Modulation of subventricular zone oligodendrogenesis: a role for hemopressin?

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Sara eXapelli

2014-02-01

Full Text Available Neural stem cells (NSCs from the subventricular zone (SVZ have been indicated as a source of new oligodendrocytes to use in regenerative medicine for myelin pathologies. Indeed, NSCs are multipotent cells that can self-renew and differentiate into all neural cell types of the central nervous system (CNS. In normal conditions, SVZ cells are poorly oligodendrogenic, nevertheless their oligodendrogenic potential is boosted following demyelination. Importantly, progressive restriction into the oligodendrocyte fate is specified by extrinsic and intrinsic factors, endocannabinoids being one of these factors. Although a role for endocannabinoids in oligodendrogenesis has already been foreseen, selective agonists and antagonists of cannabinoids receptors produce severe adverse side effects. Herein, we show that hemopressin, a modulator of CB1 receptors, increased oligodendroglial differentiation in SVZ neural stem/progenitor cell cultures derived from neonatal mice. The original results presented in this work suggest that hemopressin and derivatives may be of potential interest for the development of future strategies to treat demyelinating diseases.

Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall

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Li Shengwen

2012-09-01

Full Text Available Abstract Background The cancer stem cell (CSC hypothesis posits that deregulated neural stem cells (NSCs form the basis of brain tumors such as glioblastoma multiforme (GBM. GBM, however, usually forms in the cerebral white matter while normal NSCs reside in subventricular and hippocampal regions. We attempted to characterize CSCs from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall. Methods We described isolating CSCs from a GBM involving the lateral ventricles and characterized these cells with in vitro molecular biomarker profiling, cellular behavior, ex vivo and in vivo techniques. Results The patient’s MRI revealed a heterogeneous mass with associated edema, involving the left subventricular zone. Histological examination of the tumor established it as being a high-grade glial neoplasm, characterized by polygonal and fusiform cells with marked nuclear atypia, amphophilic cytoplasm, prominent nucleoli, frequent mitotic figures, irregular zones of necrosis and vascular hyperplasia. Recurrence of the tumor occurred shortly after the surgical resection. CD133-positive cells, isolated from the tumor, expressed stem cell markers including nestin, CD133, Ki67, Sox2, EFNB1, EFNB2, EFNB3, Cav-1, Musashi, Nucleostemin, Notch 2, Notch 4, and Pax6. Biomarkers expressed in differentiated cells included Cathepsin L, Cathepsin B, Mucin18, Mucin24, c-Myc, NSE, and TIMP1. Expression of unique cancer-related transcripts in these CD133-positive cells, such as caveolin-1 and −2, do not appear to have been previously reported in the literature. Ex vivo organotypic brain slice co-culture showed that the CD133+ cells behaved like tumor cells. The CD133-positive cells also induced tumor formation when they were stereotactically transplanted into the brains of the immune-deficient NOD/SCID mice. Conclusions This brain tumor involving the neurogenic lateral ventricular wall was comprised of tumor-forming, CD133-positive cancer

Optimizing culture medium composition to improve oligodendrocyte progenitor cell yields in vitro from subventricular zone-derived neural progenitor cell neurospheres.

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Paula G Franco

Full Text Available Neural Stem and Progenitor Cells (NSC/NPC are gathering tangible recognition for their uses in cell therapy and cell replacement therapies for human disease, as well as a model system to continue research on overall neural developmental processes in vitro. The Subventricular Zone is one of the largest NSC/NPC niches in the developing mammalian Central Nervous System, and persists through to adulthood. Oligodendrocyte progenitor cell (OPC enriched cultures are usefull tools for in vitro studies as well as for cell replacement therapies for treating demyelination diseases. We used Subventricular Zone-derived NSC/NPC primary cultures from newborn mice and compared the effects of different growth factor combinations on cell proliferation and OPC yield. The Platelet Derived Growth Factor-AA and BB homodimers had a positive and significant impact on OPC generation. Furthermore, heparin addition to the culture media contributed to further increase overall culture yields. The OPC generated by this protocol were able to mature into Myelin Basic Protein-expressing cells and to interact with neurons in an in vitro co-culture system. As a whole, we describe an optimized in vitro method for increasing OPC.

RAE-1 is expressed in the adult subventricular zone and controls cell proliferation of neurospheres

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Popa, Natalia; Cédile, Oriane; Pollet-Villard, Xavier

2011-01-01

playing either immune or nonimmune function. Among the latter, MHC functions in the central nervous system has started to receive recent interest. Here, our first goal was to investigate the potential relationship between MHC class I molecules and neurogenesis. For the first time, we report the expression......, and we demonstrate they persist in one of the main area of adult neurogenesis, the subventricular zone (SVZ). So far, RAE-1 is only known for its immune functions as a ligand of the activating receptor NKG2D expressed by natural killer (NK) cells, natural killer T, Tγδ, and some T CD8 lymphocytes. Here...

Noninvasive Evaluation of Cellular Proliferative Activity in Brain Neurogenic Regions in Rats under Depression and Treatment by Enhanced [18F]FLT-PET Imaging.

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Tamura, Yasuhisa; Takahashi, Kayo; Takata, Kumi; Eguchi, Asami; Yamato, Masanori; Kume, Satoshi; Nakano, Masayuki; Watanabe, Yasuyoshi; Kataoka, Yosky

2016-08-03

Neural stem cells in two neurogenic regions, the subventricular zone and the subgranular zone (SGZ) of the hippocampal dentate gyrus, can divide and produce new neurons throughout life. Hippocampal neurogenesis is related to emotions, including depression/anxiety, and the therapeutic effects of antidepressants, as well as learning and memory. The establishment of in vivo imaging for proliferative activity of neural stem cells in the SGZ might be used to diagnose depression and to monitor the therapeutic efficacy of antidepressants. Positron emission tomography (PET) imaging with 3'-deoxy-3'-[(18)F]fluoro-l-thymidine ([(18)F]FLT) has been studied to allow visualization of proliferative activity in two neurogenic regions of adult mammals; however, the PET imaging has not been widely used because of lower accumulation of [(18)F]FLT, which does not allow quantitative assessment of the decline in cellular proliferative activity in the SGZ under the condition of depression. We report the establishment of an enhanced PET imaging method with [(18)F]FLT combined with probenecid, an inhibitor of drug transporters at the blood-brain barrier, which can allow the quantitative visualization of neurogenic activity in rats. Enhanced PET imaging allowed us to evaluate reduced cell proliferation in the SGZ of rats with corticosterone-induced depression, and further the recovery of proliferative activity in rats under treatment with antidepressants. This enhanced [(18)F]FLT-PET imaging technique with probenecid can be used to assess the dynamic alteration of neurogenic activity in the adult mammalian brain and may also provide a means for objective diagnosis of depression and monitoring of the therapeutic effect of antidepressant treatment. Adult hippocampal neurogenesis may play a role in major depression and antidepressant therapy. Establishment of in vivo imaging for hippocampal neurogenic activity may be useful to diagnose depression and monitor the therapeutic efficacy of

NMDA modulates oligodendrocyte differentiation of subventricular zone cells through PKC activation

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Fabio eCavaliere

2013-12-01

Full Text Available Multipotent cells from the juvenile subventricular zone (SVZ possess the ability to differentiate into new neural cells. Depending on local signals, SVZ can generate new neurons, astrocytes or oligodendrocytes. We previously demonstrated that activation of NMDA receptors in SVZ progenitors increases the rate of oligodendrocyte differentiation. Here we investigated the mechanisms involved in NMDA receptor-dependent differentiation. Using functional studies performed with the reporter gene luciferase we found that activation of NMDA receptor stimulates PKC. In turn, stimulation of PKC precedes the activation of NADPH oxidase (NOX as demonstrated by translocation of the p67phox subunit to the cellular membrane. We propose that NOX2 is involved in the transduction of the signal from NMDA receptors through PKC activation as the inhibitor gp91 reduced their pro-differentiation effect. In addition, our data and that from other groups suggest that signaling through the NMDA receptor/PKC/NOX2 cascade generates ROS that activate the PI3/mTOR pathway and finally leads to the generation of new oligodendrocytes.

Btg1 is Required to Maintain the Pool of Stem and Progenitor Cells of the Dentate Gyrus and Subventricular Zone

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Farioli-Vecchioli, Stefano; Micheli, Laura; Saraulli, Daniele; Ceccarelli, Manuela; Cannas, Sara; Scardigli, Raffaella; Leonardi, Luca; Cinà, Irene; Costanzi, Marco; Ciotti, Maria Teresa; Moreira, Pedro; Rouault, Jean-Pierre; Cestari, Vincenzo; Tirone, Felice

2012-01-01

Btg1 belongs to a family of cell cycle inhibitory genes. We observed that Btg1 is highly expressed in adult neurogenic niches, i.e., the dentate gyrus and subventricular zone (SVZ). Thus, we generated Btg1 knockout mice to analyze the role of Btg1 in the process of generation of adult new neurons. Ablation of Btg1 causes a transient increase of the proliferating dentate gyrus stem and progenitor cells at post-natal day 7; however, at 2 months of age the number of these proliferating cells, as well as of mature neurons, greatly decreases compared to wild-type controls. Remarkably, adult dentate gyrus stem and progenitor cells of Btg1-null mice exit the cell cycle after completing the S phase, express p53 and p21 at high levels and undergo apoptosis within 5 days. In the SVZ of adult (two-month-old) Btg1-null mice we observed an equivalent decrease, associated to apoptosis, of stem cells, neuroblasts, and neurons; furthermore, neurospheres derived from SVZ stem cells showed an age-dependent decrease of the self-renewal and expansion capacity. We conclude that ablation of Btg1 reduces the pool of dividing adult stem and progenitor cells in the dentate gyrus and SVZ by decreasing their proliferative capacity and inducing apoptosis, probably reflecting impairment of the control of the cell cycle transition from G1 to S phase. As a result, the ability of Btg1-null mice to discriminate among overlapping contextual memories was affected. Btg1 appears, therefore, to be required for maintaining adult stem and progenitor cells quiescence and self-renewal. PMID:22969701

Notch2 Signaling Maintains NSC Quiescence in the Murine Ventricular-Subventricular Zone

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Anna Engler

2018-01-01

Full Text Available Neurogenesis continues in the ventricular-subventricular zone (V-SVZ of the adult forebrain from quiescent neural stem cells (NSCs. V-SVZ NSCs are a reservoir for new olfactory bulb (OB neurons that migrate through the rostral migratory stream (RMS. To generate neurons, V-SVZ NSCs need to activate and enter the cell cycle. The mechanisms underlying NSC transition from quiescence to activity are poorly understood. We show that Notch2, but not Notch1, signaling conveys quiescence to V-SVZ NSCs by repressing cell-cycle-related genes and neurogenesis. Loss of Notch2 activates quiescent NSCs, which proliferate and generate new neurons of the OB lineage. Notch2 deficiency results in accelerated V-SVZ NSC exhaustion and an aging-like phenotype. Simultaneous loss of Notch1 and Notch2 resembled the total loss of Rbpj-mediated canonical Notch signaling; thus, Notch2 functions are not compensated in NSCs, and Notch2 is indispensable for the maintenance of NSC quiescence in the adult V-SVZ.

Lineage analysis of quiescent regenerative stem cells in the adult brain by genetic labelling reveals spatially restricted neurogenic niches in the olfactory bulb.

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Giachino, Claudio; Taylor, Verdon

2009-07-01

The subventricular zone (SVZ) of the lateral ventricles is the major neurogenic region in the adult mammalian brain, harbouring neural stem cells within defined niches. The identity of these stem cells and the factors regulating their fate are poorly understood. We have genetically mapped a population of Nestin-expressing cells during postnatal development to study their potential and fate in vivo. Taking advantage of the recombination characteristics of a nestin::CreER(T2) allele, we followed a subpopulation of neural stem cells and traced their fate in a largely unrecombined neurogenic niche. Perinatal nestin::CreER(T2)-expressing cells give rise to multiple glial cell types and neurons, as well as to stem cells of the adult SVZ. In the adult SVZ nestin::CreER(T2)-expressing neural stem cells give rise to several neuronal subtypes in the olfactory bulb (OB). We addressed whether the same population of neural stem cells play a role in SVZ regeneration. Following anti-mitotic treatment to eliminate rapidly dividing progenitors, relatively quiescent nestin::CreER(T2)-targeted cells are spared and contribute to SVZ regeneration, generating new proliferating precursors and neuroblasts. Finally, we have identified neurogenic progenitors clustered in ependymal-like niches within the rostral migratory stream (RMS) of the OB. These OB-RMS progenitors generate neuroblasts that, upon transplantation, graft, migrate and differentiate into granule and glomerular neurons. In summary, using conditional lineage tracing we have identified neonatal cells that are the source of neurogenic and regenerative neural stem cells in the adult SVZ and occupy a novel neurogenic niche in the OB.

Pharmacogenomic identification of small molecules for lineage specific manipulation of subventricular zone germinal activity.

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Kasum Azim

2017-03-01

Full Text Available Strategies for promoting neural regeneration are hindered by the difficulty of manipulating desired neural fates in the brain without complex genetic methods. The subventricular zone (SVZ is the largest germinal zone of the forebrain and is responsible for the lifelong generation of interneuron subtypes and oligodendrocytes. Here, we have performed a bioinformatics analysis of the transcriptome of dorsal and lateral SVZ in early postnatal mice, including neural stem cells (NSCs and their immediate progenies, which generate distinct neural lineages. We identified multiple signaling pathways that trigger distinct downstream transcriptional networks to regulate the diversity of neural cells originating from the SVZ. Next, we used a novel in silico genomic analysis, searchable platform-independent expression database/connectivity map (SPIED/CMAP, to generate a catalogue of small molecules that can be used to manipulate SVZ microdomain-specific lineages. Finally, we demonstrate that compounds identified in this analysis promote the generation of specific cell lineages from NSCs in vivo, during postnatal life and adulthood, as well as in regenerative contexts. This study unravels new strategies for using small bioactive molecules to direct germinal activity in the SVZ, which has therapeutic potential in neurodegenerative diseases.

Mild myelin disruption elicits early alteration in behavior and proliferation in the subventricular zone.

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Gould, Elizabeth A; Busquet, Nicolas; Shepherd, Douglas; Dietz, Robert M; Herson, Paco S; Simoes de Souza, Fabio M; Li, Anan; George, Nicholas M; Restrepo, Diego; Macklin, Wendy B

2018-02-13

Myelin, the insulating sheath around axons, supports axon function. An important question is the impact of mild myelin disruption. In the absence of the myelin protein proteolipid protein (PLP1), myelin is generated but with age, axonal function/maintenance is disrupted. Axon disruption occurs in Plp1 -null mice as early as 2 months in cortical projection neurons. High-volume cellular quantification techniques revealed a region-specific increase in oligodendrocyte density in the olfactory bulb and rostral corpus callosum that increased during adulthood. A distinct proliferative response of progenitor cells was observed in the subventricular zone (SVZ), while the number and proliferation of parenchymal oligodendrocyte progenitor cells was unchanged. This SVZ proliferative response occurred prior to evidence of axonal disruption. Thus, a novel SVZ response contributes to the region-specific increase in oligodendrocytes in Plp1 -null mice. Young adult Plp1- null mice exhibited subtle but substantial behavioral alterations, indicative of an early impact of mild myelin disruption. © 2018, Gould et al.

Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age-associated neurogenic decline.

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Lupo, Giuseppe; Nisi, Paola S; Esteve, Pilar; Paul, Yu-Lee; Novo, Clara Lopes; Sidders, Ben; Khan, Muhammad A; Biagioni, Stefano; Liu, Hai-Kun; Bovolenta, Paola; Cacci, Emanuele; Rugg-Gunn, Peter J

2018-06-01

Adult neurogenesis declines with aging due to the depletion and functional impairment of neural stem/progenitor cells (NSPCs). An improved understanding of the underlying mechanisms that drive age-associated neurogenic deficiency could lead to the development of strategies to alleviate cognitive impairment and facilitate neuroregeneration. An essential step towards this aim is to investigate the molecular changes that occur in NSPC aging on a genomewide scale. In this study, we compare the transcriptional, histone methylation and DNA methylation signatures of NSPCs derived from the subventricular zone (SVZ) of young adult (3 months old) and aged (18 months old) mice. Surprisingly, the transcriptional and epigenomic profiles of SVZ-derived NSPCs are largely unchanged in aged cells. Despite the global similarities, we detect robust age-dependent changes at several hundred genes and regulatory elements, thereby identifying putative regulators of neurogenic decline. Within this list, the homeobox gene Dbx2 is upregulated in vitro and in vivo, and its promoter region has altered histone and DNA methylation levels, in aged NSPCs. Using functional in vitro assays, we show that elevated Dbx2 expression in young adult NSPCs promotes age-related phenotypes, including the reduced proliferation of NSPC cultures and the altered transcript levels of age-associated regulators of NSPC proliferation and differentiation. Depleting Dbx2 in aged NSPCs caused the reverse gene expression changes. Taken together, these results provide new insights into the molecular programmes that are affected during mouse NSPC aging, and uncover a new functional role for Dbx2 in promoting age-related neurogenic decline. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Microglia from neurogenic and non-neurogenic regions display differential proliferative potential and neuroblast support

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Gregory Paul Marshall

2014-07-01

Full Text Available Microglia isolated from the neurogenic subependymal zone (SEZ and hippocampus (HC are capable of massive in vitro population expansion that is not possible with microglia isolated from non-neurogenic regions. We asked if this regional heterogeneity in microglial proliferative capacity is cell intrinsic, or is conferred by interaction with respective neurogenic or non-neurogenic niches. By combining SEZ and cerebral cortex (CTX primary tissue dissociates to generate heterospatial cultures, we find that exposure to the SEZ environment does not enhance CTX microglia expansion; however, the CTX environment exerts a suppressive effect on SEZ microglia expansion. Furthermore, addition of purified donor SEZ microglia to either CTX- or SEZ-derived cultures suppresses the expansion of host microglia, while the addition of donor CTX microglia enhances the over-all microglia yield. These data suggest that SEZ and CTX microglia possess intrinsic, spatially restricted characteristics that are independent of their in vitro environment, and that they represent unique and functionally distinct populations. Finally, we determined that the repeated supplementation of neurogenic SEZ cultures with expanded SEZ microglia allows for sustained levels of inducible neurogenesis, provided that the ratio of microglia to total cells remains within a fairly narrow range.

Stroke Repair via Biomimicry of the Subventricular Zone

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Rita Matta

2018-03-01

Full Text Available Stroke is among the leading causes of death and disability worldwide, 85% of which are ischemic. Current stroke therapies are limited by a narrow effective therapeutic time and fail to effectively complete the recovery of the damaged area. Magnetic resonance imaging of the subventricular zone (SVZ following infarct/stroke has allowed visualization of new axonal connections and projections being formed, while new immature neurons migrate from the SVZ to the peri-infarct area. Such studies suggest that the SVZ is a primary source of regenerative cells for the repair and regeneration of stroke-damaged neurons and tissue. Therefore, the development of tissue engineered scaffolds that serve as a bioreplicative SVZ niche would support the survival of multiple cell types that reside in the SVZ. Essential to replication of the human SVZ microenvironment is the establishment of microvasculature that regulates both the healthy and stroke-injured blood–brain barrier, which is dysregulated poststroke. In order to reproduce this niche, understanding how cells interact in this environment is critical, in particular neural stem cells, endothelial cells, pericytes, ependymal cells, and microglia. Remodeling and repair of the matrix-rich SVZ niche by endogenous reparative mechanisms may then support functional recovery when enhanced by an artificial niche that supports the survival and proliferation of migrating vascular and neuronal cells. Critical considerations to mimic this area include an understanding of resident cell types, delivery method, and the use of biocompatible materials. Controlling stem cell survival, differentiation, and migration are key factors to consider when transplanting stem cells. Here, we discuss the role of the SVZ architecture and resident cells in the promotion and enhancement of endogenous repair mechanisms. We elucidate the interplay between the extracellular matrix composition and cell interactions prior to and following stroke

Stroke Repair via Biomimicry of the Subventricular Zone

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Matta, Rita; Gonzalez, Anjelica L.

2018-03-01

Stroke is among the leading causes of death and disability worldwide, 85% of which are ischemic. Current stroke therapies are limited by a narrow effective therapeutic time and fail to effectively complete the recovery of the damaged area. Magnetic resonance imaging of the subventricular zone (SVZ) following infarct/stroke has allowed visualization of new axonal connections and projections being formed, while new immature neurons migrate from the SVZ to the peri-infarct area. Such studies suggest that the SVZ is a primary source of regenerative cells for the repair and regeneration of stroke-damaged neurons and tissue. Therefore, the development of tissue engineered scaffolds that serve as a bioreplicative SVZ niche would support the survival of multiple cell types that reside in the SVZ. Essential to replication of the human SVZ microenvironment is the establishment of microvasculature that regulates both the healthy and stroke-injured blood brain barrier, which is dysregulated post-stroke. In order to reproduce this niche, understanding how cells interact in this environment is critical, in particular neural stem cells, endothelial cells, pericytes, ependymal cells, and microglia. Remodeling and repair of the matrix-rich SVZ niche by endogenous reparative mechanisms may then support functional recovery when enhanced by an artificial niche that supports the survival and proliferation of migrating vascular and neuronal cells. Critical considerations to mimic this area include an understanding of resident cell types, delivery method, and the use of biocompatible materials. Controlling stem cell survival, differentiation, and migration are key factors to consider when transplanting stem cells. Here, we discuss the role of the SVZ architecture and resident cells in the promotion and enhancement of endogenous repair mechanisms. We elucidate the interplay between the extracellular matrix composition and cell interactions prior to and following stroke. Lastly, we review

Perlecan is required for FGF-2 signaling in the neural stem cell niche

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Aurelien Kerever

2014-03-01

Full Text Available In the adult subventricular zone (neurogenic niche, neural stem cells double-positive for two markers of subsets of neural stem cells in the adult central nervous system, glial fibrillary acidic protein and CD133, lie in proximity to fractones and to blood vessel basement membranes, which contain the heparan sulfate proteoglycan perlecan. Here, we demonstrate that perlecan deficiency reduces the number of both GFAP/CD133-positive neural stem cells in the subventricular zone and new neurons integrating into the olfactory bulb. We also show that FGF-2 treatment induces the expression of cyclin D2 through the activation of the Akt and Erk1/2 pathways and promotes neurosphere formation in vitro. However, in the absence of perlecan, FGF-2 fails to promote neurosphere formation. These results suggest that perlecan is a component of the neurogenic niche that regulates FGF-2 signaling and acts by promoting neural stem cell self-renewal and neurogenesis.

Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

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Drew, Liam J.; Fusi, Stefano; Hen, René

2013-01-01

In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

Neural Stem Cells: Implications for the Conventional Radiotherapy of Central Nervous System Malignancies

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Barani, Igor J.; Benedict, Stanley H.; Lin, Peck-Sun

2007-01-01

Advances in basic neuroscience related to neural stem cells and their malignant counterparts are challenging traditional models of central nervous system tumorigenesis and intrinsic brain repair. Neurogenesis persists into adulthood predominantly in two neurogenic centers: subventricular zone and subgranular zone. Subventricular zone is situated adjacent to lateral ventricles and subgranular zone is confined to the dentate gyrus of the hippocampus. Neural stem cells not only self-renew and differentiate along multiple lineages in these regions, but also contribute to intrinsic brain plasticity and repair. Ionizing radiation can depopulate these exquisitely sensitive regions directly or impair in situ neurogenesis by indirect, dose-dependent and inflammation-mediated mechanisms, even at doses <2 Gy. This review discusses the fundamental neural stem cell concepts within the framework of cumulative clinical experience with the treatment of central nervous system malignancies using conventional radiotherapy

Aging results in copper accumulations in glial fibrillary acidic protein-positive cells in the subventricular zone.

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Pushkar, Yulia; Robison, Gregory; Sullivan, Brendan; Fu, Sherleen X; Kohne, Meghan; Jiang, Wendy; Rohr, Sven; Lai, Barry; Marcus, Matthew A; Zakharova, Taisiya; Zheng, Wei

2013-10-01

Analysis of rodent brains with X-ray fluorescence (XRF) microscopy combined with immunohistochemistry allowed us to demonstrate that local Cu concentrations are thousands of times higher in the glia of the subventricular zone (SVZ) than in other cells. Using XRF microscopy with subcellular resolution and intracellular X-ray absorption spectroscopy we determined the copper (I) oxidation state and the sulfur ligand environment. Cu K-edge X-ray absorption near edge spectroscopy is consistent with Cu being bound as a multimetallic Cu-S cluster similar to one present in Cu-metallothionein. Analysis of age-related changes show that Cu content in astrocytes of the SVZ increases fourfold from 3 weeks to 9 months, while Cu concentration in other brain areas remain essentially constant. This increase in Cu correlates with a decrease in adult neurogenesis assessed using the Ki67 marker (both, however, can be age-related effects). We demonstrate that the Cu distribution and age-related concentration changes in the brain are highly cell specific. © 2013 The Anatomical Society and John Wiley & Sons Ltd.

Regulation by commensal bacteria of neurogenesis in the subventricular zone of adult mouse brain.

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Sawada, Naoki; Kotani, Takenori; Konno, Tasuku; Setiawan, Jajar; Nishigaito, Yuka; Saito, Yasuyuki; Murata, Yoji; Nibu, Ken-Ichi; Matozaki, Takashi

2018-04-15

In the mouse olfactory bulb (OB), interneurons such as granule cells and periglomerular cells are continuously replaced by adult-born neurons, which are generated in the subventricular zone (SVZ) of the brain. We have now investigated the role of commensal bacteria in regulation of such neuronal cell turnover in the adult mouse brain. Administration of mixture of antibiotics to specific pathogen-free (SPF) mice markedly attenuated the incorporation of bromodeoxyuridine (BrdU) into the SVZ cells. The treatment with antibiotics also reduced newly generated BrdU-positive neurons in the mouse OB. In addition, the incorporation of BrdU into the SVZ cells of germ-free (GF) mice was markedly reduced compared to that apparent for SPF mice. In contrast, the reduced incorporation of BrdU into the SVZ cells of GF mice was recovered by their co-housing with SPF mice, suggesting that commensal bacteria promote the incorporation of BrdU into the SVZ cells. Finally, we found that administration of ampicillin markedly attenuated the incorporation of BrdU into the SVZ cells of SPF mice. Our results thus suggest that ampicillin-sensitive commensal bacteria regulate the neurogenesis in the SVZ of adult mouse brain. Copyright © 2018 Elsevier Inc. All rights reserved.

Cellular and Behavioral Effects of Cranial Irradiation of the Subventricular Zone in Adult Mice

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Lazarini, Françoise; Mouthon, Marc-André; Gheusi, Gilles; de Chaumont, Fabrice; Olivo-Marin, Jean-Christophe; Lamarque, Stéphanie; Abrous, Djoher Nora; Boussin, François D.; Lledo, Pierre-Marie

2009-01-01

Background In mammals, new neurons are added to the olfactory bulb (OB) throughout life. Most of these new neurons, granule and periglomerular cells originate from the subventricular zone (SVZ) lining the lateral ventricles and migrate via the rostral migratory stream toward the OB. Thousands of new neurons appear each day, but the function of this ongoing neurogenesis remains unclear. Methodology/Principal Findings In this study, we irradiated adult mice to impair constitutive OB neurogenesis, and explored the functional impacts of this irradiation on the sense of smell. We found that focal irradiation of the SVZ greatly decreased the rate of production of new OB neurons, leaving other brain areas intact. This effect persisted for up to seven months after exposure to 15 Gray. Despite this robust impairment, the thresholds for detecting pure odorant molecules and short-term olfactory memory were not affected by irradiation. Similarly, the ability to distinguish between odorant molecules and the odorant-guided social behavior of irradiated mice were not affected by the decrease in the number of new neurons. Only long-term olfactory memory was found to be sensitive to SVZ irradiation. Conclusion/Significance These findings suggest that the continuous production of adult-generated neurons is involved in consolidating or restituting long-lasting olfactory traces. PMID:19753118

Cellular and behavioral effects of cranial irradiation of the subventricular zone in adult mice.

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Françoise Lazarini

2009-09-01

Full Text Available In mammals, new neurons are added to the olfactory bulb (OB throughout life. Most of these new neurons, granule and periglomerular cells originate from the subventricular zone (SVZ lining the lateral ventricles and migrate via the rostral migratory stream toward the OB. Thousands of new neurons appear each day, but the function of this ongoing neurogenesis remains unclear.In this study, we irradiated adult mice to impair constitutive OB neurogenesis, and explored the functional impacts of this irradiation on the sense of smell. We found that focal irradiation of the SVZ greatly decreased the rate of production of new OB neurons, leaving other brain areas intact. This effect persisted for up to seven months after exposure to 15 Gray. Despite this robust impairment, the thresholds for detecting pure odorant molecules and short-term olfactory memory were not affected by irradiation. Similarly, the ability to distinguish between odorant molecules and the odorant-guided social behavior of irradiated mice were not affected by the decrease in the number of new neurons. Only long-term olfactory memory was found to be sensitive to SVZ irradiation.These findings suggest that the continuous production of adult-generated neurons is involved in consolidating or restituting long-lasting olfactory traces.

Regionally-specified second trimester fetal neural stem cells reveals differential neurogenic programming.

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Yiping Fan

Full Text Available Neural stem/progenitor cells (NSC have the potential for treatment of a wide range of neurological diseases such as Parkinson Disease and multiple sclerosis. Currently, NSC have been isolated only from hippocampus and subventricular zone (SVZ of the adult brain. It is not known whether NSC can be found in all parts of the developing mid-trimester central nervous system (CNS when the brain undergoes massive transformation and growth. Multipotent NSC from the mid-trimester cerebra, thalamus, SVZ, hippocampus, thalamus, cerebellum, brain stem and spinal cord can be derived and propagated as clonal neurospheres with increasing frequencies with increasing gestations. These NSC can undergo multi-lineage differentiation both in vitro and in vivo, and engraft in a developmental murine model. Regionally-derived NSC are phenotypically distinct, with hippocampal NSC having a significantly higher neurogenic potential (53.6% over other sources (range of 0%-27.5%, p<0.004. Whole genome expression analysis showed differential gene expression between these regionally-derived NSC, which involved the Notch, epidermal growth factor as well as interleukin pathways. We have shown the presence of phenotypically-distinct regionally-derived NSC from the mid-trimester CNS, which may reflect the ontological differences occurring within the CNS. Aside from informing on the role of such cells during fetal growth, they may be useful for different cellular therapy applications.

Glioblastoma Recurrence Patterns After Radiation Therapy With Regard to the Subventricular Zone

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Adeberg, Sebastian, E-mail: Sebastian.adeberg@med.uni-heidelberg [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); König, Laila; Bostel, Tilman; Harrabi, Semi; Welzel, Thomas [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Debus, Jürgen [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Heidelberg Ion Therapy Center, Heidelberg (Germany); DKFZ Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center Heidelberg (Germany); Combs, Stephanie E. [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Heidelberg Ion Therapy Center, Heidelberg (Germany)

2014-11-15

Purpose: We evaluated the influence of tumor location and tumor spread in primary glioblastoma (GBM), with respect to the subventricular zone (SVZ), on recurrence behavior, progression-free survival (PFS), and overall survival (OS). Methods and Materials: 607 patients (376 male and 231 female) with a median age of 61.3 years (range, 3.0-87.9 years) and primary GBM treated with radiation therapy (RT) from 2004 to 2012 at a single institution were included in this retrospective study. Preoperative images and follow-up examination results were assessed to evaluate tumor location. Tumors were classified according to the tumor location in relation to the SVZ. Results: The median PFS of the study population was 5.2 months (range, 1-91 months), and the median OS was 13.8 months (range, 1-102 months). Kaplan-Meier analysis showed that tumor location in close proximity to the SVZ was associated with a significant decline in PFS and OS (4.8 and 12.3 months, respectively; each P<.001). Furthermore, in cases where tumors were involved with the SVZ, distant cerebral progression (43.8%; P=.005) and multifocal progression (39.8%; P=.008) were more common. Interestingly, opening of the ventricle during the previous surgery showed no impact on PFS and OS. Conclusion: GBM in close proximity to the SVZ was associated with decreased survival and had a higher risk of multifocal or distant progression. Ventricle opening during surgery had no effect on survival rates.

Neurogenic Stuttering

Science.gov (United States)

... Teachers Speech-Language Pathologists Physicians Employers Tweet Neurogenic Stuttering Parents of Preschoolers Parents of School-Age Children ... Pathologists Physicians Employers Download brochure What is neurogenic stuttering? Neurogenic stuttering is a type of fluency disorder ...

What determines neurogenic competence in glia?

Science.gov (United States)

Costa, Marcos Romualdo; Götz, Magdalena; Berninger, Benedikt

2010-05-01

One of the most intriguing discoveries during the last decade of developmental neurobiology is the fact that both in the developing and adult nervous system neural stem cells often turn out to have a glial identity: Radial glia generates neurons in the developing telencephalon of fish, birds and mammals and astro/radial glial stem cells in specialized neurogenic zones give rise to new neurons throughout life. What are the extrinsic signals acting on and the intrinsic signals acting within these glial populations endowing these with a neurogenic potential, whilst most other glia seemingly lack it? Studies on postnatal astroglia shed interesting light on this question as they are the intermediate between neurogenic radial glia and mature parenchymal astrocytes. At least in vitro their decision to acquire a glial fate is not yet irrevocable as forced expression of a single neurogenic transcription factor enables them to transgress their lineage and to give rise to fully functional neurons acquiring specific subtype characteristics. But even bona fide non-neurogenic glia in the adult nervous system can regain some of their radial glial heritage following injury as exemplified by reactive astroglia in the cerebral cortex and Müller glia in the retina. In this review first we will follow the direction of the physiological times' arrow, along which radial glia become transformed on one side into mature astrocytes gradually losing their neurogenic potential, while some of them seem to escape this dire destiny to settle in the few neurogenic oases of the adult brain where they generate neurons and glia throughout life. But we will also see how pathophysiological conditions partially can reverse the arrow of time reactivating the parenchymal astroglia to re-acquire some of the hallmarks of neural stem cells or progenitors. We will close this review with some thoughts on the surprising compatibility of the co-existence of a neural stem cell and glial identity within the very

Effect of leukemia inhibitory factor on long-term propagation of precursor cells derived from rat forebrain subventricular zone and ventral mesencephalon

DEFF Research Database (Denmark)

Andersen, Rikke K; Zimmer, Jens; Wahlberg, Lars U

2008-01-01

Tissue blocks containing neural precursor cells were isolated from the rat forebrain subventricular zone (SVZ) and ventral mesencephalon (VM) and propagated as neural tissue-spheres (NTS). In the presence of fibroblast growth factor-2 (FGF2) and epidermal growth factor (EGF), SVZ-derived NTS were...... propagated and maintained for more than 6 months with a cell population doubling time of 21.5 days. The replacement of EGF by leukemia inhibitory factor (LIF) resulted in a cell population doubling time of 19.8 days, corresponding to a 10-fold increase in estimated cell numbers over a period of 70 days......, at which point these NTS ceased to grow. In the presence of FGF2 and LIF, VM-derived NTS displayed a cell population doubling time of 24.6 days, which was maintained over a period of more than 200 days. However, when LIF was replaced by EGF, the cell numbers only increased 1.2 fold over 50 days. Using...

Neurogenic Bladder

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Peter T. Dorsher

2012-01-01

Full Text Available Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented.

3-dimensional examination of the adult mouse subventricular zone reveals lineage-specific microdomains.

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Azim, Kasum; Fiorelli, Roberto; Zweifel, Stefan; Hurtado-Chong, Anahi; Yoshikawa, Kazuaki; Slomianka, Lutz; Raineteau, Olivier

2012-01-01

Recent studies suggest that the subventricular zone (SVZ) of the lateral ventricle is populated by heterogeneous populations of stem and progenitor cells that, depending on their exact location, are biased to acquire specific neuronal fates. This newly described heterogeneity of SVZ stem and progenitor cells underlines the necessity to develop methods for the accurate quantification of SVZ stem and progenitor subpopulations. In this study, we provide 3-dimensional topographical maps of slow cycling "stem" cells and progenitors based on their unique cell cycle properties. These maps revealed that both cell populations are present throughout the lateral ventricle wall as well as in discrete regions of the dorsal wall. Immunodetection of transcription factors expressed in defined progenitor populations further reveals that divergent lineages have clear regional enrichments in the rostro-caudal as well as in the dorso-ventral span of the lateral ventricle. Thus, progenitors expressing Tbr2 and Dlx2 were confined to dorsal and dorso-lateral regions of the lateral ventricle, respectively, while Mash1+ progenitors were more homogeneously distributed. All cell populations were enriched in the rostral-most region of the lateral ventricle. This diversity and uneven distribution greatly impede the accurate quantification of SVZ progenitor populations. This is illustrated by measuring the coefficient of error of estimates obtained by using increasing section sampling interval. Based on our empirical data, we provide such estimates for all progenitor populations investigated in this study. These can be used in future studies as guidelines to judge if the precision obtained with a sampling scheme is sufficient to detect statistically significant differences between experimental groups if a biological effect is present. Altogether, our study underlines the need to consider the SVZ of the lateral ventricle as a complex 3D structure and define methods to accurately assess neural

The effects of chronic alcoholism on cell proliferation in the human brain.

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Sutherland, G T; Sheahan, P J; Matthews, J; Dennis, C V P; Sheedy, D S; McCrossin, T; Curtis, M A; Kril, J J

2013-09-01

Neurogenesis continues in the human subventricular zone and to a lesser extent in the hippocampal subgranular zone throughout life. Subventricular zone-derived neuroblasts migrate to the olfactory bulb where survivors become integrated as interneurons and are postulated to contribute to odor discrimination. Adult neurogenesis is dysregulated in many neurological, neurovascular and neurodegenerative diseases. Alcohol abuse can result in a neurodegenerative condition called alcohol-related brain damage. Alcohol-related brain damage manifests clinically as cognitive dysfunction and the loss of smell sensation (hyposmia) and pathologically as generalized white matter atrophy and focal neuronal loss. The exact mechanism linking chronic alcohol intoxication with alcohol-related brain damage remains largely unknown but rodent models suggest that decreased neurogenesis is an important component. We investigated this idea by comparing proliferative events in the subventricular zone and olfactory bulb of a well-characterized cohort of 15 chronic alcoholics and 16 age-matched controls. In contrast to the findings in animal models there was no difference in the number of proliferative cell nuclear antigen-positive cells in the subventricular zone of alcoholics (mean±SD=28.7±20.0) and controls (27.6±18.9, p=1.0). There were also no differences in either the total (p=0.89) or proliferative cells (p=0.98) in the granular cell layer of the olfactory bulb. Our findings show that chronic alcohol consumption does not affect cell proliferation in the human SVZ or olfactory bulb. In fact only microglial proliferation could be demonstrated in the latter. Therefore neurogenic deficits are unlikely to contribute to hyposmia in chronic alcoholics. Copyright © 2013 Elsevier Inc. All rights reserved.

Radio-Protective Effects of Melatonin on Subventricular Zone in Irradiated Rat: Decrease in Apoptosis and Upregulation of Nestin.

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Naseri, Shafigheh; Moghahi, Seyed Mohammad Hossein Noori; Mokhtari, Tahmineh; Roghani, Mehrdad; Shirazi, Ali Reza; Malek, Fatemeh; Rastegar, Tayebeh

2017-10-01

Neural stem cells are self-renewing, multipotent cells that can be found in subventricular (SVZ) and subgranular (SGZ) zones of the brain. These zones are susceptible to irradiation-induced apoptosis and oxidative stress. Melatonin (MLT) is a natural protector of neural cells against toxicity. The aim of this study was to evaluate the effects of MLT as a radio-protective material effective in reducing tissue lesions in the SVZ of the brain and changing local apoptotic potential in rats. Twenty-five Gray irradiation was applied on adult rat brain for this study. One hour before irradiation, 100 mg/kg/IP MLT was injected, and 6 h later, the animals were sacrificed. The antioxidant enzymes and MDA activity levels were measured post-sacrifice. Also, the expression level of Nestin and caspase 3 were studied by immunohistochemistry. Spectrophotometric analysis showed significant increases in the amount of malondialdehyde (MDA) levels in the irradiation-exposed (RAD) group compared to that of the control (Co) group (P < 0.05). Pre-treatment with MLT (100 mg/kg) ameliorates the harmful effects of the aforementioned 25 Gy irradiation by increasing antioxidant enzyme activity and decreasing MDA levels. A significant reduction in apoptotic cells was observed in rats treated with MLT 1 h before exposure (P < 0.001). Nestin-positive cells were also reduced in the RAD group (P < 0.001). Our results confirm the anti-apoptotic and antioxidant role of MLT. The MLT concentration used may serve as a threshold for significant protection against 25 Gy gamma irradiations on neural stem cells in SVZ.

Ventricular Zone Disruption in Human Neonates With Intraventricular Hemorrhage

NARCIS (Netherlands)

McAllister, James P.; Guerra, Maria Montserrat; Ruiz, Leandro Castaneyra; Jimenez, Antonio J.; Dominguez-Pinos, Dolores; Sival, Deborah; den Dunnen, Wilfred; Morales, Diego M.; Schmidt, Robert E.; Rodriguez, Esteban M.; Limbrick, David D.

2017-01-01

To determine if ventricular zone (VZ) and subventricular zone (SVZ) alterations are associated with intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus, we compared postmortem frontal and subcortical brain samples from 12 infants with IVH and 3 nonneurological disease controls

The Role of Astrocytes in the Generation, Migration, and Integration of New Neurons in the Adult Olfactory Bulb

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Gengatharan, Archana; Bammann, Rodrigo R.; Saghatelyan, Armen

2016-01-01

In mammals, new neurons in the adult olfactory bulb originate from a pool of neural stem cells in the subventricular zone of the lateral ventricles. Adult-born cells play an important role in odor information processing by adjusting the neuronal network to changing environmental conditions. Olfactory bulb neurogenesis is supported by several non-neuronal cells. In this review, we focus on the role of astroglial cells in the generation, migration, integration, and survival of new neurons in the adult forebrain. In the subventricular zone, neural stem cells with astrocytic properties display regional and temporal specificity when generating different neuronal subtypes. Non-neurogenic astrocytes contribute to the establishment and maintenance of the neurogenic niche. Neuroblast chains migrate through the rostral migratory stream ensheathed by astrocytic processes. Astrocytes play an important regulatory role in neuroblast migration and also assist in the development of a vasculature scaffold in the migratory stream that is essential for neuroblast migration in the postnatal brain. In the olfactory bulb, astrocytes help to modulate the network through a complex release of cytokines, regulate blood flow, and provide metabolic support, which may promote the integration and survival of new neurons. Astrocytes thus play a pivotal role in various processes of adult olfactory bulb neurogenesis, and it is likely that many other functions of these glial cells will emerge in the near future. PMID:27092050

EMMPRIN overexpression in SVZ neural progenitor cells increases their migration towards ischemic cortex.

Science.gov (United States)

Kanemitsu, Michiko; Tsupykov, Oleg; Potter, Gaël; Boitard, Michael; Salmon, Patrick; Zgraggen, Eloisa; Gascon, Eduardo; Skibo, Galina; Dayer, Alexandre G; Kiss, Jozsef Z

2017-11-01

Stimulation of endogenous neurogenesis and recruitment of neural progenitors from the subventricular zone (SVZ) neurogenic site may represent a useful strategy to improve regeneration in the ischemic cortex. Here, we tested whether transgenic overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN), the regulator of matrix metalloproteinases (MMPs) expression, in endogenous neural progenitor cells (NPCs) in the subventricular zone (SVZ) could increase migration towards ischemic injury. For this purpose, we applied a lentivector-mediated gene transfer system. We found that EMMPRIN-transduced progenitors exhibited enhanced MMP-2 activity in vitro and showed improved motility in 3D collagen gel as well as in cortical slices. Using a rat model of neonatal ischemia, we showed that EMMPRIN overexpressing SVZ cells invade the injured cortical tissue more efficiently than controls. Our results suggest that EMMPRIN overexpression could be suitable approach to improve capacities of endogenous or transplanted progenitors to invade the injured cortex. Copyright © 2017 Elsevier Inc. All rights reserved.

3-dimensional examination of the adult mouse subventricular zone reveals lineage-specific microdomains.

Directory of Open Access Journals (Sweden)

Kasum Azim

Full Text Available Recent studies suggest that the subventricular zone (SVZ of the lateral ventricle is populated by heterogeneous populations of stem and progenitor cells that, depending on their exact location, are biased to acquire specific neuronal fates. This newly described heterogeneity of SVZ stem and progenitor cells underlines the necessity to develop methods for the accurate quantification of SVZ stem and progenitor subpopulations. In this study, we provide 3-dimensional topographical maps of slow cycling "stem" cells and progenitors based on their unique cell cycle properties. These maps revealed that both cell populations are present throughout the lateral ventricle wall as well as in discrete regions of the dorsal wall. Immunodetection of transcription factors expressed in defined progenitor populations further reveals that divergent lineages have clear regional enrichments in the rostro-caudal as well as in the dorso-ventral span of the lateral ventricle. Thus, progenitors expressing Tbr2 and Dlx2 were confined to dorsal and dorso-lateral regions of the lateral ventricle, respectively, while Mash1+ progenitors were more homogeneously distributed. All cell populations were enriched in the rostral-most region of the lateral ventricle. This diversity and uneven distribution greatly impede the accurate quantification of SVZ progenitor populations. This is illustrated by measuring the coefficient of error of estimates obtained by using increasing section sampling interval. Based on our empirical data, we provide such estimates for all progenitor populations investigated in this study. These can be used in future studies as guidelines to judge if the precision obtained with a sampling scheme is sufficient to detect statistically significant differences between experimental groups if a biological effect is present. Altogether, our study underlines the need to consider the SVZ of the lateral ventricle as a complex 3D structure and define methods to

RAE-1 is expressed in the adult subventricular zone and controls cell proliferation of neurospheres.

Science.gov (United States)

Popa, Natalia; Cedile, Oriane; Pollet-Villard, Xavier; Bagnis, Claude; Durbec, Pascale; Boucraut, José

2011-01-01

Improving and controlling the capacity of endogenous or grafted adult neural stem cells to repair the nervous system relies on a better knowledge of interactions between immune cells and neural stem cells. Class I major histocompatibility complex (MHC) family members comprise numerous proteins playing either immune or nonimmune function. Among the latter, MHC functions in the central nervous system has started to receive recent interest. Here, our first goal was to investigate the potential relationship between MHC class I molecules and neurogenesis. For the first time, we report the expression of two MHC class I-related members by neural stem/progenitor cells: retinoic acid early induced transcript (RAE)-1 and CD1d. The expression of RAE-1 but not CD1d disappears when differentiation of neurosphere cells is induced. Interestingly, RAE-1 transcripts are expressed in the brain during development, and we demonstrate they persist in one of the main area of adult neurogenesis, the subventricular zone (SVZ). So far, RAE-1 is only known for its immune functions as a ligand of the activating receptor NKG2D expressed by natural killer (NK) cells, natural killer T, Tγδ, and some T CD8 lymphocytes. Here, we do not detect any NKG2D expression in the SVZ either in physiological or in pathological conditions. Interestingly, inhibition of RAE-1 expression in neurosphere cells reduces cell proliferation without alteration of cell viability, which argues for a nonimmune role for RAE-1. These results reveal an unexpected role of RAE-1 in regulating adult SVZ neurogenesis by supporting stem/progenitor cells proliferation. © 2010 Wiley-Liss, Inc.

Dose-escalated intensity-modulated radiotherapy and irradiation of subventricular zones in relation to tumor control outcomes of patients with glioblastoma multiforme

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Kusumawidjaja G

2016-03-01

Full Text Available Grace Kusumawidjaja,1 Patricia Zhun Hong Gan,1 Whee Sze Ong,2 Achiraya Teyateeti,3 Pittaya Dankulchai,3 Daniel Yat Harn Tan,1 Eu Tiong Chua,1 Kevin Lee Min Chua,1 Chee Kian Tham,4 Fuh Yong Wong,1 Melvin Lee Kiang Chua1,5 1Division of Radiation Oncology, National Cancer Centre, Singapore; 2Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre, Singapore; 3Department of Radiology, Division of Radiation Oncology, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand; 4Division of Medical Oncology, National Cancer Centre, Singapore; 5Duke-NUS Graduate Medical School, Singapore Background: Glioblastoma multiforme (GBM is the most aggressive primary brain tumor with high relapse rate. In this study, we aimed to determine if dose-escalated (DE radiotherapy improved tumor control and survival in GBM patients. Methods: We conducted a retrospective analysis of 49 and 23 newly-diagnosed histology-proven GBM patients, treated with DE radiotherapy delivered in 70 Gy (2.33 Gy per fraction and conventional doses (60 Gy, respectively, between 2007 and 2013. Clinical target volumes for 70 and 60 Gy were defined by 0.5 and 2.0 cm expansion of magnetic resonance imaging T1-gadolinium-enhanced tumor/surgical cavity, respectively. Bilateral subventricular zones (SVZ were contoured on a co-registered pre-treatment magnetic resonance imaging and planning computed tomography dataset as a 5 mm wide structure along the lateral margins of the lateral ventricles. Survival outcomes of both cohorts were compared using log-rank test. Radiation dose to SVZ in the DE cohort was evaluated. Results: Median follow-up was 13.6 and 15.1 months for the DE- and conventionally-treated cohorts, respectively. Median overall survival (OS of patients who received DE radiotherapy was 15.2 months (95% confidence interval [CI] =11.0–18.6, while median OS of the latter cohort was 18.4 months (95% CI =12.5–31.4, P=0.253. Univariate analyses of

A comparative study of the structural organization of spheres derived from the adult human subventricular zone and glioblastoma biopsies

International Nuclear Information System (INIS)

Vik-Mo, Einar Osland; Sandberg, Cecilie; Joel, Mrinal; Stangeland, Biljana; Watanabe, Yasuhiro; Mackay-Sim, Alan; Moe, Morten Carstens; Murrell, Wayne; Langmoen, Iver Arne

2011-01-01

Sphere forming assays have been useful to enrich for stem like cells in a range of tumors. The robustness of this system contrasts the difficulties in defining a stem cell population based on cell surface markers. We have undertaken a study to describe the cellular and organizational composition of tumorspheres, directly comparing these to neurospheres derived from the adult human subventricular zone (SVZ). Primary cell cultures from brain tumors were found to contain variable fractions of cells positive for tumor stem cell markers (CD133 (2-93%)/SSEA1 (3-15%)/CXCR4 (1-72%)). All cultures produced tumors upon xenografting. Tumorspheres contained a heterogeneous population of cells, but were structurally organized with stem cell markers present at the core of spheres, with markers of more mature glial progenitors and astrocytes at more peripheral location. Ultrastructural studies showed that tumorspheres contained a higher fraction of electron dense cells in the core than the periphery (36% and 19%, respectively). Neurospheres also contained a heterogeneous cell population, but did not have an organization similar to tumorspheres. Although tumorspheres clearly display irregular and neoplastic cells, they establish an organized structure with an outward gradient of differentiation. We suggest that this organization is central in maintaining the tumor stem cell pool.

Brief Report: Robo1 Regulates the Migration of Human Subventricular Zone Neural Progenitor Cells During Development.

Science.gov (United States)

Guerrero-Cazares, Hugo; Lavell, Emily; Chen, Linda; Schiapparelli, Paula; Lara-Velazquez, Montserrat; Capilla-Gonzalez, Vivian; Clements, Anna Christina; Drummond, Gabrielle; Noiman, Liron; Thaler, Katrina; Burke, Anne; Quiñones-Hinojosa, Alfredo

2017-07-01

Human neural progenitor cell (NPC) migration within the subventricular zone (SVZ) of the lateral ganglionic eminence is an active process throughout early brain development. The migration of human NPCs from the SVZ to the olfactory bulb during fetal stages resembles what occurs in adult rodents. As the human brain develops during infancy, this migratory stream is drastically reduced in cell number and becomes barely evident in adults. The mechanisms regulating human NPC migration are unknown. The Slit-Robo signaling pathway has been defined as a chemorepulsive cue involved in axon guidance and neuroblast migration in rodents. Slit and Robo proteins expressed in the rodent brain help guide neuroblast migration from the SVZ through the rostral migratory stream to the olfactory bulb. Here, we present the first study on the role that Slit and Robo proteins play in human-derived fetal neural progenitor cell migration (hfNPC). We describe that Robo1 and Robo2 isoforms are expressed in the human fetal SVZ. Furthermore, we demonstrate that Slit2 is able to induce a chemorepellent effect on the migration of hfNPCs derived from the human fetal SVZ. In addition, when Robo1 expression is inhibited, hfNPCs are unable to migrate to the olfactory bulb of mice when injected in the anterior SVZ. Our findings indicate that the migration of human NPCs from the SVZ is partially regulated by the Slit-Robo axis. This pathway could be regulated to direct the migration of NPCs in human endogenous neural cell therapy. Stem Cells 2017;35:1860-1865. © 2017 AlphaMed Press.

Metallic gold treatment reduces proliferation of inflammatory cells, increases expression of VEGF and FGF, and stimulates cell proliferation in the subventricular zone following experimental traumatic brain injury

DEFF Research Database (Denmark)

Pedersen, Mie Østergaard; Larsen, Agnete; Pedersen, Dan Sonne

2009-01-01

Traumatic brain injury represents a leading cause of morbidity in young individuals and there is an imperative need for neuroprotective treatments limiting the neurologic impairment following such injury. It has recently been demonstrated that bio-liberated gold ions liberated from small metallic...... gold implants reduce inflammation and neuronal apoptosis, while generating an increased neuronal stem cell response following focal brain damage. In this study mice were subjected to a unilateral traumatic cryo-lesion with concomitant injection of 25-45 microm gold particles near the lesion. Placebo...... increase in cell proliferation in both the ipsilateral and the contralateral subventricular zone was found in response to gold-treatment. In conclusion: we confirmed the previously demonstrated anti-inflammatory effect of bio-liberated gold ions, and further show that metallic gold increases growth factor...

Notch receptor expression in neurogenic regions of the adult zebrafish brain.

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Vanessa de Oliveira-Carlos

Full Text Available The adult zebrash brain has a remarkable constitutive neurogenic capacity. The regulation and maintenance of its adult neurogenic niches are poorly understood. In mammals, Notch signaling is involved in stem cell maintenance both in embryonic and adult CNS. To better understand how Notch signaling is involved in stem cell maintenance during adult neurogenesis in zebrafish we analysed Notch receptor expression in five neurogenic zones of the adult zebrafish brain. Combining proliferation and glial markers we identified several subsets of Notch receptor expressing cells. We found that 90 [Formula: see text] of proliferating radial glia express notch1a, notch1b and notch3. In contrast, the proliferating non-glial populations of the dorsal telencephalon and hypothalamus rarely express notch3 and about half express notch1a/1b. In the non-proliferating radial glia notch3 is the predominant receptor throughout the brain. In the ventral telencephalon and in the mitotic area of the optic tectum, where cells have neuroepithelial properties, notch1a/1b/3 are expressed in most proliferating cells. However, in the cerebellar niche, although progenitors also have neuroepithelial properties, only notch1a/1b are expressed in a high number of PCNA [Formula: see text] cells. In this region notch3 expression is mostly in Bergmann glia and at low levels in few PCNA [Formula: see text] cells. Additionally, we found that in the proliferation zone of the ventral telencephalon, Notch receptors display an apical high to basal low gradient of expression. Notch receptors are also expressed in subpopulations of oligodendrocytes, neurons and endothelial cells. We suggest that the partial regional heterogeneity observed for Notch expression in progenitor cells might be related to the cellular diversity present in each of these neurogenic niches.

S phase entry of neural progenitor cells correlates with increased blood flow in the young subventricular zone.

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Benjamin Lacar

Full Text Available The postnatal subventricular zone (SVZ contains proliferating neural progenitor cells in close proximity to blood vessels. Insults and drug treatments acutely stimulate cell proliferation in the SVZ, which was assessed by labeling cells entering S phase. Although G1-to-S progression is metabolically demanding on a minute-to-hour time scale, it remains unknown whether increased SVZ cell proliferation is accompanied by a local hemodynamic response. This neurovascular coupling provides energy substrates to active neuronal assemblies. Transcardial dye perfusion revealed the presence of capillaries throughout the SVZ that constrict upon applications of the thromboxane A(2 receptor agonist U-46119 in acute brain slice preparations. We then monitored in vivo blood flow using laser Doppler flowmetry via a microprobe located either in the SVZ or a mature network. U-46119 injections into the lateral ventricle decreased blood flow in the SVZ and the striatum, which are near the ventricle. A 1-hour ventricular injection of epidermal and basic fibroblast growth factor (EGF and bFGF significantly increased the percentage of Sox2 transcription factor-positive cells in S phase 1.5 hours post-injection. This increase was accompanied by a sustained rise in blood flow in the SVZ but not in the striatum. Direct growth factor injections into the cortex did not alter local blood flow, ruling out direct effects on capillaries. These findings suggest that an acute increase in the number of G1-to-S cycling SVZ cells is accompanied by neurometabolic-vascular coupling, which may provide energy and nutrient for cell cycle progression.

Neurogenic inflammation in human and rodent skin

DEFF Research Database (Denmark)

Schmelz, M; Petersen, Lars Jelstrup

2001-01-01

The combination of vasodilation and protein extravasation following activation of nociceptors has been termed "neurogenic inflammation." In contrast to rodents, no neurogenic protein extravasation can be elicited in healthy human skin. Dermal microdialysis has considerably increased our knowledge...... about neurogenic inflammation in human skin, including the involvement of mast cells.......The combination of vasodilation and protein extravasation following activation of nociceptors has been termed "neurogenic inflammation." In contrast to rodents, no neurogenic protein extravasation can be elicited in healthy human skin. Dermal microdialysis has considerably increased our knowledge...

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

2018-05-01

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;36:761-774. © AlphaMed Press 2018.

Development and aging of a brain neural stem cell niche.

Science.gov (United States)

Conover, Joanne C; Todd, Krysti L

2017-08-01

In the anterior forebrain, along the lateral wall of the lateral ventricles, a neurogenic stem cell niche is found in a region referred to as the ventricular-subventricular zone (V-SVZ). In rodents, robust V-SVZ neurogenesis provides new neurons to the olfactory bulb throughout adulthood; however, with increasing age stem cell numbers are reduced and neurogenic capacity is significantly diminished, but new olfactory bulb neurons continue to be produced even in old age. Humans, in contrast, show little to no new neurogenesis after two years of age and whether V-SVZ neural stem cells persist in the adult human brain remains unclear. Here, we review functional and organizational differences in the V-SVZ stem cell niche of mice and humans, and examine how aging affects the V-SVZ niche and its associated functions. Copyright © 2016 Elsevier Inc. All rights reserved.

Impaired neurogenesis, learning and memory and low seizure threshold associated with loss of neural precursor cell survivin

Directory of Open Access Journals (Sweden)

Eisch Amelia

2010-01-01

Full Text Available Abstract Background Survivin is a unique member of the inhibitor of apoptosis protein (IAP family in that it exhibits antiapoptotic properties and also promotes the cell cycle and mediates mitosis as a chromosome passenger protein. Survivin is highly expressed in neural precursor cells in the brain, yet its function there has not been elucidated. Results To examine the role of neural precursor cell survivin, we first showed that survivin is normally expressed in periventricular neurogenic regions in the embryo, becoming restricted postnatally to proliferating and migrating NPCs in the key neurogenic sites, the subventricular zone (SVZ and the subgranular zone (SGZ. We then used a conditional gene inactivation strategy to delete the survivin gene prenatally in those neurogenic regions. Lack of embryonic NPC survivin results in viable, fertile mice (SurvivinCamcre with reduced numbers of SVZ NPCs, absent rostral migratory stream, and olfactory bulb hypoplasia. The phenotype can be partially rescued, as intracerebroventricular gene delivery of survivin during embryonic development increases olfactory bulb neurogenesis, detected postnatally. SurvivinCamcre brains have fewer cortical inhibitory interneurons, contributing to enhanced sensitivity to seizures, and profound deficits in memory and learning. Conclusions The findings highlight the critical role that survivin plays during neural development, deficiencies of which dramatically impact on postnatal neural function.

Molecular Targets of Chromatin Repressive Mark H3K9me3 in Primate Progenitor Cells within Adult Neurogenic Niches

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Michael R Foret

2014-07-01

Full Text Available Histone 3 Lysine 9 (H3K9 methylation is known to be associated with pericentric heterochromatin and important in genomic stability. In this study, we show that trimethylation at H3K9 (H3K9me3 is enriched in an adult neural stem cell niche- the subventricular zone (SVZ on the walls of the lateral ventricle in both rodent and non-human primate baboon brain. Previous studies have shown that there is significant correlation between baboon and human regarding genomic similarity and brain structure, suggesting that findings in baboon are relevant to human. To understand the function of H3K9me3 in this adult neurogenic niche, we performed genome-wide analyses using ChIP-Seq (chromatin immunoprecipitation and deep-sequencing and RNA-Seq for in vivo SVZ cells purified from baboon brain. Through integrated analyses of ChIP-Seq and RNA-Seq, we found that H3K9me3-enriched genes associated with cellular maintenance, post-transcriptional and translational modifications, signaling pathways, and DNA replication are expressed, while genes involved in axon/neuron, hepatic stellate cell, or immune-response activation are not expressed. As neurogenesis progresses in the adult SVZ, cell fate restriction is essential to direct proper lineage commitment. Our findings highlight that H3K9me3 repression in undifferentiated SVZ cells is engaged in the maintenance of cell type integrity, implicating a role for H3K9me3 as an epigenetic mechanism to control cell fate transition within this adult germinal niche.

Hypoxic-preconditioning enhances the regenerative capacity of neural stem/progenitors in subventricular zone of newborn piglet brain.

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Ara, Jahan; De Montpellier, Sybille

2013-09-01

Perinatal hypoxia-ischemia (HI) results in brain injury, whereas mild hypoxic episodes result in preconditioning, which can significantly reduce the vulnerability of the brain to subsequent severe hypoxia-ischemia. Hypoxic-preconditioning (PC) has been shown to enhance cell survival and differentiation of progenitor cells in the central nervous system (CNS). The purpose of this study was to determine whether pretreatment with PC prior to HI stimulates subventricular zone (SVZ) proliferation and neurogenesis in newborn piglets. One-day-old piglets were subjected to PC (8% O2/92% N2) for 3h and 24h later were exposed to HI produced by combination of hypoxia (5% FiO2) for a pre-defined period of 30min and ischemia induced by a period of 10min of hypotension. Here we demonstrate that SVZ derived neural stem/progenitor cells (NSPs) from PC, HI and PC+HI piglets proliferated as neurospheres, expressed neural progenitor and neurodevelopmental markers, and that greater proportion of the spheres generated are multipotential. Neurosphere assay revealed that preconditioning pretreatment increased the number of NSP-derived neurospheres in SVZ following HI compared to normoxic and HI controls. NSPs from preconditioned SVZ generated twice as many neurons and astrocytes in vitro. Injections with 5-Bromo-2-deoxyuridine (BrdU) after PC revealed a robust proliferative response within the SVZ that continued for one week. PC also increased neurogenesis in vivo, doublecortin positive cells with migratory profiles were observed streaming from the SVZ to striatum and neocortex. These findings show that the induction of proliferation and neurogenesis by PC might be a positive adaptation for an efficient repair and plasticity in the event of a hypoxic-ischemic insult. Copyright © 2013 Elsevier B.V. All rights reserved.

Neurogenic Pulmonary Edema (A Case Report

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Funda Gümüş

2012-08-01

Full Text Available Neurogenic pulmonary edema is a life threatening complication of severe central nervous system injury. The most common cause of neurogenic pulmonary edema is subarachnoid hemorrhage followed by head trauma and epilepsy. The rare causes are cervical spine trauma, multiplesclerosis, cerebellar hemorrhage and intracranial tumors. Neurogenic pulmonary edema is characterized by an increase in extravascular lung water in patients who have sustained a sudden change in neurologic condition. The exact pathophysiology is unclear but it probably involves an adrenergic response to the central nervous system injury which leads to increased catecholamine, pulmonary hydrostatic pressure and increased lung capillary permeability. The presenting symptoms are nonspecific and often include dyspnea, tachypnea, tachycardia, hypoxemia, pinkfroty secretion, bilateral pulmonary infiltrates and crackles. These symptoms start within minutes or hours and resolves 48-72 hours that typically for neurogenic pulmonary edema. Basic principles of treatment, surgical decompression, reduce intracranial pressure, controlled ventilation with suplemental oxygen, positive end expiratory pressure and diuresis. We report a case with neurogenic pulmonary edema that occured after head trauma. (Journal of the Turkish Society Intensive Care 2012; 10: 59-62

Neurotransmitter regulation of adult neurogenesis: putative therapeutic targets.

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Vaidya, V A; Vadodaria, K C; Jha, S

2007-10-01

The evidence that new neuron addition takes place in the mammalian brain throughout adult life has dramatically altered our perspective of the potential for plasticity in the adult CNS. Although several recent reports suggest a latent neurogenic capacity in multiple brain regions, the two major neurogenic niches that retain the ability to generate substantial numbers of new neurons in adult life are the subventricular zone (SVZ) lining the lateral ventricles and the subgranular zone (SGZ) in the hippocampal formation. The discovery of adult neurogenesis has also unveiled a novel therapeutic target for the repair of damaged neuronal circuits. In this regard, understanding the endogenous mechanisms that regulate adult neurogenesis holds promise both for a deeper understanding of this form of structural plasticity, as well as the identification of pathways that can serve as therapeutic targets to manipulate adult neurogenesis. The purpose of the present review is to discuss the regulation of adult neurogenesis by neurotransmitters and to highlight the relevance of these endogenous regulators as targets to modulate adult neurogenesis in a clinical context.

[Acute neurogenic pulmonary edema].

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Roquefeuil, B

1975-01-01

Neurogenic edema, in the strict sense of the term, has at the present time practically not benefitted from precise hemodynamic investigations in human clinical practice, and owing to this fact, authors still classify them under the heading "mixed edema or of unknown pathogenesis". In contrast with this lack of information in man, animal experimental works are surprising by their coherence and the experimental facility of producing neurogenic edema (cranial hypertension by a small inflatable balloon and cisternal infection of fibrin). If one excludes the now ancient vagal theories (CAMERON 1949; CAMPBELL, 1949) which were never confirmed, all of the most recent experimental works (SARNOFF, 1952; DUCKER, 1968; LUISADA, 1967; MORITZ, 1974) confirm the adrenergic disorder of central origin during neurogenic A.P.E. which from the hemodynamic standpoint is like an authentic hemodynamic A.P.E. with raised left atrial pressure, pulmonary venous pressure and pulmonary capillary pressure.

Abundant Occurrence of Basal Radial Glia in the Subventricular Zone of Embryonic Neocortex of a Lissencephalic Primate, the Common Marmoset Callithrix jacchus

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Kelava, Iva; Reillo, Isabel; Murayama, Ayako Y.; Kalinka, Alex T.; Stenzel, Denise; Tomancak, Pavel; Matsuzaki, Fumio; Lebrand, Cécile; Sasaki, Erika; Schwamborn, Jens C.; Okano, Hideyuki; Borrell, Víctor

2012-01-01

Subventricular zone (SVZ) progenitors are a hallmark of the developing neocortex. Recent studies described a novel type of SVZ progenitor that retains a basal process at mitosis, sustains expression of radial glial markers, and is capable of self-renewal. These progenitors, referred to here as basal radial glia (bRG), occur at high relative abundance in the SVZ of gyrencephalic primates (human) and nonprimates (ferret) but not lissencephalic rodents (mouse). Here, we analyzed the occurrence of bRG cells in the embryonic neocortex of the common marmoset Callithrix jacchus, a near-lissencephalic primate. bRG cells, expressing Pax6, Sox2 (but not Tbr2), glutamate aspartate transporter, and glial fibrillary acidic protein and retaining a basal process at mitosis, occur at similar relative abundance in the marmoset SVZ as in human and ferret. The proportion of progenitors in M-phase was lower in embryonic marmoset than developing ferret neocortex, raising the possibility of a longer cell cycle. Fitting the gyrification indices of 26 anthropoid species to an evolutionary model suggested that the marmoset evolved from a gyrencephalic ancestor. Our results suggest that a high relative abundance of bRG cells may be necessary, but is not sufficient, for gyrencephaly and that the marmoset's lissencephaly evolved secondarily by changing progenitor parameters other than progenitor type. PMID:22114084

Neurogenic bladder in Hunter's syndrome.

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Koyama, K; Moda, Y; Sone, A; Tanaka, H; Hino, Y

1994-01-01

We encountered a rare patient with Hunter's syndrome who exhibited urinary retention as a result of a neurogenic bladder, uninhibited detrusor contractions, and detrusor-sphincter dyssynergia. Neurological findings were consistent with cervical myelopathy and cervical MR imaging showed very narrow segments at the cord level C2-4. We speculate that this Hunter's syndrome patient has cervical myelopathy and that this neurological dysfunction causes the neurogenic bladder. PMID:8014981

The number of stem cells in the subependymal zone of the adult rodent brain is correlated with the number of ependymal cells and not with the volume of the niche.

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Kazanis, Ilias; Ffrench-Constant, Charles

2012-05-01

The mammalian subependymal zone (SEZ; often called subventricular) situated at the lateral walls of the lateral ventricles of the brain contains a pool of relatively quiescent adult neural stem cells whose neurogenic activity persists throughout life. These stem cells are positioned in close proximity both to the ependymal cells that provide the cerebrospinal fluid interface and to the blood vessel endothelial cells, but the relative contribution of these 2 cell types to stem cell regulation remains undetermined. Here, we address this question by analyzing a naturally occurring example of volumetric scaling of the SEZ in a comparison of the mouse SEZ with the larger rat SEZ. Our analysis reveals that the number of stem cells in the SEZ niche is correlated with the number of ependymal cells rather than with the volume, thereby indicating the importance of ependymal-derived factors in the formation and function of the SEZ. The elucidation of the factors generated by ependymal cells that regulate stem cell numbers within the SEZ is, therefore, of importance for stem cell biology and regenerative neuroscience.

Neurogenic Stuttering and Lateralized Motor Deficits Induced by Tranylcypromine

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J. D. Duffy

1994-01-01

Full Text Available A case of neurogenic stuttering induced by the monoamine oxidase inhibitor tranylcypromine is described. The association of neurogenic stuttering with acquired lateralized motor deficits in the patient described is discussed with reference to current theories regarding the pathogenesis of neurogenic stuttering.

Preoperative neurogenic pulmonary edema: A dilemma for decision making

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Siva Kumar Reddy Lakkireddigari

2012-01-01

Full Text Available Neurogenic pulmonary edema may be a less-recognized consequence of obstructive hydrocephalus. The authors report a patient with acute obstructive hydrocephalus due to cerebellar metastatic lesion, who presented with neurogenic pulmonary edema. The edema resolved on placement of the ventriculoperitonial shunt. This report addresses the importance of recognition of neurogenic pulmonary edema as a possible perioperative complication resulting from an increase in intracranial pressure and the issues involved with anesthetic management of co-existing neurogenic pulmonary edema and intracranial hypertension.

What is CAR doing in the middle of the adult neurogenic road?

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Junyent, Felix; Coré, Nathalie; Cremer, Harold

2017-01-01

ABSTRACT The molecular and cellular basis of adult neurogenesis has attracted considerable attention for fundamental and clinical applications because neural stem cells and newborn neurons may, one day, be harnessed to replace neurons and allow cognitive improvement in the diseased brain. In rodents, neural progenitors are located in the dentate gyrus and the sub/periventricular zone. In the dentate gyrus the generation of newborn neurons is associated with plasticity, including regulation of memory. The role of subventricular zone neural precursors that migrate to the olfactory bulb is less characterized. Identifying factors that impact neural stem cell proliferation, migration and differentiation is therefore sine qua non before we can harness their potential. Here, we expand upon our recent results showing that CAR, the coxsackievirus and adenovirus receptor, is among the developing list of key players when it comes to the complex process of integrating newborn neurons into existing circuits in the mature brain. PMID:28516108

Neurogenic stuttering: a review of the literature.

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Cruz, C; Amorim, H; Beca, G; Nunes, R

2018-01-16

Neurogenic stuttering is a disorder of neurologic origin in the rhythm of speech during which the patient knows exactly what he wants to say but is unable to because of an involuntary prolongation, cessation or repetition of a sound. To assemble new insights regarding the epidemiology, pathophysiology, diagnosis, evaluation and treatment of neurogenic stuttering. A review of all PubMed and Scopus published articles between January 2000 and September 2016 was performed. Thirty-three publications were analyzed. Neurogenic stuttering is a rare entity whose epidemiological incidence is yet not fully established. It is correlated with several neurological diseases and with several possible localizations within the nervous system. Notwithstanding the recent advances in the understanding of the underlying mechanism, it is not yet possible to establish a single pathophysiological mechanism of neurogenic stuttering. The differential diagnosis is complex and requires the detailed knowledge of other language disorders. The treatment is currently based on specific speech language therapy strategies. Neurogenic stuttering is a complex disorder which is not fully understood. Additional studies might help to better explain the underlying pathophysiological mechanism and to open doors to novel therapeutic methods.

Nestin Reporter Transgene Labels Multiple Central Nervous System Precursor Cells

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Avery S. Walker

2010-01-01

Full Text Available Embryonic neuroepithelia and adult subventricular zone (SVZ stem and progenitor cells express nestin. We characterized a transgenic line that expresses enhanced green fluorescent protein (eGFP specified to neural tissue by the second intronic enhancer of the nestin promoter that had several novel features. During embryogenesis, the dorsal telencephalon contained many and the ventral telencephalon few eGFP+ cells. eGFP+ cells were found in postnatal and adult neurogenic regions. eGFP+ cells in the SVZ expressed multiple phenotype markers, glial fibrillary acidic protein, Dlx, and neuroblast-specific molecules suggesting the transgene is expressed through the lineage. eGFP+ cell numbers increased in the SVZ after cortical injury, suggesting this line will be useful in probing postinjury neurogenesis. In non-neurogenic regions, eGFP was strongly expressed in oligodendrocyte progenitors, but not in astrocytes, even when they were reactive. This eGFP+ mouse will facilitate studies of proliferative neuroepithelia and adult neurogenesis, as well as of parenchymal oligodendrocytes.

Apical versus Basal Neurogenesis Directs Cortical Interneuron Subclass Fate

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Timothy J. Petros

2015-11-01

Full Text Available Fate determination in the mammalian telencephalon, with its diversity of neuronal subtypes and relevance to neuropsychiatric disease, remains a critical area of study in neuroscience. Most studies investigating this topic focus on the diversity of neural progenitors within spatial and temporal domains along the lateral ventricles. Often overlooked is whether the location of neurogenesis within a fate-restricted domain is associated with, or instructive for, distinct neuronal fates. Here, we use in vivo fate mapping and the manipulation of neurogenic location to demonstrate that apical versus basal neurogenesis influences the fate determination of major subgroups of cortical interneurons derived from the subcortical telencephalon. Somatostatin-expressing interneurons arise mainly from apical divisions along the ventricular surface, whereas parvalbumin-expressing interneurons originate predominantly from basal divisions in the subventricular zone. As manipulations that shift neurogenic location alter interneuron subclass fate, these results add an additional dimension to the spatial-temporal determinants of neuronal fate determination.

Cultured subventricular zone progenitor cells transduced with neurogenin-2 become mature glutamatergic neurons and integrate into the dentate gyrus.

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Xia Chen

Full Text Available We have previously shown that transplantation of immature DCX+/NeuN+/Prox1+ neurons (found in the neonatal DG, but not undifferentiated neuronal progenitor cells (NPCs from ventral subventricular zone (SVZ, results in neuronal maturation in vivo within the dentate niche. Here we investigated whether we could enhance the integration of SVZ NPCs by forced expression of the proneural gene Neurogenin 2 (NEUROG2. NPCs cultured from neonatal GFP-transgenic rat SVZ for 7 days in a non-differentiating medium were transduced with a retrovirus encoding NEUROG2 and DsRed or the DsRed reporter gene alone (control. By 3 days post-transduction, the NEUROG2-transduced cells maintained in culture contained mostly immature neurons (91% DCX+; 76% NeuN+, whereas the control virus-transduced cells remained largely undifferentiated (30% DCX+; <1% NeuN+. At 6 weeks following transplantation into the DG of adult male rats, there were no neurons among the transplanted cells treated with the control virus but the majority of the NEUROG2-transduced DsRed+ SVZ cells became mature neurons (92% NeuN+; DCX-negative. Although the NEUROG2-transduced SVZ cells did not express the dentate granule neuron marker Prox1, most of the NEUROG2-transduced SVZ cells (78% expressed the glutamatergic marker Tbr1, suggesting the acquisition of a glutamatergic phenotype. Moreover, some neurons extended dendrites into the molecular layer, grew axons containing Ankyrin G+ axonal initial segments, and projected into the CA3 region, thus resembling mature DG granule neurons. A proportion of NEUROG2 transduced cells also expressed c-Fos and P-CREB, two markers of neuronal activation. We conclude that NEUROG2-transduction is sufficient to promote neuronal maturation and integration of transplanted NPCs from SVZ into the DG.

Hard-Diet Feeding Recovers Neurogenesis in the Subventricular Zone and Olfactory Functions of Mice Impaired by Soft-Diet Feeding

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Utsugi, Chizuru; Miyazono, Sadaharu; Osada, Kazumi; Sasajima, Hitoshi; Noguchi, Tomohiro; Matsuda, Mitsuyoshi; Kashiwayanagi, Makoto

2014-01-01

The subventricular zone (SVZ) generates an immense number of neurons even during adulthood. These neurons migrate to the olfactory bulb (OB) and differentiate into granule cells and periglomerular cells. The information broadcast by general odorants is received by the olfactory sensory neurons and transmitted to the OB. Recent studies have shown that a reduction of mastication impairs both neurogenesis in the hippocampus and brain functions. To examine these effects, we first measured the difference in Fos-immunoreactivity (Fos-ir) at the principal sensory trigeminal nucleus (Pr5), which receives intraoral touch information via the trigeminal nerve, when female adult mice ingested a hard or soft diet to explore whether soft-diet feeding could mimic impaired mastication. Ingestion of a hard diet induced greater expression of Fos-ir cells at the Pr5 than did a soft diet or no diet. Bromodeoxyuridine-immunoreactive (BrdU-ir) structures in sagittal sections of the SVZ and in the OB of mice fed a soft or hard diet were studied to explore the effects of changes in mastication on newly generated neurons. After 1 month, the density of BrdU-ir cells in the SVZ and OB was lower in the soft-diet-fed mice than in the hard-diet-fed mice. The odor preferences of individual female mice to butyric acid were tested in a Y-maze apparatus. Avoidance of butyric acid was reduced by the soft-diet feeding. We then explored the effects of the hard-diet feeding on olfactory functions and neurogenesis in the SVZ of mice impaired by soft-diet feeding. At 3 months of hard-diet feeding, avoidance of butyric acid was reversed and responses to odors and neurogenesis were recovered in the SVZ. The present results suggest that feeding with a hard diet improves neurogenesis in the SVZ, which in turn enhances olfactory function at the OB. PMID:24817277

Vascular pattern of the dentate gyrus is regulated by neural progenitors.

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Pombero, Ana; Garcia-Lopez, Raquel; Estirado, Alicia; Martinez, Salvador

2018-05-01

Neurogenesis is a vital process that begins during early embryonic development and continues until adulthood, though in the latter case, it is restricted to the subventricular zone and the subgranular zone of the dentate gyrus (DG). In particular, the DG's neurogenic properties are structurally and functionally unique, which may be related to its singular vascular pattern. Neurogenesis and angiogenesis share molecular signals and act synergistically, supporting the concept of a neurogenic niche as a functional unit between neural precursors cells and their environment, in which the blood vessels play an important role. Whereas it is well known that vascular development controls neural proliferation in the embryonary and in the adult brain, by releasing neurotrophic factors; the potential influence of neural cells on vascular components during angiogenesis is largely unknown. We have demonstrated that the reduction of neural progenitors leads to a significant impairment of vascular development. Since VEGF is a potential regulator in the neurogenesis-angiogenesis crosstalk, we were interested in assessing the possible role of this molecule in the hippocampal neurovascular development. Our results showed that VEGF is the molecule involved in the regulation of vascular development by neural progenitor cells in the DG.

Preoperative neurogenic pulmonary edema: A dilemma for decision making

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Lakkireddigari, Siva Kumar Reddy; Durga, Padmaja; Nayak, Madhukar; Ramchandran, Gopinath

2012-01-01

Neurogenic pulmonary edema may be a less-recognized consequence of obstructive hydrocephalus. The authors report a patient with acute obstructive hydrocephalus due to cerebellar metastatic lesion, who presented with neurogenic pulmonary edema. The edema resolved on placement of the ventriculoperitonial shunt. This report addresses the importance of recognition of neurogenic pulmonary edema as a possible perioperative complication resulting from an increase in intracranial pressure and the iss...

Subventricular zone predicts high velocity of tumor expansion and poor clinical outcome in patients with low grade astrocytoma.

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Wen, Bing; Fu, Feixian; Hu, Liangbo; Cai, Qiuyi; Xie, Junshi

2018-05-01

The aim of this study is to clarify the association between subventricular zone (SVZ) involvement and velocity of diametric expansion(VDE) in patients with low-grade astrocytoma and also assessed the clinical outcome of those patients. A total of 168 adult patients with newly diagnosed supratentorial low-grade astrocytoma were studied retrospectively. There were 73 patients had SVZ involvement. Patients with SVZ involvement(7.16 ± 6.53 mm/y) had a higher VDE than patients without SVZ involvement(4.38 ± 5.35 mm/y). VDE was modeled as a categorical variable(＜4, ≥4 and, ＜8, ≥8 and, ＜12, ≥12 mm/y). Logistic regression showed that SVZ involvement was associated with high VDE after adjusting by confounding variables. On the univariate analysis, the results showed that tumor involved with SVZ, VDE ≥ 4 mm/y, VDE ≥ 8 mm/y, and VDE ≥ 8 mm/y were significant predictors of a shorter OS, progression-free survival (PFS) and malignant progression-free survival (MFS)(all p ＜0.05). The categorical variables of VDE (＜4 mm/y, ≥4 mm/y and, ＜8 mm/y, ≥8 mm/y and, ＜12 mm/y, ≥12 mm/y) were adjusted by confounding variables in multivariate analysis, respectively. The results indicated that VDE ≥ 8 mm/y, VDE ≥ 12 mm/y were worse prognostic factors for OS, while VDE ≥ 4 mm/y, VDE ≥ 8 mm/y and VDE ≥ 12 mm/y were related to shorter PFS and MFS. In addition, SVZ involvement was prognostic factors in predicting OS and PFS except MFS. Our results demonstrated that SVZ involvement predicted high VDE and worse clinical outcome, and high VDE was associated with poor prognosis in patients with low-grade astrocytoma. Copyright © 2018 Elsevier B.V. All rights reserved.

Functional organization of the transcriptome in human brain

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Oldham, Michael C; Konopka, Genevieve; Iwamoto, Kazuya; Langfelder, Peter; Kato, Tadafumi; Horvath, Steve; Geschwind, Daniel H

2009-01-01

The enormous complexity of the human brain ultimately derives from a finite set of molecular instructions encoded in the human genome. These instructions can be directly studied by exploring the organization of the brain’s transcriptome through systematic analysis of gene coexpression relationships. We analyzed gene coexpression relationships in microarray data generated from specific human brain regions and identified modules of coexpressed genes that correspond to neurons, oligodendrocytes, astrocytes and microglia. These modules provide an initial description of the transcriptional programs that distinguish the major cell classes of the human brain and indicate that cell type–specific information can be obtained from whole brain tissue without isolating homogeneous populations of cells. Other modules corresponded to additional cell types, organelles, synaptic function, gender differences and the subventricular neurogenic niche. We found that subventricular zone astrocytes, which are thought to function as neural stem cells in adults, have a distinct gene expression pattern relative to protoplasmic astrocytes. Our findings provide a new foundation for neurogenetic inquiries by revealing a robust and previously unrecognized organization to the human brain transcriptome. PMID:18849986

Novel in vivo imaging techniques for trafficking the behavior of subventricular zone neural stem cells (SVZSC) and SVZSC induced functional repair

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Anna-Liisa Brownell

2003-11-28

Adult progenitor cells hold promise for therapeutic treatment where there has been a disabling loss of function due to death of cells from trauma, disease or aging. However, it will be essential in clinical application to be able to follow the fate of the transplanted cells over time using in vivo tracking methods. We have developed protocol for labeling of progenitor cells to monitor cell trafficking by high resolution magnetic resonance imaging (MRI) and super high resolution positron emission tomography (PET). We have transfected rat subventricular zone stem cells (SVZ, progenitor cell line) and another control cell line (PC12, pheochromocytoma cells) utilizing super paramagnetic iron oxide and poly-L-lysine complex for MR imaging or radiolabeling with 18F-fluor deoxy-D- glucose for PET imaging. The labeled cells were transplanted into the rostral migratory stream (RMS) or striatum of normal or 6-hydroxydopamine lesioned Spraque-Dawley rats. Longitudinal MRI studies (up to 40 days) showed that transplantation site has significant impact to the fate of the cells; when SVZ cells were transplanted into the RMS, cells migrated several centimeter into the olfactory bulb; after transplantation into the striatum, the migration was minimal, only 2 mm. PC 12 cells grew a massive tumor after the striatal implantation and significantly smaller tumor after the RMS implantation. PET studies conducted immediately after transplantation verified the transplantation site. MRI studies were able to show the whole path of migration in one image, since part of the cells die during migration and will get detected because of iron content. Endpoint histological studies verified the cell survival and immunohistochemical studies revealed the differentiation of the transplanted cells into astrocytes and neurons.

Novel in vivo imaging techniques for trafficking the behavior of subventricular zone neural stem cells (SVZSC) and SVZSC induced functional repair

International Nuclear Information System (INIS)

Anna-Liisa Brownell

2003-01-01

Adult progenitor cells hold promise for therapeutic treatment where there has been a disabling loss of function due to death of cells from trauma, disease or aging. However, it will be essential in clinical application to be able to follow the fate of the transplanted cells over time using in vivo tracking methods. We have developed protocol for labeling of progenitor cells to monitor cell trafficking by high resolution magnetic resonance imaging (MRI) and super high resolution positron emission tomography (PET). We have transfected rat subventricular zone stem cells (SVZ, progenitor cell line) and another control cell line (PC12, pheochromocytoma cells) utilizing super paramagnetic iron oxide and poly-L-lysine complex for MR imaging or radiolabeling with 18F-fluor deoxy-D- glucose for PET imaging. The labeled cells were transplanted into the rostral migratory stream (RMS) or striatum of normal or 6-hydroxydopamine lesioned Spraque-Dawley rats. Longitudinal MRI studies (up to 40 days) showed that transplantation site has significant impact to the fate of the cells; when SVZ cells were transplanted into the RMS, cells migrated several centimeter into the olfactory bulb; after transplantation into the striatum, the migration was minimal, only 2 mm. PC 12 cells grew a massive tumor after the striatal implantation and significantly smaller tumor after the RMS implantation. PET studies conducted immediately after transplantation verified the transplantation site. MRI studies were able to show the whole path of migration in one image, since part of the cells die during migration and will get detected because of iron content. Endpoint histological studies verified the cell survival and immunohistochemical studies revealed the differentiation of the transplanted cells into astrocytes and neurons

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

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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.

Neuropeptides, neurogenic inflammation and complex regional pain syndrome (CRPS).

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Birklein, Frank; Schmelz, Martin

2008-06-06

This review explains symptoms and nature of neuropeptide signaling and its importance for clinical symptoms of CRPS. Neurogenic inflammation regularly accompanies excitation of primary afferent nociceptors. It has two major components-plasma extravasation and vasodilatation. The most important mediators are the calcitonin gene-related peptide (CGRP) and substance P (SP). After peripheral trauma immune reaction (e.g. cytokines) and the attempts of the tissue to regenerate (e.g. growth factors) sensitize nociceptors and amplify neurogenic inflammation. This cascade of events has been demonstrated in rat models of CRPS. Clinical findings in these animals strongly resemble clinical findings in CRPS, and can be prevented by anti-cytokine and anti-neuropeptide treatment. In CRPS patients, there is meanwhile also plenty of evidence that neurogenic inflammation contributes to clinical presentation. Increased cytokine production was demonstrated, as well as facilitated neurogenic inflammation. Very recently even "non-inflammatory" signs of CRPS (hyperhidrosis, cold skin) have been linked to neuropeptide signaling. Surprisingly, there was even moderately increased neurogenic inflammation in unaffected body regions. This favors the possibility that CRPS patients share genetic similarities. The future search for genetic commonalities will help us to further unravel the "mystery" CRPS.

P2X7 receptor inhibition increases CNTF in the subventricular zone, but not neurogenesis or neuroprotection after stroke in adult mice.

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Kang, Seong Su; Keasey, Matthew Phillip; Hagg, Theo

2013-10-01

Increasing endogenous ciliary neurotrophic factor (CNTF) expression with a pharmacological agent might be beneficial after stroke as CNTF both promotes neurogenesis and, separately, is neuroprotective. P2X7 purinergic receptor inhibition is neuroprotective in rats and increases CNTF release in rat CMT1A Schwann cells. We, first, investigated the role of P2X7 in regulating CNTF and neurogenesis in adult mouse subventricular zone (SVZ). CNTF expression was increased by daily intravenous injections of the P2X7 antagonist Brilliant Blue G (BBG) in naïve C57BL/6 or Balb/c mice over 3 days. Despite the ∼40-60 % increase or decrease in CNTF with BBG or the agonist BzATP, respectively, the number of proliferated BrdU+SVZ nuclei did not change. BBG failed to increase FGF2, which is involved in CNTF-regulated neurogenesis, but induced IL-6, LIF, and EGF, which are known to reduce SVZ proliferation. Injections of IL-6 next to the SVZ induced CNTF and FGF2, but not proliferation, suggesting that IL-6 counteracts their neurogenesis-inducing effects. Following ischemic injury of the striatum by middle cerebral artery occlusion (MCAO), a 3-day BBG treatment increased CNTF in the medial penumbra containing the SVZ. BBG also induced CNTF and LIF, which are known to be protective following stroke, in the whole striatum after MCAO, but not GDNF or BDNF. However, BBG treatment did not reduce the lesion area or apoptosis in the penumbra. Even so, this study shows that P2X7 can be targeted with systemic drug treatments to differentially regulate neurotrophic factors in the brain following stroke.

Etiopathogenesis of neurogenic pulmonary edema

Czech Academy of Sciences Publication Activity Database

Šedý, Jiří

2010-01-01

Roč. 160, 5-6 (2010), s. 152-154 ISSN 0043-5341 Institutional research plan: CEZ:AV0Z50390512 Keywords : neurogenic pulmonary edema * intracranial pressure * sympathetic system Subject RIV: FH - Neurology

Targeting p38 Mitogen-Activated Protein Kinase Signaling Restores Subventricular Zone Neural Stem Cells and Corrects Neuromotor Deficits in Atm Knockout Mouse

Science.gov (United States)

Kim, Jeesun

2012-01-01

Ataxia-telangiectasia (A-T) is a progressive degenerative disorder that results in major neurological disability. In A-T patients, necropsy has revealed atrophy of cerebellar cortical layers along with Purkinje and granular cell loss. We have previously identified an oxidative stress-mediated increase in phospho-p38 mitogen-activated protein kinase (MAPK) and the resultant downregulation of Bmi-1 and upregulation of p21 as key components of the mechanism causing defective proliferation of neural stem cells (NSCs) isolated from the subventricular zone (SVZ) of Atm−/− mice. However, the in vivo aspect of alteration in SVZ tissue and the functional significance of p38MAPK activation in NSCs for neuropathogenesis of ATM deficiency remain unknown. Here we show that the NSC population was abnormally decreased in the SVZ of 3-month-old Atm−/− mice; this decrease was accompanied by p38MAPK activation. However, after a 2-month treatment with the p38MAPK inhibitor SB203580, starting at 1 month old, Atm−/− mice showed restoration of normal levels of Bmi-1 and p21 with the rescue of NSC population in the SVZ. In addition, treated Atm−/− mice exhibited more Purkinje cells in the cerebellum. Most importantly, motor coordination of Atm−/− mice was significantly improved in the treatment group. Our results show for the first time in vivo evidence of depleted NSCs in the SVZ of Atm−/− mice and also demonstrate that pharmacologic inhibition of p38MAPK signaling has the potential to treat neurological defects of A-T. This study provides a promising approach targeting the oxidative stress-dependent p38 signaling pathway not only for A-T but also for other neurodegenerative disorders. PMID:23197859

Peripheral tumor and tumor-like neurogenic lesions

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Abreu, Evandro [Service de Radiologie et Imagerie Musculosquelettique, Centre de Consultation et Imagerie de l’Appareil Locomoteur, CHRU de Lille, 59037 Lille (France); Aubert, Sébastien, E-mail: sebastien.aubert@chru-lille.fr [Institut de Pathologie, Centre de Biologie-Pathologie, CHRU de Lille, 59037 Lille (France); Wavreille, Guillaume, E-mail: guillaume.wavreille@chru-lille.fr [Service d’Orthopédie B, Hôpital R Salengro, CHRU de Lille, 59037 Lille (France); Gheno, Ramon; Canella, Clarissa [Service de Radiologie et Imagerie Musculosquelettique, Centre de Consultation et Imagerie de l’Appareil Locomoteur, CHRU de Lille, 59037 Lille (France); Cotten, Anne, E-mail: anne.cotten@chru-lille.fr [Service de Radiologie et Imagerie Musculosquelettique, Centre de Consultation et Imagerie de l’Appareil Locomoteur, CHRU de Lille, 59037 Lille (France)

2013-01-15

Neoplasms of neurogenic origin account for about 12% of all benign and 8% of all malignant soft tissue neoplasms. Traumatic neuroma, Morton neuroma, lipomatosis of a nerve, nerve sheath ganglion, perineurioma, benign and malignant peripheral nerve sheath tumors (PNST) are included in this group of pathologies. Clinical and radiologic evaluation of patients with neurogenic tumors and pseudotumors often reveals distinctive features. In this context, advanced imaging techniques, especially ultrasound (US) and magnetic resonance (MR) play an important role in the characterization of these lesions. Imaging findings such as location of a soft tissue mass in the region of a major nerve, nerve entering or exiting the mass, fusiform shape, abnormalities of the muscle supplied by the nerve, split-fat sign, target sign and fascicular appearance should always evoke a peripheric nerve sheath neoplasm. Although no single imaging finding or combination of findings allows definitive differentiation between benign from malign peripheric neurogenic tumors, both US and MR imaging may show useful features that can lead us to a correct diagnosis and improve patient treatment. Traumatic neuromas and Morton neuromas are commonly associated to an amputation stump or are located in the intermetatarsal space. Lipomatosis of a nerve usually appears as a nerve enlargement, with thickened nerve fascicles, embedded in evenly distributed fat. Nerve sheath ganglion has a cystic appearance and commonly occurs at the level of the knee. Intraneural perineuroma usually affects young people and manifests as a focal and fusiform nerve enlargement. In this article, we review clinical characteristics and radiologic appearances of these neurogenic lesions, observing pathologic correlation, when possible.

Development of the adult neurogenic niche in the hippocampus of mice

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Zeina eNicola

2015-05-01

Full Text Available When does adult hippocampal neurogenesis begin? We describe the development of the neurogenic niche in the subgranular zone (SGZ of the hippocampal dentate gyrus. We did so from the perspective of the situation in the adult.Ontogeny of the dentate gyrus is complex and results in an ectopic neurogenic niche that lifelong generates new granule cells. Neurogenesis during the fetal and early postnatal periods builds the dentate gyrus and gives way to activity-dependent adult neurogenesis. We used markers most relevant to adult neurogenesis research to describe this transition: Nestin, Sox2, BLBP, GFAP, Tbr2, Doublecortin (DCX, NeuroD1 and Prox1. We found that massive changes and a local condensation of proliferating precursor cells occurs between postnatal day 7 (P7, near the peak in proliferation, and P14. Before and around P7, the spatial distribution of cells and the co-localization of markers were distinct from the situation in the adult. Unlike the adult SGZ, the marker pair Nestin/Sox2 and the radial glial marker BLBP were not overlapping during embryonic development, presumably indicating different types of radial glia-like cells. Before P7 GFAP-positive cells in the hilus lacked the radial orientation that is characteristic of the adult type-1 cells. DCX, which is concentrated in type-2b and type-3 progenitor cells and early postmitotic neurons in the adult, showed diffuse expression before P7. Intermediate progenitor cell marker Tbr2 became restricted to the SGZ but was found in the granule cell layer and hilus before. Lineage markers NeuroD1 and Prox1 confirmed this pattern.We conclude that the neurogenic niche of adult neurogenesis is in place well before true adulthood. This might indicate that consistent with the hypothesized function of adult neurogenesis in activity-dependent plasticity, the early transition from postnatal neurogenesis to adult neurogenesis coincides with the time, when the young mice start to become active themselves.

Bibliometric profile of neurogenic bladder in the literature: a 20-year bibliometric analysis

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Yuan Gao

2015-01-01

Full Text Available Neurogenic bladder is a dysfunction of the lower urinary tract caused by nervous system disorder. We investigated the trends in publication of articles under the topic "neurogenic bladder" using bibliometric analysis. Articles on neurogenic bladder, published between 1995 and 2014, were retrieved from the ISI Web of Science citation database. We analyzed the search results for authors, countries, institutions, journals, and top-cited papers. A total of 1,904 articles were retrieved. There was a small increase in the number of articles on neurogenic bladder from 1995 (n = 43 to 2014 (n = 117. The USA was the leading country in the total number of articles (n = 598. However, the number of publications from China has rapidly increased, and China was ranked second in 2014. Emmanuel Chartier-Kastler (n = 65 was the most productive author, and University of Paris VI (Paris 6 (n = 61 was the most productive institution. The Journal of Urology published the greatest number of articles on this topic (n = 285. Articles on neurogenic bladder were often published in a professional journal under the category Urology & Nephrology, Neurosciences & Neurology, or Rehabilitation. Visualization analysis based on co-citation networks was conducted using CiteSpace III. Visualization analysis revealed that the hot spots in neurogenic bladder were botulinum toxin-A, prazosin, bethanechol, and afferent pathways. These findings provide new insight into the publication trends and hot spots in neurogenic bladder.

Outcomes of bowel program in spinal cord injury patients with neurogenic bowel dysfunction

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Zuhal Ozisler

2015-01-01

Full Text Available In this study, we aimed to determine gastrointestinal problems associated with neurogenic bowel dysfunction in spinal cord injury patients and to assess the efficacy of bowel program on gastrointestinal problems and the severity of neurogenic bowel dysfunction. Fifty-five spinal cord injury patients were included in this study. A bowel program according to the characteristics of neurogenic bowel dysfunction was performed for each patient. Before and after bowel program, gastrointestinal problems (constipation, difficult intestinal evacuation, incontinence, abdominal pain, abdominal distension, loss of appetite, hemorrhoids, rectal bleeding and gastrointestinal induced autonomic dysreflexia and bowel evacuation methods (digital stimulation, oral medication, suppositories, abdominal massage, Valsalva maneuver and manual evacuation were determined. Neurogenic bowel dysfunction score was used to assess the severity of neurogenic bowel dysfunction. At least one gastrointestinal problem was identified in 44 (80% of the 55 patients before bowel program. Constipation (56%, 31/55 and incontinence (42%, 23/55 were the most common gastrointestinal problems. Digital rectal stimulation was the most common method for bowel evacuation, both before (76%, 42/55 and after (73%, 40/55 bowel program. Oral medication, enema and manual evacuation application rates were significantly decreased and constipation, difficult intestinal evacuation, abdominal distention, and abdominal pain rates were significantly reduced after bowel program. In addition, mean neurogenic bowel dysfunction score was decreased after bowel program. An effective bowel program decreases the severity of neurogenic bowel dysfunction and reduces associated gastrointestinal problems in patients with spinal cord injury.

Adult Hippocampal Neurogenesis in Parkinson’s Disease: Impact on Neuronal Survival and Plasticity

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Martin Regensburger

2014-01-01

Full Text Available In Parkinson’s disease (PD and other synucleinopathies, chronic neurodegeneration occurs within different areas of the central nervous system leading to progressive motor and nonmotor symptoms. The symptomatic treatment options that are currently available do not slow or halt disease progression. This highlights the need of a better understanding of disease mechanisms and disease models. The generation of newborn neurons in the adult hippocampus and in the subventricular zone/olfactory bulb system is affected by many different regulators and possibly involved in memory processing, depression, and olfaction, symptoms which commonly occur in PD. The pathology of the adult neurogenic niches in human PD patients is still mostly elusive, but different preclinical models have shown profound alterations of adult neurogenesis. Alterations in stem cell proliferation, differentiation, and survival as well as neurite outgrowth and spine formation have been related to different aspects in PD pathogenesis. Therefore, neurogenesis in the adult brain provides an ideal model to study disease mechanisms and compounds. In addition, adult newborn neurons have been proposed as a source of endogenous repair. Herein, we review current knowledge about the adult neurogenic niches in PD and highlight areas of future research.

Ageing with neurogenic bowel dysfunction

DEFF Research Database (Denmark)

Nielsen, S D; Faaborg, Pia Møller; Finnerup, Nanna Brix

2017-01-01

The aim of this longitudinal study with postal survey was to describe changes in the patterns of neurogenic bowel dysfunction and bowel management in a population of people with spinal cord injury (SCI) followed for two decades. In 1996, a validated questionnaire on bowel function was sent to the...

Neurogenic myopathies and imaging of muscle denervation; Neurogene Myopathien und Bildgebung der Muskeldenervation

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Wolf, M. [Universitaetsklinikum Heidelberg, Abteilung fuer Neuroradiologie, Heidelberg (Germany); Wolf, C. [Reha-Zentrum Gernsbach, Neurologie, Gernsbach (Germany); Weber, M.A. [Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie, Heidelberg (Germany)

2017-12-15

Neurogenic myopathies are primary diseases of the nervous system, which secondarily result in denervation of the target musculature. The spectrum of potential causes is manifold ranging from acute traumatic injuries and chronic compression to neurodegenerative, inflammatory, metabolic and neoplastic processes. The medical history, clinical neurological examination, and electrophysiological tests including electromyography and nerve conduction studies are crucial in diagnosing neuropathic myopathies. Electromyography is the gold standard for diagnosing muscle denervation. Additional imaging methods and magnetic resonance imaging (MRI) in particular, are capable of contributing valuable information. The MRI examination of denervated musculature shows edema, an increase in the apparent diffusion coefficient (ADC) and hyperperfusion. Chronic denervation results in fatty degeneration and atrophy of affected muscles, which are also detectable by MRI. Although the MRI findings in muscle denervation are relatively unspecific, they show a high sensitivity, comparable to electromyography. Dedicated MR neurography may often visualize the underlying lesion(s) of the innervating nerve(s). Besides high sensitivity, comparable to electromyography, MRI is capable of evaluating muscles which are inaccessible for needle electromyography. Due to its non-invasive character, MRI is ideal for follow-up examinations. The use of MRI is often a meaningful addition to the diagnostics of neurogenic myopathies. The extent and distribution pattern of muscular alterations often provide information on the localization of the causative nerve damage. A correct diagnosis or at least a narrowing down of possible differential diagnoses can often be achieved using MRI. (orig.) [German] Neurogene Myopathien sind Erkrankungen des Nervensystems, die sekundaer zur Denervierung der Zielmuskulatur fuehren. Das Spektrum potenzieller Ursachen ist vielfaeltig und umfasst akute traumatische Verletzungen

Retinoic acid-pretreated Wharton's jelly mesenchymal stem cells in combination with triiodothyronine improve expression of neurotrophic factors in the subventricular zone of the rat ischemic brain injury.

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Sabbaghziarani, Fatemeh; Mortezaee, Keywan; Akbari, Mohammad; Kashani, Iraj Ragerdi; Soleimani, Mansooreh; Moini, Ashraf; Ataeinejad, Nahid; Zendedel, Adib; Hassanzadeh, Gholamreza

2017-02-01

Stroke is the consequence of limited blood flow to the brain with no established treatment to reduce the neurological deficits. Focusing on therapeutic protocols in targeting subventricular zone (SVZ) neurogenesis has been investigated recently. This study was designed to evaluate the effects of retinoic acid (RA)-pretreated Wharton's jelly mesenchymal stem cells (WJ-MSCs) in combination with triiodothyronine (T3) in the ischemia stroke model. Male Wistar rats were used to induce focal cerebral ischemia by middle cerebral artery occlusion (MCAO). There were seven groups of six animals: Sham, Ischemic, WJ-MSCs, RA-pretreated WJ-MSCs, T3, WJ-MSCs +T3, and RA-pretreated WJ-MSCs + T3. The treatment was performed at 24 h after ischemia, and animals were sacrificed one week later for assessments of retinoid X receptor β (RXRβ), brain-derived neurotrophic factor (BDNF), Sox2 and nestin in the SVZ. Pro-inflammatory cytokines in sera were measured at days four and seven after ischemia. RXRβ, BDNF, Sox2 and nestin had the significant expressions in gene and protein levels in the treatment groups, compared with the ischemic group, which were more vivid in the RA-pretreated WJ-MSCs + T3 (p ≤ 0.05). The same trend was also resulted for the levels of TNF-α and IL-6 at four days after ischemia (p ≤ 0.05). In conclusion, application of RA-pretreated WJ-MSCs + T3 could be beneficial in exerting better neurotrophic function probably via modulation of pro-inflammatory cytokines.

Neurogenic bladder in spinal cord injury patients

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Al Taweel W

2015-06-01

Full Text Available Waleed Al Taweel, Raouf SeyamDepartment of Urology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaAbstract: Neurogenic bladder dysfunction due to spinal cord injury poses a significant threat to the well-being of patients. Incontinence, renal impairment, urinary tract infection, stones, and poor quality of life are some complications of this condition. The majority of patients will require management to ensure low pressure reservoir function of the bladder, complete emptying, and dryness. Management typically begins with anticholinergic medications and clean intermittent catheterization. Patients who fail this treatment because of inefficacy or intolerability are candidates for a spectrum of more invasive procedures. Endoscopic managements to relieve the bladder outlet resistance include sphincterotomy, botulinum toxin injection, and stent insertion. In contrast, patients with incompetent sphincters are candidates for transobturator tape insertion, sling surgery, or artificial sphincter implantation. Coordinated bladder emptying is possible with neuromodulation in selected patients. Bladder augmentation, usually with an intestinal segment, and urinary diversion are the last resort. Tissue engineering is promising in experimental settings; however, its role in clinical bladder management is still evolving. In this review, we summarize the current literature pertaining to the pathology and management of neurogenic bladder dysfunction in patients with spinal cord injury.Keywords: neurogenic bladder, spinal cord injury, urodynamics, intestine, intermittent catheterization

Effects of electrotherapy in treatment of neurogenic bladder in children with occult spinal dysraphism

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Ćirović Dragana

2009-01-01

Full Text Available Introduction Neurogenic bladder can develop as a result of various degrees of neurogenic lesion in spina bifida. The degree of bladder dysfunction depends on the level and type of spina bifida. Due to results upon complete diagnostic protocols, treatment options are applied. Objective Comparison of therapy results of patients with occult spinal dysraphism with neurogenic bladder that under-went medicamentous therapy and medicamentous with electrotherapy treatment. Methods We had 49 patients with neurogenic bladder that were treated at the University Children's Hospital in Belgrade in the period 2003-2008. The first group of children received medicamentous therapy and the second group received medicamentous therapy with transcutaneous electric nerve stimulation. In both groups we evaluated 4 symptoms: daily enuresis, enuresis nocturna, urgency and frequency and 4 urodynamic parameters: lower bladder capacity, unstable contractions and residual urine and detrusor sphincter dyssynergia. Follow-up urodynamic evaluation was done after 3, 6 and 12 months respectively. Results Our findings pointed out a high statistical significance of improvement in all evaluated urodynamic parameters of neurogenic bladder (predominantly in bladder capacity in the group of children with combined therapy as well in resolution of symptoms (predominantly enuresis nocturna, urgency and frequency. Conclusion Combined therapy is more efficient in treatment of children with neurogenic bladder. Electrotherapy is non-invasive, easily applicable and has had a significant place in treatment of children with dysfunctional voiding.

Unilateral phrenic nerve stimulation for neurogenic hypoventilation in Arnold Chiari malformation

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Nitin Garg

2013-01-01

Full Text Available Long- term ventilator dependence in patients with neurogenic hypoventilation is associated with significant morbidity and restricts mobility. Diaphragmatic pacing by phrenic nerve stimulation (PNS is a viable alternative. This is a case report of patient with Arnold-Chiari malformation with extensive syrinx who had neurogenic hypoventilation during sleep even after foramen magnum decompression and resolution of the syrinx. Unilateral PNS was done using spinal cord stimulator. With intermittent stimulation for 8 h while asleep, patient could be weaned off the ventilator completely. At 2 years follow- up, patient is ambulant and has returned to his routine activities. PNS is a good treatment tool in patients with neurogenic hypoventilation. Spinal cord stimulator can be used with optimal results. This is first such reported case of using spinal cord stimulator for PNS from India.

Neural stem cells in the immature, but not the mature, subventricular zone respond robustly to traumatic brain injury.

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Goodus, Matthew T; Guzman, Alanna M; Calderon, Frances; Jiang, Yuhui; Levison, Steven W

2015-01-01

Pediatric traumatic brain injury is a significant problem that affects many children each year. Progress is being made in developing neuroprotective strategies to combat these injuries. However, investigators are a long way from therapies to fully preserve injured neurons and glia. To restore neurological function, regenerative strategies will be required. Given the importance of stem cells in repairing damaged tissues and the known persistence of neural precursors in the subventricular zone (SVZ), we evaluated regenerative responses of the SVZ to a focal brain lesion. As tissues repair more slowly with aging, injury responses of male Sprague Dawley rats at 6, 11, 17, and 60 days of age and C57Bl/6 mice at 14 days of age were compared. In the injured immature animals, cell proliferation in the dorsolateral SVZ more than doubled by 48 h. By contrast, the proliferative response was almost undetectable in the adult brain. Three approaches were used to assess the relative numbers of bona fide neural stem cells, as follows: the neurosphere assay (on rats injured at postnatal day 11, P11), flow cytometry using a novel 4-marker panel (on mice injured at P14) and staining for stem/progenitor cell markers in the niche (on rats injured at P17). Precursors from the injured immature SVZ formed almost twice as many spheres as precursors from uninjured age-matched brains. Furthermore, spheres formed from the injured brain were larger, indicating that the neural precursors that formed these spheres divided more rapidly. Flow cytometry revealed a 2-fold increase in the percentage of stem cells, a 4-fold increase in multipotential progenitor-3 cells and a 2.5-fold increase in glial-restricted progenitor-2/multipotential-3 cells. Analogously, there was a 2-fold increase in the mitotic index of nestin+/Mash1- immunoreactive cells within the immediately subependymal region. As the early postnatal SVZ is predominantly generating glial cells, an expansion of precursors might not

Brain Barriers and a Subpopulation of Astroglial Progenitors of Developing Human Forebrain Are Immunostained for the Glycoprotein YKL-40

DEFF Research Database (Denmark)

Bjørnbak, Camilla; Brøchner, Christian B; Larsen, Lars A

2014-01-01

and subventricular zones showed specific YKL-40 reactivity confined to pericytes. Furthermore, a population of YKL-40-positive, small, rounded cells was identified in the ventricular and subventricular zones. Real-time quantitative RT-PCR analysis showed strong YKL-40 mRNA expression in the leptomeninges...

The pre-vertebrate origins of neurogenic placodes.

Science.gov (United States)

Abitua, Philip Barron; Gainous, T Blair; Kaczmarczyk, Angela N; Winchell, Christopher J; Hudson, Clare; Kamata, Kaori; Nakagawa, Masashi; Tsuda, Motoyuki; Kusakabe, Takehiro G; Levine, Michael

2015-08-27

The sudden appearance of the neural crest and neurogenic placodes in early branching vertebrates has puzzled biologists for over a century. These embryonic tissues contribute to the development of the cranium and associated sensory organs, which were crucial for the evolution of the vertebrate "new head". A previous study suggests that rudimentary neural crest cells existed in ancestral chordates. However, the evolutionary origins of neurogenic placodes have remained obscure owing to a paucity of embryonic data from tunicates, the closest living relatives to those early vertebrates. Here we show that the tunicate Ciona intestinalis exhibits a proto-placodal ectoderm (PPE) that requires inhibition of bone morphogenetic protein (BMP) and expresses the key regulatory determinant Six1/2 and its co-factor Eya, a developmental process conserved across vertebrates. The Ciona PPE is shown to produce ciliated neurons that express genes for gonadotropin-releasing hormone (GnRH), a G-protein-coupled receptor for relaxin-3 (RXFP3) and a functional cyclic nucleotide-gated channel (CNGA), which suggests dual chemosensory and neurosecretory activities. These observations provide evidence that Ciona has a neurogenic proto-placode, which forms neurons that appear to be related to those derived from the olfactory placode and hypothalamic neurons of vertebrates. We discuss the possibility that the PPE-derived GnRH neurons of Ciona resemble an ancestral cell type, a progenitor to the complex neuronal circuit that integrates sensory information and neuroendocrine functions in vertebrates.

Pathogenetic Mechanisms of Neurogenic Pulmonary Edema

Czech Academy of Sciences Publication Activity Database

Šedý, Jiří; Kuneš, Jaroslav; Zicha, Josef

2015-01-01

Roč. 32, č. 15 (2015), s. 1135-1145 ISSN 0897-7151 R&D Projects: GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : baroreflex-induced bradycardia * blood pressure rise * blood volume redistribution * neurogenic pulmonary edema * spinal cord injury * sympathetic nervous system Subject RIV: ED - Physiology Impact factor: 4.377, year: 2015

Endogenous repair mechanisms enhanced in Parkinson's disease following stem cell therapy

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Eleonora Napoli

2017-01-01

Full Text Available This mini-review highlights the innovative observation that transplanted human neural stem cells can bring about endogenous brain repair through the stimulation of multiple regenerative processes in the neurogenic area (i.e., subventricular zone [SVZ] in an animal model of Parkinson's disease (PD. In addition, we convey that identifying anti-inflammatory cytokines, therapeutic proteomes, and neurotrophic factors within the SVZ may be essential to induce brain repair and behavioral recovery. This work opens up a new area of research for further understanding the pathology and treatment of PD. This paper is a review article. Referred literature in this paper has been listed in the references section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.

Cytoarchitecture and ultrastructure of neural stem cell niches and neurogenic complexes maintaining adult neurogenesis in the olfactory midbrain of spiny lobsters, Panulirus argus.

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Schmidt, Manfred; Derby, Charles D

2011-08-15

New interneurons are continuously generated in small proliferation zones within neuronal somata clusters in the olfactory deutocerebrum of adult decapod crustaceans. Each proliferation zone is connected to a clump of cells containing one neural stem cell (i.e., adult neuroblast), thus forming a "neurogenic complex." Here we provide a detailed analysis of the cytoarchitecture of neurogenic complexes in adult spiny lobsters, Panulirus argus, based on transmission electron microscopy and labeling with cell-type-selective markers. The clump of cells is composed of unique bipolar clump-forming cells that collectively completely envelop the adult neuroblast and are themselves ensheathed by a layer of processes of multipolar cell body glia. An arteriole is attached to the clump of cells, but dye perfusion experiments show that hemolymph has no access to the interior of the clump of cells. Thus, the clump of cells fulfills morphological criteria of a protective stem cell niche, with clump-forming cells constituting the adult neuroblast's microenvironment together with the cell body glia processes separating it from other tissue components. Bromodeoxyuridine pulse-chase experiments with short survival times suggest that adult neuroblasts are not quiescent but rather cycle actively during daytime. We propose a cell lineage model in which an asymmetrically dividing adult neuroblast repopulates the pool of neuronal progenitor cells in the associated proliferation zone. In conclusion, as in mammalian brains, adult neurogenesis in crustacean brains is fueled by neural stem cells that are maintained by stem cell niches that preserve elements of the embryonic microenvironment and contain glial and vascular elements. Copyright © 2011 Wiley-Liss, Inc.

Upregulated expression of Nogo-A and NgR in an experimental model of focal microgyria regulates the migration, proliferation and self-renewal of subventricular zone neural progenitors

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Yu, Sixun; Shu, Haifeng; Yang, Tao; Huang, Haidong [Department of Neurosurgery, General Hospital of the People' s Liberation Army Chengdu Military Region, Chengdu, Sichuan, 610083 (China); Li, Song [Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Zhao, Ziyi [Central Laboratory, Teaching Hospital of Chengdu University of Traditional Chinese Medicine, 610075 (China); Kuang, Yongqin, E-mail: kuangyongqin@163.com [Department of Neurosurgery, General Hospital of the People' s Liberation Army Chengdu Military Region, Chengdu, Sichuan, 610083 (China)

2016-04-29

Nogo-A and its receptor (NgR) were first described as myelin-associated inhibitors of neuronal regeneration in response to injury. In recent years, knowledge about the important role of the Nogo-A protein in several neuronal pathologies has grown considerably. Here, we employed a neonatal cortex freeze-lesion (NFL) model in neonatal rats and measured the expression of Nogo-A and NgR in the resulting cerebrocortical microdysgenesis 5–75 days after freezing injury. We observed marked upregulation of Nogo-A and NgR in protein levels. Furthermore, the migration of neural precursor cells (NPCs) derived from the subventricular zone (SVZ) toward the sits of injury was perturbed by treatment of NgR antagonist peptide NEP1-40. In vitro analysis showed that the knockdown of NgR by lentivirus-delivered siRNA promoted in axonal regeneration and SVZ-derived neural stem cell/progenitor cell (SVZ-NPCs) adhesion and migration, findings which were similar to the effects of NEP1-40. Taken together, our results indicate an important role for NgR in regulating the physiological processes of SVZ-NPCs. The observation of upregulated Nogo-A/NgR in lesion sites in the NFL model suggest that the effects of the perturbed Nogo-A are a key feature during the development and/or the progression of cortical malformation. - Highlights: • NFL model is an accurate experimental reproduction of focal microgyria of FCD. • The increase of the Nogo-A Levels occurs in response to freeze-induced focal lesioning. • Nogo-A/NgR may play a critical role for in the pathologic progression of FCD. • Nogo-A is associated with the migration, proliferation and self-renewal of SVZ-NPCs.

Two cases of neurogenic paralysis in medieval skeletal samples from Croatia.

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Novak, Mario; Čavka, Mislav; Šlaus, Mario

2014-12-01

Osteological changes consistent with neurogenic paralysis were observed in one male and one female skeleton recovered from two Croatian medieval sites - Virje and Zadar. Both skeletons display limb asymmetry typical of neurogenic paralysis that occurs during the childhood. The male skeleton displays atrophy and shortening of the right arm and the right femur, while the female skeleton exhibits identical changes on the right arm and both legs. Additionally, both skeletons exhibit scoliotic changes of the spine, and the female skeleton also displays bilateral hip dysplasia. Differential diagnosis included disorders such as cerebral palsy, poliomyelitis, cerebrovascular accident, and Rasmussen's encephalitis. These are the first cases of neurogenic paralysis (cerebral palsy and/or paralytic poliomyelitis) identified in Croatian archeological series. The Virje skeleton is only the third case of hemiplegia identified from archeological contexts (first with spinal scoliosis), while the Zadar skeleton represents the first case of triplegia reported in the paleopathological literature. Copyright © 2014 Elsevier Inc. All rights reserved.

The reliability of differentiating neurogenic claudication from vascular claudication based on symptomatic presentation.

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Nadeau, Mélissa; Rosas-Arellano, M Patricia; Gurr, Kevin R; Bailey, Stewart I; Taylor, David C; Grewal, Ruby; Lawlor, D Kirk; Bailey, Chris S

2013-12-01

Intermittent claudication can be neurogenic or vascular. Physicians use a profile based on symptom attributes to differentiate the 2 types of claudication, and this guides their investigations for diagnosis of the underlying pathology. We evaluated the validity of these symptom attributes in differentiating neurogenic from vascular claudication. Patients with a diagnosis of lumbar spinal stenosis (LSS) or peripheral vascular disease (PVD) who reported claudication answered 14 questions characterizing their symptoms. We determined the sensitivity, specificity and positive and negative likelihood ratios (PLR and NLR) for neurogenic and vascular claudication for each symptom attribute. We studied 53 patients. The most sensitive symptom attribute to rule out LSS was the absence of "triggering of pain with standing alone" (sensitivity 0.97, NLR 0.050). Pain alleviators and symptom location data showed a weak clinical significance for LSS and PVD. Constellation of symptoms yielded the strongest associations: patients with a positive shopping cart sign whose symptoms were located above the knees, triggered with standing alone and relieved with sitting had a strong likelihood of neurogenic claudication (PLR 13). Patients with symptoms in the calf that were relieved with standing alone had a strong likelihood of vascular claudication (PLR 20.0). The classic symptom attributes used to differentiate neurogenic from vascular claudication are at best weakly valid independently. However, certain constellation of symptoms are much more indicative of etiology. These results can guide general practitioners in their evaluation of and investigation for claudication.

Neurogenic Stunned Myocardium Associated with Acute Spinal Cord Infarction: A Case Report

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Gillian A. Beauchamp

2012-01-01

Full Text Available Introduction. Neurogenic stunned myocardium (NSM is a reversible cardiomyopathy resulting in transient left ventricular apical ballooning presumed to result from catecholamine surge occurring under physiologic stress. Acute spinal cord ischemia is a rare ischemic vascular lesion. We report a case of neurogenic stunned myocardium occurring in the setting of acute spinal cord infarction. Methods. Singe case report was used. Results. We present the case of a 63-year-old female with a history of prior lacunar stroke, hypertension, chronic back pain, and hypothyroidism who presented with a brief episode of diffuse abdominal and bilateral lower extremity pain which progressed within minutes to bilateral lower extremity flaccid paralysis. MRI of the spinal cord revealed central signal hyperintensity of T2-weighted imaging from conus to T8 region, concerning for acute spinal cord ischemia. Transthoracic echocardiogram was performed to determine if a cardiac embolic phenomenon may have precipitated this ischemic event and showed left ventricular apical hypokinesis and ballooning concerning for NSM. Conclusion. Neurogenic stunned myocardium is a reversible cardiomyopathy which has been described in patients with physiologic stress resulting in ventricular apical ballooning. Our case suggests that it is possible for neurogenic stunned myocardium to occur in the setting of acute spinal cord ischemia.

Introduction to Neurogenic Communication Disorders. Fifth Edition.

Science.gov (United States)

Brookshire, Robert H.

This book provides an overview of the causes and symptoms, and the typical courses, treatments, and outcomes of neurogenic communication disorders. Chapter 1 reviews the human nervous system and neurologic causes of adult communication disorders. Chapter 2 discusses the neurologic assessment and arriving at a diagnosis, including the neurologist's…

Neurogenética en el Perú, ejemplo de investigación traslacional

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Pilar Mazzetti

Full Text Available La neurogenética es una disciplina emergente en el Perú que vincula la investigación básica con la práctica clínica. El Centro de Investigación Básica en Neurogenética, es el único centro en el Perú dedicado a la atención especializada de enfermedades neurogenéticas. La investigación en esta área está estrechamente ligada a la enfermedad de Huntington, desde la genotipificación del gen HTT por PCR, hasta los actuales estudios de haplogrupos en esta enfermedad. La investigación en otras enfermedades monogénicas permitió la implementación de metodologías alternativas para la genotipificación del síndrome X frágil y distrofia miotónica tipo 1. Esfuerzos colaborativos nacionales e internacionales han permitido conocer nuevas variantes genéticas en enfermedades complejas, como la enfermedad de Parkinson y Alzheimer. El entrenamiento multidisciplinario y la mentoría fomentan la formación de nuevos especialistas en neurogenética, permitiendo el crecimiento sostenido de esta disciplina en el país. El impulso de la investigación en el Perú ha impulsado el crecimiento de la investigación en neurogenética; sin embargo, las limitaciones en infraestructura, tecnología y capacitación aún son un reto para el crecimiento de investigación en esta disciplina

Detrusor Arreflexia as an End Stage of Neurogenic Bladder in HAM/TSP?

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Matheus Tannus

2011-01-01

Full Text Available The HTLV-1 virus is a known agent involved in the development of HAM/TSP. Past studies have typically observed patients with autonomic dysfunction consisting of detrusor overactivity and detrusor-sphincter dyssynergia, with the occasional observation of underactive detrusor or detrusor arreflexia. However, studies have not yet evaluated the progression of neurogenic bladder over time. In this paper, we describe a HAM/TSP patient with the initial development of overactive detrusor, and subsequent development of detrusor arreflexia. Given a paucity of studies characterizing the effects of HTLV-1 on the autonomic nervous system, particularly aspects controlling continence, this patient's clinical course may represent one type of end point for patients with HAM/TSP and neurogenic bladder. Further cohort or case-series studies, with particular emphasis on the progression of neurogenic bladder, are needed to evaluate the significance of this described case in relation to typical disease progression patterns.

Neurogenic pulmonary edema due to ventriculo-atrial shunt dysfunction: a case report.

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Cruz, Ana Sofia; Menezes, Sónia; Silva, Maria

2016-01-01

Pulmonary edema is caused by the accumulation of fluid within the air spaces and the interstitium of the lung. Neurogenic pulmonary edema is a clinical syndrome characterized by the acute onset of pulmonary edema following a significant central nervous system insult. It may be a less-recognized consequence of raised intracranial pressure due to obstructive hydrocephalus by blocked ventricular shunts. It usually appears within minutes to hours after the injury and has a high mortality rate if not recognized and treated appropriately. We report a patient with acute obstructive hydrocephalus due to ventriculo-atrial shunt dysfunction, proposed to urgent surgery for placement of external ventricular drainage, who presented with neurogenic pulmonary edema preoperatively. She was anesthetized and supportive treatment was instituted. At the end of the procedure the patient showed no clinical signs of respiratory distress, as prompt reduction in intracranial pressure facilitated the regression of the pulmonary edema. This report addresses the importance of recognition of neurogenic pulmonary edema as a possible perioperative complication resulting from an increase in intracranial pressure. If not recognized and treated appropriately, neurogenic pulmonary edema can lead to acute cardiopulmonary failure with global hypoperfusion and hypoxia. Therefore, awareness of and knowledge about the occurrence, clinical presentation and treatment are essential. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Neurogenic pulmonary edema due to ventriculo-atrial shunt dysfunction: a case report

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Ana Sofia Cruz

2016-04-01

Full Text Available ABSTRACT BACKGROUND AND OBJECTIVES: Pulmonary edema is caused by the accumulation of fluid within the air spaces and the interstitium of the lung. Neurogenic pulmonary edema is a clinical syndrome characterized by the acute onset of pulmonary edema following a significant central nervous system insult. It may be a less-recognized consequence of raised intracranial pressure due to obstructive hydrocephalus by blocked ventricular shunts. It usually appears within minutes to hours after the injury and has a high mortality rate if not recognized and treated appropriately. CASE REPORT: We report a patient with acute obstructive hydrocephalus due to ventriculo-atrial shunt dysfunction, proposed to urgent surgery for placement of external ventricular drainage, who presented with neurogenic pulmonary edema preoperatively. She was anesthetized and supportive treatment was instituted. At the end of the procedure the patient showed no clinical signs of respiratory distress, as prompt reduction in intracranial pressure facilitated the regression of the pulmonary edema. CONCLUSIONS: This report addresses the importance of recognition of neurogenic pulmonary edema as a possible perioperative complication resulting from an increase in intracranial pressure. If not recognized and treated appropriately, neurogenic pulmonary edema can lead to acute cardiopulmonary failure with global hypoperfusion and hypoxia. Therefore, awareness of and knowledge about the occurrence, clinical presentation and treatment are essential.

[Neurogenic communication disorders: how effective are relaxation therapy and acupuncture?].

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Ptok, M

2008-12-01

Not only neurologists but also ENT-physicians and phoniatricians have to prescribe speech and language therapy for patients with communication disorders. Complementary and alternative medicine (CAM) has gained increasing popularity among patients. Many studies have investigated these procedures and positive effects on certain physical e. g., chronic pain and anxiety disorders could be validated. Unfortunately only few empirical investigations have targeted the use of CAM to treat neurogenic disorders of communication or cognition. In this review we provide an overview over general therapeutical principals of two widely used approaches, relaxation therapy and acupuncture. Then we survey the literature and summarize existent research literature regarding the effects of the treatment of neurogenic disorders including dementia.

A One Year Prospective Study of Neurogenic Stuttering Following Stroke: Incidence and Co-Occurring Disorders

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Theys, C.; van Wieringen, A.; Sunaert, S.; Thijs, V.; De Nil, L. F.

2011-01-01

In this prospective study, data on incidence, stuttering characteristics, co-occurring speech disorders, and recovery of neurogenic stuttering in a large sample of stroke participants were assessed. Following stroke onset, 17 of 319 participants (5.3%; 95% CI, 3.2-8.3) met the criteria for neurogenic stuttering. Stuttering persisted in at least…

X-ray diagnostic sign for the differentiation of neurogenic and primary muscular diseases

International Nuclear Information System (INIS)

Palvoelgyi, R.; Gallai, M.

1981-01-01

The authors give an account of X-ray examinations of the limb musculature of 70 patients suffering from neurogenic muscular diseases, 42 suffering from primary muscular diseases and 45 suffering from senile degeneration of the muscles. Different degree of damage to different parts of the same muscle could only been observed in one case of neurogenic atrophy (in the postpoliomyelitic states) and in two cases of senile degeneration, while it was found in 11 cases (20%) for the other muscular diseases. In the latter cases the more severe muscle damage, which could be demonstrated radiographically, was always found in the part of the muscle adjacent to a tendon. On the above reasons the authors consider that radiographically demonstrable partial or uneven damage to any particular muscle can be used as a new diagnostical information in distinguishing muscular diseases from neurogenic muscular atrophy. (orig.) [de

Clinical and Treatment Features of Orbital Neurogenic Tumors

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Pınar Bingöl Kızıltunç

2013-10-01

Full Text Available Purpose: To evaluate the clinical and treatment features of orbital neurogenic tumors. Material and Method: The records of 35 patients with orbital neurogenic tumors who were diagnosed and treated at Ankara University Faculty of Medicine, Department of Ophthalmology, between 1998 and 2011 were evaluated retrospectively. Results: Orbitotomy via a cutaneous approach was performed in 21 (60% cases and orbitotomy via a transconjunctival approach was performed in 7 (20% cases. Three (8% cases had been operated at different centers. Four (12% cases were diagnosed clinically. Total excisional biopsy was performed in 11 (31.4% cases, subtotal excisional biopsy was performed in 7 (20%, and incisional biopsy was performed in 10 (28.6% cases. 14 (40% 35 cases were diagnosed as meningioma, 12 (34% as peripheral nerve sheath tumor, and 9 (26% cases were diagnosed as optic nerve glioma. Six (43% meningioma cases were optic nerve sheath meningioma, 5 (36% were sphenoid wing meningioma, 2 (14% were ectopic meningioma, and 1 (7% was perisellar meningioma. Six (50% of peripheral nerve sheath tumors were schwannoma, 2 (16% were solitary neurofibroma, 4 (34% were plexiform neurofibroma. External beam radiotherapy was performed in 15 (42.8% cases, cyberknife radiosurgery in 1 (2.8% , chemotherapy in 1 (2.8%, and enucleation ( because of neovascular glaucoma and vitreous hemorrhage was performed in 1 (2.8% case. Discussion: The most common orbital neurogenic tumors are meningioma, peripheral nerve sheath tumor, and optic nerve glioma. For meningioma and glioma, external beam radiotherapy is required; for schwannoma and solitary neurofibroma, total excisional biopsy is the preferred treatment. The success of visual and anatomic results are high after treatment. (Turk J Ophthalmol 2013; 43: 335-9

Intravesical prostatic protrusion correlates well with storage symptoms in elderly male patients with non-neurogenic overactive bladder

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Shih-Yen Lu

2016-03-01

Conclusion: In elderly male patients with non-neurogenic OAB, more severe storage symptoms are associated with a lower maximum flow rate and a more prominent IPP, indicating that a significant cause of male non-neurogenic OAB is prostate associated.

Mechanisms of neurogenic pulmonary edema development

Czech Academy of Sciences Publication Activity Database

Šedý, Jiří; Zicha, Josef; Kuneš, Jaroslav; Jendelová, Pavla; Syková, Eva

2008-01-01

Roč. 57, č. 4 (2008), s. 499-506 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LC554; GA ČR GA309/06/1246; GA MŠk 1M0538 Grant - others:GA MZd(CZ) 1A8697; GA MZd(CZ) NR8339 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50110509 Keywords : Neurogenic pulmonary edema * Rat * Lung Subject RIV: FH - Neurology Impact factor: 1.653, year: 2008

Spontaneous Bladder Perforation in an Infant Neurogenic Bladder: Laparoscopic Management

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Daniel Cabezalí Barbancho

2013-01-01

Full Text Available Spontaneous bladder perforation is an uncommon event in childhood. It is usually associated with bladder augmentation. We are presenting a case of bladder rupture in an infant with neurogenic bladder without prior bladder surgery. Three days after lipomyelomeningocele excision the patient showed signs and symptoms of acute abdomen. The ultrasound exploration revealed significant amount of intraperitoneal free fluid and therefore a laparoscopic exploration was performed. A posterior bladder rupture was diagnosed and repaired laparoscopically. Currently, being 3 years old, she keeps successfully dry with clean intermittent catheterization. Neurogenic bladder voiding function can change at any time of its evolution and lead to complications. Early diagnosis of spontaneous bladder rupture is of paramount importance, so it is essential to think about it in the differential diagnosis of acute abdomen.

Malignant neurogenic neoplasms of the head and neck

International Nuclear Information System (INIS)

Kuczkowski, J.; Starzynska, A.

1996-01-01

The authors present 17 cases of malignant neurogenic neoplasms of the head and neck observed in the Department of Otolaryngology in the years 1948-1993. The latest opinions on etiopathology, diagnosis and treatment of these tumors were described. Age and sex of patients, localization of tumor, symptoms histopathology and treatment were analyzed. Progressions of the disease were estimated retrospectively. It has been proved that these tumors develop quickly, give pain and paresthesia. Their diagnosis is very difficult because of their submucosal growth and difficult histopathological interpretation. A characteristic feature of these neurogenic tumors is the ability to give distant metastases. This feature differentiates them from squamous neoplasms, which give mainly nodal metastases. All the patients were subjected to surgery combined with conventional or high voltage radiotherapy. The positive effect of combined chemotherapy in cases of esthesioneuroblastoma is worthy of note. The prognosis in these tumors is often unfavorable. In the group under discussion 13 patients died because of recurrences, two patients are considered to be cured and the remaining 2 patients have had no recurrence for 2 and 3 years. (author)

Neurogenic bladder from occult herpes zoster.

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Rothrock, J F; Walicke, P A; Swenson, M R

1986-11-01

Active infection with herpes zoster may cause acute urinary retention, especially when it involves sacral dermatomes. Although frank retention usually develops days to weeks after eruption of the typical rash, bladder incompetence infrequently develops first, raising concern over other, more ominous etiologies. In the case presented, rash appearance was delayed until six weeks after the initial onset of urinary retention, a much longer interval than previously reported. Occult herpes zoster infection should be considered in patients presenting with an acute neurogenic bladder of obscure cause.

Increased 5-hydroxymethylation levels in the sub ventricular zone of the Alzheimer's brain

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Diego Mastroeni

2016-06-01

Full Text Available The subventricular zone (SVZ is a site of neurogenesis in the aging brain, and epigenetic mechanisms have been implicated in regulating the “normal” distribution of new nerve cells into the existing cellular milieu. In a case-control study of human primary SVZ cultures and fixed tissue from the same individuals, we have found significant increases in DNA hydroxymethylation levels in the SVZ of Alzheimer's disease patients compared with nondiseased control subjects. We show that this increase in hydroxymethylation directly correlates to an increase in cellular proliferation in Alzheimer's disease precursor cells, which implicates the hydroxymethylation tag to a higher degree of cellular proliferation.

Neurogenic effects of fingolimod in hippocampus, affecting fear memory.

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Paschalis Efstathopoulos

2014-05-01

Full Text Available Fingolimod (FTY720; Gilenya™,Novartis Pharma AG is a recently developed Sphingosine-1-Phosphate (S1P analogue, orally administered as a new therapeutic agent in Multiple Sclerosis (MS (Brinkmann V. et al. 2010. S1P receptors (S1PRs are expressed in various sites in the CNS including the subventricular zone (Waeber C. et al. 1999; Choi J.W. et al. 2013 while endogenous S1P was shown to induce proliferation and morphological changes in embryonic hippocampal neural progenitors in culture (Harada J. et al. 2004. In this study we investigated the effects of fingolimod on adult rodent hippocampal neurogenesis and their possible functional role. To this aim, thymidine analogue BrdU was injected at the end or before a 2-week i.p. administration of a therapeutic dose of Fingolimod (0,3 mg/kg in young and old mice. Stereological counts of BrdU+ cells revealed significant increase in both proliferation, and survival of neural stem cells (NSC in the area of Dentate Gyrus (DG of the hippocampus, compared to control untreated animals of young but not old ages. In the case of survival assessment, most of the BrdU + cells were also positive for NeuN, suggesting an increase of newly formed neurons. The increase in proliferation rate of NSC was also confirmed by BrdU uptake in hippocampal NSC cultures in vitro, implying that the effects of fingolimod are cell autonomous. Immunohistochemical analysis showed that S1PR was not co-localized with GFAP+ cells in the Subgranular zone (SGZ of the DG, but was strongly co-localized with transcription factor MASH1 and weakly with DcX or PSA-NCAM positive neural progenitors. These findings suggest that expression of S1PR1 in the SGZ is restricted to transit amplifying neural progenitors and maintained also in the stage of neuroblast. In addition, the effects of Fingolimod in DG neurogenesis were positively correlated to enhanced fear memory and increased context discrimination, an established DG-dependent cognitive task

Botulinum toxin A for treatment of neurogenic detrusor overactivity and incontinence in patients with spinal cord lesions

DEFF Research Database (Denmark)

Bagi, Per; Biering-Sørensen, Fin

2004-01-01

To evaluate the efficacy of intravesical botulinum toxin A (BTA) in the treatment of severe neurogenic detrusor overactivity (NDO) with incontinence in patients with spinal cord lesions (SCLs).......To evaluate the efficacy of intravesical botulinum toxin A (BTA) in the treatment of severe neurogenic detrusor overactivity (NDO) with incontinence in patients with spinal cord lesions (SCLs)....

The treatment of erectile dysfunction in patients with neurogenic disease.

Science.gov (United States)

Shridharani, Anand N; Brant, William O

2016-02-01

Erectile dysfunction (ED) related to compromise of the nervous system is an increasingly common occurrence. This may be due to the multifactorial nature of ED, the myriad of disorders affecting the neurotransmission of erectogenic signals, and improved awareness and diagnosis of ED. Nevertheless, neurogenic ED remains poorly understood and characterized. Disease related factors such as depression, decreased physical and mental function, the burden of chronic illness, and loss of independence may preclude sexual intimacy and lead to ED as well. The amount of data regarding treatment options in subpopulations of differing neurologic disorders remains scarce except for men with spinal cord injury. The treatment options including phosphodiesterase inhibitors, intracavernosal or intraurethral vasoactive agents, vacuum erection devices (VED) and penile prosthetic implantation remain constant. This review discusses the options in specific neurologic conditions, and briefly provides insight into new and future developments that may reshape the management of neurogenic ED.

Inhibition by ketamine and amphetamine analogs of the neurogenic nitrergic vasodilations in porcine basilar arteries

International Nuclear Information System (INIS)

Chen, Mei-Fang; Lai, Su-Yu; Kung, Po-Cheng; Lin, Yo-Cheng; Yang, Hui-I; Chen, Po-Yi; Liu, Ingrid Y.; Lua, Ahai Chang; Lee, Tony Jer-Fu

2016-01-01

The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O 2 demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100 μM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8 Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic-nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing α3β2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine > methamphetamine > hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism-mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic

Inhibition by ketamine and amphetamine analogs of the neurogenic nitrergic vasodilations in porcine basilar arteries

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Chen, Mei-Fang [Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Tzu Chi Center for Vascular Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Tzu Chi University of Science and Technology, Hualien, Taiwan (China); Lai, Su-Yu; Kung, Po-Cheng; Lin, Yo-Cheng [Department of Pharmacology and Toxicology, College of Medicine, Tzu Chi University, Hualien, Taiwan (China); Yang, Hui-I [Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Chen, Po-Yi [Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Department of Pharmacology and Toxicology, College of Medicine, Tzu Chi University, Hualien, Taiwan (China); Liu, Ingrid Y. [Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan (China); Lua, Ahai Chang [Department of Laboratory Medicine and Biotechnology & Graduate Institute of Medical Biotechnology, Tzu Chi University, Hualien, Taiwan (China); Lee, Tony Jer-Fu, E-mail: tlee@mail.tcu.edu.tw [Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Tzu Chi Center for Vascular Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Department of Life Sciences, College of Life Sciences, Tzu Chi University, Hualien, Taiwan (China); Department of Pharmacology and Toxicology, College of Medicine, Tzu Chi University, Hualien, Taiwan (China); Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL (United States)

2016-08-15

The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O{sub 2} demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100 μM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8 Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic-nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing α3β2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine > methamphetamine > hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism-mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic

Neurogenic muscle hypertrophy in a 12-year-old girl.

Science.gov (United States)

Zutelija Fattorini, Matija; Gagro, Alenka; Dapic, Tomislav; Krakar, Goran; Marjanovic, Josip

2017-01-01

Muscular hypertrophy secondary to denervation is very rare, but well-documented phenomena in adults. This is the first report of a child with neurogenic unilateral hypertrophy due to S1 radiculopathy. A 12-year-old girl presented with left calf hypertrophy and negative history of low back pain or trauma. The serum creatinine kinase level and inflammatory markers were normal. Magnetic resonance imaging showed muscle hypertrophy of the left gastrocnemius and revealed a protruded lumbar disc at the L5-S1 level. The protruded disc abuts the S1 root on the left side. Electromyography showed mild left S1 radiculopathy. Passive stretching and work load might clarify the origin of neurogenic hypertrophy but there is still a need for further evidence. Clinical, laboratory, magnetic resonance imaging and electromyography findings showed that S1 radiculopathy could be a cause of unilateral calf swelling in youth even in the absence of a history of back or leg pain. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Conditional reduction of adult born doublecortin-positive neurons reversibly impairs selective behaviours

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Lillian eGarrett

2015-11-01

Full Text Available Adult neurogenesis occurs in the adult mammalian subventricular zone (SVZ along the walls of the lateral ventricles and the subgranular zone (SGZ of the hippocampal dentate gyrus. While a burgeoning body of research implicates adult neurogenesis in olfactory bulb (OB - and hippocampal-related behaviors, the precise function continues to elude. To further assess the behavioral importance of adult neurogenesis, we herein generated a novel inducible transgenic mouse model of adult neurogenesis reduction where mice with CreERT2 under doublecortin (DCX promoter control were crossed with mice where diphtheria toxin A (DTA was driven by the Rosa26 promoter. Activation of DTA, through the administration of tamoxifen (TAM, results in a specific reduction of DCX+ immature neurons in both the hippocampal dentate gyrus and OB. We show that the decrease of DCX+ cells causes impaired social discrimination ability in both young adult (from 3 months and middle (from 10 months aged mice. Furthermore, these animals showed an age-independent altered coping behavior in the Forced Swim Test without clear changes in anxiety-related behavior. Notably, these behavior changes were reversible on repopulating the neurogenic zones with DCX+ cells on cessation of the tamoxifen treatment, demonstrating the specificity of this effect. Overall, these results support the notion that adult neurogenesis plays a role in social memory and in stress coping but not necessarily in anxiety-related behavior.

Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility

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Eric J. Neuberger

2017-09-01

Full Text Available Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury.

Diagnostic difficulties in the differentiation of neurogenic tumors of the parapharyngeal space in helical CT evaluations: A case report

International Nuclear Information System (INIS)

Czerniewicz-Kaminska, A.; Nowicki, J.; Jazwiec, P.; Kedzierski, B.; Janeczek, T.; Wilczynski, K.; Prudlak, E.

2005-01-01

Computerized tomography (CT) with contrast infusion and magnetic resonance imaging (MRI) play important roles in establishing the place of origin of neurogenic tumors. In this article we do not compare these two methods, but focus on the crucial role of CT imaging in the estimation and differential diagnosis of these tumors. We present the case of a 50-year-old man with clinical symptoms of peritonsillar abscess, which appeared to be a neurogenic tumor. The images obtained were deemed ambiguous. The possibility of a parotid gland tumor or a tumor of neurogenic origin was assumed. In this case we observed atypical clinical and radiological symptoms. The final diagnosis was based on a combination of radiological, clinical, and microbiological features of the tumor. Thanks to the cooperation of many professionals, we managed to establish the diagnosis of neuroangiofibroma, which exemplifies a tumor of the borderline, including elements of the neurogenic sheath and connective and chromaffin tissue. (author)

Single-Cell Transcriptomics and Fate Mapping of Ependymal Cells Reveals an Absence of Neural Stem Cell Function.

Science.gov (United States)

Shah, Prajay T; Stratton, Jo A; Stykel, Morgan Gail; Abbasi, Sepideh; Sharma, Sandeep; Mayr, Kyle A; Koblinger, Kathrin; Whelan, Patrick J; Biernaskie, Jeff

2018-05-03

Ependymal cells are multi-ciliated cells that form the brain's ventricular epithelium and a niche for neural stem cells (NSCs) in the ventricular-subventricular zone (V-SVZ). In addition, ependymal cells are suggested to be latent NSCs with a capacity to acquire neurogenic function. This remains highly controversial due to a lack of prospective in vivo labeling techniques that can effectively distinguish ependymal cells from neighboring V-SVZ NSCs. We describe a transgenic system that allows for targeted labeling of ependymal cells within the V-SVZ. Single-cell RNA-seq revealed that ependymal cells are enriched for cilia-related genes and share several stem-cell-associated genes with neural stem or progenitors. Under in vivo and in vitro neural-stem- or progenitor-stimulating environments, ependymal cells failed to demonstrate any suggestion of latent neural-stem-cell function. These findings suggest remarkable stability of ependymal cell function and provide fundamental insights into the molecular signature of the V-SVZ niche. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of neuroinflammation on the regenerative capacity of brain stem cells.

Science.gov (United States)

Russo, Isabella; Barlati, Sergio; Bosetti, Francesca

2011-03-01

In the adult brain, neurogenesis under physiological conditions occurs in the subventricular zone and in the dentate gyrus. Although the exact molecular mechanisms that regulate neural stem cell proliferation and differentiation are largely unknown, several factors have been shown to affect neurogenesis. Decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age-related brain dysfunction. Furthermore, in pathological conditions of the central nervous system associated with neuroinflammation, inflammatory mediators such as cytokines and chemokines can affect the capacity of brain stem cells and alter neurogenesis. In this review, we summarize the state of the art on the effects of neuroinflammation on adult neurogenesis and discuss the use of the lipopolysaccharide-model to study the effects of inflammation and reactive-microglia on brain stem cells and neurogenesis. Furthermore, we discuss the possible causes underlying reduced neurogenesis with normal aging and potential anti-inflammatory, pro-neurogenic interventions aimed at improving memory deficits in normal and pathological aging and in neurodegenerative diseases. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

TGFβ lengthens the G1 phase of stem cells in aged mouse brain.

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Daynac, Mathieu; Pineda, Jose R; Chicheportiche, Alexandra; Gauthier, Laurent R; Morizur, Lise; Boussin, François D; Mouthon, Marc-André

2014-12-01

Neurogenesis decreases during aging causing a progressive cognitive decline but it is still controversial whether proliferation defects in neurogenic niches result from a loss of neural stem cells or from an impairment of their progression through the cell cycle. Using an accurate fluorescence-activated cell sorting technique, we show that the pool of neural stem cells is maintained in the subventricular zone of middle-aged mice while they have a reduced proliferative potential eventually leading to the subsequent decrease of their progeny. In addition, we demonstrate that the G1 phase is lengthened during aging specifically in activated stem cells, but not in transit-amplifying cells, and directly impacts on neurogenesis. Finally, we report that inhibition of TGFβ signaling restores cell cycle progression defects in stem cells. Our data highlight the significance of cell cycle dysregulation in stem cells in the aged brain and provide an attractive foundation for the development of anti-TGFβ regenerative therapies based on stimulating endogenous neural stem cells. © 2014 AlphaMed Press.

Adult Neurogenesis in Sheep: Characterization and Contribution to Reproduction and Behavior

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Lévy, Frederic; Batailler, Martine; Meurisse, Maryse; Migaud, Martine

2017-01-01

Sheep have many advantages to study neurogenesis in comparison to the well-known rodent models. Their development and life expectancy are relatively long and they possess a gyrencephalic brain. Sheep are also seasonal breeders, a characteristic that allows studying the involvement of hypothalamic neurogenesis in the control of seasonal reproduction. Sheep are also able to individually recognize their conspecifics and develop selective and lasting bonds. Adult olfactory neurogenesis could be adapted to social behavior by supporting recognition of conspecifics. The present review reveals the distinctive features of the hippocampal, olfactory, and hypothalamic neurogenesis in sheep. In particular, the organization of the subventricular zone and the dynamic of neuronal maturation differs from that of rodents. In addition, we show that various physiological conditions, such as seasonal reproduction, gestation, and lactation differently modulate these three neurogenic niches. Last, we discuss recent evidence indicating that hypothalamic neurogenesis acts as an important regulator of the seasonal control of reproduction and that olfactory neurogenesis could be involved in odor processing in the context of maternal behavior. PMID:29109674

A systematic review and comparison of questionnaires in the management of spinal cord injury, multiple sclerosis and the neurogenic bladder.

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Tsang, B; Stothers, L; Macnab, A; Lazare, D; Nigro, M

2016-03-01

Validated questionnaires are increasingly the preferred method used to obtain historical information. Specialized questionnaires exist validated for patients with neurogenic disease including neurogenic bladder. Those currently available are systematically reviewed and their potential for clinical and research use are described. A systematic search via Medline and PubMed using the key terms questionnaire(s) crossed with Multiple Sclerosis (MS) and Spinal Cord Injury (SCI) for the years 1946 to January 22, 2014 inclusive. Additional articles were selected from review of references in the publications identified. Only peer reviewed articles published in English were included. 18 questionnaires exist validated for patients with neurogenic bladder; 14 related to MS, 3 for SCI, and 1 for neurogenic bladder in general; with 4 cross-validated in both MS and SCI. All 18 are validated for both male and female patients; 59% are available only in English. The domains of psychological impact and physical function are represented in 71% and 76% of questionnaires, respectively. None for the female population included elements to measure symptoms of prolapse. The last decade has seen an expansion of validated questionnaires to document bladder symptoms in neurogenic disease. Disease specific instruments are available for incorporation into the clinical setting for MS and SCI patients with neurogenic bladder. The availability of caregiver and interview options enhances suitability in clinical practice as they can be adapted to various extents of disability. Future developments should include expanded language validation to the top 10 global languages reported by the World Health Organization. © 2015 Wiley Periodicals, Inc.

SSEA-4 and YKL-40 positive progenitor subtypes in the subventricular zone of developing human neocortex

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Brøchner, Christian B; Møllgård, Kjeld

2016-01-01

The glycosphingolipid SSEA-4 and the glycoprotein YKL-40 have both been associated with human embryonic and neural stem cell differentiation. We investigated the distribution of SSEA-4 and YKL-40 positive cells in proliferative zones of human fetal forebrain using immunohistochemistry and double-...

[A swollen, painless calf caused by neurogenic muscle (pseudo)-hypertrophy

NARCIS (Netherlands)

Warrenburg, B.P.C. van de; Zwarts, M.J.; Engelen, B.G.M. van

2003-01-01

Neurogenic muscle (pseudo) hypertrophy of the calf was diagnosed in a 60-year-old man, who presented with chronic, painless and unilateral calf enlargement caused by a chronic S1 radiculopathy due to a lumbar disc hernia in the L5-S1 interspace. The differential diagnosis of a swelling of the calf

Urinary Tract Infection and Neurogenic Bladder.

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McKibben, Maxim J; Seed, Patrick; Ross, Sherry S; Borawski, Kristy M

2015-11-01

Urinary tract infections (UTIs) are frequent, recurrent, and lifelong for patients with neurogenic bladder and present challenges in diagnosis and treatment. Patients often present without classic symptoms of UTI but with abdominal or back pain, increased spasticity, and urinary incontinence. Failure to recognize and treat infections can quickly lead to life-threatening autonomic dysreflexia or sepsis, whereas overtreatment contributes to antibiotic resistance, thus limiting future treatment options. Multiple prevention methods are used but evidence-based practices are few. Prevention and treatment of symptomatic UTI requires a multimodal approach that focuses on bladder management as well as accurate diagnosis and appropriate antibiotic treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Neurogenic transdifferentiation of human adipose-derived stem cells? A critical protocol reevaluation with special emphasis on cell proliferation and cell cycle alterations.

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Kompisch, Kai Michael; Lange, Claudia; Steinemann, Doris; Skawran, Britta; Schlegelberger, Brigitte; Müller, Reinhard; Schumacher, Udo

2010-11-01

Adipose-derived stem cells (ASCs) are reported to display multilineage differentiation potential, including neuroectodermal pathways. The aim of the present study was to critically re-evaluate the potential neurogenic (trans-)differentiation capacity of ASCs using a neurogenic induction protocol based on the combination of isobutylmethylxanthine (IBMX), indomethacin and insulin. ASCs isolated from lipo-aspirate samples of five healthy female donors were characterized and potential neurogenic (trans-)differentiation was assessed by means of immunohistochemistry and gene expression analyses. Cell proliferation and cell cycle alterations were studied, and the expression of CREB/ATF transcription factors was analyzed. ASCs expressed CD59, CD90 and CD105, and were tested negative for CD34 and CD45. Under neurogenic induction, ASCs adopted a characteristic morphology comparable to neur(on)al progenitors and expressed musashi1, β-III-tubulin and nestin. Gene expression analyses revealed an increased expression of β-III-tubulin, GFAP, vimentin and BDNF, as well as SOX4 in induced ASCs. Cell proliferation was significantly reduced under neurogenic induction; cell cycle analyses showed a G2-cell cycle arrest accompanied by differential expression of key regulators of cell cycle progression. Differential expression of CREB/ATF transcription factors could be observed on neurogenic induction, pointing to a decisive role of the cAMP-CREB/ATF system. Our findings may point to a potential neurogenic (trans-)differentiation of ASCs into early neur(on)al progenitors, but do not present definite evidence for it. Especially, the adoption of a neural progenitor cell-like morphology must not automatically be misinterpreted as a specific characteristic of a respective (trans-)differentiation process, as this may as well be caused by alterations of cell cycle progression.

Botulinum Neurotoxin Injection for the Treatment of Recurrent Temporomandibular Joint Dislocation with and without Neurogenic Muscular Hyperactivity

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Kazuya Yoshida

2018-04-01

Full Text Available The aim of this study was to compare treatment outcomes following intramuscular injection of botulinum neurotoxin (BoNT in patients with recurrent temporomandibular joint dislocation, with and without muscle hyperactivity due to neurological diseases. Thirty-two patients (19 women and 13 men, mean age: 62.3 years with recurrent temporomandibular joint dislocation were divided into two groups: neurogenic (8 women and 12 men and habitual (11 women and 1 man. The neurogenic group included patients having neurological disorders, such as Parkinson’s disease or oromandibular dystonia, that are accompanied by muscle hyperactivity. BoNT was administered via intraoral injection to the inferior head of the lateral pterygoid muscle. In total, BoNT injection was administered 102 times (mean 3.2 times/patient. The mean follow-up duration was 29.5 months. The neurogenic group was significantly (p < 0.001 younger (47.3 years than the habitual group (84.8 years and required significantly (p < 0.01 more injections (4.1 versus 1.7 times to achieve a positive outcome. No significant immediate or delayed complications occurred. Thus, intramuscular injection of BoNT into the lateral pterygoid muscle is an effective and safe treatment for habitual temporomandibular joint dislocation. More injections are required in cases of neurogenic temporomandibular joint dislocation than in those of habitual dislocation without muscle hyperactivity.

Neurogenic gene regulatory pathways in the sea urchin embryo.

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Wei, Zheng; Angerer, Lynne M; Angerer, Robert C

2016-01-15

During embryogenesis the sea urchin early pluteus larva differentiates 40-50 neurons marked by expression of the pan-neural marker synaptotagmin B (SynB) that are distributed along the ciliary band, in the apical plate and pharyngeal endoderm, and 4-6 serotonergic neurons that are confined to the apical plate. Development of all neurons has been shown to depend on the function of Six3. Using a combination of molecular screens and tests of gene function by morpholino-mediated knockdown, we identified SoxC and Brn1/2/4, which function sequentially in the neurogenic regulatory pathway and are also required for the differentiation of all neurons. Misexpression of Brn1/2/4 at low dose caused an increase in the number of serotonin-expressing cells and at higher dose converted most of the embryo to a neurogenic epithelial sphere expressing the Hnf6 ciliary band marker. A third factor, Z167, was shown to work downstream of the Six3 and SoxC core factors and to define a branch specific for the differentiation of serotonergic neurons. These results provide a framework for building a gene regulatory network for neurogenesis in the sea urchin embryo. © 2016. Published by The Company of Biologists Ltd.

Orphan nuclear receptor TLX activates Wnt/β-catenin signalling to stimulate neural stem cell proliferation and self-renewal

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Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T.; Gage, Fred H.; Evans, Ronald M.; Shi, Yanhong

2010-01-01

The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/β-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/β-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active β-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a β-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active β-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active β-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active β-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/β-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode. PMID:20010817

Orphan nuclear receptor TLX activates Wnt/beta-catenin signalling to stimulate neural stem cell proliferation and self-renewal.

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Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T; Gage, Fred H; Evans, Ronald M; Shi, Yanhong

2010-01-01

The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/beta-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/beta-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active beta-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a beta-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active beta-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active beta-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active beta-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/beta-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode.

The adult spinal cord harbors a population of GFAP-positive progenitors with limited self-renewal potential.

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Fiorelli, Roberto; Cebrian-Silla, Arantxa; Garcia-Verdugo, Jose-Manuel; Raineteau, Olivier

2013-12-01

Adult neural stem cells (aNSCs) of the forebrain are GFAP-expressing cells that are intercalated within ependymal cells of the subventricular zone (SVZ). Cells showing NSCs characteristics in vitro can also be isolated from the periaqueductal region in the adult spinal cord (SC), but contradicting results exist concerning their glial versus ependymal identity. We used an inducible transgenic mouse line (hGFAP-CreERT2) to conditionally label GFAP-expressing cells in the adult SVZ and SC periaqueduct, and directly and systematically compared their self-renewal and multipotential properties in vitro. We demonstrate that a population of GFAP(+) cells that share the morphology and the antigenic properties of SVZ-NSCs mostly reside in the dorsal aspect of the central canal (CC) throughout the spinal cord. These cells are non-proliferative in the intact spinal cord, but incorporate the S-phase marker EdU following spinal cord injury. Multipotent, clonal YFP-expressing neurospheres (i.e., deriving from recombined GFAP-expressing cells) were successfully obtained from both the intact and injured spinal cord. These spheres however showed limited self-renewal properties when compared with SVZ-neurospheres, even after spinal cord injury. Altogether, these results demonstrate that significant differences exist in NSCs lineages between neurogenic and non-neurogenic regions of the adult CNS. Thus, although we confirm that a population of multipotent GFAP(+) cells co-exists alongside with multipotent ependymal cells within the adult SC, we identify these cells as multipotent progenitors showing limited self-renewal properties. Copyright © 2013 Wiley Periodicals, Inc.

Arginine Methylation Regulates MEIS2 Nuclear Localization to Promote Neuronal Differentiation of Adult SVZ Progenitors

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Jasmine Kolb

2018-04-01

Full Text Available Summary: Adult neurogenesis is regulated by stem cell niche-derived extrinsic factors and cell-intrinsic regulators, yet the mechanisms by which niche signals impinge on the activity of intrinsic neurogenic transcription factors remain poorly defined. Here, we report that MEIS2, an essential regulator of adult SVZ neurogenesis, is subject to posttranslational regulation in the SVZ olfactory bulb neurogenic system. Nuclear accumulation of MEIS2 in adult SVZ-derived progenitor cells follows downregulation of EGFR signaling and is modulated by methylation of MEIS2 on a conserved arginine, which lies in close proximity to nested binding sites for the nuclear export receptor CRM1 and the MEIS dimerization partner PBX1. Methylation impairs interaction with CRM1 without affecting PBX1 dimerization and thereby allows MEIS2 nuclear accumulation, a prerequisite for neuronal differentiation. Our results describe a form of posttranscriptional modulation of adult SVZ neurogenesis whereby an extrinsic signal fine-tunes neurogenesis through posttranslational modification of a transcriptional regulator of cell fate. : A hallmark of adult neurogenesis is its strong dependence on physiological stimuli and environmental signals. Schulte and colleagues show that the nuclear localization and activity of a transcriptional regulator of adult neurogenesis is controlled by posttranslational modification. Their results link intrinsic control over neuron production to external signals and help to explain how adult neurogenesis can occur “on demand.” Keywords: subventricular zone, stem cell niche, posttranslational modification, controlled nuclear import, TALE-homdomain protein, MEIS2, PBX1, CRM1, neurogenesis, stem cell niche

Urinary tract infection in the neurogenic bladder

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Vigil, Humberto R.

2016-01-01

There is a high incidence of urinary tract infection (UTI) in patients with neurogenic lower urinary tract function. This results in significant morbidity and health care utilization. Multiple well-established risk factors unique to a neurogenic bladder (NB) exist while others require ongoing investigation. It is important for care providers to have a good understanding of the different structural, physiological, immunological and catheter-related risk factors so that they may be modified when possible. Diagnosis remains complicated. Appropriate specimen collection is of paramount importance and a UTI cannot be diagnosed based on urinalysis or clinical presentation alone. A culture result with a bacterial concentration of ≥103 CFU/mL in combination with symptoms represents an acceptable definition for UTI diagnosis in NB patients. Cystoscopy, ultrasound and urodynamics should be utilized for the evaluation of recurrent infections in NB patients. An acute, symptomatic UTI should be treated with antibiotics for 5–14 days depending on the severity of the presentation. Antibiotic selection should be based on local and patient-based resistance patterns and the spectrum should be as narrow as possible if there are no concerns regarding urosepsis. Asymptomatic bacteriuria (AB) should not be treated because of rising resistance patterns and lack of clinical efficacy. The most important preventative measures include closed catheter drainage in patients with an indwelling catheter and the use of clean intermittent catheterization (CIC) over other methods of bladder management if possible. The use of hydrophilic or impregnated catheters is not recommended. Intravesical Botox, bacterial interference and sacral neuromodulation show significant promise for the prevention of UTIs in higher risk NB patients and future, multi-center, randomized controlled trials are required. PMID:26904414

Neurogenic inflammation: a study of rat trigeminal ganglion

DEFF Research Database (Denmark)

Kristiansen, Kim Anker; Edvinsson, Lars

2010-01-01

Calcitonin gene-related peptide (CGRP) is linked to neurogenic inflammation and to migraine. Activation of the trigeminovascular system plays a prominent role during migraine attacks with the release of CGRP. The trigeminal ganglion (TG) contains three main cell types: neurons, satellite glial...... cells (SGC) and Schwann cells; the first two have before been studied in vitro separately. Culture of rat TG provides a method to induce inflammation and the possibility to evaluate the different cell types in the TG simultaneously. We investigated expression levels of various inflammatory cytokines...

A Clinician Survey of Speech and Non-Speech Characteristics of Neurogenic Stuttering

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Theys, Catherine; van Wieringen, Astrid; De Nil, Luc F.

2008-01-01

This study presents survey data on 58 Dutch-speaking patients with neurogenic stuttering following various neurological injuries. Stroke was the most prevalent cause of stuttering in our patients, followed by traumatic brain injury, neurodegenerative diseases, and other causes. Speech and non-speech characteristics were analyzed separately for…

Chronic Renal Failure Secondary to Unrecognized Neurogenic Bladder in A Child with Myelodysplasia.

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Ahmed, Shameem; Paul, Siba Prosad

2017-01-01

Myelodysplasia includes a group of developmental anomalies resulting from defects that occur during neural tube closure. Urological morbidity in patients with myelodysplasia is significant and if not treated appropriately in a timely manner can potentially lead to progressive renal failure, requiring dialysis or transplantation. We report the case of a 13-year old girl with neurogenic bladder who presented chronic renal failure secondary to lipomyelomeningocele with retethering of cord. She was managed with urinary indwelling catheterization until optimization of renal function and then underwent detethering of cord with excision and repair of residual lipomeningomyelocele. Her renal parameters improved gradually over weeks and then were managed on self clean intermittent catheterization. The case emphasizes the need for considering retethering of spinal cord in children with myelodysplasia where symptoms of neurogenic bladder and recurrent urinary tract infections occur.

Neurogenic period of ascending tract neurons in the upper lumbar spinal cord of the rat

International Nuclear Information System (INIS)

Nandi, K.N.; Beal, J.A.; Knight, D.S.

1990-01-01

Although the neurogenic period for neurons in the lumbar spinal cord has been clearly established (Days 12 through 16 of gestation), it is not known when the neurogenesis of ascending tract neurons is completed within this period. The purpose of the present study was to determine the duration of the neurogenic period for projection neurons of the ascending tracts. To label neurons undergoing mitosis during this period, tritiated thymidine was administered to fetal rats on Embryonic (E) Days E13 through E16 of gestation. Ascending tract neurons of the lumbar cord were later (Postnatal Days 40-50) labeled in each animal with a retrograde tracer, Fluoro-Gold, applied at the site of a hemisection at spinal cord segment C3. Ascending tract neurons which were undergoing mitosis in the upper lumbar cord were double labeled, i.e., labeled with both tritiated thymidine and Fluoro-Gold. On Day E13, 89-92% of the ascending tract neurons were double labeled; on Day E14, 35-37%; and on Day E15, 1-4%. Results showed, then, that some ascending tract neurons were double labeled through Day E15 and were, therefore, proliferating in the final one-third of the neurogenic period. Ascending tract neurons proliferating on Day E15 were confined to laminae III, IV, V, and X and the nucleus dorsalis. Long tract neurons in the superficial dorsal horn (laminae I and II), on the other hand, were found to have completed neurogenesis on Day E14 of gestation. Results of the present study show that spinal neurogenesis of ascending projection neurons continues throughout most of the neurogenic period and does not completely follow the well-established ventral to dorsal gradient

Neurogenic heterotopic ossification: epidemiology and morphology on conventional radiographs in an early neurological rehabilitation population

International Nuclear Information System (INIS)

Seipel, R.; Langner, S.; Lippa, M.; Kuehn, J.P.; Hosten, N.; Platz, T.

2012-01-01

To retrospectively evaluate neurogenic heterotopic ossification in an early neurological rehabilitation population (phases B and C) with respect to epidemiology and morphology on conventional radiographs. Over a 4-year period, 1,463 patients treated at a clinic for early neurological rehabilitation were evaluated for clinical symptoms of neurogenic heterotopic ossification. In case of clinical suspicion, plain radiographs of the expected sites were obtained. If heterotopic ossification was detected, the initial and subsequent radiographs were retrospectively analyzed for sites, size, and morphology. Immature lesions were categorized as small (<10 mm) or large (10-100 mm). The prevalence rate of neurogenic heterotopic ossification was 2.05%. The condition was most common in young male adults. The hip was the most common site accounting for more than half of the cases. Two or more ossifications were seen in 56.7% of the affected patients with approximately two-thirds showing bilateral symmetric involvement of corresponding joint regions. The size of ossifications strongly varied interindividually. Small immature lesions demonstrated less progression in size than large lesions during maturation (P < 0.05). Standard radiographs, as a fast and inexpensive technique, allow the expected size progression of heterotopic ossifications during maturation to be estimated, which is relevant in terms of therapeutic decisions, patient mobilization, and neurological rehabilitation. (orig.)

bicaudal-C is required for the formation of anterior neurogenic ectoderm in the sea urchin embryo.

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Yaguchi, Shunsuke; Yaguchi, Junko; Inaba, Kazuo

2014-10-31

bicaudal-C (bicC) mRNA encodes a protein containing RNA-binding domains that is reported to be maternally present with deflection in the oocytes/eggs of some species. The translated protein plays a critical role in the regulation of cell fate specification along the body axis during early embryogenesis in flies and frogs. However, it is unclear how it functions in eggs in which bicC mRNA is uniformly distributed, for instance, sea urchin eggs. Here, we show the function of BicC in the formation of neurogenic ectoderm of the sea urchin embryo. Loss-of-function experiments reveal that BicC is required for serotonergic neurogenesis and for expression of ankAT-1 gene, which is essential for the formation of apical tuft cilia in the neurogenic ectoderm of the sea urchin embryo. In contrast, the expression of FoxQ2, the neurogenic ectoderm specification transcription factor, is invariant in BicC morphants. Because FoxQ2 is an upstream factor of serotonergic neurogenesis and ankAT-1 expression, these data indicate that BicC functions in regulating the events that are coordinated by FoxQ2 during sea urchin embryogenesis.

The neural elements in the lining of the ventricular-subventricular zone: making an old story new by high-resolution scanning electron microscopy

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Carlos Alexandre Dos Santos Haemmerle

2015-10-01

Full Text Available The classical description of the neural elements that compose the lining of brain ventricles introduces us to the single layer of ependymal cells. However, new findings, especially in the lateral ventricle - the major niche for the generation of new neurons in the adult brain - have provided information about additional cell elements that influence the organization of this part of the ventricular system and produce important contributions to neurogenesis. To complement the cell neurochemistry findings, we present a three-dimensional in situ description that demonstrates the anatomical details of the different types of ciliated cells and the innervation of these elements. After processing adult rat brains for ultrastructural analysis by high-resolution scanning electron microscopy and transmission electron microscopy, we observed a heterogeneous pattern of cilia distribution at the different poles of the lateral ventricle surface. Furthermore, we describe the particular three-dimensional aspects of the ciliated cells of the lateral ventricle, in addition the fiber bundles and varicose axons surrounding these cells. Therefore, we provide a unique ultrastructural description of the three-dimensional in situ organization of the lateral ventricle surface, highlighting its innervation, to corroborate the available neurochemical and functional findings regarding the factors that regulate this neurogenic niche.

Neurogenic bladder evaluation and management after spinal cord injury: Current practice among urologists working in Saudi Arabia

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Waleed Al Taweel

2011-01-01

Full Text Available Aim: The aim of this study is to determine the current trends in the management and surveillance of the NB population secondary to spinal cord injury (SCI or myelomeningocele by certified urologist working in Saudi Arabia and to compare it to the current guidelines. Materials and Methods: A cross-sectional study was conducted using a 12-points questionnaire distributed to urologists working in Saudi Arabia and registered at the Saudi medical association. The assessment and follow-up of upper and lower urinary tract function in neurogenic bladder patients, their optimal frequency and management of related infections were the topics of inquiry. Results: Of the 272 urologists surveyed, 105 responded, yielding a response rate of 38%. Eighty-nine percent of respondents said that ultrasound was their diagnostic tool of choice for upper tract evaluation. Sixty-one percent of respondents said that they would follow their patients with a multichannel urodynamic study. Forty percent of urologists stated that they would treat asymptomatic bacteriuria. Clean intermittent catheterization (CIC was the most common modality chosen for the management of neurogenic bladder in patients with emptying difficulties. Conclusion: This study confirms that most urologists in Saudi Arabia involved with neurogenic bladder management. However, more than one third of the urologists do not have urodynamic machine and only two of the reporting practitioners has a videourodynamic machine. The results emphasize the need for clear guidelines in this field of urology in Saudi Arabia. Highly specialized rehabilitation centers for neurogenic bladder secondary to SCI are required for optimal care and urologist teaching.

Neurogenic bladder evaluation and management after spinal cord injury: Current practice among urologists working in Saudi Arabia.

Science.gov (United States)

Al Taweel, Waleed; Alkhayal, Abdullah

2011-01-01

The aim of this study is to determine the current trends in the management and surveillance of the NB population secondary to spinal cord injury (SCI) or myelomeningocele by certified urologist working in Saudi Arabia and to compare it to the current guidelines. A cross-sectional study was conducted using a 12-points questionnaire distributed to urologists working in Saudi Arabia and registered at the Saudi medical association. The assessment and follow-up of upper and lower urinary tract function in neurogenic bladder patients, their optimal frequency and management of related infections were the topics of inquiry. Of the 272 urologists surveyed, 105 responded, yielding a response rate of 38%. Eighty-nine percent of respondents said that ultrasound was their diagnostic tool of choice for upper tract evaluation. Sixty-one percent of respondents said that they would follow their patients with a multichannel urodynamic study. Forty percent of urologists stated that they would treat asymptomatic bacteriuria. Clean intermittent catheterization (CIC) was the most common modality chosen for the management of neurogenic bladder in patients with emptying difficulties. This study confirms that most urologists in Saudi Arabia involved with neurogenic bladder management. However, more than one third of the urologists do not have urodynamic machine and only two of the reporting practitioners has a videourodynamic machine. The results emphasize the need for clear guidelines in this field of urology in Saudi Arabia. Highly specialized rehabilitation centers for neurogenic bladder secondary to SCI are required for optimal care and urologist teaching.

[Giant prostatic calculus with neurogenic bladder disease and prostate diverticulum: a case report and review of the literature].

Science.gov (United States)

Li, Xiao-Shi; Quan, Chang-Yi; Li, Gang; Cai, Qi-Liang; Hu, Bin; Wang, Jiu-Wei; Niu, Yuan-Jie

2013-02-01

To study the etiology, clinical manifestation, diagnosis and treatment of giant prostatic calculus with neurogenic bladder disease and prostate diverticulum. We retrospectively analyzed the clinical data of a case of giant prostatic calculus with neurogenic bladder disease and prostate diverticulum and reviewed the relevant literature. The patient was a 37-year-old man, with urinary incontinence for 22 years and intermittent dysuria with frequent micturition for 9 years, aggravated in the past 3 months. He had received surgery for spina bifida and giant vesico-prostatic calculus. The results of preoperative routine urinary examination were as follows: WBC 17 -20/HPF, RBC 12 - 15/HPF. KUB, IVU and pelvic CT revealed spina bifida occulta, neurogenic bladder and giant prostatic calculus. The patient underwent TURP and transurethral lithotripsy with holmium-YAG laser. The prostatic calculus was carbonate apatite in composition. Urinary dynamic images at 2 weeks after surgery exhibited significant improvement in the highest urine flow rate and residual urine volume. Seventeen months of postoperative follow-up showed dramatically improved urinary incontinence and thicker urine stream. Prostate diverticulum with prostatic giant calculus is very rare, and neurogenic bladder may play a role in its etiology. Cystoscopy is an accurate screening method for its diagnosis. For the young patients and those who wish to retain sexual function, TURP combined with holmium laser lithotripsy can be employed, and intraoperative rectal examination should be taken to ensure complete removal of calculi.

Neurogenic Bladder in Lyme Disease

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Mi-hwa Kim

2012-12-01

Full Text Available Lyme disease is a multi-systemic, tick-borne infectious disease caused by a spirochete, Borrelia burgdorferi. Various urologic symptoms are associated with Lyme disease, which can be primary or late manifestations of the disease. Although voiding dysfunction is a rarely reported symptom in patients with Lyme disease, it is one of the most disabling complications of Lyme disease. Korea is not an endemic area of Lyme disease, thus, fewer cases have been reported. Herein, we report a case of a 32-year-old man with rapidly progressive bilateral ptosis, dysphagia, spastic paraparesis, and voiding difficulty in whom Lyme disease was diagnosed through serologic tests for antibodies and Western blot testing. A urodynamic study demonstrated detrusor areflexia and bulbocavernosus reflex tests showed delayed latency, indicating demyelination at S2-S4 levels. He received a 4-week course of intravenous ceftriaxone (2 g/day. The patient has recovered from the bilateral ptosis and spastic paraparesis but still suffers from neurogenic bladder.

Polysaccharides from Wolfberry Prevents Corticosterone-Induced Inhibition of Sexual Behavior and Increases Neurogenesis

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Lau, Benson Wui-Man; Lee, Jada Chia-Di; Li, Yue; Fung, Sophia Man-Yuk; Sang, Yan-Hua; Shen, Jiangang; Chang, Raymond Chuen-Chung; So, Kwok-Fai

2012-01-01

Lycium barbarum, commonly known as wolfberry, has been used as a traditional Chinese medicine for the treatment of infertility and sexual dysfunction. However, there is still a scarcity of experimental evidence to support the pro-sexual effect of wolfberry. The aim of this study is to determine the effect of Lycium barbarum polysaccharides (LBP) on male sexual behavior of rats. Here we report that oral feeding of LBP for 21 days significantly improved the male copulatory performance including increase of copulatory efficiency, increase of ejaculation frequency and shortening of ejaculation latency. Furthermore, sexual inhibition caused by chronic corticosterone was prevented by LBP. Simultaneously, corticosterone suppressed neurogenesis in subventricular zone and hippocampus in adult rats, which could be reversed by LBP. The neurogenic effect of LBP was also shown in vitro. Significant correlation was found between neurogenesis and sexual performance, suggesting that the newborn neurons are associated with reproductive successfulness. Blocking neurogenesis in male rats abolished the pro-sexual effect of LBP. Taken together, these results demonstrate the pro-sexual effect of LBP on normal and sexually-inhibited rats, and LBP may modulate sexual behavior by regulating neurogenesis. PMID:22523540

Surgical Management of Anatomic Bladder Outlet Obstruction in Males with Neurogenic Bladder Dysfunction: A Systematic Review.

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Noordhoff, Toscane C; Groen, Jan; Scheepe, Jeroen R; Blok, Bertil F M

2018-03-15

Surgical treatment of anatomic bladder outlet obstruction (BOO) may be indicated in males with neurogenic bladder dysfunction. A bothersome complication after surgery is urinary incontinence. To identify the optimal practice in the surgical treatment of anatomic BOO in males with neurogenic bladder dysfunction, due to multiple sclerosis, Parkinson disease, spinal cord injury (SCI), spina bifida, or cerebrovascular accident (CVA). A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Medline, Embase, Cochrane controlled trial databases, Web of Science, and Google Scholar were searched for publications until January 2017. A total of 930 abstracts were screened. Eight studies were included. The types of anatomic BOO discussed were benign prostate obstruction, urethral stricture, and bladder neck sclerosis. The identified surgical treatments were transurethral resection of the prostate (TURP) in patients with Parkinson, CVA or SCI, endoscopic treatment of urethral stricture by laser ablation or urethrotomy (mainly in SCI patients), and bladder neck resection (BNR) in SCI patients. The outcome of TURP may be highly variable, and includes persistent or de novo urinary incontinence, regained normal micturition control, and urinary continence. Good results were seen in BNR and endoscopic urethrotomy studies. Laser ablation and cold knife urethrotomy resulted in restarting intermittent catheterization or adequate voiding. Overall, a high risk of bias was found. This systematic review provides an overview of the current literature on the outcome of several surgical approaches of different types of anatomic BOO in males with neurogenic bladder dysfunction. Identifying the optimal practice was impossible due to limited availability of high-quality studies. The outcome of several surgical approaches in males with neurogenic bladder dysfunction with benign prostate obstruction, urethral stricture

Sarcopenia, a Neurogenic Syndrome?

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Ping Kwan

2013-01-01

Full Text Available Sarcopenia is an aging-associated condition, which is currently characterized by the loss of muscle mass and muscle strength. However, there is no consensus regarding its characterization hitherto. As the world older adult population is on the rise, the impact of sarcopenia becomes greater. Due to the lack of effective treatments, sarcopenia is still a persisting problem among the global older adults and should not be overlooked. As a result, it is vital to investigate deeper into the mechanism underlying the pathogenesis of sarcopenia in order to develop more effective therapeutic interventions and to inscribe a more uniform characterization. The etiology of sarcopenia is currently found to be multifactorial, and most of the pharmacological researches are focused on the muscular factors in aging. Although the complete mechanism underlying the development of sarcopenia is still waiting to be elucidated, we propose in this article that the primary trigger of sarcopenia may be neurogenic in origin based on the intimate relationship between the nervous and muscular system, namely, the motor neuron and its underlying muscle fibers. Both of them are affected by the cellular environment and their physiological activity.

Surgical Management of Neurogenic Lower Urinary Tract Dysfunction.

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Gor, Ronak A; Elliott, Sean P

2017-08-01

Surgery for patients with neurogenic urinary tract dysfunction (nLUTD) is indicated when medical therapy fails, to correct conditions affecting patient safety, or when surgery can enhance the quality of life better than nonoperative management. Examples include failure of maximal medical therapy, inability to perform or aversion to clean intermittent catheterization, refractory incontinence, and complications from chronic, indwelling catheters. Adults with nLUTD have competing risk factors, including previous operations, obesity, poor nutritional status, complex living arrangements, impaired dexterity/paralysis, and impaired executive and cognitive function. Complications are common in this subgroup of patients requiring enduring commitments from surgeons, patients, and their caretakers. Copyright © 2017 Elsevier Inc. All rights reserved.

Thoracic rat spinal cord contusion injury induces remote spinal gliogenesis but not neurogenesis or gliogenesis in the brain.

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Steffen Franz

Full Text Available After spinal cord injury, transected axons fail to regenerate, yet significant, spontaneous functional improvement can be observed over time. Distinct central nervous system regions retain the capacity to generate new neurons and glia from an endogenous pool of progenitor cells and to compensate neural cell loss following certain lesions. The aim of the present study was to investigate whether endogenous cell replacement (neurogenesis or gliogenesis in the brain (subventricular zone, SVZ; corpus callosum, CC; hippocampus, HC; and motor cortex, MC or cervical spinal cord might represent a structural correlate for spontaneous locomotor recovery after a thoracic spinal cord injury. Adult Fischer 344 rats received severe contusion injuries (200 kDyn of the mid-thoracic spinal cord using an Infinite Horizon Impactor. Uninjured rats served as controls. From 4 to 14 days post-injury, both groups received injections of bromodeoxyuridine (BrdU to label dividing cells. Over the course of six weeks post-injury, spontaneous recovery of locomotor function occurred. Survival of newly generated cells was unaltered in the SVZ, HC, CC, and the MC. Neurogenesis, as determined by identification and quantification of doublecortin immunoreactive neuroblasts or BrdU/neuronal nuclear antigen double positive newly generated neurons, was not present in non-neurogenic regions (MC, CC, and cervical spinal cord and unaltered in neurogenic regions (dentate gyrus and SVZ of the brain. The lack of neuronal replacement in the brain and spinal cord after spinal cord injury precludes any relevance for spontaneous recovery of locomotor function. Gliogenesis was increased in the cervical spinal cord remote from the injury site, however, is unlikely to contribute to functional improvement.

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

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Sandra A Acosta

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

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

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

2013-01-01

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

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

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

2013-01-01

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

Neurogenic plasma exudation mediates grain dust-induced tissue injury in vivo.

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Gao, X P; Von Essen, S; Rubinstein, I

1997-02-01

The purpose of this study was to determine whether an aqueous extract of grain sorghum dust (GDE) elicits neurogenic plasma exudation in the oral mucosa in vivo. Using intravital microscopy, we found that GDE elicited significant, concentration-dependent leaky site formation and an increase in clearance of fluorescein isothiocyanate-labeled dextran (FITC-dextran; mol mass 70 kDa) from the hamster cheek pouch (P grain sorghum dust elicits immediate oral mucosa inflammation in vivo.

Congenital contractural arachnodactyly with neurogenic muscular atrophy: case report

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Scola Rosana Herminia

2001-01-01

Full Text Available We report the case of a 3-1/2-year-old girl with hypotonia, multiple joint contractures, hip luxation, arachnodactyly, adducted thumbs, dolichostenomelia, and abnormal external ears suggesting the diagnosis of congenital contractural arachnodactyly (CCA. The serum muscle enzimes were normal and the needle electromyography showed active and chronic denervation. The muscle biopsy demonstrated active and chronic denervation compatible with spinal muscular atrophy. Analysis of exons 7 and 8 of survival motor neuron gene through polymerase chain reaction did not show deletions. Neurogenic muscular atrophy is a new abnormality associated with CCA, suggesting that CCA is clinically heterogeneous.

Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

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Cécile eCoste

2015-06-01

Full Text Available Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL12-abundant reticular (CAR cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs, which have been recently identified as neural crest-derived cells (NCSCs. Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-to-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system.

Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

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Coste, Cécile; Neirinckx, Virginie; Gothot, André; Wislet, Sabine; Rogister, Bernard

2015-01-01

Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC) function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL) 12-abundant reticular (CAR) cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs), which have been recently identified as neural crest-derived cells (NCSCs). Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system.

[Clonazepam in therapy of neurogenic syncopal states].

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Musaeva, Z A

2001-01-01

27 patients with frequent neurogenic syncopes (NS) resistant to conventional therapy were treated with clonazepam. The average age of the patients was 29.8 +/- 11.6 years. There were 1-2 syncopes in a month. Both before and after the treatment an active orthostatic test was performed with ECG registration and following analysis of variability of the cardiac rhythm. Clonazepam was administered in a dose of 2-2.5 mg/day during 8-9 weeks. Clinical improvement in the form of a lack of syncopes was observed in 20 patients (74%); 3 patients (10%) had isolated lipothymic states; 2 patients discontinued the treatment because of side-effects (dizziness). The results of the examination of 23 patients 6 months after clonazepam therapy testified the stability of the therapeutic effect.

[Electromyographic differential diagnosis in cases of abducens nerve paresis with nuclear or distal neurogenic sive myogenic origine (author's transl)].

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Heuser, M

1979-09-01

Abducens nerve paresis may be of nuclear, of peripheral distal neurogenic origine, or is simulated by a myogenic weakness of abduction. Polygraphic emg analysis of the oculoauricularphenomenon (oap) permits a differentiation. In the emg, the oap proved to be a physiologic and constant automatic and always bilateral interaction between the hemolateral abducens nerve and both Nn. faciales with corresponding and obligatory coinnervation of the Mm. retroauricularis of the external ear. In case of medullary, nuclear or internuclear lesions, the oap is disturbed, instable, diminished or abolished, whereas in distal neurogenic or myogenic paresis, even in complete paralysis the oap is bilaterally well preserved.

[Major influential factors of the micturition alert device dedicated to neurogenic bladders].

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Wang, Jianhuo; Hou, Chunlin; Zheng, Xianyou; Xu, Zhen; Wang, Wanhong; Lin, Haodong

2008-08-01

To study major influential factors of the micturition alert device dedicated to neurogenic bladders for the product design and clinical application of the device. One ferrite permanent magnet with thickness and diameter of 3 mm and 10 mm, respectively, and three NdFeB permanent magnets with the thickness of 3 mm and diameter of 10, 15 and 20 mm, respectively, were used. The effects of thickness of the abdominal wall as well as the position and type of permanent magnets on the micturition alert device dedicated to neurogenic bladders were measured in vitro simulated test, when the abdominal wall was set to 2, 3, 4, 5, 6, 7, 8 and 9 cm, respectively, and the position of permanent magnets was 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 cm, respectively. The effect of the geomagnetic field on the device was measured under the condition that the thickness of the simulated abdominal wall was set to 2, 3, 4 and 5 cm, respectively, and the position of permanent magnets was 2, 3, 4, 5, 6, 7, 8, 9 and 10 cm, respectively. The value showed in the warning unit was positively correlated with the position of the ferrite permanent magnet only when the thickness of the simulated abdominal wall was 2 cm (r=0.632, P NdFeB permanent magnets was significant (r > 0.622, P NdFeB permanent magnets, but weakened with the increasing thickness of the simulated abdominal wall. The effect of the geomagnetic field was correlated with the exposition of the body, the position of the permanent magnet and the thickness of the abdominal wall. The major influential factors of the micturition alert device dedicated to neurogenic bladder include the magnetism and location of the permanent magnet, the thickness of the abdominal wall and the geomagnetic field. These factors are correlated with and affect each other. Reasonable allocation of these factors may optimize the device.

Disruption of neural progenitors along the ventricular and subventricular zones in periventricular heterotopia

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Ferland, Russell J.; Batiz, Luis Federico; Neal, Jason; Lian, Gewei; Bundock, Elizabeth; Lu, Jie; Hsiao, Yi-Chun; Diamond, Rachel; Mei, Davide; Banham, Alison H.; Brown, Philip J.; Vanderburg, Charles R.; Joseph, Jeffrey; Hecht, Jonathan L.; Folkerth, Rebecca; Guerrini, Renzo; Walsh, Christopher A.; Rodriguez, Esteban M.; Sheen, Volney L.

2009-01-01

Periventricular heterotopia (PH) is a disorder characterized by neuronal nodules, ectopically positioned along the lateral ventricles of the cerebral cortex. Mutations in either of two human genes, Filamin A (FLNA) or ADP-ribosylation factor guanine exchange factor 2 (ARFGEF2), cause PH (Fox et al. in ‘Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia'. Neuron, 21, 1315–1325, 1998; Sheen et al. in ‘Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex'. Nat. Genet., 36, 69–76, 2004). Recent studies have shown that mutations in mitogen-activated protein kinase kinase kinase-4 (Mekk4), an indirect interactor with FlnA, also lead to periventricular nodule formation in mice (Sarkisian et al. in ‘MEKK4 signaling regulates filamin expression and neuronal migration'. Neuron, 52, 789–801, 2006). Here we show that neurons in post-mortem human PH brains migrated appropriately into the cortex, that periventricular nodules were primarily composed of later-born neurons, and that the neuroependyma was disrupted in all PH cases. As studied in the mouse, loss of FlnA or Big2 function in neural precursors impaired neuronal migration from the germinal zone, disrupted cell adhesion and compromised neuroepithelial integrity. Finally, the hydrocephalus with hop gait (hyh) mouse, which harbors a mutation in Napa [encoding N-ethylmaleimide-sensitive factor attachment protein alpha (α-SNAP)], also develops a progressive denudation of the neuroepithelium, leading to periventicular nodule formation. Previous studies have shown that Arfgef2 and Napa direct vesicle trafficking and fusion, whereas FlnA associates dynamically with the Golgi membranes during budding and trafficking of transport vesicles. Our current findings suggest that PH formation arises from a final common pathway involving disruption of vesicle trafficking, leading to impaired cell

Neurogenic stunned myocardium following hemorrhagic cerebral contusion

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Deleu, D.; Miyares, F.; Kettern, M.; Kumar, S.; Hassens, Y.; Salim, K.

2007-01-01

Neurogenic stunned myocardium NSM is a well-known complication of subarachnoidal hemorrhage, but has been reported rarely in association with other central nervous system disorders. A case of NSM is described in a patient with hemorrhagic brain contusion associated with cerebral edema. An 18-year-old man was admitted with severe cranial trauma following a car roll-over. Six days after admission, he developed findings suggestive for NSM. The troponin T and creatine kinase-MB level were elevated and echocardiogram showed apical and inferoposterior hypokinesis and diffuse left ventricular akinesis with severely reduced ejection fraction 18%. Invasive measurements confirmed low cardiac output. His cardiac function resolved completely within 6 days after decompressive craniotomy. This case supports the presumed unifying role of the increased intracranial pressure, probably triggering a vigorous sympathetic outflow hyperactivity leading to NSM. (author)

Ceftolozane/tazobactam for febrile UTI due to multidrug-resistant Pseudomonas aeruginosa in a patient with neurogenic bladder.

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Dinh, Aurélien; Davido, Benjamin; Calin, Ruxandra; Paquereau, Julie; Duran, Clara; Bouchand, Frédérique; Phé, Véronique; Chartier-Kastler, Emmanuel; Rottman, Martin; Salomon, Jérôme; Plésiat, Patrick; Potron, Anaïs

2017-01-01

Urinary tract infections (UTI) are a major public health problem among spinal cord injury (SCI) patients. They frequently involve multidrug-resistant (MDR) bacteria. Ceftolozane/tazobactam (C/T) is a novel antibiotic combination approved for complicated intra-abdominal and UTI caused by Gram-positive and Gram-negative organisms, including some MDR strains. Little is known about the use of this agent for complicated febrile UTI occurring among SCI patients with neurogenic bladder due to MDR Pseudomonas aeruginosa (PSA). We describe the case of a 35-year-old man with SCI due to multiple sclerosis, with a neurogenic bladder necessitating a bilateral nephrostomy and double J catheter, who developed a febrile UTI due to a MDR PSA, which was susceptible only to amikacin and colistin. Because of this MDR phenotype and the underlying kidney disease, a 1000 mg (1000 mg per 500 mg) dose of C/T was given as monotherapy every 8 h for 7 days, after 3 days of colistin and amikacin. Thanks to this treatment, the patient had a favorable outcome with no clinical signs of UTI or positive urine culture up to 1 month after diagnosis. C/T seems to be an effective and safe therapeutic option for febrile UTI due to MDR PSA in SCI patients with neurogenic bladder, even when administered in monotherapy for 10 days.

Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation

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Nassini, Romina; Pedretti, Pamela; Moretto, Nadia

2012-01-01

The transient receptor potential ankyrin 1 (TRPA1) channel, localized to airway sensory nerves, has been proposed to mediate airway inflammation evoked by allergen and cigarette smoke (CS) in rodents, via a neurogenic mechanism. However the limited clinical evidence for the role of neurogenic...... inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1.By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express...... functional TRPA1 channels. By using immunohistochemistry, TRPA1 staining was observed in airway epithelial and smooth muscle cells in sections taken from human airways and lung, and from airways and lung of wild-type, but not TRPA1-deficient mice. In cultured human airway epithelial and smooth muscle cells...

Follow-up of Long-term Treatment with Clean Intermittent Catheterization for Neurogenic Bladder in Children

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Panuwat Lertsithichai

2004-04-01

Conclusions: For most patients and with close long-term follow-up, early treatment of neurogenic bladder using CIC in children born with myelomeningocele yields better results than late treatment. In our experience, treatment is recommended as soon as possible, especially during the first year of life.

Conical expansion of the outer subventricular zone and the role of neocortical folding in evolution and development

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Eric eLewitus

2013-08-01

Full Text Available There is a basic rule to mammalian neocortical expansion: as it expands, so does it fold. The degree to which it folds, however, cannot strictly be attributed to its expansion. Across species, cortical volume does not keep pace with cortical surface area, but rather folds appear more rapidly than expected. As a result, larger brains quickly become disproportionately more convoluted than smaller brains. Both the absence (lissencephaly and presence (gyrencephaly of cortical folds is observed in all mammalian orders and, while there is likely some phylogenetic signature to the evolutionary appearance of gyri and sulci, there are undoubtedly universal trends to the acquisition of folds in an expanding neocortex. Whether these trends are governed by conical expansion of neocortical germinal zones, the distribution of cortical connectivity, or a combination of growth- and connectivity-driven forces remains an open question. But the importance of cortical folding for evolution of the uniquely mammalian neocortex, as well as for the incidence of neuropathologies in humans, is undisputed. In this hypothesis and theory article, we will summarize the development of cortical folds in the neocortex, consider the relative influence of growth- versus connectivity-driven forces for the acquisition of cortical folds between and within species, assess the genetic, cell-biological, and mechanistic implications for neocortical expansion, and discuss the significance of these implications for human evolution, development, and disease. We will argue that evolutionary increases in the density of neuron production, achieved via maintenance of a basal proliferative niche in the neocortical germinal zones, drive the conical migration of neurons towards the cortical surface and ultimately lead to the establishment of cortical folds in large-brained mammal species.

Neurodegeneration and adaptation in response to low-dose photon irradiation

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Limoli, Charles L. [Univ. of California, Irvine, CA (United States)

2014-10-27

Neural stem and precursor cells (i.e. multipotent neural cells) are concentrated in the neurogenic regions of the brain (hippocampal dentate gyrus, subventricular zones), and considerable evidence suggests that these cells are important in mediating the stress response of the CNS after damage from ionizing radiation. The capability of these cells to proliferate, migrate and differentiate (i.e. to undergo neurogenesis) suggests they can participate in the repair and maintenance of CNS functions by replacing brain cells damaged or depleted due to irradiation. Importantly, we have shown that multipotent neural cells are markedly sensitive to irradiation and oxidative stress, insults that compromise neurogenesis and hasten the onset and progression of degenerative processes that are likely to have an adverse impact on cognition. Our past and current work has demonstrated that relatively low doses of radiation cause a persistent (weeks-months) oxidative stress in multipotent neural cells that can elicit a range of degenerative sequelae in the CNS. Therefore, our project is focused on determining the extent that endogenous and redox sensitive multipotent neural cells represent important radioresponsive targets for low dose radiation effects. We hypothesize that the activation of redox sensitive signaling can trigger radioadaptive changes in these cells that can be either harmful or beneficial to overall cognitive health.

The receptor for Granulocyte-colony stimulating factor (G-CSF is expressed in radial glia during development of the nervous system

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Krüger Carola

2008-03-01

Full Text Available Abstract Background Granulocyte colony-stimulating (G-CSF factor is a well-known hematopoietic growth factor stimulating the proliferation and differentiation of myeloid progenitors. Recently, we uncovered that G-CSF acts also as a neuronal growth factor in the brain, which promotes adult neural precursor differentiation and enhances regeneration of the brain after insults. In adults, the receptor for G-CSF is predominantly expressed in neurons in many brain areas. We also described expression in neurogenic regions of the adult brain, such as the subventricular zone and the subgranular layer of the dentate gyrus. In addition, we found close co-localization of the G-CSF receptor and its ligand G-CSF. Here we have conducted a systematic expression analysis of G-CSF receptor and its ligand in the developing embryo. Results Outside the central nervous system (CNS we found G-CSF receptor expression in blood vessels, muscles and their respective precursors and neurons. The expression of the G-CSF receptor in the developing CNS was most prominent in radial glia cells. Conclusion Our data imply that in addition to the function of G-CSF and its receptor in adult neurogenesis, this system also has a role in embryonic neurogenesis and nervous system development.

Conditioning pain stimulation does not affect itch induced by intra-epidermal histamine pricks but aggravates neurogenic inflammation in healthy volunteers

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Andersen, Hjalte Holm; Imai, Yosuke; Petersen, Kristian Kjær

2016-01-01

This study investigated whether itch induced by intra-epidermal histamine is subjected to modulation by a standardized conditioned pain modulation (CPM) paradigm in 24 healthy volunteers. CPM was induced by computer-controlled cuff pressure algometry and histamine was introduced to the volar...... forearm by skin prick test punctures. Moreover, neurogenic inflammation and wheal reactions induced by histamine and autonomic nervous system responses (heart rate variability and skin conductance) were monitored. CPM did not modulate the intensity of histamine-induced itch suggesting that pruriceptive...... signaling is not inhibited by pain-recruited endogenous modulation, however, CPM was found to aggravate histamine-induced neurogenic inflammation, likely facilitated by efferent sympathetic fibers....

Females have stronger neurogenic response than males after non-specific nasal challenge in patients with seasonal allergic rhinitis.

Science.gov (United States)

Tomljenovic, Dejan; Baudoin, Tomislav; Megla, Zeljka Bukovec; Geber, Goran; Scadding, Glenis; Kalogjera, Livije

2018-07-01

Epidemiological studies show female predominance in the prevalence of non- allergic rhinitis (NAR) and local allergic rhinitis (LAR). Experimental studies show female patients with allergic rhinitis (AR) demonstrate higher levels of sensitivity to irritants and airway hyperresponsiveness than males. Bronchial asthma shows female predominance in post-puberty patients, and gender interaction with severe asthma endotypes. Fibromyalgia, chronic fatigue syndrome, migraine and chronic cough, syndromes, which are commonly related to neurokinin substance P (SP) in the literature, also show strong female predominance. Studies have demonstrated that sex hormones, primarily oestrogens, affect mast cell activation. Mast cell proteases can amplify neurogenic inflammatory responses including the release of SP. Based on human epidemiological data and animal experimental data we hypothesized that female patients have different interaction between mast cell activation and neurogenic inflammation, i.e. substance P release, resulting in a different nasal symptom profile. To test the hypothesis we performed allergen and non-specific nasal challenges in patients with seasonal allergic rhinitis (SAR) out of season and looked for gender differences in subjective and objective responses. The interaction between subjective and objective reactivity was evaluated through the comparison of subjective symptom scores, concentrations of neurokinin substance P (SP) and cellular markers in nasal lavages after low doses of nasal allergen challenges. Female allergic subjects tended to have higher substance P (SP) concentrations both before and after non-specific challenges. The difference between post-allergen and post - hypertonic saline (HTS) challenge was highly significant in female patients (p = 0.001), while insignificant in male subjects (p = 0.14). Female patients had significantly stronger burning sensation after HTS challenge than male. These data indicate difference in the

Effectiveness of interspinous implant surgery in patients with intermittent neurogenic claudication: a systematic review and meta-analysis

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Moojen, W.A.; Arts, M.P.; Bartels, R.H.M.A.; Jacobs, W.C.; Peul, W.C.

2011-01-01

INTRODUCTION: Despite an increasing implantation rate of interspinous process distraction (IPD) devices in the treatment of intermittent neurogenic claudication (INC), definitive evidence on the clinical effectiveness of implants is lacking. The main objective of this review was to perform a

Malignant neurogenic neoplasms of the head and neck; Zlosliwe nowotwory neurogenne glowy i szyi

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Kuczkowski, J.; Starzynska, A. [Akademia Medyczna, Gdansk (Poland)

1996-12-31

The authors present 17 cases of malignant neurogenic neoplasms of the head and neck observed in the Department of Otolaryngology in the years 1948-1993. The latest opinions on etiopathology, diagnosis and treatment of these tumors were described. Age and sex of patients, localization of tumor, symptoms histopathology and treatment were analyzed. Progressions of the disease were estimated retrospectively. It has been proved that these tumors develop quickly, give pain and paresthesia. Their diagnosis is very difficult because of their submucosal growth and difficult histopathological interpretation. A characteristic feature of these neurogenic tumors is the ability to give distant metastases. This feature differentiates them from squamous neoplasms, which give mainly nodal metastases. All the patients were subjected to surgery combined with conventional or high voltage radiotherapy. The positive effect of combined chemotherapy in cases of esthesioneuroblastoma is worthy of note. The prognosis in these tumors is often unfavorable. In the group under discussion 13 patients died because of recurrences, two patients are considered to be cured and the remaining 2 patients have had no recurrence for 2 and 3 years. (author) 15 refs, 2 figs, 2 tabs

Effectiveness of interspinous implant surgery in patients with intermittent neurogenic claudication : a systematic review and meta-analysis

NARCIS (Netherlands)

Moojen, Wouter A.; Arts, Mark P.; Bartels, Ronald H. M. A.; Jacobs, Wilco C. H.; Peul, Wilco C.

2011-01-01

Despite an increasing implantation rate of interspinous process distraction (IPD) devices in the treatment of intermittent neurogenic claudication (INC), definitive evidence on the clinical effectiveness of implants is lacking. The main objective of this review was to perform a meta-analysis of all

Genetic deletion of Rnd3 in neural stem cells promotes proliferation via upregulation of Notch signaling.

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Dong, Huimin; Lin, Xi; Li, Yuntao; Hu, Ronghua; Xu, Yang; Guo, Xiaojie; La, Qiong; Wang, Shun; Fang, Congcong; Guo, Junli; Li, Qi; Mao, Shanping; Liu, Baohui

2017-10-31

Rnd3, a Rho GTPase, is involved in the inhibition of actin cytoskeleton dynamics through the Rho kinase-dependent signaling pathway. We previously demonstrated that mice with genetic deletion of Rnd3 developed a markedly larger brain compared with wild-type mice. Here, we demonstrate that Rnd3 knockout mice developed an enlarged subventricular zone, and we identify a novel role for Rnd3 as an inhibitor of Notch signaling in neural stem cells. Rnd3 deficiency, both in vivo and in vitro , resulted in increased levels of Notch intracellular domain protein. This led to enhanced Notch signaling and promotion of aberrant neural stem cell growth, thereby resulting in a larger subventricular zone and a markedly larger brain. Inhibition of Notch activity abrogated this aberrant neural stem cell growth.

Edema pulmonar neurogênico: relato de dois casos Neurogenic pulmonary edema: report of two cases

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Desanka Dragosavac

1997-06-01

Full Text Available O edema pulmonar neurogênico é rara e grave complicação de pacientes com traumatismo craniencefálico (TCE. Pode ocorrer também em outras patologias do sistema nervoso central, tais como acidentes vasculares cerebrais (AVC, tumores ou após crises epilépticas, entre outras. Foram avaliados 36 casos com TCE grave e quatro pacientes com AVC, internados na UTI geral, no período de janeiro a setembro 1995. Nesse intervalo de tempo foram diagnosticados dois casos de edema pulmonar neurogênico, um ocorrendo em paciente com TCE grave e outro em paciente com AVC hemorrágico. O diagnóstico foi estabelecido pelo rápido desenvolvimento de edema pulmonar, com hipoxemia grave, queda da complacência pulmonar e infiltrados difusos bilaterais sem história prévia de aspiração traqueal ou outro fator de risco para o desenvolvimento de síndrome de angústia respiratória aguda. No primeiro paciente com trauma craniencefálico, o edema neurogênico foi diagnosticado na internação, uma hora após o trauma, com concomitante reação inflamatória grave e boa evolução em três dias. O outro caso, com AVC hemorrágico, desenvolveu edema neurogênico no quarto dia após drenagem de hematoma intraparenquimatoso, evoluindo para o óbito.Neurogenic pulmonary edema is a rare and serious complication in patients with head injury. It also may develop after a variety of cerebral insults such as subarachnoid hemorrhage, brain tumors and after epileptic seizures. Thirty six patients with severe head injury and four patients with cerebrovascular insults treated in Intensive Care Unit of HC-UNICAMP from January to September 1995 were evaluated. In this period there were two patients with neurogenic pulmonary edema, one with head injury and other with intracerebral hemorrhage. Diagnosis was made by rapid onset of pulmonary edema, severe hypoxemia, decrease of pulmonary complacence and diffuse pulmonary infiltrations, without previous history of tracheal

Botulinum Toxin in Neurogenic Detrusor Overactivity

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Carlos Arturo Levi D'Ancona

2012-09-01

Full Text Available Purpose To evaluate the effects of botulinum toxin on urodynamic parameters and quality of life in patients with neurogenic detrusor overactivity. Methods Thirty four adult patients with spinal cord injury and detrusor overactivity were selected. The patients received 300 units of botulinum toxin type A. The endpoints evaluated with the episodes of urinary incontinence and measured the maximum cystometric capacity, maximum amplitude of detrusor pressure and bladder compliance at the beginning and end of the study (24 weeks and evaluated the quality of life by applying the Qualiveen questionnaire. Results A significant decrease in the episodes of urinary incontinence was observed. All urodynamic parameters presented a significant improvement. The same was observed in the quality of life index and the specific impact of urinary problems scores from the Qualiveen questionnaire. Six patients did not complete the study, two due to incomplete follow-up, and four violated protocol and were excluded from the analyses. No systemic adverse events of botulinum toxin type A were reported. Conclusions A botulinum toxin type A showed a significantly improved response in urodynamics parameters and specific and general quality of life.

Co-effects of matrix low elasticity and aligned topography on stem cell neurogenic differentiation and rapid neurite outgrowth

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Yao, Shenglian; Liu, Xi; Yu, Shukui; Wang, Xiumei; Zhang, Shuming; Wu, Qiong; Sun, Xiaodan; Mao, Haiquan

2016-05-01

The development of novel biomaterials that deliver precise regulatory signals to direct stem cell fate for nerve regeneration is the focus of current intensive research efforts. In this study, a hierarchically aligned fibrillar fibrin hydrogel (AFG) that was fabricated through electrospinning and the concurrent molecular self-assembly process mimics both the soft and oriented features of nerve tissue, thus providing hybrid biophysical cues to instruct cell behavior in vitro and in vivo. The electrospun hydrogels were examined by scanning electron microscopy (SEM), polarized light microscopy, small angle X-ray scattering assay and atomic force microscopy (AFM), showing a hierarchically linear-ordered structure from the nanoscale to the macroscale with a soft elastic character (elasticity ~1 kPa). We found that this low elasticity and aligned topography of AFG exhibit co-effects on promoting the neurogenic differentiation of human umbilical cord mesenchymal stem cells (hUMSCs) in comparison to random fibrin hydrogel (RFG) and tissue culture plate (TCP) control after two week cell culture in growth medium lacking supplementation with soluble neurogenic induction factors. In addition, AFG also induces dorsal root ganglion (DRG) neurons to rapidly project numerous long neurite outgrowths longitudinally along the AFG fibers for a total neurite extension distance of 1.96 mm in three days in the absence of neurotrophic factor supplementation. Moreover, the AFG implanted in a rat T9 dorsal hemisection spinal cord injury model was found to promote endogenous neural cell fast migration and axonal invasion along AFG fibers, resulting in aligned tissue cables in vivo. Our results suggest that matrix stiffness and aligned topography may instruct stem cell neurogenic differentiation and rapid neurite outgrowth, providing great promise for biomaterial design for applications in nerve regeneration.The development of novel biomaterials that deliver precise regulatory signals to

Aging differentially affects male and female neural stem cell neurogenic properties

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Jay Waldron

2010-09-01

Full Text Available Jay Waldron1, Althea McCourty1, Laurent Lecanu1,21The Research Institute of the McGill University Health Centre, Montreal, Canada; 2Department of Medicine, McGill University, Montreal, Quebec, CanadaPurpose: Neural stem cell transplantation as a brain repair strategy is a very promising technology. However, despite many attempts, the clinical success remains very deceiving. Despite clear evidence that sexual dimorphism rules many aspects of human biology, the occurrence of a sex difference in neural stem cell biology is largely understudied. Herein, we propose to determine whether gender is a dimension that drives the fate of neural stem cells through aging. Should it occur, we believe that neural stem cell sexual dimorphism and its variation during aging should be taken into account to refine clinical approaches of brain repair strategies.Methods: Neural stem cells were isolated from the subventricular zone of three- and 20-month-old male and female Long-Evans rats. Expression of the estrogen receptors, ERα and ERβ, progesterone receptor, androgen receptor, and glucocorticoid receptor was analyzed and quantified by Western blotting on undifferentiated neural stem cells. A second set of neural stem cells was treated with retinoic acid to trigger differentiation, and the expression of neuronal, astroglial, and oligodendroglial markers was determined using Western blotting.Conclusion: We provided in vitro evidence that the fate of neural stem cells is affected by sex and aging. Indeed, young male neural stem cells mainly expressed markers of neuronal and oligodendroglial fate, whereas young female neural stem cells underwent differentiation towards an astroglial phenotype. Aging resulted in a lessened capacity to express neuron and astrocyte markers. Undifferentiated neural stem cells displayed sexual dimorphism in the expression of steroid receptors, in particular ERα and ERβ, and the expression level of several steroid receptors increased

[Laparoscopic cystectomy and transileal ureterostomy for neurogenic vesicosphincteric disorders. Evaluation of morbidity].

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Guillotreau, Julien; Gamé, Xavier; Castel-Lacanal, Evelyne; Mallet, Richard; De Boissezon, Xavier; Malavaud, Bernard; Marque, Philippe; Rischmann, Pascal

2007-04-01

To evaluate the morbidity and mortality of laparoscopic cystectomy combined with transileal ureterostomy to treat neurogenic vesicosphincteric disorders. Prospective study performed between february 2004 and april 2006 on 26 consecutive patients with a mean age of 55.0 +/- 12.7 years treated by laparoscopic cystectomy for neurogenic vesicosphincteric disorders. The underlying neurological disease was multiple sclerosis (MS) in 20 cases, spinal cord injury in 4 cases and transverse myelitis in 2 cases. The median preoperative ASA score was 3 (range: 2-3). No open conversion was necessary. One intraoperative complication was observed (vascular injury). No perioperative death was observed. The nasogastric tube was maintained postoperatively for an average of 8.69 +/- 5.9 hours. The mean time to resumption of oral fluids was 1.4 +/- 0.7 days and mean time to resumption of solids was 2.6 +/- 1.0 days. The mean time to resumption of bowel movements was 3.8 +/- 3.2 days. The mean intensive care stay was 3.9 +/- 1.1 days. Two postoperative complications were observed in the same patient (ileus and bronchial congestion). Postoperative narcotic analgesics were necessary in 60% of cases. The mean hospital stay was 10.3 +/- 4.1 days. Two late postoperative complications were observed in the same patient (two episodes of pyelonephritis). Laparoscopic cystectomy has a low morbidity in neurological patients, allowing early return of feeding and a moderate length of hospital stay.

Synostosis Between Pubic Bones due to Neurogenic, Heterotopic Ossification

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Subramanian Vaidyanathan

2006-01-01

Full Text Available Neurogenic, heterotopic ossification is characterised by the formation of new, extraosseous (ectopic bone in soft tissue in patients with neurological disorders. A 33-year-old female, who was born with spina bifida, paraplegia, and diastasis of symphysis pubis, had indwelling urethral catheter drainage and was using oxybutynin bladder instillations. She was prescribed diuretic for swelling of feet, which aggravated bypassing of catheter. Hence, suprapubic cystostomy was performed. Despite anticholinergic therapy, there was chronic urine leak around the suprapubic catheter and per urethra. Therefore, the urethra was mobilised and closed. After closure of the urethra, there was no urine leak from the urethra, but urine leak persisted around the suprapubic catheter. Cystogram confirmed the presence of a Foley balloon inside the bladder; there was no urinary fistula. The Foley balloon ruptured frequently, leading to extrusion of the Foley catheter. X-ray of abdomen showed heterotopic bone formation bridging the gap across diastasis of symphysis pubis. CT of pelvis revealed heterotopic bone lying in close proximity to the balloon of the Foley catheter; the sharp edge of heterotopic bone probably acted like a saw and led to frequent rupture of the balloon of the Foley catheter. Unique features of this case are: (1 temporal relationship of heterotopic bone formation to suprapubic cystostomy and chronic urine leak; (2 occurrence of heterotopic ossification in pubic region; (3 complications of heterotopic bone formation viz. frequent rupture of the balloon of the Foley catheter by the irregular margin of heterotopic bone and difficulty in insertion of suprapubic catheter because the heterotopic bone encroached on the suprapubic track; (4 synostosis between pubic bones as a result of heterotopic ossification..Common aetiological factors for neurogenic, heterotopic ossification, such as forceful manipulation, trauma, or spasticity, were absent in this

A step-wise approach to sperm retrieval in men with neurogenic anejaculation

DEFF Research Database (Denmark)

Fode, Mikkel; Ohl, Dana A; Sønksen, Jens

2015-01-01

Normal fertility is dependent on intravaginal delivery of semen through ejaculation. This process is highly dependent on an intact ejaculatory reflex arc, which can be disrupted through any type of trauma or disease causing damage to the CNS and/or peripheral nerves. Neurogenic anejaculation...... is most commonly associated with spinal cord injury. This aetiology is especially relevant because most men with spinal cord injuries are injured at reproductive age. Assisted ejaculation in the form of penile vibratory stimulation is the first choice for sperm retrieval in such patients because...

Regulation of neurogenesis: factors affecting of new neurons formation in adult mammals brain

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Michalina Respondek

2015-12-01

Full Text Available Neurogenesis is a complex and multi-step process of generating completely functional neurons. This process in adult brain is based on pluripotentional neuronal stem cells (NSC, which are able to proliferation and differentiation into mature neurons or glial cells. NSC are located in subgranular zone inside hippocampus and in subventricular zone. The new neurons formation depends on many endo- and exogenous factors which modulate each step of neurogenesis. This article describes the most important regulators of adult neurogenesis, mainly: neurotrophins, growth factors, hormones, neurotransmitters and microenvironment of NSC. Some drugs, especially antipsychotics, antidepressants and normothymics may affect the neurogenic properties of adult brain. Moreover pathological processes such as neuroinflammation, stroke or epilepsy are able to induce proliferation of NSC. The proneurogenic effects of psychotropic drugs and pathological processes are associated with their ability to increase some hormones and neurotrophins level, as well as with rising the expression of antiapoptotic Bcl-2 protein and metalloproteinase MMP-2. Additionaly, some drugs, for example haloperidol, are able to block prolactin and dopaminergic neuroblasts receptors. Down-regulation of adult neurogenesis is associated with alcohol abuse and high stress level. Negative effect of many drugs, such as cytostatics, COX-2 inhibitors and opioides was also observed. The proneurogenic effect of described factors suggest their broad therapeutic potential and gives a new perspective on an effective and modern treatment of many neuropsychiatric disorders. This effect can also help to clarify the pathogenesis of disorders associated with proliferation and degeneration of adult brain cells.

The satiating hormone amylin enhances neurogenesis in the area postrema of adult rats

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Claudia G. Liberini

2016-10-01

Full Text Available Objective: Adult neurogenesis in the subgranular zone and subventricular zone is generally accepted, but its existence in other brain areas is still controversial. Circumventricular organs, such as the area postrema (AP have recently been described as potential neurogenic niches in the adult brain. The AP is the major site of action of the satiating hormone amylin. Amylin has been shown to promote the formation of neuronal projections originating from the AP in neonatal rodents but the role of amylin in adult neurogenesis remains unknown. Methods: To test this, we first performed an RNA-sequencing of the AP of adult rats acutely injected with either amylin (20 μg/kg, amylin plus the amylin receptor antagonist AC187 (500 μg/kg or vehicle. Second, animals were subcutaneously equipped with minipumps releasing either amylin (50 μg/kg/day or vehicle for 3 weeks to assess cell proliferation and differentiation with the 5′-bromo-2-deoxyuridine (BrdU technique. Results: Acute amylin injections affected genes involved in pathways and processes that control adult neurogenesis. Amylin consistently upregulated NeuroD1 transcript and protein in the adult AP, and this effect was blocked by the co-administration of AC187. Further, chronic amylin treatment increased the number of newly proliferated AP-cells and significantly promoted their differentiation into neurons rather than astrocytes. Conclusion: Our findings revealed a novel role of the satiating hormone amylin in promoting neurogenesis in the AP of adult rats. Keywords: Amylin, Adult neurogenesis, Area postrema, BrdU, Circumventricular organs

Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex.

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Bifari, Francesco; Decimo, Ilaria; Pino, Annachiara; Llorens-Bobadilla, Enric; Zhao, Sheng; Lange, Christian; Panuccio, Gabriella; Boeckx, Bram; Thienpont, Bernard; Vinckier, Stefan; Wyns, Sabine; Bouché, Ann; Lambrechts, Diether; Giugliano, Michele; Dewerchin, Mieke; Martin-Villalba, Ana; Carmeliet, Peter

2017-03-02

Whether new neurons are added in the postnatal cerebral cortex is still debated. Here, we report that the meninges of perinatal mice contain a population of neurogenic progenitors formed during embryonic development that migrate to the caudal cortex and differentiate into Satb2 + neurons in cortical layers II-IV. The resulting neurons are electrically functional and integrated into local microcircuits. Single-cell RNA sequencing identified meningeal cells with distinct transcriptome signatures characteristic of (1) neurogenic radial glia-like cells (resembling neural stem cells in the SVZ), (2) neuronal cells, and (3) a cell type with an intermediate phenotype, possibly representing radial glia-like meningeal cells differentiating to neuronal cells. Thus, we have identified a pool of embryonically derived radial glia-like cells present in the meninges that migrate and differentiate into functional neurons in the neonatal cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

Cocaine and MDMA Induce Cellular and Molecular Changes in Adult Neurogenic Systems: Functional Implications

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Vivian Capilla-Gonzalez

2011-06-01

Full Text Available The capacity of the brain to generate new adult neurons is a recent discovery that challenges the old theory of an immutable adult brain. A new and fascinating field of research now focuses on this regenerative process. The two brain systems that constantly produce new adult neurons, known as the adult neurogenic systems, are the dentate gyrus (DG of the hippocampus and the lateral ventricules/olfactory bulb system. Both systems are involved in memory and learning processes. Different drugs of abuse, such as cocaine and MDMA, have been shown to produce cellular and molecular changes that affect adult neurogenesis. This review summarizes the effects that these drugs have on the adult neurogenic systems. The functional relevance of adult neurogenesis is obscured by the functions of the systems that integrate adult neurons. Therefore, we explore the effects that cocaine and MDMA produce not only on adult neurogenesis, but also on the DG and olfactory bulbs. Finally, we discuss the possible role of new adult neurons in cocaine- and MDMA-induced impairments. We conclude that, although harmful drug effects are produced at multiple physiological and anatomical levels, the specific consequences of reduced hippocampus neurogenesis are unclear and require further exploration.

Radiological consideration of neurogenic bladder in patients with traumatic spinal injury

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Kim, Soo Han; Yu, Yun Jeong; Shin, Hyun Ja [Korea Veterans Hospital, Seoul (Korea, Republic of)

1987-10-15

We evaluated 104 patients of neurogenic bladder secondary to traumatic spinal cord injury. Those were diagnosed by I. V. P. and V. C. U. at Korea Veterans Hospital during 9 years from January, 1978 to May, 1987. The type of neurogenic bladder, complications and urethral configuration, according to the level of spinal cord injury were discusses. The result were as follows: 1. The incidence of patient according to the level of spinal cord injury was 49 out of 104 in those with vertebral level T7 or above, 15 out of 104 in those with T8-T10 level, and 40 in those with vertebral level T11 or below. The incidence of UMNB was 67.3% in those with vertebral T7 or above, 53.3% in T8-T10. The incidence of LMNB was 62.5% in those with vertebral level T11 or below. 2. Overall incidence of urinary tract calculus was 32.7%. Highest incidence of calculus was 46.7% in those with vertebral level T8-T10. 3. Overall incidence of vesicoureteral reflux was 23.1%. Highest incidence of reflux was 46.7% in those with vertebral level T11 or below. 4. Overall incidence of pyelonephritis was 26.9%. 5. Overall incidence of hydronephrosis was 20.2%. Highest incidence of hydronephrosis was 27.5% in those with vertebral level T11 or below. 6. Almost entire urethra was shown funnel type in 66 out of 73 cases. Saccular dilatation of posterior urethra was 7 cases. Saccular dilatation of posterior urethra with LMNB was 4 cases, which were occurred only in those with vertebral level T11 or below.

Radiological consideration of neurogenic bladder in patients with traumatic spinal injury

International Nuclear Information System (INIS)

Kim, Soo Han; Yu, Yun Jeong; Shin, Hyun Ja

1987-01-01

We evaluated 104 patients of neurogenic bladder secondary to traumatic spinal cord injury. Those were diagnosed by I. V. P. and V. C. U. at Korea Veterans Hospital during 9 years from January, 1978 to May, 1987. The type of neurogenic bladder, complications and urethral configuration, according to the level of spinal cord injury were discusses. The result were as follows: 1. The incidence of patient according to the level of spinal cord injury was 49 out of 104 in those with vertebral level T7 or above, 15 out of 104 in those with T8-T10 level, and 40 in those with vertebral level T11 or below. The incidence of UMNB was 67.3% in those with vertebral T7 or above, 53.3% in T8-T10. The incidence of LMNB was 62.5% in those with vertebral level T11 or below. 2. Overall incidence of urinary tract calculus was 32.7%. Highest incidence of calculus was 46.7% in those with vertebral level T8-T10. 3. Overall incidence of vesicoureteral reflux was 23.1%. Highest incidence of reflux was 46.7% in those with vertebral level T11 or below. 4. Overall incidence of pyelonephritis was 26.9%. 5. Overall incidence of hydronephrosis was 20.2%. Highest incidence of hydronephrosis was 27.5% in those with vertebral level T11 or below. 6. Almost entire urethra was shown funnel type in 66 out of 73 cases. Saccular dilatation of posterior urethra was 7 cases. Saccular dilatation of posterior urethra with LMNB was 4 cases, which were occurred only in those with vertebral level T11 or below

Graphene Functionalized Scaffolds Reduce the Inflammatory Response and Supports Endogenous Neuroblast Migration when Implanted in the Adult Brain.

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Kun Zhou

Full Text Available Electroactive materials have been investigated as next-generation neuronal tissue engineering scaffolds to enhance neuronal regeneration and functional recovery after brain injury. Graphene, an emerging neuronal scaffold material with charge transfer properties, has shown promising results for neuronal cell survival and differentiation in vitro. In this in vivo work, electrospun microfiber scaffolds coated with self-assembled colloidal graphene, were implanted into the striatum or into the subventricular zone of adult rats. Microglia and astrocyte activation levels were suppressed with graphene functionalization. In addition, self-assembled graphene implants prevented glial scarring in the brain 7 weeks following implantation. Astrocyte guidance within the scaffold and redirection of neuroblasts from the subventricular zone along the implants was also demonstrated. These findings provide new functional evidence for the potential use of graphene scaffolds as a therapeutic platform to support central nervous system regeneration.

Expression of neurotransmitters and neurotrophins in neurogenic inflammation of the rat retina

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E Bronzetti

2009-08-01

Full Text Available Antidromic stimulation of the rat trigeminal ganglion triggers the release of substance P (SP and calcitonin gene-related peptide (CGRP from sensory nerve terminals of the capsaicin sensitive C-fibers. These pro-inflammatory neuropeptides produce a marked hyperemia in the anterior segment of the eye, accompanied by increased intraocular pressure, breakdown of the blood-aqueous barrier and myosis. To assess the effects of neurogenic inflammation on the retina, specifically on the immunostaining of neurotransmitters and neurotrophins, as well as on the expression of neurotrophin receptors in the retina. RT-PCR was also accomplished in control and stimulated animals to confirm the immunohistochemical results. In the electrically stimulated eyes, immunostaining for SP, CGRP, VIP and nNOS demonstrated a marked increase in the RPE/POS (Retinal Pigment Epithelium/Photoreceptor Outer Segments, in the inner and outer granular layers and in the ganglion cells in comparison to the control eyes. CGRP and SP were found increased in stimulated animals and this result has been confirmed by RT- PCR. Changes in neurotrophin immunostaining and in receptor expression were also observed after electric stimulation of trigeminal ganglia. Decrease of BDNF and NT4 in the outer and inner layers and in ganglion cells was particularly marked. In stimulated rat retinas immunostaining and RT-PCR showed a NGF expression increase. Neurotrophin receptors remained substantially unchanged. These studies demonstrated, for the first time, that antidromic stimulation of the trigeminal ganglion and subsequent neurogenic inflammation affect immunostaining of retinal cell neurotransmitter/ neuropeptides and neurotrophins as well as the expression of neurotrophin receptors.

Urofacial syndrome: A subset of neurogenic bladder dysfunction syndromes?

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K N Stamatiou

2010-01-01

Full Text Available The urofacial syndrome is probably a subset of neurogenic bladder dysfunction syndromes characterized by detrusor-sphincter discoordination along with a characteristic inversion of facial expression with laughing. This characteristic facial expression can facilitate early detection of this disorder, which leads to poor bladder emptying with high residual urine, hydro-nephrosis with vesico-ureteral reflux and potentially renal failure if left untreated. The etiology of the urofacial syndrome is unknown. In our case, a 12-year-old boy of Middle-Eastern origin presented to the Outpatient Department of our hospital with left pyelonephritis, hydronephrosis and bladder dilatation. Voiding cystourethrography performed 15 days later revealed left vesicoureteral reflux. Cystoscopy revealed bladder trabeculation however an anatomic urethral obstruction was not noticed. Both, neurological examination and radiography of the lumbosacral spine were normal. Urodynamic evaluation revealed the typical findings of detrusor-sphincter discoordination.

N-Cadherin Upregulation Promotes the Neurogenic Differentiation of Menstrual Blood-Derived Endometrial Stem Cells.

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Liu, Yanli; Yang, Fen; Liang, Shengying; Liu, Qing; Fu, Sulei; Wang, Zhenyu; Yang, Ciqing; Lin, Juntang

2018-01-01

Peripheral nerve injuries are typically caused by either trauma or medical disorders, and recently, stem cell-based therapies have provided a promising treatment approach. Menstrual blood-derived endometrial stem cells (MenSCs) are considered an ideal therapeutic option for peripheral nerve repair due to a noninvasive collection procedure and their high proliferation rate and immunological tolerance. Here, we successfully isolated MenSCs and examined their biological characteristics including their morphology, multipotency, and immunophenotype. Subsequent in vitro studies demonstrated that MenSCs express high levels of neurotrophic factors, such as NT3, NT4, BDNF, and NGF, and are capable of transdifferentiating into glial-like cells under conventional induction conditions. Moreover, upregulation of N-cadherin (N-cad) mRNA and protein expression was observed after neurogenic differentiation. In vivo studies clearly showed that N-cad knockdown via in utero electroporation perturbed the migration and maturation of mouse neural precursor cells (NPCs). Finally, a further transfection assay also confirmed that N-cad upregulation in MenSCs results in the expression of S100. Collectively, our results confirmed the paracrine effect of MenSCs on neuroprotection as well as their potential for transdifferentiation into glial-like cells and demonstrated that N-cad upregulation promotes the neurogenic differentiation of MenSCs, thereby providing support for transgenic MenSC-based therapy for peripheral nerve injury.

The vascular and neurogenic factors associated with erectile dysfunction in patients after pelvic fractures

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Yong Guan

2015-10-01

Full Text Available ABSTRACT Erectile dysfunction (ED is a common complication of pelvic fractures. To identify the vascular and neurogenic factors associated with ED, 120 patients admitted with ED after traumatic pelvic fracture between January 2009 and June 2013 were enrolled in this study. All patients answered the International Index of Erectile Function (IIEF-5 questionnaire. Nocturnal penile tumescence (NPT testing confirmed the occurrence of ED in 96 (80% patients on whom penile duplex ultrasound and neurophysiological testing were further performed. Of these ED patients 29 (30% were demonstrated only with vascular abnormality, 41 (42.7% were detected only with neural abnormality, 26 (27.1% revealed mixed abnormalities. Of the 55 patients (29+26 with vascular problems, 7 patients (12.7% with abnormal arterial response to intracavernous injection of Bimix (15mg papaverine and 1mg phentolamine, 31 (56.4% with corporal veno-occlusive dysfunction and 17 (30.9% had both problems. Of the 67 (41+26 patients with abnormal neurophysiological outcomes, 51 (76.1% with abnormal bulbocavernosus reflex (BCR, 20 (29.9% with pathological pudendal nerve evoked potentials (PDEPs and 25 (37.3% with abnormal posterior tibial somatosensory nerve evoked potentials (PTSSEPs. Our observation indicated that neurogenic factors are important for the generation of ED in patients with pelvic fracture; venous impotence is more common than arteriogenic ED.

IGF-I: A key growth factor that regulates neurogenesis and synaptogenesis from embryonic to adult stages of the brain

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Vanesa eNieto-Estévez

2016-02-01

Full Text Available The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs. This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP and the subventricular zone-olfactory bulb (SVZ-OB. By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also, by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis and neuron integration in synaptic circuits.

IGF-I: A Key Growth Factor that Regulates Neurogenesis and Synaptogenesis from Embryonic to Adult Stages of the Brain

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Nieto-Estévez, Vanesa; Defterali, Çağla; Vicario-Abejón, Carlos

2016-01-01

The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs). This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I) exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type, and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP) and the subventricular zone-olfactory bulb (SVZ-OB). By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis, and neuron integration in synaptic circuits. PMID:26941597

Neurogenic pulmonary edema induced by spinal cord injury in spontaneously hypertensive and Dahl salt hypertensive rats

Czech Academy of Sciences Publication Activity Database

Šedý, Jiří; Kuneš, Jaroslav; Zicha, Josef

2011-01-01

Roč. 60, č. 6 (2011), s. 975-979 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GA305/09/0336; GA AV ČR(CZ) IAA500110902 Institutional research plan: CEZ:AV0Z50110509 Keywords : hypertension * neurogenic pulmonary edema * Dahl salt-sensitive rats * SHR Subject RIV: ED - Physiology Impact factor: 1.555, year: 2011

Expression and cellular localization of hepcidin mRNA and protein in normal rat brain

Czech Academy of Sciences Publication Activity Database

Raha-Chowdhury, R.; Raha, A.A.; Forostyak, Serhiy; Zhao, J.W.; Stott, S.R.W.; Bomford, A.

2015-01-01

Roč. 16, APR 21 (2015), s. 24 ISSN 1471-2202 Institutional support: RVO:68378041 Keywords : hepcidin * ferroportin * defensin * inflammatory cytokines * brain iron homeostasis * blood brain barrier * pericytes * sub-ventricular zone * neurogenesis Subject RIV: FH - Neurology Impact factor: 2.304, year: 2015

[Brain repair after ischemic stroke: role of neurotransmitters in post-ischemic neurogenesis].

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Sánchez-Mendoza, Eduardo; Bellver-Landete, Víctor; González, María Pilar; Merino, José Joaquín; Martínez-Murillo, Ricardo; Oset-Gasque, María Jesús

2012-11-01

Brain ischemia and reperfusion produce alterations in the microenvironment of the parenchyma, including ATP depletion, ionic homeostasis alterations, inflammation, release of multiple cytokines and abnormal release of neurotransmitters. As a consequence, the induction of proliferation and migration of neural stem cells towards the peri-infarct region occurs. The success of new neurorestorative treatments for damaged brain implies the need to know, with greater accuracy, the mechanisms in charge of regulating adult neurogenesis, both under physiological and pathological conditions. Recent evidence demonstrates that many neurotransmitters, glutamate in particular, control the subventricular zone, thus being part of the complex signalling network that influences the production of new neurons. Neurotransmitters provide a link between brain activity and subventricular zone neurogenesis. Therefore, a deeper knowledge of the role of neurotransmitters systems, such as glutamate and its transporters, in adult neurogenesis, may provide a valuable tool to be used as a neurorestorative therapy in this pathology.

The 'ventral organs' of Pycnogonida (Arthropoda) are neurogenic niches of late embryonic and post-embryonic nervous system development.

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Brenneis, Georg; Scholtz, Gerhard

2014-01-01

Early neurogenesis in arthropods has been in the focus of numerous studies, its cellular basis, spatio-temporal dynamics and underlying genetic network being by now comparably well characterized for representatives of chelicerates, myriapods, hexapods and crustaceans. By contrast, neurogenesis during late embryonic and/or post-embryonic development has received less attention, especially in myriapods and chelicerates. Here, we apply (i) immunolabeling, (ii) histology and (iii) scanning electron microscopy to study post-embryonic ventral nerve cord development in Pseudopallene sp., a representative of the sea spiders (Pycnogonida), the presumable sister group of the remaining chelicerates. During early post-embryonic development, large neural stem cells give rise to additional ganglion cell material in segmentally paired invaginations in the ventral ectoderm. These ectodermal cell regions - traditionally designated as 'ventral organs' - detach from the surface into the interior and persist as apical cell clusters on the ventral ganglion side. Each cluster is a post-embryonic neurogenic niche that features a tiny central cavity and initially still houses larger neural stem cells. The cluster stays connected to the underlying ganglionic somata cortex via an anterior and a posterior cell stream. Cell proliferation remains restricted to the cluster and streams, and migration of newly produced cells along the streams seems to account for increasing ganglion cell numbers in the cortex. The pycnogonid cluster-stream-systems show striking similarities to the life-long neurogenic system of decapod crustaceans, and due to their close vicinity to glomerulus-like neuropils, we consider their possible involvement in post-embryonic (perhaps even adult) replenishment of olfactory neurons - as in decapods. An instance of a potentially similar post-embryonic/adult neurogenic system in the arthropod outgroup Onychophora is discussed. Additionally, we document two transient posterior

Milrinone therapy for enterovirus 71-induced pulmonary edema and/or neurogenic shock in children: a randomized controlled trial.

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Chi, Chia-Yu; Khanh, Truong Huu; Thoa, Le Phan Kim; Tseng, Fan-Chen; Wang, Shih-Min; Thinh, Le Quoc; Lin, Chia-Chun; Wu, Han-Chieh; Wang, Jen-Ren; Hung, Nguyen Thanh; Thuong, Tang Chi; Chang, Chung-Ming; Su, Ih-Jen; Liu, Ching-Chuan

2013-07-01

Enterovirus 71-induced brainstem encephalitis with pulmonary edema and/or neurogenic shock (stage 3B) is associated with rapid mortality in children. In a small pilot study, we found that milrinone reduced early mortality compared with historical controls. This prospective, randomized control trial was designed to provide more definitive evidence of the ability of milrinone to reduce the 1-week mortality of stage 3B enterovirus 71 infections. Prospective, unicenter, open-label, randomized, controlled study. Inpatient ward of a large tertiary teaching hospital in Ho Chi Minh City, Vietnam. Children (≤ 18 yr old) admitted with proven enterovirus 71-induced pulmonary edema and/or neurogenic shock. Patients were randomly assigned to receive intravenous milrinone (0.5 μg/kg/min) (n = 22) or conventional management (n = 19). Both groups received dopamine or dobutamine and intravenous immunoglobulin. The primary endpoint was 1-week mortality. The secondary endpoints included length of ventilator dependence and hospital stay and adverse events. The median age was 2 years with a predominance of boys in both groups. The 1-week mortality was significantly lower, 18.2% (4/22) in the milrinone compared with 57.9% (11/19) in the conventional management group (relative risk = 0.314 [95% CI, 0.12-0.83], p = 0.01). The median duration of ventilator-free days was longer in the milrinone treatment group (p = 0.01). There was no apparent neurologic sequela in the survivors in either group, and no drug-related adverse events were documented. Milrinone significantly reduced the 1-week mortality of enterovirus 71-induced pulmonary edema and/or neurogenic shock without adverse effects. Further studies are needed to determine whether milrinone might be useful to prevent progression of earlier stages of brainstem encephalitis.

Co-effects of matrix low elasticity and aligned topography on stem cell neurogenic differentiation and rapid neurite outgrowth.

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Yao, Shenglian; Liu, Xi; Yu, Shukui; Wang, Xiumei; Zhang, Shuming; Wu, Qiong; Sun, Xiaodan; Mao, Haiquan

2016-05-21

The development of novel biomaterials that deliver precise regulatory signals to direct stem cell fate for nerve regeneration is the focus of current intensive research efforts. In this study, a hierarchically aligned fibrillar fibrin hydrogel (AFG) that was fabricated through electrospinning and the concurrent molecular self-assembly process mimics both the soft and oriented features of nerve tissue, thus providing hybrid biophysical cues to instruct cell behavior in vitro and in vivo. The electrospun hydrogels were examined by scanning electron microscopy (SEM), polarized light microscopy, small angle X-ray scattering assay and atomic force microscopy (AFM), showing a hierarchically linear-ordered structure from the nanoscale to the macroscale with a soft elastic character (elasticity ∼1 kPa). We found that this low elasticity and aligned topography of AFG exhibit co-effects on promoting the neurogenic differentiation of human umbilical cord mesenchymal stem cells (hUMSCs) in comparison to random fibrin hydrogel (RFG) and tissue culture plate (TCP) control after two week cell culture in growth medium lacking supplementation with soluble neurogenic induction factors. In addition, AFG also induces dorsal root ganglion (DRG) neurons to rapidly project numerous long neurite outgrowths longitudinally along the AFG fibers for a total neurite extension distance of 1.96 mm in three days in the absence of neurotrophic factor supplementation. Moreover, the AFG implanted in a rat T9 dorsal hemisection spinal cord injury model was found to promote endogenous neural cell fast migration and axonal invasion along AFG fibers, resulting in aligned tissue cables in vivo. Our results suggest that matrix stiffness and aligned topography may instruct stem cell neurogenic differentiation and rapid neurite outgrowth, providing great promise for biomaterial design for applications in nerve regeneration.

The effect of intravesical oxybutynin on the ice water test and on electrical perception thresholds in patients with neurogenic detrusor overactivity.

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Van Meel, Tom David; De Wachter, Stefan; Wyndaele, Jean Jacques

2010-03-01

The C-fiber-mediated bladder-cooling reflex and the determination of the current perception thresholds (CPTs) permit to investigate afferent LUT pathways. They have both been proposed to detect and differentiate neurologic bladder dysfunction. This study evaluates, prospectively, the effect of oxybutynin, an antimuscarinic with direct antispasmodic effect on smooth muscle, on repeated ice water test (IWT) and CPTs in patients with a known incomplete neurogenic bladder. Patients with a known incomplete lesion of the bladder innervation, detrusor overactivity during cystometric bladder filling and a continuous positive response to repeated IWT were included. After the initial tests, 30 mg intravesical oxybutynin (1 mg/ml) was instilled and left in the bladder for 15 min. Afterwards CPTs and IWT were re-assessed. After the drug application, the bladder-cooling reflex could not be initiated, even after three instillations, in 16/17 patients. The bladder CPT increased from 29.7 +/- 11.3 to 39.1 +/- 15.7 mA after oxybutynin (P = 0.001). No difference was found in CPT of the left forearm (P = 0.208). Intravesical oxybutynin blocks the bladder-cooling reflex and increases but does not block CPT sensation in the bladder in most patients with incomplete neurogenic lesion and detrusor overactivity. These results help explain the clinical effect of intravesical oxybutynin in neurogenic patients. They also indicate that a pharmacological local influence on C-fiber-related activity can give different clinical effects. (c) 2009 Wiley-Liss, Inc.

Failure of botulinum toxin injection for neurogenic detrusor overactivity: Switch of toxin versus second injection of the same toxin.

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Peyronnet, Benoit; Castel-Lacanal, Evelyne; Manunta, Andréa; Roumiguié, Mathieu; Marque, Philippe; Rischmann, Pascal; Gamé, Xavier

2015-12-01

To evaluate the efficacy of a second injection of the same toxin versus switching to a different botulinum toxin A after failure of a first detrusor injection in patients with neurogenic detrusor overactivity. The charts of all patients who underwent detrusor injections of botulinum toxin A (either abobotulinumtoxinA or onabotulinumtoxinA) for the management of neurogenic detrusor overactivity at a single institution were retrospectively reviewed. Patients in whom a first detrusor injection had failed were included in the present study. They were managed by a second injection of the same toxin at the same dosage or by a new detrusor injection using a different botulinum toxin A. Success was defined as a resolution of urgency, urinary incontinence and detrusor overactivity in a patient self-catheterizing seven times or less per 24 h. A total of 58 patients were included for analysis. A toxin switch was carried out in 29 patients, whereas the other 29 patients received a reinjection of the same toxin at the same dose. The success rate was higher in patients who received a toxin switch (51.7% vs. 24.1%, P = 0.03). Patients treated with a switch from abobotulinumtoxinA to onabotulinumtoxinA and those treated with a switch from onabotulinumtoxinA to abobotulinumtoxinA had similar success rates (52.9% vs. 50%, P = 0.88). After failure of a first detrusor injection of botulinum toxin for neurogenic detrusor overactivity, a switch to a different toxin seems to be more effective than a second injection of the same toxin. The replacement of onabotulinumtoxin by abobotulinumtoxin or the reverse provides similar results. © 2015 The Japanese Urological Association.

[Indices of 24-hour monitoring of arterial blood pressure in patients with neurogenic syncope and patients with chronic constitution- dependent hypotension].

Science.gov (United States)

Musaeva, Z A; Khapaev, B A; Fedotova, A V; Oknin, V Iu

1999-01-01

Clinical-psychologic study, spectral analysis of heart rate variability, 24-h monitoring of arterial pressure (AP) were performed in 20 patients with chronic constitutional arterial hypotension and in 18 patients with neurogenic syncopal states. Both groups were characterised by considerable manifestations of the syndrome of autonomic dystonia, by emotional-personal disorders that correlated with elevated level of slow-waves of the second order in heart rhythms' spectrum. That testified activation of supersegmental sympathetic-adrenal systems. Disorders in sympathetic-parasympathetic correlations were specific in each group. In patients with arterial hypotension disorder of circadian rhythm was observed in the form of superfluous decrease of diastolic AP during sleep. Circadian rhythms in patients with neurogenic syncopes have parameters characteristic for normals showing a preverved chronobiologic AP regulation. A role of the alterations revealed in pathogenesis of arterial hypotensionis discussed.

Plasmodium berghei ANKA: erythropoietin activates neural stem cells in an experimental cerebral malaria model

DEFF Research Database (Denmark)

Core, Andrew; Hempel, Casper; Kurtzhals, Jørgen A L

2011-01-01

investigated if EPO's neuroprotective effects include activation of endogenous neural stem cells (NSC). By using immunohistochemical markers of different NSC maturation stages, we show that EPO increased the number of nestin(+) cells in the dentate gyrus and in the sub-ventricular zone of the lateral...

Impaired TGF-beta induced growth inhibition contributes to the increased proliferation rate of neural stem cells harboring mutant p53

DEFF Research Database (Denmark)

Kumar, Praveen; Naumann, Ulrike; Aigner, Ludwig

2015-01-01

Gliomas have been classified according to their histological properties. However, their respective cells of origin are still unknown. Neural progenitor cells (NPC) from the subventricular zone (SVZ) can initiate tumors in murine models of glioma and are likely cells of origin in the human disease...

Prospective evaluation of antibiotic treatment for urological procedure in patients presenting with neurogenic bladder.

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Weglinski, L; Rouzaud, C; Even, A; Bouchand, F; Davido, B; Duran, C; Salomon, J; Perronne, C; Denys, P; Chartier-Kastler, E; Dinh, A

2016-09-01

Patients presenting with neurogenic bladder often require urological procedures (urodynamic testing and botulinum toxin injections) and a preventive antibiotic therapy. We aimed to assess the efficacy of this little known strategy in a cohort of patients. All patients presenting with neurogenic bladder who underwent urological procedure were included in the study. They received an antibiotic therapy in accordance with the urine cytobacteriological examination results. The antibiotic therapy was initiated two days before the procedure and prolonged up until two days after the procedure if the culture was positive. Patients were treated with a single dose of fosfomycin-trometamol in case of a negative culture. The main study outcome was the occurrence of urinary tract infection (UTI), defined by a positive urine culture and symptoms, up until 14 days after the procedure. A total of 80 urological procedures were performed. Mean patient age was 47±13.1 years (sex ratio 1.22); 59 (73.8%) presented with asymptomatic bacteriuria before the procedure. Nine (11.1%) UTIs were recorded on Day 14, of which one (1.2%) was febrile. Two patients required an additional curative antibiotic therapy. No patient was hospitalized. Overall, 77.8% of UTIs were cured without antibiotic therapy. Screening and treating asymptomatic bacteriuria before urological procedures seems unnecessary and vainly exposes this population at high risk of infectious diseases to antibiotic therapies. This data should be confirmed by a randomized clinical trial. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Neurogenic function in rats with unilateral hippocampal sclerosis that experienced early-life status epilepticus

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Dunleavy, Mark; Schindler, Clara K; Shinoda, Sachiko; Crilly, Shane; Henshall, David C

2014-01-01

Status epilepticus in the adult brain invariably causes an increase in hippocampal neurogenesis and the appearance of ectopic cells and this has been implicated as a causal factor in epileptogenesis. The effect of status epilepticus on neurogenesis in the developing brain is less well characterized and models of early-life seizures typically do not reproduce the hippocampal damage common to human mesial temporal sclerosis. We recently reported that evoking status epilepticus by intra-amygdala microinjection of kainic acid in post-natal (P) day 10 rats caused substantial acute neuronal death within the ipsilateral hippocampus and rats later developed unilateral hippocampal sclerosis and spontaneous recurrent seizures. Here, we examined the expression of a selection of genes associated with neurogenesis and assessed neurogenic function in this model. Protein levels of several markers of neurogenesis including polysialic acid neural cell adhesion molecule, neuroD and doublecortin were reduced in the hippocampus three days after status epilepticus in P10 rats. In contrast, protein levels of neurogenesis markers were similar to control in rats at P55. Pulse-chase experiments using thymidine analogues suggested there was a reduction in new neurons at 72 h after status epilepticus in P10 rats, whereas numbers of new neurons labelled in epileptic rats at P55 with hippocampal sclerosis were similar to controls. The present study suggests that status epilepticus in the immature brain suppresses neurogenesis but the neurogenic potential is retained in animals that later develop hippocampal sclerosis. PMID:25755841

Can adult neural stem cells create new brains? Plasticity in the adult mammalian neurogenic niches: realities and expectations in the era of regenerative biology.

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Kazanis, Ilias

2012-02-01

Since the first experimental reports showing the persistence of neurogenic activity in the adult mammalian brain, this field of neurosciences has expanded significantly. It is now widely accepted that neural stem and precursor cells survive during adulthood and are able to respond to various endogenous and exogenous cues by altering their proliferation and differentiation activity. Nevertheless, the pathway to therapeutic applications still seems to be long. This review attempts to summarize and revisit the available data regarding the plasticity potential of adult neural stem cells and of their normal microenvironment, the neurogenic niche. Recent data have demonstrated that adult neural stem cells retain a high level of pluripotency and that adult neurogenic systems can switch the balance between neurogenesis and gliogenesis and can generate a range of cell types with an efficiency that was not initially expected. Moreover, adult neural stem and precursor cells seem to be able to self-regulate their interaction with the microenvironment and even to contribute to its synthesis, altogether revealing a high level of plasticity potential. The next important step will be to elucidate the factors that limit this plasticity in vivo, and such a restrictive role for the microenvironment is discussed in more details.

Anterior Trans Cervicothoracic Approach for Complete Resection of Cervicothoracic Mediastinal Neurogenic Tumors

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Reza Bagheri

2013-10-01

Full Text Available Introduction:Neurogenic mediastinal tumors comprise a wide range of benign and malignant diseases. A group of these tumors, located at thoracic apex, sometimes spread to cervical spaces causing numerous surgical difficulties. In thoracotomy approaches, due to proximity of the tumors to major blood vessels, complete removal of these tumors from cervical spaces is impossible or may cause intraoperative severe bleeding or other dangerous incidents Because of the adjacent major vessels  that are not visible.The aim of this study is to report cases of surgical treatment of such tumors using Anterior Trans Cervicothoracic Approach (ATCA. Materials and Methods:All patients with neurogenic tumors and cervicomediastinal (CM spread who underwent surgey with ATCA technique during 2005-2011 were included in our study. Then they were evaluated in terms of age, sex, clinical symptoms, radiological and pathological findings, technical success rate of the surgery, surgical complications and first-year relapse rate after the surgery. Results:Our study included 10 patients from whom 9 were female and 1 was male (M/F= 1/9 and the mean age was 27 years. The most common symptoms were pain and feeling of a lump. All patients were operated by this technique successfully. The most common pathological finding was neurofibroma (in 5 patients and surgical complications occurred in 2 patients (20% (Wound infection in 1 patient and brachial plexus injury in another patient. There was no mortality. Disease relapse was reported in 1 patient  ganglioneuroblastoma who underwent surgical resection for the second time. Conclusion: Considering the successful removal of the tumors and favorable exposure of major vessels in cervicomediastinal spaces, this technique is recommended to resect mediastinal tumors with spread to cervical spaces. However, a more definite conclusion requires further studies.

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

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

2009-01-01

The rostral migratory stream (RMS) is the main pathway by which newly born subventricular zone (SVZ) cells reach the olfactory bulb (OB) in rodents. This migration has been well studied in vivo, but an organotypic in vitro model would facilitate more experimental investigations. Here we introduce...

New neurons in the adult brain : The role of sleep and consequences of sleep loss

NARCIS (Netherlands)

Meerlo, Peter; Mistiberger, Ralph E.; Jacobs, Barry L.; Heller, H. Craig; McGinty, Dennis; Mistlberger, Ralph E.

2009-01-01

Research over the last few decades has firmly established that new neurons are generated in selected areas of the adult mammalian brain, particularly the dentate gyrus of the hippocampal formation and the subventricular zone of the lateral ventricles. The function of adult-born neurons is still a

A cell junction pathology of neural stem cells leads to abnormal neurogenesis and hydrocephalus

NARCIS (Netherlands)

Rodríguez, Esteban M; Guerra, María M; Vío, Karin; González, César; Ortloff, Alexander; Bátiz, Luis F; Rodríguez, Sara; Jara, María C; Muñoz, Rosa I; Ortega, Eduardo; Jaque, Jaime; Guerra, Francisco; Sival, Deborah A; den Dunnen, Wilfred F A; Jiménez, Antonio J; Domínguez-Pinos, María D; Pérez-Fígares, José M; McAllister, James P; Johanson, Conrad

2012-01-01

Most cells of the developing mammalian brain derive from the ventricular (VZ) and the subventricular (SVZ) zones. The VZ is formed by the multipotent radial glia/neural stem cells (NSCs) while the SVZ harbors the rapidly proliferative neural precursor cells (NPCs). Evidence from human and animal

Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis.

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Kawaguchi, Daichi; Furutachi, Shohei; Kawai, Hiroki; Hozumi, Katsuto; Gotoh, Yukiko

2013-01-01

Stem cells often divide asymmetrically to produce one stem cell and one differentiating cell, thus maintaining the stem cell pool. Although neural stem cells (NSCs) in the adult mouse subventricular zone have been suggested to divide asymmetrically, intrinsic cell fate determinants for asymmetric NSC division are largely unknown. Stem cell niches are important for stem cell maintenance, but the niche for the maintenance of adult quiescent NSCs has remained obscure. Here we show that the Notch ligand Delta-like 1 (Dll1) is required to maintain quiescent NSCs in the adult mouse subventricular zone. Dll1 protein is induced in activated NSCs and segregates to one daughter cell during mitosis. Dll1-expressing cells reside in close proximity to quiescent NSCs, suggesting a feedback signal for NSC maintenance by their sister cells and progeny. Our data suggest a model in which NSCs produce their own niche cells for their maintenance through asymmetric Dll1 inheritance at mitosis.

Reconstitution of experimental neurogenic bladder dysfunction using skeletal muscle-derived multipotent stem cells.

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Nitta, Masahiro; Tamaki, Tetsuro; Tono, Kayoko; Okada, Yoshinori; Masuda, Maki; Akatsuka, Akira; Hoshi, Akio; Usui, Yukio; Terachi, Toshiro

2010-05-15

BACKGROUND.: Postoperative neurogenic bladder dysfunction is a major complication of radical hysterectomy for cervical cancer and is mainly caused by unavoidable damage to the bladder branch of the pelvic plexus (BBPP) associated with colateral blood vessels. Thus, we attempted to reconstitute disrupted BBPP and blood vessels using skeletal muscle-derived multipotent stem cells that show synchronized reconstitution capacity of vascular, muscular, and peripheral nervous systems. METHODS.: Under pentobarbital anesthesia, intravesical pressure by electrical stimulation of BBPP was measured as bladder function. The distal portion of BBPP with blood vessels was then cut unilaterally (experimental neurogenic bladder model). Measurements were performed before, immediately after, and at 4 weeks after transplantation as functional recovery. Stem cells were obtained from the right soleus and gastrocnemius muscles after enzymatic digestion and cell sorting as CD34/45 (Sk-34) and CD34/45 (Sk-DN). Suspended cells were autografted around the damaged region, whereas medium alone and CD45 cells were transplanted as control groups. To determine the morphological contribution of the transplanted cells, stem cells obtained from green fluorescent protein transgenic mouse muscles were transplanted into a nude rat model and were examined by immunohistochemistry and immunoelectron microscopy. RESULTS.: At 4 weeks after surgery, the transplantation group showed significantly higher functional recovery ( approximately 80%) than the two controls ( approximately 28% and 24%). The transplanted cells showed an incorporation into the damaged peripheral nerves and blood vessels after differentiation into Schwann cells, perineurial cells, vascular smooth muscle cells, pericytes, and fibroblasts around the bladder. CONCLUSION.: Transplantation of multipotent Sk-34 and Sk-DN cells is potentially useful for the reconstitution of damaged BBPP.

Vagotomy decreases the neuronal activities of medulla oblongata and alleviates neurogenic inflammation of airways induced by repeated intra-esophageal instillation of HCl in guinea pigs.

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Chen, Zhe; Chen, Hui; Chen, Fagui; Gu, Dachuan; Sun, Lejia; Zhang, Weitao; Fan, Linfeng; Lin, Yong; Dong, Rong; Lai, Kefang

2017-12-20

Neuronal activity in the medulla oblongata and neurogenic inflammation of airways were investigated in a guinea pig model induced by repeated intra-esophageal instillation of hydrochloric acid (HCl) after vagotomy. Unilateral vagotomy was performed in the vagotomy group, while a sham-operation was performed in the sham group. Operation was not conducted in sham control group. Airway inflammation was observed with hematoxylin and eosin (HE) staining. C-fos protein was measured by immunohistochemistry (IHC) and Western blot (WB). Substance P was examined by IHC and enzyme-linked immuno sorbent assay (ELISA). Airway microvascular permeability was detected by evans blue dye (EBD) fluorescence. Inflammation of airway was observed in the trachea and bronchi after chronic HCl perfusion into the lower esophagus, and was alleviated after unilateral vagotomy. C-fos expression in the medulla oblongata was lower in the vagotomy group compared to the sham control and sham groups. Substance P-like immunoreactivity (SP-li), concentration and microvascular leakage in airway were lower in the vagotomy group than that in the other groups. Our results suggest that vagotomy improved neurogenic inflammation of airways and decreased neuronal activities, the afferent nerves and neurons in medulla oblongata may be involved in neurogenic inflammation of airways mediated by esophageal-bronchial reflex.

Effectiveness of interspinous implant surgery in patients with intermittent neurogenic claudication: a systematic review and meta-analysis

OpenAIRE

Moojen, Wouter A.; Arts, Mark P.; Bartels, Ronald H. M. A.; Jacobs, Wilco C. H.; Peul, Wilco C.

2011-01-01

Introduction Despite an increasing implantation rate of interspinous process distraction (IPD) devices in the treatment of intermittent neurogenic claudication (INC), definitive evidence on the clinical effectiveness of implants is lacking. The main objective of this review was to perform a meta-analysis of all systematic reviews, randomized clinical trials and prospective cohort series to quantify the effectiveness of IPDs and to evaluate the potential side-effects. Methods Data from all stu...

Rapid but not slow spinal cord compression elicits neurogenic pulmonary edema in the rat

Czech Academy of Sciences Publication Activity Database

Šedý, Jiří; Zicha, Josef; Kuneš, Jaroslav; Jendelová, Pavla; Syková, Eva

2009-01-01

Roč. 58, č. 2 (2009), s. 269-277 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LC554; GA ČR GA309/06/1246 Grant - others:EC FP6 projekt RESCUE(FR) LSHB-CT-2005-518233; GA MZd(CZ) 1A8697; GA MZd(CZ) NR8339; GA MŠk(CZ) 1M0538; GA MŠk(CZ) 1M0510 Program:1M; 1M Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50110509 Keywords : neurogenic pulmonary edema * rat * spinal cord injury Subject RIV: FH - Neurology Impact factor: 1.430, year: 2009

The role of sympathetic nervous system in the development of neurogenic pulmonary edema in spinal cord-injured rats

Czech Academy of Sciences Publication Activity Database

Šedý, Jiří; Zicha, Josef; Nedvídková, J.; Kuneš, Jaroslav

2012-01-01

Roč. 112, č. 1 (2012), s. 1-8 ISSN 8750-7587 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GA305/08/0139; GA AV ČR(CZ) IAA500110902 Institutional research plan: CEZ:AV0Z50110509 Keywords : neurogenic pulmonary edema * sympathetic nervous system * baroreflex Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.484, year: 2012

The 'ventral organs' of Pycnogonida (Arthropoda are neurogenic niches of late embryonic and post-embryonic nervous system development.

Directory of Open Access Journals (Sweden)

Georg Brenneis

Full Text Available Early neurogenesis in arthropods has been in the focus of numerous studies, its cellular basis, spatio-temporal dynamics and underlying genetic network being by now comparably well characterized for representatives of chelicerates, myriapods, hexapods and crustaceans. By contrast, neurogenesis during late embryonic and/or post-embryonic development has received less attention, especially in myriapods and chelicerates. Here, we apply (i immunolabeling, (ii histology and (iii scanning electron microscopy to study post-embryonic ventral nerve cord development in Pseudopallene sp., a representative of the sea spiders (Pycnogonida, the presumable sister group of the remaining chelicerates. During early post-embryonic development, large neural stem cells give rise to additional ganglion cell material in segmentally paired invaginations in the ventral ectoderm. These ectodermal cell regions - traditionally designated as 'ventral organs' - detach from the surface into the interior and persist as apical cell clusters on the ventral ganglion side. Each cluster is a post-embryonic neurogenic niche that features a tiny central cavity and initially still houses larger neural stem cells. The cluster stays connected to the underlying ganglionic somata cortex via an anterior and a posterior cell stream. Cell proliferation remains restricted to the cluster and streams, and migration of newly produced cells along the streams seems to account for increasing ganglion cell numbers in the cortex. The pycnogonid cluster-stream-systems show striking similarities to the life-long neurogenic system of decapod crustaceans, and due to their close vicinity to glomerulus-like neuropils, we consider their possible involvement in post-embryonic (perhaps even adult replenishment of olfactory neurons - as in decapods. An instance of a potentially similar post-embryonic/adult neurogenic system in the arthropod outgroup Onychophora is discussed. Additionally, we document two

Spatial distribution of prominin-1 (CD133-positive cells within germinative zones of the vertebrate brain.

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József Jászai

Full Text Available In mammals, embryonic neural progenitors as well as adult neural stem cells can be prospectively isolated based on the cell surface expression of prominin-1 (CD133, a plasma membrane glycoprotein. In contrast, characterization of neural progenitors in non-mammalian vertebrates endowed with significant constitutive neurogenesis and inherent self-repair ability is hampered by the lack of suitable cell surface markers. Here, we have investigated whether prominin-1-orthologues of the major non-mammalian vertebrate model organisms show any degree of conservation as for their association with neurogenic geminative zones within the central nervous system (CNS as they do in mammals or associated with activated neural progenitors during provoked neurogenesis in the regenerating CNS.We have recently identified prominin-1 orthologues from zebrafish, axolotl and chicken. The spatial distribution of prominin-1-positive cells--in comparison to those of mice--was mapped in the intact brain in these organisms by non-radioactive in situ hybridization combined with detection of proliferating neural progenitors, marked either by proliferating cell nuclear antigen or 5-bromo-deoxyuridine. Furthermore, distribution of prominin-1 transcripts was investigated in the regenerating spinal cord of injured axolotl.Remarkably, a conserved association of prominin-1 with germinative zones of the CNS was uncovered as manifested in a significant co-localization with cell proliferation markers during normal constitutive neurogenesis in all species investigated. Moreover, an enhanced expression of prominin-1 became evident associated with provoked, compensatory neurogenesis during the epimorphic regeneration of the axolotl spinal cord. Interestingly, significant prominin-1-expressing cell populations were also detected at distinct extraventricular (parenchymal locations in the CNS of all vertebrate species being suggestive of further, non-neurogenic neural function

Characteristics of neurogenic bowel in spinal cord injury and perceived quality of life.

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Pardee, Connie; Bricker, Diedre; Rundquist, Jeanine; MacRae, Christi; Tebben, Cherisse

2012-01-01

To investigate the association between characteristics of individuals with spinal cord injury and neurogenic bowel and their perceived quality of life. The study design is an exploratory, descriptive correlational design. To measure the variables of the study the Quality of Life Survey developed by Randell et al. (2001) was used to measure perceived quality of life related to bowel management. Individual bowel management preferences and subjective costs and benefits of the preferences were gathered through the Neurogenic Bowel Characteristics Survey. PARTICIPANTS/METHOD: Data were collected from a random half of the individuals who met the inclusion criteria from the patient database (n=1193). Two hundred and forty one surveys were analyzed for this study. More than half of the sample (n=134) provided their own bowel management consisting of digital stimulation, suppositories, and other aids; 8% (n=19) had a colostomy. Regardless of the bowel management program 54% (n=127) were satisfied with current methods. Although time reported to complete bowel programs ranged from 1 to 120 minutes, there was no difference in rating of satisfaction with time. There was a statistically significant difference between those satisfied and dissatisfied with current bowel management and quality of life; those satisfied demonstrated a higher quality of life on three subscales, work function (p= .021), bowel problems (p< .001), and social function (p< .001). Those dissatisfied with their bowel program perceived a lower quality of life and indicated problems of time (p= .001), pain or discomfort (p= .033), and poor results (p< .001). Research data provide the patient's perspective on bowel management characteristics, complications, satisfaction, and their perceived quality of life. Results of this research will be incorporated into bowel management education and possible modification of the current inpatient bowel management program. © 2012 Association of Rehabilitation Nurses.

Kinin B1 Receptor Promotes Neurogenic Hypertension Through Activation of Centrally Mediated Mechanisms.

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Sriramula, Srinivas; Lazartigues, Eric

2017-12-01

Hypertension is associated with increased activity of the kallikrein-kinin system. Kinin B1 receptor (B1R) activation leads to vasoconstriction and inflammation. Despite evidence supporting a role for the B1R in blood pressure regulation, the mechanisms by which B1R could alter autonomic function and participate in the pathogenesis of hypertension remain unidentified. We sought to explore whether B1R-mediated inflammation contributes to hypertension and investigate the molecular mechanisms involved. In this study, we tested the hypothesis that activation of B1R in the brain is involved in the pathogenesis of hypertension, using the deoxycorticosterone acetate-salt model of neurogenic hypertension in wild-type and B1R knockout mice. Deoxycorticosterone acetate-salt treatment in wild-type mice led to significant increases in B1R mRNA and protein levels and bradykinin levels, enhanced gene expression of carboxypeptidase N supporting an increase in the B1R ligand, associated with enhanced blood pressure, inflammation, sympathoexcitation, autonomic dysfunction, and impaired baroreflex sensitivity, whereas these changes were blunted or prevented in B1R knockout mice. B1R stimulation was further shown to involve activation of the ASK1-JNK-ERK1/2 and NF-κB pathways in the brain. To dismiss potential developmental alterations in knockout mice, we further used B1R blockade selectively in the brain of wild-type mice. Supporting the central origin of this mechanism, intracerebroventricular infusion of a specific B1R antagonist, attenuated the deoxycorticosterone acetate-salt-induced increase in blood pressure in wild-type mice. Our data provide the first evidence of a central role for B1R-mediated inflammatory pathways in the pathogenesis of deoxycorticosterone acetate-salt hypertension and offer novel insights into possible B1R-targeted therapies for the treatment of neurogenic hypertension. © 2017 American Heart Association, Inc.

Endobronchial neurogenic tumor: A combination of traumatic neuroma and neurofibroma

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Amit Tandon

2017-01-01

Full Text Available Traumatic neuromas are uncommon and benign lesions arising from a peripheral nerve injury during surgery. Here we describe a case with histopathologic features of both a traumatic neuroma and neurofibroma in a patient without integumentary physical exam findings nor prior surgical history. A 54 year old male was admitted for surgical debridement of a foot ulcer. During pre-operative evaluation and review of imaging multiple CT scans revealed a stable, 4 mm endobronchial lesion in the left lower lobe. Given history of nicotine abuse, bronchoscopy was performed. Bronchoscopy showed a pearly, polypoid lesion. Histopathological results showed strong positivity for S-100 protein and spindle cell proliferation. Repeat CT chest showed no new lesions in the bronchial tree. The rarity of this case is noted not only by the limited number of bronchial neurogenic tumors, but the combined features in this case of a traumatic neuroma and neurofibroma which has not been described.

In vivo transcriptional profile analysis reveals RNA splicing and chromatin remodeling as prominent processes for adult neurogenesis.

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Lim, Daniel A; Suárez-Fariñas, Mayte; Naef, Felix; Hacker, Coleen R; Menn, Benedicte; Takebayashi, Hirohide; Magnasco, Marcelo; Patil, Nila; Alvarez-Buylla, Arturo

2006-01-01

Neural stem cells and neurogenesis persist in the adult mammalian brain subventricular zone (SVZ). Cells born in the rodent SVZ migrate to the olfactory bulb (Ob) where they differentiate into interneurons. To determine the gene expression and functional profile of SVZ neurogenesis, we performed three complementary sets of transcriptional analysis experiments using Affymetrix GeneChips: (1) comparison of adult mouse SVZ and Ob gene expression profiles with those of the striatum, cerebral cortex, and hippocampus; (2) profiling of SVZ stem cells and ependyma isolated by fluorescent-activated cell sorting (FACS); and (3) analysis of gene expression changes during in vivo SVZ regeneration after anti-mitotic treatment. Gene Ontology (GO) analysis of data from these three separate approaches showed that in adult SVZ neurogenesis, RNA splicing and chromatin remodeling are biological processes as statistically significant as cell proliferation, transcription, and neurogenesis. In non-neurogenic brain regions, RNA splicing and chromatin remodeling were not prominent processes. Fourteen mRNA splicing factors including Sf3b1, Sfrs2, Lsm4, and Khdrbs1/Sam68 were detected along with 9 chromatin remodeling genes including Mll, Bmi1, Smarcad1, Baf53a, and Hat1. We validated the transcriptional profile data with Northern blot analysis and in situ hybridization. The data greatly expand the catalogue of cell cycle components, transcription factors, and migration genes for adult SVZ neurogenesis and reveal RNA splicing and chromatin remodeling as prominent biological processes for these germinal cells.

Inducible Activation of ERK5 MAP Kinase Enhances Adult Neurogenesis in the Olfactory Bulb and Improves Olfactory Function

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Wang, Wenbin; Lu, Song; Li, Tan; Pan, Yung-Wei; Zou, Junhui; Abel, Glen M.; Xu, Lihong; Storm, Daniel R.

2015-01-01

Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury. PMID:25995470

β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain

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Teppei Fujioka

2017-02-01

Full Text Available Cerebral ischemic stroke is a main cause of chronic disability. However, there is currently no effective treatment to promote recovery from stroke-induced neurological symptoms. Recent studies suggest that after stroke, immature neurons, referred to as neuroblasts, generated in a neurogenic niche, the ventricular-subventricular zone, migrate toward the injured area, where they differentiate into mature neurons. Interventions that increase the number of neuroblasts distributed at and around the lesion facilitate neuronal repair in rodent models for ischemic stroke, suggesting that promoting neuroblast migration in the post-stroke brain could improve efficient neuronal regeneration. To move toward the lesion, neuroblasts form chain-like aggregates and migrate along blood vessels, which are thought to increase their migration efficiency. However, the molecular mechanisms regulating these migration processes are largely unknown. Here we studied the role of β1-class integrins, transmembrane receptors for extracellular matrix proteins, in these migrating neuroblasts. We found that the neuroblast chain formation and blood vessel-guided migration critically depend on β1 integrin signaling. β1 integrin facilitated the adhesion of neuroblasts to laminin and the efficient translocation of their soma during migration. Moreover, artificial laminin-containing scaffolds promoted neuroblast chain formation and migration toward the injured area. These data suggest that laminin signaling via β1 integrin supports vasculature-guided neuronal migration to efficiently supply neuroblasts to injured areas. This study also highlights the importance of vascular scaffolds for cell migration in development and regeneration.

The ciliary margin zone of the mammalian retina generates retinal ganglion cells

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Marcucci, Florencia; Murcia-Belmonte, Veronica; Coca, Yaiza; Ferreiro-Galve, Susana; Wang, Qing; Kuwajima, Takaaki; Khalid, Sania; Ross, M. Elizabeth; Herrera, Eloisa; Mason, Carol

2016-01-01

Summary The retina of lower vertebrates grows continuously by integrating new neurons generated from progenitors in the ciliary margin zone (CMZ). Whether the mammalian CMZ provides the neural retina with retinal cells is controversial. Live-imaging of embryonic retina expressing eGFP in the CMZ shows that cells migrate laterally from the CMZ to the neural retina where differentiated retinal ganglion cells (RGCs) reside. As Cyclin D2, a cell-cycle regulator, is enriched in ventral CMZ, we analyzed Cyclin D2−/− mice to test whether the CMZ is a source of retinal cells. Neurogenesis is diminished in Cyclin D2 mutants, leading to a reduction of RGCs in the ventral retina. In line with these findings, in the albino retina, the decreased production of ipsilateral RGCs is correlated with fewer Cyclin D2+ cells. Together, these results implicate the mammalian CMZ as a neurogenic site that produces RGCs and whose proper generation depends on Cyclin D2 activity. PMID:28009286

The ‘Ventral Organs’ of Pycnogonida (Arthropoda) Are Neurogenic Niches of Late Embryonic and Post-Embryonic Nervous System Development

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Brenneis, Georg; Scholtz, Gerhard

2014-01-01

Early neurogenesis in arthropods has been in the focus of numerous studies, its cellular basis, spatio-temporal dynamics and underlying genetic network being by now comparably well characterized for representatives of chelicerates, myriapods, hexapods and crustaceans. By contrast, neurogenesis during late embryonic and/or post-embryonic development has received less attention, especially in myriapods and chelicerates. Here, we apply (i) immunolabeling, (ii) histology and (iii) scanning electron microscopy to study post-embryonic ventral nerve cord development in Pseudopallene sp., a representative of the sea spiders (Pycnogonida), the presumable sister group of the remaining chelicerates. During early post-embryonic development, large neural stem cells give rise to additional ganglion cell material in segmentally paired invaginations in the ventral ectoderm. These ectodermal cell regions – traditionally designated as ‘ventral organs’ – detach from the surface into the interior and persist as apical cell clusters on the ventral ganglion side. Each cluster is a post-embryonic neurogenic niche that features a tiny central cavity and initially still houses larger neural stem cells. The cluster stays connected to the underlying ganglionic somata cortex via an anterior and a posterior cell stream. Cell proliferation remains restricted to the cluster and streams, and migration of newly produced cells along the streams seems to account for increasing ganglion cell numbers in the cortex. The pycnogonid cluster-stream-systems show striking similarities to the life-long neurogenic system of decapod crustaceans, and due to their close vicinity to glomerulus-like neuropils, we consider their possible involvement in post-embryonic (perhaps even adult) replenishment of olfactory neurons – as in decapods. An instance of a potentially similar post-embryonic/adult neurogenic system in the arthropod outgroup Onychophora is discussed. Additionally, we document two transient

Transcutaneous stimulation of the posterior tibial nerve for treating refractory urge incontinence of idiopathic and neurogenic origin.

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Valles-Antuña, C; Pérez-Haro, M L; González-Ruiz de L, C; Quintás-Blanco, A; Tamargo-Diaz, E M; García-Rodríguez, J; San Martín-Blanco, A; Fernandez-Gomez, J M

2017-09-01

To assess the efficacy of treatment with transcutaneous posterior tibial nerve stimulation (TPTNS) in patients with urge urinary incontinence, of neurogenic or nonneurogenic origin, refractory to first-line therapeutic options. We included 65 patients with urge urinary incontinence refractory to medical treatment. A case history review, a urodynamic study and a somatosensory evoked potentials (SEP) study were conducted before the TPTNS, studying the functional urological condition by means of a voiding diary. The treatment consisted of 10 weekly sessions of TPTNS lasting 30minutes. Some 57.7% of the patients showed abnormal tibial SEPs, and 42% showed abnormal pudendal SEPs. A statistically significant symptomatic improvement was observed in all clinical parameters after treatment with TPTNS, and 66% of the patients showed an overall improvement, regardless of sex, the presence of underlying neurological disorders, detrusor hyperactivity in the urodynamic study or SEP disorders. There were no adverse effects during the treatment. TPTNS is an effective and well tolerated treatment in patients with urge incontinence refractory to first-line therapies and should be offered early in the treatment strategy. New studies are needed to identify the optimal parameters of stimulation, the most effective treatment protocols and long-term efficacy, as well as its applicability to patients with a neurogenic substrate. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Effects and Safety of Aqueous Extract of Poncirus fructus in Spinal Cord Injury with Neurogenic Bowel

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Ji Hee Kim

2016-01-01

Full Text Available Objective. To investigate the effects and safety of the aqueous extract of the dried, immature fruit of Poncirus trifoliata (L. Raf., known as Poncirus fructus (PF, in spinal cord injury (SCI patients with neurogenic bowel. Methods. Thirty-one SCI patients with neurogenic bowel were recruited. Patients were evaluated based on clinical information, constipation score, Bristol Stool Form Scale, stool retention score using plain abdominal radiograph, and colon transit time. PF was administered in dosages of 800 mg each prior to breakfast and lunch for 14 days. Results. The morphological feature of the stool before and after administration indicated a statistically significant difference from 3.52 ± 1.33 to 4.32 ± 1.44 points (p<0.05. Stool retention score before and after administration of PF was represented with low significance (7.25 ± 1.60 to 6.46 ± 1.53 points in the whole colon (p<0.05, and the colon transit time was significantly shortened (57.41 ± 20.7 to 41.2 ± 25.5 hours in terms of the whole transit time (p<0.05. Side effects were observed in 7 people (28.0% consisting of 2 people with soft stools and 5 people with diarrhea. Conclusion. For SCI patients, PF administration significantly improved defecation patterns, defecation retention, and colon transit time. PF could be an effective aid to improve colonic motility and constipation.

PET-scan shows peripherally increased neurokinin 1 receptor availability in chronic tennis elbow: visualizing neurogenic inflammation?

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Magnus Peterson

Full Text Available In response to pain, neurokinin 1 (NK1 receptor availability is altered in the central nervous system. The NK1 receptor and its primary agonist, substance P, also play a crucial role in peripheral tissue in response to pain, as part of neurogenic inflammation. However, little is known about alterations in NK1 receptor availability in peripheral tissue in chronic pain conditions and very few studies have been performed on human beings. Ten subjects with chronic tennis elbow were therefore examined by positron emission tomography (PET with the NK1 specific radioligand [(11C]GR205171 before and after treatment with graded exercise. The radioligand signal intensity was higher in the affected arm as compared with the unaffected arm, measured as differences between the arms in volume of voxels and signal intensity of this volume above a reference threshold set as 2.5 SD above mean signal intensity of the unaffected arm before treatment. In the eight subjects examined after treatment, pain ratings decreased in all subjects but signal intensity decreased in five and increased in three. In conclusion, NK1 receptors may be activated, or up-regulated in the peripheral, painful tissue of a chronic pain condition. This up-regulation does, however, have moderate correlation to pain ratings. The increased NK1 receptor availability is interpreted as part of ongoing neurogenic inflammation and may have correlation to the pathogenesis of chronic tennis elbow.ClinicalTrials.gov NCT00888225 http://clinicaltrials.gov/

Myopathy in CRPS-I: disuse or neurogenic?

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Hulsman, Natalie M; Geertzen, Jan H B; Dijkstra, Pieter U; van den Dungen, Jan J A M; den Dunnen, Wilfred F A

2009-08-01

The diagnosis Complex Regional Pain Syndrome type I (CRPS-I) is based on clinical symptoms, including motor symptoms. Histological changes in muscle tissue may be present in the chronic phase of CRPS-I. Aim of this study was to analyze skeletal muscle tissue from amputated limbs of patients with CRPS-I, in order to gain more insight in factors that may play a role in changes in muscles in CRPS-I. These changes may be helpful in clarifying the pathophysiology of CRPS-I. Fourteen patients with therapy resistant and longstanding CRPS-I, underwent an amputation of the affected limb. In all patients histological analysis showed extensive changes in muscle tissue, such as fatty degeneration, fibre atrophy and nuclear clumping, which was not related to duration of CRPS-I prior to amputation. In all muscles affected, both type 1 and type 2 fibre atrophy was found, without selective type 2 fibre atrophy. In four patients, type grouping was observed, indicating a sequence of denervation and reinnervation of muscle tissue. In two patients even large group atrophy was present, suggesting new denervation after reinnervation. Comparison between subgroups in arms and legs showed no difference in the number of changes in muscle tissue. Intrinsic and extrinsic muscles were affected equally. Our findings show that in the chronic phase of CRPS-I extensive changes can be seen in muscle tissue, not related to duration of CRPS-I symptoms. Signs of neurogenic myopathy were present in five patients.

Gamma-Secretase Inhibitors Attenuate Neurotrauma and Neurogenic Acute Lung Injury in Rats by Rescuing the Accumulation of Hypertrophic Microglia

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Hung-Jung Lin

2017-12-01

Full Text Available Background/Aims: In response to traumatic brain injury (TBI, activated microglia exhibit changes in their morphology from the resting ramified phenotype toward the activated hypertrophic or amoeboid phenotype. Here, we provide the first description of the mechanism underlying the neuroprotective effects of γ-secretase inhibitors on TBI outcomes in rats. Methods: The neuroprotective effects of γ-secretase inhibitors such as LY411575 or CHF5074 on TBI-induced neurotoxicity were analysed using a neurological motor function evaluation, cerebral contusion assay, immunohistochemical staining for microglia phenotypes, lung injury score and Evans Blue dye extravasation assay of brain and lung oedema. Results: Hypertrophic or amoeboid microglia accumulated in the injured cortex, the blood-brain-barrier was disrupted and neurological deficits and acute lung injury were observed 4 days after TBI in adult rats. However, a subcutaneous injection of LY411575 (5 mg/kg or CHF5074 (30 mg/kg immediately after TBI and once daily for 3 consecutive days post-TBI significantly attenutaed the accumulation of hypertrophic microglia in the injured brain, neurological injury, and neurogenic acute lung injury. Conclusion: Gamma-secretase inhibitors attenuated neurotrauma and neurogenic acute lung injury in rats by reducing the accumulation of hypertrophic microglia in the vicinity of the lesion.

Neurogenic vision loss: Causes and outcome. An experience from a tertiary center in Northern India

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Rajesh Verma

2014-01-01

Full Text Available Introduction: Vision loss can be a consequence of numerous disorders of eye and neural pathway conveying visual input to brain. A variety of conditions can affect visual pathway producing neurogenic vision loss. The presentation and course of vision loss depends on the site of involvement and underlying etiology. We conducted this unprecedented study to evaluate the characteristics and outcome of various diseases of the visual pathway. Materials and Methods: In this prospective cohort study, we evaluated 64 patients with neurogenic visual impairment. Ophthalmological causes were excluded in all of them. Their presentation, ophthalmological characteristics and investigation findings were recorded. These patients were followed up till 6 months. Results: Out of 69 patients evaluated, 5 were excluded as they had ophthalmological abnormalities. The remaining 64 cases (113 eyes were enrolled. 54 cases were due to diseases of anterior visual pathway and rest 10 had cortical vision loss. The etiologic distribution is as follows: Isolated optic neuritis- 12 (19%, multiple sclerosis- 4 (6.3%, neuromyelitis optica- 5 (7.9%, tubercular meningitis- 15 (23.8%, non-arteritic ischemic optic neuropathy, ischemic optic neuropathy complicating cavernous sinus thrombosis, cryptococcal meningitis, malignant infiltration of optic nerve, Crouzon′s syndrome, calvarial thickening and traumatic occipital gliosis- 1 (1.6% case each, idiopathic intracranial hypertension, pituitary adenoma, acute disseminated encephalomyelitis, posterior reversible leukoencephalopathy- 3 (4.8% cases each, cortical venous thrombosis 5 (7.9%, subacute scleroing panencephalitis- 4 (6.3% cases. Conclusions: The diseases of anterior visual pathway were much more common than cortical vision loss. A majority of our patients had severe impairment of vision at presentation.

Neural tissue-spheres

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Andersen, Rikke K; Johansen, Mathias; Blaabjerg, Morten

2007-01-01

By combining new and established protocols we have developed a procedure for isolation and propagation of neural precursor cells from the forebrain subventricular zone (SVZ) of newborn rats. Small tissue blocks of the SVZ were dissected and propagated en bloc as free-floating neural tissue...... content, thus allowing experimental studies of neural precursor cells and their niche...

CRMP5 regulates generation and survival of newborn neurons in olfactory and hippocampal neurogenic areas of the adult mouse brain.

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Alexandra Veyrac

Full Text Available The Collapsin Response Mediator Proteins (CRMPS are highly expressed in the developing brain, and in adult brain areas that retain neurogenesis, ie: the olfactory bulb (OB and the dentate gyrus (DG. During brain development, CRMPs are essentially involved in signaling of axon guidance and neurite outgrowth, but their functions in the adult brain remain largely unknown. CRMP5 has been initially identified as the target of auto-antibodies involved in paraneoplasic neurological diseases and further implicated in a neurite outgrowth inhibition mediated by tubulin binding. Interestingly, CRMP5 is also highly expressed in adult brain neurogenic areas where its functions have not yet been elucidated. Here we observed in both neurogenic areas of the adult mouse brain that CRMP5 was present in proliferating and post-mitotic neuroblasts, while they migrate and differentiate into mature neurons. In CRMP5(-/- mice, the lack of CRMP5 resulted in a significant increase of proliferation and neurogenesis, but also in an excess of apoptotic death of granule cells in the OB and DG. These findings provide the first evidence that CRMP5 is involved in the generation and survival of newly generated neurons in areas of the adult brain with a high level of activity-dependent neuronal plasticity.

Evaluation of educational content of YouTube videos relating to neurogenic bladder and intermittent catheterization.

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Ho, Matthew; Stothers, Lynn; Lazare, Darren; Tsang, Brian; Macnab, Andrew

2015-01-01

Many patients conduct internet searches to manage their own health problems, to decide if they need professional help, and to corroborate information given in a clinical encounter. Good information can improve patients' understanding of their condition and their self-efficacy. Patients with spinal cord injury (SCI) featuring neurogenic bladder (NB) require knowledge and skills related to their condition and need for intermittent catheterization (IC). Information quality was evaluated in videos accessed via YouTube relating to NB and IC using search terms "neurogenic bladder intermittent catheter" and "spinal cord injury intermittent catheter." Video content was independently rated by 3 investigators using criteria based on European Urological Association (EAU) guidelines and established clinical practice. In total, 71 videos met the inclusion criteria. Of these, 12 (17%) addressed IC and 50 (70%) contained information on NB. The remaining videos met inclusion criteria, but did not contain information relevant to either IC or NB. Analysis indicated poor overall quality of information, with some videos with information contradictory to EAU guidelines for IC. High-quality videos were randomly distributed by YouTube. IC videos featuring a healthcare narrator scored significantly higher than patient-narrated videos, but not higher than videos with a merchant narrator. About half of the videos contained commercial content. Some good-quality educational videos about NB and IC are available on YouTube, but most are poor. The videos deemed good quality were not prominently ranked by the YouTube search algorithm, consequently user access is less likely. Study limitations include the limit of 50 videos per category and the use of a de novo rating tool. Information quality in videos with healthcare narrators was not higher than in those featuring merchant narrators. Better material is required to improve patients' understanding of their condition.

Neurogenic bowel dysfunction in patients with spinal cord injury, myelomeningocele, multiple sclerosis and Parkinson's disease

Institute of Scientific and Technical Information of China (English)

Richard A Awad

2011-01-01

Exciting new features have been described concerning neurogenic bowel dysfunction, including interactions between the central nervous system, the enteric nervous system, axonal injury, neuronal loss, neurotransmission of noxious and non-noxious stimuli, and the fields of gastroenterology and neurology. Patients with spinal cord injury, myelomeningocele, multiple sclerosis and Parkinson's disease present with serious upper and lower bowel dysfunctions characterized by constipation, incontinence, gastrointestinal motor dysfunction and altered visceral sensitivity. Spinal cord injury is associated with severe autonomic dysfunction, and bowel dysfunction is a major physical and psychological burden for these patients. An adult myelomeningocele patient commonly has multiple problems reflecting the multisystemic nature of the disease. Multiple sclerosis is a neurodegenerative disorder in which axonal injury, neuronal loss, and atrophy of the central nervous system can lead to permanent neurological damage and clinical disability. Parkinson's disease is a multisystem disorder involving dopaminergic, noradrenergic, serotoninergic and cholinergic systems, characterized by motor and non-motor symptoms. Parkinson's disease affects several neuronal structures outside the substantia nigra, among which is the enteric nervous system. Recent reports have shown that the lesions in the enteric nervous system occur in very early stages of the disease, even before the involvement of the central nervous system. This has led to the postulation that the enteric nervous system could be critical in the pathophysiology of Parkinson's disease, as it could represent the point of entry for a putative environmental factor to initiate the pathological process. This review covers the data related to the etiology, epidemiology, clinical expression, pathophysiology, genetic aspects, gastrointestinal motor dysfunction, visceral sensitivity, management, prevention and prognosis of neurogenic bowel

Dorsal Vagal Complex Modulates Neurogenic Airway Inflammation in a Guinea Pig Model With Esophageal Perfusion of HCl

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Zhe Chen

2018-05-01

Full Text Available Neurogenic airway inflammation in chronic cough and bronchial asthma related to gastroesophageal reflux (GER is involved in the esophageal–bronchial reflex, but it is unclear whether this reflex is mediated by central neurons. This study aimed to investigate the regulatory effects of the dorsal vagal complex (DVC on airway inflammation induced by the esophageal perfusion of hydrochloric acid (HCl following the microinjection of nuclei in the DVC in guinea pigs. Airway inflammation was evaluated by measuring the extravasation of Evans blue dye (EBD and substance P (SP expression in the airway. Neuronal activity was indicated by Fos expression in the DVC. The neural pathways from the lower esophagus to the DVC and the DVC to the airway were identified using DiI tracing and pseudorabies virus Bartha (PRV-Bartha retrograde tracing, respectively. HCl perfusion significantly increased plasma extravasation, SP expression in the trachea, and the expression of SP and Fos in the medulla oblongata nuclei, including the nucleus of the solitary tract (NTS and the dorsal motor nucleus of the vagus (DMV. The microinjection of glutamic acid (Glu or exogenous SP to enhance neuronal activity in the DVC significantly potentiated plasma extravasation and SP release induced by intra-esophageal perfusion. The microinjection of γ-aminobutyric acid (GABA, lidocaine to inhibit neuronal activity or anti-SP serum in the DVC alleviated plasma extravasation and SP release. In conclusion, airway inflammation induced by the esophageal perfusion of HCl is regulated by DVC. This study provides new insight for the mechanism of airway neurogenic inflammation related to GER.

Preoperative Duplex Scanning is a Helpful Diagnostic Tool in Neurogenic Thoracic Outlet Syndrome.

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Orlando, Megan S; Likes, Kendall C; Mirza, Serene; Cao, Yue; Cohen, Anne; Lum, Ying Wei; Freischlag, Julie A

2016-01-01

To evaluate the diagnostic role of venous and arterial duplex scanning in neurogenic thoracic outlet syndrome (NTOS). Retrospective review of patients who underwent duplex ultrasonography prior to first rib resection and scalenectomy (FRRS) for NTOS from 2005 to 2013. Abnormal scans included ipsilateral compression (IC) with abduction of the symptomatic extremity (>50% change in subclavian vessel flow), contralateral (asymptomatic side) compression (CC) or bilateral compression (BC). A total of 143 patients (76% female, average age 34, range 13-59) underwent bilateral preoperative duplex scanning. Ipsilateral compression was seen in 44 (31%), CC in 12 (8%), and BC in 14 (10%). Seventy-three (51%) patients demonstrated no compression. Patients with IC more often experienced intraoperative pneumothoraces (49% vs. 25%, P duplex ultrasonography can assist in NTOS diagnosis. Ipsilateral compression on abduction often correlates with Adson testing. © The Author(s) 2016.

Regenerative medicine using adult neural stem cells: the potential for diabetes therapy and other pharmaceutical applications

Institute of Scientific and Technical Information of China (English)

Tomoko Kuwabara; Makoto Asashima

2012-01-01

Neural stem cells (NSCs),which are responsible for continuous neurogenesis during the adult stage,are present in human adults.The typical neurogenic regions are the hippocampus and the subventricular zone; recent studies have revealed that NSCs also exist in the olfactory bulb.Olfactory bulb-derived neural stem cells (OB NSCs) have the potential to be used in therapeutic applications and can be easily harvested without harm to the patient.Through the combined influence of extrinsic cues and innate programming,adult neurogenesis is a finely regulated process occurring in a specialized cellular environment,a niche.Understanding the regulatory mechanisms of adult NSCs and their cellular niche is not only important to understand the physiological roles of neurogenesis in adulthood,but also to provide the knowledge necessary for developing new therapeutic applications using adult NSCs in other organs with similar regulatory environments.Diabetes is a devastating disease affecting more than 200 million people worldwide.Numerous diabetic patients suffer increased symptom severity after the onset,involving complications such as retinopathy and nephropathy.Therefore,the development of treatments for fundamental diabetes is important.The utilization of autologous cells from patients with diabetes may address challenges regarding the compatibility of donor tissues as well as provide the means to naturally and safely restore function,reducing future risks while also providing a long-term cure.Here,we review recent findings regarding the use of adult OB NSCs as a potential diabetes cure,and discuss the potential of OB NSC-based pharmaceutical applications for neuronal diseases and mental disorders.

Inducible activation of ERK5 MAP kinase enhances adult neurogenesis in the olfactory bulb and improves olfactory function.

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Wang, Wenbin; Lu, Song; Li, Tan; Pan, Yung-Wei; Zou, Junhui; Abel, Glen M; Xu, Lihong; Storm, Daniel R; Xia, Zhengui

2015-05-20

Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury. Copyright © 2015 the authors 0270-6474/15/357833-17$15.00/0.

[Posttraumatic stress disorder in patients with neurogenic amnesia for the traumatic event].

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Podoll, K; Kunert, H J; Sass, H

2000-10-01

The development of symptoms of posttraumatic stress disorder (PTSD) in patients with neurogenic amnesia for the traumatic event is recorded in 2 own patients and in 19 cases from the clinical literature. With a single exception, all patients were accident victims with closed head injuries. Only about three quarters of the patients completely fulfilled DSM-III-R criteria of PTSD. Nineteen patients displayed involuntary conscious memories of aspects of the traumatic event (presenting as recurrent intrusive thoughts, images or dreams) co-existent with a complete or partial lack of voluntary conscious memories of the trauma, suggesting that different memory systems and distinct brain mechanisms subserve these phenomena. The said clinical observations are discussed against the background of current neuropsychological models of multiple memory systems. The recorded cases demonstrate that declarative episodic memory is not necessary for symptoms of PTSD to emerge, whereas preserved functions of non-declarative memory systems represent a sufficient condition for the development of PTSD symptoms.

Is Melanoma a stem cell tumor? Identification of neurogenic proteins in trans-differentiated cells

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Chan Linda S

2005-03-01

Full Text Available Abstract Background Although several genes and proteins have been implicated in the development of melanomas, the molecular mechanisms involved in the development of these tumors are not well understood. To gain a better understanding of the relationship between the cell growth, tumorigenesis and differentiation, we have studied a highly malignant cat melanoma cell line that trans-differentiates into neuronal cells after exposure to a feline endogenous retrovirus RD114. Methods To define the repertoire of proteins responsible for the phenotypic differences between melanoma and its counterpart trans-differentiated neuronal cells we have applied proteomics technology and compared protein profiles of the two cell types and identified differentially expressed proteins by 2D-gel electrophoresis, image analyses and mass spectrometry. Results The melanoma and trans-differentiated neuronal cells could be distinguished by the presence of distinct sets of proteins in each. Although approximately 60–70% of the expressed proteins were shared between the two cell types, twelve proteins were induced de novo after infection of melanoma cells with RD114 virus in vitro. Expression of these proteins in trans-differentiated cells was significantly associated with concomitant down regulation of growth promoting proteins and up-regulation of neurogenic proteins (p = 95% proteins expressed in trans-differentiated cells could be associated with the development, differentiation and regulation of nervous system cells. Conclusion Our results indicate that the cat melanoma cells have the ability to differentiate into distinct neuronal cell types and they express proteins that are essential for self-renewal. Since melanocytes arise from the neural crest of the embryo, we conclude that this melanoma arose from embryonic precursor stem cells. This model system provides a unique opportunity to identify domains of interactions between the expressed proteins that halt the

MILD® Is an Effective Treatment for Lumbar Spinal Stenosis with Neurogenic Claudication: MiDAS ENCORE Randomized Controlled Trial.

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Benyamin, Ramsin M; Staats, Peter S; MiDAS Encore, Investigators

2016-05-01

Lumbar spinal stenosis (LSS) is a common degenerative condition of the spine, which is a major cause of pain and functional disability for the elderly. Neurogenic claudication symptoms are a hallmark of LSS, where patients develop low back or leg pain when walking or standing that is relieved by sitting or lumbar flexion. The treatment of LSS generally begins with conservative management such as physical therapy, home exercise programs, and oral analgesics. Once these therapies fail, patients commonly move forward with interventional pain treatment options such as epidural steroid injections (ESIs) or MILD® as the next step. To assess improvement of function and reduction in pain for Medicare beneficiaries following treatment with MILD (treatment group) in LSS patients with neurogenic claudication and verified ligamentum flavum hypertrophy and to compare to a control group receiving ESIs. Prospective, multi-center, randomized controlled clinical trial. Twenty-six US interventional pain management centers. Patients in this trial were randomized one to one into 2 study arms. A total of 302 patients were enrolled, with 149 randomized to MILD and 153 to the active control. Outcomes are assessed using the Oswestry Disability Index (ODI), Numeric Pain Rating Scale (NPRS) and Zurich Claudication Questionnaire (ZCQ). Primary efficacy is the proportion of ODI responders, tested for statistical superiority of the MILD group versus the ESI group. ODI responders are defined as patients achieving the validated Minimal Important Change (MIC) of = 10 point improvement in ODI from baseline to follow-up. Similarly, secondary efficacy is the proportion of NPRS and ZCQ responders using validated MIC thresholds. Primary safety is the incidence of device- or procedure-related adverse events in each group. This report presents safety and efficacy results at 1-year follow-up. Outcomes at 2 years will be collected and reported for patients in the MILD group only. At 1-year follow-up, ODI

Early Postnatal but Not Late Adult Neurogenesis Is Impaired in the Pitx3-Mutant Animal Model of Parkinson's Disease

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Moritz D. Brandt

2017-08-01

Full Text Available The generation of new neurons in the adult dentate gyrus has functional implications for hippocampal formation. Reduced hippocampal neurogenesis has been described in various animal models of hippocampal dysfunction such as dementia and depression, which are both common non-motor-symptoms of Parkinson's disease (PD. As dopamine plays an important role in regulating precursor cell proliferation, the loss of dopaminergic neurons in the substantia nigra (SN in PD may be related to the reduced neurogenesis observed in the neurogenic regions of the adult brain: subventricular zone (SVZ and dentate gyrus (DG. Here we examined adult hippocampal neurogenesis in the Pitx3-mutant mouse model of PD (aphakia mice, which phenotypically shows a selective embryonic degeneration of dopamine neurons within the SN and to a smaller extent in the ventral tegmental area (VTA. Proliferating cells were labeled with BrdU in aphakia mice and healthy controls from 3 to 42 weeks of age. Three weeks old mutant mice showed an 18% reduction of proliferating cells in the DG and of 26% in the SVZ. Not only proliferation but also the number of new neurons was impaired in young aphakia mice resulting in 33% less newborn cells 4 weeks after BrdU-labeling. Remarkably, however, the decline in the number of proliferating cells in the neurogenic regions vanished in older animals (8–42 weeks indicating that aging masks the effect of dopamine depletion on adult neurogenesis. Region specific reduction in precursor cells proliferation correlated with the extent of dopaminergic degeneration in mesencephalic subregions (VTA and SN, which supports the theory of age- and region-dependent regulatory effects of dopaminergic projections. Physiological stimulation of adult neurogenesis by physical activity (wheel running almost doubled the number of proliferating cells in the dentate gyrus of 8 weeks old aphakia mice to a number comparable to that of wild-type mice, abolishing the slight

Botulinum Toxin Is Effective in the Management of Neurogenic Dysphagia. Clinical-Electrophysiological Findings and Tips on Safety in Different Neurological Disorders

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Alfonsi, Enrico; Restivo, Domenico A.; Cosentino, Giuseppe; De Icco, Roberto; Bertino, Giulia; Schindler, Antonio; Todisco, Massimiliano; Fresia, Mauro; Cortese, Andrea; Prunetti, Paolo; Ramusino, Matteo C.; Moglia, Arrigo; Sandrini, Giorgio; Tassorelli, Cristina

2017-01-01

Background and Aims: Neurogenic dysphagia linked to failed relaxation of the upper esophageal sphincter (UES) can be treated by injecting botulinum toxin (BTX) into the cricopharyngeal (CP) muscle. We compared the effects of this treatment in different neurological disorders with dysphagia, to evaluate its efficacy over time including the response to a second injection. Materials and Methods: Sixty-seven patients with neurogenic dysphagia associated with incomplete or absent opening of the UES (24 with brainstem or hemispheric stroke, 21 with parkinsonian syndromes, 12 with multiple sclerosis, and 10 with spastic-dystonic syndromes secondary to post-traumatic encephalopathy) were treated with the injection of IncobotulinumtoxinA (dose 15–20 U) into the CP muscle under electromyographic guidance. The patients were assessed at baseline and after the first and second treatment through clinical evaluation and fiberoptic endoscopy of swallowing, while their dysphagia was quantified using the Dysphagia Outcome and Severity Scale (DOSS). An electrokinesiographic/electromyographic study of swallowing was performed at baseline. Results: Most patients responded to the first BTX treatment: 35 patients (52.2%) were classified as high responders (DOSS score increase >2 levels), while other 19 patients (28.4%) were low responders (DOSS score increase of ≤2 levels). The effect of the first treatment usually lasted longer than 4 months (67%), and in some cases up to a year. The treatment efficacy remained high also after the second injection: 31 patients (46.3%) qualified as high responders and other 22 patients (32.8%) showed a low response. Only in the parkinsonian syndromes group we observed a reduction in the percentage of high responders as compared with the first treatment. Side effects were mostly mild and reported in non-responders following the first injection. A severe side effect, consisting of ingestion pneumonia, was observed following the second BTX injection in

Botulinumtoxin-A in der Behandlung neurogener Blasenfunktionsstörungen bei Kindern: Funktionelle und histomorphologische Langzeitergebnisse

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Schulte-Baukloh H

2004-01-01

Full Text Available Die etablierte Therapie der neurogenen Detrusorhyperaktivität bei Kindern besteht in der Gabe von Anticholinergika und begleitendem intermittierendem Einmalkatheterismus. Eine hohe Nebenwirkungsrate der Anticholinergika oder eine nicht ausreichende Dämpfung der Detrusoraktivität limitiert jedoch die Anwendung und zwingt nicht selten zu einem operativen Vorgehen. Wir untersuchten deshalb die Wirksamkeit von Botulinumtoxin-A (BTX-A auf die neurogene Detrusorhyperaktivität bei Kindern mit neurogener Blasenfunktionsstörung. Hierzu wurden 24 Kinder (11 Mädchen, 13 Jungen; 2,5–20 (Ø 11,9 Jahre mit maximalem Detrusordruck 40 cm H2O trotz anticholinerger Medikation in die Studie eingeschlossen. Nach urodynamischer Evaluierung wurden gewichtsadaptiert 85–300 U BTX-A (Botox(R zystoskopisch an 30–40 Stellen in den M. detrusor injiziert. Urodynamische Kontrollen erfolgten nach 1, 3 und 6 Monaten. Urodynamisch fand sich ein erhöhtes Reflexvolumen nach 1 Monat um +84 %, nach 3 Monaten um +68 % und nach 6 Monaten um +23 %. Entsprechend verhielten sich die Maximalkapazitäten: +35 % (nach 1 Monat, +23 % (nach 3 Monaten und +36 % (nach 6 Monaten. Die Maximaldrücke veränderten sich im o.g. Zeitraum um –41 %, –22 % bzw. +4 %. Die korrespondierenden Veränderungen der Inkontinenzrate betrug –46 %, –15 % bzw. –13 %. Bei 5 Kindern konnte jedoch auch mit dieser Therapie keine zufriedenstellende Drucksituation sichergestellt werden; nach der daraufhin durchgeführten Blasenaugmentation fanden sich in den Blasenresektaten histomorphologisch typische BTX-A bedingte Veränderungen, die jedoch in ihrer Ausprägung keinen signifikanten Gradienten aufwiesen. Zusammenfassend läßt sich festhalten, daß es nach Botulinumtoxin-A-Injektion in den Detrusormuskel bei der Mehrzahl der Patienten zu einer ausgeprägten und therapeutisch relevanten Verbesserung sämtlicher urodynamischer Parameter bei sehr guter Verträglichkeit des Medikamentes kommt

Chondrosarcoma of right 1st rib presenting as neurogenic thoracic outlet syndrome; A 13th case report in world literature

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Ravisagar Patel

2016-07-01

Full Text Available Thoracic outlet syndrome [TOS] caused by a tumor of the rib is rare and has been reported only 12 times in the literature over the past one and one-half centuries, with the majority of cases due to osteochondroma. We report a case of chondrosarcoma of right 1st rib causing neurogenic TOS that was resected via posterolateral thoracotomy and biopsy confirmed a grade I chondrosarcoma. In the treatment of chondrosarcoma, chemotherapy and radiotherapy are less effective, and appropriate surgery is needed.

Neurogenic bowel dysfunction (NBD) translation and linguistic validation to classical Arabic.

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Mallek, A; Elleuch, M H; Ghroubi, S

2016-09-01

To translate and linguistically validate in classical Arabic; the French version of the neurogenic bowel dysfunction (NBD). Arabic translation of the NBD score was obtained by the "forward translation/backword translation" method. Patients with multiple sclerosis (MS) and spinal cord injury were included. Evaluation of intestinal and anorectal disorders was conducted by the self-administered questionnaire NBD, which was filled twice two weeks apart. An item-by-item analysis was made. The feasibility, acceptability, internal consistency using Cronbach's alpha, and test-retest repeatability by non-parametric Spearman correlation were studied. Twenty-three patients with colorectal disorders secondary to neurological disease were included, the average age was 40.79±9.16years and the sex-ratio was 1.85. The questionnaire was feasible and acceptable, no items were excluded. The spearman correlation was of 0.842. Internal consistency was judged good through the Cronbach's alpha was of 0.896. The Arabic version of NBD was reproducible and construct validity was satisfactory. The study of its responsiveness to change with a larger number of patients will be the subject of further work. 4. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

DYRK1A-mediated Cyclin D1 Degradation in Neural Stem Cells Contributes to the Neurogenic Cortical Defects in Down Syndrome

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Sònia Najas

2015-02-01

Full Text Available Alterations in cerebral cortex connectivity lead to intellectual disability and in Down syndrome, this is associated with a deficit in cortical neurons that arises during prenatal development. However, the pathogenic mechanisms that cause this deficit have not yet been defined. Here we show that the human DYRK1A kinase on chromosome 21 tightly regulates the nuclear levels of Cyclin D1 in embryonic cortical stem (radial glia cells, and that a modest increase in DYRK1A protein in transgenic embryos lengthens the G1 phase in these progenitors. These alterations promote asymmetric proliferative divisions at the expense of neurogenic divisions, producing a deficit in cortical projection neurons that persists in postnatal stages. Moreover, radial glial progenitors in the Ts65Dn mouse model of Down syndrome have less Cyclin D1, and Dyrk1a is the triplicated gene that causes both early cortical neurogenic defects and decreased nuclear Cyclin D1 levels in this model. These data provide insights into the mechanisms that couple cell cycle regulation and neuron production in cortical neural stem cells, emphasizing that the deleterious effect of DYRK1A triplication in the formation of the cerebral cortex begins at the onset of neurogenesis, which is relevant to the search for early therapeutic interventions in Down syndrome.

Neurogenic lower urinary tract dysfunction: Clinical management recommendations of the Neurologic Incontinence committee of the fifth International Consultation on Incontinence 2013.

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Drake, Marcus John; Apostolidis, Apostolos; Cocci, Andrea; Emmanuel, Anton; Gajewski, Jerzy B; Harrison, Simon C W; Heesakkers, John P F A; Lemack, Gary E; Madersbacher, Helmut; Panicker, Jalesh N; Radziszewski, Piotr; Sakakibara, Ryuji; Wyndaele, Jean Jacques

2016-08-01

Evidence-based guidelines for the management of neurological disease and lower urinary tract dysfunction have been produced by the International Consultations on Incontinence (ICI). These are comprehensive guidelines, and were developed to have world-wide relevance. To update clinical management of neurogenic bladder dysfunction from the recommendations of the fourth ICI, 2009. A series of evidence reviews and updates were performed by members of the working group. The resulting guidelines were presented at the 2012 meeting of the European Association of Urology for consultation, and consequently amended to deliver evidence-based conclusions and recommendations in 2013. The current review is a synthesis of the conclusions and recommendations, including the algorithms for initial and specialized management of neurogenic lower urinary tract dysfunction. The pathophysiology is categorized according to the nature of onset of neurological disease and the part(s) of the nervous system affected. Assessment requires clinical evaluation, general investigations, and specialized testing. Treatment primarily focuses on ensuring safety of the patient and optimizing quality of life. Symptom management covers conservative and interventional measures to aid urine storage and bladder emptying, along with containment of incontinence. A multidisciplinary approach to management is essential. The review offers a pragmatic review of management in the context of complex pathophysiology and varied evidence base. Neurourol. Urodynam. 35:657-665, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effects of neuroinflammation on the regenerative capacity of brain stem cells

OpenAIRE

Russo, Isabella; Barlati, Sergio; Bosetti, Francesca

2011-01-01

In the adult brain, neurogenesis under physiological conditions occurs in the subventricular zone and in the dentate gyrus. Although the exact molecular mechanisms that regulate neural stem cell proliferation and differentiation are largely unknown, several factors have been shown to affect neurogenesis. Decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age-related brain dysfunction. Furthermore, in pathological conditions of the central nervous system ...

Properties of doublecortin-(DCX-expressing cells in the piriform cortex compared to the neurogenic dentate gyrus of adult mice.

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Friederike Klempin

Full Text Available The piriform cortex receives input from the olfactory bulb and (via the entorhinal cortex sends efferents to the hippocampus, thereby connecting the two canonical neurogenic regions of the adult rodent brain. Doublecortin (DCX is a cytoskeleton-associated protein that is expressed transiently in the course of adult neurogenesis. Interestingly, the adult piriform cortex, which is usually considered non-neurogenic (even though some reports exist that state otherwise, also contains an abundant population of DCX-positive cells. We asked how similar these cells would be to DCX-positive cells in the course of adult hippocampal neurogenesis. Using BAC-generated transgenic mice that express GFP under the DCX promoter, we studied DCX-expression and electrophysiological properties of DCX-positive cells in the mouse piriform cortex in comparison with the dentate gyrus. While one class of cells in the piriform cortex indeed showed features similar to newly generated immature granule neurons, the majority of DCX cells in the piriform cortex was mature and revealed large Na+ currents and multiple action potentials. Furthermore, when proliferative activity was assessed, we found that all DCX-expressing cells in the piriform cortex were strictly postmitotic, suggesting that no DCX-positive "neuroblasts" exist here as they do in the dentate gyrus. We conclude that DCX in the piriform cortex marks a unique population of postmitotic neurons with a subpopulation that retains immature characteristics associated with synaptic plasticity. DCX is thus, per se, no marker of neurogenesis but might be associated more broadly with plasticity.

Evaluation of neurogenic dysphagia in Iraqi patients with acute stroke.

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Hasan, Zeki N; Al-Shimmery, Ehsan K; Taha, Mufeed A

2010-04-01

To clinically assess neurogenic dysphagia, and to correlate its presence with demographic features, different stroke risk factors, anatomical arterial territorial stroke types, and pathological stroke types. Seventy-two stroke inpatients were studied between July 2007 and February 2008, at the Departments of Medicine and Neurology at Al-Yarmouk Teaching Hospital, Baghdad, and Rizgary Teaching Hospital, Erbil, Iraq. All patients were assessed using the Mann Assessment of Swallowing Ability score (MASA), Modified Rankin Scale, and the Stroke Risk Scorecard. All patients were reassessed after one month. There were 40 males and 32 females. Sixty-eight patients had ischemic stroke, and 4 had primary intracerebral hemorrhage (ICH). According to the MASA score, 55% of anterior circulation stroke (ACS) cases were associated with dysphasia, and 91% of lateral medullary syndrome cases were associated with dysphagia. Fifty-six percent of ACS dysphagic cases improved within the first month. Forty percent of dysphagic patients died in the one month follow up period, and in most, death was caused by aspiration pneumonia. We observed no significant differences regarding demographic features of dysphagia. Dysphagia can be an indicator of the severity of stroke causing higher mortality and morbidity in affected patients. It was not related to the stroke risk factors and the type of stroke. It is essential from a prognostic point of view to assess swallowing, and to treat its complications early.

A Distinct Population of Microglia Supports Adult Neurogenesis in the Subventricular Zone

DEFF Research Database (Denmark)

Ribeiro Xavier, Anna L.; Kress, Benjamin T.; Goldman, Steven A.

2015-01-01

found that microglia residing in the SVZ and adjacent rostral migratory stream (RMS) comprise a morphologically and antigenically distinct phenotype of immune effectors. Whereas exhibiting characteristics of alternatively activated microglia, the SVZ/RMS microglia were clearly distinguished by their low...... STATEMENT: Microglial cells are a specialized population of macrophages in the CNS, playing key roles as immune mediators. As integral components in the CNS, the microglia stand out for using the same mechanisms, phagocytosis and cytochemokine release, to promote homeostasis, synaptic pruning, and neural...... toward olfactory bulb layers. In addition to other unique populations residing in the SVZ niche, microglia display distinct morphofunctional properties that boost neuronal progenitor survival and migration in the mammalian brain....

Abrogated inflammatory response promotes neurogenesis in a murine model of Japanese encephalitis.

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Sulagna Das

2011-03-01

Full Text Available Japanese encephalitis virus (JEV induces neuroinflammation with typical features of viral encephalitis, including inflammatory cell infiltration, activation of microglia, and neuronal degeneration. The detrimental effects of inflammation on neurogenesis have been reported in various models of acute and chronic inflammation. We investigated whether JEV-induced inflammation has similar adverse effects on neurogenesis and whether those effects can be reversed using an anti-inflammatory compound minocycline.Here, using in vitro studies and mouse models, we observed that an acute inflammatory milieu is created in the subventricular neurogenic niche following Japanese encephalitis (JE and a resultant impairment in neurogenesis occurs, which can be reversed with minocycline treatment. Immunohistological studies showed that proliferating cells were replenished and the population of migrating neuroblasts was restored in the niche following minocycline treatment. In vitro, we checked for the efficacy of minocycline as an anti-inflammatory compound and cytokine bead array showed that production of cyto/chemokines decreased in JEV-activated BV2 cells. Furthermore, mouse neurospheres grown in the conditioned media from JEV-activated microglia exhibit arrest in both proliferation and differentiation of the spheres compared to conditioned media from control microglia. These effects were completely reversed when conditioned media from JEV-activated and minocycline treated microglia was used.This study provides conclusive evidence that JEV-activated microglia and the resultant inflammatory molecules are anti-proliferative and anti-neurogenic for NSPCs growth and development, and therefore contribute to the viral neuropathogenesis. The role of minocycline in restoring neurogenesis may implicate enhanced neuronal repair and attenuation of the neuropsychiatric sequelae in JE survivors.

Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat

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Blanco-Calvo, Eduardo; Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Galeano, Pablo; Rubio, Leticia; Suárez, Juan; Rodriguez de Fonseca, Fernando

2014-01-01

Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation. To this end, we examined whether pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg) or CB2 receptors (AM630, 3 mg/kg) would affect cell proliferation [the cells were labeled with 5-bromo-2′-deoxyuridine (BrdU)] in the subventricular zone (SVZ) of the lateral ventricle and the dentate subgranular zone (SGZ). Additionally, we measured cell apoptosis (as monitored by the expression of cleaved caspase-3) and glial activation [by analyzing the expression of glial fibrillary acidic protein (GFAP) and Iba-1] in the striatum and hippocampus during acute and repeated (4 days) cocaine administration (20 mg/kg). The results showed that acute cocaine exposure decreased the number of BrdU-immunoreactive (ir) cells in the SVZ and SGZ. In contrast, repeated cocaine exposure reduced the number of BrdU-ir cells only in the SVZ. Both acute and repeated cocaine exposure increased the number of cleaved caspase-3-, GFAP- and Iba1-ir cells in the hippocampus, and this effect was counteracted by AM630 or Rimonabant, which increased the number of BrdU-, GFAP-, and Iba1-ir cells in the hippocampus. These results indicate that the changes in neurogenic, apoptotic and gliotic processes that were produced by repeated cocaine administration were normalized by pharmacological blockade of CB1 and CB2. The restorative effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with the prevention of the induction of conditioned

Hypocellularity in the Murine Model for Down Syndrome Ts65Dn Is Not Affected by Adult Neurogenesis

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López-Hidalgo, Rosa; Ballestín, Raul; Vega, Jessica; Blasco-Ibáñez, José M.; Crespo, Carlos; Gilabert-Juan, Javier; Nácher, Juan; Varea, Emilio

2016-01-01

Down syndrome (DS) is caused by the presence of an extra copy of the chromosome 21 and it is the most common aneuploidy producing intellectual disability. Neural mechanisms underlying this alteration may include defects in the formation of neuronal networks, information processing and brain plasticity. The murine model for DS, Ts65Dn, presents reduced adult neurogenesis. This reduction has been suggested to underlie the hypocellularity of the hippocampus as well as the deficit in olfactory learning in the Ts65Dn mice. Similar alterations have also been observed in individuals with DS. To determine whether the impairment in adult neurogenesis is, in fact, responsible for the hypocellularity in the hippocampus and physiology of the olfactory bulb, we have analyzed cell proliferation and neuronal maturation in the two major adult neurogenic niches in the Ts656Dn mice: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Additionally, we carried out a study to determine the survival rate and phenotypic fate of newly generated cells in both regions, injecting 5′BrdU and sacrificing the mice 21 days later, and analyzing the number and phenotype of the remaining 5′BrdU-positive cells. We observed a reduction in the number of proliferating (Ki67 positive) cells and immature (doublecortin positive) neurons in the subgranular and SVZ of Ts65Dn mice, but we did not observe changes in the number of surviving cells or in their phenotype. These data correlated with a lower number of apoptotic cells (cleaved caspase 3 positive) in Ts65Dn. We conclude that although adult Ts65Dn mice have a lower number of proliferating cells, it is compensated by a lower level of cell death. This higher survival rate in Ts65Dn produces a final number of mature cells similar to controls. Therefore, the reduction of adult neurogenesis cannot be held responsible for the neuronal hypocellularity in the hippocampus or for the olfactory learning deficit of Ts65Dn mice

Mechano growth factor, a splice variant of IGF-1, promotes neurogenesis in the aging mouse brain.

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Tang, Jason J; Podratz, Jewel L; Lange, Miranda; Scrable, Heidi J; Jang, Mi-Hyeon; Windebank, Anthony J

2017-07-07

Mechano growth factor (MGF) is a splice variant of IGF-1 first described in skeletal muscle. MGF induces muscle cell proliferation in response to muscle stress and injury. In control mice we found endogenous expression of MGF in neurogenic areas of the brain and these levels declined with age. To better understand the role of MGF in the brain, we used transgenic mice that constitutively overexpressed MGF from birth. MGF overexpression significantly increased the number of BrdU+ proliferative cells in the dentate gyrus (DG) of the hippocampus and subventricular zone (SVG). Although MGF overexpression increased the overall rate of adult hippocampal neurogenesis at the proliferation stage it did not alter the distribution of neurons at post-mitotic maturation stages. We then used the lac-operon system to conditionally overexpress MGF in the mouse brain beginning at 1, 3 and 12 months with histological and behavioral observation at 24 months of age. With conditional overexpression there was an increase of BrdU+ proliferating cells and BrdU+ differentiated mature neurons in the olfactory bulbs at 24 months when overexpression was induced from 1 and 3 months of age but not when started at 12 months. This was associated with preserved olfactory function. In vitro, MGF increased the size and number of neurospheres harvested from SVZ-derived neural stem cells (NSCs). These findings indicate that MGF overexpression increases the number of neural progenitor cells and promotes neurogenesis but does not alter the distribution of adult newborn neurons at post-mitotic stages. Maintaining youthful levels of MGF may be important in reversing age-related neuronal loss and brain dysfunction.

Blue light potentiates neurogenesis induced by retinoic acid-loaded responsive nanoparticles.

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Santos, Tiago; Ferreira, Raquel; Quartin, Emanuel; Boto, Carlos; Saraiva, Cláudia; Bragança, José; Peça, João; Rodrigues, Cecília; Ferreira, Lino; Bernardino, Liliana

2017-09-01

Neurogenic niches constitute a powerful endogenous source of new neurons that can be used for brain repair strategies. Neuronal differentiation of these cells can be regulated by molecules such as retinoic acid (RA) or by mild levels of reactive oxygen species (ROS) that are also known to upregulate RA receptor alpha (RARα) levels. Data showed that neural stem cells from the subventricular zone (SVZ) exposed to blue light (405nm laser) transiently induced NADPH oxidase-dependent ROS, resulting in β-catenin activation and neuronal differentiation, and increased RARα levels. Additionally, the same blue light stimulation was capable of triggering the release of RA from light-responsive nanoparticles (LR-NP). The synergy between blue light and LR-NP led to amplified neurogenesis both in vitro and in vivo, while offering a temporal and spatial control of RA release. In conclusion, this combinatory treatment offers great advantages to potentiate neuronal differentiation, and provides an innovative and efficient application for brain regenerative therapies. Controlling the differentiation of stem cells would support the development of promising brain regenerative therapies. Blue light transiently increased reactive oxygen species, resulting in neuronal differentiation and increased retinoic acid receptor (RARα) levels. Additionally, the same blue light stimulation was capable of triggering the release of RA from light-responsive nanoparticles (LR-NP). The synergy between blue light and LR-NP led to amplified neurogenesis, while offering a temporal and spatial control of RA release. In this sense, our approach relying on the modulation of endogenous stem cells for the generation of new neurons may support the development of novel clinical therapies. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Efficacy and Safety of Tamsulosin for the Treatment of Non-neurogenic Voiding Dysfunction in Females: A 8-Week Prospective Study

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Lee, Kyu-Sung; Han, Deok Hyun; Lee, Young-Suk; Choo, Myung-Soo; Yoo, Tag Keun; Park, Heung Jae; Yoon, Hana; Jeong, Hyeon; Lee, Sun Ju; Kim, Hayoung

2010-01-01

We evaluated the therapeutic effects of tamsulosin for women with non-neurogenic voiding dysfunction. Women who had voiding dysfunctions for at least 3 months were included. Inclusion criteria were age ≥18 yr, International Prostate Symptom Score (IPSS) of ≥15, and maximum flow rate (Qmax) of ≥12 mL/sec and/or postvoid residuals (PVR) of ≥150 mL. Patients with neurogenic voiding dysfunction or anatomical bladder outlet obstruction were excluded. All patients were classified according to the Blaivas-Groutz nomogram as having no or mild obstruction (group A) or moderate or severe obstruction (group B). After 8 weeks of treatment, treatment outcomes and adverse effects were evaluated. One hundred and six patients were evaluable (70 in group A, 36 in group B). After treatments, mean IPSS, bother scores, Qmax, PVR, diurnal and nocturnal micturition frequencies and scored form of the Bristol Female Lower Urinary Tract Symptoms questionnaire (BFLUTS-SF) were changed significantly. Eighty-nine patients (84%) reported that the treatment was beneficial. The proportion of patients reported that their bladder symptoms caused "moderate to many severe problems" were significantly decreased. No significant difference were observed between the groups in terms of IPSS, bother score, Qmax, PVR, micturition frequency, and BFLUTS-SF changes. Adverse effects related to medication were dizziness (n=3), de novo stress urinary incontinence (SUI) (n=3), aggravation of underlying SUI (n=1), fatigue (n=1). Tamsulosin was found to be effective in female patients with voiding dysfunction regardless of obstruction grade. PMID:20052356

Is forebrain neurogenesis a potential repair mechanism after stroke?

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Inta, Dragos; Gass, Peter

2015-01-01

The use of adult subventricular zone (SVZ) neurogenesis as brain repair strategy after stroke represents a hot topic in neurologic research. Recent radiocarbon-14 dating has revealed a lack of poststroke neurogenesis in the adult human neocortex; however, adult neurogenesis has been shown to occur, even under physiologic conditions, in the human striatum. Here, these results are contrasted with experimental poststroke neurogenesis in the murine brain. Both in humans and in rodents, the SVZ ge...

Conversion of MyoD to a Neurogenic Factor: Binding Site Specificity Determines Lineage

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Abraham P. Fong

2015-03-01

Full Text Available MyoD and NeuroD2, master regulators of myogenesis and neurogenesis, bind to a “shared” E-box sequence (CAGCTG and a “private” sequence (CAGGTG or CAGATG, respectively. To determine whether private-site recognition is sufficient to confer lineage specification, we generated a MyoD mutant with the DNA-binding specificity of NeuroD2. This chimeric mutant gained binding to NeuroD2 private sites but maintained binding to a subset of MyoD-specific sites, activating part of both the muscle and neuronal programs. Sequence analysis revealed an enrichment for PBX/MEIS motifs at the subset of MyoD-specific sites bound by the chimera, and point mutations that prevent MyoD interaction with PBX/MEIS converted the chimera to a pure neurogenic factor. Therefore, redirecting MyoD binding from MyoD private sites to NeuroD2 private sites, despite preserved binding to the MyoD/NeuroD2 shared sites, is sufficient to change MyoD from a master regulator of myogenesis to a master regulator of neurogenesis.

Aspiration in children and adolescents with neurogenic dysphagia: comparison of clinical judgment and fiberoptic endoscopic evaluation of swallowing.

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Beer, Sabrina; Hartlieb, Till; Müller, Arnd; Granel, Michael; Staudt, Martin

2014-12-01

A total of 30 children and adolescents with dysphagia due to various chronic neurological disorders were assessed for their risk of aspiration. This assessment was performed clinically by experienced speech and swallowing therapists, and verified thereafter by fiberoptic endoscopy. We found the clinical judgment to be correct in only 70% (for aspiration of saliva), 55% (of puree), and 67% (of thin liquids). We conclude that, because of this unacceptably high error rate of clinical assessment, a fiberoptic evaluation of swallowing is a necessary diagnostic step both for the planning of therapy and for the development of feeding strategies in children and adolescents with neurogenic dysphagia. Georg Thieme Verlag KG Stuttgart · New York.

The Felix-trial. Double-blind randomization of interspinous implant or bony decompression for treatment of spinal stenosis related intermittent neurogenic claudication

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Brand Ronald

2010-05-01

Full Text Available Abstract Background Decompressive laminotomy is the standard surgical procedure in the treatment of patients with canal stenosis related intermittent neurogenic claudication. New techniques, such as interspinous process implants, claim a shorter hospital stay, less post-operative pain and equal long-term functional outcome. A comparative (cost- effectiveness study has not been performed yet. This protocol describes the design of a randomized controlled trial (RCT on (cost- effectiveness of the use of interspinous process implants versus conventional decompression surgery in patients with lumbar spinal stenosis. Methods/Design Patients (age 40-85 presenting with intermittent neurogenic claudication due to lumbar spinal stenosis lasting more than 3 months refractory to conservative treatment, are included. Randomization into interspinous implant surgery versus bony decompression surgery will take place in the operating room after induction of anesthesia. The primary outcome measure is the functional assessment of the patient measured by the Zurich Claudication Questionnaire (ZCQ, at 8 weeks and 1 year after surgery. Other outcome parameters include perceived recovery, leg and back pain, incidence of re-operations, complications, quality of life, medical consumption, absenteeism and costs. The study is a randomized multi-institutional trial, in which two surgical techniques are compared in a parallel group design. Patients and research nurses are kept blinded of the allocated treatment during the follow-up period of 1 year. Discussion Currently decompressive laminotomy is the golden standard in the surgical treatment of lumbar spinal stenosis. Whether surgery with interspinous implants is a reasonable alternative can be determined by this trial. Trial register Dutch Trial register number: NTR1307

Application of transpulmonary thermodilution monitoring (PiCCO) in patient with neurogenic pulmonary edema and acute obstructive hydrocephalus due to a central neurocytoma: A case report

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Ryoichi Iwata; Kunikazu Yoshimura; Yoko Fujita; Tatsuo Uesaka; Hideyuki Oshige; Akio Asai

2017-01-01

Neurogenic pulmonary edema (NPE) is an acute life-threatening complication associated with many forms of central nervous system injury. Its pathophysiology is still debated. We report a patient with acute obstructive hydrocephalus due to a central neurocytoma who also had NPE, for which serial transpulmonary thermodilution monitoring (PiCCO) was performed. Insertion of the PiCCO, which provides information about the patient's cardiac output, preload status and amount of lung water, revealed a...

Women's experiences of living with neurogenic bladder and bowel after spinal cord injury: life controlled by bladder and bowel.

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Nevedal, Andrea; Kratz, Anna L; Tate, Denise G

2016-01-01

Neurogenic bladder and bowel (NBB) is a chronic condition hindering the functioning and quality of life (QOL) of people with spinal cord injury (SCI). NBB research has focused on men with SCI leaving unanswered questions about women's experiences of living with NBB. The purpose of this study was to identify and describe women's experiences of living with SCI and NBB. Secondary analysis of semi-structured interviews from a larger qualitative study of women with SCI (N = 50) was carried out. Transcripts were coded for bowel and bladder content. Pile-sorting techniques were used to identify emergent themes related to NBB. Meta-themes were categorized under the International Classification of Functioning, Disability and Health. Bladder and bowel topics were spontaneously discussed by 46 out of 50 study participants suggesting the salience of this issue for women with SCI. We identified 6 meta-themes: life controlled by bladder and bowel, bladder and bowel accidents, women's specific challenges, life course disruption, bladder and bowel medical management, and finding independence. Findings describe concerns, strategies, and the detrimental impact of NBB in the lives of women with SCI. Findings inform policy makers, health care and rehabilitation professionals to improve accessibility and quality of life for women with NBB. Women with spinal cord injury (SCI) reported gender specific challenges to living with neurogenic bladder and bowel (NBB). Interventions designed for women with SCI can address these problems and provide recommendations for prevention and treatment. Women described the detrimental impact of NBB on life course expectations, emotional, social, physical health, and quality of life domains. Psychosocial and educational programs can be developed to address these challenges and improve overall quality of life. Recommendations for special treatment and policy considerations are needed to maximize women's independence and health while living with NBB

Hyperexpressed netrin-1promoted neural stem cells migration in mice after focal cerebral ischemia

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Haiyan Lu; Xiaoyan Song; Feng Wang; Guodong Wang; Yuncheng Wu; Qiaoshu Wang; Yongting Wang; Guoyuan Yang; Zhijun Zhang

2016-01-01

Endogenous Netrin-1 (NT-1) protein was significantly increased after cerebral ischemia, which may participate in the repair after transient cerebral ischemic injury. In this work, we explored whether NT-1 can be steadily overexpressed by adeno-associated virus (AAV) and the exogenous NT-1 can promote neural stem cells migration from the subventricular zone (SVZ) region after cerebral ischemia. Adult CD-1 mice were injected stereotacticly with AAV carrying NT-1 gene (AAV-NT-1). Mice underwent ...

Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis

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Kawaguchi, Daichi; Furutachi, Shohei; Kawai, Hiroki; Hozumi, Katsuto; Gotoh, Yukiko

2013-01-01

Stem cells often divide asymmetrically to produce one stem cell and one differentiating cell, thus maintaining the stem cell pool. Although neural stem cells (NSCs) in the adult mouse subventricular zone have been suggested to divide asymmetrically, intrinsic cell fate determinants for asymmetric NSC division are largely unknown. Stem cell niches are important for stem cell maintenance, but the niche for the maintenance of adult quiescent NSCs has remained obscure. Here we show that the Notch...

Intra-articular injection of Botulinum toxin A reduces neurogenic inflammation in CFA-induced arthritic rat model.

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Wang, Lin; Wang, Kaile; Chu, Xiao; Li, Tieshan; Shen, Nana; Fan, Chenglei; Niu, Zhenyuan; Zhang, Xiaochen; Hu, Luoman

2017-02-01

Currently, administration of Botulinum toxin Type A (BoNT/A) to treat arthritic pain has promising efficacy in clinical research. However, the mechanisms underlying anti-neurogenic inflammation mediated by BoNT/A remains unclear. The aim of this study was to demonstrate the effectiveness in macro and micro levels and to explore the causal mechanism of BoNT/A. Wistar rats (n = 60) were injected with 50ul complete Freund's adjuvant (CFA) in the left ankle joint capsule to establish a model of chronic monoarthritis. Pain behaviour (Evoked pain assessment) and infrared thermal imaging testing were performed at the macroscopic level to assess the effectiveness of analgesia and anti-inflammation. Western blotting and immunofluorescence staining were used at the microscopic level in an attempt to determine the mechanisms of anti-nociceptive or anti-inflammatory effects of BoNT/A. Additionally, hematoxylin-eosin staining was also used to visualise the cartilage and the synovial degenerative conditions of arthritis. By comparing the outcome of the evoked pain test and immunofluorescence staining, there was a significant improvement in BoNT/A compared with the normal saline (NS) injected control group. In addition, thermal variations showed that the temperature of ipsilateral ankle joint increased between 1 and 2 weeks following injection of CFA, but decreased after 3 weeks (still above the contralateral side). However, the temperature showed no difference between the BoNT/A group and NS group after treatment. The expression of IL-1β or TNF-α in the ankle synovial tissue was significantly decreased in the BoNT/A group compared to the NS group (p < 0.05). Based on the HE assessment, cartilage degeneration and infiltration of inflammatory cells in the BoNT/A group was alleviated compared to the NS group after treatment. In conclusion, we proposed the hypothesis that intra-articular BoNT/A administration does play an important role in anti-neurogenic inflammation. The

The nuclear receptor TLX is required for gliomagenesis within the adult neurogenic niche.

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Zou, Yuhua; Niu, Wenze; Qin, Song; Downes, Michael; Burns, Dennis K; Zhang, Chun-Li

2012-12-01

Neural stem cells (NSCs) continually generate functional neurons in the adult brain. Due to their ability to proliferate, deregulated NSCs or their progenitors have been proposed as the cells of origin for a number of primary central nervous system neoplasms, including infiltrating gliomas. The orphan nuclear receptor TLX is required for proliferation of adult NSCs, and its upregulation promotes brain tumor formation. However, it is unknown whether TLX is required for gliomagenesis. We examined the genetic interactions between TLX and several tumor suppressors, as well as the role of TLX-dependent NSCs during gliomagenesis, using mouse models. Here, we show that TLX is essential for the proliferation of adult NSCs with a single deletion of p21, p53, or Pten or combined deletion of Pten and p53. While brain tumors still form in Tlx mutant mice, these tumors are less infiltrative and rarely associate with the adult neurogenic niches, suggesting a non-stem-cell origin. Taken together, these results indicate a critical role for TLX in NSC-dependent gliomagenesis and implicate TLX as a therapeutic target to inhibit the development of NSC-derived brain tumors.

Human dental pulp stem cells with highly angiogenic and neurogenic potential for possible use in pulp regeneration.

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Nakashima, Misako; Iohara, Koichiro; Sugiyama, Masahiko

2009-01-01

Dental caries is a common public health problem, causing early loss of dental pulp and resultant tooth loss. Dental pulp has important functions to sustain teeth providing nutrient and oxygen supply, innervation, reactionary/reparative dentin formation and immune response. Regeneration of pulp is an unmet need in endodontic therapy, and angiogenesis/vasculogenesis and neurogenesis are critical for pulp regeneration. Permanent and deciduous pulp tissue is easily available from teeth after extraction without ethical issues and has potential for clinical use. In this review, we introduce some stem cell subfractions, CD31(-)/CD146(-) SP cells and CD105(+) cells with high angiogenic and neurogenic potential, derived from human adult dental pulp tissue. Potential utility of these cells is addressed as a source of cells for treatment of cerebral and limb ischemia and pulp inflammation complete with angiogenesis and vasculogenesis.

Hemorrhagic onset of hemangioblastoma located in the dorsal medulla oblongata presenting with tako-tsubo cardiomyopathy and neurogenic pulmonary edema: a case report.

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Gekka, Masayuki; Yamaguchi, Shigeru; Kazumata, Ken; Kobayashi, Hiroyuki; Motegi, Hiroaki; Terasaka, Shunsuke; Houkin, Kiyohiro

2014-01-01

Here, we present a case of dorsal medulla oblongata hemangioblastoma with fourth ventricular hemorrhage. A 23-year-old female developed sudden consciousness disturbance, and CT revealed hemorrhage in all cerebral ventricles and a hyperdense mass in the cisterna magna. Although the reddish tumor located in the dorsal medulla oblongata was successfully removed, she suffered from severe tako-tsubo cardiomyopathy (TTC) and neurogenic pulmonary edema (NPE) because of baroreflex failure and damage to the solitary tract nuclei. After intensive care for 12 weeks following surgery, she was discharged without any neurological or radiological deficits. Pathogenesis of TTC/NPE is discussed in this paper.

Effects of Physiotherapy in the Treatment of Neurogenic Bladder in Patients Infected With Human T-Lymphotropic Virus 1.

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Andrade, Rosana C P; Neto, José A; Andrade, Luciana; Oliveira, Tatiane S; Santos, Dislene N; Oliveira, Cassius J V; Prado, Márcio J; Carvalho, Edgar M

2016-03-01

To evaluate the efficacy of physiotherapy for urinary manifestations in patients with human T-lymphotropic virus 1-associated lower urinary tract dysfunction. Open clinical trial was conducted with 21 patients attending the physiotherapy clinic of the Hospital Universitário, Bahia, Brazil. Combinations of behavioral therapy, perineal exercises, and intravaginal or intra-anal electrical stimulation were used. The mean age was 54 ± 12 years and 67% were female. After treatment, there was an improvement in symptoms of urinary urgency, frequency, incontinence, nocturia, and in the sensation of incomplete emptying (P Physiotherapy was effective in cases of human T-lymphotropic virus 1-associated neurogenic bladder, reducing symptoms, increasing perineal muscle strength, and improving urodynamic parameters and quality of life. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Physiotherapy in the Treatment of Neurogenic Bladder in Patients Infected with Human T-Lymphotropic Virus 1 (HTLV-1)

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Andrade, Rosana C.P.; Neto, José A.; Andrade, Luciana; Oliveira, Tatiane S. S.; Santos, Dislene N.; Oliveira, Cassius J.V.; Prado, Márcio J.; Carvalho, Edgar M.

2016-01-01

Objective To evaluate the efficacy of physiotherapy for urinary manifestations in patients with HTLV-1-associated lower urinary tract dysfunction. Methods Open clinical trial with 21 patients attending the physiotherapy clinic of the Hospital Universitário, Bahia, Brazil. Combinations of behavioral therapy, perineal exercises and intravaginal/intra-anal electrical stimulation were used. Results The mean age was 54±12 years and 67% were female. After treatment, there was an improvement in symptoms of urinary urgency, frequency, incontinence, nocturia and in the sensation of incomplete emptying (pPhysiotherapy was effective in cases of HTLV-1-associated neurogenic bladder, reducing symptoms, increasing perineal muscle strength, improving urodynamic parameters and quality of life. PMID:26724409

Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

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Kuan Zhang

Full Text Available Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG of the hippocampus and the sub-ventricular zone (SVZ of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCsin vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr and DG (approximately 10 Torr were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr. Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

Whole-tumor apparent diffusion coefficient (ADC) histogram analysis to differentiate benign peripheral neurogenic tumors from soft tissue sarcomas.

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Nakajo, Masanori; Fukukura, Yoshihiko; Hakamada, Hiroto; Yoneyama, Tomohide; Kamimura, Kiyohisa; Nagano, Satoshi; Nakajo, Masayuki; Yoshiura, Takashi

2018-02-22

Apparent diffusion coefficient (ADC) histogram analyses have been used to differentiate tumor grades and predict therapeutic responses in various anatomic sites with moderate success. To determine the ability of diffusion-weighted imaging (DWI) with a whole-tumor ADC histogram analysis to differentiate benign peripheral neurogenic tumors (BPNTs) from soft tissue sarcomas (STSs). Retrospective study, single institution. In all, 25 BPNTs and 31 STSs. Two-b value DWI (b-values = 0, 1000s/mm 2 ) was at 3.0T. The histogram parameters of whole-tumor for ADC were calculated by two radiologists and compared between BPNTs and STSs. Nonparametric tests were performed for comparisons between BPNTs and STSs. P histogram parameters except kurtosis and entropy differed significantly between BPNTs and STSs. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Hemorrhagic Onset of Hemangioblastoma Located in the Dorsal Medulla Oblongata Presenting with Tako-Tsubo Cardiomyopathy and Neurogenic Pulmonary Edema: A Case Report

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Masayuki Gekka

2014-03-01

Full Text Available Here, we present a case of dorsal medulla oblongata hemangioblastoma with fourth ventricular hemorrhage. A 23-year-old female developed sudden consciousness disturbance, and CT revealed hemorrhage in all cerebral ventricles and a hyperdense mass in the cisterna magna. Although the reddish tumor located in the dorsal medulla oblongata was successfully removed, she suffered from severe tako-tsubo cardiomyopathy (TTC and neurogenic pulmonary edema (NPE because of baroreflex failure and damage to the solitary tract nuclei. After intensive care for 12 weeks following surgery, she was discharged without any neurological or radiological deficits. Pathogenesis of TTC/NPE is discussed in this paper.

Chronic fluoxetine treatment in middle-aged rats induces changes in the expression of plasticity-related molecules and in neurogenesis

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Guirado Ramon

2012-01-01

Full Text Available Abstract Background Antidepressants promote neuronal structural plasticity in young-adult rodents, but little is known of their effects on older animals. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM may mediate these structural changes through its anti-adhesive properties. PSA-NCAM is expressed in immature neurons and in a subpopulation of mature interneurons and its expression is modulated by antidepressants in the telencephalon of young-adult rodents. Results We have analyzed the effects of 14 days of fluoxetine treatment on the density of puncta expressing PSA-NCAM and different presynaptic markers in the medial prefrontal cortex, hippocampus and amygdala of middle-aged (8 months old rats. The density of puncta expressing PSA-NCAM increased in the dorsal cingulate cortex, as well as in different hippocampal and amygdaloid regions. In these later regions there were also increases in the density of puncta expressing glutamic acid decarboxylase 65/67 (GAD6, synaptophysin (SYN, PSA-NCAM/SYN and PSA-NCAM/GAD6, but a decrease of those expressing vesicular glutamate transporter 1 (VGluT1. Since there is controversy on the effects of antidepressants on neurogenesis during aging, we analyzed the number of proliferating cells expressing Ki67 and that of immature neurons expressing doublecortin or PSA-NCAM. No significant changes were found in the subgranular zone, but the number of proliferating cells decreased in the subventricular zone. Conclusions These results indicate that the effects of fluoxetine in middle-aged rats are different to those previously described in young-adult animals, being more restricted in the mPFC and even following an opposite direction in the amygdala or the subventricular zone.

Feline dry eye syndrome of presumed neurogenic origin: a case report

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Lionel Sebbag

2017-12-01

Full Text Available Case summary A 14-year-old female spayed Abyssinian cat, which about 1 year previously underwent thoracic limb amputation, radiotherapy and chemotherapy for an incompletely excised vaccine-related fibrosarcoma, was presented for evaluation of corneal opacity in the left eye (OS. The ocular surface of both eyes (OU had a lackluster appearance and there was a stromal corneal ulcer OS. Results of corneal aesthesiometry, Schirmer tear test-1 (STT-1 and tear film breakup time revealed corneal hypoesthesia, and quantitative and qualitative tear film deficiency OU. Noxious olfactory stimulation caused increased lacrimation relative to standard STT-1 values suggesting an intact nasolacrimal reflex. Various lacrimostimulants were administered in succession; namely, 1% pilocarpine administered topically (15 days or orally (19 days, and topically applied 0.03% tacrolimus (47 days. Pilocarpine, especially when given orally, was associated with notable increases in STT-1 values, but corneal ulceration remained/recurred regardless of administration route, and oral pilocarpine resulted in gastrointestinal upset. Tacrolimus was not effective. After 93 days, the cat became weak and lame and a low thyroxine concentration was detected in serum. The cat was euthanized and a necropsy performed. Both lacrimal glands were histologically normal, but chronic neutrophilic keratitis and reduced conjunctival goblet cell density were noted OU. Relevance and novel information The final diagnosis was dry eye syndrome (DES of presumed neurogenic origin, associated with corneal hypoesthesia. This report reinforces the importance of conducting tearfilm testing in cats with ocular surface disease, as clinical signs of DES were different from those described in dogs.

Feline dry eye syndrome of presumed neurogenic origin: a case report.

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Sebbag, Lionel; Pesavento, Patricia A; Carrasco, Sebastian E; Reilly, Christopher M; Maggs, David J

2018-01-01

A 14-year-old female spayed Abyssinian cat, which about 1 year previously underwent thoracic limb amputation, radiotherapy and chemotherapy for an incompletely excised vaccine-related fibrosarcoma, was presented for evaluation of corneal opacity in the left eye (OS). The ocular surface of both eyes (OU) had a lackluster appearance and there was a stromal corneal ulcer OS. Results of corneal aesthesiometry, Schirmer tear test-1 (STT-1) and tear film breakup time revealed corneal hypoesthesia, and quantitative and qualitative tear film deficiency OU. Noxious olfactory stimulation caused increased lacrimation relative to standard STT-1 values suggesting an intact nasolacrimal reflex. Various lacrimostimulants were administered in succession; namely, 1% pilocarpine administered topically (15 days) or orally (19 days), and topically applied 0.03% tacrolimus (47 days). Pilocarpine, especially when given orally, was associated with notable increases in STT-1 values, but corneal ulceration remained/recurred regardless of administration route, and oral pilocarpine resulted in gastrointestinal upset. Tacrolimus was not effective. After 93 days, the cat became weak and lame and a low thyroxine concentration was detected in serum. The cat was euthanized and a necropsy performed. Both lacrimal glands were histologically normal, but chronic neutrophilic keratitis and reduced conjunctival goblet cell density were noted OU. The final diagnosis was dry eye syndrome (DES) of presumed neurogenic origin, associated with corneal hypoesthesia. This report reinforces the importance of conducting tearfilm testing in cats with ocular surface disease, as clinical signs of DES were different from those described in dogs.

Lipid-laden cells differentially distributed in the aging brain are functionally active and correspond to distinct phenotypes

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Shimabukuro, Marilia Kimie; Langhi, Larissa Gutman Paranhos; Cordeiro, Ingrid; Brito, José M.; Batista, Claudia Maria de Castro; Mattson, Mark P.; de Mello Coelho, Valeria

2016-01-01

We characterized cerebral Oil Red O-positive lipid-laden cells (LLC) of aging mice evaluating their distribution, morphology, density, functional activities and inflammatory phenotype. We identified LLC in meningeal, cortical and neurogenic brain regions. The density of cerebral LLC increased with age. LLC presenting small lipid droplets were visualized adjacent to blood vessels or deeper in the brain cortical and striatal parenchyma of aging mice. LLC with larger droplets were asymmetrically distributed in the cerebral ventricle walls, mainly located in the lateral wall. We also found that LLC in the subventricular region co-expressed beclin-1 or LC3, markers for autophagosome or autophagolysosome formation, and perilipin (PLIN), a lipid droplet-associated protein, suggesting lipophagic activity. Some cerebral LLC exhibited β galactosidase activity indicating a senescence phenotype. Moreover, we detected production of the pro-inflammatory cytokine TNF-α in cortical PLIN+ LLC. Some cortical NeuN+ neurons, GFAP+ glia limitans astrocytes, Iba-1+ microglia and S100β+ ependymal cells expressed PLIN in the aging brain. Our findings suggest that cerebral LLC exhibit distinct cellular phenotypes and may participate in the age-associated neuroinflammatory processes. PMID:27029648

Lipid-laden cells differentially distributed in the aging brain are functionally active and correspond to distinct phenotypes.

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Shimabukuro, Marilia Kimie; Langhi, Larissa Gutman Paranhos; Cordeiro, Ingrid; Brito, José M; Batista, Claudia Maria de Castro; Mattson, Mark P; Mello Coelho, Valeria de

2016-03-31

We characterized cerebral Oil Red O-positive lipid-laden cells (LLC) of aging mice evaluating their distribution, morphology, density, functional activities and inflammatory phenotype. We identified LLC in meningeal, cortical and neurogenic brain regions. The density of cerebral LLC increased with age. LLC presenting small lipid droplets were visualized adjacent to blood vessels or deeper in the brain cortical and striatal parenchyma of aging mice. LLC with larger droplets were asymmetrically distributed in the cerebral ventricle walls, mainly located in the lateral wall. We also found that LLC in the subventricular region co-expressed beclin-1 or LC3, markers for autophagosome or autophagolysosome formation, and perilipin (PLIN), a lipid droplet-associated protein, suggesting lipophagic activity. Some cerebral LLC exhibited β galactosidase activity indicating a senescence phenotype. Moreover, we detected production of the pro-inflammatory cytokine TNF-α in cortical PLIN(+) LLC. Some cortical NeuN(+) neurons, GFAP(+) glia limitans astrocytes, Iba-1(+) microglia and S100β(+) ependymal cells expressed PLIN in the aging brain. Our findings suggest that cerebral LLC exhibit distinct cellular phenotypes and may participate in the age-associated neuroinflammatory processes.

Zone separator for multiple zone vessels

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Jones, John B.

1983-02-01

A solids-gas contact vessel, having two vertically disposed distinct reaction zones, includes a dynamic seal passing solids from an upper to a lower zone and maintaining a gas seal against the transfer of the separate treating gases from one zone to the other, and including a stream of sealing fluid at the seal.

Parapapillary atrophy: histological gamma zone and delta zone.

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Jost B Jonas

Full Text Available BACKGROUND: To examine histomorphometrically the parapapillary region in human eyes. METHODOLOGY/PRINCIPAL FINDINGS: The histomorphometric study included 65 human globes (axial length:21-37 mm. On anterior-posterior histological sections, we measured the distance Bruch's membrane end (BME-optic nerve margin ("Gamma zone", BME-retinal pigment epithelium (RPE ("Beta zone", BME-beginning of non-occluded choriocapillaris, and BME-beginning of photoreceptor layer. "Delta zone" was defined as part of gamma zone in which blood vessels of at least 50 µm diameter were not present over a length of >300 µm. Beta zone (mean length:0.35±0.52 mm was significantly (P = 0.01 larger in the glaucoma group than in the non-glaucomatous group. It was not significantly (P = 0.28 associated with axial length. Beta zone was significantly (P = 0.004 larger than the region with occluded choriocapillaris. Gamma zone (mean length:0.63±1.25 mm was associated with axial length (P50 µm diameter within gamma zone was present only in highly axially elongated globes and was not related with glaucoma. Beta zone (Bruch's membrane without RPE was correlated with glaucoma but not with globe elongation. Since the region with occluded choriocapillaris was smaller than beta zone, complete loss of RPE may have occurred before complete choriocapillaris closure.

Overexpression of tissue-nonspecific alkaline phosphatase increases the expression of neurogenic differentiation markers in the human SH-SY5Y neuroblastoma cell line.

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Graser, Stephanie; Mentrup, Birgit; Schneider, Doris; Klein-Hitpass, Ludger; Jakob, Franz; Hofmann, Christine

2015-10-01

Patients suffering from the rare hereditary disease hypophosphatasia (HPP), which is based on mutations in the ALPL gene, tend to develop central nervous system (CNS) related issues like epileptic seizures and neuropsychiatric illnesses such as anxiety and depression, in addition to well-known problems with the mineralization of bones and teeth. Analyses of the molecular role of tissue-nonspecific alkaline phosphatase (TNAP) in transgenic SH-SY5Y(TNAPhigh) neuroblastoma cells compared to SH-SY5Y(TNAPlow) cells indicate that the enzyme influences the expression levels of neuronal marker genes like RNA-binding protein, fox-1 homolog 3 (NEUN) and enolase 2, gamma neuronal (NSE) as well as microtubule-binding proteins like microtubule-associated protein 2 (MAP2) and microtubule-associated protein tau (TAU) during neurogenic differentiation. Fluorescence staining of SH-SY5Y(TNAPhigh) cells reveals TNAP localization throughout the whole length of the developed projection network and even synapsin Ι co-localization with strong TNAP signals at some spots at least at the early time points of differentiation. Additional immunocytochemical staining shows higher MAP2 expression in SH-SY5Y(TNAPhigh) cells and further a distinct up-regulation of tau and MAP2 in the course of neurogenic differentiation. Interestingly, transgenic SH-SY5Y(TNAPhigh) cells are able to develop longer cellular processes compared to control cells after stimulation with all-trans retinoic acid (RA). Current therapies for HPP prioritize improvement of the bone phenotype. Unraveling the molecular role of TNAP in extraosseous tissues, like in the CNS, will help to improve treatment strategies for HPP patients. Taking this rare disease as a model may also help to dissect TNAP's role in neurodegenerative diseases and even improve future treatment of common pathologies. Copyright © 2015 Elsevier Inc. All rights reserved.

On occurrence of a neurogenic sarcoma in irradiation area after combined operative-radiogenic therapy of an adenosarcoma in kidney during childhood

International Nuclear Information System (INIS)

Eberhardt, H.J.; Friedrich, S.; Herrmann, T.; Roy, U.

1990-01-01

Malignant neoplasias in childhood generally are an increased risk for the patient to fall ill with a second tumor. Second tumors in former irradiation field are seldom, but are acknowledged radiogenically if histology is different to that of the first tumor and a sufficiently long period is between the two tumors. A patient is presented who had been operated and irradiated because of an adenosarcoma of the kidney at the age of seven and who has fallen ill with a neurogenic sarcoma in the irradiation area more than 30 years later. The same patient had to suffer from radiogenic retardation during differentiation of the lumbar apparatus of attitude and locomotion and on the other hand be became father of a healthy daughter at the age of 32. (author)

An International Continence Society (ICS) report on the terminology for adult neurogenic lower urinary tract dysfunction (ANLUTD).

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Gajewski, Jerzy B; Schurch, Brigitte; Hamid, Rizwan; Averbeck, Márcio; Sakakibara, Ryuji; Agrò, Enrico F; Dickinson, Tamara; Payne, Christopher K; Drake, Marcus J; Haylen, Bernie T

2018-03-01

The terminology for adult neurogenic lower urinary tract dysfunction (ANLUTD) should be defined and organized in a clinically based consensus Report. This Report has been created by a Working Group under the auspices and guidelines of the International Continence Society (ICS) Standardization Steering Committee (SSC) assisted at intervals by external referees. All relevant definitions for ANLUTD were updated on the basis of research over the last 14 years. An extensive process of 18 rounds of internal and external review was involved to exhaustively examine each definition, with decision-making by collective opinion (consensus). A Terminology Report for ANLUTD, encompassing 97 definitions (42 NEW and 8 CHANGED, has been developed. It is clinically based with the most common diagnoses defined. Clarity and user-friendliness have been key aims to make it interpretable by practitioners and trainees in all the different groups involved not only in lower urinary tract dysfunction but additionally in many other medical specialties. A consensus-based Terminology Report for ANLUTD has been produced to aid clinical practice and research. © 2017 Wiley Periodicals, Inc.

Fluoxetine treatment ameliorates depression induced by perinatal arsenic exposure via a neurogenic mechanism

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Tyler, Christina R.; Solomon, Benjamin R.; Ulibarri, Adam L.; Allan, Andrea M.

2014-01-01

Several epidemiological studies have reported an association between arsenic exposure and increased rates of psychiatric disorders, including depression, in exposed populations. We have previously demonstrated that developmental exposure to low amounts of arsenic induces depression in adulthood along with several morphological and molecular aberrations, particularly associated with the hippocampus and the hypothalamic–pituitary–adrenal (HPA) axis. The extent and potential reversibility of this toxin-induced damage has not been characterized to date. In this study, we assessed the effects of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on adult animals exposed to arsenic during development. Perinatal arsenic exposure (PAE) induced depressive-like symptoms in a mild learned helplessness task and in the forced swim task after acute exposure to a predator odor (2,4,5-trimethylthiazoline, TMT). Chronic fluoxetine treatment prevented these behaviors in both tasks in arsenic-exposed animals and ameliorated arsenic-induced blunted stress responses, as measured by corticosterone (CORT) levels before and after TMT exposure. Morphologically, chronic fluoxetine treatment reversed deficits in adult hippocampal neurogenesis (AHN) after PAE, specifically differentiation and survival of neural progenitor cells. Protein expression of BDNF, CREB, the glucocorticoid receptor (GR), and HDAC2 was significantly increased in the dentate gyrus of arsenic animals after fluoxetine treatment. This study demonstrates that damage induced by perinatal arsenic exposure is reversible with chronic fluoxetine treatment resulting in restored resiliency to depression via a neurogenic mechanism. PMID:24952232

Management of urinary tract infections in patients with neurogenic bladder: challenges and solutions.

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Pannek, Jürgen; Wöllner, Jens

2017-01-01

Urinary tract infections (UTIs) are one of the most common morbidities in persons with neurogenic lower urinary tract dysfunction (NLUTD). They are associated with a significant morbidity and mortality, and they affect the quality of life of the affected patients. Diagnosis and treatment of UTI in this group of patients are challenging. In this review, the current strategies regarding diagnosis, treatment, and prevention are summarized. it is important to correctly diagnose a UTI, as treatment of bacteriuria should strictly be avoided. A UTI is defined as a combination of laboratory findings (leukocyturia and bacteriuria) and symptoms. Laboratory findings without symptoms are classified as asymptomatic bacteriuria. Routine urine screening is not advised. Only UTI should be treated; treatment of asymptomatic bacteriuria is not indicated. Prior to treatment, urine for a urine culture should be obtained. Antibiotic treatment for ~7 days is advised. In recurrent UTI, bladder management should be optimized and morphologic causes for UTI should be excluded. If UTIs persist, medical prophylaxis should be considered. Currently, no prophylactic measure with evidence-based efficacy exists. Long-term antibiotic prophylaxis should be used merely as an ultimate measure. Among the various mentioned innovative approaches for UTI prevention, bacteriophages, intravesical instillations, complementary and alternative medicine techniques, and probiotics seem to be most promising. Recently, several promising innovative options for UTI prophylaxis have been developed which may help overcome the current therapeutic dilemma. However, further well designed studies are necessary to evaluate the safety and efficacy of these approaches.

MDM2 inhibition rescues neurogenic and cognitive deficits in a mouse model of fragile X syndrome.

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Li, Yue; Stockton, Michael E; Bhuiyan, Ismat; Eisinger, Brian E; Gao, Yu; Miller, Jessica L; Bhattacharyya, Anita; Zhao, Xinyu

2016-04-27

Fragile X syndrome, the most common form of inherited intellectual disability, is caused by loss of the fragile X mental retardation protein (FMRP). However, the mechanism remains unclear, and effective treatment is lacking. We show that loss of FMRP leads to activation of adult mouse neural stem cells (NSCs) and a subsequent reduction in the production of neurons. We identified the ubiquitin ligase mouse double minute 2 homolog (MDM2) as a target of FMRP. FMRP regulates Mdm2 mRNA stability, and loss of FMRP resulted in elevated MDM2 mRNA and protein. Further, we found that increased MDM2 expression led to reduced P53 expression in adult mouse NSCs, leading to alterations in NSC proliferation and differentiation. Treatment with Nutlin-3, a small molecule undergoing clinical trials for treating cancer, specifically inhibited the interaction of MDM2 with P53, and rescued neurogenic and cognitive deficits in FMRP-deficient mice. Our data reveal a potential regulatory role for FMRP in the balance between adult NSC activation and quiescence, and identify a potential new treatment for fragile X syndrome. Copyright © 2016, American Association for the Advancement of Science.

Radiation protection zoning

International Nuclear Information System (INIS)

2015-01-01

Radiation being not visible, the zoning of an area containing radioactive sources is important in terms of safety. Concerning radiation protection, 2 work zones are defined by regulations: the monitored zone and the controlled zone. The ministerial order of 15 may 2006 settles the frontier between the 2 zones in terms of radiation dose rates, the rules for access and the safety standards in both zones. Radioprotection rules and the name of the person responsible for radiation protection must be displayed. The frontier between the 2 zones must be materialized and marked with adequate equipment (specific danger signs and tapes). Both zones are submitted to selective entrance, the access for the controlled zone is limited because of the radiation risk and of the necessity of confining radioactive contamination while the limitation of the access to the monitored zone is due to radiation risk only. (A.C.)

Hippocampal Neurogenesis, Depressive Disorders, and Antidepressant Therapy

Directory of Open Access Journals (Sweden)

Eleni Paizanis

2007-01-01

Full Text Available There is a growing body of evidence that neural stem cells reside in the adult central nervous system where neurogenesis occurs throughout lifespan. Neurogenesis concerns mainly two areas in the brain: the subgranular zone of the dentate gyrus in the hippocampus and the subventricular zone, where it is controlled by several trophic factors and neuroactive molecules. Neurogenesis is involved in processes such as learning and memory and accumulating evidence implicates hippocampal neurogenesis in the physiopathology of depression. We herein review experimental and clinical data demonstrating that stress and antidepressant treatments affect neurogenesis in opposite direction in rodents. In particular, the stimulation of hippocampal neurogenesis by all types of antidepressant drugs supports the view that neuroplastic phenomena are involved in the physiopathology of depression and underlie—at least partly—antidepressant therapy.

Functional studies of microRNAs in neural stem cells: problems and perspectives.

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Malin eÅkerblom

2012-02-01

Full Text Available In adult mammals, neural stem cells (NSCs are found in two niches of the brain; the subventricular zone at the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Neurogenesis is a complex process that is tightly controlled on a molecular level. Recently, microRNAs (miRNAs have been implicated to play a central role in the regulation of NCSs. miRNAs are small, endogenously expressed RNAs that regulate gene expression at the post-transcriptional level. However, functional studies of miRNAs are complicated due to current technical limitations. In this review we describe recent findings about miRNAs in NSCs looking closely at miR-124, miR-9 and let-7. We also highlight technical strategies used to investigate miRNA function, accentuating limitations and potentials.

Potential Therapies by Stem Cell-Derived Exosomes in CNS Diseases: Focusing on the Neurogenic Niche

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Alejandro Luarte

2016-01-01

Full Text Available Neurodegenerative disorders are one of the leading causes of death and disability and one of the biggest burdens on health care systems. Novel approaches using various types of stem cells have been proposed to treat common neurodegenerative disorders such as Alzheimer’s Disease, Parkinson’s Disease, or stroke. Moreover, as the secretome of these cells appears to be of greater benefit compared to the cells themselves, the extracellular components responsible for its therapeutic benefit have been explored. Stem cells, as well as most cells, release extracellular vesicles such as exosomes, which are nanovesicles able to target specific cell types and thus to modify their function by delivering proteins, lipids, and nucleic acids. Exosomes have recently been tested in vivo and in vitro as therapeutic conveyors for the treatment of diseases. As such, they could be engineered to target specific populations of cells within the CNS. Considering the fact that many degenerative brain diseases have an impact on adult neurogenesis, we discuss how the modulation of the adult neurogenic niches may be a therapeutic target of stem cell-derived exosomes. These novel approaches should be examined in cellular and animal models to provide better, more effective, and specific therapeutic tools in the future.

Fuel conditioning facility zone-to-zone transfer administrative controls

International Nuclear Information System (INIS)

Pope, C. L.

2000-01-01

The administrative controls associated with transferring containers from one criticality hazard control zone to another in the Argonne National Laboratory (ANL) Fuel Conditioning Facility (FCF) are described. FCF, located at the ANL-West site near Idaho Falls, Idaho, is used to remotely process spent sodium bonded metallic fuel for disposition. The process involves nearly forty widely varying material forms and types, over fifty specific use container types, and over thirty distinct zones where work activities occur. During 1999, over five thousand transfers from one zone to another were conducted. Limits are placed on mass, material form and type, and container types for each zone. Ml material and containers are tracked using the Mass Tracking System (MTG). The MTG uses an Oracle database and numerous applications to manage the database. The database stores information specific to the process, including material composition and mass, container identification number and mass, transfer history, and the operators involved in each transfer. The process is controlled using written procedures which specify the zone, containers, and material involved in a task. Transferring a container from one zone to another is called a zone-to-zone transfer (ZZT). ZZTs consist of four distinct phases, select, request, identify, and completion

MRI visualization of endogenous neural progenitor cell migration along the RMS in the adult mouse brain

DEFF Research Database (Denmark)

Vreys, Ruth; Vande Velde, Greetje; Krylychkina, Olga

2010-01-01

The adult rodent brain contains neural progenitor cells (NPCs), generated in the subventricular zone (SVZ), which migrate along the rostral migratory stream (RMS) towards the olfactory bulb (OB) where they differentiate into neurons. The aim of this study was to visualize endogenous NPC migration...... by a longitudinal MRI study and validated with histology. Here, we visualized endogenous NPC migration in the mouse brain by in vivo MRI and demonstrated accumulation of MPIO-labeled NPCs in the OB over time with ex vivo MRI. Furthermore, we investigated the influence of in situ injection of MPIOs on adult...

Suprapubic cystostomy for neurogenic bladder using Lowsley retractor method: a procedure revisited.

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Edokpolo, Leonard U; Foster, Harris E

2011-11-01

To report our experience with the Lowsley retractor method for suprapubic cystostomy (SPC) in patients with neurogenic bladder (NGB). A retrospective study was performed of 44 patients with NGB who underwent SPC with the Lowsley retractor method. The subjects were selected from 90 patients undergoing SPC by 1 surgeon from 1995 to 2010. The age, sex, indication, anesthesia type, catheter type, blood loss, fluids administered, and duration and complications were recorded. A total of 49 primary catheter placements were performed in 44 patients. A total of 23 men and 21 women were included. The etiology of NGB was spinal cord injury and multiple sclerosis in 38 subjects (86%). The mean age was 44 years (range 18-86). The cases were performed under general anesthesia, except for 8 (16%) that were successfully performed with local and monitored anesthesia. The operation time documented in 19 cases (39%) was 20.2 ± 5.5 minutes (range 11-31). The Foley catheter size ranged from 16F to 22F. The blood loss was minimal, and there were no intraoperative complications or incorrect catheter placements. One patient returned with significant hematuria 1 day after the procedure. No other minor or major complications were noted. Patients with NGB have been shown to have a greater risk of complication during percutaneous suprapubic catheter placement. SPC using the Lowsley retractor was described by Zeidman et al in 1988. Their report did not detail the patient characteristics or operative experience. To our knowledge, no other institutional experience with the technique has been reported. The present report describes the Lowsley retractor method as a quick and safe ambulatory procedure for patients with NGB. Published by Elsevier Inc.

Molecular differences in transition zone and peripheral zone prostate tumors

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Sinnott, Jennifer A.; Rider, Jennifer R.; Carlsson, Jessica; Gerke, Travis; Tyekucheva, Svitlana; Penney, Kathryn L.; Sesso, Howard D.; Loda, Massimo; Fall, Katja; Stampfer, Meir J.; Mucci, Lorelei A.; Pawitan, Yudi; Andersson, Sven-Olof; Andrén, Ove

2015-01-01

Prostate tumors arise primarily in the peripheral zone (PZ) of the prostate, but 20–30% arise in the transition zone (TZ). Zone of origin may have prognostic value or reflect distinct molecular subtypes; however, it can be difficult to determine in practice. Using whole-genome gene expression, we built a signature of zone using normal tissue from five individuals and found that it successfully classified nine tumors of known zone. Hypothesizing that this signature captures tumor zone of origin, we assessed its relationship with clinical factors among 369 tumors of unknown zone from radical prostatectomies (RPs) and found that tumors that molecularly resembled TZ tumors showed lower mortality (P = 0.09) that was explained by lower Gleason scores (P = 0.009). We further applied the signature to an earlier study of 88 RP and 333 transurethral resection of the prostate (TURP) tumor samples, also of unknown zone, with gene expression on ~6000 genes. We had observed previously substantial expression differences between RP and TURP specimens, and hypothesized that this might be because RPs capture primarily PZ tumors, whereas TURPs capture more TZ tumors. Our signature distinguished these two groups, with an area under the receiver operating characteristic curve of 87% (P zones. Zone of origin may be important to consider in prostate tumor biomarker research. PMID:25870172

Deletion of protein tyrosine phosphatase 1b in proopiomelanocortin neurons reduces neurogenic control of blood pressure and protects mice from leptin- and sympatho-mediated hypertension.

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Bruder-Nascimento, Thiago; Butler, Benjamin R; Herren, David J; Brands, Michael W; Bence, Kendra K; Belin de Chantemèle, Eric J

2015-12-01

Protein tyrosine phosphatase 1b (Ptp1b), which represses leptin signaling, is a promising therapeutic target for obesity. Genome wide deletion of Ptp1b, increases leptin sensitivity, protects mice from obesity and diabetes, but alters cardiovascular function by increasing blood pressure (BP). Leptin-control of metabolism is centrally mediated and involves proopiomelanocortin (POMC) neurons. Whether these neurons contribute to leptin-mediated increases in BP remain unclear. We hypothesized that increasing leptin signaling in POMC neurons with Ptp1b deletion will sensitize the cardiovascular system to leptin and enhance neurogenic control of BP. We analyzed the cardiovascular phenotype of Ptp1b+/+ and POMC-Ptp1b-/- mice, at baseline and after 7 days of leptin infusion or sympatho-activation with phenylephrine. POMCPtp1b deletion did not alter baseline cardiovascular hemodynamics (BP, heart rate) but reduced BP response to ganglionic blockade and plasma catecholamine levels that suggests a decreased neurogenic control of BP. In contrast, POMC-Ptp1b deletion increased vascular adrenergic reactivity and aortic α-adrenergic receptors expression. Chronic leptin treatment reduced vascular adrenergic reactivity and blunted diastolic and mean BP increases in POMC-Ptp1b-/- mice only. Similarly POMC-Ptp1b-/- mice exhibited a blunted increased in diastolic and mean BP accompanied by a gradual reduction in adrenergic reactivity in response to chronic vascular sympatho-activation with phenylephrine. Together these data rule out our hypothesis but suggest that deletion of Ptp1b in POMC neurons protects from leptin- and sympatho-mediated increases in BP. Vascular adrenergic desensitization appears as a protective mechanism against hypertension, and POMC-Ptp1b as a key therapeutic target for the treatment of metabolic and cardiovascular dysfunctions associated with obesity. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prediction of outcome in neurogenic oropharyngeal dysphagia within 72 hours of acute stroke.

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Ickenstein, Guntram W; Höhlig, Carolin; Prosiegel, Mario; Koch, Horst; Dziewas, Rainer; Bodechtel, Ulf; Müller, Rainer; Reichmann, Heinz; Riecker, Axel

2012-10-01

Stroke is the most frequent cause of neurogenic oropharyngeal dysphagia (NOD). In the acute phase of stroke, the frequency of NOD is greater than 50% and, half of this patient population return to good swallowing within 14 days while the other half develop chronic dysphagia. Because dysphagia leads to aspiration pneumonia, malnutrition, and in-hospital mortality, it is important to pay attention to swallowing problems. The question arises if a prediction of severe chronic dysphagia is possible within the first 72 hours of acute stroke. On admission to the stroke unit, all stroke patients were screened for swallowing problems by the nursing staff within 2 hours. Patients showing signs of aspiration were included in the study (n = 114) and were given a clinical swallowing examination (CSE) by the swallowing/speech therapist within 24 hours and a swallowing endoscopy within 72 hours by the physician. The primary outcome of the study was the functional communication measure (FCM) of swallowing (score 1-3, tube feeding dependency) on day 90. The grading system with the FCM swallowing and the penetration-aspiration scale (PAS) in the first 72 hours was tested in a multivariate analysis for its predictive value for tube feeding-dependency on day 90. For the FCM level 1 to 3 (P dysphagia scales to prevent aspiration pneumonia and malnutrition. A dysphagia program can lead to better communication within the stroke unit team to initiate the appropriate diagnostics and swallowing therapy as soon as possible. Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Long-Term Cost-Effectiveness of Transanal Irrigation in Patients with Neurogenic Bowel Dysfunction.

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Anton Emmanuel

Full Text Available People suffering from neurogenic bowel dysfunction (NBD and an ineffective bowel regimen often suffer from fecal incontinence (FI and related symptoms, which have a huge impact on their quality of life. In these situations, transanal irrigation (TAI has been shown to reduce these symptoms and improve quality of life.To investigate the long-term cost-effectiveness of initiating TAI in patients with NBD who have failed standard bowel care (SBC.A deterministic Markov decision model was developed to project the lifetime health economic outcomes, including quality-adjusted life years (QALYs, episodes of FI, urinary tract infections (UTIs, and stoma surgery when initiating TAI relative to continuing SBC. A data set consisting of 227 patients with NBD due to spinal cord injury (SCI, multiple sclerosis, spina bifida and cauda equina syndrome was used in the analysis. In the model a 30-year old individual with SCI was used as a base-case. A probabilistic sensitivity analysis was applied to evaluate the robustness of the model.The model predicts that a 30-year old SCI patient with a life expectancy of 37 years initiating TAI will experience a 36% reduction in FI episodes, a 29% reduction in UTIs, a 35% reduction in likelihood of stoma surgery and a 0.4 improvement in QALYs, compared with patients continuing SBC. A lifetime cost-saving of £21,768 per patient was estimated for TAI versus continuing SBC alone.TAI is a cost-saving treatment strategy reducing risk of stoma surgery, UTIs, episodes of FI and improving QALYs for NBD patients who have failed SBC.

Actions of rilmenidine on neurogenic hypertension in BPH/2J genetically hypertensive mice.

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Jackson, Kristy L; Palma-Rigo, Kesia; Nguyen-Huu, Thu-Phuc; Davern, Pamela J; Head, Geoffrey A

2014-03-01

BPH/2J hypertensive mice have an exaggerated sympathetic contribution to blood pressure (BP). Premotor sympathetic neurons within the rostroventrolateral medulla (RVLM) are a major source of sympathetic vasomotor tone and major site of action of the centrally acting sympatholytic agent, rilmenidine. The relative cardiovascular effect of rilmenidine in BPH/2J versus normotensive BPN/3J mice was used as an indicator of the involvement of the RVLM in the sympathetic contribution to hypertension in BPH/2J mice. BPH/2J and BPN/3J mice were pre-implanted with telemetry devices to measure BP in conscious unrestrained mice. Rilmenidine was administered acutely (n=7-9/group), orally for 14 days, at a wide range of doses (n=5/group), and also infused intracerebroventricularly for 7 days (n=6/group). Acute intraperitoneal rilmenidine induced greater depressor and bradycardic responses in BPH/2J than BPN/3J mice (PstrainBPH/2J mice during the dark (active) period (-6.5 ± 2 mmHg; P=0.006). Chronic orally administered rilmenidine (1-12 mg/kg per day) also had minimal effect on 24-h BP in both strains (P>0.16). The sympathetic vasomotor inhibitory effect of rilmenidine is minimal in both strains and similar in hypertensive BPH/2J and BPN/3J mice. Thus, hypertension in BPH/2J mice is not likely mediated by greater neuronal activity in the RVLM, and agents such as rilmenidine would be an ineffective treatment for this form of neurogenic hypertension.

WorkZoneQ user guide for two-lane freeway work zones.

Science.gov (United States)

2013-06-01

WorkZoneQ was developed in Visual Basic for Applications (VBA) to implement the results of the previous study, : Queue and Users Costs in Highway Work Zones. This report contains the WorkZoneQ user guide. WorkZoneQ : consists of eight Excel ...

ZoneLib

DEFF Research Database (Denmark)

Jessen, Jan Jacob; Schiøler, Henrik

2006-01-01

We present a dynamic model for climate in a livestock building divided into a number of zones, and a corresponding modular Simulink library (ZoneLib). While most literature in this area consider air flow as a control parameter we show how to model climate dynamics using actual control signals...... development of ZoneLib....

PATHOPHYSIOLOGY AND PRINCIPLES OF THERAPY OF A NEUROGENIC HYPERACTIVE URINARY BLADDER IN PATIENTS AFTER CEREBROVASCULAR ACCIDENT

Directory of Open Access Journals (Sweden)

P. G. Shchvartz

2017-01-01

Full Text Available Neurogenic hyperactiv e bladder in different clinical variations is a characteristic com plication of restorativ e and residual periods of ischemic stroke and an important diagnostic criterion in vascular dementia. Mechanisms of formation of individual symptoms included in this syndrome is due to ischemic damage to cortical, subcortical and brainstem (the nucleus of Barrington centres of urination and associative areas of the brain, and the functional dissociation of these structures due to demyelination of the Central conductors of the afferent and efferent impulses. As a result of deficit of cerebral effects (such as brake and activating, is a violation of the implementation of the reflexes of urination (including carrying out continence, ongoing spinal (sympathetic, parasympathetic and somatic. The article presents a new concept of formation of the syndrome of hyperactive bladder on the basis of violations of the implementation of the 4 reflexes of urination, which provides the normal retention of urine and are responsible for the accumulation function of the bladder. First we analyzed the main point of application of drugs of anticholinergic and sympathomimetic actions in the reflexes of urination and mechanisms of restoration of function of the lower urinary tract in patients with acute and chronic v ascular diseases of the brain.

Benign and malignant neurogenic tumors of nerve sheath origin on FDG PET

International Nuclear Information System (INIS)

Yun, M. J.; Go, D. H.; Yoo, Y. H.; Shin, K. H.; Lee, J. D

2004-01-01

The differentiation between benign and malignant nerve sheath tumors is difficult based on conventional radiological imaging. This study was undertaken to investigate the value of FDG PET in distinguishing benign from malignant neurogenic tumors of nerve sheath origin. We performed a retrospective review of the medical record to select patients with nerve sheath tumors who had underdone FDG PET imaging. Fifteen patients (7F: 8M) with benign or malignant nerve sheath tumors were included in this study. Of the 15 patients, 9 were diagnosed with the known neurofibromatosis type I. A total of 19 nerve sheath tumors were included from the 15 patients. All patients had undergone FDG PET to evaluate for malignant potential of the known lesions. Images of FDG PET were semi-quantitatively analyzed and a region of interest (ROI) was placed over the area of the maximum FDG uptake and an average standardized uptake value was taken for final analysis. There were 5 malignant peripheral nerve sheath tumors, 5 schwannomas, and 9 neurofibromas. The mean SUV was 2 (ranged from 1.6 to 3.3) for schwannomas, 1.3 (0.7 to 2.5) for neurofibromas, and 8.4 (4.6 to 12.2) for malignant peripheral nerve sheath tumors. Of 14 benign tumors, all except one schwannoma showed a SUV less than 3. When a cutoff SUV of 4 was used to differentiate the nerve sheath tumors, all tumors were correctly classified as benign or malignant, respectively. Among the 9 patients diagnosed with neurofibromatosis type I. 4 had malignant peripheral nerve sheath tumors and FDG PET accurately detected all the 4 lesions with malignant transformation. According to our results, FDG PET seems to have a great potential for accurately characterizing benign versus malignant nerve sheath tumors. It appears to be extremely useful for patients with neurofibromatosis to localize the lesion with malignant transformation

Dannelse af nye nerveceller i den voksne hjerne

DEFF Research Database (Denmark)

Poulsen, Frantz Rom; Meyer, Morten; Rasmussen, Jens Zimmer

2003-01-01

neurogenesis in the adult human brain. In particular two brain regions show continuous division of neural stem and progenitor cells generating neurons and glial cells, namely the subgranular zone of the dentate gyrus and the subventricular zones of the lateral ventricles. From the latter region newly generated......Generation of new nerve cells (neurogenesis) is normally considered to be limited to the fetal and early postnatal period. Thus, damaged nerve cells are not expected to be replaced by generation of new cells. The brain is, however, more plastic than previously assumed. This also includes...... neuroblasts (immature nerve cells) migrate toward the olfactory bulb where they differentiate into neurons. In the dentate gyrus the newly generated neurons become functionally integrated in the granule cell layer, where they are believed to be of importance to learning and memory. It is at present not known...

Empowerment Zones and Enterprise Districts - MDC_EnterpriseZone

Data.gov (United States)

NSGIC Local Govt | GIS Inventory — Polygon feature class of Miami Dade County Enterprise Zones. Enterprise Zones are special areas in the county where certain incentives from the State are available...

Slip Zone versus Damage Zone Micromechanics, Arima-Takasuki Tectonic Line, Japan

Science.gov (United States)

White, J. C.; Lin, A.

2017-12-01

The Arima-Takasuki Tectonic Line (ATTL) of southern Honshu, Japan is defined by historically active faults and multiple splays producing M7 earthquakes. The damage zone of the ATTL comprises a broad zone of crushed, comminuted and pulverized granite/rhyolite1,2containing cm-scale slip zones and highly comminuted injection veins. In this presentation, prior work on the ATTL fault rocks is extending to include microstructural characterization by transmission electron microscopy (TEM) from recent trenching of the primary slip zone, as well as secondary slip zones. This is necessary to adequately characterize the extremely fine-grained material (typically less than 1mm) in both damage and core zones. Damage zone material exhibits generally random textures3 whereas slip zones are macroscopically foliated, and compositionally layered, notwithstanding a fairly homogeneous protolith. The latter reflects fluid-rock interaction during both coseismic and interseismic periods. The slip zones are microstructurally heterogeneous at all scales, comprising not only cataclasites and phyllosilicate (clay)-rich gouge zones, but Fe/Mn pellets or clasts that are contained within gouge. These structures appear to have rolled and would suggest rapid recrystallization and/or growth. A central question related to earthquake recurrence along existing faults is the nature of the gouge. In both near-surface exposures and ongoing drilling at depth, "plastic" or "viscous" gouge zones comprise ultra-fine-grained clay-siliciclastic particles that would not necessarily respond in a simple frictional manner. Depending on whether the plastic nature of these slip zones develops during or after slip, subsequent focusing of slip within them could be complicated. 1 Mitchell, T.A., Ben-Zion, Y., Shimamoto, T., 2011. Ear. Planet. Sci. Lett. 308, 284-297. 2 Lin, A., Yamashita, K, Tanaka, M. J., 2013. Struc. Geol. 48, 3-13. 3 White, J.C., Lin, A. 2016. Proc. AGU Fall Mtg., T42-02 San Francisco.

Evaluation of Ohio work zone speed zones process.

Science.gov (United States)

2014-06-01

This report describes the methodology and results of analyses performed to determine the effectiveness of Ohio Department of Transportation processes for establishing work zone speed zones. Researchers observed motorists speed choice upstream of a...

Elevated homocysteine by levodopa is detrimental to neurogenesis in parkinsonian model.

Directory of Open Access Journals (Sweden)

Jin Young Shin

Full Text Available BACKGROUND: Modulation of neurogenesis that acts as an endogenous repair mechanism would have a significant impact on future therapeutic strategies for Parkinson's disease (PD. Several studies demonstrated dopaminergic modulation of neurogenesis in the subventricular zone (SVZ of the adult brain. Levodopa, the gold standard therapy for PD, causes an increase in homocysteine levels that induces neuronal death via N-methyl-D-aspartate (NMDA receptor. The present study investigated whether elevated homocysteine by levodopa treatment in a parkinsonian model would modulate neurogenesis via NMDA receptor signal cascade and compared the effect of levodopa and pramipexol (PPX on neurogenic activity. METHODOLOGY/PRINCIPAL FINDINGS: Neurogenesis was assessed in vitro using neural progenitor cells (NPCs isolated from the SVZ and in vivo with the BrdU-injected animal model of PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Modulation of homocysteine levels was evaluated using co-cultures of NPCs and astrocytes and PD animals. Immunochemical and Western blot analyses were used to measure neurogenesis and determine the cell death signaling. Levodopa treatment increased release of homocysteine on astrocytes culture media as well as in plasma and brain of PD animals. Increased homocysteine by levodopa led to increased apoptosis of NPCs through the NMDA receptor-dependent the extracellular signal-regulated kinase (ERK signaling pathways. The administration of a NMDA antagonist significantly attenuated apoptotic cell death in levodopa-treated NPCs and markedly increased the number of BrdU-positive cells in the SVZ of levodopa-treated PD animals. Comparative analysis revealed that PPX treatment significantly increased the number of NPCs and BrdU-positive cells in the SVZ of PD animals compared to levodopa treatment. Our present study demonstrated that increased homocysteine by levodopa has a detrimental effect on neurogenesis through NMDA receptor

Neurogenic differentiation of human umbilical cord mesenchymal stem cells on aligned electrospun polypyrrole/polylactide composite nanofibers with electrical stimulation

Science.gov (United States)

Zhou, Junfeng; Cheng, Liang; Sun, Xiaodan; Wang, Xiumei; Jin, Shouhong; Li, Junxiang; Wu, Qiong

2016-09-01

Adult central nervous system (CNS) tissue has a limited capacity to recover after trauma or disease. Recent medical cell therapy using polymeric biomaterialloaded stem cells with the capability of differentiation to specific neural population has directed focuses toward the recovery of CNS. Fibers that can provide topographical, biochemical and electrical cues would be attractive for directing the differentiation of stem cells into electro-responsive cells such as neuronal cells. Here we report on the fabrication of an electrospun polypyrrole/polylactide composite nanofiber film that direct or determine the fate of mesenchymal stem cells (MSCs), via combination of aligned surface topography, and electrical stimulation (ES). The surface morphology, mechanical properties and electric properties of the film were characterized. Comparing with that on random surface film, expression of neurofilament-lowest and nestin of human umbilical cord mesenchymal stemcells (huMSCs) cultured on film with aligned surface topography and ES were obviously enhanced. These results suggest that aligned topography combining with ES facilitates the neurogenic differentiation of huMSCs and the aligned conductive film can act as a potential nerve scaffold.

On the nature of the Cu-rich aggregates in brain astrocytes

Energy Technology Data Exchange (ETDEWEB)

Sullivan, Brendan; Robison, Gregory; Osborn, Jenna; Kay, Martin; Thompson, Peter; Davis, Katherine; Zakharova, Taisiya; Antipova, Olga; Pushkar, Yulia

2017-04-01

Fulfilling a bevy of biological roles, copper is an essential metal for healthy brain function. Cu dyshomeostasis has been demonstrated to be involved in some neurological conditions including Menkes and Alzheimer’s diseases. We have previously reported localized Cu-rich aggregates in astrocytes of the subventricular zone (SVZ) in rodent brains with Cu concentrations in the hundreds of millimolar. Metallothionein, a cysteine-rich protein critical to metal homeostasis and known to participate in a variety of neuroprotective and neuroregenerative processes, was proposed as a binding protein. Here, we present an analysis of metallothionein(1,2) knockout (MTKO) mice and age-matched controls using X-ray fluorescence microscopy. In large structures such as the corpus callosum, cortex, and striatum, there is no significant difference in Cu, Fe, or Zn concentrations in MTKO mice compared to age-matched controls. In the astrocyte-rich subventricular zone where Cu-rich aggregates reside, approximately 1/3 as many Cu-rich aggregates persist in MTKO mice resulting in a decrease in periventricular Cu concentration. Aggregates in both wild-type and MTKO mice show XANES spectra characteristic of CuxSy multimetallic clusters and have similar [S]/[Cu] ratios. Consistent with assignment as a CuxSy multimetallic cluster, the astrocyte-rich SVZ of both MTKO and wild-type mice exhibit autofluorescent bodies, though MTKO mice exhibit fewer. Furthermore, XRF imaging of Au-labeled lysosomes and ubiquitin demonstrates a lack of co-localization with Cu-rich aggregates suggesting they are not involved in a degradation pathway. Overall, these data suggest that Cu in aggregates is bound by either metallothionein-3 or a yet unknown protein similar to metallothionein.

Estimated clinical benefit of protecting neurogenesis in the developing brain during radiation therapy for pediatric medulloblastoma

DEFF Research Database (Denmark)

Blomstrand, M.; Berthelsen, Anne Kiil; Munck af Rosenschöld, Per Martin

2012-01-01

to the whole-brain irradiation that is part of standard management. Neurogenesis is very sensitive to radiation, and limiting the radiation dose to the hippocampus and the subventricular zone (SVZ) may preserve neurocognitive function. Radiotherapy plans were created using 4 techniques: standard opposing...... fields, intensity-modulated radiotherapy (IMRT), intensity-modulated arc therapy (IMAT), and intensity-modulated proton therapy (IMPT). Mean dose to the hippocampus and SVZ (mean for both sites) could be limited to 88.3% (range, 83.6%-91.0%), 77.1% (range, 71.5%-81.3%), and 42.3% (range, 26......-modulated proton therapy, thus making this an attractive option to be tested in a prospective clinical trial....

An electrophysiological approach to the diagnosis of neurogenic dysphagia: implications for botulinum toxin treatment.

Science.gov (United States)

Alfonsi, E; Merlo, I M; Ponzio, M; Montomoli, C; Tassorelli, C; Biancardi, C; Lozza, A; Martignoni, E

2010-01-01

Botulinum toxin (BTX) injection into the cricopharyngeal (CP) muscle has been proposed for the treatment of neurogenic dysphagia due to CP hyperactivity. The aim was to determine whether an electrophysiological method exploring oropharyngeal swallowing could guide treatment and discriminate responders from non-responders, based on the association of CP dysfunction with other electrophysiological abnormalities of swallowing. Patients with different neurological disorders were examined: Parkinson disease, progressive supranuclear palsy, multiple system atrophy-Parkinson variant, multiple system atrophy cerebellar variant, stroke, multiple sclerosis and ataxia telangiectasia. All patients presented with clinical dysphagia, and with complete absence of CP muscle inhibition during the hypopharyngeal phase of swallowing. Each patient underwent clinical and electrophysiological investigations before and after treatment with BTX into the CP muscle of one side (15 units of Botox). Clinical and electrophysiological procedures were performed in a blind manner by two different investigators. The following electrophysiological measures were analysed: (1) duration of EMG activity of suprahyoid/submental muscles (SHEMG-D); (2) duration of laryngopharyngeal mechanogram (LPM-D); (3) duration of the inhibition of the CP muscle EMG activity (CPEMG-ID); and (4) interval between onset of EMG activity of suprahyoid/submental muscles and onset of laryngopharyngeal mechanogram (I-SHEMG-LPM). Two months after treatment, 50% of patients showed a significant improvement. Patients with prolonged or reduced SHEMG-D values and prolonged I-SHEMG-LPM values did not respond to BTX. Therefore, values for which BTX had no effect (warning values) were identified. This electrophysiological method can recognise swallowing abnormalities which may affect the outcome of the therapeutic approach to dysphagia with BTX treatment.

Endovascular Treatment for Aneurysmal Subarachnoid Hemorrhage with Neurogenic Pulmonary Edema in the Acute Stage.

Science.gov (United States)

Meguro, Toshinari; Tanabe, Tomoyuki; Muraoka, Kenichiro; Terada, Kinya; Hirotsune, Nobuyuki; Nishino, Shigeki

2016-01-01

Severe neurogenic pulmonary edema (NPE) can occur in a variety of brain insults, including subarachnoid hemorrhage (SAH), and severe case of NPE can cause devastating consequences. But the literature on the treatment strategy about aneurysmal SAH with NPE is very scant. We present that SAH patients with severe NPE, who were treated first by embolization of aneurysm followed by insertion of lumbar spinal drainage, had comparatively good outcome. We present 12 consecutive cases of aneurysmal SAH with NPE in the acute stage, which were treated by endovascular treatment between April 2002 and December 2012. We classified the patients according to the Hunt and Hess grading system as follows: grade-3 (1 patient), grade-4 (4 patients), and grade-5 (7 patients). All patients needed respiratory management, with the assistance of a ventilator, and underwent endovascular treatment for the ruptured aneurysms within 72 hours from onset. For all the patients, immediately after the endovascular treatment, we performed lumbar spinal drainage. The pulmonary edema disappeared rapidly after respiratory management and endovascular treatment. The outcomes were as follows: good recovery (GR; 3 patients), moderate disability (MD; 4 patients), severe disability (SD; 3 patients), and death (D; 2 patients). Five patients (42%) developed pneumonia, and we postponed extubation until recovery from pneumonia. The cause for severe disability and death was symptomatic vasospasm and primary brain damage. No patients had rebleeding from ruptured aneurysms. Endovascular treatment for ruptured aneurysm and placement of lumbar spinal drainage is an excellent treatment option for severe SAH with NPE.

Sciatic nerve compression by neurogenic heterotopic ossification: use of CT to determine surgical indications

International Nuclear Information System (INIS)

Salga, Marjorie; Jourdan, Claire; Durand, Marie-Christine; Hangard, Chloe; Carlier, Robert-Yves; Denormandie, Philippe; Genet, Francois

2015-01-01

To describe the characteristics of neurogenic heterotopic ossification (NHO) based on clinical tests, electroneuromyography (ENMG) and CT in a database of patients with lesions of the central nervous system who required sciatic nerve neurolysis along with posterior hip NHO resection, and to determine the respective roles of ENMG and CT in the management of posterior hip NHOs in patients who are unable to communicate or express pain. The consistency of the ENMG results with clinical findings, CT results and macroscopic signs of lesions was retrospectively assessed after sciatic nerve neurolysis and ablation of 55 posterior hip NHOs. Sciatic nerve neurolysis was necessary in 55 cases (47.4 %; 55 out of 116). CT showed contact of the NHO with the nerve in all cases: 5 in contact with no deflection, 3 in contact with deflection, 21 moulded into a gutter and 26 entrapped in the NHO. There were clinical signs of sciatic nerve lesion in 21.8 % of cases (12 out of 55). ENMG showed signs of sciatic nerve lesions in only 55.6 % (10 out of 18), only 4 of whom presented with clinical signs of a nerve lesion. No significant relationship was found between clinical symptoms and ENMG findings of sciatic nerve compression (n = 13, p = 0.77). Nerve compression by NHO is likely an underdiagnosed condition, particularly in patients who are unable to communicate. Diagnosis of sciatic compression by NHO should be based on regular clinical examinations and CT. ENMG is not sufficiently sensitive to be used alone for surgical decision-making. (orig.)

Sciatic nerve compression by neurogenic heterotopic ossification: use of CT to determine surgical indications

Energy Technology Data Exchange (ETDEWEB)

Salga, Marjorie [Hopital Raymond Poincare, APHP, CIC-IT 805, Department of Physical Medicine and Rehabilitation, Garches (France); Jourdan, Claire [Hopital Raymond Poincare, APHP, CIC-IT 805, Department of Physical Medicine and Rehabilitation, Garches (France); Universite de Versailles Saint Quentin en Yvelines, Handi-Resp, (EA4047), Versailles (France); Durand, Marie-Christine [Hopital Raymond Poincare, APHP, CIC-IT 805, Department of Neurophysiology, Garches (France); Universite de Versailles Saint Quentin en Yvelines, Groupement de Recherche Clinique et Technologique sur le Handicap (GRCTH, EA 4497), Versailles (France); Hangard, Chloe; Carlier, Robert-Yves [Hopital Raymond Poincare, APHP, CIC-IT 805, Department of Medical Imaging, Garches (France); Denormandie, Philippe [Universite de Versailles Saint Quentin en Yvelines, Groupement de Recherche Clinique et Technologique sur le Handicap (GRCTH, EA 4497), Versailles (France); Hopital Raymond Poincare, APHP, CIC-IT 805, Department of Orthopaedic Surgery, Garches (France); Genet, Francois [Hopital Raymond Poincare, APHP, CIC-IT 805, Department of Physical Medicine and Rehabilitation, Garches (France); Universite de Versailles Saint Quentin en Yvelines, Groupement de Recherche Clinique et Technologique sur le Handicap (GRCTH, EA 4497), Versailles (France); Military Medical Service, Hopital d' Instruction des Armees Percy, Department of Physical Medicine and Rehabilitation, Clamart (France)

2014-09-14

To describe the characteristics of neurogenic heterotopic ossification (NHO) based on clinical tests, electroneuromyography (ENMG) and CT in a database of patients with lesions of the central nervous system who required sciatic nerve neurolysis along with posterior hip NHO resection, and to determine the respective roles of ENMG and CT in the management of posterior hip NHOs in patients who are unable to communicate or express pain. The consistency of the ENMG results with clinical findings, CT results and macroscopic signs of lesions was retrospectively assessed after sciatic nerve neurolysis and ablation of 55 posterior hip NHOs. Sciatic nerve neurolysis was necessary in 55 cases (47.4 %; 55 out of 116). CT showed contact of the NHO with the nerve in all cases: 5 in contact with no deflection, 3 in contact with deflection, 21 moulded into a gutter and 26 entrapped in the NHO. There were clinical signs of sciatic nerve lesion in 21.8 % of cases (12 out of 55). ENMG showed signs of sciatic nerve lesions in only 55.6 % (10 out of 18), only 4 of whom presented with clinical signs of a nerve lesion. No significant relationship was found between clinical symptoms and ENMG findings of sciatic nerve compression (n = 13, p = 0.77). Nerve compression by NHO is likely an underdiagnosed condition, particularly in patients who are unable to communicate. Diagnosis of sciatic compression by NHO should be based on regular clinical examinations and CT. ENMG is not sufficiently sensitive to be used alone for surgical decision-making. (orig.)

Fault zone hydrogeology

Science.gov (United States)

Bense, V. F.; Gleeson, T.; Loveless, S. E.; Bour, O.; Scibek, J.

2013-12-01

Deformation along faults in the shallow crust (research effort of structural geologists and hydrogeologists. However, we find that these disciplines often use different methods with little interaction between them. In this review, we document the current multi-disciplinary understanding of fault zone hydrogeology. We discuss surface- and subsurface observations from diverse rock types from unlithified and lithified clastic sediments through to carbonate, crystalline, and volcanic rocks. For each rock type, we evaluate geological deformation mechanisms, hydrogeologic observations and conceptual models of fault zone hydrogeology. Outcrop observations indicate that fault zones commonly have a permeability structure suggesting they should act as complex conduit-barrier systems in which along-fault flow is encouraged and across-fault flow is impeded. Hydrogeological observations of fault zones reported in the literature show a broad qualitative agreement with outcrop-based conceptual models of fault zone hydrogeology. Nevertheless, the specific impact of a particular fault permeability structure on fault zone hydrogeology can only be assessed when the hydrogeological context of the fault zone is considered and not from outcrop observations alone. To gain a more integrated, comprehensive understanding of fault zone hydrogeology, we foresee numerous synergistic opportunities and challenges for the discipline of structural geology and hydrogeology to co-evolve and address remaining challenges by co-locating study areas, sharing approaches and fusing data, developing conceptual models from hydrogeologic data, numerical modeling, and training interdisciplinary scientists.

[Features of daily rhythm of arterial pressure in patients with primary arterial hypertension and neurogenic syncope conditions].

Science.gov (United States)

Musaeva, Z A; Oknin, V Iu; Khapaev, B A; Fedotova, A V; Veĭn, A M

2002-01-01

A comparative analysis of parameters of systemic BP in patients with primary arterial hypotension (PAH) and in patients with neurogenic syncopes (NS) in the cycle sleep-awake. Blood pressure was investigated in 20 patients with PAH aged 16-44 years and 18 patients with NS aged 16-49 years. 24-h ambulatory monitoring of BP was made on the monitor ABPM-02/M (Meditech, Hungary). Rhythm indices of BP in NS patients corresponded to age normal criteria. 24-h arrhythmia of BP in PAH patients manifests with excessive drop of diastolic BP in sleep (55% patients were overdippers). PAH and NS patients differ maximally by hypotonic load in sleep: 1.0 +/- 0.7% in NS vs 15.4 +/- 3.2% in PAH. Hypotonia episodes in awake PAH patients were registered at each 4th-5th measurement of BP, in NS patients--at each 11th-13th. Heart rate in awake PAH patients is higher than in healthy subjects. Hypotonic load in sleep carries the highest differentially-diagnostic importance. This makes more perspective examinations of such patients in the cycle sleep-awake. The changes observed in PAH patients evidence for activation of cerebral sympathico-adrenal systems participating in baroreflex regulation.

Factors that influence the urodynamic results of botulinum toxin in the treatment of neurogenic hyperactivity.

Science.gov (United States)

Gutiérrez-Martín, P; Vírseda-Chamorro, M; Salinas Casado, J; Gómez-Rodríguez, A; Esteban-Fuertes, M

2015-05-01

To determine the urodynamic efficacy and factors that influence the urodynamic results of treatment of neurogenic detrusor hyperactivity with intradetrusor injection of botulinum toxin type A (BTX-A) in patients with spinal cord injury (SCI). A retrospective study was conducted with a cohort of 70 patients composed of 40 men and 30 women with stable SCI (mean age, 39 ± 13.3 years) who underwent an intradetrusor injection of 300 IUs of BTX-A. A urodynamic study was conducted prior to the injection and 6 ± 4.3 months after the treatment. New urodynamic studies were subsequently performed up to an interval of 16 ± 12.2 months. The BTX-A significantly increased (p bladder capacity, the bladder volume of the first involuntary contraction of the detrusor and the postvoid residue. We observed a decrease that tended towards statistical significance (p bladder accommodation nor the urethral resistance index (bladder outlet obstruction index) varied significantly. The increase in vesical capacity was maintained in 50% of the sample for more than 32 months. Age, sex, anticholinergic treatment and lesion age showed no influence in terms of the increase in bladder capacity. The indwelling urinary catheter (IUC) was the only statistically significant negative factor. The urodynamic effect of BTX-A is maintained for a considerable time interval. The IUC negatively influences the result of the treatment. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

The Intensive Dysphagia Rehabilitation Approach Applied to Patients With Neurogenic Dysphagia: A Case Series Design Study.

Science.gov (United States)

Malandraki, Georgia A; Rajappa, Akila; Kantarcigil, Cagla; Wagner, Elise; Ivey, Chandra; Youse, Kathleen

2016-04-01

To examine the effects of the Intensive Dysphagia Rehabilitation approach on physiological and functional swallowing outcomes in adults with neurogenic dysphagia. Intervention study; before-after trial with 4-week follow-up through an online survey. Outpatient university clinics. A consecutive sample of subjects (N=10) recruited from outpatient university clinics. All subjects were diagnosed with adult-onset neurologic injury or disease. Dysphagia diagnosis was confirmed through clinical and endoscopic swallowing evaluations. No subjects withdrew from the study. Participants completed the 4-week Intensive Dysphagia Rehabilitation protocol, including 2 oropharyngeal exercise regimens, a targeted swallowing routine using salient stimuli, and caregiver participation. Treatment included hourly sessions twice per week and home practice for approximately 45 min/d. Outcome measures assessed pre- and posttreatment included airway safety using an 8-point Penetration Aspiration Scale, lingual isometric pressures, self-reported swallowing-related quality of life (QOL), and level of oral intake. Also, patients were monitored for adverse dysphagia-related effects. QOL and adverse effects were also assessed at the 4-week follow-up (online survey). The Intensive Dysphagia Rehabilitation approach was effective in improving maximum and mean Penetration Aspiration Scale scores (PDysphagia Rehabilitation approach was safe and improved physiological and some functional swallowing outcomes in our sample; however, further investigation is needed before it can be widely applied. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Neurogenesis in the aging brain.

Science.gov (United States)

Apple, Deana M; Solano-Fonseca, Rene; Kokovay, Erzsebet

2017-10-01

Adult neurogenesis is the process of producing new neurons from neural stem cells (NSCs) for integration into the brain circuitry. Neurogenesis occurs throughout life in the ventricular-subventricular zone (V-SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus. However, during aging, NSCs and their progenitors exhibit reduced proliferation and neuron production, which is thought to contribute to age-related cognitive impairment and reduced plasticity that is necessary for some types of brain repair. In this review, we describe NSCs and their niches during tissue homeostasis and how they undergo age-associated remodeling and dysfunction. We also discuss some of the functional ramifications in the brain from NSC aging. Finally, we discuss some recent insights from interventions in NSC aging that could eventually translate into therapies for healthy brain aging. Copyright © 2017 Elsevier Inc. All rights reserved.

33 CFR 165.169 - Safety and Security Zones: New York Marine Inspection Zone and Captain of the Port Zone.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Safety and Security Zones: New... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY... Areas First Coast Guard District § 165.169 Safety and Security Zones: New York Marine Inspection Zone...

33 CFR 165.814 - Security Zones; Captain of the Port Houston-Galveston Zone.

Science.gov (United States)

2010-07-01

... Port Houston-Galveston Zone. 165.814 Section 165.814 Navigation and Navigable Waters COAST GUARD... § 165.814 Security Zones; Captain of the Port Houston-Galveston Zone. (a) Location. The following areas are designated as security zones: (1) Houston, Texas. The Houston Ship Channel and all associated...

Botulinum toxin A for the treatment of neurogenic detrusor overactivity in multiple sclerosis patients

Directory of Open Access Journals (Sweden)

S. Deffontaines-Rufin

2011-10-01

Full Text Available PURPOSE: Neurogenic detrusor overactivity (NDO is common in patients who suffer from multiple sclerosis (MS. When the usual pharmacological treatment fails, botulinum toxin type A (BTX-A injections can be proposed. The safety and efficacy of this treatment are already well known, but only a few studies focus on its use in patients with MS. MATERIALS AND METHODS: Seventy-one patients with MS underwent their first BTX-A injection for refractory NDO. They had clinical and urodynamic cystometry assessment before and three months after injection. The patients were divided in three groups according to treatment efficacy: full success (total urinary continence, no overactive detrusor, improvement, or total failure (urge incontinence and overactive detrusor. RESULTS: 77% of the patients had clinical improvement or full success of the treatment with a reduction of their urgency and incontinence. Significant urodynamic improvement after treatment was shown on different parameters: volume at first involuntary bladder contraction (p = 0.0000001, maximum cystometric capacity (p = 0.0035, maximum detrusor pressure (p = 0.0000001. 46% of the patients were in the "full success" group. 31% of the patients had a partial improvement. 23% of the patients had no efficacy of the treatment. Duration of MS was a predictive factor of treatment failure (p = 0.015. CONCLUSIONS: Despite that a full success was obtained in 46% of the cases, BTX-A injection therapy failed to treat refractory NDO in 23% of patients suffering from MS. Duration of the disease was a predictive factor for an inefficient treatment. The injection therapy should be considered as soon as oral anticholinergic drugs fail to reduce NDO.

Minocycline treatment ameliorates interferon-alpha-induced neurogenic defects and depression-like behaviors in mice

Directory of Open Access Journals (Sweden)

Lian-Shun eZheng

2015-01-01

Full Text Available Interferon-alpha (IFN-α is a proinflammatory cytokine that is widely used for the treatment of chronic viral hepatitis and malignancy, because of its immune-activating, antiviral, and antiproliferative properties. However, long-term IFN-α treatment frequently causes depression, which limits its clinical utility. The precise molecular and cellular mechanisms of IFN-α-induced depression are not currently understood. Neural stem cells (NSCs in the hippocampus continuously generate new neurons, and some evidence suggests that decreased neurogenesis plays a role in the neuropathology of depression. We previously reported that IFN-α treatment suppressed hippocampal neurogenesis and induced depression-like behaviors via its receptors in the brain in adult mice. However, it is unclear how systemic IFN-α administration induces IFN-α signaling in the hippocampus. In this study, we analyzed the role of microglia, immune cells in the brain, in mediating the IFN-α-induced neurogenic defects and depressive behaviors. In vitro studies demonstrated that IFN-α treatment induced the secretion of endogenous IFN-α from microglia, which suppressed NSC proliferation. In vivo treatment of adult mice with IFN-α for five weeks increased the production of proinflammatory cytokines, including IFN-α, and reduced neurogenesis in the hippocampus. Both effects were prevented by simultaneous treatment with minocycline, an inhibitor of microglial activation. Furthermore, minocycline treatment significantly suppressed IFN-α-induced depressive behaviors in mice. These results suggest that microglial activation plays a critical role in the development of IFN-α-induced depression, and that minocycline is a promising drug for the treatment of IFN-α-induced depression in patients, especially those who are low responders to conventional antidepressant treatments.

The Sorong Fault Zone, Indonesia: Mapping a Fault Zone Offshore

Science.gov (United States)

Melia, S.; Hall, R.

2017-12-01

The Sorong Fault Zone is a left-lateral strike-slip fault zone in eastern Indonesia, extending westwards from the Bird's Head peninsula of West Papua towards Sulawesi. It is the result of interactions between the Pacific, Caroline, Philippine Sea, and Australian Plates and much of it is offshore. Previous research on the fault zone has been limited by the low resolution of available data offshore, leading to debates over the extent, location, and timing of movements, and the tectonic evolution of eastern Indonesia. Different studies have shown it north of the Sula Islands, truncated south of Halmahera, continuing to Sulawesi, or splaying into a horsetail fan of smaller faults. Recently acquired high resolution multibeam bathymetry of the seafloor (with a resolution of 15-25 meters), and 2D seismic lines, provide the opportunity to trace the fault offshore. The position of different strands can be identified. On land, SRTM topography shows that in the northern Bird's Head the fault zone is characterised by closely spaced E-W trending faults. NW of the Bird's Head offshore there is a fold and thrust belt which terminates some strands. To the west of the Bird's Head offshore the fault zone diverges into multiple strands trending ENE-WSW. Regions of Riedel shearing are evident west of the Bird's Head, indicating sinistral strike-slip motion. Further west, the ENE-WSW trending faults turn to an E-W trend and there are at least three fault zones situated immediately south of Halmahera, north of the Sula Islands, and between the islands of Sanana and Mangole where the fault system terminates in horsetail strands. South of the Sula islands some former normal faults at the continent-ocean boundary with the North Banda Sea are being reactivated as strike-slip faults. The fault zone does not currently reach Sulawesi. The new fault map differs from previous interpretations concerning the location, age and significance of different parts of the Sorong Fault Zone. Kinematic

A two-dimensional time domain near zone to far zone transformation

Science.gov (United States)

Luebbers, Raymond J.; Ryan, Deirdre; Beggs, John H.; Kunz, Karl S.

1991-01-01

In a previous paper, a time domain transformation useful for extrapolating 3-D near zone finite difference time domain (FDTD) results to the far zone was presented. In this paper, the corresponding 2-D transform is outlined. While the 3-D transformation produced a physically observable far zone time domain field, this is not convenient to do directly in 2-D, since a convolution would be required. However, a representative 2-D far zone time domain result can be obtained directly. This result can then be transformed to the frequency domain using a Fast Fourier Transform, corrected with a simple multiplicative factor, and used, for example, to calculate the complex wideband scattering width of a target. If an actual time domain far zone result is required it can be obtained by inverse Fourier transform of the final frequency domain result.

Root zone effects on tracer migration in arid zones

International Nuclear Information System (INIS)

Tyler, S.W.; Walker, G.R.

1994-01-01

The study of groundwater recharge and soil water movement in arid regions has received increased attention in the search for safe disposal sites for hazardous wastes. In passing through the upper 1 to 2 m of most soil profiles, tracers indicative of recharge such as Cl, 2 H, 18 O, Br, 3 H, and 56 Cl are subjected to a wide range of processes not encountered deeper in the profile. This transition zone, where water enters as precipitation and leaves as recharge, is often ignored when environmental tracers are used to estimate deep soil water flux and recharge, yet its effect may be profound. In this work, we reexamine the processes of root extraction and its effect on the velocity and distribution of tracers. Examples are presented for idealized conditions, which show clearly the relation between the root zone processes and the deep drainage or recharge. The results indicate that, when recharge is small and root zone processes are not accounted for, tracer techniques can significantly overestimate recharge until the tracer has moved well below the root zone. By incorporating simple models of root zone processes, a clearer understanding of tracer distributions and a more accurate estimate of recharge can then be made. 11 refs., 9 figs

75 FR 50700 - Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, and Drawbridge...

Science.gov (United States)

2010-08-17

...] Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, and Drawbridge Operation... notice lists temporary safety zones, security zones, special local regulations, and drawbridge operation... responsive to the safety and security needs within their jurisdiction; therefore, District Commanders and...

Radiant zone heated particulate filter

Science.gov (United States)

Gonze, Eugene V [Pinckney, MI

2011-12-27

A system includes a particulate matter (PM) filter including an upstream end for receiving exhaust gas and a downstream end. A radiant zoned heater includes N zones, where N is an integer greater than one, wherein each of the N zones includes M sub-zones, where M is an integer greater than or equal to one. A control module selectively activates at least a selected one of the N zones to initiate regeneration in downstream portions of the PM filter from the one of the N zones, restricts exhaust gas flow in a portion of the PM filter that corresponds to the selected one of the N zones, and deactivates non-selected ones of the N zones.

Clinical profile of motor neuron disease patients with lower urinary tract symptoms and neurogenic bladder.

Science.gov (United States)

Vázquez-Costa, Juan Francisco; Arlandis, Salvador; Hervas, David; Martínez-Cuenca, Esther; Cardona, Fernando; Pérez-Tur, Jordi; Broseta, Enrique; Sevilla, Teresa

2017-07-15

Lower urinary tract symptoms (LUTS) are frequent in motor neuron disease (MND) patients, but clinical factors related to them are unknown. We describe differences in LUTS among MND phenotypes and their relationship with other clinical characteristics, including prognosis. For this study, we collected clinical data of a previously published cohort of patients diagnosed with classical amyotrophic lateral sclerosis (cALS), progressive muscular atrophy (PMA) or primary lateral sclerosis (PLS) with and without LUTS. Familial history was recorded and the C9ORF72 expansion was analysed in the entire cohort. Patients were followed-up for survival until August 2016. Fifty-five ALS patients (37 cALS, 10 PMA and 8 PLS) were recruited. Twenty-four reported LUTS and neurogenic bladder (NB) could be demonstrated in nine of them. LUTS were not influenced by age, phenotype, disability, cognitive or behavioural impairment, or disease progression, but female sex appeared to be a protective factor (OR=0.39, p=0.06). Neither family history nor the C9ORF72 expansion was linked to LUTS or NB. In the multivariate analysis, patients reporting LUTS early in the disease course tended to show poorer survival. In this study, LUTS appear to be more frequent in male MND patients, but are not related to age, clinical or genetic characteristics. When reported early, LUTS could be a sign of rapid disease spread and poor prognosis. Further prospective longitudinal and neuroimaging studies are warranted to confirm this hypothesis. Copyright © 2017 Elsevier B.V. All rights reserved.

Towards stacked zone plates

International Nuclear Information System (INIS)

Werner, S; Rehbein, S; Guttman, P; Heim, S; Schneider, G

2009-01-01

Fresnel zone plates are the key optical elements for soft and hard x-ray microscopy. For short exposure times and minimum radiation load of the specimen the diffraction efficiency of the zone plate objectives has to be maximized. As the efficiency strongly depends on the height of the diffracting zone structures the achievable aspect ratio of the nanostructures determines these limits. To reach aspect ratios ≥ 20:1 for high efficient optics we propose to superimpose zone plates on top of each other. With this multiplication approach the final aspect ratio is only limited by the number of stacked zone plate layers. For the stack process several nanostructuring process steps have to be developed and/or improved. Our results show for the first time two layers of zone plates stacked on top of each other.

76 FR 70342 - Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation...

Science.gov (United States)

2011-11-14

...] Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation... published in the Federal Register. This notice lists temporary safety zones, security zones, special local... Commanders and Captains of the Port (COTP) must be immediately responsive to the safety and security needs...

76 FR 48751 - Security Zones; Captain of the Port Lake Michigan Zone

Science.gov (United States)

2011-08-09

... Jardine Water Filtration Plant security zone would encompass all U.S. navigable waters of Lake Michigan... areas near shore to Chicago's water filtration plants; the security zones have been designed to allow.... 165.910 Security Zones; Captain of the Port Lake Michigan. (a) * * * (1) Jardine Water Filtration...

Effect of fenspiride, a non-steroidal antiinflammatory agent, on neurogenic mucus secretion in ferret trachea in vitro.

Science.gov (United States)

Khawaja, A M; Liu, Y C; Rogers, D F

1999-01-01

Neural mechanisms contribute to control of mucus secretion in the airways. Fenspiride is a non-steroidal antiinflammatory agent which has a variety of actions, including inhibition of neurogenic bronchoconstriction. The effect of fenspiride on neurally-mediated mucus secretion was investigated in vitro in electrically-stimulated ferret trachea, using(35)SO(4)as a mucus marker. Cholinergic secretory responses were isolated using adrenoceptor and tachykinin receptor antagonists. Tachykinin responses were isolated using cholinoceptor and adrenoceptor antagonists. Electrical stimulation increased cholinergic secretion by;90% and tachykininergic secretion by;40%. Fenspiride (1 microM-1 mM) tended to inhibit cholinergic secretion in a concentration-dependent manner, although only at 1 mM was inhibition (by 87%) significant. Inhibition by fenspiride of tachykininergic secretion was not concentration-dependent, and again significant inhibition (by 85%) was only at 1 mM. Inhibition was not due to loss of tissue viability, as assessed by restitution of secretory response after washout. Fenspiride also inhibited secretion induced by acetylcholine, but did not inhibit substance P-induced secretion. Histamine receptor antagonists increased basal secretion by 164%, whereas fenspiride did not affect basal secretion. We conclude that, in ferret trachea in vitro, fenspiride inhibits neurally-mediated mucus secretion, with antimuscarinic action the most plausible mechanism of action, but not necessarily the only mechanism. Copyright 1999 Academic Press.

The NKG2D ligands RAE-1δ and RAE-1ε differ with respect to their receptor affinity, expression profiles and transcriptional regulation

DEFF Research Database (Denmark)

Cédile, Oriane; Popa, Natalia; Pollet-Villard, Frédéric

2010-01-01

RAE-1 is a ligand of the activating receptor NKG2D expressed by NK cells, NKT, γδT and some CD8(+)T lymphocytes. RAE-1 is overexpressed in tumor cell lines and its expression is induced after viral infection and genotoxic stress. We have recently demonstrated that RAE-1 is expressed in the adult...... subventricular zone (SVZ) from C57BL/6 mice. RAE-1 is also expressed in vitro by neural stem/progenitor cells (NSPCs) and plays a non-immune role in cell proliferation. The C57BL/6 mouse genome contains two rae-1 genes, rae-1δ and rae-1ε encoding two different proteins. The goals of this study are first...

Telocytes in meninges and choroid plexus.

Science.gov (United States)

Popescu, B O; Gherghiceanu, M; Kostin, S; Ceafalan, L; Popescu, L M

2012-05-16

Telocytes (TCs) are a recently identified type of interstitial cells present in a wide variety of organs in humans and mammals (www.telocytes.com). They are characterized by a small cell body, but extremely long cell processes - telopodes (Tp), and a specific phenotype. TCs establish close contacts with blood capillaries, nerve fibers and stem cells. We report here identification of TCs by electron microscopy and immunofluorescence in rat meninges and choroid plexus/subventricular zone, in the vicinity of putative stem cells. The presence of TCs in brain areas involved in adult neurogenesis might indicate that they have a role in modulation of neural stem cell fate. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

76 FR 44803 - Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation...

Science.gov (United States)

2011-07-27

... USCG-2009-1081 New Orleans, LA Safety Zone (Part 165)..... 12/23/2009 USCG-2009-1084 Rio Vista, CA...-1096 Port Portland Zone......... Safety Zone (Part 165)..... 7/3/2010 USCG-2009-0040 La Push, WA Safety...-0950 Madisonville, LA Safety Zone (Part 165)..... 12/31/2009 USCG-2009-0951 Lower Mississippi River...

RADIATION ACCESS ZONE AND VENTILATION CONFINEMENT ZONE CRITERIA FOR THE MGR SURFACE FACILITIES

International Nuclear Information System (INIS)

D. A. Padula

2000-01-01

The objectives of this technical report are to: (1) Establish the criteria for Radiation Access Zone (RAZ) designation. (2) Establish the criteria for the Ventilation Confinement Zone (VCZ) designation. The scope will be to formulate the RAZ and VCZ zoning designation for the Monitored Geologic Repository (MGR) surface facilities and to apply the zoning designations to the current Waste Handling Building (WHB), Waste Treatment Building (WTB), and Carrier Preparation Building (CPB) configurations

Cortical neurogenesis in the absence of centrioles.

Science.gov (United States)

Insolera, Ryan; Bazzi, Hisham; Shao, Wei; Anderson, Kathryn V; Shi, Song-Hai

2014-11-01

Neuronal production in the mammalian cortex depends on extensive mitoses of radial glial progenitors (RGPs) residing in the ventricular zone (VZ). We examined the function of centrioles in RGPs during cortical neurogenesis in mice by conditional removal of SAS-4, a protein that is required for centriole biogenesis. SAS-4 deletion led to a progressive loss of centrioles, accompanied by RGP detachment from the VZ. Delocalized RGPs did not become outer subventricular zone RGPs (oRGs). Although they remained proliferative, ectopic RGPs, as well as those in the VZ, with a centrosomal deficit exhibited prolonged mitosis, p53 upregulation and apoptosis, resulting in neuronal loss and microcephaly. Simultaneous removal of p53 fully rescued RGP death and microcephaly, but not RGP delocalization and randomized mitotic spindle orientation. Our findings define the functions of centrioles in anchoring RGPs in the VZ and ensuring their efficient mitoses, and reveal the robust adaptability of RGPs in the developing cortex.

Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindle-like (ASPM related primary) microcephaly disease

Institute of Scientific and Technical Information of China (English)

Rui Li; Le Sun; Ai Fang; Peng Li; Qian Wu; Xiaoqun Wang

2017-01-01

The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex.Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases.Several previous efforts have shown to grow neural organoid in culture dishes successfully,however we demonstrate a new paradigm that recapitulates neocortical development process with VZ,OSVZ formation and the lamination organization of cortical layer structure.In addition,using patient-specific induced pluripotent stem cells (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient,we demonstrate neurogenesis defects result in defective neuronal activity in patient organoids,suggesting a new strategy to study human developmental diseases in central nerve system.

Organotypic Cultures as a Model to Study Adult Neurogenesis in CNS Disorders

Directory of Open Access Journals (Sweden)

Fabio Cavaliere

2016-01-01

Full Text Available Neural regeneration resides in certain specific regions of adult CNS. Adult neurogenesis occurs throughout life, especially from the subgranular zone of hippocampus and the subventricular zone, and can be modulated in physiological and pathological conditions. Numerous techniques and animal models have been developed to demonstrate and observe neural regeneration but, in order to study the molecular and cellular mechanisms and to characterize multiple types of cell populations involved in the activation of neurogenesis and gliogenesis, investigators have to turn to in vitro models. Organotypic cultures best recapitulate the 3D organization of the CNS and can be explored taking advantage of many techniques. Here, we review the use of organotypic cultures as a reliable and well defined method to study the mechanisms of neurogenesis under normal and pathological conditions. As an example, we will focus on the possibilities these cultures offer to study the pathophysiology of diseases like Alzheimer disease, Parkinson’s disease, and cerebral ischemia.

Recent Advances on the Role of Neurogenesis in the Adult Brain: Therapeutic Potential in Parkinson's and Alzheimer's Diseases.

Science.gov (United States)

Radad, Khaled; Moldzio, Rudolf; Al-Shraim, Mubarak; Kranner, Barbara; Krewenka, Christopher; Rausch, Wolf-Dieter

2017-01-01

Generation of nascent functional neurons from neural stem cells in the adult brain has recently become largely accepted by the neuroscience community. In adult mammals including humans, the process of neurogenesis has been well documented in two brain regions; the subventricular zone of the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus. Some evidence has indicated neurogenesis in other regions of the adult mammalian brain such as the neocortex, cerebellum, striatum, amygdala and hypothalamus. These discoveries question a long standing dogma on nervous system regeneration and provide medical science with potential new strategies to harness the process of neurogenesis for treating neurological disabilities and neurodegenerative diseases. In this current review, we address the most recent advances on the role of neurogenesis in the adult brain and therapeutic potential in the two most common neurodegenerative disorders, Parkinson's and Alzheimer's diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Comparison of efficacies of vegetable oil based and polyethylene glycol based bisacodyl suppositories in treating patients with neurogenic bowel dysfunction after spinal cord injury: a meta-analysis.

Science.gov (United States)

Yi, Zhu; Jie, Cheng; Wenyi, Zhang; Bin, Xie; Hongzhu, Jin

2014-10-01

We performed a meta-analysis to compare the efficacies of vegetable oil based bisacodyl (VOB) and polyethylene glycol based bisacodyl (PGB) suppositories in treating patients with neurogenic bowel dysfunction (NBD) after spinal cord injury (SCI). Relevant clinical studies (up to February 2014) were retrieved through the following databases: PubMed, MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CCTR), Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wanfang, and VIP database for Chinese Technical Periodicals. Data were analyzed using the standardized weighted mean difference (SMD) and its 95% confidence interval (CI). P-values 0.05) between patients in the PGB and VOB groups. Based on the results, we conclude that the PGB suppository could act faster than the VOB suppository in the treatment of NBD in patients with SCI.

33 CFR 165.1315 - Safety Zones: Fireworks displays in the Captain of the Port Portland Zone.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Safety Zones: Fireworks displays... Coast Guard District § 165.1315 Safety Zones: Fireworks displays in the Captain of the Port Portland Zone. (a) Safety zones. The following areas are designated safety zones: (1) Cinco de Mayo Fireworks...

What do we know about neurogenic bladder prevalence and management in developing countries and emerging regions of the world?

Science.gov (United States)

Przydacz, Mikolaj; Denys, Pierre; Corcos, Jacques

2017-09-01

To summarize information on Neurogenic Bladder (NB) epidemiology, management and access to patient treatment in developing countries and emerging regions of the world in order to propose future interventions and help governmental as well as non-governmental organizations design their action plans. Different search methods were used to gather the maximum available data. They included strategic searches; reference checks; grey literature searches (reports, working papers, government documents, civil society information); contacting professional societies, registries, and authors; requesting unpublished data from organizations; and browsing related websites and journals. The incidence and prevalence rates of NB in developing countries are difficult to establish because epidemiological reports are few and far between. The frequency of bladder dysfunction in neurologically impaired populations can be approximately estimated in some of these countries. Similar information paucity affects diagnostic and therapeutic approaches to NB patients living in less-developed regions of the world. The assessment and management of NB seems to vary markedly between countries, and care of patients from emerging regions of the world is often inadequate. Strong concerted efforts are needed on the part of international scientific societies, non-governmental organizations and local governments to work together to change the prognosis for these patients and to improve their quality of life. Copyright © 2017. Published by Elsevier Masson SAS.

Diagnostic value of "dysphagia limit" for neurogenic dysphagia: 17 years of experience in 1278 adults.

Science.gov (United States)

Aydogdu, Ibrahim; Kiylioglu, Nefati; Tarlaci, Sultan; Tanriverdi, Zeynep; Alpaydin, Sezin; Acarer, Ahmet; Baysal, Leyla; Arpaci, Esra; Yuceyar, Nur; Secil, Yaprak; Ozdemirkiran, Tolga; Ertekin, Cumhur

2015-03-01

Neurogenic dysphagia (ND) is a prevalent condition that accounts for significant mortality and morbidity worldwide. Screening and follow-up are critical for early diagnosis and management which can mitigate its complications and be cost-saving. The aims of this study are to provide a comprehensive investigation of the dysphagia limit (DL) in a large diverse cohort and to provide a longitudinal assessment of dysphagia in a subset of subjects. We developed a quantitative and noninvasive method for objective assessment of dysphagia by using laryngeal sensor and submental electromyography. DL is the volume at which second or more swallows become necessary to swallow the whole amount of bolus. This study represents 17 years experience with the DL approach in assessing ND in a cohort of 1278 adult subjects consisting of 292 healthy controls, 784 patients with dysphagia, and 202 patients without dysphagia. A total of 192 of all patients were also reevaluated longitudinally over a period of 1-19 months. DL has 92% sensitivity, 91% specificity, 94% positive predictive value, and 88% negative predictive value with an accuracy of 0.92. Patients with ALS, stroke, and movement disorders have the highest sensitivity (85-97%) and positive predictive value (90-99%). The clinical severity of dysphagia has significant negative correlation with DL (r=-0.67, pdysphagia and it can be performed in an EMG laboratory. Our study provides specific quantitative features of DL test that can be readily utilized by the neurologic community and nominates DL as an objective and robust method to evaluate dysphagia in a wide range of neurologic conditions. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

77 FR 30245 - Safety Zones; Annual Fireworks Events in the Captain of the Port Detroit Zone

Science.gov (United States)

2012-05-22

...'' N, 082-51'-18.70'' W (NAD 83). This proposed zone would be enforced one evening during the last week...-AA00 Safety Zones; Annual Fireworks Events in the Captain of the Port Detroit Zone AGENCY: Coast Guard... by adding three permanent safety zones within the Captain of the Port Detroit Zone. This action is...

33 CFR 165.503 - Security Zone; Captain of the Port Hampton Roads Zone.

Science.gov (United States)

2010-07-01

... Port Hampton Roads Zone. 165.503 Section 165.503 Navigation and Navigable Waters COAST GUARD... § 165.503 Security Zone; Captain of the Port Hampton Roads Zone. (a) Definitions. As used in this... been authorized by the Captain of the Port (COTP), Hampton Roads, Virginia to act on his or her behalf...

Formulating a coastal zone health metric for landuse impact management in urban coastal zones.

Science.gov (United States)

Anilkumar, P P; Varghese, Koshy; Ganesh, L S

2010-11-01

The need for ICZM arises often due to inadequate or inappropriate landuse planning practices and policies, especially in urban coastal zones which are more complex due to the larger number of components, their critical dimensions, attributes and interactions. A survey of literature shows that there is no holistic metric for assessing the impacts of landuse planning on the health of a coastal zone. Thus there is a need to define such a metric. The proposed metric, CHI (Coastal zone Health Indicator), developed on the basis of coastal system sustainability, attempts to gauge the health status of any coastal zone. It is formulated and modeled through an expert survey and pertains to the characteristic components of coastal zones, their critical dimensions, and relevant attributes. The proposed metric is applied to two urban coastal zones and validated. It can be used for more coast friendly and sustainable landuse planning/masterplan preparation and thereby for the better management of landuse impacts on coastal zones. Copyright 2010 Elsevier Ltd. All rights reserved.

A systematic review of the diagnosis and treatment of patients with neurogenic hyperactivity of the detrusor muscle.

Science.gov (United States)

Borau, A; Adot, J M; Allué, M; Arlandis, S; Castro, D; Esteban, M; Salinas, J

Neurogenic detrusor hyperactivity (NDH) is a urodynamic observation characterised by involuntary detrusor contractions during the filling phase that are caused by an underlying neurological disease. The common and severe complications that can result from NDH warrant the preparation of healthcare protocols for the proper management of patients with NDH. The aim of this study is to standardise the criteria for the decision-making process in the management of patients with diagnosed or suspected NDH, providing personalised medical care. We performed a systematic noncomprehensive literature review on the aspects of the diagnosis and treatment of NDH. Based on the review, recommendations were issued by nominal consensus of a group of urology specialists. In general, the diagnosis of NDH is arrived at by a proper review of the medical history, physical examination and voiding diary before performing any diagnostic study. The main treatment objectives are to protect the upper urinary tract, restore function of the lower tract and improve these patients' continence and quality of life. The treatment consists of several steps aimed at obtaining proper bladder storage that allows for sufficiently spaced voidings. The follow-up should be personalised based on each patient's needs. The identification and management of NDH is important for positively redirecting the function of the lower urinary tract, in terms of filling and voiding, thereby improving the patients' quality of life. Copyright © 2017. Publicado por Elsevier España, S.L.U.

77 FR 6007 - Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation...

Science.gov (United States)

2012-02-07

...] Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation... they could be published in the Federal Register. This notice lists temporary safety zones, security... the safety and security needs within their jurisdiction; therefore, District Commanders and COTPs have...

78 FR 26508 - Safety Zone; Fireworks Event in Captain of the Port New York Zone

Science.gov (United States)

2013-05-07

... Harbor located in approximate Safety Zone, 33 CFR 165.160(3.8). position 40[deg]51'58'' N, 073[deg]39'34... Zone; Fireworks Event in Captain of the Port New York Zone AGENCY: Coast Guard, DHS. ACTION: Notice of enforcement of regulation. SUMMARY: The Coast Guard will enforce safety zones in the Captain of the Port New...

The distinguishing characteristics of interlayer oxidation zone and burial ancient ground oxidation zone

International Nuclear Information System (INIS)

Zhang Zhanshi; Zhou Wenbin

1998-01-01

The author discusses the main characteristics of interlayer oxidation zones and the burial ancient ground oxidation zones of Uranium deposit No. 512 in Xinjiang Uigur municipality. The epigenetic genesis, depending on some aquifer, the tongue-like in section, having the zonation along dip direction and having certain mineral assemblage are the typical features for interlayer oxidation zones

Zoning Districts - Volusia County HUB Zones

Data.gov (United States)

NSGIC Local Govt | GIS Inventory — Historically Underutilized Business (HUB) Zones in Volusia County. Go to http://www.sba.gov/hubzone or contact the Department of Economic Development (386) 248-8048...

VT Data - Zoning 20120709, Huntington

Data.gov (United States)

Vermont Center for Geographic Information — Zoning district data for the Town of Huntington, Vermont. For details regarding each zoning district refer to the current zoning regulations on town of Huntington's...

33 CFR 147.847 - Safety Zone; BW PIONEER Floating Production, Storage, and Offloading System Safety Zone.

Science.gov (United States)

2010-07-01

... Production, Storage, and Offloading System Safety Zone. 147.847 Section 147.847 Navigation and Navigable... ZONES § 147.847 Safety Zone; BW PIONEER Floating Production, Storage, and Offloading System Safety Zone. (a) Description. The BW PIONEER, a Floating Production, Storage and Offloading (FPSO) system, is in...

78 FR 5717 - Safety Zone; Military Ocean Terminal Concord Safety Zone, Suisun Bay, Military Ocean Terminal...

Science.gov (United States)

2013-01-28

...-AA00 Safety Zone; Military Ocean Terminal Concord Safety Zone, Suisun Bay, Military Ocean Terminal... Guard is establishing a safety zone in the navigable waters of Suisun Bay near Military Ocean Terminal Concord, CA in support of military onload and offload operations. This safety zone is established to...

The effect of recording site on extracted features of motor unit action potential.

Science.gov (United States)

Artuğ, N Tuğrul; Goker, Imran; Bolat, Bülent; Osman, Onur; Kocasoy Orhan, Elif; Baslo, M Baris

2016-06-01

Motor unit action potential (MUAP), which consists of individual muscle fiber action potentials (MFAPs), represents the electrical activity of the motor unit. The values of the MUAP features are changed by denervation and reinnervation in neurogenic involvement as well as muscle fiber loss with increased diameter variability in myopathic diseases. The present study is designed to investigate how increased muscle fiber diameter variability affects MUAP parameters in simulated motor units. In order to detect this variation, simulated MUAPs were calculated both at the innervation zone where the MFAPs are more synchronized, and near the tendon, where they show increased temporal dispersion. Reinnervation in neurogenic state increases MUAP amplitude for the recordings at both the innervation zone and near the tendon. However, MUAP duration and the number of peaks significantly increased in a case of myopathy for recordings near the tendon. Furthermore, of the new features, "number of peaks×spike duration" was found as the strongest indicator of MFAP dispersion in myopathy. MUAPs were also recorded from healthy participants in order to investigate the biological counterpart of the simulation data. MUAPs which were recorded near to tendon revealed significantly prolonged duration and decreased amplitude. Although the number of peaks was increased by moving the needle near to tendon, this was not significant. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

78 FR 24679 - Safety Zones; Fireworks Displays in Captain of the Port Long Island Sound Zone

Science.gov (United States)

2013-04-26

...-AA00 Safety Zones; Fireworks Displays in Captain of the Port Long Island Sound Zone AGENCY: Coast Guard... zones for fireworks displays within the Captain of the Port (COTP) Long Island Sound (LIS) Zone. This... Sector Long Island Sound. DATES: This rule is effective from April 27, 2013, until June 22, 2013. This...

76 FR 34867 - Safety Zones; Annual Fireworks Events in the Captain of the Port Detroit Zone

Science.gov (United States)

2011-06-15

....941(a)(51) Target Fireworks, Detroit, MI The first safety zone will be enforced from 7 a.m. on June 24... Zones; Annual Fireworks Events in the Captain of the Port Detroit Zone AGENCY: Coast Guard, DHS. ACTION: Notice of enforcement of regulation. SUMMARY: The Coast Guard will enforce various safety zones for...

Theoretical analysis of recirculation zone and buffer zone in the ADS windowless spallation target

International Nuclear Information System (INIS)

Liu, Jie; Pan, Chang-zhao; Tong, Jian-fei; Lu, Wen-qiang

2015-01-01

Highlights: • Height of recirculation zone is very important in windowless target design. • A theoretical formula for the height is derived based on the Bernoulli equation. • Numerical simulation for the LBE is performed and the height of recirculation zone is also obtained. • The theoretically-derived simulation-predicted recirculation zone heights agree with each other very well and the theoretical derivation is proved to be correct. - Abstract: The thermo-hydraulic analysis including reduction of the height of recirculation zone and stability of the free surface is very important in the design and optimization of ADS windowless spallation targets. In the present study, the Bernoulli equation is used to analyze the entire flow process in the target. Formulae for the height of the recirculation zone and the buffer zone are both obtained explicitly. Furthermore, numerical simulation for the heavy metal lead–bismuth eutectic liquid and vapor with cavitation phase change is also performed, and a novel method to calculate the height of the recirculation zone is put forward. By comparison of the theoretical formulae and numerical results, it is clearly shown that they agree with each other very well, and the heights predicted by the two methods are both determined by their own upstream flow parameters

76 FR 42048 - Safety Zones; Swimming Events in Captain of the Port Boston Zone

Science.gov (United States)

2011-07-18

...-AA00 Safety Zones; Swimming Events in Captain of the Port Boston Zone AGENCY: Coast Guard, DHS. ACTION... events within the Captain of the Port (COTP) Boston Zone for swimming events. This action is necessary to... property on navigable waters from the hazardous nature of swimming events such as large numbers of swimmers...

Application of transpulmonary thermodilution monitoring (PiCCO in patient with neurogenic pulmonary edema and acute obstructive hydrocephalus due to a central neurocytoma: A case report

Directory of Open Access Journals (Sweden)

Ryoichi Iwata

2017-06-01

Full Text Available Neurogenic pulmonary edema (NPE is an acute life-threatening complication associated with many forms of central nervous system injury. Its pathophysiology is still debated. We report a patient with acute obstructive hydrocephalus due to a central neurocytoma who also had NPE, for which serial transpulmonary thermodilution monitoring (PiCCO was performed. Insertion of the PiCCO, which provides information about the patient's cardiac output, preload status and amount of lung water, revealed a high pulmonary vascular permeability index (PVPI and low global end-diastolic volume (GEDV without cardiac dysfunction, indicating permeability edema, which led to our changing the therapeutic strategy. Using PiCCO monitoring to balance the preload and extent of pulmonary edema enabled achievement of an optimal cardiac preload for organ perfusion, resulting in normalization of pulmonary edema by day 2. PiCCO facilitates understanding of the mechanism of NPE, guiding the management of fluid balance and the choice of vasopressors in patients with life-threatening NPE.

Habitable Zones in the Universe

OpenAIRE

Gonzalez, G.

2005-01-01

Habitability varies dramatically with location and time in the universe. This was recognized centuries ago, but it was only in the last few decades that astronomers began to systematize the study of habitability. The introduction of the concept of the habitable zone was key to progress in this area. The habitable zone concept was first applied to the space around a star, now called the Circumstellar Habitable Zone. Recently, other, vastly broader, habitable zones have been proposed. We review...

Detrimental role of prolonged sleep deprivation on adult neurogenesis

Directory of Open Access Journals (Sweden)

Carina eFernandes

2015-04-01

Full Text Available Adult mammalian brains continuously generate new neurons, a phenomenon called neurogenesis. Both environmental stimuli and endogenous factors are important regulators of neurogenesis. Sleep has an important role in normal brain physiology and its disturbance causes very stressful conditions, which disrupt normal brain physiology. Recently, an influence of sleep in adult neurogenesis has been established, mainly based on sleep deprivation studies. This review provides an overview on how rhythms and sleep cycles regulate hippocampal and subventricular zone neurogenesis, discussing some potential underlying mechanisms. In addition, our review highlights some interacting points between sleep and neurogenesis in brain function, such as learning, memory and mood states, and provides some insights on the effects of antidepressants and hypnotic drugs on neurogenesis.

Oligodendrogenesis and neurogenesis in remyelination in the cuprizone model of multiple sclerosis: correlation with the degree of lesion

Science.gov (United States)

Pishchelko, A.; Khodanovich, M.; Pan, E.; Glazacheva, V.; Akulov, A.; Yarnykh, V.

2017-08-01

In this research, a cuprizone model of multiple sclerosis (MS) was used to study oligodendrogenesis and neurogenesis in remyelination. It has been shown that, with the administration of cuprizone, the amount of myelin in a number of structures of white and gray matter and the level of neurogenesis decrease, while the level of oligodendrogenesis increases. The withdrawal of cuprizone leads to the restoration of myelin content, the reduction of the excessive production of oligodendrocytes and to the restoration of the number of neurons to control values. The negative correlation between the number of oligodendrocyte precursors (OPCs) and the degree of demyelination of the corpus callosum indicates migration of OLG precursors from the subventricular zone (SVZ) to the structure during demyelination.

Mechanical properties of fracture zones

International Nuclear Information System (INIS)

Leijon, B.

1993-05-01

Available data on mechanical characteristics of fracture zones are compiled and discussed. The aim is to improve the basis for adequate representation of fracture zones in geomechanical models. The sources of data researched are primarily borehole investigations and case studies in rock engineering, involving observations of fracture zones subjected to artificial load change. Boreholes only yield local information about the components of fracture zones, i.e. intact rock, fractures and various low-strength materials. Difficulties are therefore encountered in evaluating morphological and mechanical properties of fracture zones from borehole data. Although often thought of as macroscopically planar features, available field data consistently show that fracture zones are characterized by geometrical irregularities such as thickness variations, surface undulation and jogs. These irregularities prevail on all scales. As a result, fracture zones are on all scales characterized by large, in-plane variation of strength- and deformational properties. This has important mechanical consequences in terms of non-uniform stress transfer and complex mechanisms of shear deformation. Field evidence for these findings, in particular results from the underground research laboratory in Canada and from studies of induced fault slip in deep mines, is summarized and discussed. 79 refs

Track treeing mechanism and plastic zone in solid Part 1: Initial development of plastic zone

International Nuclear Information System (INIS)

Li Boyang

2008-01-01

After neutron exposure and chemical etching in advance, latent tracks of recoil nucleon develop into pits on CR39 surface. During electrochemical etching, plastic zone is formed at top of pits. Some pits develop into tree cracks in the initial stage of plastic zone development. Physical and mathematical model of crack and plastic zone is proposed; parameter of development free path of plastic zone is presented. Based on integration of elementary theories the stress analysis is build up; based on analyses of measured parameters, a set of common relations between parameters is obtained. Integrate parameter analysis and stress analysis, depth of plastic zone development, law and phenomenon in experimental data can be interpreted completely

77 FR 42176 - Safety Zones; Annual Fireworks Events in the Captain of the Port Detroit Zone

Science.gov (United States)

2012-07-18

... fireworks launch site located at position 41-34'-18.10'' N, 082-51'-18.70'' W (NAD 83). This zone will be... at position 41-34'-18.10'' N, 082- 51'-18.70'' W (NAD 83). (ii) Expected date. This safety zone will...-AA00 Safety Zones; Annual Fireworks Events in the Captain of the Port Detroit Zone AGENCY: Coast Guard...

Neural stem cell sex dimorphism in aromatase (CYP19 expression: a basis for differential neural fate

Directory of Open Access Journals (Sweden)

Jay Waldron

2010-11-01

Full Text Available Jay Waldron1, Althea McCourty1, Laurent Lecanu1,21The Research Institute of the McGill University Health Centre, Montreal, Canada; 2Department of Medicine, McGill University, Quebec, CanadaPurpose: Neural stem cell (NSC transplantation and pharmacologic activation of endogenous neurogenesis are two approaches that trigger a great deal of interest as brain repair strategies. However, the success rate of clinical attempts using stem cells to restore neurologic functions altered either after traumatic brain injury or as a consequence of neurodegenerative disease remains rather disappointing. This suggests that factors affecting the fate of grafted NSCs are largely understudied and remain to be characterized. We recently reported that aging differentially affects the neurogenic properties of male and female NSCs. Although the sex steroids androgens and estrogens participate in the regulation of neurogenesis, to our knowledge, research on how gender-based differences affect the capacity of NSCs to differentiate and condition their neural fate is lacking. In the present study, we explored further the role of cell sex as a determining factor of the neural fate followed by differentiating NSCs and its relationship with a potential differential expression of aromatase (CYP19, the testosterone-metabolizing enzyme.Results: Using NSCs isolated from the subventricular zone of three-month-old male and female Long-Evans rats and maintained as neurospheres, we showed that differentiation triggered by retinoic acid resulted in a neural phenotype that depends on cell sex. Differentiated male NSCs mainly expressed markers of neuronal fate, including ßIII-tubulin, microtubule associated protein 2, growth-associated protein 43, and doublecortin. In contrast, female NSCs essentially expressed the astrocyte marker glial fibrillary acidic protein. Quantification of the expression of aromatase showed a very low level of expression in undifferentiated female NSCs

Sound Zones

DEFF Research Database (Denmark)

Møller, Martin Bo; Olsen, Martin

2017-01-01

Sound zones, i.e. spatially confined regions of individual audio content, can be created by appropriate filtering of the desired audio signals reproduced by an array of loudspeakers. The challenge of designing filters for sound zones is twofold: First, the filtered responses should generate...... an acoustic separation between the control regions. Secondly, the pre- and post-ringing as well as spectral deterioration introduced by the filters should be minimized. The tradeoff between acoustic separation and filter ringing is the focus of this paper. A weighted L2-norm penalty is introduced in the sound...

5-HT1A receptor-dependent modulation of emotional and neurogenic deficits elicited by prolonged consumption of alcohol.

Science.gov (United States)

Belmer, Arnauld; Patkar, Omkar L; Lanoue, Vanessa; Bartlett, Selena E

2018-02-01

Repeated episodes of binge-like alcohol consumption produce anxiety, depression and various deleterious effects including alterations in neurogenesis. While the involvement of the serotonin receptor 1 A (5-HT 1A ) in the regulation of anxiety-like behavior and neurogenesis is well documented, its contribution to alcohol withdrawal-induced anxiety and alcohol-induced deficits in neurogenesis is less documented. Using the Drinking-In-the-Dark (DID) paradigm to model chronic long-term (12 weeks) binge-like voluntary alcohol consumption in mice, we show that the selective partial activation of 5-HT 1A receptors by tandospirone (3 mg/kg) prevents alcohol withdrawal-induced anxiety in a battery of behavioral tests (marble burying, elevated-plus-maze, open-field), which is accompanied by a robust decrease in binge-like ethanol intake (1 and 3 mg/kg). Furthermore, using triple immunolabelling of proliferation and neuronal differentiation markers, we show that long-term DID elicits profound deficits in neurogenesis and neuronal fate specification in the dorsal hippocampus that are entirely reversed by a 2-week chronic treatment with the 5-HT 1A partial agonist tandospirone (3 mg/kg/day). Together, our results confirm previous observations that 5-HT 1A receptors play a pivotal role in alcohol drinking behavior and the associated emotional and neurogenic impairments, and suggest that 5-HT 1A partial agonists represent a promising treatment strategy for alcohol abuse.

33 CFR 165.154 - Safety and Security Zones: Long Island Sound Marine Inspection Zone and Captain of the Port Zone.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Safety and Security Zones: Long... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY... Areas First Coast Guard District § 165.154 Safety and Security Zones: Long Island Sound Marine...

33 CFR 165.20 - Safety zones.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Safety zones. 165.20 Section 165... WATERWAYS SAFETY REGULATED NAVIGATION AREAS AND LIMITED ACCESS AREAS Safety Zones § 165.20 Safety zones. A Safety Zone is a water area, shore area, or water and shore area to which, for safety or environmental...

Zone distillation: a new purification method

International Nuclear Information System (INIS)

Kravchenko, A.I.

2011-01-01

The features of zone distillation (with zone melting of refined material and with pulling of condensate) as a new purification method are shown. The method is based on similarity of equations of distillation and crystallization refining. The analogy between some distillation and condensation methods (particularly between zone distillation and zone recrystallization) is should up

Structure and properties of melt-spun high acrylonitrile copolymer fibers via continuous zone-drawing and zone-annealing processes

International Nuclear Information System (INIS)

Wu Zongquan; Zhang Anqiu; Percec, Simona; Jin Shi; Jing, Alexander J.; Ge, Jason J.; Cheng, Stephen Z.D.

2003-01-01

Continuous zone-drawing and zone-annealing processes have been utilized to probe improvements in mechanical performance of melt-spun high acrylonitrile copolymer fibers (AMLON TM ). The as-spun fibers were zone-drawn at different ratios in a narrow temperature range of 100-105 deg. C and then zone-annealed. As a result of these processes, the fibers show substantial increases in tensile strength and tensile modulus (about three times) and significant improvements in elongation-at-break (about two times) after zone annealing. The thermal transition behavior, dimensional stability and dynamic relaxation properties of the as-spun, zone-drawn and zone-annealed fibers have been studied using differential scanning calorimetry, thermal mechanical and dynamic mechanical experiments. Their mechanical and thermal property changes after the zone-drawing and zone-annealing processes can be associated with the microscopic structural evolution including crystallinity, crystal orientation and apparent crystallite size detected by wide angle X-ray diffraction experiments

46 CFR 76.23-5 - Zoning.

Science.gov (United States)

2010-10-01

... deck, large common areas may be zoned in accordance with table 76.23-5(b). All such zones within one common area shall be of approximately the same size. Zones of this type shall overlap in such a manner that the end sprinkler heads of both adjoining zones will cover the identical area. Table 76.23-5(b...

33 CFR 3.25-10 - Sector Hampton Roads Marine Inspection Zone and Captain of the Port Zone.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Sector Hampton Roads Marine... ZONES, AND CAPTAIN OF THE PORT ZONES Fifth Coast Guard District § 3.25-10 Sector Hampton Roads Marine Inspection Zone and Captain of the Port Zone. Sector Hampton Roads' office is located in Portsmouth, VA. The...

Irradiation damage 'displacement zone'; Dommages sous irradiation zone de deplacements

Energy Technology Data Exchange (ETDEWEB)

Genthon, J P [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1969-07-01

It is well known that a charged particle (ion, primary atom, etc...) moving in a solid slows down and can cause a cascade of displacements of the atoms in the solid. A study is made here of the extent to which the cascade is made up, or not, of independent collisions, as a function of the energy of the initial charged particle. When the distance between the collisions is small, these latter are no longer independent; the cascade, which then has to be considered as a whole, perturbs and locates, in the irradiated solid , a zone which has been named a 'displacement zone'. It is shown that the proportion of displacement zones increases with increasing atom size (high atomic number Z), with decreasing atomic distance D in the substance considered and with decreasing energy of the ion undergoing the slowing down process (although always remaining above a few hundred eV). The proportions obtained are higher than those corresponding to the calculations of J. A. Brinkman [3]. An interatomic potential required for this work has also been determined. (author) [French] On sait qu'une particule chargee (ions, atomes primaires, etc...) en mouvement dans un solide se ralentit, avec eventuellement deplacement en cascade d'atomes du solide. On etudie ici dans quelle proportion, en fonction de l'energie de la particule chargee initiale, la cascade est constituee, ou non, de 'chocs independants'. Lorsque la distance entre chocs est petite, ceux-ci ne sont plus independants; la cascade, qui doit alors etre consideree dans son ensemble, perturbe et definit dans le solide irradie, une zone qu'on a appele zone de deplacements. On montre que la proportion de zones de deplacements est d'autant plus grande que les atomes sont gros (nombre atomique Z grand), que la distance interatomique D est petite dans le corps considere, et que l'energie de l'ion en ralentissement est petite (tout en restant superieure a quelques centaines d'eV). Les proportions obtenues sont superieures a celles qui

Oxygenated gasoline release in the unsaturated zone - Part 1: Source zone behavior.

Science.gov (United States)

Freitas, Juliana G; Barker, James F

2011-11-01

Oxygenates present in gasoline, such as ethanol and MTBE, are a concern in subsurface contamination related to accidental spills. While gasoline hydrocarbon compounds have low solubility, MTBE and ethanol are more soluble, ethanol being completely miscible with water. Consequently, their fate in the subsurface is likely to differ from that of gasoline. To evaluate the fate of gasoline containing oxygenates following a release in the unsaturated zone shielded from rainfall/recharge, a controlled field test was performed at Canadian Forces Base Borden, in Ontario. 200L of a mixture composed of gasoline with 10% ethanol and 4.5% MTBE was released in the unsaturated zone, into a trench 20cm deep, about 32cm above the water table. Based on soil cores, most of the ethanol was retained in the source, above the capillary fringe, and remained there for more than 100 days. Ethanol partitioned from the gasoline to the unsaturated pore-water and was retained, despite the thin unsaturated zone at the site (~35cm from the top of the capillary fringe to ground surface). Due to its lower solubility, most of the MTBE remained within the NAPL as it infiltrated deeper into the unsaturated zone and accumulated with the gasoline on top of the depressed capillary fringe. Only minor changes in the distribution of ethanol were noted following oscillations in the water table. Two methods to estimate the capacity of the unsaturated zone to retain ethanol are explored. It is clear that conceptual models for sites impacted by ethanol-fuels must consider the unsaturated zone. Copyright © 2011 Elsevier B.V. All rights reserved.

Work zone safety analysis.

Science.gov (United States)

2013-11-01

This report presents research performed analyzing crashes in work zones in the state of New Jersey so as to : identify critical areas in work zones susceptible to crashes and key factors that contribute to these crashes. A field : data collection on ...

TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitization

Directory of Open Access Journals (Sweden)

Olivier Gouin

2017-03-01

Full Text Available ABSTRACT Cutaneous neurogenic inflammation (CNI is inflammation that is induced (or enhanced in the skin by the release of neuropeptides from sensory nerve endings. Clinical manifestations are mainly sensory and vascular disorders such as pruritus and erythema. Transient receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1, respectively are non-selective cation channels known to specifically participate in pain and CNI. Both TRPV1 and TRPA1 are co-expressed in a large subset of sensory nerves, where they integrate numerous noxious stimuli. It is now clear that the expression of both channels also extends far beyond the sensory nerves in the skin, occuring also in keratinocytes, mast cells, dendritic cells, and endothelial cells. In these non-neuronal cells, TRPV1 and TRPA1 also act as nociceptive sensors and potentiate the inflammatory process. This review discusses the role of TRPV1 and TRPA1 in the modulation of inflammatory genes that leads to or maintains CNI in sensory neurons and non-neuronal skin cells. In addition, this review provides a summary of current research on the intracellular sensitization pathways of both TRP channels by other endogenous inflammatory mediators that promote the self-maintenance of CNI.

Unsaturated Zone and Saturated Zone Transport Properties (U0100)

Energy Technology Data Exchange (ETDEWEB)

J. Conca

2000-12-20

This Analysis/Model Report (AMR) summarizes transport properties for the lower unsaturated zone hydrogeologic units and the saturated zone at Yucca Mountain and provides a summary of data from the Busted Butte Unsaturated Zone Transport Test (UZTT). The purpose of this report is to summarize the sorption and transport knowledge relevant to flow and transport in the units below Yucca Mountain and to provide backup documentation for the sorption parameters decided upon for each rock type. Because of the complexity of processes such as sorption, and because of the lack of direct data for many conditions that may be relevant for Yucca Mountain, data from systems outside of Yucca Mountain are also included. The data reported in this AMR will be used in Total System Performance Assessment (TSPA) calculations and as general scientific support for various Process Model Reports (PMRs) requiring knowledge of the transport properties of different materials. This report provides, but is not limited to, sorption coefficients and other relevant thermodynamic and transport properties for the radioisotopes of concern, especially neptunium (Np), plutonium (Pu), Uranium (U), technetium (Tc), iodine (I), and selenium (Se). The unsaturated-zone (UZ) transport properties in the vitric Calico Hills (CHv) are discussed, as are colloidal transport data based on the Busted Butte UZTT, the saturated tuff, and alluvium. These values were determined through expert elicitation, direct measurements, and data analysis. The transport parameters include information on interactions of the fractures and matrix. In addition, core matrix permeability data from the Busted Butte UZTT are summarized by both percent alteration and dispersion.

Unsaturated Zone and Saturated Zone Transport Properties (U0100)

International Nuclear Information System (INIS)

Conca, J.

2000-01-01

This Analysis/Model Report (AMR) summarizes transport properties for the lower unsaturated zone hydrogeologic units and the saturated zone at Yucca Mountain and provides a summary of data from the Busted Butte Unsaturated Zone Transport Test (UZTT). The purpose of this report is to summarize the sorption and transport knowledge relevant to flow and transport in the units below Yucca Mountain and to provide backup documentation for the sorption parameters decided upon for each rock type. Because of the complexity of processes such as sorption, and because of the lack of direct data for many conditions that may be relevant for Yucca Mountain, data from systems outside of Yucca Mountain are also included. The data reported in this AMR will be used in Total System Performance Assessment (TSPA) calculations and as general scientific support for various Process Model Reports (PMRs) requiring knowledge of the transport properties of different materials. This report provides, but is not limited to, sorption coefficients and other relevant thermodynamic and transport properties for the radioisotopes of concern, especially neptunium (Np), plutonium (Pu), Uranium (U), technetium (Tc), iodine (I), and selenium (Se). The unsaturated-zone (UZ) transport properties in the vitric Calico Hills (CHv) are discussed, as are colloidal transport data based on the Busted Butte UZTT, the saturated tuff, and alluvium. These values were determined through expert elicitation, direct measurements, and data analysis. The transport parameters include information on interactions of the fractures and matrix. In addition, core matrix permeability data from the Busted Butte UZTT are summarized by both percent alteration and dispersion

Correlation Between Intercritical Heat-Affected Zone and Type IV Creep Damage Zone in Grade 91 Steel

Science.gov (United States)

Wang, Yiyu; Kannan, Rangasayee; Li, Leijun

2018-04-01

A soft zone in Cr-Mo steel weldments has been reported to accompany the infamous Type IV cracking, the highly localized creep damage in the heat-affected zone of creep-resistant steels. However, the microstructural features and formation mechanism of this soft zone are not well understood. In this study, using microhardness profiling and microstructural verification, the initial soft zone in the as-welded condition was identified to be located in the intercritical heat-affected zone of P91 steel weldments. It has a mixed structure, consisting of Cr-rich re-austenitized prior austenite grains and fine Cr-depleted, tempered martensite grains retained from the base metal. The presence of these further-tempered retained grains, originating from the base metal, is directly responsible for the hardness reduction of the identified soft zone in the as-welded condition. The identified soft zone exhibits a high location consistency at three thermal stages. Local chemistry analysis and thermodynamic calculation show that the lower chromium concentrations inside these retained grains thermodynamically decrease their potentials for austenitic transformation during welding. Heterogeneous grain growth is observed in the soft zone during postweld heat treatment. The mismatch of strengths between the weak Cr-depleted grains and strong Cr-rich grains enhances the creep damage. Local deformation of the weaker Cr-depleted grains accelerates the formation of creep cavities.

Women in Chernobyl Exclusion Zone

International Nuclear Information System (INIS)

Balashevska, Y.; Kireev, S.; Navalikhin, V.

2015-01-01

Today, 29 years after the Chernobyl accident, the Exclusion Zone still remains an areal unsealed radiation source of around 2600 km"2. It is not just a gigantic radioactive waste storage facility (the amount of radioactive waste accumulated within the Zone, except for the Shelter, is estimated at about 2.8 million m"3), but also a unique research and engineering platform for biologists, radiologists, chemists and physicists. Taking into account the amount of the radionuclides released during the accident, it becomes quite understood that the radiological environment in the Exclusion Zone is far from favorable. However, among the Exclusion Zone personnel who numbers 5000, there are female workers. The poster represents the results of the research performed among the female employees of the largest enterprise of the Exclusion Zone, “Chornobyl Spetskombinat”. The survey was performed with the view to knowing what makes women work in the most radioactively contaminated area in Europe, and what their role is, to revealing their fears and hopes, and to estimating the chances of the brave women of Chernobyl Exclusion Zone to succeed in their careers. (author)

Problems of Chernobyl Exclusion Zone

International Nuclear Information System (INIS)

Kholosha, V.Yi.

2014-01-01

The collection comprises the results of researches and design activity in the ChNPP exclusion zone, aimed at the development of technologies, equipment and devices for radioactive waste management and ChNPP accident clean-up, at studying the composition and structure of the Exclusion zone soil activity solid bearers, form transformation of the fission products of fuel fallout radionuclide composition in the ChNPP near zone, the spatial distribution of radionuclides and other radioecological issues.. Much attention is paid to medical and biological aspects of the accident influence on the flora, fauna and people's health, labour conditions and incidence of the workers of the Exclusion zone

75 FR 19304 - Safety Zones; Annual Fireworks Events in the Captain of the Port Detroit Zone

Science.gov (United States)

2010-04-14

... previously published in Coast Guard regulations. These safety zones are necessary to protect spectators...-AA00 Safety Zones; Annual Fireworks Events in the Captain of the Port Detroit Zone AGENCY: Coast Guard, DHS. ACTION: Notice of proposed rulemaking. SUMMARY: The Coast Guard proposes establishment of safety...

A viscoplastic shear-zone model for episodic slow slip events in oceanic subduction zones

Science.gov (United States)

Yin, A.; Meng, L.

2016-12-01

Episodic slow slip events occur widely along oceanic subduction zones at the brittle-ductile transition depths ( 20-50 km). Although efforts have been devoted to unravel their mechanical origins, it remains unclear about the physical controls on the wide range of their recurrence intervals and slip durations. In this study we present a simple mechanical model that attempts to account for the observed temporal evolution of slow slip events. In our model we assume that slow slip events occur in a viscoplastic shear zone (i.e., Bingham material), which has an upper static and a lower dynamic plastic yield strength. We further assume that the hanging wall deformation is approximated as an elastic spring. We envision the shear zone to be initially locked during forward/landward motion but is subsequently unlocked when the elastic and gravity-induced stress exceeds the static yield strength of the shear zone. This leads to backward/trenchward motion damped by viscous shear-zone deformation. As the elastic spring progressively loosens, the hanging wall velocity evolves with time and the viscous shear stress eventually reaches the dynamic yield strength. This is followed by the termination of the trenchward motion when the elastic stress is balanced by the dynamic yield strength of the shear zone and the gravity. In order to account for the zig-saw slip-history pattern of typical repeated slow slip events, we assume that the shear zone progressively strengthens after each slow slip cycle, possibly caused by dilatancy as commonly assumed or by progressive fault healing through solution-transport mechanisms. We quantify our conceptual model by obtaining simple analytical solutions. Our model results suggest that the duration of the landward motion increases with the down-dip length and the static yield strength of the shear zone, but decreases with the ambient loading velocity and the elastic modulus of the hanging wall. The duration of the backward/trenchward motion depends

Coastal zone

International Nuclear Information System (INIS)

2002-01-01

The report entitled Climate Change Impacts and Adaptation : A Canadian Perspective, presents a summary of research regarding the impacts of climate change on key sectors over the past five years as it relates to Canada. This chapter on the coastal zone focuses on the impact of climate change on Canada's marine and Great Lakes coasts with tips on how to deal with the impacts associated with climate change in sensitive environments. This report is aimed at the sectors that will be most affected by adaptation decisions in the coastal zone, including fisheries, tourism, transportation and water resources. The impact of climate change in the coastal zone may include changes in water levels, wave patterns, storm surges, and thickness of seasonal ice cover. The Intergovernmental Panel on Climate Change projects global average sea level will rise between 9 and 88 centimetres between 1990 to 2100, but not all areas of Canada will experience the same rate of future sea level change. The main physical impact would be shoreline change that could result in a range of biophysical and socio-economic impacts, some beneficial, some negative. The report focuses on issues related to infrastructure and communities in coastal regions. It is noted that appropriate human adaptation will play a vital role in reducing the extent of potential impacts by decreasing the vulnerability of average zone to climate change. The 3 main trends in coastal adaptation include: (1) increase in soft protection, retreat and accommodation, (2) reliance on technology such as geographic information systems to manage information, and (3) awareness of the need for coastal adaptation that is appropriate for local conditions. 61 refs., 7 figs

Louisiana Speaks Regional Plan Vision Special Economic Zones, UTM Zone 15N NAD83, Louisiana Recovery Authority (2007), [louisiana_speaks_vision_special_economic_zones

Data.gov (United States)

Louisiana Geographic Information Center — This GIS shapefile data illustrates special economic zones included in the Louisiana Speaks Regional Plan Vision. Special economic zones include existing national,...

Developmental Patterns of Doublecortin Expression and White Matter Neuron Density in the Postnatal Primate Prefrontal Cortex and Schizophrenia

Science.gov (United States)

Fung, Samantha J.; Joshi, Dipesh; Allen, Katherine M.; Sivagnanasundaram, Sinthuja; Rothmond, Debora A.; Saunders, Richard; Noble, Pamela L.; Webster, Maree J.; Shannon Weickert, Cynthia

2011-01-01

Postnatal neurogenesis occurs in the subventricular zone and dentate gyrus, and evidence suggests that new neurons may be present in additional regions of the mature primate brain, including the prefrontal cortex (PFC). Addition of new neurons to the PFC implies local generation of neurons or migration from areas such as the subventricular zone. We examined the putative contribution of new, migrating neurons to postnatal cortical development by determining the density of neurons in white matter subjacent to the cortex and measuring expression of doublecortin (DCX), a microtubule-associated protein involved in neuronal migration, in humans and rhesus macaques. We found a striking decline in DCX expression (human and macaque) and density of white matter neurons (humans) during infancy, consistent with the arrival of new neurons in the early postnatal cortex. Considering the expansion of the brain during this time, the decline in white matter neuron density does not necessarily indicate reduced total numbers of white matter neurons in early postnatal life. Furthermore, numerous cells in the white matter and deep grey matter were positive for the migration-associated glycoprotein polysialiated-neuronal cell adhesion molecule and GAD65/67, suggesting that immature migrating neurons in the adult may be GABAergic. We also examined DCX mRNA in the PFC of adult schizophrenia patients (n = 37) and matched controls (n = 37) and did not find any difference in DCX mRNA expression. However, we report a negative correlation between DCX mRNA expression and white matter neuron density in adult schizophrenia patients, in contrast to a positive correlation in human development where DCX mRNA and white matter neuron density are higher earlier in life. Accumulation of neurons in the white matter in schizophrenia would be congruent with a negative correlation between DCX mRNA and white matter neuron density and support the hypothesis of a migration deficit in schizophrenia. PMID

Developmental patterns of doublecortin expression and white matter neuron density in the postnatal primate prefrontal cortex and schizophrenia.

Directory of Open Access Journals (Sweden)

Samantha J Fung

Full Text Available Postnatal neurogenesis occurs in the subventricular zone and dentate gyrus, and evidence suggests that new neurons may be present in additional regions of the mature primate brain, including the prefrontal cortex (PFC. Addition of new neurons to the PFC implies local generation of neurons or migration from areas such as the subventricular zone. We examined the putative contribution of new, migrating neurons to postnatal cortical development by determining the density of neurons in white matter subjacent to the cortex and measuring expression of doublecortin (DCX, a microtubule-associated protein involved in neuronal migration, in humans and rhesus macaques. We found a striking decline in DCX expression (human and macaque and density of white matter neurons (humans during infancy, consistent with the arrival of new neurons in the early postnatal cortex. Considering the expansion of the brain during this time, the decline in white matter neuron density does not necessarily indicate reduced total numbers of white matter neurons in early postnatal life. Furthermore, numerous cells in the white matter and deep grey matter were positive for the migration-associated glycoprotein polysialiated-neuronal cell adhesion molecule and GAD65/67, suggesting that immature migrating neurons in the adult may be GABAergic. We also examined DCX mRNA in the PFC of adult schizophrenia patients (n = 37 and matched controls (n = 37 and did not find any difference in DCX mRNA expression. However, we report a negative correlation between DCX mRNA expression and white matter neuron density in adult schizophrenia patients, in contrast to a positive correlation in human development where DCX mRNA and white matter neuron density are higher earlier in life. Accumulation of neurons in the white matter in schizophrenia would be congruent with a negative correlation between DCX mRNA and white matter neuron density and support the hypothesis of a migration deficit in

77 FR 9528 - Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound

Science.gov (United States)

2012-02-17

... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2012-0087] Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound AGENCY: Coast Guard, DHS... Waterway Security Zone in Commencement Bay, Tacoma, Washington from 6 a.m. on February 17, 2012, through 11...

78 FR 40396 - Safety Zone; America's Cup Safety Zone and No Loitering Area, San Francisco, CA

Science.gov (United States)

2013-07-05

...-AA00 Safety Zone; America's Cup Safety Zone and No Loitering Area, San Francisco, CA AGENCY: Coast... America's Cup races. This safety zone and no loitering area are established to enhance the safety of spectators and mariners near the north east corner of the America's Cup regulated area. All persons or...

78 FR 54588 - Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound

Science.gov (United States)

2013-09-05

... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2012-0087] Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound AGENCY: Coast Guard, DHS... Security Zone in Commencement Bay, Tacoma, Washington from 6:00 a.m. on September 2, 2013 through 11:59 p.m...

78 FR 57485 - Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound

Science.gov (United States)

2013-09-19

... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2012-0087] Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound AGENCY: Coast Guard, DHS... Security Zone in Commencement Bay, Tacoma, Washington from 6 a.m. on September 12, 2013 through 11:59 p.m...

Toward Self-Control Systems for Neurogenic Underactive Bladder: A Triboelectric Nanogenerator Sensor Integrated with a Bistable Micro-Actuator.

Science.gov (United States)

Arab Hassani, Faezeh; Mogan, Roshini P; Gammad, Gil G L; Wang, Hao; Yen, Shih-Cheng; Thakor, Nitish V; Lee, Chengkuo

2018-04-24

Aging, neurologic diseases, and diabetes are a few risk factors that may lead to underactive bladder (UAB) syndrome. Despite all of the serious consequences of UAB, current solutions, the most common being ureteric catheterization, are all accompanied by serious shortcomings. The necessity of multiple catheterizations per day for a physically able patient not only reduces the quality of life with constant discomfort and pain but also can end up causing serious complications. Here, we present a bistable actuator to empty the bladder by incorporating shape memory alloy components integrated on flexible polyvinyl chloride sheets. The introduction of two compression and restoration phases for the actuator allows for repeated actuation for a more complete voiding of the bladder. The proposed actuator exhibits one of the highest reported voiding percentages of up to 78% of the bladder volume in an anesthetized rat after only 20 s of actuation. This amount of voiding is comparable to the common catheterization method, and its one time implantation onto the bladder rectifies the drawbacks of multiple catheterizations per day. Furthermore, the scaling of the device for animal models larger than rats can be easily achieved by adjusting the number of nitinol springs. For neurogenic UAB patients with degraded nerve function as well as degenerated detrusor muscle, we integrate a flexible triboelectric nanogenerator sensor with the actuator to detect the fullness of the bladder. The sensitivity of this sensor to the filling status of the bladder shows its capability for defining a self-control system in the future that would allow autonomous micturition.

Efficacy of peripheral lidocaine application (neural therapy) in the treatment of neurogenic detrusor overactivity in multiple sclerosis patients.

Science.gov (United States)

Tamam, Yusuf; Özdemir, Hasan Hüseyin; Gedik, Abdullah; Tamam, Cüneyt; Nazlıkul, Hüseyin

2017-09-01

Many agents and treatments are used in the treatment of neurogenic detrusor overactivity (NDO) in MS patients, but no study has been conducted on the use of peripheric lidocaine (neural therapy-NT) on MS patients. We evaluated the effects of local administration of lidocaine on NDO in Multiple Sclerosis (MS) patients. For each patient local anesthetic lidocaine was injected at each session. Sessions were held once a week for 5 weeks. At each session, Th 10-L1, urogenital segment intradermal injections, Frankenhauser, and sacral epidural injections were given. The patients had clinical and urodynamic assessment 1 month before and 3, 9, and 12 months after NT. In addition, multiple sclerosis quality of life inventory (MSQL-54) and bladder control scale (BLCS) was performed for patients. Twenty-eight patients were included in the study (8 males, 20 females). The patients' average age was 31.7 ± 8.1 years. The injection therapy significantly improved volume at first involuntary bladder contraction (FCV), maximal detrusor pression during filling (P det. max.), maximal cystometric bladder capacity (MCC) after 3 months. Also, the MSQL-54 and BLCS scores were improved with treatment. However, these improvements reached a maximum 3 months after treatment, but from the 9 month a regression was seen in the parameters, and after 12 months the findings were seen to be slightly above their basal levels. These results suggest that NDO treatment in MS patients could be an effective treatment which is easy and has very few side effects, and is cost effective. © 2017 Wiley Periodicals, Inc.

A Bivalent Securinine Compound SN3-L6 Induces Neuronal Differentiation via Translational Upregulation of Neurogenic Transcription Factors

Directory of Open Access Journals (Sweden)

Yumei Liao

2018-04-01

Full Text Available Developing therapeutic approaches that target neuronal differentiation will be greatly beneficial for the regeneration of neurons and synaptic networks in neurological diseases. Protein synthesis (mRNA translation has recently been shown to regulate neurogenesis of neural stem/progenitor cells (NSPCs. However, it has remained unknown whether engineering translational machinery is a valid approach for manipulating neuronal differentiation. The present study identifies that a bivalent securinine compound SN3-L6, previously designed and synthesized by our group, induces potent neuronal differentiation through a novel translation-dependent mechanism. An isobaric tag for relative and absolute quantitation (iTRAQ-based proteomic analysis in Neuro-2a progenitor cells revealed that SN3-L6 upregulated a group of neurogenic transcription regulators, and also upregulated proteins involved in RNA processing, translation, and protein metabolism. Notably, puromycylation and metabolic labeling of newly synthesized proteins demonstrated that SN3-L6 induced rapid and robust activation of general mRNA translation. Importantly, mRNAs of the proneural transcription factors Foxp1, Foxp4, Hsf1, and Erf were among the targets that were translationally upregulated by SN3-L6. Either inhibition of translation or knockdown of these transcription factors blocked SN3-L6 activity. We finally confirmed that protein synthesis of a same set of transcription factors was upregulated in primary cortical NPCs. These findings together identify a new compound for translational activation and neuronal differentiation, and provide compelling evidence that reprogramming transcriptional regulation network at translational levels is a promising strategy for engineering NSPCs.

Global correlations between maximum magnitudes of subduction zone interface thrust earthquakes and physical parameters of subduction zones

NARCIS (Netherlands)

Schellart, W. P.; Rawlinson, N.

2013-01-01

The maximum earthquake magnitude recorded for subduction zone plate boundaries varies considerably on Earth, with some subduction zone segments producing giant subduction zone thrust earthquakes (e.g. Chile, Alaska, Sumatra-Andaman, Japan) and others producing relatively small earthquakes (e.g.

A broader classification of damage zones

Science.gov (United States)

Peacock, D. C. P.; Dimmen, V.; Rotevatn, A.; Sanderson, D. J.

2017-09-01

Damage zones have previously been classified in terms of their positions at fault tips, walls or areas of linkage, with the latter being described in terms of sub-parallel and synchronously active faults. We broaden the idea of linkage to include structures around the intersections of non-parallel and/or non-synchronous faults. These interaction damage zones can be divided into approaching damage zones, where the faults kinematically interact but are not physically connected, and intersection damage zones, where the faults either abut or cross-cut. The damage zone concept is applied to other settings in which strain or displacement variations are taken up by a range of structures, such as at fault bends. It is recommended that a prefix can be added to a wide range of damage zones, to describe the locations in which they formed, e.g., approaching, intersection and fault bend damage zone. Such interpretations are commonly based on limited knowledge of the 3D geometries of the structures, such as from exposure surfaces, and there may be spatial variations. For example, approaching faults and related damage seen in outcrop may be intersecting elsewhere on the fault planes. Dilation in intersection damage zones can represent narrow and localised channels for fluid flow, and such dilation can be influenced by post-faulting stress patterns.

33 CFR 2.30 - Exclusive Economic Zone.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Exclusive Economic Zone. 2.30... JURISDICTION Jurisdictional Terms § 2.30 Exclusive Economic Zone. (a) With respect to the United States... States exercises sovereignty, exclusive economic zone means the zone seaward of and adjacent to the...

Axons take a dive

Science.gov (United States)

Tong, Cheuk Ka; Cebrián-Silla, Arantxa; Paredes, Mercedes F; Huang, Eric J; García-Verdugo, Jose Manuel; Alvarez-Buylla, Arturo

2015-01-01

In the walls of the lateral ventricles of the adult mammalian brain, neural stem cells (NSCs) and ependymal (E1) cells share the apical surface of the ventricular–subventricular zone (V–SVZ). In a recent article, we show that supraependymal serotonergic (5HT) axons originating from the raphe nuclei in mice form an extensive plexus on the walls of the lateral ventricles where they contact E1 cells and NSCs. Here we further characterize the contacts between 5HT supraependymal axons and E1 cells in mice, and show that suprependymal axons tightly associated to E1 cells are also present in the walls of the human lateral ventricles. These observations raise interesting questions about the function of supraependymal axons in the regulation of E1 cells. PMID:26413556

Realization of the Zone Length Measurement during Zone Refining Process via Implementation of an Infrared Camera

Directory of Open Access Journals (Sweden)

Danilo C. Curtolo

2018-05-01

Full Text Available Zone refining, as the currently most common industrial process to attain ultrapure metals, is influenced by a variety of factors. One of these parameters, the so-called “zone length”, affects not only the ultimate concentration distribution of impurities, but also the rate at which this distribution is approached. This important parameter has however neither been investigated experimentally, nor ever varied for the purpose of optimization. This lack of detections may be due to the difficult temperature measurement of a moving molten area in a vacuum system, of which the zone refining methodology is comprised. Up to now, numerical simulation as a combination of complex mathematical calculations, as well as many assumptions has been the only way to reveal it. This paper aims to propose an experimental method to accurately measure the molten zone length and to extract helpful information on the thermal gradient, temperature profile and real growth rate in the zone refining of an exemplary metal, in this case aluminum. This thermographic method is based on the measurement of the molten surface temperature via an infrared camera, as well as further data analysis through the mathematical software MATLAB. The obtained results show great correlation with the visual observations of zone length and provide helpful information to determine the thermal gradient and real growth rate during the whole process. The investigations in this paper approved the application of an infrared camera for this purpose as a promising technique to automatically control the zone length during a zone refining process.

VT Data - Zoning 20070306, Marlboro

Data.gov (United States)

Vermont Center for Geographic Information — Zoning districts, Marlboro, Vermont. Surface water buffer overlay is in a separate shapefile. Data were originally created by WRC in 2005. Marlboro's zoning bylaw...

Reductive dechlorination of trichloroethene DNAPL source zones: source zone architecture versus electron donor availability

Science.gov (United States)

Krol, M.; Kokkinaki, A.; Sleep, B.

2014-12-01

The persistence of dense-non-aqueous-phase liquids (DNAPLs) in the subsurface has led practitioners and regulatory agencies to turn towards low-maintenance, low-cost remediation methods. Biological degradation has been suggested as a possible solution, based on the well-proven ability of certain microbial species to break down dissolved chlorinated ethenes under favorable conditions. However, the biodegradation of pure phase chlorinated ethenes is subject to additional constraints: the continuous release of electron acceptor at a rate governed by mass transfer kinetics, and the temporal and spatial heterogeneity of DNAPL source zones which leads to spatially and temporally variable availability of the reactants for reductive dechlorination. In this work, we investigate the relationship between various DNAPL source zone characteristics and reaction kinetics using COMPSIM, a multiphase groundwater model that considers non-equilibrium mass transfer and Monod-type kinetics for reductive dechlorination. Numerical simulations are performed for simple, homogeneous trichloroethene DNAPL source zones to demonstrate the effect of single source zone characteristics, as well as for larger, more realistic heterogeneous source zones. It is shown that source zone size, and mass transfer kinetics may have a decisive effect on the predicted bio-enhancement. Finally, we evaluate the performance of DNAPL bioremediation for realistic, thermodynamically constrained, concentrations of electron donor. Our results indicate that the latter may be the most important limitation for the success of DNAPL bioremediation, leading to reduced bio-enhancement and, in many cases, comparable performance with water flooding.

Multichannel imager for littoral zone characterization

Science.gov (United States)

Podobna, Yuliya; Schoonmaker, Jon; Dirbas, Joe; Sofianos, James; Boucher, Cynthia; Gilbert, Gary

2010-04-01

This paper describes an approach to utilize a multi-channel, multi-spectral electro-optic (EO) system for littoral zone characterization. Advanced Coherent Technologies, LLC (ACT) presents their EO sensor systems for the surf zone environmental assessment and potential surf zone target detection. Specifically, an approach is presented to determine a Surf Zone Index (SZI) from the multi-spectral EO sensor system. SZI provides a single quantitative value of the surf zone conditions delivering an immediate understanding of the area and an assessment as to how well an airborne optical system might perform in a mine countermeasures (MCM) operation. Utilizing consecutive frames of SZI images, ACT is able to measure variability over time. A surf zone nomograph, which incorporates targets, sensor, and environmental data, including the SZI to determine the environmental impact on system performance, is reviewed in this work. ACT's electro-optical multi-channel, multi-spectral imaging system and test results are presented and discussed.

The fracture zone project - final report

International Nuclear Information System (INIS)

Andersson, Peter

1993-09-01

This report summarizes the work and the experiences gained during the fracture zone project at the Finnsjoen study site. The project is probably the biggest effort, so far, to characterize a major fracture zone in crystalline bedrock. The project was running between 1984-1990 involving a large number of geological, geohydrological, geochemical, and geomechanical investigation. The methods used for identification and characterization are reviewed and discussed in terms of applicability and possible improvements for future investigations. The discussion is exemplified with results from the investigation within the project. Flow and transport properties of the zone determined from hydraulic tests and tracer tests are discussed. A large number of numerical modelling efforts performed within the fracture zone project, the INTRAVAL project, and the SKB91-study are summarized and reviewed. Finally, occurrence of similar zones and the relevance of major low angle fracture zones in connection to the siting of an underground repository is addressed

Do "Some" Enterprise Zones Create Jobs?

Science.gov (United States)

Kolko, Jed; Neumark, David

2010-01-01

We study how the employment effects of enterprise zones vary with their location, implementation, and administration, based on evidence from California. We use new establishment-level data and geographic mapping methods, coupled with a survey of enterprise zone administrators. Overall, the evidence indicates that enterprise zones do not increase…

SEMIAUTOMATIC DETECTION OF TUMORAL ZONE

Directory of Open Access Journals (Sweden)

Ezzeddine Zagrouba

2011-05-01

Full Text Available This paper describes a robust method based on the cooperation of fuzzy classification and regions segmentation algorithms, in order to detect the tumoral zone in the brain Magnetic Resonance Imaging (MRI. On one hand, the classification in fuzzy sets is done by the Fuzzy C-Means algorithm (FCM, where a study of its different parameters and its complexity has been previously realised, which led us to improve it. On the other hand, the segmentation in regions is obtained by an hierarchical method through adaptive thresholding. Then, an operator expert selects a germ in the tumoral zone, and the class containing the sick zone is localised in return for the FCM algorithm. Finally, the superposition of the two partitions of the image will determine the sick zone. The originality of our approach is the parallel exploitation of different types of information in the image by the cooperation of two complementary approaches. This allows us to carry out a pertinent approach for the detection of sick zone in MRI images.

Splenic marginal zone lymphoma.

Science.gov (United States)

Piris, Miguel A; Onaindía, Arantza; Mollejo, Manuela

Splenic marginal zone lymphoma (SMZL) is an indolent small B-cell lymphoma involving the spleen and bone marrow characterized by a micronodular tumoral infiltration that replaces the preexisting lymphoid follicles and shows marginal zone differentiation as a distinctive finding. SMZL cases are characterized by prominent splenomegaly and bone marrow and peripheral blood infiltration. Cells in peripheral blood show a villous cytology. Bone marrow and peripheral blood characteristic features usually allow a diagnosis of SMZL to be performed. Mutational spectrum of SMZL identifies specific findings, such as 7q loss and NOTCH2 and KLF2 mutations, both genes related with marginal zone differentiation. There is a striking clinical variability in SMZL cases, dependent of the tumoral load and performance status. Specific molecular markers such as 7q loss, p53 loss/mutation, NOTCH2 and KLF2 mutations have been found to be associated with the clinical variability. Distinction from Monoclonal B-cell lymphocytosis with marginal zone phenotype is still an open issue that requires identification of precise and specific thresholds with clinical meaning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cornell Mixing Zone Expert System

Science.gov (United States)

This page provides an overview Cornell Mixing Zone Expert System water quality modeling and decision support system designed for environmental impact assessment of mixing zones resulting from wastewater discharge from point sources

Irradiation in adulthood as a new model of schizophrenia.

Directory of Open Access Journals (Sweden)

Yasuhide Iwata

Full Text Available BACKGROUND: Epidemiological studies suggest that radiation exposure may be a potential risk factor for schizophrenia in adult humans. Here, we investigated whether adult irradiation in rats caused behavioral abnormalities relevant to schizophrenia. METHODOLOGY/PRINCIPAL FINDINGS: A total dose of 15-Gy irradiation in six fractionations during 3 weeks was exposed to the forebrain including the subventricular zone (SVZ and subgranular zone (SGZ with male rats in the prone position. Behavioral, immunohistochemical, and neurochemical studies were performed three months after fractionated ionizing irradiation. Three months after fractionated ionizing irradiation, the total numbers of BrdU-positive cells in both the SVZ and SGZ zones of irradiated rats were significantly lower than those of control (sham-irradiated rats. Hyperactivity after administration of the dopaminergic agonist methamphetamine, but not the N-methyl-D-aspartate (NMDA receptor antagonist dizocilpine, was significantly enhanced in the irradiated rats although spontaneous locomotion in the irradiated rats was significantly lower than that of controls. Behavioral abnormalities including auditory sensory gating deficits, social interaction deficits, and working memory deficits were observed in the irradiated rats. CONCLUSION/SIGNIFICANCE: The present study suggests that irradiation in adulthood caused behavioral abnormalities relevant to schizophrenia, and that reduction of adult neurogenesis by irradiation may be associated with schizophrenia-like behaviors in rats.

Drug-Free School Zones: Taking Charge.

Science.gov (United States)

Thomas, Carol F.

Information for planning and implementing drug-free school zones within a broader school-community prevention and intervention program is provided in this guidebook. The first section provides background information on drug-free school zone legislation and common elements of drug-free school zones. The risk and protective factors for alcohol and…

State Enterprise Zone Programs: Have They Worked?

Science.gov (United States)

Peters, Alan H.; Fisher, Peter S.

The effectiveness of state enterprise zone programs was examined by using a hypothetical-firm model called the Tax and Incentives Model-Enterprise Zones (TAIM-ez) model to analyze the value of enterprise zone incentives to businesses across the United States and especially in the 13 states that had substantial enterprise zone programs by 1990. The…

Dead zone characteristics of a gas counter

International Nuclear Information System (INIS)

Nohtomi, Akihiro; Sakae, Takeji; Matoba, Masaru; Koori, Norihiko.

1990-01-01

The dead zone was recently defined as the product of dead length and dead time in order to describe the characteristics of the self-quenching streamer (SQS) mode of a gas counter. Investigation of the dead zone characteristics has been extended for the proportional and GM modes, and the measured dead zone has been compared with that of the SQS mode. Accurate values for the dead zone could be determined by means of a newly developed method with a pulse interval time to amplitude converter. Each operation mode indicates distinct dead zone characteristics. Properties of gas counters for high counting rates may be improved on the basis of measurements of the dead zone. (author)

Street Prostitution Zones and Crime

OpenAIRE

Bisschop, Paul; Kastoryano, Stephen; van der Klaauw, Bas

2015-01-01

This paper studies the effects of introducing legal street prostitution zones on both registered and perceived crime. We exploit a unique setting in the Netherlands where legal street prostitution zones were opened in nine cities under different regulation systems. We provide evidence that the opening of these zones was not in response to changes in crime. Our difference-in-difference analysis using data on the largest 25 Dutch cities between 1994 and 2011 shows that opening a legal street pr...

76 FR 3014 - Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound, WA

Science.gov (United States)

2011-01-19

... Coast Guard will enforce the Blair Waterway security zone in Commencement Bay, WA for protection of... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2011-0015] Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound, WA AGENCY: Coast Guard, DHS...

Radiation danger of exclusion zone objects

International Nuclear Information System (INIS)

Kholosha, V.I.; Proskura, N.I.; Ivanov, Yu.A.; Kazakov, S.V.; Arkhipov, A.N.

2001-01-01

The analysis of radiation danger of the Exclusion Zone objects was made. Here, the Zone is defined as the territory from which the population has been evacuated in 1986 owing to the Chernobyl accident and possible outflow of the contaminated substances out of the borders is potentially dangerous to the Ukraine. In the present work were analyzed such problems as sources of radiation danger in the Zone, ways of radionuclide migration out of the borders of the Zone in normal and emergency situations, the non-radiation (ecological) danger factors of the Zone objects, doses (individual and collective) from various sources and on separate ways of their formation, and the characteristics of radiation danger of the Zone objects. The conclusions are: (1) Radionuclide flows both from technologic and natural sources exceed those from Shelter objects, (2) Under emergency conditions, radionuclide flows and doze loading remain comparable with those from emergency sources, (3) To solve some management tasks in radiation situation, the basic works on the Shelter objects should be oriented to decrease probability of emergency occurrence and to reduce radiation influence (prevention wash-outs during high waters, fire-prevention measures in forests and strengthening of the control behind non-authorized use of objects in the Zone). (S. Ohno)

76 FR 9646 - Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation...

Science.gov (United States)

2011-02-22

... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Parts 100, 117, 147, and 165 [USCG-2010-0399] Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation Regulations and Regulated Navigation Areas AGENCY: Coast Guard, DHS. ACTION: Notice of expired temporary rules...

Tracing the influence of the Trans-European Suture Zone into the mantle transition zone

Czech Academy of Sciences Publication Activity Database

Knapmeyer-Endrun, B.; Krüger, F.; Legendre, C. P.; Geissler, W.H.; Plomerová, Jaroslava; Babuška, Vladislav; Gaždová, Renata; Jedlička, Petr; Kolínský, Petr; Málek, Jiří; Novotný, Oldřich; Růžek, Bohuslav

2013-01-01

Roč. 363, FEB 1 (2013), s. 73-87 ISSN 0012-821X Institutional support: RVO:67985530 ; RVO:67985891 Keywords : mantle transition zone * Trans-European Suture Zone * East European Craton Subject RIV: DC - Siesmology, Volcanology, Earth Structure Impact factor: 4.724, year: 2013

VT Data - Zoning Stream Buffers 20081014, Hartford

Data.gov (United States)

Vermont Center for Geographic Information — OVERLAY DISTRICT. Models a municipality’s zoning zones and related information. Final boundary determinations must be obtained from the town Zoning Administrator....

GAMMA RAYS FROM THE TYCHO SUPERNOVA REMNANT: MULTI-ZONE VERSUS SINGLE-ZONE MODELING

Energy Technology Data Exchange (ETDEWEB)

Atoyan, Armen [Department of Mathematics, Concordia University, 1455 de Maisonneuve Blvd. West, Montreal, Quebec H3G 1M8 (Canada); Dermer, Charles D., E-mail: atoyan@mathstat.concordia.ca, E-mail: charles.dermer@nrl.navy.mil [Code 7653, Naval Research Laboratory, Washington, DC 20375-5352 (United States)

2012-04-20

Recent Fermi and VERITAS observations of the prototypical Type Ia supernova remnant (SNR) Tycho have discovered {gamma}-rays with energies E in the range 0.4 GeV {approx}< E {approx}< 10 TeV. Crucial for the theory of Galactic cosmic-ray origin is whether the {gamma}-rays from SNRs are produced by accelerated hadrons (protons and ions) or by relativistic electrons. Here we show that strong constraints on the leptonic model imposed in the framework of the commonly used single-zone model are essentially removed if the analysis of the broadband radiation spectrum of Tycho is done in the two-zone (or, in general, multi-zone) approach, which is likely to apply to every SNR. Importantly, we show that the single-zone approach may underpredict the {gamma}-ray fluxes by an order of magnitude. A hadronic model can, however, also fit the detected {gamma}-ray spectrum. The difference between {gamma}-ray fluxes of hadronic and leptonic origins becomes significant only at {approx}<300 MeV, which could be revealed by spectral measurements of Tycho and other SNRs at these energies.

Chaotic Zones around Rotating Small Bodies

Energy Technology Data Exchange (ETDEWEB)

Lages, José; Shevchenko, Ivan I. [Institut UTINAM, Observatoire des Sciences de l’Univers THETA, CNRS, Université de Franche-Comté, Besançon F-25030 (France); Shepelyansky, Dima L., E-mail: jose.lages@utinam.cnrs.fr [Laboratoire de Physique Théorique du CNRS, IRSAMC, Université de Toulouse, UPS, Toulouse F-31062 (France)

2017-06-01

Small bodies of the solar system, like asteroids, trans-Neptunian objects, cometary nuclei, and planetary satellites, with diameters smaller than 1000 km usually have irregular shapes, often resembling dumb-bells or contact binaries. The spinning of such a gravitating dumb-bell creates around it a zone of chaotic orbits. We determine its extent analytically and numerically. We find that the chaotic zone swells significantly if the rotation rate is decreased; in particular, the zone swells more than twice if the rotation rate is decreased 10 times with respect to the “centrifugal breakup” threshold. We illustrate the properties of the chaotic orbital zones in examples of the global orbital dynamics about asteroid 243 Ida (which has a moon, Dactyl, orbiting near the edge of the chaotic zone) and asteroid 25143 Itokawa.

Effects of curcumin on short-term spatial and recognition memory, adult neurogenesis and neuroinflammation in a streptozotocin-induced rat model of dementia of Alzheimer's type.

Science.gov (United States)

Bassani, Taysa B; Turnes, Joelle M; Moura, Eric L R; Bonato, Jéssica M; Cóppola-Segovia, Valentín; Zanata, Silvio M; Oliveira, Rúbia M M W; Vital, Maria A B F

2017-09-29

Curcumin is a natural polyphenol with evidence of antioxidant, anti-inflammatory and neuroprotective properties. Recent evidence also suggests that curcumin increases cognitive performance in animal models of dementia, and this effect would be related to its capacity to enhance adult neurogenesis. The aim of this study was to test the hypothesis that curcumin treatment would be able to preserve cognition by increasing neurogenesis and decreasing neuroinflammation in the model of dementia of Alzheimer's type induced by an intracerebroventricular injection of streptozotocin (ICV-STZ) in Wistar rats. The animals were injected with ICV-STZ or vehicle and curcumin treatments (25, 50 and 100mg/kg, gavage) were performed for 30days. Four weeks after surgery, STZ-lesioned animals exhibited impairments in short-term spatial memory (Object Location Test (OLT) and Y maze) and short-term recognition memory (Object Recognition Test - ORT), decreased cell proliferation and immature neurons (Ki-67- and doublecortin-positive cells, respectively) in the subventricular zone (SVZ) and dentate gyrus (DG) of hippocampus, and increased immunoreactivity for the glial markers GFAP and Iba-1 (neuroinflammation). Curcumin treatment in the doses of 50 and 100mg/kg prevented the deficits in recognition memory in the ORT, but not in spatial memory in the OLT and Y maze. Curcumin treatment exerted only slight improvements in neuroinflammation, resulting in no improvements in hippocampal and subventricular neurogenesis. These results suggest a positive effect of curcumin in object recognition memory which was not related to hippocampal neurogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

76 FR 55566 - Safety Zones; Fireworks Displays and Surfing Events in Captain of the Port Long Island Sound Zone

Science.gov (United States)

2011-09-08

...-AA00 Safety Zones; Fireworks Displays and Surfing Events in Captain of the Port Long Island Sound Zone... zones for marine events within the Captain of the Port (COTP) Long Island Sound Zone for a surfing event... unless authorized by the COTP Sector Long Island Sound. DATES: This rule is effective in the CFR on...

Light-zone(s: as Concept and Tool

Directory of Open Access Journals (Sweden)

Merete Madsen

2012-11-01

Full Text Available Daylight is essential to the experience of an architectural space. Nevertheless, amongst the handful of predominantly scientific methods available to assess daylight in architecture, there are only a few considering the spatial and form-giving characteristics of daylight. This paper investigates light-zone(s as concept and tool, which can be taken as a point of departure for a new method to perceive, consider and analyse daylight in architecture. As concept, light-zone(s are areas, fields or zones of light. It is a way of considering a space’s daylight as (forms of bubbles or spheres of light, which as light-zones can be compressed, expanded, combined, exploded, etc., all according to the character of 'the meeting' between the light-zone(s and the space itself (inclusive of the space’scontent. Thus, the daylight in a space can be regarded asa composition of light-zones.As tool, light-zone(s are (spatial groupings of the lightingvariables (intensity, direction, distribution and colour, whichare significant to the space and form-giving characteristicsof light. That is to say, the light-zone(s tool is the point ofdeparture for a method of creating a spatial ‘grasp’ on daylighting variables in a given space. The relation between the light-zone(s concept and tool respectively can be described as follows: On the one level light-zone(s can be explored as an architectural idea or notion, thus belonging more to the field of architectural theory. On another more practice-driven level, light-zone(s can be articulated and specified in relation to lighting technology.

Cues for Cure; From within

Directory of Open Access Journals (Sweden)

Editorial

2016-05-01

transplantation of exogenous stem cells, adult cells or precursors, though forms the main stream approach in regenerative medicine, in vivo stimulation of tissue resident stem cells has been postulated as a promising regenerative approach [5], probably owing to its safety compared to transplantation of exogenous cells, especially pluripotent stem cells. Further, even if exogenous cells are administered in cell-based therapies, it is the tissue resident cells with regenerative capability which actually contribute to the regeneration. Hence, unless the local niche/environment and other factors contributing to the maintenance of tissue resident stem cells or progenitor cells are studied and steps to recapitulate their contribution in moulding the function of exogenous stem cells to contribute to regeneration are performed in vitro, translational approaches in regeneration may not realize their expected outcome. The studies by Takeuchi et al and Jones and Connor in the current issue fall in line with this ideology and more such studies need to be encouraged for developing better therapies for the future. References: Barker N, Bartfeld S, Clevers H. Tissue-resident adult stem cell populations of rapidly self-renewing organs. Cell Stem Cell. 2010; 7(6:656-70. Miki K, Uenaka H, Saito A, Miyagawa S, Sakaguchi T, Higuchi T, Shimizu T, Okano T, Yamanaka S, Sawa Y. Bioengineered myocardium derived from induced pluripotent stem cells improves cardiac function and attenuates cardiac remodeling following chronic myocardial infarction in rats. Stem Cells Transl Med. 2012; 1(5:430-7. Takeuchi T, Tonooka A, Okuno Y, Hattori-Kato M, Mikami K. Oct4B, CD90, and CD73 are upregulated in bladder tissue following electro-resection of the bladder. J Stem Cells Regen Med 2016; 12(1 :10-15. Jones KS, Connor BJ. The Effect of Pro-Neurogenic Gene Expression on Adult Subventricular Zone Precursor Cell Recruitment and Fate Determination After Excitotoxic Brain Injury. J Stem Cells Regen Med 2016; 12(1 :25

Quantifying the Variation in Shear Zone Character with Depth: a Case Study from the Simplon Shear Zone, Central Alps

Science.gov (United States)

Cawood, T. K.; Platt, J. P.

2017-12-01

A widely-accepted model for the rheology of crustal-scale shear zones states that they comprise distributed strain at depth, in wide, high-temperature shear zones, which narrow to more localized, high-strain zones at lower temperature and shallower crustal levels. We test and quantify this model by investigating how the width, stress, temperature and deformation mechanisms change with depth in the Simplon Shear Zone (SSZ). The SSZ marks a major tectonic boundary in the central Alps, where normal-sense motion and rapid exhumation of the footwall have preserved evidence of older, deeper deformation in rocks progressively further into the currently-exposed footwall. As such, microstructures further from the brittle fault (which represents the most localized, most recently-active part of the SSZ) represent earlier, higher- temperature deformation from deeper crustal levels, while rocks closer to the fault have been overprinted by successively later, cooler deformation at shallower depths. This study uses field mapping and microstructural studies to identify zones representing deformation at various crustal levels, and characterize each in terms of zone width (representing width of the shear zone at that time and depth) and dominant deformation mechanism. In addition, quartz- (by Electron Backscatter Diffraction, EBSD) and feldspar grain size (measured optically) piezometry are used to calculate the flow stress for each zone, while the Ti-in-quartz thermometer (TitaniQ) is used to calculate the corresponding temperature of deformation. We document the presence of a broad zone in which quartz is recrystallized by the Grain Boundary Migration (GBM) mechanism and feldspar by Subgrain Rotation (SGR), which represents the broad, deep zone of deformation occurring at relatively high temperatures and low stresses. In map view, this transitions to successively narrower zones, respectively characterized by quartz SGR and feldspar Bulge Nucleation (BLG); quartz BLG and brittle

The male sex pheromone darcin stimulates hippocampal neurogenesis and cell proliferation in the subventricular zone in female mice

Directory of Open Access Journals (Sweden)

Emma eHoffman

2015-04-01

Full Text Available The integration of newly generated neurons persists throughout life in the mammalian olfactory bulb and hippocampus, regions involved in olfactory and spatial learning. Social cues can be potent stimuli for increasing adult neurogenesis; for example, odors from dominant but not subordinate male mice increase neurogenesis in both brain regions of adult females. However, little is known about the role of neurogenesis in social recognition or the assessment of potential mates. Dominant male mice scent-mark territories using urine that contains a number of pheromones including darcin (MUP20, a male-specific major urinary protein that stimulates rapid learned attraction to the spatial location and individual odor signature of the scent owner. Here we investigate whether exposure to darcin stimulates neurogenesis in the female brain. Hippocampal neurons and cellular proliferation in the lateral ventricles that supply neurons to the olfactory bulbs increased in females exposed for seven days to male urine containing at least 0.5µg/µl darcin. Darcin was effective whether presented alone or in the context of male urine, but other information in male urine appeared to modulate the proliferative response. When exposed to urine from wild male mice, hippocampal proliferation increased only if urine was from the same individual over seven days, suggesting that consistency of individual scent signatures is important. While seven days exposure to male scent initiated the first stages of increased neurogenesis, this caused no immediate increase in female attraction to the scent or in the strength or robustness of spatial learning in short-term conditioned place preference tests. The reliable and consistent stimulation of neurogenesis by a pheromone important in rapid social learning suggests that this may provide an excellent model to explore the relationship between the integration of new neurons and plasticity in spatial and olfactory learning in a socially-relevant context.

Empowerment Zones and Enterprise Districts - Volusia County Enterprise Zones

Data.gov (United States)

NSGIC Local Govt | GIS Inventory — Florida's Enterprise Zone Program encourages economic growth and investment in distressed areas by offering tax advantages and incentives to businesses that are...

78 FR 7265 - Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound, WA

Science.gov (United States)

2013-02-01

... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2012-0087] Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound, WA AGENCY: Coast Guard, DHS... Security Zone in Commencement Bay, Tacoma, Washington from 6 a.m. on February 1, 2013, through 11:59 p.m...

78 FR 11981 - Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound, WA

Science.gov (United States)

2013-02-21

... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2012-0087] Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound, WA AGENCY: Coast Guard, DHS... Security Zone in Commencement Bay, Tacoma, Washington from 6 a.m. on February 23, 2013, through 11:59 p.m...

Automatic detection and classification of damage zone(s) for incorporating in digital image correlation technique

Science.gov (United States)

Bhattacharjee, Sudipta; Deb, Debasis

2016-07-01

Digital image correlation (DIC) is a technique developed for monitoring surface deformation/displacement of an object under loading conditions. This method is further refined to make it capable of handling discontinuities on the surface of the sample. A damage zone is referred to a surface area fractured and opened in due course of loading. In this study, an algorithm is presented to automatically detect multiple damage zones in deformed image. The algorithm identifies the pixels located inside these zones and eliminate them from FEM-DIC processes. The proposed algorithm is successfully implemented on several damaged samples to estimate displacement fields of an object under loading conditions. This study shows that displacement fields represent the damage conditions reasonably well as compared to regular FEM-DIC technique without considering the damage zones.

New geometrical compactness measures for zones design

Directory of Open Access Journals (Sweden)

Eric Alfredo Rincón-García

2012-07-01

Full Text Available The design of compact zones has been studied because of its influence in the creation of zones with regular forms, which are easier to analyze, to investigate or to administer. This paper propose a new method to measure compactness,by means of the transformation of the original geographical spaces, into figures formed with square cells, which are used to measure the similarity between the original zone and an ideal zone with straight forms. The proposed method was applied to design electoral zones, which must satisfy constraints of compactness, contiguity and population balance, in a topographical configuration that favors the creation of twisted and diffuse shapes. The results show that the new method favors the creation of zones with straight forms, without an important effect to the population balance, which are considered zones of high quality. Keywords: Redistricting, compactness, simulated annealing, GIS. Mathematics Subject Classification: 90C59, 90C29, 68T20.

Trading Zones in Early Modern Europe.

Science.gov (United States)

Long, Pamela O

2015-12-01

This essay adopts the concept of trading zones first developed for the history of science by Peter Galison and redefines it for the early modern period. The term "trading zones" is used to mean arenas in which substantive and reciprocal communication occurred between individuals who were artisanally trained and learned (university-trained) individuals. Such trading zones proliferated in the sixteenth century. They tended to arise in certain kinds of places and not in others, but their existence must be determined empirically. The author's work on trading zones differs from the ideas of Edgar Zilsel, who emphasized the influence of artisans on the scientific revolution. In contrast, in this essay, the mutual influence of artisans and the learned on each other is stressed, and translation is used as a modality that was important to communication within trading zones.

Main principles of the Chernobyl' NPP zone development

International Nuclear Information System (INIS)

Ignatenko, E.I.; Komarov, V.I.; Zverkov, V.V.; Proskuryakov, A.G.

1989-01-01

It is suggested to divide the Chernobyl' NPP zone into two parts, which are the alienation and evacuation (buffer) zones. The alienation zone includes the areas with greatest contamination around the Chernobyl' NPP. The population residence in this zone is forbidden. The watching method of working with short-time personnel residence is suggested to be used in this zone. The buffer zone is the territory out of the alienation zone boundaries including all settlements, from which the population is evacuated. Constant residence is permitted in the buffer zone for persons 50 and more years old with introduction of restrictions for diet and residence organization. The production activity in this zone includes operation of three units of the Chernobyl' NPP, works with the Ukrytie object and researches. Operations connected with radioactive waste processing and redisposal from places of storage is not recommended to be done. It is suggested to develop methods for local radioactive waste processing

Planktonic Subsidies to Surf-Zone and Intertidal Communities

Science.gov (United States)

Morgan, Steven G.; Shanks, Alan L.; MacMahan, Jamie H.; Reniers, Ad J. H. M.; Feddersen, Falk

2018-01-01

Plankton are transported onshore, providing subsidies of food and new recruits to surf-zone and intertidal communities. The transport of plankton to the surf zone is influenced by wind, wave, and tidal forcing, and whether they enter the surf zone depends on alongshore variation in surf-zone hydrodynamics caused by the interaction of breaking waves with coastal morphology. Areas with gently sloping shores and wide surf zones typically have orders-of-magnitude-higher concentrations of plankton in the surf zone and dense larval settlement in intertidal communities because of the presence of bathymetric rip currents, which are absent in areas with steep shores and narrow surf zones. These striking differences in subsidies have profound consequences; areas with greater subsidies support more productive surf-zone communities and possibly more productive rocky intertidal communities. Recognition of the importance of spatial subsidies for rocky community dynamics has recently advanced ecological theory, and incorporating surf-zone hydrodynamics would be an especially fruitful line of investigation.

Problems of Chernobyl exclusion zone

International Nuclear Information System (INIS)

1996-01-01

The collection comprises the results of researches and design activity in the ChNPP exclusion zone with the aim to develop technology, equipment and instruments for RAW management and accident clean-up, studying of the composition and structure of the activity solid bearers in the soil of the exclusion zone and transformation of the radionuclides in the nearest zone of ChNPP. Much attention is paid to medical and biological problems of the accident influence on the flora, fauna and people's health labour conditions and incidence of the people involved

Problems of Chornobyl Exclusion Zone

International Nuclear Information System (INIS)

Kashparov, V.A.

2009-01-01

The collection comprises the results of researches and design activity in the ChNPP exclusion zone with the aim to develop technology, equipment and instruments for RAW management and accident clean-up, studying of the composition and structure of the activity solid bearers in the soil of the exclusion zone and transformation of the radionuclides in the nearest zone of ChNPP. Much attention is paid to medical and biological problems of the accident influence on the flora, fauna and people's health, labour conditions and incidence of the people involved.

Numerical calculation procedure for criticality parameters of the two-zone reflected reactor with flat central zone

International Nuclear Information System (INIS)

Bosevski, T.; Strugar, P.

1966-10-01

In determining the criticality parameters of a two-zone reactor with flat central zone one encounters a numerical problem requiring the solution of a system of two non-linear equations. To solve them the Newton method, which proved convenient, was used n this work. By comparing our results with those reported one obtains about 5% smaller values of both the radius of the flat zone and of the radial buckling of the outer zone. This discrepancy probably results from some approximations used in solving the same system of equations used in solving the same system of equations where the procedure form was applied, whereas the calculation time is by one order of magnitude smaller

Nuclear weapons free zones

International Nuclear Information System (INIS)

Stahl, K.

1990-01-01

The article analyses the concept and problems of the two nuclear weapons free zones in Latin America and in the South Pacific established by the Treaty of Tlatelolco and the Treaty of Rarotonga. So far the nuclear weapons states except China have refused to sign the additional protocols of the Treaties or have signed them only with considerable provisos. Therefore they don't fully recognize the nuclear weapons free status of those zones, or they don't recognize it at all. Both Treaties contain no provisions to regulate the transit of nuclear weapons through the zones. This allows de facto the stationing of nuclear weapons in the military bases of the US which are located within the nuclear weapons free zone of Latin America. The Treaty of Tlatelolco contains also the right of the states, party to the Treaty, to explode nuclear devices for peaceful purposes. Since peaceful and military nuclear explosions cannot be distinguished technically, this right could also undermine the nuclear weapons free status of the region. Important nuclear threshold countries like Argentina and Brazil have furthermore refrained from putting the Treaty into force. (orig.) [de

Instrumentation for coastal zone management

Digital Repository Service at National Institute of Oceanography (India)

Joseph, A.

stream_size 11 stream_content_type text/plain stream_name Trg_Course_Coast_Zone_Manage_1993_91.pdf.txt stream_source_info Trg_Course_Coast_Zone_Manage_1993_91.pdf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset...

Management of coastal zone vegetation

Digital Repository Service at National Institute of Oceanography (India)

Untawale, A.G.

stream_size 14 stream_content_type text/plain stream_name Trg_Course_Coast_Zone_Manage_1993_22.pdf.txt stream_source_info Trg_Course_Coast_Zone_Manage_1993_22.pdf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset...

[Laparoscopic cystectomy and ileal conduit urinary diversion for neurogenic bladders and related conditions. Morbidity and better quality of life].

Science.gov (United States)

Sakhri, R; Seigle-Murandi, F; Jacqmin, D; Lang, H; Saussine, C

2015-05-01

To assess morbidity and functional consequences of laparoscopic cystectomy with ileal conduit urinary diversion: in neurologic patients. We reviewed the records of forty-two patients (ten men and thirty-two women) who underwent surgery between August 2007 and October 2013. The median age of the patient was 54 years old (range between 21-79 years). A laparoscopic cystectomy was performed followed by a short laparotomy to perform the ileal conduit urinary diversion. Records were reviewed to retrieve the indications and describe the postoperative and functional course. Patients and GPs were interviewed during phone calls to appreciate the quality of life by the PGII scale in order to assess the functional outcome. The operation was performed on 42 patients, of whom 18 had multiple sclerosis, nine a post-traumatic neurogenic bladder. Among the total population, 10 patients (23.81%) required a transfusion of at least one packed red blood cells (1-7). The overall rate of early complications was 35.71%. Belated complications were seen in 52.38% of the population. The median duration of hospital stay was 16 days (range between 9-70 days). The median follow up was 34 months (range between 1-76 months). For patients, the PGII scale rating had a median value of 6 (2-7). All referring physicians described a better functional status. The laparoscopic cystectomy can make postoperative course smoother for the neurological patients. However, the surgeon must weigh individually the benefit of performing the operation. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Clinical course of a cohort of children with non-neurogenic daytime urinary incontinence symptoms followed at a tertiary center

Directory of Open Access Journals (Sweden)

Adrienne Lebl

2016-04-01

Full Text Available Abstract Objective: To characterize a cohort of children with non-neurogenic daytime urinary incontinence followed-up in a tertiary center. Methods: Retrospective analysis of 50 medical records of children who had attained bladder control or minimum age of 5 years, using a structured protocol that included lower urinary tract dysfunction symptoms, comorbidities, associated manifestations, physical examination, voiding diary, complementary tests, therapeutic options, and clinical outcome, in accordance with the 2006 and 2014 International Children's Continence Society standardizations. Results: Female patients represented 86.0% of this sample. Mean age was 7.9 years and mean follow-up was 4.7 years. Urgency (56.0%, urgency incontinence (56.0%, urinary retention (8.0%, nocturnal enuresis (70.0%, urinary tract infections (62.0%, constipation (62.0%, and fecal incontinence (16.0% were the most prevalent symptoms and comorbidities. Ultrasound examinations showed alterations in 53.0% of the cases; the urodynamic study showed alterations in 94.7%. At the last follow-up, 32.0% of patients persisted with urinary incontinence. When assessing the diagnostic methods, 85% concordance was observed between the predictive diagnosis of overactive bladder attained through medical history plus non-invasive exams and the diagnosis of detrusor overactivity achieved through the invasive urodynamic study. Conclusions: This subgroup of patients with clinical characteristics of an overactive bladder, with no history of urinary tract infection, and normal urinary tract ultrasound and uroflowmetry, could start treatment without invasive studies even at a tertiary center. Approximately one-third of the patients treated at the tertiary level remained refractory to treatment.

Is non-invasive neuromuscular electrical stimulation effective in severe chronic neurogenic dysphagia? Reporton a post-traumatic brain injury patient.

Science.gov (United States)

Calabrò, Rocco Salvatore; Nibali, Valeria Conti; Naro, Antonino; Floridia, Daniela; Pizzimenti, Maria; Salmeri, Lucia; Salviera, Carlo; Bramanti, Placido

2016-01-01

Neurogenic dysphagia is a difficulty in swallowing induced by nervous system disease. It often causes serious complications, which are preventable if dysphagia is properly managed. There is growing debate concerning the usefulness of non-invasive neuromuscular electrical stimulation (NMES) in treating swallowing dysfunction. Aim of this study was to assess the effectiveness of Vitalstim© device, and to investigate the neurophysiological mechanisms underlying functional recovery. A 34-year-old man, affected by severe chronic dysphagia following traumatic brain injury, underwent two different intensive rehabilitation trainings, including either conventional rehabilitation alone or coupled to Vitalstim training. We evaluated patient swallowing function in two separate sessions (i.e. before and after the two trainings) by means of ad hoc swallowing function scales and electrophysiological parameters (rapid paired associative stimulation). The overall Vitalstim program was articulated in 6 weekly sessions for 6 weeks. The patient did not report any side-effect either during or following both the intensive rehabilitation trainings. We observed an important improvement in swallowing function only after Vitalstim training. In fact, the patient was eventually able to safely eat even solid food. This is the first report objectively suggesting (by means of rPAS) a correlation between the brain neuroplastic changes induced by Vitalstim and the swallowing function improvement. It is hypothesizable that Vitalstim may have targeted cortical (and maybe subcortical) brain areas that are recruited during the highly coordinated function of swallowing, and it may have thus potentiated the well-known neuroplastic changes induced by repetitive and intensive swallowing exercises, probably thanks to metaplasticity phenomena.

White Light Photorefractive Phase Zone Plates

International Nuclear Information System (INIS)

Yuan-Mei, Gao; Si-Min, Liu

2008-01-01

Incoherent white light from an incandescent source is employed to fabricate volume phase zone plates in LiNbO 3 : Fe, for the first time to our knowledge, which can guide and modulate the input white light or laser light. The diffractive efficiency of the white light volume phase zone plates fabricated can reach as high as 12%. In addition, we test the volume phase zone plates by a probe beam and find that the volume phase zone plate is present in the direction perpendicular to the c-axis and absent in the direction parallel to the c-axis. This directly proves the existence of photovoltaic photorefractive anisotropy of white light

Radiopaque zones in the dentin beneath amalgam restorations

International Nuclear Information System (INIS)

You, Young Jun; Ahn, Hyung Kyu

1978-01-01

The purpose of the present investigation is determine how frequently radiopaque zones are seen on standard intraoral film and to research some other things about radiopaque bones. This study obtained the following results: 1. According to the standard intraoral films of the charts that were kept at the Dept. of Oral Diagnosis in Seoul National University Hospital, radiopaque zones were found in the rate of 4.1% among 1150 cases of amalgam-restored teeth that were treated at least two years ago. 2. Out of teeth that possessed radiopaque zones, 38.3% had radiolucent area between amalgam restoration and radiopaque zone. 3. Out of teeth that possessed radiopaque zones, 36.2% had cement base between amalgam restoration and radiopaque zone. 4. Out of teeth that possessed radiopaque zones, no tooth had periapical radiolucency. 5. Radiopaque zones were found more frequently in the mandibular teeth than the maxillary teeth. 6. According to the result of direct x-ray taking of 50 teeth that were treated at least 2 years ago, 6% had radiopaque zone.

Seismotectonic zoning of Azerbaijan territory

Science.gov (United States)

Kangarli, Talat; Aliyev, Ali; Aliyev, Fuad; Rahimov, Fuad

2017-04-01

Studying of the space-time correlation and consequences effect between tectonic events and other geological processes that have created modern earth structure still remains as one of the most important problems in geology. This problem is especially important for the East Caucasus-South Caspian geodynamic zone. Being situated at the eastern part of the Caucasian strait, this zone refers to a center of Alpine-Himalayan active folded belt, and is known as a complex tectonic unit with jointing heterogeneous structural-substantial complexes arising from different branches of the belt (Doburja-Caucasus-Kopetdag from the north and Pyrenean-Alborz from the south with Kura and South Caspian zone). According to GPS and precise leveling data, activity of regional geodynamic processes shows intensive horizontal and vertical movements of the Earth's crust as conditioned by collision of the Arabian and Eurasian continental plates continuing since the end of Miocene. So far studies related to the regional of geology-geophysical data, periodically used for the geological and tectonic modeling of the environment mainly based on the fixing ideology. There still remains a number of uncertainties in solution of issues related to regional geology, tectonics and magmatism, structure and interrelation of different structural zones, space-time interrelations between onshore and offshore complexes, etc. At the same time large dataset produced by surface geological surveys, deep geological mapping of on- and offshore areas with the use of seismic and electrical reconnaissance and geophysical field zoning methods, deep well drilling and remote sensing activities. Conducted new studies produced results including differentiation of formerly unknown nappe complexes of the different ages and scales within the structure of mountain-fold zones, identification of new zones containing ophiolites in their section, outlining of currently active faulting areas, geophysical interpretation of the deep

Application of the zone-melting technique to metal chelate systems-VI A new apparatus for zone-melting chromatography.

Science.gov (United States)

Maeda, S; Kobayashi, H; Ueno, K

1973-07-01

An improved apparatus has been constructed for zone-melting chromatography. An essential feature of the apparatus is that the length of the molten zone can be kept constant during a zone-melting operation, by employing heating and cooling compartments which are separated from each other by double partition plates. Each compartment is heated or cooled with jets of hot or cold air. The apparatus is suitable for organic materials melting in the range between 40 degrees and 180 degrees . The distribution of metal ion along the column after zone melting of copper acetylacetonate in 2-methoxynaphthalene was a smooth curve. The plot of the position of maximum concentration, x(max), against the number of zone passes, n, gave a relationship in accordance with theoretical prediction.

Differences in quantitative assessment of myocardial scar and gray zone by LGE-CMR imaging using established gray zone protocols.

Science.gov (United States)

Mesubi, Olurotimi; Ego-Osuala, Kelechi; Jeudy, Jean; Purtilo, James; Synowski, Stephen; Abutaleb, Ameer; Niekoop, Michelle; Abdulghani, Mohammed; Asoglu, Ramazan; See, Vincent; Saliaris, Anastasios; Shorofsky, Stephen; Dickfeld, Timm

2015-02-01

Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging is the gold standard for myocardial scar evaluation. Heterogeneous areas of scar ('gray zone'), may serve as arrhythmogenic substrate. Various gray zone protocols have been correlated to clinical outcomes and ventricular tachycardia channels. This study assessed the quantitative differences in gray zone and scar core sizes as defined by previously validated signal intensity (SI) threshold algorithms. High quality LGE-CMR images performed in 41 cardiomyopathy patients [ischemic (33) or non-ischemic (8)] were analyzed using previously validated SI threshold methods [Full Width at Half Maximum (FWHM), n-standard deviation (NSD) and modified-FWHM]. Myocardial scar was defined as scar core and gray zone using SI thresholds based on these methods. Scar core, gray zone and total scar sizes were then computed and compared among these models. The median gray zone mass was 2-3 times larger with FWHM (15 g, IQR: 8-26 g) compared to NSD or modified-FWHM (5 g, IQR: 3-9 g; and 8 g. IQR: 6-12 g respectively, p zone extent (percentage of total scar that was gray zone) also varied significantly among the three methods, 51 % (IQR: 42-61 %), 17 % (IQR: 11-21 %) versus 38 % (IQR: 33-43 %) for FWHM, NSD and modified-FWHM respectively (p zone and scar core. Infarct core and total myocardial scar mass also differ using these methods. Further evaluation of the most accurate quantification method is needed.

Fracture zones constrained by neutral surfaces in a fault-related fold: Insights from the Kelasu tectonic zone, Kuqa Depression

Science.gov (United States)

Sun, Shuai; Hou, Guiting; Zheng, Chunfang

2017-11-01

Stress variation associated with folding is one of the controlling factors in the development of tectonic fractures, however, little attention has been paid to the influence of neutral surfaces during folding on fracture distribution in a fault-related fold. In this study, we take the Cretaceous Bashijiqike Formation in the Kuqa Depression as an example and analyze the distribution of tectonic fractures in fault-related folds by core observation and logging data analysis. Three fracture zones are identified in a fault-related fold: a tensile zone, a transition zone and a compressive zone, which may be constrained by two neutral surfaces of fold. Well correlation reveals that the tensile zone and the transition zone reach the maximum thickness at the fold hinge and get thinner in the fold limbs. A 2D viscoelastic stress field model of a fault-related fold was constructed to further investigate the mechanism of fracturing. Statistical and numerical analysis reveal that the tensile zone and the transition zone become thicker with decreasing interlimb angle. Stress variation associated with folding is the first level of control over the general pattern of fracture distribution while faulting is a secondary control over the development of local fractures in a fault-related fold.

76 FR 7107 - Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation...

Science.gov (United States)

2011-02-09

... defined boundary for which regulations for vessels navigating within the area have been established by the...)...... 9/19/2008 USCG-2008-0814 San Diego, CA Safety Zones (Part 165)...... 9/6/2008 USCG-2008-0827 Ocean... (Part 165). USCG-2009-0402 Ocean City, NJ Safety Zones (Part 165)...... 10/10/2009 USCG-2009-0403...

Seasonal Ice Zone Reconnaissance Surveys Coordination

Science.gov (United States)

2016-03-30

Chukchi sea seasonal sea ice zone (SIZ) utilizing US Coast Guard Arctic Domain Awareness ( ADA ) flights of opportunity in the summers of 2012- 2014. In...measurements across the Beaufort-Chukchi sea seasonal sea ice zone (SIZ) utilizing US Coast Guard Arctic Domain Awareness ( ADA ) flights of...such, it contains the full range of positions of the marginal ice zone (MIZ) where sea ice interacts with open water. In addition to SIZRS

Environmental Zoning: Some methodological implications

NARCIS (Netherlands)

Ike, Paul; Voogd, Henk

1991-01-01

The purpose of this article is to discuss some methodological problems of environmental zoning. The principle of environmental zoning will be elaborated. In addition an overview is given of a number of approaches that have been followed in practice to arrive at an integral judgement. Finally some

Growth with Time Zone Differences

OpenAIRE

Toru Kikuchi; Sugata Marjit

2010-01-01

We propose a two-country growth model of intermediate business-services trade that captures the role of time zone differences. It is shown that a time-saving improvement in intermediate business-services trade involving production in different time zones can have a permanent impact on productivity.

The segmentation of zones with increased autofluorescence in the junctional zone of parapapillary atrophy

International Nuclear Information System (INIS)

Kolář, R; Jan, J; Laemmer, R; Mardin, Ch Y

2009-01-01

The autofluorescence (AF) derived from the retinal pigment epithelium has the potential to be used as a feature for early glaucoma diagnosis. The aim of this paper is to design and evaluate the method used for semi-automatic segmentation of the zones with increased autofluorescence. A randomized sample of 20 patients (age: 56 ± 10 years) with open angle glaucoma was used. A new method for semi-automatic detection and segmentation of the zones with a higher level of autofluorescence in the junctional zone of parapapillary atrophy has been evaluated. Good agreement has been observed between manually and semi-automatically segmented zones for most of the images, but higher differences may occur for larger hyperfluorescent regions. The data were evaluated using the limits of agreement, with a 2σ border. The described method allows fast and objective evaluation of AF images, preventing undesirable inter-expert variance. A large proportion of AF images could be evaluated successfully by the developed procedure, and the obtained results are comparable to the manual procedure in most cases

Double seismic zone for deep earthquakes in the izu-bonin subduction zone.

Science.gov (United States)

Iidaka, T; Furukawa, Y

1994-02-25

A double seismic zone for deep earthquakes was found in the Izu-Bonin region. An analysis of SP-converted phases confirms that the deep seismic zone consists of two layers separated by approximately 20 kilometers. Numerical modeling of the thermal structure implies that the hypocenters are located along isotherms of 500 degrees to 550 degrees C, which is consistent with the hypothesis that deep earthquakes result from the phase transition of metastable olivine to a high-pressure phase in the subducting slab.

Purification by using the zone melting technique; Purification par la technique de la zone fondue

Energy Technology Data Exchange (ETDEWEB)

Clerc, Michel

1962-06-22

The zone melting technique has first been used in metallurgy, and has been developed for the preparation of silicon and germanium for semiconductors, and then for the preparation of organic bodies of high purity. In this research thesis, the author first presents the principle of this technique, and then discusses the influence of agitation in liquid phase, and the influence of the number of passages over the zone. He discusses issues related to matter transport, and some technical details which intervene in the design of an apparatus for purification by zone melting. He finally presents examples.

ZONING DESIGN FOR HAND­WRITTEN NUMERAL RECOGNITION

NARCIS (Netherlands)

Lecce Di, V.; Dimauro, G.; Guerriero, A.; Impedovo, S.; Pirlo, G.; Salzo, A.

2004-01-01

In the field of Optical Character Recognition (OCR), zoning is used to extract topological information from patterns. In this paper zoning is considered as the result of an optimisation problem and a new technique is presented for automatic zoning. More precisely, local analysis of feature

Radially converging tracer test in a low-angle fracture zone at the Finnsjoen site, central Sweden. The fracture zone project - phase 3

International Nuclear Information System (INIS)

Gustafsson, E.; Nordqvist, R.

1993-10-01

The performance and results of a radially converging tracer test in a low-angle major fracture zone in crystalline rock are described. The extensive, about 100 m thick, zone 2 was encountered by means of borehole investigations at depths ranging from 100 to 250 metres at the Finnsjon site, central eastern Sweden. The zone studied (zone 2) consists of highly conductive, metre thick interconnected minor shear and fracture zones (sub-zones) with low conductive rock in between. The objective of the tracer test was primarily to determine flow and transport characteristics in a major fracture zone. Secondly new equipment, experimental design and methods of interpretation were developed, tested and improved. The converging flow field was created by pumping in a central borehole from a packed-off interval enclosing the whole thickness of zone 2. Tracer breakthrough was registered from all nine injection points, with first arrivals ranging from 24 to 3200 hours. Evaluated flow and transport parameters included; flow porosity, dispersivity, flow wetted surface, fracture aperture and hydraulic conductivity in fracture flow paths. Directional variations were found in the flow and transport parameters determined, which is concluded to be due to heterogeneity and/or anisotropy. This conditions is more pronounced at depth in zone 2. The results from the tracer test also clearly show that the upper boundary of zone 2 is highly conductive and consistent over hundreds of metres. Within zone 2, and between upper and lower margins, interconnected discrete minor shear and fracture zones (sub-zones) constitute flow paths of considerable variable residence times. The dispersion within the sub-zones of zone 2, expressed as Peclet numbers ranged from 16 to 40. Flow porosity was determined to be 0.001-0.05 in the upper sub-zone and 0.01-0.1 in the intermediate and lower ones and flow wetted surface area per volume of rock was calculated to be within 1-92 m 2 /m 3 . 68 refs, 61 figs, 40 tabs

Drivers׳ merging behavior data in highway work zones

Directory of Open Access Journals (Sweden)

Mahmoud Shakouri

2016-03-01

Full Text Available There have been growing research interests in finding a suitable work zone layout to improve work zone safety and traffic efficiency. This paper contains data supporting the research article entitled: Effects of work zone configurations and traffic density on performance variables and subjective workload (Shakouri et al., 2014 [1]. A full factorial experiment was conducted to compare the efficiency of two work zone configurations by using a driving simulator with two levels of work zone configuration, two levels of traffic density and three levels of sign placement as fixed factors. Seven female and 23 male participants completed the experiment. In this paper we present the data relating to demographic information of participants, driving simulator data and subjective workload evaluation of participants for each work zone. Keywords: Work zone, Merging behavior, Subjective workload, Safety

Export Processing Zones and Global Class Formation

NARCIS (Netherlands)

Neveling, Patrick

2015-01-01

This chapter is concerned with one of the most striking developments in the global political economy of capitalism after the Second World War; the rise of export processing zones and special economic zones. Building on long-term ethnohistorical research on the zones’ global spread from one zone in

Nuclear free zone

International Nuclear Information System (INIS)

Christoffel, T.

1987-01-01

Health professionals have played a leading role in alerting and educating the public regarding the danger of nuclear war which has been described as the last epidemic our civilization will know. Having convinced most people that the use of nuclear weapons would mean intolerable consequences, groups such as Physicians for Social Responsibility have focused on the second critical question how likely is it that these weapons will be used? The oultlook is grim. This article describes the nuclear free zone movement, explores relevant legal questions, and shows how the political potential of nuclear free zones threatens to open a deep rift in the American constitutional system

A geophysical cross-section of the Hockai Fault Zone (Eastern Belgium): imaging an intraplate weak crustal zone.

Science.gov (United States)

Lecocq, T.; Camelbeeck, T.

2016-12-01

The Hockai Fault Zone (HFZ) is a NNW-SSE trending structure visible in the regional geomorphology in the Ardennes, Eastern-Belgium. It is situated, between the Pays de Herve (Graben de la Minerie) to the North and the Amblève river, to the South. It crosses the Stavelot Massif, almost perpendicular to the Crête de la Vecquée (Vecquée crest), i.e. the highest crest of the Venn. Faults have been identified or suspected on a contour map of the base of the Tertiary cover (Eocene or Oligocene) in the north western and central Rhenish Massif. These faults are necessary to account for the altitude difference of the base of the cover. The deflection or capture of local rivers show a remarkable alignments on more than 42 km N-S. The alignments are mostly trending SSE-NNW, between N140 and N170, with some potential segments with slightly different orientations. This general orientation has been also evidenced from the analyses of Landsat-1 imagery products. At its crossing with the Vecquée Crest, Demoulin locates the HFZ where the Hoëgne river turns sharply towards the north and crosscuts the quarzitic crest. Demoulin identifies three subparallel faults or fault zones on the Hautes-Fagnes plateau, from East to West: the Eupen faulting zone, the Baelen faulting zone and Hockai faulted zone. In this communication, we report on a large-scale geophysical survey that was conducted in order to search of the Hockai fault zone expression at the surface. The locations to search for the Hockai Fault Zone are based on the surface projection of the 1989/1990 seismic swarm that occurred under the Stavelot Massif, geomorphological evidences and past geophysical surveys in the region. Our objective is not to prove a Quaternary movement of faults, but rather to find reliable evidences of their presence and to analyse their lateral extension. In total, 31 ERT profiles were executed almost parallel to the Vecquée Crest, i.e. a total of 10679 meters of profiles. Four zones are imaged

Advanced Vadose Zone Simulations Using TOUGH

Energy Technology Data Exchange (ETDEWEB)

Finsterle, S.; Doughty, C.; Kowalsky, M.B.; Moridis, G.J.; Pan,L.; Xu, T.; Zhang, Y.; Pruess, K.

2007-02-01

The vadose zone can be characterized as a complex subsurfacesystem in which intricate physical and biogeochemical processes occur inresponse to a variety of natural forcings and human activities. Thismakes it difficult to describe, understand, and predict the behavior ofthis specific subsurface system. The TOUGH nonisothermal multiphase flowsimulators are well-suited to perform advanced vadose zone studies. Theconceptual models underlying the TOUGH simulators are capable ofrepresenting features specific to the vadose zone, and of addressing avariety of coupled phenomena. Moreover, the simulators are integratedinto software tools that enable advanced data analysis, optimization, andsystem-level modeling. We discuss fundamental and computationalchallenges in simulating vadose zone processes, review recent advances inmodeling such systems, and demonstrate some capabilities of the TOUGHsuite of codes using illustrative examples.

Metasomatic zoning at some stratiform rare metal deposits

International Nuclear Information System (INIS)

Altyntsev, Yu.V.; Bazhenov, M.I.; Bepeshov, G.V.; Komarnitskij, G.M.; Petrov, I.Ya.; Serykh, A.S.

1985-01-01

Metasomatic zoning of stratiform deposits of rare metals (Mo, Pb, As, V, Se, U, etc.) in intermontane depresions, deposited at the postorogenic stage of Paleozoic geosyncline region development, is considered. Geochemical and geophysical characteristics of metasomatic zoning in the case of sloping and steep rock deposition are given. It is established, that in rare metal deposits in variegated deposits of molassoid formation of Middle-Upper Paleozoic the external and internal zones of metasomatic alterations are distinctly separated. The external zone is presented by mineral association: quartz + -albile + -calcite + -epidote; the internal one - by hydromica + -chlorite + -analcite, laumontite + -hematite + -ankerite + -kaolinite. Geochemical zoning is manifested quite regularly at all the deposits and it is subjected to metasomatic zoning. Changes in physical properties of rocks reflect the metasomatic zoning. The character of metasomatic alterations of rocks, geochemical zoning of metasomatites at rare metal deposits in molassoid deposits and spatially contiguous deposits in volcanogenic complexes have common features. A supposition is made on polygenic ore formation in sedimentary rocks of the depressions

Of Mice and Men: Neurogenesis, Cognition and Alzheimer’s disease

Directory of Open Access Journals (Sweden)

Orly eLazarov

2013-08-01

Full Text Available Neural stem cells are maintained in the subgranular layer of the dentate gyrus and in the subventricular zone in the adult mammalian brain throughout life. Neurogenesis is continuous, but its extent is tightly regulated by environmental factors, behavior, hormonal state, age and brain health. Increasing evidence supports a role for new neurons in cognitive function in rodents. Recent evidence delineates potential significant differences between adult neurogenesis in rodents and humans. Being context-dependent, neurogenesis in the human brain might be manifested differently than in the rodent brain. Decline in neurogenesis may play a role in cognitive deterioration, leading to the development of progressive learning and memory disorders, such as Alzheimer’s disease. This review discusses the different observations concerning neurogenesis in the rodent and human brain, and their functional implications for the healthy and diseased brain.

Recent findings relating to firefighter safety zones

Science.gov (United States)

Bret Butler; Russ Parsons; William Mell

2015-01-01

Designation of safety zones is a primary duty of all wildland firefighters. Unfortunately, information regarding what constitutes an adequate safety zone is inadequately defined. Measurements of energy release from wildland fires have been used to develop an empirically based safety zone guideline. The basis for this work is described here.

78 FR 15883 - Standard Time Zone Boundaries

Science.gov (United States)

2013-03-13

...] RIN 2105-AE20 Standard Time Zone Boundaries AGENCY: Office of the Secretary (OST), Department of... time zone boundaries regulations to reflect changes that Congress made to the Uniform Time Act. The... regulations on standard time zone boundaries, 49 CFR Part 71, need to be updated in order to ensure their...

32 CFR 643.33 - Policy-Coastal zone management.

Science.gov (United States)

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Policy-Coastal zone management. 643.33 Section... PROPERTY REAL ESTATE Policy § 643.33 Policy—Coastal zone management. (a) The Coastal Zone Management Act of... affecting the coastal zone of a state, to conduct or support those activities in a manner which is, to the...

Zoning Districts, The zoning districts dataset includes the towns in Manitowoc County, WI that have adopted the county's zoning ordinance., Published in 2013, 1:2400 (1in=200ft) scale, Manitowoc County Government.

Data.gov (United States)

NSGIC Local Govt | GIS Inventory — Zoning Districts dataset current as of 2013. The zoning districts dataset includes the towns in Manitowoc County, WI that have adopted the county's zoning ordinance..

High exhaust temperature, zoned, electrically-heated particulate matter filter

Science.gov (United States)

Gonze, Eugene V.; Paratore, Jr., Michael J.; Bhatia, Garima

2015-09-22

A system includes a particulate matter (PM) filter, an electric heater, and a control circuit. The electric heater includes multiple zones, which each correspond to longitudinal zones along a length of the PM filter. A first zone includes multiple discontinuous sub-zones. The control circuit determines whether regeneration is needed based on an estimated level of loading of the PM filter and an exhaust flow rate. In response to a determination that regeneration is needed, the control circuit: controls an operating parameter of an engine to increase an exhaust temperature to a first temperature during a first period; after the first period, activates the first zone; deactivates the first zone in response to a minimum filter face temperature being reached; subsequent to deactivating the first zone, activates a second zone; and deactivates the second zone in response to the minimum filter face temperature being reached.