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Sample records for acute brain slice

  1. Extending the viability of acute brain slices.

    PubMed

    Buskila, Yossi; Breen, Paul P; Tapson, Jonathan; van Schaik, André; Barton, Matthew; Morley, John W

    2014-01-01

    The lifespan of an acute brain slice is approximately 6-12 hours, limiting potential experimentation time. We have designed a new recovery incubation system capable of extending their lifespan to more than 36 hours. This system controls the temperature of the incubated artificial cerebral spinal fluid (aCSF) while continuously passing the fluid through a UVC filtration system and simultaneously monitoring temperature and pH. The combination of controlled temperature and UVC filtering maintains bacteria levels in the lag phase and leads to the dramatic extension of the brain slice lifespan. Brain slice viability was validated through electrophysiological recordings as well as live/dead cell assays. This system benefits researchers by monitoring incubation conditions and standardizing this artificial environment. It further provides viable tissue for two experimental days, reducing the time spent preparing brain slices and the number of animals required for research. PMID:24930889

  2. Rapid manifestation of reactive astrogliosis in acute hippocampal brain slices

    PubMed Central

    Takano, Takahiro; He, Wei; Han, Xiaoning; Wang, Fushun; Xu, Qiwu; Wang, Xiaohai; Oberheim Bush, Nancy Ann; Cruz, Nancy; Dienel, Gerald A.; Nedergaard, Maiken

    2014-01-01

    A flurry of studies over the past decade has shown that astrocytes play a more active role in neural function than previously recognized. Hippocampal slices prepared from young rodent pups have served as a popular model for studying the pathways by which astrocytes participate in synaptic transmission. It is, however, not known how well astrocytes tolerate traumatic injury and hypoxia, which are unavoidable when preparing acute slices. We here show that astrocytes exhibit striking changes in expression of several receptors and structural proteins, including re-expression of the developmental marker nestin within 90 min following preparation of live vibratome slices. Moreover, immunoelectron microscopy showed a 2.7-fold loss of astrocytic processes in acute hippocampal slices prepared from GFAP-GFP reporter mice. A sharp decrease in the number of mitochondria was also noted in acute slices, concurrently with an increase in mitochondrial size. Glycogen content decreased 3-fold upon slice preparation and did not recover despite stable recordings of field EPSC. Analysis of Ca2+ signaling showed that astrocytic responses to purine receptor and mGluR5 agonists differed in slice vs. in vivo. These observations suggest that the functional properties and the fine structure of astrocytes in slices may be reflective of early stages of reactive gliosis and should be confirmed in vivo when possible. PMID:24272704

  3. Rapid manifestation of reactive astrogliosis in acute hippocampal brain slices.

    PubMed

    Takano, Takahiro; He, Wei; Han, Xiaoning; Wang, Fushun; Xu, Qiwu; Wang, Xiaohai; Oberheim Bush, Nancy Ann; Cruz, Nancy; Dienel, Gerald A; Nedergaard, Maiken

    2014-01-01

    A flurry of studies over the past decade has shown that astrocytes play a more active role in neural function than previously recognized. Hippocampal slices prepared from young rodent pups have served as a popular model for studying the pathways by which astrocytes participate in synaptic transmission. It is, however, not known how well astrocytes tolerate traumatic injury and hypoxia, which are unavoidable when preparing acute slices. We here showed that astrocytes exhibit striking changes in expression of several receptors and structural proteins, including re-expression of the developmental marker nestin within 90 min following preparation of live vibratome slices. Moreover, immunoelectron microscopy showed a 2.7-fold loss of astrocytic processes in acute hippocampal slices prepared from glial fibrillary acidic protein-green fluorescent protein reporter mice. A sharp decrease in the number of mitochondria was also noted in acute slices, concurrently with an increase in mitochondrial size. Glycogen content decreased 3-fold upon slice preparation and did not recover despite stable recordings of field excitatory postsynaptic current. Analysis of Ca(2+) signaling showed that astrocytic responses to purine receptor and mGluR5 agonists differed in slice versus in vivo. These observations suggest that the functional properties and the fine structure of astrocytes in slices may be reflective of early stages of reactive gliosis and should be confirmed in vivo when possible. PMID:24272704

  4. Acute brain slice methods for adult and aging animals: application of targeted patch clampanalysis and optogenetics

    PubMed Central

    Daigle, Tanya L.; Chen, Qian; Feng, Guoping

    2014-01-01

    Summary The development of the living acute brain slice preparation for analyzing synaptic function roughly a half century ago was a pivotal achievement that greatly influenced the landscape of modern neuroscience. Indeed, many neuroscientists regard brain slices as the gold-standard model system for detailed cellular, molecular, and circuitry level analysis and perturbation of neuronal function. A critical limitation of this model system is the difficulty in preparing slices from adult and aging animals, and over the past several decades few substantial methodological improvements have emerged to facilitate patch clamp analysis in the mature adult stage. In this chapter we describe a robust and practical protocol for preparing brain slices from mature adult mice that are suitable for patch clamp analysis. This method reduces swelling and damage in superficial layers of the slices and improves the success rate for targeted patch clamp recordings, including recordings from fluorescently labeled populations in slices derived from transgenic mice. This adult brain slice method is suitable for diverse experimental applications, including both monitoring and manipulating neuronal activity with genetically encoded calcium indicators and optogenetic actuators, respectively. We describe the application of this adult brain slice platform and associated methods for screening kinetic properties of Channelrhodopsin (ChR) variants expressed in genetically-defined neuronal subtypes. PMID:25023312

  5. Two-Photon Excitation STED Microscopy in Two Colors in Acute Brain Slices

    PubMed Central

    Bethge, Philipp; Chéreau, Ronan; Avignone, Elena; Marsicano, Giovanni; Nägerl, U. Valentin

    2013-01-01

    Many cellular structures and organelles are too small to be properly resolved by conventional light microscopy. This is particularly true for dendritic spines and glial processes, which are very small, dynamic, and embedded in dense tissue, making it difficult to image them under realistic experimental conditions. Two-photon microscopy is currently the method of choice for imaging in thick living tissue preparations, both in acute brain slices and in vivo. However, the spatial resolution of a two-photon microscope, which is limited to ∼350 nm by the diffraction of light, is not sufficient for resolving many important details of neural morphology, such as the width of spine necks or thin glial processes. Recently developed superresolution approaches, such as stimulated emission depletion microscopy, have set new standards of optical resolution in imaging living tissue. However, the important goal of superresolution imaging with significant subdiffraction resolution has not yet been accomplished in acute brain slices. To overcome this limitation, we have developed a new microscope based on two-photon excitation and pulsed stimulated emission depletion microscopy, which provides unprecedented spatial resolution and excellent experimental access in acute brain slices using a long-working distance objective. The new microscope improves on the spatial resolution of a regular two-photon microscope by a factor of four to six, and it is compatible with time-lapse and simultaneous two-color superresolution imaging in living cells. We demonstrate the potential of this nanoscopy approach for brain slice physiology by imaging the morphology of dendritic spines and microglial cells well below the surface of acute brain slices. PMID:23442956

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

    PubMed Central

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

    2016-01-01

    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. PMID:26971573

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

    NASA Astrophysics Data System (ADS)

    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.

  8. High-strain-rate brain injury model using submerged acute rat brain tissue slices.

    PubMed

    Sarntinoranont, Malisa; Lee, Sung J; Hong, Yu; King, Michael A; Subhash, Ghatu; Kwon, Jiwoon; Moore, David F

    2012-01-20

    Blast-induced traumatic brain injury (bTBI) has received increasing attention in recent years due to ongoing military operations in Iraq and Afghanistan. Sudden impacts or explosive blasts generate stress and pressure waves that propagate at high velocities and affect sensitive neurological tissues. The immediate soft tissue response to these stress waves is difficult to assess using current in vivo imaging technologies. However, these stress waves and resultant stretching and shearing of tissue within the nano- to microsecond time scale of blast and impact are likely to cause initial injury. To visualize the effects of stress wave loading, we have developed a new ex vivo model in which living tissue slices from rat brain, attached to a ballistic gelatin substrate, were subjected to high-strain-rate loads using a polymer split Hopkinson pressure bar (PSHPB) with real-time high-speed imaging. In this study, average peak fluid pressure within the test chamber reached a value of 1584±63.3 psi. Cavitation due to a trailing underpressure wave was also observed. Time-resolved images of tissue deformation were collected and large maximum eigenstrains (0.03-0.42), minimum eigenstrains (-0.33 to -0.03), maximum shear strains (0.09-0.45), and strain rates (8.4×10³/sec) were estimated using digital image correlation (DIC). Injury at 4 and 6 h was quantified using Fluoro-Jade C. Neuronal injury due to PSHPB testing was found to be significantly greater than injury associated with the tissue slice paradigm alone. While large pressures and strains were encountered for these tests, this system provides a controllable test environment to study injury to submerged brain slices over a range of strain rate, pressure, and strain loads. PMID:21970544

  9. The relationship between decorrelation time and sample thickness in acute rat brain tissue slices (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Brake, Joshua; Jang, Mooseok; Yang, Changhuei

    2016-03-01

    The optical opacity of biological tissue has long been a challenge in biomedical optics due to the strong scattering nature of tissue in the optical regime. While most conventional optical techniques attempt to gate out multiply scattered light and use only unscattered light, new approaches in the field of wavefront shaping exploit the time reversible symmetry of optical scattering in order to focus light inside or through scattering media. While these approaches have been demonstrated effectively on static samples, it has proven difficult to apply them to dynamic biological samples since even small changes in the relative positions of the scatterers within will cause the time symmetry that wavefront shaping relies upon to decorrelate. In this paper we investigate the decorrelation curves of acute rat brain slices for thicknesses in the range 1-3 mm (1/e decorrelation time on the order of seconds) using multi-speckle diffusing wave spectroscopy (MSDWS) and compare the results with theoretical predictions. The results of this study demonstrate that the 1/L^2 relationship between decorrelation time and thickness predicted by diffusing wave spectroscopy provides a good rule of thumb for estimating how the decorrelation of a sample will change with increasing thickness. Understanding this relationship will provide insight to guide the future development of biophotonic wavefront shaping tools by giving an estimate of how fast wavefront shaping systems need to operate to overcome the dynamic nature of biological samples.

  10. Optical recording of fast neuronal membrane potential transients in acute mammalian brain slices by second-harmonic generation microscopy.

    PubMed

    Dombeck, Daniel A; Sacconi, Leonardo; Blanchard-Desce, Mireille; Webb, Watt W

    2005-11-01

    Although nonlinear microscopy and fast (approximately 1 ms) membrane potential (Vm) recording have proven valuable for neuroscience applications, their potentially powerful combination has not yet been shown for studies of Vm activity deep in intact tissue. We show that laser illumination of neurons in acute rat brain slices intracellularly filled with FM4-64 dye generates an intense second-harmonic generation (SHG) signal from somatic and dendritic plasma membranes with high contrast >125 microm below the slice surface. The SHG signal provides a linear response to DeltaVm of approximately 7.5%/100 mV. By averaging repeated line scans (approximately 50), we show the ability to record action potentials (APs) optically with a signal-to-noise ratio (S/N) of approximately 7-8. We also show recording of fast Vm steps from the dendritic arbor at depths inaccessible with previous methods. The high membrane contrast and linear response of SHG to DeltaVm provides the advantage that signal changes are not degraded by background and can be directly quantified in terms of DeltaVm. Experimental comparison of SHG and two-photon fluorescence Vm recording with the best known probes for each showed that the SHG technique is superior for Vm recording in brain slice applications, with FM4-64 as the best tested SHG Vm probe. PMID:16093337

  11. In vivo Postnatal Electroporation and Time-lapse Imaging of Neuroblast Migration in Mouse Acute Brain Slices

    PubMed Central

    Oudin, Madeleine Julie; Doherty, Patrick; Lalli, Giovanna

    2013-01-01

    The subventricular zone (SVZ) is one of the main neurogenic niches in the postnatal brain. Here, neural progenitors proliferate and give rise to neuroblasts able to move along the rostral migratory stream (RMS) towards the olfactory bulb (OB). This long-distance migration is required for the subsequent maturation of newborn neurons in the OB, but the molecular mechanisms regulating this process are still unclear. Investigating the signaling pathways controlling neuroblast motility may not only help understand a fundamental step in neurogenesis, but also have therapeutic regenerative potential, given the ability of these neuroblasts to target brain sites affected by injury, stroke, or degeneration. In this manuscript we describe a detailed protocol for in vivo postnatal electroporation and subsequent time-lapse imaging of neuroblast migration in the mouse RMS. Postnatal electroporation can efficiently transfect SVZ progenitor cells, which in turn generate neuroblasts migrating along the RMS. Using confocal spinning disk time-lapse microscopy on acute brain slice cultures, neuroblast migration can be monitored in an environment closely resembling the in vivo condition. Moreover, neuroblast motility can be tracked and quantitatively analyzed. As an example, we describe how to use in vivo postnatal electroporation of a GFP-expressing plasmid to label and visualize neuroblasts migrating along the RMS. Electroporation of shRNA or CRE recombinase-expressing plasmids in conditional knockout mice employing the LoxP system can also be used to target genes of interest. Pharmacological manipulation of acute brain slice cultures can be performed to investigate the role of different signaling molecules in neuroblast migration. By coupling in vivo electroporation with time-lapse imaging, we hope to understand the molecular mechanisms controlling neuroblast motility and contribute to the development of novel approaches to promote brain repair. PMID:24326479

  12. Analyzing the relationship between decorrelation time and tissue thickness in acute rat brain slices using multispeckle diffusing wave spectroscopy.

    PubMed

    Brake, Joshua; Jang, Mooseok; Yang, Changhuei

    2016-02-01

    Novel techniques in the field of wavefront shaping have enabled light to be focused deep inside or through scattering media such as biological tissue. However, most of these demonstrations have been limited to thin, static samples since these techniques are very sensitive to changes in the arrangement of the scatterers within. As the samples of interest get thicker, the influence of the dynamic nature of the sample becomes even more pronounced and the window of time in which the wavefront solutions remain valid shrinks further. In this paper, we examine the time scales upon which this decorrelation happens in acute rat brain slices via multispeckle diffusing wave spectroscopy and investigate the relationship between this decorrelation time and the thickness of the sample using diffusing wave spectroscopy theory and Monte Carlo photon transport simulation. PMID:26831778

  13. Analyzing the relationship between decorrelation time and tissue thickness in acute rat brain slices using multispeckle diffusing wave spectroscopy

    PubMed Central

    Brake, Joshua; Jang, Mooseok; Yang, Changhuei

    2016-01-01

    Novel techniques in the field of wavefront shaping have enabled light to be focused deep inside or through scattering media such as biological tissue. However, most of these demonstrations have been limited to thin, static samples since these techniques are very sensitive to changes in the arrangement of the scatterers within. As the samples of interest get thicker, the influence of the dynamic nature of the sample becomes even more pronounced and the window of time in which the wavefront solutions remain valid shrinks further. In this paper, we examine the time scales upon which this decorrelation happens in acute rat brain slices via multispeckle diffusing wave spectroscopy and investigate the relationship between this decorrelation time and the thickness of the sample using diffusing wave spectroscopy theory and Monte Carlo photon transport simulation. PMID:26831778

  14. Two-photon microscope for multisite microphotolysis of caged neurotransmitters in acute brain slices

    PubMed Central

    Losavio, Bradley E.; Iyer, Vijay; Saggau, Peter

    2009-01-01

    We developed a two-photon microscope optimized for physiologically manipulating single neurons through their postsynaptic receptors. The optical layout fulfills the stringent design criteria required for high-speed, high-resolution imaging in scattering brain tissue with minimal photodamage. We detail the practical compensation of spectral and temporal dispersion inherent in fast laser beam scanning with acousto-optic deflectors, as well as a set of biological protocols for visualizing nearly diffraction-limited structures and delivering physiological synaptic stimuli. The microscope clearly resolves dendritic spines and evokes electrophysiological transients in single neurons that are similar to endogenous responses. This system enables the study of multisynaptic integration and will assist our understanding of single neuron function and dendritic computation. PMID:20059271

  15. Two-photon microscope for multisite microphotolysis of caged neurotransmitters in acute brain slices

    NASA Astrophysics Data System (ADS)

    Losavio, Bradley E.; Iyer, Vijay; Saggau, Peter

    2009-11-01

    We developed a two-photon microscope optimized for physiologically manipulating single neurons through their postsynaptic receptors. The optical layout fulfills the stringent design criteria required for high-speed, high-resolution imaging in scattering brain tissue with minimal photodamage. We detail the practical compensation of spectral and temporal dispersion inherent in fast laser beam scanning with acousto-optic deflectors, as well as a set of biological protocols for visualizing nearly diffraction-limited structures and delivering physiological synaptic stimuli. The microscope clearly resolves dendritic spines and evokes electrophysiological transients in single neurons that are similar to endogenous responses. This system enables the study of multisynaptic integration and will assist our understanding of single neuron function and dendritic computation.

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

    PubMed

    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

  17. S100B secretion in acute brain slices: modulation by extracellular levels of Ca(2+) and K (+).

    PubMed

    Nardin, Patrícia; Tortorelli, Lucas; Quincozes-Santos, André; de Almeida, Lúcia Maria V; Leite, Marina C; Thomazi, Ana Paula; Gottfried, Carmem; Wofchuk, Susana T; Donato, Rosario; Gonçalves, Carlos-Alberto

    2009-09-01

    Hippocampal slices have been widely used to investigate electrophysiological and metabolic neuronal parameters, as well as parameters of astroglial activity including protein phosphorylation and glutamate uptake. S100B is an astroglial-derived protein, which extracellularly plays a neurotrophic activity during development and excitotoxic insult. Herein, we characterized S100B secretion in acute hippocampal slices exposed to different concentrations of K(+) and Ca(2+) in the extracellular medium. Absence of Ca(2+) and/or low K(+) (0.2 mM KCl) caused an increase in S100B secretion, possibly by mobilization of internal stores of Ca(2+). In contrast, high K(+) (30 mM KCl) or calcium channel blockers caused a decrease in S100B secretion. This study suggests that exposure of acute hippocampal slices to low- and high-K(+) could be used as an assay to evaluate astrocyte activity by S100B secretion: positively regulated by low K(+) (possibly involving mobilization of internal stores of Ca(2+)) and negatively regulated by high-K(+) (likely secondary to influx of K(+)). PMID:19288274

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

    PubMed Central

    Pashut, Tamar; Magidov, Dafna; Ben-Porat, Hana; Wolfus, Shuki; Friedman, Alex; Perel, Eli; Lavidor, Michal; Bar-Gad, Izhar; Yeshurun, Yosef; Korngreen, Alon

    2014-01-01

    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. PMID:24917788

  19. [A simple vibratome for brain slice].

    PubMed

    Xia, J H; Xing, B R; Gu, Q; Hua, S Y

    1989-12-01

    A simple vibratome was fabricated using double-function electric shaver and microscopic platform. Spontaneous discharge of neurons in hippocampal and hypothalamic brain slices (in 300-400 microns thick) prepared by the vibratome could kept above 12 hours in artificial cerebro-spinal fluid. PMID:2697084

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

    PubMed

    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. PMID:25648546

  1. ORGANOTYPIC BRAIN SLICE CULTURES: A REVIEW

    PubMed Central

    HUMPEL, C.

    2015-01-01

    In vitro cell cultures are an important tool for obtaining insights into cellular processes in an isolated system and a supplement to in vivo animal experiments. While primary dissociated cultures permit a single homogeneous cell population to be studied, there is a clear need to explore the function of brain cells in a three-dimensional system where the main architecture of the cells is preserved. Thus, organotypic brain slice cultures have proven to be very useful in investigating cellular and molecular processes of the brain in vitro. This review summarizes (1) the historical development of organotypic brain slices focusing on the membrane technology, (2) methodological aspects regarding culturing procedures, age of donors or media, (3) whether the cholinergic neurons serve as a model of neurodegeneration in Alzheimer’s disease, (4) or the nigrostriatal dopaminergic neurons as a model of Parkinson’s disease and (5) how the vascular network can be studied, especially with regard to a synthetic blood–brain barrier. This review will also highlight some limits of the model and give an outlook on future applications. PMID:26254240

  2. Multilayer PDMS microfluidic chamber for controlling brain slice microenvironment

    PubMed Central

    Blake, A. J.; Pearce, T. M.; Rao, N. S.; Johnson, S. M.; Williams, J. C.

    2008-01-01

    A novel three-layer microfluidic polydimethylsiloxane (PDMS) device was constructed with two fluid chambers that holds a brain slice in place with microposts while maintaining laminar perfusate flow above and below the slice. Our fabrication technique permits rapid production of PDMS layers that can be applied to brain slices of different shapes and sizes. In this study, the device was designed to fit the shape and thickness (530-700 μm) of a medullary brain slice taken from P0-P4 neonatal rats. Medullary slices in this chamber spontaneously produced rhythmic, respiratory-related motor output for up to 3 h, thereby demonstrating that brain slice viability was maintained for prolonged periods. This design is unique in that it achieves independent control of fluids through multiple channels in two separate fluid chambers. The laminar flow exhibited by the microfluidic chamber allows controlled solutions to target specific areas of the brain slice based on the input flow rates. To demonstrate this capability, a stream of Na+-free solution was focused on one half of a medullary slice to abolish spontaneous neural activity in only that half of the brain slice, while the other half remained active. We also demonstrated that flow of different solutions can be focused over the midline of the brain slice. The multilayer brain slice chamber design can integrate several traditional types of electrophysiology tools that are commonly used to measure neurophysiological properties of brain slices. Thus, this new microfluidic chamber is advantageous for experiments that involve controlled drug or solution delivery at high spatiotemporal resolution. PMID:17594002

  3. Modification of hippocampal excitability in brain slices pretreated with a low nanomolar concentration of Zn2+.

    PubMed

    Takeda, Atsushi; Shakushi, Yukina; Tamano, Haruna

    2015-11-01

    Synaptic Zn2+ homeostasis may be changed during brain slice preparation. However, much less attention has been paid to Zn2+ in artificial cerebrospinal fluid (ACSF) used for slice experiments than has been paid to Ca2+ . The present study assesses addition of Zn2+ to ACSF, focused on hippocampal excitability after acute brain slice preparation. When the static levels of intracellular Zn2+ and Ca2+ were compared between brain slices prepared with conventional ACSF without Zn2+ and those pretreated with ACSF containing 20 nM ZnCl2 for 1 hr, both levels were almost the same. On the other hand, intracellular Ca2+ levels were significantly increased in the stratum lucidum of the control brain slices after stimulation with high K+, although the increase was significantly suppressed by the pretreatment with ACSF containing Zn2+, suggesting that neuronal excitation is enhanced in brain slices prepared with ACSF without Zn2+. The increase in extracellular Zn2+ level, an index of glutamate release, after stimulation with high K+ was also significantly suppressed by pretreatment with ACSF containing Zn2+. When mossy fiber excitation was assessed in brain slices with FM4-64, an indicator of presynaptic activity, attenuation of FM 4-64 fluorescence based on presynaptic activity was suppressed in the stratum lucidum of brain slices pretreated with ACSF containing Zn2+. The present study indicates that hippocampal excitability is enhanced in brain slices prepared with ACSF without Zn2+. It is likely that a low nanomolar concentration of Zn2+ is necessary for ACSF. PMID:26268632

  4. Classification of CT-brain slices based on local histograms

    NASA Astrophysics Data System (ADS)

    Avrunin, Oleg G.; Tymkovych, Maksym Y.; Pavlov, Sergii V.; Timchik, Sergii V.; Kisała, Piotr; Orakbaev, Yerbol

    2015-12-01

    Neurosurgical intervention is a very complicated process. Modern operating procedures based on data such as CT, MRI, etc. Automated analysis of these data is an important task for researchers. Some modern methods of brain-slice segmentation use additional data to process these images. Classification can be used to obtain this information. To classify the CT images of the brain, we suggest using local histogram and features extracted from them. The paper shows the process of feature extraction and classification CT-slices of the brain. The process of feature extraction is specialized for axial cross-section of the brain. The work can be applied to medical neurosurgical systems.

  5. Developmental Decrease of Neuronal Chloride Concentration Is Independent of Trauma in Thalamocortical Brain Slices

    PubMed Central

    Glykys, Joseph; Staley, Kevin J.

    2016-01-01

    The intraneuronal chloride concentration ([Cl-]i) is paramount for determining the polarity of signaling at GABAA synapses in the central nervous system. Sectioning hippocampal brain slices increases [Cl-]i in the superficial layers. It is not known whether cutting trauma also increases [Cl-]i in the neocortex and thalamus, and whether the effects of trauma change during development. We used Cl- imaging to study the [Cl-]i vs. the distance from the cut surface in acute thalamocortical slices from mice at developmental ages ranging from post-natal day 5 (P5) to P20. We demonstrate: 1) [Cl-]i is higher in the most superficial areas in both neocortical and thalamic brain slices at all ages tested and, 2) there is a developmental decrease in [Cl-]i that is independent of acute trauma caused by brain slicing. We conclude that [Cl-]i has a developmental progression during P5-20 in both the neocortex and thalamus. However, in both brain regions and during development the neurons closest to the slicing trauma have an elevated [Cl-]i. PMID:27337272

  6. Brain Slices as Models for Neurodegenerative Disease and Screening Platforms to Identify Novel Therapeutics

    PubMed Central

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

    2007-01-01

    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. PMID:18615151

  7. Culturing thick brain slices: An interstitial 3D microperfusion system for enhanced viability

    PubMed Central

    Rambani, Komal; Vukasinovic, Jelena; Glezer, Ari; Potter, Steve M.

    2009-01-01

    Brain slice preparations are well-established models for a wide spectrum of in vitro investigations in the neuroscience discipline. However, these investigations are limited to acute preparations or thin organotypic culture preparations due to the lack of a successful method that allows culturing of thick organotypic brain slices. Thick brain slice cultures suffer necrosis due to ischemia deep in the tissue resulting from a destroyed circulatory system and subsequent diffusion-limited supply of nutrients and oxygen. Although thin organotypic brain slice cultures can be successfully cultured using a well established roller tube method (a monolayer organotypic culture) (Gahwiler B H, 1981) or a membrane insert method (up to 1–4 cell layers, <150μm)(Stoppini L et al., 1991), these methods fail to support thick tissue preparations. A few perfusion methods (using submerged or interface/microfluidic chambers) have been reported to enhance the longevity (up to few hours) of acute slice preparations (up to 600μm thick) (Hass H L et al., 1979; Nicoll R A and Alger B E, 1981; Passeraub P A et al., 2003). Here, we report a unique interstitial microfluidic perfusion technique to culture thick (700μm) organotypic brain slices. The design of the custom-made micro-perfusion chamber facilitates laminar, interstitial perfusion of oxygenated nutrient medium throughout the tissue thickness with concomitant removal of depleted medium and catabolites. We examined the utility of this perfusion method to enhance the viability of the thick organotypic brain slice cultures after 2 days and 5 days in vitro (DIV). We investigated the range of amenable flow rates that enhance the viability of 700μm thick organotypic brain slices compared to the unperfused control cultures. Our perfusion method allows up to 84.6% viability (P<0.01) and up to 700μm thickness, even after 5 DIV. Our results also confirm that these cultures are functionally active and have their in vivo cytoarchitecture

  8. Electrophysiology of Hypothalamic Magnocellular Neurons In vitro: A Rhythmic Drive in Organotypic Cultures and Acute Slices

    PubMed Central

    Israel, Jean-Marc; Oliet, Stéphane H.; Ciofi, Philippe

    2016-01-01

    Hypothalamic neurohormones are released in a pulsatile manner. The mechanisms of this pulsatility remain poorly understood and several hypotheses are available, depending upon the neuroendocrine system considered. Among these systems, hypothalamo-neurohypophyseal magnocellular neurons have been early-considered models, as they typically display an electrical activity consisting of bursts of action potentials that is optimal for the release of boluses of the neurohormones oxytocin and vasopressin. The cellular mechanisms underlying this bursting behavior have been studied in vitro, using either acute slices of the adult hypothalamus, or organotypic cultures of neonatal hypothalamic tissue. We have recently proposed, from experiments in organotypic cultures, that specific central pattern generator networks, upstream of magnocellular neurons, determine their bursting activity. Here, we have tested whether a similar hypothesis can be derived from in vitro experiments in acute slices of the adult hypothalamus. To this aim we have screened our electrophysiological recordings of the magnocellular neurons, previously obtained from acute slices, with an analysis of autocorrelation of action potentials to detect a rhythmic drive as we recently did for organotypic cultures. This confirmed that the bursting behavior of magnocellular neurons is governed by central pattern generator networks whose rhythmic drive, and thus probably integrity, is however less satisfactorily preserved in the acute slices from adult brains. PMID:27065780

  9. Diffusion of radiotracers in normal and ischemic brain slices.

    PubMed

    Patlak, C S; Hospod, F E; Trowbridge, S D; Newman, G C

    1998-07-01

    Diffusion in the extracellular space (ECS) is important in physiologic and pathologic brain processes but remains poorly understood. To learn more about factors influencing tissue diffusion and the role of diffusion in solute-tissue interactions, particularly during cerebral ischemia, we have studied the kinetics of several radiotracers in control and hypoxic 450-microm hippocampal slices and in 1,050-microm thick slices that model the ischemic penumbra. Kinetics were analyzed by nonlinear least squares methods using models that combine extracellular diffusion with tissue compartments in series or in parallel. Studies with 14C-polyethylene glycol confirmed prior measurements of extracellular volume and that ECS shrinks during ischemia. Separating diffusion from transport also revealed large amounts of 45Ca that bind to or enter brain as well as demonstrating a small, irreversibly bound compartment during ischemia. The rapidity of 3H2O entry into cells made it impossible for us to distinguish intracellular from extracellular diffusion. The diffusion-compartment analysis of 3-O-methylglucose data appears to indicate that 5 mmol/L glucose is inadequate to support glycolysis fully in thick slices. Unexpectedly, the diffusion coefficient for all four tracers rose in thick slices compared with thin slices, suggesting that ECS becomes less tortuous in the penumbra. PMID:9663508

  10. Brain tissue slice thickness monitored by ion-profile measurement.

    PubMed

    Lipinski, H G

    1992-04-01

    The thickness of a brain tissue slice preparation governs the amount of time required for substances to diffuse from the bathing solution to preparation. Slice thickness may increase during the experiment, e.g., in cases of hypoxia where osmotic pressure within the tissue changes, enabling water to enter the preparation. With increasing slice thickness diffusion paths from the bath to central layers of the preparation increase possibly resulting in an insufficient O2 supply to central layers. Therefore, the actual slice thickness should be monitored during the experiment especially in cases where osmolarity is changed or during hypoxia. This paper describes a simple method to monitor the actual slice thickness using ion profiles measured by ion selective micro-electrodes driven at a constant rate of approximately 10 microns/s (sample rate ca. 10/s). The method is based on steep changes in the concentration gradients at the upper and lower surfaces of the preparation induced by simple diffusion in the presence of concentration gradients between the non-tortuous bath and the tortuous tissue. The thickness of the preparation is derived from the location of the steep gradient changes as reflected by the registered profile. PMID:1405733

  11. Energetics of low affinity amino acid transport into brain slices.

    PubMed

    Banay-Schwartz, M; Teller, D N; Lajtha, A

    1976-01-01

    It appears possible to dissect and study some of the potential energy sources for amino acid transport in brain slices despite the apparent complexity of the tissue in comparison to that of isolated bacterial vesicles23. The uptake capability of the tissue may be inadvertently damaged in some experimental protocols so that very special controls must be used to ensure that the treatment did not somehow inactivate the very mechanism that thereafter will be tested. We have presented some evidence that brain slice amino acid transport may not be obligatorily linked to glycolysis, ATP levels, Na+, K+-ATPase activity, K+ levels or direction of flux, or to Na+ flux. However, the energy source linkage for different amino acids appears to be rather specific, so that further generalizations are difficult to sustain. For instance, the incubation media and conditions we describe here were experimentally adjusted to maximize uptake of D-glu or alpha-AIB in the absence of glucose, or in lowered K+ or Na+. Therefore, these procedures, the results of which directly challenge some common assumptions regarding the energy basis for active transport in brain slices, probably will not be universally extensible to all other actively transported amino acids. PMID:782193

  12. Time-lapse imaging of neuroblast migration in acute slices of the adult mouse forebrain.

    PubMed

    Khlghatyan, Jivan; Saghatelyan, Armen

    2012-01-01

    There is a substantial body of evidence indicating that new functional neurons are constitutively generated from an endogenous pool of neural stem cells in restricted areas of the adult mammalian brain. Newborn neuroblasts from the subventricular zone (SVZ) migrate along the rostral migratory stream (RMS) to their final destination in the olfactory bulb (OB). In the RMS, neuroblasts migrate tangentially in chains ensheathed by astrocytic processes using blood vessels as a structural support and a source of molecular factors required for migration. In the OB, neuroblasts detach from the chains and migrate radially into the different bulbar layers where they differentiate into interneurons and integrate into the existing network. In this manuscript we describe the procedure for monitoring cell migration in acute slices of the rodent brain. The use of acute slices allows the assessment of cell migration in the microenvironment that closely resembling to in vivo conditions and in brain regions that are difficult to access for in vivo imaging. In addition, it avoids long culturing condition as in the case of organotypic and cell cultures that may eventually alter the migration properties of the cells. Neuronal precursors in acute slices can be visualized using DIC optics or fluorescent proteins. Viral labeling of neuronal precursors in the SVZ, grafting neuroblasts from reporter mice into the SVZ of wild-type mice, and using transgenic mice that express fluorescent protein in neuroblasts are all suitable methods for visualizing neuroblasts and following their migration. The later method, however, does not allow individual cells to be tracked for long periods of time because of the high density of labeled cells. We used a wide-field fluorescent upright microscope equipped with a CCD camera to achieve a relatively rapid acquisition interval (one image every 15 or 30 sec) to reliably identify the stationary and migratory phases. A precise identification of the duration of

  13. Whole-cell Patch-clamp Recordings in Brain Slices.

    PubMed

    Segev, Amir; Garcia-Oscos, Francisco; Kourrich, Saïd

    2016-01-01

    Whole-cell patch-clamp recording is an electrophysiological technique that allows the study of the electrical properties of a substantial part of the neuron. In this configuration, the micropipette is in tight contact with the cell membrane, which prevents current leakage and thereby provides more accurate ionic current measurements than the previously used intracellular sharp electrode recording method. Classically, whole-cell recording can be performed on neurons in various types of preparations, including cell culture models, dissociated neurons, neurons in brain slices, and in intact anesthetized or awake animals. In summary, this technique has immensely contributed to the understanding of passive and active biophysical properties of excitable cells. A major advantage of this technique is that it provides information on how specific manipulations (e.g., pharmacological, experimenter-induced plasticity) may alter specific neuronal functions or channels in real-time. Additionally, significant opening of the plasma membrane allows the internal pipette solution to freely diffuse into the cytoplasm, providing means for introducing drugs, e.g., agonists or antagonists of specific intracellular proteins, and manipulating these targets without altering their functions in neighboring cells. This article will focus on whole-cell recording performed on neurons in brain slices, a preparation that has the advantage of recording neurons in relatively well preserved brain circuits, i.e., in a physiologically relevant context. In particular, when combined with appropriate pharmacology, this technique is a powerful tool allowing identification of specific neuroadaptations that occurred following any type of experiences, such as learning, exposure to drugs of abuse, and stress. In summary, whole-cell patch-clamp recordings in brain slices provide means to measure in ex vivo preparation long-lasting changes in neuronal functions that have developed in intact awake animals

  14. Potential sources of intrinsic optical signals imaged in live brain slices.

    PubMed

    Andrew, R D; Jarvis, C R; Obeidat, A S

    1999-06-01

    Changes in how light is absorbed or scattered in biological tissue are termed intrinsic optical signals (IOSs). Imaging IOSs in the submerged brain slice preparation provides insight into brain activity if it involves significant water movement between intracellular and extracellular compartments. This includes responses to osmotic imbalance, excitotoxic glutamate agonists, and oxygen/glucose deprivation, the latter leading to spreading depression. There are several misconceptions regarding these signals. (1) IOSs are not generated by glial swelling alone. Although neuronal and glia sources cannot yet be directly imaged, several lines of evidence indicate that neurons contribute significantly to the changes in light transmittance. (2) Excitotoxic swelling and osmotic swelling are physiologically different, as are their associated IOSs. Hyposmotic swelling involves no detectable neuronal depolarization of cortical pyramidal neurons, only the passive drawing in of water from a dilute medium across the cell membrane. In contrast excitotoxic swelling involves sustained membrane depolarization associated with inordinate amounts of Na+ and Cl- entry followed by water. IOSs demonstrate substantial damage in the latter case. (3) Osmotic perturbations do not induce volume regulatory mechanisms as measured by IOSs. The osmotic responses measured by IOSs in brain slices are passive, without the compensatory mechanisms that are assumed to be active on a scale suggested by studies of cultured brain cells under excessive osmotic stress. (4) Spreading depression (SD) can cause neuronal damage. Innocuous during migraine aura, SD induces acute neuronal damage in brain slices that are metabolically compromised by oxygen/glucose deprivation, as demonstrated by IOSs. Neighboring tissue where SD does not spread remains relatively healthy as judged by a minimal reduction in light transmittance. IOSs show that the metabolic stress of SD combined with the compromise of energy resources

  15. Scatter imaging of injured brain slices: detection of mitochondrial injury

    NASA Astrophysics Data System (ADS)

    Johnson, Lee J.; Hanley, Daniel F.; Thakor, Nitish V.

    1999-06-01

    Stroke has been shown to cause exitotoxic injury, two of its manifestations being cellular and mitochondrial swelling. In vitro models of stroke attempt to reproduce the effects of stroke by treating brain tissue with excitotoxins or hypotonic solutions. To further resolve the mechanism of stroke injury, we have designed a dual-angle scatter imaging (DASI) system sensitive to particle size. The DASI system has been used with a hippocampal slice preparation to contrast cellular swelling, induced by hypotonicity, and combined cellular and mitochondrial swelling caused by excitotoxicity. We found that both hypotonic end excitotoxic treatments caused changes in light scatter. However, only excitotoxic treatment caused a significant change in DASI.

  16. Electrophysiological recordings of patterned rat brain stem slice neurons.

    PubMed

    Lauer, L; Vogt, A; Yeung, C K; Knoll, W; Offenhäusser, A

    2002-08-01

    Dissociated neuronal cultures on substrates patterned with extracellular matrix (ECM) proteins have yielded much information in the past. However, although the culture of brain slices has many advantages over dissociated neuronal cultures, its feasibility on patterned substrates has not been demonstrated to date. In the present study, neuronal outgrowth from brain stem slices onto homogeneous control substrates, and onto laminin structures of grid- and line-shape was achieved. Cultures were evaluated by means of phase contrast microscopy, antibody staining, and patch-clamp measurements. Only patterns with line sizes of more than 4 microm yielded satisfactory neuronal outgrowth. The size of the nodes in the pattern influenced the nodal compliance of the spreading cells and the amount of unstructured overgrowth. Best grid patterns were 4 microm lines and 10 microm nodes, best line patterns were 4 microm lines and 20 microm nodes. On patterned substrates, average sodium and potassium currents were reduced by approximately 50% compared to controls, whereas area-normalized ion-currents were in the same order of magnitude. This indicates that as a consequence of the pattern-enforced geometrical confinement, neurons tend to have a smaller surface. In addition, neurons on patterned substrates were rapidly covered with glial overgrowth. This was shown by antibody staining. PMID:12102183

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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. PMID:25945319

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

    PubMed Central

    Mattei, G; Cristiani, I; Magliaro, C

    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. PMID:25945319

  20. Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices

    PubMed Central

    Engle, Staci E.; Broderick, Hilary J.; Drenan, Ryan M.

    2012-01-01

    Tobacco use leads to numerous health problems, including cancer, heart disease, emphysema, and stroke. Addiction to cigarette smoking is a prevalent neuropsychiatric disorder that stems from the biophysical and cellular actions of nicotine on nicotinic acetylcholine receptors (nAChRs) throughout the central nervous system. Understanding the various nAChR subtypes that exist in brain areas relevant to nicotine addiction is a major priority. Experiments that employ electrophysiology techniques such as whole-cell patch clamp or two-electrode voltage clamp recordings are useful for pharmacological characterization of nAChRs of interest. Cells expressing nAChRs, such as mammalian tissue culture cells or Xenopus laevis oocytes, are physically isolated and are therefore easily studied using the tools of modern pharmacology. Much progress has been made using these techniques, particularly when the target receptor was already known and ectopic expression was easily achieved. Often, however, it is necessary to study nAChRs in their native environment: in neurons within brain slices acutely harvested from laboratory mice or rats. For example, mice expressing "hypersensitive" nAChR subunits such as α4 L9′A mice 1 and α6 L9′S mice 2, allow for unambiguous identification of neurons based on their functional expression of a specific nAChR subunit. Although whole-cell patch clamp recordings from neurons in brain slices is routinely done by the skilled electrophysiologist, it is challenging to locally apply drugs such as acetylcholine or nicotine to the recorded cell within a brain slice. Dilution of drugs into the superfusate (bath application) is not rapidly reversible, and U-tube systems are not easily adapted to work with brain slices. In this paper, we describe a method for rapidly applying nAChR-activating drugs to neurons recorded in adult mouse brain slices. Standard whole-cell recordings are made from neurons in slices, and a second micropipette filled with a drug of

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

    PubMed Central

    Bennink, Edwin; Oosterbroek, Jaap; Horsch, Alexander D.; Dankbaar, Jan Willem; Velthuis, Birgitta K.; 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 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. Materials and Methods 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. Results 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. Conclusions 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

  2. Glial-Restricted Precursors Protect Neonatal Brain Slices from Hypoxic-Ischemic Cell Death Without Direct Tissue Contact.

    PubMed

    Sweda, Romy; Phillips, Andre W; Marx, Joel; Johnston, Michael V; Wilson, Mary Ann; Fatemi, Ali

    2016-07-01

    Glial-Restricted Precursors (GRPs) are tripotential progenitors that have been shown to exhibit beneficial effects in several preclinical models of neurological disorders, including neonatal brain injury. The mechanisms of action of these cells, however, require further study, as do clinically relevant questions such as timing and route of cell administration. Here, we explored the effects of GRPs on neonatal hypoxia-ischemia during acute and subacute stages, using an in vitro transwell co-culture system with organotypic brain slices exposed to oxygen-glucose deprivation (OGD). OGD-exposed slices that were then co-cultured with GRPs without direct cell contact had decreased tissue injury and cortical cell death, as evaluated by lactate dehydrogenase (LDH) release and propidium iodide (PI) staining. This effect was more pronounced when cells were added during the subacute phase of the injury. Furthermore, GRPs reduced the amount of glutamate in the slice supernatant and changed the proliferation pattern of endogenous progenitor cells in brain slices. In summary, we show that GRPs exert a neuroprotective effect on neonatal hypoxia-ischemia without the need for direct cell-cell contact, thus confirming the rising view that beneficial actions of stem cells are more likely attributable to trophic or immunomodulatory support rather than to long-term integration. PMID:27149035

  3. Development and characterization of an ex-vivo brain slice culture model of chronic wasting disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prion diseases have long incubation times in vivo, therefore, modeling the diseases ex-vivo will advance the development of rationale-based therapeutic strategies. An organotypic slice culture assay (POSCA) was recently developed for scrapie prions by inoculating mouse cerebellar brain slices with R...

  4. Autophagy in acute brain injury.

    PubMed

    Galluzzi, Lorenzo; Bravo-San Pedro, José Manuel; Blomgren, Klas; Kroemer, Guido

    2016-08-01

    Autophagy is an evolutionarily ancient mechanism that ensures the lysosomal degradation of old, supernumerary or ectopic cytoplasmic entities. Most eukaryotic cells, including neurons, rely on proficient autophagic responses for the maintenance of homeostasis in response to stress. Accordingly, autophagy mediates neuroprotective effects following some forms of acute brain damage, including methamphetamine intoxication, spinal cord injury and subarachnoid haemorrhage. In some other circumstances, however, the autophagic machinery precipitates a peculiar form of cell death (known as autosis) that contributes to the aetiology of other types of acute brain damage, such as neonatal asphyxia. Here, we dissect the context-specific impact of autophagy on non-infectious acute brain injury, emphasizing the possible therapeutic application of pharmacological activators and inhibitors of this catabolic process for neuroprotection. PMID:27256553

  5. Perfused drop microfluidic device for brain slice culture-based drug discovery.

    PubMed

    Liu, Jing; Pan, Liping; Cheng, Xuanhong; Berdichevsky, Yevgeny

    2016-06-01

    Living slices of brain tissue are widely used to model brain processes in vitro. In addition to basic neurophysiology studies, brain slices are also extensively used for pharmacology, toxicology, and drug discovery research. In these experiments, high parallelism and throughput are critical. Capability to conduct long-term electrical recording experiments may also be necessary to address disease processes that require protein synthesis and neural circuit rewiring. We developed a novel perfused drop microfluidic device for use with long term cultures of brain slices (organotypic cultures). Slices of hippocampus were placed into wells cut in polydimethylsiloxane (PDMS) film. Fluid level in the wells was hydrostatically controlled such that a drop was formed around each slice. The drops were continuously perfused with culture medium through microchannels. We found that viable organotypic hippocampal slice cultures could be maintained for at least 9 days in vitro. PDMS microfluidic network could be readily integrated with substrate-printed microelectrodes for parallel electrical recordings of multiple perfused organotypic cultures on a single MEA chip. We expect that this highly scalable perfused drop microfluidic device will facilitate high-throughput drug discovery and toxicology. PMID:27194028

  6. Imaging of molecular surface dynamics in brain slices using single-particle tracking

    PubMed Central

    Biermann, B.; Sokoll, S.; Klueva, J.; Missler, M.; Wiegert, J. S.; Sibarita, J. -B.; Heine, M.

    2014-01-01

    Organization of signalling molecules in biological membranes is crucial for cellular communication. Many receptors, ion channels and cell adhesion molecules are associated with proteins important for their trafficking, surface localization or function. These complexes are embedded in a lipid environment of varying composition. Binding affinities and stoichiometry of such complexes were so far experimentally accessible only in isolated systems or monolayers of cell culture. Visualization of molecular dynamics within signalling complexes and their correlation to specialized membrane compartments demand high temporal and spatial resolution and has been difficult to demonstrate in complex tissue like brain slices. Here we demonstrate the feasibility of single-particle tracking (SPT) in organotypic brain slices to measure molecular dynamics of lipids and transmembrane proteins in correlation to synaptic membrane compartments. This method will provide important information about the dynamics and organization of surface molecules in the complex environment of neuronal networks within brain slices. PMID:24429796

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

    NASA Astrophysics Data System (ADS)

    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.

  8. Simulated ischaemia-reperfusion conditions increase xanthine dehydrogenase and oxidase activities in rat brain slices.

    PubMed

    Battelli, M G; Buonamici, L; Virgili, M; Abbondanza, A; Contestabile, A

    1998-01-01

    Xanthine dehydrogenase and oxidase activities increased by 87% in rat brain slices after 30 min in vitro ischaemia. A further 41% increase was induced by 30 min simulated reperfusion of ischaemic slices. No conversion from the dehydrogenase to the oxidase activity was observed. The increment of enzyme activity was not due to neosynthesis of the enzyme, since it was not affected by the addition of cycloheximide during the ischaemic incubation. The increased oxygen-dependent form of the enzyme could aggravate the ischaemic brain injury by free radicals production, in particular after reperfusion. PMID:9460697

  9. Effect of slice thickness on brain magnetic resonance image texture analysis

    PubMed Central

    2010-01-01

    Background The accuracy of texture analysis in clinical evaluation of magnetic resonance images depends considerably on imaging arrangements and various image quality parameters. In this paper, we study the effect of slice thickness on brain tissue texture analysis using a statistical approach and classification of T1-weighted images of clinically confirmed multiple sclerosis patients. Methods We averaged the intensities of three consecutive 1-mm slices to simulate 3-mm slices. Two hundred sixty-four texture parameters were calculated for both the original and the averaged slices. Wilcoxon's signed ranks test was used to find differences between the regions of interest representing white matter and multiple sclerosis plaques. Linear and nonlinear discriminant analyses were applied with several separate training and test sets to determine the actual classification accuracy. Results Only moderate differences in distributions of the texture parameter value for 1-mm and simulated 3-mm-thick slices were found. Our study also showed that white matter areas are well separable from multiple sclerosis plaques even if the slice thickness differs between training and test sets. Conclusions Three-millimeter-thick magnetic resonance image slices acquired with a 1.5 T clinical magnetic resonance scanner seem to be sufficient for texture analysis of multiple sclerosis plaques and white matter tissue. PMID:20955567

  10. Modification of a Colliculo-thalamocortical Mouse Brain Slice, Incorporating 3-D printing of Chamber Components and Multi-scale Optical Imaging.

    PubMed

    Slater, Bernard J; Fan, Anthony Y; Stebbings, Kevin A; Saif, M Taher A; Llano, Daniel A

    2015-01-01

    The ability of the brain to process sensory information relies on both ascending and descending sets of projections. Until recently, the only way to study these two systems and how they interact has been with the use of in vivo preparations. Major advances have been made with acute brain slices containing the thalamocortical and cortico-thalamic pathways in the somatosensory, visual, and auditory systems. With key refinements to our recent modification of the auditory thalamocortical slice(1), we are able to more reliably capture the projections between most of the major auditory midbrain and forebrain structures: the inferior colliculus (IC), medial geniculate body (MGB), thalamic reticular nucleus (TRN), and the auditory cortex (AC). With portions of all these connections retained, we are able to answer detailed questions that complement the questions that can be answered with in vivo preparations. The use of flavoprotein autofluorescence imaging enables us to rapidly assess connectivity in any given slice and guide the ensuing experiment. Using this slice in conjunction with recording and imaging techniques, we are now better equipped to understand how information processing occurs at each point in the auditory forebrain as information ascends to the cortex, and the impact of descending cortical modulation. 3-D printing to build slice chamber components permits double-sided perfusion and broad access to networks within the slice and maintains the widespread connections key to fully utilizing this preparation. PMID:26437382

  11. Ruminant organotypic brain-slice cultures as a model for the investigation of CNS listeriosis

    PubMed Central

    Guldimann, Claudia; Lejeune, Beatrice; Hofer, Sandra; Leib, Stephen L; Frey, Joachim; Zurbriggen, Andreas; Seuberlich, Torsten; Oevermann, Anna

    2012-01-01

    Central nervous system (CNS) infections in ruminant livestock, such as listeriosis, are of major concern for veterinary and public health. To date, no host-specific in vitro models for ruminant CNS infections are available. Here, we established and evaluated the suitability of organotypic brain-slices of ruminant origin as in vitro model to study mechanisms of Listeria monocytogenes CNS infection. Ruminants are frequently affected by fatal listeric rhombencephalitis that closely resembles the same condition occurring in humans. Better insight into host–pathogen interactions in ruminants is therefore of interest, not only from a veterinary but also from a public health perspective. Brains were obtained at the slaughterhouse, and hippocampal and cerebellar brain-slices were cultured up to 49 days. Viability as well as the composition of cell populations was assessed weekly. Viable neurons, astrocytes, microglia and oligodendrocytes were observed up to 49 days in vitro. Slice cultures were infected with L. monocytogenes, and infection kinetics were monitored. Infected brain cells were identified by double immunofluorescence, and results were compared to natural cases of listeric rhombencephalitis. Similar to the natural infection, infected brain-slices showed focal replication of L. monocytogenes and bacteria were predominantly observed in microglia, but also in astrocytes, and associated with axons. These results demonstrate that organotypic brain-slice cultures of bovine origin survive for extended periods and can be infected easily with L. monocytogenes. Therefore, they are a suitable model to study aspects of host–pathogen interaction in listeric encephalitis and potentially in other neuroinfectious diseases. PMID:22804762

  12. Ruminant organotypic brain-slice cultures as a model for the investigation of CNS listeriosis.

    PubMed

    Guldimann, Claudia; Lejeune, Beatrice; Hofer, Sandra; Leib, Stephen L; Frey, Joachim; Zurbriggen, Andreas; Seuberlich, Torsten; Oevermann, Anna

    2012-08-01

    Central nervous system (CNS) infections in ruminant livestock, such as listeriosis, are of major concern for veterinary and public health. To date, no host-specific in vitro models for ruminant CNS infections are available. Here, we established and evaluated the suitability of organotypic brain-slices of ruminant origin as in vitro model to study mechanisms of Listeria monocytogenes CNS infection. Ruminants are frequently affected by fatal listeric rhombencephalitis that closely resembles the same condition occurring in humans. Better insight into host-pathogen interactions in ruminants is therefore of interest, not only from a veterinary but also from a public health perspective. Brains were obtained at the slaughterhouse, and hippocampal and cerebellar brain-slices were cultured up to 49 days. Viability as well as the composition of cell populations was assessed weekly. Viable neurons, astrocytes, microglia and oligodendrocytes were observed up to 49 days in vitro. Slice cultures were infected with L. monocytogenes, and infection kinetics were monitored. Infected brain cells were identified by double immunofluorescence, and results were compared to natural cases of listeric rhombencephalitis. Similar to the natural infection, infected brain-slices showed focal replication of L. monocytogenes and bacteria were predominantly observed in microglia, but also in astrocytes, and associated with axons. These results demonstrate that organotypic brain-slice cultures of bovine origin survive for extended periods and can be infected easily with L. monocytogenes. Therefore, they are a suitable model to study aspects of host-pathogen interaction in listeric encephalitis and potentially in other neuroinfectious diseases. PMID:22804762

  13. Microglia and macrophages differentially modulate cell death after brain injury caused by oxygen-glucose deprivation in organotypic brain slices.

    PubMed

    Girard, Sylvie; Brough, David; Lopez-Castejon, Gloria; Giles, James; Rothwell, Nancy J; Allan, Stuart M

    2013-05-01

    Macrophage can adopt several phenotypes, process call polarization, which is crucial for shaping inflammatory responses to injury. It is not known if microglia, a resident brain macrophage population, polarizes in a similar way, and whether specific microglial phenotypes modulate cell death in response to brain injury. In this study, we show that both BV2-microglia and mouse bone marrow derived macrophages (BMDMs) were able to adopt different phenotypes after LPS (M1) or IL-4 (M2) treatment in vitro, but regulated cell death differently when added to mouse organotypic hippocampal brain slices. BMDMs induced cell death when added to control slices and exacerbated damage when combined with oxygen-glucose deprivation (OGD), independently of their phenotype. In contrast, vehicle- and M2-BV2-microglia were protective against OGD-induced death. Direct treatment of brain slices with IL-4 (without cell addition) was protective against OGD and induced an M2 phenotype in the slice. In vivo, intracerebral injection of LPS or IL-4 in mice induced microglial phenotypes similar to the phenotypes observed in brain slices and in cultured cells. After injury induced by middle cerebral artery occlusion, microglial cells did not adopt classical M1/M2 phenotypes, suggesting that another subtype of regulatory phenotype was induced. This study highlights functional differences between macrophages and microglia, in response to brain injury with fundamentally different outcomes, even if both populations were able to adopt M1 or M2 phenotypes. These data suggest that macrophages infiltrating the brain from the periphery after an injury may be cytotoxic, independently of their phenotype, while microglia may be protective. PMID:23404620

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

    PubMed

    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. PMID:26488641

  15. Oxygen measurements in brain stem slices exposed to normobaric hyperoxia and hyperbaric oxygen.

    PubMed

    Mulkey, D K; Henderson, R A; Olson, J E; Putnam, R W; Dean, J B

    2001-05-01

    We previously reported (J Appl Physiol 89: 807-822, 2000) that < or =10 min of hyperbaric oxygen (HBO(2); < or = 2,468 Torr) stimulates solitary complex neurons. To better define the hyperoxic stimulus, we measured PO(2) in the solitary complex of 300-microm-thick rat medullary slices, using polarographic carbon fiber microelectrodes, during perfusion with media having PO(2) values ranging from 156 to 2,468 Torr. Under control conditions, slices equilibrated with 95% O(2) at barometric pressure of 1 atmospheres absolute had minimum PO(2) values at their centers (291 +/- 20 Torr) that were approximately 10-fold greater than PO(2) values measured in the intact central nervous system (10-34 Torr). During HBO(2), PO(2) increased at the center of the slice from 616 +/- 16 to 1,517 +/- 15 Torr. Tissue oxygen consumption tended to decrease at medium PO(2) or = 1,675 Torr to levels not different from values measured at PO(2) found in all media in metabolically poisoned slices (2-deoxy-D-glucose and antimycin A). We conclude that control medium used in most brain slice studies is hyperoxic at normobaric pressure. During HBO(2), slice PO(2) increases to levels that appear to reduce metabolism. PMID:11299283

  16. Visualizing septin and cell dynamics in mammalian brain slices.

    PubMed

    Ito, H; Morishita, R; Tabata, H; Nagata, K

    2016-01-01

    Correct neuronal migration is crucial for the brain architecture and function. During brain development, excitatory and inhibitory neurons generated in the ventricular zone (VZ) of the dorsal telencephalon and ganglionic medial eminence, respectively, move to their final destinations in tightly regulated spatiotemporal manners. While a variety of morphological methods have been applied to neurobiology, in utero electroporation (IUE) technique is one of the most powerful tools for rapid gain- and loss-of-function studies of brain development. This method enables us to introduce genes of interest into VZ progenitor and stem cells of rodent embryos, and to observe resulting phenotypes such as proliferation, migration, and cell morphology at later stages. In this chapter, we first summarize basic immunohistochemistry methods that are foundations for any advanced methods and showed data on the distribution of Sept6, Sept9, and Sept14 as examples. Then, IUE method is described where functional analyses of Sept14 during brain development are used as examples. We subsequently refer to the in vivo electroporation (IVE)-mediated gene transfer, which is conceptually the same method as IUE, into granule cells of hippocampal dentate gyrus in neonatal mice. Finally, an IUE-based time-lapse imaging method is explained as an advanced technique for the analyses of cortical neuron migration. IUE and IVE methods and the application would contribute greatly to the morphological analyses of septins as well as other molecules to elucidate their neuronal functions and pathophysiological roles in various neurological and psychiatric disorders. PMID:27473916

  17. Direct-current Stimulation and Multi-electrode Array Recording of Seizure-like Activity in Mice Brain Slice Preparation.

    PubMed

    Lu, Hsiang-Chin; Chang, Wei-Jen; Chang, Wei-Pang; Shyu, Bai-Chuang

    2016-01-01

    Cathodal transcranial direct-current stimulation (tDCS) induces suppressive effects on drug-resistant seizures. To perform effective actions, the stimulation parameters (e.g., orientation, field strength, and stimulation duration) need to be examined in mice brain slice preparations. Testing and arranging the orientation of the electrode relative to the position of the mice brain slice are feasible. The present method preserves the thalamocingulate pathway to evaluate the effect of DCS on anterior cingulate cortex seizure-like activities. The results of the multichannel array recordings indicated that cathodal DCS significantly decreased the amplitude of the stimulation-evoked responses and duration of 4-aminopyridine and bicuculline-induced seizure-like activity. This study also found that cathodal DCS applications at 15 min caused long-term depression in the thalamocingulate pathway. The present study investigates the effects of DCS on thalamocingulate synaptic plasticity and acute seizure-like activities. The current procedure can test the optimal stimulation parameters including orientation, field strength, and stimulation duration in an in vitro mouse model. Also, the method can evaluate the effects of DCS on cortical seizure-like activities at both the cellular and network levels. PMID:27341682

  18. Modulation of GABA-augmented norepinephrine release in female rat brain slices by opioids and adenosine.

    PubMed

    Fiber, J M; Etgen, A M

    2001-07-01

    GABAA receptor activation augments electrically-stimulated release of norepinephrine (NE) from rat brain slices. Because this effect is not observed in synaptoneurosomes, GABA probably acts on inhibitory interneurons to disinhibit NE release. To determine whether opioids or adenosine influence GABA-augmented NE release, hypothalamic and cortical slices from female rats were superfused with GABA or vehicle in the presence and absence of 10 microM morphine or 100 microM adenosine. GABA augments [3H]NE release in the cortex and hypothalamus. Morphine alone has no effect on [3H]NE release, but attenuates GABA augmentation of [3H]NE release in both brain regions. Adenosine alone modestly inhibits [3H]NE release in the cortex, but not in the hypothalamus. Adenosine inhibits GABA-augmented [3H]NE release in both brain regions. The general protein kinase inhibitor H-7, augments [3H]NE release in both brain regions and may have additive effects with GABA in cortical slices. These results implicate opioid and adenosine interneurons and possibly protein kinases in regulating GABAergic influences on NE transmission. PMID:11565619

  19. Brain tumor segmentation in MR slices using improved GrowCut algorithm

    NASA Astrophysics Data System (ADS)

    Ji, Chunhong; Yu, Jinhua; Wang, Yuanyuan; Chen, Liang; Shi, Zhifeng; Mao, Ying

    2015-12-01

    The detection of brain tumor from MR images is very significant for medical diagnosis and treatment. However, the existing methods are mostly based on manual or semiautomatic segmentation which are awkward when dealing with a large amount of MR slices. In this paper, a new fully automatic method for the segmentation of brain tumors in MR slices is presented. Based on the hypothesis of the symmetric brain structure, the method improves the interactive GrowCut algorithm by further using the bounding box algorithm in the pre-processing step. More importantly, local reflectional symmetry is used to make up the deficiency of the bounding box method. After segmentation, 3D tumor image is reconstructed. We evaluate the accuracy of the proposed method on MR slices with synthetic tumors and actual clinical MR images. Result of the proposed method is compared with the actual position of simulated 3D tumor qualitatively and quantitatively. In addition, our automatic method produces equivalent performance as manual segmentation and the interactive GrowCut with manual interference while providing fully automatic segmentation.

  20. A novel electrochemical approach for prolonged measurement of absolute levels of extracellular dopamine in brain slices.

    PubMed

    Burrell, Mark H; Atcherley, Christopher W; Heien, Michael L; Lipski, Janusz

    2015-11-18

    Tonic dopamine (DA) levels influence the activity of dopaminergic neurons and the dynamics of fast dopaminergic transmission. Although carbon fiber microelectrodes and fast-scan cyclic voltammetry (FSCV) have been extensively used to quantify stimulus-induced release and uptake of DA in vivo and in vitro, this technique relies on background subtraction and thus cannot provide information about absolute extracellular concentrations. It is also generally not suitable for prolonged (>90 s) recordings due to drift of the background current. A recently reported, modified FSCV approach called fast-scan controlled-adsorption voltammetry (FSCAV) has been used to assess tonic DA levels in solution and in the anesthetized mouse brain. Here we describe a novel extension of FSCAV to investigate pharmacologically induced, slowly occurring changes in tonic (background) extracellular DA concentration, and phasic (stimulated) DA release in brain slices. FSCAV was used to measure adsorption dynamics and changes in DA concentration (for up to 1.5 h, sampling interval 30 s, detection threshold < 10 nM) evoked by drugs affecting DA release and uptake (amphetamine, l-DOPA, pargyline, cocaine, Ro4-1284) in submerged striatal slices obtained from rats. We also show that combined FSCAV-FSCV recordings can be used for concurrent study of stimulated release and changes in tonic DA concentration. Our results demonstrate that FSCAV can be effectively used in brain slices to measure prolonged changes in extracellular level of endogenous DA expressed as absolute values, complementing studies conducted in vivo with microdialysis. PMID:26322962

  1. Vibrodissociation of Neurons from Rodent Brain Slices to Study Synaptic Transmission and Image Presynaptic Terminals

    PubMed Central

    Jun, Sang Beom; Cuzon Carlson, Verginia; Ikeda, Stephen; Lovinger, David

    2011-01-01

    Mechanical dissociation of neurons from the central nervous system has the advantage that presynaptic boutons remain attached to the isolated neuron of interest. This allows for examination of synaptic transmission under conditions where the extracellular and postsynaptic intracellular environments can be well controlled. A vibration-based technique without the use of proteases, known as vibrodissociation, is the most popular technique for mechanical isolation. A micropipette, with the tip fire-polished to the shape of a small ball, is placed into a brain slice made from a P1-P21 rodent. The micropipette is vibrated parallel to the slice surface and lowered through the slice thickness resulting in the liberation of isolated neurons. The isolated neurons are ready for study within a few minutes of vibrodissociation. This technique has advantages over the use of primary neuronal cultures, brain slices and enzymatically isolated neurons including: rapid production of viable, relatively mature neurons suitable for electrophysiological and imaging studies; superior control of the extracellular environment free from the influence of neighboring cells; suitability for well-controlled pharmacological experiments using rapid drug application and total cell superfusion; and improved space-clamp in whole-cell recordings relative to neurons in slice or cell culture preparations. This preparation can be used to examine synaptic physiology, pharmacology, modulation and plasticity. Real-time imaging of both pre- and postsynaptic elements in the living cells and boutons is also possible using vibrodissociated neurons. Characterization of the molecular constituents of pre- and postsynaptic elements can also be achieved with immunological and imaging-based approaches. PMID:21654624

  2. STED Nanoscopy of Actin Dynamics in Synapses Deep Inside Living Brain Slices

    PubMed Central

    Urban, Nicolai T.; Willig, Katrin I.; Hell, Stefan W.; Nägerl, U. Valentin

    2011-01-01

    It is difficult to investigate the mechanisms that mediate long-term changes in synapse function because synapses are small and deeply embedded inside brain tissue. Although recent fluorescence nanoscopy techniques afford improved resolution, they have so far been restricted to dissociated cells or tissue surfaces. However, to study synapses under realistic conditions, one must image several cell layers deep inside more-intact, three-dimensional preparations that exhibit strong light scattering, such as brain slices or brains in vivo. Using aberration-reducing optics, we demonstrate that it is possible to achieve stimulated emission depletion superresolution imaging deep inside scattering biological tissue. To illustrate the power of this novel (to our knowledge) approach, we resolved distinct distributions of actin inside dendrites and spines with a resolution of 60–80 nm in living organotypic brain slices at depths up to 120 μm. In addition, time-lapse stimulated emission depletion imaging revealed changes in actin-based structures inside spines and spine necks, and showed that these dynamics can be modulated by neuronal activity. Our approach greatly facilitates investigations of actin dynamics at the nanoscale within functionally intact brain tissue. PMID:21889466

  3. A Rapid Approach to High-Resolution Fluorescence Imaging in Semi-Thick Brain Slices

    PubMed Central

    Selever, Jennifer; Kong, Jian-Qiang; Arenkiel, Benjamin R.

    2011-01-01

    preparation, or cost-prohibitive instrumentation respectively. Here, we present a relatively rapid and simple method to visualize fluorescently labelled cells in fixed semi-thick mouse brain slices by optical clearing and imaging. In the attached protocol we describe the methods of: 1) fixing brain tissue in situ via intracardial perfusion, 2) dissection and removal of whole brain, 3) stationary brain embedding in agarose, 4) precision semi-thick slice preparation using new vibratome instrumentation, 5) clearing brain tissue through a glycerol gradient, and 6) mounting on glass slides for light microscopy and z-stack reconstruction (Figure 1). For preparing brain slices we implemented a relatively new piece of instrumentation called the 'Compresstome' VF-200 (http://www.precisionary.com/products_vf200.html). This instrument is a semi-automated microtome equipped with a motorized advance and blade vibration system with features similar in function to other vibratomes. Unlike other vibratomes, the tissue to be sliced is mounted in an agarose plug within a stainless steel cylinder. The tissue is extruded at desired thicknesses from the cylinder, and cut by the forward advancing vibrating blade. The agarose plug/cylinder system allows for reproducible tissue mounting, alignment, and precision cutting. In our hands, the 'Compresstome' yields high quality tissue slices for electrophysiology, immunohistochemistry, and direct fixed-tissue mounting and imaging. Combined with optical clearing, here we demonstrate the preparation of semi-thick fixed brain slices for high-resolution fluorescent imaging. PMID:21841756

  4. Tunicamycin produces TDP-43 cytoplasmic inclusions in cultured brain organotypic slices.

    PubMed

    Leggett, Cadman; McGehee, Daniel S; Mastrianni, James; Yang, Wenbin; Bai, Tao; Brorson, James R

    2012-06-15

    The cellular distribution of TAR DNA binding protein (TDP-43) is disrupted in several neurodegenerative disorders, including frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U subtype) and amyotrophic lateral sclerosis (ALS). In these conditions, TDP-43 is found in neuronal cytoplasmic inclusions, with loss of the normal nuclear expression. The mechanisms leading to TDP-43 redistribution and its role in disease pathophysiology remain unknown. We describe an in vitro neural tissue model that reproduces TDP-43 relocalization and inclusion formation. Two week-old coronal organotypic mouse brain slice cultures were treated with tunicamycin for 7 days. In cortical regions of treated slice cultures, cytoplasmic inclusions of TDP-43 immunoreactivity were observed, with loss of nuclear TDP-43 immunoreactivity. These inclusions were found in both astrocytes and neurons, and were of both skein-like and round morphologies. In contrast, TDP-43 cytoplasmic inclusions were not found in slices treated with staurosporine to induce apoptosis, or with trans-4-carboxy-l-proline (PDC) to induce chronic glutamate excitotoxicity. Furthermore, TDP-43 cytoplasmic inclusions did not co-localize with cleaved caspase-3, suggesting that TDP-43 mislocalization does not generally accompany caspase activation or apoptosis. The induction of TDP-43 cytoplasmic translocation in cerebrocortical slice cultures by tunicamycin provides a platform for further mechanistic investigations of pathological processing of TDP-43. PMID:22459357

  5. Resveratrol protects against oxidative injury induced by H2O2 in acute hippocampal slice preparations from Wistar rats.

    PubMed

    de Almeida, Lúcia Maria Vieira; Leite, Marina Concli; Thomazi, Ana Paula; Battu, Cíntia; Nardin, Patrícia; Tortorelli, Lucas Silva; Zanotto, Caroline; Posser, Thaís; Wofchuk, Susana Tchernin; Leal, Rodrigo Bainy; Gonçalves, Carlos-Alberto; Gottfried, Carmem

    2008-12-01

    There is a current interest in dietary compounds (such as trans-resveratrol) that can inhibit or reverse oxidative stress, the common pathway for a variety of brain disorders, including Alzheimer's disease and stroke. The objective of the present study was to investigate the effects of resveratrol, under conditions of oxidative stress induced by H(2)O(2), on acute hippocampal slices from Wistar rats. Here, we evaluated cell viability, extracellular lactate, glutathione content, ERK(MAPK) activity, glutamate uptake and S100B secretion. Resveratrol did not change the decrease in lactate levels and in cell viability (by MTT assay) induced by 1mM H(2)O(2), but prevented the increase in cell permeability to Trypan blue induced by H(2)O(2). Moreover, resveratrol per se increased total glutathione levels and prevented the decrease in glutathione induced by 1mM H(2)O(2). The reduction of S100B secretion induced by H(2)O(2) was not changed by resveratrol. Glutamate uptake was decreased in the presence of 1mM H(2)O(2) and this effect was not prevented by resveratrol. There was also a significant activation of ERK1/2 by 1mM H(2)O(2) and resveratrol was able to completely prevent this activation, leading to activity values lower than control levels. The impairments in astrocyte activities, induced by H(2)O(2), confirmed the importance of these cells as targets for therapeutic strategy in brain disorders involving oxidative stress. This study reinforces the protective role of resveratrol and indicates some possible molecular sites of activity of this compound on glial cells, in the acute damage of brain tissue during oxidative stress. PMID:18835240

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

    PubMed Central

    Komolafe, Kayode; Olaleye, Tolulope M.; Seeger, Rodrigo L.; Carvalho, Fabiano B.; Boligon, Aline A.; Athayde, Margareth L.; Klimaczewski, Claudia V.; Akindahunsi, Akintunde A.; Rocha, Joao B. T.

    2014-01-01

    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. PMID:25177688

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

    PubMed Central

    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. Localized Drug Application and Sub-Second Voltammetric Dopamine Release Measurements in a Brain Slice Perfusion Device

    PubMed Central

    2015-01-01

    The use of fast scan cyclic voltammetry (FSCV) to measure the release and uptake of dopamine (DA) as well as other biogenic molecules in viable brain tissue slices has gained popularity over the last 2 decades. Brain slices have the advantage of maintaining the functional three-dimensional architecture of the neuronal network while also allowing researchers to obtain multiple sets of measurements from a single animal. In this work, we describe a simple, easy-to-fabricate perfusion device designed to focally deliver pharmacological agents to brain slices. The device incorporates a microfluidic channel that runs under the perfusion bath and a microcapillary that supplies fluid from this channel up to the slice. We measured electrically evoked DA release in brain slices before and after the administration of two dopaminergic stimulants, cocaine and GBR-12909. Measurements were collected at two locations, one directly over and the other 500 μm away from the capillary opening. Using this approach, the controlled delivery of drugs to a confined region of the brain slice and the application of this chamber to FSCV measurements, were demonstrated. Moreover, the consumption of drugs was reduced to tens of microliters, which is thousands of times less than traditional perfusion methods. We expect that this simply fabricated device will be useful in providing spatially resolved delivery of drugs with minimum consumption for voltammetric and electrophysiological studies of a variety of biological tissues both in vitro and ex vivo. PMID:24734992

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

    PubMed

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

    2013-01-01

    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

  10. Coculture System with an Organotypic Brain Slice and 3D Spheroid of Carcinoma Cells

    PubMed Central

    Chuang, Han-Ning; Lohaus, Raphaela; Hanisch, Uwe-Karsten; Binder, Claudia

    2013-01-01

    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 prognosis1,2. Especially the tumor associated macrophages (TAM) support migration, invasion and proliferation3. 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 cells4,5. Therefore, functions of these tissue-specific cell types seem to be very important in the process of brain metastasis6,7. 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 behavior8. 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 impossible8. 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 the brain

  11. Supraresolution imaging in brain slices using stimulated-emission depletion 2-photon laser scanning microscopy

    PubMed Central

    Ding, Jun; Takasaki, Kevin T.; Sabatini, Bernardo L.

    2009-01-01

    SUMMARY Two-photon laser scanning microscopy (2PLSM) has allowed unprecedented fluorescent imaging of neuronal structure and function within neural tissue. However, the resolution of this approach is poor compared to that of conventional confocal microscopy. Here we demonstrate supraresolution 2PLSM within brain slices. Imaging beyond the diffraction limit is accomplished by using near-infrared (NIR) lasers for both pulsed 2-photon excitation and continuous wave stimulation emission depletion (STED). Furthermore, we demonstrate that Alexa Fluor-594, a bright fluorophore commonly used for both live cell and fixed tissue fluorescence imaging, is suitable for STED 2PLSM. STED 2PLSM supraresolution microscopy achieves approximately 3 fold improvement in resolution in the radial direction over conventional 2PLSM, revealing greater detail in the structure of dendritic spines located ~100 microns below the surface of brain slices. Further improvements in resolution are theoretically achievable, suggesting that STED 2PLSM will permit nanoscale imaging of neuronal structures located in relatively intact brain tissue. PMID:19709626

  12. Human cerebrospinal fluid increases the excitability of pyramidal neurons in the in vitro brain slice

    PubMed Central

    Bjorefeldt, Andreas; Andreasson, Ulf; Daborg, Jonny; Riebe, Ilse; Wasling, Pontus; Zetterberg, Henrik; Hanse, Eric

    2015-01-01

    The composition of brain extracellular fluid is shaped by a continuous exchange of substances between the cerebrospinal fluid (CSF) and interstitial fluid. The CSF is known to contain a wide range of endogenous neuromodulatory substances, but their collective influence on neuronal activity has been poorly investigated. We show here that replacing artificial CSF (aCSF), routinely used for perfusion of brain slices in vitro, with human CSF (hCSF) powerfully boosts spontaneous firing of CA1, CA3 and layer 5 pyramidal neurons in the rat brain slice. CA1 pyramidal neurons in hCSF display lowered firing thresholds, more depolarized resting membrane potentials and reduced input resistance, mimicking properties of pyramidal neurons recorded in vivo. The increased excitability of CA1 pyramidal neurons was completely occluded by intracellular application of GTPγS, suggesting that endogenous neuromodulators in hCSF act on G-protein coupled receptors to enhance excitability. We found no increase in spontaneous inhibitory synaptic transmission by hCSF, indicating a differential effect on glutamatergic and GABAergic neurons. Our findings highlight a previously unknown function of the CSF in promoting spontaneous excitatory activity, and may help to explain differences observed in the activity of pyramidal neurons recorded in vivo and in vitro. PMID:25556798

  13. Mesenchymal stem cells support neuronal fiber growth in an organotypic brain slice co-culture model.

    PubMed

    Sygnecka, Katja; Heider, Andreas; Scherf, Nico; Alt, Rüdiger; Franke, Heike; Heine, Claudia

    2015-04-01

    Mesenchymal stem cells (MSCs) have been identified as promising candidates for neuroregenerative cell therapies. However, the impact of different isolation procedures on the functional and regenerative characteristics of MSC populations has not been studied thoroughly. To quantify these differences, we directly compared classically isolated bulk bone marrow-derived MSCs (bulk BM-MSCs) to the subpopulation Sca-1(+)Lin(-)CD45(-)-derived MSCs(-) (SL45-MSCs), isolated by fluorescence-activated cell sorting from bulk BM-cell suspensions. Both populations were analyzed with respect to functional readouts, that are, frequency of fibroblast colony forming units (CFU-f), general morphology, and expression of stem cell markers. The SL45-MSC population is characterized by greater morphological homogeneity, higher CFU-f frequency, and significantly increased nestin expression compared with bulk BM-MSCs. We further quantified the potential of both cell populations to enhance neuronal fiber growth, using an ex vivo model of organotypic brain slice co-cultures of the mesocortical dopaminergic projection system. The MSC populations were cultivated underneath the slice co-cultures without direct contact using a transwell system. After cultivation, the fiber density in the border region between the two brain slices was quantified. While both populations significantly enhanced fiber outgrowth as compared with controls, purified SL45-MSCs stimulated fiber growth to a larger degree. Subsequently, we analyzed the expression of different growth factors in both cell populations. The results show a significantly higher expression of brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor in the SL45-MSCs population. Altogether, we conclude that MSC preparations enriched for primary MSCs promote neuronal regeneration and axonal regrowth, more effectively than bulk BM-MSCs, an effect that may be mediated by a higher BDNF secretion. PMID:25390472

  14. The Interplay between Inorganic Phosphate and Amino Acids determines Zinc Solubility in Brain Slices

    PubMed Central

    Rumschik, Sean M.; Nydegger, Irma; Zhao, Jinfu; Kay, Alan R

    2009-01-01

    Inorganic phosphate (Pi) is an important polyanion needed for ATP synthesis and bone formation. Since it is found at millimolar levels in plasma it is usually incorporated as a constituent of artificial cerebrospinal fluid (ACSF) formulations for maintaining brain slices. In this paper we show that Pi limits the extracellular zinc concentration by inducing metal precipitation. We present data suggesting that amino acids like histidine may counteract the Pi-induced zinc precipitation by the formation of soluble zinc complexes. We propose that the interplay between Pi and amino acids in the extracellular space may influence the availability of metals for cellular uptake. PMID:19183267

  15. Patch-clamp recording in brain slices with improved slicer technology.

    PubMed

    Geiger, J R P; Bischofberger, J; Vida, I; Fröbe, U; Pfitzinger, S; Weber, H J; Haverkampf, K; Jonas, P

    2002-01-01

    The use of advanced patch-clamp recording techniques in brain slices, such as simultaneous recording from multiple neurons and recording from dendrites or presynaptic terminals, demands slices of the highest quality. In this context the mechanics of the tissue slicer are an important factor. Ideally, a tissue slicer should generate large-amplitude and high-frequency movements of the cutting blade in a horizontal axis, with minimal vibrations in the vertical axis. We developed a vibroslicer that fulfils these in part conflicting requirements. The oscillator is a permanent-magnet-coil-leaf-spring system. Using an auto-resonant mechano-electrical feedback circuit, large horizontal oscillations (up to 3 mm peak-to-peak) with high frequency ( approximately 90 Hz) are generated. To minimize vertical vibrations, an adjustment mechanism was employed that allowed alignment of the cutting edge of the blade with the major axis of the oscillation. A vibroprobe device was used to monitor vertical vibrations during adjustment. The system is based on the shading of the light path between a light-emitting diode (LED) and a photodiode. Vibroprobe monitoring revealed that the vibroslicer, after appropriate adjustment, generated vertical vibrations of <1 microm, significantly less than many commercial tissue slicers. Light- and electron-microscopic analysis of surface layers of slices cut with the vibroslicer showed that cellular elements, dendritic processes and presynaptic terminals are well preserved under these conditions, as required for patch-clamp recording from these structures. PMID:11810221

  16. Investigation of Synaptic Tagging/Capture and Cross-capture using Acute Hippocampal Slices from Rodents

    PubMed Central

    Shetty, Mahesh Shivarama; Sharma, Mahima; Hui, Neo Sin; Dasgupta, Ananya; Gopinadhan, Suma; Sajikumar, Sreedharan

    2015-01-01

    Synaptic tagging and capture (STC) and cross-tagging are two important mechanisms at cellular level that explain how synapse-specificity and associativity is achieved in neurons within a specific time frame. These long-term plasticity-related processes are the leading candidate models to study the basis of memory formation and persistence at the cellular level. Both STC and cross-tagging involve two serial processes: (1) setting of the synaptic tag as triggered by a specific pattern of stimulation, and (2) synaptic capture, whereby the synaptic tag interacts with newly synthesized plasticity-related proteins (PRPs). Much of the understanding about the concepts of STC and cross-tagging arises from the studies done in CA1 region of the hippocampus and because of the technical complexity many of the laboratories are still unable to study these processes. Experimental conditions for the preparation of hippocampal slices and the recording of stable late-LTP/LTD are extremely important to study synaptic tagging/cross-tagging. This video article describes the experimental procedures to study long-term plasticity processes such as STC and cross-tagging in the CA1 pyramidal neurons using stable, long-term field-potential recordings from acute hippocampal slices of rats. PMID:26381286

  17. Investigation of Synaptic Tagging/Capture and Cross-capture using Acute Hippocampal Slices from Rodents.

    PubMed

    Shetty, Mahesh Shivarama; Sharma, Mahima; Hui, Neo Sin; Dasgupta, Ananya; Gopinadhan, Suma; Sajikumar, Sreedharan

    2015-01-01

    Synaptic tagging and capture (STC) and cross-tagging are two important mechanisms at cellular level that explain how synapse-specificity and associativity is achieved in neurons within a specific time frame. These long-term plasticity-related processes are the leading candidate models to study the basis of memory formation and persistence at the cellular level. Both STC and cross-tagging involve two serial processes: (1) setting of the synaptic tag as triggered by a specific pattern of stimulation, and (2) synaptic capture, whereby the synaptic tag interacts with newly synthesized plasticity-related proteins (PRPs). Much of the understanding about the concepts of STC and cross-tagging arises from the studies done in CA1 region of the hippocampus and because of the technical complexity many of the laboratories are still unable to study these processes. Experimental conditions for the preparation of hippocampal slices and the recording of stable late-LTP/LTD are extremely important to study synaptic tagging/cross-tagging. This video article describes the experimental procedures to study long-term plasticity processes such as STC and cross-tagging in the CA1 pyramidal neurons using stable, long-term field-potential recordings from acute hippocampal slices of rats. PMID:26381286

  18. Organotypic Hippocampal Slices as Models for Stroke and Traumatic Brain Injury.

    PubMed

    Li, Qian; Han, Xiaoning; Wang, Jian

    2016-08-01

    Organotypic hippocampal slice cultures (OHSCs) have been used as a powerful ex vivo model for decades. They have been used successfully in studies of neuronal death, microglial activation, mossy fiber regeneration, neurogenesis, and drug screening. As a pre-animal experimental phase for physiologic and pathologic brain research, OHSCs offer outcomes that are relatively closer to those of whole-animal studies than outcomes obtained from cell culture in vitro. At the same time, mechanisms can be studied more precisely in OHSCs than they can be in vivo. Here, we summarize stroke and traumatic brain injury research that has been carried out in OHSCs and review classic experimental applications of OHSCs and its limitations. PMID:26223803

  19. Long-Term Potentiation by Theta-Burst Stimulation Using Extracellular Field Potential Recordings in Acute Hippocampal Slices.

    PubMed

    Abrahamsson, Therese; Lalanne, Txomin; Watt, Alanna J; Sjöström, P Jesper

    2016-01-01

    This protocol describes how to carry out theta-burst long-term potentiation (LTP) with extracellular field recordings in acute rodent hippocampal slices. This method is relatively simple and noninvasive and provides a way to sample many neurons simultaneously, making it suitable for applications requiring higher throughput than whole-cell recording. PMID:27250947

  20. Regioselective Biolistic Targeting in Organotypic Brain Slices Using a Modified Gene Gun

    PubMed Central

    Arsenault, Jason; Nagy, Andras; Henderson, Jeffrey T.; O'Brien, John A.

    2014-01-01

    Transfection of DNA has been invaluable for biological sciences and with recent advances to organotypic brain slice preparations, the effect of various heterologous genes could thus be investigated easily while maintaining many aspects of in vivo biology. There has been increasing interest to transfect terminally differentiated neurons for which conventional transfection methods have been fraught with difficulties such as low yields and significant losses in viability. Biolistic transfection can circumvent many of these difficulties yet only recently has this technique been modified so that it is amenable for use in mammalian tissues. New modifications to the accelerator chamber have enhanced the gene gun's firing accuracy and increased its depths of penetration while also allowing the use of lower gas pressure (50 psi) without loss of transfection efficiency as well as permitting a focused regioselective spread of the particles to within 3 mm. In addition, this technique is straight forward and faster to perform than tedious microinjections. Both transient and stable expression are possible with nanoparticle bombardment where episomal expression can be detected within 24 hr and the cell survival was shown to be better than, or at least equal to, conventional methods. This technique has however one crucial advantage: it permits the transfection to be localized within a single restrained radius thus enabling the user to anatomically isolate the heterologous gene's effects. Here we present an in-depth protocol to prepare viable adult organotypic slices and submit them to regioselective transfection using an improved gene gun. PMID:25407047

  1. Toward a system to measure action potential on mice brain slices with local magnetoresistive probes

    SciTech Connect

    Amaral, J.; Cardoso, S.; Freitas, P. P.; Sebastiao, A. M.

    2011-04-01

    This work combines an electrophysiological system with a magnetoresistive chip to measure the magnetic field created by the synaptic/action potential currents. The chip, with 15 spin valve sensors, was designed to be integrated in a recording chamber for submerged mice brain slices used for synaptic potential measurements. Under stimulation (rectangular pulses of 0.1 ms every 10 s) through a concentric electrode placed near the CA3/CA1 border of the hippocampus, the spin valve sensor readout signals with 20 {mu}V amplitude and a pulse length of 20 to 30 ms were recorded only in the pyramidal cell bodies region and can be interpreted as being derived from action potentials/currents.

  2. Brain slice biotinylation: an ex vivo approach to measure region-specific plasma membrane protein trafficking in adult neurons.

    PubMed

    Gabriel, Luke R; Wu, Sijia; Melikian, Haley E

    2014-01-01

    Regulated endocytic trafficking is the central mechanism facilitating a variety of neuromodulatory events, by dynamically controlling receptor, ion channel, and transporter cell surface presentation on a minutes time scale. There is a broad diversity of mechanisms that control endocytic trafficking of individual proteins. Studies investigating the molecular underpinnings of trafficking have primarily relied upon surface biotinylation to quantitatively measure changes in membrane protein surface expression in response to exogenous stimuli and gene manipulation. However, this approach has been mainly limited to cultured cells, which may not faithfully reflect the physiologically relevant mechanisms at play in adult neurons. Moreover, cultured cell approaches may underestimate region-specific differences in trafficking mechanisms. Here, we describe an approach that extends cell surface biotinylation to the acute brain slice preparation. We demonstrate that this method provides a high-fidelity approach to measure rapid changes in membrane protein surface levels in adult neurons. This approach is likely to have broad utility in the field of neuronal endocytic trafficking. PMID:24747337

  3. Wide-field optical coherence microscopy of the mouse brain slice.

    PubMed

    Min, Eunjung; Lee, Junwon; Vavilin, Andrey; Jung, Sunwoo; Shin, Sungwon; Kim, Jeehyun; Jung, Woonggyu

    2015-10-01

    The imaging capability of optical coherence microscopy (OCM) has great potential to be used in neuroscience research because it is able to visualize anatomic features of brain tissue without labeling or external contrast agents. However, the field of view of OCM is still narrow, which dilutes the strength of OCM and limits its application. In this study, we present fully automated wide-field OCM for mosaic imaging of sliced mouse brains. A total of 308 segmented OCM images were acquired, stitched, and reconstructed as an en-face brain image after intensive imaging processing. The overall imaging area was 11.2×7.0  mm (horizontal×vertical), and the corresponding pixel resolution was 1.2×1.2  μm. OCM images were compared to traditional histology stained with Nissl and Luxol fast blue (LFB). In particular, the orientation of the fibers was analyzed and quantified in wide-field OCM. PMID:26421546

  4. Nimodipine enhances neurite outgrowth in dopaminergic brain slice co-cultures.

    PubMed

    Sygnecka, Katja; Heine, Claudia; Scherf, Nico; Fasold, Mario; Binder, Hans; Scheller, Christian; Franke, Heike

    2015-02-01

    Calcium ions (Ca(2+)) play important roles in neuroplasticity and the regeneration of nerves. Intracellular Ca(2+) concentrations are regulated by Ca(2+) channels, among them L-type voltage-gated Ca(2+) channels, which are inhibited by dihydropyridines like nimodipine. The purpose of this study was to investigate the effect of nimodipine on neurite growth during development and regeneration. As an appropriate model to study neurite growth, we chose organotypic brain slice co-cultures of the mesocortical dopaminergic projection system, consisting of the ventral tegmental area/substantia nigra and the prefrontal cortex from neonatal rat brains. Quantification of the density of the newly built neurites in the border region (region between the two cultivated slices) of the co-cultures revealed a growth promoting effect of nimodipine at concentrations of 0.1μM and 1μM that was even more pronounced than the effect of the growth factor NGF. This beneficial effect was absent when 10μM nimodipine were applied. Toxicological tests revealed that the application of nimodipine at this higher concentration slightly induced caspase 3 activation in the cortical part of the co-cultures, but did neither affect the amount of lactate dehydrogenase release or propidium iodide uptake nor the ratio of bax/bcl-2. Furthermore, the expression levels of different genes were quantified after nimodipine treatment. The expression of Ca(2+) binding proteins, immediate early genes, glial fibrillary acidic protein, and myelin components did not change significantly after treatment, indicating that the regulation of their expression is not primarily involved in the observed nimodipine mediated neurite growth. In summary, this study revealed for the first time a neurite growth promoting effect of nimodipine in the mesocortical dopaminergic projection system that is highly dependent on the applied concentrations. PMID:25447789

  5. Synthesis and phosphorylation of the glial fibrillary acidic protein during brain development: A tissue slice study

    SciTech Connect

    Noetzel, M.J. )

    1990-01-01

    Brain slices were incubated with either (3H) amino acids or (32P) orthophosphate in order to characterize the synthesis and phosphorylation of the glial fibrillary acidic protein (GFAP) in the rat nervous system. The incorporation of (3H) amino acids into GFAP was found to increase significantly during early postnatal development, reaching a peak of activity on day 5 of life and then declining over the next 2 weeks. Concomitant with this peak of synthetic activity the content of GFAP in rat brain was also observed to increase dramatically. GFAP continued to accumulate in brain through postnatal day 30 despite a decrease in the synthesis of the protein. These results indicate that the increase in GFAP during the first month of life cannot be ascribed solely to the rate of GFAP synthesis. The findings are consistent with the hypothesis that during later stages of astrocytic development the accumulation of GFAP may be primarily dependent upon a low rate of protein degradation. The pattern of GFAP phosphorylation in the developing rat brain differed from that observed for the incorporation of (3H) amino acids. The peak incorporation of 32P into GFAP occurred on postnatal day 10 at a time when synthesis of the protein had declined by 43%. These findings suggest that during development phosphorylation of GFAP is mediated by factors different from those directing its synthesis. In addition, phosphorylation of GFAP did not alter its solubility in cytoskeletal preparations indicating that GFAP phosphorylation is probably not a major regulatory mechanism in disassembly of the astroglial filaments.

  6. Preparation of human formalin-fixed brain slices for electron microscopic investigations.

    PubMed

    Krause, Martin; Brüne, Martin; Theiss, Carsten

    2016-07-01

    Ultra-structural analysis of human post-mortem brain tissue is important for investigations into the pathomechanism of neuropsychiatric disorders, especially those lacking alternative models of studying human-specific morphological features. For example, Von Economo Neurons (VENs) mainly located in the anterior cingulate cortex and in the anterior part of the insula, which seem to play a role in a variety of neuropsychiatric conditions, including frontotemporal dementia, autism and schizophrenia, can hardly be studied in nonhuman animals. Accordingly, little is known about the ultra-structural alterations of these neurons, though important research using qualitative stereological methods has revealed that protein expression of the VENs assigns them a role in immune function. Formaldehyde, which is the most common fixative in human pathology, interferes with the immunoreactivity of the tissue, possibly leading to unreliable results. Therefore, a method for ultra-structural investigations independent of antigenic properties of the fixated tissue is needed. Here, we propose an approach using electron microscopy to examine cytoskeletal structures, synapses and mitochondria in these cells. We also show that our methodology is able to keep tissue consumption to a minimum, while still allowing for the specimens to be handled with ease by using agar embedded slices in contrast to blocks for the embedding procedure. Accordingly, a stepwise protocol utilising 60μm thick human post mortem brain sections for electron microscopic ultra-structural investigations is presented. PMID:27136748

  7. A Finite Element Study of the Dynamic Response of Brain Based on Two Parasagittal Slice Models

    PubMed Central

    Song, Xuewei; Wang, Cong; Hu, Hao; Huang, Tianlun; Jin, Jingxu

    2015-01-01

    The objective of this study is to investigate the influence of gyri and sulci on the response of human head under transient loading. To this end, two detailed parasagittal slice models with and without gyri and sulci have been developed. The models comprised not only cerebrum and skull but also cerebellum, brain stem, CSF, and corpus callosum. In addition, white and gray matters were separated. The material properties were adopted from the literature and assigned to different parts of the models. Nahum's and Trosseille's experiments reported in relevant literature were simulated and the simulation results were compared with the test data. The results show that there is no evident difference in terms of intracranial pressure between the models with and without gyri and sulci under simulated conditions. The equivalent stress below gyri and sulci in the model with gyri and sulci is slightly higher than that in the counterpart model without gyri and sulci. The maximum principle strain in brain tissue is lower in the model with gyri and sulci. The stress and strain distributions are changed due to the existence of gyri and sulci. These findings highlight the necessity to include gyri and sulci in the finite element head modeling. PMID:26495034

  8. Spreading depression: imaging and blockade in the rat neocortical brain slice.

    PubMed

    Anderson, Trent R; Andrew, R David

    2002-11-01

    Spreading depression (SD) is a profound but transient depolarization of neurons and glia that migrates across the cortical and subcortical gray at 2-5 mm/min. Under normoxic conditions, SD occurs during migraine aura where it precedes migraine pain but does not damage tissue. During stroke and head trauma, however, SD can arise repeatedly near the site of injury and may promote neuronal damage. We developed a superfused brain slice preparation that can repeatedly support robust SD during imaging and electrophysiological recording to test drugs that may block SD. Submerged rat neocortical slices were briefly exposed to artificial cerebrospinal fluid (ACSF) with KCl elevated to 26 mM. SD was evoked within 2 min, recorded in layers II/III both as a negative DC shift and as a propagating front of elevated light transmittance (LT) representing transient cell swelling in all cortical layers. An SD episode was initiated focally and could be repeatedly evoked and imaged with no damage to slices. As reported in vivo, pretreatment with one of several N-methyl-D-aspartate (NMDA) receptor antagonists blocked SD, but a non-NMDA glutamate receptor antagonist (CNQX) had no effect. NMDA receptor (NMDAR) activation does not initiate SD nor are NMDAR antagonists tolerated therapeutically so we searched for more efficacious drugs to block SD generation. Pretreatment with the sigma-one receptor (sigma(1)R) agonists dextromethorphan (10-100 microM), carbetapentane (100 microM), or 4-IBP (30 microM) blocked SD, even when KCl exposure was extended beyond 5 min. The block was independent of NMDA receptor antagonism. Two sigma(1)R antagonists [(+)-3PPP and BD-1063] removed this block but had no effect upon SD alone. Remarkably, the sigma(1)R agonists also substantially reduced general cell swelling evoked by bath application of 26 mM KCl. More potent sigma(1)R ligands that are therapeutically tolerated could prove useful in reducing SD associated with migraine and be of potential use in

  9. Acute Methamphetamine Intoxication: Brain Hyperthermia, Blood-Brain Barrier and Brain Edema

    PubMed Central

    Kiyatkin, Eugene A.; Sharma, Hari S.

    2011-01-01

    Methamphetamine (METH) is a powerful and often abused stimulant with potent addictive and neurotoxic properties. While it is generally assumed that multiple chemical substances released in the brain following METH-induced metabolic activation (or oxidative stress) are primary factors underlying damage of neural cells, in this work we will present data suggesting a role of brain hyperthermia and associated leakage of the brain-blood barrier (BBB) in acute METH-induced toxicity. First, we show that METH induces a dose-dependent brain and body hyperthermia, which is strongly potentiated by associated physiological activation and in warm environments that prevent proper heat dissipation to the external environment. Second, we demonstrate that acute METH intoxication induces robust, widespread but structure-specific leakage of the BBB, acute glial activation, and increased water content (edema), which are related to drug-induced brain hyperthermia. Third, we document widespread morphological abnormalities of brain cells, including neurons, glia, epithelial and endothelial cells developing rapidly during acute METH intoxication. These structural abnormalities are tightly related to the extent of brain hyperthermia, leakage of the BBB, and brain edema. While it is unclear whether these rapidly developed morphological abnormalities are reversible, this study demonstrates that METH induces multiple functional and structural perturbations in the brain, determining its acute toxicity and possibly contributing to neurotoxicity. PMID:19897075

  10. Inhibition of Calpain Prevents Manganese-Induced Cell Injury and Alpha-Synuclein Oligomerization in Organotypic Brain Slice Cultures

    PubMed Central

    Xu, Bin; Liu, Wei; Deng, Yu; Yang, Tian-Yao; Feng, Shu; Xu, Zhao-Fa

    2015-01-01

    Overexposure to manganese has been known to promote alpha-synuclein oligomerization and enhance cellular toxicity. However, the exact mechanism of Mn-induced alpha-synuclein oligomerization is unclear. To explore whether alpha-synuclein oligomerization was associated with the cleavage of alpha-synuclein by calpain, we made a rat brain slice model of manganism and pretreated slices with calpain inhibitor II, a cell-permeable peptide that restricts the activity of calpain. After slices were treated with 400 μM Mn for 24 h, there were significant increases in the percentage of apoptotic cells, lactate dehydrogenase release, intracellular [Ca2+]i, calpain activity, and the mRNA and protein expression of calpain 1 and alpha-synuclein. Moreover, the number of C- and N-terminal fragments of alpha-synuclein and the amount of alpha-synuclein oligomerization also increased. These results also showed that calpain inhibitor II pretreatment could reduce Mn-induced nerve cell injury and alpha-synuclein oligomerization. Additionally, there was a significant decrease in the number of C- and N-terminal fragments of alpha-synuclein in calpain inhibitor II-pretreated slices. These findings revealed that Mn induced the cleavage of alpha-synuclein protein via overactivation of calpain and subsequent alpha-synuclein oligomerization in cultured slices. Moreover, the cleavage of alpha-synuclein by calpain 1 is an important signaling event in Mn-induced alpha-synuclein oligomerization. PMID:25756858

  11. The amiloride-sensitive Na+/H+ exchange antiporter and control of intracellular pH in hippocampal brain slices.

    PubMed

    Lin, C W; Kalaria, R N; Kroon, S N; Bae, J Y; Sayre, L M; LaManna, J C

    1996-08-26

    The intracellular pH, 7.54 +/- 0.03 (mean +/- S.D., n = 15), determined with the Neutral red method, of the hippocampal brain slice preparation under baseline incubation conditions is considerably more alkaline than the bath buffer pH. Neutralization by amiloride suggests that the alkalinity was due to Na+/H+ exchange antiporter activation. To characterize the brain Na+/H+ exchange antiporter we compared the inhibitory effects of MIA, amiloride and other 5-N substituted analogues on proton extrusion after acid loading by transient exposure to ammonium chloride in the isolated hippocampal brain slice preparation. The potencies of amiloride compounds on the initial recovery rate of intracellular pH after acid-loading were DMA > MIA > HMA = MHA > or = IPA-HCI > IPA > MNPA = Amil > Benzamil. The greater potency of the 5-N substituted analogs of amiloride over amiloride and benzamil strongly suggest that Na+/H+ exchange antiporter is the mechanism responsible for alkalinization in the isolated hippocampal brain slice in vitro. PMID:8883860

  12. Real-time monitoring of superoxide accumulation and antioxidant activity in a brain slice model using an electrochemical cytochrome c biosensor

    PubMed Central

    Ganesana, Mallikarjunarao; Erlichman, Joseph S.; Andreescu, Silvana

    2012-01-01

    The overproduction of reactive oxygen species and resulting damage are central to the pathology of many diseases. The study of the temporal and spatial accumulation of reactive oxygen species has been limited due to the lack of specific probes and techniques capable of continuous measurement. We demonstrate the use of a miniaturized electrochemical cytochrome C (Cyt C) biosensor for real-time measurements and quantitative assessment of superoxide production and inactivation by natural and engineered antioxidants in acutely prepared brain slices from mice. During control conditions, superoxide radicals produced from the hippocampal region of the brain in 400 μm thick sections were well within the range of detection of the electrode. Exposure of the slices to ischemic conditions increased the superoxide production two fold and measurements from the slices were stable over a 3–4 hour period. The stilbene derivative and anion channel inhibitor, 4,4′-diisothiocyano-2,2′-disulfonic stilbene (DIDS), markedly reduced the extracellular superoxide signal under control conditions suggesting that a transmembrane flux of superoxide into the extracellular space may occur as part of normal redox signaling. The specificity of the electrode for superoxide released by cells in the hippocampus was verified by the exogenous addition of superoxide dismutase (SOD) which decreased the superoxide signal in a dose-dependent manner. Similar results were seen with the addition of the SOD-mimetic, cerium oxide nanoparticles (nanoceria) where the superoxide anion radical scavenging activity of nanoceria with an average diameter of 15 nm was equivalent to 527 U of SOD for each 1 μg/ml of nanoceria added. This study demonstrates the potential of electrochemical biosensors for studying real-time dynamics of reactive oxygen species in a biological model and the utility of these measurements in defining the relative contribution of superoxide to oxidative injury. PMID:23085519

  13. Time- and dose-dependent changes in neuronal activity produced by x radiation in brain slices

    SciTech Connect

    Not Available

    1990-01-01

    A new method of exposing tissues to X rays in a lead Faraday cage has made it possible to examine directly radiation damage is isolated neuronal tissue. Thin slices of hippocampus from brains of euthanized guinea pigs were exposed to 17.4 keV X radiation. Electrophysiological recordings were made before, during and after exposure to doses between 5 and 65 Gy at a dose rate of 1.54 Gy/min. Following exposure to doses of 40 Gy and greater, the synaptic potential was enhanced, reaching a steady level soon after exposure. The ability of the synaptic potential to generate a spike was reduced and damage progressed after termination of the radiation exposure. Recovery was not observed following termination of exposure. These results demonstrated that an isolated neuronal network can show complex changes in electrophysiological properties following moderate doses of ionizing radiation. An investigation of radiation damage directly to neurons in vitro will contribute to the understanding of the underlying mechanisms of radiation-induced nervous system dysfunction.

  14. Time- and dose-dependent changes in neuronal activity produced by X radiation in brain slices

    SciTech Connect

    Pellmar, T.C.; Schauer, D.A.; Zeman, G.H. )

    1990-05-01

    A new method of exposing tissues to X rays in a lead Faraday cage has made it possible to examine directly radiation damage to isolated neuronal tissue. Thin slices of hippocampus from brains of euthanized guinea pigs were exposed to 17.4 ke V X radiation. Electrophysiological recordings were made before, during, and after exposure to doses between 5 and 65 Gy at a dose rate of 1.54 Gy/min. Following exposure to doses of 40 Gy and greater, the synaptic potential was enhanced, reaching a steady level soon after exposure. The ability of the synaptic potential to generate a spike was reduced and damage progressed after termination of the radiation exposure. Recovery was not observed following termination of exposure. These results demonstrate that an isolated neuronal network can show complex changes in electrophysiological properties following moderate doses of ionizing radiation. An investigation of radiation damage directly to neurons in vitro will contribute to the understanding of the underlying mechanisms of radiation-induced nervous system dysfunction.

  15. Firing Properties of Genetically Identified Dorsal Raphe Serotonergic Neurons in Brain Slices

    PubMed Central

    Mlinar, Boris; Montalbano, Alberto; Piszczek, Lukasz; Gross, Cornelius; Corradetti, Renato

    2016-01-01

    Tonic spiking of serotonergic neurons establishes serotonin levels in the brain. Since the first observations, slow regular spiking has been considered as a defining feature of serotonergic neurons. Recent studies, however, have revealed the heterogeneity of serotonergic neurons at multiple levels, comprising their electrophysiological properties, suggesting the existence of functionally distinct cellular subpopulations. In order to examine in an unbiased manner whether serotonergic neurons of the dorsal raphe nucleus (DRN) are heterogeneous, we used a non-invasive loose-seal cell-attached method to record α1 adrenergic receptor-stimulated spiking of a large sample of neurons in brain slices obtained from transgenic mice lines that express fluorescent marker proteins under the control of serotonergic system-specific Tph2 and Pet-1 promoters. We found wide homogeneous distribution of firing rates, well fitted by a single Gaussian function (r2 = 0.93) and independent of anatomical location (P = 0.45), suggesting that in terms of intrinsic firing properties, serotonergic neurons in the DRN represent a single cellular population. Characterization of the population in terms of spiking regularity was hindered by its dependence on the firing rate. For instance, the coefficient of variation of the interspike intervals (ISI), a common measure of spiking irregularity, is of limited usefulness since it correlates negatively with the firing rate (r = −0.33, P < 0.0001). Nevertheless, the majority of neurons exhibited regular, pacemaker-like activity, with coefficient of variance of the ISI lower than 0.5 in ~97% of cases. Unexpectedly, a small percentage of neurons (~1%) exhibited a particular spiking pattern, characterized by low frequency (~0.02–0.1 Hz) oscillations in the firing rate. Transitions between regular and oscillatory firing were observed, suggesting that the oscillatory firing is an alternative firing pattern of serotonergic neurons. PMID:27536220

  16. Firing Properties of Genetically Identified Dorsal Raphe Serotonergic Neurons in Brain Slices.

    PubMed

    Mlinar, Boris; Montalbano, Alberto; Piszczek, Lukasz; Gross, Cornelius; Corradetti, Renato

    2016-01-01

    Tonic spiking of serotonergic neurons establishes serotonin levels in the brain. Since the first observations, slow regular spiking has been considered as a defining feature of serotonergic neurons. Recent studies, however, have revealed the heterogeneity of serotonergic neurons at multiple levels, comprising their electrophysiological properties, suggesting the existence of functionally distinct cellular subpopulations. In order to examine in an unbiased manner whether serotonergic neurons of the dorsal raphe nucleus (DRN) are heterogeneous, we used a non-invasive loose-seal cell-attached method to record α1 adrenergic receptor-stimulated spiking of a large sample of neurons in brain slices obtained from transgenic mice lines that express fluorescent marker proteins under the control of serotonergic system-specific Tph2 and Pet-1 promoters. We found wide homogeneous distribution of firing rates, well fitted by a single Gaussian function (r (2) = 0.93) and independent of anatomical location (P = 0.45), suggesting that in terms of intrinsic firing properties, serotonergic neurons in the DRN represent a single cellular population. Characterization of the population in terms of spiking regularity was hindered by its dependence on the firing rate. For instance, the coefficient of variation of the interspike intervals (ISI), a common measure of spiking irregularity, is of limited usefulness since it correlates negatively with the firing rate (r = -0.33, P < 0.0001). Nevertheless, the majority of neurons exhibited regular, pacemaker-like activity, with coefficient of variance of the ISI lower than 0.5 in ~97% of cases. Unexpectedly, a small percentage of neurons (~1%) exhibited a particular spiking pattern, characterized by low frequency (~0.02-0.1 Hz) oscillations in the firing rate. Transitions between regular and oscillatory firing were observed, suggesting that the oscillatory firing is an alternative firing pattern of serotonergic neurons. PMID:27536220

  17. Interleukin-1 and acute brain injury

    PubMed Central

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

    2015-01-01

    Inflammation is the key host-defense response to infection and injury, yet also a major contributor to a diverse range of diseases, both peripheral and central in origin. Brain injury as a result of stroke or trauma is a leading cause of death and disability worldwide, yet there are no effective treatments, resulting in enormous social and economic costs. Increasing evidence, both preclinical and clinical, highlights inflammation as an important factor in stroke, both in determining outcome and as a contributor to risk. A number of inflammatory mediators have been proposed as key targets for intervention to reduce the burden of stroke, several reaching clinical trial, but as yet yielding no success. Many factors could explain these failures, including the lack of robust preclinical evidence and poorly designed clinical trials, in addition to the complex nature of the clinical condition. Lack of consideration in preclinical studies of associated co-morbidities prevalent in the clinical stroke population is now seen as an important omission in previous work. These co-morbidities (atherosclerosis, hypertension, diabetes, infection) have a strong inflammatory component, supporting the need for greater understanding of how inflammation contributes to acute brain injury. Interleukin (IL)-1 is the prototypical pro-inflammatory cytokine, first identified many years ago as the endogenous pyrogen. Research over the last 20 years or so reveals that IL-1 is an important mediator of neuronal injury and blocking the actions of IL-1 is beneficial in a number of experimental models of brain damage. Mechanisms underlying the actions of IL-1 in brain injury remain unclear, though increasing evidence indicates the cerebrovasculature as a key target. Recent literature supporting this and other aspects of how IL-1 and systemic inflammation in general contribute to acute brain injury are discussed in this review. PMID:25705177

  18. Electrophysiologic monitoring in acute brain injury.

    PubMed

    Claassen, Jan; Vespa, Paul

    2014-12-01

    To determine the optimal use and indications of electroencephalography (EEG) in critical care management of acute brain injury (ABI). An electronic literature search was conducted for articles in English describing electrophysiological monitoring in ABI from January 1990 to August 2013. A total of 165 studies were included. EEG is a useful monitor for seizure and ischemia detection. There is a well-described role for EEG in convulsive status epilepticus and cardiac arrest (CA). Data suggest EEG should be considered in all patients with ABI and unexplained and persistent altered consciousness and in comatose intensive care unit (ICU) patients without an acute primary brain condition who have an unexplained impairment of mental status. There remain uncertainties about certain technical details, e.g., the minimum duration of EEG studies, the montage, and electrodes. Data obtained from both EEG and EP studies may help estimate prognosis in ABI patients, particularly following CA and traumatic brain injury. Data supporting these recommendations is sparse, and high quality studies are needed. EEG is used to monitor and detect seizures and ischemia in ICU patients and indications for EEG are clear for certain disease states, however, uncertainty remains on other applications. PMID:25208668

  19. Neuroprotective effect of alkyl hydroxytyrosyl ethers in rat brain slices subjected to a hypoxia-reoxygenation model.

    PubMed

    Guerrero, A; De la Cruz, J P; Muñoz-Marín, J; López-Villodres, J A; Madrona, A; Espartero, J L; González-Correa, J A

    2012-10-15

    The aim of the present study was to investigate the antioxidant and possible neuroprotective and antioxidant effects of five alkyl hydroxytyrosyl (HT) ethers (ethyl, butyl, hexyl, octyl and dodecyl) in rat brain slices. None of the compounds modified lipid peroxidation or glutathione concentrations (GSH) in oxygenated samples. The effects of oxidative stress were investigated with ferrous salts to induce lipid peroxidation and diethylmaleate (DEM) to reduce GSH. All compounds inhibited lipid peroxidation with an inhibitory concentration 50% (IC(50)) one tenth that of HT. These compounds, especially the butyl derivative, prevented GSH depletion after incubation with DEM. We also explored the neuroprotective effect of these compounds in an experimental model of hypoxia-reoxygenation in rat brain slices. All compounds showed neuroprotective and antioxidant effects. Our results established a relationship between these effects and the length of the carbon chain (maximum effect in the range of C4-C8). PMID:23442672

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

    PubMed Central

    Fogtmann, Mads; Seshamani, Sharmishtaa; Kroenke, Christopher; Cheng, Xi; Chapman, Teresa; Wilm, Jakob; Rousseau, François

    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 3-D 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 in different anatomical planes. The algorithm is implemented using a multi-resolution iterative scheme and multiple real and synthetic data are used to evaluate the performance of the technique. An accuracy experiment using synthetically created motion data of an adult head and a experiment using synthetic motion added to sedated fetal monkey dataset show a significant improvement in motion-trajectory estimation compared to a state-of-the-art approaches. The performance of the method is then evaluated on challenging but clinically typical in utero fetal scans of four different human cases, showing improved rendition of cortical anatomy and extraction of white matter tracts. While the experimental work focuses on DTI reconstruction (second-order tensor model), the proposed reconstruction framework can employ any 5-D diffusion volume model that can be represented by the spatial parameterizations of an orientation distribution function. PMID:24108711

  1. Acute parotitis and hyperamylasemia following whole-brain radiation therapy

    SciTech Connect

    Cairncross, J.G.; Salmon, J.; Kim, J.H.; Posner, J.B.

    1980-04-01

    Parotitis, an infrequent, previously unreported complication of whole-brain radiation therapy, was observed in 4 patients. The acute symptoms, which include fever, dry mouth, pain, swelling, and tenderness, are accompanied by hyperamylasemia. Among 10 patients receiving whole-brain irradiation, 8 had serum amylase elevations without symptoms. Both acute parotitis and asymptomatic hyperamylasemia result from irradiation of the parotid glands.

  2. Dopamine Modulates Spike Timing-Dependent Plasticity and Action Potential Properties in CA1 Pyramidal Neurons of Acute Rat Hippocampal Slices

    PubMed Central

    Edelmann, Elke; Lessmann, Volkmar

    2011-01-01

    Spike timing-dependent plasticity (STDP) is a cellular model of Hebbian synaptic plasticity which is believed to underlie memory formation. In an attempt to establish a STDP paradigm in CA1 of acute hippocampal slices from juvenile rats (P15–20), we found that changes in excitability resulting from different slice preparation protocols correlate with the success of STDP induction. Slice preparation with sucrose containing ACSF prolonged rise time, reduced frequency adaptation, and decreased latency of action potentials in CA1 pyramidal neurons compared to preparation in conventional ASCF, while other basal electrophysiological parameters remained unaffected. Whereas we observed prominent timing-dependent long-term potentiation (t-LTP) to 171 ± 10% of controls in conventional ACSF, STDP was absent in sucrose prepared slices. This sucrose-induced STDP deficit could not be rescued by stronger STDP paradigms, applying either more pre- and/or postsynaptic stimuli, or by a higher stimulation frequency. Importantly, slice preparation with sucrose containing ACSF did not eliminate theta-burst stimulation induced LTP in CA1 in field potential recordings in our rat hippocampal slices. Application of dopamine (for 10–20 min) to sucrose prepared slices completely rescued t-LTP and recovered action potential properties back to levels observed in ACSF prepared slices. Conversely, acute inhibition of D1 receptor signaling impaired t-LTP in ACSF prepared slices. No similar restoring effect for STDP as seen with dopamine was observed in response to the β-adrenergic agonist isoproterenol. ELISA measurements demonstrated a significant reduction of endogenous dopamine levels (to 61.9 ± 6.9% of ACSF values) in sucrose prepared slices. These results suggest that dopamine signaling is involved in regulating the efficiency to elicit STDP in CA1 pyramidal neurons. PMID:22065958

  3. Relation between the content of acetyl-coenzyme A and acetylcholine in brain slices.

    PubMed Central

    Rícný, J; Tucek, S

    1980-01-01

    Slices of rat caudate nuclei were incubated in vitro in media containing, among other constituents, three different concentrations of glucose (0.5, 2 and 10 mM), 0.2 mM-choline, paraoxon as an inhibitor of cholinesterase, and 5 mM- or 30 mM-K+. After 30 and 60 min of incubation, the concentrations of acetyl-CoA, acetylcholine and choline in the tissue and of acetylcholine in the incubation medium were measured. The content of acetyl-CoA in the sliced varied in direct relation to the concentration of glucose in the incubation medium. The content of acetylcholine in the slices and, in experiments with high K+, also the amount of acetylcholine released into the incubation medium varied in direct relation to the concentration of glucose in the incubation medium and to the concentration of acetyl-CoA in the slices; the relation between the concentrations of acetyl-CoA and of acetylcholine in the slices was linear. It was concluded that the availability of acetyl-CoA had a decisive influence on both the rate of synthesis of acetylcholine and its steady-state concentration. The observations accord with the view that, at the ultimate level, the synthesis of acetylcholine is controlled by the Law of Mass Action. PMID:7470027

  4. Anemia management after acute brain injury.

    PubMed

    Lelubre, Christophe; Bouzat, Pierre; Crippa, Ilaria Alice; Taccone, Fabio Silvio

    2016-01-01

    Anemia is frequent among brain-injured patients, where it has been associated with an increased risk of poor outcome. The pathophysiology of anemia in this patient population remains multifactorial; moreover, whether anemia merely reflects a higher severity of the underlying disease or is a significant determinant of the neurological recovery of such patients remains unclear. Interestingly, the effects of red blood cell transfusions (RBCT) in moderately anemic patients remain controversial; although hemoglobin levels are increased, different studies observed only a modest and inconsistent improvement in cerebral oxygenation after RBCT and raised serious concerns about the risk of increased complications. Thus, considering this "blood transfusion anemia paradox", the optimal hemoglobin level to trigger RBCT in brain-injured patients has not been defined yet; also, there is insufficient evidence to provide strong recommendations regarding which hemoglobin level to target and which associated transfusion strategy (restrictive versus liberal) to select in this patient population. We summarize in this review article the more relevant studies evaluating the effects of anemia and RBCT in patients with an acute neurological condition; also, we propose some potential strategies to optimize transfusion management in such patients. PMID:27311626

  5. The tricyclic antidepressant desipramine inhibited the neurotoxic, kainate-induced [Ca(2+)]i increases in CA1 pyramidal cells in acute hippocampal slices.

    PubMed

    Koncz, István; Szász, Bernadett K; Szabó, Szilárd I; Kiss, János P; Mike, Arpád; Lendvai, Balázs; Sylvester Vizi, E; Zelles, Tibor

    2014-05-01

    Kainate (KA), used for modelling neurodegenerative diseases, evokes excitotoxicity. However, the precise mechanism of KA-evoked [Ca(2+)]i increase is unexplored, especially in acute brain slice preparations. We used [Ca(2+)]i imaging and patch clamp electrophysiology to decipher the mechanism of KA-evoked [Ca(2+)]i rise and its inhibition by the tricyclic antidepressant desipramine (DMI) in CA1 pyramidal cells in rat hippocampal slices and in cultured hippocampal cells. The effect of KA was dose-dependent and relied totally on extracellular Ca(2+). The lack of effect of dl-2-amino-5-phosphonopentanoic acid (AP-5) and abolishment of the response by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) suggested the involvement of non-N-methyl-d-aspartate receptors (non-NMDARs). The predominant role of the Ca(2+)-impermeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the initiation of the Ca(2+) response was supported by the inhibitory effect of the selective AMPAR antagonist GYKI 53655 and the ineffectiveness of 1-naphthyl acetylspermine (NASPM), an inhibitor of the Ca(2+)-permeable AMPARs. The voltage-gated Ca(2+) channels (VGCC), blocked by ω-Conotoxin MVIIC+nifedipine+NiCl2, contributed to the [Ca(2+)]i rise. VGCCs were also involved, similarly to AMPAR current, in the KA-evoked depolarisation. Inhibition of voltage-gated Na(+) channels (VGSCs; tetrodotoxin, TTX) did not affect the depolarisation of pyramidal cells but blocked the depolarisation-evoked action potential bursts and reduced the Ca(2+) response. The tricyclic antidepressant DMI inhibited the KA-evoked [Ca(2+)]i rise in a dose-dependent manner. It directly attenuated the AMPA-/KAR current, but its more potent inhibition on the Ca(2+) response supports additional effect on VGCCs, VGSCs and Na(+)/Ca(2+) exchangers. The multitarget action on decisive players of excitotoxicity holds out more promise in clinical therapy of neurodegenerative diseases. PMID:24742525

  6. Platelet-derived nerve growth factor supports the survival of cholinergic neurons in organotypic rat brain slices.

    PubMed

    Kniewallner, Kathrin M; Grimm, Natalia; Humpel, Christian

    2014-06-27

    Platelets play a role in repair of vessels and contain different growth factors, including nerve growth factor (NGF). Since NGF is the most potent growth factor to support survival of cholinergic neurons, we aimed to study the effects of platelet-derived NGF on cholinergic neurons in organotypic brain slices. Brain slices of the nucleus basalis of Meynert (nBM) were cultured with or without NGF (10ng/ml) or platelet extracts (100μg/ml) or fresh platelets (10(8) platelets/ml). In order to enhance NGF in platelets recombinant NGF (100ng) was loaded into platelets using ultrasound (3h). Our data show that recombinant NGF markedly supports survival of cholinergic neurons. The addition of fresh platelets showed a tendency for enhancing cholinergic neuron numbers, while platelet extracts had no effects. Ultrasound was highly effective to load recombinant NGF into platelets. The addition of NGF-loaded platelets markedly enhanced cholinergic neuron numbers. In conclusion, our data provide evidence that NGF-derived platelets may counteract cell death of cholinergic neurons. PMID:24861506

  7. The novel immunosuppressant SDZ-RAD protects rat brain slices from cyclosporine-induced reduction of high-energy phosphates

    PubMed Central

    Serkova, Natalie; Litt, Lawrence; Leibfritz, Dieter; Hausen, Bernard; Morris, Randall E; James, Thomas L; Benet, Leslie Z; Christians, Uwe

    2000-01-01

    SDZ-RAD, 40-O-(2-hydroxyethyl)-rapamycin, is a novel macrolide immunosuppressant. Because of its synergistic interaction, SDZ-RAD is under clinical investigation as immunosuppressant in combination with cyclosporine after organ transplantation. Neurotoxicity is a critical side-effect of cyclosporine. We studied the effect of SDZ-RAD and its combination with cyclosporine on high-energy phosphates, phosphocreatine (PCr) and nucleoside triphosphates (NTP), in brain slices using 31P-magnetic resonance spectroscopy (MRS). Cyclosporine significantly reduced high-energy phosphates after 2 h in a dose-dependent manner (100 μg l−1: 93±3% of control (NTP), 91±3% (PCr); 500 μg l−1: 84±2% (NTP), 73±2 (PCr); 5000 μg l−1: 68±3% (NTP), 55±5% (PCr); n=6; P<0.02). In contrast, after perfusion for 2 h, SDZ-RAD (500 μg l−1 and 5000 μg l−1) significantly increased high-energy phosphate concentrations in the brain slices (P<0.02). Even at the lowest concentration, SDZ-RAD protected brain energy metabolism against cyclosporine toxicity: 100 μg l−1 SDZ-RAD+5000 μg l−1 cyclosporine: 86±3% (NTP), 83±7% (PCr), n = 3, P<0.03 compared to cyclosporine alone. 5As evaluated using an algorithm based on Loewe isobolograms, the effects of SDZ-RAD/ cyclosporine combinations on brain energy reduction were antagonistic. Both drugs were found in mitochondria using h.p.l.c-MS analysis. We conclude that cyclosporine inhibits mitochondrial high-energy phosphate metabolism, which can be antagonized by SDZ-RAD. PMID:10711346

  8. Acute Slices of Mice Testis Seminiferous Tubules Unveil Spontaneous and Synchronous Ca2+ Oscillations in Germ Cell Clusters1

    PubMed Central

    Sánchez-Cárdenas, Claudia; Guerrero, Adán; Treviño, Claudia Lydia; Hernández-Cruz, Arturo; Darszon, Alberto

    2012-01-01

    ABSTRACT Spermatogenic cell differentiation involves changes in the concentration of cytoplasmic Ca2+ ([Ca2+]i); however, very few studies exist on [Ca2+]i dynamics in these cells. Other tissues display Ca2+ oscillations involving multicellular functional arrangements. These phenomena have been studied in acute slice preparations that preserve tissue architecture and intercellular communications. Here we report the implementation of intracellular Ca2+ imaging in a sliced seminiferous tubule (SST) preparation to visualize [Ca2+]i changes of living germ cells in situ within the SST preparation. Ca2+ imaging revealed that a subpopulation of male germ cells display spontaneous [Ca2+]i fluctuations resulting from Ca2+ entry possibly throughout CaV3 channels. These [Ca2+]i fluctuation patterns are also present in single acutely dissociated germ cells, but they differ from those recorded from germ cells in the SST preparation. Often, spontaneous Ca2+ fluctuations of spermatogenic cells in the SST occur synchronously, so that clusters of cells can display Ca2+ oscillations for at least 10 min. Synchronous Ca2+ oscillations could be mediated by intercellular communication via gap junctions, although intercellular bridges could also be involved. We also observed an increase in [Ca2+]i after testosterone application, suggesting the presence of functional Sertoli cells in the SST. In summary, we believe that the SST preparation is suitable to explore the physiology of spermatogenic cells in their natural environment, within the seminiferous tubules, in particular Ca2+ signaling phenomena, functional cell-cell communication, and multicellular functional arrangements. PMID:22914313

  9. Brain perfusion in acute and chronic hyperglycemia in rats

    SciTech Connect

    Kikano, G.E.; LaManna, J.C.; Harik, S.I. )

    1989-08-01

    Recent studies show that acute and chronic hyperglycemia cause a diffuse decrease in regional cerebral blood flow and that chronic hyperglycemia decreases the brain L-glucose space. Since these changes can be caused by a decreased density of perfused brain capillaries, we used 30 adult male Wistar rats to study the effect of acute and chronic hyperglycemia on (1) the brain intravascular space using radioiodinated albumin, (2) the anatomic density of brain capillaries using alkaline phosphatase histochemistry, and (3) the fraction of brain capillaries that are perfused using the fluorescein isothiocyanate-dextran method. Our results indicate that acute and chronic hyperglycemia do not affect the brain intravascular space nor the anatomic density of brain capillaries. Also, there were no differences in capillary recruitment among normoglycemic, acutely hyperglycemic, and chronically hyperglycemic rats. These results suggest that the shrinkage of the brain L-glucose space in chronic hyperglycemia is more likely due to changes in the blood-brain barrier permeability to L-glucose.

  10. Phospholipase A2, oxidative stress, and neurodegeneration in binge ethanol-treated organotypic slice cultures of developing rat brain

    PubMed Central

    Moon, Kwan-Hoon; Tajuddin, Nuzhath; Brown, James; Neafsey, Edward J.; Kim, Hee-Yong; Collins, Michael A.

    2013-01-01

    Background Brain neurodamage from chronic binge ethanol exposure is linked to neuroinflammation and associated oxidative stress. Using rat organotypic hippocampal-entorhinal cortical (HEC) slice cultures of developing brain age, we reported that binge ethanol promotes release of a neuroinflammatory instigator, arachidonic acid (AA), concomitant with neurodegeneration, and that mepacrine, a global inhibitor of phospholipase A2 (PLA2) enzymes mobilizing AA from phospholipids, is neuroprotective. Here we sought with binge ethanol-treated HEC cultures to establish that PLA2 activity is responsible in part for significant oxidative stress, and to ascertain the PLA2 families responsible for AA release and neurodegeneration. Methods HEC slices, prepared from one wk-old rats and cultured 2–2½ wks, were exposed to 100 mM ethanol over 6 successive days, with 4 daytime “withdrawals” (no ethanol). Brain 3-nitrotyrosinated (3-NT) and 4-hydroxynonenal (4-HNE)-adducted proteins, oxidative stress footprints, were immunoassayed on days 3 through 6, and mepacrine’s effect was determined on day 6. The effects of specific PLA2 inhibitors on neurodegeneration (propidium iodide staining) and AA release (ELISA levels in media) in the cultures were then determined. Also, the effect of JZL184, an inhibitor of monoacylglycerol lipase (MAGL) which is reported to mobilize AA from endocannabinoids during neuroinflammatory insults, was examined. Results 3-NT- and 4-HNE-adducted proteins were significantly increased by the binge ethanol exposure, consistent with oxidative stress, and mepacrine prevented the increases. The PLA2 inhibitor results implicated secretory PLA2 (GII sPLA2) and to some extent Ca+2-independent PLA2 (GVI iPLA2) in binge ethanol-induced neurotoxicity and in AA release, but surprisingly, Ca+2-dependent PLA2 (GIV cPLA2) did not appear important. Furthermore, unlike PLA2 inhibition, MAGL inhibition failed to prevent the neurodegeneration. Conclusions In these

  11. Non-specific inhibitors of aquaporin-4 stimulate S100B secretion in acute hippocampal slices of rats.

    PubMed

    Zanotto, Caroline; Abib, Renata Torres; Batassini, Cristiane; Tortorelli, Lucas Silva; Biasibetti, Regina; Rodrigues, Letícia; Nardin, Patrícia; Hansen, Fernanda; Gottfried, Carmem; Leite, Marina Concli; Gonçalves, Carlos-Alberto

    2013-01-23

    Aquaporin-4 (AQP-4) is the principal brain water channel and is predominantly expressed in astrocytes suggesting its dynamic involvement in water homeostasis in brain tissue. Due to the co-localization of AQP-4 and inward rectifier K(+) channels Kir 4.1, a functional coupling between these proteins has been proposed. AQP-4 has a putative role in the physiopathology of brain disorders including epilepsy and trauma. S100B is a calcium-binding protein expressed and secreted by astrocytes, and commonly used as a parameter of astroglial activation. Here, we investigate a possible link between AQP-4 activity (and Kir 4.1) and S100B secretion in hippocampal slices of rats of different ages using non-specific inhibitors of AQP-4 (AZA, acetazolamide and TEA, tetraethylammonium) and Kir 4.1 (barium chloride). We found that blockade of AQP-4 with TEA and AZA produced an increase in S100B secretion in young rats, compatible with an astroglial activation observed in many conditions of brain injury. On the other hand, BaCl(2) induced Kir 4.1 inhibition caused a decrease in S100B secretion. Both channels, AQP-4 and Kir 4.1, exhibited a similar ontogenetic profile, in spite of the functional uncoupling, in relation to S100B secretion. Moreover, we found a significant increase in the S100B secretion basal levels with the increasing of animal age and the incubation with high levels of potassium resulted in a decrease of S100B secretion in 30 and 90-day old rats. These data, together with previous observations from gap junctions and glutamate transport of astrocytes, contribute to characterize the operational system involving astroglial activation, particularly on S100B secretion, in brain disorders. PMID:23142267

  12. Adenosine receptor activation is responsible for prolonged depression of synaptic transmission after spreading depolarization in brain slices.

    PubMed

    Lindquist, B E; Shuttleworth, C W

    2012-10-25

    Spreading depolarization (SD) is a slowly propagating, coordinated depolarization of brain tissue, which is followed by a transient (5-10min) depression of synaptic activity. The mechanisms for synaptic depression after SD are incompletely understood. We examined the relative contributions of action potential failure and adenosine receptor activation to the suppression of evoked synaptic activity in murine brain slices. Focal micro-injection of potassium chloride (KCl) was used to induce SD and synaptic potentials were evoked by electrical stimulation of Schaffer collateral inputs to hippocampal area Cornu Ammonis area 1 (CA1). SD was accompanied by loss of both presynaptic action potentials (as assessed from fiber volleys) and field excitatory postsynaptic potentials (fEPSPs). Fiber volleys recovered rapidly upon neutralization of the extracellular direct current (DC) potential, whereas fEPSPs underwent a secondary suppression phase lasting several minutes. Paired-pulse ratio was elevated during the secondary suppression period, consistent with a presynaptic mechanism of synaptic depression. A transient increase in extracellular adenosine concentration was detected during the period of secondary suppression. Antagonists of adenosine A1 receptors (8-cyclopentyl-1,3-dipropylxanthine [DPCPX] or 8-cyclopentyl-1,3-dimethylxanthine [8-CPT]) greatly accelerated fEPSP recovery and abolished increases in paired-pulse ratio normally observed after SD. The duration of fEPSP suppression was correlated with both the duration of the DC shift and the area of tissue depolarized, consistent with the model that adenosine accumulates in proportion to the metabolic burden of SD. These results suggest that in brain slices, the duration of the DC shift approximately defined the period of action potential failure, but the secondary depression of evoked responses was in large part due to endogenous adenosine accumulation after SD. PMID:22864185

  13. Cascade of tau toxicity in inducible hippocampal brain slices and prevention by aggregation inhibitors

    PubMed Central

    Messing, Lars; Mandelkow, Eckhard; Mandelkow, Eva-Maria

    2016-01-01

    Mislocalization and aggregation of the axonal protein Tau are hallmarks of Alzheimer disease and other tauopathies. Here, we studied the relationship between Tau aggregation, loss of spines and neurons, and reversibility by aggregation inhibitors. To this end we established an in vitro model of tauopathy based on regulatable transgenic hippocampal organotypic slice cultures prepared from mice expressing pro-aggregant TauRDΔK. Transgene expression was monitored by a bioluminescence reporter assay. Abnormal Tau phosphorylation, mislocalization of exogenous and endogenous Tau into the somatodendritic compartment, followed by reduction of dendritic spines, altered morphology from mushroom-shaped to thin spines, dysregulation of Ca++ dynamics, Tau aggregation, neuronal loss and elevated activation of microglia. Neurotoxicity was mediated by Caspase-3 activation and correlated with the expression level of pro-aggregant TauRDΔK. Finally, Tau aggregates appeared in areas CA1 and CA3 after three weeks in vitro. Neurodegeneration was relieved by aggregation inhibitors or by switching off transgene expression. Thus the slice culture model is suitable for monitoring the development of tauopathy and the therapeutic benefit of anti-aggregation drugs. PMID:23158765

  14. In vitro electrical conductivity of seizing and non-seizing mouse brain slices at 10 kHz

    NASA Astrophysics Data System (ADS)

    Elbohouty, M.; Wilson, M. T.; Voss, L. J.; Steyn-Ross, D. A.; Hunt, L. A.

    2013-06-01

    The electrical conductivity of small samples of mouse cortex (in vitro) has been measured at 10 kHz through the four-electrode method of van der Pauw. Brain slices from three mice were prepared under seizing and non-seizing conditions by changing the concentration of magnesium in the artificial cerebrospinal fluid used to maintain the tissue. These slices provided 121 square samples of cortical tissue; the conductivity of these samples was measured with an Agilent E4980A four-point impedance monitor. Of these, 73 samples were considered acceptable on the grounds of having good electrical contact between electrodes and tissue excluding outlier measurements. Results show that there is a significant difference (p = 0.03) in the conductivities of the samples under the two conditions. The seizing and non-seizing samples have mean conductivities of 0.33 and 0.36 S m-1, respectively; however, these quantitative values should be used with caution as they are both subject to similar systematic uncertainties due to non-ideal temperature conditions and non-ideal placement of electrodes. We hypothesize that the difference between them, which is more robust to uncertainty, is due to the changing gap junction connectivity during seizures.

  15. Dual Electrophysiological Recordings of Synaptically-evoked Astroglial and Neuronal Responses in Acute Hippocampal Slices

    PubMed Central

    Rouach, Nathalie

    2012-01-01

    Astrocytes form together with neurons tripartite synapses, where they integrate and modulate neuronal activity. Indeed, astrocytes sense neuronal inputs through activation of their ion channels and neurotransmitter receptors, and process information in part through activity-dependent release of gliotransmitters. Furthermore, astrocytes constitute the main uptake system for glutamate, contribute to potassium spatial buffering, as well as to GABA clearance. These cells therefore constantly monitor synaptic activity, and are thereby sensitive indicators for alterations in synaptically-released glutamate, GABA and extracellular potassium levels. Additionally, alterations in astroglial uptake activity or buffering capacity can have severe effects on neuronal functions, and might be overlooked when characterizing physiopathological situations or knockout mice. Dual recording of neuronal and astroglial activities is therefore an important method to study alterations in synaptic strength associated to concomitant changes in astroglial uptake and buffering capacities. Here we describe how to prepare hippocampal slices, how to identify stratum radiatum astrocytes, and how to record simultaneously neuronal and astroglial electrophysiological responses. Furthermore, we describe how to isolate pharmacologically the synaptically-evoked astroglial currents. PMID:23222635

  16. A brain slice experimental model to study the generation and the propagation of focally-induced epileptiform activity

    PubMed Central

    Losi, Gabriele; Marcon, Iacopo; Mariotti, Letizia; Sessolo, Michele; Chiavegato, Angela; Carmignoto, Giorgio

    2016-01-01

    The early cellular events that in a brain network lead to seizure generation and govern seizure propagation are probably based on different cellular mechanisms. Experimental models in which these events can be separately studied would contribute to improve our understanding of epilepsy. We recently described an in vitro model in entorhinal cortex slices from young rats in which focal seizure-like discharges (SLDs) can be induced in spatially defined regions and at predictable times by local NMDA applications performed in the presence of 4-amimopyridine (4-AP) and low extracellular Mg2+. Through the use of single-dual cell patch-clamp and field potential recordings, and Ca2+ imaging from large ensembles of neurons, interneurons and astrocytes, we here extend this model to entorhinal and temporal cortex slices of rat and mouse brain, providing evidence that multiple SLDs exhibiting the typical tonic–clonic discharge pattern can be also evoked in these cortical regions by successive NMDA applications. Importantly, the temporal cortex is more accessible to viral vector injections than the entorhinal cortex: this makes it feasible in the former region the selective expression in inhibitory interneurons or principal neurons of genetically encoded Ca2+ indicators (GECI) or light-gated opsins. In this model, an optogenetic approach allows to activate specific neuronal types at spatially defined locations, i.e., the focus or the propagating region, and at precise time, i.e., before or during SLD. The NMDA/4-AP model can, therefore, represent a valuable tool to gain insights into the role of specific cell populations in seizure generation, propagation and cessation. PMID:25863141

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

    PubMed

    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. PMID:23142181

  18. Organotypic slice culture of the hypothalamic paraventricular nucleus of rat

    PubMed Central

    Cho, Eun Seong; Lee, So Yeong; Park, Jae-Yong; Hong, Seong-Geun

    2007-01-01

    Organotypic slice cultures have been developed as an alternative to acute brain slices because the neuronal viability and synaptic connectivity in these cultures can be preserved well for a prolonged period of time. This study evaluated a stationary organotypic slice culture developed for the hypothalamic paraventricular nucleus (PVN) of rat. The results showed that the slice cultures maintain the typical shape of the nucleus, the immunocytochemical signals for oxytocin, vasopressin, and corticotropin-releasing hormone, and the electrophysiological properties of PVN neurons for up to 3 weeks in vitro. The PVN neurons in the culture expressed the green fluorescent protein gene that had been delivered by the adenoviral vectors. The results indicate that the cultured slices preserve the properties of the PVN neurons, and can be used in longterm studies on these neurons in vitro. PMID:17322769

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

    PubMed

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

    2012-01-01

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

  20. NAAG reduces NMDA receptor current in CA1 hippocampal pyramidal neurons of acute slices and dissociated neurons.

    PubMed

    Bergeron, Richard; Coyle, Joseph T; Tsai, Guochan; Greene, Robert W

    2005-01-01

    N-acetylaspartylglutamate (NAAG) is an abundant neuropeptide in the nervous system, yet its functions are not well understood. Pyramidal neurons of the CA1 sector of acutely prepared hippocampal slices were recorded using the whole-cell patch-clamp technique. At low concentrations (20 microM), NAAG reduced isolated N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic currents or NMDA-induced currents. The NAAG-induced change in the NMDA concentration/response curve suggested that the antagonism was not competitive. However, the NAAG-induced change in the concentration/response curve for the NMDAR co-agonist, glycine, indicated that glycine can overcome the NAAG antagonism. The antagonism of the NMDAR induced by NAAG was still observed in the presence of LY-341495, a potent and selective mGluR3 antagonist. Moreover, in dissociated pyramidal neurons of the CA1 region, NAAG also reduced the NMDA current and this effect was reversed by glycine. These results suggest that NAAG reduces the NMDA currents in hippocampal CA1 pyramidal neurons. PMID:15354184

  1. Blood-brain barrier in acute liver failure

    PubMed Central

    Nguyen, Justin H.

    2011-01-01

    Brain edema remains a challenging obstacle in the management of acute liver failure (ALF). Cytotoxic mechanisms associated with brain edema have been well recognized, but evidence for vasogenic mechanisms in the pathogenesis of brain edema in ALF has been lacking. Recent reports have not only shown a role of matrix metalloproteinase-9 in the pathogenesis of brain edema in experimental ALF but have also found significant alterations in the tight junction elements including occludin and claudin-5, suggesting a vasogenic injury in the blood-brain barrier (BBB) integrity. This article reviews and explores the role of the paracellular tight junction proteins in the increased selective BBB permeability that leads to brain edema in ALF. PMID:22100566

  2. Brain protection therapy in acute cerebral infarction.

    PubMed

    Katsura, Ken-ichiro; Suda, Satoshi; Abe, Arata; Kanamaru, Takuya; Toda, Yusuke; Katayama, Yasuo

    2012-01-01

    Many drugs for cerebral infarction that were shown to be effective in animal experiments have shown negative results in human clinical trials. For this reason, a completely new approach is needed to develop brain protection therapies against cerebral infarction. Brain protection therapies can be categorized into 3 types: 1) lengthening the therapeutic time window for thrombolytic therapy, 2) reducing the side effects of thrombolytic therapy, and 3) brain protection drug therapy for patients with contraindications for thrombolytic therapy (including combination therapy). Here, we show our recent results of brain protection therapy. First, combination therapy with 2 effective drugs was tried, and time-lag administration was performed. Combination therapy was effective and lengthened the therapeutic time window. Next, a completely new approach to improve cerebral ischemic damage, namely, H2 gas inhalation therapy, was tried. This therapy was also effective, even in the ischemic core. PMID:22687352

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

    PubMed Central

    Eder, Claudia

    2015-01-01

    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. PMID:26011191

  4. Lithium lengthens circadian period of cultured brain slices in area specific manner.

    PubMed

    Yoshikawa, Tomoko; Honma, Sato

    2016-11-01

    Lithium has been used for the treatment of bipolar disorder (BD). However, the mechanisms how lithium exerts its mood stabilizing effects remain to be studied. The disorder in circadian pacemaking has been suggested as an underlying mechanism of the characteristic mood instability of the BD. Lithium is also known to lengthen the circadian periods. We recently proposed that chronic methamphetamine treatment induced circadian oscillation as a complex oscillator including multiple dopaminergic brain areas, and the complex oscillator regulates behavior rhythm independent from the central circadian oscillator in the suprachiasmatic nucleus (SCN). Sleep-wake pattern of rapid cycling BD exhibits similar rhythm disorganization to methamphetamine treated animals. Therefore, we hypothesized that the dysregulated circadian rhythm in BD patients is caused by desynchronization of sleep-wake rhythms from the central clock in the SCN, and that mood stabilizing effect of lithium is achieved through their resynchronization. In the present experiment, we examined how lithium affects the circadian rhythms of brain areas involved in the complex oscillator as well as the SCN. Here we report that lithium lengthens the circadian periods in the SCN, olfactory bulb, median eminence and substantia nigra with dose and area specific manner. The effective lithium dose was much higher than the plasma levels that are required for lengthening the circadian behavior rhythms as well for therapeutic use. Low dose of lithium did not lengthen the period but enhanced the amplitude of circadian rhythms, which may exert therapeutic effects on BD. PMID:27478137

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

    PubMed Central

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

    2014-01-01

    Acute post-traumatic ventricular dilation and hydrocephalus are relatively frequent consequences of traumatic brain injury (TBI). Several recent studies have indicated that high iron level in brain may relate to hydrocephalus development after intracranial hemorrhage. However, the role of iron in the development of post-traumatic hydrocephalus is still unclear. This study was to determine whether or not iron has a role in hydrocephalus development after TBI. TBI was induced by lateral fluid-percussion in male Sprague-Dawley rats. Some rats had intraventricular injection of iron. Acute hydrocephalus was measured by magnetic resonance T2-weighted imaging and brain hemorrhage was determined by T2* gradient-echo sequence imaging and brain hemoglobin levels. The effect of deferoxamine on TBI-induced hydrocephalus was examined. TBI resulted in acute hydrocephalus at 24 hours (lateral ventricle volume: 24.1±3.0 vs. 9.9±0.2 mm3 in sham group). Intraventricular injection of iron also caused hydrocephalus (25.7 ± 3.4 vs. 9.0 ± 0.6 mm3 in saline group). Deferoxamine treatment attenuated TBI-induced hydrocephalus and heme oxygenase-1 upregulation. In conclusion, iron may contribute to acute hydrocephalus after TBI. PMID:24935175

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

    PubMed

    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

    2016-01-01

    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. PMID:27172999

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

    PubMed Central

    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.

    2016-01-01

    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. PMID:27172999

  8. A setup for combined multiphoton laser scanning microscopic and multi-electrode patch clamp experiments on brain slices

    NASA Astrophysics Data System (ADS)

    Helm, P. Johannes; Reppen, Trond; Heggelund, Paul

    2009-02-01

    Multi Photon Laser Scanning Microscopy (MPLSM) appears today as one of the most powerful experimental tools in cellular neurophysiology, notably in studies of the functional dynamics of signal processing in single neurons. Simultaneous recording of fluorescence signals at high spatial and temporal resolution and electric signals by means of multi electrode patch clamp techniques have provided new paths for the systematic investigation of neuronal mechanisms. In particular, this approach has opened for direct studies of dendritic signal processing in neurons. We report about a setup optimized for simultaneous electrophysiological multi electrode patch clamp and multi photon laser scanning fluorescence microscopic experiments on brain slices. The microscopic system is based on a modified commercially available confocal scanning laser microscope (CLSM). From a technical and operational point of view, two developments are important: Firstly, in order to reduce the workload for the experimentalist, who in general is forced to concentrate on controlling the electrophysiological parameters during the recordings, a system of shutters has been installed together with dedicated electronic modules protecting the photo detectors against destructive light levels caused by erroneous opening or closing of microscopic light paths by the experimentalist. Secondly, the standard detection unit has been improved by installing the photomultiplier tubes (PMT) in a Peltier cooled thermal box shielding the detector from both room temperature and distortions caused by external electromagnetic fields. The electrophysiological system is based on an industrial standard multi patch clamp unit ergonomically arranged around the microscope stage. The electrophysiological and scanning processes can be time coordinated by standard trigger electronics.

  9. Targeted Lipid Profiling Discovers Plasma Biomarkers of Acute Brain Injury

    PubMed Central

    Sheth, Sunil A.; Iavarone, Anthony T.; Liebeskind, David S.; Won, Seok Joon; Swanson, Raymond A.

    2015-01-01

    Prior efforts to identify a blood biomarker of brain injury have relied almost exclusively on proteins; however their low levels at early time points and poor correlation with injury severity have been limiting. Lipids, on the other hand, are the most abundant molecules in the brain and readily cross the blood-brain barrier. We previously showed that certain sphingolipid (SL) species are highly specific to the brain. Here we examined the feasibility of using SLs as biomarkers for acute brain injury. A rat model of traumatic brain injury (TBI) and a mouse model of stroke were used to identify candidate SL species though our mass-spectrometry based lipid profiling approach. Plasma samples collected after TBI in the rat showed large increases in many circulating SLs following injury, and larger lesions produced proportionately larger increases. Plasma samples collected 24 hours after stroke in mice similarly revealed a large increase in many SLs. We constructed an SL score (sum of the two SL species showing the largest relative increases in the mouse stroke model) and then evaluated the diagnostic value of this score on a small sample of patients (n = 14) who presented with acute stroke symptoms. Patients with true stroke had significantly higher SL scores than patients found to have non-stroke causes of their symptoms. The SL score correlated with the volume of ischemic brain tissue. These results demonstrate the feasibility of using lipid biomarkers to diagnose brain injury. Future studies will be needed to further characterize the diagnostic utility of this approach and to transition to an assay method applicable to clinical settings. PMID:26076478

  10. Estrogen Receptor Beta and 2-arachidonoylglycerol Mediate the Suppressive Effects of Estradiol on Frequency of Postsynaptic Currents in Gonadotropin-Releasing Hormone Neurons of Metestrous Mice: An Acute Slice Electrophysiological Study

    PubMed Central

    Bálint, Flóra; Liposits, Zsolt; Farkas, Imre

    2016-01-01

    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-green fluorescent protein (GFP) mice was studied under paradigms of blocking or activating estrogen receptor subtypes and interfering with retrograde 2-arachidonoylglycerol (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 estrogen receptor (ER) α/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 tetrodotoxin (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 tetrahydrolipstatin (THL) significantly abolished

  11. Alterations of the electrophysiological properties from cortical layer 5 pyramidal neurons in temporary rapamycin-treated rodent brain slices.

    PubMed

    Ren, Keming; Chen, Lijuan; Sheng, Guoxia; Wang, Jiangping; Jin, Xiaoming; Jiang, Kewen

    2016-01-26

    The mammalian target of rapamycin (mTOR) signaling pathway is involved in neuro-developmental/degenerative and neuropsychiatric abnormalities. Rapamycin, a specific and potent inhibitor of mTOR signaling, could regulate synaptic plasticity and synaptic transmission of glutamatergic neurons following prolonged treatment. Its immediate effects on electrophysiological properties of cortical layer 5 (L5) pyramidal neurons where the information undergoes a sophisticated processing remain unknown. Here, we found that acute (within 2min) bath-application of rapamycin (0.5μgml(-1)) was able to depolarize the current-clamp baseline potentials significantly at postnatal day (P) 4, P10 in rats and P90 in mice (P<0.05), and altered the membrane current/voltage (I/V) curves in an age-dependent manner. Rapamycin not only increased the standard deviation or the peak amplitude of baseline membrane potential, but also increased the frequencies of spontaneous action potentials in more mature neurons (P10 and P90). In addition, rapamycin decreased the burst-firing frequencies of cortical L5 burst-spiking neurons from mature brains, and further switched their firing modes to regular-spiking ones. These findings suggest that acute inhibition of mTOR signaling by rapamycin induces an immediate impact on L5 pyramidal neurons' electrophysiological properties, indicating that its effects might involve mechanisms of ion channel's regulation. PMID:26639426

  12. Pediatric traumatic brain injury: acute and rehabilitation costs.

    PubMed

    Jaffe, K M; Massagli, T L; Martin, K M; Rivara, J B; Fay, G C; Polissar, N L

    1993-07-01

    Pediatric traumatic brain injury constitutes an enormous public health problem, but little is known about the economic costs of such injury. Using charges as a proxy for cost, we prospectively collected data on initial hospital charges and professional fees for emergency department services, acute inpatient care, and acute inpatient rehabilitation for 96 patients with mild, moderate, and severe traumatic brain injuries. We also examined the relationship between these costs and injury severity and etiology. Acute care and rehabilitation median costs were $5,233 per child, $11,478 for hospitalized children, and $230 for those only seen in the emergency department. Median costs for injuries due to motor vehicles, bicycles, and falls were $15,213, $6,311, and $792, respectively. Using Glasgow Coma Scale criteria, median cost of mild, moderate, and severe traumatic brain injuries were $598, $12,022, and $53,332, respectively. Injury etiology added modestly but significantly to the prediction of cost over and above that predicted by injury severity alone. Rehabilitation costs accounted for 37% of the total for all children, but 45% of those with the most severe injuries. PMID:8328886

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  14. Biomarkers and acute brain injuries: interest and limits

    PubMed Central

    2014-01-01

    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. PMID:25029344

  15. A brain slice culture model of viral encephalitis reveals an innate CNS cytokine response profile and the therapeutic potential of caspase inhibition

    PubMed Central

    Dionne, Kalen R.; Leser, J. Smith; Lorenzen, Kristi A.; Beckham, J. David; Tyler, Kenneth L.

    2011-01-01

    Viral encephalitis is a significant cause of human morbidity and mortality in large part due to suboptimal diagnosis and treatment. Murine reovirus infection serves as a classic experimental model of viral encephalitis. Infection of neonatal mice with T3 reoviruses results in lethal encephalitis associated with neuronal infection, apoptosis, and CNS tissue injury. We have developed an ex vivo brain slice culture (BSC) system that recapitulates the basic pathological features and kinetics of viral replication seen in vivo. We utilize the BSC model to identify an innate, brain-tissue specific inflammatory cytokine response to reoviral infection, which is characterized by the release of IL6, CXCL10, RANTES, and murine IL8 analog (KC). Additionally, we demonstrate the potential utility of this system as a pharmaceutical screening platform by inhibiting reovirus-induced apoptosis and CNS tissue injury with the pan-caspase inhibitor, Q-VD-OPh. Cultured brain slices not only serve to model events occurring during viral encephalitis, but can also be utilized to investigate aspects of pathogenesis and therapy that are not experimentally accessible in vivo. PMID:21241693

  16. Regulation of brain anandamide by acute administration of ethanol

    PubMed Central

    Ferrer, Belen; Bermúdez-Silva, Francisco Javier; Bilbao, Ainhoa; Alvarez-Jaimes, Lily; Sanchez-Vera, Irene; Giuffrida, Andrea; Serrano, Antonia; Baixeras, Elena; Khaturia, Satishe; Navarro, Miguel; Parsons, Loren H.; Piomelli, Daniele; Rodríguez de Fonseca, Fernando

    2007-01-01

    The endogenous cannabinoid acylethanolamide AEA (arachidonoylethanolamide; also known as anandamide) participates in the neuroadaptations associated with chronic ethanol exposure. However, no studies have described the acute actions of ethanol on AEA production and degradation. In the present study, we investigated the time course of the effects of the intraperitoneal administration of ethanol (4 g/kg of body mass) on the endogenous levels of AEA in central and peripheral tissues. Acute ethanol administration decreased AEA in the cerebellum, the hippocampus and the nucleus accumbens of the ventral striatum, as well as in plasma and adipose tissue. Parallel decreases of a second acylethanolamide, PEA (palmitoylethanolamide), were observed in the brain. Effects were observed 45–90 min after ethanol administration. In vivo studies revealed that AEA decreases were associated with a remarkable inhibition of the release of both anandamide and glutamate in the nucleus accumbens. There were no changes in the expression and enzymatic activity of the main enzyme that degrades AEA, the fatty acid amidohydrolase. Acute ethanol administration did not change either the activity of N-acyltransferase, the enzyme that catalyses the synthesis of the AEA precursor, or the expression of NAPE-PLD (N-acylphosphatidylethanolamine-hydrolysing phospholipase D), the enzyme that releases AEA from membrane phospholipid precursors. These results suggest that receptor-mediated release of acylethanolamide is inhibited by the acute administration of ethanol, and that this effect is not derived from increased fatty acid ethanolamide degradation. PMID:17302558

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

    PubMed

    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. PMID:22300952

  18. Electrically induced release of amino acids formed from (U14C) glucose in rat brain cortex slices, studied by a simplified dansylation procedure.

    PubMed

    Orrego, F; Doria de Lorenzo, M C

    1980-05-01

    The nonessential amino acids glutamate, aspartate, glutamine, gamma-aminobutyrate (GABA), alanine, glycine, and proline present in rat thin brain cortex slices were labeled by in vitro incubation of these with [U-14C]glucose, and the efflux of such endogenous radioactive amino acids and of lactate was studied in a superfused system, under control conditions or when the slices were depolarized by varous procedures. When electrical stimuli known to induce selective neurotransmitter release (1 or 1.5 volt, sine wave 60 Hz) were applied for 10 sec to the slices, no significant increase in amino acid efflux was found. When more intense stimuli (4 volt, 60 Hz) were applied for 60 sec, or extracellular potassium was raised to 56 mM, both conditions being known to induce nonselective substance release, the efflux of essentially all amino acids and of lactate was markedly increased. Increases in efflux were proportionately larger for glutamate, aspartate, and gamma-aminobutyrate, and this could be accounted for by their greater intracellular chemical (or electrochemical) potentials, but not because of a selective release mechanism for them. Amino acids were analyzed as their 1-dimethylaminoaphthalene-5-sulfonyl (dansyl) derivatives, by a modification of existing procedures in which the dansyl (DNS) derivatives were efficiently extracted from acidified incubation fluid into an organic phase. This rapidly desalted the derivatives and allowed their concentration and chromatographic separation on thin-layer silica gel sheets with little loss. PMID:7393382

  19. ALUMINUM DECREASES MUSCARINIC, ADRENERGIC, AND METABOTROPIC RECEPTOR-STIMULATED PHOSPHOINOSITIDE HYDROLYSIS IN HIPPOCAMPAL AND CORTICAL SLICES FROM RAT BRAIN

    EPA Science Inventory

    Effects of aluminum chloride (AlCl3) (0.1 to 1000 um) on inositol phosphate (IP) accumulation stimulated by carbachol (CARB), norepinephrine (NE) or quisqualate (QUIS) were examined in rat hippocampal and cortical slices. n the absence of agonist, only 1000 um AIC1 significantly ...

  20. Inhibition of GABA release from slices prepared from several brain regions of rats at various times following a convulsion.

    PubMed Central

    Green, A. R.; Minchin, M. C.; Vincent, N. D.

    1987-01-01

    1 A method is described for the measurement of the K+-evoked release of endogenous gamma-aminobutyric acid (GABA) from slices of rat cortex, hippocampus and striatum. 2 In tissue prepared 30 min following an electroconvulsive shock, K+-evoked GABA release (above basal release) was inhibited by 45% in cortex, 50% in hippocampus and 75% in striatum. A similar inhibition of release was observed with slices prepared from rats in which a convulsion had been induced by flurothyl. There was no change in spontaneous (basal) release following either procedure. 3 An inhibition of K+-evoked endogenous GABA release was also seen in tissue prepared 4 min postictally but not 2 h after the seizure. 4 No difference was observed in the release of [3H]-GABA from preloaded cortical slices prepared from rats given a single electroconvulsive shock. 5 It is proposed that a convulsion results in an inhibition of GABA release and that this inhibition may in turn inhibit GABA synthesis as described in the preceding paper. 6 It is also proposed that changes in the endogenous releasable pool of GABA may not be detected by preloading slices with [3H]-GABA. PMID:3664084

  1. Organotypic slice cultures containing the preBötzinger complex generate respiratory-like rhythms.

    PubMed

    Phillips, Wiktor S; Herly, Mikkel; Del Negro, Christopher A; Rekling, Jens C

    2016-02-01

    Study of acute brain stem slice preparations in vitro has advanced our understanding of the cellular and synaptic mechanisms of respiratory rhythm generation, but their inherent limitations preclude long-term manipulation and recording experiments. In the current study, we have developed an organotypic slice culture preparation containing the preBötzinger complex (preBötC), the core inspiratory rhythm generator of the ventrolateral brain stem. We measured bilateral synchronous network oscillations, using calcium-sensitive fluorescent dyes, in both ventrolateral (presumably the preBötC) and dorsomedial regions of slice cultures at 7-43 days in vitro. These calcium oscillations appear to be driven by periodic bursts of inspiratory neuronal activity, because whole cell recordings from ventrolateral neurons in culture revealed inspiratory-like drive potentials, and no oscillatory activity was detected from glial fibrillary associated protein-expressing astrocytes in cultures. Acute slices showed a burst frequency of 10.9 ± 4.2 bursts/min, which was not different from that of brain stem slice cultures (13.7 ± 10.6 bursts/min). However, slice cocultures that include two cerebellar explants placed along the dorsolateral border of the brainstem displayed up to 193% faster burst frequency (22.4 ± 8.3 bursts/min) and higher signal amplitude (340%) compared with acute slices. We conclude that preBötC-containing slice cultures retain inspiratory-like rhythmic function and therefore may facilitate lines of experimentation that involve extended incubation (e.g., genetic transfection or chronic drug exposure) while simultaneously being amenable to imaging and electrophysiology at cellular, synaptic, and network levels. PMID:26655824

  2. A microscopic setup for combined, and time-coordinated electrophysiological and confocal fluorescence microscopic experiments on neurons in living brain slices

    NASA Astrophysics Data System (ADS)

    Helm, P. J.

    1996-02-01

    In this paper, a microscopic system for cell physiological research is presented. The setup which is to a large extent based on commercially available products was designed to establish a platform for time-coordinated electrophysiological and fluorescence optical compound experiments on living neurons in brain slices. Instruments for infrared differential interference contrast video microscopy (IRDICM), confocal scanning laser microscopy (CSLM), and for patch clamp studies have been assembled into one unit. Using the IRDICM equipment, a neuron can be patched somatically and dendritically. Loading the neuron with a Ca2+ indicating dye substance can be examined epifluorescence optically using the Hg lamp or Xe lamp of the microscope. A stimulus initiating the propagation of an action potential through a dendrite can be synchronized to the electronic control unit of the CSLM, and changes in the concentration of Ca2+ in the dendrite can be recorded in a time-coordinated way. The setup has been used successfully in order to study in vitro the dynamics of intracellular Ca2+ in the dendritic system of living neurons in brain slices.

  3. Psychiatric Disease and Post-Acute Traumatic Brain Injury.

    PubMed

    Zgaljardic, Dennis J; Seale, Gary S; Schaefer, Lynn A; Temple, Richard O; Foreman, Jack; Elliott, Timothy R

    2015-12-01

    Psychiatric disorders are common following traumatic brain injury (TBI) and can include depression, anxiety, and psychosis, as well as other maladaptive behaviors and personality changes. The epidemiologic data of psychiatric disorders post-TBI vary widely, although the incidence and prevalence rates typically are higher than in the general population. Although the experience of psychiatric symptoms may be temporary and may resolve in the acute period, many patients with TBI can experience psychopathology that is persistent or that develops in the post-acute period. Long-term psychiatric disorder, along with cognitive and physical sequelae and greater risk for substance use disorders, can pose a number of life-long challenges for patients and their caregivers, as they can interfere with participation in rehabilitation as well as limit functional independence in the community. The current review of the literature considers the common psychiatric problems affecting individuals with TBI in the post-acute period, including personality changes, psychosis, executive dysfunction, depression, anxiety, and substance misuse. Although treatment considerations (pharmacological and nonpharmacological) are referred to, an extensive description of such protocols is beyond the scope of the current review. The impact of persistent psychiatric symptoms on perceived caregiver burden and distress is also discussed. PMID:25629222

  4. Induction of acute phase gene expression by brain irradiation

    SciTech Connect

    Hong, Ji-Hong |; Sun, Ji-Rong; Withers, H.R.

    1995-10-15

    To investigate the in vivo acute phase molecular response of the brain to ionizing radiation, C3Hf/Sed/Kam mice were given midbrain or whole-body irradiation. Cerebral expression of interleukins (IL-1{alpha}, IL-1{beta}, IL-2, IL-3, IL-4, IL-5, IL-6), interferon (IFN-{gamma}), tumor necrosis factors (TNF-{alpha} and TNF-{beta}), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthetase (iNOS), von Willebrand factor (vWF), {alpha}1-antichymotrypsin (EB22/5.3), and glial fibrillary acidic protein (GFAP) was measured at various times after various radiation doses by ribonuclease (RNase) protection assay. The effects of dexamethasone or pentoxifylline treatment of mice on radiation-induced gene expression were also examined. Levels of TNF-{alpha}, IL-1{beta}, ICAM-1, EB22/5.3, and to a lesser extent IL-1{alpha} and GFAP, messenger RNA were increased in the brain after irradiation, whether the dose was delivered to the whole body or only to the midbrain. Responses were radiation dose dependent, but were not found below 7 Gy; the exception being ICAM-1, which was increased by doses as low as 2 Gy. Most responses were rapid, peaking within 4-8 h, but antichymotrypsin and GFAP responses were delayed and still elevated at 24 h, by which time the others had subsided. Pretreatment of mice with dexamethasone or pentoxifylline suppressed radiation-induced gene expression, either partially or completely. Dexamethasone was more inhibitory than pentoxifylline at the doses chosen. The initial response of the brain to irradiation involves expression of inflammatory gene products, which are probably responsible for clinically observed early symptoms of brain radiotherapy. This mechanism explains the beneficial effects of the clinical use of steroids in such circumstances. 64 refs., 4 figs.

  5. Optimizing sedation in patients with acute brain injury.

    PubMed

    Oddo, Mauro; Crippa, Ilaria Alice; Mehta, Sangeeta; Menon, David; Payen, Jean-Francois; Taccone, Fabio Silvio; Citerio, Giuseppe

    2016-01-01

    Daily interruption of sedative therapy and limitation of deep sedation have been shown in several randomized trials to reduce the duration of mechanical ventilation and hospital length of stay, and to improve the outcome of critically ill patients. However, patients with severe acute brain injury (ABI; including subjects with coma after traumatic brain injury, ischaemic/haemorrhagic stroke, cardiac arrest, status epilepticus) were excluded from these studies. Therefore, whether the new paradigm of minimal sedation can be translated to the neuro-ICU (NICU) is unclear. In patients with ABI, sedation has 'general' indications (control of anxiety, pain, discomfort, agitation, facilitation of mechanical ventilation) and 'neuro-specific' indications (reduction of cerebral metabolic demand, improved brain tolerance to ischaemia). Sedation also is an essential therapeutic component of intracranial pressure therapy, targeted temperature management and seizure control. Given the lack of large trials which have evaluated clinically relevant endpoints, sedative selection depends on the effect of each agent on cerebral and systemic haemodynamics. Titration and withdrawal of sedation in the NICU setting has to be balanced between the risk that interrupting sedation might exacerbate brain injury (e.g. intracranial pressure elevation) and the potential benefits of enhanced neurological function and reduced complications. In this review, we provide a concise summary of cerebral physiologic effects of sedatives and analgesics, the advantages/disadvantages of each agent, the comparative effects of standard sedatives (propofol and midazolam) and the emerging role of alternative drugs (ketamine). We suggest a pragmatic approach for the use of sedation-analgesia in the NICU, focusing on some practical aspects, including optimal titration and management of sedation withdrawal according to ABI severity. PMID:27145814

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

    PubMed

    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 (p<0.05). GDI engine 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 (p<0.05), likely attributable to a combination of the gas and particulate fractions. Exposure to GDI engine exhaust contributes to upregulation of genes related to the metabolism of PAHs and oxidative stress. PMID:27369091

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  9. 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.

    PubMed

    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. PMID:27251735

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

    PubMed

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

    2016-06-01

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

  11. Automatic counting and positioning of 5-bromo-2-deoxyuridine (BrdU) positive cells in cortical layers of rat brain slices.

    PubMed

    Schmuck, Martin; Temme, Thomas; Heinz, Sabrina; Baksmeier, Christine; Mosig, Axel; Colomina, M Teresa; Barenys, Marta; Fritsche, Ellen

    2014-07-01

    5-Bromo-2-deoxyuridine (BrdU) staining is often used to evaluate cortical layer formation during mammalian brain development. This method allows the quantification of newly generated cells and therefore the study of the effects of xenobiotics or genetic factors on proliferation, cell death and migration behavior in a quantitative manner. However, these endpoints are generally assessed by time-consuming manual evaluation. In the present work, we introduce a novel procedure to identify and quantify BrdU(+) cells within cortical layers, using the commercially available vHCS-Scan V.6.3.1 software to identify BrdU(+) cell coordinates and the novel program 'BrdeLuxe' to define cortical layers and quantitatively assign BrdU(+) cells to them. This procedure is compared to BrdU(+) cell counting with the freeware 'ImageJ' in respect to the manual evaluation, all by two different researchers. BrdeLuxe shows high accuracy and precision for the determination of total number of BrdU(+) cells compared to the manual counting, while ImageJ does not reach such results. Accuracy and precision are also higher for employing the BrdeLuxe program to evaluate the percentage of BrdU(+) cells per brain layer compared to ImageJ. In terms of running time, BrdeLuxe is the fastest method of the three making it more suitable for multiple brain slices analyses. PMID:24572144

  12. Effort test performance in clinical acute brain injury, community brain injury, and epilepsy populations.

    PubMed

    Hampson, Natalie E; Kemp, Steven; Coughlan, Anthony K; Moulin, Chris J A; Bhakta, Bipin B

    2014-01-01

    Effort tests have become commonplace within medico-legal and forensic contexts and their use is rising within clinical settings. It is recognized that some patients may fail effort tests due to cognitive impairment and not because of poor effort. However, investigation of the base rate of failure among clinical populations other than dementia is limited. Forty-seven clinical participants were recruited and comprised three subgroups: acute brain injury (N = 11), community brain injury (N = 20), and intractable epilepsy (N = 16). Base rates of failure on the Word Memory Test (WMT; Green, 2003 ) and six other less well-validated measures were investigated. A significant minority of patients failed effort tests according to standard cutoff scores, particularly patients with severe traumatic brain injury and marked frontal-executive features. The WMT was able to identify failures associated with significant cognitive impairment through the application of profile analysis and/or lowered cutoff levels. Implications for clinical assessment, effort test interpretation, and future research are discussed. PMID:25084843

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

    PubMed

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

    2015-01-01

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

  14. REGULATION OF BRAIN-DERIVED NEUROTROPHIC FACTOR MESSENGER RNA LEVELS IN AVIAN HYPOTHALAMIC SLICE CULTURES. (R825294)

    EPA Science Inventory

    Mechanisms regulating the expression of brain-derived neurotrophic factor, a member of the neurotrophin family, have been extensively studied in the rat cerebral cortex, hippocampus and cerebellum. In contrast, little is known regarding the regulation of this growth factor in ...

  15. Regional variations in protein phosphorylating activity in rat brain studied in micro-slices labeled with ( sup 32 P)phosphate

    SciTech Connect

    Rodnight, R.; Leal, R. )

    1990-01-01

    Regional variations in protein phosphorylating activity in the rat brain were studied. Micro-slices (1 mm diameter) were prepared from 19 brain areas, phosphoproteins labeled by incubation with ({sup 32}P)phosphate, and the tissue analyzed by nonequilibrium two-dimensional electrophoresis and autoradiography. Attention was focused on three phosphorylating systems that showed consistent variation in activity. (1) A system that phosphorylates a substrate of 47 kDa (ppH-47) whose activity was highest in the hippocampus. The next highest activity of this system was observed in the globus pallidus, followed by the periventricular gray matter of the aqueduct, lateral septum, cerebellar cortex, entorhinal cortex, hypothalamus, mammillary nuclei, amygdala, and substantia nigra. Activity was low or undetectable in the cerebral cortex, neostriatum, and the colliculi. (2) A system that phosphorylates a substrate of 50 kDa (ppC-50) whose activity was highest in the caudate nucleus. The activity of this system was roughly inversely correlated with that of the ppH-47 system. (3) The protein kinase C system that phosphorylates an 82- to 87-kDa substrate known as MARCKS. The highest activity of this system was observed in the cerebellar cortex, followed by the hypothalamus, mammillary nuclei, periventricular gray matter of the aqueduct, and the superior colliculus. Activity of this system was relatively low in several regions of the cerebral cortex, the neostriatum, and the inferior colliculus.

  16. Validation of optical voltage reporting by the genetically encoded voltage indicator VSFP-Butterfly from cortical layer 2/3 pyramidal neurons in mouse brain slices

    PubMed Central

    Empson, Ruth M; Goulton, Chelsea; Scholtz, David; Gallero-Salas, Yasir; Zeng, Hongkui; Knöpfel, Thomas

    2015-01-01

    Understanding how behavior emerges from brain electrical activity is one of the ultimate goals of neuroscience. To achieve this goal we require methods for large-scale recording of the electrical activity of specific neuronal circuits. A very promising approach is to use optical reporting of membrane voltage transients, particularly if the voltage reporter is genetically targeted to specific neuronal populations. Targeting in this way allows population signals to be recorded and interpreted without blindness to neuronal diversity. Here, we evaluated the voltage-sensitive fluorescent protein, VSFP Butterfly 2.1, a genetically encoded voltage indicator (GEVI), for monitoring electrical activity of layer 2/3 cortical pyramidal neurons in mouse brain slices. Standard widefield fluorescence and two-photon imaging revealed robust, high signal-to-noise ratio read-outs of membrane voltage transients that are predominantly synaptic in nature and can be resolved as discrete areas of synaptically connected layer 2/3 neurons. We find that targeted expression of this GEVI in the cortex provides a flexible and promising tool for the analysis of L2/3 cortical network function. PMID:26229003

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

    PubMed

    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. PMID:26461355

  18. Lumican as a novel potential clinical indicator for acute aortic dissection: A comparative study, based on multi-slice computed tomography angiography

    PubMed Central

    GU, GUORONG; WAN, FANG; XUE, YUAN; CHENG, WEIZHONG; ZHENG, HAIYIN; ZHAO, YUN; FAN, FAN; HAN, YI; TONG, CHAOYANG; YAO, CHENLING

    2016-01-01

    The aim of the present study was to investigate the association between serum lumican levels and acute aortic dissection (AAD) severity. A total of 82 patients with chest or back pain and 30 healthy volunteers were recruited. Among the patients, there were 70 cases of AAD and 12 cases of intramural hematoma (IMH). AAD severity was determined using multi-slice computed tomography angiography (MSCTA). Serum was collected from the patients upon admission, and lumican levels were detected using an enzyme-linked immunosorbent assay. In addition, correlation analyses were conducted between lumican levels and AAD severity by designing a ‘SCORE X, RANGE Y’ system to measure the number of affected vital arteries and vertical range of false lumen, based on the MSCTA. Lumican levels differed significantly among the AAD patients (2.32±4.29 ng/ml), IMH patients (0.72±0.32 ng/ml) and healthy volunteers (0.85±0.53 ng/ml; P=0.003). In the AAD patients presenting within 12–72 h of symptom onset, the Spearman's rho correlation coefficient between lumican and SCORE or RANGE was 0.373 (P=0.046) and 0.468 (P=0.010), respectively. The present results suggest that lumican may be a potential marker for aiding the diagnosis and screening for AAD, and may be used to predict the severity of AAD. PMID:26998013

  19. Acute Brain Trauma in Mice Followed By Longitudinal Two-photon Imaging

    PubMed Central

    Paveliev, Mikhail; Kislin, Mikhail; Molotkov, Dmitry; Yuryev, Mikhail; Rauvala, Heikki; Khiroug, Leonard

    2014-01-01

    Although acute brain trauma often results from head damage in different accidents and affects a substantial fraction of the population, there is no effective treatment for it yet. Limitations of currently used animal models impede understanding of the pathology mechanism. Multiphoton microscopy allows studying cells and tissues within intact animal brains longitudinally under physiological and pathological conditions. Here, we describe two models of acute brain injury studied by means of two-photon imaging of brain cell behavior under posttraumatic conditions. A selected brain region is injured with a sharp needle to produce a trauma of a controlled width and depth in the brain parenchyma. Our method uses stereotaxic prick with a syringe needle, which can be combined with simultaneous drug application. We propose that this method can be used as an advanced tool to study cellular mechanisms of pathophysiological consequences of acute trauma in mammalian brain in vivo. In this video, we combine acute brain injury with two preparations: cranial window and skull thinning. We also discuss advantages and limitations of both preparations for multisession imaging of brain regeneration after trauma. PMID:24748024

  20. Outcome-related metabolomic patterns from 1H/31P NMR after mild hypothermia treatments of oxygen–glucose deprivation in a neonatal brain slice model of asphyxia

    PubMed Central

    Liu, Jia; Litt, Lawrence; Segal, Mark R; Kelly, Mark J S; Yoshihara, Hikari A I; James, Thomas L

    2011-01-01

    Human clinical trials using 72 hours of mild hypothermia (32°C–34°C) after neonatal asphyxia have found substantially improved neurologic outcomes. As temperature changes differently modulate numerous metabolite fluxes and concentrations, we hypothesized that 1H/31P nuclear magnetic resonance (NMR) spectroscopy of intracellular metabolites can distinguish different insults, treatments, and recovery stages. Three groups of superfused neonatal rat brain slices underwent 45 minutes oxygen–glucose deprivation (OGD) and then were: treated for 3 hours with mild hypothermia (32°C) that began with OGD, or similarly treated with hypothermia after a 15-minute delay, or not treated (normothermic control group, 37°C). Hypothermia was followed by 3 hours of normothermic recovery. Slices collected at different predetermined times were processed, respectively, for 14.1 Tesla NMR analysis, enzyme-linked immunosorbent assay (ELISA) cell-death quantification, and superoxide production. Forty-nine NMR-observable metabolites underwent a multivariate analysis. Separated clustering in scores plots was found for treatment and outcome groups. Final ATP (adenosine triphosphate) levels, severely decreased at normothermia, were restored equally by immediate and delayed hypothermia. Cell death was decreased by immediate hypothermia, but was equally substantially greater with normothermia and delayed hypothermia. Potentially important biomarkers in the 1H spectra included PCr-1H (phosphocreatine in the 1H spectrum), ATP-1H (adenosine triphosphate in the 1H spectrum), and ADP-1H (adenosine diphosphate in the 1H spectrum). The findings suggest a potential role for metabolomic monitoring during therapeutic hypothermia. PMID:20717124

  1. Outcome-related metabolomic patterns from 1H/31P NMR after mild hypothermia treatments of oxygen-glucose deprivation in a neonatal brain slice model of asphyxia.

    PubMed

    Liu, Jia; Litt, Lawrence; Segal, Mark R; Kelly, Mark J S; Yoshihara, Hikari A I; James, Thomas L

    2011-02-01

    Human clinical trials using 72 hours of mild hypothermia (32°C-34°C) after neonatal asphyxia have found substantially improved neurologic outcomes. As temperature changes differently modulate numerous metabolite fluxes and concentrations, we hypothesized that (1)H/(31)P nuclear magnetic resonance (NMR) spectroscopy of intracellular metabolites can distinguish different insults, treatments, and recovery stages. Three groups of superfused neonatal rat brain slices underwent 45 minutes oxygen-glucose deprivation (OGD) and then were: treated for 3 hours with mild hypothermia (32°C) that began with OGD, or similarly treated with hypothermia after a 15-minute delay, or not treated (normothermic control group, 37°C). Hypothermia was followed by 3 hours of normothermic recovery. Slices collected at different predetermined times were processed, respectively, for 14.1 Tesla NMR analysis, enzyme-linked immunosorbent assay (ELISA) cell-death quantification, and superoxide production. Forty-nine NMR-observable metabolites underwent a multivariate analysis. Separated clustering in scores plots was found for treatment and outcome groups. Final ATP (adenosine triphosphate) levels, severely decreased at normothermia, were restored equally by immediate and delayed hypothermia. Cell death was decreased by immediate hypothermia, but was equally substantially greater with normothermia and delayed hypothermia. Potentially important biomarkers in the (1)H spectra included PCr-(1)H (phosphocreatine in the (1)H spectrum), ATP-(1)H (adenosine triphosphate in the (1)H spectrum), and ADP-(1)H (adenosine diphosphate in the (1)H spectrum). The findings suggest a potential role for metabolomic monitoring during therapeutic hypothermia. PMID:20717124

  2. Protection of the blood-brain barrier by hypercapnia during acute hypertension

    SciTech Connect

    Baumbach, G.L.; Mayhan, W.G.; Heistad, D.D.

    1986-08-01

    The purpose of this study was to examine effects of hypercapnia on susceptibility of the blood-brain barrier to disruption during acute hypertension. Two methods were used to test the hypothesis that cerebral vasodilation during hypercapnia increases disruption of the blood-brain barrier. First, permeability of the blood-brain barrier was measured in anesthetized cats with SVI-labeled serum albumin. Severe hypertension markedly increased permeability of the blood-brain barrier during normocapnia, but not during hypercapnia. The protective effect of hypercapnia was not dependent on sympathetic nerves. Second, in anesthetized rats, permeability of the barrier was quantitated by clearance of fluorescent dextran. Disruption of the blood-brain barrier during hypertension was decreased by hypercapnia. Because disruption of the blood-brain barrier occurred primarily in pial venules, the authors also measured pial venular diameter and pressure. Acute hypertension increased pial venular pressure and diameter in normocapnic rats. Hypercapnia alone increased pial venular pressure and pial venular diameter, and acute hypertension during hypercapnia further increased venular pressure. The magnitude of increase in pial venular pressure during acute hypertension was significantly less in hypercapnic than in normocapnic rats. They conclude that hypercapnia protects the blood-brain barrier. Possible mechanisms of this effect include attenuation of the incremental increase in pial venular pressure by hypercapnia or a direct effect on the blood-brain barrier not related to venous pressure.

  3. Contrasting Acute and Slow-Growing Lesions: A New Door to Brain Plasticity

    ERIC Educational Resources Information Center

    Desmurget, Michel; Bonnetblanc, FranCois; Duffau, Hugues

    2007-01-01

    The concept of plasticity describes the mechanisms that rearrange cerebral organization following a brain injury. During the last century, plasticity has been mainly investigated in humans with acute strokes. It was then shown: (i) that the brain is organized into highly specialized functional areas, often designated "eloquent" areas and (ii) that…

  4. Oxygen Mapping within Healthy and Acutely Infarcted Brain Tissue in Humans Using the NMR Relaxation of Lipids: A Proof-Of-Concept Translational Study

    PubMed Central

    Magat, Julie; Joudiou, Nicolas; Peeters, André P.; Jordan, Bénédicte F.; Gallez, Bernard; Duprez, Thierry

    2015-01-01

    The clinical applicability of brain oxygenation mapping using the MOBILE (Mapping of Oxygen By Imaging Lipids relaxation Enhancement) magnetic resonance (MR) technique was assessed in the clinical setting of normal brain and of acute cerebral ischemia as a founding proof-of-concept translational study. Changes in the oxygenation level within healthy brain tissue can be detected by analyzing the spin-lattice proton relaxation (‘Global T1’ combining water and lipid protons) because of the paramagnetic properties of molecular oxygen. It was hypothesized that selective measurement of the relaxation of the lipid protons (‘Lipids T1’) would result in enhanced sensitivity of pO2 mapping because of higher solubility of oxygen in lipids than in water, and this was demonstrated in pre-clinical models using the MOBILE technique. In the present study, 12 healthy volunteers and eight patients with acute (48–72 hours) brain infarction were examined with the same clinical 3T MR system. Both Lipids R1 (R1 = 1/T1) and Global R1 were significantly different in the infarcted area and the contralateral unaffected brain tissue, with a higher statistical significance for Lipids R1 (median difference: 0.408 s-1; p<0.0001) than for Global R1 (median difference: 0.154 s-1; p = 0.027). Both Lipids R1 and Global R1 values in the unaffected contralateral brain tissue of stroke patients were not significantly different from the R1 values calculated in the brain tissue of healthy volunteers. The main limitations of the present prototypic version of the MOBILE sequence are the long acquisition time (4 min), hampering robustness of data in uncooperative patients, and a 2 mm slice thickness precluding accurate measurements in small infarcts because of partial volume averaging effects. PMID:26267901

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

    PubMed

    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

  6. The effects of acute alcohol administration on the human brain: Insights from neuroimaging

    PubMed Central

    Bjork, James M.; Gilman, Jodi M.

    2014-01-01

    Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These in vivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects. PMID:23978384

  7. Single-trial imaging of spikes and synaptic potentials in single neurons in brain slices with genetically encoded hybrid voltage sensor

    PubMed Central

    Ghitani, Nima; Bayguinov, Peter O.; Ma, Yihe

    2014-01-01

    Genetically encoded voltage sensors expand the optogenetics toolkit into the important realm of electrical recording, enabling researchers to study the dynamic activity of complex neural circuits in real time. However, these probes have thus far performed poorly when tested in intact neural circuits. Hybrid voltage sensors (hVOS) enable the imaging of voltage by harnessing the resonant energy transfer that occurs between a genetically encoded component, a membrane-tethered fluorescent protein that serves as a donor, and a small charged molecule, dipicrylamine, which serves as an acceptor. hVOS generates optical signals as a result of voltage-induced changes in donor-acceptor distance. We expressed the hVOS probe in mouse brain by in utero electroporation and in transgenic mice with a neuronal promoter. Under conditions favoring sparse labeling we could visualize single-labeled neurons. hVOS imaging reported electrically evoked fluorescence changes from individual neurons in slices from entorhinal cortex, somatosensory cortex, and hippocampus. These fluorescence signals tracked action potentials in individual neurons in a single trial with excellent temporal fidelity, producing changes that exceeded background noise by as much as 16-fold. Subthreshold synaptic potentials were detected in single trials in multiple distinct cells simultaneously. We followed signal propagation between different cells within one field of view and between dendrites and somata of the same cell. hVOS imaging thus provides a tool for high-resolution recording of electrical activity from genetically targeted cells in intact neuronal circuits. PMID:25411462

  8. Single-trial imaging of spikes and synaptic potentials in single neurons in brain slices with genetically encoded hybrid voltage sensor.

    PubMed

    Ghitani, Nima; Bayguinov, Peter O; Ma, Yihe; Jackson, Meyer B

    2015-02-15

    Genetically encoded voltage sensors expand the optogenetics toolkit into the important realm of electrical recording, enabling researchers to study the dynamic activity of complex neural circuits in real time. However, these probes have thus far performed poorly when tested in intact neural circuits. Hybrid voltage sensors (hVOS) enable the imaging of voltage by harnessing the resonant energy transfer that occurs between a genetically encoded component, a membrane-tethered fluorescent protein that serves as a donor, and a small charged molecule, dipicrylamine, which serves as an acceptor. hVOS generates optical signals as a result of voltage-induced changes in donor-acceptor distance. We expressed the hVOS probe in mouse brain by in utero electroporation and in transgenic mice with a neuronal promoter. Under conditions favoring sparse labeling we could visualize single-labeled neurons. hVOS imaging reported electrically evoked fluorescence changes from individual neurons in slices from entorhinal cortex, somatosensory cortex, and hippocampus. These fluorescence signals tracked action potentials in individual neurons in a single trial with excellent temporal fidelity, producing changes that exceeded background noise by as much as 16-fold. Subthreshold synaptic potentials were detected in single trials in multiple distinct cells simultaneously. We followed signal propagation between different cells within one field of view and between dendrites and somata of the same cell. hVOS imaging thus provides a tool for high-resolution recording of electrical activity from genetically targeted cells in intact neuronal circuits. PMID:25411462

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

    PubMed

    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. PMID:24795175

  10. A Brain Signature to Differentiate Acute and Chronic Pain in Rats

    PubMed Central

    Guo, Yifei; Wang, Yuzheng; Sun, Yabin; Wang, Jin-Yan

    2016-01-01

    The transition from acute pain to chronic pain entails considerable changes of patients at multiple levels of the nervous system and in psychological states. An accurate differentiation between acute and chronic pain is essential in pain management as it may help optimize analgesic treatments according to the pain state of patients. Given that acute and chronic pain could modulate brain states in different ways and that brain states could greatly shape the neural processing of external inputs, we hypothesized that acute and chronic pain would show differential effects on cortical responses to non-nociceptive sensory information. Here by analyzing auditory-evoked potentials (AEPs) to pure tones in rats with acute or chronic pain, we found opposite influences of acute and chronic pain on cortical responses to auditory inputs. In particular, compared to no-pain controls, the N100 wave of rat AEPs was significantly enhanced in rats with acute pain but significantly reduced in rats with chronic pain, indicating that acute pain facilitated cortical processing of auditory information while chronic pain exerted an inhibitory effect. These findings could be justified by the fact that individuals suffering from acute or chronic pain would have different vigilance states, i.e., the vigilance level to external sensory stimuli would be increased with acute pain, but decreased with chronic pain. Therefore, this auditory response holds promise of being a brain signature to differentiate acute and chronic pain. Instead of investigating the pain system per se, the study of pain-induced influences on cortical processing of non-nocicpetive sensory information might represent a potential strategy to monitor the progress of pain chronification in clinical applications. PMID:27199727

  11. Utility of EEG measures of brain function in patients with acute stroke.

    PubMed

    Wu, Jennifer; Srinivasan, Ramesh; Burke Quinlan, Erin; Solodkin, Ana; Small, Steven L; Cramer, Steven C

    2016-06-01

    EEG has been used to study acute stroke for decades; however, because of several limitations EEG-based measures rarely inform clinical decision-making in this setting. Recent advances in EEG hardware, recording electrodes, and EEG software could overcome these limitations. The present study examined how well dense-array (256 electrodes) EEG, acquired with a saline-lead net and analyzed with whole brain partial least squares (PLS) modeling, captured extent of acute stroke behavioral deficits and varied in relation to acute brain injury. In 24 patients admitted for acute ischemic stroke, 3 min of resting-state EEG was acquired at bedside, including in the ER and ICU. Traditional quantitative EEG measures (power in a specific lead, in any frequency band) showed a modest association with behavioral deficits [NIH Stroke Scale (NIHSS) score] in bivariate models. However, PLS models of delta or beta power across whole brain correlated strongly with NIHSS score (R(2) = 0.85-0.90) and remained robust when further analyzed with cross-validation models (R(2) = 0.72-0.73). Larger infarct volume was associated with higher delta power, bilaterally; the contralesional findings were not attributable to mass effect, indicating that EEG captures significant information about acute stroke effects not available from MRI. We conclude that 1) dense-array EEG data are feasible as a bedside measure of brain function in patients with acute stroke; 2) high-dimension EEG data are strongly correlated with acute stroke behavioral deficits and are superior to traditional single-lead metrics in this regard; and 3) EEG captures significant information about acute stroke injury not available from structural brain imaging. PMID:26936984

  12. [Acute lymphoblastic leukemia presenting with multiple hemorrhagic brain metastases (case report)].

    PubMed

    Halefoğlu, Ahmet M; Ertürk, Mehmet; Ozel, Alper; Calişkan, K Can

    2004-06-01

    Intracranial metastases represent 7-17% of all brain tumors. Renal cell carcinoma, thyroid cancer, choriocarcinoma, melanoma, retinoblastoma, lung cancer and breast cancer have a propensity for producing hemorrhagic brain metastases. Leukemias have also been rarely reported to cause hemorrhagic brain metastases. We describe an 18-year-old girl diagnosed as acute lymphoblastic leukemia presenting with multiple hemorrhagic brain metastases. MRI demonstrated high signal intensity lesions on both T1- and T2-weighted images which were characteristic for extracellular methemoglobin and consistent with hemorrhagic metastases. PMID:15236125

  13. What role does the blood brain barrier play in acute mountain sickness?

    PubMed

    Baneke, Alex

    2010-07-01

    As high altitude travel increases, acute mountain sickness (AMS) and life threatening high altitude cerebral oedema (HACE) are becoming more prevalent. Acute mountain sickness occurs in 45% of lowlanders above 4250 m. Predisposing factors are still unknown and its development is more complex than the original "tight fit" hypothesis. This review examines evidence relating to a possible role of the blood brain barrier in AMS as suggested by MRI studies. Underlying mechanisms may involve vascular endothelial growth factor and free radicals in addition to increases in hydrostatic pressure. An increased understanding is important in advising patients planning high altitude adventures. Current studies have linked increased blood brain barrier permeability to high altitude cerebral oedema, but the role of the blood brain barrier in acute mountain sickness is less clear; varied symptoms include headache. MRI shows vasogenic oedema occurs in high altitude cerebral oedema, suggesting blood brain barrier permeability increases, and acute mountain sickness typically precedes high altitude cerebral oedema. Hypoxia leads to increased hydrostatic pressure, and blood brain barrier permeability has been shown to increase in stroke patients. Vascular endothelial growth factor is upregulated in hypoxia, and may increase blood brain barrier permeability. PMID:20952272

  14. Altered Cerebellar White Matter Integrity in Patients with Mild Traumatic Brain Injury in the Acute Stage

    PubMed Central

    Wang, Zhongqiu; Wu, Wenzhong; Liu, Yongkang; Wang, Tianyao; Chen, Xiao; Zhang, Jianhua; Zhou, Guoxing; Chen, Rong

    2016-01-01

    Background and Purpose Imaging studies of traumatic brain injury demonstrate that the cerebellum is often affected. We aim to examine fractional anisotropy alteration in acute-phase mild traumatic brain injury patients in cerebellum-related white matter tracts. Materials and Methods This prospective study included 47 mild traumatic brain injury patients in the acute stage and 37 controls. MR imaging and neurocognitive tests were performed in patients within 7 days of injury. White matter integrity was examined by using diffusion tensor imaging. We used three approaches, tract-based spatial statistics, graphical-model-based multivariate analysis, and region-of-interest analysis, to detect altered cerebellar white matter integrity in mild traumatic brain injury patients. Results Results from three analysis methods were in accordance with each other, and suggested fractional anisotropy in the middle cerebellar peduncle and the pontine crossing tract was changed in the acute-phase mild traumatic brain injury patients, relative to controls (adjusted p-value < 0.05). Higher fractional anisotropy in the middle cerebellar peduncle was associated with worse performance in the fluid cognition composite (r = -0.289, p-value = 0.037). Conclusion Altered cerebellar fractional anisotropy in acute-phase mild traumatic brain injury patients is localized in specific regions and statistically associated with cognitive deficits detectable on neurocognitive testing. PMID:26967320

  15. Effect of acute and chronic cholinesterase inhibition on biogenic amines in rat brain.

    PubMed

    Soininen, H; Unni, L; Shillcutt, S

    1990-12-01

    The effects of five cholinesterase inhibitors on forebrain monoamine and their metabolite levels, and on forebrain and plasma cholinesterase (ChE) activity in rat were studied in acute and chronic conditions. Acute tetrahydroaminoacridine (THA) dosing caused lower brain (68%) and higher plasma (90%) ChE inhibition than the other drugs studied and increased levels of brain dihydroxyphenylacetic acid (DOPAC) (236%), homovanillic acid (HVA) (197%) and 5-hydroxyindoleacetic acid (5-HIAA) (130%). Acute physostigmine (PHY) administration caused a 215% increase in brain DOPAC content. Despite high brain ChE inhibition induced by metrifonate (MTF), dichlorvos (DDVP) or naled no changes in brain noradrenaline (NA), dopamine (DA) or serotonin (5-HT) occurred due to treatment with the study drugs in the acute study. In the chronic 10-day study THA or PHY caused no substantial ChE inhibition in brain when measured 18 hours after the last dose, whereas MTF induced 74% ChE inhibition. Long-term treatment with THA or MTF caused no changes in monoamine levels, but PHY treatment resulted in slightly increased 5-HT values. These results suggest that MTF, DDVP and naled seem to act solely by cholinergic mechanisms. However, the central neuropharmacological mechanism of action of THA and PHY may involve changes in cholinergic as well as dopaminergic and serotoninergic systems. PMID:1711162

  16. Brain edema in acute liver failure. Insight from experimental studies.

    PubMed

    Andres, T; Blei, M D; Judy, R; Cho, M D

    1990-07-01

    Brain edema is a leading cause of death in fulminant hepatic failure (FHP). Animal studies are needed to gain further insight into its pathogenesis. The authors describe and analyze the results of brain studies in two animal models of FHF, the rabbit with galactosamine induced hepatitis and the anhepatic model of liver desvascularization. A gravimetric technique is used to determine water content in brain samples as small as 10 mg in weight. Results showed that water content is increased and correlates with the severity of encephalopathy in both experimental models of encephalopathy. The possible pathogenic role of ammonia and octanoic acid are discussed. PMID:19256151

  17. Comparison between the pharmacology of dopamine receptors mediating the inhibition of cell firing in rat brain slices through the substantia nigra pars compacta and ventral tegmental area.

    PubMed Central

    Bowery, B.; Rothwell, L. A.; Seabrook, G. R.

    1994-01-01

    1. Electrophysiological recordings were made from presumed dopaminergic neurons in the substantia nigra pars compacta and ventral tegmental area of rat brain slices. The ability of selective dopamine receptor agonists to hyperpolarize neurones and inhibit cell firing, as well as the ability of dopamine receptor antagonists to block responses to quinpirole were compared. 2. Six dopamine receptor agonists were examined for their ability to hyperpolarize neurones within the substantia nigra pars compacta. Of these, the most potent ligand tested was naxagolide with an EC50 value of 20 nM and estimated maximum of 10 mV. The rank order of agonist potency was naxagolide > quinpirole > apomorphine > dopamine. 3. Quinpirole was more potent at inhibiting cell firing in the substantia nigra pars compacta (pIC50 = 7.65 +/ 0.06, n = 35) than in the ventral tegmental area (pIC50 = 7.24 +/- 0.06, n = 32; P < 0.01, Student's t test). 7-Hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT), a putative D3 selective agonist, had a comparable potency to quinpirole in both the ventral tegmental area (pIC50 = 7.39 +/- 0.26, n = 4), and substantia nigra pars compacta (pIC50 = 7.71 +/- 0.20; n = 4). 4. The inhibition of cell firing by quinpirole was antagonized by haloperidol, S(-)-sulpiride, clozapine, and ritanserin. S(-)-sulpiride and haloperidol had the highest estimated affinities in the substantia nigra, with pA2 values of 8.97 (slope = 0.85) and 8.20 (slope = 2.09) respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7921615

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

    NASA Astrophysics Data System (ADS)

    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.

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

    SciTech Connect

    Osada, J.; Aylagas, H.; Miro-Obradors, M.J.; Arce, C.; Palacios-Alaiz, E.; Cascales, M. )

    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.

  20. Does acute caffeine ingestion alter brain metabolism in young adults?

    PubMed

    Xu, Feng; Liu, Peiying; Pekar, James J; Lu, Hanzhang

    2015-04-15

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain's response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine's effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors. PMID:25644657

  1. Does acute caffeine ingestion alter brain metabolism in young adults?

    PubMed Central

    Xu, Feng; Liu, Peiying; Pekar, James J.; Lu, Hanzhang

    2015-01-01

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain’s response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine’s effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors. PMID:25644657

  2. Brain Abscesses Complicating Acute Pneumococcal Meningitis During Etanercept Therapy

    PubMed Central

    Kasirye, Yusuf; Epperla, Narendranath; Manne, Janaki Ram; Bapani, Sowjanya; Garcia-Montilla, Romel J

    2012-01-01

    Brain abscess formation as a sequelae of community-acquired pneumococcal meningitis is extremely rare, accounting for less than 1% of all meningitis complications. Although metastatic seeding from a distal peripheral septic focus has been observed, this phenomenon most commonly occurs in the context of ear, nose and throat infections, post-cranial neurosurgical procedures, traumatic open cranial injury, or immunosuppression. We present the case of a man, 61 years old, on etanercept therapy for ankylosing spondylitis who developed multiple brain abscesses as a complication of pneumococcal meningitis. We believe that the predisposition to this extremely rare complication of a particularly aggressive pneumococcal meningitis was most likely due to the underlying immunosuppression resulting from etanercept therapy. As far as we know, this case is the first report linking multiple brain abscess formation in a patient with community-acquired pneumococcal meningitis with etanercept therapy. PMID:22634540

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

    PubMed

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

    2013-01-01

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

  4. Acute iron overload and oxidative stress in brain.

    PubMed

    Piloni, Natacha E; Fermandez, Virginia; Videla, Luis A; Puntarulo, Susana

    2013-12-01

    An in vivo model in rat was developed by intraperitoneally administration of Fe-dextran to study oxidative stress triggered by Fe-overload in rat brain. Total Fe levels, as well as the labile iron pool (LIP) concentration, in brain from rats subjected to Fe-overload were markedly increased over control values, 6h after Fe administration. In this in vivo Fe overload model, the ascorbyl (A)/ascorbate (AH(-)) ratio, taken as oxidative stress index, was assessed. The A/AH(-) ratio in brain was significantly higher in Fe-dextran group, in relation to values in control rats. Brain lipid peroxidation indexes, thiobarbituric acid reactive substances (TBARS) generation rate and lipid radical (LR) content detected by Electron Paramagnetic Resonance (EPR), in Fe-dextran supplemented rats were similar to control values. However, values of nuclear factor-kappaB deoxyribonucleic acid (NFκB DNA) binding activity were significantly increased (30%) after 8h of Fe administration, and catalase (CAT) activity was significantly enhanced (62%) 21h after Fe administration. Significant enhancements in Fe content in cortex (2.4 fold), hippocampus (1.6 fold) and striatum (2.9 fold), were found at 6h after Fe administration. CAT activity was significantly increased after 8h of Fe administration in cortex, hippocampus and striatum (1.4 fold, 86, and 47%, respectively). Fe response in the whole brain seems to lead to enhanced NF-κB DNA binding activity, which may contribute to limit oxygen reactive species-dependent damage by effects on the antioxidant enzyme CAT activity. Moreover, data shown here clearly indicate that even though Fe increased in several isolated brain areas, this parameter was more drastically enhanced in striatum than in cortex and hippocampus. However, comparison among the net increase in LR generation rate, in different brain areas, showed enhancements in cortex lipid peroxidation, without changes in striatum and hippocampus LR generation rate after 6h of Fe overload

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

    ERIC Educational Resources Information Center

    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…

  6. Thick Slice and Thin Slice Teaching Evaluations

    ERIC Educational Resources Information Center

    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…

  7. [Histomorphometric characteristic of human brain in acute alcoholic intoxication].

    PubMed

    Shormanov, S V; Shormanova, N S

    2005-01-01

    Different brain sections were studied in 20 subjects, who died of ethanol intoxication and in 14 subjects who died of injuries of the heart and main vessels, in order to detect histological changes in the brain and for the purpose of defining spatial and quantitative ratios between cerebral tissue structures in alcoholic intoxication. Different histological, stereometric and morphometric tools were made use of. It was demonstrated that, in alcoholic intoxication, there occur severe disorders of the circulation with affection of vessels in the brain; there are also dystrophic and necrotic changes in neurocytes, glial cells and white substance. The square of neurons shrinks due to death of some of them in the cortex of hemispheres, thalamus and cerebellum. As for the medulla, they are more resistant, there, to ethanol. The diameter of capillaries in the studied brain sections diminishes due to a reduced tonus of cerebral arteries; the quantity of such vessels increases within a standard area, which is conditioned by the compensatory opening of reserve capillaries. All this can be important in dealing with issues of thanatogenesis and of forensic medical diagnosis in death of alcoholic intoxication. PMID:15881135

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

    PubMed

    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. PMID:27161374

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

    PubMed

    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 (p<0.001) and improved visualization of orbitofrontal cortex were achieved using SMS-TFL pCASL. By combining SMS acceleration with TFL pCASL, we demonstrated the feasibility for whole brain distortion-free quantitative mapping of cerebral blood flow at high and ultrahigh magnetic fields. PMID:25837601

  10. Slice-selective FID acquisition, localized by outer volume suppression (FIDLOVS) for (1)H-MRSI of the human brain at 7 T with minimal signal loss.

    PubMed

    Henning, Anke; Fuchs, Alexander; Murdoch, James B; Boesiger, Peter

    2009-08-01

    In comparison to 1.5 and 3 T, MR spectroscopic imaging at 7 T benefits from signal-to-noise ratio (SNR) gain and increased spectral resolution and should enable mapping of a large number of metabolites at high spatial resolutions. However, to take full advantage of the ultra-high field strength, severe technical challenges, e.g. related to very short T(2) relaxation times and strict limitations on the maximum achievable B(1) field strength, have to be resolved. The latter results in a considerable decrease in bandwidth for conventional amplitude modulated radio frequency pulses (RF-pulses) and thus to an undesirably large chemical-shift displacement artefact. Frequency-modulated RF-pulses can overcome this problem; but to achieve a sufficient bandwidth, long pulse durations are required that lead to undesirably long echo-times in the presence of short T(2) relaxation times. In this work, a new magnetic resonance spectroscopic imaging (MRSI) localization scheme (free induction decay acquisition localized by outer volume suppression, FIDLOVS) is introduced that enables MRSI data acquisition with minimal SNR loss due to T(2) relaxation and thus for the first time mapping of an extended neurochemical profile in the human brain at 7 T. To overcome the contradictory problems of short T(2) relaxation times and long pulse durations, the free induction decay (FID) is directly acquired after slice-selective excitation. Localization in the second and third dimension and skull lipid suppression are based on a T(1)- and B(1)-insensitive outer volume suppression (OVS) sequence. Broadband frequency-modulated excitation and saturation pulses enable a minimization of the chemical-shift displacement artefact in the presence of strict limits on the maximum B(1) field strength. The variable power RF pulses with optimized relaxation delays (VAPOR) water suppression scheme, which is interleaved with OVS pulses, eliminates modulation side bands and strong baseline distortions. Third

  11. Uncoupling of the autonomic and cardiovascular systems in acute brain injury.

    PubMed

    Goldstein, B; Toweill, D; Lai, S; Sonnenthal, K; Kimberly, B

    1998-10-01

    We hypothesized that acute brain injury results in decreased heart rate (HR) variability and baroreflex sensitivity indicative of uncoupling of the autonomic and cardiovascular systems and that the degree of uncoupling should be proportional to the degree of neurological injury. We used HR and blood pressure (BP) power spectral analysis to measure neuroautonomic regulation of HR and BP and the transfer function magnitude (TF) between BP and HR as a measure of baroreflex modulation of HR. In 24 brain-injured patients [anoxic/ischemic injury (n = 7), multiple trauma (n = 6), head trauma (n = 5), central nervous system infection (n = 4), and intracranial hemorrhage (n = 2)], neurological injury and survival was associated with low-frequency (0.01-0.15 Hz) HR and BP power and TF. Brain-dead patients showed decreased low-frequency HR power [0. 51 +/- 0.36 (SE) vs. 2.54 +/- 0.14 beats/min2, P = 0.03] and TF [0. 61 +/- 0.16 (SE) vs. 1.29 +/- 0.07 beats . min-1 . mmHg-1, P = 0.05] compared with non-brain-dead patients. We conclude that 1) severity of neurological injury and outcome are inversely associated with HR and BP variability and 2) there is direct evidence for cardiovascular and autonomic uncoupling in acute brain injury with complete uncoupling during brain death. PMID:9756562

  12. Evolution of blood-brain barrier damage associated with changes in brain metabolites following acute ischemia.

    PubMed

    Yan, Gen; Xuan, Yinghua; Dai, Zhuozhi; Zhang, Guishan; Xu, Haiyun; Mikulis, David; Wu, Renhua

    2015-11-11

    Stroke is a serious medical condition that requires emergency care. In the case of ischemic stroke, ischemia may lead to damage to the blood-brain barrier (BBB); the damage in turn may exacerbate the condition. Therefore, noninvasive detection of BBB damage represents a challenge for experimental and clinical researchers. In this study, we assessed the onset of BBB disruption by means of T1-weighted images with administration of the contrast enhancement agent gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and related BBB breakdown to brain metabolite changes in proton magnetic resonance spectrum (H-MRS) in the infarcted site following middle cerebral artery occlusion (MCAO) in rats. It was shown that MCAO for 30 min and 1.5 h caused no Gd-DTPA signal change in the T1-weighted images, whereas MCAO for 1 h significantly altered some of H-MRS brain metabolites, suggesting that brain metabolite changes occurred earlier than BBB damage after ischemic stroke. MCAO for 2 h caused BBB breakdown, which was related to changes in the levels of some brain metabolites detected by H-MRS. Between the second and the third hour after MCAO, brain metabolite changes continued as the result of BBB breakdown and the concurrent overperfusion to the infarcted site, which may ameliorate the metabolite changes, thus compensating for the functional failures of the brain after stroke. PMID:26366833

  13. Parameters of diffusional kurtosis imaging for the diagnosis of acute cerebral infarction in different brain regions

    PubMed Central

    Guo, Yue-Lin; Li, Su-Juan; Zhang, Zhong-Ping; Shen, Zhi-Wei; Zhang, Gui-Shan; Yan, Gen; Wang, Yan-Ting; Rao, Hai-Bing; Zheng, Wen-Bin; Wu, Ren-Hua

    2016-01-01

    Diffusional kurtosis imaging (DKI) is a new type diffusion-weighted sequence which measures the non-Gaussianity of water diffusion. The present study aimed to investigate whether the parameters of DKI could distinguish between differences in water molecule diffusion in various brain regions under the conditions of acute infarction and to identify the optimal DKI parameter for locating ischemic lesions in each brain region. A total of 28 patients with acute ischemic stroke in different brain regions were recruited for the present study. The relative values of DKI parameters were selected as major assessment indices, and the homogeneity of background image and contrast of adjacent structures were used as minor assessment indices. According to the brain region involved in three DKI parametric maps, including mean kurtosis (MK), axial kurtosis (Ka) and radial kurtosis (Kr), 112 groups of regions of interest were outlined in the following regions: Corpus callosum (n=17); corona radiata (n=26); thalamus (n=21); subcortical white matter (n=24); and cerebral cortex (n=24). For ischemic lesions in the corpus callosum and corona radiata, significant increases in relative Ka were detected, as compared with the other parameters (P<0.05). For ischemic lesions in the thalamus, subcortical white matter and cerebral cortices, an increase in the three parameters was detected, however this difference was not significant. Minor assessment indices demonstrated that Ka lacked tissue contrast and the background of Kr was heterogeneous; thus, MK was the superior assessment parameter for ischemic lesions in these regions. In conclusion, Ka is better suited for the diagnosis of acute ischemic lesions in highly anisotropic brain regions, such as the corpus callosum and corona radiate. MK may be appropriate for the lesions in low anisotropic or isotropic brain regions, such as the thalamus, subcortical white matter and cerebral cortices.

  14. How Acute Total Sleep Loss Affects the Attending Brain: A Meta-Analysis of Neuroimaging Studies

    PubMed Central

    Ma, Ning; Dinges, David F.; Basner, Mathias; Rao, Hengyi

    2015-01-01

    Study Objectives: Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Design: Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. Methods: The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. Results: The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Conclusion: Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity. Citation: Ma N, Dinges DF, Basner M, Rao H. How acute total

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

    NASA Astrophysics Data System (ADS)

    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.

  16. 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.

    PubMed

    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. PMID:18984021

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

    PubMed

    Curtis, L; Epstein, P

    2014-09-01

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

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

    SciTech Connect

    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.

  19. Altered Spontaneous Brain Activity in Patients with Acute Spinal Cord Injury Revealed by Resting-State Functional MRI

    PubMed Central

    Zhu, Ling; Wu, Guangyao; Zhou, Xin; Li, Jielan; Wen, Zhi; Lin, Fuchun

    2015-01-01

    Background 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. Methods 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. Results 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. Conclusion 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

  20. Adaptation of Microplate-based Respirometry for Hippocampal Slices and Analysis of Respiratory Capacity

    PubMed Central

    Schuh, Rosemary A.; Clerc, Pascaline; Hwang, Hyehyun; Mehrabian, Zara; Bittman, Kevin; Chen, Hegang; Polster, Brian M.

    2011-01-01

    Multiple neurodegenerative disorders are associated with altered mitochondrial bioenergetics. Although mitochondrial O2 consumption is frequently measured in isolated mitochondria, isolated synaptic nerve terminals (synaptosomes), or cultured cells, the absence of mature brain circuitry is a remaining limitation. Here we describe the development of a method that adapts the Seahorse Extracellular Flux Analyzer (XF24) for the microplate-based measurement of hippocampal slice O2 consumption. As a first evaluation of the technique, we compared whole slice bioenergetics to previous measurements made with synaptosomes or cultured neurons. We found that mitochondrial respiratory capacity and O2 consumption coupled to ATP synthesis could be estimated in cultured or acute hippocampal slices with preserved neural architecture. Mouse organotypic hippocampal slices oxidizing glucose displayed mitochondrial O2 consumption that was well-coupled, as determined by the sensitivity to the ATP synthase inhibitor oligomycin. However stimulation of respiration by uncoupler was modest (<120% of basal respiration) compared to previous measurements in cells or synaptosomes, although enhanced slightly (to ~150% of basal respiration) by the acute addition of the mitochondrial complex I-linked substrate pyruvate. These findings suggest a high basal utilization of respiratory capacity in slices and a limitation of glucose-derived substrate for maximal respiration. The improved throughput of microplate-based hippocampal respirometry over traditional O2 electrode-based methods is conducive to neuroprotective drug screening. When coupled with cell type-specific pharmacology or genetic manipulations, the ability to efficiently measure O2 consumption from whole slices should advance our understanding of mitochondrial roles in physiology and neuropathology. PMID:21520220

  1. The economics of treating stroke as an acute brain attack

    PubMed Central

    Bogousslavsky, Julien; Paciaroni, Maurizio

    2009-01-01

    Currently, treatments for ischemic stroke focus on restoring or improving perfusion to the ischemic area using thrombolytics. The increased hospitalization costs related to thrombolysis are offset by a decrease in rehabilitation costs, for a net cost savings to the healthcare system. However, early treatment is essential. The benefit of thrombolysis is time-dependent but only a very small proportion of patients, 2%, are presently being treated with tPA. In the United States, if the proportion of all ischemic stroke patients that receive tPA were increased to 4, 6, 8, 10, 15, or 20%, the realized cost saving would be approximately $ 15, 22, 30, 37, 55, and 74 million, respectively. Being so, efforts should be made to educate the public and paramedics regarding early stroke signs. Furthermore, additional acute stroke therapy training programs need to be established for emergency departments. Finally, hospital systems need to be re-engineered to treat patients as quickly as possible in order to optimize thrombolytic benefit as well as maximize cost-effectiveness. PMID:19775424

  2. The economics of treating stroke as an acute brain attack.

    PubMed

    Bogousslavsky, Julien; Paciaroni, Maurizio

    2009-01-01

    Currently, treatments for ischemic stroke focus on restoring or improving perfusion to the ischemic area using thrombolytics. The increased hospitalization costs related to thrombolysis are offset by a decrease in rehabilitation costs, for a net cost savings to the healthcare system. However, early treatment is essential. The benefit of thrombolysis is time-dependent but only a very small proportion of patients, 2%, are presently being treated with tPA. In the United States, if the proportion of all ischemic stroke patients that receive tPA were increased to 4, 6, 8, 10, 15, or 20%, the realized cost saving would be approximately $ 15, 22, 30, 37, 55, and 74 million, respectively. Being so, efforts should be made to educate the public and paramedics regarding early stroke signs. Furthermore, additional acute stroke therapy training programs need to be established for emergency departments. Finally, hospital systems need to be re-engineered to treat patients as quickly as possible in order to optimize thrombolytic benefit as well as maximize cost-effectiveness. PMID:19775424

  3. Neuroglobin mitigates mitochondrial impairments induced by acute inhalation of combustion smoke in the mouse brain

    PubMed Central

    Gorgun, Falih Murat; Zhuo, Ming; Singh, Shilpee; Englander, Ella W.

    2014-01-01

    Context Acute inhalation of combustion smoke adversely affects brain homeostasis and energy metabolism. We previously showed that overexpressed neuroglobin (neuron specific globin protein) attenuates the formation of smoke inhalation-induced oxidative DNA damage, in vivo, in the mouse brain, while others reported protection by neuroglobin in diverse models of brain injury, mainly involving oxidative stress and hypoxic/ischemic insults. Objective To determine to what extent elevated neuroglobin ameliorates post smoke-inhalation brain bioenergetics and homeostasis in neuroglobin overexpressing transgenic mouse. Methods Smoke inhalation induced changes in bioenergetics were measured in the wild type and neuroglobin transgene mouse brain. Modulations of mitochondrial respiration were analyzed using the Seahorse XF24 flux analyzer and changes in cytoplasmic energy metabolism were assessed by measuring enzymatic activities and lactate in the course of post smoke recovery. Results Cortical mitochondria from neuroglobin transgene, better maintained ATP synthesis-linked oxygen consumption and unlike wild type mitochondria did not increase futile oxygen consumption feeding the proton leak, reflecting lesser smoke-induced mitochondrial compromise. Measurements revealed lesser reduction of mitochondrial ATP content and lesser compensatory increases in cytosolic energy metabolism, involving pyruvate kinase and lactate dehydrogenase activities as well as cytosolic lactate levels. Additionally, induction of c-Fos, the early response gene and key neuronal stress sensor, was attenuated in neuroglobin transgene compared to wild type brain after smoke. Conclusion Considered together, these differences reflect lesser perturbations produced by acute inhalation of combustion smoke in the neuroglobin overexpressing mouse, suggesting that neuroglobin mitigates mitochondrial dysfunction and neurotoxicity and raises the threshold of smoke inhalation-induced brain injury. PMID:24730682

  4. Excessive α-tocopherol exacerbates microglial activation and brain injury caused by acute ischemic stroke

    PubMed Central

    Khanna, Savita; Heigel, Mallory; Weist, Jessica; Gnyawali, Surya; Teplitsky, Seth; Roy, Sashwati; Sen, Chandan K.; Rink, Cameron

    2015-01-01

    The vitamin E family includes both tocopherols and tocotrienols, where α-tocopherol (αTOC) is the most bioavailable form. Clinical trials testing the therapeutic efficacy of high-dose αTOC against stroke have largely failed or reported negative outcomes when a “more is better” approach to supplementation (>400 IU/d) was used. This work addresses mechanisms by which supraphysiologic αTOC may contribute to stroke-induced brain injury. Ischemic stroke injury and the neuroinflammatory response were studied in tocopherol transfer protein-deficient mice maintained on a diet containing αTOC vitamin E at the equivalent human dose of 1680 IU/d. Ischemic stroke-induced brain injury was exacerbated in the presence of supraphysiologic brain αTOC levels. At 48 h after stroke, S100B and RAGE expression was increased in stroke-affected cortex of mice with elevated brain αTOC levels. Such increases were concomitant with aggravated microglial activation and neuroinflammatory signaling. A poststroke increase in markers of oxidative injury and neurodegeneration in the presence of elevated brain αTOC establish that at supraphysiologic levels, αTOC potentiates neuroinflammatory responses to acute ischemic stroke. Exacerbation of microglial activation by excessive αTOC likely depends on its unique cell signaling regulatory properties independent of antioxidant function. Against the background of clinical failure for high-dose αTOC, outcomes of this work identify risk for exacerbating stroke-induced brain injury as a result of supplementing diet with excessive levels of αTOC.—Khanna, S., Heigel,M., Weist, J., Gnyawali, S., Teplitsky, S., Roy, S., Sen, C. K., Rink, C. Excessive α-tocopherol exacerbates microglial activation and brain injury caused by acute ischemic stroke. PMID:25411436

  5. Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection

    PubMed Central

    Sailasuta, Napapon; Ross, William; Ananworanich, Jintanat; Chalermchai, Thep; DeGruttola, Victor; Lerdlum, Sukalaya; Pothisri, Mantana; Busovaca, Edgar; Ratto-Kim, Silvia; Jagodzinski, Linda; Spudich, Serena; Michael, Nelson; Kim, Jerome H.; Valcour, Victor

    2012-01-01

    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. PMID:23229129

  6. Neurosensory Symptom Complexes after Acute Mild Traumatic Brain Injury

    PubMed Central

    Szczupak, Mikhaylo; Kiderman, Alexander; Crawford, James; Murphy, Sara; Marshall, Kathryn; Pelusso, Constanza

    2016-01-01

    Mild Traumatic Brain Injury (mTBI) is a prominent public health issue. To date, subjective symptom complaints primarily dictate diagnostic and treatment approaches. As such, the description and qualification of these symptoms in the mTBI patient population is of great value. This manuscript describes the symptoms of mTBI patients as compared to controls in a larger study designed to examine the use of vestibular testing to diagnose mTBI. Five symptom clusters were identified: Post-Traumatic Headache/Migraine, Nausea, Emotional/Affective, Fatigue/Malaise, and Dizziness/Mild Cognitive Impairment. Our analysis indicates that individuals with mTBI have headache, dizziness, and cognitive dysfunction far out of proportion to those without mTBI. In addition, sleep disorders and emotional issues were significantly more common amongst mTBI patients than non-injured individuals. A simple set of questions inquiring about dizziness, headache, and cognitive issues may provide diagnostic accuracy. The consideration of other symptoms may be critical for providing prognostic value and treatment for best short-term outcomes or prevention of long-term complications. PMID:26727256

  7. Evaluation of brain function in acute carbon monoxide poisoning with multimodality evoked potentials

    SciTech Connect

    He, Fengsheng; Liu, Xibao; Yang, Shi; Zhang, Shoulin ); Xu, Guanghua; Fang, Guangchai; Pan, Xiaowen )

    1993-02-01

    The median nerve somatosensory evoked potentials (SEP), pattern reversal visual evoked potentials (VEP), and brain stem auditory evoked potentials (BAEP) were studied in 109 healthy adults and in 88 patients with acute carbon monoxide (CO) poisoning. The upper limits for normal values of peak and interpeak latencies of multimodalities of evoked potentials in the reference group were established by a stepwise multiple regression analysis. SEP changes selectively affecting N32 and N60 were found in 78.8% of patients. There was prolonged PI00 latency of VEP in 58.2% of the cases examined. The prevalence of BAEP abnormalities in comatose patients (36%) was significantly higher than that (8.6%) in conscious patients. BAEP abnormalities were most frequently seen in comatose patients who had diminished brain stem reflexes (77.8%). It has been found that a consistent abnormality involving N2O and subsequent peaks in SEP, a remarkable prolongation of PI00 latency in VEP, or a prolongation of Ill-V interpeak latency in BAEP as well as the reoccurrence of evoked potential abnormalities after initial recovery all indicate unfavorable outcomes in patients with acute CO poisoning. The multimodality evoked potentials have proved to be sensitive indicators in the evaluation of brain dysfunction and in the prediction of prognosis of acute CO poisoning and the development of delayed encephalopathy. 16 refs., 4 figs., 6 tabs.

  8. Brain and Muscle Redox Imbalance Elicited by Acute Ethylmalonic Acid Administration

    PubMed Central

    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. PMID:26010931

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

    PubMed

    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. PMID:26010931

  10. Alterations in rat brain polyphosphoinositide metabolism due to acute ethanol administration.

    PubMed

    Chandrasekhar, R; Huang, H M; Sun, G Y

    1988-04-01

    The effects of acute ethanol administration on the polyphosphoinositide metabolism of rat brain cerebral cortex were examined. Intracerebral injections of [gamma-32P]ATP proved to be an effective in vivo method to prelabel brain phospholipids, especially the polyphosphoinositides. High acute doses of ethanol (8 or 6 g/kg b.wt.) administered by gavage significantly inhibited the breakdown of polyphosphoinositides as judged by an elevation in the concentration as well as the labeling of these compounds. Concomitantly, there was a significant reduction in the level of diacylglycerols. Low acute doses of ethanol (2 g/kg b.wt.) did not seem to have any effects on the basal levels or labeling of these compounds. The changes in polyphosphoinositide labeling due to ethanol intoxication were reverted to near control values when animals regained their righting reflex (approximately 4 hr). These studies demonstrate that, under normal conditions, polyphosphoinositides and diacylglycerols are maintained in a dynamic equilibrium and that acute doses of ethanol can suppress the signal transduction process and disturb this equilibrium. PMID:2834532

  11. Proton relaxation in acute and subacute ischemic brain edema

    SciTech Connect

    Boisvert, D.P.; Handa, Y.; Allen, P.S. )

    1990-01-01

    The relation between regional ischemic brain edema and tissue proton relaxation rates (R1 = 1/T1; R2 = 1/T2) were studied in 16 macaque monkeys subjected to MCA occlusion. In vivo R2 measurements were obtained from multiple spin-echo (eight echoes) images taken at 2-, 3-, 4-, and 72-hr postischemia. In vitro R1 and R2 values were determined for corresponding regions after sacrifice at 4 hr (n = 8) or at 72-hr postischemia in seven surviving animals. The water content of the white and gray matter tissue samples was measured by the wet/dry method. Four animals (25%) showed ipsilateral regions of increased signal intensity as early as 2 hr after MCA occlusion. All seven animals imaged at 72 hr displayed such regions. Despite the absence of measured changes in tissue water content, significant decreases in R2, but not in R1, occurred at 4 hr. At this stage, R2 values correlated more closely than R1 with individual variations in water content. At 72 hr, marked decreases in both R1 and R2 were measured in ischemic deep gray matter and white matter. Cortical gray matter was unchanged. In edematous gray and white matter, both R1 and R2 correlated closely with tissue water content, but R2 was consistently 10 to 20 times more sensitive than R1. Biexponential R2 decay was observed at 4 and 72 hr, but only in the white matter region that became severely edematous at 72 hr.

  12. Increased blood-brain transfer in a rabbit model of acute liver failure

    SciTech Connect

    Horowitz, M.E.; Schafer, D.F.; Molnar, P.; Jones, E.A.; Blasberg, R.G.; Patlak, C.S.; Waggoner, J.; Fenstermacher, J.D.

    1983-05-01

    The blood-to-brain transfer of (/sup 14/C)alpha-aminoisobutyric acid was investigated by quantitative autoradiography in normal rabbits and rabbits with acute liver failure induced by the selective hepatotoxin galactosamine. The blood-to-brain transfer of alpha-aminoisobutyric acid was similar in control animals and animals 2 and 7 h after galactosamine injections, but was increased five- to tenfold in certain gray-matter areas of the brain in animals 11 and 18 h after galactosamine treatment. No detectable differences in white-matter uptake of (/sup 14/C)alpha-aminoisobutyric acid were found between the control and treated groups. The increase in alpha-aminoisobutyric acid transfer within the gray-matter areas suggested that a general or nonspecific increase in brain capillary permeability occurred in these areas. No clinical signs of early hepatic encephalopathy were observed in the treated rabbits, except for 1 animal from the 18-h postgalactosamine group. Thus, enhanced blood-brain transfer of alpha-aminoisobutyric acid preceded the development of overt hepatic encephalopathy. The distribution of radioactivity after the intravenous administration of (/sup 14/C)galactosamine showed that virtually none of the hepatotoxin localized in the brain, suggesting that the drug itself does not have a direct effect upon the blood-brain barrier or the brain. The increased uptake of alpha-aminoisobutyric acid at 11 and 18 h implies that the transfer of other solutes would also be enhanced, that central nervous system homeostasis would be compromised, and that the resulting changes in brain fluid composition could contribute to or cause hepatic encephalopathy.

  13. Neuroprotection by gonadal steroid hormones in acute brain damage requires cooperation with astroglia and microglia.

    PubMed

    Johann, Sonja; Beyer, Cordian

    2013-09-01

    The neuroactive steroids 17β-estradiol and progesterone control a broad spectrum of neural functions. Besides their roles in the regulation of classical neuroendocrine loops, they strongly influence motor and cognitive systems, behavior, and modulate brain performance at almost every level. Such a statement is underpinned by the widespread and lifelong expression pattern of all types of classical and non-classical estrogen and progesterone receptors in the CNS. The life-sustaining power of neurosteroids for tattered or seriously damaged neurons aroused interest in the scientific community in the past years to study their ability for therapeutic use under neuropathological challenges. Documented by excellent studies either performed in vitro or in adequate animal models mimicking acute toxic or chronic neurodegenerative brain disorders, both hormones revealed a high potency to protect neurons from damage and saved neural systems from collapse. Unfortunately, neurons, astroglia, microglia, and oligodendrocytes are comparably target cells for both steroid hormones. This hampers the precise assignment and understanding of neuroprotective cellular mechanisms activated by both steroids. In this article, we strive for a better comprehension of the mutual reaction between these steroid hormones and the two major glial cell types involved in the maintenance of brain homeostasis, astroglia and microglia, during acute traumatic brain injuries such as stroke and hypoxia. In particular, we attempt to summarize steroid-activated cellular signaling pathways and molecular responses in these cells and their contribution to dampening neuroinflammation and neural destruction. This article is part of a Special Issue entitled 'CSR 2013'. PMID:23196064

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

    PubMed Central

    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. PMID:27199887

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

    PubMed

    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. PMID:20680706

  16. Parametric Trace Slicing

    NASA Technical Reports Server (NTRS)

    Rosu, Grigore (Inventor); Chen, Feng (Inventor); Chen, Guo-fang; Wu, Yamei; Meredith, Patrick O. (Inventor)

    2014-01-01

    A program trace is obtained and events of the program trace are traversed. For each event identified in traversing the program trace, a trace slice of which the identified event is a part is identified based on the parameter instance of the identified event. For each trace slice of which the identified event is a part, the identified event is added to an end of a record of the trace slice. These parametric trace slices can be used in a variety of different manners, such as for monitoring, mining, and predicting.

  17. Progesterone for Acute Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials

    PubMed Central

    Ma, Junpeng; Xu, Jianguo

    2015-01-01

    Objective To evaluate the efficacy and safety of progesterone administrated in patients with acute traumatic brain injury (TBI). Methods PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Clinicaltrials.gov, ISRCTN registry and WHO International Clinical Trials Registry Platform (ICTRP) were searched for randomized controlled trials (RCTs) comparing progesterone and placebo administrated in acute TBI patients. The primary outcome was mortality and the secondary outcomes were unfavorable outcomes and adverse events. A meta-analysis was conducted to evaluate the efficacy and safety of progesterone administrated in patients with acute TBI. Results A total of 6 studies met inclusion criteria, involving 2,476 patients. The risk of bias was considered to be low in 4 studies but high in the other 2 studies. The results of meta-analysis indicated progesterone did not reduce the mortality (RR = 0.83, 95% CI = 0.57–1.20) or unfavorable outcomes (RR = 0.89, 95% CI = 0.78–1.02) of acute TBI patients in comparison with placebo. Sensitivity analysis yielded consistent results. Progesterone was basically safe and well tolerated in TBI patients with the exception of increased risk of phlebitis or thrombophlebitis (RR = 3.03, 95% CI = 1.96–4.66). Conclusions Despite some modest bias, present evidence demonstrated that progesterone was well tolerated but did not reduce the mortality or unfavorable outcomes of adult patients with acute TBI. PMID:26473361

  18. Acute Methanol Poisoning: Prevalence and Predisposing Factors of Haemorrhagic and Non-Haemorrhagic Brain Lesions.

    PubMed

    Zakharov, Sergey; Kotikova, Katerina; Vaneckova, Manuela; Seidl, Zdenek; Nurieva, Olga; Navratil, Tomas; Caganova, Blazena; Pelclova, Daniela

    2016-08-01

    The purpose was to study the prevalence and predisposing factors of brain lesions in survivors of acute methanol poisoning. Clinical data on 106 patients with methanol poisoning were collected during the Czech mass poisoning outbreak. Of 83 survivors, in 46 (55%) patients, follow-up examinations including magnetic resonance imaging of brain (MR) were performed 3-8 and 24-28 months after discharge from the hospital. Of 46 patients with a median age of 49 (interquartile range, 35-57) years, 24 (52%) patients had a total of 40 abnormal brain findings with haemorrhagic lesions detected in 15 (33%) and non-haemorrhagic lesions found in 9 (19%) patients. The patients with haemorrhagic brain lesions were more acidemic (lower arterial blood pH, higher base deficit) and had higher glycaemia and lactacidaemia on admission than those without haemorrhages (all p < 0.05). Thirteen of 32 (41%) of patients with systemic anticoagulation and 2 of 14 (14%) of patients without it had haemorrhagic lesions (p = 0.080). Bleeding complications during the treatment occurred in 4 of 15 (27%) patients, and 5 of 15 (33%) patients had conditions predisposing to haemorrhage in the group with haemorrhagic lesions. In three cases with a series of computer tomography (CT)/MR performed during hospitalization, the necrotic lesions in the brain remained non-haemorrhagic during hospitalization and haemorrhagic lesions were detected on the follow-up MR examinations only. No association between brain haemorrhages and systemic anticoagulation during dialysis was found: brain haemorrhages might occur in severely poisoned patients treated without systemic anticoagulation, whereas treatment with high doses of heparin might not lead to brain haemorrhages. PMID:26806851

  19. 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.

    PubMed

    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. PMID:27543338

  20. Detrimental role of pericyte Nox4 in the acute phase of brain ischemia.

    PubMed

    Nishimura, Ataru; Ago, Tetsuro; Kuroda, Junya; Arimura, Koichi; Tachibana, Masaki; Nakamura, Kuniyuki; Wakisaka, Yoshinobu; Sadoshima, Junichi; Iihara, Koji; Kitazono, Takanari

    2016-06-01

    Pericytes are mural cells abundantly present in cerebral microvessels and play important roles, including the formation and maintenance of the blood-brain barrier. Nox4 is a major source of reactive oxygen species in cardiovascular cells and modulate cellular functions, particularly under pathological conditions. In the present study, we found that the expression of Nox4 was markedly induced in microvascular cells, including pericytes, in peri-infarct areas after middle cerebral artery occlusion stroke models in mice. The upregulation of Nox4 was greater in a permanent middle cerebral artery occlusion model compared with an ischemia/reperfusion transient middle cerebral artery occlusion model. We performed permanent middle cerebral artery occlusion on mice with Nox4 overexpression in pericytes (Tg-Nox4). Infarct volume was significantly greater with enhanced reactive oxygen species production and blood-brain barrier breakdown in peri-infarct areas in Tg-Nox4, compared with littermate controls. In cultured brain pericytes, Nox4 was significantly upregulated by hypoxia and was promptly downregulated by reoxygenation. Phosphorylation of NFκB and production of matrix metalloproteinase 9 were significantly increased in both cultured pericytes overexpressing Nox4 and in peri-infarct areas in Tg-Nox4. Collectively, Nox4 is upregulated in pericytes in peri-infarct areas after acute brain ischemia and may enhance blood-brain barrier breakdown through activation of NFκB and matrix metalloproteinase 9, thereby causing enlargement of infarct volume. PMID:26661159

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

    PubMed Central

    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

  2. Automated Factor Slice Sampling.

    PubMed

    Tibbits, Matthew M; Groendyke, Chris; Haran, Murali; Liechty, John C

    2014-01-01

    Markov chain Monte Carlo (MCMC) algorithms offer a very general approach for sampling from arbitrary distributions. However, designing and tuning MCMC algorithms for each new distribution, can be challenging and time consuming. It is particularly difficult to create an efficient sampler when there is strong dependence among the variables in a multivariate distribution. We describe a two-pronged approach for constructing efficient, automated MCMC algorithms: (1) we propose the "factor slice sampler", a generalization of the univariate slice sampler where we treat the selection of a coordinate basis (factors) as an additional tuning parameter, and (2) we develop an approach for automatically selecting tuning parameters in order to construct an efficient factor slice sampler. In addition to automating the factor slice sampler, our tuning approach also applies to the standard univariate slice samplers. We demonstrate the efficiency and general applicability of our automated MCMC algorithm with a number of illustrative examples. PMID:24955002

  3. Automated Factor Slice Sampling

    PubMed Central

    Tibbits, Matthew M.; Groendyke, Chris; Haran, Murali; Liechty, John C.

    2013-01-01

    Markov chain Monte Carlo (MCMC) algorithms offer a very general approach for sampling from arbitrary distributions. However, designing and tuning MCMC algorithms for each new distribution, can be challenging and time consuming. It is particularly difficult to create an efficient sampler when there is strong dependence among the variables in a multivariate distribution. We describe a two-pronged approach for constructing efficient, automated MCMC algorithms: (1) we propose the “factor slice sampler”, a generalization of the univariate slice sampler where we treat the selection of a coordinate basis (factors) as an additional tuning parameter, and (2) we develop an approach for automatically selecting tuning parameters in order to construct an efficient factor slice sampler. In addition to automating the factor slice sampler, our tuning approach also applies to the standard univariate slice samplers. We demonstrate the efficiency and general applicability of our automated MCMC algorithm with a number of illustrative examples. PMID:24955002

  4. Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic Stroke

    PubMed Central

    Lakhan, Shaheen E.; Kirchgessner, Annette; Tepper, Deborah; Leonard, Aidan

    2013-01-01

    Ischemic stroke continues to be one of the most challenging diseases in translational neurology. Tissue 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 tPA-associated hemorrhagic complications. Reactive oxygen species can enhance the effects of tPA on MMP activation through the loss of caveolin-1 (cav-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. PMID:23565108

  5. Whole-Brain Computed Tomographic Perfusion Imaging in Acute Cerebral Venous Sinus Thrombosis

    PubMed Central

    Mokin, Maxim; Ciambella, Chelsey C.; Masud, Muhammad W.; Levy, Elad I.; Snyder, Kenneth V.; Siddiqui, Adnan H.

    2016-01-01

    Background Acute cerebral venous sinus thrombosis (VST) can be difficult to diagnose because of its diverse clinical presentation. The utility of perfusion imaging for diagnosing VST is not well understood. Summary We retrospectively reviewed cases of acute VST in patients who underwent whole-brain (320-detector-row) computed tomographic (CT) perfusion imaging in combination with craniocervical CT venography. Perfusion maps that were analyzed included cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time, and time to peak. Among the 10 patients with acute VST included in this study, 9 had perfusion abnormalities. All perfusion abnormalities were localized in areas adjacent to the occluded sinus and did not match typical anterior or posterior circulation arterial territories. Bilateral perfusion deficits were seen in 4 cases. In 2 cases, parenchymal hemorrhage was diagnosed on noncontrast CT imaging; in those cases, focal CBV and CBF were reduced. Key Messages Whole-brain CT perfusion imaging with 320-detector-row scanners can further assist in establishing the diagnosis of VST by detecting perfusion abnormalities corresponding to venous and not arterial territories. CT perfusion could assist in the differentiation between focal reversible changes, such as those caused by vasogenic edema, and irreversible changes due to infarction. PMID:27051406

  6. Ultrafast multi-slice spatiotemporally encoded MRI with slice-selective dimension segmented.

    PubMed

    Zhang, Ting; Chen, Lin; Huang, Jianpan; Li, Jing; Cai, Shuhui; Cai, Congbo; Chen, Zhong

    2016-08-01

    As a recently emerging method, spatiotemporally encoded (SPEN) magnetic resonance imaging (MRI) has a high robustness to field inhomogeneity and chemical shift effect. It has been broadened from single-slice scanning to multi-slice scanning. In this paper, a novel multi-slice SPEN MRI method was proposed. In this method, the slice-selective dimension was segmented to lower the specific absorption rate (SAR) and improve the image quality. This segmented method, dubbed SeSPEN method, was theoretically analyzed and demonstrated with phantom, lemon and in vivo rat brain experiments. The experimental results were compared with the results obtained from the spin-echo EPI, spin-echo SPEN method and multi-slice global SPEN method proposed by Frydman and coauthors (abbr. GlSPEN method). All the SPEN images were super-resolved reconstructed using deconvolution method. The results indicate that the SeSPEN method retains the advantage of SPEN MRI with respect to resistance to field inhomogeneity and can provide better signal-to-noise ratio than multi-slice GlSPEN MRI technique. The SeSPEN method has comparable SAR to the GlSPEN method while the T1 signal attenuation effect is alleviated. The proposed method will facilitate the multi-slice SPEN MRI to scan more slices within one scan with better image quality. PMID:27301072

  7. Ultrafast multi-slice spatiotemporally encoded MRI with slice-selective dimension segmented

    NASA Astrophysics Data System (ADS)

    Zhang, Ting; Chen, Lin; Huang, Jianpan; Li, Jing; Cai, Shuhui; Cai, Congbo; Chen, Zhong

    2016-08-01

    As a recently emerging method, spatiotemporally encoded (SPEN) magnetic resonance imaging (MRI) has a high robustness to field inhomogeneity and chemical shift effect. It has been broadened from single-slice scanning to multi-slice scanning. In this paper, a novel multi-slice SPEN MRI method was proposed. In this method, the slice-selective dimension was segmented to lower the specific absorption rate (SAR) and improve the image quality. This segmented method, dubbed SeSPEN method, was theoretically analyzed and demonstrated with phantom, lemon and in vivo rat brain experiments. The experimental results were compared with the results obtained from the spin-echo EPI, spin-echo SPEN method and multi-slice global SPEN method proposed by Frydman and coauthors (abbr. GlSPEN method). All the SPEN images were super-resolved reconstructed using deconvolution method. The results indicate that the SeSPEN method retains the advantage of SPEN MRI with respect to resistance to field inhomogeneity and can provide better signal-to-noise ratio than multi-slice GlSPEN MRI technique. The SeSPEN method has comparable SAR to the GlSPEN method while the T1 signal attenuation effect is alleviated. The proposed method will facilitate the multi-slice SPEN MRI to scan more slices within one scan with better image quality.

  8. Intraoperative Targeted Temperature Management in Acute Brain and Spinal Cord Injury.

    PubMed

    Kraft, Jacqueline; Karpenko, Anna; Rincon, Fred

    2016-02-01

    Acute brain and spinal cord injuries affect hundreds of thousands of people worldwide. Though advances in pre-hospital and emergency and neurocritical care have improved the survival of some to these devastating diseases, very few clinical trials of potential neuro-protective strategies have produced promising results. Medical therapies such as targeted temperature management (TTM) have been trialed in traumatic brain injury (TBI), spinal cord injury (SCI), acute ischemic stroke (AIS), subarachnoid hemorrhage (SAH), and intracranial hemorrhage (ICH), but in no study has a meaningful effect on outcome been demonstrated. To this end, patient selection for potential neuro-protective therapies such as TTM may be the most important factor to effectively demonstrate efficacy in clinical trials. The use of TTM as a strategy to treat and prevent secondary neuronal damage in the intraoperative setting is an area of ongoing investigation. In this review we will discuss recent and ongoing studies that address the role of TTM in combination with surgical approaches for different types of brain injury. PMID:26759319

  9. Diffuse leukoencephalopathy and brain edema: unusual presentations of CNS relapse of acute myeloid leukemia.

    PubMed

    Schumann, Michael; Kiewe, Philipp; Hartlieb, Sissel; Neumann, Martin; Schilling, Andreas; Koch, Hans-Christian; Thiel, Eckhard; Korfel, Agnieszka

    2010-04-01

    An isolated CNS relapse is rarely seen in acute myeloid leukemia. However, it has a potentially fatal clinical outcome. We herein present the case of a 39-year-old man, who presented to our emergency room with horizontal diplopic images, vertigo, bilateral deafness, and progressing somnolence. Cerebral imaging revealed cerebral and cerebellar edema and a diffuse leukoencephalopathy. With the one-year-old history of an initially successfully treated FAB-M0 acute myeloid leukemia (AML) in mind, a lumbar puncture was carried out that showed a vast number of myeloid blasts in the morphologic analysis of the cerebrospinal fluid. In conjunction with normal findings in the peripheral blood-count with differential and the bone marrow examination a diagnosis of an isolated CNS relapse of the AML was made. Cytarabine chemotherapy was initiated and the symptoms resolved rapidly. To our surprise, cerebral imaging in the course of the treatment not only showed a resolution of the brain edema but also of the leukoencephalopathy, pointing to a direct infiltration of brain parenchyma by leukemic blasts. The case highlights the relevance of the CNS as a pharmacologic "sanctuary" for tumor cells in patients that on prior treatments have not received intrathecal chemotherapy or chemotherapeutics that cross the blood-brain barrier. PMID:18826442

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

    PubMed Central

    Ashok, Iyaswamy; Sheeladevi, Rathinasamy; Wankhar, Dapkupar

    2015-01-01

    Abstract 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. PMID:26445572

  11. [Asystolias in the acute phase of brain stroke. Report of a case].

    PubMed

    Belvis, R; Marti-Fàbregas, J; Franquet, E; Cocho, D; Valencia, C; Martí-Vilalta, J L

    2003-04-01

    Brain areas involved in heart autonomic control are not well characterized. Insulae have been proposed as control centers. A lesion in these areas may induce a cardiac autonomic dysfunction (arrhythmias, atrioventricular conduction abnormalities). Asystolia has not been previously reported. A 65-year-old man suffered an acute ischemia of the right middle cerebral artery (MCA) territory. NIHSS score was 19 points. Brain CT scan was normal. Transcranial Doppler (TCD) showed occlusion of the right MCA. Fibrinolysis was initiated 135 minutes after stroke onset with TCD monitoring. Twenty minutes later he suffered cardiac arrest with asystolia trace in the ECG monitor. Fibrinolysis was stopped during resuscitation. Four minutes later, he recovered with the same NIHSS score. Aggressive resuscitation maneuvers were not necessary. A repeated brain CT scan showed infarct signs in the whole MCA territory and a new TCD did not show any change. Serial blood analyses including cardiac nzymes were normal. The patient experienced four brief cardiac arrests in the next nine hours, so a temporary cardiac pacemaker was placed for four days. He was treated with aspirin and was discharged 14 days after admission. He has not experienced recurrences during a 6-month follow-up. We could not diagnose the etiology of the cardiac arrests. All the episodes occurred in the acute stroke stage and arrhythmia, atrioventricular block, myocardial ischemia or structural lesions were not found in the cardiac study. We propose that ischemia in the right insula induced sudden and transitory interruptions of the sympathetic cardiac tone. PMID:12677486

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

    PubMed

    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. PMID:26445572

  13. Acute lithium administration selectively lowers tyrosine levels in serum and brain

    PubMed Central

    McFarlane, Hewlet G.; Steele, John; Vinion, Keenan; Bongiovanni, Rodolfo; Double, Manda; Jaskiw, George E.

    2016-01-01

    Lithium exerts anti-dopaminergic behavioral effects. We examined whether some of these might be mediated by changes in brain levels of tyrosine (TYR), the precursor to dopamine. Lithium chloride (LiCl2) 3.0 mEq/kg IP acutely lowered serum TYR and the ratio of serum TYR to other large neutral amino acids (LNAAs); it also selectively lowered striatum TYR levels as measured in tissue or in vivo. While LiCl2 3.0 mEq/kg IP also augmented haloperidol (0.19 mg/kg SC)-induced catalepsy, this lithium effect was not attenuated by administration of TYR 100 mg/kg IP. We conclude that lithium acutely and selectively lowers brain TYR by lowering serum levels of tyrosine relative to the LNAAs that compete with it for transport across the blood–brain barrier. However, the lowering of TYR does not appear to significantly contribute to the ability of lithium to potentiate haloperidol-mediated catalepsy. PMID:21962398

  14. Acute decrease in alkaline phosphatase after brain injury: A potential mechanism for tauopathy.

    PubMed

    Arun, Peethambaran; Oguntayo, Samuel; Albert, Stephen Van; Gist, Irene; Wang, Ying; Nambiar, Madhusoodana P; Long, Joseph B

    2015-11-16

    Dephosphorylation of phosphorylated Tau (pTau) protein, which is essential for the preservation of neuronal microtubule assemblies and for protection against trauma-induced tauopathy and chronic traumatic encephalopathy (CTE), is primarily achieved in brain by tissue non-specific alkaline phosphatase (TNAP). Paired helical filaments (PHFs) and Tau isolated from Alzheimer's disease (AD) patients' brains have been shown to form microtubule assemblies with tubulin only after treatment with TNAP or protein phosphatase-2A, 2B and -1, suggesting that Tau protein in the PHFs of neurons in AD brain is hyperphosphorylated, which prevents microtubule assembly. Using blast or weight drop models of traumatic brain injury (TBI) in rats, we observed pTau accumulation in the brain as early as 6h post-injury and further accumulation which varied regionally by 24h post-injury. The pTau accumulation was accompanied by reduced TNAP expression and activity in these brain regions and a significantly decreased plasma total alkaline phosphatase activity after the weight drop. These results reveal that both blast- and impact acceleration-induced head injuries cause an acute decrease in the level/activity of TNAP in the brain, which potentially contributes to trauma-induced accumulation of pTau and the resultant tauopathy. The regional changes in the level/activity of TNAP or accumulation of pTau after these injuries did not correlate with the accumulation of amyloid precursor protein, suggesting that the basic mechanism underlying tauopathy in TBI might be distinct from that associated with AD. PMID:26483321

  15. Regulation of brain water during acute glucose-induced hyperosmolality in ovine fetuses, lambs, and adults.

    PubMed

    Stonestreet, Barbara S; Petersson, Katherine H; Sadowska, Grazyna B; Patlak, Clifford S

    2004-02-01

    We tested the hypothesis that, during acute glucose-induced hyperosmolality, the brain shrinks less than predicted on the basis of an ideal osmometer and that brain volume regulation is present in fetuses, premature and newborn lambs. Brain water responses to glucose-induced hyperosmolality were measured in the cerebral cortex, cerebellum, and medulla of fetuses at 60% of gestation, premature ventilated lambs at 90% of gestation, newborn lambs, and adult sheep. After exposure of the sheep to increases in osmolality with glucose plus NaCl, brain water and electrolytes were measured. The ideal osmometer is a system in which impermeable solutes do not enter or leave in response to an osmotic stress. In the absence of volume regulation, brain solute remains constant as osmolality changes. The osmotically active solute demonstrated direct linear correlations with plasma osmolality in the cerebral cortex of the fetuses at 60% of gestation (r = 0.72, n = 24, P = 0.0001), premature lambs (r = 0.58, n = 22, P = 0.005), newborn lambs (r = 0.57, n = 24, P = 0.004), and adult sheep (r = 0.70, n = 18, P = 0.001). Similar findings were observed in the cerebellum and medulla. Increases in the quantity of osmotically active solute over the range of plasma osmolalities indicate that volume regulation was present in the brain regions of the fetuses, premature lambs, newborn lambs, and adult sheep during glucose-induced hyperosmolality. We conclude that, during glucose-induced hyperosmolality, the brain shrinks less than predicted on the basis of an ideal osmometer and exhibits volume regulation in fetuses at 60% of gestation, premature lambs, newborn lambs, and adult sheep. PMID:14578364

  16. Effect of acute and recurrent hypoglycemia on changes in brain glycogen concentration.

    PubMed

    Herzog, Raimund I; Chan, Owen; Yu, Sunkyung; Dziura, James; McNay, Ewan C; Sherwin, Robert S

    2008-04-01

    Our objective was to evaluate whether excessive brain glycogen deposition might follow episodes of acute hypoglycemia (AH) and thus play a role in the hypoglycemia-associated autonomic failure seen in diabetic patients receiving intensive insulin treatment. We determined brain glucose and glycogen recovery kinetics after AH and recurrent hypoglycemia (RH), an established animal model of counterregulatory failure. A single bout of insulin-induced AH or RH for 3 consecutive days was used to deplete brain glucose and glycogen stores in rats. After microwave fixation and glycogen extraction, regional recovery kinetics in the brain was determined using a biochemical assay. Both AH and RH treatments reduced glycogen levels in the cerebellum, cortex, and hypothalamus from control levels of 7.78 +/- 0.55, 5.4 +/- 0.38, and 4.45 +/- 0.37 micromol/g, respectively, to approximately 50% corresponding to a net glycogen utilization rate between 0.6 and 1.2 micromol/g.h. After hypoglycemia, glycogen levels returned to baseline within 6 h in both the AH and the RH group. However, recovery of brain glycogen tended to be faster in rats exposed to RH. This effect followed more rapid recovery of brain glucose levels in the RH group, despite similar blood glucose levels in both groups. There was no statistically significant increase above baseline glycogen levels in either group. In particular, brain glycogen was not increased 24 h after the last of recurrent episodes of hypoglycemia, when a significant counterregulatory defect could be documented during a hyperinsulinemic hypoglycemic clamp study. We conclude that glycogen supercompensation is not a major contributory factor to the pathogenesis of hypoglycemia-associated autonomic failure. PMID:18187548

  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?

    SciTech Connect

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

    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

  18. Sleep in the Acute Phase of Severe Traumatic Brain Injury: A Snapshot of Polysomnography.

    PubMed

    Wiseman-Hakes, Catherine; Duclos, Catherine; Blais, Hélène; Dumont, Marie; Bernard, Francis; Desautels, Alex; Menon, David K; Gilbert, Danielle; Carrier, Julie; Gosselin, Nadia

    2016-09-01

    Background and Objectives The onset of pervasive sleep-wake disturbances associated with traumatic brain injury (TBI) is poorly understood. This study aimed to (a) determine the feasibility of using polysomnography in patients in the acute, hospitalized stage of severe TBI and (b) explore sleep quality and sleep architecture during this stage of recovery, compared to patients with other traumatic injuries. Methods A cross-sectional case-control design was used. We examined the sleep of 7 patients with severe TBI (17-47 years; 20.3 ± 15.0 days postinjury) and 6 patients with orthopedic and/or spinal cord injuries (OSCI; 19-58 years; 16.9 ± 4.9 days postinjury). One night of ambulatory polysomnography was performed at bedside. Results Compared to OSCI patients, TBI patients showed a significantly longer duration of nocturnal sleep and earlier nighttime sleep onset. Sleep efficiency was low and comparable in both groups. All sleep stages were observed in both groups with normal proportions according to age. Conclusion Patients in the acute stage of severe TBI exhibit increased sleep duration and earlier sleep onset, suggesting that the injured brain enhances sleep need and/or decreases the ability to maintain wakefulness. As poor sleep efficiency could compromise brain recovery, further studies should investigate whether strategies known to optimize sleep in healthy individuals are efficacious in acute TBI. While there are several inherent challenges, polysomnography is a useful means of examining sleep in the early stage of recovery in patients with severe TBI. PMID:26704256

  19. Corticosteroids in acute traumatic brain injury: systematic review of randomised controlled trials.

    PubMed Central

    Alderson, P.; Roberts, I.

    1997-01-01

    OBJECTIVE: To quantify the effectiveness and safety of corticosteroids in the treatment of acute traumatic brain injury. DESIGN: Systematic review of randomised controlled trials of corticosteroids in acute traumatic brain injury. Summary odds ratios were estimated as an inverse variance weighted average of the odds ratios for each study. SETTING: Randomised trials available by March 1996. SUBJECTS: The included trials with outcome data comprised 2073 randomised participants. RESULTS: The effect of corticosteroids on the risk of death was reported in 13 included trials. The pooled odds ratio for the 13 trials was 0.91 (95% confidence interval 0.74 to 1.12). Pooled absolute risk reduction was 1.8% (-2.5% to 5.7%). For the 10 trials that reported death or disability the pooled odds ratio was 0.90 (0.72 to 1.11). For infections of any type the pooled odds ratio was 0.92 (0.69 to 1.23) and for the seven trials reporting gastrointestinal bleeding it was 1.05 (0.44 to 2.52). With only those trials with the best quality of concealment of allocation, the pooled odds ratio estimates for death and death or disability became closer to unity. CONCLUSIONS: This systematic review of randomised controlled trials of corticosteroids in acute traumatic brain injury shows that there remains considerable uncertainty over their effects. Neither moderate benefits nor moderate harmful effects can be excluded. The widely practicable nature of the drugs and the importance of the health problem suggest that large simple trials are feasible and worth while to establish whether there are any benefits from use of corticosteroids in this setting. PMID:9224126

  20. Acute astrocyte activation in brain detected by MRI: new insights into T(1) hypointensity.

    PubMed

    Sibson, Nicola R; Lowe, John P; Blamire, Andrew M; Martin, Matthew J; Obrenovitch, Tiho P; Anthony, Daniel C

    2008-03-01

    Increases in the T(1) of brain tissue, which give rise to dark or hypointense areas on T(1)-weighted images using magnetic resonance imaging (MRI), are common to a number of neuropathologies including multiple sclerosis (MS) and ischaemia. However, the biologic significance of T(1) increases remains unclear. Using a multiparametric MRI approach and well-defined experimental models, we have experimentally induced increases in tissue T(1) to determine the underlying cellular basis of such changes. We have shown that a rapid acute increase in T(1) relaxation in the brain occurs in experimental models of both low-flow ischaemia induced by intrastriatal injection of endothelin-1 (ET-1), and excitotoxicity induced by intrastriatal injection of N-methyl-D-aspartate (NMDA). However, there appears to be no consistent correlation between increases in T(1) relaxation and changes in other MRI parameters (apparent diffusion coefficient, T(2) relaxation, or magnetisation transfer ratio of tissue water). Immunohistochemically, one common morphologic feature shared by the ET-1 and NMDA models is acute astrocyte activation, which was detectable within 2 h of intracerebral ET-1 injection. Pretreatment with an inhibitor of astrocyte activation, arundic acid, significantly reduced the spatial extent of the T(1) signal change induced by intrastriatal ET-1 injection. These findings suggest that an increase in T(1) relaxation may identify the acute development of reactive astrocytes within a central nervous system lesion. Early changes in T(1) may, therefore, provide insight into acute and reversible injury processes in neurologic patients, such as those observed before contrast enhancement in MS. PMID:17851455

  1. Accelerated recovery from acute brain injuries: clinical efficacy of neurotrophic treatment in stroke and traumatic brain injuries.

    PubMed

    Bornstein, N; Poon, W S

    2012-04-01

    Stroke is one of the most devastating vascular diseases in the world as it is responsible for almost five million deaths per year. Almost 90% of all strokes are ischemic and mainly due to atherosclerosis, cardiac embolism and small-vessel disease. Intracerebral or subarachnoid hemorrhage can lead to hemorrhagic stroke, which usually has the poorest prognosis. Cerebrolysin is a peptide preparation which mimics the action of a neurotrophic factor, protecting stroke-injured neurons and promoting neuroplasticity and neurogenesis. Cerebrolysin has been widely studied as a therapeutic tool for both ischemic and hemorrhagic stroke, as well as traumatic brain injury. In ischemic stroke, Cerebrolysin given as an adjuvant therapy to antiplatelet and rheologically active medication resulted in accelerated improvement in global, neurological and motor functions, cognitive performance and activities of daily living. Cerebrolysin was also safe and well tolerated when administered in patients suffering from hemorrhagic stroke. Traumatic brain injury leads to transient or chronic impairments in physical, cognitive, emotional and behavioral functions. This is associated with deficits in the recognition of basic emotions, the capacity to interpret the mental states of others, and executive functioning. Pilot clinical studies with adjuvant Cerebrolysin in the acute and postacute phases of the injury have shown faster recovery, which translates into an earlier onset of rehabilitation and shortened hospitalization time. PMID:22514794

  2. The association of the kynurenine pathway of tryptophan metabolism with acute brain dysfunction during critical illness*

    PubMed Central

    Adams Wilson, Jessica R.; Morandi, Alessandro; Girard, Timothy D.; Thompson, Jennifer L.; Boomershine, Chad S.; Shintani, Ayumi K.; Ely, E. Wesley; Pandharipande, Pratik P.

    2013-01-01

    Objectives Plasma tryptophan levels are associated with delirium in critically ill patients. Although tryptophan has been linked to the pathogenesis of other neurocognitive diseases through metabolism to neurotoxins via the kynurenine pathway, a role for kynurenine pathway activity in intensive care unit brain dysfunction (delirium and coma) remains unknown. This study examined the association between kynurenine pathway activity as determined by plasma kynurenine concentrations and kynurenine/tryptophan ratios and presence or absence of acute brain dysfunction (defined as delirium/coma-free days) in intensive care unit patients. Design, Setting, and Patients This was a prospective cohort study that utilized patient data and blood samples from the Maximizing Efficacy of Targeted Sedation and Reducing Neurologic Dysfunction trial, which compared sedation with dexmedetomidine vs. lorazepam in mechanically ventilated patients. Measurements and Main Results Baseline plasma kynurenine and tryptophan concentrations were measured using high-performance liquid chromatography with or without tandem mass spectrometry. Delirium was assessed daily using the Confusion Assessment Method for the Intensive Care Unit. Linear regression examined associations between kynurenine pathway activity and delirium/coma-free days after adjusting for sedative exposure, age, and severity of illness. Among 84 patients studied, median age was 60 yrs and Acute Physiology and Chronic Health Evaluation II score was 28.5. Elevated plasma kynurenine and kynurenine/tryptophan ratio were both independently associated with significantly fewer delirium/coma-free days (i.e., fewer days without acute brain dysfunction). Specifically, patients with plasma kynurenine or kynurenine/tryptophan ratios at the 75th percentile of our population had an average of 1.8 (95% confidence interval 0.6–3.1) and 2.1 (95% confidence interval 1.0–3.2) fewer delirium/coma-free days than those patients with values at the 25

  3. Nanowire-Based Electrode for Acute In Vivo Neural Recordings in the Brain

    PubMed Central

    Suyatin, Dmitry B.; Wallman, Lars; Thelin, Jonas; Prinz, Christelle N.; Jörntell, Henrik; Samuelson, Lars; Montelius, Lars; Schouenborg, Jens

    2013-01-01

    We present an electrode, based on structurally controlled nanowires, as a first step towards developing a useful nanostructured device for neurophysiological measurements in vivo. The sensing part of the electrode is made of a metal film deposited on top of an array of epitaxially grown gallium phosphide nanowires. We achieved the first functional testing of the nanowire-based electrode by performing acute in vivo recordings in the rat cerebral cortex and withstanding multiple brain implantations. Due to the controllable geometry of the nanowires, this type of electrode can be used as a model system for further analysis of the functional properties of nanostructured neuronal interfaces in vivo. PMID:23431387

  4. Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition.

    PubMed

    Ogasawara, Daisuke; Deng, Hui; Viader, Andreu; Baggelaar, Marc P; Breman, Arjen; den Dulk, Hans; van den Nieuwendijk, Adriann M C H; Soethoudt, Marjolein; van der Wel, Tom; Zhou, Juan; Overkleeft, Herman S; Sanchez-Alavez, Manuel; Mo, Simone; Nguyen, William; Conti, Bruno; Liu, Xiaojie; Chen, Yao; Liu, Qing-Song; Cravatt, Benjamin F; van der Stelt, Mario

    2016-01-01

    Diacylglycerol lipases (DAGLα and DAGLβ) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo. Here, we report a set of centrally active DAGL inhibitors and a structurally related control probe and their use, in combination with chemical proteomics and lipidomics, to determine the impact of acute DAGL blockade on brain lipid networks in mice. Within 2 h, DAGL inhibition produced a striking reorganization of bioactive lipids, including elevations in DAGs and reductions in endocannabinoids and eicosanoids. We also found that DAGLα is a short half-life protein, and the inactivation of DAGLs disrupts cannabinoid receptor-dependent synaptic plasticity and impairs neuroinflammatory responses, including lipopolysaccharide-induced anapyrexia. These findings illuminate the highly interconnected and dynamic nature of lipid signaling pathways in the brain and the central role that DAGL enzymes play in regulating this network. PMID:26668358

  5. Nanobodies as modulators of inflammation: potential applications for acute brain injury

    PubMed Central

    Rissiek, Björn; Koch-Nolte, Friedrich; Magnus, Tim

    2014-01-01

    Nanobodies are single domain antibodies derived from llama heavy-chain only antibodies (HCAbs). They represent a new generation of biologicals with unique properties: nanobodies show excellent tissue distribution, high temperature and pH stability, are easy to produce recombinantly and can readily be converted into different formats such as Fc-fusion proteins or hetero-dimers. Moreover, nanobodies have the unique ability to bind molecular clefts, such as the active site of enzymes, thereby interfering with the function of the target protein. Over the last decade, numerous nanobodies have been developed against proteins involved in inflammation with the aim to modulate their immune functions. Here, we give an overview about recently developed nanobodies that target immunological pathways linked to neuroinflammation. Furthermore, we highlight strategies to modify nanobodies so that they can overcome the blood brain barrier and serve as highly specific therapeutics for acute inflammatory brain injury. PMID:25374510

  6. Impact of acute and chronic stress hormone on male albino rat brain

    PubMed Central

    Han, Li-Li; Chen, Ling; Dong, Zhi-Ling

    2015-01-01

    The present investigation aimed to evaluate the acute and chronic effect of stress (stress hormone) in male albino rat brain. Nor-epinephrine was used for the treatment and saline used for the control. Nor-epinephrine was dissolved in the saline and administered orally to the rats. Following nor-epinephrine administration, the brain was removed surgically at 6 h, 12 h and 45 days. Alanine tansaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) were significantly altered in the rats. Lipid peroxidation was measured as malondialdehyde (MDA), showed altered lipid peroxidation. Hematological markers such as packed cell volume (PCV), white blood cells (WBC), neutrophil, lymphocytes and hemoglobin were significantly altered compared to controls. Altered serum biochemical and hematological markers, lipid peroxidation and enzyme activities leads to adverse effect in the cellular metabolism and physiological activities of rats. PMID:26261571

  7. A creative alternative for providing constant observation on an acute-brain-injury unit.

    PubMed

    Bailey, Marci; Amato, Shelly; Mouhlas, Christopher

    2009-01-01

    A performance improvement project to explore creative alternatives to improve the efficiency of constant observation was performed on an acute-brain-injury rehabilitation unit. The goals of the project were to increase opportunities for therapeutic cognitive stimulation among patients, increase nursing satisfaction regarding efficient use of resources to deliver rehabilitative care, decrease constant-observation salary costs, and maintain fall and restraint rates within 10% of baseline. Implementing the project involved developing a new job description (rehabilitation patient companion) and creating a day room where patients receiving constant observation could go between therapies to receive therapeutic cognitive stimulation. The program benefited patients, staff and the hospital. This project illustrates how a creative alternative to constant observation proves beneficial on many levels and improves the delivery of rehabilitative care to patients with traumatic brain injury. PMID:19160919

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

    USGS Publications Warehouse

    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 pbrain. 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. GENE EXPRESSION CHANGES IN FEMALE ZEBRAFISH (DANIO RERIO) BRAIN IN RESPONSE TO ACUTE EXPOSURE TO METHYLMERCURY

    PubMed Central

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

    2010-01-01

    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 hr) MeHg exposure was investigated. Fish were exposed by injection to 0 or 0.5 μg MeHg/g. Gene expression changes in the brain were examined using a 22,000 feature zebrafish microarray. At a significance level of p<0.01, 79 genes 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 the 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 investigate responsive genes as potential biomarkers of MeHg exposure. PMID:21082716

  10. Amplitude of Low-Frequency Fluctuations in Multiple-Frequency Bands in Acute Mild Traumatic Brain Injury

    PubMed Central

    Zhan, Jie; Gao, Lei; Zhou, Fuqing; Bai, Lijun; Kuang, Hongmei; He, Laichang; Zeng, Xianjun; Gong, Honghan

    2016-01-01

    Functional disconnectivity during the resting state has been observed in mild traumatic brain injury (mTBI) patients during the acute stage. However, it remains largely unknown whether the abnormalities are related to specific frequency bands of the low-frequency oscillations (LFO). Here, we used the amplitude of low-frequency fluctuations (ALFF) to examine the amplitudes of LFO in different frequency bands (slow-5: 0.01–0.027 Hz; slow-4: 0.027–0.073 Hz; and typical: 0.01–0.08 Hz) in patients with acute mTBI. A total of 24 acute mTBI patients and 24 age-, sex-, and education-matched healthy controls participated in this study. In the typical band, acute mTBI patients showed lower standardized ALFF in the right middle frontal gyrus and higher standardized ALFF in the right lingual/fusiform gyrus and left middle occipital gyrus. Further analyses showed that the difference between groups was concentrated in a narrower (slow-4) frequency band. In the slow-5 band, mTBI patients only exhibited higher standardized ALFF in the occipital areas. No significant correlation between the mini-mental state examination score and the standardized ALFF value was found in any brain region in the three frequency bands. Finally, no significant interaction between frequency bands and groups was found in any brain region. We concluded that the abnormality of spontaneous brain activity in acute mTBI patients existed in the frontal lobe as well as in distributed brain regions associated with integrative, sensory, and emotional roles, and the abnormal spontaneous neuronal activity in different brain regions could be better detected by the slow-4 band. These findings might contribute to a better understanding of local neural psychopathology of acute mTBI. Future studies should take the frequency bands into account when measuring intrinsic brain activity of mTBI patients. PMID:26869907

  11. Slicing black hole spacetimes

    NASA Astrophysics Data System (ADS)

    Bini, Donato; Bittencourt, Eduardo; Geralico, Andrea; Jantzen, Robert T.

    2015-04-01

    A general framework is developed to investigate the properties of useful choices of stationary spacelike slicings of stationary spacetimes whose congruences of timelike orthogonal trajectories are interpreted as the world lines of an associated family of observers, the kinematical properties of which in turn may be used to geometrically characterize the original slicings. On the other hand, properties of the slicings themselves can directly characterize their utility motivated instead by other considerations like the initial value and evolution problems in the 3-plus-1 approach to general relativity. An attempt is made to categorize the various slicing conditions or "time gauges" used in the literature for the most familiar stationary spacetimes: black holes and their flat spacetime limit.

  12. Connectomic and Surface-Based Morphometric Correlates of Acute Mild Traumatic Brain Injury.

    PubMed

    Dall'Acqua, Patrizia; Johannes, Sönke; Mica, Ladislav; Simmen, Hans-Peter; Glaab, Richard; Fandino, Javier; Schwendinger, Markus; Meier, Christoph; Ulbrich, Erika J; Müller, Andreas; Jäncke, Lutz; Hänggi, Jürgen

    2016-01-01

    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 subnetwork

  13. Connectomic and Surface-Based Morphometric Correlates of Acute Mild Traumatic Brain Injury

    PubMed Central

    Dall'Acqua, Patrizia; Johannes, Sönke; Mica, Ladislav; Simmen, Hans-Peter; Glaab, Richard; Fandino, Javier; Schwendinger, Markus; Meier, Christoph; Ulbrich, Erika J.; Müller, Andreas; Jäncke, Lutz; Hänggi, Jürgen

    2016-01-01

    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 subnetwork

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Prognostic Value of Brain and Acute Leukemia Cytoplasmic Gene Expression in Egyptian Children with Acute Myeloid Leukemia

    PubMed Central

    Hagag, Adel A.; El-Lateef, Amal Ezzat Abd

    2015-01-01

    Background Acute myeloid leukemia (AML) accounts for 25%–35% of acute leukemia in children. BAALC gene (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 Egyptian children with newly diagnosed AML who were subjected to full history taking, clinical examination and laboratory investigations including: complete blood count, LDH, bone marrow aspiration, cytochemistry, immunophenotyping and assessment of BAALC Gene by real time PCR in bone marrow aspirate mononuclear cells before the start of chemotherapy. Results Positive BAALC gene expression was found in 24 cases (60%) and negative expression in 16 cases (40%). Positive BAALC gene expression group includes 14 males and 10 females with mean age at presentation of 8.35±2.63 while negative BAALC gene expression includes 10 males and 6 females with mean age at presentation of 7.74±3.23 with no statistically significant differences between patients with positive and negative BAALC gene expression regarding age, sex and clinical presentations at time of diagnosis including pallor, purpura, splenomegaly, hepatomegaly and lymphadenopathy and laboratory investigations including WBCs and platelets counts, hemoglobin and LDH levels, and peripheral blood and bone marrow blast cell counts. There was significant association between positive BAALC gene expression and M1 and M2 compared with negative BAALC gene expression which is significantly associated with M4. There were statistically significant differences in disease outcome between positive and negative BAALC gene expression groups with higher rate of relapse and death and lower rate of complete remission and disease free survival in positive BAALC gene expression group compared with negative BAALC gene expression group. (p

  16. Experimental carbon dioxide laser brain lesions and intracranial dynamics. Part 2. Effect on brain water content and its response to acute therapy

    SciTech Connect

    Tiznado, E.G.; James, H.E.; Moore, S.

    1985-04-01

    Experimental brain lesions were created over the left parietooccipital cortex of the albino rabbit through the intact dura mater with high radiating carbon dioxide laser energy. The brain water content was studied 2, 6, and 24 hours after the insult. Another two groups of animals received acute therapy with either dexamethasone (1 mg/kg) or furosemide (1 mg/kg). In all groups, Evans blue extravasation uniformly extended from the impact crater into the surrounding white matter. The brain water content in the gray matter was elevated from the control value by 2 hours after impact and remained elevated at 6 and 24 hours. The white matter brain water content did not increase until 6 hours after impact and remained elevated in the 24-hour group. After dexamethasone treatment, there was a significant decrease of water in the gray matter, but not in the white matter. With furosemide therapy, there was no reduction of gray or white matter brain water.

  17. Acute renal failure potentiates methylmalonate-induced oxidative stress in brain and kidney of rats.

    PubMed

    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. PMID:23297832

  18. Acute Minocycline Treatment Mitigates the Symptoms of Mild Blast-Induced Traumatic Brain Injury

    PubMed Central

    Kovesdi, Erzsebet; Kamnaksh, Alaa; Wingo, Daniel; Ahmed, Farid; Grunberg, Neil E.; Long, Joseph B.; Kasper, Christine E.; Agoston, Denes V.

    2012-01-01

    Mild traumatic brain injury (mTBI) represents a significant challenge for the civilian and military health care systems due to its high prevalence and overall complexity. Our earlier works showed evidence of neuroinflammation, a late onset of neurobehavioral changes, and lasting memory impairment in a rat model of mild blast-induced TBI (mbTBI). The aim of our present study was to determine whether acute treatment with the non-steroidal anti-inflammatory drug minocycline (Minocin®) can mitigate the neurobehavioral abnormalities associated with mbTBI, Furthermore, we aimed to assess the effects of the treatment on select inflammatory, vascular, neuronal, and glial markers in sera and in brain regions associated with anxiety and memory (amygdala, prefrontal cortex, ventral, and dorsal hippocampus) following the termination (51 days post-injury) of the experiment. Four hours after a single exposure to mild blast overpressure or sham conditions, we treated animals with a daily dose of minocycline (50 mg/kg) or physiological saline (vehicle) for four consecutive days. At 8 and 45 days post-injury, we tested animals for locomotion, anxiety, and spatial memory. Injured animals exhibited significantly impaired memory and increased anxiety especially at the later testing time point. Conversely, injured and minocycline treated rats’ performance was practically identical to control (sham) animals in the open field, elevated plus maze, and Barnes maze. Protein analyses of sera and brain regions showed significantly elevated levels of all of the measured biomarkers (except VEGF) in injured and untreated rats. Importantly, minocycline treatment normalized serum and tissue levels of the majority of the selected inflammatory, vascular, neuronal, and glial markers. In summary, acute minocycline treatment appears to prevent the development of neurobehavioral abnormalities likely through mitigating the molecular pathologies of the injury in an experimental model of mb

  19. Neuroprotective effects of bloodletting at Jing points combined with mild induced hypothermia in acute severe traumatic brain injury

    PubMed Central

    Tu, Yue; Miao, Xiao-mei; Yi, Tai-long; Chen, Xu-yi; Sun, Hong-tao; Cheng, Shi-xiang; Zhang, Sai

    2016-01-01

    Bloodletting at Jing 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 at Jing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe traumatic 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 inflammatory response were lessened. These findings suggest that the combined effects of bloodletting at Jing 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. PMID:27482221

  20. Microglial polarization and plasticity: evidence from organotypic hippocampal slice cultures.

    PubMed

    Ajmone-Cat, Maria Antonietta; Mancini, Melissa; De Simone, Roberta; Cilli, Piera; Minghetti, Luisa

    2013-10-01

    Increasing evidence indicates that "functional plasticity" is not solely a neuronal attribute but a hallmark of microglial cells, the main brain resident macrophage population. Far from being a univocal phenomenon, microglial activation can originate a plethora of functional phenotypes, encompassing the classic M1 proinflammatory and the alternative M2 anti-inflammatory phenotypes. This concept overturns the popular view of microglial activation as a synonym of neurotoxicity and neurogenesis failure in brain disorders. The characterization of the alternative programs is a matter of intense investigation, but still scarce information is available on the course of microglial activation, on the reversibility of the different commitments and on the capability of preserving molecular memory of previous priming stimuli. By using organotypic hippocampal slice cultures as a model, we developed paradigms of stimulation aimed at shedding light on some of these aspects. We show that persistent stimulation of TLR4 signaling promotes an anti-inflammatory response and microglial polarization toward M2-like phenotype. Moreover, acute and chronic preconditioning regimens permanently affect the capability to respond to a later challenge, suggesting the onset of mechanisms of molecular memory. Similar phenomena could occur in the intact brain and differently affect the vulnerability of mature and newborn neurons to noxious signals. PMID:23918452

  1. Mouse models of human PIK3CA-related brain overgrowth have acutely treatable epilepsy

    PubMed Central

    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

  2. Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke.

    PubMed

    Silva, Bruno; Sousa, Larissa; Miranda, Aline; Vasconcelos, Anilton; Reis, Helton; Barcelos, Lucíola; Arantes, Rosa; Teixeira, Antonio; Rachid, Milene Alvarenga

    2015-08-01

    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. PMID:26222355

  3. Ultrasonography in acute interstitial laser irradiation of the pig brain: preliminary results.

    PubMed

    Menovsky, T; Beek, J F; Phoa, S S; Brouwer, P A; Klein, M G; Verlaan, C W; van Acker, R E; van Gemert, M J

    1995-01-01

    In this preliminary study, the use of real-time ultrasonography to visualize the effects of acute interstitial Nd:YAG laser irradiation was investigated in the normal pig brain. In six pigs, a craniotomy was performed. In the frontal or temporal lobe, a thermal laser lesion was made using a 600-micron-diameter optical fiber at powers of 1 W, 2 W, and 4 W with exposure times of 5 min and 10 min. Ten to thirty minutes after laser irradiation, the pigs were sacrificed. Ultrasound imaging was performed before, during, and after laser irradiation. During laser irradiation, a clear hyperechogenic area was observed around the fiber tip. The onset of the changes and the extent of the lesion were dependent on the power and exposure time. Histologic examination showed thermal lesions consisting of coagulation necrosis and edema. The size of the lesions correlated well with size on ultrasound imaging. The maximal lesion dimension was 12 mm in diameter (4 W for 5 min). In conclusion, within the limitations of this experimental setup, it is feasible to visualize interstitial laser-induced lesions in the brain by ultrasonography. This method is safe and simple and may be helpful in future applications of interstitial thermotherapy in brain tissue. PMID:9079450

  4. Glycine metabolism in rat kidney cortex slices.

    PubMed

    Rowsell, E V; Al-Naama, M M; Rowsell, K V

    1982-04-15

    When rat kidney cortex slices were incubated with glycine or [1-14C]glycine, after correcting for metabolite changes with control slices, product formation and glycine utilization fitted the requirements of the equation: 2 Glycine leads to ammonia + CO2 + serine. Evidence is presented that degradation via glyoxylate, by oxidation or transamination, is unlikely to have any significant role in kidney glycine catabolism. It is concluded that glycine metabolism in rat kidney is largely via glycine cleavage closely coupled with serine formation. 1-C decarboxylation and urea formation with glycine in rat hepatocyte suspensions were somewhat greater than decarboxylation or ammonia formation in kidney slices, showing that in the rat, potentially, the liver is quantitatively the more important organ in glycine catabolism. There was no evidence of ammonia formation from glycine with rat brain cortex, heart, spleen or diaphragm and 1-C decarboxylation was very weak. PMID:6810880

  5. Serum neurogranin measurement as a biomarker of acute traumatic brain injury

    PubMed Central

    Yang, Jun; Korley, Frederick K.; Dai, Min; Everett, Allen D.

    2015-01-01

    Objectives Neurogranin (NRGN) is a small neuronal protein that plays an important role in synaptic signaling by regulating calmodulin (CaM) availability. In this study, we developed an ELISA to measure NRGN quantitatively in serum samples from a cohort of acute traumatic brain injury (TBI) patients and a non-TBI control cohort, and explored the potential value of NRGN as a circulating biomarker for TBI. Design and methods Recombinant His-NRGN protein was used to develop mouse monoclonal capture and rabbit polyclonal detection antibodies, and they were used to develop a sandwich ELISA. After validation, we used this ELISA to measure serum samples from a cohort of typical adult acute TBI patients (N = 76 TBI cases) and non-TBI control patients (N = 150 controls). Results The NRGN ELISA lower limit of detection was 0.055 ng/mL, lower limit of quantification was 0.2 ng/mL, and interassay CVs were ≤ 10.7%. The average recovery was 99.9% (range from 97.2–102%). Serum NRGN concentrations in TBI cases were significantly higher than in controls (median values were 0.18 ng/mL vs. 0.02 ng/mL, p < 0.0001), but did not discriminate TBI cases with intracranial hemorrhage (p = 0.09). Conclusions We have developed a highly sensitive and reproducible ELISA for measuring circulating NRGN in blood samples. Serum NRGN concentrations in acute TBI patients were significantly higher than in controls, indicating that NRGN could have utility as a circulating biomarker for acute TBI. This report provides evidence to support larger and controlled TBI clinical studies for NRGN validation and prediction of outcomes. PMID:26025774

  6. The Virtual Slice Setup

    PubMed Central

    Lytton, William W; Neymotin, Samuel A; Hines, Michael L

    2008-01-01

    In an effort to design a simulation environment that is more similar to that of neurophysiology, we introduce a virtual slice setup in the NEURON simulator. The virtual slice setup runs continuously and permits parameter changes including changes to synaptic weights and time course and to intrinsic cell properties. The virtual slice setup permits shocks to be applied at chosen locations and activity to be sampled intra- or extracellularly from chosen locations. By default, a summed population display is shown during a run to indicate the level of activity and no states are saved. Simulations can run for hours of model time, therefore it is not practical to save all of the state variables which in any case are primarily of interest at discrete times when experiments are being run: the simulation can be stopped momentarily at such times to save activity patterns. The virtual slice setup maintains an automated notebook showing shocks and parameter changes as well as user comments. We demonstrate how interaction with a continuously running simulation encourages experimental prototyping and can suggest additional dynamical features such as ligand wash-in and wash-out – alternatives to typical instantaneous parameter change. The virtual slice setup currently uses event-driven cells and runs at approximately 2 minutes/hour on a laptop. PMID:18452996

  7. Acute care in stroke: the importance of early intervention to achieve better brain protection.

    PubMed

    Díez-Tejedor, E; Fuentes, B

    2004-01-01

    It is known that 'time is brain', and only early therapies in acute stroke have been effective, like thrombolysis within the first 3 h, and useful neuroprotective drugs are searched for that probably would be effective only with their very early administration. General care (respiratory and cardiac care, fluid and metabolic management, especially blood glucose and blood pressure control, early treatment of hyperthermia, and prevention and treatment of neurological and systemic complications) in acute stroke patients is essential and must already start in the prehospital setting and continue at the patient's arrival to hospital in the emergency room and in the stroke unit. A review of published studies analyzing the influence of general care on stroke outcome and the personal experience from observational studies was performed. Glucose levels >8 mmol/l have been found to be predictive of a poor prognosis after correcting for age, stroke severity, and stroke subtype. Although a clinical trial of glucose-insulin-potassium infusions is ongoing, increased plasma glucose levels should be treated. Moreover, insulin therapy in critically ill patients, including stroke patients, is safe and determines lower mortality and complication rates. Both high and low blood pressure levels have been related to a poor prognosis in acute stroke, although the target levels have not been defined yet in clinical trials. The body temperature has been shown to have a negative effect on stroke outcome, and its control and early treatment of hyperthermia are important. Hypoxemia also worsens the stroke prognosis, and oxygen therapy in case of <92% O(2) saturation is recommended. Besides, blood pressure stabilization avoiding falls of the diastolic pressure and the lowering of glycemia and temperature have been related to a better prognosis in stroke units patients, and homeostasis maintenance is associated with a better outcome. General care has become an emergent and first-line brain

  8. Effects of chronic and acute stimulants on brain functional connectivity hubs.

    PubMed

    Konova, Anna B; Moeller, Scott J; Tomasi, Dardo; Goldstein, Rita Z

    2015-12-01

    The spatial distribution and strength of information processing 'hubs' are essential features of the brain׳s network topology, and may thus be particularly susceptible to neuropsychiatric disease. Despite growing evidence that drug addiction alters functioning and connectivity of discrete brain regions, little is known about whether chronic drug use is associated with abnormalities in this network-level organization, and if such abnormalities could be targeted for intervention. We used functional connectivity density (FCD) mapping to evaluate how chronic and acute stimulants affect brain hubs (i.e., regions with many short-range or long-range functional connections). Nineteen individuals with cocaine use disorders (CUD) and 15 healthy controls completed resting-state fMRI scans following a randomly assigned dose of methylphenidate (MPH; 20mg) or placebo. Short-range and long-range FCD maps were computed for each participant and medication condition. CUD participants had increased short-range and long-range FCD in the ventromedial prefrontal cortex, posterior cingulate/precuneus, and putamen/amygdala, which in areas of the default mode network correlated with years of use. Across participants, MPH decreased short-range FCD in the thalamus/putamen, and decreased long-range FCD in the supplementary motor area and postcentral gyrus. Increased density of short-range and long-range functional connections to default mode hubs in CUD suggests an overrepresentation of these resource-expensive hubs. While the effects of MPH on FCD were only partly overlapping with those of CUD, MPH-induced reduction in the density of short-range connections to the putamen/thalamus, a network of core relevance to habit formation and addiction, suggests that some FCD abnormalities could be targeted for intervention. PMID:25721787

  9. Changes in brain oxidative metabolism induced by inhibitory avoidance learning and acute administration of amitriptyline.

    PubMed

    González-Pardo, Héctor; Conejo, Nélida M; Arias, Jorge L; Monleón, Santiago; Vinader-Caerols, Concepción; Parra, Andrés

    2008-05-01

    The effects of antidepressant drugs on memory have been somewhat ignored, having been considered a mere side effect of these compounds. However, the memory impairment caused by several antidepressants could be considered to form part of their therapeutic effects. Amitriptyline is currently one of the most prescribed tricyclic antidepressants, and exerts marked anticholinergic and antihistaminergic effects. In this study, we evaluated the effects of inhibitory avoidance (IA) learning and acute administration of amitriptyline on brain oxidative metabolism. Brain oxidative metabolism was measured in several limbic regions using cytochrome oxidase (CO) quantitative histochemistry. Amitriptyline produced a clear impairment in the IA task. In animals exposed only to the apparatus, amitriptyline decreased CO activity in nine brain regions, without affecting the remaining regions. In animals that underwent the IA training phase, amitriptyline reduced CO activity in only three of these nine regions. In animals treated with saline, IA acquisition increased CO activity in the medial prefrontal cortex, the prelimbic cortex, and the medial mammillary body, and diminished it in the medial septum and the nucleus basalis of Meynert with respect to animals exposed only to the IA apparatus. In animals treated with amitriptyline, IA acquisition did not modify CO activity in any of these regions, but increased it in the anteromedial nucleus of the thalamus, the diagonal band of Broca, and the dentate gyrus. The results reveal a pattern of changes in brain oxidative metabolism induced by IA training in saline-treated animals that was clearly absent in animals submitted to the same behavioural training but treated with amitriptyline. PMID:18313125

  10. The sleep lipid oleamide may represent an endogenous anticonvulsant: an in vitro comparative study in the 4-aminopyridine rat brain-slice model.

    PubMed

    Dougalis, Antonios; Lees, George; Ganellin, C Robin

    2004-03-01

    cis-Oleamide (cOA) is a putative endocannabinoid, which modulates GABA(A) receptors, Na+ channels and gap-junctions (important targets for clinical and experimental anticonvulsants). Here we address the hypothesis that cOA possesses seizure limiting properties and might represent an endogenous anticonvulsant. Field potentials were recorded from the rat hippocampus and visual cortex. The effects of cOA, were compared to carbamazepine (CBZ), pentobarbital (PB) and carbenoxolone (CRX) on 4-Aminopyridine(4AP)-induced epileptiform discharges. CBZ (100 microM), PB (50 microM) and CRX (100 microM), but not cOA (64 microM), significantly attenuated the duration of the evoked epileptiform discharges in CA1. Interictal activity in CA3 was significantly depressed by CRX and cOA (irreversible by AM251), increased by CBZ and remained unaffected by PB. CBZ, PB and CRX abolished spontaneous ictal events and attenuated evoked ictal discharges in the visual cortex. cOA did not abolish spontaneous ictal events, but significantly (albeit weakly) reduced the duration of evoked ictal events. cOA and CRX, in contrast to CBZ or PB, caused a significant delay in the development of the evoked (tonic phase) epileptiform discharges. The weak effects of cOA seem independent of cannabinoid (CB1) receptors. Enzymatic cleavage and lack of specific antagonists for cOA confound simple interpretations of its actions in slices. Its high lipophilicity, imposing a permeability barrier, may also explain the lack of anticonvulsant activity. The effects of cOA may well be masked by release of the endogenous ligand upon ictal depolarisation as we demonstrate here for established endocannabinoids. cOA does not possess profound antiepileptic actions in our hands compared to CBZ, PB or CRX. PMID:14975678

  11. Acute Supramaximal Exercise Increases the Brain Oxygenation in Relation to Cognitive Workload.

    PubMed

    Bediz, Cem Seref; Oniz, Adile; Guducu, Cagdas; Ural Demirci, Enise; Ogut, Hilmi; Gunay, Erkan; Cetinkaya, Caner; Ozgoren, Murat

    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 functional near infrared spectroscopy (fNIRS) system. Subjects performed 2-Back test before and after the supramaximal exercise wingate anerobic test (WAnT) 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, PP 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 anerobic 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 responses (oxy-, deoxy- and

  12. Acute Supramaximal Exercise Increases the Brain Oxygenation in Relation to Cognitive Workload

    PubMed Central

    Bediz, Cem Seref; Oniz, Adile; Guducu, Cagdas; Ural Demirci, Enise; Ogut, Hilmi; Gunay, Erkan; Cetinkaya, Caner; Ozgoren, Murat

    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 functional near infrared spectroscopy (fNIRS) system. Subjects performed 2-Back test before and after the supramaximal exercise wingate anerobic test (WAnT) 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, PP 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 anerobic 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 responses (oxy-, deoxy- and

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

    PubMed Central

    Wylie, Glenn R.; Freeman, Kalev; Thomas, Alex; Shpaner, Marina; OKeefe, Michael; Watts, Richard; Naylor, Magdalena R.

    2015-01-01

    Functional neuroimaging studies in mild traumatic brain injury (mTBI) have been largely limited to patients with persistent post-concussive symptoms, utilizing images obtained months to years after the actual head trauma. We sought to distinguish acute and delayed effects of mild traumatic brain injury on working memory functional brain activation patterns < 72 hours after mild traumatic brain injury (mTBI) and again one-week later. We hypothesized that clinical and fMRI measures of working memory would be abnormal in symptomatic mTBI patients assessed < 72 hours after injury, with most patients showing clinical recovery (i.e., improvement in these measures) within 1 week after the initial assessment. We also hypothesized that increased memory workload at 1 week following injury would expose different cortical activation patterns in mTBI patients with persistent post-concussive symptoms, compared to those with full clinical recovery. We performed a prospective, cohort study of working memory in emergency department patients with isolated head injury and clinical diagnosis of concussion, compared to control subjects (both uninjured volunteers and emergency department patients with extremity injuries and no head trauma). The primary outcome of cognitive recovery was defined as resolution of reported cognitive impairment and quantified by scoring the subject’s reported cognitive post-concussive symptoms at 1 week. Secondary outcomes included additional post-concussive symptoms and neurocognitive testing results. We enrolled 46 subjects: 27 with mild TBI and 19 controls. The time of initial neuroimaging was 48 (+22 S.D.) hours after injury (time 1). At follow up (8.7, + 1.2 S.D., days after injury, time 2), 18 of mTBI subjects (64%) reported moderate to complete cognitive recovery, 8 of whom fully recovered between initial and follow-up imaging. fMRI changes from time 1 to time 2 showed an increase in posterior cingulate activation in the mTBI subjects compared to

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

    PubMed

    Wylie, Glenn R; Freeman, Kalev; Thomas, Alex; Shpaner, Marina; OKeefe, Michael; Watts, Richard; Naylor, Magdalena R

    2015-01-01

    Functional neuroimaging studies in mild traumatic brain injury (mTBI) have been largely limited to patients with persistent post-concussive symptoms, utilizing images obtained months to years after the actual head trauma. We sought to distinguish acute and delayed effects of mild traumatic brain injury on working memory functional brain activation patterns < 72 hours after mild traumatic brain injury (mTBI) and again one-week later. We hypothesized that clinical and fMRI measures of working memory would be abnormal in symptomatic mTBI patients assessed < 72 hours after injury, with most patients showing clinical recovery (i.e., improvement in these measures) within 1 week after the initial assessment. We also hypothesized that increased memory workload at 1 week following injury would expose different cortical activation patterns in mTBI patients with persistent post-concussive symptoms, compared to those with full clinical recovery. We performed a prospective, cohort study of working memory in emergency department patients with isolated head injury and clinical diagnosis of concussion, compared to control subjects (both uninjured volunteers and emergency department patients with extremity injuries and no head trauma). The primary outcome of cognitive recovery was defined as resolution of reported cognitive impairment and quantified by scoring the subject's reported cognitive post-concussive symptoms at 1 week. Secondary outcomes included additional post-concussive symptoms and neurocognitive testing results. We enrolled 46 subjects: 27 with mild TBI and 19 controls. The time of initial neuroimaging was 48 (+22 S.D.) hours after injury (time 1). At follow up (8.7, + 1.2 S.D., days after injury, time 2), 18 of mTBI subjects (64%) reported moderate to complete cognitive recovery, 8 of whom fully recovered between initial and follow-up imaging. fMRI changes from time 1 to time 2 showed an increase in posterior cingulate activation in the mTBI subjects compared to

  15. Effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice

    PubMed Central

    Doeppner, T R; Kaltwasser, B; Teli, M K; Bretschneider, E; Bähr, M; Hermann, D M

    2014-01-01

    Intravenous transplantation of neural progenitor cells (NPCs) induces functional recovery after stroke, albeit grafted cells are not integrated into residing neural networks. However, a systematic analysis of intravenous NPC delivery at acute and post-acute time points and their long-term consequences does not exist. Male C57BL6 mice were exposed to cerebral ischemia, and NPCs were intravenously grafted on day 0, on day 1 or on day 28. Animals were allowed to survive for up to 84 days. Mice and tissues were used for immunohistochemical analysis, flow cytometry, ELISA and behavioral tests. Density of grafted NPCs within the ischemic hemisphere was increased when cells were transplanted on day 28 as compared with transplantation on days 0 or 1. Likewise, transplantation on day 28 yielded enhanced neuronal differentiation rates of grafted cells. Post-ischemic brain injury, however, was only reduced when NPCs were grafted at acute time points. On the contrary, reduced post-ischemic functional deficits due to NPC delivery were independent of transplantation paradigms. NPC-induced neuroprotection after acute cell delivery was due to stabilization of the blood–brain barrier (BBB), reduction in microglial activation and modulation of both peripheral and central immune responses. On the other hand, post-acute NPC transplantation stimulated post-ischemic regeneration via enhanced angioneurogenesis and increased axonal plasticity. Acute NPC delivery yields long-term neuroprotection via enhanced BBB integrity and modulation of post-ischemic immune responses, whereas post-acute NPC delivery increases post-ischemic angioneurogenesis and axonal plasticity. Post-ischemic functional recovery, however, is independent of NPC delivery timing, which offers a broad therapeutic time window for stroke treatment. PMID:25144721

  16. Effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice.

    PubMed

    Doeppner, T R; Kaltwasser, B; Teli, M K; Bretschneider, E; Bähr, M; Hermann, D M

    2014-01-01

    Intravenous transplantation of neural progenitor cells (NPCs) induces functional recovery after stroke, albeit grafted cells are not integrated into residing neural networks. However, a systematic analysis of intravenous NPC delivery at acute and post-acute time points and their long-term consequences does not exist. Male C57BL6 mice were exposed to cerebral ischemia, and NPCs were intravenously grafted on day 0, on day 1 or on day 28. Animals were allowed to survive for up to 84 days. Mice and tissues were used for immunohistochemical analysis, flow cytometry, ELISA and behavioral tests. Density of grafted NPCs within the ischemic hemisphere was increased when cells were transplanted on day 28 as compared with transplantation on days 0 or 1. Likewise, transplantation on day 28 yielded enhanced neuronal differentiation rates of grafted cells. Post-ischemic brain injury, however, was only reduced when NPCs were grafted at acute time points. On the contrary, reduced post-ischemic functional deficits due to NPC delivery were independent of transplantation paradigms. NPC-induced neuroprotection after acute cell delivery was due to stabilization of the blood-brain barrier (BBB), reduction in microglial activation and modulation of both peripheral and central immune responses. On the other hand, post-acute NPC transplantation stimulated post-ischemic regeneration via enhanced angioneurogenesis and increased axonal plasticity. Acute NPC delivery yields long-term neuroprotection via enhanced BBB integrity and modulation of post-ischemic immune responses, whereas post-acute NPC delivery increases post-ischemic angioneurogenesis and axonal plasticity. Post-ischemic functional recovery, however, is independent of NPC delivery timing, which offers a broad therapeutic time window for stroke treatment. PMID:25144721

  17. Brain sarcoma of meningeal origin after cranial irradiation in childhood acute lymphocytic leukemia. Case report

    SciTech Connect

    Tiberin, P.; Maor, E.; Zaizov, R.; Cohen, I.J.; Hirsch, M.; Yosefovich, T.; Ronen, J.; Goldstein, J.

    1984-10-01

    The authors report their experience with an unusual case of intracerebral sarcoma of meningeal cell origin in an 8 1/2-year-old girl. This tumor occurred 6 1/2 years after cranial irradiation at relatively low dosage (2200 rads) had been delivered to the head in the course of a multimodality treatment for acute lymphocytic leukemia. The tumor recurred approximately 10 months after the first surgical intervention. Macroscopic total excision of the recurrent growth followed by whole-brain irradiation (4500 rads) failed to eradicate it completely and local recurrence prompted reoperation 18 months later. This complication of treatment in long-term childhood leukemia survivors is briefly discussed, as well as the pathology of meningeal sarcomas.

  18. Low plasma levels of brain natriuretic peptide in severe acute heart failure: merely a case?

    PubMed

    Brentana, Loretta; Temporelli, Pier Luigi; Corrà, Ugo; Gattone, Marinella; Pistono, Massimo; Imparato, Alessandro; Gnemmi, Marco; Giannuzzi, Pantaleo

    2007-11-30

    Brain natriuretic peptide (BNP) is commonly used for diagnosis and prognosis of patients with congestive heart failure (HF). High levels of BNP are associated with high probability of cardiogenic dyspnea and higher risk of subsequent cardiovascular events. We describe a case of acute HF (worsening chronic HF) in a 74-year-old male with low plasma BNP levels on admission, in whom a rapid and consistent increase in the marker's concentration occurred after administration of diuretics and vasodilators, despite a prompt clinical and hemodynamic improvement. Reports of cardiogenic dyspnea with moderate increase or normal plasma levels of BNP have been recently published: does this signify a pitfall for BNP as a useful diagnostic and prognostic tool? Clinical implications of our observation are discussed, and we conclude that neurohumoral biomarkers do not obviate the need for a careful physical and instrumental examination of patient. PMID:17382416

  19. Executive Function Late Effects in Survivors of Pediatric Brain Tumors and Acute Lymphoblastic Leukemia

    PubMed Central

    Winter, Amanda L.; Conklin, Heather M.; Tyc, Vida L.; Stancel, Heather; Hinds, Pamela S.; Hudson, Melissa M.; Kahalley, Lisa S.

    2014-01-01

    BACKGROUND Survivors of pediatric brain tumors (BT) and acute lymphoblastic leukemia (ALL) are at risk for neurocognitive late effects related to executive function. PROCEDURE Survivors of BT (48) and ALL (50) completed neurocognitive assessment. Executive function was compared to estimated IQ and population norms by diagnostic group. RESULTS 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. CONCLUSION Findings suggest that pediatric BT and ALL survivors may exhibit different profiles of executive function late effects, which may necessitate distinct intervention plans. PMID:25126830

  20. [CHARACTERIZATION OF VESTIBULAR DISORDERS IN THE INJURED PERSONS WITH THE BRAIN CONCUSSION IN ACUTE PERIOD].

    PubMed

    Skobska, O E; Kadzhaya, N V; Andreyev, O A; Potapov, E V

    2015-04-01

    There were examined 32 injured persons, ageing (34.1 ± 1.3) yrs at average, for the brain commotion (BC). The adopted protocol SCAT-3 (Standardized Concussion Assessment Tool, 3rd ed.), DHI (Dizziness Handicap Inventory questionnaire), computer stabilography (KS) were applied for the vestibular disorders diagnosis. There was established, that in acute period of BC a dyssociation between regression of objective neurological symptoms and permanence of the BC indices occurs, what confirms a latent disorder of the balance function. Changes of basic indices of statokinesiography, including increase of the vibration amplitude enhancement in general centre of pressure in a saggital square and the BC square (235.3 ± 13.7) mm2 in a modified functional test of Romberg with the closed eyes is possible to apply as objective criteria for the BC diagnosis. PMID:26263645

  1. How Acute and Chronic Alcohol Consumption Affects Brain Networks: Insights from Multimodal Neuroimaging

    PubMed Central

    Schulte, Tilman; Oberlin, Brandon G.; Kareken, David A.; Marinkovic, Ksenija; Müller-Oehring, Eva M.; Meyerhoff, Dieter J.; Tapert, Susan

    2015-01-01

    Background Multimodal imaging combining 2 or more techniques is becoming increasingly important because no single imaging approach has the capacity to elucidate all clinically relevant characteristics of a network. Methods This review highlights recent advances in multimodal neuroimaging (i.e., combined use and interpretation of data collected through magnetic resonance imaging [MRI], functional MRI, diffusion tensor imaging, positron emission tomography, magnetoencephalography, MR perfusion, and MR spectroscopy methods) that leads to a more comprehensive understanding of how acute and chronic alcohol consumption affect neural networks underlying cognition, emotion, reward processing, and drinking behavior. Results Several innovative investigators have started utilizing multiple imaging approaches within the same individual to better understand how alcohol influences brain systems, both during intoxication and after years of chronic heavy use. Conclusions Their findings can help identify mechanism-based therapeutic and pharmacological treatment options, and they may increase the efficacy and cost effectiveness of such treatments by predicting those at greatest risk for relapse. PMID:22577873

  2. Decreased Regional Homogeneity in Patients With Acute Mild Traumatic Brain Injury: A Resting-State fMRI Study.

    PubMed

    Zhan, Jie; Gao, Lei; Zhou, Fuqing; Kuang, Hongmei; Zhao, Jing; Wang, Siyong; He, Laichang; Zeng, Xianjun; Gong, Honghan

    2015-10-01

    Mild traumatic brain injury (mTBI) is characterized by structural disconnection and large-scale neural network dysfunction in the resting state. However, little is known concerning the intrinsic changes in local spontaneous brain activity in patients with mTBI. The aim of the current study was to assess regional synchronization in acute mTBI patients. Fifteen acute mTBI patients and 15 sex-, age-, and education-matched healthy controls (HCs) were studied. We used the regional homogeneity (ReHo) method to map local connectivity across the whole brain and performed a two-sample t-test between the two groups. Compared with HCs, patients with acute mTBI showed significantly decreased ReHo in the left insula, left precentral/postcentral gyrus, and left supramarginal gyrus (p < 0.05, AlphaSim corrected). The ReHo index of the left insula showed a positive correlation with the Mini-Mental State Examination (MMSE) scores across all acute mTBI patients (p < 0.05, uncorrected). The ReHo method may provide an objective biomarker for evaluating the functional abnormity of mTBI in the acute setting. PMID:26348589

  3. Single nanoparticle tracking of [Formula: see text]-methyl-d-aspartate receptors in cultured and intact brain tissue.

    PubMed

    Varela, Juan A; Ferreira, Joana S; Dupuis, Julien P; Durand, Pauline; Bouchet, Delphine; Groc, Laurent

    2016-10-01

    Recent developments in single-molecule imaging have revealed many biological mechanisms, providing high spatial and temporal resolution maps of molecular events. In neurobiology, these techniques unveiled that plasma membrane neurotransmitter receptors and transporters laterally diffuse at the surface of cultured brain cells. The photostability of bright nanoprobes, such as quantum dots (QDs), has given access to neurotransmitter receptor tracking over long periods of time with a high spatial resolution. However, our knowledge has been restricted to cultured systems, i.e., neurons and organotypic slices, therefore lacking several aspects of the intact brain rheology and connectivity. Here, we used QDs to track single glutamatergic [Formula: see text]-methyl-d-aspartate receptors (NMDAR) in acute brain slices. By delivering functionalized nanoparticles in vivo through intraventricular injections to rats expressing genetically engineered-tagged NMDAR, we successfully tracked the receptors in native brain tissue. Comparing NMDAR tracking to different classical brain preparations (acute brain slices, cultured organotypic brain slices, and cultured neurons) revealed that the surface diffusion properties shared several features and are also influenced by the nature of the extracellular environment. Together, we describe the experimental procedures to track plasma membrane NMDAR in dissociated and native brain tissue, paving the way for investigations aiming at characterizing receptor diffusion biophysics in intact tissue and exploring the physiopathological roles of receptor surface dynamics. PMID:27429996

  4. Functional mitochondrial analysis in acute brain sections from adult rats reveals mitochondrial dysfunction in a rat model of migraine

    PubMed Central

    Fried, Nathan T.; Moffat, Cynthia; Seifert, Erin L.

    2014-01-01

    Mitochondrial dysfunction has been implicated in many neurological disorders that only develop or are much more severe in adults, yet no methodology exists that allows for medium-throughput functional mitochondrial analysis of brain sections from adult animals. We developed a technique for quantifying mitochondrial respiration in acutely isolated adult rat brain sections with the Seahorse XF Analyzer. Evaluating a range of conditions made quantifying mitochondrial function from acutely derived adult brain sections from the cortex, cerebellum, and trigeminal nucleus caudalis possible. Optimization of this technique demonstrated that the ideal section size was 1 mm wide. We found that sectioning brains at physiological temperatures was necessary for consistent metabolic analysis of trigeminal nucleus caudalis sections. Oxygen consumption in these sections was highly coupled to ATP synthesis, had robust spare respiratory capacities, and had limited nonmitochondrial respiration, all indicative of healthy tissue. We demonstrate the effectiveness of this technique by identifying a decreased spare respiratory capacity in the trigeminal nucleus caudalis of a rat model of chronic migraine, a neurological disorder that has been associated with mitochondrial dysfunction. This technique allows for 24 acutely isolated sections from multiple brain regions of a single adult rat to be analyzed simultaneously with four sequential drug treatments, greatly advancing the ability to study mitochondrial physiology in adult neurological disorders. PMID:25252946

  5. Acute liver failure-induced death of rats is delayed or prevented by blocking NMDA receptors in brain.

    PubMed

    Cauli, Omar; Rodrigo, Regina; Boix, Jordi; Piedrafita, Blanca; Agusti, Ana; Felipo, Vicente

    2008-09-01

    Developing procedures to delay the mechanisms of acute liver failure-induced death would increase patients' survival by allowing time for liver regeneration or to receive a liver for transplantation. Hyperammonemia is a main contributor to brain herniation and mortality in acute liver failure (ALF). Acute ammonia intoxication in rats leads to N-methyl-D-aspartate (NMDA) receptor activation in brain. Blocking these receptors prevents ammonia-induced death. Ammonia-induced activation of NMDA receptors could contribute to ALF-induced death. If this were the case, blocking NMDA receptors could prevent or delay ALF-induced death. The aim of this work was to assess 1) whether ALF leads to NMDA receptors activation in brain in vivo and 2) whether blocking NMDA receptors prevents or delays ALF-induced death of rats. It is shown, by in vivo brain microdialysis, that galactosamine-induced ALF leads to NMDA receptors activation in brain. Blocking NMDA receptors by continuous administration of MK-801 or memantine through miniosmotic pumps affords significant protection against ALF-induced death, increasing the survival time approximately twofold. Also, when liver injury is not 100% lethal (1.5 g/kg galactosamine), blocking NMDA receptors increases the survival rate from 23 to 62%. This supports that blocking NMDA receptors could have therapeutic utility to improve survival of patients with ALF. PMID:18599589

  6. Increases of CCK mRNA and peptide in different brain areas following acute and chronic administration of morphine.

    PubMed

    Ding, X Z; Bayer, B M

    1993-10-15

    The present study examined whether either acute or chronic administration of morphine resulted in changes in the content of CCK mRNA and CCK immunoactive peptide in selective areas of the rat brain and spinal cord. Two hours after a single injection of morphine (10 mg/kg, s.c.), CCK mRNA significantly increased in the hypothalamus (0.8-fold) and spinal cord (2-fold) relative to the CCK mRNA content in saline-injected controls. No significant differences in CCK mRNA were observed in the frontal cortex, hippocampus, midbrain or brainstem. There were no significant alterations in CCK immunoreactivity in any brain regions and spinal cord after the acute treatment with morphine. Upon repeated morphine administration, the content of CCK mRNA in both the hypothalamus and the spinal cord was further elevated by at least 3-fold. A significant increase of CCK mRNA content in brain stem (2.8-fold) was also observed following chronic morphine administration. In contrast to the acute exposure to morphine, chronic administration resulted in significant increases in CCK immunoactive peptide in hypothalamus (2.6-fold), spinal cord (2.1-fold) and brainstem (1.6-fold), but not in the other brain areas. These results demonstrate that morphine, especially following repeated administrations, stimulates endogenous CCK biosynthesis in selective brain regions. PMID:8242392

  7. TIMP-1 attenuates blood–brain barrier permeability in mice with acute liver failure

    PubMed Central

    Chen, Feng; Radisky, Evette S; Das, Pritam; Batra, Jyotica; Hata, Toshiyuki; Hori, Tomohide; Baine, Ann-Marie T; Gardner, Lindsay; Yue, Mei Y; Bu, Guojun; del Zoppo, Gregory; Patel, Tushar C; Nguyen, Justin H

    2013-01-01

    Blood–brain barrier (BBB) dysfunction in acute liver failure (ALF) results in increased BBB permeability that often precludes the patients from obtaining a life-saving liver transplantation. It remains controversial whether matrix metalloproteinase-9 (MMP-9) from the injured liver contributes to the deregulation of BBB function in ALF. We selectively upregulated a physiologic inhibitor of MMP-9 (TIMP-1) with a single intracerebroventricular injection of TIMP-1 cDNA plasmids at 48 and 72 hours, or with pegylated-TIMP-1 protein. Acute liver failure was induced with tumor necrosis factor-α and 𝒟-(+)-galactosamine in mice. Permeability of BBB was assessed with sodium fluorescein (NaF) extravasation. We found a significant increase in TIMP-1 within the central nervous system (CNS) after the administration of TIMP-1 cDNA plasmids and that increased TIMP-1 within the CNS resulted in an attenuation of BBB permeability, a reduction in activation of epidermal growth factor receptor and p38 mitogen-activated protein kinase signals, and a restoration of the tight junction protein occludin in mice with experimental ALF. Pegylated TIMP-1 provided similar protection against BBB permeability in mice with ALF. Our results provided a proof of principle that MMP-9 contributes to the BBB dysfunction in ALF and suggests a potential therapeutic role of TIMP-1 in ALF. PMID:23532086

  8. Gender Differences in Awareness and Outcomes During Acute Traumatic Brain Injury Recovery

    PubMed Central

    Perrin, Paul B.; Holcomb, Megan G.; Rolston, Cynthia D.; Artman, Laura K.; Lu, Juan; Nersessova, Karine S.

    2014-01-01

    Abstract Background: Recent literature on traumatic brain injury (TBI), though mixed when reporting outcomes, seems collectively to suggest possible gender advantage for women in postinjury recovery, especially in executive functions. Hormonal neuroprotection, through female reproductive hormones, is often proposed as an underlying factor in these results. We explored potential gender differences in an aspect of executive functions, self-awareness (SA), which is often impaired after TBI, limits patient effort in critical rehabilitation, and increases caregiver burden. Methods: Within a prospective survey, repeated-measures design, 121 patients with moderate or severe TBI undergoing acute rehabilitation in a Level 1 trauma center, a family member or caregiver informant, and a treating clinician were asked to complete the Patient Competency Rating Scale (PCRS) and the Frontal Systems Behavior Scale (FrSBe) at admission and discharge. Results: Although overall, women and men with TBI showed generally similar levels of SA, women had significantly better awareness of their injury-related deficits at acute rehabilitation discharge, even when controlling for age, education, and injury severity. Conclusions: Mixed findings in this study mirror the pattern of results that dominate the published literature on gender and TBI. Gender differences in executive dysfunction may not be as large or robust as some researchers argue. In addition, complex interplays of socialization, gender-role expectations, naturally occurring male and female ability differences, and differences in access to postinjury rehabilitation are understudied potential moderators. PMID:24932911

  9. Forward and inverse electroencephalographic modeling in health and in acute traumatic brain injury

    PubMed Central

    Irimia, Andrei; Goh, S.Y. Matthew; Torgerson, Carinna M.; Chambers, Micah C.; Kikinis, Ron; Van Horn, John D.

    2013-01-01

    Objective EEG source localization is demonstrated in three cases of acute traumatic brain injury (TBI) with progressive lesion loads using anatomically faithful models of the head which account for pathology. Methods Multimodal magnetic resonance imaging (MRI) volumes were used to generate head models via the finite element method (FEM). A total of 25 tissue types—including 6 types accounting for pathology— were included. To determine the effects of TBI upon source localization accuracy, a minimum-norm operator was used to perform inverse localization and to determine the accuracy of the latter. Results The importance of using a more comprehensive number of tissue types is confirmed in both health and in TBI. Pathology omission is found to cause substantial inaccuracies in EEG forward matrix calculations, with lead field sensitivity being underestimated by as much as ~200% in (peri-) contusional regions when TBI-related changes are ignored. Failing to account for such conductivity changes is found to misestimate substantial localization error by up to 35 mm. Conclusions Changes in head conductivity profiles should be accounted for when performing EEG modeling in acute TBI. Significance Given the challenges of inverse localization in TBI, this framework can benefit neurotrauma patients by providing useful insights on pathophysiology. PMID:23746499

  10. Advancements in the treatment of pediatric acute leukemia and brain tumor - continuous efforts for 100% cure.

    PubMed

    Ju, Hee Young; Hong, Che Ry; Shin, Hee Young

    2014-10-01

    Treatment outcomes of pediatric cancers have improved greatly with the development of improved treatment protocols, new drugs, and better supportive measures, resulting in overall survival rates greater than 70%. Survival rates are highest in acute lymphoblastic leukemia, reaching more than 90%, owing to risk-based treatment through multicenter clinical trials and protocols developed to prevent central nervous system relapse and testicular relapse in boys. New drugs including clofarabine and nelarabine are currently being evaluated in clinical trials, and other targeted agents are continuously being developed. Chimeric antigen receptor-modified T cells are now attracting interest for the treatment of recurrent or refractory disease. Stem cell transplantation is still the most effective treatment for pediatric acute myeloid leukemia (AML). However, in order to reduce treatment-related death after stem cell transplantation, there is need for improved treatments. New drugs and targeted agents are also needed for improved outcome of AML. Surgery and radiation therapy have been the mainstay for brain tumor treatment. However, chemotherapy is becoming more important for patients who are not eligible for radiotherapy owing to age. Stem cell transplant as a means of high dose chemotherapy and stem cell rescue is a new treatment modality and is often repeated for improved survival. Drugs such as temozolomide are new chemotherapeutic options. In order to achieve 100% cure in children with pediatric cancer, every possible treatment modality and effort should be considered. PMID:25379043

  11. Acute traumatic brain injury: is current management evidence based? An empirical analysis of systematic reviews.

    PubMed

    Lei, Jin; Gao, Guoyi; Jiang, Jiyao

    2013-04-01

    Traumatic brain injury (TBI) is a major health and socioeconomic problem worldwide with a high rate of death and long-term disability. Previous studies have summarized evidence from large-scale randomized trials, finding no intervention showing convincing efficacy for acute TBI management. The present empirical study set out to assess another crucial component of evidence base-systematic review, which contributes a lot to evidence-based health care, in terms of clinical issues, methodological aspects, and implication for practice and research. A total of 44 systematic reviews pertaining to therapeutic interventions for acute TBI were identified through electronic database searching, clinical guideline retrieval, and expert consultation, of which 21 were published in Cochrane Library and 23 in peer-reviewed journals. Their methodological quality was generally satisfactory, with the median Overview Quality Assessment Questionnaire score of 5.5 (interquartile range 2-7). Cochrane reviews are of better quality than regular journal reviews. Twenty-nine high-quality reviews provided no conclusive evidence for the investigated 22 interventions except for an adverse effect of corticosteroids. Less than one-third of the component trials were reported with adequate allocation concealment. Additionally other methodological flaws in design-for example, ignoring heterogeneity among the TBI population-also contributed to the failure of past clinical research. Based on the above findings, evidence from both systematic reviews and clinical trials does not fully support current management of acute TBI. Translating from laboratory success to clinical effect remains an unique challenge. Accordingly it may be the time to rethink the way in future practice and clinical research in TBI. PMID:23151044

  12. Acute aerobic exercise increases brain-derived neurotrophic factor levels in elderly with Alzheimer's disease.

    PubMed

    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. PMID:24164734

  13. Acute Serum Hormone Levels: Characterization and Prognosis after Severe Traumatic Brain Injury

    PubMed Central

    McCullough, Emily H.; Niyonkuru, Christian; Ozawa, Haishin; Loucks, Tammy L.; Dobos, Julie A.; Brett, Christopher A.; Santarsieri, Martina; Dixon, C. Edward; Berga, Sarah L.; Fabio, Anthony

    2011-01-01

    Abstract Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global

  14. Activation of brain NOP receptors attenuates acute and protracted alcohol withdrawal symptoms in the rat

    PubMed Central

    Economidou, Daina; Cippitelli, Andrea; Stopponi, Serena; Braconi, Simone; Clementi, Stefano; Ubaldi, Massimo; Martin-Fardon, Rèmi; Weiss, Friedbert; Massi, Maurizio; Ciccocioppo, Roberto

    2010-01-01

    BACKGROUND Alcohol withdrawal, refers to a cluster of symptoms that may occur from suddenly ceasing the use of alcohol after chronic or prolonged ingestion. These symptoms make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. In previous studies, we demonstrated that treatment with N/OFQ significantly reduces alcohol consumption and attenuates alcohol-seeking behaviour induced by environmental conditioning factors or by stress in rats. In the present study we evaluated whether activation of brain NOP receptors may also attenuate alcohol withdrawal signs in rats. METHODS For this purpose animals were subjected to a 6 day chronic alcohol intoxication (by intragastric administration) and at 8, 10 and 12 hours following cessation of alcohol exposure they were treated intracerebroventricularly (ICV) with N/OFQ (0.0, 1.0 and 3.0 μg/rat). Somatic withdrawal signs were scored after ICV treatment. In a subsequent experiment, to evaluate N/OFQ effects on alcohol withdrawal-induced anxiety another group of rats was subjected to ethanol intoxication and after one week was tested for anxiety behavior in the elevated plus maze (EPM). In the last experiment an additional group of rats was tested for anxiety elicited by acute ethanol intoxication (hangover anxiety). For this purpose, animals received an acute dose (3.0 g/kg) of 20% alcohol and 12-h later were tested in the EPM following ICV N/OFQ (0.0, 1.0 and 2.0μg/rat). RESULTS Results showed that N/OFQ significantly reduced the expression of somatic withdrawal signs and reversed anxiety-like behaviors associated with both chronic and acute alcohol intoxication. N/OFQ did not affect anxiety scores in nondependent animals. CONCLUSIONS The present findings suggest that the N/OFQ-NOP receptor system may represent a promising target for the development of new treatments to ameliorate alcohol withdrawal symptoms. PMID:21223310

  15. Acute serum hormone levels: characterization and prognosis after severe traumatic brain injury.

    PubMed

    Wagner, Amy K; McCullough, Emily H; Niyonkuru, Christian; Ozawa, Haishin; Loucks, Tammy L; Dobos, Julie A; Brett, Christopher A; Santarsieri, Martina; Dixon, C Edward; Berga, Sarah L; Fabio, Anthony

    2011-06-01

    Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global outcome for

  16. [The effect of neurotrophic treatment on the activation of reparative processes in patients with acute traumatic brain injury].

    PubMed

    Selianina, N V; Karakulova, Iu V

    2012-01-01

    The complex study of cognitive and emotional status, levels of serum serotonin and brain-derived neurotrophic factor (BDNF) were performed in 72 patients with acute traumatic brain injury, with a special focus on middle brain injuries (MBI), treated with Cerebrolysin. The neurological and cognitive impairment, mild state anxiety and depression and increased levels of humoral serotonin, which depends on the severity of the injury, were identified in patients with MBI before treatment. After the treatment, there were the decrease in the severity of neurological symptoms and a significant positive dynamics on the FAB scale as well as the increase in blood BDNF and serotonin levels. It has been concluded that using cerebrolysin in complex treatment of acute MBI promotes activation of neurotrophic processes and improves outcomes of closed craniocerebral injury. PMID:22951781

  17. Slice of Comet Dust

    NASA Technical Reports Server (NTRS)

    2006-01-01

    This image illustrates one of several ways scientists have begun extracting comet particles from the Stardust spacecraft's collector. First, a particle and its track are cut out of the collector material, called aerogel, in a wedge-shaped slice called a keystone. A specialized silicon pickle fork is then used to remove the keystone from the remaining aerogel for further analysis.

  18. An acute method for multielectrode recording from the interior of sulci and other deep brain areas.

    PubMed

    Purushothaman, Gopathy; Scott, Benjamin B; Bradley, David C

    2006-05-15

    Most current techniques for multielectrode recording involve chronically implanting planar or staggered arrays of electrodes. Such chronic implants are suited for studying a stable population of neurons over long periods of time but exploratory studies of the physiological properties of cortical subdivisions require the ability to sample multiple neural populations. This makes it necessary to penetrate frequently with small multielectrode assemblies. Some commercial systems allow daily penetrations with multiple electrodes, but they tend to be bulky, complex and expensive, and some make no provision for piercing the barrier of fibrous tissue that often covers the brain surface. We describe an apparatus for inserting bundles of 3-16 electrodes on a daily basis, thus allowing different neural populations to be sampled. The system is designed to allow penetration through a thick dura mater into deep brain structures. We discuss a simple method for performing multielectrode recording from cortical areas buried inside sulci using acute implantations of a bundle of electrodes. Our results show that it is possible to obtain stable recordings for at least 4h and that repeated implantations yield an average of two neurons per electrode with every electrode in the bundle picking up at least one single neuron in 70% of the implantations. PMID:16316688

  19. Mitochondrial energetic defects in muscle and brain of a Hmbs-/- mouse model of acute intermittent porphyria.

    PubMed

    Homedan, Chadi; Schmitt, Caroline; Laafi, Jihane; Gueguen, Naïg; Desquiret-Dumas, Valérie; Lenglet, Hugo; Karim, Zoubida; Gouya, Laurent; Deybach, Jean-Charles; Simard, Gilles; Puy, Hervé; Malthièry, Yves; Reynier, Pascal

    2015-09-01

    Acute intermittent porphyria (AIP), an autosomal dominant metabolic disease (MIM #176000), is due to a deficiency of hydroxymethylbilane synthase (HMBS), which catalyzes the third step of the heme biosynthetic pathway. The clinical expression of the disease is mainly neurological, involving the autonomous, central and peripheral nervous systems. We explored mitochondrial oxidative phosphorylation (OXPHOS) in the brain and skeletal muscle of the Hmbs(-/-) mouse model first in the basal state (BS), and then after induction of the disease with phenobarbital and treatment with heme arginate (HA). The modification of the respiratory parameters, determined in mice in the BS, reflected a spontaneous metabolic energetic adaptation to HMBS deficiency. Phenobarbital induced a sharp alteration of the oxidative metabolism with a significant decrease of ATP production in skeletal muscle that was restored by treatment with HA. This OXPHOS defect was due to deficiencies in complexes I and II in the skeletal muscle whereas all four respiratory chain complexes were affected in the brain. To date, the pathogenesis of AIP has been mainly attributed to the neurotoxicity of aminolevulinic acid and heme deficiency. Our results show that mitochondrial energetic failure also plays an important role in the expression of the disease. PMID:26071363

  20. A compact and autoclavable system for acute extracellular neural recording and brain pressure monitoring for humans.

    PubMed

    Angotzi, Gian Nicola; Baranauskas, Gytis; Vato, Alessandro; Bonfanti, Andrea; Zambra, Guido; Maggiolini, Emma; Semprini, Marianna; Ricci, Davide; Ansaldo, Alberto; Castagnola, Elisa; Ius, Tamara; Skrap, Miran; Fadiga, Luciano

    2015-02-01

    One of the most difficult tasks for the surgeon during the removal of low-grade gliomas is to identify as precisely as possible the borders between functional and non-functional brain tissue with the aim of obtaining the maximal possible resection which allows to the patient the longer survival. For this purpose, systems for acute extracellular recordings of single neuron and multi-unit activity are considered promising. Here we describe a system to be used with 16 microelectrodes arrays that consists of an autoclavable headstage, a built-in inserter for precise electrode positioning and a system that measures and controls the pressure exerted by the headstage on the brain with a twofold purpose: to increase recording stability and to avoid disturbance of local perfusion which would cause a degradation of the quality of the recording and, eventually, local ischemia. With respect to devices where only electrodes are autoclavable, our design permits the reduction of noise arising from long cable connections preserving at the same time the flexibility and avoiding long-lasting gas sterilization procedures. Finally, size is much smaller and set up time much shorter compared to commercial systems currently in use in surgery rooms, making it easy to consider our system very useful for intra-operatory mapping operations. PMID:25486648

  1. Whole-Brain CT Perfusion to Quantify Acute Ischemic Penumbra and Core.

    PubMed

    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 < .0001). Conclusion Correct threshold setting and whole-brain coverage 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. PMID:26785041

  2. Regional brain blood flow and cerebral hemispheric oxygen consumption during acute hypoxaemia in the llama fetus

    PubMed Central

    Llanos, Aníbal J; Riquelme, Raquel A; Sanhueza, Emilia M; Herrera, Emilio; Cabello, Gertrudis; Giussani, Dino A; Parer, Julian T

    2002-01-01

    Unlike fetal animals of lowland species, the llama fetus does not increase its cerebral blood flow during an episode of acute hypoxaemia. This study tested the hypothesis that the fetal llama brain maintains cerebral hemispheric O2 consumption by increasing cerebral O2 extraction rather than decreasing cerebral oxygen utilisation during acute hypoxaemia. Six llama fetuses were surgically instrumented under general anaesthesia at 217 days of gestation (term ca 350 days) with vascular and amniotic catheters in order to carry out cardiorespiratory studies. Following a control period of 1 h, the llama fetuses underwent 3 × 20 min episodes of progressive hypoxaemia, induced by maternal inhalational hypoxia. During basal conditions and during each of the 20 min of hypoxaemia, fetal cerebral blood flow was measured with radioactive microspheres, cerebral oxygen extraction was calculated, and fetal cerebral hemispheric O2 consumption was determined by the modified Fick principle. During hypoxaemia, fetal arterial O2 tension and fetal pH decreased progressively from 24 ± 1 to 20 ± 1 Torr and from 7.36 ± 0.01 to 7.33 ± 0.01, respectively, during the first 20 min episode, to 16 ± 1 Torr and 7.25 ± 0.05 during the second 20 min episode and to 14 ± 1 Torr and 7.21 ± 0.04 during the final 20 min episode. Fetal arterial partial pressure of CO2 (Pa,CO2, 42 ± 2 Torr) remained unaltered from baseline throughout the experiment. Fetal cerebral hemispheric blood flow and cerebral hemispheric oxygen extraction were unaltered from baseline during progressive hypoxaemia. In contrast, a progressive fall in fetal cerebral hemispheric oxygen consumption occurred during the hypoxaemic challenge. In conclusion, these data do not support the hypothesis that the fetal llama brain maintains cerebral hemispheric O2 consumption by increasing cerebral hemispheric O2 extraction. Rather, the data show that in the llama fetus, a reduction in cerebral hemispheric metabolism occurs during acute

  3. Acute Modulation of Brain Connectivity in Parkinson Disease after Automatic Mechanical Peripheral Stimulation: A Pilot Study

    PubMed Central

    Piervincenzi, Claudia; Galli, Manuela; Melgari, Jean Marc; Salomone, Gaetano; Sale, Patrizio; Mallio, Carlo Augusto; Carducci, Filippo; Stocchi, Fabrizio

    2015-01-01

    Objective The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease. Methods Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition. Results Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79). Conclusions Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration. Classification of Evidence This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest. Trial Registration Clinical Trials.gov NCT01815281 PMID:26469868

  4. Evaluation of changes in the parameters of brain tissue perfusion in multi-slice computed tomography in patients after carotid artery stenting

    PubMed Central

    Szarmach, Arkadiusz; Halena, Grzegorz; Buczny, Jacek; Studniarek, Michał; Markiet, Karolina; Szurowska, Edyta; Retkowski, Mariusz; Piskunowicz, Maciej

    2011-01-01

    Summary Background: CT perfusion of the brain allows functional evaluation of cerebral blood flow. Patients with chronic internal carotid artery (ICA) stenosis may suffer from malperfusion. Improvement of cerebral blood flow and remission of neurological symptoms indicate the effectiveness of treatment of internal carotid artery stenosis. Material/Methods: The aim of the study was to analyze alterations within cerebral perfusion parameters in CT brain perfusion examination in patients who were scheduled for endovascular therapy due to ICA stenosis. Forty patients with ICA stenosis of over 79% who were included in this prospective study underwent perfusion CT examination twice – 24 hours prior to stenting and after 6–8 weeks following the procedure. CBF, CBV, MTT and TTP were evaluated. Results: Prior to endovascular therapy, an increase in MTT and TTP, and a decrease in CBV and CBF were observed within arterial supply of the hemisphere ipsilateral to stenosis. After the procedure, a decrease in MTT and TTP was seen in all cases, while no statistically significant changes of CBF or CBV were observed. MTT proved to be the most sensitive indicator of ICA stenosis, as its values allowed differentiation between critical and non-critical stenosis. No correlation between the degree of ICA stenosis and TTP values was found. Mild cerebral hyperperfusion syndrome (CHS) was observed in only one patient and the difference between pre-treatment MTT values calculated for both hemispheres was shown to be a prognostic factor for CHS incidence. Conclusions: Endovascular stent placing in patients with hemodynamically significant internal carotid artery stenosis results in alteration of perfusion parameters, especially concerning TTP and MTT. PMID:22802836

  5. Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-04-08

    Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Cognitive Side Effects of Cancer Therapy; Long-Term Effects Secondary to Cancer Therapy in Children; Neurotoxicity Syndrome; Psychological Impact of Cancer; Untreated Childhood Acute Lymphoblastic Leukemia

  6. Portable Device Slices Thermoplastic Prepregs

    NASA Technical Reports Server (NTRS)

    Taylor, Beverly A.; Boston, Morton W.; Wilson, Maywood L.

    1993-01-01

    Prepreg slitter designed to slit various widths rapidly by use of slicing bar holding several blades, each capable of slicing strip of preset width in single pass. Produces material evenly sliced and does not contain jagged edges. Used for various applications in such batch processes involving composite materials as press molding and autoclaving, and in such continuous processes as pultrusion. Useful to all manufacturers of thermoplastic composites, and in slicing B-staged thermoset composites.

  7. ACUTE INDUCTION OF EPILEPTIFORM DISCHARGES BY PILOCARPINE IN THE IN VITRO ISOLATED GUINEA-PIG BRAIN REQUIRES ENHANCEMENT OF BLOOD–BRAIN BARRIER PERMEABILITY

    PubMed Central

    UVA, L.; LIBRIZZI, L.; MARCHI, N.; NOE, F.; BONGIOVANNI, R.; VEZZANI, A.; JANIGRO, D.; DE CURTIS, M.

    2008-01-01

    Systemic application of the muscarinic agonist, pilocarpine, is commonly utilized to induce an acute status epilepticus that evolves into a chronic epileptic condition characterized by spontaneous seizures. Recent findings suggest that the status epilepticus induced by pilocarpine may be triggered by changes in the blood–brain barrier (BBB) permeability. We tested the role of the BBB in an acute pilocarpine model by using the in vitro model brain preparation and compared our finding with in vivo data. Arterial perfusion of the in vitro isolated guinea-pig brain with <1 mM pilocarpine did not cause epileptiform activity, but rather reduced synaptic transmission and induced steady fast (20–25 Hz) oscillatory activity in limbic cortices. These effects were reversibly blocked by co-perfusion of the muscarinic antagonist atropine sulfate (5 μM). Brain pilocarpine measurements in vivo and in vitro suggested modest BBB penetration. Pilocarpine induced epileptiform discharges only when perfused with compounds that enhance BBB permeability, such as bradykinin (n=2) or histamine (n=10). This pro-epileptic effect was abolished when the BBB-impermeable muscarinic antagonist atropine methyl bromide (5 μM) was co-perfused with histamine and pilocarpine. In the absence of BBB permeability enhancing drugs, pilocarpine induced epileptiform activity only after arterial perfusion at concentrations >10 mM. Ictal discharges correlated with a high intracerebral pilocarpine concentration measured by high pressure liquid chromatography. We propose that acute epileptiform discharges induced by pilocarpine treatment in the in vitro isolated brain preparation are mediated by a dose-dependent, atropine-sensitive muscarinic effect promoted by an increase in BBB permeability. Pilocarpine accumulation secondary to BBB permeability changes may contribute to in vivo ictogenesis in the pilocarpine epilepsy model. PMID:18082973

  8. Traumatic brain injury and post-acute decline: what role does environmental enrichment play? A scoping review

    PubMed Central

    Frasca, Diana; Tomaszczyk, Jennifer; McFadyen, Bradford J.; Green, Robin E.

    2013-01-01

    Objectives: While a growing number of studies provide evidence of neural and cognitive decline in traumatic brain injury (TBI) survivors during the post-acute stages of injury, there is limited research as of yet on environmental factors that may influence this decline. The purposes of this paper, therefore, are to (1) examine evidence that environmental enrichment (EE) can influence long-term outcome following TBI, and (2) examine the nature of post-acute environments, whether they vary in degree of EE, and what impact these variations have on outcomes. Methods: We conducted a scoping review to identify studies on EE in animals and humans, and post-discharge experiences that relate to barriers to recovery. Results: One hundred and twenty-three articles that met inclusion criteria demonstrated the benefits of EE on brain and behavior in healthy and brain-injured animals and humans. Nineteen papers on post-discharge experiences revealed that variables such as insurance coverage, financial, and social support, home therapy, and transition from hospital to home, can have an impact on clinical outcomes. Conclusion: There is evidence to suggest that lack of EE, whether from lack of resources or limited ability to engage in such environments, may play a role in post-acute cognitive and neural decline. Maximizing EE in the post-acute stages of TBI may improve long-term outcomes for the individual, their family and society. PMID:23616755

  9. AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3.

    PubMed

    Denes, Adam; Coutts, Graham; Lénárt, Nikolett; Cruickshank, Sheena M; Pelegrin, Pablo; Skinner, Joanne; Rothwell, Nancy; Allan, Stuart M; Brough, David

    2015-03-31

    Inflammation that contributes to acute cerebrovascular disease is driven by the proinflammatory cytokine interleukin-1 and is known to exacerbate resulting injury. The activity of interleukin-1 is regulated by multimolecular protein complexes called inflammasomes. There are multiple potential inflammasomes activated in diverse diseases, yet the nature of the inflammasomes involved in brain injury is currently unknown. Here, using a rodent model of stroke, we show that the NLRC4 (NLR family, CARD domain containing 4) and AIM2 (absent in melanoma 2) inflammasomes contribute to brain injury. We also show that acute ischemic brain injury is regulated by mechanisms that require ASC (apoptosis-associated speck-like protein containing a CARD), a common adaptor protein for several inflammasomes, and that the NLRP3 (NLR family, pyrin domain containing 3) inflammasome is not involved in this process. These discoveries identify the NLRC4 and AIM2 inflammasomes as potential therapeutic targets for stroke and provide new insights into how the inflammatory response is regulated after an acute injury to the brain. PMID:25775556

  10. AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3

    PubMed Central

    Denes, Adam; Coutts, Graham; Lénárt, Nikolett; Cruickshank, Sheena M.; Pelegrin, Pablo; Skinner, Joanne; Rothwell, Nancy; Allan, Stuart M.; Brough, David

    2015-01-01

    Inflammation that contributes to acute cerebrovascular disease is driven by the proinflammatory cytokine interleukin-1 and is known to exacerbate resulting injury. The activity of interleukin-1 is regulated by multimolecular protein complexes called inflammasomes. There are multiple potential inflammasomes activated in diverse diseases, yet the nature of the inflammasomes involved in brain injury is currently unknown. Here, using a rodent model of stroke, we show that the NLRC4 (NLR family, CARD domain containing 4) and AIM2 (absent in melanoma 2) inflammasomes contribute to brain injury. We also show that acute ischemic brain injury is regulated by mechanisms that require ASC (apoptosis-associated speck-like protein containing a CARD), a common adaptor protein for several inflammasomes, and that the NLRP3 (NLR family, pyrin domain containing 3) inflammasome is not involved in this process. These discoveries identify the NLRC4 and AIM2 inflammasomes as potential therapeutic targets for stroke and provide new insights into how the inflammatory response is regulated after an acute injury to the brain. PMID:25775556

  11. Slice profile distortions in single slice continuously moving table MRI

    NASA Astrophysics Data System (ADS)

    Sengupta, Saikat; Smith, David S.; Welch, E. B.

    2015-03-01

    Continuously Moving Table (CMT) MRI is a rapid imaging technique that allows scanning of extended fields of view (FOVs) such as the whole-body in a single continuous scan.1 A highly efficient approach to CMT MRI is single slice imaging, where data are continuously acquired from a single axial slice at isocenter with concurrent movement of the patient table.2 However, the continuous motion of the scanner table and supply of fresh magnetization into the excited slice can introduce deviations in the slice magnetization profile. The goal of this work is to investigate and quantify the distortion in the slice profile in CMT MRI. CMT MRI with a table speed of 20 mm/s was implemented on a 3 Tesla whole-body MRI scanner, with continuous radial data acquisition. Simulations were performed to characterize the transient and steady state slice profiles and magnetization effects. Simulated slice profiles were compared to actual slice profile measurements performed in the scanner. Both simulations and experiments revealed an asymmetric slice profile characterized by a skew towards the lagging edge of the moving table, in contrast to the nominal profiles associated with scanning a stationary object. The true excited slice width (FWHM) and pitch of the acquisition was observed to be dependent on table velocity, with larger table speeds resulting in larger slice profile deviations from the nominal shape.

  12. Flash lamp light slicing

    NASA Astrophysics Data System (ADS)

    Saber, A. J.; Abdel-Wahab, T.; Georgallis, M.

    A light slicing system using a short-arc-length high-power flashlamp as the source is discussed, with application to the observation of fluid phenomena such as gas discharge and fuel injection into engines. The geometrical optics of the method, in addition to the attenuation of luminous intensity in the system, is considered, and varying the relative radius of curvature of the cylindrical lens with respect to the width of the laser beam is shown to change the extension of the light sheet lamina. Light slice system generation using CAD is discussed, and experimental results of the observation of pulsed gas discharges in a small scale valve system designed to simulate large-scale dispersion and mixing of gases in air are reported.

  13. Alterations in blood-brain barrier function following acute hypertension: comparison of the blood-to-brain transfer of horseradish peroxidase with that of alpha-aminisobutyric acid

    SciTech Connect

    Ellison, M.D.B.

    1985-01-01

    The blood-brain barrier (BBB) selectively restricts the blood-to-brain passage of many solutes owing to unique properties of cerebrovascular endothelial cell membranes. To date, experimental study of the BBB has been accomplished primarily through the use of two different methodological approaches. Morphological studies have mostly employed large molecular weight (MW) tracers to detect morphological alterations underlying increased permeability. Physiological studies, employing smaller, more physiologic tracers have successfully described, quantitatively, certain functional aspects of blood-to-brain transfer. The current work attempts to merge these two approaches and to consider barrier function/dysfunction from both a morphological and a functional perspective. Specifically, the study compares in rats, following acute hypertension, the cerebrovascular passage of /sup 14/C-alpha-aminoisobutyric acid (AIB) and that of horseradish peroxidase (HRP). The blood-to-brain passage of AIB and HRP were compared following acute hypertension, with regard to both the distributions of the tracer extravasation patterns and the magnitude of tracer extravasation. The results of this study suggest that traditional morphological barrier studies alone do not reveal all aspects of altered barrier status and that multiple mechanisms underlying increased BBB permeability may operate simultaneously during BBB dysfunction.

  14. Tryptophan availability modulates serotonin release from rat hypothalamic slices

    NASA Technical Reports Server (NTRS)

    Schaechter, Judith D.; Wurtman, Richard J.

    1989-01-01

    The relationship between the tryptophan availability and serononin release from rat hypothalamus was investigated using a new in vitro technique for estimating rates at which endogenous serotonin is released spontaneously or upon electrical depolarization from hypothalamic slices superfused with a solution containing various amounts of tryptophan. It was found that the spontaneous, as well as electrically induced, release of serotonin from the brain slices exhibited a dose-dependent relationship with the tryptophan concentration of the superfusion medium.

  15. Acute clinical care and care coordination for traumatic brain injury within Department of Defense.

    PubMed

    Jaffee, Michael S; Helmick, Kathy M; Girard, Philip D; Meyer, Kim S; Dinegar, Kathy; George, Karyn

    2009-01-01

    The nature of current combat situations that U.S. military forces encounter and the use of unconventional weaponry have dramatically increased service personnel's risks of sustaining a traumatic brain injury (TBI). Although the true incidence and prevalence of combat-related TBI are unknown, service personnel returning from deployment have reported rates of concussion between 10% and 20%. The Department of Defense has recently released statistics on TBI dating back to before the wars in Iraq and Afghanistan to better elucidate the impact and burden of TBI on America's warriors and veterans. Patients with severe TBI move through a well-established trauma system of care, beginning with triage of initial injury by first-responders in the war zone to acute care to rehabilitation and then returning home and to the community. Mild and moderate TBIs may pose different clinical challenges, especially when initially undetected or if treatment is delayed because more serious injuries are present. To ensure identification and prompt treatment of mild and moderate TBI, the U.S. Congress has mandated that military and Department of Veterans Affairs hospitals screen all service personnel returning from combat. Military health professionals must evaluate them for concussion and then treat the physical, emotional, and cognitive problems that may surface. A new approach to health management and care coordination is needed that will allow medical transitions between networks of care to become more centralized and allow for optimal recovery at all severity levels. This article summarizes the care systems available for the acute management of TBI from point of injury to stateside military treatment facilities. We describe TBI assessment, treatment, and overall coordination of care, including innovative clinical initiatives now used. PMID:20104395

  16. Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

    PubMed Central

    Iraji, Armin; Benson, Randall R.; Welch, Robert D.; O'Neil, Brian J.; Woodard, John L.; Imran Ayaz, Syed; Kulek, Andrew; Mika, Valerie; Medado, Patrick; Soltanian-Zadeh, Hamid; Liu, Tianming; Haacke, E. Mark

    2015-01-01

    Abstract Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were prospectively recruited from the emergency department of our local Level-1 trauma center for an advanced MRI scan at the acute stage. Sixteen age- and sex-matched controls were also recruited for comparison. Both group-based and individual-based independent component analysis of resting-state fMRI (rsfMRI) demonstrated reduced functional connectivity in both posterior cingulate cortex (PCC) and precuneus regions in comparison with controls, which is part of the default mode network (DMN). Further seed-based analysis confirmed reduced functional connectivity in these two regions and also demonstrated increased connectivity between these regions and other regions of the brain in mTBI. Seed-based analysis using the thalamus, hippocampus, and amygdala regions further demonstrated increased functional connectivity between these regions and other regions of the brain, particularly in the frontal lobe, in mTBI. Our data demonstrate alterations of multiple brain networks at the resting state, particularly increased functional connectivity in the frontal lobe, in response to brain concussion at the acute stage. Resting-state functional connectivity of the DMN could serve as a potential biomarker for improved detection of mTBI in the acute setting. PMID:25285363

  17. Preventing Flow-Metabolism Uncoupling Acutely Reduces Axonal Injury after Traumatic Brain Injury

    PubMed Central

    Mironova, Yevgeniya A.; Chen, Szu-Fu; Richards, Hugh K.; Pickard, John D.

    2012-01-01

    Abstract We have previously presented evidence that the development of secondary traumatic axonal injury is related to the degree of local cerebral blood flow (LCBF) and flow-metabolism uncoupling. We have now tested the hypothesis that augmenting LCBF in the acute stages after brain injury prevents further axonal injury. Data were acquired from rats with or without acetazolamide (ACZ) that was administered immediately following controlled cortical impact injury to increase cortical LCBF. Local cerebral metabolic rate for glucose (LCMRglc) and LCBF measurements were obtained 3 h post-trauma in the same rat via 18F-fluorodeoxyglucose and 14C-iodoantipyrine co-registered autoradiographic images, and compared to the density of damaged axonal profiles in adjacent sections, and in additional groups at 24 h used to assess different populations of injured axons stereologically. ACZ treatment significantly and globally elevated LCBF twofold above untreated-injured rats at 3 h (p<0.05), but did not significantly affect LCMRglc. As a result, ipsilateral LCMRglc:LCBF ratios were reduced by twofold to sham-control levels, and the density of β-APP-stained axons at 24 h was significantly reduced in most brain regions compared to the untreated-injured group (p<0.01). Furthermore, early LCBF augmentation prevented the injury-associated increase in the number of stained axons from 3–24 h. Additional robust stereological analysis of impaired axonal transport and neurofilament compaction in the corpus callosum and cingulum underlying the injury core confirmed the amelioration of β-APP axon density, and showed a trend, but no significant effect, on RMO14-positive axons. These data underline the importance of maintaining flow-metabolism coupling immediately after injury in order to prevent further axonal injury, in at least one population of injured axons. PMID:22321027

  18. Cerebral perfusion and neuropsychological follow up in mild traumatic brain injury: acute versus chronic disturbances?

    PubMed

    Metting, Zwany; Spikman, Jacoba M; Rödiger, Lars A; van der Naalt, Joukje

    2014-04-01

    In a subgroup of patients with mild traumatic brain injury (TBI) residual symptoms, interfering with outcome and return to work, are found. With neuropsychological assessment cognitive deficits can be demonstrated although the pathological underpinnings of these cognitive deficits are not fully understood. As the admission computed tomography (CT) often is normal, perfusion CT imaging may be a useful indicator of brain dysfunction in the acute phase after injury in these patients. In the present study, directly after admission perfusion CT imaging was performed in mild TBI patients with follow-up neuropsychological assessment in those with complaints and a normal non-contrast CT. Neuropsychological tests comprised the 15 Words test Immediate Recall, Trailmaking test part B, Zoo Map test and the FEEST, which were dichotomized into normal and abnormal. Perfusion CT results of patients with normal neuropsychological test scores were compared to those with abnormal test scores. In total eighteen patients were included. Those with an abnormal score on the Zoo Map test had a significant lower CBV in the right frontal and the bilateral parieto-temporal white matter. Patients with an abnormal score on the FEEST had a significant higher MTT in the bilateral frontal white matter and a significant decreased CBF in the left parieto-temporal grey matter. No significant relation between the perfusion CT parameters and the 15 Words test and the Trailmaking test part B was present. In conclusion, impairments in executive functioning and emotion perception assessed with neuropsychological tests during follow up were related to differences in cerebral perfusion at admission in mild TBI. The pathophysiological concept of these findings is discussed. PMID:24556319

  19. Clinical and imaging assessment of acute combat mild traumatic brain injury in Afghanistan

    PubMed Central

    Mac Donald, Christine L.; Rivet, Dennis; Ritter, John; May, Todd; Barefield, Maria; Duckworth, Josh; LaBarge, Donald; Asher, Dean; Drinkwine, Benjamin; Woods, Yvette; Connor, Michael; Brody, David L.

    2015-01-01

    Objective: To evaluate whether diffusion tensor imaging (DTI) will noninvasively reveal white matter changes not present on conventional MRI in acute blast-related mild traumatic brain injury (mTBI) and to determine correlations with clinical measures and recovery. Methods: Prospective observational study of 95 US military service members with mTBI enrolled within 7 days from injury in Afghanistan and 101 healthy controls. Assessments included Rivermead Post-Concussion Symptoms Questionnaire (RPCSQ), Post-Traumatic Stress Disorder Checklist Military (PCLM), Beck Depression Inventory (BDI), Balance Error Scoring System (BESS), Automated Neuropsychological Assessment Metrics (ANAM), conventional MRI, and DTI. Results: Significantly greater impairment was observed in participants with mTBI vs controls: RPCSQ (19.7 ± 12.9 vs 3.6 ± 7.1, p < 0.001), PCLM (32 ± 13.2 vs 20.9 ± 7.1, p < 0.001), BDI (7.4 ± 6.8 vs 2.5 ± 4.9, p < 0.001), and BESS (18.2 ± 8.4 vs 15.1 ± 8.3, p = 0.01). The largest effect size in ANAM performance decline was in simple reaction time (mTBI 74.5 ± 148.4 vs control −11 ± 46.6 milliseconds, p < 0.001). Fractional anisotropy was significantly reduced in mTBI compared with controls in the right superior longitudinal fasciculus (0.393 ± 0.022 vs 0.405 ± 0.023, p < 0.001). No abnormalities were detected with conventional MRI. Time to return to duty correlated with RPCSQ (r = 0.53, p < 0.001), ANAM simple reaction time decline (r = 0.49, p < 0.0001), PCLM (r = 0.47, p < 0.0001), and BDI (r = 0.36 p = 0.0005). Conclusions: Somatic, behavioral, and cognitive symptoms and performance deficits are substantially elevated in acute blast-related mTBI. Postconcussive symptoms and performance on measures of posttraumatic stress disorder, depression, and neurocognitive performance at initial presentation correlate with return-to-duty time. Although changes in fractional anisotropy are uncommon and subtle, DTI is more sensitive than conventional MRI in

  20. Magnetic resonance imaging of the brain in survivors of childhood acute lymphoblastic leukemia

    PubMed Central

    BADR, MOHAMED AHMED; HASSAN, TAMER HASAN; EL-GERBY, KHALED MOHAMED; LAMEY, MOHAMED EL-SAYED

    2013-01-01

    The issue of delayed neurological damage as a result of treatment is becoming increasingly important now that an increased number of children survive treatment for acute lymphoblastic leukemia (ALL). Following modification of the treatment protocols, severe symptomatic late effects are rare, and most adverse effects are detected by sensitive imaging methods such as magnetic resonance imaging (MRI) or by neuropsychological testing. In this study we aimed to determine the prevalence and characteristics of late central nervous system (CNS) damage by MRI and clinical examination in children treated for ALL. A cross-sectional study was carried out at the pediatric oncology unit of Zagazig University, Egypt, and included 25 patients who were consecutively enrolled and treated according to the modified Children’s Cancer Group (CCG) 1991 protocol for standard risk ALL and the modified CCG 1961 protocol for high-risk ALL and who had survived more than 5 years from the diagnosis. All relevant data were collected from patients’ medical records; particularly the data concerning the initial clinical presentation and initial brain imaging. All patients were subjected to thorough history and full physical examination with special emphasis on the neurological system. MRI of the brain was performed for all patients. The mean age of patients was 6.9±3.04 years at diagnosis and was 12.9±3.2 years at the time of study. The patients comprised 14 boys and 11 girls. Abnormal MRI findings were detected in six patients (24%). They were in the form of leukoencephalopathy in two patients (8%), brain atrophy in two patients (8%), old infarct in one patient (4%) and old hemorrhage in one patient (4%). The number of abnormal MRI findings was significantly higher in high-risk patients, patients who had CNS manifestations at diagnosis and patients who had received cranial irradiation. We concluded that cranial irradiation is associated with higher incidence of MRI changes in children

  1. Isolation of CA1 nuclear enriched fractions from hippocampal slices to study activity-dependent nuclear import of synapto-nuclear messenger proteins.

    PubMed

    Yuanxiang, Pingan; Bera, Sujoy; Karpova, Anna; Kreutz, Michael R; Mikhaylova, Marina

    2014-01-01

    Studying activity dependent protein expression, subcellular translocation, or phosphorylation is essential to understand the underlying cellular mechanisms of synaptic plasticity. Long-term potentiation (LTP) and long-term depression (LTD) induced in acute hippocampal slices are widely accepted as cellular models of learning and memory. There are numerous studies that use live cell imaging or immunohistochemistry approaches to visualize activity dependent protein dynamics. However these methods rely on the suitability of antibodies for immunocytochemistry or overexpression of fluorescence-tagged proteins in single neurons. Immunoblotting of proteins is an alternative method providing independent confirmation of the findings. The first limiting factor in preparation of subcellular fractions from individual tetanized hippocampal slices is the low amount of material. Second, the handling procedure is crucial because even very short and minor manipulations of living slices might induce activation of certain signaling cascades. Here we describe an optimized workflow in order to obtain sufficient quantity of nuclear enriched fraction of sufficient purity from the CA1 region of acute hippocampal slices from rat brain. As a representative example we show that the ERK1/2 phosphorylated form of the synapto-nuclear protein messenger Jacob actively translocates to the nucleus upon induction of LTP and can be detected in a nuclear enriched fraction from CA1 neurons. PMID:25145907

  2. Brain

    MedlinePlus

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  3. Sympathoadrenal Activation is Associated with Acute Traumatic Coagulopathy and Endotheliopathy in Isolated Brain Injury

    PubMed Central

    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

  4. Yueju Pill Rapidly Induces Antidepressant-Like Effects and Acutely Enhances BDNF Expression in Mouse Brain

    PubMed Central

    Xue, Wenda; Zhou, Xin; Yi, Nan; Jiang, Lihua; Tao, Weiwei; Wu, Runjie; Wang, Dan; Jiang, Jingjing; Ge, Xiaoyin; Wang, Yuyue; Wu, Haoxin; Chen, Gang

    2013-01-01

    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. PMID:23710213

  5. In vivo magnetic resonance imaging of acute brain inflammation using microparticles of iron oxide.

    PubMed

    McAteer, Martina A; Sibson, Nicola R; von Zur Muhlen, Constantin; Schneider, Jurgen E; Lowe, Andrew S; Warrick, Nicholas; Channon, Keith M; Anthony, Daniel C; Choudhury, Robin P

    2007-10-01

    Multiple sclerosis is a disease of the central nervous system that is associated with leukocyte recruitment and subsequent inflammation, demyelination and axonal loss. Endothelial vascular cell adhesion molecule-1 (VCAM-1) and its ligand, alpha4beta1 integrin, are key mediators of leukocyte recruitment, and selective inhibitors that bind to the alpha4 subunit of alpha4beta1 substantially reduce clinical relapse in multiple sclerosis. Urgently needed is a molecular imaging technique to accelerate diagnosis, to quantify disease activity and to guide specific therapy. Here we report in vivo detection of VCAM-1 in acute brain inflammation, by magnetic resonance imaging in a mouse model, at a time when pathology is otherwise undetectable. Antibody-conjugated microparticles carrying a large amount of iron oxide provide potent, quantifiable contrast effects that delineate the architecture of activated cerebral blood vessels. Their rapid clearance from blood results in minimal background contrast. This technology is adaptable to monitor the expression of endovascular molecules in vivo in various pathologies. PMID:17891147

  6. Impact of acute stress on human brain microstructure: An MR diffusion study of earthquake survivors.

    PubMed

    Chen, Long; Lui, Su; Wu, Qi-Zhu; Zhang, Wei; Zhou, Dong; Chen, Hua-Fu; Huang, Xiao-Qi; Kuang, Wei-Hong; Chan, Raymond C; Mechelli, Andrea; Gong, Qi-Yong

    2013-02-01

    A characterization of the impact of natural disasters on the brain of survivors is critical for a better understanding of posttraumatic responses and may inform the development of more effective early interventions. Here we report alterations in white matter microstructure in survivors soon after Wenchuan earthquake in China in 2008. Within 25 days after the Wenchuan earthquake, 44 healthy survivors were recruited and scanned on a 3T MR imaging system. The survivors were divided into two groups according to their self-rating anxiety scale (SAS) score, including the SAS(+) (SAS > 55 after correction) group and "SAS(-)" (SAS < 55 after correction) group. Thrity-two healthy volunteers were also recruited as control group before earthquake. Individual maps of fractional anisotropy (FA) were calculated and voxel-based analysis (VBA) was performed to allow the comparison between survivors and controls using ANCOVAs in SPM2. In addition, a correlation between SAS score and regional FA value was examined using Pearson's correlation analysis in SPSS 11.5. Compared with the healthy cohort, the whole group of 44 survivors showed significantly decreased FA values in the right prefrontal lobe, the parietal lobe, the basal ganglia, and the right parahippocampus. These effects did not appear to depend on self-rating anxiety. For the first time we provide evidence that acute trauma altered cerebral microstructure within the limbic system; furthermore, these alterations are evident shortly after the traumatic event, highlighting the need for early evaluation and intervention for trauma survivors. PMID:22042533

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

    PubMed Central

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

    2009-01-01

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

  8. Attenuation of Acute Phase Injury in Rat Intracranial Hemorrhage by Cerebrolysin that Inhibits Brain Edema and Inflammatory Response.

    PubMed

    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. PMID:26498936

  9. Acute neuro-endocrine profile and prediction of outcome after severe brain injury

    PubMed Central

    2013-01-01

    Object The aim of the study was to evaluate the early changes in pituitary hormone levels after severe traumatic brain injury (sTBI) and compare hormone levels to basic neuro-intensive care data, a systematic scoring of the CT-findings and to evaluate whether hormone changes are related to outcome. Methods Prospective study, including consecutive patients, 15–70 years, with sTBI, Glasgow Coma Scale (GCS) score ≤ 8, initial cerebral perfusion pressure > 10 mm Hg, and arrival to our level one trauma university hospital within 24 hours after head trauma (n = 48). Serum samples were collected in the morning (08–10 am) day 1 and day 4 after sTBI for analysis of cortisol, growth hormone (GH), prolactin, insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), follicular stimulating hormone (FSH), luteinizing hormone (LH), testosterone and sex hormone-binding globulin (SHBG) (men). Serum for cortisol and GH was also obtained in the evening (17–19 pm) at day 1 and day 4. The first CT of the brain was classified according to Marshall. Independent staff evaluated outcome at 3 months using GOS-E. Results Profound changes were found for most pituitary-dependent hormones in the acute phase after sTBI, i.e. low levels of thyroid hormones, strong suppression of the pituitary-gonadal axis and increased levels of prolactin. The main findings of this study were: 1) A large proportion (54% day 1 and 70% day 4) of the patients showed morning s-cortisol levels below the proposed cut-off levels for critical illness related corticosteroid insufficiency (CIRCI), i.e. <276 nmol/L (=10 ug/dL), 2) Low s-cortisol was not associated with higher mortality or worse outcome at 3 months, 3) There was a significant association between early (day 1) and strong suppression of the pituitary-gonadal axis and improved survival and favorable functional outcome 3 months after sTBI, 4) Significantly lower levels of fT3

  10. The impact of physical therapy in patients with severe traumatic brain injury during acute and post-acute rehabilitation according to coma duration

    PubMed Central

    Lendraitienė, Eglė; Petruševičienė, Daiva; Savickas, Raimondas; Žemaitienė, Ieva; Mingaila, Sigitas

    2016-01-01

    [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. PMID:27512262

  11. The impact of physical therapy in patients with severe traumatic brain injury during acute and post-acute rehabilitation according to coma duration.

    PubMed

    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. PMID:27512262

  12. Magnetic resonance analysis of the effects of acute ammonia intoxication on rat brain. Role of NMDA receptors.

    PubMed

    Cauli, Omar; López-Larrubia, Pilar; Rodrigues, Tiago B; Cerdán, Sebastián; Felipo, Vicente

    2007-11-01

    Acute ammonia intoxication leads to rapid death, which is prevented by blocking N-methyl-d-aspartate (NMDA) receptors. The subsequent mechanisms leading to death remain unclear. Brain edema seems an important step. The aim of this work was to study the effects of acute ammonia intoxication on different cerebral parameters in vivo using magnetic resonance and to assess which effects are mediated by NMDA receptors activation. To assess edema induction, we injected rats with ammonium acetate and measured apparent diffusion coefficient (ADC) in 16 brain areas. We also analyzed the effects on T1, T2, and T2* maps and whether these effects are prevented by blocking NMDA receptors. The effects of acute ammonia intoxication are different in different brain areas. T1 relaxation time is reduced in eight areas. T2 relaxation time is reduced only in ventral thalamus and globus pallidus. ADC values increased in hippocampus, caudate-putamen, substantia nigra and cerebellar cortex, reflecting vasogenic edema. ADC decreased in hypothalamus, reflecting cytotoxic edema. Myo-inositol increased in cerebellum and substantia nigra, reflecting vasogenic edema. N-acetyl-aspartate decreased in cerebellum, reflecting neuronal damage. Changes in N-acetyl-aspartate, T1 and T2 are prevented by blocking NMDA receptors with MK-801 while changes in ADC or myo-inositol (induction of edema) are not. PMID:17727627

  13. Cinnamon intake alleviates the combined effects of dietary-induced insulin resistance and acute stress on brain mitochondria.

    PubMed

    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. PMID:26878796

  14. Brain activity monitoring by compressed spectral array during deep hypothermic circulatory arrest in acute aortic dissection surgery

    PubMed Central

    Budniak, Wiktor; Buczkowski, Piotr; Perek, Bartłomiej; Walczak, Maciej; Tomczyk, Jadwiga; Katarzyński, Sławomir; Jemielity, Marek

    2014-01-01

    Introduction Monitoring the central nervous system during aortic dissection repair may improve the understanding of the intraoperative changes related to its bioactivity. Aim The aim of the study was to evaluate the influence of deep hypothermia on intraoperative brain bioactivity measured by the compressed spectral array (CSA) method and to assess the influence of the operations on postoperative cognitive function. Material and methods The study enrolled 40 patients (31 men and 9 women) at the mean age of 60.2 ± 8.6 years, diagnosed with acute aortic dissection. They underwent emergency operations in deep hypothermic circulatory arrest (DHCA). During the operations, brain bioactivity was monitored with the compressed spectral array method. Results There were no intraoperative deaths. Electrocerebral silence during DHCA was observed in 31 patients (74%). The lowest activity was observed during DHCA: it was 0.01 ± 0.05 nW in the left hemisphere and 0.01 ± 0.03 nW in the right hemisphere. The postoperative results of neurological tests deteriorated statistically significantly (26.9 ± 1.7 points vs. 22.0 ± 1.7 points; p < 0.001), especially among patients who exhibited brain activity during DHCA. Conclusions The compressed spectral array method is clinically useful in monitoring brain bioactivity during emergency operations of acute aortic dissections. Electrocerebral silence occurs in 75% of patients during DHCA. The cognitive function of patients deteriorates significantly after operations with DHCA. PMID:26336458

  15. The theory of interface slicing

    NASA Technical Reports Server (NTRS)

    Beck, Jon

    1993-01-01

    Interface slicing is a new tool which was developed to facilitate reuse-based software engineering, by addressing the following problems, needs, and issues: (1) size of systems incorporating reused modules; (2) knowledge requirements for program modification; (3) program understanding for reverse engineering; (4) module granularity and domain management; and (5) time and space complexity of conventional slicing. The definition of a form of static program analysis called interface slicing is addressed.

  16. Acute high-intensity exercise-induced cognitive enhancement and brain-derived neurotrophic factor in young, healthy adults.

    PubMed

    Hwang, Jungyun; Brothers, R Matthew; Castelli, Darla M; Glowacki, Elizabeth M; Chen, Yen T; Salinas, Mandy M; Kim, Jihoon; Jung, Yeonhak; Calvert, Hannah G

    2016-09-01

    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. PMID:27450438

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

    PubMed Central

    Teng, Sophie X.

    2014-01-01

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

  18. Brain-derived neurotrophic factor acutely inhibits AMPA-mediated currents in developing sensory relay neurons.

    PubMed

    Balkowiec, A; Kunze, D L; Katz, D M

    2000-03-01

    Brain-derived neurotrophic factor (BDNF) is expressed by many primary sensory neurons that no longer require neurotrophins for survival, indicating that BDNF may be used as a signaling molecule by the afferents themselves. Because many primary afferents also express glutamate, we investigated the possibility that BDNF modulates glutamatergic AMPA responses of newborn second-order sensory relay neurons. Perforated-patch, voltage-clamp recordings were made from dissociated neurons of the brainstem nucleus tractus solitarius (nTS), a region that receives massive primary afferent input from BDNF-containing neurons in the nodose and petrosal cranial sensory ganglia. Electrophysiological analysis was combined in some experiments with anterograde labeling of primary afferent terminals to specifically analyze responses of identified second-order neurons. Our data demonstrate that BDNF strongly inhibits AMPA-mediated currents in a large subset of nTS cells. Specifically, AMPA responses were either completely abolished or markedly inhibited by BDNF in 73% of postnatal day (P0) cells and in 82% of identified P5 second-order sensory relay neurons. This effect of BDNF is mimicked by NT-4, but not NGF, and blocked by the Trk tyrosine kinase inhibitor K252a, consistent with a requirement for TrkB receptor activation. Moreover, analysis of TrkB expression in culture revealed a close correlation between the percentage of nTS neurons in which BDNF inhibits AMPA currents and the percentage of neurons that exhibit TrkB immunoreactivity. These data document a previously undefined mechanism of acute modulation of AMPA responses by BDNF and indicate that BDNF may regulate glutamatergic transmission at primary afferent synapses. PMID:10684891

  19. Risk taking in hospitalized patients with acute and severe traumatic brain injury.

    PubMed

    Fecteau, Shirley; Levasseur-Moreau, Jean; García-Molina, Alberto; Kumru, Hatiche; Vergara, Raúl Pelayo; Bernabeu, Monste; Roig, Teresa; Pascual-Leone, Alvaro; Tormos, José Maria

    2013-01-01

    Rehabilitation can improve cognitive deficits observed in patients with traumatic brain injury (TBI). However, despite rehabilitation, the ability of making a choice often remains impaired. Risk taking is a daily activity involving numerous cognitive processes subserved by a complex neural network. In this work we investigated risk taking using the Balloon Analogue Risk Task (BART) in patients with acute TBI and healthy controls. We hypothesized that individuals with TBI will take less risk at the BART as compared to healthy individuals. We also predicted that within the TBI group factors such as the number of days since the injury, severity of the injury, and sites of the lesion will play a role in risk taking as assessed with the BART. Main findings revealed that participants with TBI displayed abnormally cautious risk taking at the BART as compared to healthy subjects. Moreover, healthy individuals showed increased risk taking throughout the task which is in line with previous work. However, individuals with TBI did not show this increased risk taking during the task. We also investigated the influence of three patients' characteristics on their performance at the BART: Number of days post injury, Severity of the head injury, and Status of the frontal lobe. Results indicate that performance at the BART was influenced by the number of days post injury and the status of the frontal lobe, but not by the severity of the head injury. Reported findings are encouraging for risk taking seems to naturally improve with time postinjury. They support the need of conducting longitudinal prospective studies to ultimately identify impaired and intact cognitive skills that should be trained postinjury. PMID:24386232

  20. Traditional reactive carbonyl scavengers do not prevent the carbonylation of brain proteins induced by acute glutathione depletion.

    PubMed

    Zheng, J; Bizzozero, O A

    2010-03-01

    This study investigated the effect of reactive carbonyl species (RCS)-trapping agents on the formation of protein carbonyls during depletion of brain glutathione (GSH). To this end, rat brain slices were incubated with the GSH-depletor diethyl maleate in the absence or presence of chemically different RCS scavengers (hydralazine, methoxylamine, aminoguanidine, pyridoxamine, carnosine, taurine and z-histidine hydrazide). Despite their strong reactivity towards the most common RCS, none of the scavengers tested, with the exception of hydralazine, prevented protein carbonylation. These findings suggest that the majority of protein-associated carbonyl groups in this oxidative stress paradigm do not derive from stable lipid peroxidation products like malondialdehyde (MDA), acrolein and 4-hydroxynonenal (4-HNE). This conclusion was confirmed by the observation that the amount of MDA-, acrolein- and 4-HNE-protein adducts does not increase upon GSH depletion. Additional studies revealed that the efficacy of hydralazine at preventing carbonylation was due to its ability to reduce oxidative stress, most likely by inhibiting mitochondrial production of superoxide and/or by scavenging lipid free radicals. PMID:20001647

  1. Transistor needle chip for recording in brain tissue

    NASA Astrophysics Data System (ADS)

    Felderer, Florian; Fromherz, Peter

    2011-07-01

    We report on a proof-of-principle experiment for the direct interfacing of transistors with intact brain tissue. A transistor needle chip (TNC) with a TiO2 surface is fabricated from a silicon-on-insulator wafer and impaled into an acute brain slice cut from hippocampus of the rat. While stimulating the Schaffer collateral, a local field potential is recorded in stratum radiatum of the CA1 region with field-effect transistors in the central part of the slice where the tissue is not damaged by the cutting process. After the impalement, the signal amplitude is small. Within an hour, it increases to a stable level around -2 mV as is recorded with a conventional micropipette electrode. The recovery indicates that the tissue is able to adapt to the impaled chip. Upon repeated impalements at the same position, the large signal is observed without delay. A profile of the transistor signal across the slice is due to the boundary conditions of a brain slice with both surfaces held near ground potential. The experiments with the TNC prototype are a basis for the development of silicon needle chips with a large multi-transistor array (MTA) for applications in brain-computer interfacing.

  2. Acute deep brain stimulation in the thalamic reticular nucleus protects against acute stress and modulates initial events of adult hippocampal neurogenesis.

    PubMed

    Magdaleno-Madrigal, Víctor Manuel; Pantoja-Jiménez, Christopher Rodrigo; Bazaldúa, Adrián; Fernández-Mas, Rodrigo; Almazán-Alvarado, Salvador; Bolaños-Alejos, Fernanda; Ortíz-López, Leonardo; Ramírez-Rodriguez, Gerardo Bernabé

    2016-11-01

    Deep brain stimulation (DBS) is used as an alternative therapeutic procedure for pharmacoresistant psychiatric disorders. Recently the thalamic reticular nucleus (TRN) gained attention due to the description of a novel pathway from the amygdala to this nucleus suggesting that may be differentially disrupted in mood disorders. The limbic system is implicated in the regulation of these disorders that are accompanied by neuroplastic changes. The hippocampus is highly plastic and shows the generation of new neurons, process affected by stress but positively regulated by antidepressant drugs. We explored the impact of applying acute DBS to the TRN (DBS-TRN) in male Wistar rats exposed to acute stress caused by the forced-swim Porsolt's test (FST) and on initial events of hippocampal neurogenesis. After the first session of forced-swim, rats were randomly subdivided in a DBS-TRN and a Sham group. Stimulated rats received 10min of DBS, thus the depressant-like behavior reflected as immobility was evaluated in the second session of forced-swim. Locomotricity was evaluated in the open field test. Cell proliferation and doublecortin-associated cells were quantified in the hippocampus of other cohorts of rats. No effects of electrode implantation were found in locomotricity. Acute DBS-TRN reduced immobility in comparison to the Sham group (p<0.001). DBS-TRN increased cell proliferation (Ki67 or BrdU-positive cells; p=0.02, p=0.02) and the number of doublecortin-cells compared to the Sham group (p<0.02). Similar effects were found in rats previously exposed to the first session of forced-swim. Our data could suggest that TRN brain region may be a promising target for DBS to treat intractable depression. PMID:27435420

  3. Effects of acute and chronic ketoconazole administration on hypothalamo--pituitary--adrenal axis activity and brain corticotropin-releasing hormone.

    PubMed

    Smagin, Gennady N; Goeders, Nick E

    2004-11-01

    We have been investigating the effects of ketoconazole on cocaine reward in rats for several years now. However, we recently confirmed that ketoconazole-induced changes in cocaine self-administration and reinstatement do not always correspond with decreases in plasma corticosterone, which suggests that other mechanisms must be underlying the behavioral effects that we observe. This experiment was therefore designed to determine the effects of acute, repeated and chronic ketoconazole administration on corticotropin-releasing hormone (CRH) content in hypothalamic and extra-hypothalamic brain sites in rats following the same dosing regimen that we use in our behavioral studies. Although ketoconazole significantly increased the concentration of ACTH in trunk blood, there were no significant effects on plasma cortisol, corticosterone or testosterone. There was also a significant increase in CRH content in the median eminence after the acute administration of ketoconazole that just failed to reach statistical significance following repeated or chronic administration. However, acute, repeated and chronic treatment with ketoconazole each significantly increased CRH content in the medial prefrontal cortex (MPC), but did not consistently affect the peptide in any other brain region studied. Since the MPC and CRH have been implicated in the neurobiology of cocaine, CRH-induced alterations in dopaminergic neurotransmission may play an important role in this peptide's effects on cocaine responsiveness. Taken together with the results from previous studies, these data suggest that ketoconazole may affect cocaine reward, at least in part, through interactions with dopamine and CRH within the MPC. PMID:15288701

  4. The Acute Phase of Mild Traumatic Brain Injury Is Characterized by a Distance-Dependent Neuronal Hypoactivity

    PubMed Central

    Johnstone, Victoria P.A.; Shultz, Sandy R.; Yan, Edwin B.; O'Brien, Terence J.

    2014-01-01

    Abstract The consequences of mild traumatic brain injury (TBI) on neuronal functionality are only now being elucidated. We have now examined the changes in sensory encoding in the whisker-recipient barrel cortex and the brain tissue damage in the acute phase (24 h) after induction of TBI (n=9), with sham controls receiving surgery only (n=5). Injury was induced using the lateral fluid percussion injury method, which causes a mixture of focal and diffuse brain injury. Both population and single cell neuronal responses evoked by both simple and complex whisker stimuli revealed a suppression of activity that decreased with distance from the locus of injury both within a hemisphere and across hemispheres, with a greater extent of hypoactivity in ipsilateral barrel cortex compared with contralateral cortex. This was coupled with an increase in spontaneous output in Layer 5a, but only ipsilateral to the injury site. There was also disruption of axonal integrity in various regions in the ipsilateral but not contralateral hemisphere. These results complement our previous findings after mild diffuse-only TBI induced by the weight-drop impact acceleration method where, in the same acute post-injury phase, we found a similar depth-dependent hypoactivity in sensory cortex. This suggests a common sequelae of events in both diffuse TBI and mixed focal/diffuse TBI in the immediate post-injury period that then evolve over time to produce different long-term functional outcomes. PMID:24927383

  5. Acute Neuroimmune Modulation Attenuates the Development of Anxiety-Like Freezing Behavior in an Animal Model of Traumatic Brain Injury

    PubMed Central

    Rodgers, Krista M.; Bercum, Florencia M.; McCallum, Danielle L.; Rudy, Jerry W.; Frey, Lauren C.; Johnson, Kirk W.; Watkins, Linda R.

    2012-01-01

    Abstract Chronic anxiety is a common and debilitating result of traumatic brain injury (TBI) in humans. While little is known about the neural mechanisms of this disorder, inflammation resulting from activation of the brain's immune response to insult has been implicated in both human post-traumatic anxiety and in recently developed animal models. In this study, we used a lateral fluid percussion injury (LFPI) model of TBI in the rat and examined freezing behavior as a measure of post-traumatic anxiety. We found that LFPI produced anxiety-like freezing behavior accompanied by increased reactive gliosis (reflecting neuroimmune inflammatory responses) in key brain structures associated with anxiety: the amygdala, insula, and hippocampus. Acute peri-injury administration of ibudilast (MN166), a glial cell activation inhibitor, suppressed both reactive gliosis and freezing behavior, and continued neuroprotective effects were apparent several months post-injury. These results support the conclusion that inflammation produced by neuroimmune responses to TBI play a role in post-traumatic anxiety, and that acute suppression of injury-induced glial cell activation may have promise for the prevention of post-traumatic anxiety in humans. PMID:22435644

  6. Brain-derived neurotrophic factor serum concentrations in acute depressive patients increase during lithium augmentation of antidepressants.

    PubMed

    Ricken, Roland; Adli, Mazda; Lange, Claudia; Krusche, Esther; Stamm, Thomas J; Gaus, Sebastian; Koehler, Stephan; Nase, Sarah; Bschor, Tom; Richter, Christoph; Steinacher, Bruno; Heinz, Andreas; Rapp, Michael A; Borgwardt, Stefan; Hellweg, Rainer; Lang, Undine E

    2013-12-01

    In recent years, lithium has proved an effective augmentation strategy of antidepressants in both acute and treatment-resistant depression. Neuroprotective and procognitive effects of lithium have been evidenced. Brain-derived neurotrophic factor (BDNF) has been shown to play a key role in the pathophysiology of several neurological and psychiatric disorders. The BDNF hypothesis of depression postulates that a loss of BDNF is directly involved in the pathophysiology of depression, and its restoration may underlie the therapeutic efficacy of antidepressant treatments. Brain-derived neurotrophic factor serum concentrations were measured in a total of 83 acutely depressed patients before and after 4 weeks of lithium augmentation. A significant BDNF increase has been found during treatment (F2,81 = 5.04, P < 0.05). Brain-derived neurotrophic factor concentrations at baseline correlated negatively with relative Hamilton Depression Scale change after treatment with lithium (n = 83; r = -0.23; P < 0.05). This is the first study showing that lithium augmentation of an antidepressant strategy can increase BDNF serum concentrations. Our study replicates previous findings showing that serum BDNF levels in patients with depressive episodes increase during effective antidepressant treatment. Further studies are needed to separate specific effects of different antidepressants on BDNF concentration and address potential BDNF downstream mechanisms. PMID:24018547

  7. Trafficking of astrocytic vesicles in hippocampal slices

    SciTech Connect

    Potokar, Maja; Kreft, Marko; Celica Biomedical Center, Technology Park 24, 1000 Ljubljana ; Lee, So-Young; Takano, Hajime; Haydon, Philip G.; Zorec, Robert; Celica Biomedical Center, Technology Park 24, 1000 Ljubljana

    2009-12-25

    The increasingly appreciated role of astrocytes in neurophysiology dictates a thorough understanding of the mechanisms underlying the communication between astrocytes and neurons. In particular, the uptake and release of signaling substances into/from astrocytes is considered as crucial. The release of different gliotransmitters involves regulated exocytosis, consisting of the fusion between the vesicle and the plasma membranes. After fusion with the plasma membrane vesicles may be retrieved into the cytoplasm and may continue to recycle. To study the mobility implicated in the retrieval of secretory vesicles, these structures have been previously efficiently and specifically labeled in cultured astrocytes, by exposing live cells to primary and secondary antibodies. Since the vesicle labeling and the vesicle mobility properties may be an artifact of cell culture conditions, we here asked whether the retrieving exocytotic vesicles can be labeled in brain tissue slices and whether their mobility differs to that observed in cell cultures. We labeled astrocytic vesicles and recorded their mobility with two-photon microscopy in hippocampal slices from transgenic mice with fluorescently tagged astrocytes (GFP mice) and in wild-type mice with astrocytes labeled by Fluo4 fluorescence indicator. Glutamatergic vesicles and peptidergic granules were labeled by the anti-vesicular glutamate transporter 1 (vGlut1) and anti-atrial natriuretic peptide (ANP) antibodies, respectively. We report that the vesicle mobility parameters (velocity, maximal displacement and track length) recorded in astrocytes from tissue slices are similar to those reported previously in cultured astrocytes.

  8. A method for measuring brain partial pressure of oxygen in unanesthetized unrestrained subjects: the effect of acute and chronic hypoxia on brain tissue PO2

    PubMed Central

    Ortiz-Prado, E.; Natah, Siraj; Srinivasan, Sathyanarayanan; Dunn, Jeff F.

    2011-01-01

    The level of tissue oxygenation provides information related to the balance between oxygen delivery, oxygen utilization, tissue reactivity and morphology during physiological conditions. Tissue partial pressure of oxygen (PtO2) is influenced by the use of anesthesia or restraint. These factors may impact the absolute level of PtO2. In this study we present a novel fibre optic method to measure brain PtO2. This method can be used in unanesthetized, unrestrained animals, provides absolute values for PO2, has a stable calibration, does not consume oxygen and is MRI compatible. Brain PtO2 was studied during acute hypoxia, as well as before and after 28 days of high altitude acclimatization. A sensor was chronically implanted in the frontal cortex of 8 Wistar rats. It is comprised of a fiber optic probe with a tip containing material that fluoresces with an oxygen dependent lifetime. Brain PtO2 declines by 80% and 76% pre- and post-acclimatization respectively, when the fraction of inspired oxygen declines from 0.21 to 0.08. In addition, a linear relationship between brain PtO2 and inspired O2 levels was demonstrated r2=0.98 and r2=0.99 (pre- and post-acclimatization). Hypoxia acclimatization resulted in an increase in the overall brain PtO2 by approximately 35%. This paper demonstrates the use of a novel chronically implanted fibre optic based sensor for measuring absolute PtO2. It shows a very strong linear relationship in awake animals between inspired O2 and tissue O2, and shows that there is a proportional increase in PtO2 over a range of inspired values after exposure to chronic hypoxia. PMID:20817029

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

    PubMed

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

    2015-01-01

    Previous studies have confirmed that traumatic brain injury (TBI) can induce general adaptation syndrome (GAS), which subsequently results in myocardial dysfunction and damage in some patients with acute TBI; this condition is also termed as cerebral-cardiac syndrome. However, most clinicians ignore the detection and treatment of myocardial dysfunction, and instead concentrate only on the serious neural damage that is observed in acute TBI, which is one of the most important fatal factors. Therefore, clarification is urgently needed regarding the relationship between TBI and myocardial dysfunction. In the present study, we evaluated 18 canine models of acute TBI, by using real-time myocardial contrast echocardiography and strain rate imaging to accurately evaluate myocardial function and regional microcirculation, including the strain rate of the different myocardial segments, time-amplitude curves, mean ascending slope of the curve, and local myocardial blood flow. Our results suggest that acute TBI often results in cerebral-cardiac syndrome, which rapidly progresses to the serious stage within 3 days. This study is the first to provide comprehensive ultrasonic characteristics of cerebral-cardiac syndrome in an animal model of TBI. PMID:26064794

  10. Acute stress exposure preceding transient global brain ischemia exacerbates the decrease in cortical remodeling potential in the rat retrosplenial cortex.

    PubMed

    Kutsuna, Nobuo; Yamashita, Akiko; Eriguchi, Takashi; Oshima, Hideki; Suma, Takeshi; Sakatani, Kaoru; Yamamoto, Takamitsu; Yoshino, Atsuo; Katayama, Yoichi

    2014-01-01

    Doublecortin (DCX)-immunoreactive (-ir) cells are candidates that play key roles in adult cortical remodeling. We have previously reported that DCX-ir cells decrease after stress exposure or global brain ischemia (GBI) in the cingulate cortex (Cg) of rats. Herein, we investigate whether the decrease in DCX-ir cells is exacerbated after GBI due to acute stress exposure preconditioning. Twenty rats were divided into 3 groups: acute stress exposure before GBI (Group P), non-stress exposure before GBI (Group G), and controls (Group C). Acute stress or GBI was induced by a forced swim paradigm or by transient bilateral common carotid artery occlusion, respectively. DCX-ir cells were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). The number of DCX-ir cells per unit area (mm(2)) decreased after GBI with or without stress preconditioning in the ACC and in the RS (ANOVA followed by a Tukey-type test, P<0.001). Moreover, compared to Group G, the number in Group P decreased significantly in RS (P<0.05), though not significantly in ACC. Many of the DCX-ir cells were co-localized with the GABAergic neuronal marker parvalbumin. The present study indicates that cortical remodeling potential of GABAergic neurons of Cg decreases after GBI, and moreover, the ratio of the decrease is exacerbated by acute stress preconditioning in the RS. PMID:24257103

  11. Reconstituted high-density lipoproteins acutely reduce soluble brain Aβ levels in symptomatic APP/PS1 mice.

    PubMed

    Robert, Jérôme; Stukas, Sophie; Button, Emily; Cheng, Wai Hang; Lee, Michael; Fan, Jianjia; Wilkinson, Anna; Kulic, Iva; Wright, Samuel D; Wellington, Cheryl L

    2016-05-01

    Many lines of evidence suggest a protective role for high-density lipoprotein (HDL) and its major apolipoprotein (apo)A-I in Alzheimer's Disease (AD). HDL/apoA-I particles are produced by the liver and intestine and, in addition to removing excess cholesterol from the body, are increasingly recognized to have vasoprotective functions. Here we tested the ability of reconstituted HDL (rHDL) consisting of human apoA-I reconstituted with soy phosphatidylcholine for its ability to lower amyloid beta (Aβ) levels in symptomatic APP/PS1 mice, a well-characterized preclinical model of amyloidosis. Animals were treated intravenously either with four weekly doses (chronic study) or a single dose of 60mg/kg of rHDL (acute study). The major finding of our acute study is that soluble brain Aβ40 and Aβ42 levels were significantly reduced within 24h of a single dose of rHDL. By contrast, no changes were observed in our chronic study with respect to soluble or deposited Aβ levels in animals assessed 7days after the final weekly dose of rHDL, suggesting that beneficial effects diminish as rHDL is cleared from the body. Further, rHDL-treated animals showed no change in amyloid burden, cerebrospinal fluid (CSF) Aβ levels, neuroinflammation, or endothelial activation in the chronic study, suggesting that the pathology-modifying effects of rHDL may indeed be acute and may be specific to the soluble Aβ pool. That systemic administration of rHDL can acutely modify brain Aβ levels provides support for further investigation of the therapeutic potential of apoA-I-based agents for AD. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26454209

  12. Expression of heat shock protein (HSP 72 kD) during acute methamphetamine intoxication depends on brain hyperthermia: neurotoxicity or neuroprotection?

    PubMed Central

    Kiyatkin, Eugene A.; Sharma, Hari S.

    2011-01-01

    In the present study, light and electron microscopy were used to examine heat shock protein (HSP 72kD) expression during acute methamphetamine (METH) intoxication in rats and evaluate its relationships with brain temperature and alterations in a number of other histochemical and morphological parameters. Freely moving rats received METH at the same dose (9 mg/kg, sc) but at different ambient temperatures (23 and 29°C), showing a wide range of brain temperature elevations (37.6–42.5°C); brains were taken for histochemical and morphological evaluations at peak of brain temperature increase. We found that acute METH intoxication induces massive and wise-spread HSP expression in neural and glial cells examined in details in the cortex, hippocampus, thalamus, and hypothalamus. In each of these structures, the number of HSP-positive cells tightly correlated with brain temperature elevation. The changes in HSP immunoreactivity were also tightly related to alterations in permeability of the blood-brain barrier, acute glial activation and brain edema assessed by albumin and GFAP immunoreactivity and measuring tissue water content, respectively. While robust and generalized HSP production normally appears to be the part of an adaptive brain response associated with METH-induced metabolic activation, activation of this protective mechanism has its natural limits and could not counteract the damaging effects of oxidative stress, high temperature and edema – the leading factors of METH-induced neurotoxicity. PMID:20931246

  13. Effect of acute progestational hypoxia on the content of biogenic amines in the brain of albino rat pups: Peptide correction.

    PubMed

    Maslova, M V; Graf, A V; Sokolova, N A; Goncharenko, E N; Shestakova, S V; Kudryashova, N Yu; Andreeva, L A

    2003-08-01

    We studied the effect of exposure to acute hypobaric hypoxia in the progestational period on the content of biogenic amines in the brainstem and cerebral cortex in rat pups of different age. The possibility of correcting hypoxia-induced changes with regulatory peptides was evaluated. We found that early antenatal hypoxia disturbs maturation of catecholaminergic systems in the brain. It should be emphasized that the differences from the control varied depending on the age of rat pups. Single intranasal administration of Semax heptapeptides and beta-casomorphine-7 to pregnant females prevented changes in the content of biogenic amines in CNS of the offspring during postnatal ontogeny. PMID:14631488

  14. Diagnostic Value of Elevated D-Dimer Level in Venous Thromboembolism in Patients With Acute or Subacute Brain Lesions

    PubMed Central

    Kim, Yeon Jin; Im, Sun; Jang, Yong Jun; Park, So Young; Sohn, Dong Gyun

    2015-01-01

    Objective To define the risk factors that influence the occurrence of venous thromboembolism (VTE) in patients with acute or subacute brain lesions and to determine the usefulness of D-dimer levels for VTE screening of these patients. Methods Medical data from January 2012 to December 2013 were retrospectively reviewed. Mean D-dimer levels in those with VTE versus those without VTE were compared. Factors associated with VTE were analyzed and the odds ratios (ORs) were calculated. The D-dimer cutoff value for patients with hemiplegia was defined using a receiver operating characteristic (ROC) curve. Results Of 117 patients with acute or subacute brain lesions, 65 patients with elevated D-dimer levels (mean, 5.1±5.8 mg/L; positive result >0.55 mg/L) were identified. Logistic regression analysis showed that the risk of VTE was 3.9 times higher in those with urinary tract infections (UTIs) (p=0.0255). The risk of VTE was 4.5 times higher in those who had recently undergone surgery (p=0.0151). Analysis of the ROC showed 3.95 mg/L to be the appropriate D-dimer cutoff value for screening for VTE (area under the curve [AUC], 0.63; 95% confidence interval [CI], 0.5-0.8) in patients with acute or subacute brain lesions. This differs greatly from the conventional D-dimer cutoff value of 0.55 mg/L. D-dimer levels less than 3.95 mg/L in the absence of surgery showed a negative predictive value of 95.8% (95% CI, 78.8-99.8). Conclusion Elevated D-dimer levels alone have some value in VTE diagnosis. However, the concomitant presence of UTI or a history of recent surgery significantly increased the risk of VTE in patients with acute or subacute brain lesions. Therefore, a different D-dimer cutoff value should be applied in these cases. PMID:26798616

  15. [Forensic medical assessment of vascular and neuronal lesions in the brain associated with acute blood loss and anemia].

    PubMed

    Indiaminov, S I

    2010-01-01

    Brain tissues available for examination in the present study were obtained from 30 subjects who died from the blood loss following injuries to blood vessels and internal organs inflicted by sharp objects. The study revealed variable character of tanatogenesis induced by acute blood loss and anemia. Tanatogenesis associated with injuries to the heart and major blood vessels is most likely due to the deficiency of blood in the microcirculatory system developing in the terminal period. The main tanatogenic factors in subjects with multiple injuries to peripheral vessels are vascular dystonia and abnormal rheological properties of blood. PMID:20394188

  16. Ethyl 3,4-dihydroxybenzoate (EDHB): a prolyl hydroxylase inhibitor attenuates acute hypobaric hypoxia mediated vascular leakage in brain.

    PubMed

    Singh, Deependra Pratap; Nimker, Charu; Paliwal, Piyush; Bansal, Anju

    2016-07-01

    Sudden exposure to altitude hypoxia is responsible for acute mountain sickness (AMS) in un-acclimatized persons. If not treated in time, AMS can worsen and leads to high altitude cerebral edema, which can be fatal. Present study explores the efficacy of ethyl 3,4-dihydroxybenzoate (EDHB), a prolyl hydroxylase enzyme inhibitor, in modulating adaptive responses to hypobaric hypoxia (HH) in rat brain. Male Sprague-Dawley rats treated with EDHB (75 mg/kg for 3 days), were subjected to acute HH exposure at 9144 m (30,000 ft) for 5 h. Animals were assessed for transvascular leakage and edema formation in brain and role of key inflammatory markers along with hypoxia responsive genes. HH stress increased transvascular permeability and edema formation in conjunction with upregulation of nuclear factor-κB (NF-κB) and its regulated proteins. There was surge in pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, interferon-γ, monocyte chemoattractant protein-1 and decrement in anti-inflammatory cytokine interleukin-10. Further, upregulation of vascular endothelial growth factor (VEGF), a vascular permeability marker and down-regulation of antioxidant and anti-inflammatory proteins hemoxygenase (HO-1) and metallothionein (MT-1) was also observed under hypoxia. EDHB supplementation effectively scaled down HH induced cerebral edema with concomitant downregulation of brain NF-κB expression. There was significant curtailment of pro-inflammatory cytokines and cell adhesion molecules. There was significant downregulation of permeability factor VEGF by EDHB with concomitant increment in hypoxia inducible factor (HIF1α) and anti-inflammatory proteins HO-1 and MT-1 compared to HH control thus accentuating the potential of EDHB as effective hypoxic preconditioning agent in ameliorating HH mediated injury in brain. PMID:26649730

  17. Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain.

    PubMed

    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. PMID:24338618

  18. Proinflammatory Cytokine, Chemokine, and Cellular Adhesion Molecule Expression during the Acute Phase of Experimental Brain Abscess Development

    PubMed Central

    Kielian, Tammy; Hickey, William F.

    2000-01-01

    Brain abscess represents the infectious disease sequelae associated with the influx of inflammatory cells and activation of resident parenchymal cells in the central nervous system. However, the immune response leading to the establishment of a brain abscess remains poorly defined. In this study, we have characterized cytokine and chemokine expression in an experimental brain abscess model in the rat during the acute stage of abscess development. RNase protection assay revealed the induction of the proinflammatory cytokines interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor-α as early as 1 to 6 hours after Staphylococcus aureus exposure. Evaluation of chemokine expression by reverse transcription-polymerase chain reaction demonstrated enhanced levels of the CXC chemokine KC 24 hours after bacterial exposure, which correlated with the appearance of neutrophils in the abscess. In addition, two CC chemokines, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1α were induced within 24 hours after S. aureus exposure and preceded the influx of macrophages and lymphocytes into the brain. Analysis of abscess lesions by in situ hybridization identified CD11b+ cells as the source of IL-1β in response to S. aureus. Both intercellular adhesion molecule-1 and platelet endothelial cell adhesion molecule expression were enhanced on microvessels in S. aureus but not sterile bead-implanted tissues at 24 and 48 hours after treatment. These results characterize proinflammatory cytokine and chemokine expression during the early response to S. aureus in the brain and provide the foundation to assess the functional significance of these mediators in brain abscess pathogenesis. PMID:10934167

  19. Neuropeptide Y administration acutely increases hypothalamic corticotropin-releasing factor immunoreactivity: lack of effect in other rat brain regions

    SciTech Connect

    Haas, D.A.; George, S.R.

    1987-12-21

    The effect of acute central administration of Neuropeptide Y (NPY) to adult male rats on the brain content of corticotropin-releasing factor immunoreactivity (CRF-ir) was investigated. The brain regions studied included frontal cortex, hippocampus, medulla-pons, midbrain-thalamus, cerebellum, neurointermediate lobe of pituitary, median eminence and the remaining hypothalamus. CRF-ir was determined in each of these regions using radioimmunoassay specific for rat CRF. CRF-ir was found to be significantly increased in the major site of CRF localization in the brain, the hypothalamus, in NPY-treated rats as compared to vehicle-treated controls either 15 minutes (p<0.025) or 45 minutes (p<0.005) post-injection. This increase was localized to the median eminence (p<0.05 after 15 minutes, p<0.01 after 45 minutes). No statistically significant differences were noted in any of the other brain regions assessed. Plasma adrenocorticotropin levels were also found to increase following NPY treatment, an effect which became significant after 45 minutes (p<0.05). These data show that NPY can alter the content of hypothalamic CRF and may play a role in its regulation. 33 references, 4 figures.

  20. Two-dimensional zymography differentiates gelatinase isoforms in stimulated microglial cells and in brain tissues of acute brain injuries.

    PubMed

    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. PMID:25859655

  1. Acute alcohol intoxication decreases glucose metabolism but increases acetate uptake in the human brain.

    PubMed

    Volkow, Nora D; Kim, Sung Won; Wang, Gene-Jack; Alexoff, David; Logan, Jean; Muench, Lisa; Shea, Colleen; Telang, Frank; Fowler, Joanna S; Wong, Christopher; Benveniste, Helene; Tomasi, Dardo

    2013-01-01

    Alcohol intoxication results in marked reductions in brain glucose metabolism, which we hypothesized reflect not just its GABAergic enhancing effects but also the metabolism of acetate as an alternative brain energy source. To test this hypothesis we separately assessed the effects of alcohol intoxication on brain glucose and acetate metabolism using Positron Emission Tomography (PET). We found that alcohol intoxication significantly decreased whole brain glucose metabolism (measured with FDG) with the largest decrements in cerebellum and occipital cortex and the smallest in the thalamus. In contrast, alcohol intoxication caused a significant increase in [1-(11)C]acetate brain uptake (measured as standard uptake value, SUV), with the largest increases occurring in the cerebellum and the smallest in the thalamus. In heavy alcohol drinkers [1-(11)C]acetate brain uptake during alcohol challenge tended to be higher than in occasional drinkers (p<0.06) and the increases in [1-(11)C]acetate uptake in cerebellum with alcohol were positively associated with the reported amount of alcohol consumed (r=0.66, p<0.01). Our findings corroborate a reduction of brain glucose metabolism during intoxication and document an increase in brain acetate uptake. The opposite changes observed between regional brain metabolic decrements and regional increases in [1-(11)C]acetate uptake support the hypothesis that during alcohol intoxication the brain may rely on acetate as an alternative brain energy source and provides preliminary evidence that heavy alcohol exposures may facilitate the use of acetate as an energy substrate. These findings raise the question of the potential therapeutic benefits that increasing plasma acetate concentration (i.e. ketogenic diets) may have in alcoholics undergoing alcohol detoxification. PMID:22947541

  2. Assessment of oxidative stress parameters of brain-derived neurotrophic factor heterozygous mice in acute stress model

    PubMed Central

    Hacioglu, Gulay; Senturk, Ayse; Ince, Imran; Alver, Ahmet

    2016-01-01

    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. PMID:27279982

  3. 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).

    PubMed

    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. PMID:25445779

  4. Concussive Brain Trauma in the Mouse Results in Acute Cognitive Deficits and Sustained Impairment of Axonal Function

    PubMed Central

    Creed, Jennifer A.; DiLeonardi, Ann Mae; Fox, Douglas P.; Tessler, Alan R.

    2011-01-01

    Abstract Concussive brain injury (CBI) accounts for approximately 75% of all brain-injured people in the United States each year and is particularly prevalent in contact sports. Concussion is the mildest form of diffuse traumatic brain injury (TBI) and results in transient cognitive dysfunction, the neuropathologic basis for which is traumatic axonal injury (TAI). To evaluate the structural and functional changes associated with concussion-induced cognitive deficits, adult mice were subjected to an impact on the intact skull over the midline suture that resulted in a brief apneic period and loss of the righting reflex. Closed head injury also resulted in an increase in the wet weight:dry weight ratio in the cortex suggestive of edema in the first 24 h, and the appearance of Fluoro-Jade-B-labeled degenerating neurons in the cortex and dentate gyrus of the hippocampus within the first 3 days post-injury. Compared to sham-injured mice, brain-injured mice exhibited significant deficits in spatial acquisition and working memory as measured using the Morris water maze over the first 3 days (p<0.001), but not after the fourth day post-injury. At 1 and 3 days post-injury, intra-axonal accumulation of amyloid precursor protein in the corpus callosum and cingulum was accompanied by neurofilament dephosphorylation, impaired transport of Fluoro-Gold and synaptophysin, and deficits in axonal conductance. Importantly, deficits in retrograde transport and in action potential of myelinated axons continued to be observed until 14 days post-injury, at which time axonal degeneration was apparent. These data suggest that despite recovery from acute cognitive deficits, concussive brain trauma leads to axonal degeneration and a sustained perturbation of axonal function. PMID:21299360

  5. The Natural History of Acute Recovery of Blast-Induced Mild Traumatic Brain Injury: A Case Series During War.

    PubMed

    Larres, David T; Carr, Walter; Gonzales, Elizandro G; Hawley, Jason S

    2016-05-01

    Traumatic brain injury (TBI) secondary to blast exposure is a common injury in the Global War on Terrorism, but little is known about the acute effects, recovery, pathophysiology, and neuropathology of blast-induced mild TBI (mTBI) in humans in a battlefield environment. Moreover, there is ongoing debate whether blast-induced mTBI is a different injury with a unique pathophysiology compared with mTBI from blunt trauma. In the case series reported here from Craig Joint Theater Hospital at Bagram Airfield, Afghanistan, 15 military service members with acute concussion/mTBI associated with blast exposure were evaluated within the first 24 hours after concussion and on days 2, 3, 5, and 7 with a Graded Symptom Checklist and a balance assessment, the Balance Error Scoring System. These data suggest that the recovery in blast-induced mTBI follows the pattern of recovery in sports-related concussion reported in The National Collegiate Athletic Association Concussion Study. In this retrospective case series, we provide the first description of the natural history of acute recovery in blast-induced mTBI, and we suspect, given our experience treating military service members, that further observations of the natural history of recovery in blast-induced mTBI will continue to mirror the natural history of recovery in sports concussion. PMID:27168549

  6. Brain acetylcholinesterase activity recovery following acute methyl parathion intoxication in two feral rodent species: comparison to laboratory rodents

    SciTech Connect

    Roberts, D.K.; Silvey, N.J.; Bailey, E.M. Jr.

    1988-07-01

    Widespread use of organophosphorus insecticides (OPs) has produced both acute and chronic intoxication among nontarget organisms. Most such studies have included fish and birds as opposed to mammals. However, numerous OP toxicity studies have been conducted on laboratory rodents creating a temptation to apply this data to feral rodents. Chronic OP exposure has been reported to produce cholinergic adaptation which in turn lowers mortality rates following a subsequent acute anticholinesterase exposure. The relevance that these laboratory rodent studies have on feral rodents is subject to debate. Field studies involving OP exposure among nontarget feral mammals have produced contradictory results. Increased mortality as a result of repeated OP application has been reported. This observation may be of considerable importance to nontarget feral rodent populations due to the repetitive nature of OP application protocols. The ability of feral rodents to recover brain AChE activity (BAA) between OP application intervals undoubtedly promotes their survival. This study investigated and compared BAA recovery following acute oral methyl parathion intoxication among 2 feral rodent species and among 2 common laboratory rodent species.

  7. Acute Administration of Branched-Chain Amino Acids Increases the Pro-BDNF/Total-BDNF Ratio in the Rat Brain.

    PubMed

    Scaini, Giselli; Morais, Meline O S; Furlanetto, Camila B; Kist, Luiza W; Pereira, Talita C B; Schuck, Patrícia F; Ferreira, Gustavo C; Pasquali, Matheus A B; Gelain, Daniel P; Moreira, José Cláudio F; Bogo, Maurício R; Streck, Emilio L

    2015-05-01

    Maple syrup urine disease (MSUD) is caused by an inborn error in metabolism resulting from a deficiency in the branched-chain α-keto acid dehydrogenase complex activity. This blockage leads to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and valine, as well as their corresponding α-keto acids and α-hydroxy acids. High levels of BCAAs are associated with neurological dysfunction and the role of pro- and mature brain-derived neurotrophic factor (BDNF) in the neurological dysfunction of MSUD is still unclear. Thus, in the present study we investigated the effect of an acute BCAA pool administration on BDNF levels and on the pro-BDNF cleavage-related proteins S100A10 and tissue plasminogen activator (tPA) in rat brains. Our results demonstrated that acute Hyper-BCAA (H-BCAA) exposure during the early postnatal period increases pro-BDNF and total-BDNF levels in the hippocampus and striatum. Moreover, tPA levels were significantly decreased, without modifications in the tPA transcript levels in the hippocampus and striatum. On the other hand, the S100A10 mRNA and S100A10 protein levels were not changed in the hippocampus and striatum. In the 30-day-old rats, we observed increased pro-BDNF, total-BDNF and tPA levels only in the striatum, whereas the tPA and S100A10 mRNA expression and the immunocontent of S100A10 were not altered. In conclusion, we demonstrated that acute H-BCAA administration increases the pro-BDNF/total-BDNF ratio and decreases the tPA levels in animals, suggesting that the BCAA effect may depend, at least in part, on changes in BDNF post-translational processing. PMID:25681161

  8. Slice-selective J-coupled coherence transfer using symmetric linear phase pulses: applications to localized GABA spectroscopy

    NASA Astrophysics Data System (ADS)

    Shen, Jun

    2003-07-01

    Symmetric, linear phase, slice-selective RF pulses were analyzed theoretically for performing slice-selective coherence transfer. It was shown using numerical simulations of product operators that, when a prefocusing gradient of the same area as that of the refocusing gradient is added, these pulses become slice-selective universal rotator pulses, therefore, capable of performing slice-selective coherence transfer. As an example, a slice-selective universal rotator pulse based on a seven-lobe hamming-filtered sinc pulse was applied to in vivo single-shot simultaneous spectral editing and spatial localization of neurotransmitter GABA in the human brain.

  9. Bedside Ultrasonography versus Brain Natriuretic Peptide in Detecting Cardiogenic Causes of Acute Dyspnea

    PubMed Central

    Golshani, Keihan; Esmailian, Mehrdad; Valikhany, Aniseh; Zamani, Majid

    2016-01-01

    Introduction: Acute dyspnea is a common cause of hospitalization in emergency departments (ED).Distinguishing the cardiac causes of acute dyspnea from pulmonary ones is a major challenge for responsible physicians in EDs. This study compares the characteristics of bedside ultrasonography with serum level of blood natriuretic peptide (BNP) in this regard. Methods: This diagnostic accuracy study compares bedside ultrasonography with serum BNP levels in differentiating cardiogenic causes of acute respiratory distress. Echocardiography was considered as the reference test. A checklist including demographic data (age and sex), vital signs, medical history, underlying diseases, serum level of BNP, as well as findings of chest radiography, chest ultrasonography, and echocardiography was filled for all patients with acute onset of dyspnea. Screening characteristics of the two studied methods were calculated and compared using SPSS software, version 20. Results: 48 patients with acute respiratory distress were evaluated (50% female). The mean age of participants was 66.94 ± 16.33 (28-94) years. Based on the results of echocardiography and final diagnosis, the cause of dyspnea was cardiogenic in 20 (41.6%) cases. Bedside ultrasonography revealed the cardiogenic cause of acute dyspnea in 18 cases (0 false positive) and BNP in 44 cases (24 false positives). The area under the ROC curve for bedside ultrasonography and BNP for differentiating the cardiogenic cause of dyspnea were 86.4 (95% CI: 74.6-98.3) and 66.3 (95% CI: 49.8-89.2), respectively (p = 0.0021). Conclusion: It seems that bedside ultrasonography could be considered as a helpful and accurate method in differentiating cardiogenic causes of acute dyspnea in emergency settings. Nevertheless, more study is needed to make a runaway algorithm to evaluate patients with respiratory distress using bedside ultrasonography, which leads to rapid therapeutic decisions in a short time. PMID:27299143

  10. Site-dependent effects of an acute intensive exercise on extracellular 5-HT and 5-HIAA levels in rat brain.

    PubMed

    Gomez-Merino, D; Béquet, F; Berthelot, M; Chennaoui, M; Guezennec, C Y

    2001-03-30

    Previous neurochemical studies have reported different pattern of 5-HT release during exercise varying across either exercise conditions or forebrain sites. This in vivo microdialysis study is the first to examine the impact of an acute intensive treadmill running (2 h at 25 m.min(-1), which is close to exhaustion time), on extracellular 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in two different brain areas in rats, the ventral hippocampus and the frontal cortex. Hippocampal and cortical 5-HT levels increased significantly after 90 min of exercise and were maximal in the first 30 min of recovery. Thereafter, cortical 5-HT levels followed a rapid and significant decrease when hippocampal levels are still maximal. During exercise, changes in extracellular 5-HIAA levels paralleled 5-HT changes, but showed no difference between the two brain areas during recovery. Thus, an intensive exercise induces a delayed increase in brain 5-HT release but recovery seems to display site-dependent patterns. PMID:11248443

  11. Association of seizures with cortical spreading depression and peri-infarct depolarisations in the acutely injured human brain

    PubMed Central

    Fabricius, Martin; Fuhr, Susanne; Willumsen, Lisette; Dreier, Jens P; Bhatia, Robin; Boutelle, Martyn G.; Hartings, Jed A; Bullock, Ross; Strong, Anthony J; Lauritzen, Martin

    2008-01-01

    Objective To test the co-occurrence and interrelation of ictal activity and cortical spreading depressions (CSDs) - including the related periinfarct depolarisations in acute brain injury caused by trauma, and spontaneous subarachnoid and/or intracerebral haemorrhage. Methods 63 patients underwent craniotomy and electrocorticographic (ECoG) recordings were taken near foci of damaged cortical tissue for up to 10 days. Results 32 of 63 patients exhibited CSDs (5 to 75 episodes), and 11 had ECoGraphic seizure activity (1-81 episodes). Occurrence of seizures was significantly associated with CSD, as 10 of 11 patients with seizures also had CSD (p=0.007, 2-tailed Fishers exact test). Clinically overt seizures were only observed in one patient. Each patient with CSD and seizures displayed one of four different patterns of interaction between CSD and seizures. In four patients CSD was immediately preceded by prolonged seizure activity. In three patients the two phenomena were separated in time: multiple CSDs were replaced by ictal activity. In one patient seizures appeared to trigger repeated CSDs at the adjacent electrode. In two patients ongoing repeated seizures were interrupted each time CSD occurred. Conclusions Seizure activity occurs in association with CSD in the injured human brain. Significance ECoG recordings in brain injury patients provide insight into pathophysiological mechanisms that is not accessible by scalp EEG recordings. PMID:18621582

  12. Neuroinflammation and Neuroimmune Dysregulation after Acute Hypoxic-Ischemic Injury of Developing Brain

    PubMed Central

    Bhalala, Utpal S.; Koehler, Raymond C.; Kannan, Sujatha

    2015-01-01

    Hypoxic-ischemic (HI) injury to developing brain results from birth asphyxia in neonates and from cardiac arrest in infants and children. It is associated with varying degrees of neurologic sequelae, depending upon the severity and length of HI. Global HI triggers a series of cellular and biochemical pathways that lead to neuronal injury. One of the key cellular pathways of neuronal injury is inflammation. The inflammatory cascade comprises activation and migration of microglia – the so-called “brain macrophages,” infiltration of peripheral macrophages into the brain, and release of cytotoxic and proinflammatory cytokines. In this article, we review the inflammatory and immune mechanisms of secondary neuronal injury after global HI injury to developing brain. Specifically, we highlight the current literature on microglial activation in relation to neuronal injury, proinflammatory and anti-inflammatory/restorative pathways, the role of peripheral immune cells, and the potential use of immunomodulators as neuroprotective compounds. PMID:25642419

  13. Global lipidomics identifies cardiolipin oxidation as a mitochondrial target for redox therapy of acute brain injury

    PubMed Central

    Ji, Jing; Kline, Anthony E; Amoscato, Andrew; Arias, Alejandro S; Sparvero, Louis J; Tyurin, Vladimir A; Tyurina, Yulia Y; Fink, Bruno; Manole, Mioara D; Puccio, Ava M; Okonkwo, David O; Cheng, Jeffrey P; Alexander, Henry; Clark, Robert SB; Kochanek, Patrick M; Wipf, Peter; Kagan, Valerian E; Bayýr, Hülya

    2013-01-01

    Brain contains a highly diversified complement of molecular species of a mitochondria-specific phospholipid, cardiolipin (CL), which - due to its polyunsaturation - can readily undergo oxygenation. Here, we used global lipidomics analysis in experimental traumatic brain injury (TBI) and showed that TBI was accompanied by oxidative consumption of polyunsaturated CL and accumulation of more than 150 new oxygenated molecular species in CL. RNAi-based manipulations of CL-synthase and CL levels conferred resistance of primary rat cortical neurons to mechanical stretch - an in vitro model of traumatic neuronal injury. By applying the novel brain permeable mitochondria-targeted electron-scavenger, we prevented CL oxygenation in the brain, achieved a substantial reduction in neuronal death both in vitro and in vivo, and markedly reduced behavioral deficits and cortical lesion volume. We conclude that CL oxygenation generates neuronal death signals and that its prevention by mitochondria-targeted small molecule inhibitors represents a new target for neuro-drug discovery. PMID:22922784

  14. Acute Exposure to Perchlorethylene alters Rat Visual Evoked Potentials in Relation to Brain Concentration

    EPA Science Inventory

    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 ...

  15. Nafamostat mesilate protects against acute cerebral ischemia via blood-brain barrier protection.

    PubMed

    Wang, Jing; Li, Chenhui; Chen, Tao; Fang, Yinquan; Shi, Xinzhong; Pang, Tao; Zhang, Luyong; Liao, Hong

    2016-06-01

    Serine proteases, such as thrombin, are contributors to the disruption of the blood-brain barrier (BBB) and exacerbate brain damage during ischemic stroke, for which the current clinical therapy remains unsatisfactory. However, the effect of nafamostat mesilate (NM), a synthetic serine protease inhibitor, on BBB disruption following cerebral ischemia is unknown. Here, we investigated the in vivo effect of NM on BBB integrity in rats subjected to transient middle cerebral artery occlusion (MCAO) and explored the possible mechanism in an in vitro BBB model comprising rat brain microvascular endothelial cells and astrocytes after oxygen and glucose deprivation (OGD) in the presence of thrombin. The results showed that NM treatment remarkably attenuated transient MCAO-induced brain infarcts, brain oedema and motor dysfunction in addition to BBB disruption, which might be related to changes in tight junction protein expression and localization. Meanwhile, NM preserved BBB integrity and alleviated the changes in tight junction protein expression and localization and cytoskeleton rearrangement in rat brain microvascular endothelial cells via thrombin inhibition. Our findings suggest that NM treatment can preserve BBB integrity through the inhibition of thrombin, which might be correlated with the regulation of PKCα/RhoA/MLC2 pathway components. PMID:26861077

  16. How Healthcare Provider Talk with Parents of Children Following Severe Traumatic Brain Injury is Perceived in Early Acute Care

    PubMed Central

    Savage, Teresa A.; Grant, Gerald; Philipsen, Gerry

    2013-01-01

    Healthcare provider talk with parents in early acute care following children’s severe traumatic brain injury (TBI) affects parents’ orientations to these locales, but this connection has been minimally studied. This lack of attention to this topic in previous research may reflect providers’ and researchers’ views that these locales are generally neutral or supportive to parents’ subsequent needs. This secondary analysis used data from a larger descriptive phenomenological study (2005 – 2007) with parents of children following moderate to severe TBI recruited from across the United States. Parents of children with severe TBI consistently had strong negative responses to the early acute care talk processes they experienced with providers, while parents of children with moderate TBI did not. Transcript data were independently coded using discourse analysis in the framework of ethnography of speaking. The purpose was to understand the linguistic and paralinguistic talk factors parents used in their meta-communications that could give a preliminary understanding of their cultural expectations for early acute care talk in these settings. Final participants included 27 parents of children with severe TBI from 23 families. We found the human constructed talk factors that parents reacted to were: a) access to the child, which is where information was; b) regular discussions with key personnel; c) updated information that is explained; d) differing expectations for talk in this context; and, e) perceived parental involvement in decisions. We found that the organization and nature of providers’ talk with parents was perceived by parents to positively or negatively shape their early acute care identities in these locales, which influenced how they viewed these locales as places that either supported them and decreased their workload or discounted them and increased their workload for getting what they needed. PMID:23746606

  17. Building a "brain attack" team to administer thrombolytic therapy for acute ischemic stroke

    PubMed Central

    Hill, M D; Barber, P A; Demchuk, A M; Sevick, R J; Newcommon, N J; Green, T; Buchan, A M

    2000-01-01

    Before tissue plasminogen activator (tPA) was licensed for use in Canada, in February 1999, the Calgary Regional Stroke Program spearheaded the development and organization of local resources to use thrombolytic therapy in patients who had experienced acute ischemic stroke. In 1996 special permission was obtained from the Calgary Regional Health Authority to use intravenously administered tPA for acute ischemic stroke, and ethical and scientific review boards approved the protocols. After 3 years our efforts have resulted in improved patient outcomes, shorter times from symptom onset to treatment and acceptable adverse event rates. Areas for continued improvement include the door-to-needle time and broader education of the public about the symptoms of acute ischemic stroke. PMID:10862236

  18. Effects of acute hyperosmolality on blood-brain barrier function in ovine fetuses and lambs.

    PubMed

    Stonestreet, Barbara S; Sadowska, Grazyna B; Leeman, Joanne; Hanumara, R Choudary; Petersson, Katherine H; Patlak, Clifford S

    2006-10-01

    We examined the effects of hyperosmolality on blood-brain barrier (BBB) permeability during development to test the vulnerability of the immature barrier to stress. The BBB response to hyperosmolality was quantified using the blood-to-brain transfer constant (Ki) with alpha-aminoisobutyric acid in fetuses at 60% and 90% gestation, premature, newborn, and older lambs. Ki plotted against osmolality increased as a function of increases in osmolality in all groups and brain regions. The relationship was described (P < 0.05) by a segmented regression model. At lower osmolalities, changes in Ki were minimal, but after a break point (threshold) was reached, the increase (P < 0.05) was linear. We examined the responses of Ki to hyperosmolality within each brain region by comparing the thresholds and slopes of the second regression segment. Lower thresholds and higher slopes imply greater vulnerability to hyperosmolality in the younger groups. Thresholds increased (P < 0.05) with development in the thalamus, superior colliculus, pons, and spinal cord, and slopes of the second regression segment decreased (P < 0.05) in the cerebellum, hippocampus, inferior colliculus, medulla, and spinal cord. BBB resistance to hyperosmolality increased (P < 0.05) with development in most brain regions. The pattern of the Ki plotted against osmolality was (P < 0.05) heterogenous among brain regions in fetuses and premature and newborn lambs, but not in older lambs. We conclude that 1) BBB permeability increased as a function of changes in osmolality, 2) the barrier becomes more resistant to hyperosmolality during development, and 3) the permeability response to hyperosmolality is heterogenous among brain regions in fetuses and premature and newborn lambs. PMID:16690764

  19. The pharmacology of neurotrophic treatment with Cerebrolysin: brain protection and repair to counteract pathologies of acute and chronic neurological disorders.

    PubMed

    Masliah, E; Díez-Tejedor, E

    2012-04-01

    Neurotrophic factors are considered as part of the therapeutic strategy for neurological disorders like dementia, stroke and traumatic brain injury. Cerebrolysin is a neuropeptide preparation which mimics the action of endogenous neurotrophic factors on brain protection and repair. In dementia models, Cerebrolysin decreases β-amyloid deposition and microtubule-associated protein tau phosphorylation by regulating glycogen synthase kinase-3β and cyclin-dependent kinase 5 activity, increases synaptic density and restores neuronal cytoarchitecture. These effects protect integrity of the neuronal circuits and thus result in improved cognitive and behavioral performance. Furthermore, Cerebrolysin enhances neurogenesis in the dentate gyrus, the basis for neuronal replacement therapy in neurodegenerative diseases. Experimental studies in stroke animal models have shown that Cerebrolysin stabilizes the structural integrity of cells by inhibition of calpain and reduces the number of apoptotic cells after ischemic lesion. Cerebrolysin induces restorative processes, decreases infarct volume and edema formation and promotes functional recovery. Stroke-induced neurogenesis in the subventricular zone was also promoted by Cerebrolysin, thus supporting the brain's self-repair after stroke. Both, traumatic brain and spinal cord injury conditions stimulate the expression of natural neurotrophic factors to promote repair and regeneration processes -axonal regeneration, neuronal plasticity and neurogenesis- that is considered to be crucial for the future recovery. Neuroprotective effects of Cerebrolysin on experimentally induced traumatic spinal cord injury have shown that Cerebrolysin prevents apoptosis of lesioned motoneurons and promotes functional recovery. This section summarizes the most relevant data on the pharmacology of Cerebrolysin obtained from in vitro assays (biochemical and cell cultures) and in vivo animal models of acute and chronic neurological disorders. PMID

  20. Methylene Blue Attenuates Traumatic Brain Injury-Associated Neuroinflammation and Acute Depressive-Like Behavior in Mice

    PubMed Central

    Fenn, Ashley M.; Skendelas, John P.; Moussa, Daniel N.; Muccigrosso, Megan M.; Popovich, Phillip G.; Lifshitz, Jonathan

    2015-01-01

    Abstract Traumatic brain injury (TBI) is associated with cerebral edema, blood brain barrier breakdown, and neuroinflammation that contribute to the degree of injury severity and functional recovery. Unfortunately, there are no effective proactive treatments for limiting immediate or long-term consequences of TBI. Therefore, the objective of this study was to determine the efficacy of methylene blue (MB), an antioxidant agent, in reducing inflammation and behavioral complications associated with a diffuse brain injury. Here we show that immediate MB infusion (intravenous; 15–30 minutes after TBI) reduced cerebral edema, attenuated microglial activation and reduced neuroinflammation, and improved behavioral recovery after midline fluid percussion injury in mice. Specifically, TBI-associated edema and inflammatory gene expression in the hippocampus were significantly reduced by MB at 1 d post injury. Moreover, MB intervention attenuated TBI-induced inflammatory gene expression (interleukin [IL]-1β, tumor necrosis factor α) in enriched microglia/macrophages 1 d post injury. Cell culture experiments with lipopolysaccharide-activated BV2 microglia confirmed that MB treatment directly reduced IL-1β and increased IL-10 messenger ribonucleic acid in microglia. Last, functional recovery and depressive-like behavior were assessed up to one week after TBI. MB intervention did not prevent TBI-induced reductions in body weight or motor coordination 1–7 d post injury. Nonetheless, MB attenuated the development of acute depressive-like behavior at 7 d post injury. Taken together, immediate intervention with MB was effective in reducing neuroinflammation and improving behavioral recovery after diffuse brain injury. Thus, MB intervention may reduce life-threatening complications of TBI, including edema and neuroinflammation, and protect against the development of neuropsychiatric complications. PMID:25070744

  1. Hemodynamic and morphologic responses in mouse brain during acute head injury imaged by multispectral structured illumination

    NASA Astrophysics Data System (ADS)

    Volkov, Boris; Mathews, Marlon S.; Abookasis, David

    2015-03-01

    Multispectral imaging has received significant attention over the last decade as it integrates spectroscopy, imaging, tomography analysis concurrently to acquire both spatial and spectral information from biological tissue. In the present study, a multispectral setup based on projection of structured illumination at several near-infrared wavelengths and at different spatial frequencies is applied to quantitatively assess brain function before, during, and after the onset of traumatic brain injury in an intact mouse brain (n=5). For the production of head injury, we used the weight drop method where weight of a cylindrical metallic rod falling along a metal tube strikes the mouse's head. Structured light was projected onto the scalp surface and diffuse reflected light was recorded by a CCD camera positioned perpendicular to the mouse head. Following data analysis, we were able to concurrently show a series of hemodynamic and morphologic changes over time including higher deoxyhemoglobin, reduction in oxygen saturation, cell swelling, etc., in comparison with baseline measurements. Overall, results demonstrates the capability of multispectral imaging based structured illumination to detect and map of brain tissue optical and physiological properties following brain injury in a simple noninvasive and noncontact manner.

  2. Acute effects of oral or parenteral aspartame on catecholamine metabolism in various regions of rat brain.

    PubMed

    Yokogoshi, H; Wurtman, R J

    1986-03-01

    Hypertensive (SHR) and nonhypertensive [Wistar-Kyoto (WKY); Sprague-Dawley (SD)] strains of rats received the dipeptide sweetener aspartame (200 mg/kg) or, as a positive control, tyrosine (200 mg/kg) by gavage or parenterally, after a brief (2-h) fast. Two hours later, compared with those of saline controls brain levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylethyleneglycol (MHPG) sulfate were significantly higher in the hypothalamus (WKY), locus coeruleus (SD and SHR) and brain stem (SHR) in tyrosine-treated animals, and in the locus coeruleus (SD) of those given aspartame. Brain norepinephrine levels were also higher, compared with those of saline-treated control rats, in the cerebral cortex (SD and SHR), amygdala (SD) and locus coeruleus (WKY) after tyrosine administration, and in the amygdala (SD) and cerebral cortex (SHR) after aspartame administration. In another study, oral aspartame was found to be at least as effective as the parenterally administered sweetener in raising regional brain levels of tyrosine or MHPG sulfate (i.e., compared with corresponding levels in saline-treated rats). Animals receiving oral aspartame also exhibited higher plasma tyrosine and phenylalanine ratios (i.e., the ratios of their plasma concentrations to the summed concentrations of other large neutral amino acids that compete with them for uptake into the brain), than animals receiving saline. PMID:3950762

  3. Systemic inflammation induces acute working memory deficits in the primed brain: relevance for delirium

    PubMed Central

    Murray, Carol; Sanderson, David J.; Barkus, Chris; Deacon, Robert M.J.; Rawlins, J. Nicholas P.; Bannerman, David M.; Cunningham, Colm

    2012-01-01

    Delirium is an acute, severe neuropsychiatric syndrome, characterized by cognitive deficits, that is highly prevalent in aging and dementia and is frequently precipitated by peripheral infections. Delirium is poorly understood and the lack of biologically relevant animal models has limited basic research. Here we hypothesized that synaptic loss and accompanying microglial priming during chronic neurodegeneration in the ME7 mouse model of prion disease predisposes these animals to acute dysfunction in the region of prior pathology upon systemic inflammatory activation. Lipopolysaccharide (LPS; 100 μg/kg) induced acute and transient working memory deficits in ME7 animals on a novel T-maze task, but did not do so in normal animals. LPS-treated ME7 animals showed heightened and prolonged transcription of inflammatory mediators in the central nervous system (CNS), compared with LPS-treated normal animals, despite having equivalent levels of circulating cytokines. The demonstration that prior synaptic loss and microglial priming are predisposing factors for acute cognitive impairments induced by systemic inflammation suggests an important animal model with which to study aspects of delirium during dementia. PMID:20471138

  4. AGE-RELATED TOXICITY PATHWAY ANALYSIS IN BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

    EPA Science Inventory

    The influence of aging on susceptibility to environmental exposures is poorly understood. To investigate-the contribution of different life stages on response to toxicants, we examined the effects of an acute exposure to the volatile organic compound, toluene (0.0 or 1.0 g/kg), i...

  5. Dopamine treatment during acute hypoxia is neuroprotective in the developing sheep brain.

    PubMed

    Brew, N; Azhan, A; den Heijer, I; Boomgardt, M; Davies, G I; Nitsos, I; Miller, S L; Walker, A M; Walker, D W; Wong, F Y

    2016-03-01

    Dopamine is often used to treat hypotension in preterm infants; these infants are at risk of developing brain injury due to impaired autoregulation and cerebral hypoperfusion. However the effects of dopamine on the immature brain under conditions of cerebral hypoxia are not known. We hypothesized that pretreatment with dopamine would protect the immature brain from injury caused by cerebral hypoxia. Preterm fetal sheep were used to determine the effects of intravenous dopamine on hypoxia-induced brain injury. In 16 pregnant sheep at 90days of gestation (0.6 of term, term=147days) catheters were implanted aseptically into the fetal carotid artery and jugular vein; an inflatable occluder was placed loosely around the umbilical cord for later induction of fetal hypoxemia. At 5days after surgery, dopamine (10μg/kg/min, n=7 fetuses) or saline (n=9 fetuses) was infused for 74h. Two hours after commencing the dopamine/saline infusion, we induced umbilical cord occlusion (UCO) for up to 25min to produce fetal asphyxia. Fetuses were allowed to recover, and brains were collected 72h later for assessment of neuropathology. Un-operated twin fetuses were used as age-matched non-UCO controls (n=8). In UCO+saline fetuses, microglial and apoptotic cell density in the subcortical and periventricular white matter, caudate nucleus and hippocampus was greater than that in age-matched controls; oxidative stress was elevated in the subcortical and periventricular white matter and caudate nucleus compared to that in age-matched controls. In UCO+dopamine fetuses microglial density and oxidative stress in the cerebral white matter and caudate nucleus were not different to that of age-matched controls. Apoptotic cell death was decreased in the cerebral white matter of UCO+dopamine brains, relative to UCO+saline brains. We conclude that pretreatment with dopamine does not exacerbate hypoxia-induced injury in the immature brain and may be neuroprotective because it led to decreased apoptosis

  6. Use of a custom RT-PCR array to analyze toxicity pathways at different life stages in Brown Norway Rat Brain following acute Toluene exposure.

    EPA Science Inventory

    To investigate the contribution of different life stages on response to toxicants, we utilized a custom designed RT-PCR array to examine the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.65 or 1.0 glkg) in the brains of ma1e Brown Norwa...

  7. Acute Reduction of Microglia Does Not Alter Axonal Injury in a Mouse Model of Repetitive Concussive Traumatic Brain Injury

    PubMed Central

    Bennett, Rachel E.

    2014-01-01

    Abstract The pathological processes that lead to long-term consequences of multiple concussions are unclear. Primary mechanical damage to axons during concussion is likely to contribute to dysfunction. Secondary damage has been hypothesized to be induced or exacerbated by inflammation. The main inflammatory cells in the brain are microglia, a type of macrophage. This research sought to determine the contribution of microglia to axon degeneration after repetitive closed-skull traumatic brain injury (rcTBI) using CD11b-TK (thymidine kinase) mice, a valganciclovir-inducible model of macrophage depletion. Low-dose (1 mg/mL) valganciclovir was found to reduce the microglial population in the corpus callosum and external capsule by 35% after rcTBI in CD11b-TK mice. At both acute (7 days) and subacute (21 days) time points after rcTBI, reduction of the microglial population did not alter the extent of axon injury as visualized by silver staining. Further reduction of the microglial population by 56%, using an intermediate dose (10 mg/mL), also did not alter the extent of silver staining, amyloid precursor protein accumulation, neurofilament labeling, or axon injury evident by electron microscopy at 7 days postinjury. Longer treatment of CD11b-TK mice with intermediate dose and treatment for 14 days with high-dose (50 mg/mL) valganciclovir were both found to be toxic in this injury model. Altogether, these data are most consistent with the idea that microglia do not contribute to acute axon degeneration after multiple concussive injuries. The possibility of longer-term effects on axon structure or function cannot be ruled out. Nonetheless, alternative strategies directly targeting injury to axons may be a more beneficial approach to concussion treatment than targeting secondary processes of microglial-driven inflammation. PMID:24797413

  8. Trumpet slices in Kerr spacetimes.

    PubMed

    Dennison, Kenneth A; Baumgarte, Thomas W; Montero, Pedro J

    2014-12-31

    We introduce a new time-independent family of analytical coordinate systems for the Kerr spacetime representing rotating black holes. We also propose a (2+1)+1 formalism for the characterization of trumpet geometries. Applying this formalism to our new family of coordinate systems we identify, for the first time, analytical and stationary trumpet slices for general rotating black holes, even for charged black holes in the presence of a cosmological constant. We present results for metric functions in this slicing and analyze the geometry of the rotating trumpet surface. PMID:25615297

  9. Nose-to-Brain Transport of Aerosolized Quantum Dots Following Acute Exposure

    PubMed Central

    Hopkins, Laurie E.; Patchin, Esther S.; Chiu, Po-Lin; Brandenberger, Christina; Smiley-Jewell, Suzette; Pinkerton, Kent E.

    2014-01-01

    Nanoparticles are of wide interest due to their potential use for diverse commercial applications. Quantum dots are semiconductor nanocrystals possessing unique optical and electrical properties. Although quantum dots are commonly made of cadmium, a metal known to have neurological effects, potential transport of quantum dots directly to the brain has not been assessed. This study evaluated whether quantum dots (CdSe/ZnS nanocrystals) could be transported from the olfactory tract to the brain via inhalation. Adult C57BL/6 mice were exposed to an aerosol of quantum dots for one hour via nasal inhalation, and nanoparticles were detected three hours post-exposure within the olfactory tract and olfactory bulb by a wide range of techniques, including visualization via fluorescent and transmission electron microscopy. We conclude that following short-term inhalation of solid quantum dot nanoparticles, there is rapid olfactory uptake and axonal transport to the brain/olfactory bulb with observed activation of microglial cells, indicating a pro-inflammatory response. To our knowledge, this is the first study to clearly demonstrate that quantum dots can be rapidly transported from the nose to the brain by olfactory uptake via axonal transport following inhalation. PMID:24040866

  10. Acute high-altitude hypoxic brain injury: Identification of ten differential proteins.

    PubMed

    Li, Jianyu; Qi, Yuting; Liu, Hui; Cui, Ying; Zhang, Li; Gong, Haiying; Li, Yaxiao; Li, Lingzhi; Zhang, Yongliang

    2013-11-01

    Hypobaric hypoxia can cause severe brain damage and mitochondrial dysfunction, and is involved in hypoxic brain injury. However, little is currently known about the mechanisms responsible for mitochondrial dysfunction in hypobaric hypoxic brain damage. In this study, a rat model of hypobaric hypoxic brain injury was established to investigate the molecular mechanisms associated with mitochondrial dysfunction. As revealed by two-dimensional electrophoresis analysis, 16, 21, and 36 differential protein spots in cerebral mitochondria were observed at 6, 12, and 24 hours post-hypobaric hypoxia, respectively. Furthermore, ten protein spots selected from each hypobaric hypoxia subgroup were similarly regulated and were identified by mass spectrometry. These detected proteins included dihydropyrimidinase-related protein 2, creatine kinase B-type, isovaleryl-CoA dehydrogenase, elongation factor Ts, ATP synthase beta-subunit, 3-mercaptopyruvate sulfurtransferase, electron transfer flavoprotein alpha-subunit, Chain A of 2-enoyl-CoA hydratase, NADH dehydrogenase iron-sulfur protein 8 and tropomyosin beta chain. These ten proteins are all involved in the electron transport chain and the function of ATP synthase. Our findings indicate that hypobaric hypoxia can induce the differential expression of several cerebral mitochondrial proteins, which are involved in the regulation of mitochondrial energy production. PMID:25206614

  11. Ferumoxytol nanoparticle uptake in brain during acute neuroinflammation is cell-specific.

    PubMed

    McConnell, Heather L; Schwartz, Daniel L; Richardson, Brian E; Woltjer, Randall L; Muldoon, Leslie L; Neuwelt, Edward A

    2016-08-01

    Ferumoxytol ultrasmall superparamagnetic iron oxide nanoparticles can enhance contrast between neuroinflamed and normal-appearing brain tissue when used as a contrast agent for high-sensitivity magnetic resonance imaging (MRI). Here we used an anti-dextran antibody (Dx1) that binds the nanoparticle's carboxymethyldextran coating to differentiate ferumoxytol from endogenous iron and localize it unequivocally in brain tissue. Intravenous injection of ferumoxytol into immune-competent rats that harbored human tumor xenograft-induced inflammatory brain lesions resulted in heterogeneous and lesion-specific signal enhancement on MRI scans in vivo. We used Dx1 immunolocalization and electron microscopy to identify ferumoxytol in affected tissue post-MRI. We found that ferumoxytol nanoparticles were taken up by astrocyte endfeet surrounding cerebral vessels, astrocyte processes, and CD163(+)/CD68(+) macrophages, but not by tumor cells. These results provide a biological basis for the delayed imaging changes seen with ferumoxytol and indicate that ferumoxytol-MRI can be used to assess the inflammatory component of brain lesions in the clinic. PMID:27071335

  12. Acute running stimulates hippocampal dopaminergic neurotransmission in rats, but has no influence on brain-derived neurotrophic factor

    PubMed Central

    Goekint, Maaike; Bos, Inge; Heyman, Elsa; Michotte, Yvette; Sarre, Sophie

    2012-01-01

    Hippocampal brain-derived neurotrophic factor (BDNF) protein is increased with exercise in rats. Monoamines seem to play a role in the regulation of BDNF, and monoamine neurotransmission is known to increase with exercise. The purpose of this study was to examine the influence of acute exercise on monoaminergic neurotransmission and BDNF protein concentrations. Hippocampal microdialysis was performed in rats that were subjected to 60 min of treadmill running at 20 m/min or rest. Two hours postexercise, the rats were killed, and the hippocampus was dissected. In experiments without microdialysis, hippocampus and serum samples were collected immediately after exercise. Exercise induced a twofold increase in hippocampal dopamine release. Noradrenaline and serotonin release were not affected. Hippocampal BDNF levels were not influenced, whether they were measured immediately or 2 h after the exercise protocol. Serum BDNF levels did not change either, but serum BDNF was negatively correlated to peripheral corticosterone concentrations, indicating a possible inhibitory reaction to the stress of running. Sixty minutes of exercise enhances dopamine release in the hippocampus of the rat in vivo. However, this increase is not associated with changes in BDNF protein levels immediately nor 2 h after the acute exercise bout. An increased corticosterone level might be the contributing factor for the absence of changes in BDNF. PMID:22134693

  13. The Quantitative Measurement of Reversible Acute Depression after Subthalamic Deep Brain Stimulation in a Patient with Parkinson Disease

    PubMed Central

    Simmons, Daniel B.; Dashtipour, Khashayar

    2015-01-01

    Background. Depression is the most commonly reported mood symptom affecting 2–8% of patients after deep brain stimulation (DBS). Usually, symptoms develop gradually; however there have been cases of reproducible events that the mood symptoms were elicited within seconds to minutes after stimulation and were immediately reversible upon cessation of the stimulus. In the current study, we applied a self-reported questionnaire to assess the patient's mood state. Objective. To objectively measure the reversible acute depression induced by DBS in a patient with Parkinson disease (PD). Methods. A statistically validated Spanish version of the Beck Depression Inventory Short Form (BDI-SF) was used. The questionnaire was administered three times. Results. The patient became acutely depressed within ninety seconds of monopolar stimulation on the right side. His symptoms resolved immediately after changing the setting to bipolar stimulation. The BDI-SF scores during stimulation off, on, and off again were 15, 19, and 6, respectively. Conclusions. The BDI-SF scores increased during stimulation and decreased after cessation. This is consistent with a reversible depressive state. The poststimulation BDI-SF score decreased to less than half of the baseline score. This may suggest that the depression was more severe than the patient was able to express during the stimulation. PMID:26090244

  14. Metabolic Changes in the Rodent Brain after Acute Administration of Salvinorin A

    PubMed Central

    Hooker, Jacob M.; Patel, Vinal; Kothari, Shiva; Schiffer, Wynne K.

    2009-01-01

    Purpose Salvinorin A (SA) is a potent and highly selective kappa opioid receptor (KOR) agonist with rapid kinetics and commensurate behavioral effects; however, brain regions associated with these effects have not been determined. Procedures Freely moving adult male rats were given SA intraperitoneally during uptake and trapping of the brain metabolic radiotracer, 18FDG, followed by image acquisition in a dedicated animal PET system. Age-matched control animals received vehicle treatment. Animal behavior during 18FDG uptake was recorded digitally and later analyzed for locomotion. Group differences in regional 18FDG uptake normalized to whole brain were determined using Statistical Parametric Mapping (SPM) and verified by region of interest (ROI) analysis. Results SA treated animals demonstrated significant increases in 18FDG uptake compared to controls in several brain regions associated with the distribution of KOR such as the periaqueductal grey, bed nucleus of the stria terminalis and the cerbellar vermis, as well as in the hypothalamus. Significant bilateral activations were also observed in the auditory, sensory and frontal cortices. Regional decreases in metabolic demand were observed bilaterally in the dorsolateral striatum and hippocampus. Locomotor activity did not differ between SA and vehicle during 18FDG uptake. Conclusions We have provided the first extensive maps of cerebral metabolic activation due to the potent κ-opioid agonist, salvinorin A. A major finding from our small animal PET studies using 18FDG was that neural circuits affected by SA may not be limited to direct activation or inhibition of kappa receptor-expressing cells. Instead, salvinorin A may trigger brain circuits that mediate the effects of the drug on cognition, mood, fear and anxiety, and motor output. PMID:19132449

  15. OCT imaging of acute vascular changes following mild traumatic brain injury in mice (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Chico-Calero, Isabel; Shishkov, Milen; Welt, Jonathan; Blatter, Cedric; Vakoc, Benjamin J.

    2016-03-01

    While most people recover completely from mild traumatic brain injuries (mTBIs) and concussions, a subset develop lasting neurological disorders. Understanding the complex pathophysiology of these injuries is critical to developing improved prognostic and therapeutic approaches. Multiple studies have shown that the structure and perfusion of brain vessels are altered after mTBI. It is possible that these vascular injuries contribute to or trigger neurodegeneration. Intravital microscopy and mouse models of TBI offer a powerful platform to study the vascular component of mTBI. Because optical coherence tomography based angiography is based on perfusion contrast and is not significantly degraded by vessel leakage or blood brain barrier disruption, it is uniquely suited to studies of brain perfusion in the setting of trauma. However, existing TBI imaging models require surgical exposure of the brain at the time of injury which conflates TBI-related vascular changes with those caused by surgery. In this work, we describe a modified cranial window preparation based on a flexible, transparent polyurethane membrane. Impact injuries were delivered directly through this membrane, and imaging was performed immediately after injury without the need for additional surgical procedures. Using this model, we demonstrate that mTBI induces a transient cessation of flow in the capillaries and smaller vessels near the injury point. Reperfusion is observed in all animals within 3 hours of injury. This work describes new insight into the transient vascular changes induced by mTBI, and demonstrates more broadly the utility of the OCT/polyurethane window model platform in preclinical studies of mTBI.

  16. Bacillus cereus bacteremia and multiple brain abscesses during acute lymphoblastic leukemia induction therapy.

    PubMed

    Hansford, Jordan R; Phillips, Marianne; Cole, Catherine; Francis, Joshua; Blyth, Christopher C; Gottardo, Nicholas G

    2014-04-01

    Bacillus cereus can cause serious infections in immunosuppressed patients. This population may be susceptible to B. cereus pneumonia, bacteremia, cellulitis, and rarely cerebral abscess. Here we report an 8-year-old boy undergoing induction therapy for acute lymphoblastic leukemia who developed multifocal B. cereus cerebral abscesses, highlighting the propensity for B. cereus to develop cerebral abscesses. A review of the literature over the past 25 years identified another 11 cases (3 children and 8 adults) of B. cereus cerebral abscess in patients undergoing cancer therapy. B. cereus cerebral abscesses were associated with a high mortality rate (42%) and significant morbidity. Notably, B. cereus bacteremia with concomitant cerebral abscess was associated with induction chemotherapy for acute leukemia in both children and adults (10 of 12 case reports). Our case report and review of the literature highlights the propensity for B. cereus to develop cerebral abscess(es). Therefore, early consideration for neuroimaging should be given for any neutropenic cancer patient identified with B. cereus bacteremia, in particular those with acute leukemia during induction therapy. PMID:23619116

  17. Acetazolamide during acute hypoxia improves tissue oxygenation in the human brain.

    PubMed

    Wang, Kang; Smith, Zachary M; Buxton, Richard B; Swenson, Erik R; Dubowitz, David J

    2015-12-15

    Low doses of the carbonic anhydrase inhibitor acetazolamide provides accelerated acclimatization to high-altitude hypoxia and prevention of cerebral and other symptoms of acute mountain sickness. We previously observed increases in cerebral O2 metabolism (CMRO2 ) during hypoxia. In this study, we investigate whether low-dose oral acetazolamide (250 mg) reduces this elevated CMRO2 and in turn might improve cerebral tissue oxygenation (PtiO2 ) during acute hypoxia. Six normal human subjects were exposed to 6 h of normobaric hypoxia with and without acetazolamide prophylaxis. We determined CMRO2 and cerebral PtiO2 from MRI measurements of cerebral blood flow (CBF) and cerebral venous O2 saturation. During normoxia, low-dose acetazolamide resulted in no significant change in CBF, CMRO2 , or PtiO2 . During hypoxia, we observed increases in CBF [48.5 (SD 12.4) (normoxia) to 65.5 (20.4) ml·100 ml(-1)·min(-1) (hypoxia), P < 0.05] and CMRO2 [1.54 (0.19) to 1.79 (0.25) μmol·ml(-1)·min(-1), P < 0.05] and a dramatic decline in PtiO2 [25.0 to 11.4 (2.7) mmHg, P < 0.05]. Acetazolamide prophylaxis mitigated these rises in CBF [53.7 (20.7) ml·100 ml(-1)·min(-1) (hypoxia + acetazolamide)] and CMRO2 [1.41 (0.09) μmol·ml(-1)·min(-1) (hypoxia + acetazolamide)] associated with acute hypoxia but also reduced O2 delivery [6.92 (1.45) (hypoxia) to 5.60 (1.14) mmol/min (hypoxia + acetazolamide), P < 0.05]. The net effect was improved cerebral tissue PtiO2 during acute hypoxia [11.4 (2.7) (hypoxia) to 16.5 (3.0) mmHg (hypoxia + acetazolamide), P < 0.05]. In addition to its renal effect, low-dose acetazolamide is effective at the capillary endothelium, and we hypothesize that local interruption in cerebral CO2 excretion accounts for the improvements in CMRO2 and ultimately in cerebral tissue oxygenation during hypoxia. This study suggests a potentially pivotal role of cerebral CO2 and pH in modulating CMRO2 and PtiO2 during acute hypoxia. PMID:26472861

  18. Protective Ventilation of Preterm Lambs Exposed to Acute Chorioamnionitis Does Not Reduce Ventilation-Induced Lung or Brain Injury

    PubMed Central

    Barton, Samantha K.; Moss, Timothy J. M.; Hooper, Stuart B.; Crossley, Kelly J.; Gill, Andrew W.; Kluckow, Martin; Zahra, Valerie; Wong, Flora Y.; Pichler, Gerhard; Galinsky, Robert; Miller, Suzanne L.

    2014-01-01

    Background The onset of mechanical ventilation is a critical time for the initiation of cerebral white matter (WM) injury in preterm neonates, particularly if they are inadvertently exposed to high tidal volumes (VT) in the delivery room. Protective ventilation strategies at birth reduce ventilation-induced lung and brain inflammation and injury, however its efficacy in a compromised newborn is not known. Chorioamnionitis is a common antecedent of preterm birth, and increases the risk and severity of WM injury. We investigated the effects of high VT ventilation, after chorioamnionitis, on preterm lung and WM inflammation and injury, and whether a protective ventilation strategy could mitigate the response. Methods Pregnant ewes (n = 18) received intra-amniotic lipopolysaccharide (LPS) 2 days before delivery, instrumentation and ventilation at 127±1 days gestation. Lambs were either immediately euthanased and used as unventilated controls (LPSUVC; n = 6), or were ventilated using an injurious high VT strategy (LPSINJ; n = 5) or a protective ventilation strategy (LPSPROT; n = 7) for a total of 90 min. Mean arterial pressure, heart rate and cerebral haemodynamics and oxygenation were measured continuously. Lungs and brains underwent molecular and histological assessment of inflammation and injury. Results LPSINJ lambs had poorer oxygenation than LPSPROT lambs. Ventilation requirements and cardiopulmonary and systemic haemodynamics were not different between ventilation strategies. Compared to unventilated lambs, LPSINJ and LPSPROT lambs had increases in pro-inflammatory cytokine expression within the lungs and brain, and increased astrogliosis (p<0.02) and cell death (p<0.05) in the WM, which were equivalent in magnitude between groups. Conclusions Ventilation after acute chorioamnionitis, irrespective of strategy used, increases haemodynamic instability and lung and cerebral inflammation and injury. Mechanical ventilation is a potential contributor

  19. Increase in cocaine- and amphetamine-regulated transcript (CART) in specific areas of the mouse brain by acute caffeine administration.

    PubMed

    Cho, Jin Hee; Cho, Yun Ha; Kim, Hyo Young; Cha, Seung Ha; Ryu, Hyun; Jang, Wooyoung; Shin, Kyung Ho

    2015-04-01

    Caffeine produces a variety of behavioral effects including increased alertness, reduced food intake, anxiogenic effects, and dependence upon repeated exposure. Although many of the effects of caffeine are mediated by its ability to block adenosine receptors, it is possible that other neural substrates, such as cocaine- and amphetamine-regulated transcript (CART), may be involved in the effects of caffeine. Indeed, a recent study demonstrated that repeated caffeine administration increases CART in the mouse striatum. However, it is not clear whether acute caffeine administration alters CART in other areas of the brain. To explore this possibility, we investigated the dose- and time-dependent changes in CART immunoreactivity (CART-IR) after a single dose of caffeine in mice. We found that a high dose of caffeine (100 mg/kg) significantly increased CART-IR 2 h after administration in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), central nucleus of the amygdala (CeA), paraventricular hypothalamic nucleus (PVN), arcuate hypothalamic nucleus (Arc), and locus coeruleus (LC), and returned to control levels after 8 h. But this increase was not observed in other brain areas. In addition, caffeine administration at doses of 25 and 50 mg/kg appears to produce dose-dependent increases in CART-IR in these brain areas; however, the magnitude of increase in CART-IR observed at a dose of 50 mg/kg was similar or greater than that observed at a dose of 100 mg/kg. This result suggests that CART-IR in AcbSh, dBNST, CeA, PVN, Arc, and LC is selectively affected by caffeine administration. PMID:25820086

  20. Urea Biosynthesis Using Liver Slices

    ERIC Educational Resources Information Center

    Teal, A. R.

    1976-01-01

    Presented is a practical scheme to enable introductory biology students to investigate the mechanism by which urea is synthesized in the liver. The tissue-slice technique is discussed, and methods for the quantitative analysis of metabolites are presented. (Author/SL)

  1. Effects of acute CDP-choline treatment on resting state brain oscillations in healthy volunteers.

    PubMed

    Knott, Verner; de la Salle, Sara; Smith, Dylan; Choueiry, Joelle; Impey, Danielle; Smith, Meaghan; Beaudry, Elise; Saghir, Salman; Ilivitsky, Vadim; Labelle, Alain

    2015-03-30

    CDP-choline (cytidine-5'-diphosphocholine) is a phospholipid used to treat cognitive disorders, presumably repairing and maintaining brain cell membranes. Additional mechanisms may include enhanced cholinergic neurotransmission as the α7 nicotinic receptor actions of choline and increased acetylcholine synthesis accompanying CDP-choline administration may modulate brain oscillations underlying cognitive processes. This study utilizes electroencephalographic (EEG) recordings in healthy volunteers to evaluate CDP-choline induction of an oscillatory response profile associated with nicotinic stimulation. Resting state EEG was acquired in 24 male volunteers administered low (500mg) and moderate (1000mg) doses of CDP-choline in a randomized placebo-controlled, crossover trial. Consistent with nicotinic agonist treatment, spectral analysis showed dose-dependent reductions in delta and increases in alpha oscillations, which were also accompanied by decreases in beta and gamma oscillatory activity. These findings support the posit that CDP-choline cognitive enhancement involves multiple mechanisms including facilitated nicotinic cholinergic action. PMID:25700947

  2. Effects of recombinant human brain natriuretic peptide on renal function in patients with acute heart failure following myocardial infarction

    PubMed Central

    Wang, Yanbo; Gu, Xinshun; Fan, Weize; Fan, Yanming; Li, Wei; Fu, Xianghua

    2016-01-01

    Objective: To investigate the effect of recombinant human brain natriuretic peptide (rhBNP) on renal function in patients with acute heart failure (AHF) following acute myocardial infarction (AMI). Methods: Consecutive patients with AHF following AMI were enrolled in this clinical trial. Eligible patients were randomly assigned to receive rhBNP (rhBNP group) or nitroglycerin (NIT group). Patients in the rhBNP group received rhBNP 0.15 μg /kg bolus injection after randomization followed by an adjusted-dose (0.0075-0.020 μg/kg/min) for 72 hours, while patients in NIT received infusion of nitroglycerin with an adjusted-dose (10-100 μg/kg/min) for 72 hours in NIT group. Standard clinical and laboratory data were collected. The levels of serum creatinine (SCr), urea, β-2 microglobulin and cystatin C were measured at baseline and repeated at the end of the 24, 48 and 72 hours after infusion. The primary end point was the incidence of acute renal dysfunction, which was defined as an increase in SCr > 0.5 mg/dl (> 44.2 μmol/L) or 25% above baseline SCr value. The occurrence of major adverse cardiac event (MACE) was followed up for 1 month. Results: Of the 50 patients enrolled, 26 were randomly assigned to rhBNP and 24 to nitroglycerin (NIT). There were no significant differences in baseline characteristics between the two groups (all P > 0.05). The baseline concentrations of SCr, urea, β-2 microglobulin and cystatin C at admission were similar in the two groups. However, the concentrations of SCr and urea were significantly higher in rhBNP group than those in NIT group at hour 24 and 48 after treatments (all P < 0.01). For both groups, the concentrations of SCr, urea, β-2 microglobulin and cystatin C were not significant changed compared with baseline levels. The levels of systolic blood pressure (SBP) and diastolic blood pressures (DBP) at admission were also similar between the two groups. In rhBNP group, levels of SBP and DBP decreased significantly at hour 24

  3. Ultrastructural mitochondria changes in perihematomal brain and neuroprotective effects of Huperzine A after acute intracerebral hemorrhage

    PubMed Central

    Lu, Haiying; Jiang, Mei; Lu, Lei; Zheng, Guo; Dong, Qiang

    2015-01-01

    Aim The purpose of the study was to observe the ultrastructural changes of neuronal mitochondria in perihematomal brain tissue and assess the therapeutic potential of Huperzine A (HA, a mitochondrial protector) following intracerebral hemorrhage (ICH). Methods Brain hemorrhage was induced in adult Sprague Dawley rats by injecting autologous blood into the striatum and then removing the brains 3, 6, 12, 24, or 48 hours later to analyze mitochondrial ultrastructure in a blinded manner. Parallel groups of ICH rats were treated with HA or saline immediately after ICH. Perihematomal apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), caspase-3 activation and cytochrome C translocation were tracked by immunoblots, and neurobehavioral test results were compared between the groups. Results Mitochondria in perihematomal neurons demonstrated dramatic changes including mitochondrial swelling, intracristal dilation, and decreased matrix density. HA treatment decreased mitochondrial injury and apoptosis, inhibited caspase-3 activation and cytochrome C translocation, and improved behavioral recovery. Conclusion These data show that ICH induces dramatic mitochondrial damage, and HA exhibits protective effects possibly through ameliorating mitochondrial injury and apoptosis. Collectively, these findings suggest a new direction for novel therapeutics. PMID:26508860

  4. Changes in the mitochondrial antioxidant systems in neurodegenerative diseases and acute brain disorders.

    PubMed

    Ruszkiewicz, Joanna; Albrecht, Jan

    2015-09-01

    Oxidative and nitrosative stress (ONS) contributes to the pathogenesis of most brain maladies, and the magnitude of ONS is related to the ability of cellular antioxidants to neutralize the accumulating reactive oxygen and nitrogen species (ROS/RNS). While the major ROS/RNS scavengers and regenerators of bio-oxidized molecules, superoxide dysmutases (SODs), glutathione (GSH), thioredoxin (Trx) and peroxiredoxin (Prx), are distributed in all cellular compartments. This review specifically focuses on the role of the systems operating in mitochondria. There is a growing consensus that the mitochondrial SOD isoform - SOD2 and GSH are critical for the cellular antioxidant defense. Variable changes of the expression or activities of one or more of the mitochondrial antioxidant systems have been documented in the brains derived from human patients and/or in animal models of neurodegenerative diseases (Alzheimer's disease, Parkinson's disease), cerebral ischemia, toxic brain cell damage associated with overexposure to mercury or excitotoxins, or hepatic encephalopathy. In many cases, ambiguity of the responses of the different antioxidant systems in one and the same disease needs to be more conclusively evaluated before the balance of the changes is viewed as beneficial or detrimental. Modulation of the mitochondrial antioxidant systems may in the future become a target of antioxidant therapy. PMID:25576182

  5. Acute effects of hydrocortisone on the human brain: An fMRI study

    PubMed Central

    Lovallo, William R.; Robinson, Jennifer L.; Glahn, David C.; Fox, Peter T.

    2009-01-01

    Cortisol is essential for regulating all cell types in the body, including those in the brain. Most information concerning cortisol’s cerebral effects comes from work in nonhumans. This is a first effort to use functional magnetic resonance imaging (fMRI) to study the time course and locus of cortisol’s effects on selected brain structures in resting humans. We repeatedly scanned 21 healthy young adults over 45 min to examine changes in the brain’s activity 5 min before, and for 40 min after, an IV injection of 10 mg of hydrocortisone (N = 11) or saline placebo (N = 10). At 15–18 min postinjection we observed in the hydrocortisone group reduced activity in the hippocampus and amygdala that reached a peak response minimum at 25–30 min postinjection (−1 Standard Deviation) relative to placebo. No such effect was seen in the thalamus. Functional MRI appears to be a safe, noninvasive method to study the time course and anatomical effects of glucocorticoids in the human brain. PMID:19836143

  6. Clinical review: Prognostic value of magnetic resonance imaging in acute brain injury and coma

    PubMed Central

    Weiss, Nicolas; Galanaud, Damien; Carpentier, Alexandre; Naccache, Lionel; Puybasset, Louis

    2007-01-01

    Progress in management of critically ill neurological patients has led to improved survival rates. However, severe residual neurological impairment, such as persistent coma, occurs in some survivors. This raises concerns about whether it is ethically appropriate to apply aggressive care routinely, which is also associated with burdensome long-term management costs. Adapting the management approach based on long-term neurological prognosis represents a major challenge to intensive care. Magnetic resonance imaging (MRI) can show brain lesions that are not visible by computed tomography, including early cytotoxic oedema after ischaemic stroke, diffuse axonal injury after traumatic brain injury and cortical laminar necrosis after cardiac arrest. Thus, MRI increases the accuracy of neurological diagnosis in critically ill patients. In addition, there is some evidence that MRI may have potential in terms of predicting outcome. Following a brief description of the sequences used, this review focuses on the prognostic value of MRI in patients with traumatic brain injury, anoxic/hypoxic encephalopathy and stroke. Finally, the roles played by the main anatomical structures involved in arousal and awareness are discussed and avenues for future research suggested. PMID:17980050

  7. Brain white matter changes during treatment of a child for acute lymphoblastic leukemia.

    PubMed

    Maeda, Miho; Hayakawa, Jun; Ueda, Takahiro; Migita, Makoto; Asano, Takeshi; Fukunaga, Yoshitaka; Amano, Yasuo

    2005-10-01

    A 13-year old boy with acute lymphoblastic leukemia had bilateral paresis of the upper extremities and aphasia 1 week after high dose methotrexate and triple intrathecal therapy (methotrexate, cytarabin, hydrocortisone). The stroke-like neurological symptoms disappeared on the third day. T2-weighted magnetic resonance imaging showed hyperintensities of white matter on the second day. Despite resolution of the neurological symptoms, magnetic resonance images were still abnormal 3 years after the attack. Methotrexate has been considered to be responsible for ischemic damage to oligodendroglial cells, resulting in demyelination. The changes are occasionally prolonged without persistent neurologic symptoms. PMID:16247223

  8. Effects of acute ammonia toxicity on nitric oxide (NO), citrulline-NO cycle enzymes, arginase and related metabolites in different regions of rat brain.

    PubMed

    Swamy, M; Zakaria, Adlin Zafrulan; Govindasamy, Chandran; Sirajudeen, K N S; Nadiger, H A

    2005-10-01

    Nitric oxide (NO) is involved in many pathophysiological processes in the brain. NO is synthesized from arginine by nitric oxide synthase (NOS) enzymes. Citrulline formed as a by-product of the NOS reaction, can be recycled to arginine by successive actions of argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL) via the citrulline-NO cycle. Hyperammonemia is known to cause poorly understood perturbations of the citrulline-NO cycle. To understand the role of citrulline-NO cycle in hyperammonemia, NOS, ASS, ASL and arginase activities, as well as nitrate/nitrite (NOx), arginine, ornithine, citrulline, glutamine, glutamate and GABA were estimated in cerebral cortex (CC), cerebellum (CB) and brain stem (BS) of rats subjected to acute ammonia toxicity. NOx concentration and NOS activity were found to increase in all the regions of brain in acute ammonia toxicity. The activities of ASS and ASL showed an increasing trend whereas the arginase was not changed. The results of this study clearly demonstrated the increased formation of NO, suggesting the involvement of NO in the pathophysiology of acute ammonia toxicity. The increased activities of ASS and ASL suggest the increased and effective recycling of citrulline to arginine in acute ammonia toxicity, making NO production more effective and contributing to its toxic effects. PMID:16009439

  9. Automatic identification of intracranial hemorrhage in non-contrast CT with large slice thickness for trauma cases

    NASA Astrophysics Data System (ADS)

    Maduskar, Pragnya; Acharyya, Mausumi

    2009-02-01

    In this paper we propose a technique for automatic detection of intracranial hemorrhage (ICH) and acute intracranial hemorrhage (AIH) in brain Computed Tomography (CT) for trauma cases where no contrast can be applied and the CT has large slice thickness. ICH or AIH comprise of internal bleeding (intra-axial) or external (extra-axial) to the brain substance. Large bleeds like in intra-axial region are easy to diagnose whereas it can be challenging if small bleed occurs in extra-axial region particularly in the absence of contrast. Bleed region needs to be distinguished from bleed-look-alike brain regions which are abnormally bright falx and fresh flowing blood. We propose an algorithm for detection of brain bleed in various anatomical locations. A preprocessing step is performed to segment intracranial contents and enhancement of region of interests(ROIs). A number of bleed and bleed-look-alike candidates are identified from a set of 11 available cases. For each candidate texture based features are extracted from non-separable quincunx wavelet transform along with some other descriptive features. The candidates are randomly divided into a training and test set consisting of both bleed and bleed-look- alike. A supervised classifier is designed based on the training sample features. A performance accuracy of 96% is attained for the independent test candidates.

  10. Wire blade development for Fixed Abrasive Slicing Technique (FAST) slicing

    NASA Technical Reports Server (NTRS)

    Khattak, C. P.; Schmid, F.; Smith, M. B.

    1982-01-01

    A low cost, effective slicing method is essential to make ingot technology viable for photovoltaics in terrestrial applications. The fixed abrasive slicing technique (FAST) combines the advantages of the three commercially developed techniques. In its development stage FAST demonstrated cutting effectiveness of 10 cm and 15 cm diameter workpieces. Wire blade development is still the critical element for commercialization of FAST technology. Both impregnated and electroplated wire blades have been developed; techniques have been developed to fix diamonds only in the cutting edge of the wire. Electroplated wires show the most near term promise and this approach is emphasized. With plated wires it has been possible to control the size and shape of the electroplating, it is expected that this feature reduces kerf and prolongs the life of the wirepack.

  11. Altered spontaneous brain activity patterns in patients with unilateral acute open globe injury using amplitude of low-frequency fluctuation: a functional magnetic resonance imaging study

    PubMed Central

    Tan, Gang; Huang, Xin; Ye, Lei; Wu, An-Hua; He, Li-Xian; Zhong, Yu-Lin; Jiang, Nan; Zhou, Fu-Qing; Shao, Yi

    2016-01-01

    Objective The aim of this study was to evaluate altered spontaneous brain activities in patients with unilateral acute open globe injury (OGI) using amplitude of low-frequency fluctuation (ALFF) method and its relationship with their clinical manifestations. Patients and methods A total of 18 patients with acute OGI (16 males and two females) and 18 healthy controls (HCs, 16 males and two females) closely matched in age, sex, and education were recruited in this study. The ALFF method was used to evaluate the altered spontaneous brain activities. The relationships between the mean ALFF signal values of different brain regions and the clinical features were evaluated by correlation analysis. Acute OGI patients were distinguished from HCs by receiver operating characteristic curve. Results Compared with HCs, acute OGI patients had significantly higher ALFF values in the left cuneus, left middle cingulum cortex, and bilateral precuneus. Furthermore, the age of OGI patients showed a negative correlation with the ALFF signal value of the left middle cingulum cortex (r=−0.557, P=0.016) and a negative correlation with the mean ALFF signal value of the bilateral precuneus (r=−0.746, P<0.001). The ALFF signal value of the bilateral precuneus was negatively correlated with the duration of OGI (r=−0.493, P=0.038) and positively correlated with the vision acuity of the injured eye (r=0.583, P=0.011). Conclusion Acute OGI mainly induces dysfunction in the left cuneus, left middle cingulum cortex, and bilateral precuneus, which may reflect the underlying pathologic mechanisms of abnormal brain activities in OGI patients. PMID:27570455

  12. Effects of ginseng saponin on acute cocaine-induced alterations in evoked dopamine release and uptake in rat brain nucleus accumbens.

    PubMed

    Nah, Seong-Yeol; Bhatia, Kamal S; Lyles, Johnnie; Ellinwood, Everett H; Lee, Tong H

    2009-01-12

    In traditional medicine, Panax ginseng has been used to treat various behavioral effects of psychostimulants (e.g., cocaine) and other drugs of abuse and to ameliorate withdrawal symptoms. The neurochemical bases for this efficacy, however, remain to be elucidated. We previously used the real-time fast-scan cyclic voltammetry in rat nucleus accumbens slices to demonstrate that cocaine not only enhances DA release evoked by single-pulse electrical stimulation and inhibits DA uptake during application but also further increases the release upon washout (termed a "rebound" release enhancement). In the present study, we determined whether co-application and washout of ginseng total saponin (GTS), the active ingredient of Panax ginseng, with cocaine attenuate cocaine-induced enhancement of evoked DA release, DA uptake inhibition and/or withdrawal-associated rebound enhancement. Cocaine rapidly potentiated the DA release within the first 10 min of application, and acute cocaine withdrawal caused a rebound increase. Co-application of GTS with cocaine inhibited the release enhancement and subsequently prevented the rebound increase during acute withdrawal. The effect of GTS was concentration-dependent. In contrast, GTS had no significant effects on the cocaine-mediated DA uptake inhibition. These results suggest that the attenuation of the cocaine-induced enhancement of impulse-dependent DA release, rather than uptake inhibition, might be one of the pharmacological bases for attenuation of behavioral effects of cocaine and amelioration of acute withdrawal symptoms by ginseng. PMID:19026615

  13. Deconstructing brain-derived neurotrophic factor actions in adult brain circuits to bridge an existing informational gap in neuro-cell biology.

    PubMed

    Bowling, Heather; Bhattacharya, Aditi; Klann, Eric; Chao, Moses V

    2016-03-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in neurodevelopment, synaptic plasticity, learning and memory, and in preventing neurodegeneration. Despite decades of investigations into downstream signaling cascades and changes in cellular processes, the mechanisms of how BDNF reshapes circuits in vivo remain unclear. This informational gap partly arises from the fact that the bulk of studies into the molecular actions of BDNF have been performed in dissociated neuronal cultures, while the majority of studies on synaptic plasticity, learning and memory were performed in acute brain slices or in vivo. A recent study by Bowling-Bhattacharya et al., measured the proteomic changes in acute adult hippocampal slices following treatment and reported changes in proteins of neuronal and non-neuronal origin that may in concert modulate synaptic release and secretion in the slice. In this paper, we place these findings into the context of existing literature and discuss how they impact our understanding of how BDNF can reshape the brain. PMID:27127458

  14. Deconstructing brain-derived neurotrophic factor actions in adult brain circuits to bridge an existing informational gap in neuro-cell biology

    PubMed Central

    Bowling, Heather; Bhattacharya, Aditi; Klann, Eric; Chao, Moses V.

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in neurodevelopment, synaptic plasticity, learning and memory, and in preventing neurodegeneration. Despite decades of investigations into downstream signaling cascades and changes in cellular processes, the mechanisms of how BDNF reshapes circuits in vivo remain unclear. This informational gap partly arises from the fact that the bulk of studies into the molecular actions of BDNF have been performed in dissociated neuronal cultures, while the majority of studies on synaptic plasticity, learning and memory were performed in acute brain slices or in vivo. A recent study by Bowling-Bhattacharya et al., measured the proteomic changes in acute adult hippocampal slices following treatment and reported changes in proteins of neuronal and non-neuronal origin that may in concert modulate synaptic release and secretion in the slice. In this paper, we place these findings into the context of existing literature and discuss how they impact our understanding of how BDNF can reshape the brain. PMID:27127458

  15. Cerebral hemodynamic changes of mild traumatic brain injury at the acute stage.

    PubMed

    Doshi, Hardik; Wiseman, Natalie; Liu, Jun; Wang, Wentao; Welch, Robert D; O'Neil, Brian J; Zuk, Conor; Wang, Xiao; Mika, Valerie; Szaflarski, Jerzy P; Haacke, E Mark; Kou, Zhifeng

    2015-01-01

    Mild traumatic brain injury (mTBI) is a significant public health care burden in the United States. However, we lack a detailed understanding of the pathophysiology following mTBI and its relation to symptoms and recovery. With advanced magnetic resonance imaging (MRI), we can investigate brain perfusion and oxygenation in regions known to be implicated in symptoms, including cortical gray matter and subcortical structures. In this study, we assessed 14 mTBI patients and 18 controls with susceptibility weighted imaging and mapping (SWIM) for blood oxygenation quantification. In addition to SWIM, 7 patients and 12 controls had cerebral perfusion measured with arterial spin labeling (ASL). We found increases in regional cerebral blood flow (CBF) in the left striatum, and in frontal and occipital lobes in patients as compared to controls (p = 0.01, 0.03, 0.03 respectively). We also found decreases in venous susceptibility, indicating increases in venous oxygenation, in the left thalamostriate vein and right basal vein of Rosenthal (p = 0.04 in both). mTBI patients had significantly lower delayed recall scores on the standardized assessment of concussion, but neither susceptibility nor CBF measures were found to correlate with symptoms as assessed by neuropsychological testing. The increased CBF combined with increased venous oxygenation suggests an increase in cerebral blood flow that exceeds the oxygen demand of the tissue, in contrast to the regional hypoxia seen in more severe TBI. This may represent a neuroprotective response following mTBI, which warrants further investigation. PMID:25659079

  16. Cerebral Hemodynamic Changes of Mild Traumatic Brain Injury at the Acute Stage

    PubMed Central

    Doshi, Hardik; Wiseman, Natalie; Liu, Jun; Wang, Wentao; Welch, Robert D.; O’Neil, Brian J.; Zuk, Conor; Wang, Xiao; Mika, Valerie; Szaflarski, Jerzy P.; Haacke, E. Mark; Kou, Zhifeng

    2015-01-01

    Mild traumatic brain injury (mTBI) is a significant public health care burden in the United States. However, we lack a detailed understanding of the pathophysiology following mTBI and its relation to symptoms and recovery. With advanced magnetic resonance imaging (MRI), we can investigate brain perfusion and oxygenation in regions known to be implicated in symptoms, including cortical gray matter and subcortical structures. In this study, we assessed 14 mTBI patients and 18 controls with susceptibility weighted imaging and mapping (SWIM) for blood oxygenation quantification. In addition to SWIM, 7 patients and 12 controls had cerebral perfusion measured with arterial spin labeling (ASL). We found increases in regional cerebral blood flow (CBF) in the left striatum, and in frontal and occipital lobes in patients as compared to controls (p = 0.01, 0.03, 0.03 respectively). We also found decreases in venous susceptibility, indicating increases in venous oxygenation, in the left thalamostriate vein and right basal vein of Rosenthal (p = 0.04 in both). mTBI patients had significantly lower delayed recall scores on the standardized assessment of concussion, but neither susceptibility nor CBF measures were found to correlate with symptoms as assessed by neuropsychological testing. The increased CBF combined with increased venous oxygenation suggests an increase in cerebral blood flow that exceeds the oxygen demand of the tissue, in contrast to the regional hypoxia seen in more severe TBI. This may represent a neuroprotective response following mTBI, which warrants further investigation. PMID:25659079

  17. Dexamethasone-induced acute excitotoxic cell death in the developing brain.

    PubMed

    Lanshakov, Dmitriy A; Sukhareva, Ekaterina V; Kalinina, Tatjana S; Dygalo, Nikolay N

    2016-07-01

    There is substantial evidence that the use of glucocorticoids in neonates is associated with an increased risk of neurodevelopmental disorders. However, it remains unclear how treatment with low doses of dexamethasone (DEX) may result in behavioral abnormalities without evident signs of immediate neurotoxicity in the neonatal brain. It is possible that cells vulnerable to the pro-apoptotic effects of low doses of DEX escaped detection due to their small number in the developing brain. In agreement with this suggestion, low-dose DEX treatment (0.2mg/kg) failed to induce apoptosis in the cortex or hippocampus proper of neonatal rats. However, this treatment was capable of inducing apoptosis specifically in the dorsal subiculum via a two-step mechanism that involves glutamate excitotoxicity. Application of DEX leads to increased activity of CA1/CA3 hippocampal MAP2-positive neurons, as determined by c-Fos expression at 0.5-1h after DEX injection. Five hours later, the apoptotic markers (fragmented nuclei, active caspase-3 and TUNEL labeling) increased in the dorsal subiculum, which receives massive glutamatergic input from CA1 neurons. Pretreatment with memantine, an antagonist of glutamate NMDA receptors, dose dependently blocked the DEX-induced expression of apoptotic markers in the subicular neurons and astrocytes. These findings provide new insights into the mechanisms of DEX-induced neurotoxicity as well as on the mechanism of therapeutic action of antagonists of NMDA receptors against neurobehavioral disorders caused by neonatal exposure to glucocorticoids. PMID:26873551

  18. Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia

    PubMed Central

    Pedata, Felicita; Pugliese, Anna Maria; Coppi, Elisabetta; Dettori, Ilaria; Maraula, Giovanna; Cellai, Lucrezia; Melani, Alessia

    2014-01-01

    The extracellular concentration of adenosine in the brain increases dramatically during ischemia. Adenosine A2A receptor is expressed in neurons and glial cells and in inflammatory cells (lymphocytes and granulocytes). Recently, adenosine A2A receptor emerged as a potential therapeutic attractive target in ischemia. Ischemia is a multifactorial pathology characterized by different events evolving in the time. After ischemia the early massive increase of extracellular glutamate is followed by activation of resident immune cells, that is, microglia, and production or activation of inflammation mediators. Proinflammatory cytokines, which upregulate cell adhesion molecules, exert an important role in promoting recruitment of leukocytes that in turn promote expansion of the inflammatory response in ischemic tissue. Protracted neuroinflammation is now recognized as the predominant mechanism of secondary brain injury progression. A2A receptors present on central cells and on blood cells account for important effects depending on the time-related evolution of the pathological condition. Evidence suggests that A2A receptor antagonists provide early protection via centrally mediated control of excessive excitotoxicity, while A2A receptor agonists provide protracted protection by controlling massive blood cell infiltration in the hours and days after ischemia. Focus on inflammatory responses provides for adenosine A2A receptor agonists a wide therapeutic time-window of hours and even days after stroke. PMID:25165414

  19. Acute effect of a high nitrate diet on brain perfusion in older adults

    PubMed Central

    Presley, Tennille D.; Morgan, Ashley R.; Bechtold, Erika; Clodfelter, William; Dove, Robin W.; Jennings, Janine M.; Kraft, Robert A.; King, S. Bruce; Laurienti, Paul J.; Rejeski, W. Jack; Burdette, Jonathan H.; Kim-Shapiro, Daniel B.; Miller, Gary D.

    2010-01-01

    Aims Poor blood flow and hypoxia/ischemia contribute to many disease states and may also be a factor in the decline of physical and cognitive function in aging. Nitrite has been discovered to be a vasodilator that is preferentially harnessed in hypoxia. Thus, both infused and inhaled nitrite are being studied as therapeutic agents for a variety of diseases. In addition, nitrite derived from nitrate in the diet has been shown to decrease blood pressure and improve exercise performance. Thus, dietary nitrate may also be important when increased blood flow in hypoxic or ischemic areas is indicated. These conditions could include age-associated dementia and cognitive decline. The goal of this study was to determine if dietary nitrate would increase cerebral blood flow in older adults. Methods and Results In this investigation we administered a high vs. low nitrate diet to older adults (74.7 ± 6.9 years) and measured cerebral perfusion using arterial spin labeling magnetic resonance imaging. We found that the high nitrate diet did not alter global cerebral perfusion, but did lead to increased regional cerebral perfusion in frontal lobe white matter, especially between the dorsolateral prefrontal cortex and anterior cingulate cortex. Conclusion These results suggest that dietary nitrate may be useful in improving regional brain perfusion in older adults in critical brain areas known to be involved in executive functioning. PMID:20951824

  20. Neocortical slices from adult chronic epileptic rats exhibit discharges of higher voltages and broader spread.

    PubMed

    Serafini, R; Dettloff, S; Loeb, J A

    2016-05-13

    Much of the current understanding of epilepsy mechanisms has been built on data recorded with one or a few electrodes from temporal lobe slices of normal young animals stimulated with convulsants. Mechanisms of adult, extratemporal, neocortical chronic epilepsy have not been characterized as much. A more advanced understanding of epilepsy mechanisms can be obtained by recording epileptiform discharges simultaneously from multiple points of an epileptic focus so as to define their sites of initiation and pathways of spreading. Brain slice recordings can characterize epileptic mechanisms in a simpler, more controlled preparation than in vivo. Yet, the intrinsic hyper-excitability of a chronic epileptic focus may not be entirely preserved in slices following the severing of connections in slice preparation. This study utilizes recordings of multiple electrode arrays to characterize which features of epileptic hyper-excitability present in in vivo chronic adult neocortical epileptic foci are preserved in brain slices. After tetanus toxin somatosensory cortex injections, adult rats manifest chronic spontaneous epileptic discharges both in the injection site (primary focus) and in the contralateral side (secondary focus). We prepared neocortical slices from these epileptic animals. When perfused with 4-Aminopyridine in a magnesium free medium, epileptic rat slices exhibit higher voltage discharges and broader spreading than control rat slices. Rates of discharges are similar in slices of epileptic and normal rats, however. Ictal and interictal discharges are distributed over most cortical layers, though with significant differences between primary and secondary foci. A chronic neocortical epileptic focus in slices does not show increased spontaneous pacemakers initiating epileptic discharges but shows discharges with higher voltages and broader spread, consistent with an enhanced synchrony of cellular and synaptic generators over wider surfaces. PMID:26892299

  1. Acute over-the-counter pharmacological intervention does not adversely affect behavioral outcome following diffuse traumatic brain injury in the mouse.

    PubMed

    Harrison, Jordan L; Rowe, Rachel K; O'Hara, Bruce F; Adelson, P David; Lifshitz, Jonathan

    2014-09-01

    Following mild traumatic brain injury (TBI), patients may self-treat symptoms of concussion, including post-traumatic headache, taking over-the-counter (OTC) analgesics. Administering one dose of OTC analgesics immediately following experimental brain injury mimics the at-home treated population of concussed patients and may accelerate the understanding of the relationship between brain injury and OTC pharmacological intervention. In the current study, we investigate the effect of acute administration of OTC analgesics on neurological function and cortical cytokine levels after experimental diffuse TBI in the mouse. Adult, male C57BL/6 mice were injured using a midline fluid percussion (mFPI) injury model of concussion (6-10 min righting reflex time for brain-injured mice). Experimental groups included mFPI paired with either ibuprofen (60 mg/kg, i.p.; n = 16), acetaminophen (40 mg/kg, i.p.; n = 9), or vehicle (15% ethanol (v/v) in 0.9% saline; n = 13) and sham injury paired OTC medicine or vehicle (n = 7-10 per group). At 24 h after injury, functional outcome was assessed using the rotarod task and a modified neurological severity score. Following behavior assessment, cortical cytokine levels were measured by multiplex ELISA at 24 h post-injury. To evaluate efficacy on acute inflammation, cortical cytokine levels were measured also at 6 h post-injury. In the diffuse brain-injured mouse, immediate pharmacological intervention did not attenuate or exacerbate TBI-induced functional deficits. Cortical cytokine levels were affected by injury, time, or their interaction. However, levels were not affected by treatment at 6 or 24 h post-injury. These data indicate that acute administration of OTC analgesics did not exacerbate or attenuate brain-injury deficits which may inform clinical recommendations for the at-home treated mildly concussed patient. PMID:24760409

  2. A Device for Long-Term Perfusion, Imaging, and Electrical Interfacing of Brain Tissue In vitro

    PubMed Central

    Killian, Nathaniel J.; Vernekar, Varadraj N.; Potter, Steve M.; Vukasinovic, Jelena

    2016-01-01

    Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 μm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3-D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step toward the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations. PMID:27065793

  3. Effects of acute aerobic exercise on a task-switching protocol and brain-derived neurotrophic factor concentrations in young adults with different levels of cardiorespiratory fitness.

    PubMed

    Tsai, Chia-Liang; Pan, Chien-Yu; Chen, Fu-Chen; Wang, Chun-Hao; Chou, Feng-Ying

    2016-07-01

    What is the central question of this study? Neurocognitive functions can be enhanced by acute aerobic exercise, which could be associated with changes in serum brain-derived neurotrophic factor (BDNF) concentrations. We aimed to explore acute exercise-induced changes in BDNF concentrations, neuropsychological and neurophysiological performances when individuals with different levels of cardiorespiratory fitness performed a cognitive task. What is the main finding and its importance? Only young adults with higher cardiorespiratory fitness could attain switching cost and neurophysiological benefits via acute aerobic exercise. The mechanisms might be fitness dependent. Although acute aerobic exercise could enhance serum BDNF concentrations, changes in peripheral BDNF concentrations could not be the potential factor involved in the beneficial effects on neurocognitive performance. This study investigated the effects of acute aerobic exercise on neuropsychological and neurophysiological performances in young adults with different cardiorespiratory fitness levels when performing a task-switching protocol and explored the potential associations between acute aerobic exercise-induced changes in serum brain-derived neurotrophic factor (BDNF) concentrations and various neurocognitive outcomes. Sixty young adults were categorized into one control group (i.e. non-exercise-intervention; n = 20) and two exercise-intervention (EI) groups [i.e. higher (EIH , n = 20) and lower (EIL , n = 20) cardiorespiratory fitness] according to their maximal oxygen consumption. At baseline and after either an acute bout of 30 min of moderate-intensity aerobic exercise or a control period, the neuropsychological and neurophysiological performances and serum BDNF concentrations were measured when the participants performed a task-switching protocol involving executive control and greater demands on working memory. The results revealed that although acute aerobic exercise decreased reaction

  4. Ingot slicing machine and method

    NASA Technical Reports Server (NTRS)

    Kuo, Y. S. (Inventor)

    1984-01-01

    An improved method for simultaneously slicing one or a multiplicity of boules of silicon into silicon wafers is described. A plurality of vertical stacks of horizontal saw blades of circular configuration are arranged in juxtaposed coaxial alignment. Each blade is characterized by having a cutting diameter slightly greater than the cutting diameter of the blade arranged immediately above, imparting a simultaneous rotation to the blades.

  5. Boussignac CPAP system for brain death confirmation with apneic test in case of acute lung injury/adult respiratory distress syndrome – series of cases

    PubMed Central

    Wieczorek, Andrzej; Gaszynski, Tomasz

    2015-01-01

    Introduction There are some patients with severe respiratory disturbances like adult respiratory distress syndrome (ARDS) and suspicion of brain death, for whom typical performance of the apneic test is difficult to complete because of quick desaturation and rapid deterioration without effective ventilation. To avoid failure of brain death confirmation and possible loss of organ donation another approach to apneic test is needed. We present two cases of patients with clinical symptoms of brain death, with lung pathology (acute lung injury, ARDS, lung embolism and lung infection), in whom apneic tests for recognizing brain death were difficult to perform. During typical performance of apneic test involving the use of oxygen catheter for apneic oxygenation we observed severe desaturation with growing hypotension and hemodynamic destabilization. But with the use of Boussignac CPAP system all necessary tests were successfully completed, confirming the patient’s brain death, which gave us the opportunity to perform procedures for organ donation. The main reason of apneic test difficulties was severe gas exchange disturbances secondary to ARDS. Thus lack of positive end expiratory pressure during classical performance of apneic test leads to quick desaturation and rapid hemodynamic deterioration, limiting the observation period below dedicated at least 10-minute interval. Conclusion The Boussignac CPAP system may be an effective tool for performing transparent apneic test in case of serious respiratory disturbances, especially in the form of acute lung injury or ARDS. PMID:26124664

  6. The Effect of Paracetamol on Core Body Temperature in Acute Traumatic Brain Injury: A Randomised, Controlled Clinical Trial

    PubMed Central

    Saxena, Manoj K.; Taylor, Colman; Billot, Laurent; Bompoint, Severine; Gowardman, John; Roberts, Jason A.; Lipman, Jeffery; Myburgh, John

    2015-01-01

    Background Strategies to prevent pyrexia in patients with acute neurological injury may reduce secondary neuronal damage. The aim of this study was to determine the safety and efficacy of the routine administration of 6 grams/day of intravenous paracetamol in reducing body temperature following severe traumatic brain injury, compared to placebo. Methods A multicentre, randomised, blind, placebo-controlled clinical trial in adult patients with traumatic brain injury (TBI). Patients were randomised to receive an intravenous infusion of either 1g of paracetamol or 0.9% sodium chloride (saline) every 4 hours for 72 hours. The primary outcome was the mean difference in core temperature during the study intervention period. Results Forty-one patients were included in this study: 21 were allocated to paracetamol and 20 to saline. The median (interquartile range) number of doses of study drug was 18 (17–18) in the paracetamol group and 18 (16–18) in the saline group (P = 0.85). From randomisation until 4 hours after the last dose of study treatment, there were 2798 temperature measurements (median 73 [67–76] per patient). The mean ± standard deviation temperature was 37.4±0.5°C in the paracetamol group and 37.7±0.4°C in the saline group (absolute difference -0.3°C; 95% confidence interval -0.6 to 0.0; P = 0.09). There were no significant differences in the use of physical cooling, or episodes of hypotension or hepatic abnormalities, between the two groups. Conclusion The routine administration of 6g/day of intravenous paracetamol did not significantly reduce core body temperature in patients with TBI. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12609000444280 PMID:26678710

  7. Refined microdialysis method for protein biomarker sampling in acute brain injury in the neurointensive care setting.

    PubMed

    Dahlin, Andreas P; Purins, Karlis; Clausen, Fredrik; Chu, Jiangtao; Sedigh, Amir; Lorant, Tomas; Enblad, Per; Lewén, Anders; Hillered, Lars

    2014-09-01

    There is growing interest in cerebral microdialysis (MD) for sampling of protein biomarkers in neurointensive care (NIC) patients. Published data point to inherent problems with this methodology including protein interaction and biofouling leading to unstable catheter performance. This study tested the in vivo performance of a refined MD method including catheter surface modification, for protein biomarker sampling in a clinically relevant porcine brain injury model. Seven pigs of both sexes (10-12 weeks old; 22.2-27.3 kg) were included. Mean arterial blood pressure, heart rate, intracranial pressure (ICP) and cerebral perfusion pressure was recorded during the stepwise elevation of intracranial pressure by inflation of an epidural balloon catheter with saline (1 mL/20 min) until brain death. One naïve MD catheter and one surface modified with Pluronic F-127 (10 mm membrane, 100 kDa molecular weight cutoff MD catheter) were inserted into the right frontal cortex and perfused with mock CSF with 3% Dextran 500 at a flow rate of 1.0 μL/min and 20 min sample collection. Naïve catheters showed unstable fluid recovery, sensitive to ICP changes, which was significantly stabilized by surface modification. Three of seven naïve catheters failed to deliver a stable fluid recovery. MD levels of glucose, lactate, pyruvate, glutamate, glycerol and urea measured enzymatically showed an expected gradual ischemic and cellular distress response to the intervention without differences between naïve and surface modified catheters. The 17 most common proteins quantified by iTRAQ and nanoflow LC-MS/MS were used as biomarker models. These proteins showed a significantly more homogeneous response to the ICP intervention in surface modified compared to naïve MD catheters with improved extraction efficiency for most of the proteins. The refined MD method appears to improve the accuracy and precision of protein biomarker sampling in the NIC setting. PMID:25075428

  8. Texture Analysis of T2-Weighted MR Images to Assess Acute Inflammation in Brain MS Lesions.

    PubMed

    Michoux, Nicolas; Guillet, Alain; Rommel, Denis; Mazzamuto, Giosué; Sindic, Christian; Duprez, Thierry

    2015-01-01

    Brain blood barrier breakdown as assessed by contrast-enhanced (CE) T1-weighted MR imaging is currently the standard radiological marker of inflammatory activity in multiple sclerosis (MS) patients. Our objective was to evaluate the performance of an alternative model assessing the inflammatory activity of MS lesions by texture analysis of T2-weighted MR images. Twenty-one patients with definite MS were examined on the same 3.0T MR system by T2-weighted, FLAIR, diffusion-weighted and CE-T1 sequences. Lesions and mirrored contralateral areas within the normal appearing white matter (NAWM) were characterized by texture parameters computed from the gray level co-occurrence and run length matrices, and by the apparent diffusion coefficient (ADC). Statistical differences between MS lesions and NAWM were analyzed. ROC analysis and leave-one-out cross-validation were performed to evaluate the performance of individual parameters, and multi-parametric models using linear discriminant analysis (LDA), partial least squares (PLS) and logistic regression (LR) in the identification of CE lesions. ADC and all but one texture parameter were significantly different within white matter lesions compared to within NAWM (p < 0.0167). Using LDA, an 8-texture parameter model identified CE lesions with a sensitivity Se = 70% and a specificity Sp = 76%. Using LR, a 10-texture parameter model performed better with Se = 86% / Sp = 84%. Using PLS, a 6-texture parameter model achieved the highest accuracy with Se = 88% / Sp = 81%. Texture parameter from T2-weighted images can assess brain inflammatory activity with sufficient accuracy to be considered as a potential alternative to enhancement on CE T1-weighted images. PMID:26693908

  9. Behavioral, neurochemical and molecular changes after acute deep brain stimulation of the infralimbic prefrontal cortex.

    PubMed

    Jiménez-Sánchez, Laura; Linge, Raquel; Campa, Leticia; Valdizán, Elsa M; Pazos, Ángel; Díaz, Álvaro; Adell, Albert

    2016-09-01

    Deep brain stimulation (DBS) is a treatment that has shown some efficacy in treatment-resistant depression. In particular, DBS of the subcallosal cingulate gyrus (Brodmann's area 25, Cg25) has been successfully applied to treat refractory depression. In the rat, we have demonstrated that DBS applied to infralimbic (IL) cortex elevates the levels of glutamate and monoamines in the prefrontal cortex, and requires the stimulation of cortical α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors for its antidepressant-like effects. However, the molecular targets of IL DBS are not fully known. To gain insight into these pathways, we have investigated whether IL DBS is able to reverse the behavioral, biochemical and molecular changes exhibited by the olfactory bulbectomized (OBX) rat. Our results revealed that 1 h IL DBS diminished hyperlocomotion, hyperemotionality and anhedonia, and increased social interaction shown by the OBX rats. Further, IL DBS increased prefrontal efflux of glutamate and serotonin in both sham-operated and OBX rats. With regard to molecular targets, IL DBS increases the synthesis of brain-derived neurotrophic factor (BDNF) and the GluA1 AMPA receptor subunit, and stimulates the Akt/mammalian target of rapamycin (mTOR) as well as the AMPA receptor/c-AMP response element binding (CREB) pathways. Temsirolimus, a known in vivo mTOR blocker, suppressed the antidepressant-like effect of IL DBS in naïve rats in the forced swim test, thus demonstrating for the first time that mTOR signaling is required for the antidepressant-like effects of IL DBS, which is in line with the antidepressant response of other rapid-acting antidepressant drugs. PMID:27108934

  10. Osteopontin Expression in Acute Immune Response Mediates Hippocampal Synaptogenesis and Adaptive Outcome Following Cortical Brain Injury

    PubMed Central

    Chan, Julie L.; Reeves, Thomas M.; Phillips, Linda L.

    2014-01-01

    Traumatic brain injury (TBI) produces axotomy, deafferentation and reactive synaptogenesis. Inflammation influences synaptic repair, and the novel brain cytokine osteopontin (OPN) has potential to support axon regeneration through exposure of its integrin receptor binding sites. This study explored whether OPN secretion and proteolysis by matrix metalloproteinases (MMPs) mediate the initial degenerative phase of synaptogenesis, targeting reactive neuroglia to affect successful repair. Adult rats received unilateral entorhinal cortex lesion (UEC) modeling adaptive synaptic plasticity. Over the first week postinjury, hippocampal OPN protein and mRNA were assayed and histology performed. At 1–2d, OPN protein increased up to 51 fold, and was localized within activated, mobilized glia. OPN transcript also increased over 50 fold, predominantly within reactive microglia. OPN fragments known to be derived from MMP proteolysis were elevated at 1d, consistent with prior reports of UEC glial activation and enzyme production. Postinjury minocycline immunosuppression attenuated MMP-9 gelatinase activity, which was correlated with reduction of neutrophil gelatinase-associated lipocalin (LCN2) expression, and reduced OPN fragment generation. The antibiotic also attenuated removal of synapsin-1 positive axons from the deafferented zone. OPN KO mice subjected to UEC had similar reduction of hippocampal MMP-9 activity, as well as lower synapsin-1 breakdown over the deafferented zone. MAP1B and N-cadherin, surrogates of cytoarchitecture and synaptic adhesion, were not affected. OPN KO mice with UEC exhibited time dependent cognitive deficits during the synaptogenic phase of recovery. This study demonstrates that OPN can mediate immune response during TBI synaptic repair, positively influencing synapse reorganization and functional recovery. PMID:25151457

  11. Acute Effects of Modafinil on Brain Resting State Networks in Young Healthy Subjects

    PubMed Central

    Pieramico, Valentina; Ferretti, Antonio; Macchia, Antonella; Tommasi, Marco; Saggino, Aristide; Ciavardelli, Domenico; Manna, Antonietta; Navarra, Riccardo; Cieri, Filippo; Stuppia, Liborio; Tartaro, Armando; Sensi, Stefano L.

    2013-01-01

    Background There is growing debate on the use of drugs that promote cognitive enhancement. Amphetamine-like drugs have been employed as cognitive enhancers, but they show important side effects and induce addiction. In this study, we investigated the use of modafinil which appears to have less side effects compared to other amphetamine-like drugs. We analyzed effects on cognitive performances and brain resting state network activity of 26 healthy young subjects. Methodology A single dose (100 mg) of modafinil was administered in a double-blind and placebo-controlled study. Both groups were tested for neuropsychological performances with the Raven’s Advanced Progressive Matrices II set (APM) before and three hours after administration of drug or placebo. Resting state functional magnetic resonance (rs-FMRI) was also used, before and after three hours, to investigate changes in the activity of resting state brain networks. Diffusion Tensor Imaging (DTI) was employed to evaluate differences in structural connectivity between the two groups. Protocol ID: Modrest_2011; NCT01684306; http://clinicaltrials.gov/ct2/show/NCT01684306. Principal Findings Results indicate that a single dose of modafinil improves cognitive performance as assessed by APM. Rs-fMRI showed that the drug produces a statistically significant increased activation of Frontal Parietal Control (FPC; p<0.04) and Dorsal Attention (DAN; p<0.04) networks. No modifications in structural connectivity were observed. Conclusions and Significance Overall, our findings support the notion that modafinil has cognitive enhancing properties and provide functional connectivity data to support these effects. Trial Registration ClinicalTrials.gov NCT01684306 http://clinicaltrials.gov/ct2/show/NCT01684306. PMID:23935959

  12. Texture Analysis of T2-Weighted MR Images to Assess Acute Inflammation in Brain MS Lesions

    PubMed Central

    Michoux, Nicolas; Guillet, Alain; Rommel, Denis; Mazzamuto, Giosué; Sindic, Christian; Duprez, Thierry

    2015-01-01

    Brain blood barrier breakdown as assessed by contrast-enhanced (CE) T1-weighted MR imaging is currently the standard radiological marker of inflammatory activity in multiple sclerosis (MS) patients. Our objective was to evaluate the performance of an alternative model assessing the inflammatory activity of MS lesions by texture analysis of T2-weighted MR images. Twenty-one patients with definite MS were examined on the same 3.0T MR system by T2-weighted, FLAIR, diffusion-weighted and CE-T1 sequences. Lesions and mirrored contralateral areas within the normal appearing white matter (NAWM) were characterized by texture parameters computed from the gray level co-occurrence and run length matrices, and by the apparent diffusion coefficient (ADC). Statistical differences between MS lesions and NAWM were analyzed. ROC analysis and leave-one-out cross-validation were performed to evaluate the performance of individual parameters, and multi-parametric models using linear discriminant analysis (LDA), partial least squares (PLS) and logistic regression (LR) in the identification of CE lesions. ADC and all but one texture parameter were significantly different within white matter lesions compared to within NAWM (p < 0.0167). Using LDA, an 8-texture parameter model identified CE lesions with a sensitivity Se = 70% and a specificity Sp = 76%. Using LR, a 10-texture parameter model performed better with Se = 86% / Sp = 84%. Using PLS, a 6-texture parameter model achieved the highest accuracy with Se = 88% / Sp = 81%. Texture parameter from T2-weighted images can assess brain inflammatory activity with sufficient accuracy to be considered as a potential alternative to enhancement on CE T1-weighted images. PMID:26693908

  13. Large-Scale Brain Network Coupling Predicts Acute Nicotine Abstinence Effects on Craving and Cognitive Function

    PubMed Central

    Lerman, Caryn; Gu, Hong; Loughead, James; Ruparel, Kosha; Yang, Yihong; Stein, Elliot A.

    2014-01-01

    IMPORTANCE Interactions of large-scale brain networks may underlie cognitive dysfunctions in psychiatric and addictive disorders. OBJECTIVES To test the hypothesis that the strength of coupling among 3 large-scale brain networks–salience, executive control, and default mode–will reflect the state of nicotine withdrawal (vs smoking satiety) and will predict abstinence-induced craving and cognitive deficits and to develop a resource allocation index (RAI) that reflects the combined strength of interactions among the 3 large-scale networks. DESIGN, SETTING, AND PARTICIPANTS A within-subject functional magnetic resonance imaging study in an academic medical center compared resting-state functional connectivity coherence strength after 24 hours of abstinence and after smoking satiety. We examined the relationship of abstinence-induced changes in the RAI with alterations in subjective, behavioral, and neural functions. We included 37 healthy smoking volunteers, aged 19 to 61 years, for analyses. INTERVENTIONS Twenty-four hours of abstinence vs smoking satiety. MAIN OUTCOMES AND MEASURES Inter-network connectivity strength (primary) and the relationship with subjective, behavioral, and neural measures of nicotine withdrawal during abstinence vs smoking satiety states (secondary). RESULTS The RAI was significantly lower in the abstinent compared with the smoking satiety states (left RAI, P = .002; right RAI, P = .04), suggesting weaker inhibition between the default mode and salience networks. Weaker inter-network connectivity (reduced RAI) predicted abstinence-induced cravings to smoke (r = −0.59; P = .007) and less suppression of default mode activity during performance of a subsequent working memory task (ventromedial prefrontal cortex, r = −0.66, P = .003; posterior cingulate cortex, r = −0.65, P = .001). CONCLUSIONS AND RELEVANCE Alterations in coupling of the salience and default mode networks and the inability to disengage from the default mode network may

  14. Studying T Cell Development in Thymic Slices.

    PubMed

    Ross, Jenny O; Melichar, Heather J; Halkias, Joanna; Robey, Ellen A

    2016-01-01

    Recently, tissue slices have been adapted to study both mouse and human T cell development. Thymic slices combine and complement the strengths of existing organotypic culture systems to study thymocyte differentiation. Specifically, the thymic slice system allows for high throughput experiments and the ability to introduce homogenous developmental intermediate populations into an environment with a well-established cortex and medulla. These qualities make thymic slices a highly versatile and technically accessible model to study thymocyte development. Here we describe methods to prepare, embed, and slice thymic lobes to study T cell development in situ. PMID:26294404

  15. Pyrethroid insecticides evoke neurotransmitter release from rabbit striatal slices

    SciTech Connect

    Eells, J.T.; Dubocovich, M.L.

    1988-08-01

    The effects of the synthetic pyrethroid insecticide fenvalerate ((R,S)-alpha-cyano-3-phenoxybenzyl(R,S)-2-(4-chlorophenyl)-3- methylbutyrate) on neurotransmitter release in rabbit brain slices were investigated. Fenvalerate evoked a calcium-dependent release of (/sup 3/H)dopamine and (/sup 3/H)acetylcholine from rabbit striatal slices that was concentration-dependent and specific for the toxic stereoisomer of the insecticide. The release of (/sup 3/H)dopamine and (/sup 3/H)acetylcholine by fenvalerate was modulated by D2 dopamine receptor activation and antagonized completely by the sodium channel blocker, tetrodotoxin. These findings are consistent with an action of fenvalerate on the voltage-dependent sodium channels of the presynaptic membrane resulting in membrane depolarization, and the release of dopamine and acetylcholine by a calcium-dependent exocytotic process. In contrast to results obtained in striatal slices, fenvalerate did not elicit the release of (/sup 3/H)norepinephrine or (/sup 3/H)acetylcholine from rabbit hippocampal slices indicative of regional differences in sensitivity to type II pyrethroid actions.

  16. Simulation and experimental study of DC electric field distribution characteristics of rat hippocampal slices in vitro

    NASA Astrophysics Data System (ADS)

    Zheng, Yu; Dong, Lei; Gao, Yang; Qiu, Qian; Li, Ze-yan; Zhao, Zhe; Chen, Rui-juan; Wang, Hui-quan

    2016-06-01

    Direct current (DC) electric field is a noninvasive neuromodulation tool that can inhibit or facilitate excitability of neurons. Despite its efficacy, the dielectric constant of artificial cerebrospinal fluid and the position and direction of brain slices and other factors can affect the field intensity and distribution acting on the surface of rat hippocampus slices, thus causing errors. In this study, we describe a new analytical method optimized for DC electric fields acting on brain slices, and the design of an external DC electric field stimulator to allow scientific evaluation of brain slices. We investigated parameters regarding the uniformity of electric field distribution and identified the maximal parameters using the finite element method. Then, we selected and simplified slice images using magnetic resonance imaging data and calculated the electric field intensity of the original and simplified models. The electric field simulator induced action potential and excitatory postsynaptic current with intensities of 1, 5, and 10 V/m. This study describes the development of a new electric field stimulator and successfully demonstrates its practicability for scientific evaluation of tissue slices.

  17. Acute human brain responses to intracortical microelectrode arrays: challenges and future prospects.

    PubMed

    Fernández, Eduardo; Greger, Bradley; House, Paul A; Aranda, Ignacio; Botella, Carlos; Albisua, Julio; Soto-Sánchez, Cristina; Alfaro, Arantxa; Normann, Richard A

    2014-01-01

    The emerging field of neuroprosthetics is focused on the development of new therapeutic interventions that will be able to restore some lost neural function by selective electrical stimulation or by harnessing activity recorded from populations of neurons. As more and more patients benefit from these approaches, the interest in neural interfaces has grown significantly and a new generation of penetrating microelectrode arrays are providing unprecedented access to the neurons of the central nervous system (CNS). These microelectrodes have active tip dimensions that are similar in size to neurons and because they penetrate the nervous system, they provide selective access to these cells (within a few microns). However, the very long-term viability of chronically implanted microelectrodes and the capability of recording the same spiking activity over long time periods still remain to be established and confirmed in human studies. Here we review the main responses to acute implantation of microelectrode arrays, and emphasize that it will become essential to control the neural tissue damage induced by these intracortical microelectrodes in order to achieve the high clinical potentials accompanying this technology. PMID:25100989

  18. Increased Risk of Post-Trauma Stroke after Traumatic Brain Injury-Induced Acute Respiratory Distress Syndrome.

    PubMed

    Chen, Gunng-Shinng; Liao, Kuo-Hsing; Bien, Mauo-Ying; Peng, Giia-Sheun; Wang, Jia-Yi

    2016-07-01

    This study determines whether acute respiratory distress syndrome (ARDS) is an independent risk factor for an increased risk of post-traumatic brain injury (TBI) stroke during 3-month, 1-year, and 5-year follow-ups, respectively, after adjusting for other covariates. Clinical data for the analysis were from the National Health Insurance Database 2000, which covered a total of 2121 TBI patients and 101 patients with a diagnosis of TBI complicated with ARDS (TBI-ARDS) hospitalized between January 1, 2001 and December 31, 2005. Each patient was tracked for 5 years to record stroke occurrences after discharge from the hospital. The prognostic value of TBI-ARDS was evaluated using a multivariate Cox proportional hazard model. The main outcome found that stroke occurred in nearly 40% of patients with TBI-ARDS, and the hazard ratio for post-TBI stroke increased fourfold during the 5-year follow-up period after adjusting for other covariates. The increased risk of hemorrhagic stroke in the ARDS group was considerably higher than in the TBI-only cohort. This is the first study to report that post-traumatic ARDS yielded an approximate fourfold increased risk of stroke in TBI-only patients. We suggest intensive and appropriate medical management and intensive follow-up of TBI-ARDS patients during the beginning of the hospital discharge. PMID:26426583

  19. Effect of acute doses of controlled-release carbamazepine on clinical, psychomotor, electrophysiological, and cognitive parameters of brain function.

    PubMed

    van der Meyden, C H; Bartel, P R; Sommers, D K; Blom, M; Becker, P; Erasmus, S; Griesel, D

    1992-01-01

    The neurotoxic effect of acute doses of carbamazepine controlled-release (CBZ-CR) divitabs (800, 1,200, and 1,600 mg) was assessed on clinical, psychomotor, electrophysiological, and cognitive parameters of brain function in 10 healthy volunteers in a double-blind, randomised, placebo-controlled, phase I study. Significant changes compared to placebo were demonstrated for the clinical scales, ataxia (AT), convergence of the near-point (CNP), peak saccadic velocity (PSV), critical flicker fusion (CFF), spectral analysis of the EEG, and brainstem auditory evoked potential (BAEP) tests. Digit repetition, digit symbol substitution, Sternberg memory scanning time, Sternberg choice reaction time, saccadic latency, and saccadic accuracy showed important negative findings. Significant clinical tolerance to side effects developed within 20 to 33 h after CBZ-CR dosage during a period in which the mean CBZ blood levels remained virtually unchanged. CBZ-CR, 800, 1,200, and 1,600 mg yielded low, medium, and high therapeutic blood levels, respectively, for +10 to +33 h after dosage without the development of severe clinical side effects. PMID:1547763

  20. Acute Nicotine Administration Increases BOLD fMRI Signal in Brain Regions Involved in Reward Signaling and Compulsive Drug Intake in Rats

    PubMed Central

    Alexander, Jon C.; Perez, Pablo D.; Bauzo-Rodriguez, Rayna; Hall, Gabrielle; Klausner, Rachel; Guerra, Valerie; Zeng, Huadong; Igari, Moe; Febo, Marcelo

    2015-01-01

    Background: Acute nicotine administration potentiates brain reward function and enhances motor and cognitive function. These studies investigated which brain areas are being activated by a wide range of doses of nicotine, and if this is diminished by pretreatment with the nonselective nicotinic receptor antagonist mecamylamine. Methods: Drug-induced changes in brain activity were assessed by measuring changes in the blood oxygen level dependent (BOLD) signal using an 11.1-Tesla magnetic resonance scanner. In the first experiment, nicotine naïve rats were mildly anesthetized and the effect of nicotine (0.03–0.6mg/kg) on the BOLD signal was investigated for 10min. In the second experiment, the effect of mecamylamine on nicotine-induced brain activity was investigated. Results: A high dose of nicotine increased the BOLD signal in brain areas implicated in reward signaling, such as the nucleus accumbens shell and the prelimbic area. Nicotine also induced a dose-dependent increase in the BOLD signal in the striato-thalamo-orbitofrontal circuit, which plays a role in compulsive drug intake, and in the insular cortex, which contributes to nicotine craving and relapse. In addition, nicotine induced a large increase in the BOLD signal in motor and somatosensory cortices. Mecamylamine alone did not affect the BOLD signal in most brain areas, but induced a negative BOLD response in cortical areas, including insular, motor, and somatosensory cortices. Pretreatment with mecamylamine completely blocked the nicotine-induced increase in the BOLD signal. Conclusions: These studies demonstrate that acute nicotine administration activates brain areas that play a role in reward signaling, compulsive behavior, and motor and cognitive function. PMID:25552431

  1. Automatic basal slice detection for cardiac analysis

    NASA Astrophysics Data System (ADS)

    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.

  2. Acute effects of a bicyclophosphate neuroconvulsant on monoamine neurotransmitter and metabolite levels in the rat brain.

    PubMed

    Lindsey, J W; Jung, A E; Narayanan, T K; Ritchie, G D

    1998-07-10

    Naive male Sprague-Dawley rats were injected intraperitoneally (i.p.) with the bicyclophosphate convulsant trimethylolpropane phosphate (TMPP) at dose levels from 0.2 to 0.6 mg/kg. Rats were observed for convulsive activity, and were sacrificed 15 min posttreatment. Levels of the monoamine neurotransmitters norepinephrine (NE), epinephrine (EPI), dopamine (DA), and serotonin (5-HT) and the major metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were assayed in forebrain, midbrain, hindbrain, cerebellum and brainstem regions. Neurotransmitter and metabolite levels were compared between control rats and rats that did and did not experience seizures. TMPP administration induced significant decreases in levels of measured neurotransmitters that varied as a function of brain region, dose, and expression of the seizure activity. These results show that tonic or tonic-clonic seizures induced by TMPP administration (0.6 mg/kg) are reliably associated with regional decreases in serotonin, dopamine, and norepinephrine. Convulsive activity resulting from lower dose administrations (0.2-0.4 mg/kg) of TMPP result only in decreased regional levels of serotonin. PMID:9650574

  3. A recording chamber for small volume slice electrophysiology.

    PubMed

    Dondzillo, Anna; Quinn, Kevin D; Cruickshank-Quinn, Charmion I; Reisdorph, Nichole; Lei, Tim C; Klug, Achim

    2015-09-01

    Electrophysiological recordings from brain slices are typically performed in small recording chambers that allow for the superfusion of the tissue with artificial extracellular solution (ECS), while the chamber holding the tissue is mounted in the optical path of a microscope to image neurons in the tissue. ECS itself is inexpensive, and thus superfusion rates and volumes of ECS consumed during an experiment using standard ECS are not critical. However, some experiments require the addition of expensive pharmacological agents or other chemical compounds to the ECS, creating a need to build superfusion systems that operate on small volumes while still delivering appropriate amounts of oxygen and other nutrients to the tissue. We developed a closed circulation tissue chamber for slice recordings that operates with small volumes of bath solution in the range of 1.0 to 2.6 ml and a constant oxygen/carbon dioxide delivery to the solution in the bath. In our chamber, the ECS is oxygenated and recirculated directly in the recording chamber, eliminating the need for tubes and external bottles/containers to recirculate and bubble ECS and greatly reducing the total ECS volume required for superfusion. At the same time, the efficiency of tissue oxygenation and health of the section are comparable to standard superfusion methods. We also determined that the small volume of ECS contains a sufficient amount of nutrients to support the health of a standard brain slice for several hours without concern for either depletion of nutrients or accumulation of waste products. PMID:26203105

  4. Multiplex immunoassay characterization and species comparison of inflammation in acute and non-acute ischemic infarcts in human and mouse brain tissue.

    PubMed

    Nguyen, Thuy-Vi V; Frye, Jennifer B; Zbesko, Jacob C; Stepanovic, Kristina; Hayes, Megan; Urzua, Alex; Serrano, Geidy; Beach, Thomas G; Doyle, Kristian P

    2016-01-01

    This study provides a parallel characterization of the cytokine and chemokine response to stroke in the human and mouse brain at different stages of infarct resolution. The study goal was to address the hypothesis that chronic inflammation may contribute to stroke-related dementia. We used C57BL/6 and BALB/c mice to control for strain related differences in the mouse immune response. Our data indicate that in both mouse strains, and humans, there is increased granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), interleukin-12 p70 (IL-12p70), interferon gamma-induced protein-10 (IP-10), keratinocyte chemoattractant/interleukin-8 (KC/IL-8), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein-1β (MIP-1β), regulated on activation, normal T cell expressed and secreted (RANTES), and Tumor necrosis factor-α (TNF-α) in the infarct core during the acute time period. Nevertheless, correlation and two-way ANOVA analyses reveal that despite this substantial overlap between species, there are still significant differences, particularly in the regulation of granulocyte colony-stimulating factor (G-CSF), which is increased in mice but not in humans. In the weeks after stroke, during the stage of liquefactive necrosis, there is significant resolution of the inflammatory response to stroke within the infarct. However, CD68+ macrophages remain present, and levels of IL-6 and MCP-1 remain chronically elevated in infarcts from both mice and humans. Furthermore, there is a chronic T cell response within the infarct in both species. This response is differentially polarized towards a T helper 1 (Th1) response in C57BL/6 mice, and a T helper 2 (Th2) response in BALB/c mice, suggesting that the chronic inflammatory response to stroke may follow a different trajectory in different patients. To control for the fact that the average age of the patients used in this study was 80 years, they

  5. Cerebrolysin Asian Pacific trial in acute brain injury and neurorecovery: design and methods.

    PubMed

    Poon, Wai; Vos, Pieter; Muresanu, Dafin; Vester, Johannes; von Wild, Klaus; Hömberg, Volker; Wang, Ernest; Lee, Tatia M C; Matula, Christian

    2015-04-15

    Traumatic brain injury (TBI) is one of the leading causes of injury-related death. In the United States alone, an estimated 1.7 million people sustain a TBI each year, and approximately 5.3 million people live with a TBI-related disability. The direct medical costs and indirect costs such as lost productivity of TBIs totaled an estimated $76.5 billion in the U.S. in the year 2000. Improving the limited treatment options for this condition remains challenging. However, recent reports from interdisciplinary working groups (consisting primarily of neurologists, neurosurgeons, neuropsychologists, and biostatisticians) have stated that to improve TBI treatment, important methodological lessons from the past must be taken into account in future clinical research. An evaluation of the neuroprotection intervention studies conducted over the last 30 years has indicated that a limited understanding of the underlying biological concepts and methodological design flaws are the major reasons for the failure of pharmacological agents to demonstrate efficacy. Cerebrolysin is a parenterally-administered neuro-peptide preparation that acts in a manner similar to endogenous neurotrophic factors. Cerebrolysin has a favorable adverse effect profile, and several meta-analyses have suggested that Cerebrolysin is beneficial as a dementia treatment. CAPTAIN is a randomized, double-blind, placebo-controlled, multi-center, multinational trial of the effects of Cerebrolysin on neuroprotection and neurorecovery after TBI using a multidimensional ensemble of outcome scales. The CAPTAIN trial will be the first TBI trial with a 'true' multidimensional approach based on full outcome scales, while avoiding prior weaknesses, such as loss of information through "dichotomization," or unrealistic assumptions such as "normal distribution." PMID:25222349

  6. Combined neuromodulatory interventions in acute experimental pain: assessment of melatonin and non-invasive brain stimulation

    PubMed Central

    da Silva, Nádia Regina Jardim; Laste, Gabriela; Deitos, Alícia; Stefani, Luciana Cadore; Cambraia-Canto, Gustavo; Torres, Iraci L. S.; Brunoni, Andre R.; Fregni, Felipe; Caumo, Wolnei

    2015-01-01

    Transcranial direct current stimulation (tDCS) and melatonin can effectively treat pain. Given their potentially complementary mechanisms of action, their combination could have a synergistic effect. Thus, we tested the hypothesis that compared to the control condition and melatonin alone, tDCS combined with melatonin would have a greater effect on pain modulatory effect, as assessed by quantitative sensory testing (QST) and by the pain level during the Conditioned Pain Modulation (CPM)-task. Furthermore, the combined treatment would have a greater cortical excitability effect as indicated by the transcranial magnetic stimulation (TMS) and on the serum BDNF level. Healthy males (n = 20), (aged 18–40 years), in a blinded, placebo-controlled, crossover, clinical trial, were randomized into three groups: sublingual melatonin (0.25 mg/kg) + a-tDCS, melatonin (0.25 mg/kg) + sham-(s)-tDCS, or sublingual placebo+sham-(s)-tDCS. Anodal stimulation (2 mA, 20 min) was applied over the primary motor cortex. There was a significant difference in the heat pain threshold (°C) for melatonin+a-tDCS vs. placebo+s-tDCS (mean difference: 4.86, 95% confidence interval [CI]: 0.9 to 8.63) and melatonin+s-tDCS vs. placebo+s-tDCS (mean: 5.16, 95% CI: 0.84 to 8.36). There was no difference between melatonin+s-tDCS and melatonin+a-tDCS (mean difference: 0.29, 95% CI: −3.72 to 4.23). The mean change from the baseline on amplitude of motor evocate potential (MEP) was significantly higher in the melatonin+a-tDCS (−19.96% ± 5.2) compared with melatonin+s-tDCS group (−1.36% ± 5.35) and with placebo+s-tDCS group (3.61% ± 10.48), respectively (p < 0.05 for both comparisons). While melatonin alone or combined with a-tDCS did not significantly affect CPM task result, and serum BDNF level. The melatonin effectively reduced pain; however, its association with a-tDCS did not present an additional modulatory effect on acute induced pain. PMID:25873871

  7. Robust reflective pupil slicing technology

    NASA Astrophysics Data System (ADS)

    Meade, Jeffrey T.; Behr, Bradford B.; Cenko, Andrew T.; Hajian, Arsen R.

    2014-07-01

    Tornado Spectral Systems (TSS) has developed the High Throughput Virtual Slit (HTVSTM), robust all-reflective pupil slicing technology capable of replacing the slit in research-, commercial- and MIL-SPEC-grade spectrometer systems. In the simplest configuration, the HTVS allows optical designers to remove the lossy slit from pointsource spectrometers and widen the input slit of long-slit spectrometers, greatly increasing throughput without loss of spectral resolution or cross-dispersion information. The HTVS works by transferring etendue between image plane axes but operating in