. With both radiolabelled compounds, the binding showed regional inhomogeneity and the specific binding values proved to be the highest in the hippocampus, temporal and parietal cortex, the basal ganglia and thalamus in the AD brains. Compared with age-matched control brains, specific binding in several brain structures (temporal and parietal lobes, thalamus and white matter) in Alzheimer brains was significantly higher, indicating that the radioligands can effectively label-activated microglia and the up-regulated PBR/TSPO system in AD. Complementary immunohistochemical studies demonstrated reactive microglia activation in the AD brain tissue and indicated that increased ligand binding coincides with increased regional microglia activation due to neuroinflammation. These investigations yield further support to the PBR/TSPO binding capacity of DAA1106 in human brain tissue, demonstrate the effective usefulness of its radio-iodinated analogues as imaging biomarkers in post mortem human studies, and indicate that its radiolabelled analogues, labelled with short half-time bioisotopes, can serve as prospective in vivo imaging biomarkers of activated microglia and the up-regulated PBR/TSPO system in the human brain.

  8. Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

    Science.gov (United States)

    Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun

    2013-05-01

    Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

  9. Effect of acute thioacetamide administration on rat brain phospholipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Osada, J.; Aylagas, H.; Miro-Obradors, M.J.; Arce, C.; Palacios-Alaiz, E.; Cascales, M. (Tufs Univ., Boston, MA (USA))

    1990-09-01

    Brain phospholipid composition and the ({sup 32}P)orthophosphate incorporation into brain phospholipids of control and rats treated for 3 days with thioacetamide were studied. Brain phospholipid content, phosphatidylcholine, phosphatidylethanolamine, lysolecithin and phosphatidic acid did not show any significant change by the effect of thioacetamide. In contrast, thioacetamide induced a significant decrease in the levels of phosphatidylserine, sphingomyelin, phosphatidylinositol and diphosphatidylglycerol. After 75 minutes of intraperitoneal label injection, specific radioactivity of all the above phospholipids with the exception of phosphatidylethanolamine and phosphatidylcholine significantly increased. After 13 hours of isotope administration the specific radioactivity of almost all studied phospholipid classes was elevated, except for phosphatidic acid, the specific radioactivity of which did not change and for diphosphatidylglycerol which showed a decrease in specific radioactivity. These results suggest that under thioacetamide treatment brain phospholipids undergo metabolic transformations that may contribute to the hepatic encephalopathy induced by thioacetamide.

  10. Brain perfusion-CT in acute stroke patients

    Energy Technology Data Exchange (ETDEWEB)

    Wintermark, M. [Dept. of Radiology, Univ. of California, San Francisco (UCSF), CA (United States)

    2005-11-15

    The role of neuro-imaging in the evaluation of acute stroke has changed dramatically in the past decade. Previously, neuro-imaging was used in this setting to provide anatomic imaging that indicated the presence or absence of acute cerebral ischemia and excluded lesions that produce symptoms or signs mimicking those of stroke, such as hemorrhage and neoplasms. More recently, the introduction of thrombolysis has changed the goals of neuro-imaging from providing solely anatomic information to providing physiologic information that could help to determine which patients might benefit from therapy. In particular, significant emphasis has been placed on the delineation of the ischemic penumbra, also called tissue at risk. Modern CT survey, consisting of three indissociable elements: noncontrast CT (NCT) of course, perfusion-CT (PCT) and CT-angiography (CTA), fulfill all the requirements for hyper-acute stroke imaging. CTA can define the occlusion site, depict arterial dissection, grade collateral blood flow, and characterize atherosclerotic disease, whereas PCT accurately delineates the infarct core and the ischemic penumbra. CT offers a number of practical advantages over other cerebral perfusion imaging methods, including its wide availability. Using PCT and CTA to define new individualized strategies for acute reperfusion will allow more acute stroke patients to benefit from thrombolytic therapy. (orig.)

  11. Acute functional reactivation of the language network during awake intraoperative brain mapping.

    Science.gov (United States)

    Spena, Giannantonio; Costi, Emanuele; Panciani, Pier Paolo; Roca, Elena; Migliorati, Karol; Fontanella, Marco Maria

    2015-01-01

    Acute brain plasticity during resection of central lesions has been recently described. In the cases reported, perilesional latent networks, useful to preserve the neurological functions, were detected in asymptomatic patients. In this paper, we presented a case of acute functional reactivation (AFR) of the language network in a symptomatic patient. Tumor resection allowed to acutely restore the neurological deficit. Intraoperative direct cortical stimulation (DCS) and functional neuroimaging showed new epicentres of activation of the language network after tumor excision. DCS in awake surgery is mandatory to reveal AFR needful to improve the extent of resection preserving the quality of life.

  12. Neuronal activity and brain-derived neurotrophic factor regulate the density of inhibitory synapses in organotypic slice cultures of postnatal hippocampus.

    Science.gov (United States)

    Marty, S; Wehrlé, R; Sotelo, C

    2000-11-01

    Hippocampal interneurons inhibit pyramidal neurons through the release of the neurotransmitter GABA. Given the importance of this inhibition for the proper functioning of the hippocampus, the development of inhibitory synapses must be tightly regulated. In this study, the possibility that neuronal activity and neurotrophins regulate the density of GABAergic inhibitory synapses was investigated in organotypic slice cultures taken from postnatal day 7 rats. In hippocampal slices cultured for 13 d in the presence of the GABA(A) receptor antagonist bicuculline, the density of glutamic acid decarboxylase (GAD) 65-immunoreactive terminals was increased in the CA1 area when compared with control slices. Treatment with the glutamate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione decreased the density of GAD65-immunoreactive terminals in the stratum oriens of CA1. These treatments had parallel effects on the density of GABA-immunoreactive processes. Electron microscopic analysis after postembedding immunogold labeling with antibodies against GABA indicated that bicuculline treatment increased the density of inhibitory but not excitatory synapses. Application of exogenous BDNF partly mimicked the stimulatory effect of bicuculline on GAD65-immunoreactive terminals. Finally, antibodies against BDNF, but not antibodies against nerve growth factor, decrease the density of GAD65-immunoreactive terminals in bicuculline-treated slices. Thus, neuronal activity regulates the density of inhibitory synapses made by postnatal hippocampal interneurons, and BDNF could mediate part of this regulation. This regulation of the density of inhibitory synapses could represent a feedback mechanism aimed at maintaining an appropriate level of activity in the developing hippocampal networks.

  13. Preconditioning of brain slices against hypoxia induced injury by a Gynostemma pentaphyllum extract--stimulation of anti-oxidative enzyme expression.

    Science.gov (United States)

    Schild, L; Cotte, T; Keilhoff, G; Brödemann, R

    2012-06-15

    A short period of hypoxia/hypoglycaemia (oxygen and glucose deprivation, OGD) induced by perfusion with O(2)/glucose-free medium caused immediate loss and incomplete restoration of evoked field potentials in the CA1 region of transverse hippocampus slices. OGD-dependent decrease in evoked field potentials can be prevented by a proceeding short OGD event (preconditioning). We report about a study investigating the effect of an ethanolic Gynostemma pentaphyllum extract on evoked field potentials when administered before the OGD episode. Using this procedure, the extract completely protected the cells of the slices from functional injury. In an astroglia rich cell culture the ethanolic Gynostemma pentaphyllum extract caused within 48 h of cultivation increased protein and activity levels of the anti-oxidative enzymes manganese superoxide dismutase (Mn-SOD) and glutathione peroxidase (GPx). Consequently, the cellular H(2)O(2) concentration remained at a low level. These data suggest that the Gynostemma pentaphyllum-mediated increase in antioxidative enzyme activities may contribute to the protection of transverse hippocampus slices from OGD induced functional injury. Our results demonstrate that the prophylactic administration of the ethanolic extract from Gynostemma pentaphyllum has a high potential to protect from ischemia/reperfusion injury. Copyright © 2012 Elsevier GmbH. All rights reserved.

  14. Initial experience of whole-brain perfusion imaging performed with 256-slice CT%256层螺旋CT全脑灌注成像的初步研究

    Institute of Scientific and Technical Information of China (English)

    唐健; 姜建威; 常军; 侯海燕; 姜旭栋; 堵红群

    2011-01-01

    目的:初步评价256层螺旋CT全脑灌注成像对正常脑血流动力学测定的可行性和价值.方法:从拟诊缺血性脑病行头颅平扫、头颅灌注成像及头颈部血管成像的114例患者中选取检查结果正常者35例,记录头颅灌注成像的辐射剂量,由两名高年资神经放射科医生分别对灌注图像进行分析,选择基底节层面和侧脑室体部层面的两侧大脑中动脉供血区的颞叶皮质进行测定,通过手动勾画选定层面的感兴趣区,CT灌注软件自动生成感兴趣区的脑血流量(CBF)、脑血容量(CBV)、平均通过时间(MTr)、达峰时间(TTP)值,测得的灌注参数均值进行单因素方差分析.结果:35例正常人的辐射剂量为(2.307±0.008)mSv.2名分析者所测得侧脑室体部层面和基底节层面的颞叶灰质的CBF、CBV、MTr、TTP值之间无明显统计学差异(P>0.05).2名分析者测得的两个层面的颞叶灰质的CBV、CBF值之间均有统计学差异(P<0.05).结论:256层螺旋CT全脑灌注成像辐射剂量低,脑灌注参数稳定,能够更真实的反应全脑血流动力学改变.%Objective;To preliminarily evaluate the feasibility and potential values of whole-brain perfusion imaging performed with 256-slice CT to assess normal adult cerebral hemodynamics. Methods; Thirty-five normal results were selected from one hundred and fourteen patients who underwent brain CT unenhanced scan.CT perfusion imaging and CT angiography in head and neck for suspicion of ischemic cerebrovascular disease. The radiation dosage of CT perfusion imaging was recorded. Two senior neuroradiologic doctors independently analyzed the CT perfusion maps. Region of interest (ROI) was placed on bilateral temporal gray matter of two slices (the basal ganglia slice and body of lateral cerebral ventricle slice) supplied by middle cerebral artery,and the cerebral blood flow(CBF),cerebral blood volume(CBV),mean transiting time(MTT), and time to peak(TTP) values of ROI

  15. Automated Computer-Assisted Diagnosis of Obstructive Coronary Artery Disease in Emergency Department Patients Undergoing 256-Slice Coronary Computed Tomography Angiography for Acute Chest Pain.

    Science.gov (United States)

    Hashoul, Sharbell; Gaspar, Tamar; Halon, David A; Lewis, Basil S; Shenkar, Yuval; Jaffe, Ronen; Peled, Nathan; Rubinshtein, Ronen

    2015-10-01

    A 256-slice coronary computed tomography angiography (CCTA) is an accurate method for detection and exclusion of obstructive coronary artery disease (OBS-CAD). However, accurate image interpretation requires expertise and may not be available at all hours. The purpose of this study was to evaluate the usefulness of a fully automated computer-assisted diagnosis (COMP-DIAG) tool for exclusion of OBS-CAD in patients in the emergency department (ED) presenting with chest pain. Three hundred sixty-nine patients in ED without known coronary disease underwent 256-slice CCTA as part of the assessment of chest pain of uncertain origin. COMP-DIAG (CorAnalyzer II) automatically reported presence or exclusion of OBS-CAD (>50% stenosis, ≥1 vessel). Performance characteristics of COMP-DIAG for exclusion and detection of OBS-CAD were determined using expert reading as the reference standard. Seventeen (5%) studies were unassessable by COMP-DIAG software, and 352 patients (1,056 vessels) were therefore available for analysis. COMP-DIAG identified 33% of assessable studies as having OBS-CAD, but the prevalence of OBS-CAD on CCTA was only 18% (66 of 352 patients) by standard expert reading. However, COMP-DIAG correctly identified 61 of the 66 patients (93%) with OBS-CAD with 21 vessels (2%) with OBS-CAD misclassified as negative. In conclusion, compared to expert reading, automated computer-assisted diagnosis using the CorAnalyzer showed high sensitivity but only moderate specificity for detection of obstructive coronary disease in patients in ED who underwent 256-slice CCTA. The high negative predictive value of this computer-assisted algorithm may be useful in the ED setting.

  16. Patients' and relatives' experience of difficulties following severe traumatic brain injury: the sub-acute stage

    DEFF Research Database (Denmark)

    Holm, Sara; Schönberger, Michael; Poulsen, Ingrid;

    2008-01-01

    The present study aimed to (1) identify the difficulties most frequently reported by individuals with severe traumatic brain injury (TBI) at the time of discharge from a sub-acute rehabilitation brain injury unit as well as difficulties reported by their relatives, (2) compare patients......' and relatives' reports of patient difficulties, and (3) explore the role of injury severity, disability and other factors on subjective experience of difficulties. The primary measure was the European Brain Injury Questionnaire (EBIQ) administered to patients and to one of their close relatives at discharge...

  17. Cognitive Impairment and Whole Brain Diffusion in Patients with Neuromyelitis Optica after Acute Relapse

    Science.gov (United States)

    He, Diane; Wu, Qizhu; Chen, Xiuying; Zhao, Daidi; Gong, Qiyong; Zhou, Hongyu

    2011-01-01

    The objective of this study investigated cognitive impairments and their correlations with fractional anisotropy (FA) and mean diffusivity (MD) in patients with neuromyelitis optica (NMO) without visible lesions on conventional brain MRI during acute relapse. Twenty one patients with NMO and 21 normal control subjects received several cognitive…

  18. Acute Alcohol Intoxication in Patients with Mild Traumatic Brain Injury: Characteristics, Recovery and Outcome

    NARCIS (Netherlands)

    Scheenen, Myrthe; de Koning, Myrthe; van der Horn, Harm; van der Naalt, Joukje; Spikman, Jacoba

    2015-01-01

    Objectives. To investigate the incidence of acute alcohol intoxication (AAI) at the time of sustaining mild traumatic brain injury (mTBI), describe the characteristics of this intoxicated subgroup, and evaluate recovery and outcome in comparison to sober mTBI patients. Methods. Multicenter cohort st

  19. A Simulation-based Approach for Improving Utilization of Thrombolysis in Acute Brain Infarction

    NARCIS (Netherlands)

    Lahr, M. M. H.; van der Zee, D. J.; Luijckx, G. J.; Vroomen, Patrick; Buskens, E.

    2013-01-01

    BACKGROUND: Treatment with tissue plasminogen activator (tPA) is the most effective treatment in acute brain infarction. However, estimated worldwide treatment rates are <10%, with many barriers hampering broad implementation. Organization and resource-intense randomized controlled trials cannot add

  20. Cognitive Impairment and Whole Brain Diffusion in Patients with Neuromyelitis Optica after Acute Relapse

    Science.gov (United States)

    He, Diane; Wu, Qizhu; Chen, Xiuying; Zhao, Daidi; Gong, Qiyong; Zhou, Hongyu

    2011-01-01

    The objective of this study investigated cognitive impairments and their correlations with fractional anisotropy (FA) and mean diffusivity (MD) in patients with neuromyelitis optica (NMO) without visible lesions on conventional brain MRI during acute relapse. Twenty one patients with NMO and 21 normal control subjects received several cognitive…

  1. Acute Ischemic Stroke After Moderate to Severe Traumatic Brain Injury: Incidence and Impact on Outcome.

    Science.gov (United States)

    Kowalski, Robert G; Haarbauer-Krupa, Juliet K; Bell, Jeneita M; Corrigan, John D; Hammond, Flora M; Torbey, Michel T; Hofmann, Melissa C; Dams-O'Connor, Kristen; Miller, A Cate; Whiteneck, Gale G

    2017-07-01

    Traumatic brain injury (TBI) leads to nearly 300 000 annual US hospitalizations and increased lifetime risk of acute ischemic stroke (AIS). Occurrence of AIS immediately after TBI has not been well characterized. We evaluated AIS acutely after TBI and its impact on outcome. A prospective database of moderate to severe TBI survivors, admitted to inpatient rehabilitation at 22 Traumatic Brain Injury Model Systems centers and their referring acute-care hospitals, was analyzed. Outcome measures were AIS incidence, duration of posttraumatic amnesia, Functional Independence Measure, and Disability Rating Scale, at rehabilitation discharge. Between October 1, 2007, and March 31, 2015, 6488 patients with TBI were enrolled in the Traumatic Brain Injury Model Systems National Database. One hundred and fifty-nine (2.5%) patients had a concurrent AIS, and among these, median age was 40 years. AIS was associated with intracranial mass effect and carotid or vertebral artery dissection. High-velocity events more commonly caused TBI with dissection. AIS predicted poorer outcome by all measures, accounting for a 13.3-point reduction in Functional Independence Measure total score (95% confidence interval, -16.8 to -9.7; PIschemic stroke is observed acutely in 2.5% of moderate to severe TBI survivors and predicts worse functional and cognitive outcome. Half of TBI patients with AIS were aged ≤40 years, and AIS patients more often had cervical dissection. Vigilance for AIS is warranted acutely after TBI, particularly after high-velocity events. © 2017 American Heart Association, Inc.

  2. Inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brain

    Directory of Open Access Journals (Sweden)

    Howe Charles L

    2012-03-01

    Full Text Available Abstract Background Neuropathology caused by acute viral infection of the brain is associated with the development of persistent neurological deficits. Identification of the immune effectors responsible for injuring the brain during acute infection is necessary for the development of therapeutic strategies that reduce neuropathology but maintain immune control of the virus. Methods The identity of brain-infiltrating leukocytes was determined using microscopy and flow cytometry at several acute time points following intracranial infection of mice with the Theiler's murine encephalomyelitis virus. Behavioral consequences of immune cell depletion were assessed by Morris water maze. Results Inflammatory monocytes, defined as CD45hiCD11b++F4/80+Gr1+1A8-, and neutrophils, defined as CD45hiCD11b+++F4/80-Gr1+1A8+, were found in the brain at 12 h after infection. Flow cytometry of brain-infiltrating leukocytes collected from LysM: GFP reporter mice confirmed the identification of neutrophils and inflammatory monocytes in the brain. Microscopy of sections from infected LysM:GFP mice showed that infiltrating cells were concentrated in the hippocampal formation. Immunostaining confirmed that neutrophils and inflammatory monocytes were localized to the hippocampal formation at 12 h after infection. Immunodepletion of inflammatory monocytes and neutrophils but not of neutrophils only resulted in preservation of hippocampal neurons. Immunodepletion of inflammatory monocytes also preserved cognitive function as assessed by the Morris water maze. Conclusions Neutrophils and inflammatory monocytes rapidly and robustly responded to Theiler's virus infection by infiltrating the brain. Inflammatory monocytes preceded neutrophils, but both cell types were present in the hippocampal formation at a timepoint that is consistent with a role in triggering hippocampal pathology. Depletion of inflammatory monocytes and neutrophils with the Gr1 antibody resulted in

  3. Understanding international differences in terminology for delirium and other types of acute brain dysfunction in critically ill patients

    NARCIS (Netherlands)

    Morandi, A; Pandharipande, P; Trabucchi, M; Rozzini, R; Mistraletti, G; Trompeo, A C; Gregoretti, C; Gattinoni, L; Ranieri, M V; Brochard, L; Annane, D; Putensen, C; Guenther, U; Fuentes, P; Tobar, E; Anzueto, A R; Esteban, A; Skrobik, Y; Salluh, J I F; Soares, M; Granja, C; Stubhaug, A; de Rooij, S E; Ely, E Wesley

    2008-01-01

    BACKGROUND: Delirium (acute brain dysfunction) is a potentially life threatening disturbance in brain function that frequently occurs in critically ill patients. While this area of brain dysfunction in critical care is rapidly advancing, striking limitations in use of terminology related to delirium

  4. Understanding international differences in terminology for delirium and other types of acute brain dysfunction in critically ill patients

    NARCIS (Netherlands)

    Morandi, A; Pandharipande, P; Trabucchi, M; Rozzini, R; Mistraletti, G; Trompeo, A C; Gregoretti, C; Gattinoni, L; Ranieri, M V; Brochard, L; Annane, D; Putensen, C; Guenther, U; Fuentes, P; Tobar, E; Anzueto, A R; Esteban, A; Skrobik, Y; Salluh, J I F; Soares, M; Granja, C; Stubhaug, A; de Rooij, S E; Ely, E Wesley

    2008-01-01

    BACKGROUND: Delirium (acute brain dysfunction) is a potentially life threatening disturbance in brain function that frequently occurs in critically ill patients. While this area of brain dysfunction in critical care is rapidly advancing, striking limitations in use of terminology related to delirium

  5. Functional MRI for Assessment of the Default Mode Network in Acute Brain Injury.

    Science.gov (United States)

    Kondziella, Daniel; Fisher, Patrick M; Larsen, Vibeke Andrée; Hauerberg, John; Fabricius, Martin; Møller, Kirsten; Knudsen, Gitte Moos

    2017-05-08

    Assessment of the default mode network (DMN) using resting-state functional magnetic resonance imaging (fMRI) may improve assessment of the level of consciousness in chronic brain injury, and therefore, fMRI may also have prognostic value in acute brain injury. However, fMRI is much more challenging in critically ill patients because of cardiovascular vulnerability, intravenous sedation, and artificial ventilation. Using resting-state fMRI, we investigated the DMN in a convenience sample of patients with acute brain injury admitted to the intensive care unit. The DMN was classified dichotomously into "normal" and "grossly abnormal." Clinical outcome was assessed at 3 months. Seven patients with acute brain injury (4 females; median age 37 years [range 14-71 years]; 1 traumatic brain injury [TBI]; 6 non-TBI) were investigated by fMRI a median of 15 days after injury (range 5-25 days). Neurological presentation included 2 coma, 1 vegetative state/unresponsive wakefulness syndrome (VS/UWS), 3 minimal conscious state (MCS) minus, and 1 MCS plus. Clinical outcomes at 3 months included 1 death, 1 VS/UWS, 1 MCS plus, and 4 conscious states (CS; 1 modified Rankin Scale 0; 2 mRS 4; 1 mRS 5). Normal DMNs were seen in 4 out of 7 patients (1 MCS plus, 3 CS at follow-up). It is feasible to assess the DMN by resting-state fMRI in patients with acute brain injury already in the very early period of intensive care unit admission. Although preliminary data, all patients with a preserved DMN regained consciousness levels at follow-up compatible with MCS+ or better.

  6. Effects of ketamine,midazolam,thiopental,and propofol on brain ischemia injury in rat cerebral cortical slices%氯胺酮,咪唑安定,硫喷妥钠和异丙酚对大鼠皮层脑片缺血性损伤的作用

    Institute of Scientific and Technical Information of China (English)

    薛庆生; 于布为; 王泽剑; 陈红专

    2004-01-01

    AIM: To compare the effects of ketamine, midazolam, thiopental, and propofol on brain ischemia by the model of oxygen-glucose deprivation (OGD) in rat cerebral cortical slices. METHODS: Cerebral cortical slices were incubated in 2 % 2,3,5-triphenyltetrazolium chloride (TTC) solution after OGD, the damages and effects of ketamine,midazolam, thiopental, and propofol were quantitativlye evaluated by ELISA reader of absorbance (A) at 490 nm,which indicated the red formazan extracted from slices, lactic dehydrogenase (LDH) releases in the incubated supernate were also measured. RESULTS: Progressive prolongation of OGD resulted in decreases of TTC staining.The percentage of tissue injury had a positive correlation with LDH releases, r=0.9609, P<0.01. Two hours of reincubation aggravated the decrease of TTC staining compared with those slices stained immediately after OGD (P<0.01). These four anesthetics had no effects on the TTC staining of slices. Ketamine completely inhibited the decrease of A value induced by 10 min of OGD injury. High concentrations of midazolam (10 μmol/L) and thiopental (400 μmol/L)partly attenuated this decrease. Propofol at high concentration (100 μmol/L) enhanced the decrease of A value induced by 10 min of OGD injury (P<0.01). CONCLUSION: Ketamine, high concentration of midazolam and thiopental have neuroprotective effects against OGD injury in rat cerebral cortical slices, while high concentration of propofol augments OGD injury in rat cerebral cortical slices.

  7. Reversible brain damage following acute organic solvents' poisoning determined by magnetic resonance

    Directory of Open Access Journals (Sweden)

    Dujmović Irena

    2005-01-01

    Full Text Available Introduction. Acute exposure to the effects of volatile solvents is characterized by the abrupt onset of symptoms and signs of poisoning, and relatively fast recovery in the majority of cases. Case report. We report a 24-year-old patient with an acute, accidental poisoning with a mixture of volatile organic solvents (most probably toluene, styrene and xylene, which led to the development of upward gaze paresis, diplopia, hemiparesis, ataxic gate, and the late onset truncal ataxia episodes. After 6 weeks, he recovered completely, while his extensive brain MRI lesions in the caudate nuclei, laterobasal putaminal regions, bilateral anterior insular cortex, central midbrain tegmental area withdrew completely after 4 months. Conclusion. Acute toxic encephalopathy should be a part of the differential diagnosis in any patient with acute neurobehavioral and neurological deficit.

  8. Effects of isoflurane and sevoflurane postconditioning and changes in JNK1/2 pathway activity on rat brain slices subjected to oxygen and glucose deprivation in vitro

    Institute of Scientific and Technical Information of China (English)

    Sheng Wang; Zhigang Dai; Xiwei Dong; Suxiang Guo; Yang Liu; Shan Jiang; Zhiping Wang

    2011-01-01

    Recent research shows that the JNK1/2 signaling pathway plays a neuroprotective role against ischemia-reperfusion injury by cross-talk with other pathways. The present study investigated the effects of isoflurane and sevoflurane postconditioning on JNK1/2 pathway activity and neuronal cell viability after oxygen and glucose deprivation injury in hippocampal slices in vitro. Techniques used included population spike analysis, propidium iodide fluorescent staining, western blot assay, and the use of JNK1/2-specific pharmacological tools such as anisomycin (agonist) and SP600125 (inhibitor). We found that both isoflurane and sevoflurane inhibited JNK pathway activity and had neuroprotective effects against oxygen and glucose deprivation injury in slices of rat hippocampus in vitro. Postconditioning with volatile anesthetics exerted neuroprotective effects on nerve cells and preserved the function of the CA1 region by inhibiting JNK1/2 phosphorylation. This suppression of JNK1/2 activity could underlie the observed synergistic neuroprotective effect produced by volatile anesthetic postconditioning.

  9. Phaco slice and separate.

    Science.gov (United States)

    Arshinoff, S A

    1999-04-01

    Phaco slice and separate retains the advantages of the chopping techniques of Nagahara, Koch, and Fukasaku but replaces chopping or snapping with slicing across the center of the phaco-tip-stabilized nucleus using a Nagahara chopper and then repositioning the chopper to optimally separate the divided lens halves. As the lens is rotated in the capsular bag, small pieces of the nuclear pie are sliced off, separated, emulsified, and aspirated. Emulsification and aspiration can alternatively be left until most or all the slices have been made. This technique works with a broader range of lens densities than other chopping techniques and uses no sculpting and very little phaco time. The phaco time required for this technique is relatively independent of nuclear density compared with a sculpting technique.

  10. MRI findings of acute cerebral swelling and brain edema in the acute stage. A report of two cases

    Energy Technology Data Exchange (ETDEWEB)

    Oki, Hideo; Ueda, Shin; Matsumoto, Keizo; Kashihara, Michiharu; Furuichi, Masashi.

    1988-08-01

    We report two cases, one of acute cerebral swelling and the other with a major stroke, whose MRI has shown very interesting findings. Case 1, a 32-year-old male, was admitted to our service because of a lowering of his consciousness immediately after a head injury. On admission, the patient was semicomatous (E/sub 1/M/sub 2/V/sub 1/, with anisocoria (R > L). His plain skull X-ray was normal. A CT scan, however, demonstrated right isodensity hemispheric swelling associated with a subarachnoid hemorrhage in the right Sylvian fissure. A right carotid angiogram showed no vascular disorders. MR imaging of the spin density demonstrated a hyperintensitive thickening of the gray matter in the whole right hemisphere. Case 2, a 58-year-old female, was admitted because of a sudden onset of loss of consciousness, with right hemiparesis and dysarthria. On admission, her consciousness was semicomatous (E/sub 1/M/sub 3/V/sub 1/), and it deteriorated to a deep coma 1 hour later. A CT scan demonstrated a diffuse left hemispheric low density, with a finding of hemorrhagic infarction in the basal ganglia. MR imaging of the spin density showed a hyperintensitive thickening of the gray matter resembling that of Case 1. The findings of the spin-echo images of our two cases showed a hyperintensitive thickening of the gray matter in both. The hyperintensity and thickening of the gray matter apparently indicated a sort of hyperemia and brain edema. These findings led us to suspect that the hyperemia associated with acute cerebral swelling and ischemic brain edema of our two cases originated in the gray matter, although it has been considered that the pathogenesis of acute cerebral swelling is not known and that brain edema, especially vasogenic edema, will mostly develop in the white matter rather than in the gray matter.

  11. Slice hyperholomorphic Schur analysis

    CERN Document Server

    Alpay, Daniel; Sabadini, Irene

    2016-01-01

    This book defines and examines the counterpart of Schur functions and Schur analysis in the slice hyperholomorphic setting. It is organized into three parts: the first introduces readers to classical Schur analysis, while the second offers background material on quaternions, slice hyperholomorphic functions, and quaternionic functional analysis. The third part represents the core of the book and explores quaternionic Schur analysis and its various applications. The book includes previously unpublished results and provides the basis for new directions of research.

  12. Acute Blast Injury Reduces Brain Abeta in Two Rodent Species

    Science.gov (United States)

    2012-12-01

    De Gasperi 1,2,3, Miguel A. Gama Sosa1,2,3, Soong Ho Kim4, John W. Steele4,5, Michael C. Shaughness6, Eric Maudlin-Jeronimo6, Aaron A. Hall 6...Wetzlar, Ger- many). Immunohistochemical staining was performed as previ- ously described ( Gama Sosa et al., 2010) using a rabbit anti-APP antibody APP369...Traumatic brain injury: football, warfare, and long- term effects. N. Engl. J. Med. 363, 1293–1296. Elder, G. A., Dorr, N. P., De Gasperi, R., Gama Sosa, M. A

  13. Serial Serum Leukocyte Apoptosis Levels as Predictors of Outcome in Acute Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Hung-Chen Wang

    2014-01-01

    Full Text Available Background. Apoptosis associates with secondary brain injury after traumatic brain injury (TBI. This study posits that serum leukocyte apoptosis levels in acute TBI are predictive of outcome. Methods. Two hundred and twenty-nine blood samples from 88 patients after acute TBI were obtained on admission and on Days 4 and 7. Serial apoptosis levels of different leukocyte subsets were examined in 88 TBI patients and 27 control subjects. Results. The leukocyte apoptosis was significantly higher in TBI patients than in controls. Brief unconsciousness (P=0.009, motor deficits (P≤0.001, GCS (P≤0.001, ISS (P=0.001, WBC count (P=0.015, late apoptosis in lymphocytes and monocytes on Day 1 (P=0.004 and P=0.022, resp., subdural hemorrhage on initial brain CT (P=0.002, neurosurgical intervention (P≤0.001, and acute posttraumatic seizure (P=0.046 were significant risk factors of outcome. Only motor deficits (P=0.033 and late apoptosis in monocytes on Day 1 (P=0.037 were independently associated with outcome. A cutoff value of 5.72% of late apoptosis in monocytes was associated with poor outcome in acute TBI patients. Conclusion. There are varying degrees of apoptosis in patients following TBI and in healthy individuals. Such differential expression suggests that apoptosis in different leukocyte subsets plays an important role in outcome following injury.

  14. The clinical usefulness of Tc-99m ECD brain SPECT in acute measles encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Seok Tae; Sohn, Myung Hee [School of Medicine, Chonbuk National Univ., Chonju (Korea, Republic of)

    2003-08-01

    Since the prognosis of measles encephalitis is poor, early diagnosis and proper management are very important to improve clinical outcomes. We compared Tc-99m ECD brain SPECT (SPECT) with MR imaging (MRI) for the detection of acute measles encephalitis. Eleven patients (M : F=4 : 7, age range 18 months-14 yrs) with acute measles encephalitis were enrolled in this studies. All of them underwent both MRI and SPECT. The results of SPECT were scored from 0 (normal) to 3 (most severe defect) according to perfusion state. We compared two image modalities for the detection of brain abnormality in acute measles encephalitis. Seven of 11 patients (63.6%) revealed high signal intensity in the white matter on T2WI of MRI, on the other hand all patients (100%) showed hypoperfusion on SPECT. Severe perfusion deficits above score 2 were located with decreasing frequencies in the frontal lobe (81.8%), temporal lobe (72.7%), occipital lobe (27.3%), basal ganglia (27.3%), and parietal lobe (9.1%). We conclude that SPECT is more useful than MRI for the detection of brain involvement in patients with acute measles encephalitis.

  15. Disruption of brain connectivity in acute stroke patients with early impairment in consciousness

    Directory of Open Access Journals (Sweden)

    Yuan-Hsiung eTsai

    2014-01-01

    Full Text Available Impairment in consciousness is common in acute stroke patients and is correlated with the clinical outcome after stroke. The underlying mechanism is not completely understood, with little known about brain activity and connectivity changes in acute stroke patients having impaired consciousness. In this study, we investigated changes in regional brain activity and brain networks of consciousness impaired stroke patients, as well as the amplitude of spontaneous low frequency fluctuation (ALFF of each time series. Regional homogeneity (ReHo of each voxel was measured, and resting state network analysis was consequently conducted. Results from this study demonstrate that, compared to normal subjects, the intensities of ALFF and ReHo, as well as the strength of the default mode network (DMN connectivity, were significantly decreased in the precuneus and posterior cingulate cortex regions among stroke patients with impaired consciousness. Furthermore, the strength of the DMN was highly correlated with differences in the Glasgow Coma Scale (GCS scores between the onset time and the scanning time. Results from this study suggest that the resting state fMRI is a feasible tool for the evaluation of acute stroke patients with an early impairment of consciousness. The detailed mechanisms, implications of these brain activities and networks exhibiting changes will require further investigation.

  16. Association between Peripheral Oxidative Stress and White Matter Damage in Acute Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Wei-Ming Lin

    2014-01-01

    Full Text Available The oxidative stress is believed to be one of the mechanisms involved in the neuronal damage after acute traumatic brain injury (TBI. However, the disease severity correlation between oxidative stress biomarker level and deep brain microstructural changes in acute TBI remains unknown. In present study, twenty-four patients with acute TBI and 24 healthy volunteers underwent DTI. The peripheral blood oxidative biomarkers, like serum thiol and thiobarbituric acid-reactive substances (TBARS concentrations, were also obtained. The DTI metrics of the deep brain regions, as well as the fractional anisotropy (FA and apparent diffusion coefficient, were measured and correlated with disease severity, serum thiol, and TBARS levels. We found that patients with TBI displayed lower FAs in deep brain regions with abundant WMs and further correlated with increased serum TBARS level. Our study has shown a level of anatomic detail to the relationship between white matter (WM damage and increased systemic oxidative stress in TBI which suggests common inflammatory processes that covary in both the peripheral and central reactions after TBI.

  17. The effect of head size∕shape, miscentering, and bowtie filter on peak patient tissue doses from modern brain perfusion 256-slice CT: how can we minimize the risk for deterministic effects?

    Science.gov (United States)

    Perisinakis, Kostas; Seimenis, Ioannis; Tzedakis, Antonis; Papadakis, Antonios E; Damilakis, John

    2013-01-01

    To determine patient-specific absorbed peak doses to skin, eye lens, brain parenchyma, and cranial red bone marrow (RBM) of adult individuals subjected to low-dose brain perfusion CT studies on a 256-slice CT scanner, and investigate the effect of patient head size∕shape, head position during the examination and bowtie filter used on peak tissue doses. The peak doses to eye lens, skin, brain, and RBM were measured in 106 individual-specific adult head phantoms subjected to the standard low-dose brain perfusion CT on a 256-slice CT scanner using a novel Monte Carlo simulation software dedicated for patient CT dosimetry. Peak tissue doses were compared to corresponding thresholds for induction of cataract, erythema, cerebrovascular disease, and depression of hematopoiesis, respectively. The effects of patient head size∕shape, head position during acquisition and bowtie filter used on resulting peak patient tissue doses were investigated. The effect of eye-lens position in the scanned head region was also investigated. The effect of miscentering and use of narrow bowtie filter on image quality was assessed. The mean peak doses to eye lens, skin, brain, and RBM were found to be 124, 120, 95, and 163 mGy, respectively. The effect of patient head size and shape on peak tissue doses was found to be minimal since maximum differences were less than 7%. Patient head miscentering and bowtie filter selection were found to have a considerable effect on peak tissue doses. The peak eye-lens dose saving achieved by elevating head by 4 cm with respect to isocenter and using a narrow wedge filter was found to approach 50%. When the eye lies outside of the primarily irradiated head region, the dose to eye lens was found to drop to less than 20% of the corresponding dose measured when the eye lens was located in the middle of the x-ray beam. Positioning head phantom off-isocenter by 4 cm and employing a narrow wedge filter results in a moderate reduction of signal-to-noise ratio

  18. The effect of head size/shape, miscentering, and bowtie filter on peak patient tissue doses from modern brain perfusion 256-slice CT: How can we minimize the risk for deterministic effects?

    Energy Technology Data Exchange (ETDEWEB)

    Perisinakis, Kostas; Seimenis, Ioannis; Tzedakis, Antonis; Papadakis, Antonios E.; Damilakis, John [Department of Medical Physics, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion 71003, Crete (Greece); Medical Diagnostic Center ' Ayios Therissos,' P.O. Box 28405, Nicosia 2033, Cyprus and Department of Medical Physics, Medical School, Democritus University of Thrace, Panepistimioupolis, Dragana 68100, Alexandroupolis (Greece); Department of Medical Physics, University Hospital of Heraklion, P.O. Box 1352, Heraklion 71110, Crete (Greece); Department of Medical Physics, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion 71003, Crete (Greece)

    2013-01-15

    Purpose: To determine patient-specific absorbed peak doses to skin, eye lens, brain parenchyma, and cranial red bone marrow (RBM) of adult individuals subjected to low-dose brain perfusion CT studies on a 256-slice CT scanner, and investigate the effect of patient head size/shape, head position during the examination and bowtie filter used on peak tissue doses. Methods: The peak doses to eye lens, skin, brain, and RBM were measured in 106 individual-specific adult head phantoms subjected to the standard low-dose brain perfusion CT on a 256-slice CT scanner using a novel Monte Carlo simulation software dedicated for patient CT dosimetry. Peak tissue doses were compared to corresponding thresholds for induction of cataract, erythema, cerebrovascular disease, and depression of hematopoiesis, respectively. The effects of patient head size/shape, head position during acquisition and bowtie filter used on resulting peak patient tissue doses were investigated. The effect of eye-lens position in the scanned head region was also investigated. The effect of miscentering and use of narrow bowtie filter on image quality was assessed. Results: The mean peak doses to eye lens, skin, brain, and RBM were found to be 124, 120, 95, and 163 mGy, respectively. The effect of patient head size and shape on peak tissue doses was found to be minimal since maximum differences were less than 7%. Patient head miscentering and bowtie filter selection were found to have a considerable effect on peak tissue doses. The peak eye-lens dose saving achieved by elevating head by 4 cm with respect to isocenter and using a narrow wedge filter was found to approach 50%. When the eye lies outside of the primarily irradiated head region, the dose to eye lens was found to drop to less than 20% of the corresponding dose measured when the eye lens was located in the middle of the x-ray beam. Positioning head phantom off-isocenter by 4 cm and employing a narrow wedge filter results in a moderate reduction of

  19. Histopathological Findings in Brains of Patients Who Died in the Acute Stage of Poor-grade Subarachnoid Hemorrhage

    Science.gov (United States)

    SATOMI, Junichiro; HADEISHI, Hiromu; YOSHIDA, Yasuji; SUZUKI, Akifumi; NAGAHIRO, Shinji

    2016-01-01

    Patients with poor-grade aneurysmal subarachnoid hemorrhage (SAH) are likely to die due to irreversible acute-stage primary brain damage. However, the mechanism(s) and pathology responsible for their high mortality rate remain unclear. We report our findings on the brains of individuals who died in the acute stage of SAH. An autopsy was performed on the brains of 11 SAH patients (World Federation of Neurosurgical Societies grade 5) who died within 3 days of admission and who did not receive respiratory assistance. All brains were free of intracranial hematoma and hydrocephalus; all harbored ruptured aneurysms. In all brains, multiple infarcts with perifocal edema were scattered throughout the cortex and subcortical white matter of the whole brain. Infarcts with a patchy – were more often seen than infarcts with a wedge-shaped pattern. Microscopic examination revealed multiple areas with cytotoxic edema and neuronal death indicative of acute ischemic changes. Edema and congestion were more obvious in areas where the subarachnoid clot tightly adhered to the pia mater. Pathologically, the brains of deceased patients with acute poor-grade SAH were characterized by edema and multifocal infarcts spread throughout the whole brain; they were thought to be attributable to venous ischemia. Diffuse disturbance in venous drainage attributable to an abrupt increase in the intracranial pressure and focal disturbances due to tight adhesion of the subarachnoid clot to the pia mater, may contribute strongly to irreversible brain damage in the acute stage of SAH. PMID:27357086

  20. Clinically relevant concentration of pregabalin has no acute inhibitory effect on excitation of dorsal horn neurons under normal or neuropathic pain conditions: An intracellular calcium-imaging study in spinal cord slices from adult rats.

    Science.gov (United States)

    Baba, Hiroshi; Petrenko, Andrey B; Fujiwara, Naoshi

    2016-10-01

    Pregabalin is thought to exert its therapeutic effect in neuropathic pain via binding to α2δ-1 subunits of voltage-gated calcium (Ca(2+)) channels. However, the exact analgesic mechanism after its binding to α2δ-1 subunits remains largely unknown. Whether a clinical concentration of pregabalin (≈10μM) can cause acute inhibition of dorsal horn neurons in the spinal cord is controversial. To address this issue, we undertook intracellular Ca(2+)-imaging studies using spinal cord slices with an intact attached L5 dorsal root, and examined if pregabalin acutely inhibits the primary afferent stimulation-evoked excitation of dorsal horn neurons in normal rats and in rats with streptozotocin-induced painful diabetic neuropathy. Under normal conditions, stimulation of a dorsal root evoked Ca(2+) signals predominantly in the superficial dorsal horn. Clinically relevant (10μM) and a very high concentration of pregabalin (100μM) did not affect the intensity or spread of dorsal root stimulation-evoked Ca(2+) signals, whereas an extremely high dose of pregabalin (300μM) slightly but significantly attenuated Ca(2+) signals in normal rats and in diabetic neuropathic (DN) rats. There was no difference between normal rats and DN rats with regard to the extent of signal attenuation at all concentrations tested. These results suggest that the activity of dorsal horn neurons in the spinal cord is not inhibited acutely by clinical doses of pregabalin under normal or DN conditions. It is very unlikely that an acute inhibitory action in the dorsal horn is the main analgesic mechanism of pregabalin in neuropathic pain states. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. A HYBRID DYNAMIC PROGRAM SLICING

    Institute of Scientific and Technical Information of China (English)

    Yi Tong; Wu Fangjun

    2005-01-01

    This letter proposes a hybrid method for computing dynamic program slicing. The key element is to construct a Coverage-Testing-based Dynamic Dependence Graph (CTDDG),which makes use of both dynamic and static information to get execution status. The approach overcomes the limitations of previous dynamic slicing methods, which have to redo slicing if slice criterion changes.

  2. Regional protein synthesis in rat brain following acute hemispheric ischemia.

    Science.gov (United States)

    Dienel, G A; Pulsinelli, W A; Duffy, T E

    1980-11-01

    Regional protein synthesis was measured in rat brain at intervals up to 48 h following occlusion of the four major arteries to the brain for either 10 or 30 min. Four-vessel occlusions produces ischemia in the cerebral hemispheres and oligemia in the midbrain-diencephalon and brainstem. During the hour following 10 min of ischemia, protein synthesis, measured by incorporation of [14C]valine into protein, was inhibited in the cerebral cortex by 67%. Normal rates of protein synthesis were attained within 4 h of recirculation. In rats subjected to 30 min of ischemia, protein synthesis was inhibited by 83% during the first hour of recirculation in the cortex, caudate-putamen, and hippocampus. Recovery of protein synthesis in these regions was slow (25-48 h). The midbrain-diencephalon showed less inhibition, 67%, and faster recovery (by 12 h). Protein synthesis was unaffected in the brainstem. [14C]Autoradiography revealed that the pyramidal neurons of the hippocampus and areas of the caudate and cortex failed to recover normal rates of protein synthesis even after 48 h. The accumulation of TCA-soluble [14C]valine was enhanced (55-65%) in the cortex, caudate, and hippocampus after 30 min of ischemia; the increase persisted for 12 h. A smaller rise in [14C]valine content (30%) and more rapid normalization of valine accumulation (by 7 h) were observed in the midbrain-diencephalon; no changes were found in the brainstem. In the cortex, recovery was more rapid when the duration of ischemia was reduced. Thus, the degree of inhibition of protein synthesis, the accumulation of valine in the tissue, and the length of time required to reestablish normal values for these processes were dependent on both the severity and the duration of the ischemic insult. Restoration of normal rates of protein synthesis after ischemia was slow compared with the normalization of cerebral energy metabolites.

  3. Coagulopathy as prognostic marker in acute traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Gaurav Chhabra

    2013-01-01

    Full Text Available Context: Coagulopathy frequently occurs following traumatic brain injury (TBI and usually occurs 6-72 hour post-trauma. The incidence and the probable risk factors for development of coagulopathy and poor outcome following TBI are largely unknown and vary considerably. Aims: To assess the incidence and probable risk factors for development of coagulopathy and to identify the risk factors for poor outcome in terms of median survival time following TBI. Materials and Methods: In this prospective study over two years, patients of isolated moderate and severe traumatic brain injury (GCS≤12 admitted to trauma center had coagulation profile (PT, APTT, thrombin time, fibrinogen and D-dimer, arterial lactate and ABG analysis done on day of admission and on day three. Coagulopathy was defined as prothrombin time (PT or/and activated partial thromboplastin time (APTT more than 1.5 times the normal control. Incidence of in-hospital mortality was assessed in all cases. Statistical Analysis: A stepwise logistic regression analysis was performed to identify risk factors for coagulopathy and mortality in these patients. Results: A total of 208 patients were enrolled in the study. The mean age was 32 ± 12 years and mean GCS was 7.1 ± 2.8. Coagulopathy was present in 46% ( n = 96 of patients. Risk factors for development of coagulopathy were found out to be severity of head injury (OR: 2.81, elevated D-dimer (OR: 3.43, low hemoglobin (OR: 3.13, and effaced cisterns in the CT scan (OR: 2.72. Presence of coagulopathy (OR: 2.97 and severity of head injury (OR: 5.70 strongly predicted poor outcome, and were associated with a decreased median survival time. Conclusions: There is a high incidence of coagulopathy following TBI. The presence of coagulopathy as well as of severity of TBI are strong predictors of in-hospital mortality in these patients.

  4. Neuron-specific enolase in cerebrospinal fluid and plasma of patients with acute ischemic brain disease

    Directory of Open Access Journals (Sweden)

    Selaković Vesna M.

    2003-01-01

    Full Text Available The objective of this research was to determine the dynamics of change of neuron-specific enolase concentration in patients with acute ischemic brain disease in cerebrospinal fluid and plasma. The study included 103 patients, their mean age 58-66 years. The control group consisted of 16 patients, of matching age and sex, with radicular lesions of discal origin, subjected to diagnostic radiculography. Concentration of neuron-specific enolase was measured by a flouroimmunometric method. The results showed that the concentration of neuron-specific enolase in cerebrospinal fluid and plasma of patients with brain ischemic disease within first seven days significantly increased compared to the control. The highest increase of concentration was established in brain infarction, somewhat lower in reversible ischemic attack, and the lowest in transient ischemic attack. Maximal concentration was established on the 3rd-4th day upon the brain infarction. Neuron-specific enolase concentration in cerebrospinal fluid and plasma may be an indicator of pathophysiological processes in the acute phase of brain ischemia and is significant in early diagnostics and therapy of the disease.

  5. Induction of acute brain injury in mice by irradiation with high-LET charged particles

    Science.gov (United States)

    Liu, Yang; Zhang, Hong

    The present study was performed to evaluate the induction of acute brain injury in mice after 235 Mev/u carbon ion irradiation. In our study, young outbred Kunming mice were divided into four treatment groups according to the penetration depth of carbon ions. Animals were irradiated with a sublethal dose of carbon ion beams prior to the Bragg curve. An experiment was performed to evaluate the acute alterations in histology, DNA double-strand breaks (DNA DSBs) as well as p53and Bax expression in the brain 96 h post-irradiation. The results demonstrated that various histopathological changes, a significant number of DNA DSBs and elevated p53 and Bax protein expression were induced in the brain following exposure to carbon ions. This was particularly true for mice irradiated with ions having a 9.1 cm-pentration depth, indicating that carbon ions can led to deleterious lesions in the brain of young animals within 96 h. Moreover, there was a remarkable increase in DNA DSBs and in the severity of histopathological changes as the penetration depths of ions increased, which may be associated with the complex track structure of heavy ions. These data reveal that carbon ions can promote serious neuropathological degeneration in the cerebral cortex of young mice. Given that damaged neurons cannot regenerate, these findings warrant further investigation of the adverse effects of the space radiation and the passage of a therapeutic heavy ion beam in the plateau region of the Bragg curve through healthy brain tissue.

  6. Setting up alcohol-associated dementia models in vitro with primary-cultured hippocampal neuron and brain slice%采用海马原代神经元和离体脑片建立乙醇性痴呆体外模型的比较

    Institute of Scientific and Technical Information of China (English)

    刘勇; 曾玉娥; 杨海玉

    2014-01-01

    Objective To set up the different alcohol-associated dementia (AAD) models in vitro and provide methods for researching the mechanism of AAD.Methods Hippocampal neurons got from fetal rats were primary cultured for 6 days and identified.Then,the cells were treated with different doses of ethanol (25-100 mol/L) for 24 h.The cell viability was analyzed with MTT assay.The staining with Hoechst33342 was used to observe the cell apoptosis.In addition,hippocampi of newbom rats 7-10 days after birth were taken out and cut to 300 μm thickness of slices; the morphological changes of the brain slices were observed with HE staining at different time points after ethanol administration.Results Primary-cultured hippocampal neurons highly expressed neuron-specific enolase (NSE) and lowly expressed glial fibrillary acidic protein (GFAP).And the cell viability was significantly decreased by ethanol administration (50-100 mol/L,24 h) in a dose-dependent manner.Increased apoptosis cells were detected when cells were treated with 50 mol/L concentration of ethanol for 24 h.For hippocampal slices,acute ethanol administration (50 mol/L,30 min) induced significant cell apoptosis and chronic ethanol administration (50 mol/L,24 h) resulted in the serious damage of hippocampal morphology.Conclusions The models that primary-cultured hippocampal neuron apoptosis induced by chronic ethanol administration is suitable for researching the mechanism of AAD.Hippocampal slices are more sensitive for ethanol toxic effects and may be used for the research of acute alcohol toxicity.%目的 建立和比较不同的乙醇性痴呆(AAD)体外研究模型,为进一步探讨其发病机制提供方法学参考. 方法 取胎鼠海马进行原代神经元培养及鉴定,给予不同浓度的乙醇作用24 h,采用四甲基偶氮唑蓝(MTT)比色法检测细胞存活率以及Hoechst33342染色观察细胞凋亡状况.另外,取新生大鼠海马切取脑片进行离体培养,采用HE染色观察不同时间

  7. Volume regulatory loss of Na, Cl, and K from rat brain during acute hyponatremia

    Energy Technology Data Exchange (ETDEWEB)

    Melton, J.E.; Patlak, C.S.; Pettigrew, K.D.; Cserr, H.F.

    1987-04-01

    This study quantitatively evaluates the contribution of tissue Na, Cl, and K loss to brain volume regulation during acute dilutional hyponatremia (DH) and examines the mechanism of Na loss. DH was produced in pentobarbital sodium-anesthetized rats by intraperitoneal infusion of distilled water and brain water and electrolytes analyzed 30 min, 1 h, 3 h, 4 h, or 6 h later. The rate of Na and Cl loss was greatest during the first 30 min of DH. Net loss of Na and Cl was maximal after 3 h of DH. K loss was slower, achieving significance after 3 h. Electrolyte loss was sufficient to account for observed brain volume regulation after three or more hours of DH. Measurements of /sup 22/Na influx and efflux across the blood brain barrier showed that barrier permeability to Na is unchanged during DH. Analysis of results using a two-compartment model of plasma-brain exchange suggests that loss of brain Na during DH does not result solely from a shift of electrolyte across the blood-brain barrier to plasma, and thus provides indirect evidence for an additional pathway for Na loss, presumably via cerebrospinal fluid.

  8. Occurrence of Asymptomatic Acute Neuromyelitis Optica Spectrum Disorder-Typical Brain Lesions during an Attack of Optic Neuritis or Myelitis

    Science.gov (United States)

    Kim, Su-Hyun; Hyun, Jae-Won; Joung, AeRan; Lee, Sang Hyun; Kim, Ho Jin

    2016-01-01

    We aimed to investigate the frequency of asymptomatic acute brain MRI abnormalities accompanying optic neuritis (ON) or myelitis in neuromyelitis optica spectrum disorder (NMOSD) patients with aquaporin-4 antibodies (AQP4-Ab). We reviewed 324 brain MRI scans that were obtained during acute attacks of ON or myelitis, in 165 NMOSD patients with AQP4-Ab. We observed that acute asymptomatic NMOSD-typical brain lesions accompanied 27 (8%) acute attacks of ON or myelitis in 24 (15%) patients. The most common asymptomatic brain abnormalities included edematous corpus callosum lesions (n = 17), followed by lesions on the internal capsule and/or cerebral peduncle lesions (n = 9), periependymal surfaces of the fourth ventricle (n = 5), large deep white matter lesions (n = 4), periependymal cerebral lesions surrounding the lateral ventricles (n = 3), and hypothalamic lesions (n = 1). If asymptomatic NMOSD-typical brain abnormalities were considered as evidence for DIS, while also assuming that the AQP4-IgG status was unknown, the median time to diagnosis using the 2015 diagnosis criteria for NMOSD was shortened from 28 months to 6 months (p = 0.008). Asymptomatic acute NMOSD-typical brain lesions can be accompanied by an acute attack of ON or myelitis. Identifying these asymptomatic brain lesions may help facilitate earlier diagnosis of NMOSD. PMID:27936193

  9. Occurrence of Asymptomatic Acute Neuromyelitis Optica Spectrum Disorder-Typical Brain Lesions during an Attack of Optic Neuritis or Myelitis.

    Science.gov (United States)

    Kim, Su-Hyun; Hyun, Jae-Won; Joung, AeRan; Lee, Sang Hyun; Kim, Ho Jin

    2016-01-01

    We aimed to investigate the frequency of asymptomatic acute brain MRI abnormalities accompanying optic neuritis (ON) or myelitis in neuromyelitis optica spectrum disorder (NMOSD) patients with aquaporin-4 antibodies (AQP4-Ab). We reviewed 324 brain MRI scans that were obtained during acute attacks of ON or myelitis, in 165 NMOSD patients with AQP4-Ab. We observed that acute asymptomatic NMOSD-typical brain lesions accompanied 27 (8%) acute attacks of ON or myelitis in 24 (15%) patients. The most common asymptomatic brain abnormalities included edematous corpus callosum lesions (n = 17), followed by lesions on the internal capsule and/or cerebral peduncle lesions (n = 9), periependymal surfaces of the fourth ventricle (n = 5), large deep white matter lesions (n = 4), periependymal cerebral lesions surrounding the lateral ventricles (n = 3), and hypothalamic lesions (n = 1). If asymptomatic NMOSD-typical brain abnormalities were considered as evidence for DIS, while also assuming that the AQP4-IgG status was unknown, the median time to diagnosis using the 2015 diagnosis criteria for NMOSD was shortened from 28 months to 6 months (p = 0.008). Asymptomatic acute NMOSD-typical brain lesions can be accompanied by an acute attack of ON or myelitis. Identifying these asymptomatic brain lesions may help facilitate earlier diagnosis of NMOSD.

  10. Altered spontaneous brain activity in patients with acute spinal cord injury revealed by resting-state functional MRI.

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    Ling Zhu

    Full Text Available Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI. However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo analysis based on resting-state functional magnetic resonance imaging.A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity.Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores.Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as potential biomarkers for

  11. 钾通道阻断剂4-氨基吡啶诱导海马CA1锥体神经元钙瞬变%Calcium transient of CA1 pyramidal neurons induced by potassium blocker 4-aminopyridine in acute hippocampal slices

    Institute of Scientific and Technical Information of China (English)

    苏涛; 丛文东; 廖卫平

    2011-01-01

    Objective To investigate the calcium transient of CA1 pyramidal neurons induced by potassium blocker 4-aminopyridine (4-AP) in acute hippocampal slices to explore the relation between potassium channel function and calcium transient, and their mechanism. Methods Fluorescent probe was employed to mark the hippocampai neurons in acute brain slices of rats; confocal microscopy was used to perform calcium imaging to observe the influences of different concentrations of 4-AP and perfusate with/without calcium on calcium transient of CA1 pyramidal neurons. Results The response of [Ca2+]I to lower concentration of 4-AP (<15 mmol/L) was in a dose-dependent manner (r2=0.910, P=0.000); the higher the concentration of 4-AP (20-80 mmol/L), the lower the peak level of calcium transient. The latency and amplitude of calcium transient induced by 4-AP were obviously reduced when the extracellular condition was switched to an absence of calcium, which was significantly different as compared with that with calcium (P<0.05). Conclusion Blockade of potassium channels with 4-AP can increase [Ca2+]I in the hippocampal pyramidal neurons of acute slices. The increase of [Ca2+]1 to 4-AP could be ascribe to calcium release from intracellular stores and calcium influx from extracellular matrix.%目的 研究4-氨基吡啶(4-AP)诱导的急性脑片海马CA1锥体神经元钙瞬变现象,探讨钾通道功能与钙瞬变的关系及可能机制.方法 荧光探针标记正常大鼠急性脑片海马神经元.共聚焦显微镜技术进行钙成像,观察不同浓度4-AP及细胞灌流液条件对神经元钙瞬变的影响.结果 低浓度(<15 mmol/L)4-AP诱导的钙瞬变峰值与剂量呈线性相关(r2=0.910,P=0.000),高浓度(20~80 mmol/L)4-AP诱导的钙瞬变峰值随浓度增高而下降.在无钙灌流液条件下,4-AP诱导的钙瞬变峰值水平下降,达峰时间延长,与含钙灌流液比较差异有统计学意义(P<0.05).结论 4-AP可诱导急性脑片海马CA1锥体神经

  12. Psychological Characteristics in Acute Mild Traumatic Brain Injury: An MMPI-2 Study.

    Science.gov (United States)

    Gass, Carlton S; Rogers, David; Kinne, Erica

    2017-01-01

    The psychological characteristics of acute traumatic brain injury (TBI) have received limited research focus, despite empirical evidence of their relevance for subsequent psychological adjustment and early therapeutic intervention. This study addressed a wide range of psychological features in 47 individuals who were hospitalized as a result of acute mild TBI (mTBI). Participants were screened from amongst consecutive TBI admissions for moderate to severe brain injury, and for pre-injury neurological, psychiatric, or substance abuse histories. Clinical and content scale scores on the MMPI-2 were explored in relation to patient gender, age, level of education, and extent of cognitive complaints. The results revealed diverse psychosocial problem areas across the sample, the most common of which were somatic and cognitive complaints, compromised insight, and a naively optimistic self-perception. The mediating roles of injury severity and demographic variables are discussed. Clinical implications and specific recommendations are presented.

  13. [Pathophysiology of brain injury and targets of treatment in acute ischemic stroke].

    Science.gov (United States)

    Tanaka, Kortaro

    2013-01-01

    Brain is very vulnerable to ischemia, and exhibits various functional impairments in a flow-dependent manner. After onset of ischemia, the following cascade ensues propagating from the ischemic core to the surrounding area; ischemic depolarization, excitatory cellular injury induced by Ca(2+) and glutamate, oxidative injury induced by reactive oxygen species including various free radicals, secondary microcirculatory disturbance, edema formation, apoptosis and inflammation. Intrinsic protective responses are also activated at the periphery of ischemic area. From the clinical view point, urgent detection of "penumbra" area by imaging modalities such as diffusion-perfusion mismatch and rescuing this area from evolving into irreversible damage (infarction) are the most important issues. Therapeutic targets in the acute phase of cerebral infarction consist of vascular therapy including acute thrombolysis, prevention of microcirculatory disturbance, protection of blood brain barrier and promotion of collateral blood flow, and cellular therapy such as neuroprotective measures aiming at neurovascular unit.

  14. Institutional Variation in Traumatic Brain Injury Acute Rehabilitation Practice.

    Science.gov (United States)

    Seel, Ronald T; Barrett, Ryan S; Beaulieu, Cynthia L; Ryser, David K; Hammond, Flora M; Cullen, Nora; Garmoe, William; Sommerfeld, Teri; Corrigan, John D; Horn, Susan D

    2015-08-01

    To describe institutional variation in traumatic brain injury (TBI) inpatient rehabilitation program characteristics and evaluate to what extent patient factors and center effects explain how TBI inpatient rehabilitation services are delivered. Secondary analysis of a prospective, multicenter, cohort database. TBI inpatient rehabilitation programs. Patients with complicated mild, moderate, or severe TBI (N=2130). Not applicable. Mean minutes; number of treatment activities; use of groups in occupational therapy, physical therapy, speech therapy, therapeutic recreation, and psychology inpatient rehabilitation sessions; and weekly hours of treatment. A wide variation was observed between the 10 TBI programs, including census size, referral flow, payer mix, number of dedicated beds, clinician experience, and patient characteristics. At the centers with the longest weekday therapy sessions, the average session durations were 41.5 to 52.2 minutes. At centers with the shortest weekday sessions, the average session durations were approximately 30 minutes. The centers with the highest mean total weekday hours of occupational, physical, and speech therapies delivered twice as much therapy as the lowest center. Ordinary least-squares regression modeling found that center effects explained substantially more variance than patient factors for duration of therapy sessions, number of activities administered per session, use of group therapy, and amount of psychological services provided. This study provides preliminary evidence that there is significant institutional variation in rehabilitation practice and that center effects play a stronger role than patient factors in determining how TBI inpatient rehabilitation is delivered. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  15. Neurosensory Symptom Complexes after Acute Mild Traumatic Brain Injury.

    Directory of Open Access Journals (Sweden)

    Michael E Hoffer

    Full Text Available Mild Traumatic Brain Injury (mTBI is a prominent public health issue. To date, subjective symptom complaints primarily dictate diagnostic and treatment approaches. As such, the description and qualification of these symptoms in the mTBI patient population is of great value. This manuscript describes the symptoms of mTBI patients as compared to controls in a larger study designed to examine the use of vestibular testing to diagnose mTBI. Five symptom clusters were identified: Post-Traumatic Headache/Migraine, Nausea, Emotional/Affective, Fatigue/Malaise, and Dizziness/Mild Cognitive Impairment. Our analysis indicates that individuals with mTBI have headache, dizziness, and cognitive dysfunction far out of proportion to those without mTBI. In addition, sleep disorders and emotional issues were significantly more common amongst mTBI patients than non-injured individuals. A simple set of questions inquiring about dizziness, headache, and cognitive issues may provide diagnostic accuracy. The consideration of other symptoms may be critical for providing prognostic value and treatment for best short-term outcomes or prevention of long-term complications.

  16. Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection.

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    Napapon Sailasuta

    Full Text Available OBJECTIVE: Single voxel proton magnetic resonance spectroscopy (MRS can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART. METHODS: Brain metabolite levels of N-acetyl aspartate (NAA, choline (tCHO, creatine (CR, myoinositol (MI, and glutamate and glutamine (GLX were measured in acute HIV subjects (n = 31 and compared to chronic HIV+individuals (n = 26 and HIV negative control subjects (n = 10 from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM, frontal white matter (FWM, occipital gray matter (OGM, and basal ganglia (BG. Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. RESULTS: After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection compared to control (p = 0.0014, as well as chronic subjects (p = 0.0023. A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022 with tCHO/CR similar to control subjects at 6 months. INTERPRETATION: We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury.

  17. The acute effects of 3,4-methylenedioxymethamphetamine on oxidative stress in rat brain

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    Simić Ivan

    2008-01-01

    Full Text Available Introduction Oxidative stress and oxygen free radicals are thought to play an important role in acute effects of a number of neurotoxic processes. 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy, a ring substituted amphetamine derivate, has attracted a great deal of media attention in recent years due to its widespread abuse as recreational drug by the young generation. The aim of the present study was to evaluate the acute effects of 3,4-methylenedioxymethamphetamine on oxidative stress parameters (index of lipid peroxidation - ILP, superoxide radicals O2-, superoxide dismutase - SOD and glutathione - GSH in frontal cortex, striatum and hippocampus in Wistar rats. Materials and methods The study included 40 male Wistar rats (200-250 g, housed 4 per cage having free access to food and water. MDMA was dissolved in distillated water and administered peroraly at 5, 10, 20 or 40 mg/kg. 8 hours following MDMA, the rats were killed by decapitation, their brains were rapidly removed and the brain structures were dissected out on ice and analyzed biochemically. Results Acute peroral administration of a single dose (5, 10, 20 and 40 mg/kg resulted in increase of ILP, O2-, SOD and decrease of GSH. Conclusion The results obtained in the present study suggest that oxidative stress plays a crucial role in MDMA-induced neurotoxicity and that the mechanism of MDMA neurotoxycity may vary between brain regions.

  18. Brain and muscle redox imbalance elicited by acute ethylmalonic acid administration.

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    Patrícia Fernanda Schuck

    Full Text Available Ethylmalonic acid (EMA accumulates in tissues and biological fluids of patients affected by short-chain acyl-CoA dehydrogenase deficiency (SCADD and ethylmalonic encephalopathy, illnesses characterized by neurological and muscular symptoms. Considering that the mechanisms responsible for the brain and skeletal muscle damage in these diseases are poorly known, in the present work we investigated the effects of acute EMA administration on redox status parameters in cerebral cortex and skeletal muscle from 30-day-old rats. Animals received three subcutaneous injections of EMA (6 μmol/g; 90 min interval between injections and were killed 1 h after the last administration. Control animals received saline in the same volumes. EMA administration significantly increased thiobarbituric acid-reactive substances levels in cerebral cortex and skeletal muscle, indicating increased lipid peroxidation. In addition, carbonyl content was increased in EMA-treated animal skeletal muscle when compared to the saline group. EMA administration also significantly increased 2',7'-dihydrodichlorofluorescein oxidation and superoxide production (reactive species markers, and decreased glutathione peroxidase activity in cerebral cortex, while glutathione levels were decreased only in skeletal muscle. On the other hand, respiratory chain complex I-III activity was altered by acute EMA administration neither in cerebral cortex nor in skeletal muscle. The present results show that acute EMA administration elicits oxidative stress in rat brain and skeletal muscle, suggesting that oxidative damage may be involved in the pathophysiology of the brain and muscle symptoms found in patients affected by SCADD and ethylmalonic encephalopathy.

  19. Brain and muscle redox imbalance elicited by acute ethylmalonic acid administration.

    Science.gov (United States)

    Schuck, Patrícia Fernanda; Milanez, Ana Paula; Felisberto, Francine; Galant, Leticia Selinger; Machado, Jéssica Luca; Furlanetto, Camila Brulezi; Petronilho, Fabricia; Dal-Pizzol, Felipe; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2015-01-01

    Ethylmalonic acid (EMA) accumulates in tissues and biological fluids of patients affected by short-chain acyl-CoA dehydrogenase deficiency (SCADD) and ethylmalonic encephalopathy, illnesses characterized by neurological and muscular symptoms. Considering that the mechanisms responsible for the brain and skeletal muscle damage in these diseases are poorly known, in the present work we investigated the effects of acute EMA administration on redox status parameters in cerebral cortex and skeletal muscle from 30-day-old rats. Animals received three subcutaneous injections of EMA (6 μmol/g; 90 min interval between injections) and were killed 1 h after the last administration. Control animals received saline in the same volumes. EMA administration significantly increased thiobarbituric acid-reactive substances levels in cerebral cortex and skeletal muscle, indicating increased lipid peroxidation. In addition, carbonyl content was increased in EMA-treated animal skeletal muscle when compared to the saline group. EMA administration also significantly increased 2',7'-dihydrodichlorofluorescein oxidation and superoxide production (reactive species markers), and decreased glutathione peroxidase activity in cerebral cortex, while glutathione levels were decreased only in skeletal muscle. On the other hand, respiratory chain complex I-III activity was altered by acute EMA administration neither in cerebral cortex nor in skeletal muscle. The present results show that acute EMA administration elicits oxidative stress in rat brain and skeletal muscle, suggesting that oxidative damage may be involved in the pathophysiology of the brain and muscle symptoms found in patients affected by SCADD and ethylmalonic encephalopathy.

  20. Evaluation of biventricular ejection fraction with ECG-gated 16-slice CT: preliminary findings in acute pulmonary embolism in comparison with radionuclide ventriculography

    Energy Technology Data Exchange (ETDEWEB)

    Coche, Emmanuel; Goncette, Louis; Maldague, Baudouin [Universite Catholique de Louvain, Department of Medical Imaging, Cliniques Universitaires St-Luc, Brussels (Belgium); Vlassenbroek, Alain [Philips Medical Systems, Cleveland, OH (United States); Roelants, Veronique [Universite Catholique de Louvain, Department of Nuclear Medicine, Cliniques Universitaires St-Luc, Brussels (Belgium); D' Hoore, William [Catholic University of Louvain, Public Health, Brussels (Belgium); Verschuren, Franck [Universite Catholique de Louvain, Department of Emergency Medicine, Cliniques Universitaires St-Luc, Brussels (Belgium)

    2005-07-01

    This study aimed to assess the feasibility of cardiac global function evaluation during a whole-chest multi-slice CT (MSCT) acquisition in patients referred for suspicion of pulmonary embolism (PE), and to compare the results with planar equilibrium radionuclide ventriculography (ERNA). Ten consecutive haemodynamically stable patients (six female, four male; mean age 69.7 years; heart rate 65-99 bpm) with suspicion of PE underwent an MSCT and ERNA within a 6 h period. CT acquisition was performed after contrast medium injection by using 16 x 1.5 mm collimation and retrospective ECG gating. Left ventricular (LVEF) and right ventricular (RVEF) ejection fractions were calculated using dedicated three-dimensional software. Relationships between measurements obtained with MSCT and ERNA were assessed using linear regression analysis and reliability of MSCT was assessed with intra-class correlation coefficient. Bland-Altman analysis was performed to calculate limits of agreement between MSCT and ERNA. MSCT was performed successfully in ten patients with a mean acquisition time of 16.5{+-}2.8 s. Functional cardiac evaluation was possible on CT for all patients except for one due to poor opacification of right ventricle. Linear regression analysis showed a good correlation between MSCT and ERNA for the LVEF (R=0.91) and the RVEF (R=0.89) measurements. Intra-class correlation was superior for LVEF (0.92) than for the RVEF (0.68). Bland-Altman plots demonstrated that MSCT substantially overestimated the ERNA RVEF. Morphological CT data demonstrated PE in four of ten of patients and alternative diagnoses in five of ten patients. Our study reveals that MSCT with retrospective ECG gating may provide in one modality a morphological and a functional cardiopulmonary evaluation. Comparison with ERNA demonstrated a good correlation for both ventricular ejection fractions. (orig.)

  1. Evaluation of biventricular ejection fraction with ECG-gated 16-slice CT: preliminary findings in acute pulmonary embolism in comparison with radionuclide ventriculography.

    Science.gov (United States)

    Coche, Emmanuel; Vlassenbroek, Alain; Roelants, Véronique; D'Hoore, William; Verschuren, Franck; Goncette, Louis; Maldague, Baudouin

    2005-07-01

    This study aimed to assess the feasibility of cardiac global function evaluation during a whole-chest multi-slice CT (MSCT) acquisition in patients referred for suspicion of pulmonary embolism (PE), and to compare the results with planar equilibrium radionuclide ventriculography (ERNA). Ten consecutive haemodynamically stable patients (six female, four male; mean age 69.7 years; heart rate 65-99 bpm) with suspicion of PE underwent an MSCT and ERNA within a 6 h period. CT acquisition was performed after contrast medium injection by using 16x1.5 mm collimation and retrospective ECG gating. Left ventricular (LVEF) and right ventricular (RVEF) ejection fractions were calculated using dedicated three-dimensional software. Relationships between measurements obtained with MSCT and ERNA were assessed using linear regression analysis and reliability of MSCT was assessed with intra-class correlation coefficient. Bland-Altman analysis was performed to calculate limits of agreement between MSCT and ERNA. MSCT was performed successfully in ten patients with a mean acquisition time of 16.5+/-2.8 s. Functional cardiac evaluation was possible on CT for all patients except for one due to poor opacification of right ventricle. Linear regression analysis showed a good correlation between MSCT and ERNA for the LVEF (R=0.91) and the RVEF (R=0.89) measurements. Intra-class correlation was superior for LVEF (0.92) than for the RVEF (0.68). Bland-Altman plots demonstrated that MSCT substantially overestimated the ERNA RVEF. Morphological CT data demonstrated PE in four of ten of patients and alternative diagnoses in five of ten patients. Our study reveals that MSCT with retrospective ECG gating may provide in one modality a morphological and a functional cardiopulmonary evaluation. Comparison with ERNA demonstrated a good correlation for both ventricular ejection fractions.

  2. A Case of Acute Motor Axonal Neuropathy Mimicking Brain Death and Review of the Literature

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    Sandhya eRavikumar

    2016-04-01

    Full Text Available We describe a case report of fulminant Guillain-Barré syndrome mimicking brain death. A previously healthy 60-year-old male was admitted to the neurointensive care unit after developing rapidly progressive weakness and respiratory failure. On presentation, the patient was found to have absent brainstem and spinal cord reflexes resembling that of brain death. Acute motor axonal neuropathy (AMAN, a subtype of Guillain-Barré syndrome, was diagnosed by cerebrospinal fluid and nerve conduction velocity testing. An electroencephalogram showed that the patient had normal, appropriately reactive brain function. Transcranial Doppler ultrasound showed appropriate blood flow to the brain. Guillain-Barré syndrome rarely presents with weakness so severe as to mimic brain death. This article provides a review of similar literature. This case demonstrates the importance of performing a proper brain death examination, which includes evaluation for irreversible cerebral injury, exclusion of any confounding conditions, and performance of tests such as electroencephalography and transcranial dopplers when uncertainty exists about the reliability of the clinical exam.

  3. Acute brain metabolic effects of cocaine in rhesus monkeys with a history of cocaine use.

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    Henry, Porche' Kirkland; Murnane, Kevin S; Votaw, John R; Howell, Leonard L

    2010-12-01

    Cocaine addiction involves an escalation in drug intake which alters many brain functions. The present study documented cocaine-induced changes in brain metabolic activity as a function of cocaine self-administration history. Experimentally naive rhesus monkeys (N = 6) were given increasing access to cocaine under a fixed-ratio schedule of intravenous (i.v.) drug self-administration. PET imaging with F-18 labeled fluorodeoxyglucose (FDG) was used to measure acute intramuscular (i.m.) cocaine-induced changes in brain metabolism in the cocaine-naïve state, following 60 sessions under limited-access conditions (1 h/day), following 60 sessions under extended-access conditions (4 h/day), and following 4 weeks of drug withdrawal. In the cocaine-naïve state, cocaine-induced increases in brain metabolism were restricted to the prefrontal cortex. As cocaine exposure increased from limited to extended access, metabolic effects expanded throughout the frontal cortex and were induced within the striatum. Conversely, cocaine-induced activation was far less robust following withdrawal. The results highlight a progressive expansion of the metabolic effects of cocaine to include previously unaffected dopamine innervated brain regions as a consequence of cocaine self-administration history. The identification of brain regions progressively influenced by drug exposure may be highly relevant toward efforts to develop treatments for cocaine addiction.

  4. Investigating metacognition, cognition, and behavioral deficits of college students with acute traumatic brain injuries.

    Science.gov (United States)

    Martinez, Sarah; Davalos, Deana

    2016-07-01

    Executive dysfunction in college students who have had an acute traumatic brain injury (TBI) was investigated. The cognitive, behavioral, and metacognitive effects on college students who endorsed experiencing a brain injury were specifically explored. Participants were 121 college students who endorsed a mild TBI, and 121 college students with no history of a TBI were matched on sex and ethnicity to examine potential differences between groups. Participants completed the Dysexecutive Questionnaire (DEX). A Rasch analysis indicated that the TBI group had significantly higher total scores on the DEX than the control group. Moreover, when compared with the control group, the students with a TBI had higher scores on all 3 subcomponents of the DEX. These findings suggest that students who endorse brain injuries may experience more difficulty with specific facets of college. Thus, the importance of academic and personal resources available for students with a TBI is discussed.

  5. A glass capillary microelectrode based on capillarity and its application to the detection of L-glutamate release from mouse brain slices.

    Science.gov (United States)

    Nakajima, Kumiko; Yamagiwa, Takashi; Hirano, Ayumi; Sugawara, Masao

    2003-01-01

    A new glass capillary microelectrode for L-glutamate is described using pulled glass capillaries (tip size, approximately 12.5 microm) with a very small volume (approximately 2 microl) of inner solution containing glutamate oxidase (GluOx) and ascorbate oxidase. The operation of the electrode is based on capillary action that samples L-glutamate into the inner solution. The enzyme reaction by GluOx generates hydrogen peroxide that is detected at an Os-gel-HRP polymer modified Pt electrode in a three-electrode configuration. The amperometric response behavior of the electrode was characterized in terms of the capillarity, response time, sensitivity and selectivity for measurements of L-glutamate. The currents at 0 V vs. Ag/AgCl increased linearly with the L-glutamate concentration from 10 to 150 microM for in vitro and in situ calibrations. The response was highly selective to L-glutamate over ascorbate, dopamine, serotonin and other amino acids. The detection of L-glutamate in the extracellular fluids of different regions of mouse hippocampal slices under stimulation of KCl was demonstrated.

  6. 肌肽对大鼠脑片缺氧缺糖/再灌损伤的保护作用%Neuroprotective of carnosine on oxygen-glucose deprivation/reperfusion induced injury in rat brain slices

    Institute of Scientific and Technical Information of China (English)

    方超; 李晴; 鲁美丽; 黄国兴; 杨菁

    2015-01-01

    目的:在离体脑片缺氧缺糖/再灌损伤模型上,评价肌肽对脑组织的保护作用。方法肌肽预处理后,用缺氧缺糖/再灌(oxygen glucose deprivation/reperfusion,OGD/RP)来制备大鼠离体脑片损伤模型。以2,3,5-三苯基氯化四氮唑(2,3,5-triphenyl tetrazolium chloride,TTC)染色法检测脑片活性;HPLC法检测海马脑片中ATP、ADP、AMP含量;荧光法检测脑组织活性氧( reactive oxygen species,ROS)。结果与对照组相比,缺氧缺糖/再灌损伤可以明显损伤大鼠海马脑片,TTC染色颜色变浅,A490 nm明显下降, ATP和ADP含量明显降低,而AMP含量明显升高,ROS明显升高,差异均具有统计学意义(P<0.01)。与模型组相比,缺氧缺糖/再灌损伤前预先加入1000、200、40μg/mL肌肽预处理15 min可显著抑制缺氧缺糖/再灌引起的损伤,TTC染色颜色加深,A490 nm明显升高,ATP、ADP、AMP含量升高,ROS含量降低,差异均具有统计学意义( P<0.01)。结论肌肽可减轻缺氧缺糖/再灌导致的损伤,其机制可能与其改善脑组织能量代谢,增强抗氧化能力有关。%Objective To investigate effect of carnosine on oxygen glucose deprivation/reperfusion ( OGD/RP) induced injury in rat brain slices. Methods Injury of brain slices was determined by TTC methods.The contents of ATP, ADP and AMP were determined by high performance liquid chromatography.Reactive Oxygen species ( ROS) were determined by fluorescence methods.Results Compared with control group, rat hippocampal slices were significantly damaged by OGD/RP, indicated by light color and decreased A490 nm value of TTC staining.Meanwhile the contents of ATP and ADP were significantly decreased, and the content of AMP and ROS were significantly increased, the difference between two group was significant ( P<0.01).Pre-incubation with Carnosine (1000, 200, 40 μg/mL) significantly inhibited the

  7. Brain natriuretic peptide improves long-term functional recovery after acute CNS injury in mice.

    Science.gov (United States)

    James, Michael L; Wang, Haichen; Venkatraman, Talaignair; Song, Pingping; Lascola, Christopher D; Laskowitz, Daniel T

    2010-01-01

    There is emerging evidence to suggest that brain natriuretic peptide (BNP) is elevated after acute brain injury, and that it may play an adaptive role in recovery through augmentation of cerebral blood flow (CBF). Through a series of experiments, we tested the hypothesis that the administration of BNP after different acute mechanisms of central nervous system (CNS) injury could improve functional recovery by improving CBF. C57 wild-type mice were exposed to either pneumatic-induced closed traumatic brain injury (TBI) or collagenase-induced intracerebral hemorrhage (ICH). After injury, either nesiritide (hBNP) (8 microg/kg) or normal saline were administered via tail vein injection at 30 min and 4 h. The mice then underwent functional neurological testing via rotorod latency over the following 5 days and neurocognitive testing via Morris water maze testing on days 24-28. Cerebral blood flow (CBF) was assessed by laser Doppler from 25 to 90 min after injury. After ICH, mRNA polymerase chain reaction (PCR) and histochemical staining were performed during the acute injury phase (<24 h) to determine the effects on inflammation. Following TBI and ICH, administration of hBNP was associated with improved functional performance as assessed by rotorod and Morris water maze latencies (p < 0.01). CBF was increased (p < 0.05), and inflammatory markers (TNF-alpha and IL-6; p < 0.05), activated microglial (F4/80; p < 0.05), and neuronal degeneration (Fluoro-Jade B; p < 0.05) were reduced in mice receiving hBNP. hBNP improves neurological function in murine models of TBI and ICH, and was associated with enhanced CBF and downregulation of neuroinflammatory responses. hBNP may represent a novel therapeutic strategy after acute CNS injury.

  8. [The importance of the cortex and subcortical structures of the brain in the perception of acute and chronic pain].

    Science.gov (United States)

    Reschetniak, V K; Kukushkin, M L; Gurko, N S

    2014-01-01

    This review presents the current data in the literature about the importance of the cortex and subcortical structures of the brain in the perception of acute and chronic pain. Discussed the importance of various areas of the brain in perception discriminative and affective components of pain. Discusses also gender differences in pain perception depending on the functional activity of brain cortex and antinociceptive subcortical structures. Analyzed the morphological changes of cortical and subcortical structures of the brain in chronic pain syndromes. It is proved that the decrease in the volume of gray and white matter of cerebral cortex and subcortical structures is a consequence and not the cause of chronic pain syndrome. Discusses the features activate and deactivate certain areas of the cortex of the brain in acute and chronic pain. Analyzed same features the activation of several brain structures in migraine and cluster headache.

  9. Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Na Zhang; Gen-Yang Cheng; Xian-Zhi Liu; Feng-Jiang Zhang

    2014-01-01

    Objective:To investigate the effect of acute renal ischemia reperfusion on brain tissue. Methods:Fourty eight rats were randomly divided into four groups(n=12): sham operation group,30 min ischemia60 min reperfusion group,60 min ischemia60 min reperfusion group, and 120 min ischemia60 min reperfusion group.The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors.Results:Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time.The detection at the molecular level showed decreasedBcl-2 expression, increasedBax expression, upregulated expression ofNF-κB and its downstream factor COX-2/PGE2.Conclusions:Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation.

  10. Significance of serum neuron-specific enolase in patients with acute traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    官卫; 杨伊林; 夏为民; 李璐; 龚德生

    2003-01-01

    Objective: To study the association between serum neuron-specific enolase (NSE) and the extent of brain damage and the outcome after acute traumatic brain injury (TBI). Methods: The release patterns of serum NSE in 78 patients after acute TBI were analyzed by using the enzyme linked immunosobent assay. The levels of NSE were compared with Glasgow coma scale, the category of brain injury and the outcome after 6 months of injury. Results: There were different NSE values in patients with minor (12.96 μg/L±2.39 μg/L), moderate (23.44 μg/L±5.33 μg/L) and severe brain injury (42.68 μg/L±4.57 μg/L). After severe TBI, the concentration of NSE in patients with epidural hematomas was 13.38 μg/L±4.01 μg/L, 24.03 μg/L±2.85 μg/L in brain contusion without surgical intervention group, 55.20 μg/L±6.35 μg/L in brain contusion with surgical intervention group, and 83.85 μg/L±15.82 μg/L in diffuse brain swelling group. There were close correlations between NSE values and Glasgow coma scale (r=-0.608, P<0.01) and the extent of brain injury (r=0.75, P<0.01). Patients with poor outcome had significantly higher initial and peak NSE values than those with good outcome (66.40 μg/L±9.46 μg/L, 94.24 μg/L±13.75 μg/L vs 32.16 μg/L±4.21 μg/L, 34.08 μg/L±4.40 μg/L, P<0.01, respectively). Initial NSE values were negatively related to the outcome (r=-0.501, P<0.01). Most patients with poor outcomes had persisting or secondary elevated NSE values. Conclusions: Serum NSE is one of the valuable neurobiochemical markers for assessment of the severity of brain injury and outcome prediction.

  11. Simultaneous multi-slice Turbo-FLASH imaging with CAIPIRINHA for whole brain distortion-free pseudo-continuous arterial spin labeling at 3 and 7 T.

    Science.gov (United States)

    Wang, Yi; Moeller, Steen; Li, Xiufeng; Vu, An T; Krasileva, Kate; Ugurbil, Kamil; Yacoub, Essa; Wang, Danny J J

    2015-06-01

    Simultaneous multi-slice (SMS) or multiband (MB) imaging has recently been attempted for arterial spin labeled (ASL) perfusion MRI in conjunction with echo-planar imaging (EPI) readout. It was found that SMS-EPI can reduce the T1 relaxation effect of the label and improve image coverage and resolution with little penalty in signal-to-noise ratio (SNR). However, EPI still suffers from geometric distortion and signal dropout from field inhomogeneity effects especially at high and ultrahigh magnetic fields. Here we present a novel scheme for achieving high fidelity distortion-free quantitative perfusion imaging by combining pseudo-continuous ASL (pCASL) with SMS Turbo-FLASH (TFL) readout at both 3 and 7 T. Bloch equation simulation was performed to characterize and optimize the TFL-based pCASL perfusion signal. Two MB factors (3 and 5) were implemented in SMS-TFL pCASL and compared with standard 2D TFL and EPI pCASL sequences. The temporal SNR of SMS-TFL pCASL relative to that of standard TFL pCASL was 0.76 ± 0.10 and 0.74 ± 0.11 at 7 T and 0.70 ± 0.05 and 0.65 ± 0.05 at 3T for MB factor of 3 and 5, respectively. By implementing background suppression in conjunction with SMS-TFL at 3T, the relative temporal SNR improved to 0.84 ± 0.09 and 0.79 ± 0.10 for MB factor of 3 and 5, respectively. Compared to EPI pCASL, significantly increased temporal SNR (pbrain distortion-free quantitative mapping of cerebral blood flow at high and ultrahigh magnetic fields.

  12. Measurement of blood–brain barrier permeability in acute ischemic stroke using standard first-pass perfusion CT data ☆

    OpenAIRE

    Nguyen, Giang Truong; Coulthard, Alan; Wong, Andrew; Sheikh, Nabeel; Henderson, Robert; O'Sullivan, John D.; Reutens, David C.

    2013-01-01

    Background and purpose Increased blood–brain barrier permeability is believed to be associated with complications following acute ischemic stroke and with infarct expansion. Measurement of blood–brain barrier permeability requires a delayed image acquisition methodology, which prolongs examination time, increasing the likelihood of movement artefacts and radiation dose. Existing quantitative methods overestimate blood–brain barrier permeability when early phase CT perfusion data are used. The...

  13. The analysis of diagnostic value of 64-slice spiral CT in acute mesenteric vascular embolism%64层螺旋CT对急性肠系膜血管栓塞的诊断价值分析

    Institute of Scientific and Technical Information of China (English)

    张浩亮; 杜海; 武轶非; 张凤翔

    2012-01-01

    目的 探讨64层螺旋CT血管造影对急性肠系膜血管栓塞(AMI)的诊断价值.方法 回顾性分析经64层螺旋CT全腹平扫加多期动态增强扫描诊断的15例AMI.其中,肠系膜上动脉栓塞3例(完全栓塞1例,不完全栓塞2例),肠系膜上静脉栓塞12例.结果 15例AMI直接征象:动脉期显示肠系膜上动脉完全或部分充盈缺损,可诊断为肠系膜上动脉完全或部分栓塞(3例).静脉期显示肠系膜上静脉完全或部分充盈缺损,可诊断为肠系膜上静脉完全或部分栓塞(12例);间接征象“缆绳征”12例,肠系膜水肿10例,肠管壁增厚12例,肠管扩张、积液8例,肠壁强化减弱7例,其中2例可见节段性未强化区,腹水6例,肾前筋膜增厚4例,肠壁积气2例.平扫肠系膜上动脉或上静脉高密度征7例(静脉栓塞6例,动脉栓塞1例),肠系膜上静脉栓塞累及门静脉、脾静脉6例,其中4例在增强扫描时,可见肝脏异常低灌注区.结论 64层螺旋CT平扫加多期动态增强扫描对急性肠系膜血管栓塞的诊断及时准确,应作为临床怀疑肠系膜血管疾病首选检查方法,值得推广应用.%Objective To explore the diagnostic value of 64-slice spiral CT in acute mesenteric vascular embolism. Methods We retrospectively analyzed the images of 15 AMI by multiphase dynamic contrast-enhanced 64-slice spiral CT, 3 superior mesenteric artery embolization (1 completely embolization, 2 incompletely embolization), and 12 superior mesenteric vein embolization. Results The direct signs: superior mesenteric artery was full or partial filling defect in arterial phase, and superior mesenteric vein was full or partial filling defect in vein phase. Indirect sign: there were 12 cases of "stranding sign", 10 cases of mesenteric edema, 8 cases of bowel expansion and effusion, and 6 cases with ascites, 7 cases of high density for the blood vessel by CT plain scan (6 in superior mesenteric vein embolization, 1 in superior mesenteric

  14. Quantitative multivoxel {sup 1}H MR spectroscopy of the brain in children with acute liver failure

    Energy Technology Data Exchange (ETDEWEB)

    Sijens, Paul E.; Alkefaji, Heyder; Meiners, Linda C.; Oudkerk, Matthijs [University Medical Center Groningen and University of Groningen, Department of Radiology, Beatrix Children' s Hospital, Groningen (Netherlands); Lunsing, Roelineke J. [University Medical Center Groningen and University of Groningen, Department of Child Neurology, Beatrix Children' s Hospital, Groningen (Netherlands); Spronsen, Francjan J. van; Verkade, Henkjan J. [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Beatrix Children' s Hospital, Groningen (Netherlands)

    2008-11-15

    Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx) and lactate in ALF and associate the results with other liver function parameters. Five pediatric patients with ALF-related encephalopathy and five controls, examined after successful liver transplantation, were examined by brain MRI/MRS. ALF patients had higher Glx and lactate concentrations in brain white matter than controls (Glx + 125%: P < 0.01; lactate + 33%, P < 0.05) and higher Glx in grey matter (Glx + 125%: P < 0.01). Within the group of ALF patients positive correlations were found between grey or white matter lactate concentration and serum ammonia (P < 0.05), and negative correlations between grey or white matter Glx and venous pH (P < 0.001). This is the first study presenting evidence of high Glx levels in both white and grey matter brain tissue in ALF-related encephalopathy. The elevations in CNS Glx and lactate concentrations appear to relate to hepatic detoxification (ammonia, venous pH), rather than to liver parenchymal integrity (aspartate aminotransferase, alanine aminotransferase) or biliary cholestasis (bilirubin, {gamma}-glutamyl transpeptidase, alkaline phosphatase). (orig.)

  15. Abnormal EEG Complexity and Functional Connectivity of Brain in Patients with Acute Thalamic Ischemic Stroke

    Science.gov (United States)

    Liu, Shuang; Guo, Jie; Meng, Jiayuan; Wang, Zhijun; Yao, Yang; Yang, Jiajia; Qi, Hongzhi; Ming, Dong

    2016-01-01

    Ischemic thalamus stroke has become a serious cardiovascular and cerebral disease in recent years. To date the existing researches mostly concentrated on the power spectral density (PSD) in several frequency bands. In this paper, we investigated the nonlinear features of EEG and brain functional connectivity in patients with acute thalamic ischemic stroke and healthy subjects. Electroencephalography (EEG) in resting condition with eyes closed was recorded for 12 stroke patients and 11 healthy subjects as control group. Lempel-Ziv complexity (LZC), Sample Entropy (SampEn), and brain network using partial directed coherence (PDC) were calculated for feature extraction. Results showed that patients had increased mean LZC and SampEn than the controls, which implied the stroke group has higher EEG complexity. For the brain network, the stroke group displayed a trend of weaker cortical connectivity, which suggests a functional impairment of information transmission in cortical connections in stroke patients. These findings suggest that nonlinear analysis and brain network could provide essential information for better understanding the brain dysfunction in the stroke and assisting monitoring or prognostication of stroke evolution. PMID:27403202

  16. THE EFFECT OF FLUOROCARBON ARTIFICIAL BLOOD (FC-34 IN ACUTE VASOGENIC BRAIN EDEMA

    Directory of Open Access Journals (Sweden)

    M NEEMATBAKHSH

    2000-03-01

    Full Text Available Background. Oxygen transport to tissue after an acute ischemia is strongly important. Fluorocarbon liquids are able to facilitated the oxygen transport. An animal experiment was designed to study the effect of FC-34 in acute brain ischemia. Methods. The left common carotid arteries were ligated in three groups of anesthetized animals for 30 minutes to obtain acute brain edema. The animals were subjected to received 15 ml/kg saline (group 1, 10% monitol (group 2 or FC-43 (group 3. All animals were recovered, and they monitored for two weeks. The electrolytes, BUN, and creatinine were measured before (all animals and after two weeks (survived animals. Pathological investigation was obtained by light and electron microscope via pathological process. Findings. The group 1 animals were died during first five days, but one and four animals were survived by two weeks in groups 2 & 3 respectively (P < 0.05. The pathological determinations indicate less cellular damages in group 3. No significant differences were detected in potassium, calcium, BUN, and creatinine before and after the experiment. Conclusion. The particle size and oxygen solubility in FC-43 is the major factors for better oxygen transport in ischem

  17. Oxidation-Reduction Potential as a Biomarker for Severity and Acute Outcome in Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Kimberly B. Bjugstad

    2016-01-01

    Full Text Available There are few reliable markers for assessing traumatic brain injury (TBI. Elevated levels of oxidative stress have been observed in TBI patients. We hypothesized that oxidation-reduction potential (ORP could be a potent biomarker in TBI. Two types of ORP were measured in patient plasma samples: the static state of oxidative stress (sORP and capacity for induced oxidative stress (icORP. Differences in ORP values as a function of time after injury, severity, and hospital discharge were compared using ANOVAs with significance at p≤0.05. Logit regression analyses were used to predict acute outcome comparing ORP, Injury Severity Score (ISS, Abbreviated Injury Scale (AIS, and Glasgow Coma Scale (GCS. Antioxidant capacity (icORP on day 4 was prognostic for acute outcomes (p 7.25 μC. IcORP was a better predictor than ISS, AIS, or GCS scores. sORP increased in those with the highest ISS values (p<0.05. Based on these findings ORP is useful biomarker for severity and acute outcome in TBI patients. Changes in ORP values on day 4 after injury were the most prognostic, suggesting that patients’ response to brain injury over time is a factor that determines outcome.

  18. Matrix metalloproteinases and blood-brain barrier disruption in acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Shaheen E Lakhan

    2013-04-01

    Full Text Available Ischemic stroke continues to be one of the most challenging diseases in translational neurology. Tissue-type plasminogen activator (tPA remains the only approved treatment for acute ischemic stroke, but its use is limited to the first hours after stroke onset due to an increased risk of hemorrhagic transformation over time resulting in enhanced brain injury. In this review we discuss the role of matrix metalloproteinases (MMPs in blood-brain barrier (BBB disruption as a consequence of ischemic stroke. MMP-9 in particular appears to play an important role in tPAassociated hemorrhagic complications.Reactive oxygen species (ROS can enhance the effects of tPA on MMP activation through the loss of caveolin-1, a protein encoded in the cav-1 gene that serves as a critical determinant of BBB permeability. This review provides an overview of MMPs' role in BBB breakdown during acute ischemic stroke. The possible role of MMPs in combination treatment of acute ischemic stroke is also examined.

  19. The Role of Gut–brain Axis in Regulating Glucose Metabolism After Acute Pancreatitis

    Science.gov (United States)

    Pendharkar, Sayali A; Asrani, Varsha M; Murphy, Rinki; Cutfield, Richard; Windsor, John A; Petrov, Maxim S

    2017-01-01

    Objectives: Diabetes has become an epidemic in developed and developing countries alike, with an increased demand for new efficacious treatments. A large body of pre-clinical evidence suggests that the gut–brain axis may be exploited as a potential therapeutic target for defective glucose homeostasis. This clinical study aimed to investigate a comprehensive panel of glucoregulatory peptides, released by both the gut and brain, in individuals after acute pancreatitis. Methods: Fasting levels of glucagon-like peptide-1 (GLP-1), glicentin, oxyntomodulin, peptide YY, ghrelin, cholecystokinin, vasoactive intestinal peptide (VIP), and secretin were studied. Modified Poisson and multivariable linear regression analyses were conducted. Pre-determined concentration ranges were used to categorize each peptide into quartiles. Results: A total of 83 individuals were included, of who 30 (36%) developed abnormal glucose metabolism (AGM) after acute pancreatitis. In individuals with AGM, the highest quartile of oxyntomodulin differed most significantly from the lowest quartile with a prevalence ratio (PR; 95% confidence interval) of 0.50 (0.21, 1.20; P=0.005); of glicentin with a PR of 0.26 (0.13, 0.54; Pcholecystokinin, ghrelin, and secretin were not significantly associated with AGM. Conclusions: Fasting circulating oxyntomodulin, glicentin, and VIP levels are significantly decreased in patients with defective glucose homeostasis after acute pancreatitis. Oxyntomodulin appears to be a promising therapeutic target for future clinical studies on diabetes associated with diseases of the exocrine pancreas. PMID:28055028

  20. CT Perfusion in Acute Stroke: "Black Holes" on Time-to-Peak Image Maps Indicate Unsalvageable Brain.

    Science.gov (United States)

    Meagher, Ruairi; Shankar, Jai Jai Shiva

    2016-11-01

    CT perfusion is becoming important in acute stroke imaging to determine optimal patient-management strategies. The purpose of this study was to examine the predictive value of time-to-peak image maps and, specifically, a phenomenon coined a "black hole" for assessing infarcted brain tissue at the time of scan. Acute stroke patients were screened for the presence of black holes and their follow-up imaging (noncontrast CT or MR) was reviewed to assess for infarcted brain tissue. Of the 23 patients with signs of acute ischemia on CT perfusion, all had black holes. The black holes corresponded with areas of infarcted brain on follow-up imaging (specificity 100%). Black holes demonstrated significantly lower cerebral blood volumes (P < .001) and cerebral blood flow (P < .001) compared to immediately adjacent tissue. Black holes on time-to-peak image maps represent areas of unsalvageable brain. Copyright © 2016 by the American Society of Neuroimaging.

  1. Acute administration of fenproporex increased acetylcholinesterase activity in brain of young rats

    Directory of Open Access Journals (Sweden)

    BRENA P. TEODORAK

    2015-08-01

    Full Text Available Fenproporex is the second most commonly amphetamine-based anorectic consumed worldwide; this drug is rapidly converted into amphetamine, in vivo, and acts by increasing dopamine levels in the synaptic cleft. Considering that fenproporex effects on the central nervous system are still poorly known and that acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine, the present study investigated the effects of acute administration of fenproporex on acetylcholinesterase activity in brain of young rats. Young male Wistar rats received a single injection of fenproporex (6.25, 12.5 or 25mg/kg i.p. or vehicle (2% Tween 80. Two hours after the injection, the rats were killed by decapitation and the brain was removed for evaluation of acetylcholinesterase activity. Results showed that fenproporex administration increased acetylcholinesterase activity in the hippocampus and posterior cortex, whereas in the prefrontal cortex, striatum and cerebellum the enzyme activity was not altered. In conclusion, in the present study we demonstrated that acute administration of fenproporex exerts an effect in the cholinergic system causing an increase in the activity of acetylcholinesterase in a dose-dependent manner in the hippocampus and posterior cortex. Thus, we suggest that the imbalance in cholinergic homeostasis could be considered as an important pathophysiological mechanism underlying the brain damage observed in patients who use amphetamines such as fenproporex.

  2. Acute effect of aspartame-induced oxidative stress in Wistar albino rat brain.

    Science.gov (United States)

    Ashok, Iyaswamy; Sheeladevi, Rathinasamy; Wankhar, Dapkupar

    2015-09-01

    The present study was carried out to investigate the acute effect of aspartame on oxidative stress in the Wistar albino rat brain. We sought to investigate whether acute administration of aspartame (75 mg/kg) could release methanol and induce oxidative stress in the rat brain 24 hours after administration. To mimic human methanol metabolism, methotrexate treated rats were used to study aspartame effects. Wistar strain male albino rats were administered with aspartame orally as a single dose and studied along with controls and methotrexate treated controls. Blood methanol and formate level were estimated after 24 hours and rats were sacrificed and free radical changes were observed in discrete regions by assessing the scavenging enzymes, reduce dglutathione (GSH), lipid peroxidation and protein thiol levels. There was a significant increase in lipid peroxidation levels, superoxide dismutase activity (SOD), glutathione peroxidase levels (GPx), and catalase activity (CAT) with a significant decrease in GSH and protein thiol. Aspartame exposure resulted in detectable methanol even after 24 hours. Methanol and its metabolites may be responsible for the generation of oxidative stress in brain regions. The observed alteration in aspartame fed animals may be due to its metabolite methanol and elevated formate. The elevated free radicals due to methanol induced oxidative stress.

  3. L-Ornithine is a potential acute satiety signal in the brain of neonatal chicks.

    Science.gov (United States)

    Tran, Phuong V; Chowdhury, Vishwajit S; Do, Phong H; Bahry, Mohammad A; Yang, Hui; Furuse, Mitsuhiro

    2016-03-01

    Recently, we observed that neonatal chicks exhibit feeding behavior characterized by frequent food intake and short resting intervals, with changes detected in the brain amino acid and monoamine concentrations. In this study, we aimed to clarify further the relationship between the appetite of neonatal chicks and brain amino acid metabolism. In Experiment 1, changes were investigated in free amino acids in the brain under conditions of regulated appetite induced by fasting and subsequent short-term re-feeding. Chicks (5 days old) were distributed into four treatment groups--namely, fasting for 3h, and fasting for 3h followed by re-feeding for 10, 20 or 30 min. Brain samples were collected after treatment to analyze free amino acid concentrations. Amino adipic acid and proline in all brain parts as well as arginine and ornithine in all brain parts--except mesencephalic arginine and cerebellar ornithine--were increased in a time-dependent manner following re-feeding. In Experiment 2, we further examined the effect of exogenous administration of some amino acids altered in association with feeding behavior in Experiment 1. We chose L-arginine and its functional metabolite, L-ornithine, to analyze their effects on food intake in chicks. Intracerebroventricular injection (2 μmol) of L-ornithine, but not L-arginine, significantly inhibited food intake in neonatal chicks. In Experiment 3, we found that central injection of L-ornithine (2, 4, and 6 μmol) dose-dependently suppressed food intake in chicks. These results suggested that L-ornithine may have an important role in the control of food intake as an acute satiety signal in the neonatal chick brain.

  4. Effects of acute heat stress on gene expression of brain-gut neuropeptides in broiler chickens.

    Science.gov (United States)

    Lei, L; Hepeng, L; Xianlei, L; Hongchao, J; Hai, L; Sheikhahmadi, A; Yufeng, W; Zhigang, S

    2013-11-01

    Heat stress-induced reduction in feed intake is an annoyance of the poultry industry. Feed intake is regulated by complex mechanisms in which brain-gut neuropeptides are involved, but the changes in such neuropeptides in broiler chickens during heat exposure remain unclear. In this study, we investigated the effects of acute heat stress (35°C, 6 h, and 65% relative humidity) on the gene expression of appetite-regulating peptides in the hypothalamus and gastrointestinal tract of broiler chickens at 42 d of age. The hypothalamic mRNA levels of neuropeptide Y, agouti-related peptide, pro-opiomelanocortin, cocaine- and amphetamine-regulated transcript, corticotropin-releasing hormone, melanocortin 4 receptor, melanin-concentrating hormone, prepro-orexin, cholecystokinin (CCK), and ghrelin did not significantly change (P>0.05) in the heat-exposed broiler chickens. However, the mRNA levels of ghrelin in the glandular stomach, duodenum, and jejunum significantly increased and the mRNA level of CCK in the duodenum significantly decreased. The results indicate that acute heat stress had no effect on the gene expression of central appetite-regulating peptides under current experimental conditions; however, some gastrointestinal tract peptides (e.g., ghrelin and CCK) might play a role in the regulation of appetite in acute heat-exposed broiler chickens. Furthermore, ghrelin in the glandular stomach, duodenum, and jejunum might be the main regulative target of acute heat stress induced anorexia.

  5. Silhouette-Slice Theorems

    Science.gov (United States)

    1987-03-20

    with standard expressions of spherical trigonometry is sinr)0 = cos0 sini//0 (4.37) which is consistent with the results obtained previously with...theorems for discrete transforms. However, sampling questions inlroduce difficult obstacles in the develop- ment of a discrete theory. First, sampling...additional obstacle to discrete represen- tations of the CT. An example of qualitative predication of the shape of silhouettes with the Silhouette-Slice

  6. Brain volume and cognitive function in adult survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Edelmann, Michelle N; Krull, Kevin R

    2013-10-01

    The survival rate for childhood acute lymphoblastic leukemia (ALL) is greater than 80%. However, many of these survivors develop long-term chronic health conditions, with a relatively common late effect being neurocognitive dysfunction. Although neurocognitive impairments have decreased in frequency and severity as treatment has evolved, there is a subset of survivors in the current treatment era that are especially vulnerable to the neurotoxic effects of ALL and its treatment. Additionally, little is known about long-term brain development as survivors mature into adulthood. A recent study by Zeller et al. compared neurocognitive function and brain volume in 130 adult survivors of childhood ALL to 130 healthy adults matched on age and sex. They identified the caudate as particularly sensitive to the neurotoxic effects of chemotherapy. We discuss the implications and limitations of this study, including how their findings support the concept of individual vulnerability to ALL and its treatment.

  7. In-111-labeled leukocyte brain SPECT imaging. Clinical significance in evaluating acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Fujinuma, Kunihiko [Kitasato Univ., Sagamihara, Kanagawa (Japan). School of Medicine

    2002-02-01

    Many experimental studies have demonstrated that leukocyte infiltration plays an important role in the progression of ischemic cellular damage or post perfusion brain injury. However, only a few clinical studies have been reported. The purpose of this study is to evaluate the clinical significance of leukocyte accumulation in the ischemic brain tissue. Seventy six patients (49 men, 27 women; mean age: 65.5{+-}13.9 years) with acute ischemic stroke were studied by leukocyte brain SPECT imaging. A diagnosis included cardioembolism (n=46), atherothrombotic infarction (n=24), TIA (n=3) and lacuna (n=3). Immediately after the CBF study using Tc-99m-ECD (600 MBq), indium-111-labeled autologous leukocytes were injected. A brain scan for leukocytes was performed 48 hours later. The leukocyte-SPECT study was made 11.1{+-}7.7 days after the onset of stroke. Regional accumulation of leukocytes in the ischemic tissue was evaluated both by visual assessment and by measuring the hemispheric asymmetry index for leukocyte (AI-leuko), and was evaluated by comparison with variable factors including age, gender, infarction size, hemorrhagic transformation, timing of study after the onset, type of stroke and functional outcome. Of the 61 patients with acute ischemic stroke within 2 weeks of onset, 28 patients showed the accumulation of leukocytes in the central zone of ischemia. Six of 7 patients with repeated studies showed a reduction in leukocyte accumulation with time after the onset. Factors significantly associated with the higher accumulation of leukocyte included cardioembolic stroke, larger size of infarct, presence of hemorrhagic transformation and significant reduction in flow. In the 61 patients within 2 weeks of onset, the functional outcome was significantly correlated with the accumulation of leukocyte (p<0.001). The accumulation of leukocytes was seen more in patients with embolic stroke, larger infarction, and hemorrhagic transformation. The higher accumulation

  8. Gene expression changes in female zebrafish (Danio rerio) brain in response to acute exposure to methylmercury

    Science.gov (United States)

    Richter, Catherine A.; Garcia-Reyero, Natàlia; Martyniuk, Chris; Knoebl, Iris; Pope, Marie; Wright-Osment, Maureen K.; Denslow, Nancy D.; Tillitt, Donald E.

    2011-01-01

    Methylmercury (MeHg) is a potent neurotoxicant and endocrine disruptor that accumulates in aquatic systems. Previous studies have shown suppression of hormone levels in both male and female fish, suggesting effects on gonadotropin regulation in the brain. The gene expression profile in adult female zebrafish whole brain induced by acute (96 h) MeHg exposure was investigated. Fish were exposed by injection to 0 or 0.5(mu or u)g MeHg/g. Gene expression changes in the brain were examined using a 22,000-feature zebrafish microarray. At a significance level of pgenes were up-regulated and 76 genes were down-regulated in response to MeHg exposure. Individual genes exhibiting altered expression in response to MeHg exposure implicate effects on glutathione metabolism in the mechanism of MeHg neurotoxicity. Gene ontology (GO) terms significantly enriched among altered genes included protein folding, cell redox homeostasis, and steroid biosynthetic process. The most affected biological functions were related to nervous system development and function, as well as lipid metabolism and molecular transport. These results support the involvement of oxidative stress and effects on protein structure in the mechanism of action of MeHg in the female brain. Future studies will compare the gene expression profile induced in response to MeHg with that induced by other toxicants and will investigate responsive genes as potential biomarkers of MeHg exposure.

  9. Effect of acute hypoxic shock on the rat brain morphology and tripeptidyl peptidase I activity.

    Science.gov (United States)

    Petrova, Emilia B; Dimitrova, Mashenka B; Ivanov, Ivaylo P; Pavlova, Velichka G; Dimitrova, Stella G; Kadiysky, Dimitar S

    2016-06-01

    Hypoxic events are known to cause substantial damage to the hippocampus, cerebellum and striatum. The impact of hypoxic shock on other brain parts is not sufficiently studied. Recent studies show that tripeptidyl peptidase I (TPPI) activity in fish is altered after a hypoxic stress pointing out at a possible enzyme involvement in response to hypoxia. Similar studies are not performed in mammals. In this work, the effect of sodium nitrite-induced acute hypoxic shock on the rat brain was studied at different post-treatment periods. Morphological changes in cerebral cortex, cerebellum, medulla oblongata, thalamus, mesencephalon and pons were assessed using silver-copper impregnation for neurodegeneration. TPPI activity was biochemically assayed and localized by enzyme histochemistry. Although less vulnerable to oxidative stress, the studied brain areas showed different histopathological changes, such as neuronal loss and tissue vacuolization, dilatation of the smallest capillaries and impairment of neuronal processes. TPPI activity was strictly regulated following the hypoxic stress. It was found to increase 12-24h post-treatment, then decreased followed by a slow process of recovery. The enzyme histochemistry revealed a temporary enzyme deficiency in all types of neurons. These findings indicate a possible involvement of the enzyme in rat brain response to hypoxic stress.

  10. 64排CT用于创伤性颅脑损伤诊断中的价值%Value of Applying 64-slice CT to Diagnosis of Traumatic Brain Injury

    Institute of Scientific and Technical Information of China (English)

    刘光祖

    2016-01-01

    Objective To research and analyze the value of applying 64-slice CT to diagnosis of traumatic brain injury. Methods 100 patients with traumatic brain injury were selected as main survey samples randomly. All patients received CT examination when they were admitted to the hospital. The patients with negative examination result received CT reexamination in 1 day. If the examination results were negative, the patients needed to receive CT examination for the third day. CT image features of 100 patients were analyzed carefully, and were divided into three types according to the actual characteristics of CT image. The condition of different injury classiifcations was analyzed. Results The sensitivity of the patients for the admission to hospital (30~180 minute), in one day and in 2~3 day was 69.00%, 73.00%and 100.00%. The light, medium and severe brain injury had different prognostic effect. The severer the injury, the higher disability rate and fatality rate, which had evident statistical signiifcance, P<0.05. Conclusion 64-slice CT achieves evident effect for diagnosing brain injury.%目的:研究分析64排CT用于创伤性颅脑损伤诊断中的价值。方法随机选取创伤性颅脑损伤患者100例作为主要的调查样本,在患者入院时均接受CT检查,对于检查结果为阴性的患者,在1天之内完成CT复查;若其检查结果还是阴性的患者,则需要在第2-3天之内第三天接受CT检查。对100例患者的CT影像特点进行缜密分析,严格按照CT影像的实际特点完成轻、中、重三型划分,对不同损伤分型影响预后的情况进行针对分析。结果刚刚入院时候(30~180分钟)、1天之内、2~3天内患者的灵敏度分别为69.00%、73.00%、100.00%。轻型、中型以及重型颅脑损伤存在不同的预后效果,即损伤越严重就会有越高的致残率以及致死率,具有明显的统计学意义,P<0.05。结论64排CT在诊断颅脑损伤优势的过程中可以取得非常明显的效果。

  11. Ventral tegmental area/substantia nigra and prefrontal cortex rodent organotypic brain slices as an integrated model to study the cellular changes induced by oxygen/glucose deprivation and reperfusion: effect of neuroprotective agents.

    Science.gov (United States)

    Colombo, Laura; Parravicini, Chiara; Lecca, Davide; Dossi, Elena; Heine, Claudia; Cimino, Mauro; Wanke, Enzo; Illes, Peter; Franke, Heike; Abbracchio, Maria P

    2014-01-01

    Unveiling the roles of distinct cell types in brain response to insults is a partially unsolved challenge and a key issue for new neuroreparative approaches. In vivo models are not able to dissect the contribution of residential microglia and infiltrating blood-borne monocytes/macrophages, which are fundamentally undistinguishable; conversely, cultured cells lack original tissue anatomical and functional complexity, which profoundly alters reactivity. Here, we tested whether rodent organotypic co-cultures from mesencephalic ventral tegmental area/substantia nigra and prefrontal cortex (VTA/SN-PFC) represent a suitable model to study changes induced by oxygen/glucose deprivation and reperfusion (OGD/R). OGD/R induced cytotoxicity to both VTA/SN and PFC slices, with higher VTA/SN susceptibility. Neurons were highly affected, with astrocytes and oligodendrocytes undergoing very mild damage. Marked reactive astrogliosis was also evident. Notably, OGD/R triggered the activation of CD68-expressing microglia and increased expression of Ym1 and Arg1, two markers of "alternatively" activated beneficial microglia. Treatment with two well-known neuroprotective drugs, the anticonvulsant agent valproic acid and the purinergic P2-antagonist PPADS, prevented neuronal damage. Thus, VTA/SN-PFC cultures are an integrated model to investigate OGD/R-induced effects on distinct cells and easily screen neuroprotective agents. The model is particularly adequate to dissect the microglia phenotypic shift in the lack of a functional vascular compartment.

  12. Brain injury due to acute organophosphate poisoning Magnetic resonance imaging manifestation and pathological characteristics

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Acute organophosphate poisoning can cause injuries of multiple visceras; especially,central nervous system injury can increase risk factors of patients with severe acute organophosphate poisoning. An application of modem image may increase diagnostic rate of brain injury in an earlier period and provide evidences for clinical treatment.OBJECTIVE: To reveal imaging manifestations, pathological characteristics and multi-ways injured mechanism of brain injury due to acute organophosphate poisoning.DESIGN: Contrast observational study.SETTING: Department of Medical Image, the Second Hospital of Hebei Medical University.MATERIALS: The experiment was carried out in the Department of Nerve Molecule Imaging Medicine and Laboratory of Neurology, the Second Hospital of Hebei Medical University from August 2003 to February 2004. A total of 30 healthy cats weighing 2.8 - 3.5 g and of both genders were selected from Animal Experimental Center of Hebei Medical University.METHODS: Thirty healthy cats were randomly divided into control group (n =5) and intoxication group (n=25). Cats in the control group were subcutaneously injected with 0.3 mL/kg saline at four points; while, cats in the intoxication group were subcutaneously injected with 400 g/L 0.3 mL/kg O,O-dimethyl-S-(methoxycarbonylmethyl) thiophosphate at four points. Two minutes after intoxication, cats received muscular injection with 0.5 mg/kg atropine sulfate, and then, brain tissues were collected from parietal lobe, basal ganglia, hippocampus, cerebellum and brain stem were observed at 3, 6, 24 hours, 3 and 7 days after intoxication respectively under optic microscope and electron microscope and expressions of acetylcholinesterase (AChE), choline acetyltransferase (ChAT), glial fibrillary acidic protein (GFAP),glutamic acid (Glu) and γ-amino butyric acid after immunohistochemical staining.MAIN OUTCOME MEASURES: Results of MRI examinations; histological changes under optic microscope and electron

  13. The One-step Imaging Study of Acute Chest Pain Trilogy by 64 Slice Spiral CT%急性胸痛三联症64层螺旋CT“一站式成像”的研究

    Institute of Scientific and Technical Information of China (English)

    李欣; 孙吉林; 戴国华; 付英杰; 李志远; 柳溪

    2011-01-01

    [Abstract] Objective To investigate the image quality and ability of one-time unified examination of the 64-slice spiral CT(MSCT)in showing coronary artery, pulmonary artery and aorta. Materials and Methods 60 patients with acute chest pain received unified examination of coronary artery .pulmonary artery, aorta with 64-slice MSCT using ECG-gated function respectively. The coronary artery,pulmonary artery and aorta were imaged by using a variety of reconstruction techniques compare to 50 cases with pure 64-slice MSCT coronary angiography ,30 cases with pulmonary artery imaging and 20 cases with aortic imaging. The results from the above examinations were analyzed to evaluate whether or not the quality of the images could meet the need of the clinical diagnosis. Results The average scan time of one step examination was(8.0 ± 1.5)S,and the dose of contrast medium injected was 100 ml,and the injection flow rate of 4.0 -4.5 ml/s. There was significant difference between the chest pain group and the control group in the images of the coronary artery (P 0.05;P=0.44, >0.05;P =0.068, >0.05).The image quality of the chest pain group was as good as the one of the control group. There was significant difference between two groups and intragroup in the images of the central, peripheral and whole pulmonary artery in chest pain group and the control group (P<0.01 ;P<0.01 ;P<0.01).The image quality of the chest pain group was better than the one of the control group. Conclusion The one-step examination of coronary artery .pulmonary artery,aorta by 64-slice MSCT can be finished within 10 seconds. The image quality of aorta, pulmonary artery is excellent. There is no significant difference between the image quality of the single aorta imaging and the unified examination of the MSCT,of which image quality is better than that of single pulmonary artery MSCT. The image of the coronary artery in one time unified examination is good,can meet the needs of the clinical diagnosis,but is

  14. Evaluation of 128-slice spiral CT whole brain perfusion imaging in grading infiltrating astrocytomas%128层螺旋CT全脑灌注对浸润性星形细胞瘤的分级评估

    Institute of Scientific and Technical Information of China (English)

    曾文兵; 王毅; 汪明全; 吴炅; 刘兴华; 罗江平; 温云

    2011-01-01

    目的:评价128层螺旋CT全脑灌注(CTP)对浸润性星形细胞瘤分级定性诊断的价值.方法:选择我院90例脑肿瘤患者进行CTP检查,经手术和病理学证实为浸润性星形细胞瘤(Ⅱ~Ⅳ级)者46例纳入本研究对象.CTP采用SOMATOM Definition AS型128层螺旋CT机进行灌注扫描,应用后处理工作站对原始数据进行后处理.获得时间-密度曲线(TDC).测定肿瘤区和对侧正常组织的脑血流量(CBF)、脑血容量(CBV)、毛细血管表面通透性(PS)及对比剂达峰值时间(TTP),并对灌注参数进行统计学分析.结果:在所有病例中,全脑灌注图像平均视觉评价分数明显高于传统灌注图(P<0 01).且对病变定位更为精确.星形细胞肿瘤高级别组的CBF、CBV和PS值均显著高于低级别组(P<0.01).而TTP值的差异无统计学意义(P>0.05).ROC曲线分析表明,CBF、CBV和PS值对鉴别高、低级别星形细胞肿瘤的ROC曲线下面积分别为0.925、0.897和0.954.采用CBF≥72.052ml/min/100g,CBV≥4.293ml/100g和PS≥6.337ml/min/100g作为分界点对鉴别高低级别星形细胞肿瘤的敏感性均为87.2%,特异性分别是83.5%、83.5%和93.0%.结论:128层螺旋CT全脑灌注有利于脑肿瘤的术前整体评估和精确定位;CTP参数CBF、CBV及PS值及TDC曲线对鉴别高、低级别星形细胞肿瘤具有较高的敏感性和特异性.%Objective:To evaluate the value of 128-slicc spiral CT whole brain perfusion (CTP) imaging in grading infil-traiing astrocytomas. Methods: Ninety patients with brain rumors underwent CTP examination and forty-six of them with astrocytic tumors (Ⅱ -Ⅳ) confirmed by operation and pathology were selected as the object of this study. 128-slice helical CT whole brain perfusion imaging was performed in the 46 patients, and the data were analyzed by the software. Cerebral blood flow (CBF). Cerebral blood volume (CBV). Time to peak (TTP) and permeability surface (PS> on the maximum perfusion area

  15. Connectomic and surface-based morphometric correlates of acute mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Patrizia eDall'Acqua

    2016-03-01

    Full Text Available Reduced integrity of white matter (WM pathways and subtle anomalies in gray matter (GM morphology have been hypothesized as mechanisms in mild traumatic brain injury (mTBI. However, findings on structural brain changes in early stages after mTBI are inconsistent and findings related to early symptoms severity are rare.Fifty-one patients were assessed with multimodal neuroimaging and clinical methods exclusively within 7 days following mTBI and compared to 53 controls. Whole-brain connectivity based on diffusion tensor imaging was subjected to network-based statistics, whereas cortical surface area, thickness, and volume based on T1-weighted MRI scans were investigated using surface-based morphometric analysis. Reduced connectivity strength within a subnetwork of 59 edges located predominantly in bilateral frontal lobes was significantly associated with higher levels of self-reported symptoms. In addition, cortical surface area decreases were associated with stronger complaints in five clusters located in bilateral frontal and postcentral cortices, and in the right inferior temporal region. Alterations in WM and GM were localized in similar brain regions and moderately-to-strongly related to each other. Furthermore, the reduction of cortical surface area in the frontal regions was correlated with poorer attentive-executive performance in the mTBI group. Finally, group differences were detected in both the WM and GM, especially when focusing on a subgroup of patients with greater complaints, indicating the importance of classifying mTBI patients according to severity of symptoms. This study provides evidence that mTBI affects not only the integrity of WM networks by means of axonal damage but also the morphology of the cortex during the initial post-injury period. These anomalies might be greater in the acute period than previously believed and the involvement of frontal brain regions was consistently pronounced in both findings. The dysconnected

  16. Association of acute adverse effects with high local SAR induced in the brain from prolonged RF head and neck hyperthermia

    Science.gov (United States)

    Adibzadeh, F.; Verhaart, R. F.; Verduijn, G. M.; Fortunati, V.; Rijnen, Z.; Franckena, M.; van Rhoon, G. C.; Paulides, M. M.

    2015-02-01

    To provide an adequate level of protection for humans from exposure to radio-frequency (RF) electromagnetic fields (EMF) and to assure that any adverse health effects are avoided. The basic restrictions in terms of the specific energy absorption rate (SAR) were prescribed by IEEE and ICNIRP. An example of a therapeutic application of non-ionizing EMF is hyperthermia (HT), in which intense RF energy is focused at a target region. Deep HT in the head and neck (H&N) region involves inducing energy at 434 MHz for 60 min on target. Still, stray exposure of the brain is considerable, but to date only very limited side-effects were observed. The objective of this study is to investigate the stringency of the current basic restrictions by relating the induced EM dose in the brain of patients treated with deep head and neck (H&N) HT to the scored acute health effects. We performed a simulation study to calculate the induced peak 10 g spatial-averaged SAR (psSAR10g) in the brains of 16 selected H&N patients who received the highest SAR exposure in the brain, i.e. who had the minimum brain-target distance and received high forwarded power during treatment. The results show that the maximum induced SAR in the brain of the patients can exceed the current basic restrictions (IEEE and ICNIRP) on psSAR10g for occupational environments by 14 times. Even considering the high local SAR in the brain, evaluation of acute effects by the common toxicity criteria (CTC) scores revealed no indication of a serious acute neurological effect. In addition, this study provides pioneering quantitative human data on the association between maximum brain SAR level and acute adverse effects when brains are exposed to prolonged RF EMF.

  17. Neurotrauma: The Crosstalk between Neurotrophins and Inflammation in the Acutely Injured Brain

    Directory of Open Access Journals (Sweden)

    Lindolfo da Silva Meirelles

    2017-05-01

    Full Text Available Traumatic brain injury (TBI is a major cause of morbidity and mortality among young individuals worldwide. Understanding the pathophysiology of neurotrauma is crucial for the development of more effective therapeutic strategies. After the trauma occurs, immediate neurologic damage is produced by the traumatic forces; this primary injury triggers a secondary wave of biochemical cascades together with metabolic and cellular changes, called secondary neural injury. In the scenario of the acutely injured brain, the ongoing secondary injury results in ischemia and edema culminating in an uncontrollable increase in intracranial pressure. These areas of secondary injury progression, or areas of “traumatic penumbra”, represent crucial targets for therapeutic interventions. Neurotrophins are a class of signaling molecules that promote survival and/or maintenance of neurons. They also stimulate axonal growth, synaptic plasticity, and neurotransmitter synthesis and release. Therefore, this review focuses on the role of neurotrophins in the acute post-injury response. Here, we discuss possible endogenous neuroprotective mechanisms of neurotrophins in the prevailing environment surrounding the injured areas, and highlight the crosstalk between neurotrophins and inflammation with focus on neurovascular unit cells, particularly pericytes. The perspective is that neurotrophins may represent promising targets for research on neuroprotective and neurorestorative processes in the short-term following TBI.

  18. PROGNOSTIC VALUE OF BRAIN AND ACUTE LEUKEMIA CYTOPLASMIC GENE EXPRESSION IN EGYPTIAN CHILDREN WITH ACUTE MYELOID LEUKEMIA

    Directory of Open Access Journals (Sweden)

    adel abd elhaleim hagag

    2015-04-01

    Full Text Available Abstract      Background: Acute myeloid leukemia (AML accounts for 25%-35% of the acute leukemia in children. BAALC (Brain and Acute Leukemia, Cytoplasmic gene is a recently identified gene on chromosome 8q22.3 that has prognostic significance in AML.  The aim of this work was to study the impact of BAALC gene expression on prognosis of AML in Egyptian children. Patients and methods: This study was conducted on 40 patients of newly diagnosed AML who were subjected to the following: Full history taking, clinical examination, laboratory investigations including: complete blood count, LDH, bone marrow aspiration, cytochemistry and immunophenotyping, assessment of BAALC Gene by real time PCR in bone marrow aspirate mononuclear cells before the start of chemotherapy. Results: BAALC gene expression showed positive expression in 24 cases (60% and negative expression in 16 cases (40%. Patients who showed positive BAALC gene expression included 10 patients achieved complete remission, 8 patients died and 6 relapsed patients, while patients who showed negative expression include 12 patients achieved complete remission, 1 relapsed patient and 3 patients died. There was significant association between BAALC gene expression and FAB classification of patients of AML patientsas positive BAALC expression is predominantly seen in FAB subtypes M1 and M2 compared with negative BAALC gene expression that was found more in M3 and M4 (8 cases with M1, 12 cases with M2, 1 case with M3 and 3 cases with M4 in positive BAALC expression versus 2 cases with M1, 3 cases with M2, 4 cases with M3 and 7 cases with M4 in BAALC gene negative expression group with significant difference regarding FAB subtypes. As regard age, sex, splenomegaly, lymphadenopathy, pallor, purpura, platelets count, WBCs count, and percentage of blast cells in BM, the present study showed no significant association with BAALC. Conclusion: BAALC expression is an important prognostic factor in AML

  19. Acute ischaemic brain lesions in intracerebral haemorrhage: multicentre cross-sectional magnetic resonance imaging study.

    Science.gov (United States)

    Gregoire, Simone M; Charidimou, Andreas; Gadapa, Naveen; Dolan, Eamon; Antoun, Nagui; Peeters, Andre; Vandermeeren, Yves; Laloux, Patrice; Baron, Jean-Claude; Jäger, Hans R; Werring, David J

    2011-08-01

    Subclinical acute ischaemic lesions on brain magnetic resonance imaging have recently been described in spontaneous intracerebral haemorrhage, and may be important to understand pathophysiology and guide treatment. The underlying mechanisms are uncertain. We tested the hypothesis that ischaemic lesions are related to magnetic resonance imaging markers of the severity and type of small-vessel disease (hypertensive arteriopathy or cerebral amyloid angiopathy) in a multicentre, cross-sectional study. We studied consecutive patients with intracerebral haemorrhage from four specialist stroke centres, and age-matched stroke service referrals without intracerebral haemorrhage. Acute ischaemic lesions were assessed on magnetic resonance imaging (imaging. White matter changes and cerebral microbleeds were rated with validated scales. We investigated associations between diffusion-weighted imaging lesions, clinical and radiological characteristics. We included 114 patients with intracerebral haemorrhage (39 with clinically probable cerebral amyloid angiopathy) and 47 age-matched controls. The prevalence of diffusion-weighted imaging lesions was 9/39 (23%) in probable cerebral amyloid angiopathy-related intracerebral haemorrhage versus 6/75 (8%) in the remaining patients with intracerebral haemorrhage (P = 0.024); no diffusion-weighted imaging lesions were found in controls. Diffusion-weighted imaging lesions were mainly cortical and were associated with mean white matter change score (odds ratio 1.14 per unit increase, 95% confidence interval 1.02-1.28, P = 0.024) and the presence of strictly lobar cerebral microbleeds (odds ratio 3.85, 95% confidence interval 1.15-12.93, P = 0.029). Acute, subclinical ischaemic brain lesions are frequent but previously underestimated after intracerebral haemorrhage, and are three times more common in cerebral amyloid angiopathy-related intracerebral haemorrhage than in other intracerebral haemorrhage types. Ischaemic brain lesions are

  20. Early CT signs of progressive hemorrhagic injury following acute traumatic brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Wu-song; Zheng, Ping; Xu, Jun-fa; Guo, Yi-jun; Zeng, Jing-song; Yang, Wen-jin; Li, Gao-yi; He, Bin; Yu, Hui [Pudong New Area People' s Hospital, Department of Neurosurgery, Shanghai (China)

    2011-05-15

    Since progressive hemorrhagic injury (PHI) was introduced in neurosurgical literatures, several studies have been performed, the results of which have influenced doctors but do not define guidelines for the best treatment of PHI. PHI may be confirmed by a serial computerized tomography (CT) scan, and it has been shown to be associated with a fivefold increase in the risk of clinical worsening and is a significant cause of morbidity and mortality as well. So, early detection of PHI is practically important in a clinical situation. To analyze the early CT signs of progressive hemorrhagic injury following acute traumatic brain injury (TBI) and explore their clinical significances, PHI was confirmed by comparing the first and repeated CT scans. Data were analyzed and compared including times from injury to the first CT and signs of the early CT scan. Logistic regression analysis was used to show the risk factors related to PHI. A cohort of 630 TBI patients was evaluated, and there were 189 (30%) patients who suffered from PHI. For patients with their first CT scan obtained as early as 2 h post-injury, there were 116 (77.25%) cases who suffered from PHI. The differences between PHIs and non-PHIs were significant in the initial CT scans showing fracture, subarachnoid hemorrhage (SAH), brain contusion, epidural hematoma (EDH), subdural hematoma (SDH), and multiple hematoma as well as the times from injury to the first CT scan (P < 0.01). Logistic regression analysis showed that early CT scans (EDH, SDH, SAH, fracture, and brain contusion) were predictors of PHI (P < 0.01). For patients with the first CT scan obtained as early as 2 h post-injury, a follow-up CT scan should be performed promptly. If the initial CT scan shows SAH, brain contusion, and primary hematoma with brain swelling, an earlier and dynamic CT scan should be performed for detection of PHI as early as possible and the medical intervention would be enforced in time. (orig.)

  1. Application Research on Multi-slice Spiral CT Perfusion Imaging in Patients with Acute Cerebral Infarction%多层螺旋 CT 灌注成像在急性脑梗死患者的应用研究

    Institute of Scientific and Technical Information of China (English)

    罗友琛

    2014-01-01

    目的:探讨急性脑梗死患者多层螺旋 CT 灌注成像特点,及其与临床预后的关系。方法选择符合标准的患者40例,行 CT 灌注成像检查,计算脑血流量(CBF)、脑血容量(CBV)、平均通过时间(MTT)及峰值时间(TTP);分别在入院时和治疗后14d 采用美国国立卫生研究院卒中量表(NIHSS)评价临床神经功能缺损,计算缺血脑组织的可恢复比率(PRR)和神经功能恢复比率。结果脑梗死病灶中心 CBV 及 CBF 最低,健侧最高,而缺血半暗带居中,差异有统计学意义(P 0.05);PRR 与患者治疗14d 时 NIHSS 评分存在负相关性(r =-0.340, P 0. 05),negatively dependent of those at day 14 after treatment (r = - 0. 340,P < 0. 05) and positive-ly dependent of patient’s neural functional recovery ratio (r = 0. 467,P < 0. 05). Conclusion Multi-slice spiral CT perfusion im-aging can reflecthemodynamic changes in acute cerebral infarction lesions and their perihemodynamic changes. PRR is closely de-pendent of the neural functional recovery. It can serve as a reliable theoretical basis for clinical treatment.

  2. Altered brain function in new onset childhood acute lymphoblastic leukemia before chemotherapy: A resting-state fMRI study.

    Science.gov (United States)

    Hu, Zhanqi; Zou, Dongfang; Mai, Huirong; Yuan, Xiuli; Wang, Lihong; Li, Yue; Liao, Jianxiang; Liu, Liwei; Liu, Guosheng; Zeng, Hongwu; Wen, Feiqiu

    2017-10-01

    Cognitive impairments had been reported in childhood acute lymphoblastic leukemia, what caused the impairments needed to be demonstrated, chemotherapy-related or the disease itself. The primary aim of this exploratory investigation was to determine if there were changes in brain function of children with acute lymphoblastic leukemia before chemotherapy. In this study, we advanced a measure named regional homogeneity to evaluate the resting-state brain activities, intelligence quotient test was performed at same time. Using regional homogeneity, we first investigated the resting state brain function in patients with new onset childhood acute lymphoblastic leukemia before chemotherapy, healthy children as control. The decreased ReHo values were mainly founded in the default mode network and left frontal lobe, bilateral inferior parietal lobule, bilateral temporal lobe, bilateral occipital lobe, precentral gyrus, bilateral cerebellum in the newly diagnosed acute lymphoblastic leukemia patients compared with the healthy control. While in contrast, increased ReHo values were mainly shown in the right frontal lobe (language area), superior frontal gyrus-R, middle frontal gyrus-R and inferior parietal lobule-R for acute lymphoblastic leukemia patients group. There were no significant differences for intelligence quotient measurements between the acute lymphoblastic leukemia patient group and the healthy control in performance intelligence quotient, verbal intelligence quotient, total intelligence quotient. The altered brain functions are associated with cognitive change and language, it is suggested that there may be cognition impairment before the chemotherapy. Regional homogeneity by functional magnetic resonance image is a sensitive way for early detection on brain damage in childhood acute lymphoblastic leukemia. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  3. The value of neurocognitive testing for acute outcomes after mild traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Latha Ganti; Yasamin Daneshvar; Sarah Ayala; Pratik Shashikant Patel; Aakash N Bodhit; Keith R Peters

    2015-01-01

    Background:Traditionally, neurocognitive testing is performed weeks to months after head injury and is mostly performed on patients who continue to have symptoms or difficulties. In this study, we sought to determine whether these tests, when administered acutely, could assist in predicting short-term outcomes after acute traumatic brain injury (TBI). Methods:This is an IRB-approved prospective study of adult patients who came to the emergency department of our Level-1 trauma center with TBI. Patients were enrolled prospectively after providing written informed consent and underwent three separate neurocognitive tests: the Galveston Orientation Amnesia Test (GOAT), the Rivermead Post-Concussion Survey Questionnaire (RPCSQ), and the Mini Mental Status Examination (MMSE). Results:A lower GOAT score was significantly associated with hospitalization (P=0.0212) and the development of post-concussion syndrome (PCS) at late follow-up (P=0.0081). A higher RPCSQ score was significantly associated with hospital admission (P=0.0098), re-admission within 30 days of discharge (P=0.0431) and evidence of PCS at early follow-up (P=0.0004). A higher MMSE score was significantly associated with not being admitted to the hospital (P=0.0002) and not returning to the emergency department (ED) within 72 hours of discharge (P=0.0078). Lower MMSE was also significantly associated with bleeding or a fracture on the brain CT (P=0.0431). Conclusions:While neurocognitive testing is not commonly performed in the ED in the setting of acute head injury, it is both feasible and appears to have value in predicting hospital admission and PCS. These data are especially important in terms of helping patients understand what to expect, thus, aiding in their recovery.

  4. Acute renal failure potentiates methylmalonate-induced oxidative stress in brain and kidney of rats.

    Science.gov (United States)

    Schuck, P F; Alves, L; Pettenuzzo, L F; Felisberto, F; Rodrigues, L B; Freitas, B W; Petronilho, F; Dal-Pizzol, F; Streck, E L; Ferreira, G C

    2013-03-01

    Tissue methylmalonic acid (MMA) accumulation is the biochemical hallmark of methylmalonic acidemia. The disease is clinically characterized by progressive neurological deterioration and kidney failure, whose pathophysiology is still unclear. In the present work we investigated the effects of acute MMA administration on various parameters of oxidative stress in cerebral cortex and kidney of young rats, as well as the influence of acute renal failure on MMA-elicited effects on these parameters. Acute renal failure was induced by gentamicin, an aminoglycoside antibiotic whose utilization over prolonged periods causes nephrotoxicity. The administration of gentamicin alone increased carbonyl content and inhibited superoxide dismutase (SOD) activity in cerebral cortex, as well as increased thiobarbituric acid-reactive substances (TBA-RS) and sulfhydryl levels and diminished glutathione peroxidase activity in kidney. On the other hand, MMA administration increased TBA-RS levels in cerebral cortex and decreased SOD activity in kidney. Furthermore, the simultaneous administration of MMA and gentamicin to the rats provoked an augment in TBA-RS levels and superoxide generation in cerebral cortex and in TBA-RS, carbonyl and sulfhydryl levels in kidney, while diminished SOD activity in both studied tissues. Finally, nitrate/nitrite content, reduced glutathione levels, 2',7'-dihydrodichlorofluorescein oxidation and catalase activity were not affected by this animal treatment in either tissue. In conclusion, our present data are in line with the hypothesis that MMA acts as a toxin in brain and kidney of rats and suggest that renal injury potentiates the toxicity of MMA on oxidative stress parameters in brain and peripheral tissues.

  5. Cerebral blood volume affects blood–brain barrier integrity in an acute transient stroke model

    Science.gov (United States)

    Huang, Shuning; Kim, Jeong Kon; Atochin, Dmitriy N; Farrar, Christian T; Huang, Paul L; Suh, Ji Yeon; Kwon, Seon Joo; Shim, Woo Hyun; Cho, Hyungjoon; Cho, Gyunggoo; Kim, Young Ro

    2013-01-01

    Insufficient vascular reserve after an ischemic stroke may induce biochemical cascades that subsequently deteriorate the blood–brain barrier (BBB) function. However, the direct relationship between poor cerebral blood volume (CBV) restoration and BBB disruption has not been examined in acute stroke. To quantify BBB integrity at acute stages of transient stroke, in particular for cases in which extravasation of the standard contrast agent (Gd-DTPA) is not observed, we adopted the water exchange index (WEI), a novel magnetic resonance image-derived parameter to estimate the water permeability across the BBB. The apparent diffusion coefficient (ADC) and R2 relaxation rate constant were also measured for outlining the tissue abnormality, while fractional CBV and WEI were quantified for assessing vascular alterations. The significantly decreased ADC and R2 in the ischemic cortices did not correlate with the changes in CBV or WEI. In contrast, a strong negative correlation between the ipsilesional WEI and CBV was found, in which stroke mice were clustered into two groups: (1) high WEI and low CBV and (2) normal WEI and CBV. The low CBV observed for mice with a disrupted BBB, characterized by a high WEI, indicates the importance of CBV restoration for maintaining BBB stability in acute stroke. PMID:23462571

  6. Acute caffeine administration effect on brain activation patterns in mild cognitive impairment.

    Science.gov (United States)

    Haller, Sven; Montandon, Marie-Louise; Rodriguez, Cristelle; Moser, Dominik; Toma, Simona; Hofmeister, Jeremy; Sinanaj, Indrit; Lovblad, Karl-Olof; Giannakopoulos, Panteleimon

    2014-01-01

    Previous studies showed that acute caffeine administration enhances task-related brain activation in elderly individuals with preserved cognition. To explore the effects of this widely used agent on cognition and brain activation in early phases of cognitive decline, we performed a double-blinded, placebo-controlled functional magnetic resonance imaging (fMRI) study during an n-back working memory task in 17 individuals with mild cognitive impairment (MCI) compared to 17 age-matched healthy controls (HC). All individuals were regular caffeine consumers with an overnight abstinence and given 200 mg caffeine versus placebo tablets 30 minutes before testing. Analyses included assessment of task-related activation (general linear model), functional connectivity (tensorial-independent component analysis, TICA), baseline perfusion (arterial spin labeling, ASL), grey matter density (voxel-based morphometry, VBM), and white matter microstructure (tract-based spatial statistics, TBSS). Acute caffeine administration induced a focal activation of the prefrontal areas in HC with a more diffuse and posteromedial activation pattern in MCI individuals. In MCI, TICA documented a significant caffeine-related enhancement in the prefrontal cortex, supplementary motor area, ventral premotor and parietal cortex as well as the basal ganglia and cerebellum. The absence of significant group differences in baseline ASL perfusion patterns supports a neuronal rather than a purely vascular origin of these differences. The VBM and TBSS analyses excluded potentially confounding differences in grey matter density and white matter microstructure between MCI and HC. The present findings suggest a posterior displacement of working memory-related brain activation patterns after caffeine administration in MCI that may represent a compensatory mechanism to counterbalance a frontal lobe dysfunction.

  7. Acute and chronic nicotine effects on behaviour and brain activation during intertemporal decision making.

    Science.gov (United States)

    Kobiella, Andrea; Ripke, Stephan; Kroemer, Nils B; Vollmert, Christian; Vollstädt-Klein, Sabine; Ulshöfer, Dorothea E; Smolka, Michael N

    2014-09-01

    Previous studies demonstrated higher discount rates for delayed rewards in smokers than non-smokers. We performed this study to determine whether those differences in intertemporal choice are due to pharmacological effects of nicotine and to track related brain regions. Thirty-three non-smokers and 27 nicotine-dependent smokers underwent functional magnetic resonance imaging while performing an intertemporal choice task consisting of 40 sets of monetary reward options that varied by delay to delivery. Smokers were investigated in a state of nicotine satiation. Non-smokers were investigated twice, receiving nicotine (2 mg) and placebo gums in a double-blinded, randomized cross-over design. Smokers displayed steeper temporal discounting than non-smokers. Those behavioural differences were reflected in the brain response during the decision between two alternative money/time pairs: smokers showed less activation in parietal and occipital areas (e.g. precuneus) than non-smokers under placebo. A single dose of nicotine in non-smokers led to a similar effect on brain activation but did not impact behaviour. Processing of the reward magnitude of money/time pairs differed between smokers and non-smokers: smokers showed decreased reactivity of the ventral striatum. Moreover, there was an acute nicotine effect in non-smokers on processing of the reward magnitude: nicotine increased the correlation of blood oxygen level-dependent response and mean amount in the left hippocampus, amygdala and anterior insula. We conclude that cross-sectional differences between smokers and non-smokers are only, in part, due to the acute pharmacological effects of nicotine. Longitudinal studies are needed to investigate pre-drug group characteristics as well as consequences of smoking on discounting behaviour and its neural correlates.

  8. Neuroprotective effects of bloodletting atJing points combined with mild induced hypothermia in acute severe traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Yue Tu; Xiao-mei Miao; Tai-long Yi; Xu-yi Chen; Hong-tao Sun; Shi-xiang Cheng; Sai Zhang

    2016-01-01

    Bloodletting atJing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting atJing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe trau-matic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and blood-brain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inlfammatory response were lessened. These ifndings suggest that the combined effects of bloodletting atJing points (20 µL, twice a day, for 2 days) and mild induced hypothermia (6 hours) are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury.

  9. Effects of Acute Lithium Treatment on Brain Levels of Inflammatory Mediators in Poststroke Rats

    Directory of Open Access Journals (Sweden)

    Matthew Boyko

    2015-01-01

    Full Text Available Stroke is a leading cause of mortality and morbidity worldwide. Few therapeutic options with proven efficacy are available for the treatment of this disabling disease. Lithium is the gold standard treatment for bipolar disorder. Moreover, lithium has been shown to exhibit neuroprotective effects and therapeutic efficacy as a treatment of other neurological disorders. This study was undertaken to examine the effects of lithium on brain inflammatory mediators levels, fever, and mortality in postischemic stroke rats. Ischemic stroke was induced by occlusion of the mid cerebral artery (MCAO. Pretreatment with a single dose of lithium at 2 hours before MCAO induction significantly reduced the elevation in interleukin- (IL- 6 and prostaglandin E2 levels in brain of post-MCAO rats, as compared to vehicle-treated animals. On the other hand, lithium did not affect the elevation in IL-1α, IL-10, IL-12, and tumor necrosis factor-α levels in brain of post-MCAO rats. Moreover, pretreatment with lithium did not alter post-MCAO fever and mortality. These results suggest that acute pretreatment with a single dose of lithium did not markedly affect post-MCAO morbidity and mortality in rats.

  10. Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Bruno Silva

    2015-08-01

    Full Text Available The present study aimed to investigate behavioral changes and neuroinflammatory process following left unilateral common carotid artery occlusion (UCCAO, a model of cerebral ischemia. Post-ischemic behavioral changes following 15 min UCCAO were recorded 24 hours after reperfusion. The novel object recognition task was used to assess learning and memory. After behavioral test, brains from sham and ischemic mice were removed and processed to evaluate central nervous system pathology by TTC and H&E techniques as well as inflammatory mediators by ELISA. UCCAO promoted long-term memory impairment after reperfusion. Infarct areas were observed in the cerebrum by TTC stain. Moreover, the histopathological analysis revealed cerebral necrotic cavities surrounded by ischemic neurons and hippocampal neurodegeneration. In parallel with memory dysfunction, brain levels of TNF-a, IL-1b and CXCL1 were increased post ischemia compared with sham-operated group. These findings suggest an involvement of central nervous system inflammatory mediators and brain damage in cognitive impairment following unilateral acute ischemia.

  11. Mouse models of human PIK3CA-related brain overgrowth have acutely treatable epilepsy

    Science.gov (United States)

    Roy, Achira; Skibo, Jonathan; Kalume, Franck; Ni, Jing; Rankin, Sherri; Lu, Yiling; Dobyns, William B; Mills, Gordon B; Zhao, Jean J; Baker, Suzanne J; Millen, Kathleen J

    2015-01-01

    Mutations in the catalytic subunit of phosphoinositide 3-kinase (PIK3CA) and other PI3K-AKT pathway components have been associated with cancer and a wide spectrum of brain and body overgrowth. In the brain, the phenotypic spectrum of PIK3CA-related segmental overgrowth includes bilateral dysplastic megalencephaly, hemimegalencephaly and focal cortical dysplasia, the most common cause of intractable pediatric epilepsy. We generated mouse models expressing the most common activating Pik3ca mutations (H1047R and E545K) in developing neural progenitors. These accurately recapitulate all the key human pathological features including brain enlargement, cortical malformation, hydrocephalus and epilepsy, with phenotypic severity dependent on the mutant allele and its time of activation. Underlying mechanisms include increased proliferation, cell size and altered white matter. Notably, we demonstrate that acute 1 hr-suppression of PI3K signaling despite the ongoing presence of dysplasia has dramatic anti-epileptic benefit. Thus PI3K inhibitors offer a promising new avenue for effective anti-epileptic therapy for intractable pediatric epilepsy patients. DOI: http://dx.doi.org/10.7554/eLife.12703.001 PMID:26633882

  12. Role of Caspase 3 in neuronal apoptosis after acute brain injury

    Institute of Scientific and Technical Information of China (English)

    杨新宇; 杨树源; 张建宁; 雪亮; 胡震

    2002-01-01

    To analyze the role of Caspase 3 in neuronal apoptosis after acute brain injury. Methods: Experiments were carried out with rat diffuse brain trauma model. The neuronal DNA injury in cortex and hippocampus was observed by TUNEL stain.The mRNA and protein expressions and enzyme activation of Caspase 3 were observed by Northern blot, in situ hybridization, immunohistochemistry stain and Western blot, respectively. Special Caspase 3 enzyme inhibitor was used to observe the therapeutic effect. Results: TUNEL positive neurons appeared 2 hours after severe trauma, peaked at 1 day and lasted for 7 days.Northern blot showed that the Caspase 3 mRNA expression was increased and peaked at 1 day, about twice higher than the control. In the area of cortex and hippocampus,positive mRNA staining neurons appeared most distinct on one day. With the antibody for Caspase 3 P20 subunit, the active Caspase 3 expression peaked at 1-3 days. The electrophoresis band of PARP degradation would be seen by Western blot. Caspase 3 enzyme inhibitor could reduce apoptotic neuronal death without any effect on Caspase 3 P20 subunit expression. Conclusions: After brain trauma, Caspase 3 mRNA and protein expressions and enzyme activation are enhanced in combination with neuronal apoptosis. Special Caspase 3 enzyme inhibitor can apparently decrease the neuronal apoptosis.

  13. Whole brain magnetization transfer histogram analysis of pediatric acute lymphoblastic leukemia patients receiving intrathecal methotrexate therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Akira [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: yakira@kuhp.kyoto-u.ac.jp; Miki, Yukio [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: mikiy@kuhp.kyoto-u.ac.jp; Adachi, Souichi [Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: sadachi@kuhp.kyoto-u.ac.jp (and others)

    2006-03-15

    Background and purpose: The purpose of this prospective study was to evaluate the hypothesis that magnetization transfer ratio (MTR) histogram analysis of the whole brain could detect early and subtle brain changes nonapparent on conventional magnetic resonance imaging (MRI) in children with acute lymphoblastic leukemia (ALL) receiving methotrexate (MTX) therapy. Materials and methods: Subjects in this prospective study comprised 10 children with ALL (mean age, 6 years; range, 0-16 years). In addition to conventional MRI, magnetization transfer images were obtained before and after intrathecal and intravenous MTX therapy. MTR values were calculated and plotted as a histogram, and peak height and location were calculated. Differences in peak height and location between pre- and post-MTX therapy scans were statistically analyzed. Conventional MRI was evaluated for abnormal signal area in white matter. Results: MTR peak height was significantly lower on post-MTX therapy scans than on pre-MTX therapy scans (p = 0.002). No significant differences in peak location were identified between pre- and post-chemotherapy imaging. No abnormal signals were noted in white matter on either pre- or post-MTX therapy conventional MRI. Conclusions: This study demonstrates that MTR histogram analysis allows better detection of early and subtle brain changes in ALL patients who receive MTX therapy than conventional MRI.

  14. Radiation induces acute alterations in neuronal function.

    Directory of Open Access Journals (Sweden)

    Peter H Wu

    Full Text Available Every year, nearly 200,000 patients undergo radiation for brain tumors. For both patients and caregivers the most distressing adverse effect is impaired cognition. Efforts to protect against this debilitating effect have suffered from inadequate understanding of the cellular mechanisms of radiation damage. In the past it was accepted that radiation-induced normal tissue injury resulted from a progressive reduction in the survival of clonogenic cells. Moreover, because radiation-induced brain dysfunction is believed to evolve over months to years, most studies have focused on late changes in brain parenchyma. However, clinically, acute changes in cognition are also observed. Because neurons are fully differentiated post-mitotic cells, little information exists on the acute effects of radiation on synaptic function. The purpose of our study was to assess the potential acute effects of radiation on neuronal function utilizing ex vivo hippocampal brain slices. The cellular localization and functional status of excitatory and inhibitory neurotransmitter receptors was identified by immunoblotting. Electrophysiological recordings were obtained both for populations of neuronal cells and individual neurons. In the dentate gyrus region of isolated ex vivo slices, radiation led to early decreases in tyrosine phosphorylation and removal of excitatory N-methyl-D-aspartate receptors (NMDARs from the cell surface while simultaneously increasing the surface expression of inhibitory gamma-aminobutyric acid receptors (GABA(ARs. These alterations in cellular localization corresponded with altered synaptic responses and inhibition of long-term potentiation. The non-competitive NMDAR antagonist memantine blocked these radiation-induced alterations in cellular distribution. These findings demonstrate acute effects of radiation on neuronal cells within isolated brain slices and open new avenues for study.

  15. Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

    Directory of Open Access Journals (Sweden)

    Mónica Millán

    2008-01-01

    Full Text Available Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA.

  16. Brain-derived neurotrophic factor and substrate utilization following acute aerobic exercise in obese individuals.

    Science.gov (United States)

    Slusher, A L; Whitehurst, M; Zoeller, R F; Mock, J T; Maharaj, A; Huang, C-J

    2015-05-01

    Brain-derived neurotrophic factor (BDNF) serves as a vital regulator of neuronal proliferation and survival, and has been shown to regulate energy homeostasis, glucose metabolism and body weight maintenance. Elevated concentrations of plasma BDNF have been associated with obesity and type 2 diabetes mellitus. Acute aerobic exercise transiently increases circulating BDNF, potentially correcting obesity-related metabolic impairment. The present study aimed to compare acute aerobic exercise elicited BDNF responses in obese and normal-weight subjects. Furthermore, we aimed to investigate whether acute exercise-induced plasma BDNF elevations would be associated with improved indices of insulin resistance, as well as substrate utilization [carbohydrate oxidation (CHOoxi) and fat oxidation (FAToxi)]. Twenty-two healthy, untrained subjects [11 obese (four men and seven women; age = 22.91 ± 4.44 years; body mass index = 35.72 ± 4.17 kg/m(2)) and 11 normal-weight (five men and six women; age = 23.27 ± 2.24 years; body mass index = 21.89 ± 1.63 kg/m(2))] performed 30 min of continuous submaximal aerobic exercise at 75% maximal oxygen consumption. Our analyses showed that the BDNF response to acute aerobic exercise was similar in obese and normal-weight subjects across time (time: P = 0.015; group: P = not significant) and was not associated with indices of IR. Although no differences in the rates of CHOoxi and FAToxi were found between both groups, total relative energy expenditure was significantly lower in obese subjects compared to normal-weight subjects (3.53 ± 0.25 versus 5.59 ± 0.85; P exercise-elicited BDNF elevation may not be sufficient to modulate indices of IR or the utilization of either carbohydrates or fats in obese individuals.

  17. Cognitive activity limitations one year post-trauma in patients admitted to sub-acute rehabilitation after severe traumatic brain injury

    DEFF Research Database (Denmark)

    Sommer, Jens Bak; Norup, Anne; Poulsen, Ingrid;

    2013-01-01

    Objective: To examine cognitive activity limitations and predictors of outcome 1 year post-trauma in patients admitted to sub-acute rehabilitation after severe traumatic brain injury. Subjects: The study included 119 patients with severe traumatic brain injury admitted to centralized sub-acute re...

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

    Directory of Open Access Journals (Sweden)

    Glenn R Wylie

    Full Text Available Functional neuroimaging studies in mild traumatic brain injury (mTBI have been largely limited to patients with persistent post-concussive symptoms, utilizing images obtained months to years after the actual head trauma. We sought to distinguish acute and delayed effects of mild traumatic brain injury on working memory functional brain activation patterns < 72 hours after mild traumatic brain injury (mTBI and again one-week later. We hypothesized that clinical and fMRI measures of working memory would be abnormal in symptomatic mTBI patients assessed < 72 hours after injury, with most patients showing clinical recovery (i.e., improvement in these measures within 1 week after the initial assessment. We also hypothesized that increased memory workload at 1 week following injury would expose different cortical activation patterns in mTBI patients with persistent post-concussive symptoms, compared to those with full clinical recovery. We performed a prospective, cohort study of working memory in emergency department patients with isolated head injury and clinical diagnosis of concussion, compared to control subjects (both uninjured volunteers and emergency department patients with extremity injuries and no head trauma. The primary outcome of cognitive recovery was defined as resolution of reported cognitive impairment and quantified by scoring the subject's reported cognitive post-concussive symptoms at 1 week. Secondary outcomes included additional post-concussive symptoms and neurocognitive testing results. We enrolled 46 subjects: 27 with mild TBI and 19 controls. The time of initial neuroimaging was 48 (+22 S.D. hours after injury (time 1. At follow up (8.7, + 1.2 S.D., days after injury, time 2, 18 of mTBI subjects (64% reported moderate to complete cognitive recovery, 8 of whom fully recovered between initial and follow-up imaging. fMRI changes from time 1 to time 2 showed an increase in posterior cingulate activation in the mTBI subjects

  19. Acute supramaximal exercise increases the brain oxygenation in relation to cognitive workload

    Directory of Open Access Journals (Sweden)

    Cem Seref Bediz

    2016-04-01

    Full Text Available Single bout of exercise can improve the performance on cognitive tasks. However, cognitive responses may be controversial due to different type, intensity, and duration of exercise. In addition, the mechanism of the effect of acute exercise on brain is still unclear. This study was aimed to investigate the effects of supramaximal exercise on cognitive tasks by means of brain oxygenation monitoring. The brain oxygenation of Prefrontal cortex (PFC was measured on 35 healthy male volunteers via functional Near Infrared Spectroscopy (fNIRS system. Subjects performed 2-Back test before and after the supramaximal exercise (Wingate Anaerobic Test lasting 30-s on cycle ergometer. The PFC oxygenation change evaluation revealed that PFC oxygenation rise during post-exercise 2-Back task was considerably higher than those in pre-exercise 2-Back task. In order to describe the relationship between oxygenation change and exercise performance, subjects were divided into two groups as high performers (HP and low performers (LP according to their peak power values (PP obtained from the supramaximal test. The oxy-hemoglobin (oxy-Hb values were compared between pre- and post-exercise conditions within subjects and also between subjects according to peak power. When performers were compared, in the HP group, the oxy-Hb values in post-exercise 2-Back test were significantly higher than those in pre-exercise 2-Back test. HP had significantly higher post-exercise oxy-Hb change (Δ than those of LP. In addition, peak power values of the total group were significantly correlated with Δoxy-Hb. The key findings of the present study revealed that acute supramaximal exercise has an impact on the brain oxygenation during a cognitive task. Also, the higher the anaerobic PP describes the larger the oxy-Hb response in post-exercise cognitive task. The current study also demonstrated a significant correlation between peak power (exercise load and post-exercise hemodynamic

  20. Microfluidics and multielectrode array-compatible organotypic slice culture method.

    Science.gov (United States)

    Berdichevsky, Yevgeny; Sabolek, Helen; Levine, John B; Staley, Kevin J; Yarmush, Martin L

    2009-03-30

    Organotypic brain slice cultures are used for a variety of molecular, electrophysiological, and imaging studies. However, the existing culture methods are difficult or expensive to apply in studies requiring long-term recordings with multielectrode arrays (MEAs). In this work, a novel method to maintain organotypic cultures of rodent hippocampus for several weeks on standard MEAs in an unmodified tissue culture incubator is described. Polydimethylsiloxane (Sylgard) mini-wells were used to stabilize organotypic cultures on glass and MEA surfaces. Hippocampus slices were successfully maintained within PDMS mini-wells for multiple weeks, with preserved pyramidal layer organization, connectivity, and activity. MEAs were used to record the development of spontaneous activity in an organotypic cultures for 4 weeks. This method is compatible with integration of microchannels into the culture substrate. Microchannels were incorporated into the mini-wells and applied to the guidance of axons originating within the slice, paving the way for studies of axonal sprouting using organotypic slices.

  1. RESULTS OF SLICE MEASUREMENTS

    CERN Document Server

    Rudolph, J

    2011-01-01

    The linear accelerator ELBE delivers high-brightness electron bunches to multiple user stations, including two IR-FEL oscillators [1], [2]. In the framework of an upgrade program the current thermionic injector is being replaced by a SRF-photoinjector [3], [4]. The SRF injector promises higher beam quality, especially required for future experiments with high power laser radiation. During the commissioning phase, the SRF-injector was running in parallel to the thermionic gun. After installation of a injection beamline (dogleg), beam from the SRF-injector can now be injected into the ELBE linac. Detailed characterization of the electron beam quality delivered by the new electron injector includes vertical slice emittance measurements in addition to measurements of projected emittance values. This report gives an overview of the status of the project and summarizes first measurement results as well as results of simulations performed with measurement settings.

  2. Brain 3-Mercaptopyruvate Sulfurtransferase (3MST: Cellular Localization and Downregulation after Acute Stroke.

    Directory of Open Access Journals (Sweden)

    Heng Zhao

    Full Text Available 3-Mercaptopyruvate sulfurtransferase (3MST is an important enzyme for the synthesis of hydrogen sulfide (H2S in the brain. We present here data that indicate an exclusively localization of 3MST in astrocytes. Regional distribution of 3MST activities is even and unremarkable. Following permanent middle cerebral artery occlusion (pMCAO, 3MST was down-regulated in both the cortex and striatum, but not in the corpus collosum. It appears that the down-regulation of astrocytic 3MST persisted in the presence of astrocytic proliferation due to gliosis. Our observations indicate that 3MST is probably not responsible for the increased production of H2S following pMCAO. Therefore, cystathionine β-synthase (CBS, the alternative H2S producing enzyme in the CNS, remains as a more likely potential therapeutic target than 3MST in the treatment of acute stroke through inhibition of H2S production.

  3. Executive function late effects in survivors of pediatric brain tumors and acute lymphoblastic leukemia.

    Science.gov (United States)

    Winter, Amanda L; Conklin, Heather M; Tyc, Vida L; Stancel, Heather; Hinds, Pamela S; Hudson, Melissa M; Kahalley, Lisa S

    2014-01-01

    Survivors of pediatric brain tumors (BT) and acute lymphoblastic leukemia (ALL) are at risk for neurocognitive late effects related to executive function. Survivors of BT (48) and ALL (50) completed neurocognitive assessment. Executive function was compared to estimated IQ and population norms by diagnostic group. Both BT and ALL demonstrated relative executive function weaknesses. As a group, BT survivors demonstrated weaker executive functioning than expected for age. Those BT survivors with deficits exhibited a profile suggestive of global executive dysfunction, while affected ALL survivors tended to demonstrate specific rapid naming deficits. Findings suggest that pediatric BT and ALL survivors may exhibit different profiles of executive function late effects, which may necessitate distinct intervention plans.

  4. The Acute Inflammatory Response in Trauma/Hemorrhage and Traumatic Brain Injury : Current State and Emerging Prospects

    NARCIS (Netherlands)

    Namas, R.; Ghuma, A.; Hermus, L.; Zamora, R.; Okonkwo, D. O.; Billiar, T. R.; Vodovotz, Y.

    2009-01-01

    Traumatic injury/hemorrhagic shock (T/HS) elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases including T/HS and traumatic brain injury

  5. Leptin acts in the brain to influence hypoglycemic counterregulation: disparate effects of acute and recurrent hypoglycemia on glucagon release.

    Science.gov (United States)

    Reno, Candace M; Ding, Yuyan; Sherwin, Robert

    2015-12-15

    Leptin has been shown to diminish hyperglycemia via reduced glucagon secretion, although it can also enhance sympathoadrenal responses. However, whether leptin can also inhibit glucagon secretion during insulin-induced hypoglycemia or increase epinephrine during acute or recurrent hypoglycemia has not been examined. To test whether leptin acts in the brain to influence counterregulation, hyperinsulinemic hypoglycemic (∼45 mg/dl) clamps were performed on rats exposed to or not exposed to recurrent hypoglycemia (3 days, ∼40 mg/dl). Intracerebroventricular artificial cerebral spinal fluid or leptin was infused during the clamp. During acute hypoglycemia, leptin decreased glucagon responses by 51% but increased epinephrine and norepinephrine by 24 and 48%, respectively. After recurrent hypoglycemia, basal plasma leptin levels were undetectable. Subsequent brain leptin infusion during hypoglycemia paradoxically increased glucagon by 45% as well as epinephrine by 19%. In conclusion, leptin acts within the brain to diminish glucagon secretion during acute hypoglycemia but increases epinephrine, potentially limiting its detrimental effects during hypoglycemia. Exposure to recurrent hypoglycemia markedly suppresses plasma leptin, whereas exogenous brain leptin delivery enhances both glucagon and epinephrine release to subsequent hypoglycemia. These data suggest that recurrent hypoglycemia may diminish counterregulatory responses in part by reducing brain leptin action.

  6. Loss of Microstructural Integrity in the Limbic-Subcortical Networks for Acute Symptomatic Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Yanan Zhu

    2014-01-01

    Full Text Available Previous studies reported discrepant white matter diffusivity in mild traumatic brain injury (mTBI on the base of Glasgow Coma Scale, which are unreliable for some TBI severity indicators and the frequency of missing documentation in the medical record. In the present study, we adopted the Mayo classification system for TBI severity. In this system, the mTBI is also divided into two groups as “probable and symptomatic” TBI. We aimed to investigate altered microstructural integrity in symptomatic acute TBI (<1 week by using tract-based spatial statics (TBSS approach. A total of 12 patients and 13 healthy volunteers were involved and underwent MRI scans including conventional scan, and SWI and DTI. All the patients had no visible lesions by using conventional and SWI neuroimaging techniques, while showing widespread declines in the fractional anisotropy (FA of gray matter and white matter throughout the TBSS skeleton, particularly in the limbic-subcortical structures. By contrast, symptomatic TBI patients showed no significant enhanced changes in FA compared to the healthy controls. A better understanding of the acute changes occurring following symptomatic TBI may increase our understanding of neuroplasticity and continuing degenerative change, which, in turn, may facilitate advances in management and intervention.

  7. Real-time ultrasound brain perfusion imaging with analysis of microbubble replenishment in acute MCA stroke.

    Science.gov (United States)

    Kern, Rolf; Diels, Anna; Pettenpohl, Johanna; Kablau, Micha; Brade, Joachim; Hennerici, Michael G; Meairs, Stephen

    2011-08-01

    Real-time ultrasound perfusion imaging (rt-UPI) allows visualization of microbubbles flowing through the cerebral microvasculature. We hypothesized that analysis of microbubble tissue replenishment would enable for characterization of perfusion deficits in acute middle cerebral artery (MCA) territory stroke. Twenty-three patients (mean age 70.2 ± 13.2 years, 9 weeks) were included. Sequential images of bubble replenishment were acquired by transcranial rt-UPI at low mechanical index immediately after microbubble destruction. Different parameters were calculated from regions of interest (ROIs): real-time time to peak (rt-TTP), rise rate (β), and plateau (A) of acoustic intensity, and A × β was used as an index of blood flow. Results were compared with diffusion-weighted and perfusion magnetic resonance imaging. Parameters of rt-UPI had lower values in ROIs of ischemic as compared with normal tissue (β=0.58 ± 0.40 versus 1.25 ± 0.83; P=0.001; A=1.44 ± 1.75 versus 2.63 ± 2.31; P=0.05; A × β=1.14 ± 2.25 versus 2.98 ± 2.70; P=0.01). Real-time time to peak was delayed in ischemic tissue (11.43 ± 2.67 versus 8.88 ± 1.66 seconds; Preplenishment correctly identifies ischemic brain tissue in acute MCA stroke.

  8. The relationship between neuron-specific enolase and prognosis of patients with acute traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Yun-yang LIU

    2015-03-01

    Full Text Available Objective To investigate the relationship between neuron-specific enolase (NSE levels in serum and cerebrospinal fluid (CSF of patients with acute traumatic brain injury (TBI and the prognosis of TBI patients.  Methods A total of 89 patients with acute TBI were divided into light, medium, heavy and severe TBI groups based on admission Glasgow Coma Scale (GCS score. Serum NSE expression levels were detected in all cases and NSE levels in CSF were detected in 18 cases within 12 h after TBI. The expression levels of serum NSE in 20 normal people, except cases of lung disease and nervous system damage, were detected as a control group. Results Compared with the control group, serum NSE expression levels of patients in each TBI group were elevated (P < 0.05, for all, and the NSE levels in severe and heavy TBI groups were higher than that in medium and light groups (P < 0.05, for all. The serum NSE expression levels of patients with cerebral contusion were higher than that of patients with diffuse axonal injury (DAI, P = 0.025, subdural hematoma (P = 0.031 and epidural hematoma (P = 0.021. Serum NSE expression levels were negatively correlated with GCS score (rs = - 0.327, P = 0.024 and Glasgow Outcome Scale (GOS score (rs = - 0.252, P = 0.049. The NSE expression levels of CSF in severe and heavy TBI patients were higher than that of serum (P = 0.039, 0.031.  Conclusions NSE expression changes can be evaluated as an auxiliary indicator in reflecting the degree of acute TBI, typing diagnosis and prognostic evaluation, and NSE levels of CSF is more sensitive than that of serum. DOI: 10.3969/j.issn.1672-6731.2015.03.013

  9. Acute aerobic exercise increases brain-derived neurotrophic factor levels in elderly with Alzheimer's disease.

    Science.gov (United States)

    Coelho, Flávia Gomes de Melo; Vital, Thays Martins; Stein, Angelica Miki; Arantes, Franciel José; Rueda, André Veloso; Camarini, Rosana; Teodorov, Elizabeth; Santos-Galduróz, Ruth Ferreira

    2014-01-01

    Studies indicate the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of Alzheimer's disease (AD). Decreased BDNF levels may constitute a lack of trophic support and contribute to cognitive impairment in AD. The benefits of acute and chronic physical exercise on BDNF levels are well-documented in humans, however, exercise effects on BDNF levels have not been analyzed in older adults with AD. The aim of this study was to investigate the effects of acute aerobic exercise on BDNF levels in older adults with AD and to verify associations among BDNF levels, aerobic fitness, and level of physical activity. Using a controlled design, twenty-one patients with AD (76.3 ± 6.2 years) and eighteen healthy older adults (74.6 ± 4.7 years) completed an acute aerobic exercise. The outcomes included measures of BDNF plasma levels, aerobic fitness (treadmill grade, time to exhaustion, VO2, and maximal lactate) and level of physical activity (Baecke Questionnaire Modified for the Elderly). The independent t-test shows differences between groups with respect to the BDNF plasma levels at baseline (p = 0.04; t = 4.53; df = 37). In two-way ANOVA, a significant effect of time was found (p = 0.001; F = 13.63; df = 37), the aerobic exercise significantly increased BDNF plasma levels in AD patients and healthy controls. A significant correlation (p = 0.04; r = 0.33) was found between BDNF levels and the level of physical activity. The results of our study suggest that aerobic exercise increases BDNF plasma levels in patients with AD and healthy controls. In addition to that, BDNF levels had association with level of physical activity.

  10. 'Spreading depression of Leão' and its emerging relevance to acute brain injury in humans

    DEFF Research Database (Denmark)

    Lauritzen, Martin; Strong, Anthony J

    2017-01-01

    experiencing the visual (or sensorimotor) aura of migraine. In this review, we trace from their first description in rabbits through to their detection and study in migraine and the injured human brain, and from our personal perspectives, the evolution of understanding of the importance of spread of mass...... to clearer concepts of how ischaemic and traumatic lesions evolve in the injured human brain, and of how to seek to improve clinical management and outcome. Recognition of the likely fundamental significance of spreading depolarisations for this wide range of serious acute encephalopathies in humans provides......A new research field in translational neuroscience has opened as a result of the recognition since 2002 that "spreading depression of Leão" can be detected in many patients with acute brain injury, whether vascular and spontaneous, or traumatic in origin, as well as in those many individuals...

  11. [Cord blood transplantation after successful treatment of brain abscess caused by Bacillus cereus in a patient with acute myeloid leukemia].

    Science.gov (United States)

    Kuwabara, Hideyuki; Kawano, Tomoko; Tanaka, Masatugu; Kobayashi, Shoichi; Okabe, Gaichi; Maruta, Atsuo; Nagao, Takeshi; Ishigatsubo, Yoshiaki; Mori, Hiraku

    2006-11-01

    Central nervous system infection caused by Bacillus cereus is a rare condition, which often progresses rapidly and is fatal in immunocompromised patients. A 54-year-old woman with acute myelogenous leukemia fell into a coma with high fever during severe neutropenia while undergoing chemotherapy. A blood culture demonstrated the presence of B. cereus and magnetic resonance imaging showed multiple abnormal lesions in her brain. The patient was treated with meropenem and vancomycin, and recovered from the coma in a week. Antibiotic therapy was administered for seven weeks, and then she underwent cord blood transplantation for refractory acute myelogenous leukemia with successful engraftment without exacerbation of the brain abscess. This case demonstrates that brain abscess caused by B. cereus can be treated without surgical treatment.

  12. Multi-slice Spiral Computed Tomography Manifestations of Brain and Cerebral Hemodynamics in Chronic Mountain Sickness%慢性高原病脑部MSCT表现与血流动力学研究

    Institute of Scientific and Technical Information of China (English)

    王铎尧; 鲍海华; 赵希鹏; 李文方

    2011-01-01

    significantly highcr in CMS group than that in normal group (t=4. 551, P<0. 01 and t= 2. 898,P<0. 01 , respectively) . In CMS group , the CT value of superior sagittal sinus and bilateral middle cerebral artery with hemoglobin level (r=0. 758 and r=0. 740 , both P<0. 01). (2) The changes of CBF were obviously in grey matter than in white matter. In grey matter,CBF reduced more in CMS group than in normal group(P<0. 01). TTP in grey matter prolonged obviously in CMS group (P<0. 05 ). MTT in grey matter and white matter both prolonged obviously in CMS group (P<0. 01 ). Conclusion Multi-slice spiral CT is a valuable tool to study the state of the whole brain and the cercbral hemodvnamics in CMS patients.

  13. Effects of different kinds of acute stress on nerve growth factor content in rat brain.

    Science.gov (United States)

    von Richthofen, Sita; Lang, Undine E; Hellweg, Rainer

    2003-10-17

    Nerve growth factor (NGF) has several effects on the central nervous system; on the one hand NGF fosters survival and function of cholinergic neurons of the basal forebrain, on the other hand this protein is implicated in the stress response of the hypothalamic-pituitary-adrenocortical axis (HPAA). In this study we tested the influence of threatening and painful stress treatments in three different intensities as well as forced motoric activity on NGF content in different brain areas in adult rats. We found that threatening treatment with or without painful stimuli was followed by a significant decrease of NGF concentration in the amygdala (44.5%; P=0.03) and the frontal cortex (-45.5%; P=0.02). We also observed that after stress of forced motoric activity NGF content in the frontal cortex (-32%; P=0.01) and the hippocampus (-32%; P=0.006) was significantly reduced. Thus, NGF content in distinct brain regions is decreased, following different forms of acute stress. This might be relevant for the pathophysiological understanding of psychiatric diseases, such as depression, which are associated with stress.

  14. Regional brain activation as a biological marker of affective responsivity to acute exercise: influence of fitness.

    Science.gov (United States)

    Petruzzello, S J; Hall, E E; Ekkekakis, P

    2001-01-01

    Previous research has shown that regional brain activation, assessed via frontal electroencephalographic (EEG) asymmetry, predicts affective responsivity to aerobic exercise. To replicate and extend this work, in the present study we examined whether resting brain activation was associated with affective responses to an acute bout of aerobic exercise and the extent to which aerobic fitness mediated this relationship. Participants (high-fit, n = 22; low/moderate-fit, n = 45) ran on a treadmill for 30 min at 75% VO2max. EEG and affect were assessed pre- and 0-, 10-, 20-, and 30-min postexercise. Resting EEG asymmetry predicted positive affect (as measured by the energetic arousal subscale of the Activation Deactivation Adjective Check List) postexercise. Furthermore, resting frontal EEG asymmetry predicted affect only in the high-fit group, suggesting the effect might be mediated by some factor related to fitness. It was also shown that subjects with relatively greater left frontal activation had significantly more energy (i.e., activated pleasant affect) following exercise than subjects with relatively greater right frontal activation. In conclusion, aerobic fitness influenced the relationship between resting frontal asymmetry and exercise-related affective responsivity.

  15. End-of-life and brain death in acute coma and disorders of consciousness.

    Science.gov (United States)

    Greer, David M; Curiale, Gioacchino G

    2013-04-01

    Consulting neurologists are often asked to evaluate patients in acute nontraumatic coma. The authors review prognostication of functional outcomes, determining brain death, and managing end-of-life care. Prognostication of outcome after cardiac arrest in comatose patients is a frequently encountered scenario with high-stakes implications. However, current guidelines are limited by a failure to address the use of therapeutic hypothermia and thus may lead to overly pessimistic outcome prediction. Pupillary light responses and corneal reflexes remain highly predictive clinical signs of a poor prognosis. Motor responses have a high false-positive rate for predicting a poor outcome, especially in patients treated with therapeutic hypothermia. Ancillary testing with electroencephalography, somatosensory evoked potentials, serum neuron-specific enolase, and neuroimaging is often useful in predicting outcomes. Brain death is a clinical condition of irreversible coma of known cause with absent brainstem reflexes and apnea. An understanding of the value of confirmatory testing and the potential for confounding factors is essential in making a correct diagnosis. As coma carries a high mortality rate, neurologists must be capable of guiding goals of care, discussing end-of-life issues, and understanding organ-procurement procedures.

  16. Bryostatin improves survival and reduces ischemic brain injury in aged rats following acute ischemic stroke

    Science.gov (United States)

    Tan, Zhenjun; Turner, Ryan C.; Leon, Rachel L.; Li, Xinlan; Hongpaisan, Jarin; Zheng, Wen; Logsdon, Aric F.; Naser, Zachary J.; Alkon, Daniel L.; Rosen, Charles L.; Huber, Jason D.

    2014-01-01

    Background and Purpose Bryostatin, a potent protein kinase C (PKC) activator, has demonstrated therapeutic efficacy in preclinical models of associative memory, Alzheimer's disease, global ischemia, and traumatic brain injury. In this study, we tested the hypothesis that administration of bryostatin provides a therapeutic benefit in reducing brain injury and improving stroke outcome using a clinically relevant model of cerebral ischemia with tissue plasminogen activator (tPA) reperfusion in aged rats. Methods Acute cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery (MCAO) in 18-20 month old female Sprague-Dawley rats using an autologous blood clot with tPA-mediated reperfusion. Bryostatin was administered at 6 h post-MCAO then at 3, 6, 9, 12, 15, and 18 d after MCAO. Functional assessment was conducted at 2, 7, 14, and 21 d after MCAO. Lesion volume and hemispheric swelling/atrophy were performed at 2, 7, and 21 d post-MCAO. Histological assessment of PKC isozymes was performed at 24 h post-MCAO. Results Bryostatin-treated rats showed improved survival post-MCAO, especially during the first 4 d. Repeated administration of bryostatin post-MCAO resulted in reduced infarct volume, hemispheric swelling/atrophy, and improved neurological function at 21 d post-MCAO. Changes in PKC alpha expression and PKC epsilon expression in neurons were noted in bryostatin-treated rats at 24 h post-MCAO. Conclusions Repeated bryostatin administration post-MCAO protected the brain from severe neurological injury post-MCAO. Bryostatin treatment improved survival rate, reduced lesion volume, salvaged tissue in infarcted hemisphere by reducing necrosis and peri-infarct astrogliosis, and improved functional outcome following MCAO. PMID:24172582

  17. Bryostatin improves survival and reduces ischemic brain injury in aged rats after acute ischemic stroke.

    Science.gov (United States)

    Tan, Zhenjun; Turner, Ryan C; Leon, Rachel L; Li, Xinlan; Hongpaisan, Jarin; Zheng, Wen; Logsdon, Aric F; Naser, Zachary J; Alkon, Daniel L; Rosen, Charles L; Huber, Jason D

    2013-12-01

    Bryostatin, a potent protein kinase C (PKC) activator, has demonstrated therapeutic efficacy in preclinical models of associative memory, Alzheimer disease, global ischemia, and traumatic brain injury. In this study, we tested the hypothesis that administration of bryostatin provides a therapeutic benefit in reducing brain injury and improving stroke outcome using a clinically relevant model of cerebral ischemia with tissue plasminogen activator reperfusion in aged rats. Acute cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery (MCAO) in 18- to 20-month-old female Sprague-Dawley rats using an autologous blood clot with tissue plasminogen activator-mediated reperfusion. Bryostatin was administered at 6 hours post-MCAO, then at 3, 6, 9, 12, 15, and 18 days after MCAO. Functional assessment was conducted at 2, 7, 14, and 21 days after MCAO. Lesion volume and hemispheric swelling/atrophy were performed at 2, 7, and 21 days post-MCAO. Histological assessment of PKC isozymes was performed at 24 hours post-MCAO. Bryostatin-treated rats showed improved survival post-MCAO, especially during the first 4 days. Repeated administration of bryostatin post-MCAO resulted in reduced infarct volume, hemispheric swelling/atrophy, and improved neurological function at 21 days post-MCAO. Changes in αPKC expression and εPKC expression in neurons were noted in bryostatin-treated rats at 24 hours post-MCAO. Repeated bryostatin administration post-MCAO protected the brain from severe neurological injury post-MCAO. Bryostatin treatment improved survival rate, reduced lesion volume, salvaged tissue in infarcted hemisphere by reducing necrosis and peri-infarct astrogliosis, and improved functional outcome after MCAO.

  18. Acute White Matter Tract Damage after Frontal Mild Traumatic Brain Injury.

    Science.gov (United States)

    Herrera, Juan J; Bockhorst, Kurt; Kondraganti, Shakuntala; Stertz, Laura; Quevedo, João; Narayana, Ponnada A

    2017-01-15

    Our understanding of mild traumatic brain injury (mTBI) is still in its infancy and to gain a greater understanding, relevant animal models should replicate many of the features seen in human mTBI. These include changes to diffusion tensor imaging (DTI) parameters, absence of anatomical lesions on conventional neuroimaging, and neurobehavioral deficits. The Maryland closed head TBI model causes anterior-posterior plus sagittal rotational acceleration of the brain, frequently observed with motor vehicle and sports-related TBI injuries. The injury reflects a concussive injury model without skull fracture. The goal of our study was to characterize the acute (72 h) pathophysiological changes occurring following a single mTBI using magnetic resonance imaging (MRI), behavioral assays, and histology. We assessed changes in fractional anisotropy (FA), mean (MD), longitudinal (LD), and radial (RD) diffusivities relative to pre-injury baseline measures. Significant differences were observed in both the longitudinal and radial diffusivities in the fimbria compared with baseline. A significant difference in radial diffusivity was also observed in the splenium of the corpus callosum compared with baseline. The exploratory activity of the mTBI animals was also assessed using computerized activity monitoring. A significant decrease was observed in ambulatory distance, average velocity, stereotypic counts, and vertical counts compared with baseline. Histological examination of the mTBI brain sections indicated a significant decrease in the expression of myelin basic protein in the fimbria, splenium, and internal capsule. Our findings demonstrate the vulnerability of the white matter tracts, specifically the fimbria and splenium, and the ability of DTI to identify changes to the integrity of the white matter tracts following mTBI.

  19. Acute strength exercise and the involvement of small or large muscle mass on plasma brain-derived neurotrophic factor levels

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Correia

    2010-01-01

    Full Text Available OBJECTIVE: Blood neurotrophins, such as the brain-derived neurotrophic factor, are considered to be of great importance in mediating the benefits of physical exercise. In this study, the effect of acute strength exercise and the involvement of small versus large muscle mass on the levels of plasma brain-derived neurotrophic factor were evaluated in healthy individuals. METHODS: The concentric strengths of knee (large and elbow (small flexor and extensor muscles were measured on two separate days. Venous blood samples were obtained from 16 healthy subjects before and after exercise. RESULTS: The levels of brain-derived neurotrophic factor in the plasma did not significantly increase after both arm and leg exercise. There was no significant difference in the plasma levels of the brain-derived neurotrophic factor in the arms and legs. CONCLUSION: The present results demonstrate that acute strength exercise does not induce significant alterations in the levels of brain-derived neurotrophic factor plasma concentrations in healthy individuals. Considering that its levels may be affected by various factors, such as exercise, these findings suggest that the type of exercise program may be a decisive factor in altering peripheral brain-derived neurotrophic factor.

  20. Primary Experiences in 320-Row-640-Slice Dynamic CT for Checking Acute Chest Pain%320排640层动态容积CT 在急性胸痛检查中的初步探讨

    Institute of Scientific and Technical Information of China (English)

    马国军; 于淑靖; 何翔; 郑婧; 魏书恒; 王燕

    2011-01-01

    Objective: To evaluate the image quality and clinic value of dynamic CT checking triple rule-out.Method:38 patients suffering acute chest pain were continuously selected and accepted 320-row-640-slice dynamic CT examination.The scan protocol was helical scanning the whole chest, under ECG-gate,intelligent and automatically trigger.80~90ml contrast media was needed.Two professional doctors measure the CT value of ascending main aorta,decline main aorta and pulmonary artery separately in pulmonary trunk level .The image quality of coronary artery was evaluated,which was graded in three levels:good,well,bad.The dose of radiation was also evaluated .Result: The average CT value of ascending main aorta, decline main aorta and pulmonary artery was (401 ±57)HU,(397±49) HU,(331 ±31)HU.84.7% of all image quality of coronary artery were good,13.2% were well,2.1% were bad.4 patients were diagnosed lung infection with pleurar effusion, 1 patient was lung cancer,2 patients pulmonary embolism,1 patient dissection of aorta,2 patients artrial myxoma.The degree of stenosis was more than 50% in 12 patients' coronary artery.Average radiation dose was (22 ±2.1)mSv. Conclusion:This scanning protocol can achieve high quality image of main aorta,pulmonary artery and coronary artery comparing with the reports of literature.lt is very valuable for finding pathogen of acute chest pain.The dose of contrast media and radiation were lower.%目的:探讨320 排640 层动态容积CT 胸痛三联检查的图像质量及临床价值.方法:连续选取38 例急性胸痛患者行320 排640 层动态容积CT 检查.扫描方案为心电门控下全胸部螺旋扫描(160 mm×0.5mm),采用智能自动触发技术.对比剂用量为80~90ml( 碘海醇350).分别由2位专业医生测定肺动脉干层面的升主动脉、降主动脉、肺动脉干CT 值并评价冠脉质量,冠脉质量分为优、良、差三级.同时评价辐射剂量.结果:升主动脉、降主动脉、肺动脉平均CT

  1. Evaluating acute or chronic portal vein system thrombosis using multiple slice spiral computer tomography%CT增强扫描评价急慢性门静脉系统血栓

    Institute of Scientific and Technical Information of China (English)

    张青; 鲜军舫; 燕飞; 刘中林; 郭鹏德; 史旭波

    2014-01-01

    目的:采用多排螺旋CT增强扫描及三维重建技术评价急慢性门静脉系统血栓(PVT)。方法回顾性分析已证实的住院患者PVT的增强螺旋CT表现。根据症状发作时间将PVT分为急性期、慢性期,根据形态将血栓分为Ⅰ型完全型和Ⅱ型偏心型,分别评价门静脉直径、血栓位置、形态、密度、强化及伴随征象。结果 PVT形成患者19例。急性期3例,均为完全型;2例同时累及门静脉主干、左右分支、肠系膜上静脉及脾静脉,1例累及除门静脉主干外的其他3支血管。血栓CT值平均为(39±19)Hu,2例在血栓内部或边缘可见轻度强化。均有肠壁增厚、肠腔扩张积液、肠系膜水肿、腹水及侧支循环形成。慢性期16例,3例累及4支血管,4例累及3支,7例累及2支,2例累及1支。5例为完全型,11例为偏心型(68.8%),其中8例(72.7%)血栓宽径小于门脉宽径的50%。血栓 CT值平均为(41±12)Hu,3例强化。腹水15例,肠系膜水肿10例,侧支循环形成14例。结论 MSCT增强扫描可对急慢性PVT的累及范围及形态特点做出准确评价。%Objective To evaluate acute or chronic portal vein system thrombosis(PVT)using multiple slice spiral computer tomography(MSCT).Enhancement MSCT and three-dimensional CT reconstruction technique were applied in all patients.Methods Findings from inpatients proved portal vein system thrombosis were retrospectively reviewed.The portal venous system thrombosis was divided into acute or chronic stages according to the time from the onset of symptoms.The form of the blood clots fell into Ⅰ complete type and Ⅱ eccentric type.The diameter of the portal vein(DPV)was measured,and the location,shape,density,enhancement of the thrombi and the accompanying signs were assessed.Results Nineteen inpatients with portal vein system thrombosis were enrolled.Three cases were acute PVT and all were type Ⅰ.There were

  2. Whole-Brain CT Perfusion to Quantify Acute Ischemic Penumbra and Core.

    Science.gov (United States)

    Lin, Longting; Bivard, Andrew; Krishnamurthy, Venkatesh; Levi, Christopher R; Parsons, Mark W

    2016-06-01

    underestimated when brain coverage was 40 mm or less (P CT perfusion allowed differentiation of the penumbra from the ischemic core in patients with acute ischemic stroke. (©) RSNA, 2016 Online supplemental material is available for this article.

  3. Venous or arterial blood components trigger more brain swelling, tissue death after acute subdural hematoma compared to elderly atrophic brain with subdural effusion (SDE) model rats.

    Science.gov (United States)

    Wajima, Daisuke; Sato, Fumiya; Kawamura, Kenya; Sugiura, Keisuke; Nakagawa, Ichiro; Motoyama, Yasushi; Park, Young-Soo; Nakase, Hiroyuki

    2017-09-01

    Acute subdural hematoma (ASDH) is a frequent complication of severe head injury, whose secondary ischemic lesions are often responsible for the severity of the disease. We focused on the differences of secondary ischemic lesions caused by the components, 0.4ml venous- or arterial-blood, or saline, infused in the subdural space, evaluating the differences in vivo model, using rats. The saline infused rats are made for elderly atrophic brain with subdural effusion (SDE) model. Our data showed that subdural blood, both venous- and arterial-blood, aggravate brain edema and lesion development more than SDE. This study is the first study, in which different fluids in rats' subdural space, ASDH or SDE are compared with the extension of early and delayed brain damage by measuring brain edema and histological lesion volume. Blood constituents started to affect the degree of ischemia underneath the subdural hemorrhage, leading to more pronounced breakdown of the blood-brain barrier and brain damage. This indicates that further strategies to treat blood-dependent effects more efficiently are in view for patients with ASDH. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Transient Ischemic Attacks and Presence of an Acute Brain Lesion in Diffusion-Weighted MRI: Study of 50 Patients

    Directory of Open Access Journals (Sweden)

    SM Paknejad

    2012-10-01

    Full Text Available Background: Finding an acute brain lesion by diffusion-weighted (DW MRI upon an episode of transient ischemic attack (TIA is a predictor of imminent stroke in the near future. Therefore, exploring risk factors associated with lesions in DW-MRI of the brain is important in adopting an approach to TIA management. In the current study, we tried to determine the risk factors associated with lesions in DW-MRI of the brain in patients experiencing TIA episodes.Methods: Fifty patients with TIA were recruited consecutively in Sina Hospital, Tehran, Iran, over a 6-month period between July 2008 and January 2009. All of the patients underwent a complete neurological examination and laboratory tests. Brain DW-MRIs were performed for all the patients within 72 hours of a TIA episode.Results: DW-MRI revealed an acute lesion in 16% of the participants. There was a significant correlation between presence of an acute lesion in DW-MRI and TIA duration, history of diabetes mellitus and presence of unilateral facial palsy (P=0.0003, P=0.02 and P=0.008, respectively. Other variables such as age, hypertension, hyperlipidemia, past history of TIA, headache, vertigo, and sensory or visual disturbances had no significant relation with the presence of an acute lesion in DW-MRI.Conclusion: Duration of TIA, presence of diabetes mellitus and unilateral facial palsy are risk factors for an acute lesion in DW-MRI, meaning that patients with such risk factors are at risk for stroke in the near future.

  5. Acute and chronic glucocorticoid treatments regulate astrocyte-enriched mRNAs in multiple brain regions in vivo

    Directory of Open Access Journals (Sweden)

    Bradley S. Carter

    2013-08-01

    Full Text Available Previous studies have primarily interpreted gene expression regulation by glucocorticoids in the brain in terms of impact on neurons; however, less is known about the corresponding impact of glucocorticoids on glia and specifically astrocytes in vivo. Recent microarray experiments have identified glucocorticoid-sensitive mRNAs in primary astrocyte cell culture, including a number of mRNAs that have reported astrocyte-enriched expression patterns relative to other brain cell types. Here, we have tested whether elevations of glucocorticoids regulate a subset of these mRNAs in vivo following acute and chronic corticosterone exposure in adult mice. Acute corticosterone exposure was achieved by a single injection of 10 mg/kg corticosterone, and tissue samples were harvested two hours post-injection. Chronic corticosterone exposure was achieved by administering 10 mg/mL corticosterone via drinking water for two weeks. Gene expression was then assessed in two brain regions associated with glucocorticoid action (prefrontal cortex and hippocampus by qPCR and by in situ hybridization. The majority of measured mRNAs regulated by glucocorticoids in astrocytes in vitro were similarly regulated by acute and/or chronic glucocorticoid exposure in vivo. In addition, the expression levels for mRNAs regulated in at least one corticosterone exposure condition (acute/chronic demonstrated moderate positive correlation between the two conditions by brain region. In situ hybridization analyses suggest that select mRNAs are regulated by chronic corticosterone exposure specifically in astroctyes based on (1 similar general expression patterns between corticosterone-treated and vehicle-treated animals and (2 similar expression patterns to the pan-astrocyte marker Aldh1l1. Our findings demonstrate that glucocorticoids regulate astrocyte-enriched mRNAs in vivo and suggest that glucocorticoids regulate gene expression in the brain in a cell type-dependent fashion.

  6. Antibodies to human myelin proteins and gangliosides in patients with acute neuroparalytic accidents induced by brain-derived rabies vaccine.

    Science.gov (United States)

    Laouini, D; Kennou, M F; Khoufi, S; Dellagi, K

    1998-11-02

    Antibody responses to myelin antigens were analysed in 15 patients who developed acute neuroparalytic accidents (ANPA) during post-exposure rabies vaccination using a rabies vaccine prepared on brain tissues and in 30 individuals who were uneventfully vaccinated. High titers (> or = 100) of IgG and IgM antibodies to GM1 or GD1a gangliosides were detected by enzyme linked immunosorbent-assay (ELISA) in plasmas from ANPA patients but not in controls. These data suggest that antibodies to GM1 and GD1a gangliosides may play a pathogenic role in the demyelinating and/or inflammatory processes characteristic of rabies vaccine-induced acute neurologic complications.

  7. Pituitary dysfunction in traumatic brain injury: Is evaluation in the acute phase worthwhile?

    Science.gov (United States)

    Dalwadi, Pradip P.; Bhagwat, Nikhil M.; Tayde, Parimal S.; Joshi, Ameya S.; Varthakavi, Premlata K.

    2017-01-01

    Introduction: Traumatic brain injury (TBI) is an under-recognized cause of hypopituitarism. According to recent data, it could be more frequent than previously known. However, there is a scarcity of data in Indian population. Aims: The main aim of the study was to determine the prevalence of pituitary hormone deficiencies in the acute phase of TBI. The secondary objectives were to correlate the severity of trauma with basal hormone levels and to determine whether initial hormone deficiencies predict mortality. Subjects and Methods: Forty-nine TBI patients (41 men and 8 women) were included in this study. Pituitary functions were evaluated within 24 h of admission. Results: Gonadotropin deficiency was found in 65.3% patient while 46.9% had low insulin-like growth factor-1, 12.24% had cortisol level <7 mcg/dl. Cortisol and prolactin level were positively correlated with the severity of TBI suggestive of stress response. Free triiodothyronine (fT3) and free thyroxine were significantly lower in patients with increasing severity of tuberculosis. Logistic regression analysis revealed that mortality after TBI was unrelated to the basal pituitary hormone levels except low T3 level, which was found to be positively related to mortality. Conclusions: Pituitary dysfunction is common after TBI and the most commonly affected axes are growth hormone and gonadotropin axis. Low fT3 correlates best with mortality. During the acute phase of TBI, at least an assessment of cortisol is vital as undetected cortisol deficiency can be life-threatening PMID:28217503

  8. Pituitary dysfunction in traumatic brain injury: Is evaluation in the acute phase worthwhile?

    Directory of Open Access Journals (Sweden)

    Pradip P Dalwadi

    2017-01-01

    Full Text Available Introduction: Traumatic brain injury (TBI is an under-recognized cause of hypopituitarism. According to recent data, it could be more frequent than previously known. However, there is a scarcity of data in Indian population. Aims: The main aim of the study was to determine the prevalence of pituitary hormone deficiencies in the acute phase of TBI. The secondary objectives were to correlate the severity of trauma with basal hormone levels and to determine whether initial hormone deficiencies predict mortality. Subjects and Methods: Forty-nine TBI patients (41 men and 8 women were included in this study. Pituitary functions were evaluated within 24 h of admission. Results: Gonadotropin deficiency was found in 65.3% patient while 46.9% had low insulin-like growth factor-1, 12.24% had cortisol level <7 mcg/dl. Cortisol and prolactin level were positively correlated with the severity of TBI suggestive of stress response. Free triiodothyronine (fT3 and free thyroxine were significantly lower in patients with increasing severity of tuberculosis. Logistic regression analysis revealed that mortality after TBI was unrelated to the basal pituitary hormone levels except low T3 level, which was found to be positively related to mortality. Conclusions: Pituitary dysfunction is common after TBI and the most commonly affected axes are growth hormone and gonadotropin axis. Low fT3 correlates best with mortality. During the acute phase of TBI, at least an assessment of cortisol is vital as undetected cortisol deficiency can be life-threatening

  9. Acute treatment with fluvoxamine elevates rat brain serotonin synthesis in some terminal regions: An autoradiographic study

    Science.gov (United States)

    Muck-Seler, Dorotea; Pivac, Nela; Diksic, Mirko

    2013-01-01

    Introduction A considerable body of evidence indicates the involvement of the neurotransmitter serotonin (5-HT) in the pathogenesis and treatment of depression. Methods The acute effect of fluvoxamine, on 5-HT synthesis rates was investigated in rat brain regions, using α-14C-methyl-L-tryptophan as a tracer. Fluvoxamine (25 mg/kg) and saline (control) were injected intraperitoneally, one hour before the injection of the tracer (30 μCi). Results There was no significant effect of fluvoxamine on plasma free tryptophan. After Benjamini–Hochberg False Discovery Rate correction, a significant decrease in the 5-HT synthesis rate in the fluvoxamine treated rats, was found in the raphe magnus (−32%), but not in the median (−14%) and dorsal (−3%) raphe nuclei. In the regions with serotonergic axon terminals, significant increases in synthesis rates were observed in the dorsal (+41%) and ventral (+43%) hippocampus, visual (+38%), auditory (+65%) and parietal (+37%) cortex, and the substantia nigra pars compacta (+56%). There were no significant changes in the 5-HT synthesis rates in the median (+11%) and lateral (+24%) part of the caudate-putamen, nucleus accumbens (+5%), VTA (+16%) or frontal cortex (+ 6%). Conclusions The data show that the acute administration of fluvoxamine affects 5-HT synthesis rates in a regionally specific pattern, with a general elevation of the synthesis in the terminal regions and a reduction in some cell body structures. The reasons for the regional specific effect of fluvoxamine on 5-HT synthesis are unclear, but may be mediated by the presynaptic serotonergic autoreceptors. PMID:22560971

  10. Brain modifications after acute alcohol consumption analyzed by resting state fMRI.

    Science.gov (United States)

    Spagnolli, Federica; Cerini, Roberto; Cardobi, Nicolò; Barillari, Marco; Manganotti, Paolo; Storti, Silvia; Mucelli, Roberto Pozzi

    2013-10-01

    Resting-state functional magnetic resonance imaging (fMRI) is a recent breakthrough in neuroimaging research able to describe "in vivo" the spontaneous baseline neuronal activity characterized by blood oxygen level dependent (BOLD) signal fluctuations at slow frequency (0.01-0.1Hz) that, in the absence of any task, forms spatially distributed functional connectivity networks, called resting state networks (RSNs). The aim of this study was to investigate, in the young and healthy population, the changing of the RSNs after acute ingestion of an alcohol dose able to determine a blood concentration (0.5g/L) that barely exceeds the legal limits for driving in the majority of European Countries. Fifteen healthy volunteers underwent two fMRI sessions using a 1.5T MR scanner before and after alcohol oral consumption. The main sequence acquired was EPI 2D BOLD, one per each session. To prevent the excessive alcohol consumption the subjects underwent the estimation of blood rate by breath test and after the stabilization of blood alcohol level (BAL) at 0.5g/L the subjects underwent the second fMRI session. Functional data elaboration was carried out using the probabilistic independent component analysis (PICA). Spatial maps so obtained were further organized, with MELODIC multisession temporal concatenation FSL option, in a cluster representing the group of pre-alcohol sessions and the group of post-alcohol sessions, followed by the dual regression approach in order to evaluate the increase or decrease in terms of connectivity in the RSNs between the two sessions at group level. The results we obtained reveal that acute consumption of alcohol reduces in a significant way the BOLD signal fluctuations in the resting brain selectively in the sub-callosal cortex (SCC), in left temporal fusiform cortex (TFC) and left inferior temporal gyrus (ITG), which are cognitive regions known to be part of the reward brain network and the ventral visual system. Copyright © 2013 Elsevier Inc

  11. A novel formal approach to program slicing

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Program slicing is a well-known program analysis technique that extracts the elements of a program related to a particular computation. The current slicing methods, however, are singular (mainly based on a program or system dependence graph), and lack good reusability and flexibility. In this paper, we present a novel formal method for program slicing, modular monadic program slicing, which abstracts the computation of program slicing as a slice monad transformer, and applies it to semantic descriptions of the program analyzed in a modular way, forming the corresponding monadic slicing algorithms. The modular abstraction mechanism allows our slicing method to possess excellent modularity and language-flexibility properties. We also give the related axioms of our slice monad transformer, the proof of the correctness and the implementation of monadic slicing algorithms. We reveal the relations of our algorithms and graph-reachable slicing algorithms.

  12. Effect of thyrotropin-releasing hormone on cerebral free radical reactions following acute brain injury in rabbits

    Institute of Scientific and Technical Information of China (English)

    牛光明; 顾秀娟; 苏玉林; 万锋; 苏芳忠; 薛德麟

    2003-01-01

    Objective: To investigate the early effect of thyrotropin-releasing hormone (TRH) on cerebral free radical reactions after acute brain injury in rabbits.Methods: 30 healthy white rabbits were randomly divided into three groups: Group A (n=10), Group B (n=12) and Group C (n=8). The rabbits in Group A and Group B were injured by direct hit. At 0.5-4 hours after injury, the rabbits in Group A were injected with TRH (8 mg/kg body weight) through a vein and the rabbits in Group B were injected with normal saline of equal volume. The rabbits in Group C served as the normal control. Then all the rabbits were killed and brain tissues were obtained. The content of lipoperoxide (LPO), the activity of superoxide dismutase (SOD) and the water content of the brain tissues were measured.Results: The contents of LPO and water in brain tissues in Group A were lower and the activity of SOD was higher than those of Group B (P<0.05). After injury, intracranial pressure (ICP) rose rapidly and continuously with time passing by. When TRH was given to the animals in Group A, the rising speed of ICP slowed down significantly.Conclusions: TRH can decrease the cerebral free radical reactions and cerebral edema after acute brain injury in rats.

  13. Association between neuroserpin and molecular markers of brain damage in patients with acute ischemic stroke

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    Leira Rogelio

    2011-05-01

    Full Text Available Abstract Background Neuroserpin has shown neuroprotective effects in animal models of cerebral ischemia and has been associated with functional outcome after ischemic stroke. Our aim was to study whether neuroserpin serum levels could be associated to biomarkers of excitotoxicity, inflammation and blood brain barrier disruption. Methods We prospectively included 129 patients with ischemic stroke (58.1% male; mean age, 72.4 ± 9.6 years not treated with tPA within 12 hours (h of symptoms onset (mean time, 4.7 ± 2.1 h. Poor functional outcome at 3 months was considered as a modified Rankin scale score >2. Serum levels of neuroserpin, Interleukin 6 (IL-6, Intercellular adhesion molecule-1 (ICAM-1, active Matrix metalloproteinase 9 (MMP-9, and cellular fibronectin (cFn (determined by ELISA and glutamate (determined by HPLC were measured on admission, 24 and 72 h. The main variable was considered the decrease of neuroserpin levels within the first 24 h. ROC analysis was used to select the best predictive value for neuroserpin to predict poor functional outcome due to a lack of linearity. Results The decrease of neuroserpin levels within the first 24 h was negatively correlated with serum levels at 24 hours of glutamate (r = -0.642, IL-6 (r = -0.678, ICAM-1 (r = -0.345, MMP-9 (r = -0.554 and cFn (r = -0.703 (all P Conclusions These findings suggest that neuroprotective properties of neuroserpin may be related to the inhibition of excitotoxicity, inflammation, as well as blood brain barrier disruption that occur after acute ischemic stroke.

  14. Ethosuximide and phenytoin dose-dependently attenuate acute nonconvulsive seizures after traumatic brain injury in rats.

    Science.gov (United States)

    Mountney, Andrea; Shear, Deborah A; Potter, Brittney; Marcsisin, Sean R; Sousa, Jason; Melendez, Victor; Tortella, Frank C; Lu, Xi-Chun M

    2013-12-01

    Acute seizures frequently occur following severe traumatic brain injury (TBI) and have been associated with poor patient prognosis. Silent or nonconvulsive seizures (NCS) manifest in the absence of motor convulsion, can only be detected via continuous electroencephalographic (EEG) recordings, and are often unidentified and untreated. Identification of effective anti-epileptic drugs (AED) against post-traumatic NCS remains crucial to improve neurological outcome. Here, we assessed the anti-seizure profile of ethosuximide (ETX, 12.5-187.5 mg/kg) and phenytoin (PHT, 5-30 mg/kg) in a spontaneously occurring NCS model associated with penetrating ballistic-like brain injury (PBBI). Rats were divided between two drug cohorts, PHT or ETX, and randomly assigned to one of four doses or vehicle within each cohort. Following PBBI, NCS were detected by continuous EEG monitoring for 72 h post-injury. Drug efficacy was evaluated on NCS parameters of incidence, frequency, episode duration, total duration, and onset latency. Both PHT and ETX attenuated NCS in a dose-dependent manner. In vehicle-treated animals, 69-73% experienced NCS (averaging 9-10 episodes/rat) with average onset of NCS occurring at 30 h post-injury. Compared with control treatment, the two highest PHT and ETX doses significantly reduced NCS incidence to 13-40%, reduced NCS frequency (1.8-6.2 episodes/rat), and delayed seizure onset: <20% of treated animals exhibited NCS within the first 48 h. NCS durations were also dose-dependently mitigated. For the first time, we demonstrate that ETX and PHT are effective against spontaneously occurring NCS following PBBI, and suggest that these AEDs may be effective at treating post-traumatic NCS.

  15. Effects of acute gamma-irradiation on extracellular adenine nucleotide hydrolysis in developing rat brain

    Science.gov (United States)

    Stanojević, I.; Drakulić, D.; Veličković, N.; Milošević, M.; Petrović, S.; Horvat, A.

    2009-09-01

    Cell membrane is highly sensitive to irradiation which, acting directly or indirectly, may disturb functions of constitutive proteins including membrane enzymes. Plasma membrane surface-located enzyme chain of ecto-nucleotide triphospho diphosphohydrolases (NTPDases) and 5'-nucleotidase are involved in termination of cell purinergic signalization by hydrolyzing extracellular, excitatory adenosine triphosphate (ATP), as well as nucleotide di-, and mono-phosphate (ADP and AMP) to neuroprotective adenosine. Extracellular ATP, ADP, and AMP hydrolyzes were examined in purified synaptic plasma membranes after whole-body acute irradiation. All measurements were done 24 h after irradiation of developing (15-, 30-day-old) and adult (90-day-old) rats with low (50 cGy) and high (2 Gy) dose of gamma-rays. Both, high and low doses inhibited nucleotide hydrolyses in 15-day-old rats; in 30-day-old rats low dose of radiation inhibited ADP and AMP hydrolyses while high dose inhibited only ATP hydrolyse. In adult rats high dose induced no effects, while low dose stimulated nucleotides hydrolyses. According to obtained results it was concluded that ecto-nucleotidases of young rats are more sensitive to irradiation, since even low dose induces inhibition of ecto-nucleotidases activities. Ionizing radiation, by decreasing brain nucleotide hydrolyses in developing rats, induces accumulation of ATP and decreases production of adenosine in synaptic cleft which could be neurocytotoxic. On the contrary, in adult rats low dose of radiation stimulates NTPDase and 5'-nucleotidase activity and protective adenosine production which indicates protective and adaptive mechanisms developed in adult brain neuronal cells.

  16. Covariance-Adaptive Slice Sampling

    OpenAIRE

    Thompson, Madeleine; Neal, Radford M.

    2010-01-01

    We describe two slice sampling methods for taking multivariate steps using the crumb framework. These methods use the gradients at rejected proposals to adapt to the local curvature of the log-density surface, a technique that can produce much better proposals when parameters are highly correlated. We evaluate our methods on four distributions and compare their performance to that of a non-adaptive slice sampling method and a Metropolis method. The adaptive methods perform favorably on low-di...

  17. Acute and chronic administration of cannabidiol increases mitochondrial complex and creatine kinase activity in the rat brain

    Directory of Open Access Journals (Sweden)

    Samira S. Valvassori

    2013-12-01

    Full Text Available Objective: To investigate the effects of cannabidiol (CBD on mitochondrial complex and creatine kinase (CK activity in the rat brain using spectrophotometry. Method: Male adult Wistar rats were given intraperitoneal injections of vehicle or CBD (15, 30, or 60 mg/kg in an acute (single dose or chronic (once daily for 14 consecutive days regimen. The activities of mitochondrial complexes and CK were measured in the hippocampus, striatum, and prefrontal cortex. Results: Both acute and chronic injection of CBD increased the activity of the mitochondrial complexes (I, II, II-III, and IV and CK in the rat brain. Conclusions: Considering that metabolism impairment is certainly involved in the pathophysiology of mood disorders, the modulation of energy metabolism (e.g., by increased mitochondrial complex and CK activity by CBD could be an important mechanism implicated in the action of CBD.

  18. Early platelet dysfunction in a rodent model of blunt traumatic brain injury reflects the acute traumatic coagulopathy found in humans.

    Science.gov (United States)

    Donahue, Deborah L; Beck, Julia; Fritz, Braxton; Davis, Patrick; Sandoval-Cooper, Mayra J; Thomas, Scott G; Yount, Robert A; Walsh, Mark; Ploplis, Victoria A; Castellino, Francis J

    2014-02-15

    Acute coagulopathy is a serious complication of traumatic brain injury (TBI) and is of uncertain etiology because of the complex nature of TBI. However, recent work has shown a correlation between mortality and abnormal hemostasis resulting from early platelet dysfunction. The aim of the current study was to develop and characterize a rodent model of TBI that mimics the human coagulopathic condition so that mechanisms of the early acute coagulopathy in TBI can be more readily assessed. Studies utilizing a highly reproducible constrained blunt-force brain injury in rats demonstrate a strong correlation with important postinjury pathological changes that are observed in human TBI patients, namely, diminished platelet responses to agonists, especially adenosine diphosphate (ADP), and subarachnoid bleeding. Additionally, administration of a direct thrombin inhibitor, preinjury, recovers platelet functionality to ADP stimulation, indicating a direct role for excess thrombin production in TBI-induced early platelet dysfunction.

  19. Yueju Pill Rapidly Induces Antidepressant-Like Effects and Acutely Enhances BDNF Expression in Mouse Brain

    Directory of Open Access Journals (Sweden)

    Wenda Xue

    2013-01-01

    Full Text Available The traditional antidepressants have a major disadvantage in delayed onset of efficacy, and the emerging fast-acting antidepressant ketamine has adverse behavioral and neurotoxic effects. Yueju pill, an herb medicine formulated eight hundred years ago by Doctor Zhu Danxi, has been popularly prescribed in China for alleviation of depression-like symptoms. Although several clinical outcome studies reported the relative short onset of antidepressant effects of Yueju, this has not been scientifically investigated. We, therefore, examined the rapid antidepressant effect of Yueju in mice and tested the underlying molecular mechanisms. We found that acute administration of ethanol extract of Yueju rapidly attenuated depressive-like symptoms in learned helpless paradigm, and the antidepressant-like effects were sustained for at least 24 hours in tail suspension test in ICR mice. Additionally, Yueju, like ketamine, rapidly increased the expression of brain-derived neurotrophic factor (BDNF in the hippocampus, whereas the BDNF mRNA expression remained unaltered. Yueju rapidly reduced the phosphorylation of eukaryotic elongation factor 2 (eEF2, leading to desuppression of BDNF synthesis. Unlike ketamine, both the BDNF expression and eEF2 phosphorylation were revered at 24 hours after Yueju administration. This study is the first to demonstrate the rapid antidepressant effects of an herb medicine, offering an opportunity to improve therapy of depression.

  20. The postreperfusion syndrome is associated with acute kidney injury following donation after brain death liver transplantation.

    Science.gov (United States)

    Kalisvaart, Marit; de Haan, Jubi E; Hesselink, Dennis A; Polak, Wojciech G; Hansen, Bettina E; IJzermans, Jan N M; Gommers, Diederik; Metselaar, Herold J; de Jonge, Jeroen

    2016-11-19

    Acute kidney injury (AKI) is frequently observed after donation after brain death (DBD) liver transplantation (LT) and associated with impaired recipient survival and chronic kidney disease. Hepatic ischemia/reperfusion injury (IRI) is suggested to be an important factor in this process. The postreperfusion syndrome (PRS) is the first manifestation of severe hepatic IRI directly after reperfusion. We performed a retrospective study on the relation between hepatic IRI and PRS and their impact on AKI in 155 DBD LT recipients. Severity of hepatic IRI was measured by peak postoperative AST levels and PRS was defined as >30% decrease in MAP ≥1 min within 5 min after reperfusion. AKI was observed in 39% of the recipients. AKI was significantly more observed in recipients with PRS (53% vs. 32%; P = 0.013). Median peak AST level was higher in recipients with PRS (1388 vs. 771 U/l; P PRS as an independent factor for postoperative AKI (OR 2.28; 95% CI 1.06-4.99; P = 0.035). In conclusion, PRS reflects severe hepatic IRI and predicts AKI after DBD LT. PRS immediately after reperfusion is an early warning sign and creates opportunities to preserve postoperative renal function.

  1. The Acute Inflammatory Response in Trauma / Hemorrhage and Traumatic Brain Injury: Current State and Emerging Prospects

    Directory of Open Access Journals (Sweden)

    Y Vodovotz

    2009-01-01

    Full Text Available Traumatic injury/hemorrhagic shock (T/HS elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases including T/HS and traumatic brain injury (TBI. Inflammation is a finely tuned, dynamic, highly-regulated process that is not inherentlydetrimental, but rather required for immune surveillance, optimal post-injury tissue repair, and regeneration. The inflammatory response is driven by cytokines and chemokines and is partiallypropagated by damaged tissue-derived products (Damage-associated Molecular Patterns; DAMP’s.DAMPs perpetuate inflammation through the release of pro-inflammatory cytokines, but may also inhibit anti-inflammatory cytokines. Various animal models of T/HS in mice, rats, pigs, dogs, and nonhumanprimates have been utilized in an attempt to move from bench to bedside. Novel approaches, including those from the field of systems biology, may yield therapeutic breakthroughs in T/HS andTBI in the near future.

  2. Sympathoadrenal Activation is Associated with Acute Traumatic Coagulopathy and Endotheliopathy in Isolated Brain Injury

    Science.gov (United States)

    Di Battista, Alex P.; Rizoli, Sandro B.; Lejnieks, Brandon; Min, Arimie; Shiu, Maria Y.; Peng, Henry T.; Baker, Andrew J.; Hutchison, Michael G.; Churchill, Nathan; Inaba, Kenji; Nascimento, Bartolomeu B.; de Oliveira Manoel, Airton Leonardo; Beckett, Andrew; Rhind, Shawn G.

    2016-01-01

    ABSTRACT Background: Acute coagulopathy after traumatic brain injury (TBI) involves a complex multifactorial hemostatic response that is poorly characterized. Objectives: To examine early posttraumatic alterations in coagulofibrinolytic, endothelial, and inflammatory blood biomarkers in relation to sympathetic nervous system (SNS) activation and 6-month patient outcomes, using multivariate partial least-squares (PLS) analysis. Patients and Methods: A multicenter observational study of 159 adult isolated TBI patients admitted to the emergency department at an urban level I trauma center, was performed. Plasma concentrations of 6 coagulofibrinolytic, 10 vascular endothelial, 19 inflammatory, and 2 catecholamine biomarkers were measured by immunoassay on admission and 24 h postinjury. Neurological outcome at 6 months was assessed using the Extended Glasgow Outcome Scale. PLS-discriminant analysis was used to identify salient biomarker contributions to unfavorable outcome, whereas PLS regression analysis was used to evaluate the covariance between SNS correlates (catecholamines) and biomarkers of coagulopathy, endotheliopathy, and inflammation. Results: Biomarker profiles in patients with an unfavorable outcome displayed procoagulation, hyperfibrinolysis, glycocalyx and endothelial damage, vasculature activation, and inflammation. A strong covariant relationship was evident between catecholamines and biomarkers of coagulopathy, endotheliopathy, and inflammation at both admission and 24 h postinjury. Conclusions: Biomarkers of coagulopathy and endotheliopathy are associated with poor outcome after TBI. Catecholamine levels were highly correlated with endotheliopathy and coagulopathy markers within the first 24 h after injury. Further research is warranted to characterize the pathogenic role of SNS-mediated hemostatic alterations in isolated TBI. PMID:27206278

  3. The Effects of Acute Exercise on Memory and Brain-Derived Neurotrophic Factor (BDNF).

    Science.gov (United States)

    Etnier, Jennifer L; Wideman, Laurie; Labban, Jeffrey D; Piepmeier, Aaron T; Pendleton, Daniel M; Dvorak, Kelly K; Becofsky, Katie

    2016-08-01

    Acute exercise benefits cognition, and some evidence suggests that brain-derived neurotrophic factor (BDNF) plays a role in this effect. The purpose of this study was to explore the dose-response relationship between exercise intensity, memory, and BDNF. Young adults completed 3 exercise sessions at different intensities relative to ventilator threshold (Vt) (VO2max, Vt - 20%, Vt + 20%). For each session, participants exercised for approximately 30 min. Following exercise, they performed the Rey Auditory Verbal Learning Test (RAVLT) to assess short-term memory, learning, and long-term memory recall. Twenty-four hours later, they completed the RAVLT recognition trial, which provided another measure of long-term memory. Blood was drawn before exercise, immediately postexercise, and after the 30-min recall test. Results indicated that long-term memory as assessed after the 24-hr delay differed as a function of exercise intensity with the largest benefits observed following maximal intensity exercise. BDNF data showed a significant increase in response to exercise; however, there were no differences relative to exercise intensity and there were no significant associations between BDNF and memory. Future research is warranted so that we can better understand how to use exercise to benefit cognitive performance.

  4. Attenuation of Acute Phase Injury in Rat Intracranial Hemorrhage by Cerebrolysin that Inhibits Brain Edema and Inflammatory Response.

    Science.gov (United States)

    Yang, Yang; Zhang, Yan; Wang, Zhaotao; Wang, Shanshan; Gao, Mou; Xu, Ruxiang; Liang, Chunyang; Zhang, Hongtian

    2016-04-01

    The outcome of intracerebral hemorrhage (ICH) is mainly determined by the volume of the hemorrhage core and the secondary brain damage to penumbral tissues due to brain swelling, microcirculation disturbance and inflammation. The present study aims to investigate the protective effects of cerebrolysin on brain edema and inhibition of the inflammation response surrounding the hematoma core in the acute stage after ICH. The ICH model was induced by administration of type VII bacterial collagenase into the stratum of adult rats, which were then randomly divided into three groups: ICH + saline; ICH + Cerebrolysin (5 ml/kg) and sham. Cerebrolysin or saline was administered intraperitoneally 1 h post surgery. Neurological scores, extent of brain edema content and Evans blue dye extravasation were recorded. The levels of pro-inflammatory factors (IL-1β, TNF-α and IL-6) were assayed by Real-time PCR and Elisa kits. Aquaporin-4 (AQP4) and tight junction proteins (TJPs; claudin-5, occludin and zonula occluden-1) expression were measured at multiple time points. The morphological and intercellular changes were characterized by Electron microscopy. It is found that cerebrolysin (5 ml/kg) improved the neurological behavior and reduced the ipsilateral brain water content and Evans blue dye extravasation. After cerebrolysin treated, the levels of pro-inflammatory factors and AQP4 in the peri-hematomal areas were markedly reduced and were accompanied with higher expression of TJPs. Electron microscopy showed the astrocytic swelling and concentrated chromatin in the ICH group and confirmed the cell junction changes. Thus, early cerebrolysin treatment ameliorates secondary injury after ICH and promotes behavioral performance during the acute phase by reducing brain edema, inflammatory response, and blood-brain barrier permeability.

  5. BM-16INCREASED ACUTE RADIATION EFFECT (ARE) WITH IPILUMUMAB AND RADIOSURGERY IN PATIENTS WITH MELANOMA BRAIN METASTASES

    Science.gov (United States)

    Khoja, Leila; Kurtz, Goldie; Zadeh, Gelareh; Laperriere, Normand; Menard, Cynthia; Millar, Barbara-Ann; Bernstein, Mark; Kongkham, Paul; Joshua, Anthony; Hogg, David; Butler, Marcus; Chung, Caroline

    2014-01-01

    BACKGROUND: Ipilumumab (Ipi), an antibody that enhances T-cell activation, has been shown to improve survival in patients with metastatic melanoma. Ipilumumab may have synergistic effects with radiotherapy but this may result in increased toxicity. This study investigated the incidence of acute radiation effect (ARE) in patients with melanoma brain metastases treated with Ipi and radiosurgery (SRS) or whole brain radiotherapy (WBRT). METHODOLOGY: This retrospective study included metastatic melanoma patients treated at our institution from 2008-2013 who received SRS or WBRT for brain metastases within 4 months of Ipi treatment. We evaluated the incidence, timing and factors associated with acute radiation effect (ARE). RESULTS: From 159 patients treated with Ipi, 22 patients also received brain RT within 4 months of treatment. Three patients were excluded for lack of follow-up brain imaging, thus 19 were analysed: 14 males and 5 females, with median age 58 years (range 24-82). Ten were treated with SRS, 7 with WBRT, and 2 with SRS plus WBRT. Median dose for SRS was 21 Gy (range: 15-24 Gy). Five of 13 patients treated with SRS (38%) experienced symptomatic edema requiring steroids within 1 month of starting Ipi, and within 4 months of RT. One patient had a haemorrhage and 1 required surgical resection, which demonstrated viable disease. Therefore 3 patients (23%) treated with SRS developed isolated ARE. These metastases had volumes less than 4.2 cm3 and were treated within 4 months of Ipi to a median dose of 19.5 Gy (range 15-21 Gy). No patients with WBRT alone developed ARE. CONCLUSIONS: Following SRS for brain mets and Ipi, ARE was seen in 23% of patients within 4 months of starting Ipi treatment. This is greater than the commonly reported 10% risk of ARE after SRS alone for brain metastasis. No increased toxicity was seen with WBRT and Ipi.

  6. Gastrodin protects neonatal rat brain against hypoxic-ischemic encephalopathy Acute therapeutic drug effects

    Institute of Scientific and Technical Information of China (English)

    Yanjun Niu; Zhengyong Jin

    2008-01-01

    BACKGROUND:Pharmacological experiments have demonstrated that gastrodin has a protective effect on neonatal rat brain subjected to hypoxia-ischemia; however,the underlying mechanism has not been fully elucidated. OBJECTIVE:The aim of this study was to investigate the acute therapeutic effects of gastrodin by observing prostaglandin B2 and 6-keto-prostaglandin F 1 a in brain issue of neonatal rats that received gastrodin injections immediately after hypoxia-ischemia.DESIGN:Single-factor design.SETTING:Department of Pediatrics,Affiliated Hospital of Yanbian University. MATERIALS:This study was performed in the Laboratory of the Department of Pediatrics,Affiliated Hospital of Yanbian University(key laboratory of provincial Health Department)from April to December 2003.Fifty-five Wistar rats of either gender,aged 7 days,were provided by the Laboratory Animal Center of Affiliated Hospital of Yanbian University.The rats were randomly divided into normal control(n=10), model(n=15),gastrodin-treated(n=15),and Danshen-treated(n=15)groups.The protocol was performed in accordance with guidelines from the Institute of Health Sciences for the use and care of animals.The following reagents were.used:Gastrodin(Sancai Medicine Group Co.,Ltd.,Zhongshan,Guangdong Province,China;component:gastrodin),Danshen(Conba Stock Company,Jinhua,Zhengjiang Province,China; component:salvia miltiorrhiza),and reagent kits for 125I-prostaglandin B2 and 125I-6-prostaglandin F 1 a (Research and Development Center for Science and Technology,General Hospital of Chinese PLA). METHODS:Rats in the normal control group received no treatment.Rats in the remaining 3 groups were anesthetized,followed by ligation of the left common carotid artery.One hour later,the rats were placed in a closed hypoxic box and allowed to inhale 8% oxygen-air(2.0-3.0 L/min)for 2 hours to develop hypoxic-ischemic encephalopathy.Immediately after lesion,rats in the gastrodin and Danshen-treated groups were intraperitoneally

  7. Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions

    Directory of Open Access Journals (Sweden)

    Salvadore Christopher

    2004-09-01

    Full Text Available Abstract Background The mitogen-activated protein kinases (MAPKs have been shown to participate in a wide array of cellular functions. A role for some MAPKs (e.g., extracellular signal-regulated kinase, Erk1/2 has been documented in response to certain physiological stimuli, such as ischemia, visceral pain and electroconvulsive shock. We recently demonstrated that restraint stress activates the Erk MAPK pathway, but not c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK or p38MAPK, in several rat brain regions. In the present study, we investigated the effects of a different stressor, acute forced swim stress, on the phosphorylation (P state of these MAPKs in the hippocampus, neocortex, prefrontal cortex, amygdala and striatum. In addition, effects on the phosphorylation state of the upstream activators of the MAPKs, their respective MAPK kinases (MAPKKs; P-MEK1/2, P-MKK4 and P-MKK3/6, were determined. Finally, because the Erk pathway can activate c-AMP response element (CRE binding (CREB protein, and swim stress has recently been reported to enhance CREB phosphorylation, changes in P-CREB were also examined. Results A single 15 min session of forced swimming increased P-Erk2 levels 2–3-fold in the neocortex, prefrontal cortex and striatum, but not in the hippocampus or amygdala. P-JNK levels (P-JNK1 and/or P-JNK2/3 were increased in all brain regions about 2–5-fold, whereas P-p38MAPK levels remained essentially unchanged. Surprisingly, levels of the phosphorylated MAPKKs, P-MEK1/2 and P-MKK4 (activators of the Erk and JNK pathways, respectively were increased in all five brain regions, and much more dramatically (P-MEK1/2, 4.5 to > 100-fold; P-MKK4, 12 to ~300-fold. Consistent with the lack of forced swim on phosphorylation of p38MAPK, there appeared to be no change in levels of its activator, P-MKK3/6. P-CREB was increased in all but cortical (prefrontal, neocortex areas. Conclusions Swim stress specifically and markedly

  8. Epidemiological and clinical studies on aseptic meningitis in 377 cases, 3. A study on brain CT scan in acute phase

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Masaaki; Kondo, Tomio; Takashima, Akira; Kono, Shinya; Yamashina, Manabu (Ogaki Shimin Hospital, Gifu (Japan))

    1984-02-01

    Brain CT scan performed in the acute phase of aseptic meningitis in 88 cases revealed abnormal findings in 5 consisting of 2 of cerebral edema, 2 of subdural hygroma and one of cerebral atrophy. Clinical findings showed no particular relation to the age, but cerebral edema was observed in the cases of possible cephalomeningitis diagnosed on the basis of accompanying convulsion and disturbance of consciousness. Abnormal findings were associated with 25% of symptoms diagnosed more than 4 days after onset.

  9. Selective brain responses to acute and chronic low-dose X-ray irradiation in males and females.

    Science.gov (United States)

    Silasi, Greg; Diaz-Heijtz, Rochellys; Besplug, Jill; Rodriguez-Juarez, Rocio; Titov, Viktor; Kolb, Bryan; Kovalchuk, Olga

    2004-12-24

    Radiation exposure is known to have profound effects on the brain, leading to precursor cell dysfunction and debilitating cognitive declines [Nat. Med. 8 (2002) 955]. Although a plethora of data exist on the effects of high radiation doses, the effects of low-dose irradiation, such as ones received during repetitive diagnostic and therapeutic exposures, are still under-investigated [Am. J. Otolaryngol. 23 (2002) 215; Proc. Natl. Acad. Sci. USA 97 (2000) 889; Curr. Opin. Neurol. 16 (2003) 129]. Furthermore, most studies of the biological effects of ionizing radiation have been performed using a single acute dose, while clinically and environmentally relevant exposures occur predominantly under chronic/repetitive conditions. Here, we have used a mouse model to compare the effects of chronic/repetitive and acute low-dose radiation (LDR) exposure (0.5Gy) to ionizing radiation on the brain in vivo. We examined the LDR effects on p42/44 MAPK (ERK1/ERK2), CaMKII, and AKT signaling-the interconnected pathways that have been previously shown to be crucial for neuronal survival upon irradiation. We report perturbations in ERK1/2, AKT, and CREB upon acute and chronic/repetitive low-dose exposure in the hippocampus and frontal cortex of mice. These studies were paralleled by the analysis of radiation effects on neurogenesis and cellular proliferation. Repetitive exposure had a much more pronounced effect on cellular signaling and neurogenesis than acute exposure. These results suggest that studies of single acute exposures might be limited in terms of their predictive value. We also present the first evidence of sex differences in radiation-induced signaling in the hippocampus and frontal cortex. We show the role of estrogens in brain radiation responses and discuss the implications of the observed changes.

  10. Protein-Energy Malnutrition Developing after Global Brain Ischemia Induces an Atypical Acute-Phase Response and Hinders Expression of GAP-43: e107570

    National Research Council Canada - National Science Library

    Shari E Smith; Sarah A Figley; David J Schreyer; Phyllis G Paterson

    2014-01-01

      Protein-energy malnutrition (PEM) is a common post-stroke problem. PEM can independently induce a systemic acute-phase response, and pre-existing malnutrition can exacerbate neuroinflammation induced by brain ischemia...

  11. Protein-energy malnutrition developing after global brain ischemia induces an atypical acute-phase response and hinders expression of GAP-43

    National Research Council Canada - National Science Library

    Smith, Shari E; Figley, Sarah A; Schreyer, David J; Paterson, Phyllis G

    2014-01-01

    Protein-energy malnutrition (PEM) is a common post-stroke problem. PEM can independently induce a systemic acute-phase response, and pre-existing malnutrition can exacerbate neuroinflammation induced by brain ischemia...

  12. Computer simulations suggest that acute correction of hyperglycaemia with an insulin bolus protocol might be useful in brain FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Buchert, R.; Brenner, W.; Apostolova, I.; Mester, J.; Clausen, M. [University Medical Center Hamburg-Eppendorf (Germany). Dept. of Nuclear Medicine; Santer, R. [University Medical Center Hamburg-Eppendorf (Germany). Center for Gynaecology, Obstetrics and Paediatrics; Silverman, D.H.S. [David Geffen School of Medicine at UCLA, Los Angeles, CA (United States). Dept. of Molecular and Medical Pharmacology

    2009-07-01

    FDG PET in hyperglycaemic subjects often suffers from limited statistical image quality, which may hamper visual and quantitative evaluation. In our study the following insulin bolus protocol is proposed for acute correction of hyperglycaemia (> 7.0 mmol/l) in brain FDG PET. (i) Intravenous bolus injection of short-acting insulin, one I.E. for each 0.6 mmol/l blood glucose above 7.0. (ii) If 20 min after insulin administration plasma glucose is {<=} 7.0 mmol/l, proceed to (iii). If insulin has not taken sufficient effect step back to (i). Compute insulin dose with the updated blood glucose level. (iii) Wait further 20 min before injection of FDG. (iv) Continuous supervision of the patient during the whole scanning procedure. The potential of this protocol for improvement of image quality in brain FDG PET in hyperglycaemic subjects was evaluated by computer simulations within the Sokoloff model. A plausibility check of the prediction of the computer simulations on the magnitude of the effect that might be achieved by correction of hyperglycaemia was performed by retrospective evaluation of the relation between blood glucose level and brain FDG uptake in 89 subjects in whom FDG PET had been performed for diagnosis of Alzheimer's disease. The computer simulations suggested that acute correction of hyperglycaemia according to the proposed bolus insulin protocol might increase the FDG uptake of the brain by up to 80%. The magnitude of this effect was confirmed by the patient data. The proposed management protocol for acute correction of hyperglycaemia with insulin has the potential to significantly improve the statistical quality of brain FDG PET images. This should be confirmed in a prospective study in patients. (orig.)

  13. Symptoms of epilepsy and organic brain dysfunctions in patients with acute, brief depression combined with other fluctuating psychiatric symptoms: a controlled study from an acute psychiatric department

    Directory of Open Access Journals (Sweden)

    Linaker Olav M

    2009-09-01

    Full Text Available Abstract Background In psychiatric acute departments some patients present with brief depressive periods accompanied with fluctuating arrays of other psychiatric symptoms like psychosis, panic or mania. For the purpose of the present study we call this condition Acute Unstable Depressive Syndrome (AUDS. The aims of the present study were to compare clinical signs of organic brain dysfunctions and epilepsy in patients with AUDS and Major Depressive Episode (MDE. Methods Out of 1038 consecutive patients admitted to a psychiatric acute ward, 16 patients with AUDS and 16 age- and gender-matched MDE patients were included in the study. Using standardized instruments and methods we recorded clinical data, EEG and MRI. Results A history of epileptic seizures and pathologic EEG activity was more common in the AUDS group than in the MDE group (seizures, n = 6 vs. 0, p = 0.018; pathologic EEG activity, n = 8 vs. 1, p = 0.015. Five patients in the AUDS group were diagnosed as having epilepsy, whereas none of those with MDE had epilepsy (p = 0.043. There were no differences between the groups regarding pathological findings in neurological bedside examination and cerebral MRI investigation. Conclusion Compared to patients admitted with mood symptoms fulfilling DSM 4 criteria of a major depressive disorder, short-lasting atypical depressive symptoms seem to be associated with a high frequency of epileptic and pathologic EEG activity in patients admitted to psychiatric acute departments. Trial registration NCT00201474

  14. The impact of physical therapy in patients with severe traumatic brain injury during acute and post-acute rehabilitation according to coma duration.

    Science.gov (United States)

    Lendraitienė, Eglė; Petruševičienė, Daiva; Savickas, Raimondas; Žemaitienė, Ieva; Mingaila, Sigitas

    2016-07-01

    [Purpose] The aim of study was to evaluate the impact of physical therapy on the recovery of motor and mental status in patients who sustained a severe traumatic brain injury, according to coma duration in acute and post-acute rehabilitation. [Subjects and Methods] The study population comprised patients with levels of consciousness ranging from 3 to 8 according to Glasgow Coma Scale score. The patients were divided into 2 groups based on coma duration as follows: group 1, those who were in a coma up to 1 week, and group 2, those who were in a coma for more than 2 weeks. The recovery of the patients' motor function was evaluated according to the Motor Assessment Scale and the recovery of mental status according to the Mini-Mental State Examination. [Results] The evaluation of motor and mental status recovery revealed that the patients who were in a coma up to 1 week recovered significantly better after physical therapy during the acute rehabilitation than those who were in a coma for longer than 2 weeks. [Conclusion] The recovery of motor and mental status of the patients in acute rehabilitation was significantly better for those in a coma for a shorter period.

  15. A Model for Slicing JAVA Programs Hierarchically

    Institute of Scientific and Technical Information of China (English)

    Bi-Xin Li; Xiao-Cong Fan; Jun Pang; Jian-Jun Zhao

    2004-01-01

    Program slicing can be effectively used to debug, test, analyze, understand and maintain objectoriented software. In this paper, a new slicing model is proposed to slice Java programs based on their inherent hierarchical feature. The main idea of hierarchical slicing is to slice programs in a stepwise way, from package level, to class level, method level, and finally up to statement level. The stepwise slicing algorithm and the related graph reachability algorithms are presented, the architecture of the Java program Analyzing Tool (JATO) based on hierarchical slicing model is provided, the applications and a small case study are also discussed.

  16. Acute brain injury following illicit drug abuse in adolescent and young adult patients: spectrum of neuroimaging findings.

    Science.gov (United States)

    Shrot, Shai; Poretti, Andrea; Tucker, Elizabeth W; Soares, Bruno P; Huisman, Thierry Agm

    2017-04-01

    The use of illicit drugs is currently a major medical problem among adolescents. Several illicit drugs have a high abuse potential and can be neurotoxic causing high morbidity and mortality. The clinical manifestation of adolescents with acute drug-induced neurotoxicity is often characterized by non-specific symptoms and findings. Early diagnosis is important to prevent death and permanent long-term neurological impairments. We report on clinical and neuroimaging findings in five adolescents with acute brain imaging following illicit drug intoxication to highlight the role of neuroimaging findings in the diagnostic work-up of pediatric acute drug-induced neurotoxicity. Our patients reveal two main neuroimaging patterns of brain injury: diffuse symmetric subcortical white matter injury with preferential cerebellar involvement (leukoencephalopathy pattern) or multiple foci of ischemic infarctions in a non-arterial territory distribution (ischemic pattern). Familiarity with these two neuroimaging patterns of findings in the evaluation of magnetic resonance imaging studies in adolescents with acutely altered mental status may suggest the correct diagnosis, narrow the differential diagnosis, and consequently allow early initiation of targeted laboratory investigations and treatment, potentially improving outcome.

  17. Brain temperature measured by {sup 1}H-magnetic resonance spectroscopy in acute and subacute carbon monoxide poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Shunrou; Nishimoto, Hideaki; Murakami, Toshiyuki; Ogawa, Akira; Ogasawara, Kuniaki [Iwate Medical University, Department of Neurosurgery, Morioka, Iwate (Japan); Yoshioka, Yoshichika [Osaka University, Laboratory of Biofunctional Imaging, WPI Immunology Frontier Research Center, Osaka (Japan); Matsuda, Tsuyoshi [MR Applications and Workflow Asia Pacific, GE Healthcare Japan, Tokyo (Japan); Beppu, Takaaki [Iwate Medical University, Department of Neurosurgery, Morioka, Iwate (Japan); Iwate Medical University, Department of Hyperbaric Medicine, Iwate (Japan)

    2016-01-15

    Brain temperature (BT) is associated with the balance between cerebral blood flow and metabolism according to the ''heat-removal'' theory. The present study investigated whether BT is abnormally altered in acute and subacute CO-poisoned patients by using {sup 1}H-magnetic resonance spectroscopy (MRS). Eight adult CO-poisoned patients underwent 3-T magnetic resonance imaging in the acute and subacute phases after CO exposure. MRS was performed on deep cerebral white matter in the centrum semiovale, and MRS-based BT was estimated by the chemical shift difference between water and the N-acetyl aspartate signal. We defined the mean BT + 1.96 standard deviations of the BT in 15 healthy controls as the cutoff value for abnormal BT increases (p < 0.05) in CO-poisoned patients. BT of CO-poisoned patients in both the acute and subacute phases was significantly higher than that of the healthy control group. However, BT in the subacute phase was significantly lower than in the acute phase. On the other hand, no significant difference in body temperature was observed between acute and subacute CO-poisoned patients. BT weakly correlated with body temperature, but this correlation was not statistically significant (rho = 0.304, p = 0.2909). The present results suggest that BT in CO-poisoned patients is abnormally high in the acute phase and remains abnormal in the subacute phase. BT alteration in these patients may be associated with brain perfusion and metabolism rather than other factors such as systemic inflammation and body temperature. (orig.)

  18. Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain.

    Science.gov (United States)

    Cauli, Omar; González-Usano, Alba; Cabrera-Pastor, Andrea; Gimenez-Garzó, Carla; López-Larrubia, Pilar; Ruiz-Sauri, Amparo; Hernández-Rabaza, Vicente; Duszczyk, Malgorzata; Malek, Michal; Lazarewicz, Jerzy W; Carratalá, Arturo; Urios, Amparo; Miguel, Alfonso; Torregrosa, Isidro; Carda, Carmen; Montoliu, Carmina; Felipo, Vicente

    2014-06-01

    Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration.

  19. Altered brain concentrations of citalopram and escitalopram in P-glycoprotein deficient mice after acute and chronic treatment.

    Science.gov (United States)

    Karlsson, Louise; Carlsson, Björn; Hiemke, Christoph; Ahlner, Johan; Bengtsson, Finn; Schmitt, Ulrich; Kugelberg, Fredrik C

    2013-11-01

    According to both in vitro and in vivo data P-glycoprotein (P-gp) may restrict the uptake of several antidepressants into the brain, thus contributing to the poor success rate of current antidepressant therapies. The therapeutic activity of citalopram resides in the S-enantiomer, whereas the R-enantiomer is practically devoid of serotonin reuptake potency. To date, no in vivo data are available that address whether the enantiomers of citalopram and its metabolites are substrates of P-gp. P-gp knockout (abcb1ab (-/-)) and wild-type (abcb1ab (+/+)) mice underwent acute (single-dose) and chronic (two daily doses for 10 days) treatment with citalopram (10mg/kg) or escitalopram (5mg/kg) Serum and brain samples were collected 1-6h after the first or last i.p. injection for subsequent drug analysis by an enantioselective HPLC method. In brain, 3-fold higher concentrations of S- and R-citalopram, and its metabolites, were found in abcb1ab (-/-) mice than in abcb1ab (+/+) mice after both acute and chronic citalopram treatments. After escitalopram treatment, the S-citalopram brain concentration was 3-5 times higher in the knockout mice than in controls. The results provide novel evidence that the enantiomers of citalopram are substrates of P-gp. Possible clinical and toxicological implications of this finding need to be further elucidated.

  20. Reformatted images improve the detection rate of acute traumatic subdural hematomas on brain CT compared with axial images alone.

    Science.gov (United States)

    Amrhein, Timothy J; Mostertz, William; Matheus, Maria Gisele; Maass-Bolles, Genevieve; Sharma, Komal; Collins, Heather R; Kranz, Peter G

    2017-02-01

    Subdural hematomas (SDHs) comprise a significant percentage of missed intracranial hemorrhage on axial brain CT. SDH detection rates could be improved with the addition of reformatted images. Though performed at some centers, the potential additional diagnostic sensitivity of reformatted images has not yet been investigated. The purpose of our study is to determine if the addition of coronal and sagittal reformatted images to an axial brain CT increases the sensitivity and specificity for detection of acute traumatic SDH. We retrospectively reviewed consecutive brain CTs acquired for acute trauma that contained new SDHs. An equivalent number of normal brain CTs served as control. Paired sets of images were created for each case: (1) axial images only ("axial only") and (2) axial, coronal, sagittal images ("reformat added"). Three readers interpreted both the axial only and companion reformat added for each case, separated by 1 month. Reading times and SDH detection rates were compared. One hundred SDH and 100 negative examinations were collected. Sensitivity and specificity for the axial-only scans were 75.7 and 94.3 %, respectively, compared with 88.3 and 98.3 % for reformat added. There was a 24.3 % false negative (missed SDH) rate with axial-only scans versus 11.7 % with reformat added (p = negatives by greater than 50 %. Reformatted images substantially reduce the number of missed SDHs compared with axial images alone.

  1. Cinnamon intake alleviates the combined effects of dietary-induced insulin resistance and acute stress on brain mitochondria.

    Science.gov (United States)

    Couturier, Karine; Hininger, Isabelle; Poulet, Laurent; Anderson, Richard A; Roussel, Anne-Marie; Canini, Frédéric; Batandier, Cécile

    2016-02-01

    Insulin resistance (IR), which is a leading cause of the metabolic syndrome, results in early brain function alterations which may alter brain mitochondrial functioning. Previously, we demonstrated that rats fed a control diet and submitted to an acute restraint stress exhibited a delayed mitochondrial permeability transition pore (mPTP) opening. In this study, we evaluated the combined effects of dietary and emotional stressors as found in western way of life. We studied, in rats submitted or not to an acute stress, the effects of diet-induced IR on brain mitochondria, using a high fat/high fructose diet (HF(2)), as an IR inducer, with addition or not of cinnamon as an insulin sensitizer. We measured Ca(2+) retention capacity, respiration, ROS production, enzymatic activities and cell signaling activation. Under stress, HF(2) diet dramatically decreased the amount of Ca(2+) required to open the mPTP (13%) suggesting an adverse effect on mitochondrial survival. Cinnamon added to the diet corrected this negative effect and resulted in a partial recovery (30%). The effects related to cinnamon addition to the diet could be due to its antioxidant properties or to the observed modulation of PI3K-AKT-GSK3β and MAPK-P38 pathways or to a combination of both. These data suggest a protective effect of cinnamon on brain mitochondria against the negative impact of an HF(2) diet. Cinnamon could be beneficial to counteract deleterious dietary effects in stressed conditions.

  2. Evidence that acute taurine treatment alters extracellular AMP hydrolysis and adenosine deaminase activity in zebrafish brain membranes.

    Science.gov (United States)

    Rosemberg, Denis Broock; Kist, Luiza Wilges; Etchart, Renata Jardim; Rico, Eduardo Pacheco; Langoni, Andrei Silveira; Dias, Renato Dutra; Bogo, Maurício Reis; Bonan, Carla Denise; Souza, Diogo Onofre

    2010-09-06

    Taurine is one of the most abundant free amino acids in excitable tissues. In the brain, extracellular taurine may act as an inhibitory neurotransmitter, neuromodulator, and neuroprotector. Nucleotides are ubiquitous signaling molecules that play crucial roles for brain function. The inactivation of nucleotide-mediated signaling is controlled by ectonucleotidases, which include the nucleoside triphosphate diphosphohydrolase (NTPDase) family and ecto-5'-nucleotidase. These enzymes hydrolyze ATP/GTP to adenosine/guanosine, which exert a modulatory role controlling several neurotransmitter systems. The nucleoside adenosine can be inactivated in extracellular or intracellular milieu by adenosine deaminase (ADA). In this report, we tested whether acute taurine treatment at supra-physiological concentrations alters NTPDase, ecto-5'-nucleotidase, and ADA activities in zebrafish brain. Fish were treated with 42, 150, and 400 mg L(-1) taurine for 1h, the brains were dissected and the enzyme assays were performed. Although the NTPDase activities were not altered, 150 and 400 mg L(-1) taurine increased AMP hydrolysis (128 and 153%, respectively) in zebrafish brain membranes and significantly decreased ecto-ADA activity (29 and 38%, respectively). In vitro assays demonstrated that taurine did not change AMP hydrolysis, whereas it promoted a significant decrease in ecto-ADA activity at 150 and 400 mg L(-1) (24 and 26%, respectively). Altogether, our data provide the first evidence that taurine exposure modulates the ecto-enzymes responsible for controlling extracellular adenosine levels in zebrafish brain. These findings could be relevant to evaluate potential beneficial effects promoted by acute taurine treatment in the central nervous system (CNS) of this species. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  3. Acute Cognitive Impairment After Lateral Fluid Percussion Brain Injury Recovers by One Month: Evaluation by Conditioned Fear Response

    Science.gov (United States)

    Lifshitz, Jonathan; Witgen, Brent M.; Grady, M. Sean

    2007-01-01

    Conditioned fear associates a contextual environment and cue stimulus to a foot shock in a single training trial, where fear expressed to the trained context or cue indicates cognitive performance. Lesion, aspiration or inactivation of the hippocampus and amygdala impair conditioned fear to the trained context and cue, respectively. Moreover, only bilateral experimental manipulations, in contrast to unilateral, abolish cognitive performance. In a model of unilateral brain injury, we sought to test whether a single lateral fluid percussion brain injury impairs cognitive performance in conditioned fear. Brain-injured mice were evaluated for anterograde cognitive deficits, with the hypothesis that acute injury-induced impairments improve over time. Male C57BL/6J mice were brain-injured, trained at five or 27 days post-injury, and tested 48 hours later for recall of the association between the conditioned stimuli (trained context or cue) and the unconditioned stimulus (foot shock) by quantifying fear-associated freezing behavior. A significant anterograde hippocampal-dependent cognitive deficit was observed at seven days in brain-injured compared to sham. Cued fear conditioning could not detect amygdala-dependent cognitive deficits after injury and stereological estimation of amygdala neuron number corroborated this finding. The absence of injury-related freezing in a novel context substantiated injury-induced hippocampal-dependent cognitive dysfunction, rather than generalized fear. Variations in the training and testing paradigms demonstrated a cognitive deficit in consolidation, rather than acquisition or recall. By one month post-injury, cognitive function recovered in brain-injured mice. Hence, the acute injury-induced cognitive impairment may persist while transient pathophysiological sequelae are underway, and improve as global dysfunction subsides. PMID:17169443

  4. Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: evaluation by conditioned fear response.

    Science.gov (United States)

    Lifshitz, Jonathan; Witgen, Brent M; Grady, M Sean

    2007-02-27

    Conditioned fear associates a contextual environment and cue stimulus to a foot shock in a single training trial, where fear expressed to the trained context or cue indicates cognitive performance. Lesion, aspiration or inactivation of the hippocampus and amygdala impair conditioned fear to the trained context and cue, respectively. Moreover, only bilateral experimental manipulations, in contrast to unilateral, abolish cognitive performance. In a model of unilateral brain injury, we sought to test whether a single lateral fluid percussion brain injury impairs cognitive performance in conditioned fear. Brain-injured mice were evaluated for anterograde cognitive deficits, with the hypothesis that acute injury-induced impairments improve over time. Male C57BL/6J mice were brain-injured, trained at 5 or 27 days post-injury, and tested 48h later for recall of the association between the conditioned stimuli (trained context or cue) and the unconditioned stimulus (foot shock) by quantifying fear-associated freezing behavior. A significant anterograde hippocampal-dependent cognitive deficit was observed at 7 days in brain-injured compared to sham. Cued fear conditioning could not detect amygdala-dependent cognitive deficits after injury and stereological estimation of amygdala neuron number corroborated this finding. The absence of injury-related freezing in a novel context substantiated injury-induced hippocampal-dependent cognitive dysfunction, rather than generalized fear. Variations in the training and testing paradigms demonstrated a cognitive deficit in consolidation, rather than acquisition or recall. By 1-month post-injury, cognitive function recovered in brain-injured mice. Hence, the acute injury-induced cognitive impairment may persist while transient pathophysiological sequelae are underway, and improve as global dysfunction subsides.

  5. Blood brain barrier permeability and acute inflammation in two models of traumatic brain injury in the immature rat: a preliminary report.

    Science.gov (United States)

    Adelson, P D; Whalen, M J; Kochanek, P M; Robichaud, P; Carlos, T M

    1998-01-01

    We sought to investigate the course and magnitude of blood brain barrier (BBB) permeability following focal and diffuse traumatic brain injury (TBI) in immature rats and examine the time course of markers of acute inflammation (neutrophil accumulation and E-selectin [E-sel] expression) following these two types of injury. We measured BBB permeability using i.v. injection Evans Blue (EB) and the extent of inflammation using immunohistochemical techniques identifying neutrophils (monoclonal antibody RP-3) and the endothelial adhesion molecule, E-selectin. Male Sprague-Dawley immature (17 day-old) rats (30-45 g, n = 80) were subjected to a controlled cortical impact (CCI: 2 mm, 4 m/s), a closed head diffuse injury (DI: 150 g/2m) or a corresponding sham procedure (with or without craniotomy). EB was injected i.v. at 30 min before sacrifice, which occurred at 1 h, 4 h, or 24 h after injury. BBB permeability was observed in both the CCI and DI rats at 1 h after injury which largely resolved by 24 h. In the CCI, EB extravasation was seen within and around the contusion. In DI, diffuse BBB permeability was seen. DI was not associated with acute inflammation since there was neither neutrophil accumulation nor E-selectin expression. The CCI rats though had 5.1 +/- 2.2 neutrophils/hpf and 3.0 +/- 0.4 endothelial cells/hpf expressing E-selectin (mean +/- SEM) (both p < 0.05 vs sham and DI). These data suggest that BBB breakdown occurs in the immature rat after both focal and diffuse TBI. This early BBB permeability was not associated with acute inflammation in DI but was in CCI. These data also suggest that contusion is a key factor in the development of a traditional acute inflammatory response after TBI in the immature rat.

  6. Calcium Imaging of AM Dyes Following Prolonged Incubation in Acute Neuronal Tissue.

    Science.gov (United States)

    Cameron, Morven; Kékesi, Orsolya; Morley, John W; Tapson, Jonathan; Breen, Paul P; van Schaik, André; Buskila, Yossi

    2016-01-01

    Calcium-imaging is a sensitive method for monitoring calcium dynamics during neuronal activity. As intracellular calcium concentration is correlated to physiological and pathophysiological activity of neurons, calcium imaging with fluorescent indicators is one of the most commonly used techniques in neuroscience today. Current methodologies for loading calcium dyes into the tissue require prolonged incubation time (45-150 min), in addition to dissection and recovery time after the slicing procedure. This prolonged incubation curtails experimental time, as tissue is typically maintained for 6-8 hours after slicing. Using a recently introduced recovery chamber that extends the viability of acute brain slices to more than 24 hours, we tested the effectiveness of calcium AM staining following long incubation periods post cell loading and its impact on the functional properties of calcium signals in acute brain slices and wholemount retinae. We show that calcium dyes remain within cells and are fully functional >24 hours after loading. Moreover, the calcium dynamics recorded >24 hrs were similar to the calcium signals recorded in fresh tissue that was incubated for 24hrs after dissection. These methods will not only extend experimental time for those using acute neuronal tissue, but also may reduce the number of animals required to complete experimental goals.

  7. Study on changes of partial pressure of brain tissue oxygen and brain temperature in acute phase of severe head injury during mild hypothermia therapy

    Institute of Scientific and Technical Information of China (English)

    朱岩湘; 姚杰; 卢尚坤; 章更生; 周关仁

    2003-01-01

    Objective: To study the changes of partial pressure of brain tissue oxygen (PbtO2) and brain temperature in acute phase of severe head injury during mild hypothermia therapy and the clinical significance.Methods: One hundred and sixteen patients with severe head injury were selected and divided into a mild hypothermia group (n=58), and a control group (n=58) according to odd and even numbers of hospitalization. While mild hypothermia therapy was performed PbtO2 and brain temperature were monitored for 1-7 days (mean=86 hours), simultaneously, the intracranial pressure, rectum temperature, cerebral perfusion pressure, PaO2 and PaCO2 were also monitored. The patients were followed up for 6 months and the prognosis was evaluated with GOS (Glasgow outcome scale).Results: The mean value of PbtO2 within 24 hour monitoring in the 116 patients was 13.7 mm Hg±4.94 mm Hg, lower than the normal value (16 mm Hg±40 mm Hg) The time of PbtO2 recovering to the normal value in the mild hypothermia group was shortened by 10±4.15 hours compared with the control group (P<0.05). The survival rate of the mild hypothermia group was 60.43%, higher than that of the control group (46.55%). After the recovery of the brain temperature, PbtO2 increased with the rise of the brain temperature. Conclusions: Mild hypothermia can improve the survival rate of severe head injury. The technique of monitoring PbtO2 and the brain temperature is safe and reliable, and has important clinical significance in judging disease condition and instructing clinical therapy.

  8. Acute Effects of Viral Exposure on P-Glycoprotein Function in the Mouse Fetal Blood-Brain Barrier

    Directory of Open Access Journals (Sweden)

    Enrrico Bloise

    2017-02-01

    Full Text Available Background/Aims: Viral infection during pregnancy is known to affect the fetal brain. The toll-like receptor (TLR-3 is a pattern recognition receptor activated by viruses known to elicit adverse fetal neurological outcomes. The P-glycoprotein (P-gp efflux transporter protects the developing fetus by limiting the transfer of substrates across both the placenta and the fetal blood-brain barrier (BBB. As such, inhibition of P-gp at these blood-barrier sites may result in increased exposure of the developing fetus to environmental toxins and xenobiotics present in the maternal circulation. We hypothesized that viral exposure during pregnancy would impair P-gp function in the placenta and in the developing BBB. Here we investigated whether the TLR-3 ligand, polyinosinic:polycytidylic acid (PolyI:C, increased accumulation of one P-gp substrate in the fetus and in the developing fetal brain. Methods: Pregnant C57BL/6 mice (GD15.5 were injected (i.p. with PolyI:C (5 mg/kg or 10 mg/kg or vehicle (saline. [3H]digoxin (P-gp substrate was injected (i.v. 3 or 23h post-treatment and animals were euthanized 1h later. Maternal plasma, ‘fetal-units’ (fetal membranes, amniotic fluid and whole fetus, and fetal brains were collected. Results: PolyI:C exposure (4h significantly elevated maternal plasma IL-6 (P<0.001 and increased [3H]digoxin accumulation in the fetal brain (P<0.05. In contrast, 24h after PolyI:C exposure, no effect on IL-6 or fetal brain accumulation of P-gp substrate was observed. Conclusion: Viral infection modeled by PolyI:C causes acute increases in fetal brain accumulation of P-gp substrates and by doing so, may increase fetal brain exposure to xenobiotics and environmental toxins present in the maternal circulation.

  9. Acute high-intensity exercise-induced cognitive enhancement and brain-derived neurotrophic factor in young, healthy adults.

    Science.gov (United States)

    Hwang, Jungyun; Brothers, R Matthew; Castelli, Darla M; Glowacki, Elizabeth M; Chen, Yen T; Salinas, Mandy M; Kim, Jihoon; Jung, Yeonhak; Calvert, Hannah G

    2016-09-06

    Acute exercise can positively impact cognition. The present study examined the effect of acute high-intensity aerobic exercise on prefrontal-dependent cognitive performance and brain-derived neurotrophic factor (BDNF). Fifty-eight young adults were randomly assigned to one of two experimental groups: (a) an acute bout of high-intensity exercise (n=29) or (b) a non-exercise control (n=29). Participants in the exercise group improved performance on inhibitory control in Stroop interference and on cognitive flexibility in Trail Making Test (TMT) Part-B compared with participants in the control group and increased BDNF immediately after exercise. There was a significant relationship between BDNF and TMT Part-B on the pre-post change following exercise. These findings provide support for the association between improved prefrontal-dependent cognitive performance and increased BDNF in response to acute exercise. We conclude that the changes in BDNF concentration may be partially responsible for prefrontal-dependent cognitive functioning following an acute bout of exercise.

  10. Changes in Glutamate/NMDA Receptor Subunit 1 Expression in Rat Brain after Acute and Subacute Exposure to Methamphetamine

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    Walailuk Kerdsan

    2009-01-01

    Full Text Available Methamphetamine (METH is a psychostimulant drug of abuse that produces long-term behavioral changes including behavioral sensitization, tolerance, and dependence. METH has been reported to induce neurotoxic effects in several areas of the brain via the dopaminergic system. Changes of dopamine function can induce malfunction of the glutamatergic system. Therefore, the aim of the present study was to examine the effects of METH administration on the expression of glutamate N-methyl-D-aspartate receptor subunit 1 (NMDAR1 in frontal cortex, striatum, and hippocampal formation after acute and subacute exposure to METH by western blotting. Male Sprague-Dawley rats were injected intraperitoneally with a single dose of 8 mg/kg METH, 4 mg/kg/day METH for 14 days and saline in acute, subacute, and control groups, respectively. A significant increase in NMDAR1 immunoreactive protein was found in frontal cortex in the subacute group (P=.036 but not in the acute group (P=.580. Moreover, a significant increase in NMDAR1 was also observed in striatum in both acute (P=.025 and subacute groups (P=.023. However, no significant differences in NMDAR1 in hippocampal formation were observed in either acute or subacute group. The results suggest that an upregulation of NMDA receptor expression may be a consequence of glutamatergic dysfunction induced by METH.

  11. Distributed Slicing in Dynamic Systems

    CERN Document Server

    Fernandez, Antonio; Jimenez, Ernesto; Kermarrec, Anne-Marie; Raynal, Michel

    2007-01-01

    Peer to peer (P2P) systems are moving from application specific architectures to a generic service oriented design philosophy. This raises interesting problems in connection with providing useful P2P middleware services capable of dealing with resource assignment and management in a large-scale, heterogeneous and unreliable environment. The slicing service, has been proposed to allow for an automatic partitioning of P2P networks into groups (slices) that represent a controllable amount of some resource and that are also relatively homogeneous with respect to that resource. In this paper we propose two gossip-based algorithms to solve the distributed slicing problem. The first algorithm speeds up an existing algorithm sorting a set of uniform random numbers. The second algorithm statistically approximates the rank of nodes in the ordering. The scalability, efficiency and resilience to dynamics of both algorithms rely on their gossip-based models. These algorithms are proved viable theoretically and experimenta...

  12. Branched chain amino acid transaminase and branched chain alpha-ketoacid dehydrogenase activity in the brain, liver and skele­tal muscle of acute hepatic failure rats

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    Takei,Nobuyuki

    1985-02-01

    Full Text Available Branched chain amino acid (BCAA transaminase activity increased in both the mitochondrial and supernatant fractions of brain from hepatic failure rats, in which a partial hepatectomy was performed 24h following carbon tetrachloride (CCl4 administration, although the activity of liver and skeletal muscle was the same as in control rats. The elevation of mitochondrial BCAA transaminase activity in liver-injured rats was partly due to increased activity of brain specific Type III isozyme. Branched chain alpha-ketoacid (BCKA dehydrogenase in the brain homogenates was not significantly altered in acute hepatic failure rats, while the liver enzyme activity was markedly diminished. BCKA dehydrogenase activity in the brain homogenates was inhibited by adding ATP to the assay system, and was activated in vitro by preincubating the brain homogenate at 37 degrees C for 15 min. These findings suggest that brain BCAA catabolism is accelerated in acute hepatic failure rats.

  13. Alteration of Plasma Brain Natriuretic Peptide Level After Acute Moderate Exercise in Professional Athletes

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    Homa Sheikhani

    2011-12-01

    Full Text Available Background: Cardiac fatigue or myocardial damage following exercise until complete exhaustion can increase blood levels of brain natriuretic peptide (BNP in athletes. Objectives: The aim of the present study was to investigate the effect of resistance and acute moderate aerobic exercise on alterations in BNP levels in professional athletes. Materials and Methods: Forty professional athletes who had at least 3 years of a championship background in track and field (aerobic group or body building (resistance group volunteered to participate in the present study. Track and field athletes (n = 20 were requested to run 8 km at 60% to 70% of maximum heart rate. Body building athletes (n = 20 performed a resistance training session of 5 exercises in 3 sets of 10 repetitions at 75% of 1 RM (bench press, seated row, leg extension, leg curl, and leg press. Before and immediately after the exercise, plasma BNP levels of both groups of athletes were measured by PATHFASTTM NT-proBNP assay, an immunochemiluminescent assay using two polyclonal antibodies in sandwich test format, on a PATHFASTTM automated analyzer. Results: Plasma BNP levels immediately following exercise increased significantly as compared with baseline values. Plasma BNP concentrations in the aerobic group were significantly higher than in the resistance group before and after exercise. Moreover, the increase in mean BNP concentrations in aerobic athletes was 7 times more than in resistance athletes. Conclusions: BNP levels in athlete who performed distance exercises increased significantly compared with resistance training. Possibly exercise program type, intensity of exercise, volume of exercise program, and field sport can be factors of changes in BNP levels

  14. Cognitive Training for Post-Acute Traumatic Brain Injury: A Systematic Review and Meta-Analysis

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    Harry Hallock

    2016-10-01

    Full Text Available Objective: To quantitatively aggregate effects of cognitive training (CT on cognitive and functional outcome measures in patients with traumatic brain injury (TBI more than 12-months post-injury.Design: We systematically searched six databases for non-randomized and randomized controlled trials (RCTs of CT in TBI patients at least 12-months post-injury reporting cognitive and/or functional outcomes. Main Measures: Efficacy was measured as standardized mean difference (Hedges’ g of post-training change. We investigated heterogeneity across studies using subgroup analyses and meta-regressions. Results: Fourteen studies encompassing 575 patients were included. The effect of CT on overall cognition was small and statistically significant (g=0.22, 95%CI 0.05 to 0.38; p=0.01, with low heterogeneity (I2=11.71% and no evidence of publication bias. A moderate effect size was found for overall functional outcomes (g=0.32, 95%CI 0.08 to 0.57, p=0.01 with low heterogeneity (I2=14.27% and possible publication bias. Statistically significant effects were also found only for executive function (g=0.20, 95%CI 0.02 to 0.39, p=0.03 and verbal memory (g=0.32, 95%CI 0.14 to 0.50, p<0.01. Conclusions: Despite limited studies in this field, this meta-analysis indicates that CT is modestly effective in improving cognitive and functional outcomes in patients with post-acute TBI and should therefore play a more significant role in TBI rehabilitation.

  15. Acute tryptophan depletion attenuates brain-heart coupling following external feedback

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    Erik M Mueller

    2012-04-01

    Full Text Available External and internal performance feedback triggers neural and visceral modulations such as reactions in the medial prefrontal cortex and insulae or changes of heart period (HP. The functional coupling of neural and cardiac responses following feedback (cortico-cardiac connectivity is not well understood. While linear time-lagged within-subjects correlations of single-trial EEG and HP (cardio-electroencephalographic covariance-tracing, CECT indicate a robust negative coupling of EEG magnitude 300 ms after presentation of an external feedback stimulus with subsequent alterations of heart period (the so-called N300H phenomenon, the neurotransmitter systems underlying feedback-evoked cortico-cardiac connectivity are largely unknown. Because it has been shown that acute tryptophan depletion (ATD, attenuating brain serotonin (5-HT, decreases cardiac but not neural correlates of feedback processing, we hypothesized that 5-HT may be involved in feedback-evoked cortico-cardiac connectivity. In a placebo-controlled double-blind crossover design, twelve healthy participants received a tryptophan-free amino-acid drink at one session and a balanced amino-acid control-drink on another and twice performed a time-estimation task with feedback presented after each trial. N300H magnitude and plasma tryptophan levels were assessed. Results indicated a robust N300H after the control drink, which was significantly attenuated following ATD. Moreover, plasma tryptophan levels during the control session were correlated with N300H amplitude such that individuals with lower tryptophan levels showed reduced N300H. Together, these findings indicate that 5-HT is important for feedback-induced covariation of cortical and cardiac activity. Because individual differences in anxiety have previously been linked to 5-HT, cortico-cardiac coupling and feedback processing, the present findings may be particularly relevant for futures studies linking 5-HT to anxiety.

  16. Findings of chronic sinusitis on brain computed tomography are not associated with acute headaches.

    Science.gov (United States)

    Kroll, Katherine E; Camacho, Marc A; Gautam, Shiva; Levenson, Robin B; Edlow, Jonathan A

    2014-06-01

    Headache is a common complaint in emergency department (ED) patients. Nearly 15% of ED headache patients will have brain computed tomography (CT) done. One frequent finding on these scans is "chronic sinusitis." Assuming that "chronic sinusitis" is the cause of the patient's headache is a potential source of mis-diagnosis. We hypothesized that CT findings of chronic sinusitis occur with equal frequency in patients with atraumatic headache as in control patients with minor head injury. This is a retrospective, single-center medical record review of consecutive discharged patients who received noncontrast head CT scans in an urban ED for either minor closed head injury or atraumatic headache. Each patient's head CT radiologic report was reviewed for findings of sinusitis and classified as chronic sinusitis, indeterminate for sinusitis, air-fluid levels, or no findings of sinusitis. We enrolled 500 patients (234 in the atraumatic headache group, 266 in the minor head injury group). The two groups were similar except that more women were enrolled in the atraumatic headache group. CT findings of chronic sinusitis in the atraumatic headache group (22.2%) and the minor head injury group (17.7%; difference 4.5%; 95% confidence interval of -2.5-11.6%). Prevalence of CT findings of sinusitis in ED patients with atraumatic headaches and mild head injury are similar. This strongly suggests that CT findings of chronic sinusitis in patients with atraumatic headache may be incidental, and are rarely the cause of a patient's acute headache. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Acute hyperglycemia worsens ischemic stroke-induced brain damage via high mobility group box-1 in rats.

    Science.gov (United States)

    Huang, Jingyang; Liu, Baoyi; Yang, Chenghui; Chen, Haili; Eunice, Dzivor; Yuan, Zhongrui

    2013-10-16

    Hyperglycemia adversely affects the outcome of ischemic stroke. Extracellular HMGB1 plays a role in aggravating brain damage in the postischemic brain. The aim of this study was to determine whether the extracellular HMGB1 is involved in the worsened ischemic damage during hyperglycemic stroke. Male Wistar rats underwent middle cerebral artery occlusion (MCAO) for 90 min with reperfusion. Acute hyperglycemia was induced by an injection of 50% dextrose. Rats received glycyrrhizin, a specific HMGB1 inhibitor, or vehicle. HMGB-1 in cerebrospinal fluid and in brain parenchyma was detected at 2 or 4 h post-reperfusion. Neurological deficits, infarct volume and cerebral edema were assessed 24 h post-MCAO the disruption of blood-brain barrier (BBB) and the expression of tight junction protein Occludin were measured at 4 h post-reperfusion. Hyperglycemia enhanced the early release of HMGB1 from ischemic brain tissue, which was accompanied by increased infarct volume, neurological deficit, cerebral edema and BBB disruption. Glycyrrhizin alleviated the aggravation of infarct volume, neurological deficit, cerebral edema and BBB disruption by decreasing the degradation of tight junction protein Occludin in the ischemic hemisphere of hyperglycemic rats. In conclusion, enhanced early extracellular release of HMGB1 might represent an important mechanism for worsened ischemic damage, particularly early BBB disruption, during hyperglycemic stroke. An HMGB1 inhibitor glycyrrhizin is a potential therapeutic option for hyperglycemic stroke.

  18. Inflammatory responses are not sufficient to cause delayed neuronal death in ATP-induced acute brain injury.

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    Hey-Kyeong Jeong

    Full Text Available BACKGROUND: Brain inflammation is accompanied by brain injury. However, it is controversial whether inflammatory responses are harmful or beneficial to neurons. Because many studies have been performed using cultured microglia and neurons, it has not been possible to assess the influence of multiple cell types and diverse factors that dynamically and continuously change in vivo. Furthermore, behavior of microglia and other inflammatory cells could have been overlooked since most studies have focused on neuronal death. Therefore, it is essential to analyze the precise roles of microglia and brain inflammation in the injured brain, and determine their contribution to neuronal damage in vivo from the onset of injury. METHODS AND FINDINGS: Acute neuronal damage was induced by stereotaxic injection of ATP into the substantia nigra pars compacta (SNpc and the cortex of the rat brain. Inflammatory responses and their effects on neuronal damage were investigated by immunohistochemistry, electron microscopy, quantitative RT-PCR, and stereological counting, etc. ATP acutely caused death of microglia as well as neurons in a similar area within 3 h. We defined as the core region the area where both TH(+ and Iba-1(+ cells acutely died, and as the penumbra the area surrounding the core where Iba-1(+ cells showed activated morphology. In the penumbra region, morphologically activated microglia arranged around the injury sites. Monocytes filled the damaged core after neurons and microglia died. Interestingly, neither activated microglia nor monocytes expressed iNOS, a major neurotoxic inflammatory mediator. Monocytes rather expressed CD68, a marker of phagocytic activity. Importantly, the total number of dopaminergic neurons in the SNpc at 3 h (∼80% of that in the contralateral side did not decrease further at 7 d. Similarly, in the cortex, ATP-induced neuron-damage area detected at 3 h did not increase for up to 7 d. CONCLUSIONS: Different cellular

  19. Acute antipsychotic treatments induce distinct c-Fos expression patterns in appetite-related neuronal structures of the rat brain.

    Science.gov (United States)

    Rajkumar, Ramamoorthy; See, Lionel Kee Yon; Dawe, Gavin Stewart

    2013-05-01

    A number of atypical antipsychotic drugs are known to perturb appetite regulation causing greater hyperphagia in humans and rodents than earlier generation typical agents. However, the neuronal structures that underlie hyperphagic effects are poorly understood. Arcuate nucleus (ArcN), paraventricular hypothalamic nucleus (PVN), paraventricular thalamic nucleus (PVA) and nucleus incertus (NI) have been implicated in appetite regulation. The NI is the principal source of the relaxin-3 (RLN3) peptide, which is reported to have orexigenic effects. Moreover, ArcN, PVN, and PVA receive RLN3 immunoreactive fibers from the NI and express relaxin family peptide type 3 (RXFP3) receptor. The present study was designed to evaluate the acute effects of clozapine (atypical), chlorpromazine (typical) and fluphenazine (typical) on c-Fos expression (a marker of neuronal response) in these appetite-related centers of the rat brain. The numbers of c-Fos expressing neurons in these structures were counted in immunofluorescence stained brain sections. Acute treatment with clozapine, chlorpromazine and fluphenazine differentially influenced c-Fos expression in these brain structures. This study is also the first demonstration that antipsychotics influence the NI. The patterns of the effects of these antipsychotics are related to their reported hyperphagic properties.

  20. The acute phase of mild traumatic brain injury is characterized by a distance-dependent neuronal hypoactivity.

    Science.gov (United States)

    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.

  1. Translational neurochemical research in acute human brain injury: the current status and potential future for cerebral microdialysis.

    Science.gov (United States)

    Hillered, Lars; Vespa, Paul M; Hovda, David A

    2005-01-01

    Microdialysis (MD) was introduced as an intracerebral sampling method for clinical neurosurgery by Hillered et al. and Meyerson et al. in 1990. Since then MD has been embraced as a research tool to measure the neurochemistry of acute human brain injury and epilepsy. In general investigators have focused their attention to relative chemical changes during neurointensive care, operative procedures, and epileptic seizure activity. This initial excitement surrounding this technology has subsided over the years due to concerns about the amount of tissue sampled and the complicated issues related to quantification. The interpretation of mild to moderate MD fluctuations in general remains an issue relating to dynamic changes of the architecture and size of the interstitial space, blood-brain barrier (BBB) function, and analytical imprecision, calling for additional validation studies and new methods to control for in vivo recovery variations. Consequently, the use of this methodology to influence clinical decisions regarding the care of patients has been restricted to a few institutions. Clinical studies have provided ample evidence that intracerebral MD monitoring is useful for the detection of overt adverse neurochemical conditions involving hypoxia/ischemia and seizure activity in subarachnoid hemorrhage (SAH), traumatic brain injury (TBI), thromboembolic stroke, and epilepsy. There is some data strongly suggesting that MD changes precede the onset of secondary neurological deterioration following SAH, hemispheric stroke, and surges of increased ICP in fulminant hepatic failure. These promising investigations have relied on MD-markers for disturbed glucose metabolism (glucose, lactate, and pyruvate) and amino acids. Others have focused on trying to capture other important neurochemical events, such as excitotoxicity, cell membrane degradation, reactive oxygen species (ROS) and nitric oxide (NO) formation, cellular edema, and BBB dysfunction. However, these other

  2. Brain-derived neurotrophic factor (BDNF as a potential mechanism of the effects of acute exercise on cognitive performance

    Directory of Open Access Journals (Sweden)

    Aaron T. Piepmeier

    2015-03-01

    Full Text Available The literature shows that improvements in cognitive performance may be observed following an acute bout of exercise. However, evidence in support of the biological mechanisms of this effect is still limited. Findings from both rodent and human studies suggest brain-derived neurotrophic factor (BDNF as a potential mechanism of the effect of acute exercise on memory. The molecular properties of BDNF allow this protein to be assessed in the periphery (pBDNF (i.e., blood serum, blood plasma, making measurements of acute exercise-induced changes in BDNF concentration relatively accessible. Studies exploring the acute exercise–pBDNF–cognitive performance relationship have had mixed findings, but this may be more reflective of methodological differences between studies than it is a statement about the role of BDNF. For example, significant associations have been observed between acute exercise-induced changes in pBDNF concentration and cognitive performance in studies assessing memory, and non-significant associations have been found in studies assessing non-memory cognitive domains. Three suggestions are made for future research aimed at understanding the role of BDNF as a biological mechanism of this relationship: 1 Assessments of cognitive performance may benefit from a focus on various types of memory (e.g., relational, spatial, long-term; 2 More fine-grained measurements of pBDNF will allow for the assessment of concentrations of specific isoforms of the BDNF protein (i.e., immature, mature; 3 Statistical techniques designed to test the mediating role of pBDNF in the acute exercise-cognitive performance relationship should be utilized in order to make causal inferences.

  3. Abnormalities on magnetic resonance imaging seen acutely following mild traumatic brain injury: correlation with neuropsychological tests and delayed recovery

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, David G.; Jackson, Alan [Department of Neuroradiology, Hope Hospital, M6 8HD, Salford (United Kingdom); Mason, Damon L.; Berry, Elizabeth [Department of Behavioural Medicine, Hope Hospital, M6 8HD, Salford (United Kingdom); Hollis, Sally [Medical Statistics Unit, Lancaster University, Lancaster (United Kingdom); Yates, David W. [Department of Emergency Medicine, Hope Hospital, M6 8HD, Salford (United Kingdom)

    2004-07-01

    Mild traumatic brain injury (MTBI) is a common reason for hospital attendance and is associated with significant delayed morbidity. We studied a series of 80 persons with MTBI. Magnetic resonance imaging (MRI) and neuropsychological testing were used in the acute phase and a questionnaire for post-concussion syndrome (PCS) and return to work status at 6 months. In 26 subjects abnormalities were seen on MRI, of which 5 were definitely traumatic. There was weak correlation with abnormal neuropsychological tests for attention in the acute period. There was no significant correlation with a questionnaire for PCS and return to work status. Although non-specific abnormalities are frequently seen, standard MRI techniques are not helpful in identifying patients with MTBI who are likely to have delayed recovery. (orig.)

  4. Trimethyltin (TMT) neurotoxicity in organotypic rat hippocampal slice cultures

    DEFF Research Database (Denmark)

    Noraberg, J; Gramsbergen, J B; Fonnum, F

    1998-01-01

    The neurotoxic effects of trimethyltin (TMT) on the hippocampus have been extensively studied in vivo. In this study, we examined whether the toxicity of TMT to hippocampal neurons could be reproduced in organotypic brain slice cultures in order to test the potential of this model for neurotoxico......The neurotoxic effects of trimethyltin (TMT) on the hippocampus have been extensively studied in vivo. In this study, we examined whether the toxicity of TMT to hippocampal neurons could be reproduced in organotypic brain slice cultures in order to test the potential of this model...... for neurotoxicological studies, including further studies of neurotoxic mechanisms of TMT. Four-week-old cultures, derived from 7-day-old donor rats and grown in serum-free medium, were exposed to TMT (0.5-100 microM) for 24 h followed by 24 h in normal medium. TMT-induced neurodegeneration was then monitored by (a...... of TMT neurotoxicity....

  5. Postmortem changes in lungs in severe closed traumatic brain injury complicated by acute respiratory failure

    Directory of Open Access Journals (Sweden)

    V. A. Tumanskiy

    2013-08-01

    Full Text Available V.А. Tumanskіy, S.І. Ternishniy, L.M. Tumanskaya Pathological changes in the lungs were studied in the work of 42 patiens who died from severe closed intracranial injury (SCII. It was complicated with acute respiratory insufficient (ARI. The most modified subpleural areas were selected from every lobe of the lungs for pathological studies. Prepared histological sections were stained by means of hemotoxylin and eosin and by Van Giеson for light microscopy. The results of the investigation have shown absence of the significant difference of pathological changes in the lungs of patients who died from ARI because of severe brain injury and traumatic intracranial hemorrhage. Pathognomic pathological changes in the lungs as a result of acute lung injury syndrome (ALIS were found in deceased patients on the third day since the SCII (n=8. There was a significant bilateral interstitial edema and mild alveolar edema with the presence of red and blood cells in the alveoli, vascular plethora of the septum interalveolar and stasis of blood in the capillaries, the slight pericapillary leukocyte infiltration, subpleural hemorrhage and laminar pulmonary atelectasis. In deceased patients on 4-6 days after SCII that was complicated with ARI (n=14, morphological changes had been detected in the lungs. It was pathognomic for acute respiratory distress syndrome (ARDS with local pneumonic to be layered. A significant interstitial pulmonary edema was observed in the respiratory part of the lungs. The edema has spread from the walls of the alveoli into the interstitial spaces of the bronchioles and blood vessels, and also less marked serous-hemorrhagic alveolar edema with presence of the fibrin in the alveoli and macrophages. The ways of intrapleural lymphatic drainage were dilatated. Histopathological changes in the lungs of those who died on the 7-15th days after severe closed craniocerebral injury with ARI to be complicated (n=12 have been indicative of two

  6. Altered free radical metabolism in acute mountain sickness: implications for dynamic cerebral autoregulation and blood-brain barrier function

    DEFF Research Database (Denmark)

    Bailey, D M; Evans, K A; James, P E

    2008-01-01

    (2)) and following 6 h passive exposure to hypoxia (12% O(2)). Blood flow velocity in the middle cerebral artery (MCAv) and mean arterial blood pressure (MAP) were measured for determination of CA following calculation of transfer function analysis and rate of regulation (RoR). Nine subjects......We tested the hypothesis that dynamic cerebral autoregulation (CA) and blood-brain barrier (BBB) function would be compromised in acute mountain sickness (AMS) subsequent to a hypoxia-mediated alteration in systemic free radical metabolism. Eighteen male lowlanders were examined in normoxia (21% O...

  7. Two-dimensional zymography differentiates gelatinase isoforms in stimulated microglial cells and in brain tissues of acute brain injuries.

    Science.gov (United States)

    Chen, Shanyan; Meng, Fanjun; Chen, Zhenzhou; Tomlinson, Brittany N; Wesley, Jennifer M; Sun, Grace Y; Whaley-Connell, Adam T; Sowers, James R; Cui, Jiankun; Gu, Zezong

    2015-01-01

    Excessive activation of gelatinases (MMP-2/-9) is a key cause of detrimental outcomes in neurodegenerative diseases. A single-dimension zymography has been widely used to determine gelatinase expression and activity, but this method is inadequate in resolving complex enzyme isoforms, because gelatinase expression and activity could be modified at transcriptional and posttranslational levels. In this study, we investigated gelatinase isoforms under in vitro and in vivo conditions using two-dimensional (2D) gelatin zymography electrophoresis, a protocol allowing separation of proteins based on isoelectric points (pI) and molecular weights. We observed organomercuric chemical 4-aminophenylmercuric acetate-induced activation of MMP-2 isoforms with variant pI values in the conditioned medium of human fibrosarcoma HT1080 cells. Studies with murine BV-2 microglial cells indicated a series of proform MMP-9 spots separated by variant pI values due to stimulation with lipopolysaccharide (LPS). The MMP-9 pI values were shifted after treatment with alkaline phosphatase, suggesting presence of phosphorylated isoforms due to the proinflammatory stimulation. Similar MMP-9 isoforms with variant pI values in the same molecular weight were also found in mouse brains after ischemic and traumatic brain injuries. In contrast, there was no detectable pI differentiation of MMP-9 in the brains of chronic Zucker obese rats. These results demonstrated effective use of 2D zymography to separate modified MMP isoforms with variant pI values and to detect posttranslational modifications under different pathological conditions.

  8. Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After Traumatic Brain Injury

    Science.gov (United States)

    2016-07-01

    removal of excess glutamate from the brain. Scope: We will test this novel and powerful neuroprotective treatment in a rat model of repetitive mild...produce a brain-to-blood gradient of glutamate which will enhance the removal of excess glutamate from the brain. We will test this novel and powerful ...not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION

  9. The acute phase response and soman-induced status epilepticus: temporal, regional and cellular changes in rat brain cytokine concentrations

    Directory of Open Access Journals (Sweden)

    Kan Robert K

    2010-07-01

    Full Text Available Abstract Background Neuroinflammation occurs following brain injury, including soman (GD induced status epilepticus (SE, and may contribute to loss of neural tissue and declined behavioral function. However, little is known about this important pathological process following GD exposure. Limited transcriptional information on a small number of brain-expressed inflammatory mediators has been shown following GD-induced SE and even less information on protein upregulation has been elucidated. The purpose of this study is to further characterize the regional and temporal progression of the neuroinflammatory process following acute GD-induced SE. Methods The protein levels of 10 cytokines was quantified using bead multiplex immunoassays in damaged brain regions (i.e., piriform cortex, hippocampus and thalamus up to 72 hours following seizure onset. Those factors showing significant changes were then localized to neural cells using fluorescent IHC. Results A significant concentration increase was observed in all injured brain regions for four acute phase response (APR induction cytokines: interleukin (IL-1α, IL-1β, IL-6, and tumor necrosis factor (TNF-α. Increases in these APR cytokines corresponded both temporally and regionally to areas of known seizure damage and neuronal death. Neurotoxic cytokines IL-1α and IL-1β were primarily expressed by activated microglia whereas the potentially neuroprotective cytokine IL-6 was expressed by neurons and hypertrophic astrocytes. Conclusions Increases in neurotoxic cytokines likely play an active role in the progression of GD-induced SE neuropathology though the exact role that these and other cytokines play in this process require further study.

  10. Effect of slice orientation on reproducibility of fMRI motor activation at 3 Tesla.

    Science.gov (United States)

    Gustard, S; Fadili, J; Williams, E J; Hall, L D; Carpenter, T A; Brett, M; Bullmore, E T

    2001-12-01

    The effect of slice orientation on reproducibility and sensitivity of 3T fMRI activation using a motor task has been investigated in six normal volunteers. Four slice orientations were used; axial, oblique axial, coronal and sagittal. We applied analysis of variance (ANOVA) to suprathreshold voxel statistics to quantify variability in activation between orientations and between subjects. We also assessed signal detection accuracy in voxels across the whole brain by using a finite mixture model to fit receiver operating characteristic (ROC) curves to the data. Preliminary findings suggest that suprathreshold cluster characteristics demonstrate high motor reproducibility across subjects and orientations, although a significant difference between slice orientations in number of activated voxels was demonstrated in left motor cortex but not cerebellum. Subtle inter-orientation differences are highlighted in the ROC analyses, which are not obvious by ANOVA; the oblique axial slice orientation offers the highest signal detection accuracy, whereas coronal slices give the lowest.

  11. Surviving Traumatic Brain Injury: A Study of Post Acute Rehabilitation Services.

    Science.gov (United States)

    Schuyler, Suellen

    The problems facing a rehabilitation counselor in successfully working with survivors of brain trauma are myriad. This review examined evaluation techniques, rehabilitation therapies, and existing services that have proven effective with traumatic brain injury (TBI) clients. There is a gap in rehabilitation services that results in the TBI…

  12. GFAP-BDP as an acute diagnostic marker in traumatic brain injury: results from the prospective transforming research and clinical knowledge in traumatic brain injury study.

    Science.gov (United States)

    Okonkwo, David O; Yue, John K; Puccio, Ava M; Panczykowski, David M; Inoue, Tomoo; McMahon, Paul J; Sorani, Marco D; Yuh, Esther L; Lingsma, Hester F; Maas, Andrew I R; Valadka, Alex B; Manley, Geoffrey T

    2013-09-01

    Reliable diagnosis of traumatic brain injury (TBI) is a major public health need. Glial fibrillary acidic protein (GFAP) is expressed in the central nervous system, and breakdown products (GFAP-BDP) are released following parenchymal brain injury. Here, we evaluate the diagnostic accuracy of elevated levels of plasma GFAP-BDP in TBI. Participants were identified as part of the prospective Transforming Research And Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study. Acute plasma samples (<24 h post-injury) were collected from patients presenting with brain injury who had CT imaging. The ability of GFAP-BDP level to discriminate patients with demonstrable traumatic lesions on CT, and with failure to return to pre-injury baseline at 6 months, was evaluated by the area under the receiver operating characteristic curve (AUC). Of the 215 patients included for analysis, 83% had mild, 4% had moderate, and 13% had severe TBI; 54% had acute traumatic lesions on CT. The ability of GFAP-BDP level to discriminate patients with traumatic lesions on CT as evaluated by AUC was 0.88 (95% confidence interval [CI], 0.84-0.93). The optimal cutoff of 0.68 ng/mL for plasma GFAP-BDP level was associated with a 21.61 odds ratio for traumatic findings on head CT. Discriminatory ability of unfavorable 6 month outcome was lower, AUC 0.65 (95% CI, 0.55-0.74), with a 2.07 odds ratio. GFAP-BDP levels reliably distinguish the presence and severity of CT scan findings in TBI patients. Although these findings confirm and extend prior studies, a larger prospective trial is still needed to validate the use of GFAP-BDP as a routine diagnostic biomarker for patient care and clinical research. The term "mild" continues to be a misnomer for this patient population, and underscores the need for evolving classification strategies for TBI targeted therapy. (ClinicalTrials.gov number NCT01565551; NIH Grant 1RC2 NS069409).

  13. Time Slice Analysis Method Based on OTCA Used in fMRI Weak Signal Function Extraction

    Institute of Scientific and Technical Information of China (English)

    LUO Sen-lin; LI Li; ZHANG Xin-li; ZHANG Tie-mei

    2007-01-01

    The original temporal clustering analysis (OTCA) is an effective technique for obtaining brain activation maps when the timing and location of the activation are completely unknown, but its deficiency of sensitivity is exposed in processing brain activation signal which is relatively weak. The time slice analysis method based on OTCA is proposed considering the weakness of the functional magnetic resonance imaging (fMRI) signal of the rat model. By dividing the stimulation period into several time slices and analyzing each slice to detect the activated pixels respectively after the background removal, the sensitivity is significantly improved. The inhibitory response in the hypothalamus after glucose loading is detected successfully with this method in the experiment on rat. Combined with the OTCA method, the time slice analysis method based on OTCA is effective on detecting when, where and which type of response will happen after stimulation, even if the fMRI signal is weak.

  14. Viscous fingering of miscible slices

    CERN Document Server

    De Wit, A; Martin, M; Wit, Anne De; Bertho, Yann; Martin, Michel

    2005-01-01

    Viscous fingering of a miscible high viscosity slice of fluid displaced by a lower viscosity fluid is studied in porous media by direct numerical simulations of Darcy's law coupled to the evolution equation for the concentration of a solute controlling the viscosity of miscible solutions. In contrast with fingering between two semi-infinite regions, fingering of finite slices is a transient phenomenon due to the decrease in time of the viscosity ratio across the interface induced by fingering and dispersion processes. We show that fingering contributes transiently to the broadening of the peak in time by increasing its variance. A quantitative analysis of the asymptotic contribution of fingering to this variance is conducted as a function of the four relevant parameters of the problem i.e. the log-mobility ratio R, the length of the slice l, the Peclet number Pe and the ratio between transverse and axial dispersion coefficients $\\epsilon$. Relevance of the results is discussed in relation with transport of vi...

  15. Effects of an acute and a sub-chronic 900 MHz GSM exposure on brain activity and behaviors of rats

    Energy Technology Data Exchange (ETDEWEB)

    Elsa Brillaud; Aleksandra Piotrowski; Anthony Lecomte; Franck Robidel; Rene de Seze [Toxicology Unit, INERIS, Verneuil en Halatte (France)

    2006-07-01

    Radio frequencies are suspected to produce health effects. Concerning the mobile phone technology, according to position during use (close to the head), possible effects of radio frequencies on the central nervous system have to be evaluated. Previous works showed contradictory results, possibly due to experimental design diversity. In the framework of R.A.M.P. 2001 project, we evaluated possible effect of a 900 MHz GSM exposure on the central nervous system of rat at a structural, a functional and a behavioral level after acute or sub-chronic exposures. Rats were exposed using a loop antenna system to different S.A.R. levels and durations, according to results of the French C.O.M.O.B.I.O. 2001 project. A functional effect was found (modification of the cerebral activity and increase of the glia surface) after an acute exposure, even at a low level of brain averaged S.A.R. (1.5 W/kg). No cumulative effect was observed after a sub-chronic exposure (same amplitude of the effect). No structural or behavioral consequence was noted. We do not conclude on the neurotoxicity of the 900 MHz GSM exposure on the rat brain. Our results do not indicate any health risk. (authors)

  16. Computerized cognitive training and brain derived neurotrophic factor during bed rest: mechanisms to protect individual during acute stress

    Science.gov (United States)

    Passaro, Angelina; Soavi, Cecilia; Sanz, Juana M.; Morieri, Mario L.; Dalla Nora, Edoardo; Kavcic, Voyko; Narici, Marco V.; Reggiani, Carlo; Biolo, Gianni; Zuliani, Giovanni; Lazzer, Stefano; Pišot, Rado

    2017-01-01

    Acute stress, as bed rest, was shown to increase plasma level of the neurotrophin brain-derived neurotrophic factor (BDNF) in older, but not in young adults. This increase might represent a protective mechanism towards acute insults in aging subjects. Since computerized cognitive training (CCT) is known to protect brain, herein we evaluated the effect of CCT during bed rest on BDNF, muscle mass, neuromuscular function and metabolic parameters. The subjects that underwent CCT did not show an increase of BDNF after bed rest, and showed an anti-insular modification pattern in metabolism. Neuromuscular function parameters, already shown to beneficiate from CCT, negatively correlated with BDNF in research participants undergoing CCT, while positively correlated in the control group. In conclusion, BDNF increase can be interpreted as a standardized protective mechanism taking place whenever an insult occurs; it gives low, but consistent preservation of neuromuscular function. CCT, acting as an external protective mechanism, seems to modify this standardized response, avoiding BDNF increase or possibly modifying its time course. Our results suggest the possibility of differential neuroprotective mechanisms among ill and healthy individuals, and the importance of timing in determining the effects of protective mechanisms. PMID:28161695

  17. Aquaporin-4 deficiency attenuates acute lesions but aggravates delayed lesions and microgliosis after cryoinjury to mouse brain

    Institute of Scientific and Technical Information of China (English)

    Wen-Zhen Shi; Chun-Zhen Zhao; Bing Zhao; Xiao-Liang Zheng; San-Hua Fang; Yun-Bi Lu; Wei-Ping Zhang; Zhong Chen; Er-Qing Wei

    2012-01-01

    Objective To determine whether aquaporin-4 (AQP4) regulates acute lesions,delayed lesions,and the associated microglial activation after cryoinjury to the brain.Methods Brain cryoinjury was applied to AQP4 knockout (KO)and wild-type mice.At 24 h and on days 7 and 14 after cryoinjury,lesion volume,neuronal loss,and densities of microglia and astrocytes were determined,and their changes were compared between AQP4 KO and wild-type mice.Results Lesion volume and neuronal loss in AQP4 KO mice were milder at 24 h following cryoinjury,but worsened on days 7 and 14,compared to those in wild-type mice.Besides,microglial density increased more,and astrocyte proliferation and glial scar formation were attenuated on days 7 and 14 in AQP4 KO mice.Conclusion AQP4 deficiency ameliorates acute lesions,but worsens delayed lesions,perhaps due to the microgliosis in the late phase.

  18. Assessment of oxidative stress parameters of brain-derived neurotrophic factor heterozygous mice in acute stress model

    Directory of Open Access Journals (Sweden)

    Gulay Hacioglu

    2016-04-01

    Full Text Available Objective(s: Exposing to stress may be associated with increased production of reactive oxygen species (ROS. Therefore, high level of oxidative stress may eventually give rise to accumulation of oxidative damage and development of numerous neurodegenerative diseases. It has been presented that brain-derived neurotrophic factor (BDNF supports neurons against various neurodegenerative conditions. Lately, there has been growing evidence that changes in the cerebral neurotrophic support and especially in the BDNF expression and its engagement with ROS might be important in various disorders and neurodegenerative diseases. Hence, we aimed to investigate protective effects of BDNF against stress-induced oxidative damage. Materials and Methods: Five- to six-month-old male wild-type and BDNF knock-down mice were used in this study. Activities of catalase (CAT and superoxide dismutase (SOD enzymes, and the amount of malondialdehyde (MDA were assessed in the cerebral homogenates of studied groups in response to acute restraint stress. Results: Exposing to acute physiological stress led to significant elevation in the markers of oxidative stress in the cerebral cortexes of experimental groups. Conclusion: As BDNF-deficient mice were observed to be more susceptible to stress-induced oxidative damage, it can be suggested that there is a direct interplay between oxidative stress indicators and BDNF levels in the brain.

  19. Multi-modal magnetic resonance imaging in the acute and sub-acute phase of mild traumatic brain injury: can we see the difference?

    Science.gov (United States)

    Toth, Arnold; Kovacs, Noemi; Perlaki, Gabor; Orsi, Gergely; Aradi, Mihaly; Komaromy, Hedvig; Ezer, Erzsebet; Bukovics, Peter; Farkas, Orsolya; Janszky, Jozsef; Doczi, Tamas; Buki, Andras; Schwarcz, Attila

    2013-01-01

    Advanced magnetic resonance imaging (MRI) methods were shown to be able to detect the subtle structural consequences of mild traumatic brain injury (mTBI). The objective of this study was to investigate the acute structural alterations and recovery after mTBI, using diffusion tensor imaging (DTI) to reveal axonal pathology, volumetric analysis, and susceptibility weighted imaging (SWI) to detect microhemorrhage. Fourteen patients with mTBI who had computed tomography with negative results underwent MRI within 3 days and 1 month after injury. High resolution T1-weighted imaging, DTI, and SWI, were performed at both time points. A control group of 14 matched volunteers were also examined following the same imaging protocol and time interval. Tract-Based Spatial Statistics (TBSS) were performed on DTI data to reveal group differences. T1-weighted images were fed into Freesurfer volumetric analysis. TBSS showed fractional anisotropy (FA) to be significantly (corrected p<0.05) lower, and mean diffusivity (MD) to be higher in the mTBI group in several white matter tracts (FA=40,737; MD=39,078 voxels) compared with controls at 72 hours after injury and still 1month later for FA. Longitudinal analysis revealed significant change (i.e., normalization) of FA and MD over 1 month dominantly in the left hemisphere (FA=3408; MD=7450 voxels). A significant (p<0.05) decrease in cortical volumes (mean 1%) and increase in ventricular volumes (mean 3.4%) appeared at 1 month after injury in the mTBI group. SWI did not reveal microhemorrhage in our patients. Our findings present dynamic micro- and macrostructural changes occurring in the acute to sub-acute phase in mTBI, in very mildly injured patients lacking microhemorrhage detectable by SWI. These results underscore the importance of strictly defined image acquisition time points when performing MRI studies on patients with mTBI.

  20. Assessing Metabolism and Injury in Acute Human Traumatic Brain Injury with Magnetic Resonance Spectroscopy: Current and Future Applications

    Directory of Open Access Journals (Sweden)

    Matthew G. Stovell

    2017-09-01

    Full Text Available Traumatic brain injury (TBI triggers a series of complex pathophysiological processes. These include abnormalities in brain energy metabolism; consequent to reduced tissue pO2 arising from ischemia or abnormal tissue oxygen diffusion, or due to a failure of mitochondrial function. In vivo magnetic resonance spectroscopy (MRS allows non-invasive interrogation of brain tissue metabolism in patients with acute brain injury. Nuclei with “spin,” e.g., 1H, 31P, and 13C, are detectable using MRS and are found in metabolites at various stages of energy metabolism, possessing unique signatures due to their chemical shift or spin–spin interactions (J-coupling. The most commonly used clinical MRS technique, 1H MRS, uses the great abundance of hydrogen atoms within molecules in brain tissue. Spectra acquired with longer echo-times include N-acetylaspartate (NAA, creatine, and choline. NAA, a marker of neuronal mitochondrial activity related to adenosine triphosphate (ATP, is reported to be lower in patients with TBI than healthy controls, and the ratio of NAA/creatine at early time points may correlate with clinical outcome. 1H MRS acquired with shorter echo times produces a more complex spectrum, allowing detection of a wider range of metabolites.31 P MRS detects high-energy phosphate species, which are the end products of cellular respiration: ATP and phosphocreatine (PCr. ATP is the principal form of chemical energy in living organisms, and PCr is regarded as a readily mobilized reserve for its replenishment during periods of high utilization. The ratios of high-energy phosphates are thought to represent a balance between energy generation, reserve and use in the brain. In addition, the chemical shift difference between inorganic phosphate and PCr enables calculation of intracellular pH.13 C MRS detects the 13C isotope of carbon in brain metabolites. As the natural abundance of 13C is low (1.1%, 13C MRS is typically performed following

  1. Slice stretching effects for maximal slicing of a Schwarzschild black hole

    OpenAIRE

    Reimann, B.

    2005-01-01

    Slice stretching effects such as slice sucking and slice wrapping arise when foliating the extended Schwarzschild spacetime with maximal slices. For arbitrary spatial coordinates these effects are quantified here in the context of boundary conditions where the lapse arises as a linear combination of odd and even lapse. Favourable boundary conditions are then derived which make the overall slice stretching occur late in numerical simulations. Allowing the lapse to become negative, this require...

  2. Relationships between acute imaging biomarkers and theory of mind impairment in post-acute pediatric traumatic brain injury: A prospective analysis using susceptibility weighted imaging (SWI).

    Science.gov (United States)

    Ryan, Nicholas P; Catroppa, Cathy; Cooper, Janine M; Beare, Richard; Ditchfield, Michael; Coleman, Lee; Silk, Timothy; Crossley, Louise; Rogers, Kirrily; Beauchamp, Miriam H; Yeates, Keith O; Anderson, Vicki A

    2015-01-01

    Theory of Mind (ToM) forms an integral component of socially skilled behavior, and is critical for attaining developmentally appropriate goals. The protracted development of ToM is mediated by increasing connectivity between regions of the anatomically distributed 'mentalizing network', and may be vulnerable to disruption from pediatric traumatic brain injury (TBI). The present study aimed to evaluate the post-acute effects of TBI on first-order ToM, and examine relations between ToM and both local and global indices of macrostructural damage detected using susceptibility-weighted imaging (SWI). 104 children and adolescents with TBI and 43 age-matched typically developing (TD) controls underwent magnetic resonance imaging including a susceptibility-weighted imaging (SWI) sequence 2-8 weeks post-injury and were assessed on cognitive ToM tasks at 6-months after injury. Compared to TD controls and children with mild-moderate injuries, children with severe TBI showed significantly poorer ToM. Moreover, impairments in ToM were related to diffuse neuropathology, and parietal lobe lesions. Our findings support the vulnerability of the immature social brain network to disruption from TBI, and suggest that global macrostructural damage commonly associated with traumatic axonal injury (TAI) may contribute to structural disconnection of anatomically distributed regions that underlie ToM. This study suggests that SWI may be a valuable imaging biomarker to predict outcome and recovery of social cognition after pediatric TBI.

  3. Reversible brain damage following acute organic solvents' poisoning determined by magnetic resonance

    OpenAIRE

    2005-01-01

    Introduction. Acute exposure to the effects of volatile solvents is characterized by the abrupt onset of symptoms and signs of poisoning, and relatively fast recovery in the majority of cases. Case report. We report a 24-year-old patient with an acute, accidental poisoning with a mixture of volatile organic solvents (most probably toluene, styrene and xylene), which led to the development of upward gaze paresis, diplopia, hemiparesis, ataxic gate, and the late onset truncal ataxia episodes. A...

  4. Constrained reverse diffusion for thick slice interpolation of 3D volumetric MRI images.

    Science.gov (United States)

    Neubert, Aleš; Salvado, Olivier; Acosta, Oscar; Bourgeat, Pierrick; Fripp, Jurgen

    2012-03-01

    Due to physical limitations inherent in magnetic resonance imaging scanners, three dimensional volumetric scans are often acquired with anisotropic voxel resolution. We investigate several interpolation approaches to reduce the anisotropy and present a novel approach - constrained reverse diffusion for thick slice interpolation. This technique was compared to common methods: linear and cubic B-Spline interpolation and a technique based on non-rigid registration of neighboring slices. The methods were evaluated on artificial MR phantoms and real MR scans of human brain. The constrained reverse diffusion approach delivered promising results and provides an alternative for thick slice interpolation, especially for higher anisotropy factors.

  5. Correlation of acetylcholinesterase activity in the brain and blood of wistar rats acutely infected with Trypanosoma congolense

    Institute of Scientific and Technical Information of China (English)

    Habila N; Inuwa HM; Aimola IA; Lasisi OI; Chechet DG; Okafor IA

    2012-01-01

    Objective: To investigate the neurotransmitter enzyme Acetylcholinesterase (AChE) activity in the brain and blood of rats infected with Trypanosoma congolense (T. congo). Methods: Presence and degree of parasitemia was determined daily for each rat by the rapid matching method. AChE activity was determined by preparing a reaction mixture of brain homogenate and whole blood with 5, 5-dithiobisnitrobenzioc acid (DTNB or Ellman’s reagent) and Acetylthiocholine (ATC). The increase in absorbance was recorded at 436 nm over 10 min at 2 min intervals. Trypanosome species identification (before inoculation and on day 10 post infection) was done by Polymerase chain reaction using specific primers. Results: The AChE activity in the brain and blood decreased significantly as compared with the uninfected control. The AChE activity dropped to 0.32 from 2.20 μmol ACTC min-1mg protein-1 in the brain and 4.57 to 0.76 μmol ACTC min-1mg protein-1 in the blood. The animals treated with Diminaveto at 3.5 mg/kg/d were observed to have recovered significantly from parasitemia and were able to regain AChE activity in the blood but not in the brain as compared to the control groups. We also observed, that progressive parasitemia resulted to alterations in PCV, Hb, RBC, WBC, neurophils, total protein, lymphocytes, monocytes and eosinophil in acute infections of T. congo. Polymerase chain reaction (PCR) of infected blood before inoculation and on day 10 post infection revealed 600 bp on agarose gel electrophoresis. Conclusions: This finding suggest that decrease in AChE activity increases acetylcholine concentration in the synaptic cleft resulting to neurological failures in impulse transfer in T. congo infection rats.

  6. SLIMMER: SLIce MRI motion estimation and reconstruction tool for studies of fetal anatomy

    Science.gov (United States)

    Kim, Kio; Habas, Piotr A.; Rajagopalan, Vidya; Scott, Julia; Rousseau, Francois; Barkovich, A. James; Glenn, Orit A.; Studholme, Colin

    2011-03-01

    We describe a free software tool which combines a set of algorithms that provide a framework for building 3D volumetric images of regions of moving anatomy using multiple fast multi-slice MRI studies. It is specifically motivated by the clinical application of unsedated fetal brain imaging, which has emerged as an important area for image analysis. The tool reads multiple DICOM image stacks acquired in any angulation into a consistent patient coordinate frame and allows the user to select regions to be locally motion corrected. It combines algorithms for slice motion estimation, bias field inconsistency correction and 3D volume reconstruction from multiple scattered slice stacks. The tool is built onto the RView (http://rview.colin-studholme.net) medical image display software and allows the user to inspect slice stacks, and apply both stack and slice level motion estimation that incorporates temporal constraints based on slice timing and interleave information read from the DICOM data. Following motion estimation an algorithm for bias field inconsistency correction provides the user with the ability to remove artifacts arising from the motion of the local anatomy relative to the imaging coils. Full 3D visualization of the slice stacks and individual slice orientations is provided to assist in evaluating the quality of the motion correction and final image reconstruction. The tool has been evaluated on a range of clinical data acquired on GE, Siemens and Philips MRI scanners.

  7. Glycogen Supercompensation in the Rat Brain After Acute Hypoglycemia is Independent of Glucose Levels During Recovery.

    Science.gov (United States)

    Duarte, João M N; Morgenthaler, Florence D; Gruetter, Rolf

    2017-01-12

    Patients with diabetes display a progressive decay in the physiological counter-regulatory response to hypoglycemia, resulting in hypoglycemia unawareness. The mechanism through which the brain adapts to hypoglycemia may involve brain glycogen. We tested the hypothesis that brain glycogen supercompensation following hypoglycemia depends on blood glucose levels during recovery. Conscious rats were submitted to hypoglycemia of 2 mmol/L for 90 min and allowed to recover at different glycemia, controlled by means of i.v. glucose infusion. Brain glycogen concentration was elevated above control levels after 24 h of recovery in the cortex, hippocampus and striatum. This glycogen supercompensation was independent of blood glucose levels in the post-hypoglycemia period. In the absence of a preceding hypoglycemia insult, brain glycogen concentrations were unaltered after 24 h under hyperglycemia. In the hypothalamus, which controls peripheral glucose homeostasis, glycogen levels were unaltered. Overall, we conclude that post-hypoglycemia glycogen supercompensation occurs in several brain areas and its magnitude is independent of plasma glucose levels. By supporting brain metabolism during recurrent hypoglycemia periods, glycogen may have a role in the development of hypoglycemia unawareness.

  8. Physical exercise and acute restraint stress differentially modulate hippocampal brain-derived neurotrophic factor transcripts and epigenetic mechanisms in mice.

    Science.gov (United States)

    Ieraci, Alessandro; Mallei, Alessandra; Musazzi, Laura; Popoli, Maurizio

    2015-11-01

    Physical exercise and stressful experiences have been shown to exert opposite effects on behavioral functions and brain plasticity, partly by involving the action of brain-derived neurotrophic factor (BDNF). Although epigenetic modifications are known to play a pivotal role in the regulation of the different BDNF transcripts, it is poorly understood whether epigenetic mechanisms are also implied in the BDNF modulation induced by physical exercise and stress. Here, we show that total BDNF mRNA levels and BDNF transcripts 1, 2, 3, 4, 6, and 7 were reduced immediately after acute restraint stress (RS) in the hippocampus of mice, and returned to control levels 24 h after the stress session. On the contrary, exercise increased BDNF mRNA expression and counteracted the stress-induced decrease of BDNF transcripts. Physical exercise-induced up-regulation of BDNF transcripts was accounted for by increase in histone H3 acetylated levels at specific BDNF promoters, whereas the histone H3 trimethylated lysine 27 and dimethylated lysine 9 levels were unaffected. Acute RS did not change the levels of acetylated and methylated histone H3 at the BDNF promoters. Furthermore, we found that physical exercise and RS were able to differentially modulate the histone deacetylases mRNA levels. Finally, we report that a single treatment with histone deacetylase inhibitors, prior to acute stress exposure, prevented the down-regulation of total BDNF and BDNF transcripts 1, 2, 3, and 6, partially reproducing the effect of physical exercise. Overall, these results suggest that physical exercise and stress are able to differentially modulate the expression of BDNF transcripts by possible different epigenetic mechanisms. © 2015 Wiley Periodicals, Inc.

  9. Diagnostic utility of C-reactive Protein combined with brain natriuretic peptide in acute pulmonary edema: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Murakami Junji

    2011-06-01

    Full Text Available Abstract Introduction Discriminating acute lung injury (ALI or acute respiratory distress syndrome (ARDS from cardiogenic pulmonary edema (CPE using the plasma level of brain natriuretic peptide (BNP alone remains controversial. The aim of this study was to determine the diagnostic utility of combination measurements of BNP and C-reactive protein (CRP in critically ill patients with pulmonary edema. Methods This was a cross-sectional study. BNP and CRP data from 147 patients who presented to the emergency department due to acute respiratory failure with bilateral pulmonary infiltrates were analyzed. Results There were 53 patients with ALI/ARDS, 71 with CPE, and 23 with mixed edema. Median BNP and CRP levels were 202 (interquartile range 95-439 pg/mL and 119 (62-165 mg/L in ALI/ARDS, and 691 (416-1,194 pg/mL (p Conclusions Measurement of CRP is useful as well as that of BNP for distinguishing ALI/ARDS from CPE. Furthermore, a combination of BNP and CRP can provide higher accuracy for the diagnosis.

  10. Prediction of behavioural and cognitive deficits in patients with traumatic brain injury at an acute rehabilitation setting.

    Science.gov (United States)

    de Guise, E; LeBlanc, J; Feyz, M; Lamoureux, J; Greffou, S

    2017-01-01

    The goal of this study was to identify factors that would predict short-term neuropsychological outcome in patients with traumatic brain injury (TBI) hospitalized in an acute rehabilitation setting. Data was collected in the context of an acute early rehabilitation setting of a trauma centre. A brief neuropsychological assessment was carried out for 348 patients within a month following their trauma. Length of post-traumatic amnesia (PTA) was the best predictor of behavioural, memory and executive function variables within a month post TBI. The odds of being agitated, labile, irritable and disinhibited at one month post trauma were almost six times higher for those with PTA that lasted more than 7 days compared to those with a PTA of less than 24 hours. Also, the odds of having a higher mental manipulation score (less significant executive function impairment) were almost two times lower for those with frontal lesions, and three to six times lower for those with PTA of more than 24 hours. In addition, TBI severity, education and age were considered good predictors of some aspects of neuropsychological outcome. This model may help clinicians and administrators recognize the probable post-traumatic deficits as quickly as possible and to plan interventions as well as post-acute discharge orientation accordingly and early on.

  11. Long-term medical utilization following ventilator-associated pneumonia in acute stroke and traumatic brain injury patients: a case-control study

    OpenAIRE

    Yang, Chih-Chieh; Shih, Nai-Ching; Chang, Wen-Chiung; Huang, San-Kuei; Chien, Ching-Wen

    2011-01-01

    Background The economic burden of ventilator-associated pneumonia (VAP) during the index hospitalization has been confirmed in previous studies. However, the long-term economic impact is still unclear. The aim of this study is to examine the effect of VAP on medical utilization in the long term. Methods This is a retrospective case-control study. Study subjects were patients experiencing their first traumatic brain injury, acute hemorrhagic stroke, or acute ischemic stroke during 2004. All su...

  12. Long-term medical utilization following ventilator-associated pneumonia in acute stroke and traumatic brain injury patients: a case-control study

    OpenAIRE

    Huang San-Kuei; Chang Wen-Chiung; Shih Nai-Ching; Yang Chih-Chieh; Chien Ching-Wen

    2011-01-01

    Abstract Background The economic burden of ventilator-associated pneumonia (VAP) during the index hospitalization has been confirmed in previous studies. However, the long-term economic impact is still unclear. The aim of this study is to examine the effect of VAP on medical utilization in the long term. Methods This is a retrospective case-control study. Study subjects were patients experiencing their first traumatic brain injury, acute hemorrhagic stroke, or acute ischemic stroke during 200...

  13. Automatic basal slice detection for cardiac analysis

    Science.gov (United States)

    Paknezhad, Mahsa; Marchesseau, Stephanie; Brown, Michael S.

    2016-03-01

    Identification of the basal slice in cardiac imaging is a key step to measuring the ejection fraction (EF) of the left ventricle (LV). Despite research on cardiac segmentation, basal slice identification is routinely performed manually. Manual identification, however, has been shown to have high inter-observer variability, with a variation of the EF by up to 8%. Therefore, an automatic way of identifying the basal slice is still required. Prior published methods operate by automatically tracking the mitral valve points from the long-axis view of the LV. These approaches assumed that the basal slice is the first short-axis slice below the mitral valve. However, guidelines published in 2013 by the society for cardiovascular magnetic resonance indicate that the basal slice is the uppermost short-axis slice with more than 50% myocardium surrounding the blood cavity. Consequently, these existing methods are at times identifying the incorrect short-axis slice. Correct identification of the basal slice under these guidelines is challenging due to the poor image quality and blood movement during image acquisition. This paper proposes an automatic tool that focuses on the two-chamber slice to find the basal slice. To this end, an active shape model is trained to automatically segment the two-chamber view for 51 samples using the leave-one-out strategy. The basal slice was detected using temporal binary profiles created for each short-axis slice from the segmented two-chamber slice. From the 51 successfully tested samples, 92% and 84% of detection results were accurate at the end-systolic and the end-diastolic phases of the cardiac cycle, respectively.

  14. Morphological changes in the brain of acutely ill and weight-recovered patients with anorexia nervosa. A meta-analysis and qualitative review.

    Science.gov (United States)

    Seitz, Jochen; Bühren, Katharina; von Polier, Georg G; Heussen, Nicole; Herpertz-Dahlmann, Beate; Konrad, Kerstin

    2014-01-01

    Acute anorexia nervosa (AN) leads to reduced gray (GM) and white matter (WM) volume in the brain, which however improves again upon restoration of weight. Yet little is known about the extent and clinical correlates of these brain changes, nor do we know much about the time-course and completeness of their recovery. We conducted a meta-analysis and a qualitative review of all magnetic resonance imaging studies involving volume analyses of the brain in both acute and recovered AN. We identified structural neuroimaging studies with a total of 214 acute AN patients and 177 weight-recovered AN patients. In acute AN, GM was reduced by 5.6% and WM by 3.8% compared to healthy controls (HC). Short-term weight recovery 2-5 months after admission resulted in restitution of about half of the GM aberrations and almost full WM recovery. After 2-8 years of remission GM and WM were nearly normalized, and differences to HC (GM: -1.0%, WM: -0.7%) were no longer significant, although small residual changes could not be ruled out. In the qualitative review some studies found GM volume loss to be associated with cognitive deficits and clinical prognosis. GM and WM were strongly reduced in acute AN. The completeness of brain volume rehabilitation remained equivocal.

  15. Acute Exposure to Perchlorethylene alters Rat Visual Evoked Potentials in Relation to Brain Concentration

    Science.gov (United States)

    These experiments sought to establish a dose-effect relationship between the concentration of perchloroethylene (PCE) in brain tissue and concurrent changes in visual function. A physiologically-based pharmacokinetic (PBPK) model was implemented to predict concentrations of PCE ...

  16. Acute Exposure to Perchlorethylene alters Rat Visual Evoked Potentials in Relation to Brain Concentration

    Science.gov (United States)

    These experiments sought to establish a dose-effect relationship between the concentration of perchloroethylene (PCE) in brain tissue and concurrent changes in visual function. A physiologically-based pharmacokinetic (PBPK) model was implemented to predict concentrations of PCE ...