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Sample records for brain stem slices

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    differentiation, we co-cultured cells from a human neural forebrain-derived stem cell line (hNS1) with rat striatal brain slices. In brief, coronal slices of neonatal rat striatum were cultured on semiporous membrane inserts placed in six-well trays overlying monolayers of hNS1 cells. After 12 days of co......Properly committed neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. To establish a setting for identification of secreted neural compounds promoting dopaminergic...

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

    DEFF Research Database (Denmark)

    Rekling, J C; Theophilidis, G

    1995-01-01

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

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

    DEFF Research Database (Denmark)

    Rekling, J C; Theophilidis, G

    1995-01-01

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

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

    Science.gov (United States)

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

    2014-05-30

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  6. Novel culturing platform for brain slices and neuronal cells

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jai Jai Shiva Shankar

    2011-01-01

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

  8. Slices

    KAUST Repository

    McCrae, James

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    Slices of developing brain tissue can be grown for several weeks as so-called organotypic slice cultures. Here we summarize and review studies using hippocampal slice cultures to investigate mechanisms and treatment strategies for the neurodegenerative disorders like stroke (cerebral ischemia), A...

  11. Radioisotopic investigations of zinc uptake into brain slices

    International Nuclear Information System (INIS)

    Howell, G.A.

    1983-01-01

    The presence of zinc in the vicinity of the hippocampal mossy fibers has been repeatedly demonstrated, and several lines of evidence suggest that the mossy-fiber zinc is concentrated within the terminals of mossy fibers. In search of insight into the metabolism and function of mossy-fiber zinc, the present study investigated the transport of zinc into tissue slices and the response of the zinc transport to depolarization. Kinetic analysis of zinc accumulation by mouse brain slices in vitro revealed the presence of a high affinity uptake component with an apparent Km of 17.7 μM for hippocampus, 16.6 μM< for cortex and 25 μM for striatum and a V/sub max/ of 9.2 ng/mg/hr for the hippocampus, 10.1 ng/mg/hr for cortex and 9.6 ng/mg/hr for striatum. Cytoarchitectonic differences in zinc transport between the different hippocampal subregions were found with those regions containing granule cells or mossy fiber axons accumulating greater amounts of zinc than the CA 1 region. The present finding that mossy-fiber neuropil selectivity accumulates zinc suggests the presence of a zinc-binding substance unique to mossy-fiber tissue

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

    Directory of Open Access Journals (Sweden)

    G Mattei

    2015-04-01

    Full Text Available 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.

  13. Brain slice on a chip: opportunities and challenges of applying microfluidic technology to intact tissues.

    Science.gov (United States)

    Huang, Yu; Williams, Justin C; Johnson, Stephen M

    2012-06-21

    Isolated brain tissue, especially brain slices, are valuable experimental tools for studying neuronal function at the network, cellular, synaptic, and single channel levels. Neuroscientists have refined the methods for preserving brain slice viability and function and converged on principles that strongly resemble the approach taken by engineers in developing microfluidic devices. With respect to brain slices, microfluidic technology may 1) overcome the traditional limitations of conventional interface and submerged slice chambers and improve oxygen/nutrient penetration into slices, 2) provide better spatiotemporal control over solution flow/drug delivery to specific slice regions, and 3) permit successful integration with modern optical and electrophysiological techniques. In this review, we highlight the unique advantages of microfluidic devices for in vitro brain slice research, describe recent advances in the integration of microfluidic devices with optical and electrophysiological instrumentation, and discuss clinical applications of microfluidic technology as applied to brain slices and other non-neuronal tissues. We hope that this review will serve as an interdisciplinary guide for both neuroscientists studying brain tissue in vitro and engineers as they further develop microfluidic chamber technology for neuroscience research.

  14. Childhood Brain Stem Glioma Treatment

    Science.gov (United States)

    ... the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds , ... is used to treat DIPG. External and/or internal radiation therapy may be used to treat focal brain stem ...

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

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

    2001-01-01

    In this study we examined the passive biocompatibility of a three-dimensional microelectrode array (MEA), designed to be coupled to organotypic brain slice cultures for multisite recording of electrophysiological signals. Hippocampal (and corticostriatal) brain slices from 1-week-old (and newborn......) rats were grown for 4-8 weeks on the perforated silicon chips with silicon nitride surfaces and 40 microm sized holes and compared with corresponding tissue slices grown on conventional semiporous membranes. In terms of preservation of the basic cellular and connective organization, as visualized......-methyl-D-aspartate (NMDA) and the neurotoxin trimethyltin (TMT), as demonstrated by the cellular uptake of propidium iodide (PI), which was used as a reproducible and quantifiable marker for neuronal degeneration. We conclude that organotypic brain slice cultures can grow on silicon-based three-dimensional microelectrode...

  17. Thyrotropin-releasing hormone (TRH) depolarizes a subset of inspiratory neurons in the newborn mouse brain stem in vitro

    DEFF Research Database (Denmark)

    Rekling, J C; Champagnat, J; Denavit-Saubié, M

    1996-01-01

    in a thick brain stem slice preparation from the newborn mouse. The action of TRH on the respiratory output from the slice was investigated by recordings from the XII nerve. Cellular responses to TRH were investigated using whole cell recordings from hypoglossal motoneurons and three types of inspiratory...... mice through an action at the level of the brain stem.(ABSTRACT TRUNCATED AT 250 WORDS)...

  18. Three-dimensional electrode array for brain slice culture

    DEFF Research Database (Denmark)

    Vazquez Rodriguez, Patricia

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

  19. Accumulation of pantothenic acid by the isolated choroid plexus and brain slices in vitro. [Rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Spector, R.; Boose, B.

    1984-08-01

    In vitro, the transport of (/sup 14/C)pantothenic acid into and from the isolated rabbit choroid plexus, an anatomical locus of the blood-CSF barrier, and brain slices was studied. The choroid plexus accumulated (/sup 14/C)pantothenic acid from the medium against a concentration gradient, although at low concentrations (less than 1 microM) there was substantial intracellular phosphorylation and binding of the (/sup 14/C)pantothenic acid. The saturable accumulation process in choroid plexus was inhibited by probenecid and caproic acid but not by nicotinic acid or by weak bases. The accumulation process was markedly inhibited by N-ethylmaleimide, poly-L-lysine (which blocks sodium transport), and low temperatures. (/sup 14/C)Pantothenic acid was readily released from choroid plexus by a temperature-dependent process. Brain slices also accumulated and, at low concentrations, phosphorylated (/sup 14/C)pantothenic acid from the medium by a temperature-, probenecid-, and N-ethylmaleimide-sensitive saturable process. However, unlike choroid plexus, brain slices did not concentrate free pantothenic acid and (/sup 14/C)pantothenic acid accumulation was not sensitive to poly-L-lysine. (/sup 14/C)Pantothenic acid was readily released from brain slices by a temperature-sensitive process. These results are consistent with the view that (/sup 14/C)pantothenic acid enters the isolated choroid plexus and brain slices by active transport and facilitated diffusion, respectively.

  20. Electroresponsive properties and membrane potential trajectories of three types of inspiratory neurons in the newborn mouse brain stem in vitro

    DEFF Research Database (Denmark)

    Rekling, J C; Champagnat, J; Denavit-Saubié, M

    1996-01-01

    1. The electrophysiological properties of inspiratory neurons were studied in a rhythmically active thick-slice preparation of the newborn mouse brain stem maintained in vitro. Whole cell patch recordings were performed from 60 inspiratory neurons within the rostral ventrolateral part of the slice...

  1. Functional network integration of embryonic stem cell-derived astrocytes in hippocampal slice cultures.

    Science.gov (United States)

    Scheffler, Björn; Schmandt, Tanja; Schröder, Wolfgang; Steinfarz, Barbara; Husseini, Leila; Wellmer, Jörg; Seifert, Gerald; Karram, Khalad; Beck, Heinz; Blümcke, Ingmar; Wiestler, Otmar D; Steinhäuser, Christian; Brüstle, Oliver

    2003-11-01

    Embryonic stem (ES) cells provide attractive prospects for neural transplantation. So far, grafting strategies in the CNS have focused mainly on neuronal replacement. Employing a slice culture model, we found that ES cell-derived glial precursors (ESGPs) possess a remarkable capacity to integrate into the host glial network. Following deposition on the surface of hippocampal slices, ESGPs actively migrate into the recipient tissue and establish extensive cell-cell contacts with recipient glia. Gap junction-mediated coupling between donor and host astrocytes permits widespread delivery of dye from single donor cells. During maturation, engrafted donor cells display morphological, immunochemical and electrophysiological properties that are characteristic of differentiating native glia. Our findings provide the first evidence of functional integration of grafted astrocytes, and depict glial network integration as a potential route for widespread transcellular delivery of small molecules to the CNS.

  2. [The protective effect of propofol pretreatment on glutamate injury of neonatal rat brain slices].

    Science.gov (United States)

    Zhou, Xiao-feng; Huang, Ding-ding; Wang, Di-fen; Fu, Jiang-quan

    2012-12-01

    To study the protective effect of propofol precondition against glutamate (Glu) neurotoxicity to neonatal rat cerebrocortical slices. Brain slices of Sprague-Dawley (SD) rats were cultured in vitro and observed the morphologic changes. Brain slices were randomly divided into three groups: blank control group, Glu injury group (1 mmol/L Glu for 0.5 hour), propofol precondition group (20 mg/L propofol for 24 hours), each n=12. Changes in pathological and ultra-structure of cells were observed using microscope. Lactate dehydrogenase (LDH) leakage rate was measured. Meanwhile, the expression of glial fibrillary acidic protein (GFAP) was detected by immunohistochemical technology, then the positive cell were counted. Cultured brain slices of cell were intact and survived well. Hematoxylin-eosin (HE) staining, electron microscopy and LDH test results showed that cerebral film neuron severely damage, gliosis, edema, LDH leakage rate in Glu injury group were significantly more severe compared with blank control group [(68.5±2.0)% vs. (16.0±2.5)%, P<0.01]. Reduce the brain slice of the propofol pretreatment group of neuronal cell jury, cell shape recovery significantly reduced LDH leakage rate compared with the Glu injury group [(38.5±2.4)% vs. (68.5±2.0)%, P<0.05]. Immunohistochemical detection of GFAP expression of Glu injury group glial cell body swelling, producing increase in the number of GFAP positive reaction strong, the number of positive cells compared with blank control group was significantly increased (50±5 cells/HP vs. 10±3 cells/HP, P<0.01). The recovery of propofol pretreatment group glial cell morphology, cell processes slender GFAP positive reaction decreased the number of positive cells compared with the Glu injury group was significantly decreased (30±4 cells/HP vs. 50±5 cells/HP, P<0.05). Propofol pretreatment has protective effect against Glu injured rat cerebrocortical slices.

  3. Microfluidic culture chamber for the long-term perfusion and precise chemical stimulation of organotypic brain tissue slices

    DEFF Research Database (Denmark)

    Caicedo, H. H.; Vignes, M.; Brugg, B.

    2010-01-01

    We have developed a microfluidic perfusion-based culture system to study long-term in-vitro responses of organo-typic brain slices exposed to localized neurochemical stimulation. Using this microperfusion chamber we show that hip-pocampal organotypic brain slices cultures grown on nitrocellulose ...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2009-04-01

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

  6. Automated fetal brain segmentation from 2D MRI slices for motion correction.

    Science.gov (United States)

    Keraudren, K; Kuklisova-Murgasova, M; Kyriakopoulou, V; Malamateniou, C; Rutherford, M A; Kainz, B; Hajnal, J V; Rueckert, D

    2014-11-01

    Motion correction is a key element for imaging the fetal brain in-utero using Magnetic Resonance Imaging (MRI). Maternal breathing can introduce motion, but a larger effect is frequently due to fetal movement within the womb. Consequently, imaging is frequently performed slice-by-slice using single shot techniques, which are then combined into volumetric images using slice-to-volume reconstruction methods (SVR). For successful SVR, a key preprocessing step is to isolate fetal brain tissues from maternal anatomy before correcting for the motion of the fetal head. This has hitherto been a manual or semi-automatic procedure. We propose an automatic method to localize and segment the brain of the fetus when the image data is acquired as stacks of 2D slices with anatomy misaligned due to fetal motion. We combine this segmentation process with a robust motion correction method, enabling the segmentation to be refined as the reconstruction proceeds. The fetal brain localization process uses Maximally Stable Extremal Regions (MSER), which are classified using a Bag-of-Words model with Scale-Invariant Feature Transform (SIFT) features. The segmentation process is a patch-based propagation of the MSER regions selected during detection, combined with a Conditional Random Field (CRF). The gestational age (GA) is used to incorporate prior knowledge about the size and volume of the fetal brain into the detection and segmentation process. The method was tested in a ten-fold cross-validation experiment on 66 datasets of healthy fetuses whose GA ranged from 22 to 39 weeks. In 85% of the tested cases, our proposed method produced a motion corrected volume of a relevant quality for clinical diagnosis, thus removing the need for manually delineating the contours of the brain before motion correction. Our method automatically generated as a side-product a segmentation of the reconstructed fetal brain with a mean Dice score of 93%, which can be used for further processing. Copyright

  7. Neural stem cells improve neuronal survival in cultured postmortem brain tissue from aged and Alzheimer patients

    NARCIS (Netherlands)

    Wu, L.; Sluiter, A.A.; Guo, Ho Fu; Balesar, R. A.; Swaab, D. F.; Zhou, Jiang Ning; Verwer, R. W H

    Neurodegenerative diseases are progressive and incurable and are becoming ever more prevalent. To study whether neural stem cell can reactivate or rescue functions of impaired neurons in the human aging and neurodegenerating brain, we co-cultured postmortem slices from Alzheimer patients and control

  8. Neuropeptide processing in regional brain slices: Effect of conformation and sequence

    International Nuclear Information System (INIS)

    Li, Z.W.; Bijl, W.A.; van Nispen, J.W.; Brendel, K.; Davis, T.P.

    1990-01-01

    The central enzymatic stability of des-enkephalin-gamma-endorphin and its synthetic analogs [cycloN alpha 6, C delta 11]beta-endorphin-[6-17] and [Pro7, Lys(Ac)9]-beta-endorphin[6-17] was studied in vitro using a newly developed, regionally dissected rat brain slice, time course incubation procedure. Tissue slice viability was estimated as the ability of the brain slice to take up or release gamma-[3H]aminobutyric acid after high K+ stimulation. Results demonstrated stability of uptake/release up to 5 hr of incubation, suggesting tissue viability over this period. The estimated half-life of peptides based on the results obtained in our incubation protocol suggest that the peptides studied are metabolized at different rates in the individual brain regions tested. A good correlation exists between the high enzyme activity of neutral endopeptidase and the rapid degradation of des-enkephalin-gamma-endorphin and [cycloN alpha 6, C delata 11]beta-endorphin-[6-17] in caudate putamen. Proline substitution combined with lysine acetylation appears to improve resistance to enzymatic metabolism in caudate putamen and hypothalamus. However, cyclization of des-enkephalin-gamma-endorphin forming an amide bond between the alpha-NH2 of the N-terminal threonine and the gamma-COOH of glutamic acid did not improve peptide stability in any brain region tested. The present study has shown that the brain slice technique is a valid and unique approach to study neuropeptide metabolism in small, discrete regions of rat brain where peptides, peptidases and receptors are colocalized and that specific structural modifications can improve peptide stability

  9. Neuropeptide processing in regional brain slices: Effect of conformation and sequence

    Energy Technology Data Exchange (ETDEWEB)

    Li, Z.W.; Bijl, W.A.; van Nispen, J.W.; Brendel, K.; Davis, T.P. (Univ. of Arizona, Tucson (USA))

    1990-05-01

    The central enzymatic stability of des-enkephalin-gamma-endorphin and its synthetic analogs (cycloN alpha 6, C delta 11)beta-endorphin-(6-17) and (Pro7, Lys(Ac)9)-beta-endorphin(6-17) was studied in vitro using a newly developed, regionally dissected rat brain slice, time course incubation procedure. Tissue slice viability was estimated as the ability of the brain slice to take up or release gamma-(3H)aminobutyric acid after high K+ stimulation. Results demonstrated stability of uptake/release up to 5 hr of incubation, suggesting tissue viability over this period. The estimated half-life of peptides based on the results obtained in our incubation protocol suggest that the peptides studied are metabolized at different rates in the individual brain regions tested. A good correlation exists between the high enzyme activity of neutral endopeptidase and the rapid degradation of des-enkephalin-gamma-endorphin and (cycloN alpha 6, C delata 11)beta-endorphin-(6-17) in caudate putamen. Proline substitution combined with lysine acetylation appears to improve resistance to enzymatic metabolism in caudate putamen and hypothalamus. However, cyclization of des-enkephalin-gamma-endorphin forming an amide bond between the alpha-NH2 of the N-terminal threonine and the gamma-COOH of glutamic acid did not improve peptide stability in any brain region tested. The present study has shown that the brain slice technique is a valid and unique approach to study neuropeptide metabolism in small, discrete regions of rat brain where peptides, peptidases and receptors are colocalized and that specific structural modifications can improve peptide stability.

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

    Directory of Open Access Journals (Sweden)

    Oliver eKann

    2012-01-01

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

  11. Brain tumor stem cell dancing.

    Science.gov (United States)

    Bozzuto, Giuseppina; Toccacieli, Laura; Mazzoleni, Stefania; Frustagli, Gianluca; Chistolini, Pietro; Galli, Rossella; Molinari, Agnese

    2014-01-01

    Issues regarding cancer stem cell (CSC) movement are important in neurosphere biology as cell-cell or cell-environment interactions may have significant impacts on CSC differentiation and contribute to the heterogeneity of the neurosphere. Despite the growing body of literature data on the biology of brain tumor stem cells, floating CSC-derived neurospheres have been scarcely characterized from a morphological and ultrastructural point of view. Here we report a morphological and ultrastructural characterization performed by live imaging and scanning electron microscopy. Glioblastoma multiforme (GBM) CSC-derived neurospheres are heterogeneous and are constituted by cells, morphologically different, capable of forming highly dynamic structures. These dynamic structures are regulated by not serendipitous cell-cell interactions, and they synchronously pulsate following a cyclic course made of "fast" and "slow" alternate phases. Autocrine/paracrine non canonical Wnt signalling appears to be correlated with the association status of neurospheres. The results obtained suggest that GBM CSCs can behave both as independents cells and as "social" cells, highly interactive with other members of its species, giving rise to a sort of "multicellular organism".

  12. [Relationship between anti-myelin basic protein antibody and myelinoclasis in rat brain stem after brain trauma].

    Science.gov (United States)

    Li, Wei; Chen, Shan-Cheng; Wang, Zhi-Gang; Song, Xiu-Bao; Wang, Yu-Ping; Zhang, Mei

    2008-06-01

    To investigate the relations between anti-myelin basic protein antibody (anti-MBP) variation and myelinoclasis in the brain stem following brain trauma. In rat models of brain trauma, MBP content and anti-MBP titer in the blood were measured using enzyme-linked immunosorbent assay (ELISA) at different time points after brain trauma, and the degree of myelinoclasis in the brain stem slices was assessed with osmic acid staining. Early after brain trauma, MBP content in the blood increased followed by significant reduction 10 days later. Four days after the trauma, anti-MBP titer was markedly increased, accompanied by obvious exacerbation of myelinoclasis in the brain stem, both reaching the highest levels on day 10, at the point of which anti-MBP titer increased by 4 folds and the number of myelinoclasis by 10 folds compared with the control group. Anti-MBP titer and brain stem myelinolysis both lowered 30 days later. Correlation analysis showed an intimate positive correlation between anti-MBP titer and the degree of myelinoclasis. After brain trauma, MBP is released as a specific antigen into the blood to stimulate the immune system for anti-MBP production, and the antibody is intimately related to the brain stem myelinoclasis.

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

    Directory of Open Access Journals (Sweden)

    Agneta Mewes

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

  14. Towards 1H-MRSI of the human brain at 7T with slice-selective adiabatic refocusing pulses.

    NARCIS (Netherlands)

    Scheenen, T.W.J.; Heerschap, A.; Klomp, D.W.J.

    2008-01-01

    OBJECTIVE: To explore the possibilities of proton spectroscopic imaging (1H-MRSI) of the human brain at 7 Tesla with adiabatic refocusing pulses. MATERIALS AND METHODS: A combination of conventional slice selective excitation and two pairs of slice selective adiabatic refocusing pulses (semi-LASER)

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    This paper presents an approach to 3-D diffusion tensor image (DTI) reconstruction from multi-slice diffusion weighted (DW) magnetic resonance imaging acquisitions of the moving fetal brain. Motion scatters the slice measurements in the spatial and spherical diffusion domain with respect to the u...

  17. Temporal slice registration and robust diffusion-tensor reconstruction for improved fetal brain structural connectivity analysis.

    Science.gov (United States)

    Marami, Bahram; Mohseni Salehi, Seyed Sadegh; Afacan, Onur; Scherrer, Benoit; Rollins, Caitlin K; Yang, Edward; Estroff, Judy A; Warfield, Simon K; Gholipour, Ali

    2017-08-01

    Diffusion weighted magnetic resonance imaging, or DWI, is one of the most promising tools for the analysis of neural microstructure and the structural connectome of the human brain. The application of DWI to map early development of the human connectome in-utero, however, is challenged by intermittent fetal and maternal motion that disrupts the spatial correspondence of data acquired in the relatively long DWI acquisitions. Fetuses move continuously during DWI scans. Reliable and accurate analysis of the fetal brain structural connectome requires careful compensation of motion effects and robust reconstruction to avoid introducing bias based on the degree of fetal motion. In this paper we introduce a novel robust algorithm to reconstruct in-vivo diffusion-tensor MRI (DTI) of the moving fetal brain and show its effect on structural connectivity analysis. The proposed algorithm involves multiple steps of image registration incorporating a dynamic registration-based motion tracking algorithm to restore the spatial correspondence of DWI data at the slice level and reconstruct DTI of the fetal brain in the standard (atlas) coordinate space. A weighted linear least squares approach is adapted to remove the effect of intra-slice motion and reconstruct DTI from motion-corrected data. The proposed algorithm was tested on data obtained from 21 healthy fetuses scanned in-utero at 22-38 weeks gestation. Significantly higher fractional anisotropy values in fiber-rich regions, and the analysis of whole-brain tractography and group structural connectivity, showed the efficacy of the proposed method compared to the analyses based on original data and previously proposed methods. The results of this study show that slice-level motion correction and robust reconstruction is necessary for reliable in-vivo structural connectivity analysis of the fetal brain. Connectivity analysis based on graph theoretic measures show high degree of modularity and clustering, and short average

  18. Brain stem type neuro-Behcet's syndrome

    International Nuclear Information System (INIS)

    Kataoka, Satoshi; Hirose, Genjiro; Kosoegawa, Hiroshi; Oda, Rokuhei; Yoshioka, Akira

    1987-01-01

    Two cases of brain stem type Neuro-Behcet's syndrome were evaluated by brain CT and Magnetic Resonance Imaging (Super-conducting type, 0.5 tesla) to correlate with the neurological findings. In the acute phase, low density area with peripheral enhancement effect and mass effect were seen at the brain stem in brain CT. MRI revealed a extensive high intensity signal area mainly involving the corticospinal tract in the meso-diencephalon as well as pons by T 2 weighted images (spin echo, TR = 1, 600 msec, TE = 90 msec) and the value of T 1 , T 2 , at the brain stem lesion were prolonged moderately. After high dose steroid treatment, the low density area in brain CT and high signal area in MRI were gradually reduced in its size. Peripheral enhancement effect in brain CT disappeared within 10 months in case 1, one month in the other case. In the chronic stage, the reduction of low density area and atrophy of brain stem were noted in brain CT. The lesion in chronic stage had low intensity in T 1 , T 2 weighted images and the T 1 , T 2 values at the lesion were mildly prolonged in MRI. Sequentially CT with enhancement and MRI examinations with T 1 , T 2 weighted images were useful to detect the lesion and to evaluate the activity, evolution of brain stem type Neuro-Behcet's syndrome. (author)

  19. Neuroprotective effects of cactus polysaccharide on oxygen and glucose deprivation induced damage in rat brain slices.

    Science.gov (United States)

    Huang, Xianju; Li, Qin; Zhang, Yingpei; Lü, Qing; Guo, Lianjun; Huang, Lin; He, Zhi

    2008-06-01

    1. The neuroprotective effect of cactus polysaccharide (CP) on oxygen and glucose deprivation (OGD) and reoxygenation (REO)-induced damage in the cortical and hippocampal slices of rat brain was investigated. 2. Cell viability was evaluated by using the 2, 3, 5-triphenyl tetrazolium chloride (TTC) method. The fluorescence of propidium iodide (PI) staining was used for quantification of cellular survival, and lactate dehydrogenase (LDH) activity in incubation medium was assessed by LDH assay to evaluate the degree of injury. 3. The OGD ischemic condition significantly decreased cellular viability and increased LDH release in the incubation medium. CP (0.2 mg/l approximately 2 mg/l) protected brain slices from OGD injury in a dosage dependent manner as demonstrated by increased A 490 value of TTC, decreased PI intensity and LDH release. At the above concentration, CP also prevented the increase of nitric oxide (NO) content and inducible nitric oxide synthase (iNOS) activity induced by OGD. 4. CP can protect the brain slices (cortical and hippocampus) against injury induced by OGD. Its neuroprotective effect may be partly mediated by the NO/iNOS system induced by OGD insult.

  20. Intersection Based Motion Correction of Multi-Slice MRI for 3D in utero Fetal Brain Image Formation

    Science.gov (United States)

    Kim, Kio; Habas, Piotr A.; Rousseau, Francois; Glenn, Orit A.; Barkovich, Anthony J.; Studholme, Colin

    2012-01-01

    In recent years post-processing of fast multi-slice MR imaging to correct fetal motion has provided the first true 3D MR images of the developing human brain in utero. Early approaches have used reconstruction based algorithms, employing a two step iterative process, where slices from the acquired data are re-aligned to an approximate 3D reconstruction of the fetal brain, which is then refined further using the improved slice alignment. This two step slice-to-volume process, although powerful, is computationally expensive in needing a 3D reconstruction, and is limited in its ability to recover sub-voxel alignment. Here, we describe an alternative approach which we term slice intersection motion correction (SIMC), that seeks to directly co-align multiple slice stacks by considering the matching structure along all intersecting slice pairs in all orthogonally planned slices that are acquired in clinical imaging studies. A collective update scheme for all slices is then derived, to simultaneously drive slices into a consistent match along their lines of intersection. We then describe a 3D reconstruction algorithm that, using the final motion corrected slice locations, suppresses through-plane partial volume effects to provide a single high isotropic resolution 3D image. The method is tested on simulated data with known motions and is applied to retrospectively reconstruct 3D images from a range of clinically acquired imaging studies. The quantitative evaluation of the registration accuracy for the simulated data sets demonstrated a significant improvement over previous approaches. An initial application of the technique to studying clinical pathology is included, where the proposed method recovered up to 15 mm of translation and 30 degrees of rotation for individual slices, and produced full 3D reconstructions containing clinically useful additional information not visible in the original 2D slices. PMID:19744911

  1. Image-guided recording system for spatial and temporal mapping of neuronal activities in brain slice.

    Science.gov (United States)

    Choi, Geonho; Lee, Jeonghyeon; Kim, Hyeongeun; Jang, Jaemyung; Im, Changkyun; Jeon, Nooli; Jung, Woonggyu

    2018-03-01

    In this study, we introduce the novel image-guided recording system (IGRS) for efficient interpretation of neuronal activities in the brain slice. IGRS is designed to combine microelectrode array (MEA) and optical coherence tomography at the customized upright microscope. It allows to record multi-site neuronal signals and image of the volumetric brain anatomy in a single body configuration. For convenient interconnection between a brain image and neuronal signals, we developed the automatic mapping protocol that enables us to project acquired neuronal signals on a brain image. To evaluate the performance of IGRS, hippocampal signals of the brain slice were monitored, and corresponding with two-dimensional neuronal maps were successfully reconstructed. Our results indicated that IGRS and mapping protocol can provide the intuitive information regarding long-term and multi-sites neuronal signals. In particular, the temporal and spatial mapping capability of neuronal signals would be a very promising tool to observe and analyze the massive neuronal activity and connectivity in MEA-based electrophysiological studies. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Application of Automated Image-guided Patch Clamp for the Study of Neurons in Brain Slices.

    Science.gov (United States)

    Wu, Qiuyu; Chubykin, Alexander A

    2017-07-31

    Whole-cell patch clamp is the gold-standard method to measure the electrical properties of single cells. However, the in vitro patch clamp remains a challenging and low-throughput technique due to its complexity and high reliance on user operation and control. This manuscript demonstrates an image-guided automatic patch clamp system for in vitro whole-cell patch clamp experiments in acute brain slices. Our system implements a computer vision-based algorithm to detect fluorescently labeled cells and to target them for fully automatic patching using a micromanipulator and internal pipette pressure control. The entire process is highly automated, with minimal requirements for human intervention. Real-time experimental information, including electrical resistance and internal pipette pressure, are documented electronically for future analysis and for optimization to different cell types. Although our system is described in the context of acute brain slice recordings, it can also be applied to the automated image-guided patch clamp of dissociated neurons, organotypic slice cultures, and other non-neuronal cell types.

  3. Somatosensory and acoustic brain stem reflex myoclonus.

    OpenAIRE

    Shibasaki, H; Kakigi, R; Oda, K; Masukawa, S

    1988-01-01

    A patient with brain stem reflex myoclonus due to a massive midbrain infarct was studied electrophysiologically. Myoclonic jerks were elicited at variable latencies by tapping anywhere on the body or by acoustic stimuli, and mainly involved flexor muscles of upper extremities. The existence of convergence of somatosensory and acoustic inputs in the brain stem was suggested. This myoclonus seemed to be mediated by a mechanism similar to the spino-bulbo-spinal reflex.

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    Using organotypic slice cultures of hippocampus and cortex-striatum from newborn to 7 day old rats, we are currently studying the excitotoxic effects of kainic acid (KA), AMPA and NMDA and the neuroprotective effects of glutamate receptor blockers, like NBQX. For detection and quantitation...... of the induced neurodegeneration, we have developed standardized protocols, including--a) densitometric measurements of the cellular uptake of propidium iodide (PI), --b) histological staining by Flouro-Jade, --c) lactate dehydrogenase (LDH) release to the culture medium, --d) immunostaining for microtubulin......-induced excitotoxicity and KA-glutamate receptor subunit mRNA expression after long-term exposure to low, non-toxic doses of KA and NBQX. We conclude that organotypic brain slice cultures, combined with standardized procedures for quantitation of cell damage and receptor subunit changes is of great potential use...

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    Using organotypic slice cultures of hippocampus and cortex-striatum from newborn to 7 day old rats, we are currently studying the excitotoxic effects of kainic acid (KA), AMPA and NMDA and the neuroprotective effects of glutamate receptor blockers, like NBQX. For detection and quantitation......-induced excitotoxicity and KA-glutamate receptor subunit mRNA expression after long-term exposure to low, non-toxic doses of KA and NBQX. We conclude that organotypic brain slice cultures, combined with standardized procedures for quantitation of cell damage and receptor subunit changes is of great potential use...... for studies of excitotoxic, glutamate receptor-induced neuronal cell death, receptor modulation and related neuroprotection....

  6. Stem cells to regenerate the newborn brain

    NARCIS (Netherlands)

    van Velthoven, C.T.J.

    2011-01-01

    Perinatal hypoxia-ischemia (HI) is a frequent cause of perinatal morbidity and mortality with limited therapeutic options. In this thesis we investigate whether mesenchymal stem cells (MSC) regenerate the neonatal brain after HI injury. We show that transplantation of MSC after neonatal brain injury

  7. Auditory brain stem responses in the detection of brain death.

    Science.gov (United States)

    Ozgirgin, O Nuri; Ozçelik, Tuncay; Sevimli, Nilay Kizilkaya

    2003-01-01

    We evaluated comatose patients by auditory brain stem responses (ABR) to determine the role of ABR in the diagnosis of impending brain death. Sixty comatose patients in the intensive care unit were evaluated by brain stem evoked response audiometry. Correlations were sought between the absence or presence of ABRs and the presenting pathology, the Glasgow Coma Scale (GCS) scores, and ultimate diagnoses. The brain stem responses were totally absent in 41 patients. Presence of wave I could be obtained in only 10 patients. All the waveforms were found in nine patients; however, in eight patients the potentials disappeared as the GCS scores decreased to 3. Detection of wave I alone strongly suggested dysfunction of the brain stem. However, loss of wave I particularly in trauma patients aroused doubt as to whether the absence was associated with auditory end organ injury or brain stem dysfunction. The results suggest that evaluation of ABR may support brain death in a comatose patient (i) when wave I is present alone, (ii) the absence of wave I is accompanied by a documented auditory end organ injury, or (iii) when previously recorded potentials are no longer detectable.

  8. Neurofibromatosis type 1: brain stem tumours

    International Nuclear Information System (INIS)

    Bilaniuk, L.T.; Molloy, P.T.; Zimmerman, R.A.; Phillips, P.C.; Vaughan, S.N.; Liu, G.T.; Sutton, L.N.; Needle, M.

    1997-01-01

    We describe the clinical and imaging findings of brain stem tumours in patients with neurofibromatosis type 1 (NF1). The NF1 patients imaged between January 1984 and January 1996 were reviewed and 25 patients were identified with a brain stem tumour. Clinical, radiographical and pathological results were obtained by review of records and images. Brain stem tumour identification occurred much later than the clinical diagnosis of NF1. Medullary enlargement was most frequent (68 %), followed by pontine (52 %) and midbrain enlargement (44 %). Patients were further subdivided into those with diffuse (12 patients) and those with focal (13 patients) tumours. Treatment for hydrocephalus was required in 67 % of the first group and only 15 % of the second group. Surgery was performed in four patients and revealed fibrillary astrocytomas, one of which progressed to an anaplastic astrocytoma. In 40 % of patients both brain stem and optic pathway tumours were present. The biological behaviour of brain stem tumours in NF1 is unknown. Diffuse tumours in the patients with NF1 appear to have a much more favourable prognosis than patients with similar tumours without neurofibromatosis type 1. (orig.). With 7 figs., 3 tabs

  9. Domoic acid disrupts the activity and connectivity of neuronal networks in organotypic brain slice cultures.

    Science.gov (United States)

    Hiolski, E M; Ito, S; Beggs, J M; Lefebvre, K A; Litke, A M; Smith, D R

    2016-09-01

    Domoic acid is a neurotoxin produced by algae and is found in seafood during harmful algal blooms. As a glutamate agonist, domoic acid inappropriately stimulates excitatory activity in neurons. At high doses, this leads to seizures and brain lesions, but it is unclear how lower, asymptomatic exposures disrupt neuronal activity. Domoic acid has been detected in an increasing variety of species across a greater geographical range than ever before, making it critical to understand the potential health impacts of low-level exposure on vulnerable marine mammal and human populations. To determine whether prolonged domoic acid exposure altered neuronal activity in hippocampal networks, we used a custom-made 512 multi-electrode array with high spatial and temporal resolution to record extracellular potentials (spikes) in mouse organotypic brain slice cultures. We identified individual neurons based on spike waveform and location, and measured the activity and functional connectivity within the neuronal networks of brain slice cultures. Domoic acid exposure significantly altered neuronal spiking activity patterns, and increased functional connectivity within exposed cultures, in the absence of overt cellular or neuronal toxicity. While the overall spiking activity of neurons in domoic acid-exposed cultures was comparable to controls, exposed neurons spiked significantly more often in bursts. We also identified a subset of neurons that were electrophysiologically silenced in exposed cultures, and putatively identified those neurons as fast-spiking inhibitory neurons. These results provide evidence that domoic acid affects neuronal activity in the absence of cytotoxicity, and suggest that neurodevelopmental exposure to domoic acid may alter neurological function in the absence of clinical symptoms. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Ionizing radiation action of transport systems of Na+ and K+ of neutronal membranes. Potassium ions reaccumulation with brain slices

    International Nuclear Information System (INIS)

    Dvoretsky, A.I.; Shainskaya, A.M.; Ananyeva, T.V.; Kulikova, I.A.

    1990-01-01

    The biological effect of ionizing radiation (IR) on the Na,K pump of the surviving brain cortex slices was investigated. It was shown that IR leads to marked disturbances in the Na,K pump activity and causes essential phasic changes in potassium ion reaccumulation by brain slices in different time after exposure. The possibility of modelling the radiation effect with the help of phospholipase A2 and decylenic acid was shown. The mechanisms of the functional disturbance of Na-K pump of nerve cells after irradiation are under discussion. (author)

  11. Probing oxygen consumption in epileptic brain slices with QDs-based FRET sensors

    Science.gov (United States)

    Zhang, Chunfeng; Ingram, Justin; Schiff, Steven; Xu, Jian; Xiao, Min

    2011-02-01

    We developed ratiometric optical oxygen sensors to probe the oxygen consumption during epileptic events in rat brain slices. The oxygen sensors consist of the sensing part of phosphorescence dyes (Platinum (II) octaethylporphine ketone) and reference part of nanocystal quantum dots (NQDs) embedded in polymer blends, with pre-designed excitation through fluorescence resonance energy transfer (FRET) from NQDs to the oxygen sensitive dyes (OSDs). The ratiometric FRET sensors with fast temporal response and excellent bio-compatibility are suitable for real time quantitative dissolved oxygen (D.O.) probes in biological microenvironment. Coating the sensors onto the micro-pipettes, we performed simultaneous oxygen probes at pyramidal and oriens layers in rat hippocampal CA1. Different spatiotemporal patterns with maximum D.O. decreases of 9.9+/-1.1 mg/L and 4.9+/-0.7 mg/L during seizure events were observed in pyramidal and oriens layers, respectively.

  12. Enhanced loading of Fura-2/AM calcium indicator dye in adult rodent brain slices via a microfluidic oxygenator.

    Science.gov (United States)

    Mauleon, Gerardo; Lo, Joe F; Peterson, Bethany L; Fall, Christopher P; Eddington, David T

    2013-06-15

    A microfluidic oxygenator is used to deliver constant oxygen to rodent brain slices, enabling the loading of the cell-permeant calcium indicator Fura-2/AM into cells of adult brain slices. When compared to traditional methods, our microfluidic oxygenator improves loading efficiency, measured by the number of loaded cells per unit area, for all tested age groups. Loading in slices from 1-year-old mice was achieved, which has not been possible with current bulk loading methods. This technique significantly expands the age range for which calcium studies are possible without cellular injection. This technique will facilitate opportunities for the study of calcium signaling of aging and long term stress related diseases. Moreover, it should be applicable to other membrane-permeant physiological indicator varieties. Published by Elsevier B.V.

  13. The brain stem function in patients with brain bladder

    International Nuclear Information System (INIS)

    Takahashi, Toshihiro

    1990-01-01

    A syndrome of detrusor-sphincter dyssynergia (DSD) is occasionally found in patients with brain bladder. To evaluate the brain stem function in cases of brain bladder, urodynamic study, dynamic CT scan of the brain stem (DCT) and auditory brainstem response (ABR) were performed. The region of interest of DCT aimed at the posterolateral portion of the pons. The results were analysed in contrast with the presense of DSD in urodynamic study. DCT studies were performed in 13 cases with various brain diseases and 5 control cases without neurological diseases. Abnormal patterns of the time-density curve consisted of low peak value, prolongation of filling time and low rapid washout ratio (low clearance ratio) of the contrast medium. Four of 6 cases with DSD showed at least one of the abnormal patterns of the time-density curve bilaterally. In 7 cases without DSD none showed bilateral abnormality of the curve and in 2 of 7 cases only unilateral abnormality was found. ABR was performed in 8 patients with brain diseases. The interpeak latency of the wave I-V (I-V IPL) was considered to be prolonged in 2 cases with DSD compared to that of 4 without DSD. In 2 cases with DSD who had normal DCT findings, measurement of the I-V IPL was impossible due to abnormal pattern of the ABR wave. Above mentioned results suggests the presence of functional disturbance at the posterolateral portion of the pons in cases of brain bladder with DSD. (author)

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

    DEFF Research Database (Denmark)

    Hansen, Suzanne L.; Sterjev, Zoran; Werngreen, Marie

    2012-01-01

    screening model for AEDs. To this end, we compared the in vitro and in vivo pharmacological profile of several selected AEDs (phenobarbital, phenytoin, tiagabine, fosphenytoin, valproate, and carbamazepine) along with citalopram using the PTZ-kindled model and brain slices from naïve, saline...

  15. PARP Inhibition Prevents Ethanol-Induced Neuroinflammatory Signaling and Neurodegeneration in Rat Adult-Age Brain Slice Cultures

    Science.gov (United States)

    Tajuddin, Nuzhath; Kim, Hee-Yong

    2018-01-01

    Using rat adult-age hippocampal-entorhinal cortical (HEC) slice cultures, we examined the role of poly [ADP-ribose] polymerase (PARP) in binge ethanol’s brain inflammatory and neurodegenerative mechanisms. Activated by DNA strand breaks, PARP (principally PARP1 in the brain) promotes DNA repair via poly [ADP-ribose] (PAR) products, but PARP overactivation triggers regulated neuronal necrosis (e.g., parthanatos). Previously, we found that brain PARP1 levels were upregulated by neurotoxic ethanol binges in adult rats and HEC slices, and PARP inhibitor PJ34 abrogated slice neurodegeneration. Binged HEC slices also exhibited increased Ca+2-dependent phospholipase A2 (PLA2) isoenzymes (cPLA2 IVA and sPLA2 IIA) that mobilize proinflammatory ω6 arachidonic acid (ARA). We now find in 4-day–binged HEC slice cultures (100 mM ethanol) that PARP1 elevations after two overnight binges precede PAR, cPLA2, and sPLA2 enhancements by 1 day and high-mobility group box-1 (HMGB1), an ethanol-responsive alarmin that augments proinflammatory cytokines via toll-like receptor-4 (TLR4), by 2 days. After verifying that PJ34 effectively blocks PARP activity (↑PAR), we demonstrated that, like PJ34, three other PARP inhibitors—olaparib, veliparib, and 4-aminobenzamide—provided neuroprotection from ethanol. Importantly, PJ34 and olaparib also prevented ethanol’s amplification of the PLA2 isoenzymes, and two PLA2 inhibitors were neuroprotective—thus coupling PARP to PLA2, with PLA2 activity promoting neurodegeneration. Also, PJ34 and olaparib blocked ethanol-induced HMGB1 elevations, linking brain PARP induction to TLR4 activation. The results provide evidence in adult brains that induction of PARP1 may mediate dual neuroinflammatory pathways (PLA2→phospholipid→ARA and HMGB1→TLR4→proinflammatory cytokines) that are complicit in binge ethanol-induced neurodegeneration. PMID:29339456

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

    DEFF Research Database (Denmark)

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

    and electrochemical sensor system that enables real time detection of metabolites, e.g. dopamine from cell cultures and brain slices. In summary we present results on culturing of brain slices and cells in the microfluidic system as well as on the incorporation of an electrochemical sensor system for characterization......The brain is the center of the nervous system, where serious neurodegenerative diseases such as Parkinson’s, Alzheimer’s and Huntington’s are products of functional loss in the neural cells (1). Typical techniques used to investigate these diseases lack precise control of the cellular surroundings......, in addition to isolating the neural tissue from nutrient delivery and to creating unwanted gradients (2). This means that typical techniques used to investigate neurodegenerative diseases cannot mimic in vivo conditions, as closely as desired. We have developed a novel microfluidic system for culturing PC12...

  17. Characterization of Cancer Stem Cells in Patients with Brain ...

    African Journals Online (AJOL)

    Background: Gliomas, in general, and astrocytomas, in particular, represent the most frequent primary brain tumors. Nowadays, it is increasingly believed that gliomas may arise from cancer stem cells, which share several characteristics with normal neural stem cells. Brain tumor stem cells have been found to express a ...

  18. Correlation of brain stem diffusion-weighted imaging score with vertebrobasilar artery stenosis in patients with acute brain stem infarction

    OpenAIRE

    Jing-sheng YU; Hui-sheng CHEN

    2015-01-01

    Objective To investigate the correlation of brain stem diffusion-weighted imaging (DWI) lesion score with vertebrobasilar artery stenosis as revealed by magnetic resonance angiography (MRA) in patients with acute brain stem infarction. Methods A total of 253 patients diagnosed as acute brain stem infarction by means of brain magnetic resonance imaging were analyzed retrospectively. Of them 211 patients were enrolled in the present study, and they were qualified with the enrolling standard, an...

  19. The role of glutamine transport in metabolism in the brain cortical tissue slice

    International Nuclear Information System (INIS)

    Hare, N.; Bubb, W.A.; Rae, C.; Broeer, S.

    2001-01-01

    The widely accepted 'glutamate/glutamine cycle' holds that glutamate released as a neurotransmitter in the brain is taken up by surrounding astrocytes, converted to neuro-inactive glutamine and transported back to neurons for reconversion to glutamate. Little, however, is known about the role of glutamine transport in this process. The situation is complicated by the fact that glutamine is transported by a variety of general amino-acid transporters of low specificity. The role of these transporters in flux of glutamine through the glutamate/glutamine cycle was investigated by 13 C NMR monitoring of the flux of C from [3- 13 C]L-lactate in guinea pig cortical tissue slices in the presence of competitive inhibitors of the A-type(α-(methylamino)isobutyrate; MeAIB) and N-type (histidine) transporters. The presence of each inhibitor (10 mM) produced no significant decrease in total metabolite pool size but resulted in a significant decrease in flux of [ 13 C] into the neurotransmitters glutamate and GABA and also into glutamine and alanine. The factional enrichment of glutamate and GABA was also significantly lower. By contrast there was no effect on the amount of [ 13 C] incorporated into aspartate isotopomers which may represent a predominantly astrocyte-labelled pool. These results are consistent with involvement of glutamine transporters in the recycling of synaptic glutamate by demonstrating partial blockage of incorporation of [ 13 C] label into neuronal metabolites

  20. Wallerian degeneration of the corticospinal tract in the brain stem

    International Nuclear Information System (INIS)

    Uchino, Akira; Onomura, Kentaro; Ohno, Masato

    1989-01-01

    Magnetic resonance imaging (MRI) of wallerian degeneration of the corticospinal tract in the brain stem was studied in 25 patients with chronic supratentorial vascular accidents. In the relatively early stages, at least three months after ictus, increased signal intensities in axial T 2 -weighted images - with or without decreased signal intensities in axial T 1 -weighted images - were observed in the brain stem ipsilaterally. In later stages, at least six months after ictus, shrinkage of the brain stem ipsilaterally - with or without decreased signal intensities - was clearly observed in axial T 1 -weighted images. MRI is therefore regarded a sensitive diagnostic modality for evaluating wallerian degeneration in the brain stem. (author)

  1. The effect of nucleotides and adenosine on stimulus-evoked glutamate release from rat brain cortical slices

    OpenAIRE

    Bennett, Gillian C; Boarder, Michael R

    2000-01-01

    Evidence has previously been presented that P1 receptors for adenosine, and P2 receptors for nucleotides such as ATP, regulate stimulus-evoked release of biogenic amines from nerve terminals in the brain. Here we investigated whether adenosine and nucleotides exert presynaptic control over depolarisation-elicited glutamate release.Slices of rat brain cortex were perfused and stimulated with pulses of 46 mM K+ in the presence of the glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxyl...

  2. Taurine Induces Proliferation of Neural Stem Cells and Synapse Development in the Developing Mouse Brain

    Science.gov (United States)

    Shivaraj, Mattu Chetana; Marcy, Guillaume; Low, Guoliang; Ryu, Jae Ryun; Zhao, Xianfeng; Rosales, Francisco J.; Goh, Eyleen L. K.

    2012-01-01

    Taurine is a sulfur-containing amino acid present in high concentrations in mammalian tissues. It has been implicated in several processes involving brain development and neurotransmission. However, the role of taurine in hippocampal neurogenesis during brain development is still unknown. Here we show that taurine regulates neural progenitor cell (NPC) proliferation in the dentate gyrus of the developing brain as well as in cultured early postnatal (P5) hippocampal progenitor cells and hippocampal slices derived from P5 mice brains. Taurine increased cell proliferation without having a significant effect on neural differentiation both in cultured P5 NPCs as well as cultured hippocampal slices and in vivo. Expression level analysis of synaptic proteins revealed that taurine increases the expression of Synapsin 1 and PSD 95. We also found that taurine stimulates the phosphorylation of ERK1/2 indicating a possible role of the ERK pathway in mediating the changes that we observed, especially in proliferation. Taken together, our results demonstrate a role for taurine in neural stem/progenitor cell proliferation in developing brain and suggest the involvement of the ERK1/2 pathways in mediating these actions. Our study also shows that taurine influences the levels of proteins associated with synapse development. This is the first evidence showing the effect of taurine on early postnatal neuronal development using a combination of in vitro, ex-vivo and in vivo systems. PMID:22916184

  3. Taurine induces proliferation of neural stem cells and synapse development in the developing mouse brain.

    Directory of Open Access Journals (Sweden)

    Mattu Chetana Shivaraj

    Full Text Available Taurine is a sulfur-containing amino acid present in high concentrations in mammalian tissues. It has been implicated in several processes involving brain development and neurotransmission. However, the role of taurine in hippocampal neurogenesis during brain development is still unknown. Here we show that taurine regulates neural progenitor cell (NPC proliferation in the dentate gyrus of the developing brain as well as in cultured early postnatal (P5 hippocampal progenitor cells and hippocampal slices derived from P5 mice brains. Taurine increased cell proliferation without having a significant effect on neural differentiation both in cultured P5 NPCs as well as cultured hippocampal slices and in vivo. Expression level analysis of synaptic proteins revealed that taurine increases the expression of Synapsin 1 and PSD 95. We also found that taurine stimulates the phosphorylation of ERK1/2 indicating a possible role of the ERK pathway in mediating the changes that we observed, especially in proliferation. Taken together, our results demonstrate a role for taurine in neural stem/progenitor cell proliferation in developing brain and suggest the involvement of the ERK1/2 pathways in mediating these actions. Our study also shows that taurine influences the levels of proteins associated with synapse development. This is the first evidence showing the effect of taurine on early postnatal neuronal development using a combination of in vitro, ex-vivo and in vivo systems.

  4. Electrical Guidance of Human Stem Cells in the Rat Brain

    Directory of Open Access Journals (Sweden)

    Jun-Feng Feng

    2017-07-01

    Full Text Available Limited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream. Transplanted cells were observed at 3 weeks and 4 months after stimulation in areas guided by the stimulation currents, and with indications of differentiation. Electrical stimulation thus may provide a potential approach to facilitate brain stem cell therapies.

  5. Milrinone in Enterovirus 71 Brain Stem Encephalitis

    Directory of Open Access Journals (Sweden)

    SHIH-MIN eWANG

    2016-03-01

    Full Text Available Enterovirus 71 (EV71 was implicated in a widespread outbreak of hand-foot-and-mouth disease (HFMD across the Asia Pacific area since 1997 and has also been reported sporadically in patients with brain stem encephalitis. Neurogenic shock with pulmonary edema (PE is a fatal complication of EV71 infection. Among inotropic agents, milrinone is selected as a therapeutic agent for EV71- induced PE due to its immunopathogenesis. Milrinone is a type III phosphodiesterase inhibitor that has both inotropic and vasodilator effects. Its clinical efficacy has been shown by modulating inflammation, reducing sympathetic over-activity, and improving survival in patients with EV71-associated PE. Milrinone exhibits immunoregulatory and anti-inflammatory effects in the management of systemic inflammatory responses in severe EV71 infection.

  6. Neural Stem Cells in the Diabetic Brain

    Directory of Open Access Journals (Sweden)

    Tomás P. Bachor

    2012-01-01

    Full Text Available Experimental diabetes in rodents rapidly affects the neurogenic niches of the adult brain. Moreover, behavioral disorders suggest that a similar dysfunction of the neurogenic niches most likely affects diabetic and prediabetic patients. Here, we review our present knowledge about adult neural stem cells, the methods used for their study in diabetic models, and the effects of experimental diabetes. Variations in diet and even a short hyperglycemia profoundly change the structure and the proliferative dynamics of the neurogenic niches. Moreover, alterations of diabetic neurogenic niches appear to be associated with diabetic cognitive disorders. Available evidence supports the hypothesis that, in the adult, early changes of the neurogenic niches might enhance development of the diabetic disease.

  7. Milrinone in Enterovirus 71 Brain Stem Encephalitis.

    Science.gov (United States)

    Wang, Shih-Min

    2016-01-01

    Enterovirus 71 (EV71) was implicated in a widespread outbreak of hand-foot-and-mouth disease (HFMD) across the Asia Pacific area since 1997 and has also been reported sporadically in patients with brain stem encephalitis. Neurogenic shock with pulmonary edema (PE) is a fatal complication of EV71 infection. Among inotropic agents, milrinone is selected as a therapeutic agent for EV71- induced PE due to its immunopathogenesis. Milrinone is a type III phosphodiesterase inhibitor that has both inotropic and vasodilator effects. Its clinical efficacy has been shown by modulating inflammation, reducing sympathetic over-activity, and improving survival in patients with EV71-associated PE. Milrinone exhibits immunoregulatory and anti-inflammatory effects in the management of systemic inflammatory responses in severe EV71 infection.

  8. Brain Cancer Stem Cells: Current Status on Glioblastoma Multiforme

    International Nuclear Information System (INIS)

    Facchino, Sabrina; Abdouh, Mohamed; Bernier, Gilbert

    2011-01-01

    Glioblastoma multiforme (GBM), an aggressive brain tumor of astrocytic/neural stem cell origin, represents one of the most incurable cancers. GBM tumors are highly heterogeneous. However, most tumors contain a subpopulation of cells that display neural stem cell characteristics in vitro and that can generate a new brain tumor upon transplantation in mice. Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cell self-renewal mechanism. GBM tumors are also notorious for their resistance to radiation therapy. Notably, GBM “cancer stem cells” were also found to be responsible for this radioresistance. Herein, we will analyze the data supporting or not the cancer stem cell model in GBM, overview the current knowledge regarding GBM stem cell self-renewal and radioresistance molecular mechanisms, and discuss the potential therapeutic application of these findings

  9. The impact of computed tomography slice thickness on the assessment of stereotactic, 3D conformal and intensity-modulated radiotherapy of brain tumors.

    Science.gov (United States)

    Caivano, R; Fiorentino, A; Pedicini, P; Califano, G; Fusco, V

    2014-05-01

    To evaluate radiotherapy treatment planning accuracy by varying computed tomography (CT) slice thickness and tumor size. CT datasets from patients with primary brain disease and metastatic brain disease were selected. Tumor volumes ranging from about 2.5 to 100 cc and CT scan at different slice thicknesses (1, 2, 4, 6 and 10 mm) were used to perform treatment planning (1-, 2-, 4-, 6- and 10-CT, respectively). For any slice thickness, a conformity index (CI) referring to 100, 98, 95 and 90 % isodoses and tumor size was computed. All the CI and volumes obtained were compared to evaluate the impact of CT slice thickness on treatment plans. The smallest volumes reduce significantly if defined on 1-CT with respect to 4- and 6-CT, while the CT slice thickness does not affect target definition for the largest volumes. The mean CI for all the considered isodoses and CT slice thickness shows no statistical differences when 1-CT is compared to 2-CT. Comparing the mean CI of 1- with 4-CT and 1- with 6-CT, statistical differences appear only for the smallest volumes with respect to 100, 98 and 95 % isodoses-the CI for 90 % isodose being not statistically significant for all the considered PTVs. The accuracy of radiotherapy tumor volume definition depends on CT slice thickness. To achieve a better tumor definition and dose coverage, 1- and 2-CT would be suitable for small targets, while 4- and 6-CT are suitable for the other volumes.

  10. In situ formation of protease-resistant prion protein in transmissible spongiform encephalopathy-infected brain slices.

    Science.gov (United States)

    Bessen, R A; Raymond, G J; Caughey, B

    1997-06-13

    The transmissible spongiform encephalopathies (TSEs) comprise a group of fatal neurodegenerative diseases that are characterized by the conversion of the normal host cellular prion protein (PrPC), to the abnormal protease-resistant prion protein isoform (PrP-res). It has been proposed, though not proven, that the infectious TSE agent consists solely of PrP-res and that PrP-res-induced conformational conversion of PrPC to additional PrP-res represents agent replication. In this study we demonstrate in situ conversion of protease-sensitive PrPC to PrP-res in TSE-infected brain slices. One step in this process is the binding of soluble PrPC to endogenous PrP-res deposits. The newly formed PrP-res associated with the slices in a pattern that correlated with the pre-existing brain distribution of PrP-res. Punctate in situ PrP conversion was observed in brain regions containing PrP-res amyloid plaques, and a more dispersed conversion product was detected in areas containing diffuse PrP-res deposits. These studies provide direct evidence that PrP-res formation involves the incorporation of soluble PrPC into both nonfibrillar and fibrillar PrP-res deposits in TSE-infected brain. Our findings suggest that the in situ PrP conversion reaction leads to additional polymerization of endogenous PrP-res aggregates and is analogous to the process of PrP-res fibril and subfibril growth in vivo.

  11. Combination cell therapy with mesenchymal stem cells and neural stem cells for brain stroke in rats.

    Science.gov (United States)

    Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

    2015-05-01

    Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.

  12. Neurosyphilis Involving Cranial Nerves in Brain Stem: 2 Case Reports

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Ji Hye [Dept. of Radiology, Kyung Hee University College of Medicine, Seoul (Korea, Republic of); Choi, Woo Suk; Kim, Eui Jong [Dept. of Radiology, Kyung Hee University Hospital, Seoul (Korea, Republic of); Yoon, Sung Sang; Heo, Sung Hyuk [Dept. of Neurology, Kyung Hee University Hospital, Seoul (Korea, Republic of)

    2012-01-15

    Neurosyphilis uncommonly presents with cranial neuropathies in acute syphilitic meningitis and meningovascular neurosyphilis. We now report two cases in which the meningeal form of neurosyphilis involved cranial nerves in the brain stem: the oculomotor and trigeminal nerve.

  13. Neonatal bilateral diaphragmatic paralysis caused by brain stem haemorrhage.

    OpenAIRE

    Blazer, S; Hemli, J A; Sujov, P O; Braun, J

    1989-01-01

    We describe a neonate with severe bilateral diaphragmatic paralysis caused by haemorrhage in the lower brain stem. To our knowledge this association has not been previously reported in the English medical literature.

  14. Training stem cells for treatment of malignant brain tumors

    Science.gov (United States)

    Li, Shengwen Calvin; Kabeer, Mustafa H; Vu, Long T; Keschrumrus, Vic; Yin, Hong Zhen; Dethlefs, Brent A; Zhong, Jiang F; Weiss, John H; Loudon, William G

    2014-01-01

    The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for patients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution (i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system. PMID:25258664

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

    Science.gov (United States)

    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.

  16. Correlation of brain stem diffusion-weighted imaging score with vertebrobasilar artery stenosis in patients with acute brain stem infarction

    Directory of Open Access Journals (Sweden)

    Jing-sheng YU

    2015-07-01

    Full Text Available Objective To investigate the correlation of brain stem diffusion-weighted imaging (DWI lesion score with vertebrobasilar artery stenosis as revealed by magnetic resonance angiography (MRA in patients with acute brain stem infarction. Methods A total of 253 patients diagnosed as acute brain stem infarction by means of brain magnetic resonance imaging were analyzed retrospectively. Of them 211 patients were enrolled in the present study, and they were qualified with the enrolling standard, and they underwent examination of brain DWI and MRA simultaneously. The DWI lesion scores and imaging data were analyzed comparatively and statistically. Results Significant correlation was found between DWI lesion score and the main trunk stenosis degree of vertebrobasilar artery in patients with acute brain stem infarction (P=0.009. An increase in overall stenosis degree was found along with an increase in DWI lesion score (P=0.005. When the DWI lesion score was ≥4, occlusion of the main trunk of vertebrobasilar artery could be predicted with sensitivity of 74.5% and specificity of 93.2%, respectively (P=0.000. Conclusions  The DWI lesion score increases as the degree of main trunk stenosis of vertebrobasilar artery increased in patients with acute brain stem infarction. The DWI lesion score, in certain extent, may predict the existence and degree of stenosis of the main trunk of vertebrobasilar artery. DOI: 10.11855/j.issn.0577-7402.2015.06.04

  17. Brain stem hypoplasia associated with Cri-du-Chat syndrome

    International Nuclear Information System (INIS)

    Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu

    2013-01-01

    Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries.

  18. Brain stem hypoplasia associated with Cri-du-Chat syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu [Dept. of Radiology, Inha University Hospital, Inha University School of Medicine, Incheon (Korea, Republic of)

    2013-12-15

    Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries.

  19. The effect of nucleotides and adenosine on stimulus-evoked glutamate release from rat brain cortical slices.

    Science.gov (United States)

    Bennett, G C; Boarder, M R

    2000-10-01

    Evidence has previously been presented that P1 receptors for adenosine, and P2 receptors for nucleotides such as ATP, regulate stimulus-evoked release of biogenic amines from nerve terminals in the brain. Here we investigated whether adenosine and nucleotides exert presynaptic control over depolarisation-elicited glutamate release. Slices of rat brain cortex were perfused and stimulated with pulses of 46 mM K(+) in the presence of the glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (0.2 mM). High K(+) substantially increased efflux of glutamate from the slices. Basal glutamate release was unchanged by the presence of nucleotides or adenosine at concentrations of 300 microM. Adenosine, ATP, ADP and adenosine 5'-O-(3-thiotriphoshate) at 300 microM attenuated depolarisation-evoked release of glutamate. However UTP, 2-methylthio ATP, 2-methylthio ADP, and alpha,beta-methylene ATP at 300 microM had no effect on stimulated glutamate efflux. Adenosine deaminase blocked the effect of adenosine, but left the response to ATP unchanged. The A(1) antagonist 8-cyclopentyl-1, 3-dipropylxanthine antagonised the inhibitory effect of both adenosine and ATP. Cibacron blue 3GA inhibited stimulus-evoked glutamate release when applied alone. When cibacron blue 3GA was present with ATP, stimulus-evoked glutamate release was almost eliminated. However, this P2 antagonist had no effect on the inhibition by adenosine. These results show that the release of glutamate from depolarised nerve terminals of the rat cerebral cortex is inhibited by adenosine and ATP. ATP appears to act directly and not through conversion to adenosine.

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

    Directory of Open Access Journals (Sweden)

    Laurent Chazalviel

    2016-01-01

    Full Text Available Normobaric oxygen (NBO and hyperbaric oxygen (HBO are emerging as a possible co-treatment of acute ischemic stroke. Both have been shown to reduce infarct volume, to improve neurologic outcome, to promote endogenous tissue plasminogen activator-induced thrombolysis and cerebral blood flow, and to improve tissue oxygenation through oxygen diffusion in the ischemic areas, thereby questioning the interest of HBO compared to NBO. In the present study, in order to investigate and compare the oxygen diffusion effects of NBO and HBO on acute ischemic stroke independently of their effects at the vascular level, we used acute brain slices exposed to oxygen and glucose deprivation, an ex vivo model of brain ischemia that allows investigating the acute effects of NBO (partial pressure of oxygen (pO 2 = 1 atmospheres absolute (ATA = 0.1 MPa and HBO (pO 2 = 2.5 ATA = 0.25 MPa through tissue oxygenation on ischemia-induced cell injury as measured by the release of lactate dehydrogenase. We found that HBO, but not NBO, reduced oxygen and glucose deprivation-induced cell injury, indicating that passive tissue oxygenation (i.e. without vascular support of the brain parenchyma requires oxygen partial pressure higher than 1 ATA.

  1. Three Dimensional Volumetric Modeling of the Internal Brain Structure Using Magnetic Resonance Imaging Slices

    National Research Council Canada - National Science Library

    Sallam, A

    2001-01-01

    ...) scanners, comprise a sparse dataset of 2-D gray-level images, that is neither capable of representing the 3-D nature of the brain, nor differentiating its various component parts in a convenient way...

  2. Feasibility and resolution limits of opto-magnetic imaging of neural network activity in brain slices using color centers in diamond

    DEFF Research Database (Denmark)

    Karadas, Mürsel; Wojciechowski, Adam M.; Huck, Alexander

    2018-01-01

    We suggest a novel approach for wide-field imaging of the neural network dynamics of brain slices that uses highly sensitivity magnetometry based on nitrogen-vacancy (NV) centers in diamond. Invitro recordings in brain slices is a proven method for the characterization of electrical neural activity...... and has strongly contributed to our understanding of the mechanisms that govern neural information processing. However, this traditional approach only acquires signals from a few positions, which severely limits its ability to characterize the dynamics of the underlying neural networks. We suggest...... to extend its scope using NV magnetometry-based imaging of the neural magnetic fields across the slice. Employing comprehensive computational simulations and theoretical analyses, we determine the spatiotemporal characteristics of the neural fields and the required key performance parameters of an NV...

  3. Head Stabilization Reflex in Patients with Brain Stem Vascular Lesions

    Directory of Open Access Journals (Sweden)

    Ferah Kızılay

    2009-03-01

    Full Text Available OBJECTIVE: The head stabilization reflex (HSR elicited by stimulating the accessory nerve is an oligo-polysynaptic/plurisegmental flexor reflex, which brings the head back to its previous position in response to a variety of sudden head position changes. This reflex was studied in numerous diseases and was inhibited in patients with cerebellar lesions. The present study aimed to investigate how HSR is affected in patients with brain stem vascular lesions. METHODS: The study included 18 patients with brain stem vascular lesions and 18 normal control subjects. Concentric needle electrodes were inserted into the belly of both the sternocleidomastoid muscle and the accessory nerve, and were stimulated separately from the posterior triangle. In all, 8 HSR responses were recorded and mean onset latencies were measured. RESULTS: By stimulating the left accessory nerve in patients with brain stem vascular lesions, contralateral HSR could not be elicited. Similarly, by stimulating the right accessory nerve, contralateral HSR response was elicited only in 3 of the 18 patients. In contrast, stimulation of both the left and right accessory nerves elicited contralateral HSR in all the controls. CONCLUSION: HSR was inhibited in patients with brain stem vascular lesions. This observation shows that the descending pathways in the brain stem facilitate HSR in a similar fashion as the cerebellum was shown to do in a previous study

  4. Electrochemical Sensor Array and Its Application to Real Time Imaging of a Brain Slice

    Science.gov (United States)

    Kasai, Nahoko; Shimada, Akiyoshi; Nyberg, Tobias; Torimitsu, Keiichi

    An electrochemical sensing system using a planar microelectrode array has been developed to monitor biological molecules with relatively high special and temporal resolutions. This enables us a real time imaging of the biological molecules release from a tissue invasively. In this study, we have established a multichannel hydrogen peroxide (H2O2) sensing system to monitor the real time H2O2 distribution in a tissue using a planar sensor array. H2O2 has been recognized in association with the pathology of neurological diseases because it is a by-product of a degenerative reaction of reactive oxygen species, one of the major causes of oxidative stress in mammalian cells. The sensor array is based on a 64-channel ITO electrode array of 50x50 μm electrodes modified with an enzyme, horseradish peroxidase, and an electron transfer mediator. Then we place a cultured rat hippocampal slice on the array and measure the current at each sensor using a multipotentiostat. When we introduce bicuculline into the solution as a stimulant, in the presence of a catalase inhibitor, we can observe a distinct increase in the H2O2 concentration. This real-time H2O2 distribution monitoring system will be a powerful tool with which to explore the neuronal cell death mechanism in biological systems.

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

    OpenAIRE

    Cui, Hong; Han, Weijuan; Yang, Lijun; Chang, Yanzhong

    2013-01-01

    Oligodendrocyte lineage gene-1 expressed in oligodendrocytes may trigger the repair of neuronal myelin impairment, and play a crucial role in myelin repair. Hypoxia-inducible factor 1α, a transcription factor, is of great significance in premature infants with hypoxic-ischemic brain damage. There is little evidence of direct regulatory effects of hypoxia-inducible factor 1α on oligodendrocyte lineage gene-1. In this study, brain slices of Sprague-Dawley rats were cultured and subjected to oxy...

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

    Science.gov (United States)

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

    2016-12-01

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

  7. Alteration of tricarboxylic acid cycle metabolism in rat brain slices by halothane

    International Nuclear Information System (INIS)

    Cheng, S.C.; Brunner, E.A.

    1978-01-01

    Metabolism of [2- 14 C] pyruvate, [1- 14 C] acetate and [5- 14 C] citrate in rat cerebral cortex slices was studied in the presence of halothane. Metabolites assayed include acetylcholine (ACh), citrate, glutamate, glutamineγ-aminobutyrate (GABA) and aspartate. The trichloroacetic acid soluble extract, the trichloracetic acid insoluble precipitate and its lipid extract were also studied. In control experiments, pyruvate preferentially labelled ACh, citrate, glutamate, GABA and aspartate. Acetate labelled ACh, but to a lesser extent than pyruvate. Acetate also labelled lipids and glutamine. Citrate labelled lipids but not ACh and served as a preferential precursor for glutamine. These data support a three-compartment model for cerebral tricarboxylic acid cycle metabolism. Halothane caused increases in GABA and aspartate contents and a decrease in ACh content. It has no effect on the contents of citrate, glutamate and glutamine. Halothane preferentially inhibited the metabolic transfer of radioactivity from pyruvate into almost all metabolites, an effect probably not related to pyruvate permeability. This is interpreted as halothane depression of the large metabolic compartment which includes the nerve endings. Halothane increased the metabolic transfer of radioactivity from acetate into lipids but did not alter such a transfer into the trichloroacetic acid extract. Halothane increased the metabolic transfer of radioactivity from citrate into the trichloroacetic acid precipitate, lipids and especially glutamine. Transfer of citrate radioactivity into GABA was somewhat decreased. The differential effects of halothane on acetate and citrate utilization suggest that the small metabolic compartment should be subdivided. Therefore, at least three metabolic compartments are demonstrated. Halothane did not interfere with the dicarboxylic acid portion of the tricarboxylic acid cycle. (author)

  8. Mapping the calcitonin receptor in human brain stem

    DEFF Research Database (Denmark)

    Bower, Rebekah L; Eftekhari, Sajedeh; Waldvogel, Henry J

    2016-01-01

    receptors (AMY) are a heterodimer formed by the coexpression of CTR with receptor activity-modifying proteins (RAMPs). CTR with RAMP1 responds potently to both amylin and CGRP. The brain stem is a major site of action for circulating amylin and is a rich site of CGRP binding. This study aimed to enhance our...... understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract...

  9. Brain stem auditory evoked responses in human infants and adults

    Science.gov (United States)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  10. Human Brain Stem Structures Respond Differentially to Noxious Heat

    Directory of Open Access Journals (Sweden)

    Alexander eRitter

    2013-09-01

    Full Text Available Concerning the physiological correlates of pain, the brain stem is considered to be one core region that is activated by noxious input. In animal studies, different slopes of skin heating (SSH with noxious heat led to activation in different columns of the midbrain periaqueductal grey (PAG. The present study aimed at finding a method for differentiating structures in PAG and other brain stem structures, which are associated with different qualities of pain in humans according to the structures that were associated with different behavioral significances to noxious thermal stimulation in animals. Brain activity was studied by fMRI in healthy subjects in response to steep and shallow SSH with noxious heat. We found differential activation to different SSH in the PAG and the rostral ventromedial medulla (RVM. In a second experiment we demonstrate that the different SSH were associated with different pain qualities. Our experiments provide evidence that brainstem structures, i.e. the PAG and the RVM, become differentially activated by different SSH. Therefore, different SSH can be utilized when brain stem structures are investigated and when it is aimed to activate these structures differentially. Moreover, percepts of first pain were elicited by shallow SSH whereas percepts of second pain were elicited by steep SSH. The stronger activation of these brain stem structures to SSH, eliciting percepts of second vs. first pain, might be of relevance for activating different coping strategies in response to the noxious input with the two types of SSH.

  11. All-optical functional synaptic connectivity mapping in acute brain slices using the calcium integrator CaMPARI.

    Science.gov (United States)

    Zolnik, Timothy A; Sha, Fern; Johenning, Friedrich W; Schreiter, Eric R; Looger, Loren L; Larkum, Matthew E; Sachdev, Robert N S

    2017-03-01

    The genetically encoded fluorescent calcium integrator calcium-modulated photoactivatable ratiobetric integrator (CaMPARI) reports calcium influx induced by synaptic and neural activity. Its fluorescence is converted from green to red in the presence of violet light and calcium. The rate of conversion - the sensitivity to activity - is tunable and depends on the intensity of violet light. Synaptic activity and action potentials can independently initiate significant CaMPARI conversion. The level of conversion by subthreshold synaptic inputs is correlated to the strength of input, enabling optical readout of relative synaptic strength. When combined with optogenetic activation of defined presynaptic neurons, CaMPARI provides an all-optical method to map synaptic connectivity. The calcium-modulated photoactivatable ratiometric integrator (CaMPARI) is a genetically encoded calcium integrator that facilitates the study of neural circuits by permanently marking cells active during user-specified temporal windows. Permanent marking enables measurement of signals from large swathes of tissue and easy correlation of activity with other structural or functional labels. One potential application of CaMPARI is labelling neurons postsynaptic to specific populations targeted for optogenetic stimulation, giving rise to all-optical functional connectivity mapping. Here, we characterized the response of CaMPARI to several common types of neuronal calcium signals in mouse acute cortical brain slices. Our experiments show that CaMPARI is effectively converted by both action potentials and subthreshold synaptic inputs, and that conversion level is correlated to synaptic strength. Importantly, we found that conversion rate can be tuned: it is linearly related to light intensity. At low photoconversion light levels CaMPARI offers a wide dynamic range due to slower conversion rate; at high light levels conversion is more rapid and more sensitive to activity. Finally, we employed Ca

  12. Characterization of Cancer Stem Cells in Patients with Brain ...

    African Journals Online (AJOL)

    Brain tumor stem cells have been found to express a variety of markers including Nestin, which can be potentially used as therapeutic targets. Dysregulation of the intermediate filament protein Nestin, the tumor-suppressor gene TP53, and Ki67 labeling index are implicated in glioma genesis and therapeutic resistance.

  13. CT findings of traumatic primary brain-stem injury

    International Nuclear Information System (INIS)

    Hosaka, Yasuaki; Hatashita, Shizuo; Bandou, Kuniaki; Ueki, Yasuyuki; Abe, Kouzou; Koga, Nobunori; Sugimura, Jun; Sakakibara, Tokiwa; Takagi, Suguru

    1984-01-01

    A series of 27 consecutive patients with traumatic primary brain stem injuries was studied. They were diagnosed by means of clinical signs, neurological examination, and computerized tomography (CT). The CT findings of the brain-stem lesions were classified into 4 types: Type H, spotty, high-density; Type H and L, high- and low-densities; Type L, low-density; Type I, isodensity. The Glasgow coma scale (GCS), neurological findings on admission, CT findings (findings in the brain stem, obliteration of perimesencephalic cistern (PMC), and other findings), and the Glasgow outcome scale (GOS) were examined. In the 9 cases of Type H, there was a correlation between the GCS and the GOS, and the spotty, high-density lesions were localized mainly in the dorsal and/or ventral midbrain parenchyma, but these lesions did not show focal signs and symptoms. Without an obliteration of the PMC, Type-H patients did not always have a bad outcome. In the 4 cases of Type H and L, the 2 cases of Type L, and the 12 cases of Type I, there was an obliteration of the PMC. All of the these cases had a bad outcome (1 case of moderate disability, 3 cases of severe disability, and 14 cases of death). The mechanism producing a spotty, high-density area was discussed. The weaker impact (than the other types) and individual anatomical differences weresupposed to make for a spotty, high-density are in the brain stem. (author)

  14. Evaluating doses of multi-slice CT in brain examinations using various methods.

    Science.gov (United States)

    Lin, Hung-Chih; Lai, Te-Jen; Tseng, Hsien-Chun; Lin, Cheng-Hsun; Tseng, Yen-Ling; Chen, Chien-Yi

    2017-12-01

    The effective dose (H E ) and organ or tissue equivalent dose (H T ) of a Rando phantom undergoing two brain computed tomography (CT) examination protocols were evaluated using thermoluminescent dosimeters (TLD-100H) and dose length product (DLP) methods. TLDs were inserted into the correlated positions of an organ or tissue of Rando phantom, such as thyroid, brain, and salivary gland, using (A) axial scan: scanning the maxillae ranging from external auditory meatus to the parietal bone, and (B) helical scan: scanning from the mandible to the parietal bone. CT examinations were performed on a Philips computer tomography (Brilliance CT) at Lukang Christian Hospital. TLDs were measured using a Harshaw 3500 TLD reader. The HT of organ and tissue during the two protocols was discussed. H E were calculated using ICRP 60 and 103 at 2.67 ± 0.18 and 1.89 ± 0.23 mSv based on an axial scan, and 4.70 ± 0.38 and 4.39 ± 0.37 mSv based on a helical scan, respectively. In the DLP method, H E was estimated from CTDI vol that was recorded directly from the console display of the CT unit and then calculated using AAPM 96. Finally, experimental results are compared with those in literature. Radiologists should choose and adjust protocols to prevent unnecessary radiation to patients and satisfying the as low as reasonably achievable (ALARA) principle. These findings will be valuable to patients, physicians, radiologists, and the public.

  15. Increased spread and replication efficiency of Listeria monocytogenes in organotypic brain-slices is related to multilocus variable number of tandem repeat analysis (MLVA) complex.

    Science.gov (United States)

    Guldimann, Claudia; Bärtschi, Michelle; Frey, Joachim; Zurbriggen, Andreas; Seuberlich, Torsten; Oevermann, Anna

    2015-07-03

    Listeria (L.) monocytogenes causes fatal infections in many species including ruminants and humans. In ruminants, rhombencephalitis is the most prevalent form of listeriosis. Using multilocus variable number tandem repeat analysis (MLVA) we recently showed that L. monocytogenes isolates from ruminant rhombencephalitis cases are distributed over three genetic complexes (designated A, B and C). However, the majority of rhombencephalitis strains and virtually all those isolated from cattle cluster in MLVA complex A, indicating that strains of this complex may have increased neurotropism and neurovirulence. The aim of this study was to investigate whether ruminant rhombencephalitis strains have an increased ability to propagate in the bovine hippocampal brain-slice model and can be discriminated from strains of other sources. For this study, forty-seven strains were selected and assayed on brain-slice cultures, a bovine macrophage cell line (BoMac) and a human colorectal adenocarcinoma cell line (Caco-2). They were isolated from ruminant rhombencephalitis cases (n = 21) and other sources including the environment, food, human neurolisteriosis cases and ruminant/human non-encephalitic infection cases (n = 26). All but one L. monocytogenes strain replicated in brain slices, irrespectively of the source of the isolate or MLVA complex. The replication of strains from MLVA complex A was increased in hippocampal brain-slice cultures compared to complex C. Immunofluorescence revealed that microglia are the main target cells for L. monocytogenes and that strains from MLVA complex A caused larger infection foci than strains from MLVA complex C. Additionally, they caused larger plaques in BoMac cells, but not CaCo-2 cells. Our brain slice model data shows that all L. monocytogenes strains should be considered potentially neurovirulent. Secondly, encephalitis strains cannot be conclusively discriminated from non-encephalitis strains with the bovine organotypic brain slice

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Tamar ePashut

    2014-06-01

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

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

    Science.gov (United States)

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

    2016-05-12

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

  19. Growth hormone (GH), brain development and neural stem cells.

    Science.gov (United States)

    Waters, M J; Blackmore, D G

    2011-12-01

    A range of observations support a role for GH in development and function of the brain. These include altered brain structure in GH receptor null mice, and impaired cognition in GH deficient rodents and in a subgroup of GH receptor defective patients (Laron dwarfs). GH has been shown to alter neurogenesis, myelin synthesis and dendritic branching, and both the GH receptor and GH itself are expressed widely in the brain. We have found a population of neural stem cells which are activated by GH infusion, and which give rise to neurons in mice. These stem cells are activated by voluntary exercise in a GH-dependent manner. Given the findings that local synthesis of GH occurs in the hippocampus in response to a memory task, and that GH replacement improves memory and cognition in rodents and humans, these new observations warrant a reappraisal of the clinical importance of GH replacement in GH deficient states.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-03-18

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

  1. The effect of α-, β-adrenergic receptor agonists and antagonists of the efflux of 22Na and uptake of 42K by rat brain cortical slices

    International Nuclear Information System (INIS)

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

    1982-01-01

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

  2. The integral biologically effective dose to predict brain stem toxicity of hypofractionated stereotactic radiotherapy

    International Nuclear Information System (INIS)

    Clark, B. G.; Souhami, L.; Pla, C.; Al-Amro, A.; Bahary, J-P.; Villemure, J-G.; Caron, J-L.; Podgorsak, E. B.

    1996-01-01

    Objective: The aim of this work is to develop a parameter for use during hypofractionated stereotactic treatment planning to predict brain stem toxicity prior to treatment and to aid in the determination of the appropriate treatment volume and fractionation regimen which will minimize risk of late damage to normal tissue. Materials and Methods: We have used the linear quadratic model to provide a simple and convenient method for assessing the dose in volumes with rapidly changing dose gradients. Although the steep dose fall-off at the edge of stereotactic radiotherapy treatment volumes provides a measure of protection for normal tissue surrounding the target, accurate dose-volume analysis prior to treatment is essential to assess clinical tolerance. In cases where the treatment volume is very close to or in contact with sensitive structures, relatively small portions of these structures may receive high doses and appropriate methods of analysis have not yet been established. This paper reports a retrospective study of 57 patients with malignant and benign intracranial lesions treated with hypofractionated stereotactic radiotherapy. The treatments were delivered between June 1989 and February 1993 with the dynamic rotation technique in 6 fractions over a period of 2 weeks, to a total dose of 42 Gy prescribed at the 90% isodose surface. All treatment volumes were spherical, irradiated with a single isocentre and circular collimators ranging in diameter from 2 to 4 cm. The treatment plans were repeated using a new planning system considerably more sophisticated than that used at the time of treatment. On each axial image slice, the tumor and the normal structures at risk for each patient were delineated. We calculated differential dose volume histograms to divide the structures into dose-bands and to determine the fractional volume within each dose band. Using the linear quadratic model, a biologically effective dose (BED) was evaluated for each of these dose

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

    Directory of Open Access Journals (Sweden)

    Jun Zhang

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

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

    Science.gov (United States)

    Zhang, Jun; Wang, Jianhong; Geng, Daoying; Li, Yuxin; Song, Donglei; Gu, Yuxiang

    2013-01-01

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

  5. Pathological and immunohistochemical study of lethal primary brain stem injuries

    Directory of Open Access Journals (Sweden)

    Rongchao Sun

    2012-05-01

    Full Text Available Abstract Background Many of the deaths that occur shortly after injury or in hospitals are caused by mild trauma. Slight morphological changes are often found in the brain stems of these patients during autopsy. The purpose of this study is to investigate the histopathological changes involved in primary brain stem injuries (PBSI and their diagnostic significance. Methods A total of 65 patients who had died of PBSI and other conditions were randomly selected. They were divided into 2 groups, an injury group (25 cases and a control group (20 cases. Slides of each patient’s midbrain, pons, and medulla oblongata were prepared and stained with HE, argentaffin, and immunohistochemical agents (GFAP, NF, amyloid-ß, MBP. Under low power (×100 and NF staining, the diameter of the thickest longitudinal axon was measured at its widest point. Ten such diameters were collected for each part of the brain (midbrain, pons, and medulla oblongata. Data were recorded and analyzed statistically. Results Brain stem contusions, astrocyte activity, edema, and pathological changes in the neurons were visibly different in the injury and control groups (P P  Conclusions These histopathological changes may prove beneficial to the pathological diagnosis of PBSI during autopsy. The measurement of axon diameters provides a referent quantitative index for the diagnosis of the specific causes of death involved in PBSI. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1345298818712204

  6. Stem Cell Technology for (Epi)genetic Brain Disorders.

    Science.gov (United States)

    Riemens, Renzo J M; Soares, Edilene S; Esteller, Manel; Delgado-Morales, Raul

    2017-01-01

    Despite the enormous efforts of the scientific community over the years, effective therapeutics for many (epi)genetic brain disorders remain unidentified. The common and persistent failures to translate preclinical findings into clinical success are partially attributed to the limited efficiency of current disease models. Although animal and cellular models have substantially improved our knowledge of the pathological processes involved in these disorders, human brain research has generally been hampered by a lack of satisfactory humanized model systems. This, together with our incomplete knowledge of the multifactorial causes in the majority of these disorders, as well as a thorough understanding of associated (epi)genetic alterations, has been impeding progress in gaining more mechanistic insights from translational studies. Over the last years, however, stem cell technology has been offering an alternative approach to study and treat human brain disorders. Owing to this technology, we are now able to obtain a theoretically inexhaustible source of human neural cells and precursors in vitro that offer a platform for disease modeling and the establishment of therapeutic interventions. In addition to the potential to increase our general understanding of how (epi)genetic alterations contribute to the pathology of brain disorders, stem cells and derivatives allow for high-throughput drugs and toxicity testing, and provide a cell source for transplant therapies in regenerative medicine. In the current chapter, we will demonstrate the validity of human stem cell-based models and address the utility of other stem cell-based applications for several human brain disorders with multifactorial and (epi)genetic bases, including Parkinson's disease (PD), Alzheimer's disease (AD), fragile X syndrome (FXS), Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Rett syndrome (RTT).

  7. Synaptic inputs from stroke-injured brain to grafted human stem cell-derived neurons activated by sensory stimuli.

    Science.gov (United States)

    Tornero, Daniel; Tsupykov, Oleg; Granmo, Marcus; Rodriguez, Cristina; Grønning-Hansen, Marita; Thelin, Jonas; Smozhanik, Ekaterina; Laterza, Cecilia; Wattananit, Somsak; Ge, Ruimin; Tatarishvili, Jemal; Grealish, Shane; Brüstle, Oliver; Skibo, Galina; Parmar, Malin; Schouenborg, Jens; Lindvall, Olle; Kokaia, Zaal

    2017-03-01

    Transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. However, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. Here we studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured rat cerebral cortex. Using the rabies virus-based trans-synaptic tracing method and immunoelectron microscopy, we demonstrate that the grafted neurons receive direct synaptic inputs from neurons in different host brain areas located in a pattern similar to that of neurons projecting to the corresponding endogenous cortical neurons in the intact brain. Electrophysiological in vivo recordings from the cortical implants show that physiological sensory stimuli, i.e. cutaneous stimulation of nose and paw, can activate or inhibit spontaneous activity in grafted neurons, indicating that at least some of the afferent inputs are functional. In agreement, we find using patch-clamp recordings that a portion of grafted neurons respond to photostimulation of virally transfected, channelrhodopsin-2-expressing thalamo-cortical axons in acute brain slices. The present study demonstrates, for the first time, that the host brain regulates the activity of grafted neurons, providing strong evidence that transplanted human induced pluripotent stem cell-derived cortical neurons can become incorporated into injured cortical circuitry. Our findings support the idea that these neurons could contribute to functional recovery in stroke and other conditions causing neuronal loss in cerebral cortex. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. CRISPR/Cas9-induced disruption of gene expression in mouse embryonic brain and single neural stem cells in vivo.

    Science.gov (United States)

    Kalebic, Nereo; Taverna, Elena; Tavano, Stefania; Wong, Fong Kuan; Suchold, Dana; Winkler, Sylke; Huttner, Wieland B; Sarov, Mihail

    2016-03-01

    We have applied the CRISPR/Cas9 system in vivo to disrupt gene expression in neural stem cells in the developing mammalian brain. Two days after in utero electroporation of a single plasmid encoding Cas9 and an appropriate guide RNA (gRNA) into the embryonic neocortex of Tis21::GFP knock-in mice, expression of GFP, which occurs specifically in neural stem cells committed to neurogenesis, was found to be nearly completely (≈ 90%) abolished in the progeny of the targeted cells. Importantly, upon in utero electroporation directly of recombinant Cas9/gRNA complex, near-maximal efficiency of disruption of GFP expression was achieved already after 24 h. Furthermore, by using microinjection of the Cas9 protein/gRNA complex into neural stem cells in organotypic slice culture, we obtained disruption of GFP expression within a single cell cycle. Finally, we used either Cas9 plasmid in utero electroporation or Cas9 protein complex microinjection to disrupt the expression of Eomes/Tbr2, a gene fundamental for neocortical neurogenesis. This resulted in a reduction in basal progenitors and an increase in neuronal differentiation. Thus, the present in vivo application of the CRISPR/Cas9 system in neural stem cells provides a rapid, efficient and enduring disruption of expression of specific genes to dissect their role in mammalian brain development. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  9. Primary brain tumors, neural stem cell, and brain tumor cancer cells: where is the link?

    Science.gov (United States)

    Germano, Isabelle; Swiss, Victoria; Casaccia, Patrizia

    2010-01-01

    The discovery of brain tumor-derived cells (BTSC) with the properties of stem cells has led to the formulation of the hypothesis that neural stem cells could be the cell of origin of primary brain tumors (PBT). In this review we present the most common molecular changes in PBT, define the criteria of identification of BTSC and discuss the similarities between the characteristics of these cells and those of the endogenous population of neural stem cells (NPCs) residing in germinal areas of the adult brain. Finally, we propose possible mechanisms of cancer initiation and progression and suggest a model of tumor initiation that includes intrinsic changes of resident NSC and potential changes in the microenvironment defining the niche where the NSC reside. PMID:20045420

  10. Brain tissue banking for stem cells for our future.

    Science.gov (United States)

    Palmero, Emily; Palmero, Sheryl; Murrell, Wayne

    2016-12-19

    In our lab we study neurogenesis and the development of brain tumors. We work towards treatment strategies for glioblastoma and towards using autologous neural stem cells for tissue regeneration strategies for brain damage and neurodegenerative disorders. It has been our policy to try to establish living cell cultures from all human biopsy material that we obtain. We hypothesized that small pieces of brain tissue could be cryopreserved and that live neural stem cells could be recovered at a later time. DMSO has been shown to possess a remarkable ability to diffuse through cell membranes and pass into cell interiors. Its chemical properties prevent the formation of damaging ice crystals thus allowing cell storage at or below -180 C. We report here a protocol for successful freezing of small pieces of tissue derived from human brain and human brain tumours. Virtually all specimens could be successfully revived. Assays of phenotype and behaviour show that the cell cultures derived were equivalent to those cultures previously derived from fresh tissue.

  11. Olivary degeneration after cerebellar or brain stem haemorrhage: MRI

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, A. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan) Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Hasuo, K. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Uchida, K. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Matsumoto, S. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Tsukamoto, Y. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Ohno, M. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Masuda, K. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan))

    1993-05-01

    Magnetic resonance (MR) images of seven patients with olivary degeneration caused by cerebellar or brain stem haemorrhages were reviewed. In four patients with cerebellar haemorrhage, old haematomas were identified as being located in the dentate nucleus; the contralateral inferior olivary nuclei were hyperintense on proton-density- and T2-weighted images. In two patients with pontine haemorrhages, the old haematomas were in the tegmentum and the ipsilateral inferior olivary nuclei, which were hyperintense. In one case of midbrain haemorrhage, the inferior olivary nuclei were hyperintense bilaterally. The briefest interval from the ictus to MRI was 2 months. Hypertrophic olivary nuclei were observed only at least 4 months after the ictus. Olivary degeneration after cerebellar or brain stem haemorrhage should not be confused with ischaemic, neoplastic, or other primary pathological conditions of the medulla. (orig.)

  12. In vitro uptake of [1-{sup 14}C]Octanoate in brain slices of rats: basic studies for assessing [1-{sup 11}C]Octanoate as a PET tracer of glial functions

    Energy Technology Data Exchange (ETDEWEB)

    Kuge, Yuji E-mail: kuge@med.hokudai.ac.jp; Hikosaka, Kenji; Seki, Koh-ichi; Ohkura, Kazue; Nishijima, Ken-ichi; Tsukamoto, Eriko; Tamaki, Nagara

    2002-04-01

    To clarify the contribution of glial cells to octanoate uptake into the brain, we determined the effects of fluoroacetate, a selective inhibitor of glial metabolism, on in vitro brain uptake of [1-{sup 14}C]octanoate, using rat brain slices. The [1-{sup 14}C]octanoate uptake significantly decreased, depending on the concentration of fluoroacetate (p=0.001). The [1-{sup 14}C]octanoate uptakes at 5 mM (0.23{+-}0.05% uptake/mg slice) and 25 mM fluoroacetate (0.12{+-}0.01% uptake/mg slice) were significantly lower than that at control (0.29{+-}0.02% uptake/mg slice, p<0.05 and p<0.001, respectively). The results demonstrate the contribution of glial cells to octanoate uptake into the brain. The potential of [1-{sup 11}C]octanoate as a PET tracer for studying glial functions is suggested.

  13. Acute traumatic brain-stem hemorrhage produced by sudden caudal displacement of the brain

    International Nuclear Information System (INIS)

    Mirvis, S.E.; Wolf, A.L.; Thompson, R.K.

    1990-01-01

    This paper determines in an experimental canine study and a clinical review, whether acute caudal displacement of the brain following blunt trauma produces hemorrhage in the rostral anterior midline of the brain stem by tethering the basilar to the fixed carotid arteries. In four dogs, a balloon catheter was suddenly inflated over the frontal lobe; in two, the carotid-basilar vascular connections were severed prior to balloon inflation. ICP was monitored during and after balloon inflation. Hemorrhage was verified by MR imaging and direct inspection of the fixed brain specimens. Admission CT scans demonstrating acute traumatic brain stem hemorrhage (TBH) in human patients were reviewed to determine the site of TBH, predominant site of impact, and neurologic outcome

  14. Copine1 regulates neural stem cell functions during brain development.

    Science.gov (United States)

    Kim, Tae Hwan; Sung, Soo-Eun; Cheal Yoo, Jae; Park, Jae-Yong; Yi, Gwan-Su; Heo, Jun Young; Lee, Jae-Ran; Kim, Nam-Soon; Lee, Da Yong

    2018-01-01

    Copine 1 (CPNE1) is a well-known phospholipid binding protein in plasma membrane of various cell types. In brain cells, CPNE1 is closely associated with AKT signaling pathway, which is important for neural stem cell (NSC) functions during brain development. Here, we investigated the role of CPNE1 in the regulation of brain NSC functions during brain development and determined its underlying mechanism. In this study, abundant expression of CPNE1 was observed in neural lineage cells including NSCs and immature neurons in human. With mouse brain tissues in various developmental stages, we found that CPNE1 expression was higher at early embryonic stages compared to postnatal and adult stages. To model developing brain in vitro, we used primary NSCs derived from mouse embryonic hippocampus. Our in vitro study shows decreased proliferation and multi-lineage differentiation potential in CPNE1 deficient NSCs. Finally, we found that the deficiency of CPNE1 downregulated mTOR signaling in embryonic NSCs. These data demonstrate that CPNE1 plays a key role in the regulation of NSC functions through the activation of AKT-mTOR signaling pathway during brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Triazolam-induced modulation of muscarinic acetylcholine receptor in living brain slices as revealed by a new positron-based imaging technique

    International Nuclear Information System (INIS)

    Murata, T.; Matsumura, K.; Onoe, H.; Watanabe, Y.; Sihver, S.; Sihver, W.; Langstroem, B.; Bergstroem, M.; Yonekura, Y.

    1997-01-01

    The effect of triazolam, a potent benzodiazepine (BZ) agonist, on muscarinic acetylcholinergic receptor (mAChR) binding was investigated in living brain slices by use of a novel positron-based imaging technique. Fresh rat brain slices were incubated with [ 11 C]N-methyl-4-piperidylbenzilate ([ 11 C]NMPB), a mAChR antagonist, in oxygenated Krebs-Ringer solution at 37 degree C. During incubation, time-resolved imaging of [ 11 C]NMPB binding in the slices was constructed on the storage phosphor screens. Addition of triazolam (1 μM) plus muscimol (30 μM), a GABA A receptor agonist, to the incubation mixture decreased the specific binding of [ 11 C]NMPB. Ro15-1788, a BZ receptor antagonist, prevented this effect, indicating that the effect was exerted through the GABA A /BZ receptor complex. These results demonstrated that stimulation of the GABA A /BZ receptor lowers the affinity of the mAChR for its ligand, which may underlie the BZ-induced amnesia, a serious clinical side effect of BZ. No such effect in the P2-fraction instead implies that the integrity of the neuronal cells and/or their environment is prerequisite for the modulation of mAChR by GABA A /BZ stimulation. (author)

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    maintains that antibody staining for enzymes involved in synthesis or transport, of acetylcholine would be a more definitive marker and hence, preferable. NEW METHOD: Colocalization of bNOS and CHAT in the LDT/PPT, and presence of parvalbumin (PV), was examined in non-ideally prepared mouse brain slices...... using currently available antibodies. RESULTS: Using fluorescent-based immunohistochemistry in LDT/PPT slices prepared for in vitro recordings, a near 100% colocalization of bNOS and CHAT was observed. COMPARISON WITH EXISTING METHOD: We confirm in the mouse, findings of near 100% colocalization of b......NOS and CHAT in the LDT/PPT, and we expand upon data from rat studies using optimally prepared tissue, that for dendritic visualization, bNOS staining exceeded the quality of CHAT staining for visualization of a higher degree of detail of fine processes. PV is not highly present in the mouse LDT...

  17. Differences between the release of radiolabelled and endogenous dopamine from superfused rat brain slices: effects of depolarizing stimuli, amphetamine and synthesis inhibition

    International Nuclear Information System (INIS)

    Herdon, H.; Strupish, J.; Nahorski, S.R.

    1985-01-01

    Direct comparisons between radiolabelled and endogenous dopamine (DA) release from superfused rat brain slices have been made. Striatal slices were prelabelled with [ 3 H]dopamine ([ 3 H]DA), then superfused at 0.5 ml/min and the released catecholamines analyzed by HPLC with electrochemical detection and radioactivity present in superfusate fractions also counted. The studies indicate that labelled and endogenous amine release do not always occur in parallel, and that major causes of discrepancy between them may include the presence of a large newly-synthesized component in endogenous release and the uneven distribution of labelled amine within endogenous releasable pools. The results also suggest that the prelabelling process itself may alter the pools contributing to subsequent endogenous release. (Auth.)

  18. Rescue of Brain Function Using Tunneling Nanotubes Between Neural Stem Cells and Brain Microvascular Endothelial Cells.

    Science.gov (United States)

    Wang, Xiaoqing; Yu, Xiaowen; Xie, Chong; Tan, Zijian; Tian, Qi; Zhu, Desheng; Liu, Mingyuan; Guan, Yangtai

    2016-05-01

    Evidence indicates that neural stem cells (NSCs) can ameliorate cerebral ischemia in animal models. In this study, we investigated the mechanism underlying one of the neuroprotective effects of NSCs: tunneling nanotube (TNT) formation. We addressed whether the control of cell-to-cell communication processes between NSCs and brain microvascular endothelial cells (BMECs) and, particularly, the control of TNT formation could influence the rescue function of stem cells. In an attempt to mimic the cellular microenvironment in vitro, a co-culture system consisting of terminally differentiated BMECs from mice in a distressed state and NSCs was constructed. Additionally, engraftment experiments with infarcted mouse brains revealed that control of TNT formation influenced the effects of stem cell transplantation in vivo. In conclusion, our findings provide the first evidence that TNTs exist between NSCs and BMECs and that regulation of TNT formation alters cell function.

  19. Isolated brain stem edema in a pediatric patient with head trauma: a case report.

    Science.gov (United States)

    Basarslan, K; Basarslan, F; Karakus, A; Yilmaz, C

    2015-01-01

    Brain stem is the most vital part of our body and is a transitional region of the brain that connects the cerebrum with the spinal cord. Though, being small in size, it is full of indispensible functions such as the breathing, heart beat. Injury to the brain stem has similar effects as a brain injury, but it is more fatal. Use of the Glasgow Coma Score as a prognostic indicator of outcome in patients with head injuries is widely accepted in clinical practice. Traumatic brain stem edema in children is rare, but is associated with poor outcome. The question is that whether it is being aware of computerized tomography appearance of the posterior fossa when initial evaluating pediatric patients with head trauma at emergency clinics. Normal and edematous brain stem without an additional pathology are slightly different and not distinguished easily. On the other hand, brain stem edema should be promptly identified and appropriately treated in a short time.

  20. Brain stem evoked response to forward and reversed speech in humans.

    Science.gov (United States)

    Galbraith, Gary C; Amaya, Elizabeth M; de Rivera, Jacinta M Diaz; Donan, Namee M; Duong, Mylien T; Hsu, Jeffrey N; Tran, Kim; Tsang, Lian P

    2004-09-15

    Speech stimuli played in reverse are perceived as unfamiliar and alien-sounding, even though phoneme duration and fundamental voicing frequency are preserved. Although language perception ultimately resides in the neocortex, the brain stem plays a vital role in processing auditory information, including speech. The present study measured brain stem frequency-following responses (FFR) evoked by forward and reverse speech stimuli recorded from electrodes oriented horizontally and vertically to measure signals with putative origins in auditory nerve and rostral brain stem, respectively. The vertical FFR showed increased amplitude due to forward speech. It is concluded that familiar phonological and prosodic properties of forward speech selectively activate central brain stem neurons.

  1. Brain computed tomography using iterative reconstruction to diagnose acute middle cerebral artery stroke: usefulness in combination of narrow window setting and thin slice reconstruction.

    Science.gov (United States)

    Inoue, Taihei; Nakaura, Takeshi; Yoshida, Morikatsu; Yokoyama, Koichi; Uetani, Hiroyuki; Oda, Seitaro; Utsunomiya, Daisuke; Kitajima, Mika; Harada, Kazunori; Yamashita, Yasuyuki

    2018-04-01

    The purpose of this study is to determine whether iterative model reconstruction (IMR) optimized for brain CT could improve the detection of acute stroke in the setting of thin image slices and narrow window settings. We retrospectively reviewed 27 patients who presented acute middle cerebral artery (MCA) stroke. Images were reconstructed using filtered back projection (FBP; 1- and 5-mm slice thickness) and IMR (1 mm thickness), and contrast-to-noise ratios (CNRs) of infarcted and non-infarcted areas were compared. To analyze the performance of acute MCA stroke detection, we used receiver operating characteristic (ROC) curve techniques and compared 5-mm FBP with standard and narrow window settings, and 1-mm FBP and IMR with narrow window settings. The CNR in 1-mm IMR (1.1 ± 1.0) was significantly higher than in 5- (0.8 ± 0.7) and 1-mm FBP (0.4 ± 0.4) (p window settings (0.90, 95% CI: 0.86, 0.94) than it was with 5-mm FBP (0.78, 95% CI: 0.72, 0.83). The combination of thin image slices and narrow window settings under IMR reconstruction provide better diagnostic performance for acute MCA stroke than conventional reconstruction methods.

  2. Tomographic criteria of gliomas in the brain stem in infants

    International Nuclear Information System (INIS)

    Machado Junior, M.A.; Bracchi, M.; D'Incerti, L.; Passerini, A.

    1994-01-01

    The relationship between Computed Tomography Imaging, histopathological and prognostic data is evaluated by reviewing 37 cases of brain stem neoplasm in infants. The results indicate a presence of a cystic lesion with solid mural nodule as the single prognostic criteria of a greater survival rate. Such finding frequently corresponds to Pilocytic Astrocytomas. No correlations between contrast enhancement and prognostic was found. The association between the prognostic value to the densitometric characteristics of the lesions was not possible. It was concluded that the evaluations of the extension of such lesion is fundamental. Therefore, Magnetic Resonance Imaging has more value than computed tomography. (M.A.C.)

  3. Stem cell-paved biobridges facilitate stem transplant and host brain cell interactions for stroke therapy.

    Science.gov (United States)

    Duncan, Kelsey; Gonzales-Portillo, Gabriel S; Acosta, Sandra A; Kaneko, Yuji; Borlongan, Cesar V; Tajiri, Naoki

    2015-10-14

    Distinguished by an infarct core encased within a penumbra, stroke remains a primary source of mortality within the United States. While our scientific knowledge regarding the pathology of stroke continues to improve, clinical treatment options for patients suffering from stroke are extremely limited. Tissue plasminogen activator (tPA) remains the sole FDA-approved drug proven to be helpful following stroke. However, due to the need to administer the drug within 4.5h of stroke onset its usefulness is constrained to less than 5% of all patients suffering from ischemic stroke. One experimental therapy for the treatment of stroke involves the utilization of stem cells. Stem cell transplantation has been linked to therapeutic benefit by means of cell replacement and release of growth factors; however the precise means by which this is accomplished has not yet been clearly delineated. Using a traumatic brain injury model, we recently demonstrated the ability of transplanted mesenchymal stromal cells (MSCs) to form a biobridge connecting the area of injury to the neurogenic niche within the brain. We hypothesize that MSCs may also have the capacity to create a similar biobridge following stroke; thereby forming a conduit between the neurogenic niche and the stroke core and peri-infarct area. We propose that this biobridge could assist and promote interaction of host brain cells with transplanted stem cells and offer more opportunities to enhance the effectiveness of stem cell therapy in stroke. This article is part of a Special Issue entitled SI: Cell Interactions In Stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Calcium-dependent plateau potentials in rostral ambiguus neurons in the newborn mouse brain stem in vitro

    DEFF Research Database (Denmark)

    Rekling, J C; Feldman, J L

    1997-01-01

    Calcium-dependent plateau potentials in rostral ambiguus neurons in the newborn mouse brain stem in vitro. J. Neurophysiol. 78: 2483-2492, 1997. The nucleus ambiguus contains vagal and glossopharyngeal motoneurons and preganglionic neurons involved in respiration, swallowing, vocalization......, and control of heart beat. Here we show that the rostral compact formation's ambiguus neurons, which control the esophageal phase of swallowing, display calcium-dependent plateau potentials in response to tetanic orthodromic stimulation or current injection. Whole cell recordings were made from visualized...... neurons in the rostral nucleus ambiguus using a slice preparation from the newborn mouse. Biocytin-labeling revealed dendritic trees with pronounced rostrocaudal orientations confined to the nucleus ambiguus, a morphological profile matching that of vagal motoneurons projecting to the esophagus. Single...

  5. Cytokine Immunopathogenesis of Enterovirus 71 Brain Stem Encephalitis

    Directory of Open Access Journals (Sweden)

    Shih-Min Wang

    2012-01-01

    Full Text Available Enterovirus 71 (EV71 is one of the most important causes of herpangina and hand, foot, and mouth disease. It can also cause severe complications of the central nervous system (CNS. Brain stem encephalitis with pulmonary edema is the severe complication that can lead to death. EV71 replicates in leukocytes, endothelial cells, and dendritic cells resulting in the production of immune and inflammatory mediators that shape innate and acquired immune responses and the complications of disease. Cytokines, as a part of innate immunity, favor the development of antiviral and Th1 immune responses. Cytokines and chemokines play an important role in the pathogenesis EV71 brain stem encephalitis. Both the CNS and the systemic inflammatory responses to infection play important, but distinctly different, roles in the pathogenesis of EV71 pulmonary edema. Administration of intravenous immunoglobulin and milrinone, a phosphodiesterase inhibitor, has been shown to modulate inflammation, to reduce sympathetic overactivity, and to improve survival in patients with EV71 autonomic nervous system dysregulation and pulmonary edema.

  6. Age and Gender Effects On Auditory Brain Stem Response (ABR

    Directory of Open Access Journals (Sweden)

    Yones Lotfi

    2012-10-01

    Full Text Available Objectives: Auditory Brain Stem Response (ABR is a result of eight nerve and brain stem nuclei stimulation. Several factors may affect the latencies, interpeak latencies and amplitudes in ABR especially sex and age. In this study, age and sex influence on ABR were studied. Methods: This study was performed on 120 cases (60 males and 60 females at Akhavan rehabilitation center of university of welfare and rehabilitation sciences, Tehran, Iran. Cases were divided in three age groups: 18-30, 31-50 and 51-70 years old. Each age group consists of 20 males and 20 females. Age and sex influences on absolute latency of wave I and V, and IPL of I-V were examined. Results: Independent t test showed that females have significantly shorter latency of wave I, V, and IPL I-V latency (P<0.001 than males. Two way ANOVA showed that latency of wave I, V and IPL I-V in 51-70 years old group was significantly higher than 18-30 and 31-50 years old groups (P<0.001 Discussion: According to the results of present study and similar studies, in clinical practice, different norms for older adults and both genders should be established.

  7. Pathological and immunohistochemical study of lethal primary brain stem injuries.

    Science.gov (United States)

    Rongchao, Sun; Shudong, Yang; Zhiyi, Zhou

    2012-05-21

    Many of the deaths that occur shortly after injury or in hospitals are caused by mild trauma. Slight morphological changes are often found in the brain stems of these patients during autopsy. The purpose of this study is to investigate the histopathological changes involved in primary brain stem injuries (PBSI) and their diagnostic significance. A total of 65 patients who had died of PBSI and other conditions were randomly selected. They were divided into 2 groups, an injury group (25 cases) and a control group (20 cases). Slides of each patient's midbrain, pons, and medulla oblongata were prepared and stained with HE, argentaffin, and immunohistochemical agents (GFAP, NF, amyloid-β, MBP). Under low power (×100) and NF staining, the diameter of the thickest longitudinal axon was measured at its widest point. Ten such diameters were collected for each part of the brain (midbrain, pons, and medulla oblongata). Data were recorded and analyzed statistically. Brain stem contusions, astrocyte activity, edema, and pathological changes in the neurons were visibly different in the injury and control groups (P < 0.05). Characteristic changes occurred in the neural axons, axon diameter varied from axon to axon and even over different segments of one axon, and several pathological phenomena were observed. These included segmental thickening and curving, wave-like processing, disarrangement, and irregular swelling. A few axons ruptured and intumesced into retraction balls. Immunohistochemical MBP staining showed enlargement and curving of spaces between the myelin sheaths and axons in certain areas. The myelin sheaths lining the surfaces of the axons were in some cases incomplete and even exfoliated, and segmentation disappeared. These pathological changes increased in severity over time (P < 0.05). These histopathological changes may prove beneficial to the pathological diagnosis of PBSI during autopsy. The measurement of axon diameters provides a referent quantitative index

  8. Typical and atypical stem cells in the brain, vitamin C effect and neuropathology

    Directory of Open Access Journals (Sweden)

    Francisco Nualart

    2012-01-01

    Full Text Available Stem cells are considered a valuable cellular resource for tissue replacement therapies in most brain disorders. Stem cells have the ability to self-replicate and differentiate into numerous cell types, including neurons, oligodendrocytes and astrocytes. As a result, stem cells have been considered the "holy grail" of modern medical neuroscience. Despite their tremendous therapeutic potential, little is known about the mechanisms that regulate their differentiation. In this review, we analyze stem cells in embryonic and adult brains, and illustrate the differentiation pathways that give origin to most brain cells. We also evaluate the emergent role of the well known anti-oxidant, vitamin C, in stem cell differentiation. We believe that a complete understanding of all molecular players, including vitamin C, in stem cell differentiation will positively impact on the use of stem cell transplantation for neurodegenerative diseases.

  9. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model

    DEFF Research Database (Denmark)

    Jensen, Stine Skov; Meyer, Morten; Petterson, Stine Asferg

    2016-01-01

    AIMS: Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking...... invasion and tumor stemness into account. METHODS: Glioblastoma stem cell-like containing spheroid (GSS) cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains...... of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models. RESULTS: We observed a pronounced invasion into brain slice...

  10. Semiautomated volumetry of the cerebrum, cerebellum-brain stem, and temporal lobe on brain magnetic resonance images

    International Nuclear Information System (INIS)

    Hayashi, Norio; Matsuura, Yukihiro; Kawahara, Kazuhiro; Tsujii, Hideo; Yamamoto, Tomoyuki; Sanada, Shigeru; Suzuki, Masayuki; Matsui, Osamu

    2008-01-01

    The aim of this study was to develop an automated method of segmenting the cerebrum, cerebellum-brain stem, and temporal lobe simultaneously on magnetic resonance (MR) images. We obtained T1-weighted MR images from 10 normal subjects and 19 patients with brain atrophy. To perform automated volumetry from MR images, we performed the following three steps: segmentation of the brain region; separation between the cerebrum and the cerebellum-brain stem; and segmentation of the temporal lobe. Evaluation was based on the correctly recognized region (CRR) (i.e., the region recognized by both the automated and manual methods). The mean CRRs of the normal and atrophic brains were 98.2% and 97.9% for the cerebrum, 87.9% and 88.5% for the cerebellum-brain stem, and 76.9% and 85.8% for the temporal lobe, respectively. We introduce an automated volumetric method for the cerebrum, cerebellum-brain stem, and temporal lobe on brain MR images. Our method can be applied to not only the normal brain but also the atrophic brain. (author)

  11. Prospects and Limitations of Using Endogenous Neural Stem Cells for Brain Regeneration

    OpenAIRE

    Kaneko, Naoko; Kako, Eisuke; Sawamoto, Kazunobu

    2011-01-01

    Neural stem cells (NSCs) are capable of producing a variety of neural cell types, and are indispensable for the development of the mammalian brain. NSCs can be induced in vitro from pluripotent stem cells, including embryonic stem cells and induced-pluripotent stem cells. Although the transplantation of these exogenous NSCs is a potential strategy for improving presently untreatable neurological conditions, there are several obstacles to its implementation, including tumorigenic, immunologica...

  12. Effect of cocaine, lidocaine kindling and carbamazepine on batrachotoxin-induced phosphoinositide hydrolysis in rat brain slices.

    Science.gov (United States)

    Margolis, R L; Chuang, D M; Dick, D; Weiss, S R; Post, R M

    1993-06-18

    Repeated administration of a subconvulsant dose of a local anesthetic will eventually induce seizures, a phenomenon similar to electrical kindling. We have investigated the effect of repeated lidocaine and cocaine administration on the phosphoinositide (PI) hydrolysis induced by batrachotoxin (BTX), a specific Na channel activator. Rats were injected with cocaine or saline daily for 6 days and PI hydrolysis was assayed in sliced frontal cortex. Cocaine treatment had no effect on BTX-induced PI hydrolysis while in vitro cocaine blocked the BTX effect. In a second experiment, rats received daily injections of lidocaine or saline. After a rat developed at least two seizures, it was sacrificed together with a rat receiving lidocaine injections which had never seized and a rat receiving saline injections. Basal, BTX and ibotenic acid (IBO; a glutamate receptor agonist)-stimulated PI hydrolysis did not differ among the three groups in slices of either hippocampus (HC) or piriform cortex (PC) though IBO-stimulated PI hydrolysis was much greater in the HC than in the PC. Neither in vitro nor in vivo carbamazepine altered the effect of cocaine on BTX-induced PI hydrolysis. These results demonstrate that local anesthetic kindling does not alter PI hydrolysis coupled to Na channel or IBO activation.

  13. Progressive multifocal leukoencephalopathy limited to the brain stem

    International Nuclear Information System (INIS)

    Kastrup, O.; Maschke, M.; Diener, H.C.; Wanke, I.

    2002-01-01

    Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating slow-virus encephalitis caused by the JC polyomavirus in 2-5% of patients with AIDS. MRI typically shows multiple lesions in the cerebral hemispheres. We present a rare case of rapidly evolving and lethal PML with a severe bulbar syndrome and spastic tetraparesis in a patient with AIDS. MRI showed high-signal lesions on T2-weighted images confined to the brain stem, extending from the medulla oblongata to the midbrain. JC virus polymerase chain reaction in cerebrospinal fluid was positive, and neuropathology showed the findings of PML. This case was also notable because of the rapid progression despite improved immune status with antiretroviral therapy. (orig.)

  14. Line-scan diffusion tensor imaging of the posttraumatic brain stem: changes with neuropathologic correlation.

    Science.gov (United States)

    Yen, K; Weis, J; Kreis, R; Aghayev, E; Jackowski, C; Thali, M; Boesch, C; Maier, S E; Dirnhofer, R; Lövblad, K O

    2006-01-01

    Following trauma, imaging of brain stem lesions is often inconclusive. In a man who suffered a lethal accident, postmortem MR diffusion tensor (DT) imaging of the brain and neuropathologic examination were performed. DT imaging showed a disorganization of fibers in the brain stem that was not found in 2 controls and corresponded to changes on neuropathologic correlation. Diffusion tensor imaging provides an insight into the organization of myelinated structures of the CNS, potentially allowing diagnosis of traumatic fiber tract rupture.

  15. Implantation of glioblastoma spheroids into organotypic brain slice cultures as a model for investigating effects of irradiation

    DEFF Research Database (Denmark)

    Petterson, Stine Asferg; Jakobsen, Ida Pind; Jensen, Stine Skov

    2016-01-01

    Glioblastoma is the most frequent malignant brain tumor with an overall survival of only 14.6 months. Novel in vitro models preserving both tumor tissue and the interface between tumor and brain tissue are highly needed in order to develop novel efficient therapeutic strategies. Additionally, mod...

  16. Salicylate-Induced Suppression of Electrically Driven Activity in Brain Slices from the Auditory Cortex of Aging Mice.

    Science.gov (United States)

    Namikawa, Minoru; Sano, Ayaka; Tateno, Takashi

    2017-01-01

    The prevalence of tinnitus is known to increase with age. The age-dependent mechanisms of tinnitus may have important implications for the development of new therapeutic treatments. High doses of salicylate can be used experimentally to induce transient tinnitus and hearing loss. Although accumulating evidence indicates that salicylate induces tinnitus by directly targeting neurons in the peripheral and central auditory systems, the precise effect of salicylate on neural networks in the auditory cortex (AC) is unknown. Here, we examined salicylate-induced changes in stimulus-driven laminar responses of AC slices with salicylate superfusion in young and aged senescence-accelerated-prone (SAMP) and -resistant (SAMR) mice. Of the two strains, SAMP1 is known to be a more suitable model of presbycusis. We recorded stimulus-driven laminar local field potential (LFP) responses at multi sites in AC slice preparations. We found that for all AC slices in the two strains, salicylate always reduced stimulus-driven LFP responses in all layers. However, for the amplitudes of the LFP responses, the two senescence-accelerated mice (SAM) strains showed different laminar properties between the pre- and post-salicylate conditions, reflecting strain-related differences in local circuits. As for the relationships between auditory brainstem response (ABR) thresholds and the LFP amplitude ratios in the pre- vs. post-salicylate condition, we found negative correlations in layers 2/3 and 4 for both older strains, and in layer 5 (L5) in older SAMR1. In contrast, the GABAergic agonist muscimol (MSC) led to positive correlations between ABR thresholds and LFP amplitude ratios in the pre- vs. post-MSC condition in younger SAM mice from both strains. Further, in younger mice, salicylate decreased the firing rate in AC L4 pyramidal neurons. Thus, salicylate can directly reduce neural excitability of L4 pyramidal neurons and thereby influence AC neural circuit activity. That we observed age

  17. Salicylate-Induced Suppression of Electrically Driven Activity in Brain Slices from the Auditory Cortex of Aging Mice

    Directory of Open Access Journals (Sweden)

    Minoru Namikawa

    2017-12-01

    Full Text Available The prevalence of tinnitus is known to increase with age. The age-dependent mechanisms of tinnitus may have important implications for the development of new therapeutic treatments. High doses of salicylate can be used experimentally to induce transient tinnitus and hearing loss. Although accumulating evidence indicates that salicylate induces tinnitus by directly targeting neurons in the peripheral and central auditory systems, the precise effect of salicylate on neural networks in the auditory cortex (AC is unknown. Here, we examined salicylate-induced changes in stimulus-driven laminar responses of AC slices with salicylate superfusion in young and aged senescence-accelerated-prone (SAMP and -resistant (SAMR mice. Of the two strains, SAMP1 is known to be a more suitable model of presbycusis. We recorded stimulus-driven laminar local field potential (LFP responses at multi sites in AC slice preparations. We found that for all AC slices in the two strains, salicylate always reduced stimulus-driven LFP responses in all layers. However, for the amplitudes of the LFP responses, the two senescence-accelerated mice (SAM strains showed different laminar properties between the pre- and post-salicylate conditions, reflecting strain-related differences in local circuits. As for the relationships between auditory brainstem response (ABR thresholds and the LFP amplitude ratios in the pre- vs. post-salicylate condition, we found negative correlations in layers 2/3 and 4 for both older strains, and in layer 5 (L5 in older SAMR1. In contrast, the GABAergic agonist muscimol (MSC led to positive correlations between ABR thresholds and LFP amplitude ratios in the pre- vs. post-MSC condition in younger SAM mice from both strains. Further, in younger mice, salicylate decreased the firing rate in AC L4 pyramidal neurons. Thus, salicylate can directly reduce neural excitability of L4 pyramidal neurons and thereby influence AC neural circuit activity. That we

  18. Neurodevelopment. Live imaging of adult neural stem cell behavior in the intact and injured zebrafish brain.

    Science.gov (United States)

    Barbosa, Joana S; Sanchez-Gonzalez, Rosario; Di Giaimo, Rossella; Baumgart, Emily Violette; Theis, Fabian J; Götz, Magdalena; Ninkovic, Jovica

    2015-05-15

    Adult neural stem cells are the source for restoring injured brain tissue. We used repetitive imaging to follow single stem cells in the intact and injured adult zebrafish telencephalon in vivo and found that neurons are generated by both direct conversions of stem cells into postmitotic neurons and via intermediate progenitors amplifying the neuronal output. We observed an imbalance of direct conversion consuming the stem cells and asymmetric and symmetric self-renewing divisions, leading to depletion of stem cells over time. After brain injury, neuronal progenitors are recruited to the injury site. These progenitors are generated by symmetric divisions that deplete the pool of stem cells, a mode of neurogenesis absent in the intact telencephalon. Our analysis revealed changes in the behavior of stem cells underlying generation of additional neurons during regeneration. Copyright © 2015, American Association for the Advancement of Science.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    week old cultures. For testing the migratory abilities of exogenous precursor cells, rat SVZ neurospheres and human neural (HNS1 cells) and mesenchymal (hMSC-TERT) stem cell lines were micrografted to the rostral SVZ of 1 and 7 day old cultures. Two weeks later graft derivatives were identified...

  20. Auditory Brain-Stem and Middle-and Long-Latency Evoked Potentials in Coma

    OpenAIRE

    Rosenberg, C; Wogensen, K; Starr, A

    1984-01-01

    Twenty-five patients in coma, each with a Glascow Coma Scale measure less than or equal to five, were studied within the first three days of hospitalization with auditory brain-stem and middle- and long-latency evoked potentials. Survival was related to the simultaneous preservation of long- and middle-latency and brain-stem evoked potentials. The preservation of just middle-latency and/or brain-stem components did not correlate with survival. However, if the group of patients in coma due to ...

  1. Breaking the Blood-Brain Barrier With Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain.

    Science.gov (United States)

    Tajiri, Naoki; Lee, Jea Young; Acosta, Sandra; Sanberg, Paul R; Borlongan, Cesar V

    2016-01-01

    Blood-brain barrier (BBB) permeabilizers, such as mannitol, can facilitate peripherally delivered stem cells to exert therapeutic benefits on the stroke brain. Although this BBB permeation-aided stem cell therapy has been demonstrated in the acute stage of stroke, such BBB permeation in the chronic stage of the disease remains to be examined. Adult Sprague-Dawley rats initially received sham surgery or experimental stroke via the 1-h middle cerebral artery occlusion (MCAo) model. At 1 month after the MCAo surgery, stroke animals were randomly assigned to receive human umbilical cord stem cells only (2 million viable cells), mannitol only (1.1 mol/L mannitol at 4°C), combined human umbilical cord stem cells (200,000 viable cells) and mannitol (1.1 mol/L mannitol at 4°C), and vehicle (phosphate-buffered saline) only. Stroke animals that received human umbilical cord blood cells alone or combined human umbilical cord stem cells and mannitol exhibited significantly improved motor performance and significantly better brain cell survival in the peri-infarct area compared to stroke animals that received vehicle or mannitol alone, with mannitol treatment reducing the stem cell dose necessary to afford functional outcomes. Enhanced neurogenesis in the subventricular zone accompanied the combined treatment of human umbilical cord stem cells and mannitol. We showed that BBB permeation facilitates the therapeutic effects of a low dose of peripherally transplanted stem cells to effectively cause functional improvement and increase neurogenesis in chronic stroke.

  2. An in vivo-like tumor stem cell-related glioblastoma in vitro model for drug discovery

    DEFF Research Database (Denmark)

    Jensen, Stine Skov; Aaberg-Jessen, Charlotte; Nørregaard, Annette

    the effects of new drugs on tumor cells including tumor stem cells. Implantation of glioblastoma cells into organotypic brain slice cultures has previously been published as a model system, but not using a stem cell favourable environment. Organotypic corticostriatal rat brain slice cultures were prepared...... and cultured in a serum containing medium replaced after three days with a serum-free stem cell medium. Thereafter fluorescent DiI labelled glioblastoma spheroids from the cell line U87 and the tumor stem cell line SJ-1 established in our laboratory were implanted into the brain slices between cortex......The discovery of tumor stem cells being highly resistant against therapy makes new demands to model systems suitable for evaluation of the effects of new drugs on tumor stem cells. The aim of the present study was therefore to develop an in vivo-like in vitro glioblastoma model for testing...

  3. NFL-lipid nanocapsules for brain neural stem cell targeting in vitro and in vivo.

    Science.gov (United States)

    Carradori, Dario; Saulnier, Patrick; Préat, Véronique; des Rieux, Anne; Eyer, Joel

    2016-09-28

    The replacement of injured neurons by the selective stimulation of neural stem cells in situ represents a potential therapeutic strategy for the treatment of neurodegenerative diseases. The peptide NFL-TBS.40-63 showed specific interactions towards neural stem cells of the subventricular zone. The aim of our work was to produce a NFL-based drug delivery system able to target neural stem cells through the selective affinity between the peptide and these cells. NFL-TBS.40-63 (NFL) was adsorbed on lipid nanocapsules (LNC) whom targeting efficiency was evaluated on neural stem cells from the subventricular zone (brain) and from the central canal (spinal cord). NFL-LNC were incubated with primary neural stem cells in vitro or injected in vivo in adult rat brain (right lateral ventricle) or spinal cord (T10). NFL-LNC interactions with neural stem cells were different depending on the origin of the cells. NFL-LNC showed a preferential uptake by neural stem cells from the brain, while they did not interact with neural stem cells from the spinal cord. The results obtained in vivo correlate with the results observed in vitro, demonstrating that NFL-LNC represent a promising therapeutic strategy to selectively deliver bioactive molecules to brain neural stem cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke.

    Science.gov (United States)

    Tatebayashi, Kotaro; Tanaka, Yasue; Nakano-Doi, Akiko; Sakuma, Rika; Kamachi, Saeko; Shirakawa, Manabu; Uchida, Kazutaka; Kageyama, Hiroto; Takagi, Toshinori; Yoshimura, Shinichi; Matsuyama, Tomohiro; Nakagomi, Takayuki

    2017-06-01

    Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to understand the traits of iSCs in the poststroke human brain for possible applications in stem cell-based therapies for stroke patients. In this study, we report for the first time that iSCs can be isolated from the poststroke human brain. Putative iSCs were derived from poststroke brain tissue obtained from elderly stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction. Immunohistochemistry showed that these iSCs were localized near blood vessels within poststroke areas containing apoptotic/necrotic neurons and expressed both the stem cell marker nestin and several pericytic markers. Isolated iSCs expressed these same markers and demonstrated high proliferative potential without loss of stemness. Furthermore, isolated iSCs expressed other stem cell markers, such as Sox2, c-myc, and Klf4, and differentiated into multiple cells in vitro, including neurons. These results show that iSCs, which are likely brain pericyte derivatives, are present within the poststroke human brain. This study suggests that iSCs can contribute to neural repair in patients with stroke.

  5. An in vivo-like tumor stem cell-related glioblastoma in vitro model for drug discovery

    DEFF Research Database (Denmark)

    Jensen, Stine Skov; Aaberg-Jessen, Charlotte; Nørregaard, Annette

    the effects of new drugs on tumor cells including tumor stem cells. Implantation of glioblastoma cells into organotypic brain slice cultures has previously been published as a model system, but not using a stem cell favourable environment. Organotypic corticostriatal rat brain slice cultures were prepared...... and cultured in a serum containing medium replaced after three days with a serum-free stem cell medium. Thereafter fluorescent DiI labelled glioblastoma spheroids from the cell line U87 and the tumor stem cell line SJ-1 established in our laboratory were implanted into the brain slices between cortex...... growth of the U87 implants, but no invasion of cells into the brain tissue, neither in vitro nor in vivo. In contrast, SJ-1 was clearly invasive both in vitro and in vivo, but not very expansive. The co-cultures and brains with xenografts were immunohistochemically stained with anti-human vimentin...

  6. Wallerian degeneration of the corticospinal tract in the brain stem; MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, Akira; Onomura, Kentaro; Ohno, Masato (Kyushu Rosai Hospital, Kitakyushu, Fukuoka (Japan))

    1989-04-01

    Magnetic resonance imaging (MRI) of wallerian degeneration of the corticospinal tract in the brain stem was studied in 25 patients with chronic supratentorial vascular accidents. In the relatively early stages, at least three months after ictus, increased signal intensities in axial T{sub 2}-weighted images - with or without decreased signal intensities in axial T{sub 1}-weighted images - were observed in the brain stem ipsilaterally. In later stages, at least six months after ictus, shrinkage of the brain stem ipsilaterally - with or without decreased signal intensities - was clearly observed in axial T{sub 1}-weighted images. MRI is therefore regarded a sensitive diagnostic modality for evaluating wallerian degeneration in the brain stem. (author).

  7. Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation in the first Polish patient

    NARCIS (Netherlands)

    Mierzewska, H.; van der Knaap, M.S.; Scheper, G.C.; Bekiesinska-Figatowska, M.; Szczepanik, E.; Jurkiewicz, E.

    2011-01-01

    Leukoencephalopathy with brain stem and spinal cord involvement and elevated white matter lactate (LBSL) is a very rare autosomal recessive mitochondrial disorder. Clinically patients have slowly progressive ataxia, pyramidal syndrome and dorsal column dysfunction. The disease is defined on the

  8. Auditory Brain Stem Processing in Reptiles and Amphibians: Roles of Coupled Ears

    DEFF Research Database (Denmark)

    Willis, Katie L.; Christensen-Dalsgaard, Jakob; Carr, Catherine

    2014-01-01

    Comparative approaches to the auditory system have yielded great insight into the evolution of sound localization circuits, particularly within the nonmammalian tetrapods. The fossil record demonstrates multiple appearances of tympanic hearing, and examination of the auditory brain stem of variou...

  9. High-fat diet-induced downregulation of anorexic leukemia inhibitory factor in the brain stem.

    Science.gov (United States)

    Licursi, Maria; Alberto, Christian O; Dias, Alex; Hirasawa, Kensuke; Hirasawa, Michiru

    2016-11-01

    High-fat diet (HFD) is known to induce low-grade hypothalamic inflammation. Whether inflammation occurs in other brain areas remains unknown. This study tested the effect of short-term HFD on cytokine gene expression and identified leukemia inhibitory factor (LIF) as a responsive cytokine in the brain stem. Thus, functional and cellular effects of LIF in the brain stem were investigated. Male rats were fed chow or HFD for 3 days, and then gene expression was analyzed in different brain regions for IL-1β, IL-6, TNF-α, and LIF. The effect of intracerebroventricular injection of LIF on chow intake and body weight was also tested. Patch clamp recording was performed in the nucleus tractus solitarius (NTS). HFD increased pontine TNF-α mRNA while downregulating LIF in all major parts of the brain stem, but not in the hypothalamus or hippocampus. LIF injection into the cerebral aqueduct suppressed food intake without conditioned taste aversion, suggesting that LIF can induce anorexia via lower brain regions without causing malaise. In the NTS, a key brain stem nucleus for food intake regulation, LIF induced acute changes in neuronal excitability. HFD-induced downregulation of anorexic LIF in the brain stem may provide a permissive condition for HFD overconsumption. This may be at least partially mediated by the NTS. © 2016 The Obesity Society.

  10. The impact of aging, hearing loss, and body weight on mouse hippocampal redox state, measured in brain slices using fluorescence imaging.

    Science.gov (United States)

    Stebbings, Kevin A; Choi, Hyun W; Ravindra, Aditya; Llano, Daniel Adolfo

    2016-06-01

    The relationships between oxidative stress in the hippocampus and other aging-related changes such as hearing loss, cortical thinning, or changes in body weight are not yet known. We measured the redox ratio in a number of neural structures in brain slices taken from young and aged mice. Hearing thresholds, body weight, and cortical thickness were also measured. We found striking aging-related increases in the redox ratio that were isolated to the stratum pyramidale, while such changes were not observed in thalamus or cortex. These changes were driven primarily by changes in flavin adenine dinucleotide, not nicotinamide adenine dinucleotide hydride. Multiple regression analysis suggested that neither hearing threshold nor cortical thickness independently contributed to this change in hippocampal redox ratio. However, body weight did independently contribute to predicted changes in hippocampal redox ratio. These data suggest that aging-related changes in hippocampal redox ratio are not a general reflection of overall brain oxidative state but are highly localized, while still being related to at least one marker of late aging, weight loss at the end of life. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Possible role of brain stem respiratory neurons in mediating vomiting during space motion sickness

    Science.gov (United States)

    Miller, A. D.; Tan, L. K.

    1987-01-01

    The object of this study was to determine if brain stem expiratory neurons control abdominal muscle activity during vomiting. The activity of 27 ventral respiratory group expiratory neurons, which are known to be of primary importance for control of abdominal muscle activity during respiration, was recorded. It is concluded that abdominal muscle activity during vomiting must be controlled not only by some brain stem expiratory neurons but also by other input(s).

  12. Childhood Brain Stem Glioma Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Childhood brain stem glioma presents as a diffuse intrinsic pontine glioma (DIPG; a fast-growing tumor that is difficult to treat and has a poor prognosis) or a focal glioma (grows more slowly, is easier to treat, and has a better prognosis). Learn about the diagnosis, cellular classification, staging, treatment, and clinical trials for pediatric brain stem glioma in this expert-reviewed summary.

  13. [The forensic medical assessment of the micromorphology of brain stem hemorrhages in craniocerebral trauma].

    Science.gov (United States)

    Pushakov, S M

    1999-01-01

    Microscopic features of primary and secondary hemorrhages in the stem portion of the brain in craniocerebral injuries are described. Criteria of differential diagnosis between primary and secondary hemorrhages in the stem in subjects dead during 24 h after isolated and combined craniocerebral injuries are defined. The forensic medical significance of differential diagnosis of hemorrhages in the stem for the solution of many expert problems is evaluated.

  14. [Isolation and identification of brain tumor stem cells from human brain neuroepithelial tumors].

    Science.gov (United States)

    Fang, Jia-sheng; Deng, Yong-wen; Li, Ming-chu; Chen, Feng-Hua; Wang, Yan-jin; Lu, Ming; Fang, Fang; Wu, Jun; Yang, Zhuan-yi; Zhou, Xang-yang; Wang, Fei; Chen, Cheng

    2007-01-30

    To establish a simplified culture system for the isolation of brain tumor stem cells (BTSCs) from the tumors of human neuroepithelial tissue, to observe the growth and differentiation pattern of BTSCs, and to investigate their expression of the specific markers. Twenty-six patients with brain neuroepithelial tumors underwent tumor resection. Two pieces of tumor tissues were taken from each tumor to be dissociated, triturated into single cells in sterile DMEM-F12 medium, and then filtered. The tumor cells were seeded at a concentration of 200,000 viable cells per mL into serum-free DMEM-F12 medium simply supplemented with B27, human basic fibroblast growth factor (20 microg/L), human epidermal growth factor (20 microg /L), insulin (4 U/L), L-glutamine, penicillin and streptomycin. After the primary brain tumor spheres (BTSs) were generated, they were triturated again and passed in fresh medium. Limiting dilution assay was performed to observe the monoclone formation. 5-bromodeoxyuridine (BrdU) incorporation test was performed to observe the proliferation of the BTS. The BTSCs were cultured in mitogen-free DMEM-F12 medium supplemented with 10% fetal bovine serum to observe their differentiation. Immunocytochemistry was used to examine the expression of CD133 and nestin, specific markers of BTSC, and the rate of CD133 positive cells. Only a minority of subsets of cells from the tumors of neuroepithelial tissue had the capacity to survive, proliferate, and generate free-floating neurosphere-like BTSs in the simplified serum-free medium. These cells attached to the poly-L-lysine coated coverslips in the serum-supplemented medium and differentiated. The BTSCs were CD133 and nestin positive. The rate of CD133 positive cells in the tumor specimens was (21 +/- 6.2)% - (38 +/- 7.0)%. A new simplified culture system for the isolation of BTSCs is established. The tumors of human neuroepithelial tissue contain CD133 and nestin positive tumor stem cells which can be isolated

  15. Invasion Precedes Tumor Mass Formation in a Malignant Brain Tumor Model of Genetically Modified Neural Stem Cells

    Directory of Open Access Journals (Sweden)

    Oltea Sampetrean

    2011-09-01

    Full Text Available Invasiveness, cellular atypia, and proliferation are hallmarks of malignant gliomas. To effectively target each of these characteristics, it is important to understand their sequence during tumorigenesis. However, because most gliomas are diagnosed at an advanced stage, the chronology of gliomagenesis milestones is not well understood. The aim of the present study was to determine the onset of these characteristics during tumor development. Brain tumor-initiating cells (BTICs were established by overexpressing H-RasV12 in normal neural stem/progenitor cells isolated from the subventricular zone of adult mice harboring a homozygous deletion of the Ink4a/Arf locus. High-grade malignant brain tumors were then created by orthotopic implantation of 105 BTICs into the forebrain of 6-week-old wild-type mice. Micewere killed every week for 5 weeks, and tumors were assessed for cellular atypia, proliferation, hemorrhage, necrosis, and invasion. All mice developed highly invasive, hypervascular glioblastoma-like tumors. A 100% penetrance rate and a 4-week median survival were achieved. Tumor cell migration along fiber tracts started within days after implantation and was followed by perivascular infiltration of tumor cells with marked recruitment of reactive host cells. Next, cellular atypia became prominent. Finally, mass proliferation and necrosis were observed in the last stage of the disease. Video monitoring of BTICs in live brain slices confirmed the early onset of migration, as well as the main cell migration patterns. Our results showed that perivascular and intraparenchymal tumor cell migration precede tumor mass formation in the adult brain, suggesting the need for an early and sustained anti-invasion therapy.

  16. 3D brain Organoids derived from pluripotent stem cells: promising experimental models for brain development and neurodegenerative disorders.

    Science.gov (United States)

    Lee, Chun-Ting; Bendriem, Raphael M; Wu, Wells W; Shen, Rong-Fong

    2017-08-20

    Three-dimensional (3D) brain organoids derived from human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), appear to recapitulate the brain's 3D cytoarchitectural arrangement and provide new opportunities to explore disease pathogenesis in the human brain. Human iPSC (hiPSC) reprogramming methods, combined with 3D brain organoid tools, may allow patient-derived organoids to serve as a preclinical platform to bridge the translational gap between animal models and human clinical trials. Studies using patient-derived brain organoids have already revealed novel insights into molecular and genetic mechanisms of certain complex human neurological disorders such as microcephaly, autism, and Alzheimer's disease. Furthermore, the combination of hiPSC technology and small-molecule high-throughput screening (HTS) facilitates the development of novel pharmacotherapeutic strategies, while transcriptome sequencing enables the transcriptional profiling of patient-derived brain organoids. Finally, the addition of CRISPR/Cas9 genome editing provides incredible potential for personalized cell replacement therapy with genetically corrected hiPSCs. This review describes the history and current state of 3D brain organoid differentiation strategies, a survey of applications of organoids towards studies of neurodevelopmental and neurodegenerative disorders, and the challenges associated with their use as in vitro models of neurological disorders.

  17. Activity-dependent developmental plasticity of the auditory brain stem in children who use cochlear implants.

    Science.gov (United States)

    Gordon, Karen A; Papsin, Blake C; Harrison, Robert V

    2003-12-01

    1) To determine if a period of early auditory deprivation influences neural activity patterns as revealed by human auditory brain stem potentials evoked by electrical stimulation from a cochlear implant. 2) To examine the potential for plasticity in the human auditory brain stem. Specifically, we asked if electrically evoked auditory potentials from the auditory nerve and brain stem in children show evidence of development as a result of implant use. 3) To assess whether a sensitive or critical period exists in auditory brain stem development. Specifically, is there an age of implantation after which there are no longer developmental changes in auditory brain stem activity as revealed by electrically evoked potentials? The electrically evoked compound potential of the auditory nerve (ECAP) and the electrically evoked auditory brain stem response (EABR) were recorded repeatedly during the first year of implant use in each of 50 children. The children all had pre- or peri-lingual onset of severe to profound sensorineural hearing loss and received their implants at ages ranging from 12 mo to 17 yr. All children received Nucleus cochlear implant devices. All children were in therapy and in school programs that emphasized listening and required the children to wear their implants consistently. Initial stimulation from the cochlear implant evoked clear responses from the auditory nerve and auditory brain stem in most children. There was no correlation between minimum latency, maximum amplitude, or slope of amplitude growth of initial responses with age at implantation for ECAP eN1, EABR eIII and eV components (p > 0.05). During the first year of implant use, minimum latency of these waves significantly decreased (p brain stem and EABR eIII-eV for upper brain stem, decreased during the period of 6 to 12 mo of cochlear implant use (p children underwent implantation (p plasticity that we have shown in the human auditory brain stem does not appear from EABR data to be

  18. Early metabolic/cellular-level resuscitation following terminal brain stem herniation: implications for organ transplantation.

    Science.gov (United States)

    Arbour, Richard B

    2013-01-01

    Patients with terminal brain stem herniation experience global physiological consequences and represent a challenging population in critical care practice as a result of multiple factors. The first factor is severe depression of consciousness, with resulting compromise in airway stability and lung ventilation. Second, with increasing severity of brain trauma, progressive brain edema, mass effect, herniation syndromes, and subsequent distortion/displacement of the brain stem follow. Third, with progression of intracranial pathophysiology to terminal brain stem herniation, multisystem consequences occur, including dysfunction of the hypothalamic-pituitary axis, depletion of stress hormones, and decreased thyroid hormone bioavailability as well as biphasic cardiovascular state. Cardiovascular dysfunction in phase 1 is a hyperdynamic and hypertensive state characterized by elevated systemic vascular resistance and cardiac contractility. Cardiovascular dysfunction in phase 2 is a hypotensive state characterized by decreased systemic vascular resistance and tissue perfusion. Rapid changes along the continuum of hyperperfusion versus hypoperfusion increase risk of end-organ damage, specifically pulmonary dysfunction from hemodynamic stress and high-flow states as well as ischemic changes consequent to low-flow states. A pronounced inflammatory state occurs, affecting pulmonary function and gas exchange and contributing to hemodynamic instability as a result of additional vasodilatation. Coagulopathy also occurs as a result of consumption of clotting factors as well as dilution of clotting factors and platelets consequent to aggressive crystalloid administration. Each consequence of terminal brain stem injury complicates clinical management within this patient demographic. In general, these multisystem consequences are managed with mechanism-based interventions within the context of caring for the donor's organs (liver, kidneys, heart, etc.) after death by neurological

  19. Severe traumatic head injury: prognostic value of brain stem injuries detected at MRI.

    Science.gov (United States)

    Hilario, A; Ramos, A; Millan, J M; Salvador, E; Gomez, P A; Cicuendez, M; Diez-Lobato, R; Lagares, A

    2012-11-01

    Traumatic brain injuries represent an important cause of death for young people. The main objectives of this work are to correlate brain stem injuries detected at MR imaging with outcome at 6 months in patients with severe TBI, and to determine which MR imaging findings could be related to a worse prognosis. One hundred and eight patients with severe TBI were studied by MR imaging in the first 30 days after trauma. Brain stem injury was categorized as anterior or posterior, hemorrhagic or nonhemorrhagic, and unilateral or bilateral. Outcome measures were GOSE and Barthel Index 6 months postinjury. The relationship between MR imaging findings of brain stem injuries, outcome, and disability was explored by univariate analysis. Prognostic capability of MR imaging findings was also explored by calculation of sensitivity, specificity, and area under the ROC curve for poor and good outcome. Brain stem lesions were detected in 51 patients, of whom 66% showed a poor outcome, as expressed by the GOSE scale. Bilateral involvement was strongly associated with poor outcome (P brain stem injuries detected at MR imaging are poor prognostic signs. Nonhemorrhagic injuries showed the highest positive predictive value for good outcome.

  20. Four cases with localized brain-stem lesion on CT scan following closed head injury

    International Nuclear Information System (INIS)

    Saeki, Naokatsu; Odaki, Masaru; Oka, Nobuo; Takase, Manabu; Ono, Junichi.

    1981-01-01

    Cases of primary brain-stem injury following closed head injury, verified by a CT scan, have been increasingly reported. However, most of them have other intracranial lesions in addition to the brain stem, resulting in a poor outcome. The CT scan of 200 cases with severe head injury-Araki's classification of types 3 and 4 - were analysed. Four cases out of them had localized brain-stem lesion without any other significant intracranial injury on a CT scan at the acute stage and had a better outcome than had previously been reported. In this analysis, these 4 cases were studied, and the CT findings, prognosis, and pathogenesis of the localized brain-stem injury were discussed. Follow-up CT of three cases, and taken one month or more later, showed diffuse cortical atrophy. This may indicate the presence of diffuse cerebral injury which could not be seen on CT scans at the acute stage. This atrophic change may also be related with the mechanism of posttraumatic conscious impairment and posttraumatic neurological deficits, such as mental symptoms and impairment of the higher cortical function. Shearing injury is a probable pathogenesis for this diffuse cortical injury. On the other hand, one case did not have any cortical atrophy on a follow-up CT scan. Therefore, this is a case with a localized primary brain-stem injury. Coup injury against the brain stem by a tentorial margin in a case with a small tentorial opening is a possible mechanism producing the localized brain-stem injury. (J.P.N.)

  1. STEM Tones Pre-Activate Suffixes in the Brain

    Science.gov (United States)

    Söderström, Pelle; Horne, Merle; Roll, Mikael

    2017-01-01

    Results from the present event-related potentials (ERP) study show that tones on Swedish word stems can rapidly pre-activate upcoming suffixes, even when the word stem does not carry any lexical meaning. Results also show that listeners are able to rapidly restore suffixes which are replaced with a cough. Accuracy in restoring suffixes correlated…

  2. Development and Characterization of a Brain Endothelial Cell Phenotype using Human Induced Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Goldeman, Charlotte; Saaby, Lasse; Holst, Bjørn

    The transport of substances from blood to brain is regulated by the blood-brain barrier (BBB), i.e. the barrier properties of the brain endothelium. The endothelium restricts the transport into the brain of the majority of new drug candidates. Cultured monolayers of brain endothelial cells can...... be used to investigate drug transport in vitro, and screen candidates for permeation properties. One recent approach is to develop in vitro models of the BBB using human induced pluripotent stem cells (hIPSCs) as described by Stebbins et al. (2015).The aim of the present study was to investigate whether...... the published protocols were generically applicable and thus to develop and characterize in vitro models of the BBB using hIPSCs from different sources. Two stem cell lines, Bioni010-C and WTSli024-A, were seeded and maintained on Matrigel in mTesR1 media. Cells were then seeded as single cells at different...

  3. [Stem Cells in the Brain of Mammals and Human: Fundamental and Applied Aspects].

    Science.gov (United States)

    Aleksandrova, M A; Marey, M V

    2015-01-01

    Brain stem cells represent an extremely intriguing phenomenon. The aim of our review is to present an integrity vision of their role in the brain of mammals and humans, and their clinical perspectives. Over last two decades, investigations of biology of the neural stem cells produced significant changes in general knowledge about the processes of development and functioning of the brain. Researches on the cellular and molecular mechanisms of NSC differentiation and behavior led to new understanding of their involvement in learning and memory. In the regenerative medicine, original therapeutic approaches to neurodegenerative brain diseases have been elaborated due to fundamental achievements in this field. They are based on specific regenerative potential of neural stem cells and progenitor cells, which possess the ability to replace dead cells and express crucially significant biologically active factors that are missing in the pathological brain. For the needs of cell substitution therapy in the neural diseases, adequate methods of maintaining stem cells in culture and their differentiation into different types of neurons and glial cells, have been developed currently. The success of modern cellular technologies has significantly expanded the range of cells used for cell therapy. The near future may bring new perspective and distinct progress in brain cell therapy due to optimizing the cells types most promising for medical needs.

  4. The brain stem function in patients with brain bladder; Clinical evaluation using dynamic CT scan and auditory brainstem response

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Toshihiro (Yokohama City Univ. (Japan). Faculty of Medicine)

    1990-11-01

    A syndrome of detrusor-sphincter dyssynergia (DSD) is occasionally found in patients with brain bladder. To evaluate the brain stem function in cases of brain bladder, urodynamic study, dynamic CT scan of the brain stem (DCT) and auditory brainstem response (ABR) were performed. The region of interest of DCT aimed at the posterolateral portion of the pons. The results were analysed in contrast with the presense of DSD in urodynamic study. DCT studies were performed in 13 cases with various brain diseases and 5 control cases without neurological diseases. Abnormal patterns of the time-density curve consisted of low peak value, prolongation of filling time and low rapid washout ratio (low clearance ratio) of the contrast medium. Four of 6 cases with DSD showed at least one of the abnormal patterns of the time-density curve bilaterally. In 7 cases without DSD none showed bilateral abnormality of the curve and in 2 of 7 cases only unilateral abnormality was found. ABR was performed in 8 patients with brain diseases. The interpeak latency of the wave I-V (I-V IPL) was considered to be prolonged in 2 cases with DSD compared to that of 4 without DSD. In 2 cases with DSD who had normal DCT findings, measurement of the I-V IPL was impossible due to abnormal pattern of the ABR wave. Above mentioned results suggests the presence of functional disturbance at the posterolateral portion of the pons in cases of brain bladder with DSD. (author).

  5. Targeting breast to brain metastatic tumours with death receptor ligand expressing therapeutic stem cells.

    Science.gov (United States)

    Bagci-Onder, Tugba; Du, Wanlu; Figueiredo, Jose-Luiz; Martinez-Quintanilla, Jordi; Shah, Khalid

    2015-06-01

    Characterizing clinically relevant brain metastasis models and assessing the therapeutic efficacy in such models are fundamental for the development of novel therapies for metastatic brain cancers. In this study, we have developed an in vivo imageable breast-to-brain metastasis mouse model. Using real time in vivo imaging and subsequent composite fluorescence imaging, we show a widespread distribution of micro- and macro-metastasis in different stages of metastatic progression. We also show extravasation of tumour cells and the close association of tumour cells with blood vessels in the brain thus mimicking the multi-foci metastases observed in the clinics. Next, we explored the ability of engineered adult stem cells to track metastatic deposits in this model and show that engineered stem cells either implanted or injected via circulation efficiently home to metastatic tumour deposits in the brain. Based on the recent findings that metastatic tumour cells adopt unique mechanisms of evading apoptosis to successfully colonize in the brain, we reasoned that TNF receptor superfamily member 10A/10B apoptosis-inducing ligand (TRAIL) based pro-apoptotic therapies that induce death receptor signalling within the metastatic tumour cells might be a favourable therapeutic approach. We engineered stem cells to express a tumour selective, potent and secretable variant of a TRAIL, S-TRAIL, and show that these cells significantly suppressed metastatic tumour growth and prolonged the survival of mice bearing metastatic breast tumours. Furthermore, the incorporation of pro-drug converting enzyme, herpes simplex virus thymidine kinase, into therapeutic S-TRAIL secreting stem cells allowed their eradication post-tumour treatment. These studies are the first of their kind that provide insight into targeting brain metastasis with stem-cell mediated delivery of pro-apoptotic ligands and have important clinical implications. © The Author (2015). Published by Oxford University Press on

  6. Sumoylation of hypoxia-inducible factor-1α ameliorates failure of brain stem cardiovascular regulation in experimental brain death.

    Directory of Open Access Journals (Sweden)

    Julie Y H Chan

    2011-03-01

    Full Text Available One aspect of brain death is cardiovascular deregulation because asystole invariably occurs shortly after its diagnosis. A suitable neural substrate for mechanistic delineation of this aspect of brain death resides in the rostral ventrolateral medulla (RVLM. RVLM is the origin of a life-and-death signal that our laboratory detected from blood pressure of comatose patients that disappears before brain death ensues. At the same time, transcriptional upregulation of heme oxygenase-1 in RVLM by hypoxia-inducible factor-1α (HIF-1α plays a pro-life role in experimental brain death, and HIF-1α is subject to sumoylation activated by transient cerebral ischemia. It follows that sumoylation of HIF-1α in RVLM in response to hypoxia may play a modulatory role on brain stem cardiovascular regulation during experimental brain death.A clinically relevant animal model that employed mevinphos as the experimental insult in Sprague-Dawley rat was used. Biochemical changes in RVLM during distinct phenotypes in systemic arterial pressure spectrum that reflect maintained or defunct brain stem cardiovascular regulation were studied. Western blot analysis, EMSA, ELISA, confocal microscopy and immunoprecipitation demonstrated that drastic tissue hypoxia, elevated levels of proteins conjugated by small ubiquitin-related modifier-1 (SUMO-1, Ubc9 (the only known conjugating enzyme for the sumoylation pathway or HIF-1α, augmented sumoylation of HIF-1α, nucleus-bound translocation and enhanced transcriptional activity of HIF-1α in RVLM neurons took place preferentially during the pro-life phase of experimental brain death. Furthermore, loss-of-function manipulations by immunoneutralization of SUMO-1, Ubc9 or HIF-1α in RVLM blunted the upregulated nitric oxide synthase I/protein kinase G signaling cascade, which sustains the brain stem cardiovascular regulatory machinery during the pro-life phase.We conclude that sumoylation of HIF-1α in RVLM ameliorates brain stem

  7. Transcriptional profiling of adult neural stem-like cells from the human brain.

    Directory of Open Access Journals (Sweden)

    Cecilie Jonsgar Sandberg

    Full Text Available There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60. Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate. We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6, foetal human neural stem cells (n = 1 and human brain tissues (n = 12. The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular

  8. Patient-derived stem cells: pathways to drug discovery for brain diseases

    Directory of Open Access Journals (Sweden)

    Alan eMackay-Sim

    2013-03-01

    Full Text Available The concept of drug discovery through stem cell biology is based on technological developments whose genesis is now coincident. The first is automated cell microscopy with concurrent advances in image acquisition and analysis, known as high content screening (HCS. The second is patient-derived stem cells for modelling the cell biology of brain diseases. HCS has developed from the requirements of the pharmaceutical industry for high throughput assays to screen thousands of chemical compounds in the search for new drugs. HCS combines new fluorescent probes with automated microscopy and computational power to quantify the effects of compounds on cell functions. Stem cell biology has advanced greatly since the discovery of genetic reprogramming of somatic cells into induced pluripotent stem cells (iPSCs. There is now a rush of papers describing their generation from patients with various diseases of the nervous system. Although the majority of these have been genetic diseases, iPSCs have been generated from patients with complex diseases (schizophrenia and sporadic Parkinson’s disease. Some genetic diseases are also modelled in embryonic stem cells generated from blastocysts rejected during in vitro fertilisation. Neural stem cells have been isolated from post-mortem brain of Alzheimer’s patients and neural stem cells generated from biopsies of the olfactory organ of patients is another approach. These olfactory neurosphere-derived cells demonstrate robust disease-specific phenotypes in patients with schizophrenia and Parkinson’s disease. High content screening is already in use to find small molecules for the generation and differentiation of embryonic stem cells and induced pluripotent stem cells. The challenges for using stem cells for drug discovery are to develop robust stem cell culture methods that meet the rigorous requirements for repeatable, consistent quantities of defined cell types at the industrial scale necessary for high

  9. Brain-stem atrophy secondary to supratentorial cerebrovascular diseases as demonstrated by computed tomography

    International Nuclear Information System (INIS)

    Tsuchiya, Kazuhiro; Machida, Tohru; Iio, Masahiro.

    1985-01-01

    We reviewed the CT findings of 9 cases with supratentorial cerebrovascular diseases which also showed atrophic changes in their ipsilateral brain stem due to a Wallerian degeneration of the corticospinal tract. Although similar findings have been reported in cases of supratentorial infarcts, our cases consisted of 5 old intracerebral hemorrhages and 4 old infarcts. This finding can occur at any level of the supratentorial corticospinal tract, but the volume changes in the brain stem seemed to be prominent in cases where the motor cortex was involved. A correlation was found between the duration of the supratentorial disease and the volume loss of the brain stem. The shortest duration of our cases was 12 months. This CT finding is considered to be that of the chronic stage of the supratentorial lesion involving the corticospinal tract. (author)

  10. Control of abdominal muscles by brain stem respiratory neurons in the cat

    Science.gov (United States)

    Miller, Alan D.; Ezure, Kazuhisa; Suzuki, Ichiro

    1985-01-01

    The nature of the control of abdominal muscles by the brain stem respiratory neurons was investigated in decerebrate unanesthetized cats. First, it was determined which of the brain stem respiratory neurons project to the lumbar cord (from which the abdominal muscles receive part of their innervation), by stimulating the neurons monopolarly. In a second part of the study, it was determined if lumbar-projecting respiratory neurons make monosynaptic connections with abdominal motoneurons; in these experiments, discriminate spontaneous spikes of antidromically acivated expiratory (E) neurons were used to trigger activity from both L1 and L2 nerves. A large projection was observed from E neurons in the caudal ventral respiratory group to the contralateral upper lumber cord. However, cross-correlation experiments found only two (out of 47 neuron pairs tested) strong monosynaptic connections between brain stem neurons and abdominal motoneurons.

  11. MRI of the brain stem using fluid attenuated inversion recivery pulse sequences

    International Nuclear Information System (INIS)

    De Coene, B.; Hajnal, J.V.; Pennock, J.M.; Bydder, G.M.

    1993-01-01

    Heavily T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences with inversion times of 2000-2500 ms and echo times of 130-200 ms were used to image the brain stem of a normal adult and five patients. These sequences produce high signal from many white matter tracts and display high lesion contrast. The corticospinal and parietopontine tracts, lateral and medial lemnisci, superior and inferior cerebellar peduncles, medial longitudinal fasciculi, thalamo-olivary tracts the cuneate and gracile fasiculi gave high signal and were directly visualised. The oculomotor and trigeminal nerves were demonstrated within the brain stem. Lesions not seen with conventional T2-weighted spin echo sequences were seen with high contrast in patients with infarction, multiple sclerosis, sarcoidosis, chunt obstruction and metastatic tumour. The anatomical detail and high lesion contrast given by the FLAIR pulse sequence appear likely to be of value in diagnosis of disease in the brain stem. (orig.)

  12. Paving the way towards complex blood-brain barrier models using pluripotent stem cells

    DEFF Research Database (Denmark)

    Lauschke, Karin; Frederiksen, Lise; Hall, Vanessa Jane

    2017-01-01

    to the unique tightness and selective permeability of the BBB and has been shown to be disrupted in many diseases and brain disorders, such as, vascular dementia, stroke, multiple sclerosis and Alzheimer's disease. Given the progress that pluripotent stem cells (PSCs) have made in the last two decades......A tissue with great need to be modelled in vitro is the blood-brain barrier (BBB). The BBB is a tight barrier that covers all blood vessels in the brain and separates the brain microenvironment from the blood system. It consists of three cell types (neurovascular unit (NVU)) that contribute...

  13. Correlation of auditory brain stem response and the MRI measurements in neuro-degenerative disorders

    International Nuclear Information System (INIS)

    Kamei, Hidekazu

    1989-01-01

    The purpose of this study is to elucidate correlations of several MRI measurements of the cranium and brain, functioning as a volume conductor, to the auditory brain stem response (ABR) in neuro-degenerative disorders. The subjects included forty-seven patients with spinocerebellar degeneration (SCD) and sixteen of amyotrophic lateral sclerosis (ALS). Statistically significant positive correlations were found between I-V and III-V interpeak latencies (IPLs) and the area of cranium and brain in the longitudinal section of SCD patients, and between I-III and III-V IPLs and the area in the longitudinal section of those with ALS. And, also there were statistically significant correlations between the amplitude of the V wave and the area of brain stem as well as that of the cranium in the longitudinal section of SCD patients, and between the amplitude of the V wave and the area of the cerebrum in the longitudinal section of ALS. In conclusion, in the ABR, the IPLs were prolonged and the amplitude of the V wave was decreased while the MRI size of the cranium and brain increased. When the ABR is applied to neuro-degenerative disorders, it might be important to consider not only the conduction of the auditory tracts in the brain stem, but also the correlations of the size of the cranium and brain which act as a volume conductor. (author)

  14. Isolation of a Pluripotent Neural Stem Cell from the Embryonic Bovine Brain

    Directory of Open Access Journals (Sweden)

    Yuhua Gao

    2015-03-01

    Full Text Available We recently isolated stem cells derived from the brain of a bovine fetus, utilizing a particular mechanical separation method. After improving our experimental conditions, we obtained neural stem cells using an optimized culture medium system. The cells were expanded, established in continuous cell culture and used for immunofluorescence cytochemistry. RT-PCR showed that embryonic neural stem cells (NSCs not only expresses the protein Sox2, Nestin but also Pax6, Musashi proteins and were differentiated into the three classical neuronal phenotypes (neurons, astrocytes, and oligodendrocytes.

  15. Stem Tones Pre-activate Suffixes in the Brain.

    Science.gov (United States)

    Söderström, Pelle; Horne, Merle; Roll, Mikael

    2017-04-01

    Results from the present event-related potentials (ERP) study show that tones on Swedish word stems can rapidly pre-activate upcoming suffixes, even when the word stem does not carry any lexical meaning. Results also show that listeners are able to rapidly restore suffixes which are replaced with a cough. Accuracy in restoring suffixes correlated positively with the amplitude of an anterior negative ERP elicited by stem tones. This effect is proposed to reflect suffix pre-activation. Suffixes that were cued by an incorrect tone elicited a left-anterior negativity and a P600, suggesting that the correct processing of the suffix is crucially tied to the activation of the preceding validly associated tone.

  16. Gap junction proteins in the blood-brain barrier control nutrient-dependent reactivation of Drosophila neural stem cells.

    Science.gov (United States)

    Spéder, Pauline; Brand, Andrea H

    2014-08-11

    Neural stem cells in the adult brain exist primarily in a quiescent state but are reactivated in response to changing physiological conditions. How do stem cells sense and respond to metabolic changes? In the Drosophila CNS, quiescent neural stem cells are reactivated synchronously in response to a nutritional stimulus. Feeding triggers insulin production by blood-brain barrier glial cells, activating the insulin/insulin-like growth factor pathway in underlying neural stem cells and stimulating their growth and proliferation. Here we show that gap junctions in the blood-brain barrier glia mediate the influence of metabolic changes on stem cell behavior, enabling glia to respond to nutritional signals and reactivate quiescent stem cells. We propose that gap junctions in the blood-brain barrier are required to translate metabolic signals into synchronized calcium pulses and insulin secretion. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model.

    Directory of Open Access Journals (Sweden)

    Stine Skov Jensen

    Full Text Available Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking invasion and tumor stemness into account.Glioblastoma stem cell-like containing spheroid (GSS cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models.We observed a pronounced invasion into brain slice cultures both by confocal time-lapse microscopy and immunohistochemistry. This invasion closely resembled the invasion in vivo. The Ki-67 proliferation indexes in spheroids implanted into brain slices were lower than in free-floating spheroids. The expression of stem cell markers varied between free-floating spheroids, spheroids implanted into brain slices and tumors in vivo.The established invasion model kept in stem cell medium closely mimics tumor cell invasion into the brain in vivo preserving also to some extent the expression of stem cell markers. The model is feasible and robust and we suggest the model as an in vivo-like model with a great potential in glioma studies and drug discovery.

  18. Physics strategies for sparing neural stem cells during whole-brain radiation treatments

    Energy Technology Data Exchange (ETDEWEB)

    Kirby, Neil; Chuang, Cynthia; Pouliot, Jean; Hwang, Andrew; Barani, Igor J. [Department of Radiation Oncology, University of California San Francisco, San Francisco, California 94143-1708 (United States)

    2011-10-15

    Purpose: Currently, there are no successful long-term treatments or preventive strategies for radiation-induced cognitive impairments, and only a few possibilities have been suggested. One such approach involves reducing the dose to neural stem cell compartments (within and outside of the hippocampus) during whole-brain radiation treatments for brain metastases. This study investigates the fundamental physics issues associated with the sparing of neural stem cells during photon radiotherapy for brain metastases. Methods: Several factors influence the stem cell dose: intracranial scattering, collimator leakage, beam energy, and total number of beams. The relative importance of these factors is investigated through a set of radiation therapy plans, which are all variations of an initial 6 MV intensity-modulated radiation therapy (IMRT) plan designed to simultaneously deliver a whole-brain dose of 30 Gy and maximally reduce stem cell compartment dose. Additionally, an in-house leaf segmentation algorithm was developed that utilizes jaw motion to minimize the collimator leakage. Results: The plans are all normalized such that 50% of the PTV receives 30 Gy. For the initial 6 MV IMRT plan, 50% of the stem cells receive a dose greater than 6.3 Gy. Calculations indicate that 3.6 Gy of this dose originates from intracranial scattering. The jaw-tracking segmentation algorithm, used in conjunction with direct machine parameter optimization, reduces the 50% stem cell dose to 4.3 and 3.7 Gy for 6 and 10 MV treatment beams, respectively. Conclusions: Intracranial scattering alone is responsible for a large dose contribution to the stem cell compartment. It is, therefore, important to minimize other contributing factors, particularly the collimator leakage, to maximally reduce dose to these critical structures. The use of collimator jaw tracking in conjunction with modern collimators can minimize this leakage.

  19. Physics strategies for sparing neural stem cells during whole-brain radiation treatments.

    Science.gov (United States)

    Kirby, Neil; Chuang, Cynthia; Pouliot, Jean; Hwang, Andrew; Barani, Igor J

    2011-10-01

    Currently, there are no successful long-term treatments or preventive strategies for radiation-induced cognitive impairments, and only a few possibilities have been suggested. One such approach involves reducing the dose to neural stem cell compartments (within and outside of the hippocampus) during whole-brain radiation treatments for brain metastases. This study investigates the fundamental physics issues associated with the sparing of neural stem cells during photon radiotherapy for brain metastases. Several factors influence the stem cell dose: intracranial scattering, collimator leakage, beam energy, and total number of beams. The relative importance of these factors is investigated through a set of radiation therapy plans, which are all variations of an initial 6 MV intensity-modulated radiation therapy (IMRT) plan designed to simultaneously deliver a whole-brain dose of 30 Gy and maximally reduce stem cell compartment dose. Additionally, an in-house leaf segmentation algorithm was developed that utilizes jaw motion to minimize the collimator leakage. The plans are all normalized such that 50% of the PTV receives 30 Gy. For the initial 6 MV IMRT plan, 50% of the stem cells receive a dose greater than 6.3 Gy. Calculations indicate that 3.6 Gy of this dose originates from intracranial scattering. The jaw-tracking segmentation algorithm, used in conjunction with direct machine parameter optimization, reduces the 50% stem cell dose to 4.3 and 3.7 Gy for 6 and 10 MV treatment beams, respectively. Intracranial scattering alone is responsible for a large dose contribution to the stem cell compartment. It is, therefore, important to minimize other contributing factors, particularly the collimator leakage, to maximally reduce dose to these critical structures. The use of collimator jaw tracking in conjunction with modern collimators can minimize this leakage.

  20. Brain stem and cerebellar atrophy in chronic progressive neuro-Behçet's disease

    Energy Technology Data Exchange (ETDEWEB)

    Kanoto, Masafumi, E-mail: mkanoto@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Hosoya, Takaaki, E-mail: thosoya@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Toyoguchi, Yuuki, E-mail: c-elegans_0201g@mail.goo.ne.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Oda, Atsuko, E-mail: a.oda@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan)

    2013-01-15

    Purpose: Chronic progressive neuro-Behçet's disease (CPNBD) resembles multiple sclerosis (MS) on patient background and image findings, and therefore is difficult to diagnose. The purpose is to identify the characteristic magnetic resonance imaging (MRI) findings of CPNBD and to clarify the differences between the MRI findings of CPNBD and those of MS. Materials and methods: The subjects consist of a CPNBD group (n = 4; 1 male and 3 females; mean age, 51 y.o.), a MS group (n = 19; 3 males and 16 females; mean age, 45 y.o.) and a normal control group (n = 23; 10 males and 13 females; mean age, 45 y.o.). Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were retrospectively evaluated in each subjects. In middle sagittal brain MR images, the prepontine distance was measured as an indirect index of brain stem and cerebellar atrophy and the pontine and mesencephalic distance was measured as a direct index of brain stem atrophy. These indexes were statistically analyzed. Results: Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were seen in all CPNBD cases. Prepontine distance was significantly different between the CPNBD group and the MS group (p < 0.05), and between the CPNBD group and the normal control group (p < 0.001). Pontine and mesencephalic distance were significantly different between the CPNBD group and the MS group (p < 0.001, p < 0.01 respectively), and between the CPNBD group and the normal control group (p < 0.001). Conclusions: Chronic progressive neuro-Behçet's disease should be considered in patients with brain stem and cerebellar atrophy in addition to leukoencephalopathy similar to that seen in multiple sclerosis.

  1. Stem cells and treatment of brain and spinal cord injury

    Czech Academy of Sciences Publication Activity Database

    Syková, Eva

    2009-01-01

    Roč. 276, Suppl.1 (2009), s. 40-40 ISSN 1742-464X. [Congress of the Federation-of-European-Biochemical-Societies /34./. 04.07.2009-09.07.2009, Prague] Institutional research plan: CEZ:AV0Z50390703 Keywords : Stem cells Subject RIV: FH - Neurology

  2. Role of adrenal catecholamines in cerebrovasodilation evoked from brain stem

    International Nuclear Information System (INIS)

    Iadecola, C.; Lacombe, P.M.; Underwood, M.D.; Ishitsuka, T.; Reis, D.J.

    1987-01-01

    The authors studied whether adrenal medullary catecholamines (CAs) contribute to the metabolically linked increase in regional cerebral blood flow (rCBF) elicited by electrical stimulation of the dorsal medullary reticular formation (DMRF). Rats were anesthetized, paralyzed, and artificially ventilated. The DMRF was electrically stimulated with intermittent trains of pulses through microelectrodes stereotaxically implanted. Blood gases were controlled and, during stimulation, arterial pressure was maintained within the autoregulated range for rCBF. rCBF and blood-brain barrier (BBB) permeability were determined in homogenates of brain regions by using [ 14 C]iodoantipyrine and α-aminoisobutyric acid (AIB), respectively, as tracers. Plasma CAs (epinephrine and norepinephrine) were measured radioenzymatically. DMRF stimulation increased rCBF throughout the brain and elevated plasma CAs substantially. Acute bilateral adrenalectomy abolished the increase in plasma epinephrine, reduced the increases in flow in cerebral cortex, and abolished them elsewhere in brain. They conclude that the increases in rCBF elicited from the DMRF has two components, one dependent on, and the other independent of CAs. Since the BBB is impermeable to CAs and DMRF stimulation fails to open the BBB, the results suggest that DMRF stimulations allows, through a mechanism not yet determined, circulating CAs to act on brain and affect brain function

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

    Science.gov (United States)

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

    2016-08-01

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

  4. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

    Directory of Open Access Journals (Sweden)

    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II

  5. Combined high cervical spine and brain stem injuries: a complex and devastating injury in children.

    Science.gov (United States)

    Meyer, Philippe-Gabriel; Meyer, Fabien; Orliaguet, Gilles; Blanot, Stéphane; Renier, Dominique; Carli, Pierre

    2005-10-01

    In young children, high cervical spine injuries (HCSI) can result in inaugural reversible, cardiac arrest or apnea. We noted in children sustaining such injuries an unusual incidence of associated brain stem injuries and defined a special pattern of combined lesions. Children with HSCI surviving inaugural cardiac arrest/apnea were selected for a retrospective analysis of a trauma data bank. Epidemiologic, clinical, and radiological characteristics, and outcome were reviewed and compared with those of the rest of the trauma population with severe neurologic injuries (defined by a Glasgow Coma Scale brain stem injury in all patients. Children with combined lesions had more frequent severe facial and skull base fractures compared with the rest of the population. They also were younger and sustained more frequent severe distracting injury to the neck than the rest of the population. Mortality rate (69%) was 2.6-fold higher than that observed in children without HCSI. In survivors, none demonstrated spinal cord injury resulting in persistent peripheral neurologic deficits, but only one achieved a good recovery. Combined HCSI and brain stem injuries must be suspected in young children sustaining a severe distracting injury to the craniocervical junction. Early recognition of these catastrophic injuries by systematic spiral cervical spine and brain stem computed tomographic scan evaluation is mandatory.

  6. Conductive Hearing Loss during Infancy: Effects on Later Auditory Brain Stem Electrophysiology.

    Science.gov (United States)

    Gunnarson, Adele D.; Finitzo, Terese

    1991-01-01

    Long-term effects on auditory electrophysiology from early fluctuating hearing loss were studied in 27 children, aged 5 to 7 years, who had been evaluated originally in infancy. Findings suggested that early fluctuating hearing loss disrupts later auditory brain stem electrophysiology. (Author/DB)

  7. Cell Therapy in Parkinson's Disease: Host Brain Repair Machinery Gets a Boost From Stem Cell Grafts.

    Science.gov (United States)

    Napoli, Eleonora; Borlongan, Cesar V

    2017-06-01

    This commentary highlights the major findings and future research directions arising from the recent publication by Zuo and colleagues in Stem Cells 2017 (in press). Here, we discuss the novel observations that transplanted human neural stem cells can induce endogenous brain repair by specifically stimulating a host of regenerative processes in the neurogenic niche (i.e., subventricular zone [SVZ]) in an animal model of Parkinson's disease. That the identified therapeutic proteomes, neurotrophic factors, and anti-inflammatory cytokines in the SVZ may facilitate brain regeneration and behavioral recovery open a new venue of research for our understanding of the pathology and treatment of Parkinson's disease. Stem Cells 2017;35:1443-1445. © 2017 AlphaMed Press.

  8. Breath-holding spells may be associated with maturational delay in myelination of brain stem.

    Science.gov (United States)

    Vurucu, Sebahattin; Karaoglu, Abdulbaki; Paksu, Sukru M; Oz, Oguzhan; Yaman, Halil; Gulgun, Mustafa; Babacan, Oguzhan; Unay, Bulent; Akin, Ridvan

    2014-02-01

    To evaluate possible contribution of maturational delay of brain stem in the etiology of breath-holding spells in children using brain stem auditory evoked potentials. The study group included children who experienced breath-holding spells. The control group consisted of healthy age- and sex-matched children. Age, gender, type and frequency of spell, hemoglobin, and ferritin levels in study group and brain stem auditory evoked potentials results in both groups were recorded. Study group was statistically compared with control group for brain stem auditory evoked potentials. The mean age of study and control groups was 26.3 ± 14.6 and 28.9 ± 13.9 months, respectively. The III-V and I-V interpeak latencies were significantly prolonged in the study group compared with the control group (2.07 ± 0.2 milliseconds; 1.92 ± 0.13 milliseconds and 4.00 ± 0.27 milliseconds; 3.83 ± 0.19 milliseconds; P = 0.009 and P = 0.03, respectively). At the same time, III-V and I-V interpeak latencies of patients without anemia in the study group compared with those of control group were significantly prolonged (2.09 ± 0.24 milliseconds; 1.92 ± 0.13 milliseconds and 4.04 ± 0.28 milliseconds; 3.83 ± 0.19 milliseconds; P = 0.007 and P = 0.01, respectively). Our results consider that maturational delay in myelination of brain stem may have a role in the etiology of breath-holding spells in children.

  9. MRI measurements of the brain stem and cerebellum in high functioning autistic children

    International Nuclear Information System (INIS)

    Hashimoto, Toshiaki; Tayama, Masanobu; Miyazaki, Masahito; Murakawa, Kazuyoshi; Kuroda, Yasuhiro

    1994-01-01

    To determine involvements of the brain stem and/or cerebellum in autism, we compared midsagittal magnetic resonance images of the brains of high functioning autistic children with those of normal controls. We found that the midbrain and medulla oblongata were significantly smaller in these autistic children than in the control children. The pons area did not differ between the two groups, nor was there any difference in the cerebellar vermis area. The ratio of the brain stem and cerebellum to the posterior fossa area did not differ significantly between the high functioning autistic and the control children. The development of the cerebellar vermis area was delayed in autistic children as compared with that in the control children. Thus, it was suggested that significant anatomical changes in the midbrain and medulla oblongata existed in the autistic children. (author)

  10. MRI measurements of the brain stem and cerebellum in high functioning autistic children

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Toshiaki; Tayama, Masanobu; Miyazaki, Masahito; Murakawa, Kazuyoshi; Kuroda, Yasuhiro (Tokushima Univ. (Japan). School of Medicine)

    1994-01-01

    To determine involvements of the brain stem and/or cerebellum in autism, we compared midsagittal magnetic resonance images of the brains of high functioning autistic children with those of normal controls. We found that the midbrain and medulla oblongata were significantly smaller in these autistic children than in the control children. The pons area did not differ between the two groups, nor was there any difference in the cerebellar vermis area. The ratio of the brain stem and cerebellum to the posterior fossa area did not differ significantly between the high functioning autistic and the control children. The development of the cerebellar vermis area was delayed in autistic children as compared with that in the control children. Thus, it was suggested that significant anatomical changes in the midbrain and medulla oblongata existed in the autistic children. (author).

  11. Brain Tumor Tropism of Transplanted Human Neural Stem Cells Is Induced by Vascular Endothelial Growth Factor

    Directory of Open Access Journals (Sweden)

    Nils Ole Schmidt

    2005-06-01

    Full Text Available The transplantation of neural stem cells (NSCs offers a new potential therapeutic approach as a cell-based delivery system for gene therapy in brain tumors. This is based on the unique capacity of NSCs to migrate throughout the brain and to target invading tumor cells. However, the signals controlling the targeted migration of transplanted NSCs are poorly defined. We analyzed the in vitro and in vivo effects of angiogenic growth factors and protein extracts from surgical specimens of brain tumor patients on NSC migration. Here, we demonstrate that vascular endothelial growth factor (VEGF is able to induce a long-range attraction of transplanted human NSCs from distant sites in the adult brain. Our results indicate that tumorupregulated VEGF and angiogenic-activated microvasculature are relevant guidance signals for NSC tropism toward brain tumors.

  12. Basal ganglia germinoma in children with associated ipsilateral cerebral and brain stem hemiatrophy

    Energy Technology Data Exchange (ETDEWEB)

    Ozelame, Rodrigo V.; Shroff, Manohar; Wood, Bradley; Bouffet, Eric; Bartels, Ute; Drake, James M.; Hawkins, Cynthia; Blaser, Susan [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, Ontario (Canada)

    2006-04-15

    Germinoma is the most common and least-malignant intracranial germ cell tumor, usually found in the midline. Germinoma that arises in the basal ganglia, called ectopic germinoma, is a rare and well-documented entity representing 5% to 10% of all intracranial germinomas. The association of cerebral and/or brain stem atrophy with basal ganglia germinoma on CT and MRI is found in 33% of the cases. To review the literature and describe the CT and MRI findings of basal ganglia germinoma in children, known as ectopic germinoma, with associated ipsilateral cerebral and brain stem hemiatrophy. Three brain CT and six brain MRI studies performed in four children at two institutions were retrospectively reviewed. All patients were male (case 1, 14 years; case 2, 13 years; case 3, 9 years; case 4, 13 years), with pathologically proved germinoma arising in the basal ganglia, and associated ipsilateral cerebral and/or brain stem hemiatrophy on the first imaging study. It is important to note that three of these children presented with cognitive decline, psychosis and slowly progressive hemiparesis as their indication for imaging. Imaging results on initial scans were varied. In all patients, the initial study showed ipsilateral cerebral and/or brain stem hemiatrophy, representing Wallerian degeneration. All patients who underwent CT imaging presented with a hyperdense or calcified lesion in the basal ganglia on unenhanced scans. Only one of these lesions had a mass effect on the surrounding structures. In one of these patients a large, complex, heterogeneous mass appeared 15 months later. Initial MR showed focal or diffusely increased T2 signal in two cases and heterogeneous signal in the other two. (orig.)

  13. Basal ganglia germinoma in children with associated ipsilateral cerebral and brain stem hemiatrophy

    International Nuclear Information System (INIS)

    Ozelame, Rodrigo V.; Shroff, Manohar; Wood, Bradley; Bouffet, Eric; Bartels, Ute; Drake, James M.; Hawkins, Cynthia; Blaser, Susan

    2006-01-01

    Germinoma is the most common and least-malignant intracranial germ cell tumor, usually found in the midline. Germinoma that arises in the basal ganglia, called ectopic germinoma, is a rare and well-documented entity representing 5% to 10% of all intracranial germinomas. The association of cerebral and/or brain stem atrophy with basal ganglia germinoma on CT and MRI is found in 33% of the cases. To review the literature and describe the CT and MRI findings of basal ganglia germinoma in children, known as ectopic germinoma, with associated ipsilateral cerebral and brain stem hemiatrophy. Three brain CT and six brain MRI studies performed in four children at two institutions were retrospectively reviewed. All patients were male (case 1, 14 years; case 2, 13 years; case 3, 9 years; case 4, 13 years), with pathologically proved germinoma arising in the basal ganglia, and associated ipsilateral cerebral and/or brain stem hemiatrophy on the first imaging study. It is important to note that three of these children presented with cognitive decline, psychosis and slowly progressive hemiparesis as their indication for imaging. Imaging results on initial scans were varied. In all patients, the initial study showed ipsilateral cerebral and/or brain stem hemiatrophy, representing Wallerian degeneration. All patients who underwent CT imaging presented with a hyperdense or calcified lesion in the basal ganglia on unenhanced scans. Only one of these lesions had a mass effect on the surrounding structures. In one of these patients a large, complex, heterogeneous mass appeared 15 months later. Initial MR showed focal or diffusely increased T2 signal in two cases and heterogeneous signal in the other two. (orig.)

  14. Does State Merit-Based Aid Stem Brain Drain?

    Science.gov (United States)

    Zhang, Liang; Ness, Erik C.

    2010-01-01

    In this study, the authors use college enrollment and migration data to test the brain drain hypothesis. Their results suggest that state merit scholarship programs do indeed stanch the migration of "best and brightest" students to other states. In the aggregate and on average, the implementation of state merit aid programs increases the…

  15. Parametric Trace Slicing

    Science.gov (United States)

    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.

  16. Frequency of primary brain stem lesions after head injuries. A CT scan analysis from 186 cases of severe head trauma

    Energy Technology Data Exchange (ETDEWEB)

    George, B.; Thurel, C.; Pierron, D.; Ragueneau, J.L. (Hopital Lariboisiere, 75 - Paris (France))

    1981-01-01

    Analysis of level of brain stem dysfunction, evolution, and CT scan profile was made on 76 cases of head injuries with prolonged unconsciousness and without hemispheric focal lesion and midline shift on CT scan. Eleven cases were considered normal on CT scan. The CT scan aspect of primary brain stem lesion was identified in 31.5% of these series, and in 14.5% of all severe head traumas (186 cases), from which this series is taken. Primary and secondary CT scan profiles were observed whatever the clinical level of dysfunction and its evolution. Pontine lesions were mainly associated with haemorrhage in the brain stem and diffuse brain swelling; but minimal signs (cortical level) and benign outcome can also be related to axial haemorrhage. These results emphasize the frequency of primary brain stem lesions and the value of CT scan in head injuries.

  17. Aberrant brain-stem morphometry associated with sleep disturbance in drug-naïve subjects with Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Lee JH

    2016-08-01

    Full Text Available Ji Han Lee,1 Won Sang Jung,2 Woo Hee Choi,3 Hyun Kook Lim4 1Washington University in St Louis, St Louis, MO, USA; 2Department of Radiology, 3Department of Nuclear Medicine, 4Department of Psychiatry, Saint Vincent Hospital, College of Medicine, The Catholic University of Korea, Suwon, South Korea Objective: Among patients with Alzheimer’s disease (AD, sleep disturbances are common and serious noncognitive symptoms. Previous studies of AD patients have identified deformations in the brain stem, which may play an important role in the regulation of sleep. The aim of this study was to further investigate the relationship between sleep disturbances and alterations in brain stem morphology in AD.Materials and methods: In 44 patients with AD and 40 healthy elderly controls, sleep disturbances were measured using the Neuropsychiatry Inventory sleep subscale. We employed magnetic resonance imaging-based automated segmentation tools to examine the relationship between sleep disturbances and changes in brain stem morphology.Results: Analyses of the data from AD subjects revealed significant correlations between the Neuropsychiatry Inventory sleep-subscale scores and structural alterations in the left posterior lateral region of the brain stem, as well as normalized brain stem volumes. In addition, significant group differences in posterior brain stem morphology were observed between the AD group and the control group.Conclusion: This study is the first to analyze an association between sleep disturbances and brain stem morphology in AD. In line with previous findings, this study lends support to the possibility that brain stem structural abnormalities might be important neurobiological mechanisms underlying sleep disturbances associated with AD. Further longitudinal research is needed to confirm these findings. Keywords: Alzheimer’s disease, sleep, brain stem, MRI, shape analysis

  18. BLINK REFLEX IN MULTIPLE SCLEROSIS: AN ANCILLARY TEST FOR DETECTING BRAIN STEM LESIONS

    Directory of Open Access Journals (Sweden)

    M ETEMEDYFAR

    2001-09-01

    Full Text Available Introduction. Electrodiagnostic tests are one of the ancillary procedures that are used for diagnosis of multiple sclerosis (MS. This study investigates the frequency of abnormal blink reflex in patients with MS. Methods. In this cross sectional diagnostic study, 100 patients (26 male and 74 female with definite MS were selected based on clinical and MRI findings. they were referred to Al- zahra hospital (affiliated to iUMSHS during year 2000. Blink reflex (BR waves including R1, R2, R2 were recorded inpatients through the stimulation of supraorbital nerve. Results. The frequency of abnormal BR in MS patients with brain stem involvement was 77.9 percent and in those without brain stem involvement was 36.6 percent (P < 0.001. There was a significant relationship between the duration of MS and the abnormality in BR. Discussion. The frequency of abnormal blink reflex in MS is significantly associated with site of involvement in the brain. The majority of MS patients with brain stem involvement have abnormal BR. It is proposed that in patients with symptoms and signs of MS if there was no accessibility for MRI or if the results of MRI were equivocal, blink reflex test should be performed in addition to other ancillary tests.

  19. Neurogenesis in the brain stem of the rabbit: an autoradiographic study

    International Nuclear Information System (INIS)

    Oblinger, M.M.; Das, G.D.

    1981-01-01

    With the aid of ( 3 H)-thymidine autoradiography, neurogenesis was documented in the nuclear groups of the medulla oblongata, pons, and mid-brain, as well as in the brain stem reticular formation of the rabbit. Following single injections of ( 3 H)-thymidine, counts were taken of intensely labeled neurons within the nuclei of the functional columns related to the cranial nerves, nuclei of several other functional classifications, and nuclei that did not fit into a functional category. In the brain stem as a whole, neurogenesis was found to occur between days 10.0 and 18.5 of gestation: however, the majority of nuclei studied contained intensely neurons only between days 12.0 and 15.0. Only in the pontine nucleus and the tectum were intensely labeled cells observed as late as day 18.5. Directional gradients of histogenesis were often observed within, as well as between, various nuclei. Within the nuclear columns related to the cranial nerves, a clear mediolateral spread of neurogenesis was observable such that nuclei of the motor columns reached a peak in neurogenesis before those in the sensory columns. Likewise, a mediolateral proliferation pattern was seen in the brain stem reticular formation. Other individual directional gradients were discernible; however, in the brain stem as a whole, distinct overall gradients were not observable. In many individual nuclei, gradients in neuron size were observed such that large neurons preferentially arose prior to smaller neurons. Information pertaining to gradients in neurogenesis, as well as to relationships among functionally related nuclei, are discussed

  20. Identifying endogenous neural stem cells in the adult brain in vitro and in vivo: novel approaches.

    Science.gov (United States)

    Rueger, Maria Adele; Androutsellis-Theotokis, Andreas

    2013-01-01

    In the 1960s, Joseph Altman reported that the adult mammalian brain is capable of generating new neurons. Today it is understood that some of these neurons are derived from uncommitted cells in the subventricular zone lining the lateral ventricles, and the dentate gyrus of the hippocampus. The first area generates new neuroblasts which migrate to the olfactory bulb, whereas hippocampal neurogenesis seems to play roles in particular types of learning and memory. A part of these uncommitted (immature) cells is able to divide and their progeny can generate all three major cell types of the nervous system: neurons, astrocytes, and oligodendrocytes; these properties define such cells as neural stem cells. Although the roles of these cells are not yet clear, it is accepted that they affect functions including olfaction and learning/memory. Experiments with insults to the central nervous system also show that neural stem cells are quickly mobilized due to injury and in various disorders by proliferating, and migrating to injury sites. This suggests a role of endogenous neural stem cells in disease. New pools of stem cells are being discovered, suggesting an even more important role for these cells. To understand these cells and to coax them to contribute to tissue repair it would be very useful to be able to image them in the living organism. Here we discuss advances in imaging approaches as well as new concepts that emerge from stem cell biology with emphasis on the interface between imaging and stem cells.

  1. Use of stem sliced from in vitro plants of papaya (hybrid IBP 42-99 by obtained callus with embryogenic structure

    Directory of Open Access Journals (Sweden)

    Jorge Gallardo Colina

    2004-10-01

    Full Text Available Inside in vitro propagation via, the somatic embriogenesis offers possibilities of obtaining top volumes of production in a minor period of time and a lower cost, which are a method potentially more efficient than the regeneration via organogenesis. In papaya the somatic embryogenesis could have developed from zigotic embryos and axis hipocotilos, nevertheless in case of the hybrids these methods cannot be used and it becomes necessary to develop it from a somatic fabric, without link with the sexual reproduction. This work chased as main objective Evaluated the use of in vitro plants stem sections of the Carica papaya IBP 42-99 hybrid for the formation of callus with embryogenic structures. As plant material were use in vitro plants of the papaya hybrid IBP 42-99. For it there took sections of different parts of the stem from the meristem up to the base of the in vitro plants, was use the culture medium Nitsh and Nitsh supplemented with 1.5 mg.l-1 of 6-BAP and 1.5 mg.l-1 of AIA. It was achieved to obtain callus from the stem sections with the culture medium used, nevertheless, in the treatments where used cylinders inside 1.0 cm from the apex down, the best results were achieved. The use of in vitro plants stem sections as explant for the formation of callus in this vegetable species it opens new possibilities for his in vitro propagation, specially in case of resultant hybrids of genetic improvement programs. Key words: apexes, Carica papaya, callogenesis, somatic embryogenesis

  2. Long-term meditation is associated with increased gray matter density in the brain stem

    DEFF Research Database (Denmark)

    Vestergaard-Poulsen, Peter; Beek, Martijn van; Skewes, Joshua

    2009-01-01

    density in lower brain stem regions of experienced meditators compared with age-matched nonmeditators. Our findings show that long-term practitioners of meditation have structural differences in brainstem regions concerned with cardiorespiratory control. This could account for some......Extensive practice involving sustained attention can lead to changes in brain structure. Here, we report evidence of structural differences in the lower brainstem of participants engaged in the long-term practice of meditation. Using magnetic resonance imaging, we observed higher gray matter...

  3. From pluripotent stem cells to multifunctional cordocytic phenotypes in the human brain: an ultrastructural study.

    Science.gov (United States)

    Pais, Viorel; Danaila, Leon; Pais, Emil

    2012-08-01

    Light microscopy and transmission electron microscopy were used to investigate surgical cases in a variety of pathological conditions (thromboses, tumors, cerebrovascular malformations, Moyamoya disease) to identify and characterize different phenotypes belonging to a new interstitial cell recently described ultrastructurally in the brain and here named "cordocyte." Also, this work is an attempt to identify and characterize precursor/stem cells for cordocytic lineage in the perivascular areas, within perivascular nerves and pia mater (now considered a cordocytic-vascular tissue). Unexpected relationships and functions emerge from observations concerning these phenotypes, almost ubiquitous, but not yet fully studied in the brain.

  4. Early changes of auditory brain stem evoked response after radiotherapy for nasopharyngeal carcinoma - a prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Lau, S.K.; Wei, W.I.; Sham, J.S.T.; Choy, D.T.K.; Hui, Y. (Queen Mary Hospital, Hong Kong (Hong Kong))

    1992-10-01

    A prospective study of the effect of radiotherapy for nasopharyngeal carcinoma on hearing was carried out on 49 patients who had pure tone, impedance audiometry and auditory brain stem evoked response (ABR) recordings before, immediately, three, six and 12 months after radiotherapy. Fourteen patients complained of intermittent tinnitus after radiotherapy. We found that 11 initially normal ears of nine patients developed a middle ear effusion, three to six months after radiotherapy. There was mixed sensorineural and conductive hearing impairment after radiotherapy. Persistent impairment of ABR was detected immediately after completion of radiotherapy. The waves I-III and I-V interpeak latency intervals were significantly prolonged one year after radiotherapy. The study shows that radiotherapy for nasopharyngeal carcinoma impairs hearing by acting on the middle ear, the cochlea and the brain stem auditory pathway. (Author).

  5. Early changes of auditory brain stem evoked response after radiotherapy for nasopharyngeal carcinoma - a prospective study

    International Nuclear Information System (INIS)

    Lau, S.K.; Wei, W.I.; Sham, J.S.T.; Choy, D.T.K.; Hui, Y.

    1992-01-01

    A prospective study of the effect of radiotherapy for nasopharyngeal carcinoma on hearing was carried out on 49 patients who had pure tone, impedance audiometry and auditory brain stem evoked response (ABR) recordings before, immediately, three, six and 12 months after radiotherapy. Fourteen patients complained of intermittent tinnitus after radiotherapy. We found that 11 initially normal ears of nine patients developed a middle ear effusion, three to six months after radiotherapy. There was mixed sensorineural and conductive hearing impairment after radiotherapy. Persistent impairment of ABR was detected immediately after completion of radiotherapy. The waves I-III and I-V interpeak latency intervals were significantly prolonged one year after radiotherapy. The study shows that radiotherapy for nasopharyngeal carcinoma impairs hearing by acting on the middle ear, the cochlea and the brain stem auditory pathway. (Author)

  6. Endovascular treatment of brain-stem arteriovenous malformations: safety and efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Liu, H.M.; Wang, Y.H.; Chen, Y.F.; Huang, K.M. [Department of Medical Imaging, National Taiwan University Hospital, 7 Chung-Shan South Road, 10016, Taipei (Taiwan); Tu, Y.K. [Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, 7 Chung-Shan South Road, 1001, Taipei (Taiwan)

    2003-09-01

    Our purpose was to evaluate the safety and efficacy of endovascular treatment of brain-stem arteriovenous malformations (AVMs), reviewing six cases managed in the last 5 years. There were four patients who presented with bleeding, one with a progressive neurological deficit and one with obstructive hydrocephalus. Of the six patients, one showed 100%, one 90%, two 75% and two about 50% angiographic obliteration of the AVM after embolisation; the volume decreased about 75% on average. Five patients had a good outcome and one an acceptable outcome, with a mild postprocedure neurological deficit; none had further bleeding during midterm follow-up. Endovascular management of a brain-stem AVM may be an alternative to treatment such as radiosurgery and microsurgery in selected cases. It may be not as risky as previously thought. Embolisation can reduce the size of the AVM and possibly make it more treatable by radiosurgery and decrease the possibility of radiation injury. (orig.)

  7. Robotics, Stem Cells and Brain Computer Interfaces in Rehabilitation and Recovery from Stroke; Updates and Advances

    Science.gov (United States)

    Boninger, Michael L; Wechsler, Lawrence R.; Stein, Joel

    2014-01-01

    Objective To describe the current state and latest advances in robotics, stem cells, and brain computer interfaces in rehabilitation and recovery for stroke. Design The authors of this summary recently reviewed this work as part of a national presentation. The paper represents the information included in each area. Results Each area has seen great advances and challenges as products move to market and experiments are ongoing. Conclusion Robotics, stem cells, and brain computer interfaces all have tremendous potential to reduce disability and lead to better outcomes for patients with stroke. Continued research and investment will be needed as the field moves forward. With this investment, the potential for recovery of function is likely substantial PMID:25313662

  8. Murine cytomegalovirus infection of neural stem cells alters neurogenesis in the developing brain.

    Directory of Open Access Journals (Sweden)

    Manohar B Mutnal

    2011-01-01

    Full Text Available Congenital cytomegalovirus (CMV brain infection causes serious neuro-developmental sequelae including: mental retardation, cerebral palsy, and sensorineural hearing loss. But, the mechanisms of injury and pathogenesis to the fetal brain are not completely understood. The present study addresses potential pathogenic mechanisms by which this virus injures the CNS using a neonatal mouse model that mirrors congenital brain infection. This investigation focused on, analysis of cell types infected with mouse cytomegalovirus (MCMV and the pattern of injury to the developing brain.We used our MCMV infection model and a multi-color flow cytometry approach to quantify the effect of viral infection on the developing brain, identifying specific target cells and the consequent effect on neurogenesis. In this study, we show that neural stem cells (NSCs and neuronal precursor cells are the principal target cells for MCMV in the developing brain. In addition, viral infection was demonstrated to cause a loss of NSCs expressing CD133 and nestin. We also showed that infection of neonates leads to subsequent abnormal brain development as indicated by loss of CD24(hi cells that incorporated BrdU. This neonatal brain infection was also associated with altered expression of Oct4, a multipotency marker; as well as down regulation of the neurotrophins BDNF and NT3, which are essential to regulate the birth and differentiation of neurons during normal brain development. Finally, we report decreased expression of doublecortin, a marker to identify young neurons, following viral brain infection.MCMV brain infection of newborn mice causes significant loss of NSCs, decreased proliferation of neuronal precursor cells, and marked loss of young neurons.

  9. Calcium-dependent plateau potentials in rostral ambiguus neurons in the newborn mouse brain stem in vitro

    DEFF Research Database (Denmark)

    Rekling, J C; Feldman, J L

    1997-01-01

    Calcium-dependent plateau potentials in rostral ambiguus neurons in the newborn mouse brain stem in vitro. J. Neurophysiol. 78: 2483-2492, 1997. The nucleus ambiguus contains vagal and glossopharyngeal motoneurons and preganglionic neurons involved in respiration, swallowing, vocalization...

  10. Stem cells distribution, cellular proliferation and migration in the adult Austrolebias charrua brain.

    Science.gov (United States)

    Torres-Pérez, Maximiliano; Rosillo, Juan Carlos; Berrosteguieta, Ines; Olivera-Bravo, Silvia; Casanova, Gabriela; García-Verdugo, José Manuel; Fernández, Anabel Sonia

    2017-10-15

    Our previous studies demonstrated that Austrolebias charrua annual fish is an excellent model to study adult brain cell proliferation and neurogenesis due to the presence of active and fast neurogenesis in several regions during its short lifespan. Our main goal was to identify and localize the cells that compose the neurogenic areas throughout the Austrolebias brain. To do this, we used two thymidine halogenated analogs to detect cell proliferation at different survival times: 5-chloro-2'-deoxyuridine (CldU) at 1day and 5-iodo-2'-deoxyuridine (IdU) at 30days. Three types of proliferating cells were identified: I - transient amplifying or fast cycling cells that uptake CldU; II - stem cells or slow cycling cells, that were labeled with both CldU and IdU and did not migrate; and III - migrant cells that uptake IdU. Mapping and 3D-reconstruction of labeled nuclei showed that type I and type II cells were preferentially found close to ventricle walls. Type III cells appeared widespread and migrating in tangential and radial routes. Use of proliferation markers together with Vimentin or Nestin evidenced that type II cells are the putative stem cells that are located at the ventricular lumen. Double label cells with IdU+ and NeuN or HuC/D allowed us identify migrant neurons. Quantitation of labeled nuclei indicates that the proportion of putative stem cells is around 10% in all regions of the brain. This percentage of stem cells suggests the existence of a constant brain cell population in Austrolebias charrua that seems functional to the maintainance of adult neurogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Astrocytic Calcium Waves Signal Brain Injury to Neural Stem and Progenitor Cells

    OpenAIRE

    Anna Kraft; Eduardo Rosales Jubal; Ruth von Laer; Claudia Döring; Adriana Rocha; Moyo Grebbin; Martin Zenke; Helmut Kettenmann; Albrecht Stroh; Stefan Momma

    2017-01-01

    Summary Brain injuries, such as stroke or trauma, induce neural stem cells in the subventricular zone (SVZ) to a neurogenic response. Very little is known about the molecular cues that signal tissue damage, even over large distances, to the SVZ. Based on our analysis of gene expression patterns in the SVZ, 48?hr after an ischemic lesion caused by middle cerebral artery occlusion, we hypothesized that the presence of an injury might be transmitted by an astrocytic traveling calcium wave rather...

  12. Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

    Science.gov (United States)

    Anselmi, L; Toti, L; Bove, C; Travagli, R A

    2017-11-01

    Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1 ) assess the gastric effects of brain stem DA application, 2 ) identify the DA receptor subtype, and, 3 ) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility. NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway. Copyright © 2017 the American Physiological Society.

  13. Feasibility and resolution limits of opto-magnetic imaging of neural network activity in brain slices using color centers in diamond

    DEFF Research Database (Denmark)

    Karadas, Mürsel; Wojciechowski, Adam M; Huck, Alexander

    2018-01-01

    activity and has strongly contributed to our understanding of the mechanisms that govern neural information processing. However, this traditional approach only acquires signals from a few positions, which severely limits its ability to characterize the dynamics of the underlying neural networks. We suggest...... cell. Our results suggest that imaging of slice activity will be possible with the upcoming generation of NV magnetic field sensors, while single-shot imaging of planar cell activity remains challenging....

  14. VEGF-mediated angiogenesis stimulates neural stem cell proliferation and differentiation in the premature brain

    International Nuclear Information System (INIS)

    Sun, Jinqiao; Sha, Bin; Zhou, Wenhao; Yang, Yi

    2010-01-01

    This study investigated the effects of angiogenesis on the proliferation and differentiation of neural stem cells in the premature brain. We observed the changes in neurogenesis that followed the stimulation and inhibition of angiogenesis by altering vascular endothelial growth factor (VEGF) expression in a 3-day-old rat model. VEGF expression was overexpressed by adenovirus transfection and down-regulated by siRNA interference. Using immunofluorescence assays, Western blot analysis, and real-time PCR methods, we observed angiogenesis and the proliferation and differentiation of neural stem cells. Immunofluorescence assays showed that the number of vWF-positive areas peaked at day 7, and they were highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at every time point. The number of neural stem cells, neurons, astrocytes, and oligodendrocytes in the subventricular zone gradually increased over time in the VEGF up-regulation group. Among the three groups, the number of these cells was highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at the same time point. Western blot analysis and real-time PCR confirmed these results. These data suggest that angiogenesis may stimulate the proliferation of neural stem cells and differentiation into neurons, astrocytes, and oligodendrocytes in the premature brain.

  15. 1.5-T high-resolution MR imaging of oculomotor disturbances due to intrinsic brain-stem disease

    International Nuclear Information System (INIS)

    Patel, S.C.; Quint, D.J.; Sanders, W.P.; Mehta, B.A.; Boulos, R.S.; Froelich, J.W.

    1987-01-01

    Seventeen patients who presented with oculomotor disturbances (internuclear ophthalmoplegia, ophthalmoparesis) underwent MR imaging, which demonstrated brain-stem abnormalities in 11 cases. Lesions identified included occult vascular malformation with hemorrhage (two), hypertensive hemorrhage (one), infarction (two), neoplasm (two), and demyelinating disease (four). The authors' exhibit illustrates the exquisite anatomic detail displayed by high-field MR imaging in localizing various intrinsic brain-stem lesions in the region of the third, fourth, and sixth cranial nuclei and the medial longitudinal fasciculus

  16. Influence of Brain Stem on Axial and Hindlimb Spinal Locomotor Rhythm Generating Circuits of the Neonatal Mouse

    Directory of Open Access Journals (Sweden)

    Céline Jean-Xavier

    2018-02-01

    Full Text Available The trunk plays a pivotal role in limbed locomotion. Yet, little is known about how the brain stem controls trunk activity during walking. In this study, we assessed the spatiotemporal activity patterns of axial and hindlimb motoneurons (MNs during drug-induced fictive locomotor-like activity (LLA in an isolated brain stem-spinal cord preparation of the neonatal mouse. We also evaluated the extent to which these activity patterns are affected by removal of brain stem. Recordings were made in the segments T7, L2, and L5 using calcium imaging from individual axial MNs in the medial motor column (MMC and hindlimb MNs in lateral motor column (LMC. The MN activities were analyzed during both the rhythmic and the tonic components of LLA, the tonic component being used as a readout of generalized increase in excitability in spinal locomotor networks. The most salient effect of brain stem removal was an increase in locomotor rhythm frequency and a concomitant reduction in burst durations in both MMC and LMC MNs. The lack of effect on the tonic component of LLA indicated specificity of action during the rhythmic component. Cooling-induced silencing of the brain stem reproduced the increase in rhythm frequency and accompanying decrease in burst durations in L2 MMC and LMC, suggesting a dependency on brain stem neuron activity. The work supports the idea that the brain stem locomotor circuits are operational already at birth and further suggests an important role in modulating trunk activity. The brain stem may influence the axial and hindlimb spinal locomotor rhythm generating circuits by extending their range of operation. This may represent a critical step of locomotor development when learning how to walk in different conditions and environments is a major endeavor.

  17. MRI findings of radiation encephalopathy of brain stem after radiotherapy for nasopharyngeal cancer

    International Nuclear Information System (INIS)

    Liang Changhong; Li Guoye; Huang Biao; Huang Meiping; Zheng Junhui; Tan Shaoheng; Zeng Qiongxin

    1998-01-01

    Purpose: To study MRI findings and clinical manifestation of radiation encephalopathy (RE) of brain stem. Methods: MRI findings and clinical symptoms in 51 patients with RE of brain stem after radiotherapy for nasopharyngeal cancer were reviewed. Results: Clinical symptoms included number weakness or paralysis in the limbs and symptoms of damaged cranial nerves. All lesions appeared hypo- or iso-intense on spin echo(SE) T 1 -weighted images and inhomogeneous and mixed hyper- and iso-intense on Turbo spin echo (TSE) T 2 -weighted images. The lesions were located in mesencephalon, pons, medulla, basilar part of pons, basilar part of pons and medulla oblongata in 2,7,3,9 and 30 patients respectively. The enhancement patterns included irregular rings in 39 patients, spotty in 3 and no enhancement in 9 patients. Mass effect was minimal in all patients. On follow-up MRI, the lesions disappeared in 4 patients, did not change in size and shape in 8 patients and enlarged in 2 patients. Conclusion: MRI could demonstrate the characteristic findings of RE of brain stem. MRI findings sometimes are not consistent with the clinical symptoms

  18. Diffusion tensor imaging for nerve fiber bundles in the brain stem and spinocerebellar degeneration

    International Nuclear Information System (INIS)

    Honma, Tsuguo

    2009-01-01

    Diffusion tensor imaging (DTI) can create an image of the anisotropic nature of diffusion and express it quantitatively. Nerve fibers have a large anisotropic diffusion, and it is possible to obtain images of the nerve fiber bundle. The purpose of this study is to observe the nerve fiber bundles in the brain stem using DTI and study its potential for diagnosing the type of spinocerebellar degeneration (SCD). Fractional anisotropy (FA) maps and 3D-tractography images were obtained for 41 subjects with no brain stem abnormalities. We created an apparent diffusion coefficient (ADC) map and an FA map using DTI for 16 subjects in the disease group (11 with hereditary SCD and 5 with non-hereditary SCD) and 25 in the control group. The diffusion value of the pons and middle cerebellar peduncle was measured using ADC, and the degree of anisotropic diffusion was measured using FA. The pyramidal tract, superior cerebellar peduncle, and inferior cerebellar peduncle were clearly demonstrated for all cases. ADC for the middle cerebellar peduncle in spinocerebellar ataxin (SCA)1 was significantly higher, similar to that for the pons in dentatorubro-pallidoluysian atrophy (DRPLA). In MSA-C, ADC for both the pons and middle cerebellar peduncle was significantly elevated and FA was significantly decreased. There were no significant changes in SCA3. We could observe the nerve fiber bundles in the brain stem using DTI. FA and ADC measurements with DTI can aid in diagnosing the type of SCD. (author)

  19. Can mobile phone emissions affect auditory functions of cochlea or brain stem?

    Science.gov (United States)

    Sievert, Uwe; Eggert, Siegfried; Pau, Hans Wilhelm

    2005-03-01

    Despite their abundant spread, mobile phones are suspected by a major share of the population to cause adverse effects on health and welfare. The ear as the sense organ next to the individual device has rarely been investigated for short-term effects in this regard. In a previous article, we could not prove any impact on the vestibular part of the inner ear. Our present examinations are concerned with the question whether mobile phone emissions could affect cochlear or auditory brain stem functions. In 12 healthy test persons with normal hearing, auditory brain stem reflexes recordings were performed before, during, and after exposure to electromagnetic emissions by standardized mobile phone devices. Two modes of electromagnetic emissions fields were administered: pulsed and continuous. For acoustic stimulation simultaneous to field exposure, special "plug-in" earphones had to be used. No impact on auditory brain stem reflexes recordings in terms of absolute and interpeak latencies could be found. Together with the results of a previous article concerned with the vestibular part of the inner ear, we can state that there are no adverse effects of mobile phone emissions on the ear function, at least on a short-term range. Of course, any long-term effects cannot be excluded by our study.

  20. [Distribution of human enterovirus 71 in brainstem of infants with brain stem encephalitis and infection mechanism].

    Science.gov (United States)

    Hao, Bo; Gao, Di; Tang, Da-Wei; Wang, Xiao-Guang; Liu, Shui-Ping; Kong, Xiao-Ping; Liu, Chao; Huang, Jing-Lu; Bi, Qi-Ming; Quan, Li; Luo, Bin

    2012-04-01

    To explore the mechanism that how human enterovirus 71 (EV71) invades the brainstem and how intercellular adhesion molecules-1 (ICAM-1) participates by analyzing the expression and distribution of human EV71, and ICAM-1 in brainstem of infants with brain stem encephalitis. Twenty-two brainstem of infants with brain stem encephalitis were collected as the experimental group and 10 brainstems of fatal congenital heart disease were selected as the control group. The sections with perivascular cuffings were selected to observe EV71-VP1 expression by immunohistochemistry method and ICAM-1 expression was detected for the sections with EV71-VP1 positive expression. The staining image analysis and statistics analysis were performed. The experiment and control groups were compared. (1) EV71-VP1 positive cells in the experimental group were mainly astrocytes in brainstem with nigger-brown particles, and the control group was negative. (2) ICAM-1 positive cells showed nigger-brown. The expression in inflammatory cells (around blood vessels of brain stem and in glial nodules) and gliocytes increased. The results showed statistical difference comparing with control group (P diagnose fatal EV71 infection in infants. EV71 can invade the brainstem via hematogenous route. ICAM-1 may play an important role in the pathogenic process.

  1. Therapeutic Potential of Umbilical Cord Blood Stem Cells on Brain Damage of a Model of Stroke

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Nikravesh

    2011-11-01

    Full Text Available Introduction: Human cord blood-derived stem cells are a rich source of stem cells as well as precursors. With regard to the researchers have focused on the therapeutic potential of stem cell in the neurological disease such as stroke, the aim of this study was the investiga-tion of the therapeutic effects of human cord blood-derived stem cells in cerebral ischemia on rat. Methods: This study was carried out on young rats. Firstly, to create a laboratory model of ischemic stroke, carotid artery of animals was occluded for 30 minutes. Then, umbilical cord blood cells were isolated and labeled using bromodeoxyuridine and 2×105 cells were injected into the experimental group via the tail vein. Rats with hypoxic condi-tions were used as a sham group. A group of animals did not receive any injection or sur-geries were used as a control. Results: Obtained results were evaluated based on behavior-al responses and immunohistochemistry, with emphasis on areas of putamen and caudate nucleus in the control, sham and experimental groups. Our results indicated that behavioral recovery was observed in the experimental group compared to the either the sham or the control group. However, histological studies demonstrated a low percent of tissue injury in the experimental group in comparison with the sham group. Conclusion: Stem cell trans-plantation is beneficial for the brain tissue reparation after hypoxic ischemic cell death.

  2. A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Romeo Cecchelli

    Full Text Available The human blood brain barrier (BBB is a selective barrier formed by human brain endothelial cells (hBECs, which is important to ensure adequate neuronal function and protect the central nervous system (CNS from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.

  3. Macrophage enzyme and reduced inflammation drive brain correction of mucopolysaccharidosis IIIB by stem cell gene therapy.

    Science.gov (United States)

    Holley, Rebecca J; Ellison, Stuart M; Fil, Daniel; O'Leary, Claire; McDermott, John; Senthivel, Nishanthi; Langford-Smith, Alexander W W; Wilkinson, Fiona L; D'Souza, Zelpha; Parker, Helen; Liao, Aiyin; Rowlston, Samuel; Gleitz, Hélène F E; Kan, Shih-Hsin; Dickson, Patricia I; Bigger, Brian W

    2018-01-01

    Mucopolysaccharidosis IIIB is a paediatric lysosomal storage disease caused by deficiency of the enzyme α-N-acetylglucosaminidase (NAGLU), involved in the degradation of the glycosaminoglycan heparan sulphate. Absence of NAGLU leads to accumulation of partially degraded heparan sulphate within lysosomes and the extracellular matrix, giving rise to severe CNS degeneration with progressive cognitive impairment and behavioural problems. There are no therapies. Haematopoietic stem cell transplant shows great efficacy in the related disease mucopolysaccharidosis I, where donor-derived monocytes can transmigrate into the brain following bone marrow engraftment, secrete the missing enzyme and cross-correct neighbouring cells. However, little neurological correction is achieved in patients with mucopolysaccharidosis IIIB. We have therefore developed an ex vivo haematopoietic stem cell gene therapy approach in a mouse model of mucopolysaccharidosis IIIB, using a high-titre lentiviral vector and the myeloid-specific CD11b promoter, driving the expression of NAGLU (LV.NAGLU). To understand the mechanism of correction we also compared this with a poorly secreted version of NAGLU containing a C-terminal fusion to IGFII (LV.NAGLU-IGFII). Mucopolysaccharidosis IIIB haematopoietic stem cells were transduced with vector, transplanted into myeloablated mucopolysaccharidosis IIIB mice and compared at 8 months of age with mice receiving a wild-type transplant. As the disease is characterized by increased inflammation, we also tested the anti-inflammatory steroidal agent prednisolone alone, or in combination with LV.NAGLU, to understand the importance of inflammation on behaviour. NAGLU enzyme was substantially increased in the brain of LV.NAGLU and LV.NAGLU-IGFII-treated mice, with little expression in wild-type bone marrow transplanted mice. LV.NAGLU treatment led to behavioural correction, normalization of heparan sulphate and sulphation patterning, reduced inflammatory cytokine

  4. Classic and novel stem cell niches in brain homeostasis and repair.

    Science.gov (United States)

    Lin, Ruihe; Iacovitti, Lorraine

    2015-12-02

    Neural stem cells (NSCs) critical for the continued production of new neurons and glia are sequestered in distinct areas of the brain called stem cell niches. Until recently, only two forebrain sites, the subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampus, have been recognized adult stem cell niches (Alvarez-Buylla and Lim, 2004; Doetsch et al., 1999a, 1999b; Doetsch, 2003a, 2003b; Lie et al., 2004; Ming and Song, 2005). Nonetheless, the last decade has been witness to a growing literature suggesting that in fact the adult brain contains stem cell niches along the entire extent of the ventricular system. These niches are capable of widespread neurogenesis and gliogenesis, particularly after injury (Barnabé-Heider et al., 2010; Carlén et al., 2009; Decimo et al., 2012; Lin et al., 2015; Lindvall and Kokaia, 2008; Robins et al., 2013) or other inductive stimuli (Bennett et al., 2009; Cunningham et al., 2012; Decimo et al., 2011; Kokoeva et al., 2007, 2005; Lee et al., 2012a, 2012b; Migaud et al., 2010; Pencea et al., 2001b; Sanin et al., 2013; Suh et al., 2007; Sundholm-Peters et al., 2004; Xu et al., 2005; Zhang et al., 2007). This review focuses on the role of these novel and classic brain niches in maintaining adult neurogenesis and gliogenesis in response to normal physiological and injury-related pathological cues. This article is part of a Special Issue entitled SI: Neuroprotection. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Prostate stem cell antigen is expressed in normal and malignant human brain tissues.

    Science.gov (United States)

    Ono, Hiroe; Sakamoto, Hiromi; Yoshida, Teruhiko; Saeki, Norihisa

    2018-03-01

    Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein and exhibits an organ-dependent expression pattern in cancer. PSCA is upregulated in prostate cancer and downregulated in gastric cancer. PSCA is expressed in a variety of human organs. Although certain studies previously demonstrated its expression in the mammalian and avian brain, its expression in the human brain has not been thoroughly elucidated. Additionally, it was previously reported that PSCA is weakly expressed in the astrocytes of the normal human brain but aberrantly expressed in glioma, suggesting that PSCA is a promising target of glioma therapy and prostate cancer therapy. The current study identified PSCA expression in the neural and choroid plexus cells of the normal human brain by immunohistochemistry. In brain tumors, PSCA was expressed in medulloblastoma and glioma, and its expression was also observed in papilloma and papillary carcinoma of the choroid plexus, ependymoma and meningioma. The results suggest that PSCA may have a tumor-promoting function in brain tumors and is a potential target for their therapy. However, its expression in normal neuronal and choroid plexus cells implies that a PSCA-targeted therapy may lead to certain adverse phenomena.

  6. Using induced pluripotent stem cells derived neurons to model brain diseases

    Directory of Open Access Journals (Sweden)

    Cindy E McKinney

    2017-01-01

    Full Text Available The ability to use induced pluripotent stem cells (iPSC to model brain diseases is a powerful tool for unraveling mechanistic alterations in these disorders. Rodent models of brain diseases have spurred understanding of pathology but the concern arises that they may not recapitulate the full spectrum of neuron disruptions associated with human neuropathology. iPSC derived neurons, or other neural cell types, provide the ability to access pathology in cells derived directly from a patient's blood sample or skin biopsy where availability of brain tissue is limiting. Thus, utilization of iPSC to study brain diseases provides an unlimited resource for disease modelling but may also be used for drug screening for effective therapies and may potentially be used to regenerate aged or damaged cells in the future. Many brain diseases across the spectrum of neurodevelopment, neurodegenerative and neuropsychiatric are being approached by iPSC models. The goal of an iPSC based disease model is to identify a cellular phenotype that discriminates the disease-bearing cells from the control cells. In this mini-review, the importance of iPSC cell models validated for pluripotency, germline competency and function assessments is discussed. Selected examples for the variety of brain diseases that are being approached by iPSC technology to discover or establish the molecular basis of the neuropathology are discussed.

  7. Specificity of exogenous acetate and glutamate as astrocyte substrates examined in acute brain slices from female mice using methionine sulfoximine (MSO) to inhibit glutamine synthesis

    DEFF Research Database (Denmark)

    Andersen, Jens Velde; McNair, Laura Frendrup; Schousboe, Arne

    2017-01-01

    cortical slices from female NMRI mice were incubated in media containing [1,2-(13) C]acetate or [U-(13) C]glutamate, with or without methionine sulfoximine (MSO) to inhibit glutamine synthetase (GS). Tissue extracts were analyzed by gas chromatography-mass spectrometry. Blocking GS abolished the majority...... of glutamine (13) C-labeling from [1,2-(13) C]acetate as intended. However, (13) C-labeling of GABA was only 40-50% reduced by MSO, suggesting considerable neuronal uptake of acetate. Moreover, labeling of glutamate from [1,2-(13) C]acetate in the presence of MSO exceeded the level probable from exclusive...

  8. Nanoparticle-mediated transcriptional modification enhances neuronal differentiation of human neural stem cells following transplantation in rat brain.

    Science.gov (United States)

    Li, Xiaowei; Tzeng, Stephany Y; Liu, Xiaoyan; Tammia, Markus; Cheng, Yu-Hao; Rolfe, Andrew; Sun, Dong; Zhang, Ning; Green, Jordan J; Wen, Xuejun; Mao, Hai-Quan

    2016-04-01

    Strategies to enhance survival and direct the differentiation of stem cells in vivo following transplantation in tissue repair site are critical to realizing the potential of stem cell-based therapies. Here we demonstrated an effective approach to promote neuronal differentiation and maturation of human fetal tissue-derived neural stem cells (hNSCs) in a brain lesion site of a rat traumatic brain injury model using biodegradable nanoparticle-mediated transfection method to deliver key transcriptional factor neurogenin-2 to hNSCs when transplanted with a tailored hyaluronic acid (HA) hydrogel, generating larger number of more mature neurons engrafted to the host brain tissue than non-transfected cells. The nanoparticle-mediated transcription activation method together with an HA hydrogel delivery matrix provides a translatable approach for stem cell-based regenerative therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Initial Attempts of Development and Characterization of an In Vitro Blood Brain Barrier Model Derived from Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Goldeman, Charlotte; Saaby, Lasse; Hall, Vanessa Jane

    The human blood brain barrier has yet to be successfully replicated as an in vitro model. One of the more promising approaches has been to develop an in vitro model derived from human pluripotent stem cells. However, as promising as this model may be, a successful replication of the differentiation...... method on different kinds of pluripotent stem cell lines have yet to be accomplished. We try to approach the promising method as described by Stebbins et al. (2015) to differentiate human pluripotent stem cells into brain like endothelial cells (BECs). Five different human pluripotent stem cell lines...... were screened for the possibility to differentiate into BECs. Tüb1159, Tüb16423, Bioni010-C, WTSli024-A and WTSli002-A stem cell lines were initially seeded on Matrigel cultured with mTESR1 media to confluence, then seeded on Matrigel as a single cell suspension. After two-three days of culture we...

  10. Effect of (+)-amphetamine on the retention of 3H-catecholamines in slices of normal and reserpinized rat brain and heart

    International Nuclear Information System (INIS)

    Ross, S.B.; Renyi, A.L.

    1978-01-01

    The effect of reserpine on the inhibition by (+)-amphetamine and cocaine of the accumulation of 3 H-dopamine (DA) in striatal slices and 3 H-noradrenaline (NA) in slices of cerebral occipital cortex and heart atrium of rats and the release of the 3 H-amines from these tissues were examined. Reserpine (5 mg/kg intraperitoneally) was injected 18 hours before the experiments. It was found that reserpine markedly enhanced the in vitro potency of amphetamine in the striatum and heart but only slightly in the cortex. After administration in vivo (+)-amphetamine was about 10 times more potent in reducing the amine accumulation in the cortex as in the striatum. Reserpine enhanced the effect in both regions. The inhibitory potency of cocaine in vitro was unchanged by reserpine in the striatum but was reduced in the cortex and heart. Reserpine did not change the inhibitory potency of desipramine in the cortex and heart. The release of the 3 H-amines by (+)-amphetamine was enhanced by reserpine in the striatum and heart but the small release produced in the cortex was not increased. The release produced by cocaine was similarly enhanced by reserpine but cocaine was much less active than (+)-amphetamine. The results indicate that (+)-amphetamine and cocaine inhibit the amine accumulation by different mechanisms. (author)

  11. Glial cells as progenitors and stem cells: new roles in the healthy and diseased brain.

    Science.gov (United States)

    Dimou, Leda; Götz, Magdalena

    2014-07-01

    The diverse functions of glial cells prompt the question to which extent specific subtypes may be devoted to a specific function. We discuss this by reviewing one of the most recently discovered roles of glial cells, their function as neural stem cells (NSCs) and progenitor cells. First we give an overview of glial stem and progenitor cells during development; these are the radial glial cells that act as NSCs and other glial progenitors, highlighting the distinction between the lineage of cells in vivo and their potential when exposed to a different environment, e.g., in vitro. We then proceed to the adult stage and discuss the glial cells that continue to act as NSCs across vertebrates and others that are more lineage-restricted, such as the adult NG2-glia, the most frequent progenitor type in the adult mammalian brain, that remain within the oligodendrocyte lineage. Upon certain injury conditions, a distinct subset of quiescent astrocytes reactivates proliferation and a larger potential, clearly demonstrating the concept of heterogeneity with distinct subtypes of, e.g., astrocytes or NG2-glia performing rather different roles after brain injury. These new insights not only highlight the importance of glial cells for brain repair but also their great potential in various aspects of regeneration. Copyright © 2014 the American Physiological Society.

  12. Brain stem and cerebellum volumetric analysis of Machado Joseph disease patients

    Directory of Open Access Journals (Sweden)

    S T Camargos

    2011-01-01

    Full Text Available Machado-Joseph disease, or spinocerebellar ataxia type 3(MJD/SCA3, is the most frequent late onset spinocerebellar ataxia and results from a CAG repeat expansion in the ataxin-3 gene. Previous studies have found correlation between atrophy of cerebellum and brainstem with age and CAG repeats, although no such correlation has been found with disease duration and clinical manifestations. In this study we test the hypothesis that atrophy of cerebellum and brainstem in MJD/SCA3 is related to clinical severity, disease duration and CAG repeat length as well as to other variables such as age and ICARS (International Cooperative Ataxia Rating Scale. Whole brain high resolution MRI and volumetric measurement with cranial volume normalization were obtained from 15 MJD/SCA3 patients and 15 normal, age and sex-matchedcontrols. We applied ICARS and compared the score with volumes and CAG number, disease duration and age. We found significant correlation of both brain stem and cerebellar atrophy with CAG repeat length, age, disease duration and degree of disability. The Spearman rank correlation was stronger with volumetric reduction of the cerebellum than with brain stem. Our data allow us to conclude that volumetric analysis might reveal progressive degeneration after disease onset, which in turn is linked to both age and number of CAG repeat expansions in SCA 3.

  13. Stemming the impact of health professional brain drain from Africa: a systemic review of policy options

    Directory of Open Access Journals (Sweden)

    Edward Zimbudzi

    2013-06-01

    Full Text Available Africa has been losing professionally trained health workers who are the core of the health system of this continent for many years. Faced with an increased burden of disease and coupled by a massive exodus of the health workforce, the health systems of many African nations are risking complete paralysis. Several studies have suggested policy options to reduce brain drain from Africa. The purpose of this paper is to review possible policies, which can stem the impact of health professional brain drain from Africa. A systemic literature review was conducted. Cinahl, Science Direct and PubMed databases were searched with the following terms: health professional brain drain from Africa and policies for reducing impact of brain drain from Africa. References were also browsed for relevant articles. A total of 425 articles were available for the study but only 23 articles met the inclusion criteria. The review identified nine policy options, which were being implemented in Africa, but the most common was task shifting which had success in several African countries. This review has demonstrated that there is considerable consensus on task shifting as the most appropriate and sustainable policy option for reducing the impact of health professional brain drain from Africa.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-01-15

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

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

    Science.gov (United States)

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

    2013-01-01

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

  16. The extracellular matrix niche microenvironment of neural and cancer stem cells in the brain.

    Science.gov (United States)

    Reinhard, Jacqueline; Brösicke, Nicole; Theocharidis, Ursula; Faissner, Andreas

    2016-12-01

    Numerous studies demonstrated that neural stem cells and cancer stem cells (NSCs/CSCs) share several overlapping characteristics such as self-renewal, multipotency and a comparable molecular repertoire. In addition to the intrinsic cellular properties, NSCs/CSCs favor a similar environment to acquire and maintain their characteristics. In the present review, we highlight the shared properties of NSCs and CSCs in regard to their extracellular microenvironment called the NSC/CSC niche. Moreover, we point out that extracellular matrix (ECM) molecules and their complementary receptors influence the behavior of NSCs/CSCs as well as brain tumor progression. Here, we focus on the expression profile and functional importance of the ECM glycoprotein tenascin-C, the chondroitin sulfate proteoglycan DSD-1-PG/phosphacan but also on other important glycoprotein/proteoglycan constituents. Within this review, we specifically concentrate on glioblastoma multiforme (GBM). GBM is the most common malignant brain tumor in adults and is associated with poor prognosis despite intense and aggressive surgical and therapeutic treatment. Recent studies indicate that GBM onset is driven by a subpopulation of CSCs that display self-renewal and recapitulate tumor heterogeneity. Based on the CSC hypothesis the cancer arises just from a small subpopulation of self-sustaining cancer cells with the exclusive ability to self-renew and maintain the tumor. Besides the fundamental stem cell properties of self-renewal and multipotency, GBM stem cells share further molecular characteristics with NSCs, which we would like to review in this article. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Regional brain stem atrophy in idiopathic Parkinson's disease detected by anatomical MRI.

    Directory of Open Access Journals (Sweden)

    Thomas Jubault

    Full Text Available Idiopathic Parkinson's disease (PD is a neurodegenerative disorder characterized by the dysfunction of dopaminergic dependent cortico-basal ganglia loops and diagnosed on the basis of motor symptoms (tremors and/or rigidity and bradykinesia. Post-mortem studies tend to show that the destruction of dopaminergic neurons in the substantia nigra constitutes an intermediate step in a broader neurodegenerative process rather than a unique feature of Parkinson's disease, as a consistent pattern of progression would exist, originating from the medulla oblongata/pontine tegmentum. To date, neuroimaging techniques have been unable to characterize the pre-symptomatic stages of PD. However, if such a regular neurodegenerative pattern were to exist, consistent damages would be found in the brain stem, even at early stages of the disease. We recruited 23 PD patients at Hoenn and Yahr stages I to II of the disease and 18 healthy controls (HC matched for age. T1-weighted anatomical scans were acquired (MPRAGE, 1 mm3 resolution and analyzed using an optimized VBM protocol to detect white and grey matter volume reduction without spatial a priori. When the HC group was compared to the PD group, a single cluster exhibited statistical difference (p<0.05 corrected for false detection rate, 4287 mm3 in the brain stem, between the pons and the medulla oblongata. The present study provides in-vivo evidence that brain stem damage may be the first identifiable stage of PD neuropathology, and that the identification of this consistent damage along with other factors could help with earlier diagnosis in the future. This damage could also explain some non-motor symptoms in PD that often precede diagnosis, such as autonomic dysfunction and sleep disorders.

  18. Dosimetric analysis of trigeminal nerve, brain stem doses in CyberKnife radiosurgery of trigeminal neuralgia

    International Nuclear Information System (INIS)

    Sudahar, H.; Kurup, P.G.G.; Murali, V.; Velmurugan, J.

    2012-01-01

    CyberKnife radiosurgery treatment of Trigeminal neuralgia (TN) is performed as a non-invasive image guided procedure. The prescription dose for TN is very high. The brainstem is the adjacent critical organ at risk (OAR) which is prone to receive the very high target dose of TN. The present study is to analyze the dose distribution inside the tiny trigeminal nerve target and also to analyze the dose fall off in the brain stem. Seven TN cases treated between November 2010 and January 2012 were taken for this study retrospectively. The treatment plans were analyzed for target dose conformity, homogeneity and dose coverage. In the brainstem the volume doses D 1% and D 2% were taken for analyzing the higher doses in the brain stem. The dose fall off was analyzed in terms of D 5% and D 10% . The mean value of maximum dose within the trigeminal nerve target was 73.5±2.1 Gy (P=0.0007) and the minimum dose was 50.0±4.1Gy (P=0.1315). The mean conformity index was 2.19 and the probable reason could be the smallest CyberKnife collimator of 5mm used in the treatment plan. The mean D 1% , of the brainstem was 10.5±2.1Gy(P=0.5316) and the mean value of the maximum point dose within the brainstem was 35.6±3.8Gy. This shows the degree of dose fall off within the brainstem. Though the results of the present study are showing superior sparing of brain stem and reasonable of target coverage, it is necessary to execute the treatment plan with greater accuracy in CyberKnife as the immobilization is noninvasive and frameless. (author)

  19. The treatment of brain stem and thalamic gliomas with 78 Gy of hyperfractionated radiation therapy

    International Nuclear Information System (INIS)

    Prados, Michael D.; Wara, William M.; Edwards, Michael S. B.; Larson, David A.; Lamborn, Kathleen; Levin, Victor A.

    1995-01-01

    Purpose: To see whether increasing the dose of hyperfractionated radiation therapy from 72 to 78 Gy would increase survival time in patients with gliomas, particularly those with brain stem or thalamic tumors. Methods: Seventy-eight patients with a clinical and radiographic diagnosis of a brain stem or thalamic glioma were enrolled in a trial to receive 78 Gy (1.0 Gy twice a day). Six patients with disease in other sites were also treated. The initial response to therapy was determined by comparing pretreatment magnetic resonance images and neurological examinations with those obtained within 2 weeks of completing therapy; subsequent responses were determined from bimonthly follow-up images. Time-to-tumor progression was measured from the date radiation therapy began until the date of documented radiographic or clinical progression. Survival time was measured from the date radiation therapy began until the date of death. Cox proportional hazards analysis was used to estimate the effects of specific variables on survival. Results: Of 81 evaluable patients, 68 received ≥ 76 Gy, 10 received between 70 and 75 Gy, and 3 received between 60 and 68 Gy. The overall response or stabilization rate was 70.4%. Tumor size decreased in 30.8% of patients; 39.5% had stable disease, and 29.6% had immediate progression. The median survival time was 12.7 months (16.1 months for adults and 10.8 months for children). The median time to tumor progression was 9.0 months (11.4 months for adults and 8.4 months for children). A duration of symptoms ≤ 2 months and a diffuse lesion were each associated with shorter survival and progression times. Conclusions: For patients with brain stem or thalamic gliomas, increasing the dose of radiation therapy from 72 to 78 Gy did not significantly improve survival. Different treatment strategies are clearly needed

  20. Neural Stem Cell Transplantation Promotes Functional Recovery from Traumatic Brain Injury via Brain Derived Neurotrophic Factor-Mediated Neuroplasticity.

    Science.gov (United States)

    Xiong, Liu-Lin; Hu, Yue; Zhang, Piao; Zhang, Zhuo; Li, Li-Hong; Gao, Guo-Dong; Zhou, Xin-Fu; Wang, Ting-Hua

    2017-04-18

    Traumatic brain injury (TBI) induces cognitive impairments, motor and behavioral deficits. Previous evidences have suggested that neural stem cell (NSC) transplantation could facilitate functional recovery from brain insults, but their underlying mechanisms remains to be elucidated. Here, we established TBI model by an electromagnetic-controlled cortical impact device in the rats. Then, 5 μl NSCs (5.0 × 10 5 /μl), derived from green fluorescent protein (GFP) transgenic mouse, was transplanted into the traumatic brain regions of rats at 24 h after injury. After differentiation of the NSCs was determined using immunohistochemistry, neurological severity scores (NSS) and rotarod test were conducted to detect the neurological behavior. Western blot and RT-PCR as well as ELASA were used to evaluate the expression of synaptophysin and brain-derived neurotrophic factor (BDNF). In order to elucidate the role of BDNF on the neural recovery after NSC transplantation, BDNF knockdown in NSC was performed and transplanted into the rats with TBI, and potential mechanism for BDNF knockdown in the NSC was analyzed using microassay analysis. Meanwhile, BDNF antibody blockade was conducted to further confirm the effect of BDNF on neural activity. As a result, an increasing neurological function improvement was seen in NSC transplanted rats, which was associated with the upregulation of synaptophysin and BDNF expression. Moreover, transplantation of BDNF knockdown NSCs and BDNF antibody block reduced not only the level of synaptophysin but also exacerbated neurological function deficits. Microassay analysis showed that 14 genes such as Wnt and Gsk3-β were downregulated after BDNF knockdown. The present data therefore showed that BDNF-mediated neuroplasticity underlie the mechanism of NSC transplantation for the treatment of TBI in adult rats.

  1. Adult neurogenesis in the crayfish brain: the hematopoietic anterior proliferation center has direct access to the brain and stem cell niche.

    Science.gov (United States)

    Chaves da Silva, Paula Grazielle; Benton, Jeanne L; Sandeman, David C; Beltz, Barbara S

    2013-04-01

    Neuronal stem cells residing in a niche on the surface of the adult crayfish (Procambarus clarkii) brain are not self-renewing. However, the neuronal precursors in the niche are not depleted despite continued neurogenesis and the exit of precursor cells from the niche throughout the organism's life. The neurogenic niche is therefore not a closed system, and we have previously proposed that the stem cell pool is replenished from the hematopoietic system. Noonin et al. (2012) demonstrated that the hematopoietic system in the crayfish Pacifastacus leniusculus includes an anterior proliferation center (APC) lying near the brain; they suggest that multipotent stem cells are concentrated in this region, and that the APC may provide neuronal stem cells for adult neurogenesis. The present study extends this work by describing the location and cellular organization of hematopoietic tissues in P. clarkii. We find that the APC lies within the cor frontale, or auxiliary heart, which pumps hemolymph to the brain and eyes through the cerebral and ophthalmic arteries, respectively. Vascular extensions of the cerebral artery converge on the neurogenic niche. APC cells lie in layered sheets within the cor frontale and form rosette-like structures reminiscent of stem cells in other developing tissues. We confirm here that APC cells in P. clarkii have characteristics of multipotent stem cells, and that their location within the cor frontale allows direct access to regions in the central nervous system in which adult neurogenesis occurs.

  2. Music modulation of pain perception and pain-related activity in the brain, brain stem, and spinal cord: a functional magnetic resonance imaging study.

    Science.gov (United States)

    Dobek, Christine E; Beynon, Michaela E; Bosma, Rachael L; Stroman, Patrick W

    2014-10-01

    The oldest known method for relieving pain is music, and yet, to date, the underlying neural mechanisms have not been studied. Here, we investigate these neural mechanisms by applying a well-defined painful stimulus while participants listened to their favorite music or to no music. Neural responses in the brain, brain stem, and spinal cord were mapped with functional magnetic resonance imaging spanning the cortex, brain stem, and spinal cord. Subjective pain ratings were observed to be significantly lower when pain was administered with music than without music. The pain stimulus without music elicited neural activity in brain regions that are consistent with previous studies. Brain regions associated with pleasurable music listening included limbic, frontal, and auditory regions, when comparing music to non-music pain conditions. In addition, regions demonstrated activity indicative of descending pain modulation when contrasting the 2 conditions. These regions include the dorsolateral prefrontal cortex, periaqueductal gray matter, rostral ventromedial medulla, and dorsal gray matter of the spinal cord. This is the first imaging study to characterize the neural response of pain and how pain is mitigated by music, and it provides new insights into the neural mechanism of music-induced analgesia within the central nervous system. This article presents the first investigation of neural processes underlying music analgesia in human participants. Music modulates pain responses in the brain, brain stem, and spinal cord, and neural activity changes are consistent with engagement of the descending analgesia system. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

  3. Transcranial Magnetic Stimulation of Human Adult Stem Cells in the Mammalian Brain.

    Science.gov (United States)

    Kremer, Karlea L; Smith, Ashleigh E; Sandeman, Lauren; Inglis, Joshua M; Ridding, Michael C; Koblar, Simon A

    2016-01-01

    The burden of stroke on the community is growing, and therefore, so is the need for a therapy to overcome the disability following stroke. Cellular-based therapies are being actively investigated at a pre-clinical and clinical level. Studies have reported the beneficial effects of exogenous stem cell implantation, however, these benefits are also associated with limited survival of implanted stem cells. This exploratory study investigated the use of transcranial magnetic stimulation (TMS) as a complementary therapy to increase stem cell survival following implantation of human dental pulp stem cells (DPSC) in the rodent cortex. Sprague-Dawley rats were anesthetized and injected with 6 × 10(5) DPSC or control media via an intracranial injection, and then received real TMS (TMS0.2 Hz) or sham TMS (TMSsham) every 2nd day beginning on day 3 post DPSC injection for 2 weeks. Brain sections were analyzed for the survival, migration and differentiation characteristics of the implanted cells. In animals treated with DPSC and TMS0.2 Hz there were significantly less implanted DPSC and those that survived remained in the original cerebral hemisphere compared to animals that received TMSsham. The surviving implanted DPSC in TMS0.2 Hz were also found to express the apoptotic marker Caspase-3. We suggest that TMS at this intensity may cause an increase in glutamate levels, which promotes an unfavorable environment for stem cell implantation, proliferation and differentiation. It should be noted that only one paradigm of TMS was tested as this was conducted as a exploratory study, and further TMS paradigms should be investigated in the future.

  4. Reelin signaling in the migration of ventral brain stem and spinal cord neurons

    Directory of Open Access Journals (Sweden)

    Sandra eBlaess

    2016-03-01

    Full Text Available The extracellular matrix protein Reelin is an important orchestrator of neuronal migration during the development of the central nervous system. While its role and mechanism of action have been extensively studied and reviewed in the formation of dorsal laminar brain structures like the cerebral cortex, hippocampus, and cerebellum, its functions during the neuronal migration events that result in the nuclear organization of the ventral central nervous system are less well understood. In an attempt to delineate an underlying pattern of Reelin action in the formation of neuronal cell clusters, this review highlights the role of Reelin signaling in the migration of neuronal populations that originate in the ventral brain stem and the spinal cord.

  5. Paving the Way Toward Complex Blood-Brain Barrier Models Using Pluripotent Stem Cells.

    Science.gov (United States)

    Lauschke, Karin; Frederiksen, Lise; Hall, Vanessa Jane

    2017-06-15

    A tissue with great need to be modeled in vitro is the blood-brain barrier (BBB). The BBB is a tight barrier that covers all blood vessels in the brain and separates the brain microenvironment from the blood system. It consists of three cell types [neurovascular unit (NVU)] that contribute to the unique tightness and selective permeability of the BBB and has been shown to be disrupted in many diseases and brain disorders, such as vascular dementia, stroke, multiple sclerosis, and Alzheimer's disease. Given the progress that pluripotent stem cells (PSCs) have made in the past two decades, it is now possible to produce many cell types from the BBB and even partially recapitulate this complex tissue in vitro. In this review, we summarize the most recent developments in PSC differentiation and modeling of the BBB. We also suggest how patient-specific human-induced PSCs could be used to model BBB dysfunction in the future. Lastly, we provide perspectives on how to improve production of the BBB in vitro, for example by improving pericyte differentiation protocols and by better modeling the NVU in the dish.

  6. Injection of SDF-1 loaded nanoparticles following traumatic brain injury stimulates neural stem cell recruitment.

    Science.gov (United States)

    Zamproni, Laura N; Mundim, Mayara V; Porcionatto, Marimelia A; des Rieux, Anne

    2017-03-15

    Recruiting neural stem cell (NSC) at the lesion site is essential for central nervous system repair. This process could be triggered by the local delivery of the chemokine SDF-1. We compared two PLGA formulations for local brain SDF-1 delivery: SDF-1 loaded microspheres (MS) and SDF-1 loaded nanoparticles (NP). Both formulations were able to encapsulate more than 80% of SDF-1 but presented different release profiles, with 100% of SDF-1 released after 6days for the MS and with 25% of SDF-1 released after 2 weeks for NP. SDF-1 bioactivity was demonstrated by a chemotactic assay. When injected in mouse brain after traumatic brain injury, only SDF-1 nanoparticles induced NSC migration to the damage area. More neuroblasts (DCX+ cells) could be visualized around the lesions treated with NP SDF-1 compared to the other conditions. Rostral migratory stream destabilization with massive migration of DCX+ cell toward the perilesional area was observed 2 weeks after NP SDF-1 injection. Local injection of SDF-1-loaded nanoparticles induces recruitment of NSC and could be promising for brain injury lesion. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Sex differences in morphology of the brain stem and cerebellum with normal ageing

    International Nuclear Information System (INIS)

    Oguro, H.; Okada, K.; Yamaguchi, S.; Kobayashi, S.

    1998-01-01

    The cerebral hemispheres become atrophic with age. The sex of the individual may affect this process. There are few studies of the effects of age and sex on the brain stem and cerebellum. We used MRI morphometry to study changes in these structures in 152 normal subjects over 40 years of age. In the linear measurements, men showed significant age-associated atrophy in the tegmentum and pretectum of the midbrain and the base of the pons. In women, only the pretectum of the midbrain showed significant ageing effects after the age of 50 years, and thereafter remained rather constant. Only men had significant age-associated reduction in area of the crebellar vermis area after the age of 70 years. Both men and women showed supratentorial brain atrophy that progressed by decades. There were significant correlations between supratentorial brain atrophy and the diameter of the ventral midbrain, pretectum, and base of the pons in men, and between brain atrophy and the diameter of the fourth ventricle in women. (orig.)

  8. Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications.

    Science.gov (United States)

    Abou-Antoun, Tamara J; Hale, James S; Lathia, Justin D; Dombrowski, Stephen M

    2017-04-01

    Brain tumors represent some of the most malignant cancers in both children and adults. Current treatment options target the majority of tumor cells but do not adequately target self-renewing cancer stem cells (CSCs). CSCs have been reported to resist the most aggressive radiation and chemotherapies, and give rise to recurrent, treatment-resistant secondary malignancies. With advancing technologies, we now have a better understanding of the genetic, epigenetic and molecular signatures and microenvironmental influences which are useful in distinguishing between distinctly different tumor subtypes. As a result, efforts are now underway to identify and target CSCs within various tumor subtypes based on this foundation. This review discusses progress in CSC biology as it relates to targeted therapies which may be uniquely different between pediatric and adult brain tumors. Studies to date suggest that pediatric brain tumors may benefit more from genetic and epigenetic targeted therapies, while combination treatments aimed specifically at multiple molecular pathways may be more effective in treating adult brain tumors which seem to have a greater propensity towards microenvironmental interactions. Ultimately, CSC targeting approaches in combination with current clinical therapies have the potential to be more effective owing to their ability to compromise CSCs maintenance and the mechanisms which underlie their highly aggressive and deadly nature.

  9. Cerebral transplantation of encapsulated mesenchymal stem cells improves cellular pathology after experimental traumatic brain injury

    DEFF Research Database (Denmark)

    Heile, Anna M B; Wallrapp, Christine; Klinge, Petra M

    2009-01-01

    PURPOSE: "Naked" human mesenchymal stem cells (MSC) are neuro-protective in experimental brain injury (TBI). In a controlled cortical impact (CCI) rat model, we investigated whether encapsulated MSC (eMSC) act similarly, and whether efficacy is augmented using cells transfected to produce the neuro......-protective substance glucagon-like peptide-1 (GLP-1). METHODS: Thirty two Sprague-Dawley rats were randomized to five groups: controls (no CCI), CCI-only, CCI+eMSC, CCI+GLP-1 eMSC, and CCI+empty capsules. On day 14, cisternal cerebro-spinal fluid (CSF) was sampled for measurement of GLP-1 concentration. Brains were....../capsule/h. Cells were still secreting GLP-1 at a rate of 3.68+/-0.49, 2.85+/-0.45 and 3.53+/-0.55 after 2, 7 and 14 days, respectively. In both of the stem cell treated CCI groups, hippocampal cell loss was reduced, along with an attenuation of cortical neuronal and glial abnormalities, as measured by MAP-2...

  10. Morphological and histochemical changes in the brain stem in case of experimental hemispheric intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    S. I. Tertishniy

    2015-10-01

    Full Text Available Aim. Investigation of the extent of morphological changes and activity of biogenic amines (according to the intensity of luminescence in the neurons of the brain stem in intracerebral hemorrhage (ICH. Methods and results. ICH was designed on 29 white rats of Vistar line by the administration of autologous blood in the cerebral hemisphere. It was revealed that increased luminescence intensity by 18.4±5.5% was registered in monoaminergic neurons in 1–6 hours after experimental ICH. After 12 hours – 1 day development of dislocation syndrome leads to mosaic focal ischemic neuronal injuries with maximum reduction in the level of catecholamines by 29.5±5.0% compared with control cases. Three–6 days after ICH on a background of selective neuronal necrosis in substantial number of neurons in the nuclei of the brainstem the level of catecholamines is significantly reduced. Conclusion. Disclosed observations reflect significant functional pathology of neurons responsible for the regulation of cardiorespiratory function and may underlie disturbances of integrative activity in the brain stem in general.

  11. The value of whole-brain CT perfusion imaging and CT angiography using a 320-slice CT scanner in the diagnosis of MCI and AD patients.

    Science.gov (United States)

    Zhang, Bo; Gu, Guo-Jun; Jiang, Hong; Guo, Yi; Shen, Xing; Li, Bo; Zhang, Wei

    2017-11-01

    To validate the value of whole-brain computed tomography perfusion (CTP) and CT angiography (CTA) in the diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Whole-brain CTP and four-dimensional CT angiography (4D-CTA) images were acquired in 30 MCI, 35 mild AD patients, 35 moderate AD patients, 30 severe AD patients and 50 normal controls (NC). Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and correlation between CTP and 4D-CTA were analysed. Elevated CBF in the left frontal and temporal cortex was found in MCI compared with the NC group. However, TTP was increased in the left hippocampus in mild AD patients compared with NC. In moderate and severe AD patients, hypoperfusion was found in multiple brain areas compared with NC. Finally, we found that the extent of arterial stenosis was negatively correlated with CBF in partial cerebral cortex and hippocampus, and positively correlated with TTP in these areas of AD and MCI patients. Our findings suggest that whole-brain CTP and 4D-CTA could serve as a diagnostic modality in distinguishing MCI and AD, and predicting conversion from MCI based on TTP of left hippocampus. • Whole-brain perfusion using the full 160-mm width of 320 detector rows • Provide clinical experience of 320-row CT in cerebrovascular disorders of Alzheimer's disease • Initial combined 4D CTA-CTP data analysed perfusion and correlated with CT angiography • Whole-brain CTP and 4D-CTA have high value for monitoring MCI to AD progression • TTP in the left hippocampus may predict the transition from MCI to AD.

  12. Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential.

    Science.gov (United States)

    Lojewski, Xenia; Srimasorn, Sumitra; Rauh, Juliane; Francke, Silvan; Wobus, Manja; Taylor, Verdon; Araúzo-Bravo, Marcos J; Hallmeyer-Elgner, Susanne; Kirsch, Matthias; Schwarz, Sigrid; Schwarz, Johannes; Storch, Alexander; Hermann, Andreas

    2015-10-01

    Brain perivascular cells have recently been identified as a novel mesodermal cell type in the human brain. These cells reside in the perivascular niche and were shown to have mesodermal and, to a lesser extent, tissue-specific differentiation potential. Mesenchymal stem cells (MSCs) are widely proposed for use in cell therapy in many neurological disorders; therefore, it is of importance to better understand the "intrinsic" MSC population of the human brain. We systematically characterized adult human brain-derived pericytes during in vitro expansion and differentiation and compared these cells with fetal and adult human brain-derived neural stem cells (NSCs) and adult human bone marrow-derived MSCs. We found that adult human brain pericytes, which can be isolated from the hippocampus and from subcortical white matter, are-in contrast to adult human NSCs-easily expandable in monolayer cultures and show many similarities to human bone marrow-derived MSCs both regarding both surface marker expression and after whole transcriptome profile. Human brain pericytes showed a negligible propensity for neuroectodermal differentiation under various differentiation conditions but efficiently generated mesodermal progeny. Consequently, human brain pericytes resemble bone marrow-derived MSCs and might be very interesting for possible autologous and endogenous stem cell-based treatment strategies and cell therapeutic approaches for treating neurological diseases. Perivascular mesenchymal stem cells (MSCs) recently gained significant interest because of their appearance in many tissues including the human brain. MSCs were often reported as being beneficial after transplantation in the central nervous system in different neurological diseases; therefore, adult brain perivascular cells derived from human neural tissue were systematically characterized concerning neural stem cell and MSC marker expression, transcriptomics, and mesodermal and inherent neuroectodermal differentiation

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

    DEFF Research Database (Denmark)

    Hauberg, Katrine; Kohlmeier, Kristi Anne

    2015-01-01

    Ghrelin, a gut and brain peptide, has recently been shown to be involved in motivated behavior and regulation of the sleep and wakefulness cycle. The laterodorsal tegmental nucleus (LDT) is involved in appetitive behavior and control of the arousal state of an organism, and accordingly, behaviora...

  14. The value of whole-brain CT perfusion imaging and CT angiography using a 320-slice CT scanner in the diagnosis of MCI and AD patients

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bo; Gu, Guo-jun; Jiang, Hong; Guo, Yi [Medical School of Tongji University, Department of Medical Imaging, Tongji Hospital, Shanghai (China); Shen, Xing [Traditional Chinese Hospital, Department of Radiology, Kun Shan, Jiangsu Province (China); Li, Bo; Zhang, Wei [Medical School of Jiaotong University, Department of Medical Imaging, Renji Hospital, Shanghai (China)

    2017-11-15

    To validate the value of whole-brain computed tomography perfusion (CTP) and CT angiography (CTA) in the diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Whole-brain CTP and four-dimensional CT angiography (4D-CTA) images were acquired in 30 MCI, 35 mild AD patients, 35 moderate AD patients, 30 severe AD patients and 50 normal controls (NC). Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and correlation between CTP and 4D-CTA were analysed. Elevated CBF in the left frontal and temporal cortex was found in MCI compared with the NC group. However, TTP was increased in the left hippocampus in mild AD patients compared with NC. In moderate and severe AD patients, hypoperfusion was found in multiple brain areas compared with NC. Finally, we found that the extent of arterial stenosis was negatively correlated with CBF in partial cerebral cortex and hippocampus, and positively correlated with TTP in these areas of AD and MCI patients. Our findings suggest that whole-brain CTP and 4D-CTA could serve as a diagnostic modality in distinguishing MCI and AD, and predicting conversion from MCI based on TTP of left hippocampus. (orig.)

  15. Rapid whole-brain resting-state fMRI at 3 T: Efficiency-optimized three-dimensional EPI versus repetition time-matched simultaneous-multi-slice EPI.

    Science.gov (United States)

    Stirnberg, Rüdiger; Huijbers, Willem; Brenner, Daniel; Poser, Benedikt A; Breteler, Monique; Stöcker, Tony

    2017-12-01

    State-of-the-art simultaneous-multi-slice (SMS-)EPI and 3D-EPI share several properties that benefit functional MRI acquisition. Both sequences employ equivalent parallel imaging undersampling with controlled aliasing to achieve high temporal sampling rates. As a volumetric imaging sequence, 3D-EPI offers additional means of acceleration complementary to 2D-CAIPIRINHA sampling, such as fast water excitation and elliptical sampling. We performed an application-oriented comparison between a tailored, six-fold CAIPIRINHA-accelerated 3D-EPI protocol at 530 ms temporal and 2.4 mm isotropic spatial resolution and an SMS-EPI protocol with identical spatial and temporal resolution for whole-brain resting-state fMRI at 3 T. The latter required eight-fold slice acceleration to compensate for the lack of elliptical sampling and fast water excitation. Both sequences used vendor-supplied on-line image reconstruction. We acquired test/retest resting-state fMRI scans in ten volunteers, with simultaneous acquisition of cardiac and respiration data, subsequently used for optional physiological noise removal (nuisance regression). We found that the 3D-EPI protocol has significantly increased temporal signal-to-noise ratio throughout the brain as compared to the SMS-EPI protocol, especially when employing motion and nuisance regression. Both sequence types reliably identified known functional networks with stronger functional connectivity values for the 3D-EPI protocol. We conclude that the more time-efficient 3D-EPI primarily benefits from reduced parallel imaging noise due to a higher, actual k-space sampling density compared to SMS-EPI. The resultant BOLD sensitivity increase makes 3D-EPI a valuable alternative to SMS-EPI for whole-brain fMRI at 3 T, with voxel sizes well below 3 mm isotropic and sampling rates high enough to separate dominant cardiac signals from BOLD signals in the frequency domain. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Análise comparativa de cortes de encéfalos humanos com coloração por três técnicas diferentes Comparative analysis of human brain slices with three different staining techniques

    Directory of Open Access Journals (Sweden)

    Murilo Sousa de Meneses

    2004-06-01

    Full Text Available O estudo anatômico do encéfalo em cortes é facilitado empregando-se métodos de coloração para substância cinzenta. Os métodos mais freqüentemente empregados são os de Barnard, Robert e Brown, Mulligan e Green. O objetivo deste estudo foi determinar qual dessas técnicas apresenta melhores resultados com relação à diferenciação entre substâncias branca e cinzenta. Trinta cortes coronais de hemisfério cerebral humano foram submetidos às três técnicas, comparados entre si e analisados de acordo com três parâmetros estabelecidos: grau de diferenciação entre as substâncias branca e cinzenta; presença de linha única e contínua separando a substância branca do córtex cerebral; grau de impregnação da coloração em outros locais de substância branca. Atribuíram-se pontuações de 0 a 3 conforme a presença destes parâmetros, cada corte recebendo pontuação total que variava de 0 a 9. Após análise estatística, a técnica de Barnard, Robert e Brown apresentou média 8,33; a de Green 7,93 e a de Mulligan, 7,5, com diferença estatisticamente significativa.Studing neuroanatomy at brain slices with gray matter staining techniques has several advantages. More often, the models described by Barnard, Robert and Brown, Mulligan, and Green are used. The aim of this study was to identify which of them achieves the best results on differentiation between the gray and the white matter. Thirty coronal slices of human brains underwent staining by the three techniques, and thus compared and analysed according this three parameters: degree of differentiation between white and gray matter, presence of a single and uninterrupted line dividing the white matter from the brain cortex; and degree of impregnation of the color staining in the white matter; scores from 0 to 3 have been given for the three parameters, with total score from 0 to 9. After statistic analysis, the Barnard, Robert and Brown model showed the best results, followed

  17. Fractones: extracellular matrix niche controlling stem cell fate and growth factor activity in the brain in health and disease.

    Science.gov (United States)

    Mercier, Frederic

    2016-12-01

    The stem cell niche refers to a specific microenvironment where stem cells proliferate and differentiate to produce new specialized cells throughout an organism's adulthood. Growth factors are crucial signaling molecules that diffuse through the extracellular space, reach the stem cell niche, and ultimately promote stem cell proliferation and differentiation. However, it is not well known how multiple growth factors, often with antagonistic activities, work together in the stem cell niche to select target stem cell populations and determine stem cell fate. There is accumulating evidence suggesting that extracellular matrix (ECM) molecules play an important role in promoting growth factor access and activity in the stem cell niche. In the adult brain neurogenic zone, where neural stem cells (NSCs) reside, there exist specialized ECM structures, which we have named fractones. The processes of NSC allow them to come into contact with fractones and interact with its individual components, which include heparan sulfate proteoglycans (HSPGs) and laminins. We have demonstrated that fractone-associated HSPGs bind growth factors and regulate NSC proliferation in the neurogenic zone. Moreover, emerging results show that fractones are structurally altered in animal models with autism and adult hydrocephalus, as demonstrated by changes in fractone size, quantity, or HSPG content. Interestingly, ECM structures similar to fractones have been found throughout β-amyloid plaques in the brain of patients with Alzheimer's disease. Pathological fractones may cause imbalances in growth factor activity and impair neurogenesis, leading to inflammation and disorder. Generally speaking, these stem cell niche structures play a potentially vital role in controlling growth factor activity during both health and disease.

  18. Physical weight loading induces expression of tryptophan hydroxylase 2 in the brain stem.

    Directory of Open Access Journals (Sweden)

    Joon W Shim

    Full Text Available Sustaining brain serotonin is essential in mental health. Physical activities can attenuate mental problems by enhancing serotonin signaling. However, such activity is not always possible in disabled individuals or patients with dementia. Knee loading, a form of physical activity, has been found to mimic effects of voluntary exercise. Focusing on serotonergic signaling, we addressed a question: Does local mechanical loading to the skeleton elevate expression of tryptophan hydroxylase 2 (tph2 that is a rate-limiting enzyme for brain serotonin? A 5 min knee loading was applied to mice using 1 N force at 5 Hz for 1,500 cycles. A 5-min treadmill running was used as an exercise (positive control, and a 90-min tail suspension was used as a stress (negative control. Expression of tph2 was determined 30 min - 2 h in three brain regions --frontal cortex (FC, ventromedial hypothalamus (VMH, and brain stem (BS. We demonstrated for the first time that knee loading and treadmill exercise upregulated the mRNA level of tph2 in the BS, while tail suspension downregulated it. The protein level of tph2 in the BS was also upregulated by knee loading and downregulated by tail suspension. Furthermore, the downregulation of tph2 mRNA by tail suspension can be partially suppressed by pre-application of knee loading. The expression of tph2 in the FC and VMH was not significantly altered with knee loading. In this study we provided evidence that peripheral mechanical loading can activate central tph2 expression, suggesting that physical cues may mediate tph2-cathalyzed serotonergic signaling in the brain.

  19. Guidelines for the pathoanatomical examination of the lower brain stem in ingestive and swallowing disorders and its application to a dysphagic spinocerebellar ataxia type 3 patient

    NARCIS (Netherlands)

    Rub, U; Brunt, ER; Del Turco, D; de Vos, RAI; Gierga, K; Paulson, H; Braak, H

    Despite the fact that considerable progress has been made in the last 20 years regarding the three-phase process of ingestion and the lower brain stem nuclei involved in it, no comprehensive descriptions of the ingestion-related lower brain stem nuclei are available for neuropathologists confronted

  20. Establishment of 9L/F344 rat intracerebral glioma model of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Zong-yu XIAO

    2015-04-01

    Full Text Available Objective To establish the 9L/F344 rat intracerebral glioma model of brain tumor stem cells.  Methods Rat 9L gliosarcoma stem-like cells were cultured in serum-free suspension. The expression of CD133 and nestin were tested by immunohistochemistry. A total of 48 inbredline male F344 rats were randomly divided into 2 groups, and 9L tumor sphere cells and 9L monolayer cells were respectively implanted into the right caudate nucleus of F344 rats in 2 groups. Survival time was observed and determined using the method of Kaplan-Meier survival analysis. Fourteen days after implantation or when the rats were dying, their brains were perfused and sectioned for HE staining, and CD133 and nestin were detected by immunohistochemistry.  Results Rat 9L tumor spheres were formed with suspension culture in serum-free medium. The gliomas formed in both groups were invasive without obvious capsule. More new vessels, bleeding and necrosis could be detected in 9L tumor spheres group. The tumor cells in both groups were positive for CD133 and nestin. There was no significant difference in the expression of CD133 and nestin between 2 groups (P > 0.05, for all. According to the expression of nestin, the tumors formed by 9L tumor sphere cells were more invasive. The median survival time of the rats bearing 9L tumor sphere cells was 15 d (95%CI: 15.219-15.781, and the median survival time of the rats bearing 9L monolayer cells was 21 d (95%CI: 20.395-21.605. There was significant difference between 2 groups (χ2 = 12.800, P = 0.000.  Conclusions 9L/F344 rat intracerebral glioma model of brain tumor stem cells is successfully established, which provides a glioma model for the future research. DOI: 10.3969/j.issn.1672-6731.2015.04.012

  1. Nop2 is expressed during proliferation of neural stem cells and in adult mouse and human brain

    Czech Academy of Sciences Publication Activity Database

    Kosi, N.; Alic, I.; Kolacevic, M.; Vrsaljko, N.; Milosevic, N.J.; Sobol, Margaryta; Philimonenko, Anatoly; Hozák, Pavel; Gajovic, S.; Pochet, R.; Mitrecic, D.

    2015-01-01

    Roč. 1597, FEB 9 (2015), s. 65-76 ISSN 1872-6240 R&D Projects: GA TA ČR(CZ) TE01020118; GA MPO FR-TI3/588 Institutional support: RVO:68378050 Keywords : Nop2 * Brain * Stem cells * Stroke * Nucleolus * Cell cycle Subject RIV: EB - Genetics ; Molecular Biology

  2. Nop2 is expressed during proliferation of neural stem cells and in adult mouse and human brain

    Czech Academy of Sciences Publication Activity Database

    Kosi, N.; Alic, I.; Kolačevic, M.; Vrsaljko, N.; Miloševic, N.J.; Sobol, Margaryta; Filimonenko, Anatolij; Hozák, Pavel; Gajovic, S.; Pochet, R.; Mitrečic, D.

    2015-01-01

    Roč. 1597, February (2015), s. 65-76 ISSN 1872-6240 R&D Projects: GA TA ČR(CZ) TE01020118; GA MPO FR-TI3/588 Institutional support: RVO:68378050 Keywords : Nop2 * Brain * Stem cells * Stroke Subject RIV: EB - Genetics ; Molecular Biology

  3. Evaluation of quality of life in long-term survivors of paediatric brain stem tumors, treated with radiotherapy

    International Nuclear Information System (INIS)

    Skowronska-Gardas, Anna; Pedziwiatr, Katarzyna; Chojnacka, Marzanna

    2004-01-01

    The quality of life in long-term survivors of paediatric brain stem tumors, treated with radiotherapy is evaluated. They suffer predominantly from pre-treatment neurological impairments, which seriously influence their quality of life. The most often observed treatment sequelae are pituitary insufficiency and hearing loss

  4. Collateralization of the pathways descending from the cerebral cortex to brain stem and spinal cord in cat and monkey

    NARCIS (Netherlands)

    K. Keizer (Koos)

    1989-01-01

    textabstractThe present study deals with the collateralization of the descending pathways from the cerebral cortex to the brain stem and the spinal cord in cat and monkey. The distributions of the branching cortical neurons were studied using retrograde fluorescent tracers. In addition, a new

  5. Human umbilical cord blood stem cells and brain-derived neurotrophic factor for optic nerve injury: a biomechanical evaluation

    Science.gov (United States)

    Zhang, Zhong-jun; Li, Ya-jun; Liu, Xiao-guang; Huang, Feng-xiao; Liu, Tie-jun; Jiang, Dong-mei; Lv, Xue-man; Luo, Min

    2015-01-01

    Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood stem cells. After 30 days, the maximum load, maximum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neurotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These findings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, improve biomechanical properties, and contribute to the recovery after injury. PMID:26330839

  6. Mesenchymal stem cell-derived extracellular vesicles ameliorate inflammation-induced preterm brain injury.

    Science.gov (United States)

    Drommelschmidt, Karla; Serdar, Meray; Bendix, Ivo; Herz, Josephine; Bertling, Frederik; Prager, Sebastian; Keller, Matthias; Ludwig, Anna-Kristin; Duhan, Vikas; Radtke, Stefan; de Miroschedji, Kyra; Horn, Peter A; van de Looij, Yohan; Giebel, Bernd; Felderhoff-Müser, Ursula

    2017-02-01

    Preterm brain injury is a major cause of disability in later life, and may result in motor, cognitive and behavioural impairment for which no treatment is currently available. The aetiology is considered as multifactorial, and one underlying key player is inflammation leading to white and grey matter injury. Extracellular vesicles secreted by mesenchymal stem/stromal cells (MSC-EVs) have shown therapeutic potential in regenerative medicine. Here, we investigated the effects of MSC-EV treatment on brain microstructure and maturation, inflammatory processes and long-time outcome in a rodent model of inflammation-induced brain injury. 3-Day-old Wistar rats (P3) were intraperitoneally injected with 0.25mg/kg lipopolysaccharide or saline and treated with two repetitive doses of 1×10 8 cell equivalents of MSC-EVs per kg bodyweight. Cellular degeneration and reactive gliosis at P5 and myelination at P11 were evaluated by immunohistochemistry and western blot. Long-term cognitive and motor function was assessed by behavioural testing. Diffusion tensor imaging at P125 evaluated long-term microstructural white matter alterations. MSC-EV treatment significantly ameliorated inflammation-induced neuronal cellular degeneration reduced microgliosis and prevented reactive astrogliosis. Short-term myelination deficits and long-term microstructural abnormalities of the white matter were restored by MSC-EV administration. Morphological effects of MSC-EV treatment resulted in improved long-lasting cognitive functions INTERPRETATION: MSC-EVs ameliorate inflammation-induced cellular damage in a rat model of preterm brain injury. MSC-EVs may serve as a novel therapeutic option by prevention of neuronal cell death, restoration of white matter microstructure, reduction of gliosis and long-term functional improvement. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Biomimetic brain tumor niche regulates glioblastoma cells towards a cancer stem cell phenotype.

    Science.gov (United States)

    Liu, Yung-Chiang; Lee, I-Chi; Chen, Pin-Yuan

    2018-05-01

    Glioblastoma (GBM) is the most malignant primary brain tumor and contains tumorigenic cancer stem cells (CSCs), which support the progression of tumor growth. The selection of CSCs and facilitation of the brain tumor niches may assist the development of novel therapeutics for GBM. Herein, hydrogel materials composed of agarose and hydroxypropyl methyl cellulose (HMC) in different concentrations were established and compared to emulate brain tumor niches and CSC microenvironments within a label-free system. Human GBM cell line, U-87 MG, was cultured on a series of HMC-agarose based culture system. Cell aggregation and spheroids formation were investigated after 4 days of culture, and 2.5% HMC-agarose based culture system demonstrated the largest spheroids number and size. Moreover, CD133 marker expression of GBM cells after 6 days of culture in 2.5% HMC-agarose based culture system was 60%, relatively higher than the control group at only 15%. Additionally, cells on 2.5% HMC-agarose based culture system show the highest chemoresistance, even at the high dose of 500 µM temozolomide for 72 h, the live cell ratio was still > 80%. Furthermore, the results also indicate that the expression of ABCG2 gene was up-regulated after culture in 2.5% HMC-agarose based culture system. Therefore, our results demonstrated that biomimetic brain tumor microenvironment may regulate GBM cells towards the CSC phenotype and expression of CSC characteristics. The microenvironment selection and spheroids formation in HMC-agarose based culture system may provide a label-free CSC selection strategy and drug testing model for future biomedical applications.

  8. Modeling learning in brain stem and cerebellar sites responsible for VOR plasticity

    Science.gov (United States)

    Quinn, K. J.; Didier, A. J.; Baker, J. F.; Peterson, B. W.

    1998-01-01

    A simple model of vestibuloocular reflex (VOR) function was used to analyze several hypotheses currently held concerning the characteristics of VOR plasticity. The network included a direct vestibular pathway and an indirect path via the cerebellum. An optimization analysis of this model suggests that regulation of brain stem sites is critical for the proper modification of VOR gain. A more physiologically plausible learning rule was also applied to this network. Analysis of these simulation results suggests that the preferred error correction signal controlling gain modification of the VOR is the direct output of the accessory optic system (AOS) to the vestibular nuclei vs. a signal relayed through the cerebellum via floccular Purkinje cells. The potential anatomical and physiological basis for this conclusion is discussed, in relation to our current understanding of the latency of the adapted VOR response.

  9. Exogenous stem cells pioneer a biobridge to the advantage of host brain cells following stroke: New insights for clinical applications

    Directory of Open Access Journals (Sweden)

    Marci G Crowley

    2017-01-01

    Full Text Available Stroke continues to maintain its status as one of the top causes of mortality within the United States. Currently, the only Food and Drug Administration (FDA-approved drug in place for stroke patients, tissue plasminogen activator (tPA, has a rigid therapeutic window, closing at approximately 4.5 h after stroke onset. Due to this short time frame and other restrictions, such as any condition that increases a patient's risk for hemorrhaging, it has been predicted that <5% of ischemic stroke patients benefit from tPA. Given that rehabilitation therapy remains the only other option for stroke victims, there is a clear unmet clinical need for treatment available for the remaining 95%. While still considered an experimental treatment, the utilization of stem cell therapies for stroke holds consistent promise. Copious preclinical studies report the capacity for transplanted stem cells to rescue the brain parenchyma surrounding the stroke-induced infarct core. At present, the exact mechanisms in which stem cells contribute a robust therapeutic benefit remains unclear. Following stem cell administration, researchers have observed cell replacement, an increase in growth factors, and a reduction in inflammation. With a deeper understanding of the precise mechanism of stem cells, these therapies can be optimized in the clinic to afford the greatest therapeutic benefit. Recent studies have depicted a unique method of endogenous stem cell activation as a result of stem cell therapy. In both traumatic brain injury and stroke models, transplanted mesenchymal stromal cells (MSCs facilitated a pathway between the neurogenic niches of the brain and the damaged area through extracellular matrix remodeling. The biobridge pioneered by the MSCs was utilized by the endogenous stem cells, and these cells were able to travel to the damaged areas distal to the neurogenic niches, a feat unachievable without prior remodeling. These studies broaden our understanding of stem

  10. Control of abdominal muscles by brain stem respiratory neurons in the cat.

    Science.gov (United States)

    Miller, A D; Ezure, K; Suzuki, I

    1985-07-01

    Control of abdominal musculature by brain stem respiratory neurons was studied in decerebrate unanesthetized cats by determining 1) which brain stem respiratory neurons could be antidromically activated from the lumbar cord, from which the abdominal muscles receive part of their innervation, and 2) if lumbar-projecting respiratory neurons make monosynaptic connections with abdominal motoneurons. A total of 462 respiratory neurons, located between caudal C2 and the retrofacial nucleus (Bötzinger complex), were tested for antidromic activation from the upper lumbar cord. Fifty-eight percent of expiratory (E) neurons (70/121) in the caudal ventral respiratory group (VRG) between the obex and rostral C1 were antidromically activated from contralateral L1. Eight of these neurons were activated at low thresholds from lamina VIII and IX in the L1-2 gray matter. One-third (14/41) of the E neurons that projected to L1 could also be activated from L4-5. Almost all antidromic E neurons had an augmenting firing pattern. Ten scattered inspiratory (I) neurons projected to L1 but could not be activated from L4-5. No neurons that fired during both E and I phases (phase-spanning neurons) were antidromically activated from the lumbar cord. In order to test for possible monosynaptic connections between descending E neurons and abdominal motoneurons, cross-correlations were obtained between 27 VRG E neurons, which were antidromically activated from caudal L2 and contralateral L1 and L2 abdominal nerve activity (47 neuron-nerve combinations). Only two neurons showed a correlation with one of the two nerves tested. Although there is a large projection to the lumbar cord from expiratory neurons in the ventral respiratory group caudal to the obex, cross-correlation analyses suggest that strong monosynaptic connections between these neurons and abdominal motoneurons are scarce.

  11. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection

    Directory of Open Access Journals (Sweden)

    Erica L. McGrath

    2017-03-01

    Full Text Available Zika virus (ZIKV infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7, to infect primary human neural stem cells (hNSCs originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection.

  12. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection.

    Science.gov (United States)

    McGrath, Erica L; Rossi, Shannan L; Gao, Junling; Widen, Steven G; Grant, Auston C; Dunn, Tiffany J; Azar, Sasha R; Roundy, Christopher M; Xiong, Ying; Prusak, Deborah J; Loucas, Bradford D; Wood, Thomas G; Yu, Yongjia; Fernández-Salas, Ildefonso; Weaver, Scott C; Vasilakis, Nikos; Wu, Ping

    2017-03-14

    Zika virus (ZIKV) infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7), to infect primary human neural stem cells (hNSCs) originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Recovery from a possible cytomegalovirus meningoencephalitis-induced apparent brain stem death in an immunocompetent man: a case report.

    Science.gov (United States)

    Rahardjo, Theresia Monica; Maskoen, Tinni Trihartini; Redjeki, Ike Sri

    2016-08-26

    Recovery from cytomegalovirus meningoencephalitis with brain stem death in an immunocompetent patient is almost impossible. We present a remarkable recovery from a possible cytomegalovirus infection in an immunocompetent man who had severe neurological syndromes, suggesting brain stem death complicated by pneumonia and pleural effusion. A 19-year-old Asian man presented at our hospital's emergency department with reduced consciousness and seizures following high fever, headache, confusion, and vomitus within a week before arrival. He was intubated and sent to our intensive care unit. He had nuchal rigidity and tetraparesis with accentuated tendon reflexes. Electroencephalography findings suggested an acute structural lesion at his right temporal area or an epileptic state. A cerebral spinal fluid examination suggested viral infection. A computed tomography scan was normal at the early stage of disease. Immunoglobulin M, immunoglobulin G anti-herpes simplex virus, and immunoglobulin M anti-cytomegalovirus were negative. However, immunoglobulin G anti-cytomegalovirus was positive, which supported a diagnosis of cytomegalovirus meningoencephalitis. His clinical condition deteriorated, spontaneous respiration disappeared, cranial reflexes became negative, and brain stem death was suspected. Therapy included antivirals, corticosteroids, antibiotics, anticonvulsant, antipyretics, antifungal agents, and a vasopressor to maintain hemodynamic stability. After 1 month, he showed a vague response to painful stimuli at his supraorbital nerve and respiration started to appear the following week. After pneumonia and pleural effusion were resolved, he was weaned from the ventilator and moved from the intensive care unit on day 90. This case highlights several important issues that should be considered. First, the diagnosis of brain stem death must be confirmed with caution even if there are negative results of brain stem death test for a long period. Second, cytomegalovirus

  14. Tryptophan availability modulates serotonin release from rat hypothalamic slices

    Science.gov (United States)

    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. High-resolution anatomy of the human brain stem using 7-T MRI: improved detection of inner structures and nerves?

    Energy Technology Data Exchange (ETDEWEB)

    Gizewski, Elke R. [Medical University Innsbruck, Department of Neuroradiology, Innsbruck (Austria); Maderwald, Stefan [University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Linn, Jennifer; Bochmann, Katja [LMU Munich, Department of Neuroradiology, Munich (Germany); Dassinger, Benjamin [Medical University Innsbruck, Department of Neuroradiology, Innsbruck (Austria); Justus-Liebig-University Giessen, Department of Neuroradiology, Giessen (Germany); Forsting, Michael [University Hospital, University Duisburg-Essen, Departments of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Ladd, Mark E. [University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); University Hospital, University Duisburg-Essen, Departments of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany)

    2014-03-15

    The purpose of this paper is to assess the value of 7 Tesla (7 T) MRI for the depiction of brain stem and cranial nerve (CN) anatomy. Six volunteers were examined at 7 T using high-resolution SWI, MPRAGE, MP2RAGE, 3D SPACE T2, T2, and PD images to establish scanning parameters targeted at optimizing spatial resolution. Direct comparisons between 3 and 7 T were performed in two additional subjects using the finalized sequences (3 T: T2, PD, MPRAGE, SWAN; 7 T: 3D T2, MPRAGE, SWI, MP2RAGE). Artifacts and the depiction of structures were evaluated by two neuroradiologists using a standardized score sheet. Sequences could be established for high-resolution 7 T imaging even in caudal cranial areas. High in-plane resolution T2, PD, and SWI images provided depiction of inner brain stem structures such as pons fibers, raphe, reticular formation, nerve roots, and periaqueductal gray. MPRAGE and MP2RAGE provided clear depiction of the CNs. 3D T2 images improved depiction of inner brain structure in comparison to T2 images at 3 T. Although the 7-T SWI sequence provided improved contrast to some inner structures, extended areas were influenced by artifacts due to image disturbances from susceptibility differences. Seven-tesla imaging of basal brain areas is feasible and might have significant impact on detection and diagnosis in patients with specific diseases, e.g., trigeminal pain related to affection of the nerve root. Some inner brain stem structures can be depicted at 3 T, but certain sequences at 7 T, in particular 3D SPACE T2, are superior in producing anatomical in vivo images of deep brain stem structures. (orig.)

  16. Gold nanoparticle-cell labeling methodology for tracking stem cells within the brain

    Science.gov (United States)

    Betzer, Oshra; Meir, Rinat; Motiei, Menachem; Yadid, Gal; Popovtzer, Rachela

    2017-02-01

    Cell therapy provides a promising approach for diseases and injuries that conventional therapies cannot cure effectively. Mesenchymal stem cells (MSCs) can be used as effective targeted therapy, as they exhibit homing capabilities to sites of injury and inflammation, exert anti-inflammatory effects, and can differentiate in order to regenerate damaged tissue. Despite the potential efficacy of cell therapy, applying cell-based therapy in clinical practice is very challenging; there is a need to uncover the mystery regarding the fate of the transplanted cells. Therefore, in this study, we developed a method for longitudinal and quantitative in vivo cell tracking, based on the superior visualization abilities of classical X-ray computed tomography (CT), and combined with gold nanoparticles as labeling agents. We applied this technique for non-invasive imaging of MSCs transplanted in a rat model for depression, a highly prevalent and disabling neuropsychiatric disorder lacking effective treatment. Our results, which demonstrate that cell migration could be detected as early as 24 hours and up to one month post-transplantation, revealed that MSCs specifically navigated and homed to distinct depression related brain regions. This research further reveals that cell therapy is a beneficial approach for treating neuropsychiatric disorders; Behavioral manifestations of core symptoms of depressive behavior, were significantly attenuated following treatment. We expect This CT-based technique to lead to a significant enhancement in cellular therapy both for basic research and clinical applications of brain pathologies.

  17. Transmigration of neural stem cells across the blood brain barrier induced by glioma cells.

    Directory of Open Access Journals (Sweden)

    Mónica Díaz-Coránguez

    Full Text Available Transit of human neural stem cells, ReNcell CX, through the blood brain barrier (BBB was evaluated in an in vitro model of BBB and in nude mice. The BBB model was based on rat brain microvascular endothelial cells (RBMECs cultured on Millicell inserts bathed from the basolateral side with conditioned media (CM from astrocytes or glioma C6 cells. Glioma C6 CM induced a significant transendothelial migration of ReNcells CX in comparison to astrocyte CM. The presence in glioma C6 CM of high amounts of HGF, VEGF, zonulin and PGE2, together with the low abundance of EGF, promoted ReNcells CX transmigration. In contrast cytokines IFN-α, TNF-α, IL-12p70, IL-1β, IL-6, IL-8 and IL-10, as well as metalloproteinases -2 and -9 were present in equal amounts in glioma C6 and astrocyte CMs. ReNcells expressed the tight junction proteins occludin and claudins 1, 3 and 4, and the cell adhesion molecule CRTAM, while RBMECs expressed occludin, claudins 1 and 5 and CRTAM. Competing CRTAM mediated adhesion with soluble CRTAM, inhibited ReNcells CX transmigration, and at the sites of transmigration, the expression of occludin and claudin-5 diminished in RBMECs. In nude mice we found that ReNcells CX injected into systemic circulation passed the BBB and reached intracranial gliomas, which overexpressed HGF, VEGF and zonulin/prehaptoglobin 2.

  18. Transmigration of neural stem cells across the blood brain barrier induced by glioma cells.

    Science.gov (United States)

    Díaz-Coránguez, Mónica; Segovia, José; López-Ornelas, Adolfo; Puerta-Guardo, Henry; Ludert, Juan; Chávez, Bibiana; Meraz-Cruz, Noemi; González-Mariscal, Lorenza

    2013-01-01

    Transit of human neural stem cells, ReNcell CX, through the blood brain barrier (BBB) was evaluated in an in vitro model of BBB and in nude mice. The BBB model was based on rat brain microvascular endothelial cells (RBMECs) cultured on Millicell inserts bathed from the basolateral side with conditioned media (CM) from astrocytes or glioma C6 cells. Glioma C6 CM induced a significant transendothelial migration of ReNcells CX in comparison to astrocyte CM. The presence in glioma C6 CM of high amounts of HGF, VEGF, zonulin and PGE2, together with the low abundance of EGF, promoted ReNcells CX transmigration. In contrast cytokines IFN-α, TNF-α, IL-12p70, IL-1β, IL-6, IL-8 and IL-10, as well as metalloproteinases -2 and -9 were present in equal amounts in glioma C6 and astrocyte CMs. ReNcells expressed the tight junction proteins occludin and claudins 1, 3 and 4, and the cell adhesion molecule CRTAM, while RBMECs expressed occludin, claudins 1 and 5 and CRTAM. Competing CRTAM mediated adhesion with soluble CRTAM, inhibited ReNcells CX transmigration, and at the sites of transmigration, the expression of occludin and claudin-5 diminished in RBMECs. In nude mice we found that ReNcells CX injected into systemic circulation passed the BBB and reached intracranial gliomas, which overexpressed HGF, VEGF and zonulin/prehaptoglobin 2.

  19. Regional Susceptibility to Domoic Acid in Primary Astrocyte Cells Cultured from the Brain Stem and Hippocampus

    Directory of Open Access Journals (Sweden)

    Olga M. Pulido

    2008-02-01

    Full Text Available Domoic acid is a marine biotoxin associated with harmful algal blooms and is the causative agent of amnesic shellfish poisoning in marine animals and humans. It is also an excitatory amino acid analog to glutamate and kainic acid which acts through glutamate receptors eliciting a very rapid and potent neurotoxic response. The hippocampus, among other brain regions, has been identified as a specific target site having high sensitivity to DOM toxicity. Histopathology evidence indicates that in addition to neurons, the astrocytes were also injured. Electron microscopy data reported in this study further supports the light microscopy findings. Furthermore, the effect of DOM was confirmed by culturing primary astrocytes from the hippocampus and the brain stem and subsequently exposing them to domoic acid. The RNA was extracted and used for biomarker analysis. The biomarker analysis was done for the early response genes including c-fos, c-jun, c-myc, Hsp-72; specific marker for the astrocytes- GFAP and the glutamate receptors including GluR 2, NMDAR 1, NMDAR 2A and B. Although, the astrocyte-GFAP and c-fos were not affected, c-jun and GluR 2 were down-regulated. The microarray analysis revealed that the chemokines / cytokines, tyrosine kinases (Trk, and apoptotic genes were altered. The chemokines that were up-regulated included - IL1-a, IL-1B, IL-6, the small inducible cytokine, interferon protein IP-10, CXC chemokine LIX, and IGF binding proteins. The Bax, Bcl-2, Trk A and Trk B were all downregulated. Interestingly, only the hippocampal astrocytes were affected. Our findings suggest that astrocytes may present a possible target for pharmacological interventions for the prevention and treatment of amnesic shellfish poisoning and for other brain pathologies involving excitotoxicity

  20. Recent advances in the involvement of long non-coding RNAs in neural stem cell biology and brain pathophysiology

    Directory of Open Access Journals (Sweden)

    Daphne eAntoniou

    2014-04-01

    Full Text Available Exploration of non-coding genome has recently uncovered a growing list of formerly unknown regulatory long non-coding RNAs (lncRNAs with important functions in stem cell pluripotency, development and homeostasis of several tissues. Although thousands of lncRNAs are expressed in mammalian brain in a highly patterned manner, their roles in brain development have just begun to emerge. Recent data suggest key roles for these molecules in gene regulatory networks controlling neuronal and glial cell differentiation. Analysis of the genomic distribution of genes encoding for lncRNAs indicates a physical association of these regulatory RNAs with transcription factors (TFs with well-established roles in neural differentiation, suggesting that lncRNAs and TFs may form coherent regulatory networks with important functions in neural stem cells (NSCs. Additionally, many studies show that lncRNAs are involved in the pathophysiology of brain-related diseases/disorders. Here we discuss these observations and investigate the links between lncRNAs, brain development and brain-related diseases. Understanding the functions of lncRNAs in NSCs and brain organogenesis could revolutionize the basic principles of developmental biology and neuroscience.

  1. Store-Operated Calcium Entries Control Neural Stem Cell Self-Renewal in the Adult Brain Subventricular Zone.

    Science.gov (United States)

    Domenichini, Florence; Terrié, Elodie; Arnault, Patricia; Harnois, Thomas; Magaud, Christophe; Bois, Patrick; Constantin, Bruno; Coronas, Valérie

    2018-01-23

    The subventricular zone (SVZ) is the major stem cell niche in the brain of adult mammals. Within this region, neural stem cells (NSC) proliferate, self-renew and give birth to neurons and glial cells. Previous studies underlined enrichment in calcium signaling-related transcripts in adult NSC. Because of their ability to mobilize sustained calcium influxes in response to a wide range of extracellular factors, store-operated channels (SOC) appear to be, among calcium channels, relevant candidates to induce calcium signaling in NSC whose cellular activities are continuously adapted to physiological signals from the microenvironment. By Reverse Transcription Polymerase Chain Reaction (RT-PCR), Western blotting and immunocytochemistry experiments, we demonstrate that SVZ cells express molecular actors known to build up SOC, namely transient receptor potential canonical 1 (TRPC1) and Orai1, as well as their activator stromal interaction molecule 1 (STIM1). Calcium imaging reveals that SVZ cells display store-operated calcium entries. Pharmacological blockade of SOC with SKF-96365 or YM-58483 (also called BTP2) decreases proliferation, impairs self-renewal by shifting the type of SVZ stem cell division from symmetric proliferative to asymmetric, thereby reducing the stem cell population. Brain section immunostainings show that TRPC1, Orai1, and STIM1 are expressed in vivo, in SOX2-positive SVZ NSC. Injection of SKF-96365 in brain lateral ventricle diminishes SVZ cell proliferation and reduces the ability of SVZ cells to form neurospheres in vitro. The present study combining in vitro and in vivo approaches uncovers a major role for SOC in the control of SVZ NSC population and opens new fields of investigation for stem cell biology in health and disease. Stem Cells 2018. © AlphaMed Press 2018.

  2. A phase I trial of etanidazole and hyperfractionated radiotherapy in children with diffuse brain stem glioma

    International Nuclear Information System (INIS)

    Dutton, S.C.; Pomeroy, S.L.; Billett, A.L.; Barnes, P.; Kuhlman, C.; Riese, N.E.; Goumnerova, L.; Scott, R.M.; Coleman, C.N.; Tarbell, N.J.

    1997-01-01

    Objective: Prospective phase I study to evaluate the toxicity and maximum tolerated dose of etanidazole administered concurrently with hyperfractionated radiation therapy (HRT) for children with brain stem glioma. Materials and Methods: Eighteen patients with brain stem glioma were treated with etanidazole and HRT from 1990-1996. Eligibility required MRI confirmation of diffuse glioma of medulla, pons or mesencephalon, and signs/symptoms of cranial nerve deficit, ataxia or long tract signs of ≤ 6 months duration. Cervico-medullary tumors were excluded. Patients (median age 8.5 years; 11 males, 7 females) received HRT to the tumor volume plus a 2 cm margin with parallel opposed 6-15 MV photons. The total dose was 66 Gy for the first 3 patients, followed by 63 Gy over 4.2 weeks (1.5 Gy BID with 6 hours between fractions) for the subsequent 15 patients. Etanidazole was administered as a rapid IV infusion 30 minutes prior to the morning fraction of HRT at doses of 1.8 gm/m2 x 17 doses (30.6 gm/m2) at step 1 to a maximum of 2.4 gm/m2 x 21 doses (50.4 gm/m2) at step 8. Dose escalation was planned with 3 patients at each of the 8 levels. Results: Three patients were treated at each dose level except level 2, on which only one patient was treated. The highest dose level achieved was step 7 which delivered a total etanidazole dose of 46.2 gm/m2. Two patients were treated at this level, and both patients experienced grade 3 toxicity in the form of a diffuse cutaneous rash. Three patients received a lower dose of 42 gm/m2 without significant toxicity, and this represents the maximum tolerated dose (MTD). There were 24 cases of grade 1 toxicity (10 vomiting, 5 peripheral neuropathy, 2 rash, 2 constipation, 1 skin erythema, 1 weight loss, 3 other), eleven cases of grade 2 toxicity (4 vomiting, 2 skin erythema, 2 constipation, 1 arthalgia, 1 urinary retention, 1 hematologic), and four grade b 3 toxicities (2 rash, 1 vomiting, 1 skin desquamation). Grade 2 or 3 peripheral

  3. A cGMP-applicable expansion method for aggregates of human neural stem and progenitor cells derived from pluripotent stem cells or fetal brain tissue.

    Science.gov (United States)

    Shelley, Brandon C; Gowing, Geneviève; Svendsen, Clive N

    2014-06-15

    A cell expansion technique to amass large numbers of cells from a single specimen for research experiments and clinical trials would greatly benefit the stem cell community. Many current expansion methods are laborious and costly, and those involving complete dissociation may cause several stem and progenitor cell types to undergo differentiation or early senescence. To overcome these problems, we have developed an automated mechanical passaging method referred to as "chopping" that is simple and inexpensive. This technique avoids chemical or enzymatic dissociation into single cells and instead allows for the large-scale expansion of suspended, spheroid cultures that maintain constant cell/cell contact. The chopping method has primarily been used for fetal brain-derived neural progenitor cells or neurospheres, and has recently been published for use with neural stem cells derived from embryonic and induced pluripotent stem cells. The procedure involves seeding neurospheres onto a tissue culture Petri dish and subsequently passing a sharp, sterile blade through the cells effectively automating the tedious process of manually mechanically dissociating each sphere. Suspending cells in culture provides a favorable surface area-to-volume ratio; as over 500,000 cells can be grown within a single neurosphere of less than 0.5 mm in diameter. In one T175 flask, over 50 million cells can grow in suspension cultures compared to only 15 million in adherent cultures. Importantly, the chopping procedure has been used under current good manufacturing practice (cGMP), permitting mass quantity production of clinical-grade cell products.

  4. Metformin and Ara-a Effectively Suppress Brain Cancer by Targeting Cancer Stem/Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Tarek H. Mouhieddine

    2015-11-01

    Full Text Available Background: Gliomas and neuroblastomas pose a great health burden worldwide with a poor and moderate prognosis, respectively. Many studies have tried to find effective treatments for these primary malignant brain tumors. Of interest, the AMP-activated protein kinase (AMPK pathway was found to be associated with tumorigenesis and tumor survival, leading to many studies on AMPK drugs, especially Metformin, and their potential role as anti-cancer treatments. Cancer stem cells (CSCs are a small population of slowly-dividing, treatment-resistant, undifferentiated cancer cells that are being discovered in a multitude of cancers. They are thought to be responsible for replenishing the tumor with highly proliferative cells and increasing the risk of recurrence. Methods: Metformin and 9-β-d-Arabinofuranosyl Adenine (Ara-a were used to study the role of the AMPK pathway in vitro on U251 (glioblastoma and SHSY-5Y (neuroblastoma cell lines.Results: We found that both drugs are able to decrease the survival of U251 and SH-SY5Y cell lines in a 2D as well as a 3D culture model. Metformin and Ara-a significantly decreased the invasive ability of these cancer cell lines. Treatment with these drugs decreased the sphere-forming units (SFU of U251 cells, with Ara-a being more efficient, signifying the extinction of the CSC population. However, if treatment is withdrawn before all SFUs are extinguished, the CSCs regain some of their sphere-forming capabilities in the case of Metformin but not Ara-a treatment. Conclusion: Metformin and Ara-a have proved to be effective in the treatment of glioblastomas and neuroblastomas, in vitro, by targeting their cancer stem/progenitor cell population, which prevents recurrence.

  5. Presenilins are required for maintenance of neural stem cells in the developing brain

    Directory of Open Access Journals (Sweden)

    Kim Woo-Young

    2008-01-01

    Full Text Available Abstract The early embryonic lethality of mutant mice bearing germ-line deletions of both presenilin genes precluded the study of their functions in neural development. We therefore employed the Cre-loxP technology to generate presenilin conditional double knockout (PS cDKO mice, in which expression of both presenilins is inactivated in neural progenitor cells (NPC or neural stem cells and their derivative neurons and glia beginning at embryonic day 11 (E11. In PS cDKO mice, dividing NPCs labeled by BrdU are decreased in number beginning at E13.5. By E15.5, fewer than 20% of NPCs remain in PS cDKO mice. The depletion of NPCs is accompanied by severe morphological defects and hemorrhages in the PS cDKO embryonic brain. Interkinetic nuclear migration of NPCs is also disrupted in PS cDKO embryos, as evidenced by displacement of S-phase and M-phase nuclei in the ventricular zone of the telencephalon. Furthermore, the depletion of neural progenitor cells in PS cDKO embryos is due to NPCs exiting cell cycle and differentiating into neurons rather than reentering cell cycle between E13.5 and E14.5 following PS inactivation in most NPCs. The length of cell cycle, however, is unchanged in PS cDKO embryos. Expression of Notch target genes, Hes1 and Hes5, is significantly decreased in PS cDKO brains, whereas Dll1 expression is up-regulated, indicating that Notch signaling is effectively blocked by PS inactivation. These findings demonstrate that presenilins are essential for neural progenitor cells to re-enter cell cycle and thus ensure proper expansion of neural progenitor pool during embryonic neural development.

  6. Estradiol receptors mediate estradiol-induced inhibition of mitochondrial Ca^{2+} efflux in rat caudate nucleus and brain stem

    OpenAIRE

    PETROVIC, SNJEZANA; MILOSEVIC, MAJA; RISTIC-MEDIC, DANIJELA; VELICKOVIC, NATASA; DRAKULIC, DUNJA; GRKOVIC, IVANA; HORVAT, ANICA

    2015-01-01

    Our earlier studies found that in vitro estradiol modulates mitochondrial Ca2+ transport in discrete brain regions. The present study examined the role of estradiol receptors (ERs) in estradiol-induced inhibition of Ca^{2+} efflux from synaptosomal mitochondria isolated from rat caudate nuclei and brain stems. Radioactively labeled CaCl_2 (0.6?0.75 µCi ^45CaCl_{2}) was used for Ca^{2+} transport monitoring. The results revealed that in the presence of ER antagonist 7\\alpha,17ß-[9[(4,4,5,5,5-...

  7. Robotics, stem cells, and brain-computer interfaces in rehabilitation and recovery from stroke: updates and advances.

    Science.gov (United States)

    Boninger, Michael L; Wechsler, Lawrence R; Stein, Joel

    2014-11-01

    The aim of this study was to describe the current state and latest advances in robotics, stem cells, and brain-computer interfaces in rehabilitation and recovery for stroke. The authors of this summary recently reviewed this work as part of a national presentation. The article represents the information included in each area. Each area has seen great advances and challenges as products move to market and experiments are ongoing. Robotics, stem cells, and brain-computer interfaces all have tremendous potential to reduce disability and lead to better outcomes for patients with stroke. Continued research and investment will be needed as the field moves forward. With this investment, the potential for recovery of function is likely substantial.

  8. Pathophysiological changes of the cerebellum and brain stem in a rabbit model after superior petrosal vein sacrifice.

    Science.gov (United States)

    Cheng, Lei; Guo, Pin; Liao, Yi-Wei; Zhang, Hong-Liang; Li, Huan-Ting; Yuan, Xianrui

    2017-11-13

    In certain surgical procedures sacrifice of the superior petrosal vein (SPV) is required. Previous studies have reported transient cerebellar edema, venous infarction or hemorrhage might occur after sectioning of the SPV. This study investigated the pathophysiological changes of cerebellum and brain stem after SPV sacrifice. Rabbits were divided into the operation group where the SPV was sacrificed and the control group where the SPV remained intact. Each group was further subdivided into 4, 8, 12, 24, 48 and 72 hours groups which represented the time period from sacrifice of the SPV to sacrifice of the rabbits. The water content (WC), Na + content, K + content and pathophysiological changes of cerebellum and brain stem tissue were measured. In comparison to the control, the WC and Na + content of cerebellar tissue were increased in the 4h, 8h, 12h and 24h operation subgroups (psacrifice of the SPV in the rabbit model. ©2017 The Author(s).

  9. Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation is associated with cell-type-dependent splicing of mtAspRS mRNA

    NARCIS (Netherlands)

    van Berge, Laura; Dooves, Stephanie; van Berkel, Carola G. M.; Polder, Emiel; van der Knaap, Marjo S.; Scheper, Gert C.

    2012-01-01

    LBSL (leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation) is an autosomal recessive white matter disorder with slowly progressive cerebellar ataxia, spasticity and dorsal column dysfunction. Magnetic resonance imaging shows characteristic abnormalities in the

  10. Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

    Science.gov (United States)

    2013-10-07

    Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  11. Brain plasticity, cognitive functions and neural stem cells: a pivotal role for the brain-specific neural master gene |-SRGAP2-FAM72-|.

    Science.gov (United States)

    Ho, Nguyen Thi Thanh; Kutzner, Arne; Heese, Klaus

    2017-12-20

    Due to an aging society with an increased dementia-induced threat to higher cognitive functions, it has become imperative to understand the molecular and cellular events controlling the memory and learning processes in the brain. Here, we suggest that the novel master gene pair |-SRGAP2-FAM72-| (SLIT-ROBO Rho GTPase activating the protein 2, family with sequence similarity to 72) reveals a new dogma for the regulation of neural stem cell (NSC) gene expression and is a distinctive player in the control of human brain plasticity. Insight into the specific regulation of the brain-specific neural master gene |-SRGAP2-FAM72-| may essentially contribute to novel therapeutic approaches to restore or improve higher cognitive functions.

  12. Primary and Secondary Vestibular Connections in the Brain Stem and Cerebellum: An Axoplasmic Transport Study in the Monkey and Cat

    Science.gov (United States)

    1983-08-25

    CONTINUING EDUCATION TEACHINQ HOSPITALS WALTER REED ARMY MEDICAL CENTER NATIONAL NAVAL MEDICAL CENTER MALCOLM GROW AIR FORCE MEDICAL CENTER WILFORD HALL...AIR FORCE MEDICAL CENTER APPROVAL SHEET Title of Thesis: Primary and Secondary Vestibular Connections in the Brain Stem and Cerebellum Name of...the Labyrinth 11 TABLE II: HRP Injections of the Labyrinth , 12 TABLE III: HRP Injections of the Vestibular Nuclei 13 TABLE IV: I, sotope Injections

  13. Neuroanesthesia management of neurosurgery of brain stem tumor requiring neurophysiology monitoring in an iMRI OT setting

    Directory of Open Access Journals (Sweden)

    Sabbagh Abdulrahman

    2009-01-01

    Full Text Available This report describes a rare case of ventrally exophytic pontine glioma describing operative and neuroanesthesia management. The combination of intraoperative neuromonitoring was used. It constituted: Brain stem evoked responses/potentials, Motor EP: recording from cranial nerve supplied muscle, and Sensory EP: Medial/tibial. Excision of the tumor was done with intra-operative magnatic resonance imaging (iMRI, which is considered a new modality.

  14. Recovery function of the human brain stem auditory-evoked potential.

    Science.gov (United States)

    Kevanishvili, Z; Lagidze, Z

    1979-01-01

    Amplitude reduction and peak latency prolongation were observed in the human brain stem auditory-evoked potential (BEP) with preceding (conditioning) stimulation. At a conditioning interval (CI) of 5 ms the alteration of BEP was greater than at a CI of 10 ms. At a CI of 10 ms the amplitudes of some BEP components (e.g. waves I and II) were more decreased than those of others (e.g. wave V), while the peak latency prolongation did not show any obvious component selectivity. At a CI of 5 ms, the extent of the amplitude decrement of individual BEP components differed less, while the increase in the peak latencies of the later components was greater than that of the earlier components. The alterations of the parameters of the test BEPs at both CIs are ascribed to the desynchronization of intrinsic neural events. The differential amplitude reduction at a CI of 10 ms is explained by the different durations of neural firings determining various effects of desynchronization upon the amplitudes of individual BEP components. The decrease in the extent of the component selectivity and the preferential increase in the peak latencies of the later BEP components observed at a CI of 5 ms are explained by the intensification of the mechanism of the relative refractory period.

  15. Neural stem cells show bidirectional experience-dependent plasticity in the perinatal mammalian brain.

    Science.gov (United States)

    Kippin, Tod E; Cain, Sean W; Masum, Zahra; Ralph, Martin R

    2004-03-17

    Many of the effects of prenatal stress on the endocrine function, brain morphology, and behavior in mammals can be reversed by brief sessions of postnatal separation and handling. We have tested the hypothesis that the effects of both the prenatal and postnatal experiences are mediated by negative and positive regulation of neural stem cell (NSC) number during critical stages in neurodevelopment. We used the in vitro clonal neurosphere assay to quantify NSCs in hamsters that had experienced prenatal stress (maternal restraint stress for 2 hr per day, for the last 7 d of gestation), postnatal handling (maternal-offspring separation for 15 min per day during postnatal days 1-21), orboth. Prenatal stress reduced the number of NSCs derived from the subependyma of the lateral ventricle. The effect was already present at postnatal day 1 and persisted into adulthood (at least 14 months of age). Similarly, prenatal stress reduced in vivo proliferation in the adult subependyma of the lateral ventricle. Conversely, postnatal handling increased NSC number and reversed the effect of prenatal stress. The effects of prenatal stress on NSCs and proliferation and the effect of postnatal handling on NSCs did not differ between male and females. The findings demonstrate that environmental factors can produce changes in NSC number that are present at birth and endure into late adulthood. These changes may underlie some of the behavioral effects produced by prenatal stress and postnatal handling.

  16. Moving stem cells to the clinic: potential and limitations for brain repair.

    Science.gov (United States)

    Steinbeck, Julius A; Studer, Lorenz

    2015-04-08

    Stem cell-based therapies hold considerable promise for many currently devastating neurological disorders. Substantial progress has been made in the derivation of disease-relevant human donor cell populations. Behavioral data in relevant animal models of disease have demonstrated therapeutic efficacy for several cell-based approaches. Consequently, cGMP grade cell products are currently being developed for first in human clinical trials in select disorders. Despite the therapeutic promise, the presumed mechanism of action of donor cell populations often remains insufficiently validated. It depends greatly on the properties of the transplanted cell type and the underlying host pathology. Several new technologies have become available to probe mechanisms of action in real time and to manipulate in vivo cell function and integration to enhance therapeutic efficacy. Results from such studies generate crucial insight into the nature of brain repair that can be achieved today and push the boundaries of what may be possible in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Susceptibility-weighted imaging of the venous networks around the brain stem

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Ming; Lin, Zhong-Xiao; Zhang, Nu [Wenzhou Medical University, Department of Neurosurgery, The 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou (China); Zhang, Xiao-Fen; Qiao, Hui-Huang; Chen, Cheng-Chun [Wenzhou Medical University, Department of Human Anatomy, Wenzhou (China); Ren, Chuan-Gen; Li, Jian-Ce [Wenzhou Medical University, Department of Radiology, The 1nd Affiliated Hospital of Wenzhou Medical University, Wenzhou (China)

    2014-10-18

    The venous network of the brainstem is complex and significant. Susceptibility-weighted imaging (SWI) is a practical technique which is sensitive to veins, especially tiny veins. Our purpose of this study was to evaluate the visualization of the venous network of brainstem by using SWI at 3.0 T. The occurrence rate of each superficial veins of brainstem was evaluated by using SWI on a 3 T MR imaging system in 60 volunteers. The diameter of the lateral mesencephalic vein and peduncular vein were measured by SWI using the reconstructed mIP images in the sagittal view. And the outflow of the veins of brainstem were studied and described according to the reconstructed images. The median anterior pontomesencephalic vein, median anterior medullary vein, peduncular vein, right vein of the pontomesencephalic sulcus, and right lateral anterior pontomesencephalic vein were detected in all the subjects (100 %). The outer diameter of peduncular vein was 1.38 ± 0.26 mm (range 0.8-1.8 mm). The lateral mesencephalic vein was found in 75 % of the subjects and the mean outer diameter was 0.81 ± 0.2 mm (range 0.5-1.2 mm). The inner veins of mesencephalon were found by using SWI. The venous networks around the brain stem can be visualized by SWI clearly. This result can not only provide data for anatomical study, but also may be available for the surgical planning in the infratentorial region. (orig.)

  18. Contributions of an adiabatic initial inversion pulse and K-space Re-ordered by inversion-time at each slice position (KRISP) to control of CSF artifacts and visualization of the brain in FLAIR magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Curati, Walter L.; Oatridge, Angela; Herlihy, Amy H.; Hajnal, Joseph V.; Puri, Basant K.; Bydder, Graeme M

    2001-05-01

    AIM: The aim of this study was to compare the performance of three fluid attenuated inversion recovery (FLAIR) pulse sequences for control of cerebrospinal fluid (CSF) and blood flow artifacts in imaging of the brain. The first of these sequences had an initial sinc inversion pulse which was followed by conventional k-space mapping. The second had an initial sinc inversion pulse followed by k-space re-ordered by inversion time at each slice position (KRISP) and the third had an adiabatic initial inversion pulse followed by KRISP. MATERIALS AND METHODS: Ten patients with established disease were studied with all three pulse sequences. Seven were also studied with the adiabatic KRISP sequence after contrast enhancement. Their images were evaluated for patient motion artifact, CSF and blood flow artifact as well as conspicuity of the cortex, meninges, ventricular system, brainstem and cerebellum. The conspicuity of lesions and the degree of enhancement were also evaluated. RESULTS: Both the sinc and adiabatic KRISP FLAIR sequences showed better control of CSF and blood flow artifacts than the conventional FLAIR sequence. In addition the adiabatic KRISP FLAIR sequence showed better control of CSF artifact at the inferior aspect of the posterior fossa. The lesion conspicuity was similar for each of the FLAIR sequences as was the degree of contrast enhancement to that shown with a T{sub 1}weighted spin echo sequence. CONCLUSION: The KRISP FLAIR sequence controls high signal artifacts from CSF flow and blood flow and the adiabatic pulse controls high signal artifacts due to inadequate inversion of the CSF magnetization at the periphery of the head transmitter coil. The KRISP FLAIR sequence also improves cortical and meningeal definition as a result of an edge enhancement effect. The effects are synergistic and can be usefully combined in a single pulse sequence. Curati, W.L. et al. (2001)

  19. De Novo Arteriovenous Malformation Growth Secondary to Implantation of Genetically Modified Allogeneic Mesenchymal Stem Cells in the Brain.

    Science.gov (United States)

    Nakamura, Makoto; Samii, Amir; Lang, Josef M; Götz, Friedrich; Samii, Madjid; Krauss, Joachim K

    2016-04-01

    Local biological drug delivery in the brain is an innovative field of medicine that developed rapidly in recent years. Our report illustrates a unique case of de novo development of a cerebral arteriovenous malformation (AVM) after implantation of genetically modified allogeneic mesenchymal stem cells in the brain. A 50-year-old man was included in a prospective clinical study (study ID number CM GLP-1/01, 2007-004516-31) investigating a novel neuroprotective approach in stroke patients to prevent perihematomal neuronal damage. In this study, alginate microcapsules containing genetically modified allogeneic mesenchymal stem cells producing the neuroprotective glucagon-like peptide-1 (GLP-1) were implanted. Three years later, the patient presented with aphasia and a focal seizure due to a new left frontal intracerebral hemorrhage. Angiography revealed a de novo left frontal AVM. The development of an AVM within a period of 3 years after implantation of the glucagon-like peptide-1-secreting mesenchymal stem cells suggests a possible relationship. This case exemplifies that further investigations are necessary to assess the safety of genetically modified cell lines for local biological drug delivery in the brain.

  20. Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve: viscoelasticity characterization

    Science.gov (United States)

    Lv, Xue-man; Liu, Yan; Wu, Fei; Yuan, Yi; Luo, Min

    2016-01-01

    The optic nerve is a viscoelastic solid-like biomaterial. Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury. We hypothesized that stress relaxation and creep properties of the optic nerve change after injury. More-over, human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal. To validate this hypothesis, a rabbit model of optic nerve injury was established using a clamp approach. At 7 days after injury, the vitreous body re-ceived a one-time injection of 50 μg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells. At 30 days after injury, stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly, with patho-logical changes in the injured optic nerve also noticeably improved. These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves, and thereby contributes to nerve recovery. PMID:27212930

  1. Brain stem tumors in children - therapeutic results in patients of the University Children's Hospital of Cracow in Poland

    International Nuclear Information System (INIS)

    Korab-Chrzanowska, E.; Bartoszewska, J.; Kwiatkowski, S.

    2005-01-01

    To analyse the treatment results achieved in children treated for brain stem tumours at one institution between the years 1990 and 2004. Material. 20 patients (10 girls, 10 boys) aged 2.8-15.6 years were treated for brain stem tumors at the University Children's Hospital of Cracow (UCHC) in the years 1990-2004. The tumour type was defined basing on imaging studies (CT, MRI), and, in the case of 7 patients, additionally basing on histopathological results. In the collected material the predominant tumor type was benign glioma, detected in 17 patients. Malignant gliomas were diagnosed in 3 children. 7 children were treated by radiotherapy only. Surgical procedures and adjuvant radiotherapy were employed in 3 patients. 6 children underwent radiotherapy and chemotherapy. Combined surgical treatment followed by radiotherapy and chemotherapy was employed in 4 patients. Of the 20 patients 6 have died (30%). The surviving group (70%) includes 1 patient with tumor progression (5%), 5 - with stable tumors (25%), and 8 (40%) - with tumor regression. The probability of three-year overall survival for the entire group as calculated by the Kaplan-Meier method was 70% while the probability of three-year progression-free survival was 65%. Conclusions. Diffuse brain stem tumors, mostly those involving the pons, and malignant gliomas have poor prognosis. In the presented material we achieved the best treatment results in patients with exophytic or focal tumors, treated surgically with adjuvant therapy. (author)

  2. Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve: viscoelasticity characterization

    Directory of Open Access Journals (Sweden)

    Xue-man Lv

    2016-01-01

    Full Text Available The optic nerve is a viscoelastic solid-like biomaterial. Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury. We hypothesized that stress relaxation and creep properties of the optic nerve change after injury. More-over, human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal. To validate this hypothesis, a rabbit model of optic nerve injury was established using a clamp approach. At 7 days after injury, the vitreous body re-ceived a one-time injection of 50 µg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells. At 30 days after injury, stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly, with patho-logical changes in the injured optic nerve also noticeably improved. These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves, and thereby contributes to nerve recovery.

  3. Slice accelerated gradient-echo spin-echo dynamic susceptibility contrast imaging with blipped CAIPI for increased slice coverage.

    Science.gov (United States)

    Eichner, Cornelius; Jafari-Khouzani, Kourosh; Cauley, Stephen; Bhat, Himanshu; Polaskova, Pavlina; Andronesi, Ovidiu C; Rapalino, Otto; Turner, Robert; Wald, Lawrence L; Stufflebeam, Steven; Setsompop, Kawin

    2014-09-01

    To improve slice coverage of gradient echo spin echo (GESE) sequences for dynamic susceptibility contrast (DSC) MRI using a simultaneous-multiple-slice (SMS) method. Data were acquired on 3 Tesla (T) MR scanners with a 32-channel head coil. To evaluate use of SMS for DSC, an SMS GESE sequence with two-fold slice coverage and same temporal sampling was compared with a standard GESE sequence, both with 2× in-plane acceleration. A signal to noise ratio (SNR) comparison was performed on one healthy subject. Additionally, data with Gadolinium injection were collected on three patients with glioblastoma using both sequences, and perfusion analysis was performed on healthy tissues as well as on tumor. Retained SNR of SMS DSC is 90% for a gradient echo (GE) and 99% for a spin echo (SE) acquisition, compared with a standard acquisition without slice acceleration. Comparing cerebral blood volume maps, it was observed that the results of standard and SMS acquisitions are comparable for both GE and SE images. Two-fold slice accelerated DSC MRI achieves similar SNR and perfusion metrics as a standard acquisition, while allowing a significant increase in slice coverage of the brain. The results also point to a possibility to improve temporal sampling rate, while retaining the same slice coverage. Copyright © 2013 Wiley Periodicals, Inc.

  4. Trafficking of astrocytic vesicles in hippocampal slices

    International Nuclear Information System (INIS)

    Potokar, Maja; Kreft, Marko; Lee, So-Young; Takano, Hajime; Haydon, Philip G.; Zorec, Robert

    2009-01-01

    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.

  5. The time slice system

    International Nuclear Information System (INIS)

    DeWitt, J.

    1990-01-01

    We have designed a fast readout system for silicon microstrip detectors which could be used at HERA, LHC, and SSC. The system consists of an analog amplifier-comparator chip (AACC) and a digital time slice chip (DTSC). The analog ship is designed in dielectric isolated bipolar technology for low noise and potential radiation hardness. The DTSC is built in CMOS for low power use and high circuit density. The main implementation aims are low power consumption and compactness. The architectural goal is automatic data reduction, and ease of external interface. The pipelining of event information is done digitally in the DTSC. It has a 64 word deep level 1 buffer acting as a FIFO, and a 16 word deep level 2 buffer acting as a dequeue. The DTSC also includes an asynchronous bus interface. We are first building a scaled up (100 μm instead of 25 μm pitch) and slower (10 MHz instead of 60 MHz) version in 2 μm CMOS and plan to test the principle of operation of this system in the Leading Proton Spectrometer (LPS) of the ZEUS detector at HERA. Another very important development will be tested there: the radiation hardening of the chips. We have started a collaboration with a rad-hard foundry and with Los Alamos National Laboratories to test and evaluate rad-hard processes and the final rad-hard product. Initial data are very promising, because radiation resistance of up to many Mrad have been achieved. (orig.)

  6. Scientific and ethical issues related to stem cell research and interventions in neurodegenerative disorders of the brain.

    Science.gov (United States)

    Barker, Roger A; de Beaufort, Inez

    2013-11-01

    Should patients with Parkinson's disease participate in research involving stem cell treatments? Are induced pluripotent stem cells (iPSC) the ethical solution to the moral issues regarding embryonic stem cells? How can we adapt trial designs to best assess small numbers of patients in receipt of invasive experimental therapies? Over the last 20 years there has been a revolution in our ability to make stem cells from different sources and use them for therapeutic gain in disorders of the brain. These cells, which are defined by their capacity to proliferate indefinitely as well as differentiate into selective phenotypic cell types, are viewed as being especially attractive for studying disease processes and for grafting in patients with chronic incurable neurodegenerative disorders of the CNS such as Parkinson's disease (PD). In this review we briefly discuss and summarise where our understanding of stem cell biology has taken us relative to the clinic and patients, before dealing with some of the major ethical issues that work of this nature generates. This includes issues to do with the source of the cells, their ownership and exploitation along with questions about patient recruitment, consent and trial design when they translate to the clinic for therapeutic use. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Early morphologic and spectroscopic magnetic resonance in severe traumatic brain injuries can detect "invisible brain stem damage" and predict "vegetative states".

    Science.gov (United States)

    Carpentier, Alexandre; Galanaud, Damien; Puybasset, Louis; Muller, Jean-Charles; Lescot, Thomas; Boch, Anne-Laure; Riedl, Valentin; Riedl, Vincent; Cornu, Philippe; Coriat, Pierre; Dormont, Didier; van Effenterre, Remy

    2006-05-01

    A precise evaluation of the brain damage in the first days of severe traumatic brain injured (TBI) patients is still uncertain despite numerous available cerebral evaluation methods and imaging. In 5-10% of severe TBI patients, clinicians remain concerned with prolonged coma and long-term marked cognitive impairment unexplained by normal morphological T2 star, flair, and diffusion magnetic resonance imaging (MRI). For this reason, we prospectively assessed the potential value of magnetic resonance spectroscopy (MRS) of the brain stem to evaluate the functionality of the consciousness areas. Forty consecutive patients with severe TBI were included. Single voxel proton MRS of the brain stem and morphological MRI of the whole brain were performed at day 17.5 +/- 6.4. Disability Rating Scale and Glasgow Outcome Scale (GOS) were evaluated at 18 months posttrauma. MRS appeared to be a reliable tool in the exploration of brainstem metabolism in TBI. Three different spectra were observed (normal, cholinergic reaction, or neuronal damage) allowing an evaluation of functional damage. MRS disturbances were not correlated with anatomical MRI lesions suggesting that the two techniques are strongly complementarity. In two GOS 2 vegetative patients with normal morphological MRI, MRS detected severe functional damage of the brainstem (NAA/Cr brain stem damage." MRI and MRS taken separately could not distinguish patients GOS 3 (n = 7) from GOS 1-2 (n = 11) and GOS 4-5 (n = 20). However, a principal component analysis of combined MRI and MRS data enabled a clear-cut separation between GOS 1-2, GOS 3, and GOS 4-5 patients with no overlap between groups. This study showed that combined MRI and MRS provide a reliable evaluation of patients presenting in deep coma, specially when there are insufficient MRI lesions of the consciousness pathways to explain their status. In the first few days post-trauma metabolic (brainstem spectroscopy) and morphological (T2 star and Flair) MRI studies

  8. The role of CXC chemokine ligand (CXCL)12-CXC chemokine receptor (CXCR)4 signalling in the migration of neural stem cells towards a brain tumour

    NARCIS (Netherlands)

    van der Meulen, A. A. E.; Biber, K.; Lukovac, S.; Balasubramaniyan, V.; den Dunnen, W. F. A.; Boddeke, H. W. G. M.; Mooij, J. J. A.

    2009-01-01

    Aims: It has been shown that neural stem cells (NSCs) migrate towards areas of brain injury or brain tumours and that NSCs have the capacity to track infiltrating tumour cells. The possible mechanism behind the migratory behaviour of NSCs is not yet completely understood. As chemokines are involved

  9. Trimethyltin (TMT) neurotoxicity in organotypic rat hippocampal slice cultures

    DEFF Research Database (Denmark)

    Noraberg, J; Gramsbergen, J B; Fonnum, F

    1998-01-01

    The neurotoxic effects of trimethyltin (TMT) on the hippocampus have been extensively studied in vivo. In this study, we examined whether the toxicity of TMT to hippocampal neurons could be reproduced in organotypic brain slice cultures in order to test the potential of this model for neurotoxico...

  10. Variation of radiation-sensitivity of neural stem and progenitor cell populations within the developing mouse brain

    International Nuclear Information System (INIS)

    Etienne, Olivier; Roque, Telma; Haton, Celine; Boussin, Francois D.

    2012-01-01

    We investigated the DNA damage response (DDR) of fetal neural stem and progenitor cells (NSPC), since exposure to ionizing radiation can severely impair the brain development. We compared apoptosis induction in the dorsal tel-encephalon and the lateral ganglionic eminences (LGE) of mouse embryos after an in utero irradiation. We used two thymidine analogs, together with the physical position of nuclei within brain structures, to determine the fate of irradiated NSPC. NSPC did not activate an apparent protein 21(p21)- dependent G1/S checkpoint within the LGE as their counterparts within the dorsal tel-encephalon. However, the levels of radiation induced apoptosis differed between the two tel-encephalic regions, due to the high radiation sensitivity of intermediate progenitors of the LGE. Besides radial glial cells, that function as neural stem cells, were more resistant and were reoriented toward self-renewing within hours following irradiation. The lack of the p21-dependent-cell cycle arrest at the G1/S transition appears to be a general feature of NSPC in the developing brain. However, we found variation of radiation response in function of the types of NSPC. Factors involved in DDR and those involved in the regulation of neurogenesis are intricately linked in determining the cell fate after irradiations. (authors)

  11. Human Neural Stem Cell Transplantation-Mediated Alteration of Microglial/Macrophage Phenotypes after Traumatic Brain Injury.

    Science.gov (United States)

    Gao, Junling; Grill, Raymond J; Dunn, Tiffany J; Bedi, Supinder; Labastida, Javier Allende; Hetz, Robert A; Xue, Hasen; Thonhoff, Jason R; DeWitt, Douglas S; Prough, Donald S; Cox, Charles S; Wu, Ping

    2016-10-01

    Neural stem cells (NSCs) promote recovery from brain trauma, but neuronal replacement is unlikely the sole underlying mechanism. We hypothesize that grafted NSCs enhance neural repair at least partially through modulating the host immune response after traumatic brain injury (TBI). C57BL/6 mice were intracerebrally injected with primed human NSCs (hNSCs) or vehicle 24 h after a severe controlled cortical impact injury. Six days after transplantation, brain tissues were collected for Western blot and immunohistochemical analyses. Observations included indicators of microglia/macrophage activation, M1 and M2 phenotypes, axonal injury detected by amyloid precursor protein (APP), lesion size, and the fate of grafted hNSCs. Animals receiving hNSC transplantation did not show significant decreases of brain lesion volumes compared to transplantation procedures with vehicle alone, but did show significantly reduced injury-dependent accumulation of APP. Furthermore, intracerebral transplantation of hNSCs reduced microglial activation as shown by a diminished intensity of Iba1 immunostaining and a transition of microglia/macrophages toward the M2 anti-inflammatory phenotype. The latter was represented by an increase in the brain M2/M1 ratio and increases of M2 microglial proteins. These phenotypic switches were accompanied by the increased expression of anti-inflammatory interleukin-4 receptor α and decreased proinflammatory interferon-γ receptor β. Finally, grafted hNSCs mainly differentiated into neurons and were phagocytized by either M1 or M2 microglia/macrophages. Thus, intracerebral transplantation of primed hNSCs efficiently leads host microglia/macrophages toward an anti-inflammatory phenotype that presumably contributes to stem cell-mediated neuroprotective effects after severe TBI in mice.

  12. CD44v6 regulates growth of brain tumor stem cells partially through the AKT-mediated pathway.

    Directory of Open Access Journals (Sweden)

    Mayumi Jijiwa

    Full Text Available Identification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC has gained substantial attention by scientists and physicians. However, the mechanism of tumor initiation and proliferation is still poorly understood. CD44 is a cell surface protein linked to tumorigenesis in various cancers. In particular, one of its variant isoforms, CD44v6, is associated with several cancer types. To date its expression and function in BTSC is yet to be identified. Here, we demonstrate the presence and function of the variant form 6 of CD44 (CD44v6 in BTSC of a subset of glioblastoma multiforme (GBM. Patients with CD44(high GBM exhibited significantly poorer prognoses. Among various variant forms, CD44v6 was the only isoform that was detected in BTSC and its knockdown inhibited in vitro growth of BTSC from CD44(high GBM but not from CD44(low GBM. In contrast, this siRNA-mediated growth inhibition was not apparent in the matched GBM sample that does not possess stem-like properties. Stimulation with a CD44v6 ligand, osteopontin (OPN, increased expression of phosphorylated AKT in CD44(high GBM, but not in CD44(low GBM. Lastly, in a mouse spontaneous intracranial tumor model, CD44v6 was abundantly expressed by tumor precursors, in contrast to no detectable CD44v6 expression in normal neural precursors. Furthermore, overexpression of mouse CD44v6 or OPN, but not its dominant negative form, resulted in enhanced growth of the mouse tumor stem-like cells in vitro. Collectively, these data indicate that a subset of GBM expresses high CD44 in BTSC, and its growth may depend on CD44v6/AKT pathway.

  13. Motor-Evoked Potential Confirmation of Functional Improvement by Transplanted Bone Marrow Mesenchymal Stem Cell in the Ischemic Rat Brain

    Science.gov (United States)

    Jang, Dong-Kyu; Park, Sang-In; Han, Young-Min; Jang, Kyung-Sool; Park, Moon-Seo; Chung, Young-An; Kim, Min-Wook; Maeng, Lee-So; Huh, Pil-Woo; Yoo, Do-Sung; Jung, Seong-Whan

    2011-01-01

    This study investigated the effect of bone marrow mesenchymal stem cells (BMSCs) on the motor pathway in the transient ischemic rat brain that were transplanted through the carotid artery, measuring motor-evoked potential (MEP) in the four limbs muscle and the atlantooccipital membrane, which was elicited after monopolar and bipolar transcortical stimulation. After monopolar stimulation, the latency of MEP was significantly prolonged, and the amplitude was less reduced in the BMSC group in comparison with the control group (P < .05). MEPs induced by bipolar stimulation in the left forelimb could be measured in 40% of the BMSC group and the I wave that was not detected in the control group was also detected in 40% of the BMSC group. Our preliminary results imply that BMSCs transplanted to the ischemic rat brain mediate effects on the functional recovery of the cerebral motor cortex and the motor pathway. PMID:21772790

  14. Motor-Evoked Potential Confirmation of Functional Improvement by Transplanted Bone Marrow Mesenchymal Stem Cell in the Ischemic Rat Brain

    Directory of Open Access Journals (Sweden)

    Dong-Kyu Jang

    2011-01-01

    Full Text Available This study investigated the effect of bone marrow mesenchymal stem cells (BMSCs on the motor pathway in the transient ischemic rat brain that were transplanted through the carotid artery, measuring motor-evoked potential (MEP in the four limbs muscle and the atlantooccipital membrane, which was elicited after monopolar and bipolar transcortical stimulation. After monopolar stimulation, the latency of MEP was significantly prolonged, and the amplitude was less reduced in the BMSC group in comparison with the control group (<.05. MEPs induced by bipolar stimulation in the left forelimb could be measured in 40% of the BMSC group and the I wave that was not detected in the control group was also detected in 40% of the BMSC group. Our preliminary results imply that BMSCs transplanted to the ischemic rat brain mediate effects on the functional recovery of the cerebral motor cortex and the motor pathway.

  15. Rapid whole-brain resting-state fMRI at 3 T : Efficiency-optimized three-dimensional EPI versus repetition time-matched simultaneous-multi-slice EPI

    NARCIS (Netherlands)

    Stirnberg, Rüdiger; Huijbers, Willem; Brenner, Daniel; Poser, Benedikt; Breteler, Monique; Stoecker, Tony

    2017-01-01

    State-of-the-art simultaneous-multi-slice (SMS-)EPI and 3D-EPI share several properties that benefit functional MRI acquisition. Both sequences employ equivalent parallel imaging undersampling with controlled aliasing to achieve high temporal sampling rates. As a volumetric imaging sequence, 3D-EPI

  16. Rapid whole-brain resting-state fMRI at 3 T : Efficiency-optimized three-dimensional EPI versus repetition time-matched simultaneous-multi-slice EPI

    NARCIS (Netherlands)

    Stirnberg, Rüdiger; Huijbers, Willem; Brenner, Daniel; Poser, Benedikt A; Breteler, Monique; Stöcker, Tony

    2017-01-01

    State-of-the-art simultaneous-multi-slice (SMS-)EPI and 3D-EPI share several properties that benefit functional MRI acquisition. Both sequences employ equivalent parallel imaging undersampling with controlled aliasing to achieve high temporal sampling rates. As a volumetric imaging sequence, 3D-EPI

  17. Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells.

    Science.gov (United States)

    Suzuki, Ikuo K; Vanderhaeghen, Pierre

    2015-09-15

    The human brain is arguably the most complex structure among living organisms. However, the specific mechanisms leading to this complexity remain incompletely understood, primarily because of the poor experimental accessibility of the human embryonic brain. Over recent years, technologies based on pluripotent stem cells (PSCs) have been developed to generate neural cells of various types. While the translational potential of PSC technologies for disease modeling and/or cell replacement therapies is usually put forward as a rationale for their utility, they are also opening novel windows for direct observation and experimentation of the basic mechanisms of human brain development. PSC-based studies have revealed that a number of cardinal features of neural ontogenesis are remarkably conserved in human models, which can be studied in a reductionist fashion. They have also revealed species-specific features, which constitute attractive lines of investigation to elucidate the mechanisms underlying the development of the human brain, and its link with evolution. © 2015. Published by The Company of Biologists Ltd.

  18. A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources

    Science.gov (United States)

    Lippmann, Ethan S.; Al-Ahmad, Abraham; Azarin, Samira M.; Palecek, Sean P.; Shusta, Eric V.

    2014-02-01

    Blood-brain barrier (BBB) models are often used to investigate BBB function and screen brain-penetrating therapeutics, but it has been difficult to construct a human model that possesses an optimal BBB phenotype and is readily scalable. To address this challenge, we developed a human in vitro BBB model comprising brain microvascular endothelial cells (BMECs), pericytes, astrocytes and neurons derived from renewable cell sources. First, retinoic acid (RA) was used to substantially enhance BBB phenotypes in human pluripotent stem cell (hPSC)-derived BMECs, particularly through adherens junction, tight junction, and multidrug resistance protein regulation. RA-treated hPSC-derived BMECs were subsequently co-cultured with primary human brain pericytes and human astrocytes and neurons derived from human neural progenitor cells (NPCs) to yield a fully human BBB model that possessed significant tightness as measured by transendothelial electrical resistance (~5,000 Ωxcm2). Overall, this scalable human BBB model may enable a wide range of neuroscience studies.

  19. Overexpression of HIF-1α in mesenchymal stem cells contributes to repairing hypoxic-ischemic brain damage in rats.

    Science.gov (United States)

    Lin, Deju; Zhou, Liping; Wang, Biao; Liu, Lizhen; Cong, Li; Hu, Chuanqin; Ge, Tingting; Yu, Qin

    2017-01-01

    Preclinical researches on mesenchymal stem cells (MSCs) transplantation, which is used to treat hypoxic-ischemic (HI) brain damage, have received inspiring achievements. However, the insufficient migration of active cells to damaged tissues has limited their potential therapeutic effects. There are some evidences that hypoxia inducible factor-1 alpha (HIF-1α) promotes the viability and migration of the cells. Here, we aim to investigate whether overexpression of HIF-1α in MSCs could improve the viability and migration capacity of cells, and its therapeutic efficiency on HI brain damage. In the study, MSCs with HIF-1α overexpression was achieved by recombinant lentiviral vector and transplanted to the rats subsequent to HI. Our data indicated that overexpression of HIF-1α promoted the viability and migration of MSCs, HIF-1α overexpressed MSCs also had a stronger therapeutic efficiency on HI brain damaged treatment by mitigating the injury on behavioral and histological changes evoked by HI insults, accompanied with more MSCs migrating to cerebral damaged area. This study demonstrated that HIF-1α overexpression could increase the MSCs' therapeutic efficiency in HI and the promotion of the cells' directional migration to cerebral HI area by overexpression may be responsible for it, which showed that transplantation of MSCs with HIF-1α overexpression is an attractive therapeutic option to treat HI-induced brain injury in the future. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  20. Clinical significance of measurement of serum NSE, NPY and TNF-α levels in pediatric patients with hand-foot and mouth disease complicated with brain stem encephalitis

    International Nuclear Information System (INIS)

    Zhao Peiguang

    2010-01-01

    Objective: To explore the clinical significance of changes of serum NSE, NPY and TNF-α levels in pediatric patients with hand-foot and mouth disease complicated with brain stem encephalitis. Methods: Serum NSE, NPY and TNF-α levels were determined with RIA in 34 pediatric patients with hand-foot and mouth disease complicated with brain stem encephalitis and 30 controls. Results: The serum NSE, NPY and TNF-α levels in the patients were significantly higher than those in controls (P<0.01), Serum TNF-α and NSE, NPY levels were mutually positively correlated (r=0.4716, 0.5184, P<0.01). Conclusion: Detection of NSE, NPY and TNF-α levels was helpful for the prediction of treatment efficacy in patients with hand-foot and mouth disease complicated with brain stem encephalitis. (authors)

  1. A case of hypertrophic olivary degeneration after resection of cavernomas of the brain stem and review of the literature

    Directory of Open Access Journals (Sweden)

    Zhang M

    2015-10-01

    Full Text Available Meng Zhang, Gengfan Ye, Lin Deng, Shuo Xu, Yunyan Wang Department of Neurosurgery, Qi Lu Hospital, Shandong University, Jinan, People’s Republic of China Abstract: Hypertrophic olivary degeneration is a transsynaptic form of degeneration, which is also a result of primary or secondary lesion and can damage the dento-rubro-olivary pathway. The dento-rubro-olivary pathway was first described by Guillain and Mollaret and is referred to as “the triangle of Guillain and Mollaret”. Multiple factors can destroy the dento-rubro-olivary pathway, such as surgical operation, hemorrhage, tumor, trauma, inflammation, demyelination, degeneration, and radiation damage. All of the above factors can result in delayed hypertrophic olivary degeneration. Articles related to this disease cover etiology, clinical presentation, pathology changes, etc. However, to our knowledge, there has been no literature reporting the use of diffusion tensor imaging and diffusion tensor tractography to improve the diagnosis of hypertrophic olivary degeneration following resection of cavernomas in the brain stem. Herein, we report a case who was diagnosed with hypertrophic olivary degeneration following resection of cavernomas of the brain stem, verify the significance of diffusion tensor imaging and diffusion tensor tractography, and review previous literature. The development of imageology promotes and improves hypertrophic olivary degeneration diagnosis and differential diagnosis. Keywords: HOD, diffusion tensor imaging, diffusion tensor tractography

  2. Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach.

    Science.gov (United States)

    Nih, Lina R; Moshayedi, Pouria; Llorente, Irene L; Berg, Andrew R; Cinkornpumin, Jessica; Lowry, William E; Segura, Tatiana; Carmichael, S Thomas

    2017-02-01

    This article presents data related to the research article "Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain" (P. Moshayedi, L.R. Nih, I.L. Llorente, A.R. Berg, J. Cinkornpumin, W.E. Lowry et al., 2016) [1] and focuses on the biocompatibility aspects of the hydrogel, including its stiffness and the inflammatory response of the transplanted organ. We have developed an injectable hyaluronic acid (HA)-based hydrogel for stem cell culture and transplantation, to promote brain tissue repair after stroke. This 3D biomaterial was engineered to bind bioactive signals such as adhesive motifs, as well as releasing growth factors while supporting cell growth and tissue infiltration. We used a Design of Experiment approach to create a complex matrix environment in vitro by keeping the hydrogel platform and cell type constant across conditions while systematically varying peptide motifs and growth factors. The optimized HA hydrogel promoted survival of encapsulated human induced pluripotent stem cell derived-neural progenitor cells (iPS-NPCs) after transplantation into the stroke cavity and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. The highlights of this article include: (1) Data of cell and bioactive signals addition on the hydrogel mechanical properties and growth factor diffusion, (2) the use of a design of Experiment (DOE) approach (M.W. 2 Weible and T. Chan-Ling, 2007) [2] to select multi-factorial experimental conditions, and (3) Inflammatory response and cell survival after transplantation.

  3. Magnetic Resonance Imaging of Ferumoxytol-Labeled Human Mesenchymal Stem Cells in the Mouse Brain.

    Science.gov (United States)

    Lee, Na Kyung; Kim, Hyeong Seop; Yoo, Dongkyeom; Hwang, Jung Won; Choi, Soo Jin; Oh, Wonil; Chang, Jong Wook; Na, Duk L

    2017-02-01

    The success of stem cell therapy is highly dependent on accurate delivery of stem cells to the target site of interest. Possible ways to track the distribution of MSCs in vivo include the use of reporter genes or nanoparticles. The U.S. Food and Drug Administration (FDA) has approved ferumoxytol (Feraheme® [USA], Rienso® [UK]) as a treatment for iron deficiency anemia. Ferumoxytol is an ultrasmall superparamagnetic iron oxide nanoparticle (USPIO) that has recently been used to track the fate of transplanted cells using magnetic resonance imaging (MRI). The major objectives of this study were to demonstrate the feasibility of labeling hUCB-MSCs with ferumoxytol and to observe, through MRI, the engraftment of ferumoxytol-labeled human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) delivered via stereotactic injection into the hippocampi of a transgenic mouse model of familial Alzheimer's disease (5XFAD). Ferumoxytol had no toxic effects on the viability or stemness of hUCB-MSCs when assessed in vitro. Through MRI, hypointense signals were discernible at the site where ferumoxytol-labeled human MSCs were injected. Iron-positive areas were also observed in the engrafted hippocampi. The results from this study support the use of nanoparticle labeling to monitor transplanted MSCs in real time as a follow-up for AD stem cell therapy in the clinical field.

  4. IL-6 deficiency leads to reduced metallothionein-I+II expression and increased oxidative stress in the brain stem after 6-aminonicotinamide treatment

    DEFF Research Database (Denmark)

    Penkowa, M; Hidalgo, J

    2000-01-01

    in brain stem gray matter areas and BM toxicity. In both normal and genetically IL-6-deficient mice (IL-6 knockout (IL-6KO) mice), the extent of astroglial degeneration/cell death in the brain stem was similar as determined from disappearance of GFAP immunoreactivity. In 6-AN-injected normal mice reactive......We examined the effects of interleukin-6 (IL-6) deficiency on brain inflammation and the accompanying bone marrow (BM) leukopoiesis and spleen immune reaction after systemic administration of a niacin antagonist, 6-aminonicotinamide (6-AN), which causes both astroglial degeneration/cell death...... tyrosine and malondialdehyde, was increased by 6-AN to a greater extent in IL-6KO mice. The blood-brain barrier to albumin was only disrupted in 6-AN-injected normal mice, which likely is due to the substantial migration of blood-derived inflammatory cells into the CNS. The present results demonstrate...

  5. Neural stem cells and neuro/gliogenesis in the central nervous system: understanding the structural and functional plasticity of the developing, mature, and diseased brain.

    Science.gov (United States)

    Yamaguchi, Masahiro; Seki, Tatsunori; Imayoshi, Itaru; Tamamaki, Nobuaki; Hayashi, Yoshitaka; Tatebayashi, Yoshitaka; Hitoshi, Seiji

    2016-05-01

    Neurons and glia in the central nervous system (CNS) originate from neural stem cells (NSCs). Knowledge of the mechanisms of neuro/gliogenesis from NSCs is fundamental to our understanding of how complex brain architecture and function develop. NSCs are present not only in the developing brain but also in the mature brain in adults. Adult neurogenesis likely provides remarkable plasticity to the mature brain. In addition, recent progress in basic research in mental disorders suggests an etiological link with impaired neuro/gliogenesis in particular brain regions. Here, we review the recent progress and discuss future directions in stem cell and neuro/gliogenesis biology by introducing several topics presented at a joint meeting of the Japanese Association of Anatomists and the Physiological Society of Japan in 2015. Collectively, these topics indicated that neuro/gliogenesis from NSCs is a common event occurring in many brain regions at various ages in animals. Given that significant structural and functional changes in cells and neural networks are accompanied by neuro/gliogenesis from NSCs and the integration of newly generated cells into the network, stem cell and neuro/gliogenesis biology provides a good platform from which to develop an integrated understanding of the structural and functional plasticity that underlies the development of the CNS, its remodeling in adulthood, and the recovery from diseases that affect it.

  6. Regulating the balance between symmetric and asymmetric stem cell division in the developing brain.

    Science.gov (United States)

    Egger, Boris; Gold, Katrina S; Brand, Andrea H

    2011-01-01

    Stem cells proliferate through symmetric division or self-renew through asymmetric division whilst generating differentiating cell types. The balance between symmetric and asymmetric division requires tight control to either expand a stem cell pool or to generate cell diversity. In the Drosophila optic lobe, symmetrically dividing neuroepithelial cells transform into asymmetrically dividing neuroblasts. The switch from neuroepithelial cells to neuroblasts is triggered by a proneural wave that sweeps across the neuroepithelium. Here we review recent findings showing that the orchestrated action of the Notch, EGFR, Fat-Hippo, and JAK/STAT signalling pathways controls the progression of the proneural wave and the sequential transition from symmetric to asymmetric division. The neuroepithelial to neuroblast transition in the optic lobe bears many similarities to the switch from neuroepithelial cell to radial glial cell in the developing mammalian cerebral cortex. The Notch signalling pathway has a similar role in the transition from proliferating to differentiating stem cell pools in the developing vertebrate retina and in the neural tube. Therefore, findings in the Drosophila optic lobe provide insights into the transitions between proliferative and differentiative division in the stem cell pools of higher organisms.

  7. Severe encephalopathy after high-dose chemotherapy with autologous stem cell support for brain tumours

    NARCIS (Netherlands)

    van den Berkmortel, F.; Gidding, C.; de Kanter, M.; Punt, C. J. A.

    2006-01-01

    Recurrent medulloblastoma carries a poor prognosis. Long-term survival has been obtained with high-dose chemotherapy with autologous stem cell transplantation and secondary irradiation. A 21-year-old woman with recurrent medulloblastoma after previous chemotherapy and radiotherapy is presented. The

  8. Neural Stem Cell Delivery of Therapeutic Antibodies to Treat Breast Cancer Brain Metastases

    Science.gov (United States)

    2009-10-01

    deliver antineoplastic gene products directly to the tumor-producing cells. This potential therapeutic strategy may safely eradicate tumor-producing cells...surgical manipulation since activated microglial cells were never detected in the same brain regions of animals injected with medium alone (Fig. 4B-a right...steps of metastatic invasion remain to be elucidated. Unraveling the underlying mechanisms in vivo might lead to targeted manipulation of the brain

  9. In vivo Brain Delivery of v-myc Overproduced Human Neural Stem Cells via the Intranasal Pathway: Tumor Characteristics in the Lung of a Nude Mouse

    Directory of Open Access Journals (Sweden)

    Eun Seong Lee

    2015-01-01

    Full Text Available We aimed to monitor the successful brain delivery of stem cells via the intranasal route and to observe the long-term consequence of the immortalized human neural stem cells in the lungs of a nude mouse model. Stably immortalized HB1.F3 human neural stem cells with firefly luciferase gene (F3-effluc were intranasally delivered to BALB/c nude mice. Bioluminescence images were serially acquired until 41 days in vivo and at 4 hours and 41 days ex vivo after intranasal delivery. Lungs were evaluated by histopathology. After intranasal delivery of F3-effluc cells, the intense in vivo signals were detected in the nasal area, migrated toward the brain areas at 4 hours (4 of 13, 30.8%, and gradually decreased for 2 days. The brain signals were confirmed by ex vivo imaging (2 of 4, 50%. In the mice with initial lung signals (4 of 9, 44.4%, the lung signals disappeared for 5 days but reappeared 2 weeks later. The intense lung signals were confirmed to originate from the tumors in the lungs formed by F3-effluc cells by ex vivo imaging and histopathology. We propose that intranasal delivery of immortalized stem cells should be monitored for their successful delivery to the brain and their tumorigenicity longitudinally.

  10. Mesenchymal stem cells induce T-cell tolerance and protect the preterm brain after global hypoxia-ischemia.

    Directory of Open Access Journals (Sweden)

    Reint K Jellema

    Full Text Available Hypoxic-ischemic encephalopathy (HIE in preterm infants is a severe disease for which no curative treatment is available. Cerebral inflammation and invasion of activated peripheral immune cells have been shown to play a pivotal role in the etiology of white matter injury, which is the clinical hallmark of HIE in preterm infants. The objective of this study was to assess the neuroprotective and anti-inflammatory effects of intravenously delivered mesenchymal stem cells (MSC in an ovine model of HIE. In this translational animal model, global hypoxia-ischemia (HI was induced in instrumented preterm sheep by transient umbilical cord occlusion, which closely mimics the clinical insult. Intravenous administration of 2 x 10(6 MSC/kg reduced microglial proliferation, diminished loss of oligodendrocytes and reduced demyelination, as determined by histology and Diffusion Tensor Imaging (DTI, in the preterm brain after global HI. These anti-inflammatory and neuroprotective effects of MSC were paralleled by reduced electrographic seizure activity in the ischemic preterm brain. Furthermore, we showed that MSC induced persistent peripheral T-cell tolerance in vivo and reduced invasion of T-cells into the preterm brain following global HI. These findings show in a preclinical animal model that intravenously administered MSC reduced cerebral inflammation, protected against white matter injury and established functional improvement in the preterm brain following global HI. Moreover, we provide evidence that induction of T-cell tolerance by MSC might play an important role in the neuroprotective effects of MSC in HIE. This is the first study to describe a marked neuroprotective effect of MSC in a translational animal model of HIE.

  11. Pivotal Role of Brain-Derived Neurotrophic Factor Secreted by Mesenchymal Stem Cells in Severe Intraventricular Hemorrhage in Newborn Rats.

    Science.gov (United States)

    Ahn, So Yoon; Chang, Yun Sil; Sung, Dong Kyung; Sung, Se In; Ahn, Jee-Yin; Park, Won Soon

    2017-01-24

    Mesenchymal stem cell (MSC) transplantation protects against neonatal severe intraventricular hemorrhage (IVH)-induced brain injury by a paracrine rather than regenerative mechanism; however, the paracrine factors involved and their roles have not yet been delineated. This study aimed to identify the paracrine mediator(s) and to determine their role in mediating the therapeutic effects of MSCs in severe IVH. We first identified significant upregulation of brain-derived neurotrophic factor (BDNF) in MSCs compared with fibroblasts, in both DNA and antibody microarrays, after thrombin exposure. We then knocked down BDNF in MSCs by transfection with small interfering (si)RNA specific for human BDNF. The therapeutic effects of MSCs with or without BDNF knockdown were evaluated in vitro in rat neuronal cells challenged with thrombin, and in vivo in newborn Sprague-Dawley rats by injecting 200 μl of blood on postnatal day 4 (P4), and transplanting MSCs (1 × 105 cells) intraventricularly on P6. siRNA-induced BDNF knockdown abolished the in vitro benefits of MSCs on thrombin-induced neuronal cell death. BDNF knockdown also abolished the in vivo protective effects against severe IVH-induced brain injuries such as the attenuation of posthemorrhagic hydrocephalus, impaired behavioral test performance, increased astrogliosis, increased number of TUNEL cells, ED-1+ cells, and inflammatory cytokines, and reduced myelin basic protein expression. Our data indicate that BDNF secreted by transplanted MSCs is one of the critical paracrine factors that play a seminal role in attenuating severe IVH-induced brain injuries in newborn rats.

  12. Effects of root and stem extracts of Asparagus cochinchinensis on biochemical indicators related to aging in the brain and liver of mice.

    Science.gov (United States)

    Xiong, Dasheng; Yu, Long-Xi; Yan, Xiao; Guo, Chunqiu; Xiong, Ying

    2011-01-01

    Asparagus cochinchinensis is a traditional Chinese medicine used for treating lung and spleen-related diseases. In this study, we compared the medicinal effects of A. cochinchinensis root and stem extracts on the activity of superoxide dismutase (SOD), the content of malonaldehyde (MDA) and total protein content in the brain, liver and plasma of mice. Polysaccharides and aqueous extracts of the roots significantly increased the spleen index and the SOD activity but reduced the MDA content and slowed down the aging process. In contrast, feeding with the stem extracts significantly reduced the SOD activity and increased the MDA accumulation in the brain and liver of mice, suggesting that the stem extracts may not be appropriate for treating aging-related diseases.

  13. Blindness, dancing extremities, and corpus callosum and brain stem involvement: an unusual presentation of fulminant subacute sclerosing panencephalitis.

    Science.gov (United States)

    Singhi, Pratibha; Saini, Arushi Gahlot; Sankhyan, Naveen; Gupta, Pankaj; Vyas, Sameer

    2015-01-01

    A 4-year-old girl presented with acute visual loss followed 2 weeks later with loss of speech and audition, fulminant neuroregression, and choreo-athetoid movements of extremities. Fundus showed bilateral chorioretinitis. Electroencephalography showed periodic complexes. Measles antibody titers were elevated in both serum and cerebrospinal fluid, consistent with subacute sclerosing panencephalitis. Neuroimaging showed discontiguous involvement of splenium of the corpus callosum and ventral pons with sparing of cortical white matter. Our case highlights the atypical clinical and radiologic presentations of subacute sclerosing panencephalitis. Pediatricians need to be aware that necrotizing chorioretinitis in a child and/or atypical brain stem changes could be the heralding feature of this condition in endemic countries. © The Author(s) 2014.

  14. Fatal injuries of the brain stem and/or upper cervical spinal cord in traffic accidents: nine autopsy cases.

    Science.gov (United States)

    Kondo, T; Saito, K; Nishigami, J; Ohshima, T

    1995-01-01

    Nine forensic autopsy cases were studied. All had injuries of the brain stem and/or upper cervical spinal cord due to traffic accidents. Among the nine subjects, eight were pedestrians and one was a left, front seat occupant of a vehicle. Examination of these 9 cases revealed that three had ponto-medullary avulsion, two had medullary avulsion and the other four had laceration of the upper cervical spinal cord. Atlanto-occipital dislocation was observed in five cases, and a ring fracture around the foramen magnum in the other two cases. Intraventricular haemorrhage, probably due to tears of the choroid plexus caused by hyperextension or hyperflexion of the head, was found in seven cases. In just one of these seven cases, both of the lateral ventricles were filled with dark red haemocoagulum. Hyperextension is considered to occur more commonly in road trauma cases where the victim is alcoholically intoxicated.

  15. Heme oxygenase-1 plays a pro-life role in experimental brain stem death via nitric oxide synthase I/protein kinase G signaling at rostral ventrolateral medulla

    Directory of Open Access Journals (Sweden)

    Dai Kuang-Yu

    2010-09-01

    Full Text Available Abstract Background Despite its clinical importance, a dearth of information exists on the cellular and molecular mechanisms that underpin brain stem death. A suitable neural substrate for mechanistic delineation on brain stem death resides in the rostral ventrolateral medulla (RVLM because it is the origin of a life-and-death signal that sequentially increases (pro-life and decreases (pro-death to reflect the advancing central cardiovascular regulatory dysfunction during the progression towards brain stem death in critically ill patients. The present study evaluated the hypothesis that heme oxygnase-1 (HO-1 may play a pro-life role as an interposing signal between hypoxia-inducible factor-1 (HIF-1 and nitric oxide synthase I (NOS I/protein kinase G (PKG cascade in RVLM, which sustains central cardiovascular regulatory functions during brain stem death. Methods We performed cardiovascular, pharmacological, biochemical and confocal microscopy experiments in conjunction with an experimental model of brain stem death that employed microinjection of the organophosphate insecticide mevinphos (Mev; 10 nmol bilaterally into RVLM of adult male Sprague-Dawley rats. Results Western blot analysis coupled with laser scanning confocal microscopy revealed that augmented HO-1 expression that was confined to the cytoplasm of RVLM neurons occurred preferentially during the pro-life phase of experimental brain stem death and was antagonized by immunoneutralization of HIF-1α or HIF-1β in RVLM. On the other hand, the cytoplasmic presence of HO-2 in RVLM neurons manifested insignificant changes during both phases. Furthermore, immunoneutralization of HO-1 or knockdown of ho-1 gene in RVLM blunted the augmented life-and-death signals exhibited during the pro-life phase. Those pretreatments also blocked the upregulated pro-life NOS I/PKG signaling without affecting the pro-death NOS II/peroxynitrite cascade in RVLM. Conclusions We conclude that transcriptional

  16. [Comparative study between auditory steady-state responses, auditory brain-stem responses and liminar tonal audiometry].

    Science.gov (United States)

    Martínez Fernández, Asunción; Alañón Fernández, Miguel Angel; Ayala Martínez, Luis Félix; Alvarez Alvarez, Ana Belén; Miranda León, María Teresa; Sainz Quevedo, Manuel

    2007-01-01

    Auditory steady-state responses (ASSR) using frequencies of modulation between 70-110 Hz are a new auditive exploration technique. The aim of the study was to evaluate the contribution of the ASSR to diagnostic of the audition. Different aportations of auditory steady-states responses (ASSR) and auditory brain-stem responses (ABR) to diagnostic of threshold of audition were studied Differences between these thresholds and thresholds obtained by liminar tonal audiometry (LTA) were studied too. Correlations between thresholds obtained by ASSR and LTA were studied. ASSR detected rest of audition that transients ABR did not detect. Differences about -13.750 dB HL (-5.209 to -22.291) and -13.250 dB HL (-7.337 to -19.163) were found between registered values for carriers of 500 and 1000 Hz and the thresholds by LTA for these carriers. Differences about 1.625 dB HL (-6.967 to 10.217) and -2.875 dB HL (-7.446 to 1.696) were found between estimations for the carries of 500 and 1000 Hz and thresholds by TLA. Statistically very significant (P=.01) coefficients of correlation were found between registered and estimated thresholds by ASSR for carrier of 500 and 1000 Hz and threshold by TLA for these frequencies. Auditory steady-state responses (ASSR) using frequencies of modulation between 70-110 Hz are a new auditive technique of exploration. This stimulus is more frequency-specific than clicks for auditory brain-stem responses (ABR). Response is not modificated by steady of consciousness. The technique is doublely objective. Thresholds obtained by ASSR permits to estimation of the audition threshold.

  17. Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure.

    Science.gov (United States)

    Cauley, Edmund; Wang, Xin; Dyavanapalli, Jhansi; Sun, Ke; Garrott, Kara; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Mendelowitz, David

    2015-10-01

    Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases. Copyright © 2015 the American Physiological Society.

  18. Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach

    Directory of Open Access Journals (Sweden)

    Lina R. Nih

    2017-02-01

    Full Text Available This article presents data related to the research article “Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain” (P. Moshayedi, L.R. Nih, I.L. Llorente, A.R. Berg, J. Cinkornpumin, W.E. Lowry et al., 2016 [1] and focuses on the biocompatibility aspects of the hydrogel, including its stiffness and the inflammatory response of the transplanted organ. We have developed an injectable hyaluronic acid (HA-based hydrogel for stem cell culture and transplantation, to promote brain tissue repair after stroke. This 3D biomaterial was engineered to bind bioactive signals such as adhesive motifs, as well as releasing growth factors while supporting cell growth and tissue infiltration. We used a Design of Experiment approach to create a complex matrix environment in vitro by keeping the hydrogel platform and cell type constant across conditions while systematically varying peptide motifs and growth factors. The optimized HA hydrogel promoted survival of encapsulated human induced pluripotent stem cell derived-neural progenitor cells (iPS-NPCs after transplantation into the stroke cavity and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. The highlights of this article include: (1 Data of cell and bioactive signals addition on the hydrogel mechanical properties and growth factor diffusion, (2 the use of a design of Experiment (DOE approach (M.W. 2 Weible and T. Chan-Ling, 2007 [2] to select multi-factorial experimental conditions, and (3 Inflammatory response and cell survival after transplantation.

  19. Quiescent Oct4+ Neural Stem Cells (NSCs) Repopulate Ablated Glial Fibrillary Acidic Protein+ NSCs in the Adult Mouse Brain.

    Science.gov (United States)

    Reeve, Rachel L; Yammine, Samantha Z; Morshead, Cindi M; van der Kooy, Derek

    2017-09-01

    Adult primitive neural stem cells (pNSCs) are a rare population of glial fibrillary acidic protein (GFAP) - Oct4 + cells in the mouse forebrain subependymal zone bordering the lateral ventricles that give rise to clonal neurospheres in leukemia inhibitory factor in vitro. pNSC neurospheres can be passaged to self-renew or give rise to GFAP + NSCs that form neurospheres in epidermal growth factor and fibroblast growth factor 2, which we collectively refer to as definitive NSCs (dNSCs). Label retention experiments using doxycycline-inducible histone-2B (H2B)-green fluorescent protein (GFP) mice and several chase periods of up to 1 year quantified the adult pNSC cell cycle time as 3-5 months. We hypothesized that while pNSCs are not very proliferative at baseline, they may exist as a reserve pool of NSCs in case of injury. To test this function of pNSCs, we obtained conditional Oct4 knockout mice, Oct4 fl/fl ;Sox1 Cre (Oct4 CKO ), which do not yield adult pNSC-derived neurospheres. When we ablated the progeny of pNSCs, namely all GFAP + dNSCs, in these Oct4 CKO mice, we found that dNSCs did not recover as they do in wild-type mice, suggesting that pNSCs are necessary for dNSC repopulation. Returning to the H2B-GFP mice, we observed that the cytosine β-d-arabinofuranoside ablation of proliferating cells including dNSCs-induced quiescent pNSCs to proliferate and significantly dilute their H2B-GFP label. In conclusion, we demonstrate that pNSCs are the most quiescent stem cells in the adult brain reported to date and that their lineage position upstream of GFAP + dNSCs allows them to repopulate a depleted neural lineage. Stem Cells 2017;35:2071-2082. © 2017 AlphaMed Press.

  20. MR tracking of stem cells labeled with superparamagnetic nanoparticles in ischemic brain

    Czech Academy of Sciences Publication Activity Database

    Jendelová, Pavla; Růžičková, Kateřina; Urdzíková, Lucia; Kroupová, Jana; Herynek, V.; Dvořák, Petr; Hájek, M.; Syková, Eva

    č. 2 (2003), s. 35 ISSN 0894-1491. [European Meeting on Glial Cell Function in Health and Disease /6./. Berlín, 03.09.2003-06.09.2003] R&D Projects: GA MŠk LN00A065; GA ČR GA304/03/1189 Institutional research plan: CEZ:AV0Z5039906; CEZ:MSM 111300004 Keywords : Stem cells * Nanoparticles Subject RIV: FH - Neurology Impact factor: 4.677, year: 2003

  1. Geminin Participates in Differentiation Decisions of Adult Neural Stem Cells Transplanted in the Hemiparkinsonian Mouse Brain.

    Science.gov (United States)

    Taouki, Ioanna; Tasiudi, Eve; Lalioti, Maria-Eleni; Kyrousi, Christina; Skavatsou, Eleni; Kaplani, Konstantina; Lygerou, Zoi; Kouvelas, Elias D; Mitsacos, Adamantia; Giompres, Panagiotis; Taraviras, Stavros

    2017-08-15

    Neural stem cells have been considered as a source of stem cells that can be used for cell replacement therapies in neurodegenerative diseases, as they can be isolated and expanded in vitro and can be used for autologous grafting. However, due to low percentages of survival and varying patterns of differentiation, strategies that will enhance the efficacy of transplantation are under scrutiny. In this article, we have examined whether alterations in Geminin's expression, a protein that coordinates the balance between self-renewal and differentiation, can improve the properties of stem cells transplanted in 6-OHDA hemiparkinsonian mouse model. Our results indicate that, in the absence of Geminin, grafted cells differentiating into dopaminergic neurons were decreased, while an increased number of oligodendrocytes were detected. The number of proliferating multipotent cells was not modified by the absence of Geminin. These findings encourage research related to the impact of Geminin on transplantations for neurodegenerative disorders, as an important molecule in influencing differentiation decisions of the cells composing the graft.

  2. Benchmark test of accelerated multi-slice simulation by GPGPU.

    Science.gov (United States)

    Hosokawa, Fumio; Shinkawa, Takao; Arai, Yoshihiro; Sannomiya, Takumi

    2015-11-01

    A fast multi-slice image simulation by parallelized computation using a graphics processing unit (GPU) has been developed. The image simulation contains multiple sets of computing steps, such as Fourier transform and pixel-to-pixel operation. The efficiency of GPU varies depending on the type of calculation. In the effective case of utilizing GPU, the calculation speed is conducted hundreds of times faster than a central processing unit (CPU). The benchmark test of parallelized multi-slice was performed, and the results of contents, such as TEM imaging, STEM imaging and CBD calculation are reported. Some features of the simulation software are also introduced. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Controlling micro- and nano-environment of tumor and stem cells for novel research and therapy of brain cancer

    Science.gov (United States)

    Smith, Christopher Lloyd

    The use of modern technologies in cancer research has engendered a great deal of excitement. Many of these advanced approaches involve in-depth mathematical analyses of the inner working of cells, via genomic and proteomic analyses. However these techniques may not be ideal for the study of complex cell phenotypes and behaviors. This dissertation explores cancer and potential therapies through phenotypic analysis of cell behaviors, an alternative approach. We employ this experimental framework to study brain cancer (glioma), a particularly formidable example of this diverse ailment. Through the application of micro- and nanotechnology, we carefully control the surrounding environments of cells to understand their responses to various cues and to manipulate their behaviors. Subsequently we obtain clinically relevant information that allows better understanding of glioma, and enhancement of potential therapies. We first aim to address brain tumor dispersal, through analysis of cell migration. Utilizing nanometer-scale topographic models of the extracellular matrix, we study the migratory response of glioma cells to various stimuli in vitro. Second, we implement knowledge gained from these investigations to define characteristics of tumor progression in patients, and to develop treatments inhibiting cell migration. Next we use microfluidic and nanotopographic models to study the behaviors of stem cells in vitro. Here we attempt to improve their abilities to deliver therapeutic proteins to cancer, an innovative treatment approach. We analyze the multi-step process by which adipose-derived stem cells naturally home to tumor sites, and identify numerous environmental perturbations to enhance this behavior. Finally, we attempt to demonstrate that these cell culture-based manipulations can enhance the localization of adipose stem cells to glioma in vivo using animal models. Throughout this work we utilize environmental cues to analyze and induce particular behaviors in

  4. Endogenous 24S-hydroxycholesterol modulates NMDAR-mediated function in hippocampal slices.

    Science.gov (United States)

    Sun, Min-Yu; Izumi, Yukitoshi; Benz, Ann; Zorumski, Charles F; Mennerick, Steven

    2016-03-01

    N-methyl-D-aspartate receptors (NMDARs), a major subtype of glutamate receptors mediating excitatory transmission throughout the central nervous system (CNS), play critical roles in governing brain function and cognition. Because NMDAR dysfunction contributes to the etiology of neurological and psychiatric disorders including stroke and schizophrenia, NMDAR modulators are potential drug candidates. Our group recently demonstrated that the major brain cholesterol metabolite, 24S-hydroxycholesterol (24S-HC), positively modulates NMDARs when exogenously administered. Here, we studied whether endogenous 24S-HC regulates NMDAR activity in hippocampal slices. In CYP46A1(-/-) (knockout; KO) slices where endogenous 24S-HC is greatly reduced, NMDAR tone, measured as NMDAR-to-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) excitatory postsynaptic current (EPSC) ratio, was reduced. This difference translated into more NMDAR-driven spiking in wild-type (WT) slices compared with KO slices. Application of SGE-301, a 24S-HC analog, had comparable potentiating effects on NMDAR EPSCs in both WT and KO slices, suggesting that endogenous 24S-HC does not saturate its NMDAR modulatory site in ex vivo slices. KO slices did not differ from WT slices in either spontaneous neurotransmission or in neuronal intrinsic excitability, and exhibited LTP indistinguishable from WT slices. However, KO slices exhibited higher resistance to persistent NMDAR-dependent depression of synaptic transmission induced by oxygen-glucose deprivation (OGD), an effect restored by SGE-301. Together, our results suggest that loss of positive NMDAR tone does not elicit compensatory changes in excitability or transmission, but it protects transmission against NMDAR-mediated dysfunction. We expect that manipulating this endogenous NMDAR modulator may offer new treatment strategies for neuropsychiatric dysfunction. Copyright © 2016 the American Physiological Society.

  5. Reduced 5-HT(1B) receptor binding in the dorsal brain stem after cognitive behavioural therapy of major depressive disorder.

    Science.gov (United States)

    Tiger, Mikael; Rück, Christian; Forsberg, Anton; Varrone, Andrea; Lindefors, Nils; Halldin, Christer; Farde, Lars; Lundberg, Johan

    2014-08-30

    Major depression is a significant contributor to the global burden of disease, and its pathophysiology is largely unknown. The serotonin hypothesis is, however, the model with most supporting data, although the details are only worked out to some extent. Recent clinical imaging measurements indeed imply a role in major depressive disorder (MDD) for the inhibitory serotonin autoreceptor 5-hydroxytryptamine1B (5-HT1B). The aim of the current study was to examine 5-HT1B receptor binding in the brain of MDD patients before and after psychotherapy. Ten patients with an ongoing untreated moderate depressive episode were examined with positron emission tomography (PET) and the 5-HT1B receptor selective radioligand [(11)C]AZ10419369, before and after treatment with internet-based cognitive behavioural therapy. All of the patients examined responded to treatment, and 70% were in remission by the time of the second PET measurement. A statistically significant 33% reduction of binding potential (BPND) was found in the dorsal brain stem (DBS) after treatment. No other significant changes in BPND were found. The DBS contains the raphe nuclei, which regulate the serotonin system. This study gives support for the importance of serotonin and the 5-HT1B receptor in the biological response to psychological treatment of MDD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Perforating eyelid injury extending to the brain stem in a 17-year-old woman: a case report

    Directory of Open Access Journals (Sweden)

    Yoshikawa-Kobayashi Izumi

    2010-01-01

    Full Text Available Abstract Introduction This case report describes a patient who had a perforating eyelid injury that extended to the brain stem. Case presentation A 17-year-old Japanese woman complained of decreased vision in her right eye, with severe ocular pain and headaches, after the metal tip of an umbrella struck her upper right eyelid accidentally. Her vision in the right eye decreased to light perception with commotio retinae, intraretinal hemorrhage, and severe lid swelling. Magnetic resonance imaging (MRI demonstrated edema of the head of the caudate nucleus and putamen, and the edema extended to the hypothalamus. The MRI findings indicated that the umbrella tip had penetrated through the eyelid and the posterior orbital wall. Vision improved to 20/50 in the right eye, with subretinal fibrosis caused by the choroidal rupture. Conclusions We recommend that MRI be performed on the orbit and brain in patients who appear to have symptoms that are inconsistent with the observed injury and when a severe orbitocranial injury is suspected.

  7. Imaging of human glioblastoma cells and their interactions with mesenchymal stem cells in the zebrafish (Danio rerio) embryonic brain

    International Nuclear Information System (INIS)

    Vittori, Milos; Breznik, Barbara; Gredar, Tajda; Hrovat, Katja; Bizjak Mali, Lilijana; Lah, Tamara T

    2016-01-01

    An attractive approach in the study of human cancers is the use of transparent zebrafish (Danio rerio) embryos, which enable the visualization of cancer progression in a living animal. We implanted mixtures of fluorescently labeled glioblastoma (GBM) cells and bonemarrow-derived mesenchymal stem cells (MSCs) into zebrafish embryos to study the cellular pathways of their invasion and the interactions between these cells in vivo. By developing and applying a carbocyanine-dye-compatible clearing protocol for observation of cells in deep tissues, we showed that U87 and U373 GBM cells rapidly aggregated into tumor masses in the ventricles and midbrain hemispheres of the zebrafish embryo brain, and invaded the central nervous system, often using the ventricular system and the central canal of the spinal cord. However, the GBM cells did not leave the central nervous system. With co-injection of differentially labeled cultured GBM cells and MSCs, the implanted cells formed mixed tumor masses in the brain. We observed tight associations between GBM cells and MSCs, and possible cell-fusion events. GBM cells and MSCs used similar invasion routes in the central nervous system. This simple model can be used to study the molecular pathways of cellular processes in GBM cell invasion, and their interactions with various types of stromal cells in double or triple cell co-cultures, to design anti-GBM cell therapies that use MSCs as vectors

  8. Astroglial Activation by an Enriched Environment after Transplantation of Mesenchymal Stem Cells Enhances Angiogenesis after Hypoxic-Ischemic Brain Injury

    Directory of Open Access Journals (Sweden)

    Sung-Rae Cho

    2016-09-01

    Full Text Available Transplantation of mesenchymal stem cells (MSCs has paracrine effects; however, the effects are known to be largely limited. Here we investigated the combination effects of cell transplantation and enriched environment (EE in a model of hypoxic-ischemic brain injury. Brain damage was induced in seven-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min. At six weeks of age, the mice were randomly assigned to four groups: phosphate-buffered saline (PBS-control (CON, PBS-EE, MSC-CON, and MSC-EE. Rotarod and grip strength tests were performed to evaluate neurobehavioral functions. Histologic evaluations were also performed to confirm the extent of astrocyte activation and endogenous angiogenesis. An array-based multiplex ELISA and Western blot were used to identify growth factors in vivo and in vitro. Two weeks after treatment, levels of astrocyte density and angiogenic factors were increased in MSC-EE mice, but glial scarring was not increased. Eight weeks after treatment, angiogenesis was increased, and behavioral outcomes were synergistically improved in the MSC-EE group. Astrocytes co-cultured with MSCs expressed higher levels of angiogenic factors than astrocytes cultured alone. The mechanisms of this synergistic effect included enhanced repair processes, such as increased endogenous angiogenesis and upregulation of angiogenic factors released from activated astrocytes.

  9. MRI/DTI of the Brain Stem Reveals Reversible and Irreversible Disruption of the Baroreflex Neural Circuits: Clinical Implications.

    Science.gov (United States)

    Su, Chia-Hao; Tsai, Ching-Yi; Chang, Alice Y W; Chan, Julie Y H; Chan, Samuel H H

    2016-01-01

    Baroreflex is the physiological mechanism for the maintenance of blood pressure and heart rate. Impairment of baroreflex is not a disease per se. However, depending on severity, the eventuality of baroreflex dysfunction varies from inconvenience in daily existence to curtailment of mobility to death. Despite universal acceptance, neuronal traffic within the contemporary neural circuits during the execution of baroreflex has never been visualized. By enhancing signal detection and fine-tuning the scanning parameters, we have successfully implemented tractographic analysis of the medulla oblongata in mice that allowed for visualization of connectivity between key brain stem nuclei in the baroreflex circuits. When viewed in conjunction with radiotelemetric analysis of the baroreflex, we found that under pathophysiological conditions when the disrupted connectivity between key nuclei in the baroreflex circuits was reversible, the associated disease condition (e.g. neurogenic hypertension) was amenable to remedial measures. Nevertheless, fatality ensues under pathological conditions (e.g. hepatic encephalopathy) when the connectivity between key substrates in the baroreflex circuits was irreversibly severed. MRI/DTI also prompted partial re-wiring of the contemporary circuit for baroreflex-mediated sympathetic vasomotor tone, and unearthed an explanation for the time lapse between brain death and the inevitable asystole signifying cardiac death that follows.

  10. Repair of neonatal brain injury : bringing stem cell-based therapy into clinical practice

    NARCIS (Netherlands)

    Wagenaar, Nienke; Nijboer, Cora H.; van Bel, Frank

    2017-01-01

    Hypoxic-ischaemic brain injury is one of most important causes of neonatal mortality and long-term neurological morbidity in infants born at term. At present, only hypothermia in infants with perinatal hypoxic-ischaemic encephalopathy has shown benefit as a neuroprotective strategy. Otherwise,

  11. Cortical and brain stem changes in neural activity during static handgrip and postexercise ischemia in humans

    DEFF Research Database (Denmark)

    Sander, Mikael; Macefield, Vaughan G; Henderson, Luke A

    2010-01-01

    , and to differentiate between central command and reflex inputs, we used blood oxygen level-dependent (BOLD) functional MRI (fMRI) of the whole brain (3 T). Subjects performed submaximal static handgrip exercise for 2 min followed by 6 min of PEI; MSNA was recorded on a separate day. During the contraction phase...

  12. Hypoxia-Mediated Epigenetic Regulation of Stemness in Brain Tumor Cells.

    Science.gov (United States)

    Prasad, Pankaj; Mittal, Shivani Arora; Chongtham, Jonita; Mohanty, Sujata; Srivastava, Tapasya

    2017-06-01

    Activation of pluripotency regulatory circuit is an important event in solid tumor progression and the hypoxic microenvironment is known to enhance the stemness feature of some cells. The distinct population of cancer stem cells (CSCs)/tumor initiating cells exist in a niche and augment invasion, metastasis, and drug resistance. Previously, studies have reported global hypomethylation and site-specific aberrant methylation in gliomas along with other epigenetic modifications as important contributors to genomic instability during glioma progression. Here, we have demonstrated the role of hypoxia-mediated epigenetic modifications in regulating expression of core pluripotency factors, OCT4 and NANOG, in glioma cells. We observe hypoxia-mediated induction of demethylases, ten-eleven-translocation (TET) 1 and 3, but not TET2 in our cell-line model. Immunoprecipitation studies reveal active demethylation and direct binding of TET1 and 3 at the Oct4 and Nanog regulatory regions. Tet1 and 3 silencing assays further confirmed induction of the pluripotency pathway involving Oct4, Nanog, and Stat3, by these paralogues, although with varying degrees. Knockdown of Tet1 and Tet3 inhibited the formation of neurospheres in hypoxic conditions. We observed independent roles of TET1 and TET3 in differentially regulating pluripotency and differentiation associated genes in hypoxia. Overall, this study demonstrates an active demethylation in hypoxia by TET1 and 3 as a mechanism of Oct4 and Nanog overexpression thus contributing to the formation of CSCs in gliomas. Stem Cells 2017;35:1468-1478. © 2017 AlphaMed Press.

  13. Effect of all-trans retinoic acid on the proliferation and differentiation of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Niu Chao

    2010-08-01

    Full Text Available Abstract Objective To investigate the effect of all-trans retinoic acid(ATRA on the proliferation and differentiation of brain tumor stem cells(BTSCs in vitro. Methods Limiting dilution and clonogenic assay were used to isolate and screen BTSCs from the fresh specimen of human brain glioblastoma. The obtained BTSCs, which were cultured in serum-free medium, were classified into four groups in accordance with the composition of the different treatments. The proliferation of the BTSCs was evaluated by MTT assay. The BTSCs were induced to differentiate in serum-containing medium, and classified into the ATRA group and control group. On the 10th day of induction, the expressions of CD133 and glial fibrillary acidic protein (GFAP in the differentiated BTSCs were detected by immunofluorescence. The differentiated BTSCs were cultured in serum-free medium, the percentage and the time required for formation of brain tumor spheres (BTS were observed. Results BTSCs obtained by limiting dilution were all identified as CD133-positive by immunofluorescence. In serum-free medium, the proliferation of BTSCs in the ATRA group was observed significantly faster than that in the control group, but slower than that in the growth factor group and ATRA/growth factor group, and the size of the BTS in the ATRA group was smaller than that in the latter two groups(P P P P Conclusion ATRA can promote the proliferation and induce the differentiation of BTSCs, but the differentiation is incomplete, terminal differentiation cannot be achieved and BTSs can be formed again.

  14. Discrete frequency slice wavelet transform

    Science.gov (United States)

    Yan, Zhonghong; Tao, Ting; Jiang, Zhongwei; Wang, Haibin

    2017-11-01

    This paper introduces a new kind of Time-Frequency Representation (TFR) method called Discrete Frequency Slice Wavelet Transform (DFSWT). It is an improved version of Frequency Slice Wavelet Transform (FSWT). The previous researches on FSWT show that it is a new efficient TFR in an easy way without strict limitation as traditional wavelet theory. DFSWT as well as FSWT are defined directly in frequency domain, and still keep its properties in time-frequency domain as FSWT decomposition, reconstruction and filter design, etc. However, the original signal is decomposed and reconstructed on a Chosen Frequency Domains (CFD) as need of application. CFD means that the decomposition and reconstruction are not completed on all frequency components. At first, it is important to discuss the necessary condition of CFD to reconstruct the original signal. And then based on norm l2, an optimization algorithm is introduced to reconstruct the original signal even accurately. Finally, for a test example, the TFR analysis of a real life signal is shown. Some conclusions are drawn that the concept of CFD is very useful to application, and the DFSWT can become a simple and easy tool of TFR method, and also provide a new idea of low speed sampling of high frequency signal in applications.

  15. Long-term survival of human neural stem cells in the ischemic rat brain upon transient immunosuppression.

    Directory of Open Access Journals (Sweden)

    Laura Rota Nodari

    Full Text Available Understanding the physiology of human neural stem cells (hNSCs in the context of cell therapy for neurodegenerative disorders is of paramount importance, yet large-scale studies are hampered by the slow-expansion rate of these cells. To overcome this issue, we previously established immortal, non-transformed, telencephalic-diencephalic hNSCs (IhNSCs from the fetal brain. Here, we investigated the fate of these IhNSC's immediate progeny (i.e. neural progenitors; IhNSC-Ps upon unilateral implantation into the corpus callosum or the hippocampal fissure of adult rat brain, 3 days after global ischemic injury. One month after grafting, approximately one fifth of the IhNSC-Ps had survived and migrated through the corpus callosum, into the cortex or throughout the dentate gyrus of the hippocampus. By the fourth month, they had reached the ipsilateral subventricular zone, CA1-3 hippocampal layers and the controlateral hemisphere. Notably, these results could be accomplished using transient immunosuppression, i.e administering cyclosporine for 15 days following the ischemic event. Furthermore, a concomitant reduction of reactive microglia (Iba1+ cells and of glial, GFAP+ cells was also observed in the ipsilateral hemisphere as compared to the controlateral one. IhNSC-Ps were not tumorigenic and, upon in vivo engraftment, underwent differentiation into GFAP+ astrocytes, and β-tubulinIII+ or MAP2+ neurons, which displayed GABAergic and GLUTAmatergic markers. Electron microscopy analysis pointed to the formation of mature synaptic contacts between host and donor-derived neurons, showing the full maturation of the IhNSC-P-derived neurons and their likely functional integration into the host tissue. Thus, IhNSC-Ps possess long-term survival and engraftment capacity upon transplantation into the globally injured ischemic brain, into which they can integrate and mature into neurons, even under mild, transient immunosuppressive conditions. Most notably

  16. Stationary hyperboloidal slicings with evolved gauge conditions

    Energy Technology Data Exchange (ETDEWEB)

    Ohme, Frank [Max-Planck-Institut fuer Gravitationsphysik, Albert-Einstein-Institut, Am Muehlenberg 1, 14476 Golm (Germany); Hannam, Mark; Murchadha, Niall O [Physics Department, University College Cork, Cork (Ireland); Husa, Sascha, E-mail: frank.ohme@aei.mpg.d [Departament de Fisica, Universitat de les Illes Balears, Cra. Valldemossa Km. 7.5, Palma de Mallorca E-07122 (Spain)

    2009-09-07

    We analyze stationary slicings of the Schwarzschild spacetime defined by members of the Bona-Masso family of slicing conditions. Our main focus is on the influence of a non-vanishing offset to the trace of the extrinsic curvature, which forbids the existence of standard Cauchy foliations but at the same time allows gauge choices that are adapted to include null infinity (I) in the evolution. These hyperboloidal slicings are especially interesting for observing outgoing gravitational waves. We show that the standard 1+log slicing condition admits no overall regular hyperboloidal slicing, but by appropriately combining with harmonic slicing, we construct a gauge condition that leads to a strongly singularity-avoiding hyperboloidal foliation that connects the black hole to I.

  17. Colchicine induces apoptosis in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne W; Noer, Helle; Gramsbergen, Jan Bert

    2003-01-01

    The microtubule-disrupting agent colchicine is known to be particular toxic for certain types of neurons, including the granule cells of the dentate gyrus. In this study we investigated whether colchicine could induce such neuron-specific degeneration in developing (1 week in vitro) and mature (3...... weeks in vitro) organotypic hippocampal slice cultures and whether the induced cell death was apoptotic and/or necrotic. When applied to 1-week-old cultures for 48 h, colchicine induced primarily apoptotic, but also a minor degree of necrotic cell death in the dentate granule cells, as investigated...... the formation of active caspase 3 protein and apoptotic nuclei induced by colchicine, but the formation of necrotic nuclei increased correspondingly and the PI uptake was unaffected. We conclude that colchicine induces caspase 3-dependent apoptotic cell death of dentate granule cells in hippocampal brain slice...

  18. Ethanol induces MAP2 changes in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Noraberg, J; Zimmer, J

    1998-01-01

    Microtubule-associated protein 2 (MAP2) and neuron-specific protein (NeuN) immunostains were used to demonstrate neurotoxic effects in mature hippocampal slice cultures exposed to ethanol (50, 100, 200 mM) for 4 weeks. At the low dose the density of MAP2 immunostaining in the dentate molecular...... layer was 118% of the control cultures, with no detectable changes in CA1 and CA3. At 100 mM no changes were detected, while 200 mM ethanol significantly reduced the MAP2 density in both dentate (19%) and hippocampal dendritic fields (CA3, 52%; CA1, 55%). At this dose NeuN staining showed considerable...... loss of CA3 pyramidal cells and moderate loss of dentate granule cells, as seen in vivo. The results indicate that brain slice cultures combined with immunostaining for cytoskeleton and neuronal markers can be used for studies of ethanol and organic solvent neurotoxicity....

  19. A functional study of EGFR and Notch signaling in brain cancer stem-like cells from glioblastoma multiforme (Ph.d.)

    DEFF Research Database (Denmark)

    Kristoffersen, Karina

    2013-01-01

    for new molecular and cellular targets that can improve the prognosis for GBM patients. One such target is the brain cancer stem-like cells (bCSC) that are believed to be responsible for tumor initiation, progression, treatment resistance and ultimately relapse. bCSC are identified based......Glioblastoma Multiforme (GBM) is the most common and aggressive brain tumor in adults with a median survival for newly diagnosed GBM patients at less than 1.5 year. Despite intense treatment efforts the vast majority of patients will experience relapse and much research today is therefore searching...... on their resemblance to normal neural stem cells (NSC) and their tumorigenic potential. Like for NSC, the epidermal growth factor receptor (EGFR) and Notch receptor signaling pathways are believed to be important for the maintenance of bCSC. These pathways as such present promising targets in a future anti-bCSC GBM...

  20. Exophytic pilocytic astrocytoma of the brain stem in an adult with encasement of the caudal cranial nerve complex (IX-XII): presurgical anatomical neuroimaging using MRI

    Energy Technology Data Exchange (ETDEWEB)

    Yousry, Indra; Yousry, Tarek A. [Department of Neuroradiology, Klinikum Grosshadern, Ludwig-Maximilians University, Marchioninistr. 15, 81377, Munich (Germany); Muacevic, Alexander; Olteanu-Nerbe, Vlad [Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians University, Munich (Germany); Naidich, Thomas P. [Department of Radiology, Section of Neuroradiology, Mount Sinai Hospital, New York (United States)

    2004-07-01

    We describe a rare case of adult pilocytic astrocytoma in which exophytic growth from the brain stem presented as a right cerebellopontine angle mass. An initial MRI examination using T2- and T1-weighted images without and with contrast suggested the diagnosis of schwannoma. Subsequent use of 3D CISS (three-dimensional constructive interference in steady state) and T1-weighted contrast-enhanced 3D MP-RAGE (three-dimensional magnetization prepared rapid acquisition gradient echo) sequences led to the diagnosis of an exophytic brain stem tumor, documented the precise relationships of the tumor to cranial nerve VIII, revealed encasement of cranial nerves IX-XII (later confirmed intraoperatively), and provided the proper basis for planning surgical management. (orig.)

  1. Slice of LHC dipole wiring

    CERN Multimedia

    Dipole model slice made in 1994 by Ansaldo. The high magnetic fields needed for guiding particles around the Large Hadron Collider (LHC) ring are created by passing 12’500 amps of current through coils of superconducting wiring. At very low temperatures, superconductors have no electrical resistance and therefore no power loss. The LHC is the largest superconducting installation ever built. The magnetic field must also be extremely uniform. This means the current flowing in the coils has to be very precisely controlled. Indeed, nowhere before has such precision been achieved at such high currents. 50’000 tonnes of steel sheets are used to make the magnet yokes that keep the wiring firmly in place. The yokes constitute approximately 80% of the accelerator's weight and, placed side by side, stretch over 20 km!

  2. It takes two to tango, a dance between the cells of origin and cancer stem cells in the Drosophila larval brain.

    Science.gov (United States)

    Janssens, Derek H; Lee, Cheng-Yu

    2014-04-01

    During malignant transformation the cells of origin give rise to cancer stem cells which possess the capacity to undergo limitless rounds of self-renewing division, regenerating themselves while producing more tumor cells. Within normal tissues, a limitless self-renewal capacity is unique to the stem cells, which divide asymmetrically to produce more restricted progenitors. Accumulating evidence suggests that misregulation of the self-renewal machinery in stem cell progeny can lead to tumorigenesis, but how it influences the properties of the resulting tumors remains unclear. Studies of the type II neural stem cell (neuroblast) lineages in the Drosophila larval brain have identified a regulatory cascade that promotes commitment to a progenitor cell identity by restricting their response to the self-renewal machinery. Brain tumor (Brat) and Numb initiate this cascade by asymmetrically extinguishing the activity of the self-renewal factors. Subsequently, Earmuff (Erm) and the SWI/SNF complex stably restrict the competence of the progenitor cell to respond to reactivation of self-renewal mechanisms. Together, this cascade programs the progenitor cell to undergo limited rounds of division, generating exclusive differentiated progeny. Here we review how defects in this cascade lead to tumor initiation and how inhibiting the self-renewal mechanisms may be an effective strategy to block CSC expansion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Comparative transcriptome analysis in induced neural stem cells reveals defined neural cell identities in vitro and after transplantation into the adult rodent brain.

    Science.gov (United States)

    Hallmann, Anna-Lena; Araúzo-Bravo, Marcos J; Zerfass, Christina; Senner, Volker; Ehrlich, Marc; Psathaki, Olympia E; Han, Dong Wook; Tapia, Natalia; Zaehres, Holm; Schöler, Hans R; Kuhlmann, Tanja; Hargus, Gunnar

    2016-05-01

    Reprogramming technology enables the production of neural progenitor cells (NPCs) from somatic cells by direct transdifferentiation. However, little is known on how neural programs in these induced neural stem cells (iNSCs) differ from those of alternative stem cell populations in vitro and in vivo. Here, we performed transcriptome analyses on murine iNSCs in comparison to brain-derived neural stem cells (NSCs) and pluripotent stem cell-derived NPCs, which revealed distinct global, neural, metabolic and cell cycle-associated marks in these populations. iNSCs carried a hindbrain/posterior cell identity, which could be shifted towards caudal, partially to rostral but not towards ventral fates in vitro. iNSCs survived after transplantation into the rodent brain and exhibited in vivo-characteristics, neural and metabolic programs similar to transplanted NSCs. However, iNSCs vastly retained caudal identities demonstrating cell-autonomy of regional programs in vivo. These data could have significant implications for a variety of in vitro- and in vivo-applications using iNSCs. Copyright © 2016 Roslin Cells Ltd. Published by Elsevier B.V. All rights reserved.

  4. Neuronal coupling by endogenous electric fields: cable theory and applications to coincidence detector neurons in the auditory brain stem.

    Science.gov (United States)

    Goldwyn, Joshua H; Rinzel, John

    2016-04-01

    The ongoing activity of neurons generates a spatially and time-varying field of extracellular voltage (Ve). This Ve field reflects population-level neural activity, but does it modulate neural dynamics and the function of neural circuits? We provide a cable theory framework to study how a bundle of model neurons generates Ve and how this Ve feeds back and influences membrane potential (Vm). We find that these "ephaptic interactions" are small but not negligible. The model neural population can generate Ve with millivolt-scale amplitude, and this Ve perturbs the Vm of "nearby" cables and effectively increases their electrotonic length. After using passive cable theory to systematically study ephaptic coupling, we explore a test case: the medial superior olive (MSO) in the auditory brain stem. The MSO is a possible locus of ephaptic interactions: sounds evoke large (millivolt scale)Vein vivo in this nucleus. The Ve response is thought to be generated by MSO neurons that perform a known neuronal computation with submillisecond temporal precision (coincidence detection to encode sound source location). Using a biophysically based model of MSO neurons, we find millivolt-scale ephaptic interactions consistent with the passive cable theory results. These subtle membrane potential perturbations induce changes in spike initiation threshold, spike time synchrony, and time difference sensitivity. These results suggest that ephaptic coupling may influence MSO function. Copyright © 2016 the American Physiological Society.

  5. [A case of primary brain-stem injury recovered from persistent vegetative state after L-dopa administration].

    Science.gov (United States)

    Matsuda, W; Sugimoto, K; Sato, N; Watanabe, T; Yanaka, K; Matsumura, A; Nose, T

    1999-12-01

    A 51-year-old male was transferred to our hospital just after traffic accident. On admission, the patient was comatose (Glasgow Coma Scale of 6) and showed a left hemiparesis with a left oculomotor nerve palsy. Computed tomography demonstrated a traumatic subarachnoid hemorrhage without mass lesion. Magnetic resonance imaging showed high intensity lesions on the left dorsolateral midbrain and the right cerebral peduncle. The distribution of lesions implied diffuse axonal injury involving dopaminergic systems such as the substantia nigra and the ventral tegmental area. After several months of conservative management, the patient showed no recovery and was diagnosed as persistent vegetable state. The administration of L-dopa was then started and the patient showed remarkable neurological improvement. Therefore the patient's neurological status was thought to be modified with primary brain stem injury and accompanying traumatic Parkinson's syndrome. It is important to understand "pseudo" persistent vegetative state in the management of patients showing prolonged consciousness disturbance. L-dopa should be considered as the drugs of pharmacological intervention for the patients of masked parkinsonism behind "pseudo" persistent vegetative state whose dopaminergic systems might have been damaged.

  6. In vivo near-infrared imaging for the tracking of systemically delivered mesenchymal stem cells: tropism for brain tumors and biodistribution.

    Science.gov (United States)

    Kim, Seong Muk; Jeong, Chang Hyun; Woo, Ji Sun; Ryu, Chung Heon; Lee, Jeong-Hwa; Jeun, Sin-Soo

    2016-01-01

    Mesenchymal stem cell (MSC)-based gene therapy is a promising tool for the treatment of various neurological diseases, including brain tumors. However, the tracking of in vivo stem cell migration, distribution, and survival need to be defined for their clinical application. The systemic routes of stem cell delivery must be determined because direct intracerebral injection as a cure for brain tumors is an invasive method. In this study, we show for the first time that near-infrared (NIR) imaging can reveal the distribution and tumor tropism of intravenously injected MSCs in an intracranial xenograft glioma model. MSCs were labeled with NIR fluorescent nanoparticles, and the effects of the NIR dye on cell proliferation and migratory capacity were evaluated in vitro. We investigated the tumor-targeting properties and tissue distribution of labeled MSCs introduced by intravenous injection and followed by in vivo imaging analysis, histological analysis, and real-time quantitative polymerase chain reaction. We observed no cytotoxicity or change in the overall growth rate and characteristics of labeled MSCs compared with control MSCs. NIR fluorescent imaging showed the organ distribution and targeted tumor tropism of systemically injected human MSCs. A significant number of MSCs accumulated specifically at the tumor site in the mouse brain. These results suggest that NIR-based cell tracking is a potentially useful imaging technique to visualize cell survival, migration, and distribution for the application of MSC-mediated therapies in the treatment of malignant gliomas.

  7. Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain

    Science.gov (United States)

    Moshayedi, Pouria; Nih, Lina R.; Llorente, Irene L.; Berg, Andrew R.; Cinkornpumin, Jessica; Lowry, William E.; Segura, Tatiana; Carmichael, S. Thomas

    2016-01-01

    Stem cell therapies have shown promise in promoting recovery in stroke but have been limited by poor cell survival and differentiation. We have developed a hyaluronic acid (HA)-based self-polymerizing hydrogel that serves as a platform for adhesion of structural motifs and a depot release for growth factors to promote transplant stem cell survival and differentiation. We took an iterative approach in optimizing the complex combination of mechanical, biochemical and biological properties of an HA cell scaffold. First, we optimized stiffness for a minimal reaction of adjacent brain to the transplant. Next hydrogel crosslinkers sensitive to matrix metalloproteinases (MMP) were incorporated as they promoted vascularization. Finally, candidate adhesion motifs and growth factors were systemically changed in vitro using a design of experiment approach to optimize stem cell survival or proliferation. The optimized HA hydrogel, tested in vivo, promoted survival of encapsulated human neural progenitor cells (iPS-NPCs) after transplantation into the stroke core and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. This HA hydrogel can be tracked in vivo with MRI. A hydrogel can serve as a therapeutic adjunct in a stem cell therapy through selective control of stem cell survival and differentiation in vivo. PMID:27521617

  8. Gene targeting study reveals unexpected expression of brain-expressed X-linked 2 in endocrine and tissue stem/progenitor cells in mice.

    Science.gov (United States)

    Ito, Keiichi; Yamazaki, Satoshi; Yamamoto, Ryo; Tajima, Yoko; Yanagida, Ayaka; Kobayashi, Toshihiro; Kato-Itoh, Megumi; Kakuta, Shigeru; Iwakura, Yoichiro; Nakauchi, Hiromitsu; Kamiya, Akihide

    2014-10-24

    Identification of genes specifically expressed in stem/progenitor cells is an important issue in developmental and stem cell biology. Genome-wide gene expression analyses in liver cells performed in this study have revealed a strong expression of X-linked genes that include members of the brain-expressed X-linked (Bex) gene family in stem/progenitor cells. Bex family genes are expressed abundantly in the neural cells and have been suggested to play important roles in the development of nervous tissues. However, the physiological role of its individual members and the precise expression pattern outside the nervous system remain largely unknown. Here, we focused on Bex2 and examined its role and expression pattern by generating knock-in mice; the enhanced green fluorescence protein (EGFP) was inserted into the Bex2 locus. Bex2-deficient mice were viable and fertile under laboratory growth conditions showing no obvious phenotypic abnormalities. Through an immunohistochemical analysis and flow cytometry-based approach, we observed unique EGFP reporter expression patterns in endocrine and stem/progenitor cells of the liver, pyloric stomach, and hematopoietic system. Although Bex2 seems to play redundant roles in vivo, these results suggest the significance and potential applications of Bex2 in studies of endocrine and stem/progenitor cells. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Integrating interface slicing into software engineering processes

    Science.gov (United States)

    Beck, Jon

    1993-01-01

    Interface slicing is a tool which was developed to facilitate software engineering. As previously presented, it was described in terms of its techniques and mechanisms. The integration of interface slicing into specific software engineering activities is considered by discussing a number of potential applications of interface slicing. The applications discussed specifically address the problems, issues, or concerns raised in a previous project. Because a complete interface slicer is still under development, these applications must be phrased in future tenses. Nonetheless, the interface slicing techniques which were presented can be implemented using current compiler and static analysis technology. Whether implemented as a standalone tool or as a module in an integrated development or reverse engineering environment, they require analysis no more complex than that required for current system development environments. By contrast, conventional slicing is a methodology which, while showing much promise and intuitive appeal, has yet to be fully implemented in a production language environment despite 12 years of development.

  10. Phosphorylation of proteins in hippocampal slices: effects of noradrenaline and of pretreatment with kainic acid

    Energy Technology Data Exchange (ETDEWEB)

    Hofstein, R.; Segal, M.

    1982-08-01

    Hippocampal slices were incubated in the presence of (/sup 32/P)P1, and protein phosphorylation was examined by means of sodium dodecyl sulfate-gel electrophoresis. Incubation for at least 30 min with 300 muCi of (/sup 32/P)P1/brain slice gave rise to the phosphorylation of 8-10 protein bands. Most of these bands showed enhanced phosphorylation in response to noradrenaline. The basal phosphorylation of kainic acid-pretreated hippocampal slices was enhanced two- to threefold compared with controls. There was also an additional increase in kainic acid-pretreatment slices in the response to noradrenaline. 8-Br-Cyclic AMP and phosphodiesterase inhibitors, such as papaverine or isobutylmethylxanthine, had no effect on the phosphorylation patterns.

  11. The selective alpha7 nicotinic acetylcholine receptor agonist PNU-282987 [N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride] enhances GABAergic synaptic activity in brain slices and restores auditory gating deficits in anesthetized rats.

    Science.gov (United States)

    Hajós, M; Hurst, R S; Hoffmann, W E; Krause, M; Wall, T M; Higdon, N R; Groppi, V E

    2005-03-01

    Schizophrenic patients are thought to have an impaired ability to process sensory information. This deficit leads to disrupted auditory gating measured electrophysiologically as a reduced suppression of the second of paired auditoryevoked responses (P50) and is proposed to be associated with decreased function and/or expression of the homomeric alpha7 nicotinic acetylcholine receptor (nAChR). Here, we provide evidence that N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-282987), a novel selective agonist of the alpha7 nAChR, evoked whole-cell currents from cultured rat hippocampal neurons that were sensitive to the selective alpha7 nAChR antagonist methyllycaconitine (MLA) and enhanced GABAergic synaptic activity when applied to hippocampal slices. Amphetamine-induced sensory gating deficit, determined by auditory-evoked potentials in hippocampal CA3 region, was restored by systemic administration of PNU-282987 in chloral hydrate-anesthetized rats. Auditory gating of rat reticular thalamic neurons was also disrupted by amphetamine; however, PNU-282987 normalized gating deficit only in a subset of tested neurons (6 of 11). Furthermore, PNU-282987 improved the inherent hippocampal gating deficit occurring in a subpopulation of anesthetized rats, and enhanced amphetamine-induced hippocampal oscillation. We propose that the alpha7 nAChR agonist PNU-282987, via modulating/enhancing hippocampal GABAergic neurotransmission, improves auditory gating and enhances hippocampal oscillatory activity. These results provide further support for the concept that drugs that selectively activate alpha7 nAChRs may offer a novel, potential pharmacotherapy in treatment of schizophrenia.

  12. IL4/STAT6 Signaling Activates Neural Stem Cell Proliferation and Neurogenesis upon Amyloid-β42 Aggregation in Adult Zebrafish Brain

    Directory of Open Access Journals (Sweden)

    Prabesh Bhattarai

    2016-10-01

    Full Text Available Human brains are prone to neurodegeneration, given that endogenous neural stem/progenitor cells (NSPCs fail to support neurogenesis. To investigate the molecular programs potentially mediating neurodegeneration-induced NSPC plasticity in regenerating organisms, we generated an Amyloid-β42 (Aβ42-dependent neurotoxic model in adult zebrafish brain through cerebroventricular microinjection of cell-penetrating Aβ42 derivatives. Aβ42 deposits in neurons and causes phenotypes reminiscent of amyloid pathophysiology: apoptosis, microglial activation, synaptic degeneration, and learning deficits. Aβ42 also induces NSPC proliferation and enhanced neurogenesis. Interleukin-4 (IL4 is activated primarily in neurons and microglia/macrophages in response to Aβ42 and is sufficient to increase NSPC proliferation and neurogenesis via STAT6 phosphorylation through the IL4 receptor in NSPCs. Our results reveal a crosstalk between neurons and immune cells mediated by IL4/STAT6 signaling, which induces NSPC plasticity in zebrafish brains.

  13. Bilateral cerebellar and brain stem infarction resulting from vertebral artery injury following cervical trauma without radiographic damage of the spinal column: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Mimata, Yoshikuni; Sato, Kotaro; Suzuki, Yoshiaki [Iwate Prefectural Chubu Hospital, Department of Orthopaedic Surgery, Kitakami (Japan); Murakami, Hideki [Iwate Medical University, Department of Orthopaedic Surgery, School of Medicine, Morioka (Japan)

    2014-01-15

    Vertebral artery injury can be a complication of cervical spine injury. Although most cases are asymptomatic, the rare case progresses to severe neurological impairment and fatal outcomes. We experienced a case of bilateral cerebellar and brain stem infarction with fatal outcome resulting from vertebral artery injury associated with cervical spine trauma. A 69-year-old male was admitted to our hospital because of tetraplegia after falling down the stairs and hitting his head on the floor. Marked bony damage of the cervical spine was not apparent on radiographs and CT scans, so the injury was initially considered to be a cervical cord injury without bony damage. However, an intensity change in the intervertebral disc at C5/C6, and a ventral epidural hematoma were observed on MRI. A CT angiogram of the neck showed the right vertebral artery was completely occluded at the C4 level of the spine. Forty-eight hours after injury, the patient lapsed into drowsy consciousness. The cranial CT scan showed a massive low-density area in the bilateral cerebellar hemispheres and brain stem. Anticoagulation was initiated after a diagnosis of the right vertebral artery injury, but the patient developed bilateral cerebellar and brain stem infarction. The patient's brain herniation progressed and the patient died 52 h after injury. We considered that not only anticoagulation but also treatment for thrombosis would have been needed to prevent cranial embolism. We fully realize that early and appropriate treatment are essential to improve the treatment results, and constructing a medical system with a team of orthopedists, radiologists, and neurosurgeons is also very important. (orig.)

  14. Bilateral cerebellar and brain stem infarction resulting from vertebral artery injury following cervical trauma without radiographic damage of the spinal column: a case report.

    Science.gov (United States)

    Mimata, Yoshikuni; Murakami, Hideki; Sato, Kotaro; Suzuki, Yoshiaki

    2014-01-01

    Vertebral artery injury can be a complication of cervical spine injury. Although most cases are asymptomatic, the rare case progresses to severe neurological impairment and fatal outcomes. We experienced a case of bilateral cerebellar and brain stem infarction with fatal outcome resulting from vertebral artery injury associated with cervical spine trauma. A 69-year-old male was admitted to our hospital because of tetraplegia after falling down the stairs and hitting his head on the floor. Marked bony damage of the cervical spine was not apparent on radiographs and CT scans, so the injury was initially considered to be a cervical cord injury without bony damage. However, an intensity change in the intervertebral disc at C5/C6, and a ventral epidural hematoma were observed on MRI. A CT angiogram of the neck showed the right vertebral artery was completely occluded at the C4 level of the spine. Forty-eight hours after injury, the patient lapsed into drowsy consciousness. The cranial CT scan showed a massive low-density area in the bilateral cerebellar hemispheres and brain stem. Anticoagulation was initiated after a diagnosis of the right vertebral artery injury, but the patient developed bilateral cerebellar and brain stem infarction. The patient's brain herniation progressed and the patient died 52 h after injury. We considered that not only anticoagulation but also treatment for thrombosis would have been needed to prevent cranial embolism. We fully realize that early and appropriate treatment are essential to improve the treatment results, and constructing a medical system with a team of orthopedists, radiologists, and neurosurgeons is also very important.

  15. Bilateral cerebellar and brain stem infarction resulting from vertebral artery injury following cervical trauma without radiographic damage of the spinal column: A case report

    International Nuclear Information System (INIS)

    Mimata, Yoshikuni; Sato, Kotaro; Suzuki, Yoshiaki; Murakami, Hideki

    2014-01-01

    Vertebral artery injury can be a complication of cervical spine injury. Although most cases are asymptomatic, the rare case progresses to severe neurological impairment and fatal outcomes. We experienced a case of bilateral cerebellar and brain stem infarction with fatal outcome resulting from vertebral artery injury associated with cervical spine trauma. A 69-year-old male was admitted to our hospital because of tetraplegia after falling down the stairs and hitting his head on the floor. Marked bony damage of the cervical spine was not apparent on radiographs and CT scans, so the injury was initially considered to be a cervical cord injury without bony damage. However, an intensity change in the intervertebral disc at C5/C6, and a ventral epidural hematoma were observed on MRI. A CT angiogram of the neck showed the right vertebral artery was completely occluded at the C4 level of the spine. Forty-eight hours after injury, the patient lapsed into drowsy consciousness. The cranial CT scan showed a massive low-density area in the bilateral cerebellar hemispheres and brain stem. Anticoagulation was initiated after a diagnosis of the right vertebral artery injury, but the patient developed bilateral cerebellar and brain stem infarction. The patient's brain herniation progressed and the patient died 52 h after injury. We considered that not only anticoagulation but also treatment for thrombosis would have been needed to prevent cranial embolism. We fully realize that early and appropriate treatment are essential to improve the treatment results, and constructing a medical system with a team of orthopedists, radiologists, and neurosurgeons is also very important. (orig.)

  16. Conventional and cross-correlation brain-stem auditory evoked responses in the white leghorn chick: rate manipulations

    Science.gov (United States)

    Burkard, R.; Jones, S.; Jones, T.

    1994-01-01

    Rate-dependent changes in the chick brain-stem auditory evoked response (BAER) using conventional averaging and a cross-correlation technique were investigated. Five 15- to 19-day-old white leghorn chicks were anesthetized with Chloropent. In each chick, the left ear was acoustically stimulated. Electrical pulses of 0.1-ms duration were shaped, attenuated, and passed through a current driver to an Etymotic ER-2 which was sealed in the ear canal. Electrical activity from stainless-steel electrodes was amplified, filtered (300-3000 Hz) and digitized at 20 kHz. Click levels included 70 and 90 dB peSPL. In each animal, conventional BAERs were obtained at rates ranging from 5 to 90 Hz. BAERs were also obtained using a cross-correlation technique involving pseudorandom pulse sequences called maximum length sequences (MLSs). The minimum time between pulses, called the minimum pulse interval (MPI), ranged from 0.5 to 6 ms. Two BAERs were obtained for each condition. Dependent variables included the latency and amplitude of the cochlear microphonic (CM), wave 2 and wave 3. BAERs were observed in all chicks, for all level by rate combinations for both conventional and MLS BAERs. There was no effect of click level or rate on the latency of the CM. The latency of waves 2 and 3 increased with decreasing click level and increasing rate. CM amplitude decreased with decreasing click level, but was not influenced by click rate for the 70 dB peSPL condition. For the 90 dB peSPL click, CM amplitude was uninfluenced by click rate for conventional averaging. For MLS BAERs, CM amplitude was similar to conventional averaging for longer MPIs.(ABSTRACT TRUNCATED AT 250 WORDS).

  17. Unusually severe food poisoning from vanilla slices.

    Science.gov (United States)

    Fenton, P. A.; Dobson, K. W.; Eyre, A.; McKendrick, M. W.

    1984-01-01

    Thirty six people suffered from severe vomiting and diarrhoea 15 min to 3 h after eating vanilla slices from the same bakery. Five patients were admitted to hospital, and one developed unusual skin lesions after admission. Staphylococcus aureus was isolated in large numbers from vanilla slices of the same batch as those giving rise to symptoms, and from five faecal specimens obtained from affected persons. Bacillus cereus and Bacillus subtilis were also isolated from the slices. Unbaked custard provides an ideal environment for bacterial multiplication, especially when (as on this occasion) the ambient temperature is persistently high. PMID:6438231

  18. Comparing brain-derived neurotrophic factor and ciliary neurotrophic factor secretion of induced neurotrophic factor secreting cells from human adipose and bone marrow-derived stem cells.

    Science.gov (United States)

    Razavi, Shahnaz; Razavi, Mohamad Reza; Zarkesh Esfahani, Hamid; Kazemi, Mohammad; Mostafavi, Fatemeh Sadat

    2013-08-01

    Adipose derived stem cells (ADSCs) and bone marrow stem cells (BMSCs) may be equally beneficial in treating neurodegenerative diseases. However, ADSCs have practical advantages. In this study, we aimed to induce neurotrophic factors secreting cells in human ADSCs. Then, we compared the level of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) secretion in neurotrophic factors secreting cells from human adipose and bone marrow-derived stem cells. Isolated human ADSCs and BMSCs were induced to neurotrophic factor (NTF)-secreting cells. The levels of expression and secretion of BDNF and CTNF of induced cells were assessed using immunocytochemical, Real-Time polymerase chain reaction, and enzyme linked immunosorbent assay (ELISA). The level of BDNF significantly increased in both the induced mesenchymal stem cells (MSCs) relative to ADSCs and the BMSCs (P < 0.01). Moreover, ELISA analysis showed that the release of BDNF in the induced BMSCs was almost twofold more than the induced ADSCs. Overall, NTF-secreting factor cells derived BMSCs and ADSCs could secret a range of different growth factors. Therefore, the variation in neurotrophic factors of different induced MSC populations suggest the possible beneficial effect of each specific kind of neurotrophic factor secreting cells for the treatment of a particular neurodegenerative disease. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

  19. Comparative study of expression and activity of glucose transporters between stem cell-derived brain microvascular endothelial cells and hCMEC/D3 cells.

    Science.gov (United States)

    Al-Ahmad, Abraham J

    2017-10-01

    Glucose constitutes a major source of energy of mammalian brains. Glucose uptake at the blood-brain barrier (BBB) occurs through a facilitated glucose transport, through glucose transporter 1 (GLUT1), although other isoforms have been described at the BBB. Mutations in GLUT1 are associated with the GLUT1 deficiency syndrome, yet none of the current in vitro models of the human BBB maybe suited for modeling such a disorder. In this study, we investigated the expression of glucose transporters and glucose diffusion across brain microvascular endothelial cells (BMECs) derived from healthy patient-derived induced pluripotent stem cells (iPSCs). We investigated the expression of different glucose transporters at the BBB using immunocytochemistry and flow cytometry and measured glucose uptake and diffusion across BMEC monolayers obtained from two iPSC lines and from hCMEC/D3 cells. BMEC monolayers showed expression of several glucose transporters, in particular GLUT1, GLUT3, and GLUT4. Diffusion of glucose across the monolayers was mediated via a saturable transcellular mechanism and partially inhibited by pharmacological inhibitors. Taken together, our study suggests the presence of several glucose transporters isoforms at the human BBB and demonstrates the feasibility of modeling glucose across the BBB using patient-derived stem cells. Copyright © 2017 the American Physiological Society.

  20. GDNF and neublastin protect against NMDA-induced excitotoxicity in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Bonde, C; Kristensen, B W; Blaabjerg, M

    2000-01-01

    The potential neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF) and neublastin (NBN) against NMDA-induced excitotoxicity were examined in hippocampal brain slice cultures. Recombinant human GDNF (25-100 ng/ ml) or NBN, in medium conditioned by growth of transfected, NBN...

  1. PTEN, a negative regulator of PI3K/Akt signaling, sustains brain stem cardiovascular regulation during mevinphos intoxication.

    Science.gov (United States)

    Tsai, Ching-Yi; Wu, Jacqueline C C; Fang, Chi; Chang, Alice Y W

    2017-09-01

    Activation of PI3K/Akt signaling, leading to upregulation of nitric oxide synthase II (NOS II)/peroxynitrite cascade in the rostral ventrolateral medulla (RVLM), the brain stem site that maintains blood pressure and sympathetic vasomotor tone, underpins cardiovascular depression induced by the organophosphate pesticide mevinphos. By exhibiting dual-specificity protein- and lipid-phosphatase activity, phosphatase and tensin homolog (PTEN) directly antagonizes the PI3K/Akt signaling by dephosphorylation of phosphatidylinositol-3,4,5-trisphosphate, the lipid product of PI3K. Based on the guiding hypothesis that PTEN may sustain brain stem cardiovascular regulation during mevinphos intoxication as a negative regulator of PI3K/Akt signaling in the RVLM, we aimed in this study to clarify the mechanistic role of PTEN in mevinphos-induced circulatory depression. Microinjection bilaterally of mevinphos (10 nmol) into the RVLM of anesthetized Sprague-Dawley rats induced a progressive hypotension and a decrease in baroreflex-mediated sympathetic vasomotor tone. There was progressive augmentation in PTEN activity as reflected by a decrease in the oxidized form of PTEN in the RVLM during mevinhpos intoxication, without significant changes in the mRNA or protein level of PTEN. Loss-of-function manipulations of PTEN in the RVLM by immunoneutralization, pharmacological blockade or siRNA pretreatment significantly potentiated the increase in Akt activity or NOS II/peroxynitrite cascade in the RVLM, enhanced the elicited hypotension and exacerbated the already reduced baroreflex-mediated sympathetic vasomotor tone. We conclude that augmented PTEN activity via a decrease of its oxidized form in the RVLM sustains brain stem cardiovascular regulation during mevinphos intoxication via downregulation of the NOS II/peroxynitrite cascade as a negative regulator of PI3K/Akt signaling. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Inhibition of cyclophosphamide-induced oxidative stress in brain by dietary inclusion of red dye extracts from sorghum (Sorghum bicolor) stem.

    Science.gov (United States)

    Oboh, Ganiya; Akomolafe, Toyin L; Adetuyi, Abayomi O

    2010-10-01

    The stem of sorghum is used as color additives in cooking meals and taken as beverages when steeped or boiled in water as folklore for the management of anemia and some other diseases. This study sought to assess the antioxidant and neuroprotective potentials of red dye extract from sorghum stem on cyclophosphamide-induced oxidative stress in rat brain. Wistar strain albino rats were fed diet supplemented with the red dye (0.5% and 1.0% inclusion) for 14 days. There was no significant difference (P > .05) in average feed intake and weight gain of rats fed the basal diet and the red dye-supplemented diet. However, intraperitoneal administration of cyclophosphamide (75 mg/kg of body weight) 24 hours prior the termination of the experiment caused a significant (P brain malondialdehyde (MDA) content and serum activities of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in those rats fed diet without the dye supplement, whereas there was a significant decrease (P brain MDA content and serum enzyme activities in rats fed diet with the dye in a concentration-dependent manner. The protective effect of the red dye against cyclophosphamide-induced oxidative stress could be attributed to the high phenolic content (56.2%) and antioxidant activities of the red dye as typified by 2,2-diphenyl-1-picrylhydrazyl free radical scavenging ability, reducing properties, and Fe(2+) chelating ability. Therefore, dietary inclusion of the red dye from sorghum stem could be harnessed in the management of neurodegenerative diseases associated with oxidative stress.

  3. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial.

    Science.gov (United States)

    Gondi, Vinai; Pugh, Stephanie L; Tome, Wolfgang A; Caine, Chip; Corn, Ben; Kanner, Andrew; Rowley, Howard; Kundapur, Vijayananda; DeNittis, Albert; Greenspoon, Jeffrey N; Konski, Andre A; Bauman, Glenn S; Shah, Sunjay; Shi, Wenyin; Wendland, Merideth; Kachnic, Lisa; Mehta, Minesh P

    2014-12-01

    Hippocampal neural stem-cell injury during whole-brain radiotherapy (WBRT) may play a role in memory decline. Intensity-modulated radiotherapy can be used to avoid conformally the hippocampal neural stem-cell compartment during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with prespecified comparison with a historical control of patients treated with WBRT without hippocampal avoidance. Eligible adult patients with brain metastases received HA-WBRT to 30 Gy in 10 fractions. Standardized cognitive function and quality-of-life (QOL) assessments were performed at baseline and 2, 4, and 6 months. The primary end point was the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR) at 4 months. The historical control demonstrated a 30% mean relative decline in HVLT-R DR from baseline to 4 months. To detect a mean relative decline ≤ 15% in HVLT-R DR after HA-WBRT, 51 analyzable patients were required to ensure 80% statistical power with α = 0.05. Of 113 patients accrued from March 2011 through November 2012, 42 patients were analyzable at 4 months. Mean relative decline in HVLT-R DR from baseline to 4 months was 7.0% (95% CI, -4.7% to 18.7%), significantly lower in comparison with the historical control (P memory and QOL as compared with historical series. © 2014 by American Society of Clinical Oncology.

  4. Attempt to identify the functional areas of the cerebral cortex on CT slices parallel to the orbito-meatal line

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, Hirotaka; Okuda, Junichiro; Nishikawa, Takashi; Nishimura, Tsuyoshi (Osaka Univ. (Japan). Faculty of Medicine); Shiraishi, Junzo

    1982-06-01

    In order to identify the functional brain areas, such as Broca's area, on computed tomography slices parallel to the orbito-meatal line, the numbers of Brodmann's cortical mapping were shown on a diagram of representative brain sections parallel to the orbito-meatal line. Also, we described a method, using cerebral sulci as anatomical landmarks, for projecting lesions shown by CT scan onto the lateral brain diagram. The procedures were as follows. The distribution of lesions on CT slices was determined by the identification of major cerebral sulci and fissures, such as the Sylvian fissure, the central sulcus, and the superior frontal sulcus. Those lesions were then projected onto the lateral diagram by comparing each CT slice with the horizontal diagrams of brain sections. The method was demonstrated in three cases developing neuropsychological symptoms.

  5. Myelination is Decreased in the Brain Stem of Small Piglets Compared to Larger Littermates During Late Gestation

    Science.gov (United States)

    Preweaning mortality is associated with low birth weights. Reduced myelination in the brain of low birth weight piglets has been reported, however, these studies measured brain cholesterol, which is not myelin. Thus, we compared myelination in brain regions associated with coordinated movement and r...

  6. dp53 Restrains ectopic neural stem cell formation in the Drosophila brain in a non-apoptotic mechanism involving Archipelago and cyclin E.

    Directory of Open Access Journals (Sweden)

    Yingshi Ouyang

    Full Text Available Accumulating evidence suggests that tumor-initiating stem cells or cancer stem cells (CSCs possibly originating from normal stem cells may be the root cause of certain malignancies. How stem cell homeostasis is impaired in tumor tissues is not well understood, although certain tumor suppressors have been implicated. In this study, we use the Drosophila neural stem cells (NSCs called neuroblasts as a model to study this process. Loss-of-function of Numb, a key cell fate determinant with well-conserved mammalian counterparts, leads to the formation of ectopic neuroblasts and a tumor phenotype in the larval brain. Overexpression of the Drosophila tumor suppressor p53 (dp53 was able to suppress ectopic neuroblast formation caused by numb loss-of-function. This occurred in a non-apoptotic manner and was independent of Dacapo, the fly counterpart of the well-characterized mammalian p53 target p21 involved in cellular senescence. The observation that dp53 affected Edu incorporation into neuroblasts led us to test the hypothesis that dp53 acts through regulation of factors involved in cell cycle progression. Our results show that the inhibitory effect of dp53 on ectopic neuroblast formation was mediated largely through its regulation of Cyclin E (Cyc E. Overexpression of Cyc E was able to abrogate dp53's ability to rescue numb loss-of-function phenotypes. Increasing Cyc E levels by attenuating Archipelago (Ago, a recently identified transcriptional target of dp53 and a negative regulator of Cyc E, had similar effects. Conversely, reducing Cyc E activity by overexpressing Ago blocked ectopic neuroblast formation in numb mutant. Our results reveal an intimate connection between cell cycle progression and NSC self-renewal vs. differentiation control, and indicate that p53-mediated regulation of ectopic NSC self-renewal through the Ago/Cyc E axis becomes particularly important when NSC homeostasis is perturbed as in numb loss-of-function condition. This has

  7. Initial Attempts of Development and Characterization of an In Vitro Blood Brain Barrier Model Derived from Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Goldeman, Charlotte; Saaby, Lasse; Hall, Vanessa Jane

    observed for several days after seeding by measuring the trans-endothelial electrical resistance (TEER). Initial pilot studies have shown a significant difference between stem cells grown as a mono culture and stem cells grown in co-culture with rat astrocytes. The stem cell line WTSli024-A had...... configurations (mono culture, non-contact co-culture and contact co-culture) with primary rat astrocytes to induce barrier-like properties. Endothelial cell media supplemented with retinoic acid were then applied to the cells to ensure selective expansion of BECs. The different culture configurations were...

  8. Human Cytomegalovirus IE2 Protein Disturbs Brain Development by the Dysregulation of Neural Stem Cell Maintenance and the Polarization of Migrating Neurons.

    Science.gov (United States)

    Han, Dasol; Byun, Sung-Hyun; Kim, Juwan; Kwon, Mookwang; Pleasure, Samuel J; Ahn, Jin-Hyun; Yoon, Keejung

    2017-09-01

    Despite the high incidence of severe defects in the central nervous system caused by human cytomegalovirus (HCMV) congenital infection, the mechanism of HCMV neuropathogenesis and the roles of individual viral genes have not yet been fully determined. In this study, we show that the immediate-early 2 (IE2) protein may play a key role in HCMV-caused neurodevelopmental disorders. IE2-transduced neural progenitor cells gave rise to neurospheres with a lower frequency and produced smaller neurospheres than control cells in vitro , indicating reduction of self-renewal and expansion of neural progenitors by IE2. At 2 days after in utero electroporation into the ventricle of the developing brain, a dramatically lower percentage of IE2-expressing cells was detected in the ventricular zone (VZ) and cortical plate (CP) compared to control cells, suggesting that IE2 concurrently dysregulates neural stem cell maintenance in the VZ and neuronal migration to the CP. In addition, most IE2 + cells in the lower intermediate zone either showed multipolar morphology with short neurites or possessed nonradially oriented processes, whereas control cells had long, radially oriented monopolar or bipolar neurites. IE2 + callosal axons also failed to cross the midline to form the corpus callosum. Furthermore, we provide molecular evidence that the cell cycle arrest and DNA binding activities of IE2 appear to be responsible for the increased neural stem cell exit from the VZ and cortical migrational defects, respectively. Collectively, our results demonstrate that IE2 disrupts the orderly process of brain development in a stepwise manner to further our understanding of neurodevelopmental HCMV pathogenesis. IMPORTANCE HCMV brain pathogenesis has been studied in limited experimental settings, such as in vitro HCMV infection of neural progenitor cells or in vivo murine CMV infection of the mouse brain. Here, we show that IE2 is a pivotal factor that contributes to HCMV-induced abnormalities in

  9. 5-Fluorouracil and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) followed by hydroxyurea, misonidazole, and irradiation for brain stem gliomas: a pilot study of the Brain Tumor Research Center and the Childrens Cancer Group

    International Nuclear Information System (INIS)

    Levin, V.A.; Edwards, M.S.; Wara, W.M.; Allen, J.; Ortega, J.; Vestnys, P.

    1984-01-01

    Twenty-eight evaluable children with the diagnosis of brain stem glioma were treated with 5-fluorouracil and CCNU before posterior fossa irradiation (5500 rads); during irradiation, the children received hydroxyurea and misonidazole. The treatment was well tolerated, and minimal toxicity was produced. The median relapse-free survival was 32 weeks, and the median survival was 44 weeks. Analysis of covariates showed that, in patients between the ages of 2 and 19 years, survival was longest in the older children (P less than 0.02). Tumor histology, sex, extent of operation (if any), Karnofsky score, and radiation dose did not correlate with survival

  10. GDNF and neublastin protect against NMDA-induced excitotoxicity in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Bonde, C; Kristensen, B W; Blaabjerg, M

    2000-01-01

    The potential neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF) and neublastin (NBN) against NMDA-induced excitotoxicity were examined in hippocampal brain slice cultures. Recombinant human GDNF (25-100 ng/ ml) or NBN, in medium conditioned by growth of transfected, NBN......-producing HiB5 cells, were added to slice cultures I h before exposure to 10 microM NMDA for 48h. Neuronal cell death was monitored, before and during the NMDA exposure, by densitometric measurements of propidium iodide (PI) uptake and loss of Nissl staining. Both the addition of rhGDNF and NBN...

  11. The anatomical classification of AICA/PICA branching and configurations in the cerebellopontine angle area on 3D-drive thin slice T2WI MRI.

    Science.gov (United States)

    Kazawa, Nobukata; Togashi, Kaori; Ito, Juichi

    2013-01-01

    With the technical advance of magnetic resonance imaging (MRI), we have been able to observe not only the small cranial nerves arising from the brain stem but also the branches of vertebrobasilar artery in the cerebellopontine angle (CPA) cistern. The purpose was to demonstrate the courses and configurations of the anterior inferior cerebellar artery (AICA) or posterior inferior cerebellar artery (PICA) branch including the internal auditory artery in the CPA cistern and evaluate the relationship between the facial-vestibulocochlear (VIIth-VIIIth) nerves and AICA/PICA on high-resolution, thin-slice, three-dimensional T2-weighted MRI using driven equilibrium pulse. Thirty-three men and 27 women aged 8-85 years old with sensory hearing loss or vertigo, and/or tinnitus were evaluated by thin-slice (0.75 mm) T2-weighted MRI. Five subjects (3 men, 2 women) without any auditory symptoms were also examined. Thin-slice T2WI drive MRI revealed several variations of the AICA/PICA coursing, such as a loop formation (n=30, 48 sides) or the IAC extension (n=19, 30 sides). Contact with the vestibulocochlear nerve was seen in 31.7% subjects (n=19, 27 sides). The AICA/PICA branching and shape patterns relative to the CPA and IAC were classified into four major types: type 1A, nonloop AICA/PICA in the CPA cistern; type 1 B, nonloop AICA/PICA (internal auditory artery) entering the IAC; type 2A, loop-type AICA/PICA in the CPA cistern; and type 2B, loop-type AICA/PICA entering the IAC. There was statistically significant association between types 1A and 2A (P<.01) regarding the existence of any auditory 3 symptoms. The results of our study suggest that this classification is simple and very useful for the elucidation of the mechanism of auditory symptoms and deciding the therapeutic strategies. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. The Anti-Tumor Effects of Adipose Tissue Mesenchymal Stem Cell Transduced with HSV-Tk Gene on U-87-Driven Brain Tumor.

    Directory of Open Access Journals (Sweden)

    Suely Maymone de Melo

    Full Text Available Glioblastoma (GBM is an infiltrative tumor that is difficult to eradicate. Treating GBM with mesenchymal stem cells (MSCs that have been modified with the HSV-Tk suicide gene has brought significant advances mainly because MSCs are chemoattracted to GBM and kill tumor cells via a bystander effect. To use this strategy, abundantly present adipose-tissue-derived mesenchymal stem cells (AT-MSCs were evaluated for the treatment of GBM in mice. AT-MSCs were prepared using a mechanical protocol to avoid contamination with animal protein and transduced with HSV-Tk via a lentiviral vector. The U-87 glioblastoma cells cultured with AT-MSC-HSV-Tk died in the presence of 25 or 50 μM ganciclovir (GCV. U-87 glioblastoma cells injected into the brains of nude mice generated tumors larger than 3.5 mm2 after 4 weeks, but the injection of AT-MSC-HSV-Tk cells one week after the U-87 injection, combined with GCV treatment, drastically reduced tumors to smaller than 0.5 mm2. Immunohistochemical analysis of the tumors showed the presence of AT-MSC-HSV-Tk cells only within the tumor and its vicinity, but not in other areas of the brain, showing chemoattraction between them. The abundance of AT-MSCs and the easier to obtain them mechanically are strong advantages when compared to using MSCs from other tissues.

  13. Effective treatment of glioblastoma requires crossing the blood–brain barrier and targeting tumors including cancer stem cells: The promise of nanomedicine

    Science.gov (United States)

    Kim, Sang-Soo; Harford, Joe B.; Pirollo, Kathleen F.; Chang, Esther H.

    2015-01-01

    Glioblastoma multiforme (GBM) is the most aggressive and lethal type of brain tumor. Both therapeutic resistance and restricted permeation of drugs across the blood–brain barrier (BBB) play a major role in the poor prognosis of GBM patients. Accumulated evidence suggests that in many human cancers, including GBM, therapeutic resistance can be attributed to a small fraction of cancer cells known as cancer stem cells (CSCs). CSCs have been shown to have stem cell-like properties that enable them to evade traditional cytotoxic therapies, and so new CSC-directed anti-cancer therapies are needed. Nanoparticles have been designed to selectively deliver payloads to relevant target cells in the body, and there is considerable interest in the use of nanoparticles for CSC-directed anti-cancer therapies. Recent advances in the field of nanomedicine offer new possibilities for overcoming CSC-mediated therapeutic resistance and thus significantly improving management of GBM. In this review, we will examine the current nanomedicine approaches for targeting CSCs and their therapeutic implications. The inhibitory effect of various nanoparticle-based drug delivery system towards CSCs in GBM tumors is the primary focus of this review. PMID:26116770

  14. Effective treatment of glioblastoma requires crossing the blood-brain barrier and targeting tumors including cancer stem cells: The promise of nanomedicine.

    Science.gov (United States)

    Kim, Sang-Soo; Harford, Joe B; Pirollo, Kathleen F; Chang, Esther H

    2015-12-18

    Glioblastoma multiforme (GBM) is the most aggressive and lethal type of brain tumor. Both therapeutic resistance and restricted permeation of drugs across the blood-brain barrier (BBB) play a major role in the poor prognosis of GBM patients. Accumulated evidence suggests that in many human cancers, including GBM, therapeutic resistance can be attributed to a small fraction of cancer cells known as cancer stem cells (CSCs). CSCs have been shown to have stem cell-like properties that enable them to evade traditional cytotoxic therapies, and so new CSC-directed anti-cancer therapies are needed. Nanoparticles have been designed to selectively deliver payloads to relevant target cells in the body, and there is considerable interest in the use of nanoparticles for CSC-directed anti-cancer therapies. Recent advances in the field of nanomedicine offer new possibilities for overcoming CSC-mediated therapeutic resistance and thus significantly improving management of GBM. In this review, we will examine the current nanomedicine approaches for targeting CSCs and their therapeutic implications. The inhibitory effect of various nanoparticle-based drug delivery system towards CSCs in GBM tumors is the primary focus of this review. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Brain blood flow studies with single photon emission computed tomography in patients with plateau waves

    International Nuclear Information System (INIS)

    Hayashi, Minoru; Kobayashi, Hidenori; Kawano, Hirokazu; Handa, Yuji; Noguchi, Yoshiyuki; Shirasaki, Naoki; Hirose, Satoshi

    1986-01-01

    The authors studied brain blood flow with single photon emission computed tomography (SPECT) in two patients with plateau waves. The intracranial pressure and blood pressure were also monitored continuously in these patients. They included one patient with brain-tumor (rt. sphenoid ridge meningioma) and another with hydrocephalus after subarachnoid hemorrhage due to rupture of lt. internal carotid aneurysm. The intracranial pressure was monitored through an indwelling ventricular catheter attached to a pressure transducer. The blood pressure was recorded through an intraarterial catheter placed in the dorsalis pedis artery. Brain blood flow was studied with Headtome SET-011 (manufactured by Shimazu Co., Ltd.). For this flow measurement study, an intravenous injection of Xenon-133 of about 30 mCi was given via an antecubital vein. The position of the slice for the SPECT was selected so as to obtain information not only from the cerebral hemisphere but also from the brain stem : a cross section 25 deg over the orbito-meatal line, passing through the inferior aspect of the frontal horn, the basal ganglia, the lower recessus of the third ventricle and the brain stem. The results indicated that, in the cerebral hemisphere, plateau waves were accompanied by a decrease in blood flow, whereas, in the brain stem, the blood flow showed little change during plateau waves as compared with the interval phase between two plateau waves. These observations may explain why there is no rise in the blood pressure and why patients are often alert during plateau waves. (author)

  16. Interactive Slice of the CMS detector

    CERN Multimedia

    Davis, Siona Ruth

    2016-01-01

    This slice shows a colorful cross-section of the CMS detector with all parts of the detector labelled. Viewers are invited to click on buttons associated with five types of particles to see what happens when each type interacts with the sections of the detector. The five types of particles users can select to send through the slice are muons, electrons, neutral hadrons, charged hadrons and photons. Supplementary information on each type of particles is given. Useful for inclusion into general talks on CMS etc. *Animated CMS "slice" for Powerpoint (Mac & PC) Original version - 2004 Updated version - July 2010 *Six slides required - first is a set of buttons; others are for each particle type (muon, electron, charged/neutral hadron, photon) Recommend putting slide 1 anywhere in your presentation and the rest at the end

  17. Slice through an LHC bending magnet

    CERN Multimedia

    Slice through an LHC superconducting dipole (bending) magnet. The slice includes a cut through the magnet wiring (niobium titanium), the beampipe and the steel magnet yokes. Particle beams in the Large Hadron Collider (LHC) have the same energy as a high-speed train, squeezed ready for collision into a space narrower than a human hair. Huge forces are needed to control them. Dipole magnets (2 poles) are used to bend the paths of the protons around the 27 km ring. Quadrupole magnets (4 poles) focus the proton beams and squeeze them so that more particles collide when the beams’ paths cross. There are 1232 15m long dipole magnets in the LHC.

  18. Introduction to bit slices and microprogramming

    International Nuclear Information System (INIS)

    Van Dam, A.

    1981-01-01

    Bit-slice logic blocks are fourth-generation LSI components which are natural extensions of traditional mulitplexers, registers, decoders, counters, ALUs, etc. Their functionality is controlled by microprogramming, typically to implement CPUs and peripheral controllers where both speed and easy programmability are required for flexibility, ease of implementation and debugging, etc. Processors built from bit-slice logic give the designer an alternative for approaching the programmibility of traditional fixed-instruction-set microprocessors with a speed closer to that of hardwired random logic. (orig.)

  19. Melatonin disturbs SUMOylation mediated crosstalk between c-Myc and Nestin via MT1 activation and promotes the sensitivity of Paclitaxel in brain cancer stem cells.

    Science.gov (United States)

    Lee, Hyemin; Lee, Hyo-Jung; Jung, Ji Hoon; Shin, Eun Ah; Kim, Sung-Hoon

    2018-04-14

    Here the underlying antitumor mechanism of melatonin and its potency as a sensitizer of Paclitaxel was investigated in X02 cancer stem cells. Melatonin suppressed sphere formation and induced G2/M arrest in X02 cells expressing Nestin, CD133, CXCR4 and SOX-2 as biomarkers of stemness. Furthermore, melatonin reduced the expression of CDK2, CDK4, cyclin D1, cyclin E, and c-Myc and upregulated cyclin B1 in X02 cells. Notably, genes of c-Myc related mRNAs were differentially expressed in melatonin treated X02 cells by microarray analysis. Consistently, melatonin reduced the expression of c-Myc at mRNA and protein levels, which was blocked by MG132. Of note, overexpression of c-Myc increased the expression of Nestin, while overexpression of Nestin enhanced c-Myc through crosstalk despite different locations, nucleus and cytoplasm. Interestingly, melatonin attenuated small ubiquitin-related modifier-1 (SUMO-1) more than SUMO-2 or SUMO-3 and disturbed nuclear translocation of Nestin for direct binding to c-Myc by SUMOylation of SUMO-1 protein by immunofluorescence and immunoprecipitation. Also, melatonin reduced trimethylated histone H3K4me3 and H3K36me3 more than dimethylation in X02 cells by Western blotting and Chromatin immunoprecipitation assay. Notably, melatonin upregulated MT1, not MT2, in X02 cells and melatonin receptor inhibitor Luzindole blocked the ability of melatonin to decrease the expression of Nestin, p-c-Myc(S62) and c-Myc. Furthermore, melatonin promoted cytotoxicity, sub G1 accumulation and apoptotic body formation by Paclitaxcel in X02 cells. Taken together, these findings suggest that melatonin inhibits stemness via suppression of c-Myc, Nestin, and histone methylation via MT1 activation and promotes anticancer effect of Paclitaxcel in brain cancer stem cells. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. The effects of slice thickness and reconstructive parameters on VR image quality in multi-slice CT

    International Nuclear Information System (INIS)

    Gao Zhenlong; Wang Qiang; Liu Caixia

    2005-01-01

    Objective: To explore the effects of slice thickness, reconstructive thickness and reconstructive interval on VR image quality in multi-slice CT, in order to select the best slice thickness and reconstructive parameters for the imaging. Methods: Multi-slice CT scan was applied on a rubber dinosaur model with different slice thickness. VR images were reconstructed with different reconstructive thickness and reconstructive interval. Five radiologists were invited to evaluate the quality of the images without knowing anything about the parameters. Results: The slice thickness, reconstructive thickness and reconstructive interval did have effects on VR image quality and the effective degree was different. The effective coefficients were V 1 =1413.033, V 2 =563.733, V 3 =390.533, respectively. The parameters interacted with the others (P<0.05). The smaller of those parameters, the better of the image quality. With a small slice thickness and a reconstructive slice equal to slice thickness, the image quality had no obvious difference when the reconstructive interval was 1/2, 1/3, 1/4 of the slice thickness. Conclusion: A relative small scan slice thickness, a reconstructive slice equal to slice thickness and a reconstructive interval 1/2 of the slice thickness should be selected for the best VR image quality. The image quality depends mostly on the slice thickness. (authors)

  1. Fatal outcome after brain stem infarction related to bilateral vertebral artery occlusion - case report of a detrimental complication of cervical spine trauma.

    Science.gov (United States)

    Yoshihara, Hiroyuki; Vanderheiden, Todd F; Harasaki, Yasuaki; Beauchamp, Kathryn M; Stahel, Philip F

    2011-07-14

    Vertebral artery injury (VAI) after blunt cervical trauma occurs more frequently than historically believed. The symptoms due to vertebral artery (VA) occlusion usually manifest within the first 24 hours after trauma. Misdiagnosed VAI or delay in diagnosis has been reported to cause acute deterioration of previously conscious and neurologically intact patients. A 67 year-old male was involved in a motor vehicle crash (MVC) sustaining multiple injuries. Initial evaluation by the emergency medical response team revealed that he was alert, oriented, and neurologically intact. He was transferred to the local hospital where cervical spine computed tomography (CT) revealed several abnormalities. Distraction and subluxation was present at C5-C6 and a comminuted fracture of the left lateral mass of C6 with violation of the transverse foramen was noted. Unavailability of a spine specialist prompted the patient's transfer to an area medical center equipped with spine care capabilities. After arrival, the patient became unresponsive and neurological deficits were noted. His continued deterioration prompted yet another transfer to our Level 1 regional trauma center. A repeat cervical spine CT at our institution revealed significantly worsened subluxation at C5-C6. CT angiogram also revealed complete occlusion of bilateral VA. The following day, a repeat CT of the head revealed brain stem infarction due to bilateral VA occlusion. Shortly following, the patient was diagnosed with brain death and care was withdrawn. Brain stem infarction secondary to bilateral VA occlusion following cervical spine trauma resulted in fatal outcome. Prompt imaging evaluation is necessary to assess for VAI in cervical trauma cases with facet joint subluxation/dislocation or transverse foramen fracture so that treatment is not delayed. Additionally, multiple transportation events are risk factors for worsening when unstable cervical injuries are present. Close attention to proper immobilization and

  2. Fatal outcome after brain stem infarction related to bilateral vertebral artery occlusion - case report of a detrimental complication of cervical spine trauma

    Directory of Open Access Journals (Sweden)

    Beauchamp Kathryn M

    2011-07-01

    Full Text Available Abstract Background Vertebral artery injury (VAI after blunt cervical trauma occurs more frequently than historically believed. The symptoms due to vertebral artery (VA occlusion usually manifest within the first 24 hours after trauma. Misdiagnosed VAI or delay in diagnosis has been reported to cause acute deterioration of previously conscious and neurologically intact patients. Case presentation A 67 year-old male was involved in a motor vehicle crash (MVC sustaining multiple injuries. Initial evaluation by the emergency medical response team revealed that he was alert, oriented, and neurologically intact. He was transferred to the local hospital where cervical spine computed tomography (CT revealed several abnormalities. Distraction and subluxation was present at C5-C6 and a comminuted fracture of the left lateral mass of C6 with violation of the transverse foramen was noted. Unavailability of a spine specialist prompted the patient's transfer to an area medical center equipped with spine care capabilities. After arrival, the patient became unresponsive and neurological deficits were noted. His continued deterioration prompted yet another transfer to our Level 1 regional trauma center. A repeat cervical spine CT at our institution revealed significantly worsened subluxation at C5-C6. CT angiogram also revealed complete occlusion of bilateral VA. The following day, a repeat CT of the head revealed brain stem infarction due to bilateral VA occlusion. Shortly following, the patient was diagnosed with brain death and care was withdrawn. Conclusion Brain stem infarction secondary to bilateral VA occlusion following cervical spine trauma resulted in fatal outcome. Prompt imaging evaluation is necessary to assess for VAI in cervical trauma cases with facet joint subluxation/dislocation or transverse foramen fracture so that treatment is not delayed. Additionally, multiple transportation events are risk factors for worsening when unstable cervical

  3. Inter-slice Leakage Artifact Reduction Technique for Simultaneous Multi-Slice Acquisitions

    Science.gov (United States)

    Cauley, Stephen F.; Polimeni, Jonathan R.; Bhat, Himanshu; Wang, Dingxin; Wald, Lawrence L.; Setsompop, Kawin

    2015-01-01

    Purpose Controlled aliasing techniques for simultaneously acquired EPI slices have been shown to significantly increase the temporal efficiency for both diffusion-weighted imaging (DWI) and fMRI studies. The “slice-GRAPPA” (SG) method has been widely used to reconstruct such data. We investigate robust optimization techniques for SG to ensure image reconstruction accuracy through a reduction of leakage artifacts. Methods Split slice-GRAPPA (SP-SG) is proposed as an alternative kernel optimization method. The performance of SP-SG is compared to standard SG using data collected on a spherical phantom and in-vivo on two subjects at 3T. Slice accelerated and non-accelerated data were collected for a spin-echo diffusion weighted acquisition. Signal leakage metrics and time-series SNR were used to quantify the performance of the kernel fitting approaches. Results The SP-SG optimization strategy significantly reduces leakage artifacts for both phantom and in-vivo acquisitions. In addition, a significant boost in time-series SNR for in-vivo diffusion weighted acquisitions with in-plane 2× and slice 3× accelerations was observed with the SP-SG approach. Conclusion By minimizing the influence of leakage artifacts during the training of slice-GRAPPA kernels, we have significantly improved reconstruction accuracy. Our robust kernel fitting strategy should enable better reconstruction accuracy and higher slice-acceleration across many applications. PMID:23963964

  4. SDF-1α/CXCR4 Axis Mediates The Migration of Mesenchymal Stem Cells to The Hypoxic-Ischemic Brain Lesion in A Rat Model.

    Science.gov (United States)

    Yu, Qin; Liu, Lizhen; Lin, Jie; Wang, Yan; Xuan, Xiaobo; Guo, Ying; Hu, Shaojun

    2015-01-01

    Transplantation of mesenchymal stem cells (MSCs) can promote functional recovery of the brain after hypoxic-ischemic brain damage (HIBD). However, the mechanism regulating MSC migration to a hypoxic-ischemic lesion is poorly understood. Interaction between stromal cell-derived factor-1α (SDF-1α) and its cognate receptor CXC chemokine receptor 4 (CXCR4) is crucial for homing and migration of multiple stem cell types. In this study, we investigate the potential role of SDF-1α/CXCR4 axis in mediating MSC migration in an HIBD model. In this experimental study, we first established the animal model of HIBD using the neonatal rat. Bone marrow MSCs were cultured and labeled with 5-bromo-21-deoxyuridine (BrdU) after which 6×10(6) cells were intravenously injected into the rat. BrdU positive MSCs in the hippocampus were detected by immunohistochemical analyses. The expression of hypoxia-inducible factor-1α (HIF-1α) and SDF-1α in the hippocampus of hypoxic-ischemic rats was detected by Western blotting. To investigate the role of hypoxia and SDF-1α on migration of MSCs in vitro, MSCs isolated from normal rats were cultured in a hypoxic environment (PO2=1%). Migration of MSCs was detected by the transwell assay. The expression of CXCR4 was tested using Western blotting and flow cytometry. BrdU-labeled MSCs were found in the rat brain, which suggested that transplanted MSCs migrated to the site of the hypoxic-ischemic brain tissue. HIF-1α and SDF-1α significantly increased in the hippocampal formations of HIBD rats in a time-dependent manner. They peaked on day 7 and were stably expressed until day 21. Migration of MSCs in vitro was promoted by SDF-1α under hypoxia and inhibited by the CXCR4 inhibitor AMD3100. The expression of CXCR4 on MSCs was elevated by hypoxia stimulation as well as microdosage treatment of SDF-1α. This observation illustrates that SDF-1α/CXCR4 axis mediate the migration of MSCs to a hypoxic-ischemic brain lesion in a rat model.

  5. Mesenchymal stem cell transplantation attenuates blood brain barrier damage and neuroinflammation and protects dopaminergic neurons against MPTP toxicity in the substantia nigra in a model of Parkinson's disease.

    Science.gov (United States)

    Chao, Yin Xia; He, Bei Ping; Tay, Samuel Sam Wah

    2009-11-30

    Immunomodulatory effects of transplanted mesenchymal stem cells (MSCs) in the treatment of Parkinson's disease were studied in the MPTP-induced mouse model. MPTP treatment induced a significant loss of dopaminergic neurons, decreased expressions of claudin 1, claudin 5 and occludin in the substantia nigra compacta (SNc), and functional damage of the blood brain barrier (BBB). Our study further discovered that infiltration of MBLs into the brain to bind with microglia was detected in the SNc of MPTP-treated mice, suggesting that the BBB compromise and MBL infiltration might be involved in the pathogenesis of MPTP-induced PD. In addition, MPTP treatment also increased the expression of mannose-binding lectins (MBLs) in the liver tissue. Intravenous transplantation of MSCs into MPTP-treated mice led to recovery of BBB integrity, suppression of MBL infiltration at SNc and MBL expression in the liver, suppression of microglial activation and prevention of dopaminergic neuron death. No transplanted MSCs were observed to differentiate into dopaminergic neurons, while the MSCs migrated into the SNc and released TGF-beta1 there. Therefore, intravenous transplantation of MSCs which protect dopaminergic neurons from MPTP toxicity may be engaged in anyone or a combination of these mechanisms: repair of the BBB, reduction of MBL in the brain, inhibition of microglial cytotoxicity, and direct protection of dopaminergic neurons.

  6. [Ferumoxide labeled Flk1+ CD31- CD34- human bone marrow mesenchymal stem cells and its in vivo tracing in the brains of Macaca Fascicularis].

    Science.gov (United States)

    Feng, Ming; Wang, Ren-Zhi; Zhu, Hua; Zhang, Nan; Wang, Chang-Jun; Wei, Jun-Ji; Lu, Shan; Li, Qin; Yin, Xiao-Ming; Han, Qin; Ma, Wen-Bin; Qin, Chuang; Zhao, Chun-Hua; An, Yi-Hua; Kong, Yan-Guo

    2008-10-01

    To explore the method for labeling Flk1+ CD31- CD34- human bone marrow mesenchymal stem cells (hBMSCs) with ferumoxide-PLL and evaluate the feasibility of its tracing after transplantation into the brains of Macaca Fascicularis. The hBMSCs were incubated with ferumoxide-PLL. Trypan blue staining, Prussian blue staining, and transmission electron microscope were performed to show intracellular iron, marking efficiency, and the vigor of the labeled cells. After the hBMSCs were transplanted into the brains of cynomolgus monkeys by stereotaxis, magnetic resonance imaging (MRI) was performed to trace the cells in vivo. Cell survival and differentiation were studied with immunohistochemistry, Prussian blue staining, and HE staining. The marking efficiency of the ferumoxide-PLL was 96%. Iron particles were found intracytoplasmic of the hBMSCs by Prussian blue staining and transmission electron microscopy. The relaxation rates of labeled cells in MRI were 4.4 and 4.2 times higher than those of the unlabeled cells. Hypointensity area was found by MRI three weeks after transplantation. Many hBMSCs and new vessels were found in the transplantation zone by pathological and immunofluorescence methods. Ferumoxide-PLL can effectively label hBMSCs and thus increase its contrast in MRI results. The cells can survive in the brains of cynomolgus monkeys. The labeled hBMSCs can be traced in vivo by MRI.

  7. Detecting Psychopathy from Thin Slices of Behavior

    Science.gov (United States)

    Fowler, Katherine A.; Lilienfeld, Scott O.; Patrick, Christopher J.

    2009-01-01

    This study is the first to demonstrate that features of psychopathy can be reliably and validly detected by lay raters from "thin slices" (i.e., small samples) of behavior. Brief excerpts (5 s, 10 s, and 20 s) from interviews with 96 maximum-security inmates were presented in video or audio form or in both modalities combined. Forty raters used…

  8. Adaptive slices for acquisition of anisotropic BRDF

    Czech Academy of Sciences Publication Activity Database

    Vávra, Radomír; Filip, Jiří

    (2018) ISSN 2096-0433 R&D Projects: GA ČR GA17-18407S Institutional support: RVO:67985556 Keywords : anisotropic BRDF * slice * sampling Subject RIV: BD - Theory of Information http://library.utia.cas.cz/separaty/2018/RO/vavra-0486116.pdf

  9. Thin-Slice Perception Develops Slowly

    Science.gov (United States)

    Balas, Benjamin; Kanwisher, Nancy; Saxe, Rebecca

    2012-01-01

    Body language and facial gesture provide sufficient visual information to support high-level social inferences from "thin slices" of behavior. Given short movies of nonverbal behavior, adults make reliable judgments in a large number of tasks. Here we find that the high precision of adults' nonverbal social perception depends on the slow…

  10. In Vitro Manganese Exposure Disrupts MAPK Signaling Pathways in Striatal and Hippocampal Slices from Immature Rats

    Directory of Open Access Journals (Sweden)

    Tanara Vieira Peres

    2013-01-01

    Full Text Available The molecular mechanisms mediating manganese (Mn-induced neurotoxicity, particularly in the immature central nervous system, have yet to be completely understood. In this study, we investigated whether mitogen-activated protein kinases (MAPKs and tyrosine hydroxylase (TH could represent potential targets of Mn in striatal and hippocampal slices obtained from immature rats (14 days old. The aim of this study was to evaluate if the MAPK pathways are modulated after subtoxic Mn exposure, which do not significantly affect cell viability. The concentrations of manganese chloride (MnCl2; 10–1,000 μM caused no change in cell viability in slices exposed for 3 or 6 hours. However, Mn exposure significantly increased extracellular signal-regulated kinase (ERK 1/2, as well as c-Jun N-terminal kinase (JNK 1/2/3 phosphorylation at both 3 and 6 hours incubations, in both brain structures. Furthermore, Mn exposure did not change the total content or phosphorylation of TH at the serine 40 site in striatal slices. Thus, Mn at concentrations that do not disrupt cell viability causes activation of MAPKs (ERK1/2 and JNK1/2/3 in immature hippocampal and striatal slices. These findings suggest that altered intracellular MAPKs signaling pathways may represent an early event concerning the effects of Mn in the immature brain.

  11. CENTRAL ASSESSMENT OF COMPUTED TOMOGRAPHY BRAIN SCANS

    Directory of Open Access Journals (Sweden)

    Lesley Ann Cala

    2016-08-01

    Full Text Available Development of multislice CT (MSCT scanners since 1998 has resulted in submillimetre thick slices being able to be acquired, without increasing the radiation dose to the patient. Although the incident x-ray beam is widened in the slice thickness direction (Z-direction, the emergent x-rays fall upon multiple rows of small detectors. This means data can be collected simultaneously for more than one slice per rotation of the x-ray tube. For example, the dose received by the patient will be the same for four thin slices of 2.5 mm, as for one slice of 10 mm thickness. A 64-slice MSCT can create 0.625 mm thick slices. This leads to high diagnostic value in the detection of small abnormalities in stroke patients and in the reconstruction of data from CT angiography (CTA of the brain.

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

    Science.gov (United States)

    2015-04-01

    techniques were used to resolve the shock front as it propagated from the air medium through the aquarium Poly( methyl methacrylate) (PMMA) material and into...Karanian DA, Baude A, Brown QB, Parsons C, Bahr BA. 3-Nitropropionic acid toxicity in hippocampus: Protection through N- methyl -D-aspartate receptor...RDRL CIO LL IMAL HRA MAIL & RECORDS MGMT 1 GOVT PRINTG OFC (PDF) A MALHOTRA 6 DIR USARL (PDF) RDRL WML C S AUBERT R BENJAMIN

  13. The "pseudo-CT myelogram sign": an aid to the diagnosis of underlying brain stem and spinal cord trauma in the presence of major craniocervical region injury on post-mortem CT.

    Science.gov (United States)

    Bolster, F; Ali, Z; Daly, B

    2017-12-01

    To document the detection of underlying low-attenuation spinal cord or brain stem injuries in the presence of the "pseudo-CT myelogram sign" (PCMS) on post-mortem computed tomography (PMCT). The PCMS was identified on PMCT in 20 decedents (11 male, nine female; age 3-83 years, mean age 35.3 years) following fatal blunt trauma at a single forensic centre. Osseous and ligamentous craniocervical region injuries and brain stem or spinal cord trauma detectable on PMCT were recorded. PMCT findings were compared to conventional autopsy in all cases. PMCT-detected transection of the brain stem or high cervical cord in nine of 10 cases compared to autopsy (90% sensitivity). PMCT was 92.86% sensitive in detection of atlanto-occipital joint injuries (n=14), and 100% sensitive for atlanto-axial joint (n=8) injuries. PMCT detected more cervical spine and skull base fractures (n=22, and n=10, respectively) compared to autopsy (n=13, and n=5, respectively). The PCMS is a novel description of a diagnostic finding, which if present in fatal craniocervical region trauma, is very sensitive for underlying spinal cord and brain stem injuries not ordinarily visible on PMCT. Its presence may also predict major osseous and/or ligamentous injuries in this region when anatomical displacement is not evident on PMCT. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  14. Cryopreservation of Brain Endothelial Cells Derived from Human Induced Pluripotent Stem Cells Is Enhanced by Rho-Associated Coiled Coil-Containing Kinase Inhibition.

    Science.gov (United States)

    Wilson, Hannah K; Faubion, Madeline G; Hjortness, Michael K; Palecek, Sean P; Shusta, Eric V

    2016-12-01

    The blood-brain barrier (BBB) maintains brain homeostasis but also presents a major obstacle to brain drug delivery. Brain microvascular endothelial cells (BMECs) form the principal barrier and therefore represent the major cellular component of in vitro BBB models. Such models are often used for mechanistic studies of the BBB in health and disease and for drug screening. Recently, human induced pluripotent stem cells (iPSCs) have emerged as a new source for generating BMEC-like cells for use in in vitro human BBB studies. However, the inability to cryopreserve iPSC-BMECs has impeded implementation of this model by requiring a fresh differentiation to generate cells for each experiment. Cryopreservation of differentiated iPSC-BMECs would have a number of distinct advantages, including enabling production of larger scale lots, decreasing lead time to generate purified iPSC-BMEC cultures, and facilitating use of iPSC-BMECs in large-scale screening. In this study, we demonstrate that iPSC-BMECs can be successfully cryopreserved at multiple differentiation stages. Cryopreserved iPSC-BMECs retain high viability, express standard endothelial and BBB markers, and reach a high transendothelial electrical resistance (TEER) of ∼3000 Ω·cm 2 , equivalent to nonfrozen controls. Rho-associated coiled coil-containing kinase (ROCK) inhibitor Y-27632 substantially increased survival and attachment of cryopreserved iPSC-BMECs, as well as stabilized TEER above 800 Ω·cm 2 out to 7 days post-thaw. Overall, cryopreservation will ease handling and storage of high-quality iPSC-BMECs, reducing a key barrier to greater implementation of these cells in modeling the human BBB.

  15. Validation of the 133Xe inhalation method for measuring brain stem and cerebellar blood flow in human subjects and the baboon

    International Nuclear Information System (INIS)

    Sakai, F.; Meyer, J. St.; Yamaguchi, F.; Yamamoto, M.; Shaw, T.; Juge, O.

    1979-01-01

    Regional cerebral blood flow (rCBF) measurements recorded by probes placed over the posterior fossa after 133 Xe inhalation have been validated here in. After inhalation, 133 Xe gas is distributed via arterial blood of both carotid an vertebrobasilar systems, so that it should be possible to measure rCBF of the brain stem and cerebellum if appropriate collimation, probe placement and selection of activity are employed. Detectors placed over the suboccipital regions may be subject to distortion by radioactivity derived from extracerebral sources so that the following questions were asked: 1) What is the counting geometry for each probe looking at this area 2) What is the extent of contamination from surrounding tissues 3) Are the flow values reproducible and in accordance with values obtained by other techniques 4) Are the flow values able to show predictable changes under physiological and pathological conditions Animal and human experiments designed to answer these questions are reported. (Auth.)

  16. A clinico-radiological study on 254 cases of pontine high signals on magnetic resonance imaging in relation to brain stem semiology

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Masaki; Takahashi, Akira (Nagoya Univ. (Japan). Faculty of Medicine); Arahata, Yutaka; Motegi, Yoshimasa; Furuse, Masahiro

    1993-11-01

    A total of 254 patients who were proved to have pontine high intensity areas on T[sub 2]-weighted magnetic resonance imaging (MRI) were analyzed in relation to brain stem semiology. A comparative study on MRI and MR angiography was made between 254 patients with pontine high signals and 276 control cases showing no abnormality either on T[sub 1] or T[sub 2]-weighted images. Of the 254 patients, 62 had transient subjective complaints such as vertigo-dizziness. Supratentorial high signals, basilar artery tortuousness and vertebral artery asymmetry on MR angiography were seen more frequently in patients with pontine high signals than in the controls. In conclusion, pontine high signals may result from diffuse arteriosclerosis and MR angiography is considered to be a useful screening method. (author).

  17. Long-term outcome of high-precision radiotherapy in patients with brain stem gliomas: Results from a difficult-to-treat patient population using fractionated stereotactic radiotherapy

    International Nuclear Information System (INIS)

    Combs, Stephanie E.; Steck, Iris; Schulz-Ertner, Daniela; Welzel, Thomas; Kulozik, Andreas E.; Behnisch, Wolfgang; Huber, Peter E.; Debus, Juergen

    2009-01-01

    Introduction: To assess long-term outcome in 85 patients with brain stem gliomas treated with fractionated stereotactic radiation therapy (FSRT). Patient and methods: Thirty-nine patients were females, and 46 were males. Median age at primary diagnosis was 26 years. Thirty-one patients were younger than 18 years. Histopathological examination confirmed a low-grade glioma in 57 patients. Of the group of high-grade gliomas, six were anaplastic astrocytomas, and two were classified as glioblastoma. Radiation therapy was performed as FSRT. The median target volume was 101 ml. We applied a median dose of 54 Gy in conventional fractionation of 1.8 Gy. In seven of 85 patients (8%) FSRT was performed as re-irradiation. Results: The median follow-up time was 42 months. Median overall survival (OS) was 81 months. OS rates were 77% at 12 months, 70% at 24 months, and 63% at 36 months. Significant impact on OS could be shown for pilocytic histology, age, neurosurgical resection as well as for the presence of cyst on MR-imaging. Median progression-free survival (PFS) after FSRT was 52 months. PFS rates at 12 months were 70%, and 63% and 58% at 24 and 36 months, respectively. Histology, partial neurosurgical resection and the duration of symptoms could be identified as significant prognostic factors. Conclusion: Long-term outcome of FSRT in patients with brain stem gliomas is acceptable with low rates of side effects. Significant impact on outcome could be shown for histology, age, extent of neurosurgical resection as well as for cyst formation. No dose-response relationship could be observed.

  18. Hypoxia-cultured human adipose-derived mesenchymal stem cells are non-oncogenic and have enhanced viability, motility, and tropism to brain cancer.

    Science.gov (United States)

    Feng, Y; Zhu, M; Dangelmajer, S; Lee, Y M; Wijesekera, O; Castellanos, C X; Denduluri, A; Chaichana, K L; Li, Q; Zhang, H; Levchenko, A; Guerrero-Cazares, H; Quiñones-Hinojosa, A

    2014-12-11

    Adult human adipose-derived mesenchymal stem cells (hAMSCs) are multipotent cells, which are abundant, easily collected, and bypass the ethical concerns that plague embryonic stem cells. Their utility and accessibility have led to the rapid development of clinical investigations to explore their autologous and allogeneic cellular-based regenerative potential, tissue preservation capabilities, anti-inflammatory properties, and anticancer properties, among others. hAMSCs are typically cultured under ambient conditions with 21% oxygen. However, physiologically, hAMSCs exist in an environment of much lower oxygen tension. Furthermore, hAMSCs cultured in standard conditions have shown limited proliferative and migratory capabilities, as well as limited viability. This study investigated the effects hypoxic culture conditions have on primary intraoperatively derived hAMSCs. hAMSCs cultured under hypoxia (hAMSCs-H) remained multipotent, capable of differentiation into osteogenic, chondrogenic, and adipogenic lineages. In addition, hAMSCs-H grew faster and exhibited less cell death. Furthermore, hAMSCs-H had greater motility than normoxia-cultured hAMSCs and exhibited greater homing ability to glioblastoma (GBM) derived from brain tumor-initiating cells from our patients in vitro and in vivo. Importantly, hAMSCs-H did not transform into tumor-associated fibroblasts in vitro and were not tumorigenic in vivo. Rather, hAMSCs-H promoted the differentiation of brain cancer cells in vitro and in vivo. These findings suggest an alternative culturing technique that can enhance the function of hAMSCs, which may be necessary for their use in the treatment of various pathologies including stroke, myocardial infarction, amyotrophic lateral sclerosis, and GBM.

  19. The pattern of thalamocortical and brain stem projections to the vibrissae-related sensory and motor cortices in de-whiskered congenital hypothyroid rats.

    Science.gov (United States)

    Afarinesh, Mohammad Reza; Behzadi, Gila

    2017-08-01

    The present study is designed to investigate the plastic organization of the thalamo-cortical (TC) and brain stem afferents of whisker primary sensory (wS1) and motor (wM1) cortical areas in congenital hypothyroid (CH) pups following whisker deprivation (WD) from neonatal to adolescence period. Maternal hypothyroidism was induced by adding propylthiouracil (PTU) to the drinking water from early embryonic day 16 to postnatal day (PND) 60. Pregnant rats were divided into intact and CH groups (n = 8). In each group, the total whiskers of pups (4 of 8) were trimmed continuously from PND 1 to PND 60. Retrograde tracing technique with WGA-HRP was performed in the present study. Retrogradely labeled neurons were observed in the specific thalamic nuclei (VPM and VL) following separately WGA-HRP injections into wS1/M1 cortical areas. The number of labeled cells in the VPM, VL, VM and PO nuclei of the thalamus significantly decreased in CH offsprings rats (P < 0.05). Neonatal WD did not show any significant effects on the number of VPM, VL, VM and PO labeled projection neurons to wS1 and wM1 cortical areas. In addition, retrogradely labeled neurons in dorsal raphe (DR) and locus coeruleus (LC) nuclei were observed in all experimental groups. The number of DR and LC labeled neurons were higher in the CH and whisker deprived groups compared to their matching controls (P < 0.05). Upon our results, CH and WD had no synergic or additive effects on the TC and brain stem afferent patterns of barrel sensory and motor cortices.

  20. Establishment of a Human Blood-Brain Barrier Co-culture Model Mimicking the Neurovascular Unit Using Induced Pluri- and Multipotent Stem Cells.

    Science.gov (United States)

    Appelt-Menzel, Antje; Cubukova, Alevtina; Günther, Katharina; Edenhofer, Frank; Piontek, Jörg; Krause, Gerd; Stüber, Tanja; Walles, Heike; Neuhaus, Winfried; Metzger, Marco

    2017-04-11

    In vitro models of the human blood-brain barrier (BBB) are highly desirable for drug development. This study aims to analyze a set of ten different BBB culture models based on primary cells, human induced pluripotent stem cells (hiPSCs), and multipotent fetal neural stem cells (fNSCs). We systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression. The quadruple culture models, based on these four cell types, achieved BBB characteristics including transendothelial electrical resistance (TEER) up to 2,500 Ω cm 2 and distinct upregulation of typical BBB genes. A complex in vivo-like tight junction (TJ) network was detected by freeze-fracture and transmission electron microscopy. Treatment with claudin-specific TJ modulators caused TEER decrease, confirming the relevant role of claudin subtypes for paracellular tightness. Drug permeability tests with reference substances were performed and confirmed the suitability of the models for drug transport studies. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. Persistent gliosis interferes with neurogenesis in organotypic hippocampal slice cultures

    Directory of Open Access Journals (Sweden)

    Johannes eGerlach

    2016-05-01

    Full Text Available Neurogenesis in the adult hippocampus has become an intensively investigated research topic, as it is essential for proper hippocampal function and considered to bear therapeutic potential for the replacement of pathologically lost neurons. On the other hand, neurogenesis itself is frequently affected by CNS insults. To identify processes leading to the disturbance of neurogenesis, we made use of organotypic hippocampal slice cultures (OHSC, which, for unknown reasons, lose their neurogenic potential during cultivation. In the present study, we show by BrdU/Prox1 double-immunostaining that the generation of new granule cells drops by 90% during the first week of cultivation. Monitoring neurogenesis dynamically in OHSC from POMC-eGFP mice, in which immature granule cells are endogenously labeled, revealed a gradual decay of the eGFP signal, reaching 10% of initial values within seven days of cultivation. Accordingly, RT-qPCR analysis showed the downregulation of the neurogenesis-related genes doublecortin and Hes5, a crucial target of the stem cell-maintaining Notch signaling pathway. In parallel, we demonstrate a strong and long-lasting activation of astrocytes and microglial cells, both, morphologically and on the level of gene expression. Enhancement of astroglial activation by treating OHSC with ciliary neurotrophic factor (CNTF accelerated the loss of neurogenesis, whereas treatment with indomethacin or an antagonist of the purinergic P2Y12 receptor exhibited potent protective effects on the neurogenic outcome. Therefore, we conclude that OHSC rapidly lose their neurogenic capacity due to persistent inflammatory processes taking place after the slice preparation. As inflammation is also considered to affect neurogenesis in many CNS pathologies, OHSC appear as a useful tool to study this interplay and its molecular basis. Furthermore, we propose that modification of glial activation might bear the therapeutic potential of enabling

  2. Electrophysiology and biochemical analysis of cyclocreatine uptake and effect in hippocampal slices.

    Science.gov (United States)

    Enrico, Adriano; Patrizia, Garbati; Luisa, Perasso; Alessandro, Parodi; Gianluigi, Lunardi; Carlo, Gandolfo; Maurizio, Balestrino

    2013-06-01

    In in vitro mouse hippocampal slices we investigated whether cyclocreatine is capable of entering brain cells independently of the creatine transporter and if it reproduces the neuroprotective effect of creatine. Our study shows that cyclocreatine does not increase the creatine content, but is taken up as such and then phosphorylated to phosphocyclocreatine. This uptake is largely blocked by inactivation of the creatine transporter, however some cyclocreatine is taken up and posphorylated even after such inactivation. Thus, cyclocreatine sets up a cyclocreatine/phosphocyclocreatine system in the brain independently of the creatine transporter. Cyclocreatine did not delay the disappearance of the evoked synaptic potentials during anoxia in hippocampal slices, unlike creatine which exerts a neuroprotective effect.

  3. Development of a bread slicing machine from locally sourced ...

    African Journals Online (AJOL)

    This paper presents the development of a bread slicing machine which is a mechanical device that is used for slicing bread instead of the crude cumbersome and unhygienic method of manual slicing of bread. In an attempt to facilitate the final processing of bread which is a common daily food requirement of most Nigerians ...

  4. Slice through an LHC focusing magnet

    CERN Multimedia

    Slice through an LHC superconducting quadrupole (focusing) magnet. The slice includes a cut through the magnet wiring (niobium titanium), the beampipe and the steel magnet yokes. Particle beams in the Large Hadron Collider (LHC) have the same energy as a high-speed train, squeezed ready for collision into a space narrower than a human hair. Huge forces are needed to control them. Dipole magnets (2 poles) are used to bend the paths of the protons around the 27 km ring. Quadrupole magnets (4 poles) focus the proton beams and squeeze them so that more particles collide when the beams’ paths cross. Bringing beams into collision requires a precision comparable to making two knitting needles collide, launched from either side of the Atlantic Ocean.

  5. Slice of a LEP bending magnet

    CERN Multimedia

    This is a slice of a LEP dipole bending magnet, made as a concrete and iron sandwich. The bending field needed in LEP is small (about 1000 Gauss), equivalent to two of the magnets people stick on fridge doors. Because it is very difficult to keep a low field steady, a high field was used in iron plates embedded in concrete. A CERN breakthrough in magnet design, LEP dipoles can be tuned easily and are cheaper than conventional magnets.

  6. Metabolic changes in the rat brain after a photochemical lesion treated by stem cell transplantation assessed by 1H MRS

    Czech Academy of Sciences Publication Activity Database

    Herynek, V.; Růžičková, Kateřina; Jendelová, Pavla; Syková, Eva; Hájek, M.

    2009-01-01

    Roč. 22, č. 4 (2009), s. 211-220 ISSN 0968-5243 R&D Projects: GA AV ČR KAN201110651; GA MŠk(CZ) LC554; GA ČR(CZ) GA309/06/1594 Grant - others:GA MŠk(CZ) 1M0538; EC-FP6 project DiMI(XE) LSHB-CT-2005-512146; GA MZd(CZ) MZ01IKEM2005 Program:1M Institutional research plan: CEZ:AV0Z50390703 Keywords : mesenchymal stem cell transplantation * magnetic resonance spectroscopy * rats Subject RIV: FH - Neurology Impact factor: 1.859, year: 2009

  7. Stem Cells

    Science.gov (United States)

    Stem cells are cells with the potential to develop into many different types of cells in the body. They serve as a repair ... body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  8. A Review of Variable Slicing in Fused Deposition Modeling

    Science.gov (United States)

    Nadiyapara, Hitesh Hirjibhai; Pande, Sarang

    2017-06-01

    The paper presents a literature survey in the field of fused deposition of plastic wires especially in the field of slicing and deposition using extrusion of thermoplastic wires. Various researchers working in the field of computation of deposition path have used their algorithms for variable slicing. In the study, a flowchart has also been proposed for the slicing and deposition process. The algorithm already been developed by previous researcher will be used to be implemented on the fused deposition modelling machine. To demonstrate the capabilities of the fused deposition modeling machine a case study has been taken. It uses a manipulated G-code to be fed to the fused deposition modeling machine. Two types of slicing strategies, namely uniform slicing and variable slicing have been evaluated. In the uniform slicing, the slice thickness has been used for deposition is varying from 0.1 to 0.4 mm. In the variable slicing, thickness has been varied from 0.1 in the polar region to 0.4 in the equatorial region Time required and the number of slices required to deposit a hemisphere of 20 mm diameter have been compared with that using the variable slicing.

  9. Experimental demonstration of spectrum-sliced elastic optical path network (SLICE).

    Science.gov (United States)

    Kozicki, Bartłomiej; Takara, Hidehiko; Tsukishima, Yukio; Yoshimatsu, Toshihide; Yonenaga, Kazushige; Jinno, Masahiko

    2010-10-11

    We describe experimental demonstration of spectrum-sliced elastic optical path network (SLICE) architecture. We employ optical orthogonal frequency-division multiplexing (OFDM) modulation format and bandwidth-variable optical cross-connects (OXC) to generate, transmit and receive optical paths with bandwidths of up to 1 Tb/s. We experimentally demonstrate elastic optical path setup and spectrally-efficient transmission of multiple channels with bit rates ranging from 40 to 140 Gb/s between six nodes of a mesh network. We show dynamic bandwidth scalability for optical paths with bit rates of 40 to 440 Gb/s. Moreover, we demonstrate multihop transmission of a 1 Tb/s optical path over 400 km of standard single-mode fiber (SMF). Finally, we investigate the filtering properties and the required guard band width for spectrally-efficient allocation of optical paths in SLICE.

  10. An attempt to identify the functional areas of the cerebral cortex on CT slices parallel to the orbito-meatal line

    International Nuclear Information System (INIS)

    Tanabe, Hirotaka; Okuda, Junichiro; Nishikawa, Takashi; Nishimura, Tsuyoshi; Shiraishi, Junzo.

    1982-01-01

    In order to identify the functional brain areas, such as Broca's area, on computed tomography slices parallel to the orbito-meatal line, the numbers of Brodmann's cortical mapping were shown on a diagram of representative brain sections parallel to the orbito-meatal line. Also, we described a method, using cerebral sulci as anatomical landmarks, for projecting lesions shown by CT scan onto the lateral brain diagram. The procedures were as follows. The distribution of lesions on CT slices was determined by the identification of major cerebral sulci and fissures, such as the Sylvian fissure, the central sulcus, and the superior frontal sulcus. Those lesions were then projected onto the lateral diagram by comparing each CT slice with the horizontal diagrams of brain sections. The method was demonstrated in three cases developing neuropsychological symptoms. (author)

  11. Effects of new beta-type Ti-40Nb implant materials, brain-derived neurotrophic factor, acetylcholine and nicotine on human mesenchymal stem cells of osteoporotic and non osteoporotic donors.

    Science.gov (United States)

    Kauschke, Vivien; Gebert, Annett; Calin, Mariana; Eckert, Jürgen; Scheich, Sebastian; Heiss, Christian; Lips, Katrin Susanne

    2018-01-01

    Treatment of osteoporotic fractures is still challenging and an urgent need exists for new materials, better adapted to osteoporotic bone by adjusted Young's modulus, appropriate surface modification and pharmaceuticals. Titanium-40-niobium alloys, mechanically ground or additionally etched and titanium-6-aluminium-4-vanadium were analyzed in combination with brain-derived neurotrophic factor, acetylcholine and nicotine to determine their effects on human mesenchymal stem cells in vitro over 21 days using lactate dehydrogenase and alkaline phosphatase assays, live cell imaging and immunofluorescence microscopy. Cell number of human mesenchymal stem cells of osteoporotic donors was increased after 14 d in presence of ground titanium-40-niobium or titanium-6-aluminium-4-vanadium, together with brain-derived neurotrophic factor. Cell number of human mesenchymal stem cells of non osteoporotic donors increased after 21 d in presence of titanium-6-aluminium-4-vanadium without pharmaceuticals. No significant increase was measured for ground or etched titanium-40-niobium after 21 d. Osteoblast differentiation of osteoporotic donors was significantly higher than in non osteoporotic donors after 21 d in presence of etched, ground titanium-40-niobium or titanium-6-aluminium-4-vanadium accompanied by all pharmaceuticals tested. In presence of all alloys tested brain-derived neurotrophic factor, acetylcholine and nicotine increased differentiation of cells of osteoporotic donors and accelerated it in non osteoporotic donors. We conclude that ground titanium-40-niobium and brain-derived neurotrophic factor might be most suitable for subsequent in vivo testing.

  12. Body composition estimation from selected slices

    DEFF Research Database (Denmark)

    Lacoste Jeanson, Alizé; Dupej, Ján; Villa, Chiara

    2017-01-01

    Background Estimating volumes and masses of total body components is important for the study and treatment monitoring of nutrition and nutrition-related disorders, cancer, joint replacement, energy-expenditure and exercise physiology. While several equations have been offered for estimating total...... the whole-body composition volume and mass from areas measured in selected slices were modeled with ordinary least squares (OLS) linear regressions and support vector machine regression (SVMR). Results and Discussion The best predictive equation for total body AT volume was based on the AT area of a single...

  13. TRANSFORM DOMAIN SLICE BASED DISTRIBUTED VIDEO CODING

    Directory of Open Access Journals (Sweden)

    SAMIR BELHOUARI

    2011-10-01

    Full Text Available Distributed video coding depends heavily on the virtual channel model. Due to the limitations of the side information estimation one stationary model does not properly describe the virtual channel. In this work the correlation noise is modelled per slice to obtain location-specific correlation noise model. The resulting delay from the lengthy Slepian-Wolf (SW codec input is also reduced by reducing the length of SW codec input. The proposed solution does not impose any extra complexity, it utilizes the existing resources. The results presented here support the proposed algorithm.

  14. Methods to induce primary and secondary traumatic damage in organotypic hippocampal slice cultures.

    Science.gov (United States)

    Adamchik, Y; Frantseva, M V; Weisspapir, M; Carlen, P L; Perez Velazquez, J L

    2000-04-01

    Organotypic brain slice cultures have been used in a variety of studies on neurodegenerative processes [K.M. Abdel-Hamid, M. Tymianski, Mechanisms and effects of intracellular calcium buffering on neuronal survival in organotypic hippocampal cultures exposed to anoxia/aglycemia or to excitotoxins, J. Neurosci. 17, 1997, pp. 3538-3553; D.W. Newell, A. Barth, V. Papermaster, A.T. Malouf, Glutamate and non-glutamate receptor mediated toxicity caused by oxygen and glucose deprivation in organotypic hippocampal cultures, J. Neurosci. 15, 1995, pp. 7702-7711; J.L. Perez Velazquez, M.V. Frantseva, P.L. Carlen, In vitro ischemia promotes glutamate mediated free radical generation and intracellular calcium accumulation in pyramidal neurons of cultured hippocampal slices, J. Neurosci. 23, 1997, pp. 9085-9094; L. Stoppini, L.A. Buchs, D. Muller, A simple method for organotypic cultures of nervous tissue, J. Neurosci. Methods 37, 1991, pp. 173-182; R.C. Tasker, J.T. Coyle, J.J. Vornov, The regional vulnerability to hypoglycemia induced neurotoxicity in organotypic hippocampal culture: protection by early tetrodotoxin or delayed MK 801, J. Neurosci. 12, 1992, pp. 4298-4308.]. We describe two methods to induce traumatic cell damage in hippocampal organotypic cultures. Primary trauma injury was achieved by rolling a stainless steel cylinder (0.9 g) on the organotypic slices. Secondary injury was followed after dropping a weight (0.137 g) on a localised area of the organotypic slice, from a height of 2 mm. The time course and extent of cell death were determined by measuring the fluorescence of the viability indicator propidium iodide (PI) at several time points after the injury. The initial localised impact damage spread 24 and 67 h after injury, cell death being 25% and 54%, respectively, when slices were kept at 37 degrees C. To validate these methods as models to assess neuroprotective strategies, similar insults were applied to slices at relatively low temperatures (30

  15. A human brain microphysiological system derived from induced pluripotent stem cells to study neurological diseases and toxicity.

    Science.gov (United States)

    Pamies, David; Barreras, Paula; Block, Katharina; Makri, Georgia; Kumar, Anupama; Wiersma, Daphne; Smirnova, Lenna; Zang, Ce; Bressler, Joseph; Christian, Kimberly M; Harris, Georgina; Ming, Guo-Li; Berlinicke, Cindy J; Kyro, Kelly; Song, Hongjun; Pardo, Carlos A; Hartung, Thomas; Hogberg, Helena T

    2017-01-01

    Human in vitro models of brain neurophysiology are needed to investigate molecular and cellular mechanisms associated with neurological disorders and neurotoxicity. We have developed a reproducible iPSC-derived human 3D brain microphysiological system (BMPS), comprised of differentiated mature neurons and glial cells (astrocytes and oligodendrocytes) that reproduce neuronal-glial interactions and connectivity. BMPS mature over eight weeks and show the critical elements of neuronal function: synaptogenesis and neuron-to-neuron (e.g., spontaneous electric field potentials) and neuronal-glial interactions (e.g., myelination), which mimic the microenvironment of the central nervous system, rarely seen in vitro before. The BMPS shows 40% overall myelination after 8 weeks of differentiation. Myelin was observed by immunohistochemistry and confirmed by confocal microscopy 3D reconstruction and electron microscopy. These findings are of particular relevance since myelin is crucial for proper neuronal function and development. The ability to assess oligodendroglial function and mechanisms associated with myelination in this BMPS model provide an excellent tool for future studies of neurological disorders such as multiple sclerosis and other demyelinating diseases. The BMPS provides a suitable and reliable model to investigate neuron-neuroglia function as well as pathogenic mechanisms in neurotoxicology.

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

    DEFF Research Database (Denmark)

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

    1993-01-01

    Viral vectors derived from herpes simplex virus, type-1 (HSV), can transfer and express genes into fully differentiated, post-mitotic neurons. These vectors also transduce cells effectively in organotypic hippocampal slice cultures. Nanoliter quantities of a virus stock of HSVlac, an HSV vector...

  17. The action of piracetam on 14C-glucose metabolism in normal and posthypoxic rat cerebral cortex slices

    International Nuclear Information System (INIS)

    Domanska-Janik, K.; Zaleska, M.

    1977-01-01

    The stimulating effect of piracetam on the respiration and glycolysis was observed in rat brain cortex slices incubated under oxygen atmosphere. After preincubation of the slices under pure nitrogen atmosphere, piracetam influenced also decarboxylation of the C 1 -glucose carbon, indicating stimulation of the pentose cycle. Any significant effect of piracetam on the lowered by anoxia incorporation of 14 C from U- 14 C-glucose into macromolecular fractions was not observed. The results have supported a protective effect of piracetam against oxygen deficiency, caused mainly by stimulation of metabolic glucose pathways, connected with energy production in CNS. (author)

  18. [Learning and memory amelioration of transplantation of the neural stem cells modified with human brain-derived neurotrophic factor gene on Alzheimer disease model rat].

    Science.gov (United States)

    Zhao, Zhiying; Hu, Haitao; Feng, Gaifeng

    2005-05-01

    To investigate the memory amelioration of the Alzheimer disease (AD) model rat after being transplanted the single neural stem cells (NSC) and NSC modified with human brain-derived neurotrophic factor (hBDNF) gene. Forty SD rats were divided evenly into 4 groups randomly. The AD model rats were made by cutting unilaterally the fibria-fornix of male rats. Ten to twelve days after surgery, the genetically modified and unmodified NSC were implanted into the lateral cerebral ventricle of group III and group IV respectively. Two weeks after transplantation, the amelioration of memory impairment of the rats was detected by Morris water maze. The average escaping latency of the group III and group IV (41.84 +/- 21.76 s, 25.23 +/- 17.06 s respectively) was shorter than that of the group II (70.91 +/- 23.67 s) (P0.05). More lineal and oriented strategies were used in group IV. The behavioral amelioration of AD model rat was obtained by transplanting single NSC and hBDNF-gene-modified NSC. The effect of the NSC group modified with hBDNF gene is better than that of the group III.

  19. [Design and accuracy analysis of upper slicing system of MSCT].

    Science.gov (United States)

    Jiang, Rongjian

    2013-05-01

    The upper slicing system is the main components of the optical system in MSCT. This paper focuses on the design of upper slicing system and its accuracy analysis to improve the accuracy of imaging. The error of slice thickness and ray center by bearings, screw and control system were analyzed and tested. In fact, the accumulated error measured is less than 1 microm, absolute error measured is less than 10 microm. Improving the accuracy of the upper slicing system contributes to the appropriate treatment methods and success rate of treatment.

  20. Chemo-predictive assay for targeting cancer stem-like cells in patients affected by brain tumors.

    Directory of Open Access Journals (Sweden)

    Sarah E Mathis

    Full Text Available Administration of ineffective anticancer therapy is associated with unnecessary toxicity and development of resistant clones. Cancer stem-like cells (CSLCs resist chemotherapy, thereby causing relapse of the disease. Thus, development of a test that identifies the most effective chemotherapy management offers great promise for individualized anticancer treatments. We have developed an ex vivo chemotherapy sensitivity assay (ChemoID, which measures the sensitivity of CSLCs as well as the bulk of tumor cells to a variety of chemotherapy agents. Two patients, a 21-year old male (patient 1 and a 5-month female (patient 2, affected by anaplastic WHO grade-III ependymoma were screened using the ChemoID assay. Patient 1 was found sensitive to the combination of irinotecan and bevacizumab, which resulted in a prolonged disease progression free period of 18 months. Following recurrence, the combination of various chemotherapy drugs was tested again with the ChemoID assay. We found that benzyl isothiocyanate (BITC greatly increased the chemosensitivity of the ependymoma cells to the combination of irinotecan and bevacizumab. After patient 1 was treated for two months with irinotecan, bevacizumab and supplements of cruciferous vegetable extracts containing BITC, we observed over 50% tumoral regression in comparison with pre-ChemoID scan as evidenced by MRI. Patient 2 was found resistant to all treatments tested and following 6 cycles of vincristine, carboplatin, cyclophosphamide, etoposide, and cisplatin in various combinations, the tumor of this patient rapidly progressed and proton beam therapy was recommended. As expected animal studies conducted with patient derived xenografts treated with ChemoID screened drugs recapitulated the clinical observation. This assay demonstrates that patients with the same histological stage and grade of cancer may vary considerably in their clinical response, suggesting that ChemoID testing which measures the sensitivity

  1. Multiple single-unit long-term tracking on organotypic hippocampal slices using high-density microelectrode arrays

    Directory of Open Access Journals (Sweden)

    Wei Gong

    2016-11-01

    Full Text Available A novel system to cultivate and record from organotypic brain slices directly on high-density microelectrode arrays (HD-MEA was developed. This system allows for continuous recording of electrical activity of specific individual neurons at high spatial resolution while monitoring at the same time, neuronal network activity. For the first time, the electrical activity patterns of single neurons and the corresponding neuronal network in an organotypic hippocampal slice culture were studied during several consecutive weeks at daily intervals. An unsupervised iterative spike-sorting algorithm, based on PCA and k-means clustering, was developed to assign the activities to the single units. Spike-triggered average extracellular waveforms of an action potential recorded across neighboring electrodes, termed ‘footprints’ of single-units were generated and tracked over weeks. The developed system offers the potential to study chronic impacts of drugs or genetic modifications on individual neurons in slice preparations over extended times.

  2. Focal traumatic brain stem injury is a rare type of head injury resulting from assault: a forensic neuropathological study.

    Science.gov (United States)

    Al-Sarraj, Safa; Fegan-Earl, Ashley; Ugbade, Antonia; Bodi, Istvan; Chapman, Rob; Poole, Simon; Swift, Ben; Jerreat, Peter; Cary, Nat

    2012-04-01

    Brainstem haemorrhage is common in cases of head injury when it is associated with space-occupying lesion and increases in the intracranial pressure (duret haemorrhage), in cases of diffuse axonal injury (in dorso-lateral quadrant) and diffuses vascular injury (in the periventricular tissue). However focal traumatic brainstem injury is rare. We identified 12 cases of focal traumatic brainstem injury from review of 319 case of head injury. The head trauma had been caused by different mechanisms of complex fall from height and assault. 10/12 are associated with skull fracture, 11/12 with contre coup contusions in the frontal and temporal lobes, 5/12 direct contusions to cerebellum, 5/12 haemorrhage in corpus callosum and 2/11 have gliding contusions. None of the cases had pathological evidence of increase in the intracranial pressure. The bleeding in the pons was at the edge in 2/12 and cross the section in 10/12. The majority of patients were unconscious immediately after the incident (10/12) and 9/12 died within one day. Focal traumatic brainstem injury occurs most likely due to direct impact at the back of the head or stretching forces affecting the brainstem in cases of complex fall from height and after assault, particularly those associated with kicks. It is a serious and commonly fatal brain damage, which needed to be differentiated from other causes of brainstem haemorrhages. Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  3. Metabolic Therapy for Temporal Lobe Epilepsy in a Dish: Investigating Mechanisms of Ketogenic Diet using Electrophysiological Recordings in Hippocampal Slices.

    Science.gov (United States)

    Kawamura, Masahito Jr; Ruskin, David N; Masino, Susan A

    2016-01-01

    The hippocampus is prone to epileptic seizures and is a key brain region and experimental platform for investigating mechanisms associated with the abnormal neuronal excitability that characterizes a seizure. Accordingly, the hippocampal slice is a common in vitro model to study treatments that may prevent or reduce seizure activity. The ketogenic diet is a metabolic therapy used to treat epilepsy in adults and children for nearly 100 years; it can reduce or eliminate even severe or refractory seizures. New insights into its underlying mechanisms have been revealed by diverse types of electrophysiological recordings in hippocampal slices. Here we review these reports and their relevant mechanistic findings. We acknowledge that a major difficulty in using hippocampal slices is the inability to reproduce precisely the in vivo condition of ketogenic diet feeding in any in vitro preparation, and progress has been made in this in vivo/in vitro transition. Thus far at least three different approaches are reported to reproduce relevant diet effects in the hippocampal slices: (1) direct application of ketone bodies; (2) mimicking the ketogenic diet condition during a whole-cell patch-clamp technique; and (3) reduced glucose incubation of hippocampal slices from ketogenic diet-fed animals. Significant results have been found with each of these methods and provide options for further study into short- and long-term mechanisms including Adenosine triphosphate (ATP)-sensitive potassium (K ATP ) channels, vesicular glutamate transporter (VGLUT), pannexin channels and adenosine receptors underlying ketogenic diet and other forms of metabolic therapy.

  4. Metabolic Therapy for Temporal Lobe Epilepsy in a Dish: Investigating Mechanisms of Ketogenic Diet using Electrophysiological Recordings in Hippocampal Slices

    Science.gov (United States)

    Kawamura, Masahito Jr.; Ruskin, David N.; Masino, Susan A.

    2016-01-01

    The hippocampus is prone to epileptic seizures and is a key brain region and experimental platform for investigating mechanisms associated with the abnormal neuronal excitability that characterizes a seizure. Accordingly, the hippocampal slice is a common in vitro model to study treatments that may prevent or reduce seizure activity. The ketogenic diet is a metabolic therapy used to treat epilepsy in adults and children for nearly 100 years; it can reduce or eliminate even severe or refractory seizures. New insights into its underlying mechanisms have been revealed by diverse types of electrophysiological recordings in hippocampal slices. Here we review these reports and their relevant mechanistic findings. We acknowledge that a major difficulty in using hippocampal slices is the inability to reproduce precisely the in vivo condition of ketogenic diet feeding in any in vitro preparation, and progress has been made in this in vivo/in vitro transition. Thus far at least three different approaches are reported to reproduce relevant diet effects in the hippocampal slices: (1) direct application of ketone bodies; (2) mimicking the ketogenic diet condition during a whole-cell patch-clamp technique; and (3) reduced glucose incubation of hippocampal slices from ketogenic diet–fed animals. Significant results have been found with each of these methods and provide options for further study into short- and long-term mechanisms including Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, vesicular glutamate transporter (VGLUT), pannexin channels and adenosine receptors underlying ketogenic diet and other forms of metabolic therapy. PMID:27847463

  5. Metabolic therapy for temporal lobe epilepsy in a dish: investigating mechanisms of ketogenic diet using electrophysiological recordings in hippocampal slices

    Directory of Open Access Journals (Sweden)

    Masahito Kawamura

    2016-11-01

    Full Text Available The hippocampus is prone to epileptic seizures and is a key brain region and experimental platform for investigating mechanisms associated with the abnormal neuronal excitability that characterizes a seizure. Accordingly, the hippocampal slice is a common in vitro model to study treatments that may prevent or reduce seizure activity. The ketogenic diet is a metabolic therapy used to treat epilepsy in adults and children for nearly 100 years; it can reduce or eliminate even severe or refractory seizures. New insights into its underlying mechanisms have been revealed by diverse types of electrophysiological recordings in hippocampal slices. Here we review these reports and their relevant mechanistic findings. We acknowledge that a major difficulty in using hippocampal slices is the inability to reproduce precisely the in vivo condition of ketogenic diet feeding in any in vitro preparation, and progress has been made in this in vivo/in vitro transition. Thus far at least three different approaches are reported to reproduce relevant diet effects in the hippocampal slices: (1 direct application of ketone bodies, (2 mimicking the ketogenic diet condition during a whole-cell patch-clamp technique, and (3 reduced glucose incubation of hippocampal slices from ketogenic diet–fed animals. Significant results have been found with each of these methods and provide options for further study into short- and long-term mechanisms including ATP-sensitive potassium channels, vesicular glutamate transporter, pannexin channels and adenosine receptors underlying ketogenic diet and other forms of metabolic therapy.

  6. Mathematical Modeling of Thin Layer Microwave Drying of Taro Slices

    Science.gov (United States)

    Kumar, Vivek; Sharma, H. K.; Singh, K.

    2016-03-01

    The present study investigated the drying kinetics of taro slices precooked in different medium viz water (WC), steam (SC) and Lemon Solution (LC) and dried at different microwave power 360, 540 and 720 W. Drying curves of all precooked slices at all microwave powers showed falling rate period along with a very short accelerating period at the beginning of the drying. At all microwave powers, higher drying rate was observed for LC slices as compared to WC and SC slices. To select a suitable drying curve, seven thin-layer drying models were fitted to the experimental data. The data revealed that the Page model was most adequate in describing the microwave drying behavior of taro slices precooked in different medium. The highest effective moisture diffusivity value of 2.11 × 10-8 m2/s was obtained for LC samples while the lowest 0.83 × 10-8 m2/s was obtained for WC taro slices. The activation energy (E a ) of LC taro slices was lower than the E a of WC and SC taro slices.

  7. Color changes and acrylamide formation in fried potato slices

    DEFF Research Database (Denmark)

    Pedreschi, Franco; Moyano, Pedro; Kaack, Karl

    2005-01-01

    at 85degreesC for 3.5 min. Unblanched slices were used as the control. Control and blanched potato slices (Panda variety, diameter: 37 mm, width: 2.2 mm) were fried at 120, 150 and 180degreesC until reaching moisture contents of similar to1.8% (total basis) and their acrylamide content and final color...

  8. The Brain Tourniquet: Physiological Isolation of Brain Regions Damaged by Traumatic Head Injury

    Science.gov (United States)

    2008-06-19

    brain slices were treated after injury with either a nootropic agent (aniracetam, cyclothiazide, IDRA 21, or 1-BCP) or the antiepileptic drug...pharmacological approach. 15. SUBJECT TERMS traumatic brain injury, cell necrosis, neuroprotection, nootropics , epilepsy, long-term potentiation...render their use problematic in an effective brain tourniquet system. We chose to focus our investigations on the nootropic (cognition enhancing) drugs

  9. Acetic acid pretreatment improves the hardness of cooked potato slices.

    Science.gov (United States)

    Zhao, Wenlin; Shehzad, Hussain; Yan, Shoulei; Li, Jie; Wang, Qingzhang

    2017-08-01

    The effects of acetic acid pretreatment on the texture of cooked potato slices were investigated in this work. Potato slices were pretreated with acetic acid immersion (AAI), distilled water immersion (DWI), or no immersion (NI). Subsequently, the cell wall material of the pretreated samples was isolated and fractioned to evaluate changes in the monosaccharide content and molar mass (MM), and the hardness and microscopic structure of the potato slices in different pretreatments before and after cooking were determined. The results showed that the highest firmness was obtained with more intact structure of the cell wall for cooked potato slices with AAI pretreatment. Furthermore, the MM and sugar ratio demonstrated that the AAI pretreated potato slices contained a higher content of the small molecular polysaccharides of cell walls, especially in the hemicellulose fraction. This work may provide a reference for potato processing. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Seamless Ligation Cloning Extract (SLiCE) cloning method.

    Science.gov (United States)

    Zhang, Yongwei; Werling, Uwe; Edelmann, Winfried

    2014-01-01

    SLiCE (Seamless Ligation Cloning Extract) is a novel cloning method that utilizes easy to generate bacterial cell extracts to assemble multiple DNA fragments into recombinant DNA molecules in a single in vitro recombination reaction. SLiCE overcomes the sequence limitations of traditional cloning methods, facilitates seamless cloning by recombining short end homologies (15-52 bp) with or without flanking heterologous sequences and provides an effective strategy for directional subcloning of DNA fragments from bacterial artificial chromosomes or other sources. SLiCE is highly cost-effective and demonstrates the versatility as a number of standard laboratory bacterial strains can serve as sources for SLiCE extract. We established a DH10B-derived E. coli strain expressing an optimized λ prophage Red recombination system, termed PPY, which facilitates SLiCE with very high efficiencies.

  11. A survey of program slicing for software engineering

    Science.gov (United States)

    Beck, Jon

    1993-01-01

    This research concerns program slicing which is used as a tool for program maintainence of software systems. Program slicing decreases the level of effort required to understand and maintain complex software systems. It was first designed as a debugging aid, but it has since been generalized into various tools and extended to include program comprehension, module cohesion estimation, requirements verification, dead code elimination, and maintainence of several software systems, including reverse engineering, parallelization, portability, and reuse component generation. This paper seeks to address and define terminology, theoretical concepts, program representation, different program graphs, developments in static slicing, dynamic slicing, and semantics and mathematical models. Applications for conventional slicing are presented, along with a prognosis of future work in this field.

  12. Thermoluminescence results on slices from a Hiroshima tile UHFSFT03

    International Nuclear Information System (INIS)

    Stoneham, Doreen

    1987-01-01

    As was reported at the May 1984 Utah thermoluminescence (TL) workshop, high fired tiles and porcelain fragments can be sliced into 200 μm sections with constant surface area. When conventional pre-dose measurements were carried out on these slices the doses evaluated were in good agreement with results obtained by other workers using conventional quartz separation techniques. There are several advantages in using slices. First, less sample is needed as about 50 consecutive slices can be cut from a block measuring typically 1 cm 2 cross section and 2 cm in length. There are no problems with securing grains to the plate or loss of grains during measurement. Hypothetically there is less damage to the grains when they are cut slowly under cold water than when they are crushed. The disadvantage is that other minerals besides quartz are present in the slice and the signal is weaker than that obtained using quartz inclusions

  13. Lead induces similar gene expression changes in brains of gestationally exposed adult mice and in neurons differentiated from mouse embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Francisco Javier Sánchez-Martín

    Full Text Available Exposure to environmental toxicants during embryonic life causes changes in the expression of developmental genes that may last for a lifetime and adversely affect the exposed individual. Developmental exposure to lead (Pb, an ubiquitous environmental contaminant, causes deficits in cognitive functions and IQ, behavioral effects, and attention deficit hyperactivity disorder (ADHD. Long-term effects observed after early life exposure to Pb include reduction of gray matter, alteration of myelin structure, and increment of criminal behavior in adults. Despite growing research interest, the molecular mechanisms responsible for the effects of lead in the central nervous system are still largely unknown. To study the molecular changes due to Pb exposure during neurodevelopment, we exposed mice to Pb in utero and examined the expression of neural markers, neurotrophins, transcription factors and glutamate-related genes in hippocampus, cortex, and thalamus at postnatal day 60. We found that hippocampus was the area where gene expression changes due to Pb exposure were more pronounced. To recapitulate gestational Pb exposure in vitro, we differentiated mouse embryonic stem cells (ESC into neurons and treated ESC-derived neurons with Pb for the length of the differentiation process. These neurons expressed the characteristic neuronal markers Tubb3, Syp, Gap43, Hud, Ngn1, Vglut1 (a marker of glutamatergic neurons, and all the glutamate receptor subunits, but not the glial marker Gafp. Importantly, several of the changes observed in Pb-exposed mouse brains in vivo were also observed in Pb-treated ESC-derived neurons, including those affecting expression of Ngn1, Bdnf exon IV, Grin1, Grin2D, Grik5, Gria4, and Grm6. We conclude that our ESC-derived model of toxicant exposure during neural differentiation promises to be a useful model to analyze mechanisms of neurotoxicity induced by Pb and other environmental agents.

  14. Localized delivery of brain-derived neurotrophic factor-expressing mesenchymal stem cells enhances functional recovery following cervical spinal cord injury.

    Science.gov (United States)

    Gransee, Heather M; Zhan, Wen-Zhi; Sieck, Gary C; Mantilla, Carlos B

    2015-02-01

    Neurotrophins, such as brain-derived neurotrophic factor (BDNF), are important in modulating neuroplasticity and promoting recovery after spinal cord injury. Intrathecal delivery of BDNF enhances functional recovery following unilateral spinal cord hemisection (SH) at C2, a well-established model of incomplete cervical spinal cord injury. We hypothesized that localized delivery of BDNF-expressing mesenchymal stem cells (BDNF-MSCs) would promote functional recovery of rhythmic diaphragm activity after SH. In adult rats, bilateral diaphragm electromyographic (EMG) activity was chronically monitored to determine evidence of complete SH at 3 days post-injury, and recovery of rhythmic ipsilateral diaphragm EMG activity over time post-SH. Wild-type, bone marrow-derived MSCs (WT-MSCs) or BDNF-MSCs (2×10(5) cells) were injected intraspinally at C2 at the time of injury. At 14 days post-SH, green fluorescent protein (GFP) immunoreactivity confirmed MSCs presence in the cervical spinal cord. Functional recovery in SH animals injected with WT-MSCs was not different from untreated SH controls (n=10; overall, 20% at 7 days and 30% at 14 days). In contrast, functional recovery was observed in 29% and 100% of SH animals injected with BDNF-MSCs at 7 days and 14 days post-SH, respectively (n=7). In BDNF-MSCs treated SH animals at 14 days, root-mean-squared EMG amplitude was 63±16% of the pre-SH value compared with 12±9% in the control/WT-MSCs group. We conclude that localized delivery of BDNF-expressing MSCs enhances functional recovery of diaphragm muscle activity following cervical spinal cord injury. MSCs can be used to facilitate localized delivery of trophic factors such as BDNF in order to promote neuroplasticity following spinal cord injury.

  15. [Comprehensive management of a child with a post-traumatic brain stem and spinal cord injury. A case study and presentation of current therapeutic modalities].

    Science.gov (United States)

    Kobylarz, Krzysztof; Kwiatkowski, Stanisław; Inglot, Barbara; Mróz, Adam

    2008-01-01

    Less than twenty years ago, a high spinal cord injury accompanied by paralysis of the diaphragm and the resulting apnea and tetraplegia led to certain death within a short time after the trauma, mostly due to respiratory complications associated with ventilatory therapy in hospitals. The objective of this paper is to present the case of a paediatric brain stem trauma with spinal cord injury, consisting of spinal cord rupture in the upper cervical segment. Thanks to appropriate management at all treatment stages (prompt, fully professional assistance in the ambulance, followed by appropriate management at ICU), the child survived. Owing to currently available technical solutions, the boy has achieved considerable self-dependence and an opportunity of having post-traumatic complications treated using a diaphragm pacing stimulator and a baclofen pump. The report presents therapeutic problems encountered in children with post-traumatic spinal cord injury, emphasizing technical opportunities of managing diaphragm paralysis, as exemplified by the five-year treatment and rehabilitation process of a boy with spinal cord injury at C1 level managed at the University Children's Hospital of Cracow, Poland, in whom phrenic nerve stimulation was employed. The implanted stimulator and a specially constructed controller have allowed the boy to achieve mobility using a wheelchair, being able to use a PC and being taught by an individual teacher at home despite his tetraparesis. Recurrent respiratory tract infections and occasional decubitus required periodic hospitalizations. As the patient grew, in consequence of uncontrolled sudden increases of muscle tone of the trunk spine. Increased muscle tone was increasingly resistant to pharmacotherapy and negatively affected the effectiveness of home rehabilitation. In consequence, a decision was made to implant an intraspinal baclofen pump.

  16. Effect of brain-derived neurotrophic factor on mesenchymal stem cell-seeded electrospinning biomaterial for treating ischemic diabetic ulcers via milieu-dependent differentiation mechanism.

    Science.gov (United States)

    He, Siyi; Shen, Lei; Wu, Yangxiao; Li, Li; Chen, Wen; Hou, Chunli; Yang, Mingcan; Zeng, Wen; Zhu, Chuhong

    2015-03-01

    Great challenges in transplantation of mesenchymal stem cells (MSCs) for treating ischemic diabetic ulcers (IDUs) are to find a suitable carrier and create a beneficial microenvironment. Brain-derived neurotrophic factor (BDNF), a member of neurotrophin family, is considered angiogenic and neuroprotective. Given that IDUs are caused by vascular disease and peripheral neuropathy, we used BDNF as a stimulant, and intended to explore the role of new biomaterials complex with MSCs in wound healing. BDNF promoted the proliferation and migration of MSCs using MTT, transwell, and cell scratch assays. The activity of human umbilical vein endothelial cells (HUVECs) was also enhanced by the MSC-conditioned medium in the presence of BDNF, via a vascular endothelial growth factor-independent pathway. Since proliferated HUVECs in the BDNF group made the microenvironment more conducive to endothelial differentiation of MSCs, by establishing co-culture systems with the two cell types, endothelial cells derived from MSCs increased significantly. A new biomaterial made of polylactic acid, silk and collagen was used as the carrier dressing. After transplantation of the BDNF-stimulated MSC/biomaterial complex, the ulcers in hindlimb ischemic mice healed prominently. More blood vessel formation was observed in the wound tissue, and more MSCs were co-stained with some endothelial-specific markers such as cluster of differentiation (CD)31 and von Willebrand Factor (vWF) in the treatment group than in the control group. These results demonstrated that BDNF could improve microenvironment in the new biomaterial, and induce MSCs to differentiate into endothelial cells indirectly, thus accelerating ischemic ulcer healing.

  17. Postnatal development of glycine receptor subunits α1, α2, α3, and β immunoreactivity in multiple brain stem respiratory-related nuclear groups of the rat.

    Science.gov (United States)

    Liu, Qiuli; Wong-Riley, Margaret T T

    2013-11-13

    The respiratory system is immature at birth and significant development occurs postnatally. A critical period of respiratory development occurs in rats around postnatal days 12-13, when enhanced inhibition dominates over suppressed excitation. The mechanisms underlying the heightened inhibition are not fully understood. The present study tested our hypothesis that the inhibition is marked by a switch in glycine receptor subunits from neonatal to adult form around the critical period. An in-depth immunohistochemical and single neuron optical densitometric study was undertaken on four respiratory-related nuclear groups (the pre-Bötzinger complex, nucleus ambiguus, hypoglossal nucleus, and ventrolateral subnucleus of solitary tract nucleus), and a non-respiratory cuneate nucleus in P2-21 rats. Our data revealed that in the respiratory-related nuclear groups: (1) the expressions of GlyRα2 and GlyRα3 were relatively high at P2, but declined after 1-1½ weeks to their lowest levels at P21; (2) the expression of GlyRα1 increased with age and reached significance at P12; and (3) the expression of GlyRβ rose from P2 to P12 followed by a slight decline until P21. No distinct increase in GlyRα1 at P12 was noted in the cuneate nucleus. Thus, there is a switch in dominance of expression from neonatal GlyRα2/α3 to the adult GlyRα1 and a heightened expression of GlyRα1 around the critical period in all respiratory-related nuclear groups, thereby supporting enhanced inhibition at that time. The rise in the expression of GlyRβ around P12 indicates that it plays an important role in forming the mature heteropentameric glycine receptors in these brain stem nuclear groups. © 2013 Elsevier B.V. All rights reserved.

  18. Comparison of digitally reconstructed radiographs (DRRs) generated from 4-slice and 64-slice helical CT scanners, a phantom study

    International Nuclear Information System (INIS)

    Nelson, Vinod; Deshpande, S.; Vial, P.; Holloway, L.

    2011-01-01

    Full text: Digitally reconstructed radiographs (DRRs) are generated from CT data sets and playa vital role for verifying patient position for many radiotherapy treatments. The present study aimed to investigate the impact on the image quality of DRRs due to changes in the original CT data acquisition; specifically a 4-slice CT scanner and a 64-slice CT scanner have been considered. A specifically designed CT simulation phantom (Nuclear Associates Model 76--417) with test patterns to measure low contrast and modulation transfer function (MTF) was used to evaluate DRR characteristics for Siemens Somatom Sensation 4 and Sensation 64 CT scanners. The phantom was scanned as described in the manufacturer's manual, using the departmental protocol for head CT. The CT images were obtained with 120 kV, 300 mAs, a scanning and reconstruction pitch of I and collimation of I mm. Each of the test patterns from the DRRs was compared for the 4-slice and the 64-slice helical scans. Results The calculated relative MTF (RMTF) showed higher spatial resolution for DRRs generated from 64-slice scans compared with 4-slice scans, Fig. 1. The low contrast values for hole diameter patterns on the DRRs ranged from 0.01-8.04% for 64 slice scans and 0.06-6.15% for 4 slice scans.

  19. Integral dose delivered to normal brain with conventional intensity-modulated radiotherapy (IMRT) and helical tomotherapy IMRT during partial brain radiotherapy for high-grade gliomas with and without selective sparing of the hippocampus, limbic circuit and neural stem cell compartment

    International Nuclear Information System (INIS)

    Marsh, James C.; Ziel, Ellis G; Diaz, Aidnag Z; Turian, Julius V; Wendt, Julie A.; Gobole, Rohit

    2013-01-01

    We compared integral dose with uninvolved brain (ID brain ) during partial brain radiotherapy (PBRT) for high-grade glioma patients using helical tomotherapy (HT) and seven field traditional inverse-planned intensity-modulated radiotherapy (IMRT) with and without selective sparing (SPA) of contralateral hippocampus, neural stem cell compartment (NSC) and limbic circuit. We prepared four PBRT treatment plans for four patients with high-grade gliomas (60Gy in 30 fractions delivered to planning treatment volume (PTV60Gy)). For all plans, a structure denoted 'uninvolved brain' was created, which included all brain tissue not part of PTV or standard (STD) organs at risk (OAR). No dosimetric constraints were included for uninvolved brain. Selective SPA plans were prepared with IMRT and HT; contralateral hippocampus, NSC and limbic circuit were contoured; and dosimetric constraints were entered for these structures without compromising dose to PTV or STD OAR. We compared V100 and D95 for PTV46Gy and PTV60Gy, and ID brain for all plans. There were no significant differences in V100 and D95 for PTV46Gy and PTV60Gy. ID brain was lower in traditional IMRT versus HT plans for STD and SPA plans (mean ID brain 23.64Gy vs. 28Gy and 18.7Gy vs. 24.5Gy, respectively) and in SPA versus STD plans both with IMRT and HT (18.7Gy vs. 23.64Gy and 24.5Gy vs. 28Gy, respectively). n the setting of PBRT for high-grade gliomas, IMRT reduces ID brain compared with HT with or without selective SPA of contralateral hippocampus, limbic circuit and NSC, and the use of selective SPA reduces ID brain compared with STD PBRT delivered with either traditional IMRT or HT.

  20. Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen/glucose deprivation

    DEFF Research Database (Denmark)

    Rekling, Jens C

    2003-01-01

    Some anticonvulsants show neuroprotective effects, and may be of use in reducing neuronal death resulting from stroke or traumatic brain injury. Here I report that a broad range of anticonvulsants protect cells in hippocampal slice cultures from death induced by oxygen/glucose deprivation (OGD...... cell death induced by OGD. The newer anticonvulsants carbamazepine, felbamate, lamotrigine, tiagabine, and oxcarbazepine also had significant neuroprotective effects, but gabapentin, valproic acid (10 mM), levetiracetam and retigabine were not neuroprotective at a concentration up to 300 micro......M. In conclusion, several classical and newer anticonvulsants have neuroprotective properties in an in vitro model that simulates cerebral ischemia....

  1. Angiogenic factors stimulate growth of adult neural stem cells.

    Directory of Open Access Journals (Sweden)

    Andreas Androutsellis-Theotokis

    2010-02-01

    Full Text Available The ability to grow a uniform cell type from the adult central nervous system (CNS is valuable for developing cell therapies and new strategies for drug discovery. The adult mammalian brain is a source of neural stem cells (NSC found in both neurogenic and non-neurogenic zones but difficulties in culturing these hinders their use as research tools.Here we show that NSCs can be efficiently grown in adherent cell cultures when angiogenic signals are included in the medium. These signals include both anti-angiogenic factors (the soluble form of the Notch receptor ligand, Dll4 and pro-angiogenic factors (the Tie-2 receptor ligand, Angiopoietin 2. These treatments support the self renewal state of cultured NSCs and expression of the transcription factor Hes3, which also identifies the cancer stem cell population in human tumors. In an organotypic slice model, angiogenic factors maintain vascular structure and increase the density of dopamine neuron processes.We demonstrate new properties of adult NSCs and a method to generate efficient adult NSC cultures from various central nervous system areas. These findings will help establish cellular models relevant to cancer and regeneration.

  2. Pro-life role for c-Jun N-terminal kinase and p38 mitogen-activated protein kinase at rostral ventrolateral medulla in experimental brain stem death.

    Science.gov (United States)

    Chang, Alice Y W

    2012-11-17

    Based on an experimental brain stem death model, we demonstrated previously that activation of the mitogen-activated protein kinase kinase 1/2 (MEK1/2)/extracellular signal-regulated kinase 1/2 (ERK1/2)/ mitogen-activated protein kinase signal-interacting kinase 1/2 (MNK1/2) cascade plays a pro-life role in the rostral ventrolateral medulla (RVLM), the origin of a life-and-death signal detected from systemic arterial pressure, which sequentially increases (pro-life) and decreases (pro-death) to reflect progressive dysfunction of central cardiovascular regulation during the advancement towards brain stem death in critically ill patients. The present study assessed the hypothesis that, in addition to ERK1/2, c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK), the other two mammalian members of MAPKs that are originally identified as stress-activated protein kinases, are activated specifically by MAPK kinase 4 (MAP2K4) or MAP2K6 and play a pro-life role in RVLM during experimental brain stem death. We further delineated the participation of phosphorylating activating transcriptional factor-2 (ATF-2) and c-Jun, the classical transcription factor activated by JNK or p38MAPK, in this process. An experimental model of brain stem death that employed microinjection of the organophosphate insecticide mevinphos (Mev; 10 nmol) bilaterally into RVLM of Sprague-Dawley rats was used, alongside cardiovascular, pharmacological and biochemical evaluations. Results from ELISA showed that whereas the total JNK, p38MAPK, MAP2K4 and MAP2K6 were not affected, augmented phosphorylation of JNK at Thr183 and Tyr185 and p38MAPK at Thr180 and Tyr182, accompanied by phosphorylation of their upstream activators MAP2K4 at Ser257 and Thr261 and MAP2K6 at Ser207 and Thr211 in RVLM occurred preferentially during the pro-life phase of experimental brain stem death. Moreover, the activity of transcription factors ATF-2 at Thr71 and c-Jun at Ser73, rather than Elk-1 at

  3. Maternal obesity affects gene expression and cellular development in fetal brains.

    Science.gov (United States)

    Stachowiak, Ewa K; Oommen, Saji; Vasu, Vihas T; Srinivasan, Malathi; Stachowiak, Michal; Gohil, Kishorchandra; Patel, Mulchand S

    2013-05-01

    Female rat neonates reared on a high carbohydrate (HC) milk formula developed chronic hyperinsulinemia and adult-onset obesity (HC phenotype). Furthermore, we have shown that fetal development in the HC intrauterine environment (maternal obesity complicated with hyperinsulinemia, hyperleptinemia, and increased levels of proinflammatory markers) resulted in increased levels of serum insulin and leptin in term HC fetuses and the spontaneous transfer of the HC phenotype to the adult offspring. The objectives of this study are to identify changes in global gene expression pattern and cellular development in term HC fetal brains in response to growth in the adverse intrauterine environment of the obese HC female rat. GeneChip analysis was performed on total RNA obtained from fetal brains for global gene expression studies and immunohistochemical analysis was performed on fetal brain slices for investigation of cellular development in term HC fetal brains. Gene expression profiling identified changes in several clusters of genes that could contribute to the transfer of the maternal phenotype (chronic hyperinsulinemia and adult-onset obesity) to the HC offspring. Immunohistochemical analysis indicated diminished proliferation and neuronal maturation of stem-like cells lining the third ventricle, hypothalamic region, and the cerebral cortex in HC fetal brains. These results suggest that maternal obesity during pregnancy could alter the developmental program of specific fetal brain cell-networks. These defects could underlie pathologies such as metabolic syndrome and possibly some neurological disorders in the offspring at a later age.

  4. Cholera toxin regulates a signaling pathway critical for the expansion of neural stem cell cultures from the fetal and adult rodent brains.

    Directory of Open Access Journals (Sweden)

    Andreas Androutsellis-Theotokis

    2010-05-01

    Full Text Available New mechanisms that regulate neural stem cell (NSC expansion will contribute to improved assay systems and the emerging regenerative approach that targets endogenous stem cells. Expanding knowledge on the control of stem cell self renewal will also lead to new approaches for targeting the stem cell population of cancers.Here we show that Cholera toxin regulates two recently characterized NSC markers, the Tie2 receptor and the transcription factor Hes3, and promotes the expansion of NSCs in culture. Cholera toxin increases immunoreactivity for the Tie2 receptor and rapidly induces the nuclear localization of Hes3. This is followed by powerful cultured NSC expansion and induction of proliferation both in the presence and absence of mitogen.Our data suggest a new cell biological mechanism that regulates the self renewal and differentiation properties of stem cells, providing a new logic to manipulate NSCs in the context of regenerative disease and cancer.

  5. Systematic review and meta-analysis of efficacy of mesenchymal stem cells on locomotor recovery in animal models of traumatic brain injury.

    Science.gov (United States)

    Peng, Weijun; Sun, Jing; Sheng, Chenxia; Wang, Zhe; Wang, Yang; Zhang, Chunhu; Fan, Rong

    2015-03-26

    The therapeutic potential of mesenchymal stem cells (MSCs) for traumatic brain injury (TBI) is attractive. Conducting systematic review and meta-analyses based on data from animal studies can be used to inform clinical trial design. To conduct a systematic review and meta-analysis to (i) systematically review the literatures describing the effect of MSCs therapy in animal models of TBI, (ii) determine the estimated effect size of functional locomotor recovery after experimental TBI, and (iii) to provide empirical evidence of biological factors associated with greater efficacy. We conducted a systematic search of PubMed, EMBASE, and Web of Science and hand searched related references. Studies were selected if they reported the efficacy of MSCs in animal models of TBI. Two investigators independently assessed the identified studies. We extracted the details of individual study characteristics from each publication, assessed study quality, evaluated the effect sizes of MSCs treatment, and performed stratified meta-analysis and meta-regression, to assess the influence of study design on the estimated effect size. The presence of small effect sizes was investigated using funnel plots and Egger's tests. Twenty-eight eligible controlled studies were identified. The study quality was modest. Between-study heterogeneity was large. Meta-analysis showed that MSCs exert statistically significant positive effects on sensorimotor and neurological motor function. For sensorimotor function, maximum effect size in studies with a quality score of 5 was found in the weight-drop impact injury TBI model established in male SD rats, to which syngeneic umbilical cord-derived MSCs intracerebrally at cell dose of (1-5)×10(6) was administered r 6 hours following TBI, using ketamine as anesthetic agent. For neurological motor function, effect size was maximum for studies with a quality score of 5, in which the weight-drop impact injury TBI models of the female Wistar rats were adopted, with

  6. Selection of reference genes for normalisation of real-time RT-PCR in brain-stem death injury in Ovis aries

    Directory of Open Access Journals (Sweden)

    Fraser John F

    2009-07-01

    Full Text Available Abstract Background Heart and lung transplantation is frequently the only therapeutic option for patients with end stage cardio respiratory disease. Organ donation post brain stem death (BSD is a pre-requisite, yet BSD itself causes such severe damage that many organs offered for donation are unusable, with lung being the organ most affected by BSD. In Australia and New Zealand, less than 50% of lungs offered for donation post BSD are suitable for transplantation, as compared with over 90% of kidneys, resulting in patients dying for lack of suitable lungs. Our group has developed a novel 24 h sheep BSD model to mimic the physiological milieu of the typical human organ donor. Characterisation of the gene expression changes associated with BSD is critical and will assist in determining the aetiology of lung damage post BSD. Real-time PCR is a highly sensitive method involving multiple steps from extraction to processing RNA so the choice of housekeeping genes is important in obtaining reliable results. Little information however, is available on the expression stability of reference genes in the sheep pulmonary artery and lung. We aimed to establish a set of stably expressed reference genes for use as a standard for analysis of gene expression changes in BSD. Results We evaluated the expression stability of 6 candidate normalisation genes (ACTB, GAPDH, HGPRT, PGK1, PPIA and RPLP0 using real time quantitative PCR. There was a wide range of Ct-values within each tissue for pulmonary artery (15–24 and lung (16–25 but the expression pattern for each gene was similar across the two tissues. After geNorm analysis, ACTB and PPIA were shown to be the most stably expressed in the pulmonary artery and ACTB and PGK1 in the lung tissue of BSD sheep. Conclusion Accurate normalisation is critical in obtaining reliable and reproducible results in gene expression studies. This study demonstrates tissue associated variability in the selection of these

  7. Magnetic resonance and photoacoustic imaging of brain tumor mediated by mesenchymal stem cell labeled with multifunctional nanoparticle introduced via carotid artery injection

    Science.gov (United States)

    Qiao, Yang; Gumin, Joy; MacLellan, Christopher J.; Gao, Feng; Bouchard, Richard; Lang, Frederick F.; Stafford, R. Jason; Melancon, Marites P.

    2018-04-01

    Objective. To evaluate the feasibility of visualizing bone marrow-derived human mesenchymal stem cells (MSCs) labeled with a gold-coated magnetic resonance (MR)-active multifunctional nanoparticle and injected via the carotid artery for assessing the extent of MSC homing in glioma-bearing mice. Materials and methods. Nanoparticles containing superparamagnetic iron oxide coated with gold (SPIO@Au) with a diameter of ˜82 nm and maximum absorbance in the near infrared region were synthesized. Bone marrow-derived MSCs conjugated with green fluorescent protein (GFP) were successfully labeled with SPIO@Au at 4 μg ml-1 and injected via the internal carotid artery in six mice bearing orthotopic U87 tumors. Unlabeled MSCs were used as a control. The ability of SPIO@Au-loaded MSCs to be imaged using MR and photoacoustic (PA) imaging at t = 0 h, 2 h, 24 h, and 72 h was assessed using a 7 T Bruker Biospec experimental MR scanner and a Vevo LAZR PA imaging system with a 5 ns laser as the excitation source. Histological analysis of the brain tissue was performed 72 h after MSC injection using GFP fluorescence, Prussian blue staining, and hematoxylin-and-eosin staining. Results. MSCs labeled with SPIO@Au at 4 μg ml-1 did not exhibit cell death or any adverse effects on differentiation or migration. The PA signal in tumors injected with SPIO@Au-loaded MSCs was clearly more enhanced post-injection, as compared with the tumors injected with unlabeled MSCs at t = 72 h. Using the same mice, T2-weighted MR imaging results taken before injection and at t = 2 h, 24 h, and 72 h were consistent with the PA imaging results, showing significant hypointensity of the tumor in the presence of SPIO@Au-loaded MSCs. Histological analysis also showed co-localization of GFP fluorescence and iron, thereby confirming that SPIO@Au-labeled MSCs continue to carry their nanoparticle payloads even at 72 h after injection. Conclusions. Our results demonstrated the feasibility of tracking carotid artery

  8. Seamless Ligation Cloning Extract (SLiCE) Cloning Method

    OpenAIRE

    Zhang, Yongwei; Werling, Uwe; Edelmann, Winfried

    2014-01-01

    SLiCE (Seamless Ligation Cloning Extract) is a novel cloning method that utilizes easy to generate bacterial cell extracts to assemble multiple DNA fragments into recombinant DNA molecules in a single in vitro recombination reaction. SLiCE overcomes the sequence limitations of traditional cloning methods, facilitates seamless cloning by recombining short end homologies (15–52 bp) with or without flanking heterologous sequences and provides an effective strategy for directional subcloning of D...

  9. The metabotropic glutamate receptor agonist 1S,3R-ACPD stimulates and modulates NMDA receptor mediated excitotoxicity in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Blaabjerg, M; Kristensen, Bjarne Winther; Bonde, C

    2001-01-01

    The potential toxic effects of the metabotropic glutamate receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) and its interactions with the N-methyl-D-aspartate (NMDA) receptor were studied in hippocampal brain slice cultures, using densitometric measurements of the cellular...

  10. Novel active contour model based on multi-variate local Gaussian distribution for local segmentation of MR brain images

    Science.gov (United States)

    Zheng, Qiang; Li, Honglun; Fan, Baode; Wu, Shuanhu; Xu, Jindong

    2017-12-01

    Active contour model (ACM) has been one of the most widely utilized methods in magnetic resonance (MR) brain image segmentation because of its ability of capturing topology changes. However, most of the existing ACMs only consider single-slice information in MR brain image data, i.e., the information used in ACMs based segmentation method is extracted only from one slice of MR brain image, which cannot take full advantage of the adjacent slice images' information, and cannot satisfy the local segmentation of MR brain images. In this paper, a novel ACM is proposed to solve the problem discussed above, which is based on multi-variate local Gaussian distribution and combines the adjacent slice images' information in MR brain image data to satisfy segmentation. The segmentation is finally achieved through maximizing the likelihood estimation. Experiments demonstrate the advantages of the proposed ACM over the single-slice ACM in local segmentation of MR brain image series.

  11. Generalized Fourier slice theorem for cone-beam image reconstruction.

    Science.gov (United States)

    Zhao, Shuang-Ren; Jiang, Dazong; Yang, Kevin; Yang, Kang

    2015-01-01

    The cone-beam reconstruction theory has been proposed by Kirillov in 1961, Tuy in 1983, Feldkamp in 1984, Smith in 1985, Pierre Grangeat in 1990. The Fourier slice theorem is proposed by Bracewell 1956, which leads to the Fourier image reconstruction method for parallel-beam geometry. The Fourier slice theorem is extended to fan-beam geometry by Zhao in 1993 and 1995. By combining the above mentioned cone-beam image reconstruction theory and the above mentioned Fourier slice theory of fan-beam geometry, the Fourier slice theorem in cone-beam geometry is proposed by Zhao 1995 in short conference publication. This article offers the details of the derivation and implementation of this Fourier slice theorem for cone-beam geometry. Especially the problem of the reconstruction from Fourier domain has been overcome, which is that the value of in the origin of Fourier space is 0/0. The 0/0 type of limit is proper handled. As examples, the implementation results for the single circle and two perpendicular circle source orbits are shown. In the cone-beam reconstruction if a interpolation process is considered, the number of the calculations for the generalized Fourier slice theorem algorithm is O(N^4), which is close to the filtered back-projection method, here N is the image size of 1-dimension. However the interpolation process can be avoid, in that case the number of the calculations is O(N5).

  12. Slope Stability Analysis Using Slice-Wise Factor of Safety

    Directory of Open Access Journals (Sweden)

    Yu Zhao

    2014-01-01

    Full Text Available The concept of slice-wise factor of safety is introduced to investigate the state of both the whole slope and each slice. The assumption that the interslice force ratio is the same between any two slices is made and the eccentric moment of slice weight is also taken into account. Then four variables equations are formulated based on the equilibrium of forces and moment and the assumption of interslice forces, and then the slice-wise factor of safety along the slip surface can be obtained. The active and passive sections of the slope can be determined based on the distribution of factor of safety. The factor of safety of the whole slope is also defined as the ratio of the sum of antisliding force to the sum of sliding force on the slip surface. Two examples with different slip surface shapes are analysed to demonstrate the usage of the proposed method. The slice-wise factor of safety enables us to determine the sliding mechanism and pattern of a slope. The reliability is verified by comparing the overall factor of safety with that calculated by conventional methods.

  13. NMR surprizes with thin slices and strong gradients

    Energy Technology Data Exchange (ETDEWEB)

    Gaedke, Achim; Kresse, Benjamin [Institute of Condensed Matter Physics, Technische Universitaet Darmstadt (Germany); Nestle, Nikolaus

    2008-07-01

    In the context of our work on diffusion-relaxation-coupling in thin excited slices, we perform NMR experiments in static magnetic field gradients up to 200 T/m. For slice thicknesses in the range of 10{mu}m, the frequency bandwidth of the excited slices becomes sufficiently narrow that free induction decays (FIDs) become observable despite the presence of the strong static gradient. The observed FIDs were also simulated using standard methods from MRI physics. Possible effects of diffusion during the FID duration are still minor at this slice thickness in water but might become dominant for smaller slices or more diffusive media. Furthermore, the detailed excitation structure of the RF pulses was studied in profiling experiments over the edge of a plane liquid cell. Side lobe effects to the slices will be discussed along with approaches to control them. The spatial resolution achieved in the profiling experiments furthermore allows the identification of thermal expansion phenomena in the NMR magnet. Measures to reduce the temperature drift problems are presented.

  14. Culture of Mouse Neural Stem Cell Precursors

    OpenAIRE

    Currle, D. Spencer; Hu, Jia Sheng; Kolski-Andreaco, Aaron; Monuki, Edwin S.

    2007-01-01

    Primary neural stem cell cultures are useful for studying the mechanisms underlying central nervous system development. Stem cell research will increase our understanding of the nervous system and may allow us to develop treatments for currently incurable brain diseases and injuries. In addition, stem cells should be used for stem cell research aimed at the detailed study of mechanisms of neural differentiation and transdifferentiation and the genetic and environmental signals that direct the...

  15. Drug resistance in cortical and hippocampal slices from resected tissue of epilepsy patients: no significant impact of P-glycoprotein and Multidrug resistance associated proteins.

    Directory of Open Access Journals (Sweden)

    Nora eSandow

    2015-02-01

    Full Text Available Drug resistant patients undergoing epilepsy surgery have a good chance to become sensitive to anticonvulsant medication, suggesting that the resected brain tissue is responsible for drug resistance. Here, we address the question whether P-glycoprotein (Pgp and multidrug resistance associated proteins (MRPs expressed in the resected tissue contribute to drug resistance in vitro. Effects of anti-epileptic drugs (carbamazepine, sodium valproate, phenytoin and two unspecific inhibitors of Pgp and MRPs (verapamil and probenecid on seizure-like events induced in slices from 35 hippocampal and 35 temporal cortex specimens of altogether 51 patients (161 slices were studied. Although in slice preparations the blood brain barrier is not functional, we found that seizure-like events predominantly persisted in the presence of anticonvulsant drugs (90% and also in the presence of verapamil and probenecid (86%. Following subsequent co-administration of antiepileptic drugs and drug transport inhibitors, seizure-like events continued in 63% of 143 slices. Drug sensitivity in slices was recognized either as transition to recurrent epileptiform transients (30% or as suppression (7%, particularly by perfusion with carbamazepine in probenecid containing solutions (43%, 9%. Summarizing responses to co-administration from more than one slice per patient revealed that suppression of seizure-like activity in all slices was only observed in 7 % of patients. Patients whose tissue was completely or partially sensitive (65 % presented with higher seizure frequencies than those with resistant tissue (35 %. However, corresponding subgroups of patients don’t differ with respect to expression rates of drug transporters. Our results imply that parenchymal MRPs and Pgp are not responsible for drug resistance in resected tissue.

  16. Mycoflora of sun-dried sweet potato ( Ipomoea batatas L .) slices in ...

    African Journals Online (AJOL)

    A study was carried out to isolate and quantify the fungi present in sun-dried sweet potato slices in Benin City, Nigeria. Potato tubers were peeled, washed, sliced and sun-dried for 30 days. Oven-dried slices served as control. Meteorological data were obtained for the period of study. Fungal colonies on slices were counted ...

  17. Local establishment of repetitive long-term potentiation-induced synaptic enhancement in cultured hippocampal slices with divided input pathways.

    Science.gov (United States)

    Oe, Yuki; Tominaga-Yoshino, Keiko; Ogura, Akihiko

    2011-09-01

    Long-term potentiation (LTP) in the rodent hippocampus is a popular model for synaptic plasticity, which is considered the cellular basis for brain memory. Because most LTP analysis involves acutely prepared brain slices, however, the longevity of single LTP has not been well documented. Using stable hippocampal slice cultures for long-term examination, we previously found that single LTP disappeared within 1 day. In contrast, repeated induction of LTP led to the development of a distinct type of plasticity that lasted for more than 3 weeks and was accompanied by the formation of new synapses. Naming this novel plastic phenomenon repetitive LTP-induced synaptic enhancement (RISE), we proposed it as a model for the cellular processes involved in long-term memory formation. However, because in those experiments LTP was induced pharmacologically in the whole slice, it is not known whether RISE has input-pathway specificity, an essential property for memory. In this study, we divided the input pathway of CA1 pyramidal neurons by a knife cut and induced LTP three times, the third by tetanic stimulation in one of the divided pathways to express RISE specifically. Voltage-sensitive dye imaging and Golgi-staining performed 2 weeks after the three LTP inductions revealed both enhanced synaptic strength and increased dendritic spine density confined to the tetanized region. These results demonstrate that RISE is a feasible cellular model for long-term memory. Copyright © 2011 Wiley-Liss, Inc.

  18. Two approaches for applet-based visible human slice extraction

    Science.gov (United States)

    Gerlach, Sebastian; Hersch, Roger D.

    2001-12-01

    Real-time interactive slicing is a tool of choice for exploring 3D anatomic data sets such as the Visible Human. We offer real-time slicing on the Web by partitioning the application between a Java applet (the client) and the Web server. Two approaches for partitioning the work between the client and the server are presented and compared. In the first approach, we transfer complete compressed slices from the server to the client. In the second approach, we successively build a local cache on the client by transferring small subvolumes of increasing resolution from the server to the client. The client is responsible for extracting the displayed slices from the local data cache. The Web-based Real-time Visible Human navigator can be accessed at our Visible Human Web site at http://visiblehuman.epfl.ch. A high-bandwidth network connection is recommended. The web server offering real-time interactive slicing together with anatomic structure labeling opens new perspectives for teaching anatomy to paramedical and medical professions.

  19. Fractal Segmentation and Clustering Analysis for Seismic Time Slices

    Science.gov (United States)

    Ronquillo, G.; Oleschko, K.; Korvin, G.; Arizabalo, R. D.

    2002-05-01

    Fractal analysis has become part of the standard approach for quantifying texture on gray-tone or colored images. In this research we introduce a multi-stage fractal procedure to segment, classify and measure the clustering patterns on seismic time slices from a 3-D seismic survey. Five fractal classifiers (c1)-(c5) were designed to yield standardized, unbiased and precise measures of the clustering of seismic signals. The classifiers were tested on seismic time slices from the AKAL field, Cantarell Oil Complex, Mexico. The generalized lacunarity (c1), fractal signature (c2), heterogeneity (c3), rugosity of boundaries (c4) and continuity resp. tortuosity (c5) of the clusters are shown to be efficient measures of the time-space variability of seismic signals. The Local Fractal Analysis (LFA) of time slices has proved to be a powerful edge detection filter to detect and enhance linear features, like faults or buried meandering rivers. The local fractal dimensions of the time slices were also compared with the self-affinity dimensions of the corresponding parts of porosity-logs. It is speculated that the spectral dimension of the negative-amplitude parts of the time-slice yields a measure of connectivity between the formation's high-porosity zones, and correlates with overall permeability.

  20. [Transport of lithium in rat renal cortex slices].

    Science.gov (United States)

    Günther, C; Kersten, L; Bräunlich, H

    1983-01-01

    Slices of the renal cortex take up lithium from the incubation medium; this uptake does not follow a saturation kinetics and is demonstrable under aerobic and anaerobic conditions alike. The lithium uptake is associated with a variation of the sodium and potassium content in the slices. These changes are distinguishable from the electrolyte movements caused by the introduction of the slices into the incubation medium. The present findings characterize the lithium uptake into the renal tissue as a passive process. With the in vivo experiments, accumulation of lithium in the renal tissue against the serum should presuppose glomerular filtration and enrichment of lithium in the lumen of the tubuli through processes of urine concentration. In slices of the renal cortex, like in the intact animal the uptake of lithium can be influenced by inhibitors of the renal electrolyte movement. The present findings have provided evidence that lithium enters the tubular cells passively, and that slices of the renal cortex are suited for testing substances acting on the renal handling of lithium.

  1. Types of Stem Cells

    Science.gov (United States)

    ... PDF) Download an introduction to stem cells and stem cell research. Stem Cell Glossary Stem cell terms to know. ... stem cells blog from the International Society for Stem Cell Research. Learn About Stem Cells From Lab to You ...

  2. Road for understanding cancer stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Erzik, Can

    2007-01-01

    in tumor biopsies such as brain and breast. Evidence supporting the cancer stem cell hypothesis has gained impact due to progress in stem cell biology and development of new models to validate the self-renewal potential of stem cells. Recent evidence on the possible identification of cancer stem cells may......There is increasing evidence suggesting that stem cells are susceptive to carcinogenesis and, consequently, can be the origin of many cancers. Recently, the neoplastic potential of stem cells has been supported by many groups showing the existence of subpopulations with stem cell characteristics...... offer an opportunity to use these cells as future therapeutic targets. Therefore, model systems in this field have become very important and useful. This review will focus on the state of knowledge on cancer stem cell research, including cell line models for cancer stem cells. The latter will, as models...

  3. Successful Large-volume Leukapheresis for Hematopoietic Stem Cell Collection in a Very-low-weight Brain Tumor Infant with Coagulopathy

    Directory of Open Access Journals (Sweden)

    Yu-Mei Liao

    2013-06-01

    Full Text Available Peripheral apheresis has become a safe procedure to collect hematopoietic stem cells, even in pediatric patients and donors. However, the apheresis procedure for small and sick children is more complicated due to difficult venous access, relatively large extracorporeal volume, toxicity of citrate, and unstable hemostasis. We report a small and sick child with refractory medulloblastoma, impaired liver function, and coagulopathy after several major cycles of cisplatin-based chemotherapy. She successfully received large-volume leukapheresis for hematopoietic stem cell collection, although the patient experienced severe coagulopathy during the procedures. Health care providers should be alert to this potential risk.

  4. Preparing polished crystal slices with high precision orientation

    DEFF Research Database (Denmark)

    Mathiesen, S. Ipsen; Gerward, Leif; Pedersen, O.

    1974-01-01

    A polishing procedure is described which utilizes a high precision Laue technique for crystal orientation. Crystal slices with their final polished surfaces parallel to a crystallographic plane within 0.02° can be prepared. ©1974 The American Institute of Physics......A polishing procedure is described which utilizes a high precision Laue technique for crystal orientation. Crystal slices with their final polished surfaces parallel to a crystallographic plane within 0.02° can be prepared. ©1974 The American Institute of Physics...

  5. Verification of Software Product Lines with Delta-Oriented Slicing

    Science.gov (United States)

    Bruns, Daniel; Klebanov, Vladimir; Schaefer, Ina

    Software product line (SPL) engineering is a well-known approach to develop industry-size adaptable software systems. SPL are often used in domains where high-quality software is desirable; the overwhelming product diversity, however, remains a challenge for assuring correctness. In this paper, we present delta-oriented slicing, an approach to reduce the deductive verification effort across an SPL where individual products are Java programs and their relations are described by deltas. On the specification side, we extend the delta language to deal with formal specifications. On the verification side, we combine proof slicing and similarity-guided proof reuse to ease the verification process.

  6. Using 31P NMR spectroscopy at 14.1 Tesla to investigate PARP-1 associated energy failure and metabolic rescue in cerebrocortical slices.

    Science.gov (United States)

    Zeng, Jianying; Hirai, Kiyoshi; Yang, Guo-Yuan; Ying, Weihai; Swanson, Raymond A; Kelly, Mark; Mayer, Moriz; James, Thomas L; Litt, Lawrence

    2004-08-01

    PARP-1 activation by H(2)O(2) in an acute preparation of superfused, respiring, neonatal cerebrocortical slices was assessed from PAR-polymer formation detected with immunohistochemistry and Western blotting. (31)P NMR spectroscopy at 14.1 Tesla of perchloric acid slice extracts was used to assess energy failure in a 1-h H(2)O(2) exposure as well as in a subsequent 4-h recovery period where the superfusate had no H(2)O(2) and specifically chosen metabolic substrates. Although more data are needed to fully characterize different bioenergetic responses, a high NMR spectral resolution (PCr full-width at half-max approximately.01 ppm) and narrow widths for most metabolites (energy phosphates. It appears possible to use brain slices to quantitatively study PARP-related, NAD-associated energy failure, and rescue with TCA metabolites.

  7. The bantam microRNA acts through Numb to exert cell growth control and feedback regulation of Notch in tumor-forming stem cells in the Drosophila brain.

    Science.gov (United States)

    Wu, Yen-Chi; Lee, Kyu-Sun; Song, Yan; Gehrke, Stephan; Lu, Bingwei

    2017-05-01

    Notch (N) signaling is central to the self-renewal of neural stem cells (NSCs) and other tissue stem cells. Its deregulation compromises tissue homeostasis and contributes to tumorigenesis and other diseases. How N regulates stem cell behavior in health and disease is not well understood. Here we show that N regulates bantam (ban) microRNA to impact cell growth, a process key to NSC maintenance and particularly relied upon by tumor-forming cancer stem cells. Notch signaling directly regulates ban expression at the transcriptional level, and ban in turn feedback regulates N activity through negative regulation of the Notch inhibitor Numb. This feedback regulatory mechanism helps maintain the robustness of N signaling activity and NSC fate. Moreover, we show that a Numb-Myc axis mediates the effects of ban on nucleolar and cellular growth independently or downstream of N. Our results highlight intricate transcriptional as well as translational control mechanisms and feedback regulation in the N signaling network, with important implications for NSC biology and cancer biology.

  8. The Use of Human-Induced Pluripotent Stem Cell-Derived Neural Precursors in the Treatment of Brain and Spinal Cord Injury

    Czech Academy of Sciences Publication Activity Database

    Jendelová, Pavla; Kozubenko, Nataliya; Amemori, Takashi; Turnovcová, Karolína; Seminatore, CH.; Jirák, D.; Onteniente, B.; Syková, Eva

    2011-01-01

    Roč. 20, č. 4 (2011), s. 564-564 ISSN 0963-6897. [International Neural Transplantatioin and Repair Meeting/18th Annual Meeting of the American-Society-for-Neural-Therapy- and -Repair /11./. 04.05.2011-08.05.2011, Clearwater] Institutional research plan: CEZ:AV0Z50390703 Keywords : spinal cord * stem cell Subject RIV: FH - Neurology

  9. Imaging skeletal anatomy of injured cervical spine specimens: comparison of single-slice vs multi-slice helical CT

    Energy Technology Data Exchange (ETDEWEB)

    Obenauer, S.; Alamo, L.; Herold, T.; Funke, M.; Kopka, L.; Grabbe, E. [Department of Radiology, Georg August-University Goettingen, Robert-Koch-Strasse 40, 37075 Goettingen (Germany)

    2002-08-01

    Our objective was to compare a single-slice CT (SS-CT) scanner with a multi-slice CT (MS-CT) scanner in the depiction of osseous anatomic structures and fractures of the upper cervical spine. Two cervical spine specimens with artificial trauma were scanned with a SS-CT scanner (HighSpeed, CT/i, GE, Milwaukee, Wis.) by using various collimations (1, 3, 5 mm) and pitch factors (1, 1.5, 2, 3) and a four-slice helical CT scanner (LightSpeed, QX/i, GE, Milwaukee, Wis.) by using various table speeds ranging from 3.75 to 15 mm/rotation for a pitch of 0.75 and from 7.5 to 30 mm/rotation for a pitch of 1.5. Images were reconstructed with an interval of 1 mm. Sagittal and coronal multiplanar reconstructions of the primary and reconstructed data set were performed. For MS-CT a tube current resulting in equivalent image noise as with SS-CT was used. All images were judged by two observers using a 4-point scale. The best image quality for SS-CT was achieved with the smallest slice thickness (1 mm) and a pitch smaller than 2 resulting in a table speed of up to 2 mm per gantry rotation (4 points). A reduction of the slice thickness rather than of the table speed proved to be beneficial at MS-CT. Therefore, the optimal scan protocol in MS-CT included a slice thickness of 1.25 mm with a table speed of 7.5 mm/360 using a pitch of 1.5 (4 points), resulting in a faster scan time than when a pitch of 0.75 (4 points) was used. This study indicates that MS-CT could provide equivalent image quality at approximately four times the volume coverage speed of SS-CT. (orig.)

  10. Metabolomics of Therapy Response in Preclinical Glioblastoma: A Multi-Slice MRSI-Based Volumetric Analysis for Noninvasive Assessment of Temozolomide Treatment.

    Science.gov (United States)

    Arias-Ramos, Nuria; Ferrer-Font, Laura; Lope-Piedrafita, Silvia; Mocioiu, Victor; Julià-Sapé, Margarida; Pumarola, Martí; Arús, Carles; Candiota, Ana Paula

    2017-05-18

    Glioblastoma (GBM) is the most common aggressive primary brain tumor in adults, with a short survival time even after aggressive therapy. Non-invasive surrogate biomarkers of therapy response may be relevant for improving patient survival. Previous work produced such biomarkers in preclinical GBM using semi-supervised source extraction and single-slice Magnetic Resonance Spectroscopic Imaging (MRSI). Nevertheless, GBMs are heterogeneous and single-slice studies could prevent obtaining relevant information. The purpose of this work was to evaluate whether a multi-slice MRSI approach, acquiring consecutive grids across the tumor, is feasible for preclinical models and may produce additional insight into therapy response. Nosological images were analyzed pixel-by-pixel and a relative responding volume, the Tumor Responding Index ( TRI ), was defined to quantify response. Heterogeneous response levels were observed and treated animals were ascribed to three arbitrary predefined groups: high response (HR, n = 2), TRI = 68.2