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Sample records for adult mouse spinal

  1. Protein composition and synthesis in the adult mouse spinal cord

    International Nuclear Information System (INIS)

    Stodieck, L.S.; Luttges, M.W.

    1983-01-01

    Properties of spinal cord proteins were studied in adult mice subjected to unilateral crush or electrical stimulation of sciatic nerve. The protein composition of spinal tissue was determined using SDS-polyacrylamide gel electrophoresis coupled with subcellular fractionation. Comparisons of mouse spinal cord and brain revealed similarities in the types but differences in the concentrations of myelin associated proteins, nuclear histones and other proteins. Comparisons with sciatic nerve proteins demonstrated differences in types of proteins but similarities in the concentration of myelin proteins and nuclear histones. The short term (less than 2 hrs.) incorporation of radioactive amino acids into spinal cord proteins revealed heterogeneous rates of incorporation. Neither nerve crush six days prior to testing nor sciatic nerve stimulation had a significant effect on the protein composition or amino acid incorporation rates of spinal cord tissue. These observations suggest that known differences in spinal cord function following alterations in nerve input may be dependent upon different mechanisms than have been found in the brain

  2. An ex vivo spinal cord injury model to study ependymal cells in adult mouse tissue.

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    Fernandez-Zafra, Teresa; Codeluppi, Simone; Uhlén, Per

    2017-08-15

    Traumatic spinal cord injury is characterized by an initial cell loss that is followed by a concerted cellular response in an attempt to restore the damaged tissue. Nevertheless, little is known about the signaling mechanisms governing the cellular response to injury. Here, we have established an adult ex vivo system that exhibits multiple hallmarks of spinal cord injury and allows the study of complex processes that are difficult to address using animal models. We have characterized the ependymal cell response to injury in this model system and found that ependymal cells can become activated, proliferate, migrate out of the central canal lining and differentiate in a manner resembling the in vivo situation. Moreover, we show that these cells respond to external adenosine triphosphate and exhibit spontaneous Ca 2+ activity, processes that may play a significant role in the regulation of their response to spinal cord injury. This model provides an attractive tool to deepen our understanding of the ependymal cell response after spinal cord injury, which may contribute to the development of new treatment options for spinal cord injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Fictive locomotion in the adult decerebrate and spinal mouse in vivo

    DEFF Research Database (Denmark)

    Meehan, Claire Francesca; Grøndahl, Lillian; Nielsen, Jens Bo

    2012-01-01

    Recently, transgenic mice have been created with mutations affecting the components of the mammalian spinal central pattern generator (CPG) for locomotion, however, it has currently only been possible to evoke fictive locomotion in mice, using neonatal in vitro preparations. Here, we demonstrate...... organisation and allowing for future results in transgenic mice to be extrapolated to existing knowledge of CPG components and circuitry obtained in larger species....

  4. Selective activation of microglia in spinal cord but not higher cortical regions following nerve injury in adult mouse

    Directory of Open Access Journals (Sweden)

    Shang Yuze

    2008-04-01

    Full Text Available Abstract Neuronal plasticity along the pathway for sensory transmission including the spinal cord and cortex plays an important role in chronic pain, including inflammatory and neuropathic pain. While recent studies indicate that microglia in the spinal cord are involved in neuropathic pain, a systematic study has not been performed in other regions of the central nervous system (CNS. In the present study, we used heterozygous Cx3cr1GFP/+mice to characterize the morphological phenotypes of microglia following common peroneal nerve (CPN ligation. We found that microglia showed a uniform distribution throughout the CNS, and peripheral nerve injury selectively activated microglia in the spinal cord dorsal horn and related ventral horn. In contrast, microglia was not activated in supraspinal regions of the CNS, including the anterior cingulate cortex (ACC, prefrontal cortex (PFC, primary and secondary somatosensory cortex (S1 and S2, insular cortex (IC, amygdala, hippocampus, periaqueductal gray (PAG and rostral ventromedial medulla (RVM. Our results provide strong evidence that nerve injury primarily activates microglia in the spinal cord of adult mice, and pain-related cortical plasticity is likely mediated by neurons.

  5. Decerebrate mouse model for studies of the spinal cord circuits

    DEFF Research Database (Denmark)

    Meehan, Claire Francesca; Mayr, Kyle A; Manuel, Marin

    2017-01-01

    The adult decerebrate mouse model (a mouse with the cerebrum removed) enables the study of sensory-motor integration and motor output from the spinal cord for several hours without compromising these functions with anesthesia. For example, the decerebrate mouse is ideal for examining locomotor be......, which is ample time to perform most short-term procedures. These protocols can be modified for those interested in cardiovascular or respiratory function in addition to motor function and can be performed by trainees with some previous experience in animal surgery....

  6. Cytoarchitecture of the spinal cord of the postnatal (P4) mouse.

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    Sengul, Gulgun; Puchalski, Ralph B; Watson, Charles

    2012-05-01

    Interpretation of the new wealth of gene expression and molecular mechanisms in the developing mouse spinal cord requires an accurate anatomical base on which data can be mapped. Therefore, we have assembled a spinal cord atlas of the P4 mouse to facilitate direct comparison with the adult specimens and to contribute to studies of the development of the mouse spinal cord. This study presents the anatomy of the spinal cord of the P4 C57Bl/6J mouse using Nissl and acetyl cholinesterase-stained sections. It includes a detailed map of the laminar organization of selected spinal cord segments and a description of named cell groups of the spinal cord such as the central cervical (CeCv), lateral spinal nucleus, lateral cervical, and dorsal nuclei. The motor neuron groups have also been identified according to the muscle groups they are likely to supply. General features of Rexed's laminae of the P4 spinal cord showed similarities to that of the adult (P56). However, certain differences were observed with regard to the extent of laminae and location of certain cell groups, such as the dorsal nucleus having a more dispersed structure and a more ventral and medial position or the CeCv being located in the medial part of lamina 5 in contrast to the adult where it is located in lamina 7. Motor neuron pools appeared to be more tightly packed in the P4 spinal cord. The dorsal horn was relatively larger and there was more white matter in the P56 spinal cord. Copyright © 2012 Wiley Periodicals, Inc.

  7. Inhibitory zinc-enriched terminals in mouse spinal cord

    DEFF Research Database (Denmark)

    Danscher, G; Jo, S M; Varea, E

    2001-01-01

    The ultrastructural localization of zinc transporter-3, glutamate decarboxylase and zinc ions in zinc-enriched terminals in the mouse spinal cord was studied by zinc transporter-3 and glutamate decarboxylase immunohistochemistry and zinc selenium autometallography, respectively.The distribution...

  8. A Fab fragment directed against the neural cell adhesion molecule L1 enhances functional recovery after injury of the adult mouse spinal cord.

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    Loers, Gabriele; Cui, Yi-Fang; Neumaier, Irmgard; Schachner, Melitta; Skerra, Arne

    2014-06-15

    Lack of permissive mechanisms and abundance of inhibitory molecules in the lesioned central nervous system of adult mammals contribute to the failure of functional recovery, which leads to severe disabilities in motor functions or pain. Previous studies have indicated that the neural cell adhesion molecule L1 constitutes a viable target to promote regeneration. In the present study, we describe the cloning, functional expression in Escherichia coli cells and purification of a recombinant αL1 Fab fragment that binds to L1 with comparable activity as the function-triggering monoclonal antibody 557.B6 and induces neurite outgrowth and neuronal survival in cultured neurons, despite its monovalent function. Infusion of αL1 Fab into the lesioned spinal cord of mice enhanced functional recovery after thoracic spinal cord compression injury. αL1 Fab treatment resulted in reduced scar volume, enhanced number of tyrosine hydroxylase-positive axons and increased linear density of VGLUT1 (vesicular glutamate transporter 1) on motoneurons. Furthermore, the number and soma size of ChAT (choline acetyltransferase)-positive motoneurons and the linear density of ChAT-positive boutons on motoneurons as well as parvalbumin-positive interneurons in the lumbar spinal cord were elevated. Stimulation of endogenous L1 by application of the αL1 Fab opens new avenues for recombinant antibody technology, offering prospects for therapeutic applications after traumatic nervous system lesions.

  9. Zinc-enriched (ZEN) terminals in mouse spinal cord

    DEFF Research Database (Denmark)

    Jo, S M; Danscher, G; Schrøder, H D

    2000-01-01

    The general distribution of zinc-enriched (ZEN) terminals in mouse spinal cord was investigated at light microscopic level by means of zinc transporter-3 immunohistochemistry (ZnT3(IHC)) and zinc selenium autometallography (ZnSe(AMG)). Staining for ZnT3(IHC) corresponded closely to the Zn...... dendrites. These ZEN terminals in the ventral horn were in general larger than those in the dorsal horn. This is the first description of the pattern of ZEN terminals in mouse spinal cord....

  10. Cervical spinal cord injury without radiological abnormality in adults.

    OpenAIRE

    Bhatoe H

    2000-01-01

    Spinal cord injury occurring without concomitant radiologically demonstrable trauma to the skeletal elements of the spinal canal rim, or compromise of the spinal canal rim without fracture, is a rare event. Though documented in children, the injury is not very well reported in adults. We present seventeen adult patients with spinal cord injury without accompanying fracture of the spinal canal rim, or vertebral dislocation, seen over seven years. None had preexisting spinal canal stenosis or c...

  11. Glycoconjugates distribution during developing mouse spinal cord motor organizers.

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    Vojoudi, Elham; Ebrahimi, Vahid; Ebrahimzadeh-Bideskan, Alireza; Fazel, Alireza

    2015-01-01

    The aim of this research was to study the distribution and changes of glycoconjugates particularly their terminal sugars by using lectin histochemistry during mouse spinal cord development. Formalin-fixed sections of mouse embryo (10-16 fetal days) were processed for lectin histochemical method. In this study, two groups of horseradish peroxidase-labeled specific lectins were used: N-acetylgalactosamine, including Dolichos biflorus, Wisteria floribunda agglutinin (WFA), Vicia villosa, Glycine max as well as focuse-binding lectins, including tetragonolobus, Ulex europaeus, and Orange peel fungus (OFA). All sections were counterstained with alcian blue (pH 2.5). Our results showed that only WFA and OFA reacted strongly with the floor plate cells from early to late embryonic period of developing spinal cord. The strongest reactions were related to the 14, 15, and 16 days of tissue sections incubated with OFA and WFA lectins. The present study demonstrated that cellular and molecular differentiation of the spinal cord organizers is a wholly regulated process, and α-L-fucose, α-D-GalNAc, and α/β-D-GalNAc terminal sugars play a significant role during the prenatal spinal cord development.

  12. Neurogenesis in spinal cord of mouse: an autoradiographic analysis

    International Nuclear Information System (INIS)

    Nornes, H.O.; Carry, M.

    1978-01-01

    An autoradiographic analysis of the time and sites of origin, and the migration and setting patterns of neurons was made in the spinal cord of the mouse. The neurons originated on days 10-15 of gestation with temporal gradients along the ventrodorsal and rostrocaudal axes. The motor neurons originated on days 10-11 of gestation; the neurons in the intermediate gray region originated on days 11-14 of gestation; the neurons of the head of the dorsal horn originated on days 12-14 of gestation. The neurons that originated on days 10 and 11 originated and migrated primarily from the basal plate, and they settled in the adjacent regions of the intermediate zone; those neurons formed on days 12-14 originated and migrated primarily from the alar plate, and it was concluded that these neuroblasts similarly settled in the adjacent regions of the intermediate zone. Extraventricular proliferation, which presumably signaled the initial stages of gliogenesis, was first observed on day 12 of gestation. This study supports the classical idea of the mosaic pattern of neurogenesis in the embryonic spinal cord. (Auth.)

  13. Silencing neuronal mutant androgen receptor in a mouse model of spinal and bulbar muscular atrophy.

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    Sahashi, Kentaro; Katsuno, Masahisa; Hung, Gene; Adachi, Hiroaki; Kondo, Naohide; Nakatsuji, Hideaki; Tohnai, Genki; Iida, Madoka; Bennett, C Frank; Sobue, Gen

    2015-11-01

    Spinal and bulbar muscular atrophy (SBMA), an adult-onset neurodegenerative disease that affects males, results from a CAG triplet repeat/polyglutamine expansions in the androgen receptor (AR) gene. Patients develop progressive muscular weakness and atrophy, and no effective therapy is currently available. The tissue-specific pathogenesis, especially relative pathological contributions between degenerative motor neurons and muscles, remains inconclusive. Though peripheral pathology in skeletal muscle caused by toxic AR protein has been recently reported to play a pivotal role in the pathogenesis of SBMA using mouse models, the role of motor neuron degeneration in SBMA has not been rigorously investigated. Here, we exploited synthetic antisense oligonucleotides to inhibit the RNA levels of mutant AR in the central nervous system (CNS) and explore its therapeutic effects in our SBMA mouse model that harbors a mutant AR gene with 97 CAG expansions and characteristic SBMA-like neurogenic phenotypes. A single intracerebroventricular administration of the antisense oligonucleotides in the presymptomatic phase efficiently suppressed the mutant gene expression in the CNS, and delayed the onset and progression of motor dysfunction, improved body weight gain and survival with the amelioration of neuronal histopathology in motor units such as spinal motor neurons, neuromuscular junctions and skeletal muscle. These findings highlight the importance of the neurotoxicity of mutant AR protein in motor neurons as a therapeutic target. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. MicroRNA expression in the adult mouse central nervous system

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    Bak, Mads; Silahtaroglu, Asli; Møller, Morten

    2008-01-01

    distinct areas of the adult mouse central nervous system (CNS). Microarray profiling in combination with real-time RT-PCR and LNA (locked nucleic acid)-based in situ hybridization uncovered 44 miRNAs displaying more than threefold enrichment in the spinal cord, cerebellum, medulla oblongata, pons......RNA-related gene regulatory networks in the mammalian central nervous system. Udgivelsesdato: 2008-Mar...

  15. Ileus Following Adult Spinal Deformity Surgery.

    Science.gov (United States)

    Durand, Wesley M; Ruddell, Jack H; Eltorai, Adam E M; DePasse, J Mason; Daniels, Alan H

    2018-05-23

    Postoperative ileus (POI) is a common complication after spine surgery, with particularly high rates after adult spinal deformity surgery (ASD). Few investigations have been conducted, however, on predictors of POI following ASD. The objective of this investigation was to determine risk factors for POI in patients undergoing ASD. We also sought to determine the association between POI and in-hospital mortality, length of stay, and total charges. Data were obtained from the National/Nationwide Inpatient Sample, years 2010 - 2014. ASD patients aged ≥26 years-old were selected using ICD-9-CM codes. Multiple logistic and linear regression were utilized. In total, 59,410 patients were included in the analysis. 7.4% of patients experienced POI. On adjusted analysis, the following variables were associated with increased risk of POI: male sex (OR 1.43, CI 1.10 - 1.85), anterior surgical approach (OR 1.78, CI 1.22 - 2.60), 9+ levels fused (OR 1.84, CI 1.24 - 2.73), electrolyte disorders (OR 2.70, CI 2.15 - 3.39), and pathologic weight loss (OR 1.94, CI 1.08 - 3.46). POI was associated with significantly longer length of stay (+39%, CI 29% - 51%) and higher total charges (+23%, CI 14% - 31%). Risk factors for POI were identified. Patients suffering from ileus exhibited 2.9 days longer length of stay and ∼$80,000 higher total charges. These results may be applied clinically to identify patients at risk of POI and to consider addressing modifiable risk factors preoperatively. Future studies should be conducted with additional data to develop models capable of accurately predicting and preventing POI. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Spinal Accessory Motor Neurons in the Mouse: A Special Type of Branchial Motor Neuron?

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    Watson, Charles; Tvrdik, Petr

    2018-04-16

    The spinal accessory nerve arises from motor neurons in the upper cervical spinal cord. The axons of these motor neurons exit dorsal to the ligamentum denticulatum and form the spinal accessory nerve. The nerve ascends in the spinal subarachnoid space to enter the posterior cranial fossa through the foramen magnum. The spinal accessory nerve then turns caudally to exit through the jugular foramen alongside the vagus and glossopharyngeal nerves, and then travels to supply the sternomastoid and trapezius muscles in the neck. The unusual course of the spinal accessory nerve has long prompted speculation that it is not a typical spinal motor nerve and that it might represent a caudal remnant of the branchial motor system. Our cell lineage tracing data, combined with images from public databases, show that the spinal accessory motor neurons in the mouse transiently express Phox2b, a transcription factor that is required for development of brain stem branchial motor nuclei. While this is strong prima facie evidence that the spinal accessory motor neurons should be classified as branchial motor, the evolutionary history of these motor neurons in anamniote vertebrates suggests that they may be considered to be an atypical branchial group that possesses both branchial and somatic characteristics. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  17. A neonatal mouse spinal cord injury model for assessing post-injury adaptive plasticity and human stem cell integration.

    Directory of Open Access Journals (Sweden)

    Jean-Luc Boulland

    Full Text Available Despite limited regeneration capacity, partial injuries to the adult mammalian spinal cord can elicit variable degrees of functional recovery, mediated at least in part by reorganization of neuronal circuitry. Underlying mechanisms are believed to include synaptic plasticity and collateral sprouting of spared axons. Because plasticity is higher in young animals, we developed a spinal cord compression (SCC injury model in the neonatal mouse to gain insight into the potential for reorganization during early life. The model provides a platform for high-throughput assessment of functional synaptic connectivity that is also suitable for testing the functional integration of human stem and progenitor cell-derived neurons being considered for clinical cell replacement strategies. SCC was generated at T9-T11 and functional recovery was assessed using an integrated approach including video kinematics, histology, tract tracing, electrophysiology, and high-throughput optical recording of descending inputs to identified spinal neurons. Dramatic degeneration of axons and synaptic contacts was evident within 24 hours of SCC, and loss of neurons in the injured segment was evident for at least a month thereafter. Initial hindlimb paralysis was paralleled by a loss of descending inputs to lumbar motoneurons. Within 4 days of SCC and progressively thereafter, hindlimb motility began to be restored and descending inputs reappeared, but with examples of atypical synaptic connections indicating a reorganization of circuitry. One to two weeks after SCC, hindlimb motility approached sham control levels, and weight-bearing locomotion was virtually indistinguishable in SCC and sham control mice. Genetically labeled human fetal neural progenitor cells injected into the injured spinal cord survived for at least a month, integrated into the host tissue and began to differentiate morphologically. This integrative neonatal mouse model provides opportunities to explore early

  18. The cellular and subcellular localization of zinc transporter 7 in the mouse spinal cord

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    The present work addresses the cellular and subcellular localization of the zinc transporter 7 (ZNT7, SLC30a7) protein and the distribution of zinc ions (Zn2+) in the mouse spinal cord. Our results indicated that the ZNT7 immunoreactive neurons were widely distributed in the Rexed’s laminae of the g...

  19. Radiation therapy for primary spinal cord tumors in adults

    International Nuclear Information System (INIS)

    Jeremic, B.; Grujicic, D.; Jovanovic, D.; Djuric, L.; Mijatovic, L.

    1990-01-01

    This paper evaluates the role of radiation therapy in management of primary spinal cord tumors in adults. Records of 21 patients with primary spinal cord tumors treated with radiation therapy after surgery were retrospectively reviewed. Histologic examination showed two diffuse and 10 localized ependymomas, six low-grade gliomas, and three malignant gliomas. Surgery consisted of gross tumor resection in six patients, subtotal resection in three patients, and biopsy in 12 patients. Three patients also received chemotherapy. Radiation dose range from 45 to 55 Cy

  20. Synaptic defects in the spinal and neuromuscular circuitry in a mouse model of spinal muscular atrophy.

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    Karen K Y Ling

    2010-11-01

    Full Text Available Spinal muscular atrophy (SMA is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7. In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3-5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy.

  1. Lifestyle and health conditions of adults with spinal cord injury

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    Inacia Sátiro Xavier de França

    2014-07-01

    Full Text Available Objective. To describe the lifestyle of adults with spinal cord injury and explore its relation with some health conditions. Methodology. Cross sectional study, in which a questionnaire containing sociodemographic, habits and health conditions variables was used. Forty-seven people with spinal cord injury participated and answered the self-report questionnaire. Results. The group under study was predominantly male (92%, under 40 years of age (47%, and had low educational level (76%. The most frequent risk factors related to the lifestyle were: smoking (28%, alcohol consumption (36%, coffee consumption (92% and being physically inactive (64%. Association was found between having four or more risk factors related to lifestyle and the loss of appetite, as well as constipation. Conclusion. The actual inadequate lifestyle is associated with the health conditions of patients, and the nursing team should pay special attention to the education and promotion of health related to people with spinal cord injury.

  2. Lifestyle and health conditions of adults with spinal cord injury.

    Science.gov (United States)

    Xavier de França, Inacia Sátiro; Cruz Enders, Bertha; Silva Coura, Alexsandro; Pereira Cruz, Giovanna Karinny; da Silva Aragão, Jamilly; Carvalho de Oliveira, Déborah Raquel

    2014-01-01

    . To describe the lifestyle of adults with spinal cord injury and explore its relation with some health conditions. Cross sectional study, in which a questionnaire containing sociodemographic, habits and health conditions variables was used. Forty-seven people with spinal cord injury participated and answered the self-report questionnaire. The group under study was predominantly male (92%), under 40 years of age (47%), and had low educational level (76%). The most frequent risk factors related to the lifestyle were: smoking (28%), alcohol consumption (36%), coffee consumption (92%) and being physically inactive (64%). Association was found between having four or more risk factors related to lifestyle and the loss of appetite, as well as constipation. . The actual inadequate lifestyle is associated with the health conditions of patients, and the nursing team should pay special attention to the education and promotion of health related to people with spinal cord injury.

  3. Sim1 is required for the migration and axonal projections of V3 interneurons in the developing mouse spinal cord.

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    Blacklaws, Jake; Deska-Gauthier, Dylan; Jones, Christopher T; Petracca, Yanina L; Liu, Mingwei; Zhang, Han; Fawcett, James P; Glover, Joel C; Lanuza, Guillermo M; Zhang, Ying

    2015-09-01

    V3 spinal interneurons (INs) are a group of excitatory INs that play a crucial role in producing balanced and stable gaits in vertebrate animals. In the developing mouse spinal cord, V3 INs arise from the most ventral progenitor domain and form anatomically distinctive subpopulations in adult spinal cords. They are marked by the expression of transcription factor Sim1 postmitotically, but the function of Sim1 in V3 development remains unknown. Here, we used Sim1(Cre) ;tdTomato mice to trace the fate of V3 INs in a Sim1 mutant versus control genetic background during development. In Sim1 mutants, V3 INs are produced normally and maintain a similar position and organization as in wild types before E12.5. Further temporal analysis revealed that the V3 INs in the mutants failed to migrate properly to form V3 subgroups along the dorsoventral axis of the spinal cord. At birth, in the Sim1 mutant the number of V3 INs in the ventral subgroup was normal, but they were significantly reduced in the dorsal subgroup with a concomitant increase in the intermediate subgroup. Retrograde labeling at lumbar level revealed that loss of Sim1 led to a reduction in extension of contralateral axon projections both at E14.5 and P0 without affecting ipsilateral axon projections. These results demonstrate that Sim1 is essential for proper migration and the guidance of commissural axons of the spinal V3 INs. © 2015 Wiley Periodicals, Inc.

  4. Expression of Lymphatic Markers in the Adult Rat Spinal Cord.

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    Kaser-Eichberger, Alexandra; Schroedl, Falk; Bieler, Lara; Trost, Andrea; Bogner, Barbara; Runge, Christian; Tempfer, Herbert; Zaunmair, Pia; Kreutzer, Christina; Traweger, Andreas; Reitsamer, Herbert A; Couillard-Despres, Sebastien

    2016-01-01

    Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1-expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with

  5. 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.

  6. Segmental, synaptic actions of commissural interneurons in the mouse spinal cord

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    Quinlan, Katharina A.; Kiehn, Ole

    2007-01-01

    outlines the basic connectivity pattern of CINs in the mouse spinal cord on a segmental level. Our study suggests that, based on observed synaptic connectivity, both short- and long-range CINs are likely involved in segmental left-right coordination and that the CIN system is organized into a dual......-inhibitory and single-excitatory system. These systems are organized in a way that they could provide appropriate coordination during locomotion....

  7. Co-expression of GAD67 and choline acetyltransferase in neurons in the mouse spinal cord: A focus on lamina X.

    Science.gov (United States)

    Gotts, Jittima; Atkinson, Lucy; Yanagawa, Yuchio; Deuchars, Jim; Deuchars, Susan A

    2016-09-01

    Lamina X of the spinal cord is a functionally diverse area with roles in locomotion, autonomic control and processing of mechano and nociceptive information. It is also a neurochemically diverse region. However, the different populations of cells in lamina X remain to be fully characterised. To determine the co-localisation of the enzymes responsible for the production of GABA and acetylcholine (which play major roles in the spinal cord) in lamina X of the adult and juvenile mouse, we used a transgenic mouse expressing green fluorescent protein (GFP) in glutamate decarboxylase 67 (GAD67) neurons, combined with choline acetyltransferase (ChAT) immunohistochemistry. ChAT-immunoreactive (IR) and GAD67-GFP containing neurons were observed in lamina X of both adult and juvenile mice and in both age groups a population of cells containing both ChAT-IR and GAD67-GFP were observed in lumbar, thoracic and cervical spinal cord. Such dual labelled cells were predominantly located ventral to the central canal. Immunohistochemistry for vesicular acetylcholine transporter (VAChT) and GAD67 revealed a small number of double labelled terminals located lateral, dorsolateral and ventrolateral to the central canal. This study therefore describes in detail a population of ChAT-IR/GAD67-GFP neurons predominantly ventral to the central canal of the cervical, thoracic and lumbar spinal cord of adult and juvenile mice. These cells potentially correspond to a sub-population of the cholinergic central canal cluster cells which may play a unique role in controlling spinal cord circuitry. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Neurologic Outcomes of Complex Adult Spinal Deformity Surgery

    DEFF Research Database (Denmark)

    Lenke, Lawrence G; Fehlings, Michael G; Shaffrey, Christopher I

    2016-01-01

    STUDY DESIGN: Prospective, multicenter, international observational study. OBJECTIVE: To evaluate motor neurologic outcomes in patients undergoing surgery for complex adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA: The neurologic outcomes after surgical correction for ASD have been...... and 16.42% showed an improvement. At 6 months, 10.82% patients showed a decline in preoperative LEMS, 20.52% improvement, and 68.66% maintenance. This was a significant change compared with 6 weeks and at discharge. CONCLUSION: Although complex ASD surgery can restore neurologic function in patients...

  9. Imaging of infectious spinal disorders in children and adults

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    James, S.L.J. [Department of Radiology, Royal Orthopaedic Hospital, Birmingham B31 2AP (United Kingdom)]. E-mail: jamesslj@email.com; Davies, A.M. [Department of Radiology, Royal Orthopaedic Hospital, Birmingham B31 2AP (United Kingdom)]. E-mail: wendy.turner@roh.nhs.uk

    2006-04-15

    The aim of this review article is to outline the imaging of infectious disorders of the spine in adults and children. The clinical presentation, potential routes of infection and the pathogens commonly identified are discussed. The value of different imaging modalities in the diagnosis of spinal infection is presented including radiographic, CT, MR imaging and Nuclear Medicine including PET. The use of image guided techniques for diagnosis and subsequent treatment is briefly covered. The major differential diagnoses of infectious disorders of the spine are identified and contrasted with the typical findings in infection. The use of follow up imaging is evaluated.

  10. Effect of BCNU on mouse skin and spinal cord in single drug and radiation exposures

    International Nuclear Information System (INIS)

    Lelieveld, P.; Brown, J.M.; Goffinet, D.R.; Schoeppel, S.L.; Scoles, M.

    1979-01-01

    We set out to determine whether any interaction occurs between BCNU and radiation for the mouse skin and spinal cord. Single doses of BCNU of 10, 20, or 30 mg/kg were injected intraperitoneally as a function of time before or after irradiation of the foot or spinal cord of anesthesized C3H mice. Enhancement of the radiation skin reaction (dose enhancement factor = 1.3) was seen when BCNU (30 mg/kg) was given 1 day, 6 hr, and 2 hr prior to irradiation of the foot with 2,500 rad, and a larger DEF of 1.6 was observed when BCNU was given immediately before the radiation dose. However, with a different mouse strain (BALB/c) not anesthetized at the time of irradiation, no significant enhancement following a dose of 20 mg/kg BCNU was observed. Experiments are in progress to determine the cause of these differences. BCNU (10 mg/kg) was given 24 hr or immediately prior to various single doses of radiation to a 12 mm segment of the mouse spinal cord (T/sub 11-12/ to L/sub 1-2/), and the subsequent myelitis was scored monthly. The addition of BCNU to irradiation did not accelerate the development of myelitis, not the ultimate proportion of animals developing hind limb paralysis: the 50% myelitis dose at 10 months (MD/sub 50/10/sub mo/) values for irradiation alone, BCNU at the time of irradiation and 24 hr before were 3,722, 3,795 and 3,853 rad, respectively

  11. Cortex-dependent recovery of unassisted hindlimb locomotion after complete spinal cord injury in adult rats

    Science.gov (United States)

    Manohar, Anitha; Foffani, Guglielmo; Ganzer, Patrick D; Bethea, John R; Moxon, Karen A

    2017-01-01

    After paralyzing spinal cord injury the adult nervous system has little ability to ‘heal’ spinal connections, and it is assumed to be unable to develop extra-spinal recovery strategies to bypass the lesion. We challenge this assumption, showing that completely spinalized adult rats can recover unassisted hindlimb weight support and locomotion without explicit spinal transmission of motor commands through the lesion. This is achieved with combinations of pharmacological and physical therapies that maximize cortical reorganization, inducing an expansion of trunk motor cortex and forepaw sensory cortex into the deafferented hindlimb cortex, associated with sprouting of corticospinal axons. Lesioning the reorganized cortex reverses the recovery. Adult rats can thus develop a novel cortical sensorimotor circuit that bypasses the lesion, probably through biomechanical coupling, to partly recover unassisted hindlimb locomotion after complete spinal cord injury. DOI: http://dx.doi.org/10.7554/eLife.23532.001 PMID:28661400

  12. The increased prevalence of cervical spondylosis in patients with adult thoracolumbar spinal deformity.

    Science.gov (United States)

    Schairer, William W; Carrer, Alexandra; Lu, Michael; Hu, Serena S

    2014-12-01

    Retrospective cohort study. To assess the concomitance of cervical spondylosis and thoracolumbar spinal deformity. Patients with degenerative cervical spine disease have higher rates of degeneration in the lumbar spine. In addition, degenerative cervical spine changes have been observed in adult patients with thoracolumbar spinal deformities. However, to the best of our knowledge, there have been no studies quantifying the association between cervical spondylosis and thoracolumbar spinal deformity in adult patients. Patients seen by a spine surgeon or spine specialist at a single institution were assessed for cervical spondylosis and/or thoracolumbar spinal deformity using an administrative claims database. Spinal radiographic utilization and surgical intervention were used to infer severity of spinal disease. The relative prevalence of each spinal diagnosis was assessed in patients with and without the other diagnosis. A total of 47,560 patients were included in this study. Cervical spondylosis occurred in 13.1% overall, but was found in 31.0% of patients with thoracolumbar spinal deformity (OR=3.27, Pspondylosis (OR=3.26, Pspondylosis or thoracolumbar spinal deformity had significantly higher rates of the other spinal diagnosis. This correlation was increased with increased severity of disease. Patients with both diagnoses were significantly more likely to have received a spine fusion. Further research is warranted to establish the cause of this correlation. Clinicians should use this information to both screen and counsel patients who present for cervical spondylosis or thoracolumbar spinal deformity.

  13. Early development of the circumferential axonal pathway in mouse and chick spinal cord.

    Science.gov (United States)

    Holley, J A

    1982-03-10

    The early development of the circumferential axonal pathway in the brachial and lumbar spinal cord of mouse and chick embryos was studied by scanning and transmission electron microscopy. The cellular processes which comprise this pathway grow in the transverse plane and along the lateral margin of the marginal zone (i.e., circumferentially oriented), as typified by the early embryonic commissural axons. The first formative event observed was in the ventrolateral margin of the primitive spinal cord ventricular zone. Cellular processes were found near the external limiting membrane that appeared to grow a variable distance either dorsally or ventrally. Later in development, presumptive motor column neurons migrated into the ventrolateral region, distal to these early circumferentially oriented processes. Concurrently, other circumferentially oriented perikarya and processes appeared along the dorsolateral margin. Due to their aligned sites of origin and parallel growth, the circumferential processes formed a more or less continuous line or pathway, which in about 10% of the scanned specimens could be followed along the entire lateral margin of the embryonic spinal cord. Several specimens later in development had two sets of aligned circumferential processes in the ventral region. Large numbers of circumferential axons were then found to follow the preformed pathway by fasciculation, after the primitive motor column had become established. Since the earliest circumferential processes appeared to differentiate into axons and were found nearly 24 hours prior to growth of most circumferential axons, their role in guidance as pioneering axons was suggested.

  14. Spinal metastasis of medulloblastoma in adults: A case report

    Directory of Open Access Journals (Sweden)

    Živković Nenad

    2014-01-01

    Full Text Available Introduction. Medulloblastoma is a primitive neuro-ectodermal malignant tumor most commonly seen in childhood and rarely and uncommonly in adult age. Treatment consists of surgery followed by radiotherapy. In the case of a relapse there is no overall accepted treatment. Tumor metastasis can be seen along the neural axis, lymph nodes, soft tissues, bones and distant organs. Case Outline. In this paper we present a 45-year-old female patient with a thoraco-spinal extramedullary metastatic medulloblastoma and progressive neurological deterioration seen 11 months after the first operation and description of magnetic resonance and intraoperative finding. Conclusion. Although rare, the presence of metastasis is a poor prognostic factor. The treatment options for patients with metastases are limited and their prognosis continues to remain poor.

  15. Protective Effects of Butyrate-based Compounds on a Mouse Model for Spinal Muscular Atrophy

    Science.gov (United States)

    Butchbach, Matthew E. R.; Lumpkin, Casey J.; Harris, Ashlee W.; Saieva, Luciano; Edwards, Jonathan D.; Workman, Eileen; Simard, Louise R.; Pellizzoni, Livio; Burghes, Arthur H. M.

    2016-01-01

    Proximal spinal muscular atrophy (SMA) is a childhood-onset degenerative disease resulting from the selective loss of motor neurons in the spinal cord. SMA is caused by the loss of SMN1 (survival motor neuron 1) but retention of SMN2. The number of copies of SMN2 modifies disease severity in SMA patients as well as in mouse models, making SMN2 a target for therapeutics development. Sodium butyrate (BA) and its analogue (4PBA) have been shown to increase SMN2 expression in SMA cultured cells. In this study, we examined the effects of BA, 4PBA as well as two BA prodrugs—glyceryl tributyrate (BA3G) and VX563—on the phenotype of SMNΔ7 SMA mice. Treatment with 4PBA, BA3G and VX563 but not BA beginning at PND04 significantly improved the lifespan and delayed disease end stage, with administration of VX563 also improving the growth rate of these mice. 4PBA and VX563 improved the motor phenotype of SMNΔ7 SMA mice and prevented spinal motor neuron loss. Interestingly, neither 4PBA nor VX563 had an effect on SMN expression in the spinal cords of treated SMNΔ7 SMA mice; however, they inhibited histone deacetylase (HDAC) activity and restored the normal phosphorylation states of Akt and glycogen synthase kinase 3β, both of which are altered by SMN deficiency in vivo. These observations show that BA-based compounds with favourable pharmacokinetics ameliorate SMA pathology possibly by modulating HDAC and Akt signaling. PMID:26892876

  16. The late and dual origin of cerebrospinal fluid-contacting neurons in the mouse spinal cord.

    Science.gov (United States)

    Petracca, Yanina L; Sartoretti, Maria Micaela; Di Bella, Daniela J; Marin-Burgin, Antonia; Carcagno, Abel L; Schinder, Alejandro F; Lanuza, Guillermo M

    2016-03-01

    Considerable progress has been made in understanding the mechanisms that control the production of specialized neuronal types. However, how the timing of differentiation contributes to neuronal diversity in the developing spinal cord is still a pending question. In this study, we show that cerebrospinal fluid-contacting neurons (CSF-cNs), an anatomically discrete cell type of the ependymal area, originate from surprisingly late neurogenic events in the ventral spinal cord. CSF-cNs are identified by the expression of the transcription factors Gata2 and Gata3, and the ionic channels Pkd2l1 and Pkd1l2. Contrasting with Gata2/3(+) V2b interneurons, differentiation of CSF-cNs is independent of Foxn4 and takes place during advanced developmental stages previously assumed to be exclusively gliogenic. CSF-cNs are produced from two distinct dorsoventral regions of the mouse spinal cord. Most CSF-cNs derive from progenitors circumscribed to the late-p2 and the oligodendrogenic (pOL) domains, whereas a second subset of CSF-cNs arises from cells bordering the floor plate. The development of these two subgroups of CSF-cNs is differentially controlled by Pax6, they adopt separate locations around the postnatal central canal and they display electrophysiological differences. Our results highlight that spatiotemporal mechanisms are instrumental in creating neural cell diversity in the ventral spinal cord to produce distinct classes of interneurons, motoneurons, CSF-cNs, glial cells and ependymal cells. © 2016. Published by The Company of Biologists Ltd.

  17. Spinal Implant Density and Postoperative Lumbar Lordosis as Predictors for the Development of Proximal Junctional Kyphosis in Adult Spinal Deformity.

    Science.gov (United States)

    McClendon, Jamal; Smith, Timothy R; Sugrue, Patrick A; Thompson, Sara E; O'Shaughnessy, Brian A; Koski, Tyler R

    2016-11-01

    To evaluate spinal implant density and proximal junctional kyphosis (PJK) in adult spinal deformity (ASD). Consecutive patients with ASD receiving ≥5 level fusions were retrospectively analyzed between 2007 and 2010. ASD, elective fusions, minimum 2-year follow-up. age lordosis (LL) were predictors for PJK (P = 0.018 and 0.045, respectively). Controlling for age, BMI, and gender, postoperative LL (not implant density) continued to show significance in multivariate logistic regression model. PJK, although influenced by a multitude of factors, may be statistically related to implant density and LL. Copyright © 2016. Published by Elsevier Inc.

  18. Transplanted Human Stem Cell-Derived Interneuron Precursors Mitigate Mouse Bladder Dysfunction and Central Neuropathic Pain after Spinal Cord Injury.

    Science.gov (United States)

    Fandel, Thomas M; Trivedi, Alpa; Nicholas, Cory R; Zhang, Haoqian; Chen, Jiadong; Martinez, Aida F; Noble-Haeusslein, Linda J; Kriegstein, Arnold R

    2016-10-06

    Neuropathic pain and bladder dysfunction represent significant quality-of-life issues for many spinal cord injury patients. Loss of GABAergic tone in the injured spinal cord may contribute to the emergence of these symptoms. Previous studies have shown that transplantation of rodent inhibitory interneuron precursors from the medial ganglionic eminence (MGE) enhances GABAergic signaling in the brain and spinal cord. Here we look at whether transplanted MGE-like cells derived from human embryonic stem cells (hESC-MGEs) can mitigate the pathological effects of spinal cord injury. We find that 6 months after transplantation into injured mouse spinal cords, hESC-MGEs differentiate into GABAergic neuron subtypes and receive synaptic inputs, suggesting functional integration into host spinal cord. Moreover, the transplanted animals show improved bladder function and mitigation of pain-related symptoms. Our results therefore suggest that this approach may be a valuable strategy for ameliorating the adverse effects of spinal cord injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Shenfu injection attenuates neurotoxicity of bupivacaine in cultured mouse spinal cord neurons

    Institute of Scientific and Technical Information of China (English)

    XIONG Li-ze; WANG Qiang; LIU Mu-yun; PENG Ye; LI Qing-bo; LU Zhi-hong; LEI Chong

    2007-01-01

    Background Our previous in vivo study in the rat demonstrates that Shenfu injection, a clinically used extract preparation from Chinese herbs, attenuates neural and cardiac toxicity induced by intravenous infusion of bupivacaine, a local anesthetic. This study was designed to investigate whether bupivacaine could induce a toxic effect in primary cultured mouse spinal cord neuron and if so, whether the Shenfu injection had a similar neuroprotective effect in the cell model. Methods The spinal cords from 11- to 14-day-old fetal mice were minced and incubated. Cytarabine was added into the medium to inhibit the proliferation of non-neuronal cells. The immunocytochemical staining of β-tubulin was used to determine the identity of cultured cells. The cultured neurons were randomly assigned into three sets treated with various doses of bupivacaine, Shenfu and bupivacaine+Shenfu, for 48 hours respectively. Cell viability in each group was analyzed by methyl thiazoleterazolium (MTT) assay. Results The viability of the cultured neurons treated with bupivacaine at concentrations of 0.01%, 0.02%, 0.04% and 0.08% was decreased in a dose-dependent manner. Although the Shenfu injection at concentrations ranging from 1/50 to 1/12.5 (V/V) had no significant influence on the viability of cultured neurons (P<0.05 vs control), the injection significantly increased the cellular viability of cultured neurons pretreated with 0.03% bupivacaine (P<0.05). Conclusion Although Shenfu injection itself has no effect on spinal neurons, it was able to reduce the bupivacaine induced neurotoxicity in vitro.

  20. The Smn-independent beneficial effects of trichostatin A on an intermediate mouse model of spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Hong Liu

    Full Text Available Spinal muscular atrophy is an autosomal recessive neuromuscular disease characterized by the progressive loss of alpha motor neurons in the spinal cord. Trichostatin A (TSA is a histone deacetylase inhibitor with beneficial effects in spinal muscular atrophy mouse models that carry the human SMN2 transgene. It is currently unclear whether TSA specifically targets the SMN2 gene or whether other genes respond to TSA and in turn provide neuroprotection in SMA mice. We have taken advantage of the Smn2B/- mouse model that does not harbor the human SMN2 transgene, to test the hypothesis that TSA has its beneficial effects through a non-SMN mediated pathway. TSA increased the median lifespan of Smn2B/- mice from twenty days to eight weeks. As well, there was a significant attenuation of weight loss and improved motor behavior. Pen test and righting reflex both showed significant improvement, and motor neurons in the spinal cord of Smn2B/- mice were protected from degeneration. Both the size and maturity of neuromuscular junctions were significantly improved in TSA treated Smn2B/- mice. Of interest, TSA treatment did not increase the levels of Smn protein in mouse embryonic fibroblasts or myoblasts obtained from the Smn2B/- mice. In addition, no change in the level of Smn transcripts or protein in the brain or spinal cord of TSA-treated SMA model mice was observed. Furthermore, TSA did not increase Smn protein levels in the hind limb muscle, heart, or liver of Smn2B/- mice. We therefore conclude that TSA likely exerts its effects independent of the endogenous mouse Smn gene. As such, identification of the pathways regulated by TSA in the Smn2B/- mice could lead to the development of novel therapeutics for treating SMA.

  1. Lumbar spinal mobility changes among adults with advancing age

    Directory of Open Access Journals (Sweden)

    Ismaila Adamu Saidu

    2011-01-01

    Conclusion : Using these data, we developed normative values of spinal mobility for each sex and age group. This study helps the clinicians to understand and correlate the restrictions of lumbar spinal mobility due to age and differentiate the limitations due to disease.

  2. Radiographic Predictors for Mechanical Failure After Adult Spinal Deformity Surgery

    DEFF Research Database (Denmark)

    Hallager, Dennis W; Karstensen, Sven; Bukhari, Naeem

    2017-01-01

    spinal deformity surgery range 12% to 37% in literature. Although the importance of spinal and spino-pelvic alignment is well documented for surgical outcome and ideal alignment has been proposed as sagittal vertical axis (SVA) lordosis (LL) = pelvic incidence ± 9...

  3. ATM localization and gene expression in the adult mouse eye.

    Science.gov (United States)

    Leemput, Julia; Masson, Christel; Bigot, Karine; Errachid, Abdelmounaim; Dansault, Anouk; Provost, Alexandra; Gadin, Stéphanie; Aoufouchi, Said; Menasche, Maurice; Abitbol, Marc

    2009-01-01

    High levels of metabolism and oxygen consumption in most adult murine ocular compartments, combined with exposure to light and ultraviolet (UV) radiation, are major sources of oxidative stress, causing DNA damage in ocular cells. Of all mammalian body cells, photoreceptor cells consume the largest amount of oxygen and generate the highest levels of oxidative damage. The accumulation of such damage throughout life is a major factor of aging tissues. Several multiprotein complexes have recently been identified as the major sensors and mediators involved in the maintenance of DNA integrity. The activity of these complexes initially seemed to be restricted to dividing cells, given their ultimate role in major cell cycle checkpoints. However, it was later established that they are also active in post-mitotic cells. Recent findings demonstrate that the DNA damage response (DDR) is essential for the development, maintenance, and normal functioning of the adult central nervous system. One major molecular factor in the DDR is the protein, ataxia telangiectasia mutated (ATM). It is required for the rapid induction of cellular responses to DNA double-strand breaks. These cytotoxic DNA lesions may be caused by oxidative damage. To understand how ATM prevents oxidative stress and participates in the maintenance of genomic integrity and cell viability of the adult retina, we determined the ATM expression patterns and studied its localization in the adult mouse eye. Atm gene expression was analyzed by RT-PCR experiments and its localization by in situ hybridization on adult mouse ocular and cerebellar tissue sections. ATM protein expression was determined by western blot analysis of proteins homogenates extracted from several mouse tissues and its localization by immunohistochemistry experiments performed on adult mouse ocular and cerebellar tissue sections. In addition, subcellular localization was realized by confocal microscopy imaging of ocular tissue sections, with a special

  4. A Comprehensive Atlas of the Adult Mouse Penis

    Science.gov (United States)

    Phillips, Tiffany R.; Wright, David K.; Gradie, Paul E.; Johnston, Leigh A.; Pask, Andrew J.

    2016-01-01

    Mice are routinely used to study the development of the external genitalia and, in particular, the process of male urethral closure. This is because misplacement of the male penile urethra, or hypospadias, is amongst the most common birth defects reported in humans. While mice present a tractable model to study penile development, several structures differ between mice and humans, and there is a lack of consensus in the literature on their annotation and developmental origins. Defining the ontology of the mouse prepuce is especially important for the relevance and interpretation of mouse models of hypospadias to human conditions. We have developed a detailed annotation of the adult mouse penis that addresses these differences and enables an accurate comparison of murine and human hypospadias phenotypes. Through MRI data, gross morphology and section histology, we define the origin of the mouse external and internal prepuces, their relationship to the single human foreskin as well as provide a comprehensive view of the various structures of the mouse penis and their associated muscle attachments within the body. These data are combined to annotate structures in a novel 3D adult penis atlas that can be downloaded, viewed at any angle, and manipulated to examine the relationship of various structures. PMID:26112156

  5. New Insights on the Morphology of Adult Mouse Penis1

    Science.gov (United States)

    Rodriguez, Esequiel; Weiss, Dana A.; Yang, Jennifer H.; Menshenina, Julia; Ferretti, Max; Cunha, Tristan J.; Barcellos, Dale; Chan, Lok Yun; Risbridger, Gail; Cunha, Gerald R.; Baskin, Laurence S.

    2011-01-01

    ABSTRACT The adult mouse penis represents the end point of masculine sex differentiation of the embryonic genital tubercle and contains bone, cartilage, the urethra, erectile bodies, several types of epithelium, and many individual cell types arrayed into specific anatomical structures. Using contemporary high-resolution imaging techniques, we sought to provide new insights to the current description of adult mouse penile morphology to enable understanding of penile abnormalities, including hypospadias. Examination of serial transverse and longitudinal sections, scanning electron microscopy, and three-dimensional (3D) reconstruction provided a new appreciation of the individual structures in the adult mouse penis and their 3D interrelationships. In so doing, we discovered novel paired erectile bodies, the male urogenital mating protuberance (MUMP), and more accurately described the urethral meatus. These morphological observations were quantified by morphometric analysis and now provide accurate morphological end points of sex differentiation of mouse penis that will be the foundation of future studies to identify normal and abnormal penile development. PMID:21918128

  6. Spontaneous recovery of locomotion induced by remaining fibers after spinal cord transection in adult rats.

    Science.gov (United States)

    You, Si-Wei; Chen, Bing-Yao; Liu, Hui-Ling; Lang, Bing; Xia, Jie-Lai; Jiao, Xi-Ying; Ju, Gong

    2003-01-01

    A major issue in analysis of experimental results after spinal cord injury is spontaneous functional recovery induced by remaining nerve fibers. The authors investigated the relationship between the degree of locomotor recovery and the percentage and location of the fibers that spared spinal cord transection. The spinal cords of 12 adult rats were transected at T9 with a razor blade, which often resulted in sparing of nerve fibers in the ventral spinal cord. The incompletely-transected animals were used to study the degree of spontaneous recovery of hindlimb locomotion, evaluated with the BBB rating scale, in correlation to the extent and location of the remaining fibers. Incomplete transection was found in the ventral spinal cord in 42% of the animals. The degree of locomotor recovery was highly correlated with the percentage of the remaining fibers in the ventral and ventrolateral funiculi. In one of the rats, 4.82% of remaining fibers in unilateral ventrolateral funiculus were able to sustain a certain recovery of locomotion. Less than 5% of remaining ventrolateral white matter is sufficient for an unequivocal motor recovery after incomplete spinal cord injury. Therefore, for studies with spinal cord transection, the completeness of sectioning should be carefully checked before any conclusion can be reached. The fact that the degree of locomotor recovery is correlated with the percentage of remaining fibers in the ventrolateral spinal cord, exclusive of most of the descending motor tracts, may imply an essential role of propriospinal connections in the initiation of spontaneous locomotor recovery.

  7. Radiation-induced apoptosis in the neonatal and adult rat spinal cord.

    Science.gov (United States)

    Li, Y Q; Wong, C S

    2000-09-01

    This study was designed to characterize radiation-induced apoptosis in the spinal cord of the neonatal and young adult rat. Spinal cords (C2-T2) of 1-, 2- and 10-week-old rats were irradiated with a single dose of 8, 18 or 22 Gy. Apoptosis was assessed histologically according to its specific morphological features or by using the TUNEL assay. Cell proliferation was assessed immunohistochemically using BrdU. Identities of cell types undergoing apoptosis were assessed using immunohistochemistry or in situ hybridization using markers for neurons, glial progenitor cells, microglia, oligodendrocytes and astrocytes. The time course of radiation-induced apoptosis in 1- or 2-week-old rat spinal cord was similar to that in the young adult rat spinal cord. A peak response was observed at about 8 h after irradiation, and the apoptosis index returned to the levels in nonirradiated spinal cords at 24 h. The neonatal rat spinal cord demonstrated increased apoptosis compared to the adult. Values for total yield of apoptosis over 24 h induced by 8 Gy in the neonatal rat spinal cord were significantly greater than that in the adult. Immunohistochemistry studies using Leu7, galactocerebroside, Rip and adenomatous polyposis coli tumor suppressor protein indicated that most apoptotic cells were cells of the oligodendroglial lineage regardless of the age of the animal. No evidence of Gfap or factor VIII-related antigen-positive apoptotic cells was observed, and there was a small number of apoptotic microglial cells (lectin-Rca1 positive) in the neonatal and adult rat spinal cord. In the neonatal but not adult rat spinal cord, about 10% of the apoptotic cells appeared to be neurons and were immunoreactive for synaptophysin. Labeling indices (LI) for BrdU in nonirradiated 1- and 2-week-old rat spinal cord were 20.0 and 16.3%, respectively, significantly greater than the LI of 1.0% in the 10-week-old rat spinal cord. At 8 h after a single dose of 8 Gy, 13.4% of the apoptotic cells were

  8. High-speed video analysis improves the accuracy of spinal cord compression measurement in a mouse contusion model.

    Science.gov (United States)

    Fournely, Marion; Petit, Yvan; Wagnac, Éric; Laurin, Jérôme; Callot, Virginie; Arnoux, Pierre-Jean

    2018-01-01

    Animal models of spinal cord injuries aim to utilize controlled and reproducible conditions. However, a literature review reveals that mouse contusion studies using equivalent protocols may show large disparities in the observed impact force vs. cord compression relationship. The overall purpose of this study was to investigate possible sources of bias in these measurements. The specific objective was to improve spinal cord compression measurements using a video-based setup to detect the impactor-spinal cord time-to-contact. A force-controlled 30kDyn unilateral contusion at C4 vertebral level was performed in six mice with the Infinite Horizon impactor (IH). High-speed video was used to determine the time-to-contact between the impactor tip and the spinal cord and to compute the related displacement of the tip into the tissue: the spinal cord compression and the compression ratio. Delayed time-to-contact detection with the IH device led to an underestimation of the cord compression. Compression values indicated by the IH were 64% lower than those based on video analysis (0.33mm vs. 0.88mm). Consequently, the mean compression ratio derived from the device was underestimated when compared to the value derived from video analysis (22% vs. 61%). Default time-to-contact detection from the IH led to significant errors in spinal cord compression assessment. Accordingly, this may explain some of the reported data discrepancies in the literature. The proposed setup could be implemented by users of contusion devices to improve the quantative description of the primary injury inflicted to the spinal cord. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Peripheral Androgen Receptor Gene Suppression Rescues Disease in Mouse Models of Spinal and Bulbar Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Andrew P. Lieberman

    2014-05-01

    Full Text Available Spinal and bulbar muscular atrophy (SBMA is caused by the polyglutamine androgen receptor (polyQ-AR, a protein expressed by both lower motor neurons and skeletal muscle. Although viewed as a motor neuronopathy, data from patients and mouse models suggest that muscle contributes to disease pathogenesis. Here, we tested this hypothesis using AR113Q knockin and human bacterial artificial chromosome/clone (BAC transgenic mice that express the full-length polyQ-AR and display androgen-dependent weakness, muscle atrophy, and early death. We developed antisense oligonucleotides that suppressed AR gene expression in the periphery but not the CNS after subcutaneous administration. Suppression of polyQ-AR in the periphery rescued deficits in muscle weight, fiber size, and grip strength, reversed changes in muscle gene expression, and extended the lifespan of mutant males. We conclude that polyQ-AR expression in the periphery is an important contributor to pathology in SBMA mice and that peripheral administration of therapeutics should be explored for SBMA patients.

  10. Functional characterization of dI6 interneurons in the neonatal mouse spinal cord.

    Science.gov (United States)

    Dyck, Jason; Lanuza, Guillermo M; Gosgnach, Simon

    2012-06-01

    Our understanding of the neural control of locomotion has been greatly enhanced by the ability to identify and manipulate genetically defined populations of interneurons that comprise the locomotor central pattern generator (CPG). To date, the dI6 interneurons are one of the few populations that settle in the ventral region of the postnatal spinal cord that have not been investigated. In the present study, we utilized a novel transgenic mouse line to electrophysiologically characterize dI6 interneurons located close to the central canal and study their function during fictive locomotion. The majority of dI6 cells investigated were found to be rhythmically active during fictive locomotion and could be divided into two electrophysiologically distinct populations of interneurons. The first population fired rhythmic trains of action potentials that were loosely coupled to ventral root output and contained several intrinsic membrane properties of rhythm-generating neurons, raising the possibility that these cells may be involved in the generation of rhythmic activity in the locomotor CPG. The second population fired rhythmic trains of action potentials that were tightly coupled to ventral root output and lacked intrinsic oscillatory mechanisms, indicating that these neurons may be driven by a rhythm-generating network. Together these results indicate that dI6 neurons comprise an important component of the locomotor CPG that participate in multiple facets of motor behavior.

  11. Predictors of Health-Related Quality-of-Life After Complex Adult Spinal Deformity Surgery

    DEFF Research Database (Denmark)

    Carreon, Leah Y.; Glassman, Steven D.; Shaffrey, Christopher I.

    2017-01-01

    , treatment effectiveness is assessed by the extent to which the procedure improves a patient's health-related quality of life (HRQOL). This is especially true in patients with complex adult spinal deformity. Methods The data set from the Scoli-Risk-1 study was queried for patients with complete 2-year SF-36......Study Design Longitudinal cohort. Objectives To identify variables that predict 2-year Short Form-36 Physical Composite Summary Score (SF-36PCS) and the Scoliosis Research Society-22R (SRS22-R) Total score after surgery for complex adult spinal deformity. Summary of Background Data Increasingly...... = .049) and type of neurologic complication (p = .068). Factors predictive of 2-year SRS-22R Total scores were maximum preoperative Cobb angle (p = .001) and the number of serious adverse events (p = .071). Conclusions Factors predictive of lower 2-year HRQOLs after surgery for complex adult spinal...

  12. The adult spinal cord injury without radiographic abnormalities syndrome: magnetic resonance imaging and clinical findings in adults with spinal cord injuries having normal radiographs and computed tomography studies.

    Science.gov (United States)

    Kasimatis, Georgios B; Panagiotopoulos, Elias; Megas, Panagiotis; Matzaroglou, Charalambos; Gliatis, John; Tyllianakis, Minos; Lambiris, Elias

    2008-07-01

    Spinal cord injury without radiographic abnormalities (SCIWORA) is thought to represent mostly a pediatric entity and its incidence in adults is rather underreported. Some authors have also proposed the term spinal cord injury without radiologic evidence of trauma, as more precisely describing the condition of adult SCIWORA in the setting of cervical spondylosis. The purpose of the present study was to evaluate adult patients with cervical spine injuries and radiological-clinical examination discrepancy, and to discuss their characteristics and current management. During a 16-year period, 166 patients with a cervical spine injury were admitted in our institution (Level I trauma center). Upper cervical spine injuries (occiput to C2, 54 patients) were treated mainly by a Halo vest, whereas lower cervical spine injuries (C3-T1, 112 patients) were treated surgically either with an anterior, or posterior procedure, or both. Seven of these 166 patients (4.2%) had a radiologic-clinical mismatch, i.e., they presented with frank spinal cord injury with no signs of trauma, and were included in the study. Magnetic resonance imaging was available for 6 of 7 patients, showing intramedullary signal changes in 5 of 6 patients with varying degrees of compression from the disc and/or the ligamentum flavum, whereas the remaining patient had only traumatic herniation of the intervertebral disc and ligamentum flavum bulging. Follow-up period was 6.4 years on average (1-10 years). This retrospective chart review provides information on adult patients with cervical spinal cord injuries whose radiographs and computed tomography studies were normal. It furthers reinforces the pathologic background of SCIWORA in an adult population, when evaluated by magnetic resonance imaging. Particularly for patients with cervical spondylosis, special attention should be paid with regard to vascular compromise by predisposing factors such as smoking or vascular disease, since they probably contribute in

  13. Diagnosis and treatment of adult medulloblastoma seeding in the intracranial-spinal subarachnoid space

    Directory of Open Access Journals (Sweden)

    Ji-wei WANG

    2015-10-01

    Full Text Available Objective To investigate the clinical diagnosis and treatment of adult medulloblastoma seeding in the intracranial-spinal subarachnoid space. Methods Eleven cases of adult medulloblastoma seeding in the intracranial-spinal subarachnoid space were retrospectively analyzed on the clinical features, cerebrospinal fluid (CSF cytology, radiological characteristics and treatments. Results All patients underment neurosurgical procedures to remove medulloblastomas. In 10 patients, tumor was removed through suboccipital posterior midline approach and in one patient through post-sigmoid sinus approach. In 7 patients tumor cell seeding was found in the intracranial-spinal subarachnoid space before postoperative radiotherapy and disappeared after radiological and chemical treatment, while in other 4 patients tumor cell seeding was found in the intracranial-spinal subarachnoid space at 3 months to 3 years follow-up period (average 20 months after radiotherapy. In 2 of all the patients tumor cells were found by CSF cytology before operation. All the patients were treated with radiotherapy and adjuvant chemotherapy. Two patients were still alive, while 9 patients were dead. Conclusions Patients with adult medulloblastoma seeding in intracranial-spinal subarachnoid space have a poor prognosis. In the diagnosis of adult medulloblastomas seeding in the intracranial-spinal subarachnoid space, MRI is more sensitive than CSF cytology. Once the seeding in intracranial-spinal subarachnoid space was found, the patients should be treated with radiotherapy and adjuvant chemotherapy, which can prolong the survival time and improve the quality of life. DOI: 10.3969/j.issn.1672-6731.2015.10.012 

  14. Resilience and the rehabilitation of adult spinal cord injury survivors: A qualitative systematic review.

    Science.gov (United States)

    Kornhaber, Rachel; Mclean, Loyola; Betihavas, Vasiliki; Cleary, Michelle

    2018-01-01

    To synthesize the qualitative research evidence that explored how survivors of adult spinal cord injury experience and make sense of resilience. Spinal cord injury is often a sudden and unexpected life-changing event requiring complex and long-term rehabilitation. The development of resilience is essential in determining how spinal cord injury survivors negotiate this injury and rehabilitation. A qualitative systematic review and thematic synthesis of the research evidence. CINAHL, PubMed, Embase, Scopus and PsycINFO were searched, no restriction dates were used. Methodological quality was assessed using the Critical Appraisal Skills Programme checklist. Thematic synthesis focused on how survivors of adult spinal cord injury experience and make sense of resilience. Six qualitative research articles reported the experiences of 84 spinal cord injury survivors. Themes identified were: uncertainty and regaining independence; prior experiences of resilience; adopting resilient thinking; and strengthening resilience through supports. Recovery and rehabilitation following spinal cord survivors is influenced by the individual's capacity for resilience. Resilience may be influenced by previous life experiences and enhanced by supportive nursing staff encouraging self-efficacy. Survivors identified the need for active involvement in decision-making about their care to enable a sense of regaining control of their lives. This has the potential to have a significant impact on their self-efficacy and in turn health outcomes. © 2017 John Wiley & Sons Ltd.

  15. A brain-specific gene cluster isolated from the region of the mouse obesity locus is expressed in the adult hypothalamus and during mouse development

    Energy Technology Data Exchange (ETDEWEB)

    Laig-Webster, M.; Lim, M.E.; Chehab, F.F. [Univ. of California, San Francisco, CA (United States)

    1994-09-01

    The molecular defect underlying an autosomal recessive form of genetic obesity in a classical mouse model C57 BL/6J-ob/ob has not yet been elucidated. Whereas metabolic and physiological disturbances such as diabetes and hypertension are associated with obesity, the site of expression and the nature of the primary lesion responsible for this cascade of events remains elusive. Our efforts aimed at the positional cloning of the ob gene by YAC contig mapping and gene identification have resulted in the cloning of a brain-specific gene cluster from the ob critical region. The expression of this gene cluster is remarkably complex owing to the multitude of brain-specific mRNA transcripts detected on Northern blots. cDNA cloning of these transcripts suggests that they are expressed from different genes as well as by alternate splicing mechanisms. Furthermore, the genomic organization of the cluster appears to consist of at least two identical promoters displaying CpG islands characteristic of housekeeping genes, yet clearly involving tissue-specific expression. Sense and anti-sense synthetic RNA probes were derived from a common DNA sequence on 3 cDNA clones and hybridized to 8-16 days mouse embryonic stages and mouse adult brain sections. Expression in development was noticeable as of the 11th day of gestation and confined to the central nervous system mainly in the telencephalon and spinal cord. Coronal and sagittal sections of the adult mouse brain showed expression only in 3 different regions of the brain stem. In situ hybridization to mouse hypothalamus sections revealed the presence of a localized and specialized group of cells expressing high levels of mRNA, suggesting that this gene cluster may also be involved in the regulation of hypothalamic activities. The hypothalamus has long been hypothesized as a primary candidate tissue for the expression of the obesity gene mainly because of its well-established role in the regulation of energy metabolism and food intake.

  16. Analysis of the fibroblast growth factor system reveals alterations in a mouse model of spinal muscular atrophy.

    Science.gov (United States)

    Hensel, Niko; Ratzka, Andreas; Brinkmann, Hella; Klimaschewski, Lars; Grothe, Claudia; Claus, Peter

    2012-01-01

    The monogenetic disease Spinal Muscular Atrophy (SMA) is characterized by a progressive loss of motoneurons leading to muscle weakness and atrophy due to severe reduction of the Survival of Motoneuron (SMN) protein. Several models of SMA show deficits in neurite outgrowth and maintenance of neuromuscular junction (NMJ) structure. Survival of motoneurons, axonal outgrowth and formation of NMJ is controlled by neurotrophic factors such as the Fibroblast Growth Factor (FGF) system. Besides their classical role as extracellular ligands, some FGFs exert also intracellular functions controlling neuronal differentiation. We have previously shown that intracellular FGF-2 binds to SMN and regulates the number of a subtype of nuclear bodies which are reduced in SMA patients. In the light of these findings, we systematically analyzed the FGF-system comprising five canonical receptors and 22 ligands in a severe mouse model of SMA. In this study, we demonstrate widespread alterations of the FGF-system in both muscle and spinal cord. Importantly, FGF-receptor 1 is upregulated in spinal cord at a pre-symptomatic stage as well as in a mouse motoneuron-like cell-line NSC34 based model of SMA. Consistent with that, phosphorylations of FGFR-downstream targets Akt and ERK are increased. Moreover, ERK hyper-phosphorylation is functionally linked to FGFR-1 as revealed by receptor inhibition experiments. Our study shows that the FGF system is dysregulated at an early stage in SMA and may contribute to the SMA pathogenesis.

  17. Functional expression of T-type Ca2+ channels in spinal motoneurons of the adult turtle.

    Directory of Open Access Journals (Sweden)

    Martha Canto-Bustos

    Full Text Available Voltage-gated Ca2+ (CaV channels are transmembrane proteins comprising three subfamilies named CaV1, CaV2 and CaV3. The CaV3 channel subfamily groups the low-voltage activated Ca2+ channels (LVA or T-type a significant role in regulating neuronal excitability. CaV3 channel activity may lead to the generation of complex patterns of action potential firing such as the postinhibitory rebound (PIR. In the adult spinal cord, these channels have been found in dorsal horn interneurons where they control physiological events near the resting potential and participate in determining excitability. In motoneurons, CaV3 channels have been found during development, but their functional expression has not yet been reported in adult animals. Here, we show evidence for the presence of CaV3 channel-mediated PIR in motoneurons of the adult turtle spinal cord. Our results indicate that Ni2+ and NNC55-0396, two antagonists of CaV3 channel activity, inhibited PIR in the adult turtle spinal cord. Molecular biology and biochemical assays revealed the expression of the CaV3.1 channel isotype and its localization in motoneurons. Together, these results provide evidence for the expression of CaV3.1 channels in the spinal cord of adult animals and show also that these channels may contribute to determine the excitability of motoneurons.

  18. Differences in health, participation and life satisfaction outcomes in adults following paediatric- versus adult-sustained spinal cord injury

    NARCIS (Netherlands)

    Ma, J. K.; Post, M. W. M.; Gorter, J. W.; Ginis, K. A. Martin

    2016-01-01

    Study design: Cross-sectional. Objectives: To compare differences in self-reported health status, participation and life satisfaction outcomes between adults with a spinal cord injury (SCI) sustained during paediatric (P) versus adulthood (A) years. Setting: Ontario, Canada. Methods: Secondary

  19. Spinal Cord Preparation from Adult Red-eared Turtles for Electrophysiological Recordings during Motor Activity

    DEFF Research Database (Denmark)

    Petersen, Peter Christian Hvidberg; Berg, Rune W.

    2017-01-01

    systems using other animals. The high resistance to anoxia allows for investigation of the fully developed and adult spinal circuitry, as opposed to mammals, which are sensitive to anoxia and where using neonates are often required to remedy the problems. The turtle is mechanically stable and natural...

  20. BAMOS: A recording application for BAsso MOuse scale of locomotion in experimental models of spinal cord injury.

    Science.gov (United States)

    Gómez, Alberto; Nieto-Díaz, Manuel; Del Águila, Ángela; Arias, Enrique

    2018-05-01

    Transparency in science is increasingly a hot topic. Scientists are required to show not only results but also evidence of how they have achieved these results. In experimental studies of spinal cord injury, there are a number of standardized tests, such as the Basso-Beattie-Bresnahan locomotor rating scale for rats and Basso Mouse Scale for mice, which researchers use to study the pathophysiology of spinal cord injury and to evaluate the effects of experimental therapies. Although the standardized data from the Basso-Beattie-Bresnahan locomotor rating scale and the Basso Mouse Scale are particularly suited for storage and sharing in databases, systems of data acquisition and repositories are still lacking. To the best of our knowledge, both tests are usually conducted manually, with the data being recorded on a paper form, which may be documented with video recordings, before the data is transferred to a spreadsheet for analysis. The data thus obtained is used to compute global scores, which is the information that usually appears in publications, with a wealth of information being omitted. This information may be relevant to understand locomotion deficits or recovery, or even important aspects of the treatment effects. Therefore, this paper presents a mobile application to record and share Basso Mouse Scale tests, meeting the following criteria: i) user-friendly; ii) few hardware requirements (only a smartphone or tablet with a camera running under Android Operating System); and iii) based on open source software such as SQLite, XML, Java, Android Studio and Android SDK. The BAMOS app can be downloaded and installed from the Google Market repository and the app code is available at the GitHub repository. The BAMOS app demonstrates that mobile technology constitutes an opportunity to develop tools for aiding spinal cord injury scientists in recording and sharing experimental data. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Mini-open spinal column shortening for the treatment of adult tethered cord syndrome.

    Science.gov (United States)

    Safaee, Michael M; Winkler, Ethan A; Chou, Dean

    2017-10-01

    Tethered cord syndrome (TCS) is a challenging entity characterized by adhesions at the caudal spinal cord that prevent upward movement during growth and result in stretching of the cord with a concomitant constellation of neurologic symptoms. Although growth in height stops in adulthood, some patients still develop progressive symptoms; many underwent detethering as a child or adolescent, resulting in significant scar tissue and re-tethering. Recent strategies have focused on spinal column shortening to reduce tension on the spinal cord without exposing the previous de-tethering site. Mini-open and minimally invasive approaches avoid the large dissection and exposure associated with traditional approaches and are associated with reduced blood loss, shorter hospital stay, and similar outcomes when compared to conventional open approaches. We describe a technique for mini-open spinal column shortening. Using intraoperative navigation pedicle screws were placed at T10, T11, L1, and L2. A mini-open 3-column "egg shell" decancellation osteotomy of T12 was performed through a transpedicular approach with preservation of the superior and inferior endplates. This procedure was performed on a 28year old male with recurrent TCS and neurogenic bladder. Postoperative imaging showed a reduction in spinal column length of 1.5cm and evidence of decreased tension on the spinal cord. At last follow-up he was recovering well with improved urinary function. Spinal column shortening for adult TCS can be safely achieved through a mini-open approach. Future studies should compare the efficacy of this technique to both traditional de-tethering and open spinal column shortening. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Increased excitability of spinal pain reflexes and altered frequency-dependent modulation in the dopamine D3-receptor knockout mouse.

    Science.gov (United States)

    Keeler, Benjamin E; Baran, Christine A; Brewer, Kori L; Clemens, Stefan

    2012-12-01

    Frequency-dependent modulation and dopamine (DA) receptors strongly modulate neural circuits in the spinal cord. Of the five known DA receptor subtypes, the D3 receptor has the highest affinity to DA, and D3-mediated actions are mainly inhibitory. Using an animal model of spinal sensorimotor dysfunction, the D3 receptor knockout mouse (D3KO), we investigated the physiological consequences of D3 receptor dysfunction on pain-associated signaling pathways in the spinal cord, the initial integration site for the processing of pain signaling. In the D3KO spinal cord, inhibitory actions of DA on the proprioceptive monosynaptic stretch reflex are converted from depression to facilitation, but its effects on longer-latency and pain-associated reflex responses and the effects of FM have not been studied. Using behavioral approaches in vivo, we found that D3KO animals exhibit reduced paw withdrawal latencies to thermal pain stimulation (Hargreaves' test) over wild type (WT) controls. Electrophysiological and pharmacological approaches in the isolated spinal cord in vitro showed that constant current stimulation of dorsal roots at a pain-associated frequency was associated with a significant reduction in the frequency-dependent modulation of longer-latency reflex (LLRs) responses but not monosynaptic stretch reflexes (MSRs) in D3KO. Application of the D1 and D2 receptor agonists and the voltage-gated calcium-channel ligand, pregabalin, but not DA, was able to restore the frequency-dependent modulation of the LLR in D3KO to WT levels. Thus we demonstrate that nociception-associated LLRs and proprioceptive MSRs are differentially modulated by frequency, dopaminergics and the Ca(2+) channel ligand, pregabalin. Our data suggest a role for the DA D3 receptor in pain modulation and identify the D3KO as a possible model for increased nociception. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Association of Neuromuscular Attributes With Performance-Based Mobility Among Community-Dwelling Older Adults With Symptomatic Lumbar Spinal Stenosis.

    Science.gov (United States)

    Schmidt, Catherine T; Ward, Rachel E; Suri, Pradeep; Kiely, Dan K; Ni, Pengsheng; Anderson, Dennis E; Bean, Jonathan F

    2017-07-01

    To identify differences in health factors, neuromuscular attributes, and performance-based mobility among community-dwelling older adults with symptomatic lumbar spinal stenosis; and to determine which neuromuscular attributes are associated with performance-based measures of mobility. Cross-sectional; secondary data analysis of a cohort study. Outpatient rehabilitation center. Community-dwelling adults aged ≥65 years with self-reported mobility limitations and symptomatic lumbar spinal stenosis (N=54). Not applicable. Short Physical Performance Battery score, habitual gait speed, and chair stand test. Symptomatic lumbar spinal stenosis was classified using self-reported symptoms of neurogenic claudication and imaging. Among 430 community-dwelling older adults, 54 (13%) met criteria for symptomatic lumbar spinal stenosis. Compared with participants without symptomatic lumbar spinal stenosis, those with symptomatic lumbar spinal stenosis had more comorbidities, higher body mass index, greater pain, and less balance confidence. Participants with symptomatic lumbar spinal stenosis had greater impairment in trunk extensor muscle endurance, leg strength, leg strength asymmetry, knee flexion range of motion (ROM), knee extension ROM, and ankle ROM compared with participants without symptomatic lumbar spinal stenosis. Five neuromuscular attributes were associated with performance-based mobility among participants with symptomatic lumbar spinal stenosis: trunk extensor muscle endurance, leg strength, leg strength asymmetry, knee flexion ROM, and knee extension ROM asymmetry. Community-dwelling older adults with self-reported mobility limitations and symptomatic lumbar spinal stenosis exhibit poorer health characteristics, greater neuromuscular impairment, and worse mobility when compared with those without symptomatic lumbar spinal stenosis. Poorer trunk extensor muscle endurance, leg strength, leg strength asymmetry, knee flexion ROM, and knee extension ROM asymmetry

  4. Potent spinal parenchymal AAV9-mediated gene delivery by subpial injection in adult rats and pigs

    Directory of Open Access Journals (Sweden)

    Atsushi Miyanohara

    2016-01-01

    Full Text Available Effective in vivo use of adeno-associated virus (AAV-based vectors to achieve gene-specific silencing or upregulation in the central nervous system has been limited by the inability to provide more than limited deep parenchymal expression in adult animals using delivery routes with the most clinical relevance (intravenous or intrathecal. Here, we demonstrate that the spinal pia membrane represents the primary barrier limiting effective AAV9 penetration into the spinal parenchyma after intrathecal AAV9 delivery. We develop a novel subpial AAV9 delivery technique and AAV9-dextran formulation. We use these in adult rats and pigs to show (i potent spinal parenchymal transgene expression in white and gray matter including neurons, glial and endothelial cells after single bolus subpial AAV9 delivery; (ii delivery to almost all apparent descending motor axons throughout the length of the spinal cord after cervical or thoracic subpial AAV9 injection; (iii potent retrograde transgene expression in brain motor centers (motor cortex and brain stem; and (iv the relative safety of this approach by defining normal neurological function for up to 6 months after AAV9 delivery. Thus, subpial delivery of AAV9 enables gene-based therapies with a wide range of potential experimental and clinical utilizations in adult animals and human patients.

  5. Spinal Arachnoiditis as a Complication of Cryptococcal Meningoencephalitis in Non-HIV Previously Healthy Adults

    Science.gov (United States)

    Komori, Mika; Kosa, Peter; Khan, Omar; Hammoud, Dima A.; Rosen, Lindsey B.; Browne, Sarah K.; Lin, Yen-Chih; Romm, Elena; Ramaprasad, Charu; Fries, Bettina C.; Bennett, John E.; Bielekova, Bibiana; Williamson, Peter R.

    2017-01-01

    Background. Cryptococcus can cause meningoencephalitis (CM) among previously healthy non-HIV adults. Spinal arachnoiditis is under-recognized, since diagnosis is difficult with concomitant central nervous system (CNS) pathology. Methods. We describe 6 cases of spinal arachnoiditis among 26 consecutively recruited CM patients with normal CD4 counts who achieved microbiologic control. We performed detailed neurological exams, cerebrospinal fluid (CSF) immunophenotyping and biomarker analysis before and after adjunctive immunomodulatory intervention with high dose pulse corticosteroids, affording causal inference into pathophysiology. Results. All 6 exhibited severe lower motor neuron involvement in addition to cognitive changes and gait disturbances from meningoencephalitis. Spinal involvement was associated with asymmetric weakness and urinary retention. Diagnostic specificity was improved by MRI imaging which demonstrated lumbar spinal nerve root enhancement and clumping or lesions. Despite negative fungal cultures, CSF inflammatory biomarkers, sCD27 and sCD21, as well as the neuronal damage biomarker, neurofilament light chain (NFL), were elevated compared to healthy donor (HD) controls. Elevations in these biomarkers were associated with clinical symptoms and showed improvement with adjunctive high dose pulse corticosteroids. Conclusions. These data suggest that a post-infectious spinal arachnoiditis is an important complication of CM in previously healthy individuals, requiring heightened clinician awareness. Despite microbiological control, this syndrome causes significant pathology likely due to increased inflammation and may be amenable to suppressive therapeutics. PMID:28011613

  6. Anatomical and electrophysiological characterization of a population of dI6 interneurons in the neonatal mouse spinal cord.

    Science.gov (United States)

    Griener, Anna; Zhang, Wei; Kao, Henry; Haque, Farhia; Gosgnach, Simon

    2017-10-24

    The locomotor central pattern generator is a neural network located in the ventral aspect of the caudal spinal cord that underlies stepping in mammals. While many genetically defined interneurons that are thought to comprise this neural network have been identified and characterized, the dI6 cells- which express the transcription factors WT1 and/or DMRT3- are one population that settle in this region, are active during locomotion, whose function is poorly understood. These cells were originally hypothesized to be commissural premotor interneurons, however evidence in support of this is sparse. Here we characterize this population of cells using the TgDbx1 Cre ;R26 EFP ;Dbx1 LacZ transgenic mouse line, which has been shown to be an effective marker of dI6 interneurons. We show dI6 cells to be abundant in laminae VII and VIII along the entire spinal cord and provide evidence that subtypes outside the WT1/DMRT3 expressing dI6 cells may exist. Retrograde tracing experiments indicate that the majority of dI6 cells project descending axons, and some make monosynaptic or disynaptic contacts onto motoneurons on either side of the spinal cord. Analysis of their activity during non-resetting deletions, which occur during bouts of fictive locomotion, suggests that these cells are involved in both locomotor rhythm generation and pattern formation. This study provides a thorough characterization of the dI6 cells labeled in the TgDbx1 Cre ;R26 EFP ;Dbx1 LacZ transgenic mouse, and supports previous work suggesting that these cells play multiple roles during locomotor activity. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Adult opossums (Didelphis virginiana) demonstrate near normal locomotion after spinal cord transection as neonates.

    Science.gov (United States)

    Wang, X M; Basso, D M; Terman, J R; Bresnahan, J C; Martin, G F

    1998-05-01

    When the thoracic spinal cord of the North American opossum (Didelphis virginiana) is transected on postnatal day (PD) 5, the site of injury becomes bridged by histologically recognizable spinal cord and axons which form major long tracts grow through the lesion. In the present study we asked whether opossums lesioned on PD5 have normal use of the hindlimbs as adults and, if so, whether that use is dependent upon axons which grow through the lesion site. The thoracic spinal cord was transected on PD5 and 6 months later, hindlimb function was evaluated using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. All animals supported their weight with the hindlimbs and used their hindlimbs normally during overground locomotion. In some cases, the spinal cord was retransected at the original lesion site or just caudal to it 6 months after the original transection and paralysis of the hindlimbs ensued. Surprisingly, however, these animals gradually recovered some ability to support their weight and to step with the hindlimbs. Similar recovery was not seen in animals transected only as adults. In order to verify that descending axons which grew through the lesion during development were still present in the adult animal, opossums subjected to transection of the thoracic cord on PD5 were reoperated and Fast blue was injected several segments caudal to the lesion. In all cases, neurons were labeled rostral to the lesion in each of the spinal and supraspinal nuclei labeled by comparable injections in unlesioned, age-matched controls. The results of orthograde tracing studies indicated that axons which grew through the lesion innervated areas that were appropriate for them. Copyright 1998 Academic Press.

  8. Characterization of Proliferating Neural Progenitors after Spinal Cord Injury in Adult Zebrafish.

    Directory of Open Access Journals (Sweden)

    Subhra Prakash Hui

    Full Text Available Zebrafish can repair their injured brain and spinal cord after injury unlike adult mammalian central nervous system. Any injury to zebrafish spinal cord would lead to increased proliferation and neurogenesis. There are presences of proliferating progenitors from which both neuronal and glial loss can be reversed by appropriately generating new neurons and glia. We have demonstrated the presence of multiple progenitors, which are different types of proliferating populations like Sox2+ neural progenitor, A2B5+ astrocyte/ glial progenitor, NG2+ oligodendrocyte progenitor, radial glia and Schwann cell like progenitor. We analyzed the expression levels of two common markers of dedifferentiation like msx-b and vimentin during regeneration along with some of the pluripotency associated factors to explore the possible role of these two processes. Among the several key factors related to pluripotency, pou5f1 and sox2 are upregulated during regeneration and associated with activation of neural progenitor cells. Uncovering the molecular mechanism for endogenous regeneration of adult zebrafish spinal cord would give us more clues on important targets for future therapeutic approach in mammalian spinal cord repair and regeneration.

  9. Abundance of gap junctions at glutamatergic mixed synapses in adult Mosquitofish spinal cord neurons

    Directory of Open Access Journals (Sweden)

    Jose L Serrano-Velez

    2014-06-01

    Full Text Available Dye-coupling, whole-mount immunohistochemistry for gap junction channel protein connexin 35 (Cx35, and freeze-fracture replica immunogold labeling (FRIL reveal an abundance of electrical synapses/gap junctions at glutamatergic mixed synapses in the 14th spinal segment that innervates the adult male gonopodium of Western Mosquitofish, Gambusia affinis (Mosquitofish.To study gap junctions’ role in fast motor behavior, we used a minimally-invasive neural-tract-tracing technique to introduce gap junction-permeant or -impermeant dyes into deep muscles controlling the gonopodium of the adult male Mosquitofish, a teleost fish that rapidly transfers (complete in 50 of the 62 gap junctions at mixed synapses are in the 14th spinal segment.Our results support and extend studies showing gap junctions at mixed synapses in spinal cord segments involved in control of genital reflexes in rodents, and they suggest a link between mixed synapses and fast motor behavior. The findings provide a basis for studies of specific roles of spinal neurons in the generation/regulation of sex-specific behavior and for studies of gap junctions’ role in regulating fast motor behavior. Finally, the CoPA IN provides a novel candidate neuron for future studies of gap junctions and neural control of fast motor behaviors.

  10. A 3D nanofibrous hydrogel and collagen sponge scaffold promotes locomotor functional recovery, spinal repair, and neuronal regeneration after complete transection of the spinal cord in adult rats

    International Nuclear Information System (INIS)

    Kaneko, Ai; Matsushita, Akira; Sankai, Yoshiyuki

    2015-01-01

    Central nervous system neurons in adult mammals display limited regeneration after injury, and functional recovery is poor following complete transection (>4 mm gap) of a rat spinal cord. A novel combination scaffold composed of 3D nanofibrous hydrogel PuraMatrix and a honeycomb collagen sponge was used to promote spinal repair and locomotor functional recovery following complete transection of the spinal cord in rats. We transplanted this scaffold into 5 mm spinal cord gaps and assessed spinal repair and functional recovery using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. The BBB score of the scaffold-transplanted group was significantly higher than that of the PBS-injected control group from 24 d to 4 months after the operation (P < 0.001–0.01), reaching 6.0  ±  0.75 (mean ± SEM) in the transplant and 0.70  ±  0.46 in the control groups. Neuronal regeneration and spinal repair were examined histologically using Pan Neuronal Marker, glial fibrillary acidic protein, growth-associated protein 43, and DAPI. The scaffolds were well integrated into the spinal cords, filling the 5 mm gaps with higher numbers of regenerated and migrated neurons, astrocytes, and other cells than in the control group. Mature and immature neurons and astrocytes in the scaffolds became colocalized and aligned longitudinally over >2 mm, suggesting their differentiation, maturation, and function. The spinal cord NF200 content of the transplant group, analyzed by western blot, was more than twice that of the control group, supporting the histological results. Transplantation of this novel scaffold promoted functional recovery, spinal repair, and neuronal regeneration. (paper)

  11. A Comprehensive Analysis of the SRS-Schwab Adult Spinal Deformity Classification and Confounding Variables

    DEFF Research Database (Denmark)

    Hallager, Dennis Winge; Hansen, Lars Valentin; Dragsted, Casper Rokkjær

    2016-01-01

    STUDY DESIGN: Cross-sectional analyses on a consecutive, prospective cohort. OBJECTIVE: To evaluate the ability of the Scoliosis Research Society (SRS)-Schwab Adult Spinal Deformity Classification to group patients by widely used health-related quality-of-life (HRQOL) scores and examine possible...... to confounding. However, age group and aetiology had individual significant effects. CONCLUSION: The SRS-Schwab sagittal modifiers reliably grouped patients graded 0 versus + / +  + according to the most widely used HRQOL scores and the effects of increasing grade level on odds for worse ODI scores remained...... confounding variables. SUMMARY OF BACKGROUND DATA: The SRS-Schwab Adult Spinal Deformity Classification includes sagittal modifiers considered important for HRQOL and the clinical impact of the classification has been validated in patients from the International Spine Study Group database; however, equivocal...

  12. [Isolation, purification and primary culture of adult mouse cardiac fibroblasts].

    Science.gov (United States)

    Li, Rujun; Gong, Kaizheng; Zhang, Zhengang

    2017-01-01

    Objective To establish a method for primary culture of adult mouse cardiac fibroblasts. Methods Myocardial tissues from adult mice were digested with 1 g/L trypsin and 0.8 g/L collagenase IV by oscillating water bath for a short time repeatedly. Cardiac fibroblasts and myocardial cells were isolated with differential adhesion method. Immunofluorescence staining was used to assess the purity of cardiac fibroblasts. The cell morphology was observed under an inverted phase contrast microscope. The proliferation of cardiac fibroblasts was analyzed by growth curve and CCK-8 assay. The Smad2/3 phosphorylation induced by TGF-β1 was detected by Western blotting. Results After 90 minutes of differential adhesion, adherent fibroblasts formed spherical cell mass and after 3 days, cells were spindle-shaped and proliferated rapidly. Cells were confluent after 5 days and the growth curve presented nearly "S" shape. The positive expression rate of vimentin was 95%. CCK-8 assay showed that the optimal cell proliferating activity was found from day 3 to day 5. The level of phosphorylated Smad2/3 obviously increased at the second passage induced by TGF-β1. Conclusion This method is economical and stable to isolate cardiac fibroblasts with high activity and high purity from adult mice.

  13. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    International Nuclear Information System (INIS)

    Webb, Carol F.; Ratliff, Michelle L.; Powell, Rebecca; Wirsig-Wiechmann, Celeste R.; Lakiza, Olga; Obara, Tomoko

    2015-01-01

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development

  14. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    Energy Technology Data Exchange (ETDEWEB)

    Webb, Carol F., E-mail: carol-webb@omrf.org [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Ratliff, Michelle L., E-mail: michelle-ratliff@omrf.org [Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Powell, Rebecca, E-mail: rebeccapowell@gmail.com [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Wirsig-Wiechmann, Celeste R., E-mail: celeste-wirsig@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Lakiza, Olga, E-mail: olga-lakiza@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Obara, Tomoko, E-mail: tomoko-obara@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

    2015-08-07

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.

  15. Calcium imaging of living astrocytes in the mouse spinal cord following sensory stimulation.

    Science.gov (United States)

    Cirillo, Giovanni; De Luca, Daniele; Papa, Michele

    2012-01-01

    Astrocytic Ca(2+) dynamics have been extensively studied in ex vivo models; however, the recent development of two-photon microscopy and astrocyte-specific labeling has allowed the study of Ca(2+) signaling in living central nervous system. Ca(2+) waves in astrocytes have been described in cultured cells and slice preparations, but evidence for astrocytic activation during sensory activity is lacking. There are currently few methods to image living spinal cord: breathing and heart-beating artifacts have impeded the widespread application of this technique. We here imaged the living spinal cord by two-photon microscopy in C57BL6/J mice. Through pressurized injection, we specifically loaded spinal astrocytes using the red fluorescent dye sulforhodamine 101 (SR101) and imaged astrocytic Ca(2+) levels with Oregon-Green BAPTA-1 (OGB). Then, we studied astrocytic Ca(2+) levels at rest and after right electrical hind paw stimulation. Sensory stimulation significantly increased astrocytic Ca(2+) levels within the superficial dorsal horn of the spinal cord compared to rest. In conclusion, in vivo morphofunctional imaging of living astrocytes in spinal cord revealed that astrocytes actively participate to sensory stimulation.

  16. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Topic Resources Peer Counseling Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury 101 Adult Injuries Spinal Cord Injury 101 David ...

  17. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Topic Resources Peer Counseling Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury 101 Adult Injuries Spinal Cord Injury 101 ...

  18. Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse

    DEFF Research Database (Denmark)

    Caldeira, Vanessa; Dougherty, Kimberly J.; Borgius, Lotta

    2017-01-01

    Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we...... than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion....... use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype...

  19. Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy

    Science.gov (United States)

    Mentis, George Z.; Blivis, Dvir; Liu, Wenfang; Drobac, Estelle; Crowder, Melissa E.; Kong, Lingling; Alvarez, Francisco J.; Sumner, Charlotte J.; O'Donovan, Michael J.

    2011-01-01

    SUMMARY To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes illustrating the reversibility of these synaptic defects. De-afferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention. PMID:21315257

  20. Complete reorganization of the motor cortex of adult rats following long-term spinal cord injuries.

    Science.gov (United States)

    Tandon, Shashank; Kambi, Niranjan; Mohammed, Hisham; Jain, Neeraj

    2013-07-01

    Understanding brain reorganization following long-term spinal cord injuries is important for optimizing recoveries based on residual function as well as developing brain-controlled assistive devices. Although it has been shown that the motor cortex undergoes partial reorganization within a few weeks after peripheral and spinal cord injuries, it is not known if the motor cortex of rats is capable of large-scale reorganization after longer recovery periods. Here we determined the organization of the rat (Rattus norvegicus) motor cortex at 5 or more months after chronic lesions of the spinal cord at cervical levels using intracortical microstimulation. The results show that, in the rats with the lesions, stimulation of neurons in the de-efferented forelimb motor cortex no longer evokes movements of the forelimb. Instead, movements of the body parts in the adjacent representations, namely the whiskers and neck were evoked. In addition, at many sites, movements of the ipsilateral forelimb were observed at threshold currents. The extent of representations of the eye, jaw and tongue movements was unaltered by the lesion. Thus, large-scale reorganization of the motor cortex leads to complete filling-in of the de-efferented cortex by neighboring representations following long-term partial spinal cord injuries at cervical levels in adult rats. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  1. Delayed post-traumatic spinal cord infarction in an adult after minor head and neck trauma: a case report

    Directory of Open Access Journals (Sweden)

    Bartanusz Viktor

    2012-09-01

    Full Text Available Abstract Introduction Delayed post-traumatic spinal cord infarction is a devastating complication described in children. In adults, spinal cord ischemia after cardiovascular interventions, scoliosis correction, or profound hypotension has been reported in the literature. However, delayed spinal cord infarction after minor head trauma has not been described yet. Case presentation We report the case of a 45-year-old Hispanic man who had a minor head trauma. He was admitted to our hospital because of paresthesias in his hands and neck pain. A radiological workup showed cervical spinal canal stenosis and chronic cervical spondylotic myelopathy. Twelve hours after admission, our patient became unresponsive and, despite full resuscitation efforts, died. The autopsy revealed spinal cord necrosis involving the entire cervical spinal cord and upper thoracic region. Conclusions This case illustrates the extreme fragility of spinal cord hemodynamics in patients with chronic cervical spinal canal stenosis, in which any further perturbations, such as cervical hyperflexion related to a minor head injury, can have catastrophic consequences. Furthermore, the delayed onset of spinal cord infarction in this case shows that meticulous maintenance of blood pressure in the acute post-traumatic period is of paramount importance, even in patients with minimal post-traumatic symptoms.

  2. Neurotrophic factors and receptors in the immature and adult spinal cord after mechanical injury or kainic acid.

    Science.gov (United States)

    Widenfalk, J; Lundströmer, K; Jubran, M; Brene, S; Olson, L

    2001-05-15

    Delivery of neurotrophic factors to the injured spinal cord has been shown to stimulate neuronal survival and regeneration. This indicates that a lack of sufficient trophic support is one factor contributing to the absence of spontaneous regeneration in the mammalian spinal cord. Regulation of the expression of neurotrophic factors and receptors after spinal cord injury has not been studied in detail. We investigated levels of mRNA-encoding neurotrophins, glial cell line-derived neurotrophic factor (GDNF) family members and related receptors, ciliary neurotrophic factor (CNTF), and c-fos in normal and injured spinal cord. Injuries in adult rats included weight-drop, transection, and excitotoxic kainic acid delivery; in newborn rats, partial transection was performed. The regulation of expression patterns in the adult spinal cord was compared with that in the PNS and the neonate spinal cord. After mechanical injury of the adult rat spinal cord, upregulations of NGF and GDNF mRNA occurred in meningeal cells adjacent to the lesion. BDNF and p75 mRNA increased in neurons, GDNF mRNA increased in astrocytes close to the lesion, and GFRalpha-1 and truncated TrkB mRNA increased in astrocytes of degenerating white matter. The relatively limited upregulation of neurotrophic factors in the spinal cord contrasted with the response of affected nerve roots, in which marked increases of NGF and GDNF mRNA levels were observed in Schwann cells. The difference between the ability of the PNS and CNS to provide trophic support correlates with their different abilities to regenerate. Kainic acid delivery led to only weak upregulations of BDNF and CNTF mRNA. Compared with several brain regions, the overall response of the spinal cord tissue to kainic acid was weak. The relative sparseness of upregulations of endogenous neurotrophic factors after injury strengthens the hypothesis that lack of regeneration in the spinal cord is attributable at least partly to lack of trophic support.

  3. Distribution and densitometry mapping of L1-CAM Immunoreactivity in the adult mouse brain – light microscopic observation

    Directory of Open Access Journals (Sweden)

    Yamasaki Hironobu

    2003-04-01

    Full Text Available Abstract Background The importance of L1 expression in the matured brain is suggested by physiological and behavioral studies showing that L1 is related to hippocampal plasticity and fear conditioning. The distribution of L1 in mouse brain might provide a basis for understanding its role in the brain. Results We examined the overall distribution of L1 in the adult mouse brain by immunohistochemistry using two polyclonal antibodies against different epitopes for L1. Immunoreactive L1 was widely but unevenly distributed from the olfactory bulb to the upper cervical cord. The accumulation of immunoreactive L1 was greatest in a non-neuronal element of the major fibre bundles, i.e. the lateral olfactory tract, olfactory and temporal limb of the anterior commissure, corpus callosum, stria terminalis, globus pallidus, fornix, mammillothalamic tract, solitary tract, and spinal tract of the trigeminal nerve. High to highest levels of non-neuronal and neuronal L1 were found in the grey matter; i.e. the piriform and entorhinal cortices, hypothalamus, reticular part of the substantia nigra, periaqueductal grey, trigeminal spinal nucleus etc. High to moderate density of neuronal L1 was found in the olfactory bulb, layer V of the cerebral cortex, amygdala, pontine grey, superior colliculi, cerebellar cortex, solitary tract nucleus etc. Only low to lowest levels of neuronal L1 were found in the hippocampus, grey matter in the caudate-putamen, thalamus, cerebellar nuclei etc. Conclusion L1 is widely and unevenly distributed in the matured mouse brain, where immunoreactivity was present not only in neuronal elements; axons, synapses and cell soma, but also in non-neuronal elements.

  4. Spatial and temporal expression levels of specific microRNAs in a spinal cord injury mouse model and their relationship to the duration of compression.

    Science.gov (United States)

    Ziu, Mateo; Fletcher, Lauren; Savage, Jennifer G; Jimenez, David F; Digicaylioglu, Murat; Bartanusz, Viktor

    2014-02-01

    MicroRNAs, a class of small nonprotein-coding RNAs, are thought to control gene translation into proteins. The latter are the ultimate effectors of the biochemical cascade occurring in any physiological and pathological process. MicroRNAs have been shown to change their expression levels during injury of spinal cord in contusion rodent models. Compression is the most frequent mode of damage of neural elements in spinal cord injury. The cellular and molecular changes occurring in the spinal cord during prolonged compression are not very well elucidated. Understanding the underlying molecular events that occur during sustained compression is paramount in building new therapeutic strategies. The purpose of our study was to probe the relationship between the expression level changes of different miRNAs and the timing of spinal cord decompression in a mouse model. A compression spinal cord injury mouse model was used for the study. A laminectomy was performed in the thoracic spine of C57BL/6 mice. Then, the thecal sac was compressed to create the injury. Decompression was performed early for one group and it was delayed in the second group. The spinal cord at the epicenter of the injury and one level rostral to it were removed at 3, 6, and 24 hours after trauma, and RNA was extracted. Expression levels of six different microRNAs and the relationship to the duration of compression were analyzed. This work was supported in part by the University Research Council Grants Program at the University of Texas Health Science Center San Antonio (Grant 130267). There are no specific conflicts of interest to be disclosed for this work. Expression levels of microRNAs in the prolonged compression of spinal cord model were significantly different compared with the expression levels in the short duration of compression spinal cord injury model. Furthermore, microRNAs show a different expression pattern in different regions of the injured spinal cord. Our findings demonstrate that

  5. Microarray analysis of gene expression by skeletal muscle of three mouse models of Kennedy disease/spinal bulbar muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Kaiguo Mo

    2010-09-01

    Full Text Available Emerging evidence implicates altered gene expression within skeletal muscle in the pathogenesis of Kennedy disease/spinal bulbar muscular atrophy (KD/SBMA. We therefore broadly characterized gene expression in skeletal muscle of three independently generated mouse models of this disease. The mouse models included a polyglutamine expanded (polyQ AR knock-in model (AR113Q, a polyQ AR transgenic model (AR97Q, and a transgenic mouse that overexpresses wild type AR solely in skeletal muscle (HSA-AR. HSA-AR mice were included because they substantially reproduce the KD/SBMA phenotype despite the absence of polyQ AR.We performed microarray analysis of lower hindlimb muscles taken from these three models relative to wild type controls using high density oligonucleotide arrays. All microarray comparisons were made with at least 3 animals in each condition, and only those genes having at least 2-fold difference and whose coefficient of variance was less than 100% were considered to be differentially expressed. When considered globally, there was a similar overlap in gene changes between the 3 models: 19% between HSA-AR and AR97Q, 21% between AR97Q and AR113Q, and 17% between HSA-AR and AR113Q, with 8% shared by all models. Several patterns of gene expression relevant to the disease process were observed. Notably, patterns of gene expression typical of loss of AR function were observed in all three models, as were alterations in genes involved in cell adhesion, energy balance, muscle atrophy and myogenesis. We additionally measured changes similar to those observed in skeletal muscle of a mouse model of Huntington's Disease, and to those common to muscle atrophy from diverse causes.By comparing patterns of gene expression in three independent models of KD/SBMA, we have been able to identify candidate genes that might mediate the core myogenic features of KD/SBMA.

  6. Calcium dynamics and buffering in motoneurones of the mouse spinal cord

    Czech Academy of Sciences Publication Activity Database

    Paleček, Jiří; Lips, M. B.; Keller, B. U.

    1999-01-01

    Roč. 520, č. 2 (1999), s. 485-502 ISSN 0928-4257 R&D Projects: GA ČR(CZ) GA305/96/0680 Institutional research plan: CEZ:AV0Z5011922 Keywords : spinal cord * motor neuron toxicity * amyotrophic lateral sclerosis Subject RIV: FH - Neurology Impact factor: 1.130, year: 1999

  7. Spinal cord stimulation for cancer-related pain in adults.

    Science.gov (United States)

    Peng, Lihua; Min, Su; Zejun, Zhou; Wei, Ke; Bennett, Michael I

    2015-06-29

    This is an update of a review first published in The Cochrane Library in Issue 3, 2013. Cancer-related pain places a heavy burden on public health with related high expenditure. Severe pain is associated with a decreased quality of life in patients with cancer. A significant proportion of patients with cancer-related pain are under-treated. There is a need for more effective control of cancer-related pain. Spinal cord stimulation (SCS) may have a role in pain management. The effectiveness and safety of SCS for patients with cancer-related pain is currently unknown. This systematic review evaluated the effectiveness of SCS for cancer-related pain compared with standard care using conventional analgesic medication. We also appraised risk and potential adverse events associated with the use of SCS. This is an update of a review first published in The Cochrane Library in Issue 3, 2013. The search strategy for the update was the same as in the original review. We searched the following bibliographic databases in order to identify relevant studies: the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library; MEDLINE; EMBASE; and CBM (Chinese Biomedical Database) in October 2014. We also handsearched relevant journals. There were no language restrictions. We planned to include randomised controlled trials (RCTs) that directly compared SCS with other interventions with regards to the effectiveness of pain management. We also planned to include cross-over trials that compared SCS with another treatment. We planned to identify non-randomised controlled trials but these would only be included if no RCTs could be found. The literature search for the update of this review found 121 potentially eligible articles. The initial search strategy yielded 430 articles. By scrutinising titles and abstracts, we found 412 articles irrelevant to the analytical purpose of this systematic review due to different scopes of diseases or different methods of intervention

  8. Body and Corporality in adolescents and young adults with spinal cord injury.

    Science.gov (United States)

    Duarte Torres, Diana Milena; Torres Bolaños, Yuri Marcela; Moreno Fergusson, María Elisa

    2016-04-01

    To describe the meaning given by adolescents and young adults to the changes in their bodies and corporality after a spinal cord injury. Qualitative study based on symbolic interactionism in which 12 adolescents and young adults, who had suffered spinal cord injury 6 months or more before, participated. The information was recollected through a series of in-depth interviews and field journals. The guidelines proposed by Corbin and Strauss were followed for the process of codification and categorization of the data. Four categories were identified that describe the meanings given by participants to the changes in their bodies and corporality: Transformation of self-image, living with contradictions in the relationships with others, withstanding the burden of a disability and adapting to the new conditions. The results allow for the comprehension of the meanings that are given by the people who have suffered a spinal cord lesion to their situation. This will in turn open the possibility of offering these people a better individual nursing care that focuses more on the particular needs, so that both they and their families can be helped on their way to adaptation to the new situation.

  9. Defining a core outcome set for adolescent and young adult patients with a spinal deformity

    DEFF Research Database (Denmark)

    de Kleuver, Marinus; Faraj, Sayf S A; Holewijn, Roderick M

    2017-01-01

    Background and purpose - Routine outcome measurement has been shown to improve performance in several fields of healthcare. National spine surgery registries have been initiated in 5 Nordic countries. However, there is no agreement on which outcomes are essential to measure for adolescent and young...... adult patients with a spinal deformity. The aim of this study was to develop a core outcome set (COS) that will facilitate benchmarking within and between the 5 countries of the Nordic Spinal Deformity Society (NSDS) and other registries worldwide. Material and methods - From August 2015 to September...... consensus rounds were held. Consensus was defined as agreement between at least 5 of the 7 representatives. Data were analyzed qualitatively and quantitatively. Results - Consensus was reached on the inclusion of 13 core outcome domains: "satisfaction with overall outcome of surgery", "satisfaction...

  10. Valproic Acid Arrests Proliferation but Promotes Neuronal Differentiation of Adult Spinal NSPCs from SCI Rats.

    Science.gov (United States)

    Chu, Weihua; Yuan, Jichao; Huang, Lei; Xiang, Xin; Zhu, Haitao; Chen, Fei; Chen, Yanyan; Lin, Jiangkai; Feng, Hua

    2015-07-01

    Although the adult spinal cord contains a population of multipotent neural stem/precursor cells (NSPCs) exhibiting the potential to replace neurons, endogenous neurogenesis is very limited after spinal cord injury (SCI) because the activated NSPCs primarily differentiate into astrocytes rather than neurons. Valproic acid (VPA), a histone deacetylase inhibitor, exerts multiple pharmacological effects including fate regulation of stem cells. In this study, we cultured adult spinal NSPCs from chronic compressive SCI rats and treated with VPA. In spite of inhibiting the proliferation and arresting in the G0/G1 phase of NSPCs, VPA markedly promoted neuronal differentiation (β-tubulin III(+) cells) as well as decreased astrocytic differentiation (GFAP(+) cells). Cell cycle regulator p21(Cip/WAF1) and proneural genes Ngn2 and NeuroD1 were increased in the two processes respectively. In vivo, to minimize the possible inhibitory effects of VPA to the proliferation of NSPCs as well as avoid other neuroprotections of VPA in acute phase of SCI, we carried out a delayed intraperitoneal injection of VPA (150 mg/kg/12 h) to SCI rats from day 15 to day 22 after injury. Both of the newborn neuron marker doublecortin and the mature neuron marker neuron-specific nuclear protein were significantly enhanced after VPA treatment in the epicenter and adjacent segments of the injured spinal cord. Although the impaired corticospinal tracks had not significantly improved, Basso-Beattie-Bresnahan scores in VPA treatment group were better than control. Our study provide the first evidence that administration of VPA enhances the neurogenic potential of NSPCs after SCI and reveal the therapeutic value of delayed treatment of VPA to SCI.

  11. Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse.

    Science.gov (United States)

    Caldeira, Vanessa; Dougherty, Kimberly J; Borgius, Lotta; Kiehn, Ole

    2017-01-27

    Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype and progenitor domain, but does not overlap with the Shox2 non-V2a population. We also show that Hb9::Cre-derived INs include the comparatively small medial population of INs which continues to express Hb9 postnatally. When excitatory neurotransmission is selectively blocked by deleting Vglut2 from Hb9::Cre-derived INs, there is no difference in left-right and/or flexor-extensor phasing between these cords and controls, suggesting that excitatory Hb9::Cre-derived INs do not affect pattern generation. In contrast, the frequencies of locomotor activity are significantly lower in cords from Hb9::Cre-Vglut2 Δ/Δ mice than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion.

  12. Fisetin exerts antihyperalgesic effect in a mouse model of neuropathic pain: engagement of spinal serotonergic system

    Science.gov (United States)

    Zhao, Xin; Wang, Chuang; Cui, Wu-Geng; Ma, Qing; Zhou, Wen-Hua

    2015-01-01

    Fisetin, a natural flavonoid, has been shown in our previous studies to exert antidepressant-like effect. As antidepressant drugs are clinically used to treat chronic neuropathic pain, this work aimed to investigate the potential antinociceptive efficacies of fisetin against neuropathic pain and explore mechanism(s). We subjected mice to chronic constriction injury (CCI) by loosely ligating the sciatic nerves, and Hargreaves test or von Frey test was used to assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic fisetin treatment (5, 15 or 45 mg/kg, p.o.) ameliorated thermal hyperalgesia (but not mechanical allodynia) in CCI mice, concomitant with escalated levels of spinal monoamines and suppressed monoamine oxidase (MAO)-A activity. The antihyperalgesic action of fisetin was abolished by chemical depletion of spinal serotonin (5-HT) but potentiated by co-treatment with 5-HTP, a precursor of 5-HT. Moreover, intraperitoneal (i.p.) or intrathecal (i.t.) co-treatment with 5-HT7 receptor antagonist SB-258719 completely abrogated fisetin's antihyperalgesia. These findings confirm that chronic fisetin treatment exerts antinociceptive effect on thermal hyperalgesia in neuropathic mice, with spinal serotonergic system (coupled with 5-HT7) being critically involved. Of special benefit, fisetin attenuated co-morbidly behavioral symptoms of depression and anxiety (evaluated in forced swim test, novelty suppressed feeding test and light-dark test) evoked by neuropathic pain. PMID:25761874

  13. Study Protocol- Lumbar Epidural Steroid Injections for Spinal Stenosis (LESS: a double-blind randomized controlled trial of epidural steroid injections for lumbar spinal stenosis among older adults

    Directory of Open Access Journals (Sweden)

    Friedly Janna L

    2012-03-01

    Full Text Available Abstract Background Lumbar spinal stenosis is one of the most common causes of low back pain among older adults and can cause significant disability. Despite its prevalence, treatment of spinal stenosis symptoms remains controversial. Epidural steroid injections are used with increasing frequency as a less invasive, potentially safer, and more cost-effective treatment than surgery. However, there is a lack of data to judge the effectiveness and safety of epidural steroid injections for spinal stenosis. We describe our prospective, double-blind, randomized controlled trial that tests the hypothesis that epidural injections with steroids plus local anesthetic are more effective than epidural injections of local anesthetic alone in improving pain and function among older adults with lumbar spinal stenosis. Methods We will recruit up to 400 patients with lumbar central canal spinal stenosis from at least 9 clinical sites over 2 years. Patients with spinal instability who require surgical fusion, a history of prior lumbar surgery, or prior epidural steroid injection within the past 6 months are excluded. Participants are randomly assigned to receive either ESI with local anesthetic or the control intervention (epidural injections with local anesthetic alone. Subjects receive up to 2 injections prior to the primary endpoint at 6 weeks, at which time they may choose to crossover to the other intervention. Participants complete validated, standardized measures of pain, functional disability, and health-related quality of life at baseline and at 3 weeks, 6 weeks, and 3, 6, and 12 months after randomization. The primary outcomes are Roland-Morris Disability Questionnaire and a numerical rating scale measure of pain intensity at 6 weeks. In order to better understand their safety, we also measure cortisol, HbA1c, fasting blood glucose, weight, and blood pressure at baseline, and at 3 and 6 weeks post-injection. We also obtain data on resource utilization

  14. Nestin- and doublecortin-positive cells reside in adult spinal cord meninges and participate in injury-induced parenchymal reaction.

    Science.gov (United States)

    Decimo, Ilaria; Bifari, Francesco; Rodriguez, Francisco Javier; Malpeli, Giorgio; Dolci, Sissi; Lavarini, Valentina; Pretto, Silvia; Vasquez, Sandra; Sciancalepore, Marina; Montalbano, Alberto; Berton, Valeria; Krampera, Mauro; Fumagalli, Guido

    2011-12-01

    Adult spinal cord has little regenerative potential, thus limiting patient recovery following injury. In this study, we describe a new population of cells resident in the adult rat spinal cord meninges that express the neural stem/precursor markers nestin and doublecortin. Furthermore, from dissociated meningeal tissue a neural stem cell population was cultured in vitro and subsequently shown to differentiate into functional neurons or mature oligodendrocytes. Proliferation rate and number of nestin- and doublecortin-positive cells increased in vivo in meninges following spinal cord injury. By using a lentivirus-labeling approach, we show that meningeal cells, including nestin- and doublecortin-positive cells, migrate in the spinal cord parenchyma and contribute to the glial scar formation. Our data emphasize the multiple roles of meninges in the reaction of the parenchyma to trauma and indicate for the first time that spinal cord meninges are potential niches harboring stem/precursor cells that can be activated by injury. Meninges may be considered as a new source of adult stem/precursor cells to be further tested for use in regenerative medicine applied to neurological disorders, including repair from spinal cord injury. Copyright © 2011 AlphaMed Press.

  15. Ligament augmentation for prevention of proximal junctional kyphosis and proximal junctional failure in adult spinal deformity.

    Science.gov (United States)

    Safaee, Michael M; Deviren, Vedat; Dalle Ore, Cecilia; Scheer, Justin K; Lau, Darryl; Osorio, Joseph A; Nicholls, Fred; Ames, Christopher P

    2018-05-01

    OBJECTIVE Proximal junctional kyphosis (PJK) is a well-recognized, yet incompletely defined, complication of adult spinal deformity surgery. There is no standardized definition for PJK, but most studies describe PJK as an increase in the proximal junctional angle (PJA) of greater than 10°-20°. Ligament augmentation is a novel strategy for PJK reduction that provides strength to the upper instrumented vertebra (UIV) and adjacent segments while also reducing junctional stress at those levels. METHODS In this study, ligament augmentation was used in a consecutive series of adult spinal deformity patients at a single institution. Patient demographics, including age; sex; indication for surgery; revision surgery; surgical approach; and use of 3-column osteotomies, vertebroplasty, or hook fixation at the UIV, were collected. The PJA was measured preoperatively and at last follow-up using 36-inch radiographs. Data on change in PJA and need for revision surgery were collected. Univariate and multivariate analyses were performed to identify factors associated with change in PJA and proximal junctional failure (PJF), defined as PJK requiring surgical correction. RESULTS A total of 200 consecutive patients were included: 100 patients before implementation of ligament augmentation and 100 patients after implementation of this technique. The mean age of the ligament augmentation cohort was 66 years, and 67% of patients were women. Over half of these cases (51%) were revision surgeries, with 38% involving a combined anterior or lateral and posterior approach. The mean change in PJA was 6° in the ligament augmentation group compared with 14° in the control group (p historical cohort, ligament augmentation is associated with a significant decrease in PJK and PJF. These data support the implementation of ligament augmentation in surgery for adult spinal deformity, particularly in patients with a high risk of developing PJK and PJF.

  16. Spinal column shortening for tethered cord syndrome associated with myelomeningocele, lumbosacral lipoma, and lipomyelomeningocele in children and young adults.

    Science.gov (United States)

    Aldave, Guillermo; Hansen, Daniel; Hwang, Steven W; Moreno, Amee; Briceño, Valentina; Jea, Andrew

    2017-06-01

    OBJECTIVE Tethered cord syndrome is the clinical manifestation of an abnormal stretch on the spinal cord, presumably causing mechanical injury, a compromised blood supply, and altered spinal cord metabolism. Tethered cord release is the standard treatment for tethered cord syndrome. However, direct untethering of the spinal cord carries potential risks, such as new neurological deficits from spinal cord injury, a CSF leak from opening the dura, and retethering of the spinal cord from normal scar formation after surgery. To avoid these risks, the authors applied spinal column shortening to children and transitional adults with primary and secondary tethered cord syndrome and report treatment outcomes. The authors' aim with this study was to determine the safety and efficacy of spinal column shortening for tethered cord syndrome by analyzing their experience with this surgical technique. METHODS The authors retrospectively reviewed the demographic and procedural data of children and young adults who had undergone spinal column shortening for primary or secondary tethered cord syndrome. RESULTS Seven patients with tethered cord syndrome caused by myelomeningocele, lipomyelomeningocele, and transitional spinal lipoma were treated with spinal column shortening. One patient with less than 24 months of follow-up was excluded from further analysis. There were 3 males and 4 females; the average age at the time was surgery was 16 years (range 8-30 years). Clinical presentations for our patients included pain (in 5 patients), weakness (in 4 patients), and bowel/bladder dysfunction (in 4 patients). Spinal column osteotomy was most commonly performed at the L-1 level, with fusion between T-12 and L-2 using a pedicle screw-rod construct. Pedicle subtraction osteotomy was performed in 6 patients, and vertebral column resection was performed in 1 patient. The average follow-up period was 31 months (range 26-37 months). Computed tomography-based radiographic outcomes showed solid

  17. Dissection of Hippocampal Dentate Gyrus from Adult Mouse

    Science.gov (United States)

    Hagihara, Hideo; Toyama, Keiko; Yamasaki, Nobuyuki; Miyakawa, Tsuyoshi

    2009-01-01

    The hippocampus is one of the most widely studied areas in the brain because of its important functional role in memory processing and learning, its remarkable neuronal cell plasticity, and its involvement in epilepsy, neurodegenerative diseases, and psychiatric disorders. The hippocampus is composed of distinct regions; the dentate gyrus, which comprises mainly granule neurons, and Ammon's horn, which comprises mainly pyramidal neurons, and the two regions are connected by both anatomic and functional circuits. Many different mRNAs and proteins are selectively expressed in the dentate gyrus, and the dentate gyrus is a site of adult neurogenesis; that is, new neurons are continually generated in the adult dentate gyrus. To investigate mRNA and protein expression specific to the dentate gyrus, laser capture microdissection is often used. This method has some limitations, however, such as the need for special apparatuses and complicated handling procedures. In this video-recorded protocol, we demonstrate a dissection technique for removing the dentate gyrus from adult mouse under a stereomicroscope. Dentate gyrus samples prepared using this technique are suitable for any assay, including transcriptomic, proteomic, and cell biology analyses. We confirmed that the dissected tissue is dentate gyrus by conducting real-time PCR of dentate gyrus-specific genes, tryptophan 2,3-dioxygenase (TDO2) and desmoplakin (Dsp), and Ammon's horn enriched genes, Meis-related gene 1b (Mrg1b) and TYRO3 protein tyrosine kinase 3 (Tyro3). The mRNA expressions of TDO2 and Dsp in the dentate gyrus samples were detected at obviously higher levels, whereas Mrg1b and Tyro3 were lower levels, than those in the Ammon's horn samples. To demonstrate the advantage of this method, we performed DNA microarray analysis using samples of whole hippocampus and dentate gyrus. The mRNA expression of TDO2 and Dsp, which are expressed selectively in the dentate gyrus, in the whole hippocampus of alpha

  18. Defining a core outcome set for adolescent and young adult patients with a spinal deformity.

    Science.gov (United States)

    de Kleuver, Marinus; Faraj, Sayf S A; Holewijn, Roderick M; Germscheid, Niccole M; Adobor, Raphael D; Andersen, Mikkel; Tropp, Hans; Dahl, Benny; Keskinen, Heli; Olai, Anders; Polly, David W; van Hooff, Miranda L; Haanstra, Tsjitske M

    2017-12-01

    Background and purpose - Routine outcome measurement has been shown to improve performance in several fields of healthcare. National spine surgery registries have been initiated in 5 Nordic countries. However, there is no agreement on which outcomes are essential to measure for adolescent and young adult patients with a spinal deformity. The aim of this study was to develop a core outcome set (COS) that will facilitate benchmarking within and between the 5 countries of the Nordic Spinal Deformity Society (NSDS) and other registries worldwide. Material and methods - From August 2015 to September 2016, 7 representatives (panelists) of the national spinal surgery registries from each of the NSDS countries participated in a modified Delphi study. With a systematic literature review as a basis and the International Classification of Functioning, Disability and Health framework as guidance, 4 consensus rounds were held. Consensus was defined as agreement between at least 5 of the 7 representatives. Data were analyzed qualitatively and quantitatively. Results - Consensus was reached on the inclusion of 13 core outcome domains: "satisfaction with overall outcome of surgery", "satisfaction with cosmetic result of surgery", "pain interference", physical functioning", "health-related quality of life", "recreation and leisure", "pulmonary fatigue", "change in deformity", "self-image", "pain intensity", "physical function", "complications", and "re-operation". Panelists agreed that the SRS-22r, EQ-5D, and a pulmonary fatigue questionnaire (yet to be developed) are the most appropriate set of patient-reported measurement instruments that cover these outcome domains. Interpretation - We have identified a COS for a large subgroup of spinal deformity patients for implementation and validation in the NSDS countries. This is the first study to further develop a COS in a global perspective.

  19. Endogenous stem cell proliferation induced by intravenous hedgehog agonist administration after contusion in the adult rat spinal cord.

    Science.gov (United States)

    Bambakidis, Nicholas C; Horn, Eric M; Nakaji, Peter; Theodore, Nicholas; Bless, Elizabeth; Dellovade, Tammy; Ma, Chiyuan; Wang, Xukui; Preul, Mark C; Coons, Stephen W; Spetzler, Robert F; Sonntag, Volker K H

    2009-02-01

    Sonic hedgehog (Shh) is a glycoprotein molecule that upregulates the transcription factor Gli1. The Shh protein plays a critical role in the proliferation of endogenous neural precursor cells when directly injected into the spinal cord after a spinal cord injury in adult rodents. Small-molecule agonists of the hedgehog (Hh) pathway were used in an attempt to reproduce these findings through intravenous administration. The expression of Gli1 was measured in rat spinal cord after the intravenous administration of an Hh agonist. Ten adult rats received a moderate contusion and were treated with either an Hh agonist (10 mg/kg, intravenously) or vehicle (5 rodents per group) 1 hour and 4 days after injury. The rats were killed 5 days postinjury. Tissue samples were immediately placed in fixative. Samples were immunohistochemically stained for neural precursor cells, and these cells were counted. Systemic dosing with an Hh agonist significantly upregulated Gli1 expression in the spinal cord (p < 0.005). After spinal contusion, animals treated with the Hh agonist had significantly more nestin-positive neural precursor cells around the rim of the lesion cavity than in vehicle-treated controls (means +/- SDs, 46.9 +/- 12.9 vs 20.9 +/- 8.3 cells/hpf, respectively, p < 0.005). There was no significant difference in the area of white matter injury between the groups. An intravenous Hh agonist at doses that upregulate spinal cord Gli1 transcription also increases the population of neural precursor cells after spinal cord injury in adult rats. These data support previous findings based on injections of Shh protein directly into the spinal cord.

  20. Serotonin, dopamine and noradrenaline adjust actions of myelinated afferents via modulation of presynaptic inhibition in the mouse spinal cord.

    Directory of Open Access Journals (Sweden)

    David L García-Ramírez

    Full Text Available Gain control of primary afferent neurotransmission at their intraspinal terminals occurs by several mechanisms including primary afferent depolarization (PAD. PAD produces presynaptic inhibition via a reduction in transmitter release. While it is known that descending monoaminergic pathways complexly regulate sensory processing, the extent these actions include modulation of afferent-evoked PAD remains uncertain. We investigated the effects of serotonin (5HT, dopamine (DA and noradrenaline (NA on afferent transmission and PAD. Responses were evoked by stimulation of myelinated hindlimb cutaneous and muscle afferents in the isolated neonatal mouse spinal cord. Monosynaptic responses were examined in the deep dorsal horn either as population excitatory synaptic responses (recorded as extracellular field potentials; EFPs or intracellular excitatory postsynaptic currents (EPSCs. The magnitude of PAD generated intraspinally was estimated from electrotonically back-propagating dorsal root potentials (DRPs recorded on lumbar dorsal roots. 5HT depressed the DRP by 76%. Monosynaptic actions were similarly depressed by 5HT (EFPs 54%; EPSCs 75% but with a slower time course. This suggests that depression of monosynaptic EFPs and DRPs occurs by independent mechanisms. DA and NA had similar depressant actions on DRPs but weaker effects on EFPs. IC50 values for DRP depression were 0.6, 0.8 and 1.0 µM for 5HT, DA and NA, respectively. Depression of DRPs by monoamines was nearly-identical in both muscle and cutaneous afferent-evoked responses, supporting a global modulation of the multimodal afferents stimulated. 5HT, DA and NA produced no change in the compound antidromic potentials evoked by intraspinal microstimulation indicating that depression of the DRP is unrelated to direct changes in the excitability of intraspinal afferent fibers, but due to metabotropic receptor activation. In summary, both myelinated afferent-evoked DRPs and monosynaptic

  1. LncRNA expression in the spinal cord modulated by minocycline in a mouse model of spared nerve injury

    Directory of Open Access Journals (Sweden)

    Liu ZH

    2017-10-01

    Full Text Available Zihao Liu, Ying Liang, Honghua Wang, Zhenhe Lu, Jinsheng Chen, Qiaodong Huang, Lei Sheng, Yinghong Ma, Huiying Du, Qingjuan GongDepartment of Pain Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China Abstract: Neuropathic pain is a common and refractory chronic pain that affects millions of people worldwide. Its underlying mechanisms are still unclear, but they may involve long noncoding RNAs (lncRNAs, which play crucial roles in a variety of biological functions, including nociception. We used microarrays to investigate the possible interactions between lncRNAs and neuropathic pain and identified 22,213 lncRNAs and 19,528 mRNAs in the spinal cord in a mouse model of spared nerve injury (SNI-induced neuropathic pain. The abundance levels of 183 lncRNAs and 102 mRNAs were significantly modulated by both SNI and administration of minocycline. A quantitative real-time polymerase chain reaction analysis validated expression changes in three lncRNAs (NR_015491, ENSMUST00000174263, and ENSMUST00000146263. Class distribution analysis of differentially expressed lncRNAs revealed intergenic lncRNAs as the largest category. Functional analysis indicated that SNI-induced gene regulations might be involved in the activities of cytokines (IL17A and IL17F and chemokines (CCL2, CCL5, and CCL7, whereas minocycline might exert a pain-alleviating effect on mice through actin binding, thereby regulating nociception by controlling the cytoskeleton. Thus, lncRNAs might be responsible for SNI-induced neuropathic pain and the attenuation caused by minocycline. Our study could implicate lncRNAs as potential targets for future treatment of neuropathic pain. Keywords: LncRNA, neuropathic pain, spinal cord, minocycline

  2. Neuronal activity in the isolated mouse spinal cord during spontaneous deletions in fictive locomotion: insights into locomotor central pattern generator organization

    Science.gov (United States)

    Zhong, Guisheng; Shevtsova, Natalia A; Rybak, Ilya A; Harris-Warrick, Ronald M

    2012-01-01

    We explored the organization of the spinal central pattern generator (CPG) for locomotion by analysing the activity of spinal interneurons and motoneurons during spontaneous deletions occurring during fictive locomotion in the isolated neonatal mouse spinal cord, following earlier work on locomotor deletions in the cat. In the isolated mouse spinal cord, most spontaneous deletions were non-resetting, with rhythmic activity resuming after an integer number of cycles. Flexor and extensor deletions showed marked asymmetry: flexor deletions were accompanied by sustained ipsilateral extensor activity, whereas rhythmic flexor bursting was not perturbed during extensor deletions. Rhythmic activity on one side of the cord was not perturbed during non-resetting spontaneous deletions on the other side, and these deletions could occur with no input from the other side of the cord. These results suggest that the locomotor CPG has a two-level organization with rhythm-generating (RG) and pattern-forming (PF) networks, in which only the flexor RG network is intrinsically rhythmic. To further explore the neuronal organization of the CPG, we monitored activity of motoneurons and selected identified interneurons during spontaneous non-resetting deletions. Motoneurons lost rhythmic synaptic drive during ipsilateral deletions. Flexor-related commissural interneurons continued to fire rhythmically during non-resetting ipsilateral flexor deletions. Deletion analysis revealed two classes of rhythmic V2a interneurons. Type I V2a interneurons retained rhythmic synaptic drive and firing during ipsilateral motor deletions, while type II V2a interneurons lost rhythmic synaptic input and fell silent during deletions. This suggests that the type I neurons are components of the RG, whereas the type II neurons are components of the PF network. We propose a computational model of the spinal locomotor CPG that reproduces our experimental results. The results may provide novel insights into the

  3. Leisure time physical activity among older adults with long-term spinal cord injury.

    Science.gov (United States)

    Jörgensen, S; Martin Ginis, K A; Lexell, J

    2017-09-01

    Cross-sectional. To describe participation in leisure time physical activity (LTPA) (amount, intensity and type) among older adults with long-term spinal cord injury (SCI), and to investigate the associations with sociodemographics, injury characteristics and secondary health conditions (SHCs). Home settings in southern Sweden. Data from the Swedish Aging with Spinal Cord Injury Study (SASCIS). The physical activity recall assessment for people with SCI was used to assess LTPA among 84 men and 35 women (mean age 63.5 years, mean time since injury 24 years, injury levels C1-L5, American Spinal Injury Association Impairment Scale A-D). Associations were analyzed statistically using hierarchical multivariable regression. Twenty-nine percent reported no LTPA, whereas 53% performed moderate-to-heavy intensity LTPA. The mean minutes per day of total LTPA was 34.7 (±41.5, median 15, range 0-171.7) and of moderate-to-heavy LTPA 22.5 (±35.1, median 5.0, range 0-140.0). The most frequently performed activities were walking and wheeling. Sociodemographics, injury characteristics and SHCs (bowel-related and bladder-related problems, spasticity and pain) explained 10.6% and 13.4%, respectively, of the variance in total and moderate-to-heavy LTPA. Age and wheelchair use were significantly, negatively associated with total LTPA. Women, wheelchair users and employed participants performed significantly less moderate-to-heavy LTPA than men, those using walking devices/no mobility device and unemployed participants. Many older adults with long-term SCI do not reach the amount or intensity of LTPA needed to achieve fitness benefits. Research is needed on how to increase LTPA and to identify modifiable factors that could enhance their participation.

  4. Conduction of impulses by axons regenerated in a Schwann cell graft in the transected adult rat thoracic spinal cord.

    Science.gov (United States)

    Pinzon, A; Calancie, B; Oudega, M; Noga, B R

    2001-06-01

    Central nervous system axons regenerate into a Schwann cell implant placed in the transected thoracic spinal cord of an adult rat. The present study was designed to test whether these regenerated axons are capable of conducting action potentials. Following the transection and removal of a 4- to 5-mm segment of the thoracic spinal cord (T8-T9), a polymer guidance channel filled with a mixture of adult rat Schwann cells and Matrigel was grafted into a 4- to 5-mm-long gap in the transected thoracic spinal cord. The two cut ends of the spinal cord were eased into the guidance channel openings. Transected control animals received a channel containing Matrigel only. Three months after implantation, electrophysiological studies were performed. Tungsten microelectrodes were used for monopolar stimulation of regenerated axons within the Schwann cell graft. Glass microelectrodes were used to record responses in the spinal cord rostral to the stimulation site. Evoked responses to electrical stimulation of the axon cable were found in two out of nine Schwann cell-grafted animals. These responses had approximate latencies in the range of those of myelinated axons. No responses were seen in any of the Matrigel-grafted animals. Histological analysis revealed that the two cases that showed evoked potentials had the largest number of myelinated axons present in the cable. This study demonstrates that axons regenerating through Schwann cell grafts in the complete transected spinal cord can produce measurable evoked responses following electrical stimulation. Copyright 2001 Wiley-Liss, Inc.

  5. eGFP expression under the Uchl1 promoter labels corticospinal motor neurons and a subpopulation of degeneration resistant spinal motor neurons in ALS mouse models

    Science.gov (United States)

    Yasvoina, Marina V.

    Current understanding of basic cellular and molecular mechanisms for motor neuron vulnerability during motor neuron disease initiation and progression is incomplete. The complex cytoarchitecture and cellular heterogeneity of the cortex and spinal cord greatly impedes our ability to visualize, isolate, and study specific neuron populations in both healthy and diseased states. We generated a novel reporter line, the Uchl1-eGFP mouse, in which cortical and spinal components of motor neuron circuitry are genetically labeled with eGFP under the Uchl1 promoter. A series of cellular and anatomical analyses combined with retrograde labeling, molecular marker expression, and electrophysiology were employed to determine identity of eGFP expressing cells in the motor cortex and the spinal cord of novel Uchl1-eGFP reporter mice. We conclude that eGFP is expressed in corticospinal motor neurons (CSMN) in the motor cortex and a subset of S-type alpha and gamma spinal motor neurons (SMN) in the spinal cord. hSOD1G93A and Alsin-/- mice, mouse models for amyotrophic lateral sclerosis (ALS), were bred to Uchl1-eGFP reporter mouse line to investigate the pathophysiology and underlying mechanisms of CSMN degeneration in vivo. Evidence suggests early and progressive degeneration of CSMN and SMN in the hSOD1G93A transgenic mice. We show an early increase of autophagosome formation in the apical dendrites of vulnerable CSMN in hSOD1G93A-UeGFP mice, which is localized to the apical dendrites. In addition, labeling S-type alpha and gamma SMN in the hSOD1G93A-UeGFP mice provide a unique opportunity to study basis of their resistance to degeneration. Mice lacking alsin show moderate clinical phenotype and mild CSMN axon degeneration in the spinal cord, which suggests vulnerability of CSMN. Therefore, we investigated the CSMN cellular and axon defects in aged Alsin-/- mice bred to Uchl1-eGFP reporter mouse line. We show that while CSMN are preserved and lack signs of degeneration, CSMN axons

  6. Primary Spinal OPC Culture System from Adult Zebrafish to Study Oligodendrocyte Differentiation In Vitro

    Directory of Open Access Journals (Sweden)

    Volker Kroehne

    2017-09-01

    Full Text Available Endogenous oligodendrocyte progenitor cells (OPCs are a promising target to improve functional recovery after spinal cord injury (SCI by remyelinating denuded, and therefore vulnerable, axons. Demyelination is the result of a primary insult and secondary injury, leading to conduction blocks and long-term degeneration of the axons, which subsequently can lead to the loss of their neurons. In response to SCI, dormant OPCs can be activated and subsequently start to proliferate and differentiate into mature myelinating oligodendrocytes (OLs. Therefore, researchers strive to control OPC responses, and utilize small molecule screening approaches in order to identify mechanisms of OPC activation, proliferation, migration and differentiation. In zebrafish, OPCs remyelinate axons of the optic tract after lysophosphatidylcholine (LPC-induced demyelination back to full thickness myelin sheaths. In contrast to zebrafish, mammalian OPCs are highly vulnerable to excitotoxic stress, a cause of secondary injury, and remyelination remains insufficient. Generally, injury induced remyelination leads to shorter internodes and thinner myelin sheaths in mammals. In this study, we show that myelin sheaths are lost early after a complete spinal transection injury, but are re-established within 14 days after lesion. We introduce a novel, easy-to-use, inexpensive and highly reproducible OPC culture system based on dormant spinal OPCs from adult zebrafish that enables in vitro analysis. Zebrafish OPCs are robust, can easily be purified with high viability and taken into cell culture. This method enables to examine why zebrafish OPCs remyelinate better than their mammalian counterparts, identify cell intrinsic responses, which could lead to pro-proliferating or pro-differentiating strategies, and to test small molecule approaches. In this methodology paper, we show efficient isolation of OPCs from adult zebrafish spinal cord and describe culture conditions that enable

  7. Left–right coordination from simple to extreme conditions during split‐belt locomotion in the chronic spinal adult cat

    Science.gov (United States)

    Desrochers, Étienne; Thibaudier, Yann; Hurteau, Marie‐France; Dambreville, Charline

    2016-01-01

    Key points Coordination between the left and right sides is essential for dynamic stability during locomotion.The immature or neonatal mammalian spinal cord can adjust to differences in speed between the left and right sides during split‐belt locomotion by taking more steps on the fast side.We show that the adult mammalian spinal cord can also adjust its output so that the fast side can take more steps.During split‐belt locomotion, only certain parts of the cycle are modified to adjust left–right coordination, primarily those associated with swing onset.When the fast limb takes more steps than the slow limb, strong left–right interactions persist.Therefore, the adult mammalian spinal cord has a remarkable adaptive capacity for left–right coordination, from simple to extreme conditions. Abstract Although left–right coordination is essential for locomotion, its control is poorly understood, particularly in adult mammals. To investigate the spinal control of left–right coordination, a spinal transection was performed in six adult cats that were then trained to recover hindlimb locomotion. Spinal cats performed tied‐belt locomotion from 0.1 to 1.0 m s−1 and split‐belt locomotion with low to high (1:1.25–10) slow/fast speed ratios. With the left hindlimb stepping at 0.1 m s−1 and the right hindlimb stepping from 0.2 to 1.0 m s−1, 1:1, 1:2, 1:3, 1:4 and 1:5 left–right step relationships could appear. The appearance of 1:2+ relationships was not linearly dependent on the difference in speed between the slow and fast belts. The last step taken by the fast hindlimb displayed longer cycle, stance and swing durations and increased extensor activity, as the slow limb transitioned to swing. During split‐belt locomotion with 1:1, 1:2 and 1:3 relationships, the timing of stance onset of the fast limb relative to the slow limb and placement of both limbs at contact were invariant with increasing slow/fast speed ratios. In contrast, the timing of

  8. [Post-traumatic reconnection of the cervical spinal cord with skeletal striated muscles. Study in adult rats and marmosets].

    Science.gov (United States)

    Horvat, J C; Affane-Boulaid, F; Baillet-Derbin, C; Davarpanah, Y; Destombes, J; Duchossoy, Y; Emery, E; Kassar-Duchossoy, L; Mira, J C; Moissonnier, P; Pécot-Dechavassine, M; Reviron, T; Rhrich-Haddout, F; Tadié, M; Ye, J H

    1997-01-01

    In an attempt at repairing the injured spinal cord of adult mammals (rat, dog and marmoset) and its damaged muscular connections, we are currently using: 1) peripheral nerve autografts (PNG), containing Schwann cells, to trigger and direct axonal regrowth from host and/or transplanted motoneurons towards denervated muscular targets; 2) foetal spinal cord transplants to replace lost neurons. In adult rats and marmosets, a PNG bridge was used to joint the injured cervical spinal cord to a denervated skeletal muscle (longissimus atlantis [rat] or biceps brachii [rat and marmoset]). The spinal lesion was obtained by the implantation procedure of the PNG. After a post-operative delay ranging from 2 to 22 months, the animals were checked electrophysiologically for functional muscular reconnection and processed for a morphological study including retrograde axonal tracing (HRP, Fast Blue, True Blue), histochemistry (AChE, ATPase), immunocytochemistry (ChAT) and EM. It was thus demonstrated that host motoneurons of the cervical enlargement could extend axons all the way through the PNG bridge as: a) in anaesthetized animals, contraction of the reconnected muscle could be obtained by electrical stimulation of the grafted nerve; b) the retrograde axonal tracing studies indicated that a great number of host cervical neurons extended axons into the PNG bridge up to the muscle; c) many of them were assumed to be motoneurons (double labelling with True Blue and an antibody against ChAT); and even alpha-motoneurons (type C axosomatic synapses in HRP labelled neurons seen in EM in the rat); d) numerous ectopic endplates were seen around the intramuscular tip of the PNG. In larger (cavitation) spinal lesions (rat), foetal motoneurons contained in E14 spinal cord transplants could similarly grow axons through PNG bridges up to the reconnected muscle. Taking all these data into account, it can be concluded that neural transplants are interesting tools for evaluating both the

  9. Steadiness of Spinal Regions during Single-Leg Standing in Older Adults with and without Chronic Low Back Pain

    OpenAIRE

    Kuo, Yi-Liang; Huang, Kuo-Yuan; Chiang, Pei-Tzu; Lee, Pei-Yun; Tsai, Yi-Ju

    2015-01-01

    The aims of this study were to compare the steadiness index of spinal regions during single-leg standing in older adults with and without chronic low back pain (LBP) and to correlate measurements of steadiness index with the performance of clinical balance tests. Thirteen community-dwelling older adults (aged 55 years or above) with chronic LBP and 13 age- and gender-matched asymptomatic volunteers participated in this study. Data collection was conducted in a university research laboratory. ...

  10. Evidence for a role of srGAP3 in the positioning of commissural axons within the ventrolateral funiculus of the mouse spinal cord.

    Directory of Open Access Journals (Sweden)

    Claire Bacon

    Full Text Available Slit-Robo signaling guides commissural axons away from the floor-plate of the spinal cord and into the longitudinal axis after crossing the midline. In this study we have evaluated the role of the Slit-Robo GTPase activating protein 3 (srGAP3 in commissural axon guidance using a knockout (KO mouse model. Co-immunoprecipitation experiments confirmed that srGAP3 interacts with the Slit receptors Robo1 and Robo2 and immunohistochemistry studies showed that srGAP3 co-localises with Robo1 in the ventral and lateral funiculus and with Robo2 in the lateral funiculus. Stalling axons have been reported in the floor-plate of Slit and Robo mutant spinal cords but our axon tracing experiments revealed no dorsal commissural axon stalling in the floor plate of the srGAP3 KO mouse. Interestingly we observed a significant thickening of the ventral funiculus and a thinning of the lateral funiculus in the srGAP3 KO spinal cord, which has also recently been reported in the Robo2 KO. However, axons in the enlarged ventral funiculus of the srGAP3 KO are Robo1 positive but do not express Robo2, indicating that the thickening of the ventral funiculus in the srGAP3 KO is not a Robo2 mediated effect. We suggest a role for srGAP3 in the lateral positioning of post crossing axons within the ventrolateral funiculus.

  11. Adult-onset intradural spinal teratoma: report of 18 consecutive cases and outcomes in a single center.

    Science.gov (United States)

    Wan, Wei; Yang, Cheng; Yan, Wangjun; Liu, Tielong; Yang, Xinghai; Song, Dianwen; Xiao, Jianru

    2017-07-01

    Eighteen consecutive patients with adult-onset intradural spinal teratoma underwent surgical treatment in our center from 1998 to 2013. Teratoma is defined as a neoplasm composed of elements derived from three germ cell layers (ectoderm, endoderm and mesoderm). Intraspinal teratoma is extremely rare and accounts for 0.2-0.5% of all spinal cord tumors. Moreover, teratoma occurs primarily in neonates and young children. Adult-onset intradural spinal teratoma is even rare. The aim of this study was to discuss the clinical characteristics, diagnosis and therapeutic strategies of adult-onset intradural spinal teratoma. This retrospective study included 18 consecutive adult patients with intradural teratoma who were surgically treated in our center between 1998 and 2013. The clinical features, pathogenesis, diagnostic strategies and surgical outcomes were discussed. Neurological function outcomes were evaluated by the JOA scoring system. Of the 18 included patients, 4 patients received subtotal resection and the other 14 patients received total resection. All the 18 cases were diagnosed with mature teratoma. The mean follow-up period was 79.7 (median 60.5; range 27-208) months. Local recurrence occurred in two of the four patients who underwent subtotal resection and in no patient who underwent total resection. The neurologic status improved in 16 cases and remained unchanged in the other two patients. Adult-onset intradural spinal teratoma is extremely rare. To the best of our knowledge, this is the largest series of patients with this disease. Despite the slow-growth and indolent nature, radical resection remains the recommended treatment to reduce tumor recurrence.

  12. Analysis of the modifying influence of Plastin 3 (PLS3) on Spinal Muscular Atrophy (SMA) by generation of transgenic mouse models

    OpenAIRE

    Ackermann, Bastian

    2011-01-01

    Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by the loss of α-motor neurons in the ventral horn of the spinal cord. Depending on the severity, the clinical spectrum of SMA ranges from early infant death to normal adult life with only mild muscle weakness. To date, no cure is available. SMA is caused by the homozygous loss of the survival motor neuron gene 1 (SMN1). Besides SMN1, another nearly identical copy of the gene is present in the human genome, thus called...

  13. External validation of the adult spinal deformity (ASD) frailty index (ASD-FI).

    Science.gov (United States)

    Miller, Emily K; Vila-Casademunt, Alba; Neuman, Brian J; Sciubba, Daniel M; Kebaish, Khaled M; Smith, Justin S; Alanay, Ahmet; Acaroglu, Emre R; Kleinstück, Frank; Obeid, Ibrahim; Sánchez Pérez-Grueso, Francisco Javier; Carreon, Leah Y; Schwab, Frank J; Bess, Shay; Scheer, Justin K; Lafage, Virginie; Shaffrey, Christopher I; Pellisé, Ferran; Ames, Christopher P

    2018-03-30

    To assess the ability of the recently developed adult spinal deformity frailty index (ASD-FI) to predict odds of perioperative complications, odds of reoperation, and length of hospital stay after adult spinal deformity (ASD) surgery using a database other than the one used to create the index. We used the ASD-FI to calculate frailty scores for 266 ASD patients who had minimum postoperative follow-up of 2 years in the European Spine Study Group (ESSG) database. Patients were enrolled from 2012 through 2013. Using ASD-FI scores, we categorized patients as not frail (NF) ( 0.5 points). Multivariable logistic regression, adjusted for preoperative and surgical factors such as operative time and blood loss, was performed to determine the relationship between ASD-FI category and odds of major complications, odds of reoperation, and length of hospital stay. We categorized 135 patients (51%) as NF, 90 patients (34%) as frail, and 41 patients (15%) as SF. Overall mean ASD-FI score was 0.29 (range 0-0.8). The adjusted odds of experiencing a major intraoperative or postoperative complication (OR 4.5, 95% CI 2.0-10) or having a reoperation (OR 3.9, 95% CI 1.7-8.9) were higher for SF patients compared with NF patients. Mean hospital stay was 2.1 times longer (95% CI 1.8-2.4) for SF patients compared with NF patients. Greater patient frailty, as measured by the ASD-FI, is associated with longer hospital stays and greater odds of major complications and reoperation. These slides can be retrieved under Electronic Supplementary Material.

  14. The spatiotemporal relationships between chondroitin sulfate proteoglycans and terminations of calcitonin gene related peptide and parvalbumin immunoreactive afferents in the spinal cord of mouse embryos.

    Science.gov (United States)

    Wang, Liqing; Yu, Chao; Wang, Jun; Zhao, Hui; Chan, Sun-On

    2017-08-10

    Chondroitin sulfate (CS) proteoglycans (PGs) are a family of complex molecules in the extracellular matrix and cell surface that regulate axon growth and guidance during development of the central nervous system. In this study, the expression of CSPGs was investigated in the mouse spinal cord at late embryonic and neonatal stages using CS-56 antibody. CS immunoreactivity was observed abundantly in ventral regions of spinal cord of embryonic day (E) 15 embryos. At E16 to E18, CS expression spread dorsally, but never reached the superficial layers of the dorsal horn. This pattern was maintained until postnatal day 4, the latest stage examined. Antibodies against calcitonin gene related peptide (CGRP) and parvalbumin (PV) were employed to label primary afferents from nociceptors and proprioceptors, respectively. CGRP-immunoreactive fibers terminated in the superficial regions of the dorsal horn where CSPGs were weakly expressed, whereas PV-immunoreactive fibers were found in CSPG-rich regions in the ventral horn. Therefore, we conclude that CS expression is spatiotemporally regulated in the spinal cord, which correlates to the termination of sensory afferents. This pattern suggests a role of CSPGs on patterning afferents in the spinal cord, probably through a differential response of axons to these growth inhibitory molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. A method for unit recording in the lumbar spinal cord during locomotion of the conscious adult rat

    DEFF Research Database (Denmark)

    Berg, Rune W; Chen, Ming-Teh; Huang, Hsueh-Chen

    2009-01-01

    Extracellular recordings from single units in the brain, for example the neocortex, have proven feasible in moving, awake rats, but have not yet been possible in the spinal cord. Single-unit activity during locomotor-like activity in reduced preparations from adult cats and rats have provided...... valuable insights for the development of hypotheses about the organization of functional networks in the spinal cord. However, since reduced preparations could result in spurious conclusions, it is crucial to test these hypotheses in animals that are awake and behaving. Furthermore, unresolved issues...

  16. Spinal shape analysis in 1,020 healthy young adults aged from 19 to 30 years

    Directory of Open Access Journals (Sweden)

    Jakub Krejčí

    2016-03-01

    Full Text Available Background: A number of studies on diseased spine have been published; however, there is a relative paucity of studies investigating spine shape characteristics in healthy populations. Such characteristics are needed for diagnostics of spine disorders and assessment of changes in the spinal shape that may have been caused by influence of the modern life style or intensive sport activity. Objective: The aim of the study was to determine characteristics of the spine shape in a large sample of healthy young adults. Methods: Population cross-sectional study. A non-radiographic surface method (system DTP-3 was used for the assessment of spine shape in the sagittal and frontal planes. A total of 1,020 participants (440 men, 580 women took part in the study, their mean (± SD age was 21.8 ± 1.9 years (range 19.1-29.7 for men and 21.9 ± 1.8 years (range 19.3-29.7 for women. All data were checked for normality and are presented as means, standard deviations, ranges, skewness, and kurtosis. Differences between the sexes were assessed with the two-sample t-test. Results: The average sagittal spinal shape was C3 - 12.9° - C7 - 43.0° - T10 - 27.1° - L5 for men and C3 - 12.1° - C6 - 44.5° - T11 - 34.1° - L5 for women. Men showed a significantly smaller thoracic kyphosis and lumbar lordosis curvatures than women. The average curvature due to the lateral deviation in the frontal plane was 6.1° for both sexes, the curvature was larger than 10° in 9.1% of men and 8.8% of women. We found left lateral deviation in 72.5% of men and in 63.6% of women. Conclusions: The study provides characteristics of the spine shape in a large sample of healthy young adults. Such characteristics should be part and parcel of determining the cut-off level for physiological spinal shape. Based on the results of the study, we suggest a lateral deviation of 10° as the maximum for a curvature to be still considered non-pathological.

  17. Short-scan-time multi-slice diffusion MRI of the mouse cervical spinal cord using echo planar imaging.

    Science.gov (United States)

    Callot, Virginie; Duhamel, Guillaume; Cozzone, Patrick J; Kober, Frank

    2008-10-01

    Mouse spinal cord (SC) diffusion-weighted imaging (DWI) provides important information on tissue morphology and structural changes that may occur during pathologies such as multiple sclerosis or SC injury. The acquisition scheme of the commonly used DWI techniques is based on conventional spin-echo encoding, which is time-consuming. The purpose of this work was to investigate whether the use of echo planar imaging (EPI) would provide good-quality diffusion MR images of mouse SC, as well as accurate measurements of diffusion-derived metrics, and thus enable diffusion tensor imaging (DTI) and highly resolved DWI within reasonable scan times. A four-shot diffusion-weighted spin-echo EPI (SE-EPI) sequence was evaluated at 11.75 T on a group of healthy mice (n = 10). SE-EPI-derived apparent diffusion coefficients of gray and white matter were compared with those obtained using a conventional spin-echo sequence (c-SE) to validate the accuracy of the method. To take advantage of the reduction in acquisition time offered by the EPI sequence, multi-slice DTI acquisitions were performed covering the cervical segments (six slices, six diffusion-encoding directions, three b values) within 30 min (vs 2 h for c-SE). From these measurements, fractional anisotropy and mean diffusivities were calculated, and fiber tracking along the C1 to C6 cervical segments was performed. In addition, high-resolution images (74 x 94 microm(2)) were acquired within 5 min per direction. Clear delineation of gray and white matter and identical apparent diffusion coefficient values were obtained, with a threefold reduction in acquisition time compared with c-SE. While overcoming the difficulties associated with high spatially and temporally resolved DTI measurements, the present SE-EPI approach permitted identification of reliable quantitative parameters with a reproducibility compatible with the detection of pathologies. The SE-EPI method may be particularly valuable when multiple sets of images

  18. Assessment of the effects of different sample perfusion procedures on phase-contrast tomographic images of mouse spinal cord

    Science.gov (United States)

    Stefanutti, E.; Sierra, A.; Miocchi, P.; Massimi, L.; Brun, F.; Maugeri, L.; Bukreeva, I.; Nurmi, A.; Begani Provinciali, G.; Tromba, G.; Gröhn, O.; Giove, F.; Cedola, A.; Fratini, M.

    2018-03-01

    Synchrotron X-ray Phase Contrast micro-Tomography (SXrPCμT) is a powerful tool in the investigation of biological tissues, including the central nervous system (CNS), and it allows to simultaneously detect the vascular and neuronal network avoiding contrast agents or destructive sample preparations. However, specific sample preparation procedures aimed to optimize the achievable contrast- and signal-to-noise ratio (CNR and SNR, respectively) are required. Here we report and discuss the effects of perfusion with two different fixative agents (ethanol and paraformaldehyde) and with a widely used contrast medium (MICROFIL®) on mouse spinal cord. As a main result, we found that ethanol enhances contrast at the grey/white matter interface and increases the contrast in correspondence of vascular features and fibres, thus providing an adequate spatial resolution to visualise the vascular network at the microscale. On the other hand, ethanol is known to induce tissue dehydration, likely reducing cell dimensions below the spatial resolution limit imposed by the experimental technique. Nonetheless, neurons remain well visible using either perfused paraformaldehyde or MICROFIL® compound, as these latter media do not affect tissues with dehydration effects. Paraformaldehyde appears as the best compromise: it is not a contrast agent, like MICROFIL®, but it is less invasive than ethanol and permits to visualise well both cells and blood vessels. However, a quantitative estimation of the relative grey matter volume of each sample has led us to conclude that no significant alterations in the grey matter extension compared to the white matter occur as a consequence of the perfusion procedures tested in this study.

  19. Steadiness of Spinal Regions during Single-Leg Standing in Older Adults with and without Chronic Low Back Pain.

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    Yi-Liang Kuo

    Full Text Available The aims of this study were to compare the steadiness index of spinal regions during single-leg standing in older adults with and without chronic low back pain (LBP and to correlate measurements of steadiness index with the performance of clinical balance tests. Thirteen community-dwelling older adults (aged 55 years or above with chronic LBP and 13 age- and gender-matched asymptomatic volunteers participated in this study. Data collection was conducted in a university research laboratory. Measurements were steadiness index of spinal regions (trunk, thoracic spine, lumbar spine, and pelvis during single-leg standing including relative holding time (RHT and relative standstill time (RST, and clinical balance tests (timed up and go test and 5-repetition sit to stand test. The LBP group had a statistically significantly smaller RHT than the control group, regardless of one leg stance on the painful or non-painful sides. The RSTs on the painful side leg in the LBP group were not statistically significantly different from the average RSTs of both legs in the control group; however, the RSTs on the non-painful side leg in the LBP group were statistically significantly smaller than those in the control group for the trunk, thoracic spine, and lumbar spine. No statistically significant intra-group differences were found in the RHTs and RSTs between the painful and non-painful side legs in the LBP group. Measurements of clinical balance tests also showed insignificant weak to moderate correlations with steadiness index. In conclusion, older adults with chronic LBP demonstrated decreased spinal steadiness not only in the symptomatic lumbar spine but also in the other spinal regions within the kinetic chain of the spine. When treating older adults with chronic LBP, clinicians may also need to examine their balance performance and spinal steadiness during balance challenging tests.

  20. Bone marrow stromal cells elicit tissue sparing after acute but not delayed transplantation into the contused adult rat thoracic spinal cord.

    NARCIS (Netherlands)

    Tewarie, R.D.; Hurtado, A.; Ritfeld, G.J.; Rahiem, S.T.; Wendell, D.F.; Barroso, M.M.; Grotenhuis, J.A.; Oudega, M.

    2009-01-01

    Bone marrow stromal cells (BMSC) transplanted into the contused spinal cord may support repair by improving tissue sparing. We injected allogeneic BMSC into the moderately contused adult rat thoracic spinal cord at 15 min (acute) and at 3, 7, and 21 days (delayed) post-injury and quantified tissue

  1. Cerebellar stem cells do not produce neurons and astrocytes in adult mouse

    International Nuclear Information System (INIS)

    Su, Xin; Guan, Wuqiang; Yu, Yong-Chun; Fu, Yinghui

    2014-01-01

    Highlights: • No new neurons and astrocytes are generated in adult mouse cerebellum. • Very few mash1 + or nestin + stem cells exist, and most of them are quiescent. • Cell proliferation rate is diversified among cerebellar regions and decreases over time. - Abstract: Although previous studies implied that cerebellar stem cells exist in some adult mammals, little is known about whether these stem cells can produce new neurons and astrocytes. In this study by bromodeoxyuridine (BrdU) intraperitoneal (i.p.) injection, we found that there are abundant BrdU + cells in adult mouse cerebellum, and their quantity and density decreases significantly over time. We also found cell proliferation rate is diversified in different cerebellar regions. Among these BrdU + cells, very few are mash1 + or nestin + stem cells, and the vast majority of cerebellar stem cells are quiescent. Data obtained by in vivo retrovirus injection indicate that stem cells do not produce neurons and astrocytes in adult mouse cerebellum. Instead, some cells labeled by retrovirus are Iba1 + microglia. These results indicate that very few stem cells exist in adult mouse cerebellum, and none of these stem cells contribute to neurogenesis and astrogenesis under physiological condition

  2. {sup 18}F-FDG PET/CT evaluation of children and young adults with suspected spinal fusion hardware infection

    Energy Technology Data Exchange (ETDEWEB)

    Bagrosky, Brian M. [University of Colorado School of Medicine, Department of Pediatric Radiology, Children' s Hospital Colorado, 12123 E. 16th Ave., Box 125, Aurora, CO (United States); University of Colorado School of Medicine, Department of Radiology, Division of Nuclear Medicine, Aurora, CO (United States); Hayes, Kari L.; Fenton, Laura Z. [University of Colorado School of Medicine, Department of Pediatric Radiology, Children' s Hospital Colorado, 12123 E. 16th Ave., Box 125, Aurora, CO (United States); Koo, Phillip J. [University of Colorado School of Medicine, Department of Radiology, Division of Nuclear Medicine, Aurora, CO (United States)

    2013-08-15

    Evaluation of the child with spinal fusion hardware and concern for infection is challenging because of hardware artifact with standard imaging (CT and MRI) and difficult physical examination. Studies using {sup 18}F-FDG PET/CT combine the benefit of functional imaging with anatomical localization. To discuss a case series of children and young adults with spinal fusion hardware and clinical concern for hardware infection. These people underwent FDG PET/CT imaging to determine the site of infection. We performed a retrospective review of whole-body FDG PET/CT scans at a tertiary children's hospital from December 2009 to January 2012 in children and young adults with spinal hardware and suspected hardware infection. The PET/CT scan findings were correlated with pertinent clinical information including laboratory values of inflammatory markers, postoperative notes and pathology results to evaluate the diagnostic accuracy of FDG PET/CT. An exempt status for this retrospective review was approved by the Institution Review Board. Twenty-five FDG PET/CT scans were performed in 20 patients. Spinal fusion hardware infection was confirmed surgically and pathologically in six patients. The most common FDG PET/CT finding in patients with hardware infection was increased FDG uptake in the soft tissue and bone immediately adjacent to the posterior spinal fusion rods at multiple contiguous vertebral levels. Noninfectious hardware complications were diagnosed in ten patients and proved surgically in four. Alternative sources of infection were diagnosed by FDG PET/CT in seven patients (five with pneumonia, one with pyonephrosis and one with superficial wound infections). FDG PET/CT is helpful in evaluation of children and young adults with concern for spinal hardware infection. Noninfectious hardware complications and alternative sources of infection, including pneumonia and pyonephrosis, can be diagnosed. FDG PET/CT should be the first-line cross-sectional imaging study in

  3. Targeting the Full Length of the Motor End Plate Regions in the Mouse Forelimb Increases the Uptake of Fluoro-Gold into Corresponding Spinal Cord Motor Neurons

    Directory of Open Access Journals (Sweden)

    Andrew Paul Tosolini

    2013-05-01

    Full Text Available Lower motor neuron dysfunction is one of the most debilitating motor conditions. In this regard, transgenic mouse models of various lower motor neuron dysfunctions provide insight into the mechanisms underlying these pathologies and can also aid the development of new therapies. Viral-mediated gene therapy can take advantage of the muscle-motor neuron topographical relationship to shuttle therapeutic genes into specific populations of motor neurons in these mouse models. In this context, motor end plates (MEPs are highly specialised regions on the skeletal musculature that offer direct access to the pre-synaptic nerve terminals, henceforth to the spinal cord motor neurons. The aim of this study was two-folded. First it was to characterise the exact position of the MEP regions for several muscles of the mouse forelimb using acetylcholinesterase histochemistry. This MEP-muscle map was then used to guide a series of intramuscular injections of Fluoro-Gold (FG in order to characterise the distribution of the innervating motor neurons. This analysis revealed that the MEPs are typically organised in an orthogonal fashion across the muscle fibres and extending throughout the full width of each muscle. Furthermore, targeting the full length of the MEP regions gave rise to a seemingly greater number of labelled motor neurons that are organised into columns spanning through more spinal cord segments than previously reported. The present analysis suggests that targeting the full width of the muscles’ MEP regions with FG increases the somatic availability of the tracer. This process ensures a greater uptake of the tracer by the pre-synaptic nerve terminals, hence maximising the labelling in spinal cord motor neurons. This investigation should have positive implications for future studies involving the somatic delivery of therapeutic genes into motor neurons for the treatment of various motor dysfunctions.

  4. Effects of exercise on fitness and health of adults with spinal cord injury: A systematic review.

    Science.gov (United States)

    van der Scheer, Jan W; Martin Ginis, Kathleen A; Ditor, David S; Goosey-Tolfrey, Victoria L; Hicks, Audrey L; West, Christopher R; Wolfe, Dalton L

    2017-08-15

    To synthesize and appraise research testing the effects of exercise interventions on fitness, cardiometabolic health, and bone health among adults with spinal cord injury (SCI). Electronic databases were searched (1980-2016). Included studies employed exercise interventions for a period ≥2 weeks, involved adults with acute or chronic SCI, and measured fitness (cardiorespiratory fitness, power output, or muscle strength), cardiometabolic health (body composition or cardiovascular risk factors), or bone health outcomes. Evidence was synthesized and appraised using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). A total of 211 studies met the inclusion criteria (22 acute, 189 chronic). For chronic SCI, GRADE confidence ratings were moderate to high for evidence showing exercise can improve all of the reviewed outcomes except bone health. For acute SCI, GRADE ratings were very low for all outcomes. For chronic SCI, there was low to moderate confidence in the evidence showing that 2-3 sessions/week of upper body aerobic exercise at a moderate to vigorous intensity for 20-40 minutes, plus upper body strength exercise (3 sets of 10 repetitions at 50%-80% 1-repetition maximum for all large muscle groups), can improve cardiorespiratory fitness, power output, and muscle strength. For chronic SCI, there was low to moderate confidence in the evidence showing that 3-5 sessions per week of upper body aerobic exercise at a moderate to vigorous intensity for 20-44 minutes can improve cardiorespiratory fitness, muscle strength, body composition, and cardiovascular risk. Exercise improves fitness and cardiometabolic health of adults with chronic SCI. The evidence on effective exercise types, frequencies, intensities, and durations should be used to formulate exercise guidelines for adults with SCI. © 2017 American Academy of Neurology.

  5. Involvement of TRPM2 in peripheral nerve injury-induced infiltration of peripheral immune cells into the spinal cord in mouse neuropathic pain model.

    Directory of Open Access Journals (Sweden)

    Kouichi Isami

    Full Text Available Recent evidence suggests that transient receptor potential melastatin 2 (TRPM2 expressed in immune cells plays an important role in immune and inflammatory responses. We recently reported that TRPM2 expressed in macrophages and spinal microglia contributes to the pathogenesis of inflammatory and neuropathic pain aggravating peripheral and central pronociceptive inflammatory responses in mice. To further elucidate the contribution of TRPM2 expressed by peripheral immune cells to neuropathic pain, we examined the development of peripheral nerve injury-induced neuropathic pain and the infiltration of immune cells (particularly macrophages into the injured nerve and spinal cord by using bone marrow (BM chimeric mice by crossing wildtype (WT and TRPM2-knockout (TRPM2-KO mice. Four types of BM chimeric mice were prepared, in which irradiated WT or TRPM2-KO recipient mice were transplanted with either WT-or TRPM2-KO donor mouse-derived green fluorescence protein-positive (GFP(+ BM cells (TRPM2(BM+/Rec+, TRPM2(BM-/Rec+, TRPM2(BM+/Rec-, and TRPM2(BM-/Rec- mice. Mechanical allodynia induced by partial sciatic nerve ligation observed in TRPM2(BM+/Rec+ mice was attenuated in TRPM2(BM-/Rec+, TRPM2(BM+/Rec-, and TRPM2(BM-/Rec- mice. The numbers of GFP(+ BM-derived cells and Iba1/GFP double-positive macrophages in the injured sciatic nerve did not differ among chimeric mice 14 days after the nerve injury. In the spinal cord, the number of GFP(+ BM-derived cells, particularly GFP/Iba1 double-positive macrophages, was significantly decreased in the three TRPM2-KO chimeric mouse groups compared with TRPM2(BM+/Rec+ mice. However, the numbers of GFP(-/Iba1(+ resident microglia did not differ among chimeric mice. These results suggest that TRPM2 plays an important role in the infiltration of peripheral immune cells, particularly macrophages, into the spinal cord, rather than the infiltration of peripheral immune cells into the injured nerves and activation of spinal

  6. Effect of stretching program in an industrial workplace on hamstring flexibility and sagittal spinal posture of adult women workers: a randomized controlled trial.

    Science.gov (United States)

    Muyor, José M; López-Miñarro, Pedro A; Casimiro, Antonio J

    2012-01-01

    To determine the effect of a stretching program performed in the workplace on the hamstring muscle extensibility and sagittal spinal posture of adult women. Fifty-eight adult women volunteers (mean age of 44.23 ± 8.87 years) from a private fruit and vegetable company were randomly assigned to experimental (n=27) or control (n=31) groups. The experimental group performed three exercises of hamstrings stretching of 20 seconds per exercise, three sessions a week for a period of 12 weeks. The control group did not participate in any hamstring stretching program. Hamstring flexibility was evaluated through the passive straight leg raise test and toe-touch test, performed both before and after the stretching program. Thoracic and lumbar curvatures and pelvic inclination were measured in relaxed standing and toe-touch test with a Spinal Mouse. Significant increases (p < 0.01) in toe-touch score and straight leg raise angle (in both legs) were found in the experimental group during post-test, while the control group showed a non-significant decrease for both toe-touch score and straight leg raise test. A significant decrease in thoracic curve and significant increase in pelvic inclination were found in the toe-touch test for the experimental group (p <0.05). However, no significant changes were found in standing posture for any group. Hamstring stretching exercises performed in the working place are effective for increasing hamstring muscle extensibility. This increase generates a more aligned thoracic curve and more anterior pelvic inclination when maximal trunk flexion is performed.

  7. Comparison of Diffusion MRI Acquisition Protocols for the In Vivo Characterization of the Mouse Spinal Cord: Variability Analysis and Application to an Amyotrophic Lateral Sclerosis Model.

    Science.gov (United States)

    Figini, Matteo; Scotti, Alessandro; Marcuzzo, Stefania; Bonanno, Silvia; Padelli, Francesco; Moreno-Manzano, Victoria; García-Verdugo, José Manuel; Bernasconi, Pia; Mantegazza, Renato; Bruzzone, Maria Grazia; Zucca, Ileana

    2016-01-01

    Diffusion-weighted Magnetic Resonance Imaging (dMRI) has relevant applications in the microstructural characterization of the spinal cord, especially in neurodegenerative diseases. Animal models have a pivotal role in the study of such diseases; however, in vivo spinal dMRI of small animals entails additional challenges that require a systematical investigation of acquisition parameters. The purpose of this study is to compare three acquisition protocols and identify the scanning parameters allowing a robust estimation of the main diffusion quantities and a good sensitivity to neurodegeneration in the mouse spinal cord. For all the protocols, the signal-to-noise and contrast-to noise ratios and the mean value and variability of Diffusion Tensor metrics were evaluated in healthy controls. For the estimation of fractional anisotropy less variability was provided by protocols with more diffusion directions, for the estimation of mean, axial and radial diffusivity by protocols with fewer diffusion directions and higher diffusion weighting. Intermediate features (12 directions, b = 1200 s/mm2) provided the overall minimum inter- and intra-subject variability in most cases. In order to test the diagnostic sensitivity of the protocols, 7 G93A-SOD1 mice (model of amyotrophic lateral sclerosis) at 10 and 17 weeks of age were scanned and the derived diffusion parameters compared with those estimated in age-matched healthy animals. The protocols with an intermediate or high number of diffusion directions provided the best differentiation between the two groups at week 17, whereas only few local significant differences were highlighted at week 10. According to our results, a dMRI protocol with an intermediate number of diffusion gradient directions and a relatively high diffusion weighting is optimal for spinal cord imaging. Further work is needed to confirm these results and for a finer tuning of acquisition parameters. Nevertheless, our findings could be important for the

  8. Exploring factors facilitating adults with spinal cord injury rejoining the workforce: a pilot study.

    Science.gov (United States)

    Wilbanks, Susan R; Ivankova, Nataliya V

    2015-01-01

    Return-to-work (RTW) rates after spinal cord injury (SCI) in the USA are very low and are continuing to decline. Previous research has attempted to identify factors facilitating RTW; however, the phenomenon of RTW involves many personal factors and predicting RTW success remains difficult. The purpose of this pilot study was to explore the factors facilitating adults with SCI rejoining the workforce in an urban area in order to identify items that may be emphasized in the rehabilitation process. The study was completed using qualitative methods. Four adults who had acquired a traumatic SCI in adulthood and were currently employed participated. Their experiences in RTW after injury were collected via semi-structured interviews and photography of assistive devices. The most common facilitating factor was motivation, with family and rehabilitation professionals serving as extrinsic motivators. Other facilitators were resources and perceived benefits. Motivation and resources were important facilitators, including rehabilitation professional's personal influence and therapies, and resource assistance from state agencies. The results indicate that practitioners can play an important role in influencing RTW, and resources from state agencies are helpful when individuals know how to access and utilize them. Assistive technology supports successful return to work after SCI. Motivation strongly influences return to work after SCI and can be influenced by rehabilitation professionals, family and community members. Patients should be well informed about how to access assistance programs such as vocational rehabilitation.

  9. A prospective evaluation of a pressure ulcer prevention and management E-Learning Program for adults with spinal cord injury.

    Science.gov (United States)

    Brace, Jacalyn A; Schubart, Jane R

    2010-08-01

    Pressure ulcers are a common complication of spinal cord injury (SCI). Pressure ulcer education programs for spinal cord injured individuals have been found to have a positive effect on care protocol adherence. A prospective study was conducted among hospitalized spinal cord-injured men and women to determine if viewing the Pressure Ulcer Prevention and Management Education for Adults with Spinal Cord Injury: E-Learning Program affects their knowledge scores. A 20-question multiple-choice pre-/post learning test was developed and validated by 12 rehabilitation nurses. Twenty (20) patients (13 men, seven women; mean age 49 years, [SD: 18.26] with injuries to the cervical [seven], thoracic [six], and lumbar [six] regions) volunteered. Most (42%) had completed high school and time since SCI ranged from 2 weeks to 27 years. Eighteen (18) participants completed both the pre- and post test. Of those, 16 showed improvement in pressure ulcer knowledge scores. The median scores improved from 65 (range 25 to 100) pre-program to 92.5 (range 75 to 100) post-program. Descriptive statistics, Student's t-test, and analysis of variance (ANOVA) were used to analyze the data. The results suggest that a single viewing of this e-learning program could improve pressure ulcer knowledge of hospitalized adults with SCI. Research to ascertain the effects of this and other educational programs on pressure ulcer rates is needed.

  10. The familial dysautonomia disease gene IKBKAP is required in the developing and adult mouse central nervous system

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    Marta Chaverra

    2017-05-01

    Full Text Available Hereditary sensory and autonomic neuropathies (HSANs are a genetically and clinically diverse group of disorders defined by peripheral nervous system (PNS dysfunction. HSAN type III, known as familial dysautonomia (FD, results from a single base mutation in the gene IKBKAP that encodes a scaffolding unit (ELP1 for a multi-subunit complex known as Elongator. Since mutations in other Elongator subunits (ELP2 to ELP4 are associated with central nervous system (CNS disorders, the goal of this study was to investigate a potential requirement for Ikbkap in the CNS of mice. The sensory and autonomic pathophysiology of FD is fatal, with the majority of patients dying by age 40. While signs and pathology of FD have been noted in the CNS, the clinical and research focus has been on the sensory and autonomic dysfunction, and no genetic model studies have investigated the requirement for Ikbkap in the CNS. Here, we report, using a novel mouse line in which Ikbkap is deleted solely in the nervous system, that not only is Ikbkap widely expressed in the embryonic and adult CNS, but its deletion perturbs both the development of cortical neurons and their survival in adulthood. Primary cilia in embryonic cortical apical progenitors and motile cilia in adult ependymal cells are reduced in number and disorganized. Furthermore, we report that, in the adult CNS, both autonomic and non-autonomic neuronal populations require Ikbkap for survival, including spinal motor and cortical neurons. In addition, the mice developed kyphoscoliosis, an FD hallmark, indicating its neuropathic etiology. Ultimately, these perturbations manifest in a developmental and progressive neurodegenerative condition that includes impairments in learning and memory. Collectively, these data reveal an essential function for Ikbkap that extends beyond the peripheral nervous system to CNS development and function. With the identification of discrete CNS cell types and structures that depend on

  11. Doublecortin-like knockdown in the adult mouse brain : implications for neurogenesis, neuroplasticity and behaviour

    NARCIS (Netherlands)

    Saaltink, Dirk-Jan

    2014-01-01

    The results in this thesis showed for the first time doublecortin-like (DCL)-specific expression in the adult mouse brain. Besides the expected regions with the capacity to generate new neurons (hippocampus and olfactory forebrain), DCL expression was found in three novel brain areas namely

  12. The influence of secondary conditions on job acquisition and retention in adults with spinal cord injury.

    Science.gov (United States)

    Meade, Michelle A; Forchheimer, Martin B; Krause, James S; Charlifue, Susan

    2011-03-01

    To examine the associations of job acquisition and job retention to secondary conditions, hospitalizations, and nursing home stays for adults with spinal cord injury (SCI). Retrospective analysis of longitudinal data from multicenter study. Community setting. Two samples of adults participating in the SCI Model Systems; the first sample consisted of persons who reported being unemployed at follow-up (n=9501); the second sample consisted of those who reported working at follow-up (n=5,150). Not applicable. Job acquisition (change from not working at 1 anniversary of injury to working at the following data collection) and job retention (maintenance of work between 2 assessment periods). Discrete time hazard modeling was used to assess how secondary conditions affect job acquisition. After controlling for the effects of demographic and injury characteristics, hospitalizations within the last 12 months were associated with decreased chance of having obtained employment. Hierarchic logistic regression analyses were used to examine job retention. Hospitalizations and the presence of PUs were associated with lower odds of job retention once demographic and injury characteristics were controlled. Secondary conditions from the previous assessment period were not significantly related to either job acquisition or job retention after the variance from demographic and injury characteristics and current secondary conditions were controlled. Hospitalization, as well as a limited number of secondary conditions, were associated with reduced odds of both job acquisition and job retention among adults with SCI. Interventions that can prevent secondary conditions and reduce the need for hospitalizations may be beneficial in improving employment for this population. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  13. Teriparatide versus low-dose bisphosphonates before and after surgery for adult spinal deformity in female Japanese patients with osteoporosis.

    Science.gov (United States)

    Seki, Shoji; Hirano, Norikazu; Kawaguchi, Yoshiharu; Nakano, Masato; Yasuda, Taketoshi; Suzuki, Kayo; Watanabe, Kenta; Makino, Hiroto; Kanamori, Masahiko; Kimura, Tomoatsu

    2017-08-01

    Complications of adult spinal deformity surgery are problematic in osteoporotic individuals. We compared outcomes between Japanese patients treated perioperatively with teriparatide vs. low-dose bisphosphonates. Fifty-eight osteoporotic adult Japanese female patients were enrolled and assigned to perioperative teriparatide (33 patients) and bisphosphonate (25 patients) groups in non-blinded fashion. Pre- and post-operative X-ray and computed tomography imaging were used to assess outcome, and rates were compared between the groups and according to age. Pain scores and Oswestry Disability Indices (ODI) were calculated before and 2 years after surgery. Adjacent vertebral fractures and implant failure, fusion failure, and poor pain and ODI outcomes were significantly more common in the bisphosphonates group than the teriparatide group. Perioperative administration of teriparatide is more effective than that of low-dose bisphosphonates in preventing complications and maintaining fusion rates in osteoporotic Japanese females with spinal deformities undergoing surgery.

  14. Peer mentoring of adults with spinal cord injury: a transformational leadership perspective.

    Science.gov (United States)

    Beauchamp, Mark R; Scarlett, Louisa J; Ruissen, Geralyn R; Connelly, Catherine E; McBride, Christopher B; Casemore, Sheila; Martin Ginis, Kathleen A

    2016-09-01

    Drawing from the tenets of transformational leadership theory, the purpose of this study was to examine the nature of effective peer mentoring of adults with a spinal cord injury (SCI) from the perspective of mentees. The study utilised a qualitative methodology (informed by a social constructionist approach), involving 15 adult mentees with a SCI (mean age = 47.2; mean time since injury = 14.5 years), in which data were obtained via semi-structured interviews. The results revealed that effective mentoring, as used by mentors with SCIs, closely aligns with the core components of transformational leadership. Specifically, all four dimensions of transformational leadership (idealised influence, inspirational motivation, individualised consideration and intellectual stimulation) as displayed by mentors with a SCI were evident in their interactions with mentees. Participants who perceived their mentors to use transformational leadership behaviours reported increases in motivation, self-confidence, hope and overall well-being, relatedness with their mentor, greater comfort/acceptance of their situation, a redefined sense of their limitations, as well as greater engagement in various life pursuits. Displays of transformational leadership by peer mentors (i.e. transformational mentoring) were reported by mentees to be associated with a range of adaptive psychological and behavioural outcomes. The results have the potential to inform the development and dissemination of peer mentor-based interventions and initiatives. Implications for Rehabilitation Within the context of spinal cord injury (SCI) rehabilitation, positive peer mentorship is reflected in mentors' use of transformational leadership behaviours (idealised influence, inspirational motivation, individualised consideration and intellectual stimulation). When SCI peer mentors use transformational leadership behaviours, mentees report a redefined sense of their limitations, and increased self-confidence, hope

  15. A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA

    Directory of Open Access Journals (Sweden)

    Andrea Luchetti

    2015-08-01

    Full Text Available Spinal muscular atrophy (SMA is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1, encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs, leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA.

  16. A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA).

    Science.gov (United States)

    Luchetti, Andrea; Ciafrè, Silvia Anna; Murdocca, Michela; Malgieri, Arianna; Masotti, Andrea; Sanchez, Massimo; Farace, Maria Giulia; Novelli, Giuseppe; Sangiuolo, Federica

    2015-08-06

    Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA.

  17. Isolation and culture of adult mouse vestibular nucleus neurons

    Science.gov (United States)

    Him, Aydın; Altuntaş, Serap; Öztürk, Gürkan; Erdoğan, Ender; Cengiz, Nureddin

    2017-12-19

    Background/aim: Isolated cell cultures are widely used to study neuronal properties due to their advantages. Although embryonic animals are preferred for culturing, their morphological or electrophysiological properties may not reflect adult neurons, which may be important in neurodegenerative diseases. This paper aims to develop a method for preparing isolated cell cultures of medial vestibular nucleus (MVN) from adult mice and describe its morphological and electrophysiological properties.Materials and methods: Vestibular nucleus neurons were mechanically and enzymatically isolated and cultured using a defined medium with known growth factors. Cell survival was measured with propidium iodide, and electrophysiological properties were investigated with current-clamp recording.Results: Vestibular neurons grew neurites in cultures, gaining adult-like morphological properties, and stayed viable for 3 days in culture. Adding bovine calf serum, nerve growth factor, or insulin-like growth factor into the culture medium enhanced neuronal viability. Current-clamp recording of the cultured neurons revealed tonic and phasic-type neurons with similar input resistance, resting membrane potential, action potential amplitude, and duration. Conclusion: Vestibular neurons from adult mice can be cultured, and regenerate axons in a medium containing appropriate growth factors. Culturing adult vestibular neurons provides a new method to study age-related pathologies of the vestibular system.

  18. Adult spinal deformity treated with minimally invasive surgery. Description of surgical technique, radiological results and literature review.

    Science.gov (United States)

    Domínguez, I; Luque, R; Noriega, M; Rey, J; Alía, J; Urda, A; Marco, F

    The prevalence of adult spinal deformity has been increasing exponentially over time. Surgery has been credited with good radiological and clinical results. The incidence of complications is high. MIS techniques provide good results with fewer complications. This is a retrospective study of 25 patients with an adult spinal deformity treated by MIS surgery, with a minimum follow-up of 6 months. Radiological improvement was SVA from 5 to 2cm, coronal Cobb angle from 31° to 6°, and lumbar lordosis from 18° to 38°. All of these parameters remained stable over time. We also present the complications that appeared in 4 patients (16%). Only one patient needed reoperation. We describe the technique used and review the references on the subject. We conclude that the MIS technique for treating adult spinal deformity has comparable results to those of the conventional techniques but with fewer complications. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Identification of a Peptide for Systemic Brain Delivery of a Morpholino Oligonucleotide in Mouse Models of Spinal Muscular Atrophy

    Science.gov (United States)

    Shabanpoor, Fazel; Hammond, Suzan M; Abendroth, Frank; Hazell, Gareth; Wood, Matthew J.A.

    2017-01-01

    Splice-switching antisense oligonucleotides are emerging treatments for neuromuscular diseases, with several splice-switching oligonucleotides (SSOs) currently undergoing clinical trials such as for Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA). However, the development of systemically delivered antisense therapeutics has been hampered by poor tissue penetration and cellular uptake, including crossing of the blood–brain barrier (BBB) to reach targets in the central nervous system (CNS). For SMA application, we have investigated the ability of various BBB-crossing peptides for CNS delivery of a splice-switching phosphorodiamidate morpholino oligonucleotide (PMO) targeting survival motor neuron 2 (SMN2) exon 7 inclusion. We identified a branched derivative of the well-known ApoE (141–150) peptide, which as a PMO conjugate was capable of exon inclusion in the CNS following systemic administration, leading to an increase in the level of full-length SMN2 transcript. Treatment of newborn SMA mice with this peptide-PMO (P-PMO) conjugate resulted in a significant increase in the average lifespan and gains in weight, muscle strength, and righting reflexes. Systemic treatment of adult SMA mice with this newly identified P-PMO also resulted in small but significant increases in the levels of SMN2 pre-messenger RNA (mRNA) exon inclusion in the CNS and peripheral tissues. This work provides proof of principle for the ability to select new peptide paradigms to enhance CNS delivery and activity of a PMO SSO through use of a peptide-based delivery platform for the treatment of SMA potentially extending to other neuromuscular and neurodegenerative diseases. PMID:28118087

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

    Science.gov (United States)

    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.

  1. Severe spinal stenosis in an adult achondroplastic dwarf – case report

    Directory of Open Access Journals (Sweden)

    B. Iliescu1, S. Gaivas1, C. Apetrei1, I. Poeată1,2

    2010-11-01

    Full Text Available Achondroplasia is the most commonform of human short-limbed dwarfism andis one of a spectrum of diseases caused bymutations in the FGFR3 gene.Achondroplasia is estimated to occur in 1 in10,000–30,000 live births4,7. The disease isautosomal dominant, but 80% of patientshave new mutations. It is commonlyassociated with several neurologicalconditions such as hydrocephalus,cervicomedullary compression, cervical orthoracic cord compression, and lumbarspinal compression due to bone stenosisalong the neuraxis. We report a case withsevere spinal stenosis at the lumbar andthoracic levels, with minimal involvementof the cervical spine with late neurologicalonset in an adult patient withachondroplasia. Neurological andradiological findings and surgicalprocedures are discussed. The patient wasadmitted with profound spastic lowerparaparesis and urinary incontinence. In thefirst operation we performed lumbardecompression and the patient improvedand on the fifth day she was able to take ashort walk. 3 months after the first surgerywe intervened on the thoracic spine with amulti-level decompression which allowedfor further neurological improvement,continued in a specialized medical facility.The case stands out as the clinical picturewas dominated by the lumbar stenosis(although both lumbar and thoracicstenosis were severe at the time ofpresentation with a late onset and sparingof the cervical spine.

  2. Magnetic resonance imaging of the normal and chronically injured adult rat spinal cord in vivo

    International Nuclear Information System (INIS)

    Guizar-Sahagun, G.; Rivera, F.; Babinski, E.; Berlanga, E.; Madrazo, M.; Franco-Bourland, R.; Grijalva, I.; Gonzalez, J.; Contreras, B.; Madrazo, I.

    1994-01-01

    We assessed the capacity of MRI to show and characterise the spinal cord (SC) in vivo in normal and chronically injured adult rats. In the chronically injured animals the SC was studied by MRI and histological examination. MRI was performed at 1.5 T, using gradient-echo and spin-echo (SE) sequences, the latter with and without gadolinium-DTPA (Gd-DTPA). Several positions were tried for good alignment and to diminish interference by respiratory movements. Images of the SC were obtained in sagittal, coronal, and axial planes. Normal SC was observed as a continuous intensity in both sequences, although contrast resolution was better using SE; it was not possible to differentiate the grey and white matter. Low signal was seen in the damaged area in chronically injured rats, which corresponded to cysts, trabeculae, mononuclear infiltrate, and fibroglial wall on histological examination. Gd-DTPA failed to enhance the SC in normal or chronically injured rats. It did, however, cause enhancement of the lesion after acute SC injury. (orig.)

  3. Magnetic resonance imaging of the normal and chronically injured adult rat spinal cord in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Guizar-Sahagun, G [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Clinical Research in Neurology and Neurosurgery, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Inst. Mexicano del Seguro Social, Mexico City (Mexico); Rivera, F [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico); Babinski, E [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico); Berlanga, E [Dept. of Magnetic Resonance Imaging, Hospital Angeles del Pedregal, Mexico City (Mexico); Madrazo, M [Dept. of Magnetic Resonance Imaging, Hospital Angeles del Pedregal, Mexico City (Mexico); Franco-Bourland, R [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Biochemistry, Inst. Nacional de la Nutricion, Mexico City (Mexico); Grijalva, I [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Clinical Research in Neurology and Neurosurgery, Hospital de Especialidades, Centro Medico Nacional Siglo

    1994-08-01

    We assessed the capacity of MRI to show and characterise the spinal cord (SC) in vivo in normal and chronically injured adult rats. In the chronically injured animals the SC was studied by MRI and histological examination. MRI was performed at 1.5 T, using gradient-echo and spin-echo (SE) sequences, the latter with and without gadolinium-DTPA (Gd-DTPA). Several positions were tried for good alignment and to diminish interference by respiratory movements. Images of the SC were obtained in sagittal, coronal, and axial planes. Normal SC was observed as a continuous intensity in both sequences, although contrast resolution was better using SE; it was not possible to differentiate the grey and white matter. Low signal was seen in the damaged area in chronically injured rats, which corresponded to cysts, trabeculae, mononuclear infiltrate, and fibroglial wall on histological examination. Gd-DTPA failed to enhance the SC in normal or chronically injured rats. It did, however, cause enhancement of the lesion after acute SC injury. (orig.)

  4. Clinical and stereoradiographic analysis of adult spinal deformity with and without rotatory subluxation.

    Science.gov (United States)

    Ferrero, E; Lafage, R; Challier, V; Diebo, B; Guigui, P; Mazda, K; Schwab, F; Skalli, W; Lafage, V

    2015-09-01

    In degenerative adult spinal deformity (ASD), sagittal malalignment and rotatory subluxation (RS) correlate with clinical symptomatology. RS is defined as axial rotation with lateral listhesis. Stereoradiography, recently developed for medical applications, provides full-body standing radiographs and 3D reconstruction of the spine, with low radiation dose. 3D stereoradiography improves analysis of RS and of its relations with transverse plane and spinopelvic parameters and clinical impact. One hundred and thirty adults with lumbar ASD and full-spine EOS® radiographs (EOS Imaging, Paris, France) were included. Spinopelvic sagittal parameters and lateral listhesis in the coronal plane were measured. The transverse plane study parameters were: apical axial vertebral rotation (apex AVR), axial intervertebral rotation (AIR) and torsion index (TI). Two groups were compared: with RS (lateral listhesis>5mm) and without RS (without lateral listhesis exceeding 5mm: non-RS). Correlations between radiologic and clinical data were assessed. RS patients were significantly older, with larger Cobb angle (37.4° vs. 26.6°, P=0.0001), more severe sagittal deformity, and greater apex AVR and TI (respectively: 22.9° vs. 11.3°, P10° without visible RS on 2D radiographs. RS patients reported significantly more frequent low back pain and radiculalgia. In this EOS® study, ASD patients with RS had greater coronal curvature and sagittal and transverse deformity, as well as greater pain. Further transverse plane analysis could allow earlier diagnosis and prognosis to guide management. 4, retrospective study. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  5. Isolation of mineralizing Nestin+ Nkx6.1+ vascular muscular cells from the adult human spinal cord

    Directory of Open Access Journals (Sweden)

    Guillon Hélène

    2011-10-01

    Full Text Available Abstract Background The adult central nervous system (CNS contains different populations of immature cells that could possibly be used to repair brain and spinal cord lesions. The diversity and the properties of these cells in the human adult CNS remain to be fully explored. We previously isolated Nestin+ Sox2+ neural multipotential cells from the adult human spinal cord using the neurosphere method (i.e. non adherent conditions and defined medium. Results Here we report the isolation and long term propagation of another population of Nestin+ cells from this tissue using adherent culture conditions and serum. QPCR and immunofluorescence indicated that these cells had mesenchymal features as evidenced by the expression of Snai2 and Twist1 and lack of expression of neural markers such as Sox2, Olig2 or GFAP. Indeed, these cells expressed markers typical of smooth muscle vascular cells such as Calponin, Caldesmone and Acta2 (Smooth muscle actin. These cells could not differentiate into chondrocytes, adipocytes, neuronal and glial cells, however they readily mineralized when placed in osteogenic conditions. Further characterization allowed us to identify the Nkx6.1 transcription factor as a marker for these cells. Nkx6.1 was expressed in vivo by CNS vascular muscular cells located in the parenchyma and the meninges. Conclusion Smooth muscle cells expressing Nestin and Nkx6.1 is the main cell population derived from culturing human spinal cord cells in adherent conditions with serum. Mineralization of these cells in vitro could represent a valuable model for studying calcifications of CNS vessels which are observed in pathological situations or as part of the normal aging. In addition, long term propagation of these cells will allow the study of their interaction with other CNS cells and their implication in scar formation during spinal cord injury.

  6. Teaching Adult Rats Spinalized as Neonates to Walk Using Trunk Robotic Rehabilitation: Elements of Success, Failure, and Dependence.

    Science.gov (United States)

    Udoekwere, Ubong I; Oza, Chintan S; Giszter, Simon F

    2016-08-10

    Robot therapy promotes functional recovery after spinal cord injury (SCI) in animal and clinical studies. Trunk actions are important in adult rats spinalized as neonates (NTX rats) that walk autonomously. Quadrupedal robot rehabilitation was tested using an implanted orthosis at the pelvis. Trunk cortical reorganization follows such rehabilitation. Here, we test the functional outcomes of such training. Robot impedance control at the pelvis allowed hindlimb, trunk, and forelimb mechanical interactions. Rats gradually increased weight support. Rats showed significant improvement in hindlimb stepping ability, quadrupedal weight support, and all measures examined. Function in NTX rats both before and after training showed bimodal distributions, with "poor" and "high weight support" groupings. A total of 35% of rats initially classified as "poor" were able to increase their weight-supported step measures to a level considered "high weight support" after robot training, thus moving between weight support groups. Recovered function in these rats persisted on treadmill with the robot both actuated and nonactuated, but returned to pretraining levels if they were completely disconnected from the robot. Locomotor recovery in robot rehabilitation of NTX rats thus likely included context dependence and/or incorporation of models of robot mechanics that became essential parts of their learned strategy. Such learned dependence is likely a hurdle to autonomy to be overcome for many robot locomotor therapies. Notwithstanding these limitations, trunk-based quadrupedal robot rehabilitation helped the rats to visit mechanical states they would never have achieved alone, to learn novel coordinations, and to achieve major improvements in locomotor function. Neonatal spinal transected rats without any weight support can be taught weight support as adults by using robot rehabilitation at trunk. No adult control rats with neonatal spinal transections spontaneously achieve similar changes

  7. Transcriptome signature of the adult mouse choroid plexus

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    Marques Fernanda

    2011-01-01

    Full Text Available Abstract Background Although the gene expression profile of several tissues in humans and in rodent animal models has been explored, analysis of the complete choroid plexus (CP transcriptome is still lacking. A better characterization of the CP transcriptome can provide key insights into its functions as one of the barriers that separate the brain from the periphery and in the production of cerebrospinal fluid. Methods This work extends further what is known about the mouse CP transcriptome through a microarray analysis of CP tissue from normal mice under physiological conditions. Results We found that the genes most highly expressed are those implicated in energy metabolism (oxidative phosphorylation, glycolysis/gluconeogenesis and in ribosomal function, which is in agreement with the secretory nature of the CP. On the other hand, genes encoding for immune mediators are among those with lower expression in basal conditions. In addition, we found genes known to be relevant during brain development, and not previously identified to be expressed in the CP, including those encoding for various axonal guidance and angiogenesis molecules and for growth factors. Some of these are known to influence the neural stem cell niche in the subventricular zone, highlighting the involvement of the CP as a likely modulator of neurogenesis. Interestingly, our observations confirm that the CP transcriptome is unique, displaying low homology with that of other tissues. Of note, we describe here that the closest similarity is with the transcriptome of the endothelial cells of the blood-brain barrier. Conclusions Based on the data presented here, it will now be possible to further explore the function of particular proteins of the CP secretome in health and in disease.

  8. Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers.

    Science.gov (United States)

    Guerrero-Bosagna, Carlos; Covert, Trevor R; Haque, Md M; Settles, Matthew; Nilsson, Eric E; Anway, Matthew D; Skinner, Michael K

    2012-12-01

    The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Incidence of spinal deformity in adults and its distribution according SRS-Schwab classification

    Directory of Open Access Journals (Sweden)

    Marcus Vinicius Amaral Barreto

    2015-06-01

    Full Text Available OBJECTIVE: To evaluate the incidence of spinal deformity in adults, as well as its distribution according the curve type and the occurrence of sagittal modifiers of the SRS-Schwab classification..METHODS: Radiographs in frontal and lateral views of the entire column were performed and radiographic parameters were used to diagnose the vertebral deformity for the classification according to the SRS-Schwab system.RESULTS: We included 302 patients in the study, 236 (78.1% women and 66 (21.9% men. Fifty-six of the participants were diagnosed with ASD, 50 women and 6 men. The incidence of ASD was 18.5% in the total population, ranging from 9.1% in males and 21.2% in females (p=0.04. As to age group, the incidence was 11.9% in patients between 18 and 39 years, 12% between 40 and 59 years and 28.8% in patients with 60 years of age or older, significantly higher in the oldest group (p=0.002. When analyzing the correlation between age and progression of sagittal modifiers, there was no significant difference in the PI-LL and PT modifiers, but there was significant difference of SVA modifier (p=0.008, with a higher age in individuals "++".CONCLUSION: This study presented demographic data on ASD in a Brazilian population sample. There was a higher incidence of ASD in females and individuals aged ≥ 60 years. As for the sagittal modifiers of SRS-Schwab classification, there was a correlation between increasing age and degree of progression of SVA.

  10. Cost Implications of Primary Versus Revision Surgery in Adult Spinal Deformity.

    Science.gov (United States)

    Qureshi, Rabia; Puvanesarajah, Varun; Jain, Amit; Kebaish, Khaled; Shimer, Adam; Shen, Francis; Hassanzadeh, Hamid

    2017-08-01

    Adult spinal deformity (ASD) is an important problem to consider in the elderly. Although studies have examined the complications of ASD surgery and have compared functional and radiographic results of primary surgery versus revision, no studies have compared the costs of primary procedures with revisions. We assessed the in-hospital costs of these 2 surgery types in patients with ASD. The PearlDiver Database, a database of Medicare records, was used in this study. Mutually exclusive groups of patients undergoing primary or revision surgery were identified. Patients in each group were queried for age, sex, and comorbidities. Thirty-day readmission rates, 30-day and 90-day complication rates, and postoperative costs of care were assessed with multivariate analysis. For analyses, significance was set at P average reimbursement of the primary surgery cohort was $57,078 ± $30,767. Reimbursement of revision surgery cohort was $52,999 ± $27,658. The adjusted difference in average costs between the 2 groups is $4773 ± $1069 (P day and 90-day adjusted difference in cost of care when sustaining any of the major medical complications in primary surgery versus revision surgery was insignificant. Patients undergoing primary and revision corrective procedures for ASD have similar readmission rates, lengths of stays, and complication rates. Our data showed a higher cost of primary surgery compared with revision surgery, although costs of sustaining postoperative complications were similar. This finding supports the decision to perform revision procedures in patients with ASD when indicated because neither outcomes nor costs are a hindrance to correction. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Experiences with Holistic Health Practices among Adults with Spinal Cord Injury

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    Farah M. Shroff

    2015-01-01

    Full Text Available Purpose To explore experiences with holistic practices (HP by people with spinal cord injury (SCI in British Columbia, Canada, including the types of HP they access and the reasons they utilize these forms of treatment. Method This was a qualitative study of 53 adults with SCI. Participants were engaged in semistructured interviews in focus-group and one-to-one settings. Inductive thematic analysis was used to identify prominent themes. Results Eighty-seven percent of participants had accessed some form of HP. They reported a variety of reasons for accessing HP, such as symptom relief and the desire to avoid side effects of conventional therapy. Caregivers and healthcare providers had important roles in encouraging HP. The perceived benefits of HP included physical, emotional, and spiritual components. Barriers to access included logistics, time, and financial constraints. Participants frequently mentioned the use of marijuana as a form of relaxation and pain relief—this was a surprise finding because marijuana is generally not considered a form of HP. Conclusion Eighty-seven percent of the participants in our study were actively engaged in various efforts to improve their health, including the use of HP. Reasons for accessing HP were based on a desire to improve mental, emotional, and physical health as well as to provide hope. Participants chose HP to alleviate pain, boost the immune system, gain strength, improve physical appearance, enhance relaxation, improve mood, feel empowered, and more. Rehabilitation professionals may wish to inform themselves of the range of products and services incorporated in the HP spectrum, and of their potential benefits for SCI patients.

  12. 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...

  13. Adult Mouse Liver Contains Two Distinct Populations of Cholangiocytes

    Directory of Open Access Journals (Sweden)

    Bin Li

    2017-08-01

    Full Text Available The biliary system plays an important role in several acquired and genetic disorders of the liver. We have previously shown that biliary duct epithelium contains cells giving rise to proliferative Lgr5+ organoids in vitro. However, it remained unknown whether all biliary cells or only a specific subset had this clonogenic activity. The cell surface protease ST14 was identified as a positive marker for the clonogenic subset of cholangiocytes and was used to separate clonogenic and non-clonogenic duct cells by fluorescence-activated cell sorting. Only ST14hi duct cells had the ability to generate organoids that could be serially passaged. The gene expression profiles of clonogenic and non-clonogenic duct cells were similar, but several hundred genes were differentially expressed. RNA fluorescence in situ hybridization showed that clonogenic duct cells are interspersed among regular biliary epithelium at a ∼1:3 ratio. We conclude that adult murine cholangiocytes can be subdivided into two populations differing in their proliferative capacity.

  14. The Adhesion Molecule-Characteristic HNK-1 Carbohydrate Contributes to Functional Recovery After Spinal Cord Injury in Adult Zebrafish.

    Science.gov (United States)

    Ma, Liping; Shen, Hui-Fan; Shen, Yan-Qin; Schachner, Melitta

    2017-07-01

    The human natural killer cell antigen-1 (HNK-1) is functionally important in development, synaptic activity, and regeneration after injury in the nervous system of several mammalian species. It contains a sulfated glucuronic acid which is carried by neural adhesion molecules and expressed in nonmammalian species, including zebrafish, which, as opposed to mammals, spontaneously regenerate after injury in the adult. To evaluate HNK-1's role in recovery of function after spinal cord injury (SCI) of adult zebrafish, we assessed the effects of the two HNK-1 synthesizing enzymes, glucuronyl transferase and HNK-1 sulfotransferase. Expression of these two enzymes was increased at the messenger RNA (mRNA) level 11 days after injury in the brainstem nuclei that are capable of regrowth of severed axons, namely, the nucleus of medial longitudinal fascicle and intermediate reticular formation, but not at earlier time points after SCI. mRNA levels of glucuronyl transferase and sulfotransferase were increased in neurons, not only of these nuclei but also in the spinal cord caudal to the injury site at 11 days. Mauthner neurons which are not capable of regeneration did not show increased levels of enzyme mRNAs after injury. Reducing protein levels of the enzymes by application of anti-sense morpholinos resulted in reduction of locomotor recovery for glucuronyl transferase, but not for HNK-1 sulfotransferase. The combined results indicate that HNK-1 is upregulated in expression only in those neurons that are intrinsically capable of regeneration and contributes to regeneration after spinal cord injury in adult zebrafish in the absence of its sulfate moiety.

  15. Association between seeking oral health information online and knowledge in adults with spinal cord injury: A pilot study

    Science.gov (United States)

    Yuen, Hon K.; Azuero, Andres; London, Steven

    2011-01-01

    Objective To characterize adults with spinal cord injury (SCI) who seek oral health information online, and investigate whether seeking oral health information online is associated with oral health knowledge and behaviors. Methods An online oral health survey was posted on the South Carolina Spinal Cord Injury Association website. Respondents were 192 adult residents of the US ages 19–83 years who identified themselves as having SCI occurring at least 1 year before the survey date. Results About 12% (n = 23) of the respondents searched oral health information online in the past 12 months. Significant associations between the proportion of respondents who searched for oral health information online and socio-demographic and the proportion of respondents who engaged in various oral health behaviors were not detected. However, multivariable logistic regression indicated that respondents who searched oral health information online in the past 12 months have 3.4 times the odds of possessing adequate oral health knowledge compared to respondents who did not search oral health information online (adjusted odds ratio = 3.41, 95% confidence interval = 1.35, 8.62, P = 0.01). Conclusions Given the significant association between seeking oral health information online and adequate oral health knowledge, this study suggests that online oral health information may be a potential avenue for dental health professionals to supplement oral health education in adults with SCI. PMID:21903017

  16. Systematic review of behavioral and educational interventions to prevent pressure ulcers in adults with spinal cord injury.

    Science.gov (United States)

    Cogan, Alison M; Blanchard, Jeanine; Garber, Susan L; Vigen, Cheryl Lp; Carlson, Mike; Clark, Florence A

    2017-07-01

    To investigate the efficacy of behavioral or educational interventions in preventing pressure ulcers in community-dwelling adults with spinal cord injury (SCI). Cochrane, Clinical Trials, PubMed, and Web of Science were searched in June 2016. The search combined related terms for pressure ulcers, spinal cord injury, and behavioral intervention. Each database was searched from its inception with no restrictions on year of publication. Inclusion criteria required that articles were (a) published in a peer-reviewed journal in English, (b) evaluated a behavioral or educational intervention for pressure ulcer prevention, (c) included community-dwelling adult participants aged 18 years and older with SCI, (d) measured pressure ulcer occurrence, recurrence, or skin breakdown as an outcome, and (e) had a minimum of 10 participants. All study designs were considered. Two reviewers independently screened titles and abstracts. Extracted information included study design, sample size, description of the intervention and control condition, pressure ulcer outcome measures, and corresponding results. The search strategy yielded 444 unique articles of which five met inclusion criteria. Three were randomized trials and two were quasi-experimental designs. A total of 513 participants were represented. The method of pressure ulcer or skin breakdown measurement varied widely among studies. Results on pressure ulcer outcomes were null in all studies. Considerable methodological problems with recruitment, intervention fidelity, and participant adherence were reported. At present, there is no positive evidence to support the efficacy of behavioral or educational interventions in preventing pressure ulcer occurrence in adults with SCI.

  17. Validity of a smartphone protractor to measure sagittal parameters in adult spinal deformity.

    Science.gov (United States)

    Kunkle, William Aaron; Madden, Michael; Potts, Shannon; Fogelson, Jeremy; Hershman, Stuart

    2017-10-01

    Smartphones have become an integral tool in the daily life of health-care professionals (Franko 2011). Their ease of use and wide availability often make smartphones the first tool surgeons use to perform measurements. This technique has been validated for certain orthopedic pathologies (Shaw 2012; Quek 2014; Milanese 2014; Milani 2014), but never to assess sagittal parameters in adult spinal deformity (ASD). This study was designed to assess the validity, reproducibility, precision, and efficiency of using a smartphone protractor application to measure sagittal parameters commonly measured in ASD assessment and surgical planning. This study aimed to (1) determine the validity of smartphone protractor applications, (2) determine the intra- and interobserver reliability of smartphone protractor applications when used to measure sagittal parameters in ASD, (3) determine the efficiency of using a smartphone protractor application to measure sagittal parameters, and (4) elucidate whether a physician's level of experience impacts the reliability or validity of using a smartphone protractor application to measure sagittal parameters in ASD. An experimental validation study was carried out. Thirty standard 36″ standing lateral radiographs were examined. Three separate measurements were performed using a marker and protractor; then at a separate time point, three separate measurements were performed using a smartphone protractor application for all 30 radiographs. The first 10 radiographs were then re-measured two more times, for a total of three measurements from both the smartphone protractor and marker and protractor. The parameters included lumbar lordosis, pelvic incidence, and pelvic tilt. Three raters performed all measurements-a junior level orthopedic resident, a senior level orthopedic resident, and a fellowship-trained spinal deformity surgeon. All data, including the time to perform the measurements, were recorded, and statistical analysis was performed to

  18. Dedifferentiation of intrinsic response properties of motoneurons in organotypic cultures of the spinal cord of the adult turtle

    DEFF Research Database (Denmark)

    Perrier, J.F.; Noraberg, J.; Simon, M.

    2000-01-01

    Explant cultures from the spinal cord of adult turtles were established and used to study the sensitivity of the intrinsic response properties of motoneurons to the changes in connectivity and milieu imposed by isolation in culture. Transverse sections 700 microm thick were explanted on cover slips...... the ability to fire repetitively. By the second week in culture, a fraction of motoneurons displayed fast and slow transient outward rectification and low-threshold calcium spikes, features not seen in turtle motoneurons in acute slices. On the other hand, properties mediated by L-type Ca2+ channels...

  19. An adult passive transfer mouse model to study desmoglein 3 signaling in pemphigus vulgaris.

    Science.gov (United States)

    Schulze, Katja; Galichet, Arnaud; Sayar, Beyza S; Scothern, Anthea; Howald, Denise; Zymann, Hillard; Siffert, Myriam; Zenhäusern, Denise; Bolli, Reinhard; Koch, Peter J; Garrod, David; Suter, Maja M; Müller, Eliane J

    2012-02-01

    Evidence has accumulated that changes in intracellular signaling downstream of desmoglein 3 (Dsg3) may have a significant role in epithelial blistering in the autoimmune disease pemphigus vulgaris (PV). Currently, most studies on PV involve passive transfer of pathogenic antibodies into neonatal mice that have not finalized epidermal morphogenesis, and do not permit analysis of mature hair follicles (HFs) and stem cell niches. To investigate Dsg3 antibody-induced signaling in the adult epidermis at defined stages of the HF cycle, we developed a model with passive transfer of AK23 (a mouse monoclonal pathogenic anti-Dsg3 antibody) into adult 8-week-old C57Bl/6J mice. Validated using histopathological and molecular methods, we found that this model faithfully recapitulates major features described in PV patients and PV models. Two hours after AK23 transfer, we observed widening of intercellular spaces between desmosomes and EGFR activation, followed by increased Myc expression and epidermal hyperproliferation, desmosomal Dsg3 depletion, and predominant blistering in HFs and oral mucosa. These data confirm that the adult passive transfer mouse model is ideally suited for detailed studies of Dsg3 antibody-mediated signaling in adult skin, providing the basis for investigations on novel keratinocyte-specific therapeutic strategies.

  20. Brain transcriptional stability upon prion protein-encoding gene invalidation in zygotic or adult mouse

    Directory of Open Access Journals (Sweden)

    Béringue Vincent

    2010-07-01

    Full Text Available Abstract Background The physiological function of the prion protein remains largely elusive while its key role in prion infection has been expansively documented. To potentially assess this conundrum, we performed a comparative transcriptomic analysis of the brain of wild-type mice with that of transgenic mice invalidated at this locus either at the zygotic or at the adult stages. Results Only subtle transcriptomic differences resulting from the Prnp knockout could be evidenced, beside Prnp itself, in the analyzed adult brains following microarray analysis of 24 109 mouse genes and QPCR assessment of some of the putatively marginally modulated loci. When performed at the adult stage, neuronal Prnp disruption appeared to sequentially induce a response to an oxidative stress and a remodeling of the nervous system. However, these events involved only a limited number of genes, expression levels of which were only slightly modified and not always confirmed by RT-qPCR. If not, the qPCR obtained data suggested even less pronounced differences. Conclusions These results suggest that the physiological function of PrP is redundant at the adult stage or important for only a small subset of the brain cell population under classical breeding conditions. Following its early reported embryonic developmental regulation, this lack of response could also imply that PrP has a more detrimental role during mouse embryogenesis and that potential transient compensatory mechanisms have to be searched for at the time this locus becomes transcriptionally activated.

  1. Effects of core instability strength training on trunk muscle strength, spinal mobility, dynamic balance and functional mobility in older adults.

    Science.gov (United States)

    Granacher, Urs; Lacroix, Andre; Muehlbauer, Thomas; Roettger, Katrin; Gollhofer, Albert

    2013-01-01

    Age-related postural misalignment, balance deficits and strength/power losses are associated with impaired functional mobility and an increased risk of falling in seniors. Core instability strength training (CIT) involves exercises that are challenging for both trunk muscles and postural control and may thus have the potential to induce benefits in trunk muscle strength, spinal mobility and balance performance. The objective was to investigate the effects of CIT on measures of trunk muscle strength, spinal mobility, dynamic balance and functional mobility in seniors. Thirty-two older adults were randomly assigned to an intervention group (INT; n = 16, aged 70.8 ± 4.1 years) that conducted a 9-week progressive CIT or to a control group (n = 16, aged 70.2 ± 4.5 years). Maximal isometric strength of the trunk flexors/extensors/lateral flexors (right, left)/rotators (right, left) as well as of spinal mobility in the sagittal and the coronal plane was measured before and after the intervention program. Dynamic balance (i.e. walking 10 m on an optoelectric walkway, the Functional Reach test) and functional mobility (Timed Up and Go test) were additionally tested. Program compliance was excellent with participants of the INT group completing 92% of the training sessions. Significant group × test interactions were found for the maximal isometric strength of the trunk flexors (34%, p training-related improvements were found for spinal mobility in the sagittal (11%, p velocity (9%, p velocity (31%, p training regimen could be used as an adjunct or even alternative to traditional balance and/or resistance training. Copyright © 2012 S. Karger AG, Basel.

  2. Extended magnetic resonance imaging studies on the effect of classically activated microglia transplantation on white matter regeneration following spinal cord focal injury in adult rats

    Science.gov (United States)

    Marcol, Wiesław; Ślusarczyk, Wojciech; Larysz-Brysz, Magdalena; Łabuzek, Krzysztof; Kapustka, Bartosz; Staszkiewicz, Rafał; Rosicka, Paulina; Kalita, Katarzyna; Węglarz, Władysław; Lewin-Kowalik, Joanna

    2017-01-01

    Spinal cord injuries are still a serious problem for regenerative medicine. Previous research has demonstrated that activated microglia accumulate in spinal lesions, influencing the injured tissues in various ways. Therefore, transplantation of activated microglia may have a beneficial role in the regeneration of the nervous system. The present study examined the influence of transplanted activated microglial cells in adult rats with injured spinal cords. Rats were randomly divided into an experimental (M) and control (C) group, and were subjected to non-laminectomy focal injury of spinal cord white matter by means of a high-pressured air stream. In group M, activated cultured microglial cells were injected twice into the site of injury. Functional outcome and morphological features of regeneration were analyzed during a 12-week follow-up. The lesions were characterized by means of magnetic resonance imaging (MRI). Neurons in the brain stem and motor cortex were labeled with FluoroGold (FG). A total of 12 weeks after surgery, spinal cords and brains were collected and subjected to histopathological and immunohistochemical examinations. Lesion sizes in the spinal cord were measured and the number of FG-positive neurons was counted. Rats in group M demonstrated significant improvement of locomotor performance when compared with group C (PMRI analysis demonstrated moderate improvement in water diffusion along the spinal cord in the group M following microglia treatment, as compared with group C. The water diffusion perpendicular to the spinal cord in group M was closer to the reference values for a healthy spinal cord than it was in group C. The sizes of lesions were also significantly smaller in group M than in the group C (P<0.05). The number of brain stem and motor cortex FG-positive neurons in group M was significantly higher than in group C. The present study demonstrated that delivery of activated microglia directly into the injured spinal cord gives some

  3. Adult-type myogenesis of the frog Xenopus laevis specifically suppressed by notochord cells but promoted by spinal cord cells in vitro.

    Science.gov (United States)

    Yamane, Hitomi; Ihara, Setsunosuke; Kuroda, Masaaki; Nishikawa, Akio

    2011-08-01

    Larval-to-adult myogenic conversion occurs in the dorsal muscle but not in the tail muscle during Xenopus laevis metamorphosis. To know the mechanism for tail-specific suppression of adult myogenesis, response character was compared between adult myogenic cells (Ad-cells) and larval tail myogenic cells (La-cells) to a Sonic hedgehog (Shh) inhibitor, notochord (Nc) cells, and spinal cord (SC) cells in vitro. Cyclopamine, an Shh inhibitor, suppressed the differentiation of cultured Ad (but not La) cells, suggesting the significance of Shh signaling in promoting adult myogenesis. To test the possibility that Shh-producing axial elements (notochord and spinal cord) regulate adult myogenesis, Ad-cells or La-cells were co-cultured with Nc or SC cells. The results showed that differentiation of Ad-cells were strongly inhibited by Nc cells but promoted by SC cells. If Ad-cells were "separately" co-cultured with Nc cells without direct cell-cell interactions, adult differentiation was not inhibited but rather promoted, suggesting that Nc cells have two roles, one is a short-range suppression and another is a long-range promotion for adult myogenesis. Immunohistochemical analysis showed both notochord and spinal cord express the N-terminal Shh fragment throughout metamorphosis. The "spinal cord-promotion" and long-range effect by Nc cells on adult myogenesis is thus involved in Shh signaling, while the signaling concerning the short-range "Nc suppression" will be determined by future studies. Interestingly, these effects, "Nc suppression" and "SC promotion" were not observed for La-cells. Situation where the spinal cord/notochord cross-sectional ratio is quite larger in tadpole trunk than in the tail seems to contribute to trunk-specific promotion and tail-specific suppression of adult myogenesis during Xenopus metamorphosis.

  4. Prospective multicenter surveillance and risk factor analysis of deep surgical site infection after posterior thoracic and/or lumbar spinal surgery in adults.

    Science.gov (United States)

    Ogihara, Satoshi; Yamazaki, Takashi; Maruyama, Toru; Oka, Hiroyuki; Miyoshi, Kota; Azuma, Seiichi; Yamada, Takashi; Murakami, Motoaki; Kawamura, Naohiro; Hara, Nobuhiro; Terayama, Sei; Morii, Jiro; Kato, So; Tanaka, Sakae

    2015-01-01

    Surgical site infection is a serious and significant complication after spinal surgery and is associated with high morbidity rates, high healthcare costs and poor patient outcomes. Accurate identification of risk factors is essential for developing strategies to prevent devastating infections. The purpose of this study was to identify independent risk factors for surgical site infection among posterior thoracic and/or lumbar spinal surgery in adult patients using a prospective multicenter surveillance research method. From July 2010 to June 2012, we performed a prospective surveillance study in adult patients who had developed surgical site infection after undergoing thoracic and/or lumbar posterior spinal surgery at 11 participating hospitals. Detailed preoperative and operative patient characteristics were prospectively recorded using a standardized data collection format. Surgical site infection was based on the definition established by the Centers for Disease Control and Prevention. A total of 2,736 consecutive adult patients were enrolled, of which 24 (0.9%) developed postoperative deep surgical site infection. Multivariate regression analysis indicated four independent risk factors. Preoperative steroid therapy (P = 0.001), spinal trauma (P = 0.048) and gender (male) (P = 0.02) were statistically significant independent patient-related risk factors, whereas an operating time ≥3 h (P operating time ≥3 h were independent risk factors for deep surgical site infection after thoracic and/or lumbar spinal surgery in adult patients. Identification of these risk factors can be used to develop protocols aimed at decreasing the risk of surgical site infection.

  5. Immunostaining for Homer reveals the majority of excitatory synapses in laminae I?III of the mouse spinal dorsal horn

    OpenAIRE

    Gutierrez-Mecinas, Maria; Kuehn, Emily D.; Abraira, Victoria E.; Polg?r, Erika; Watanabe, Masahiko; Todd, Andrew J.

    2016-01-01

    The spinal dorsal horn processes somatosensory information before conveying it to the brain. The neuronal organization of the dorsal horn is still poorly understood, although recent studies have defined several distinct populations among the interneurons, which account for most of its constituent neurons. All primary afferents, and the great majority of neurons in laminae I–III are glutamatergic, and a major factor limiting our understanding of the synaptic circuitry has been the difficulty i...

  6. Detection of phosphorylated mitogen-activated protein kinase in the developing spinal cord of the mouse embryo

    International Nuclear Information System (INIS)

    Teraishi, Toshiya; Miura, Kenji

    2011-01-01

    Highlights: → We detected physiologically phosphorylated MAPKs in developing spinal cord. → We detected physiologically phosphorylated MAPKs by an improved method. → p-ERK1/2 and p-JNK1/2 were detected in the marginal layer and the dorsal horn. → p-ERK1/2 and p-JNK1/2 might play critical roles in the developing spinal cord. → Constructing phosphoprotein atlases will be possible if expanding this work. -- Abstract: Global understanding of the proteome is a major research topic. The comprehensive visualization of the distribution of proteins in vivo or the construction of in situ protein atlases may be a valuable strategy for proteomic researchers. Information about the distribution of various proteins under physiological and pathological conditions should be extremely valuable for the basic and clinical sciences. The mitogen-activated protein kinase (MAPK) cascade plays an essential role in intracellular signaling in organisms. This cascade also regulates biological processes involving development, differentiation, and proliferation. Phosphorylation and dephosphorylation are integral reactions in regulating the activity of MAPKs. Changes in the phosphorylation state of MAPKs are rapid and reversible; therefore, the localizations of physiologically phosphorylated MAPKs in vivo are difficult to accurately detect. Furthermore, phosphorylated MAPKs are likely to change phosphorylated states through commonly used experimental manipulations. In the present study, as a step toward the construction of in situ phosphoprotein atlases, we attempted to detect physiologically phosphorylated MAPKs in vivo in developing spinal cords of mice. We previously reported an improved immunohistochemical method for detecting unstable phosphorylated MAPKs. The distribution patterns of phosphorylated MAPKs in the spinal cords of embryonic mice from embryonic day 13 (E13) to E17 were observed with an improved immunohistochemical method. Phosphorylated extracellular signal

  7. Depressive symptoms among older adults with long-term spinal cord injury: Associations with secondary health conditions, sense of coherence, coping strategies and physical activity

    Directory of Open Access Journals (Sweden)

    Sophie Jörgensen

    2017-07-01

    Full Text Available Objectives: To assess the presence of depressive symptoms among older adults with long-term spinal cord injury and investigate the association with sociodemographic and injury characteristics; and to determine how potentially modifiable factors, i.e. secondary health conditions, sense of coherence, coping strategies and leisure-time physical activity, are associated with depressive symptoms. Design: Cross-sectional study. Subjects: A total of 122 individuals (70% men, injury levels C1–L5, American Spinal Injury Association Impairment Scale A–D, mean age 63 years, mean time since injury 24 years. Methods: Data from the Swedish Aging with Spinal Cord Injury Study, collected using the Geriatric Depression Scale-15, the 13-item Sense of Coherence Scale, the Spinal Cord Lesion-related Coping Strategies Questionnaire and the Physical Activity Recall Assessment for people with Spinal Cord Injury. Associations were analysed using multivariable linear regression. Results: A total of 29% reported clinically relevant depressive symptoms and 5% reported probable depression. Sense of coherence, the coping strategy Acceptance, neuropathic pain and leisure-time physical activity explained 53% of the variance in depressive symptoms. Conclusion: Older adults with long-term spinal cord injury report a low presence of probable depression. Mental health may be supported through rehabilitation that strengthens the ability to understand and confront life stressors, promotes acceptance of the injury, provides pain management and encourages participation in leisure-time physical activity.

  8. Sertoli cells maintain Leydig cell number and peritubular myoid cell activity in the adult mouse testis.

    Directory of Open Access Journals (Sweden)

    Diane Rebourcet

    Full Text Available The Sertoli cells are critical regulators of testis differentiation and development. In the adult, however, their known function is restricted largely to maintenance of spermatogenesis. To determine whether the Sertoli cells regulate other aspects of adult testis biology we have used a novel transgenic mouse model in which Amh-Cre induces expression of the receptor for Diphtheria toxin (iDTR specifically within Sertoli cells. This causes controlled, cell-specific and acute ablation of the Sertoli cell population in the adult animal following Diphtheria toxin injection. Results show that Sertoli cell ablation leads to rapid loss of all germ cell populations. In addition, adult Leydig cell numbers decline by 75% with the remaining cells concentrated around the rete and in the sub-capsular region. In the absence of Sertoli cells, peritubular myoid cell activity is reduced but the cells retain an ability to exclude immune cells from the seminiferous tubules. These data demonstrate that, in addition to support of spermatogenesis, Sertoli cells are required in the adult testis both for retention of the normal adult Leydig cell population and for support of normal peritubular myoid cell function. This has implications for our understanding of male reproductive disorders and wider androgen-related conditions affecting male health.

  9. Identification and characterization of adult mouse meniscus stem/progenitor cells.

    Science.gov (United States)

    Gamer, Laura W; Shi, Rui Rui; Gendelman, Ashira; Mathewson, Dylan; Gamer, Jackson; Rosen, Vicki

    Meniscal damage is a common problem that accelerates the onset of knee osteoarthritis. Stem cell-based tissue engineering treatment approaches have shown promise in preserving meniscal tissue and restoring meniscal function. The purpose of our study was to identify meniscus-derived stem/progenitor cells (MSPCs) from mouse, a model system that allows for in vivo analysis of the mechanisms underlying meniscal injury and healing. MSPCs were isolated from murine menisci grown in explant culture and characterized for stem cell properties. Flow cytometry was used to detect the presence of surface antigens related to stem cells, and qRT-PCR was used to examine the gene expression profile of MSPCs. Major proteins associated with MSPCs were localized in the adult mouse knee using immunohistochemistry. Our data show that MSPCs have universal stem cell-like properties including clonogenicity and multi-potentiality. MSPCs expressed the mesenchymal stem cell markers CD44, Sca-1, CD90, and CD73 and when cultured had elevated levels of biglycan and collagen type I, important extracellular matrix components of adult meniscus. MSPC also expressed significant levels of Lox and Igf-1, genes associated with the embryonic meniscus. Localization studies showed staining for these same proteins in the superficial and outer zones of the adult mouse meniscus, regions thought to harbor endogenous repair cells. MSPCs represent a novel resident stem cell population in the murine meniscus. Analysis of MSPCs in mice will allow for a greater understanding of the cell biology of the meniscus, essential information for enhancing therapeutic strategies for treating knee joint injury and disease.

  10. Effects of enriched housing on functional recovery after spinal cord contusive injury in the adult rat

    NARCIS (Netherlands)

    Gispen, W.H.; Lankhorst, A.J.; Laak, M.P. ter; Laar, T.J. van

    2001-01-01

    To date, most research performed in the area of spinal cord injury focuses on treatments designed to either prevent spreading lesion (secondary injury) or to enhance outgrowth of long descending and ascending fiber tracts around or through the lesion. In the last decade, however, several authors

  11. BAG3 regulates contractility and Ca2+ homeostasis in adult mouse ventricular myocytes

    OpenAIRE

    Feldman, Arthur M.; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Myers, Valerie D.; Tilley, Douglas G.; Gao, Erhe; Hoffman, Nicholas E.; Tomar, Dhanendra; Madesh, Muniswamy; Rabinowitz, Joseph; Koch, Walter J.; Su, Feifei; Khalili, Kamel

    2016-01-01

    Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations, including mutations leading to loss of protein, are associated with familial cardiomyopathy. Furthermore, BAG3 levels have been found to be reduced in end-stage non-familial failing myocardium. In contrast to neonatal myocytes in which BAG3 is found in the cytoplasm and involved in protein quality control and apoptosis, in adult mouse left ventricular (...

  12. The lumbar lordosis index: a new ratio to detect spinal malalignment with a therapeutic impact for sagittal balance correction decisions in adult scoliosis surgery.

    Science.gov (United States)

    Boissière, Louis; Bourghli, Anouar; Vital, Jean-Marc; Gille, Olivier; Obeid, Ibrahim

    2013-06-01

    Sagittal malalignment is frequently observed in adult scoliosis. C7 plumb line, lumbar lordosis and pelvic tilt are the main factors to evaluate sagittal balance and the need of a vertebral osteotomy to correct it. We described a ratio: the lumbar lordosis index (ratio lumbar lordosis/pelvic incidence) (LLI) and analyzed its relationships with spinal malalignment and vertebral osteotomies. 53 consecutive patients with a surgical adult scoliosis had preoperative and postoperative full spine EOS radiographies to measure spino-pelvic parameters and LLI. The lack of lordosis was calculated after prediction of theoretical lumbar lordosis. Correlation analysis between the different parameters was performed. All parameters were correlated with spinal malalignment but LLI is the most correlated parameter (r = -0.978). It is also the best parameter in this study to predict the need of a spinal osteotomy (r = 1 if LLI <0.5). LLI is a statistically validated parameter for sagittal malalignment analysis. It can be used as a mathematical tool to detect spinal malalignment in adult scoliosis and guides the surgeon decision of realizing a vertebral osteotomy for adult scoliosis sagittal correction. It can be used as well for the interpretation of clinical series in adult scoliosis.

  13. Alterations in mouse hypothalamic adipokine gene expression and leptin signaling following chronic spinal cord injury and with advanced age.

    Directory of Open Access Journals (Sweden)

    Gregory E Bigford

    Full Text Available Chronic spinal cord injury (SCI results in an accelerated trajectory of several cardiovascular disease (CVD risk factors and related aging characteristics, however the molecular mechanisms that are activated have not been explored. Adipokines and leptin signaling are known to play a critical role in neuro-endocrine regulation of energy metabolism, and are now implicated in central inflammatory processes associated with CVD. Here, we examine hypothalamic adipokine gene expression and leptin signaling in response to chronic spinal cord injury and with advanced age. We demonstrate significant changes in fasting-induced adipose factor (FIAF, resistin (Rstn, long-form leptin receptor (LepRb and suppressor of cytokine-3 (SOCS3 gene expression following chronic SCI and with advanced age. LepRb and Jak2/stat3 signaling is significantly decreased and the leptin signaling inhibitor SOCS3 is significantly elevated with chronic SCI and advanced age. In addition, we investigate endoplasmic reticulum (ER stress and activation of the uncoupled protein response (UPR as a biological hallmark of leptin resistance. We observe the activation of the ER stress/UPR proteins IRE1, PERK, and eIF2alpha, demonstrating leptin resistance in chronic SCI and with advanced age. These findings provide evidence for adipokine-mediated inflammatory responses and leptin resistance as contributing to neuro-endocrine dysfunction and CVD risk following SCI and with advanced age. Understanding the underlying mechanisms contributing to SCI and age related CVD may provide insight that will help direct specific therapeutic interventions.

  14. A novel type of self-beating cardiomyocytes in adult mouse ventricles

    International Nuclear Information System (INIS)

    Omatsu-Kanbe, Mariko; Matsuura, Hiroshi

    2009-01-01

    This study was designed to investigate the presence of resident heart cells that are distinct from terminally-differentiated cardiomyocytes. Adult mouse heart was coronary perfused with collagenase, and ventricles were excised and further digested. After spinning cardiomyocyte-containing fractions down, the supernatant fraction was collected and cultured without adding any chemicals. Two to five days after plating, some of rounded cells adhered to the culture dish, gradually changed their shape and then started self-beating. These self-beating cells did not appreciably proliferate but underwent a further morphological maturation process to form highly branched shapes with many projections. These cells were mostly multinucleated, well sarcomeric-organized and expressed cardiac marker proteins, defined as atypically-shaped cardiomyocytes (ACMs). Patch-clamp experiments revealed that ACMs exhibited spontaneous action potentials arising from the preceding slow diastolic depolarization. We thus found a novel type of resident heart cells in adult cardiac ventricles that spontaneously develop into self-beating cardiomyocytes.

  15. Cathepsin B-dependent motor neuron death after nerve injury in the adult mouse

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Li; Wu, Zhou; Baba, Masashi [Department of Aging Science and Pharmacology, Faculty of Dental Sciences, Kyushu University, Maidashi 3-1-1, Fukuoka 812-8582 (Japan); Peters, Christoph [Institute fuer Molekulare Medizin und Zellforshung, Albert-Ludwings-Universitaet Freiburg, D-79104 Freiburg (Germany); Uchiyama, Yasuo [Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, Tokyo (Japan); Nakanishi, Hiroshi, E-mail: nakan@dent.kyushu-u.ac.jp [Department of Aging Science and Pharmacology, Faculty of Dental Sciences, Kyushu University, Maidashi 3-1-1, Fukuoka 812-8582 (Japan)

    2010-08-27

    Research highlights: {yields} Cathepsin B (CB), a lysosomal cysteine protease, is expressed in neuron and glia. {yields} CB increased in hypogrossal nucleus neurons after nerve injury in adult mice. {yields} CB-deficiency significantly increased the mean survival ratio of injured neurons. {yields} Thus, CB plays a critical role in axotomy-induced neuronal death in adult mice. -- Abstract: There are significant differences in the rate of neuronal death after peripheral nerve injury between species. The rate of neuronal death of motor neurons after nerve injury in the adult rats is very low, whereas that in adult mice is relatively high. However, the understanding of the mechanism underlying axotomy-induced motor neuron death in adult mice is limited. Cathepsin B (CB), a typical cysteine lysosomal protease, has been implicated in three major morphologically distinct pathways of cell death; apoptosis, necrosis and autophagic cell death. The possible involvement of CB in the neuronal death of hypogrossal nucleus (HGN) neurons after nerve injury in adult mice was thus examined. Quantitative analyses showed the mean survival ratio of HGN neurons in CB-deficient (CB-/-) adult mice after nerve injury was significantly greater than that in the wild-type mice. At the same time, proliferation of microglia in the injured side of the HGN of CB-/- adult mice was markedly reduced compared with that in the wild-type mice. On the injured side of the HGN in the wild-type adult mice, both pro- and mature forms of CB markedly increased in accordance with the increase in the membrane-bound form of LC3 (LC3-II), a marker protein of autophagy. Furthermore, the increase in CB preceded an increase in the expression of Noxa, a major executor for axotomy-induced motor neuron death in the adult mouse. Conversely, expression of neither Noxa or LC3-II was observed in the HGN of adult CB-/- mice after nerve injury. These observations strongly suggest that CB plays a critical role in axotomy

  16. Cathepsin B-dependent motor neuron death after nerve injury in the adult mouse

    International Nuclear Information System (INIS)

    Sun, Li; Wu, Zhou; Baba, Masashi; Peters, Christoph; Uchiyama, Yasuo; Nakanishi, Hiroshi

    2010-01-01

    Research highlights: → Cathepsin B (CB), a lysosomal cysteine protease, is expressed in neuron and glia. → CB increased in hypogrossal nucleus neurons after nerve injury in adult mice. → CB-deficiency significantly increased the mean survival ratio of injured neurons. → Thus, CB plays a critical role in axotomy-induced neuronal death in adult mice. -- Abstract: There are significant differences in the rate of neuronal death after peripheral nerve injury between species. The rate of neuronal death of motor neurons after nerve injury in the adult rats is very low, whereas that in adult mice is relatively high. However, the understanding of the mechanism underlying axotomy-induced motor neuron death in adult mice is limited. Cathepsin B (CB), a typical cysteine lysosomal protease, has been implicated in three major morphologically distinct pathways of cell death; apoptosis, necrosis and autophagic cell death. The possible involvement of CB in the neuronal death of hypogrossal nucleus (HGN) neurons after nerve injury in adult mice was thus examined. Quantitative analyses showed the mean survival ratio of HGN neurons in CB-deficient (CB-/-) adult mice after nerve injury was significantly greater than that in the wild-type mice. At the same time, proliferation of microglia in the injured side of the HGN of CB-/- adult mice was markedly reduced compared with that in the wild-type mice. On the injured side of the HGN in the wild-type adult mice, both pro- and mature forms of CB markedly increased in accordance with the increase in the membrane-bound form of LC3 (LC3-II), a marker protein of autophagy. Furthermore, the increase in CB preceded an increase in the expression of Noxa, a major executor for axotomy-induced motor neuron death in the adult mouse. Conversely, expression of neither Noxa or LC3-II was observed in the HGN of adult CB-/- mice after nerve injury. These observations strongly suggest that CB plays a critical role in axotomy-induced mortor neuron

  17. Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons

    OpenAIRE

    Lee, Young il; Mikesh, Michelle; Smith, Ian; Rimer, Mendell; Thompson, Wesley

    2011-01-01

    A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precedes the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any ...

  18. The modulatory role of alpha-melanocyte stimulating hormone administered spinally in the regulation of blood glucose level in d-glucose-fed and restraint stress mouse models.

    Science.gov (United States)

    Sim, Yun-Beom; Park, Soo-Hyun; Kim, Sung-Su; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won

    2014-08-01

    Alpha-melanocyte stimulating hormone (α-MSH) is known as a regulator of the blood glucose homeostasis and food intake. In the present study, the possible roles of α-MSH located in the spinal cord in the regulation of the blood glucose level were investigated in d-glucose-fed and immobilization stress (IMO) mouse models. We found in the present study that intrathecal (i.t.) injection with α-MSH alone did not affect the blood glucose level. However, i.t. administration with α-MSH reduced the blood glucose level in d-glucose-fed model. The plasma insulin level was increased in d-glucose-fed model and was further increased by α-MSH, whereas α-MSH did not affect plasma corticosterone level in d-glucose-fed model. In addition, i.t. administration with glucagon alone enhanced blood glucose level and, i.t. injection with glucagon also increased the blood glucose level in d-glucose-fed model. In contrasted to results observed in d-glucose-fed model, i.t. treatment with α-MSH caused enhancement of the blood glucose level in IMO model. The plasma insulin level was increased in IMO model. The increased plasma insulin level by IMO was reduced by i.t. treatment with α-MSH, whereas i.t. pretreatment with α-MSH did not affect plasma corticosterone level in IMO model. Taken together, although spinally located α-MSH itself does not alter the blood glucose level, our results suggest that the activation of α-MSH system located in the spinal cord play important modulatory roles for the reduction of the blood glucose level in d-glucose fed model whereas α-MSH is responsible for the up-regulation of the blood glucose level in IMO model. The enhancement of insulin release may be responsible for modulatory action of α-MSH in down-regulation of the blood glucose in d-glucose fed model whereas reduction of insulin release may be responsible for modulatory action of α-MSH in up-regulation of the blood glucose in IMO model. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Relationship between anthropometric measures and sagittal spinal curvatures in adult male handball players

    Directory of Open Access Journals (Sweden)

    Ameer Mariam Abdul-Moneem

    2017-12-01

    Full Text Available Purpose. Increasing anthropometric measures bring considerable spinal loads during sports practice, which inversely affects the adaptation abilities of the spinal structures; this in turn influences the spinal curvatures. The study was conducted to explore the relationship between anthropometric measures and sagittal spinal curvatures in handball players. Method. The total of 83 male handball players were divided into 2 groups, depending on their body height: group 1 (age, 23.62 ± 2.07 years consisted of 40 handball players with height above average, group 2 (age, 24.63 ± 2.58 years consisted of 43 handball players with height below average. The thoracic and lumbar curvatures and trunk height were measured with the Formetric III 4D spine and posture analysis system. Results. The thoracic kyphosis of group 1 was significantly higher than that of group 2 (p = 0.038, without a significant difference in lumbar lordosis (p = 0.312, and significant difference in the coefficient of compensation between thoracic kyphosis and lumbar lordosis (p = 0.026. Group 1 showed strong positive correlation between body height and kyphotic angle (r = 0.897, and moderate positive correlation with lordosis angle (r = 0.496. In group 2, there was weak positive correlation with kyphotic angle (r = 0.381, and weak negative correlation with lumbar lordosis angle (r = -0.355. Conclusions. Increasing body height of handball players is associated with bigger kyphotic and lordotic angles. Owing to frequent sagittal asymmetric overloading of the spine during handball training, exercises that help maintain good posture and correct the thoracic kyphosis are required, especially for taller players.

  20. Serotonin(2) receptors mediate respiratory recovery after cervical spinal cord hemisection in adult rats.

    Science.gov (United States)

    Zhou, S Y; Basura, G J; Goshgarian, H G

    2001-12-01

    The aim of the present study was to specifically investigate the involvement of serotonin [5-hydroxytryptamine (5-HT(2))] receptors in 5-HT-mediated respiratory recovery after cervical hemisection. Experiments were conducted on C(2) spinal cord-hemisected, anesthetized (chloral hydrate, 400 mg/kg ip), vagotomized, pancuronium- paralyzed, and artificially ventilated female Sprague-Dawley rats in which CO(2) levels were monitored and maintained. Twenty-four hours after spinal hemisection, the ipsilateral phrenic nerve displayed no respiratory-related activity indicative of a functionally complete hemisection. Intravenous administration of the 5-HT(2A/2C)-receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) induced respiratory-related activity in the phrenic nerve ipsilateral to hemisection under conditions in which CO(2) was maintained at constant levels and augmented the activity induced under conditions of hypercapnia. The effects of DOI were found to be dose dependent, and the recovery of activity could be maintained for up to 2 h after a single injection. DOI-induced recovery was attenuated by the 5-HT(2)-receptor antagonist ketanserin but not with the 5-HT(2C)-receptor antagonist RS-102221, suggesting that 5-HT(2A) and not necessarily 5-HT(2C) receptors may be involved in the induction of respiratory recovery after cervical spinal cord injury.

  1. Spinal cord compression secondary to extramedullary hematopoiesis: A rareness in a young adult with thalassemia major.

    Science.gov (United States)

    Fareed, Shehab; Soliman, Ashraf T; De Sanctis, Vincenzo; Kohla, Samah; Soliman, Dina; Khirfan, Diala; Tambuerello, Adriana; Talaat, Mohamed; Nashwan, Abdulqadir; Caparrotti, Palmira; Yassin, Mohamed A

    2017-08-23

    We report a case of a thalassemia major male patient with back pain associated to severe weakness in lower extremities resulting in the ability to ambulate only with assistance. An urgent magnetic resonance imaging (MRI) of  thoracic and lumbosacral spine was requested. A posterior intraspinal extradural mass lesion compressing the spinal cord at the level of thoracic T5-8 was present, suggesting an extramedullary hematopoietic centre, compressing the spinal cord. He was treated successfully with thalassemia major alone. The patient was treated with blood transfusion, dexamethasone, morphine and paracetamol, followed by radiotherapy in 10 fractions to the spine (daily fraction of 2Gy from T3 to T9, total dose 20 Gy). His pain and neurologic examination quickly improved. A new MRI of the spine, one week after radiotherapy, showed an improvement of the extramedullary hematopoietic mass compression. In conclusion, EMH should be considered in every patient with ineffective erythropoiesis and spinal cord symptoms. MRI is the most effective method of demonstrating EMH. The rapid recognition and treatment can dramatically alleviate symptoms. There is still considerable controversy regarding indications, benefits, and risks of each of modality of treatment due to the infrequency of this disorder.

  2. Improved Neural Regeneration with Olfactory Ensheathing Cell Inoculated PLGA Scaffolds in Spinal Cord Injury Adult Rats

    Directory of Open Access Journals (Sweden)

    Changxing Wang

    2017-03-01

    Full Text Available Background/Aims: Every year, around the world, between 250000 and 500000 people suffer from spinal cord injury (SCI. This study investigated the potential for poly (lactic-co-glycolic acid (PLGA complex inoculated with olfactory ensheathing cells (OECs to treat spinal cord injury in a rat model. Methods: OECs were identified by immunofluorescence based on the nerve growth factor receptor (NGFR p75. The Basso, Beattie, and Bresnahan (BBB score, together with an inclined plane (IP test were used to detect functional recovery. Nissl staining along with the luxol fast blue (LFB staining were independently employed to illustrate morphological alterations. More so, immunofluorescence labeling of the glial fibrillary acidic protein (GFAP and the microtubule-associated protein-2 (MAP-2, representing astrocytes and neurons respectively, were investigated at time points of weeks 2 and 8 post-operation. Results: The findings showed enhanced locomotor recovery, axon myelination and better protected neurons post SCI when compared with either PLGA or untreated groups (P < 0.05. Conclusion: PLGA complexes inoculated with OECs improve locomotor functional recovery in transected spinal cord injured rat models, which is most likely due to the fact it is conducive to a relatively benevolent microenvironment, has nerve protective effects, as well as the ability to enhance remyelination, via a promotion of cell differentiation and inhibition of astrocyte formation.

  3. Measuring outcomes in adult spinal deformity surgery: a systematic review to identify current strengths, weaknesses and gaps in patient-reported outcome measures

    NARCIS (Netherlands)

    Faraj, S.S.; Hooff, M.L. Van; Holewijn, R.M.; Polly, D.W.; Haanstra, T.M.; Kleuver, M. de

    2017-01-01

    PURPOSE: Adult spinal deformity (ASD) causes severe disability, reduces overall quality of life, and results in a substantial societal burden of disease. As healthcare is becoming more value based, and to facilitate global benchmarking, it is critical to identify and standardize patient-reported

  4. Clinical assessment, design and performance testing of mobile shower commodes for adults with spinal cord injury: an exploratory review.

    Science.gov (United States)

    Friesen, Emma; Theodoros, Deborah; Russell, Trevor

    2013-07-01

    The purpose of this article is to explore evidence concerning clinical assessment, design and performance testing of mobile shower commodes used by adults with spinal cord injury (SCI). Searches of electronic databases, conference proceedings and key journals were undertaken with no restriction on language or study design. Keywords included spinal cord injury, lesion, sanichair, sanitary chair, shower chair, bowel chair and commode. A total of 20 publications were included in this review. Common approaches to clinical assessments were questionnaires and observational analysis to assess bowel care routines, function and skin integrity. Design features addressed access for bowel care, postural support, transfers, stability, use in wet environments and skin integrity. Objective performance measures addressed requirements for static stability, backward-sloping seat angles, arm supports and seat materials. Evidence reviewed was of low methodological quality and lacking in validated instruments to guide clinical practice. Further high-quality research is needed to identify bathing, showering and personal hygiene tasks affecting mobile shower commodes use and to develop validated clinical assessment tools. Performance testing to published standards is also needed.

  5. Extended magnetic resonance imaging studies on the effect of classically activated microglia transplantation on white matter regeneration following spinal cord focal injury in adult rats.

    Science.gov (United States)

    Marcol, Wiesław; Ślusarczyk, Wojciech; Larysz-Brysz, Magdalena; Łabuzek, Krzysztof; Kapustka, Bartosz; Staszkiewicz, Rafał; Rosicka, Paulina; Kalita, Katarzyna; Węglarz, Władysław; Lewin-Kowalik, Joanna

    2017-11-01

    Spinal cord injuries are still a serious problem for regenerative medicine. Previous research has demonstrated that activated microglia accumulate in spinal lesions, influencing the injured tissues in various ways. Therefore, transplantation of activated microglia may have a beneficial role in the regeneration of the nervous system. The present study examined the influence of transplanted activated microglial cells in adult rats with injured spinal cords. Rats were randomly divided into an experimental (M) and control (C) group, and were subjected to non-laminectomy focal injury of spinal cord white matter by means of a high-pressured air stream. In group M, activated cultured microglial cells were injected twice into the site of injury. Functional outcome and morphological features of regeneration were analyzed during a 12-week follow-up. The lesions were characterized by means of magnetic resonance imaging (MRI). Neurons in the brain stem and motor cortex were labeled with FluoroGold (FG). A total of 12 weeks after surgery, spinal cords and brains were collected and subjected to histopathological and immunohistochemical examinations. Lesion sizes in the spinal cord were measured and the number of FG-positive neurons was counted. Rats in group M demonstrated significant improvement of locomotor performance when compared with group C (Pspinal cord in the group M following microglia treatment, as compared with group C. The water diffusion perpendicular to the spinal cord in group M was closer to the reference values for a healthy spinal cord than it was in group C. The sizes of lesions were also significantly smaller in group M than in the group C (Pspinal cord gives some positive effects for the regeneration of the white matter.

  6. Hyperbaric Versus Isobaric Bupivacaine for Spinal Anesthesia: Systematic Review and Meta-analysis for Adult Patients Undergoing Noncesarean Delivery Surgery.

    Science.gov (United States)

    Uppal, Vishal; Retter, Susanne; Shanthanna, Harsha; Prabhakar, Christopher; McKeen, Dolores M

    2017-11-01

    It is widely believed that the choice between isobaric bupivacaine and hyperbaric bupivacaine formulations alters the block characteristics for the conduct of surgery under spinal anesthesia. The aim of this study was to systematically review the comparative evidence regarding the effectiveness and safety of the 2 formulations when used for spinal anesthesia for adult noncesarean delivery surgery. Key electronic databases were searched for randomized controlled trials, excluding cesarean delivery surgeries under spinal anesthesia, without any language or date restrictions. The primary outcome measure for this review was the failure of spinal anesthesia. Two independent reviewers selected the studies and extracted the data. Results were expressed as relative risk (RR) or mean differences (MDs) with 95% confidence intervals (CIs). Seven hundred fifty-one studies were identified between 1946 and 2016. After screening, there were 16 randomized controlled clinical trials, including 724 participants, that provided data for the meta-analysis. The methodological reporting of most studies was poor, and appropriate judgment of their individual risk of bias elements was not possible. There was no difference between the 2 drugs regarding the need for conversion to general anesthesia (RR, 0.60; 95% CI, 0.08-4.41; P = .62; I = 0%), incidence of hypotension (RR, 1.15; 95% CI, 0.69-1.92; P = .58; I = 0%), nausea/vomiting (RR, 0.29; 95% CI, 0.06-1.32; P = .11; I = 7%), or onset of sensory block (MD = 1.7 minutes; 95% CI, -3.5 to 0.1; P = .07; I = 0%). The onset of motor block (MD = 4.6 minutes; 95% CI, 7.5-1.7; P = .002; I = 78%) was significantly faster with hyperbaric bupivacaine. Conversely, the duration of motor (MD = 45.2 minutes; 95% CI, 66.3-24.2; P bupivacaine. Both hyperbaric bupivacaine and isobaric bupivacaine provided effective anesthesia with no difference in the failure rate or adverse effects. The hyperbaric formulation allows for a relatively rapid motor block onset

  7. Nogo-A is a reliable oligodendroglial marker in adult human and mouse CNS and in demyelinated lesions

    DEFF Research Database (Denmark)

    Kuhlmann, Tanja; Remington, Leah; Maruschak, Brigitte

    2007-01-01

    to be strongly expressed in mature oligodendrocytes in vivo. In the present investigation we analyzed the expression patterns of Nogo-A in adult mouse and human CNS as well as in demyelinating animal models and multiple sclerosis lesions. Nogo-A expression was compared with that of other frequently used...... oligodendroglial markers such as CC1, CNP, and in situ hybridization for proteolipid protein mRNA. Nogo-A strongly and reliably labeled oligodendrocytes in the adult CNS as well as in demyelinating lesions and thus represents a valuable tool for the identification of oligodendrocytes in human and mouse CNS tissue...

  8. Characterization and therapeutic evaluation of a Nestin⁺ CNP⁺ NG2⁺ cell population on mouse spinal cord injury.

    Science.gov (United States)

    Liu, Rui; Zhang, Si; Yang, Haijie; Ju, Peijun; Xia, Yinyan; Shi, Yu; Lim, Tse Hui; Lim, Alvin St; Liang, Fengyi; Feng, Zhiwei

    2015-07-01

    The NG2 chondroitin sulfate proteoglycan-expressing neural cells (NG2 cells) have originally been considered as oligodendrocyte progenitor cells (OPCs). However, recent findings on their diverse functions and lineage heterogeneity demonstrated that the NG2 cells contain various sub-populations whose concrete features and therapeutic potential yet remained elucidated. In the present study, we characterized a Nestin(+) 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP)(+) NG2(+) subpopulation from embryonic rat cerebral cortex. The Nestin(+) CNP(+) NG2(+) cells exhibited remarkable progenitor characteristics. Having been immortalized by human telomerase reverse transcriptase (hTERT), the life span of Nestin(+) CNP(+) NG2(+) cells was extended to 230 population doublings (PDs). With immortalized NG2 cells, we demonstrated their differentiation capacities to oligodendrocytes, astrocytes and neurons. Furthermore, transplanted into injured spinal cord of a mouse model, they were able to promote remyelination and neuronal regeneration, thereby enhancing the functional recovery. Our findings suggest that the Nestin(+) CNP(+) NG2(+) progenitor cells could be a good alternative cell source of cell therapy for neurological disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Identifying the Long-Term Role of Inducible Nitric Oxide Synthase after Contusive Spinal Cord Injury Using a Transgenic Mouse Model

    Directory of Open Access Journals (Sweden)

    Dominic M. Maggio

    2017-01-01

    Full Text Available Inducible nitric oxide synthase (iNOS is a potent mediator of oxidative stress during neuroinflammation triggered by neurotrauma or neurodegeneration. We previously demonstrated that acute iNOS inhibition attenuated iNOS levels and promoted neuroprotection and functional recovery after spinal cord injury (SCI. The present study investigated the effects of chronic iNOS ablation after SCI using inos-null mice. iNOS−/− knockout and wild-type (WT control mice underwent a moderate thoracic (T8 contusive SCI. Locomotor function was assessed weekly, using the Basso Mouse Scale (BMS, and at the endpoint (six weeks, by footprint analysis. At the endpoint, the volume of preserved white and gray matter, as well as the number of dorsal column axons and perilesional blood vessels rostral to the injury, were quantified. At weeks two and three after SCI, iNOS−/− mice exhibited a significant locomotor improvement compared to WT controls, although a sustained improvement was not observed during later weeks. At the endpoint, iNOS−/− mice showed significantly less preserved white and gray matter, as well as fewer dorsal column axons and perilesional blood vessels, compared to WT controls. While short-term antagonism of iNOS provides histological and functional benefits, its long-term ablation after SCI may be deleterious, blocking protective or reparative processes important for angiogenesis and tissue preservation.

  10. Response of Ependymal Progenitors to Spinal Cord Injury or Enhanced Physical Activity in Adult Rat

    Czech Academy of Sciences Publication Activity Database

    Čížková, D.; Nagyová, M.; Slovinská, L.; Novotná, I.; Radoňák, J.; Čížek, M.; Mechirová, E.; Tomori, Z.; Hlučilová, Jana; Motlík, Jan; Sulla, I.; Vanický, I.

    2009-01-01

    Roč. 29, 6-7 (2009), s. 999-1013 ISSN 0272-4340 R&D Projects: GA MŠk MEB0808108 Grant - others:Agentúra na podporu výskumu a vývoja(SK) APVV SK-CZ-0045-07; Agentúra na podporu výskumu a vývoja(SK) APVV SK-CZ-0682-07 Institutional research plan: CEZ:AV0Z50450515 Keywords : Spinal cord injury * Neural stem cells * BrdU Subject RIV: FH - Neurology Impact factor: 2.107, year: 2009

  11. Defining a core outcome set for adolescent and young adult patients with a spinal deformity

    DEFF Research Database (Denmark)

    de Kleuver, Marinus; Faraj, Sayf S A; Holewijn, Roderick M

    2017-01-01

    2016, 7 representatives (panelists) of the national spinal surgery registries from each of the NSDS countries participated in a modified Delphi study. With a systematic literature review as a basis and the International Classification of Functioning, Disability and Health framework as guidance, 4...... consensus rounds were held. Consensus was defined as agreement between at least 5 of the 7 representatives. Data were analyzed qualitatively and quantitatively. Results - Consensus was reached on the inclusion of 13 core outcome domains: "satisfaction with overall outcome of surgery", "satisfaction...

  12. The Thoc1 encoded ribonucleoprotein is required for myeloid progenitor cell homeostasis in the adult mouse.

    Science.gov (United States)

    Pitzonka, Laura; Ullas, Sumana; Chinnam, Meenalakshmi; Povinelli, Benjamin J; Fisher, Daniel T; Golding, Michelle; Appenheimer, Michelle M; Nemeth, Michael J; Evans, Sharon; Goodrich, David W

    2014-01-01

    Co-transcriptionally assembled ribonucleoprotein (RNP) complexes are critical for RNA processing and nuclear export. RNPs have been hypothesized to contribute to the regulation of coordinated gene expression, and defects in RNP biogenesis contribute to genome instability and disease. Despite the large number of RNPs and the importance of the molecular processes they mediate, the requirements for individual RNP complexes in mammalian development and tissue homeostasis are not well characterized. THO is an evolutionarily conserved, nuclear RNP complex that physically links nascent transcripts with the nuclear export apparatus. THO is essential for early mouse embryonic development, limiting characterization of the requirements for THO in adult tissues. To address this shortcoming, a mouse strain has been generated allowing inducible deletion of the Thoc1 gene which encodes an essential protein subunit of THO. Bone marrow reconstitution was used to generate mice in which Thoc1 deletion could be induced specifically in the hematopoietic system. We find that granulocyte macrophage progenitors have a cell autonomous requirement for Thoc1 to maintain cell growth and viability. Lymphoid lineages are not detectably affected by Thoc1 loss under the homeostatic conditions tested. Myeloid lineages may be more sensitive to Thoc1 loss due to their relatively high rate of proliferation and turnover.

  13. The Thoc1 encoded ribonucleoprotein is required for myeloid progenitor cell homeostasis in the adult mouse.

    Directory of Open Access Journals (Sweden)

    Laura Pitzonka

    Full Text Available Co-transcriptionally assembled ribonucleoprotein (RNP complexes are critical for RNA processing and nuclear export. RNPs have been hypothesized to contribute to the regulation of coordinated gene expression, and defects in RNP biogenesis contribute to genome instability and disease. Despite the large number of RNPs and the importance of the molecular processes they mediate, the requirements for individual RNP complexes in mammalian development and tissue homeostasis are not well characterized. THO is an evolutionarily conserved, nuclear RNP complex that physically links nascent transcripts with the nuclear export apparatus. THO is essential for early mouse embryonic development, limiting characterization of the requirements for THO in adult tissues. To address this shortcoming, a mouse strain has been generated allowing inducible deletion of the Thoc1 gene which encodes an essential protein subunit of THO. Bone marrow reconstitution was used to generate mice in which Thoc1 deletion could be induced specifically in the hematopoietic system. We find that granulocyte macrophage progenitors have a cell autonomous requirement for Thoc1 to maintain cell growth and viability. Lymphoid lineages are not detectably affected by Thoc1 loss under the homeostatic conditions tested. Myeloid lineages may be more sensitive to Thoc1 loss due to their relatively high rate of proliferation and turnover.

  14. Expression of the Norrie disease gene (Ndp) in developing and adult mouse eye, ear, and brain.

    Science.gov (United States)

    Ye, Xin; Smallwood, Philip; Nathans, Jeremy

    2011-01-01

    The Norrie disease gene (Ndp) codes for a secreted protein, Norrin, that activates canonical Wnt signaling by binding to its receptor, Frizzled-4. This signaling system is required for normal vascular development in the retina and for vascular survival in the cochlea. In mammals, the pattern of Ndp expression beyond the retina is poorly defined due to the low abundance of Norrin mRNA and protein. Here, we characterize Ndp expression during mouse development by studying a knock-in mouse that carries the coding sequence of human placental alkaline phosphatase (AP) inserted at the Ndp locus (Ndp(AP)). In the CNS, Ndp(AP) expression is apparent by E10.5 and is dynamic and complex. The anatomically delimited regions of Ndp(AP) expression observed prenatally in the CNS are replaced postnatally by widespread expression in astrocytes in the forebrain and midbrain, Bergman glia in the cerebellum, and Müller glia in the retina. In the developing and adult cochlea, Ndp(AP) expression is closely associated with two densely vascularized regions, the stria vascularis and a capillary plexus between the organ of Corti and the spiral ganglion. These observations suggest the possibility that Norrin may have developmental and/or homeostatic functions beyond the retina and cochlea. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Living with SCI Personal Experiences by Topic Resources Peer ... Adult Injuries Spinal Cord Injury 101 David Chen, MD Preventing Pressure Sores Mary Zeigler, MS Transition from Hospital to ...

  16. Meis1 Is Required for Adult Mouse Erythropoiesis, Megakaryopoiesis and Hematopoietic Stem Cell Expansion.

    Directory of Open Access Journals (Sweden)

    Michelle Erin Miller

    Full Text Available Meis1 is recognized as an important transcriptional regulator in hematopoietic development and is strongly implicated in the pathogenesis of leukemia, both as a Hox transcription factor co-factor and independently. Despite the emerging recognition of Meis1's importance in the context of both normal and leukemic hematopoiesis, there is not yet a full understanding of Meis1's functions and the relevant pathways and genes mediating its functions. Recently, several conditional mouse models for Meis1 have been established. These models highlight a critical role for Meis1 in adult mouse hematopoietic stem cells (HSCs and implicate reactive oxygen species (ROS as a mediator of Meis1 function in this compartment. There are, however, several reported differences between these studies in terms of downstream progenitor populations impacted and effectors of function. In this study, we describe further characterization of a conditional knockout model based on mice carrying a loxP-flanked exon 8 of Meis1 which we crossed onto the inducible Cre localization/expression strains, B6;129-Gt(ROSA26Sor(tm1(Cre/ERTNat/J or B6.Cg-Tg(Mx1-Cre1Cgn/J. Findings obtained from these two inducible Meis1 knockout models confirm and extend previous reports of the essential role of Meis1 in adult HSC maintenance and expansion and provide new evidence that highlights key roles of Meis1 in both megakaryopoiesis and erythropoiesis. Gene expression analyses point to a number of candidate genes involved in Meis1's role in hematopoiesis. Our data additionally support recent evidence of a role of Meis1 in ROS regulation.

  17. Phenotyping of nNOS neurons in the postnatal and adult female mouse hypothalamus.

    Science.gov (United States)

    Chachlaki, Konstantina; Malone, Samuel A; Qualls-Creekmore, Emily; Hrabovszky, Erik; Münzberg, Heike; Giacobini, Paolo; Ango, Fabrice; Prevot, Vincent

    2017-10-15

    Neurons expressing nitric oxide (NO) synthase (nNOS) and thus capable of synthesizing NO play major roles in many aspects of brain function. While the heterogeneity of nNOS-expressing neurons has been studied in various brain regions, their phenotype in the hypothalamus remains largely unknown. Here we examined the distribution of cells expressing nNOS in the postnatal and adult female mouse hypothalamus using immunohistochemistry. In both adults and neonates, nNOS was largely restricted to regions of the hypothalamus involved in the control of bodily functions, such as energy balance and reproduction. Labeled cells were found in the paraventricular, ventromedial, and dorsomedial nuclei as well as in the lateral area of the hypothalamus. Intriguingly, nNOS was seen only after the second week of life in the arcuate nucleus of the hypothalamus (ARH). The most dense and heavily labeled population of cells was found in the organum vasculosum laminae terminalis (OV) and the median preoptic nucleus (MEPO), where most of the somata of the neuroendocrine neurons releasing GnRH and controlling reproduction are located. A great proportion of nNOS-immunoreactive neurons in the OV/MEPO and ARH were seen to express estrogen receptor (ER) α. Notably, almost all ERα-immunoreactive cells of the OV/MEPO also expressed nNOS. Moreover, the use of EYFP Vglut2 , EYFP Vgat , and GFP Gad67 transgenic mouse lines revealed that, like GnRH neurons, most hypothalamic nNOS neurons have a glutamatergic phenotype, except for nNOS neurons of the ARH, which are GABAergic. Altogether, these observations are consistent with the proposed role of nNOS neurons in physiological processes. © 2017 Wiley Periodicals, Inc.

  18. Spinal cord pathology is ameliorated by P2X7 antagonism in a SOD1-mutant mouse model of amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Savina Apolloni

    2014-09-01

    Full Text Available In recent years there has been an increasing awareness of the role of P2X7, a receptor for extracellular ATP, in modulating physiopathological mechanisms in the central nervous system. In particular, P2X7 has been shown to be implicated in neuropsychiatry, chronic pain, neurodegeneration and neuroinflammation. Remarkably, P2X7 has also been shown to be a ‘gene modifier’ in amyotrophic lateral sclerosis (ALS: the receptor is upregulated in spinal cord microglia in human and rat at advanced stages of the disease; in vitro, activation of P2X7 exacerbates pro-inflammatory responses in microglia that have an ALS phenotype, as well as toxicity towards neuronal cells. Despite this detrimental in vitro role of P2X7, in SOD1-G93A mice lacking P2X7, the clinical onset of ALS was significantly accelerated and disease progression worsened, thus indicating that the receptor might have some beneficial effects, at least at certain stages of disease. In order to clarify this dual action of P2X7 in ALS pathogenesis, in the present work we used the antagonist Brilliant Blue G (BBG, a blood-brain barrier permeable and safe drug that has already been proven to reduce neuroinflammation in traumatic brain injury, cerebral ischemia-reperfusion, neuropathic pain and experimental autoimmune encephalitis. We tested BBG in the SOD1-G93A ALS mouse model at asymptomatic, pre-symptomatic and late pre-symptomatic phases of disease. BBG at late pre-onset significantly enhanced motor neuron survival and reduced microgliosis in lumbar spinal cord, modulating inflammatory markers such as NF-κB, NADPH oxidase 2, interleukin-1β, interleukin-10 and brain-derived neurotrophic factor. This was accompanied by delayed onset and improved general conditions and motor performance, in both male and female mice, although survival appeared unaffected. Our results prove the twofold role of P2X7 in the course of ALS and establish that P2X7 modulation might represent a promising

  19. Familial adult spinal muscular atrophy associated with the VAPB gene: report of 42 cases in Brazil

    Directory of Open Access Journals (Sweden)

    Victor Kosac

    2013-10-01

    Full Text Available Familial spinal muscular atrophy (FSMA associated with the vesicle-associated membrane protein-associated protein B (VAPB gene is a rare autosomal dominant disease with late onset and slow progression. We studied 10 of 42 patients from 5 families by taking clinical histories and performing physical exams, electrophysiological studies, and genetic tests. All patients presented late onset disease with slow progression characterized by fasciculations, proximal weakness, amyotrophy, and hypoactive deep tendon reflex, except two who exhibited brisk reflex. Two patients showed tongue fasciculations and respiratory insufficiency. Electrophysiological studies revealed patterns of lower motor neuron disease, and genetic testing identified a P56S mutation of the VAPB gene. Although it is a rare motor neuron disease, FSMA with this mutation might be much more prevalent in Brazil than expected, and many cases may be undiagnosed. Genetic exams should be performed whenever it is suspected in Brazil.

  20. Organotypic hippocampal slice culture from the adult mouse brain: a versatile tool for translational neuropsychopharmacology.

    Science.gov (United States)

    Kim, Hyunjeong; Kim, Eosu; Park, Minsun; Lee, Eun; Namkoong, Kee

    2013-03-05

    One of the most significant barriers towards translational neuropsychiatry would be an unavailability of living brain tissues. Although organotypic brain tissue culture could be a useful alternative enabling observation of temporal changes induced by various drugs in living brain tissues, a proper method to establish a stable organotypic brain slice culture system using adult (rather than neonatal) hippocampus has been still elusive. In this study, we evaluated our simple method using the serum-free culture medium for successful adult organotypic hippocampal slice culture. Several tens of hippocampal slices from a single adult mouse (3-5 months old) were cultured in serum-free versus serum-containing conventional culture medium for 30 days and underwent various experiments to validate the effects of the existence of serum in the culture medium. Neither the excessive regression of neuronal viability nor metabolic deficiency was observed in the serum-free medium culture in contrast to the serum-containing medium culture. Despite such viability, newly generated immature neurons were scarcely detected in the serum-free culture, suggesting that the original neurons in the brain slice persist rather than being replaced by neurogenesis. Key structural features of in vivo neural tissue constituting astrocytes, neural processes, and pre- and post-synapses were also well preserved in the serum-free culture. In conclusion, using the serum-free culture medium, the adult hippocampal slice culture system will serve as a promising ex vivo tool for various fields of neuroscience, especially for studies on aging-related neuropsychiatric disorders or for high throughput screening of potential agents working against such disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Sarcopenic Obesity in Adults With Spinal Cord Injury: A Cross-Sectional Study.

    Science.gov (United States)

    Pelletier, Chelsea A; Miyatani, Masae; Giangregorio, Lora; Craven, B Catharine

    2016-11-01

    To describe (1) the frequency and utility of clinically relevant spinal cord injury (SCI)-specific and general population thresholds for obesity and sarcopenic obesity; and (2) the fat and lean soft tissue distributions based on the neurologic level of injury and the American Spinal Injury Association Impairment Scale. Cross-sectional. Tertiary SCI rehabilitation hospital. Persons (N=136; men, n=100; women, n=36) with chronic (mean ± SD: 15.6±11.3y postinjury) tetraplegia (n=66) or paraplegia (n=70). Not applicable. Body composition was assessed with anthropometrics and whole-body dual-energy x-ray absorptiometry. Muscle atrophy was quantified using a sarcopenia threshold of appendicular lean mass index (ALMI) (men, ≤7.26kg/m 2 ; women, ≤5.5kg/m 2 ). Obesity was defined by percentage body fat (men, ≥25%; women, ≥35%), visceral adipose tissue (≥130cm 2 ), and SCI-specific obesity thresholds (body mass index [BMI] ≥22kg/m 2 ; waist circumference ≥94cm). Sarcopenic obesity was defined as the presence of both sarcopenia and obesity. Groups were compared based on impairment characteristics using an analysis of covariance. Sarcopenic obesity was prevalent in 41.9% of the sample. ALMI was lower among participants with motor-complete (6.2±1.3kg/m 2 ) versus motor-incomplete (7.5±1.6kg/m 2 ) injuries (Ppopulation guidelines (20.6%), SCI-specific BMI thresholds identified all the participants with obesity (77.9%) based on percentage body fat (72.1%). The observed frequency of sarcopenic obesity in this sample of individuals with chronic SCI is very high, and identification of obesity is dissimilar when using SCI-specific versus general population criteria. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  2. Effect of Tranexamic Acid on Blood Loss, D-Dimer, and Fibrinogen Kinetics in Adult Spinal Deformity Surgery.

    Science.gov (United States)

    Pong, Ryan P; Leveque, Jean-Christophe A; Edwards, Alicia; Yanamadala, Vijay; Wright, Anna K; Herodes, Megan; Sethi, Rajiv K

    2018-05-02

    Antifibrinolytics such as tranexamic acid reduce operative blood loss and blood product transfusion requirements in patients undergoing surgical correction of scoliosis. The factors involved in the unrelenting coagulopathy seen in scoliosis surgery are not well understood. One potential contributor is activation of the fibrinolytic system during a surgical procedure, likely related to clot dissolution and consumption of fibrinogen. The addition of tranexamic acid during a surgical procedure may mitigate the coagulopathy by impeding the derangement in D-dimer and fibrinogen kinetics. We retrospectively studied consecutive patients who had undergone surgical correction of adult spinal deformity between January 2010 and July 2016 at our institution. Intraoperative hemostatic data, surgical time, estimated blood loss, and transfusion records were analyzed for patients before and after the addition of tranexamic acid to our protocol. Each patient who received tranexamic acid and met inclusion criteria was cohort-matched with a patient who underwent a surgical procedure without tranexamic acid administration. There were 17 patients in the tranexamic acid cohort, with a mean age of 60.7 years, and 17 patients in the control cohort, with a mean age of 60.9 years. Estimated blood loss (932 ± 539 mL compared with 1,800 ± 1,029 mL; p = 0.005) and packed red blood-cell transfusions (1.5 ± 1.6 units compared with 4.0 ± 2.1 units; p = 0.001) were significantly lower in the tranexamic acid cohort. In all single-stage surgical procedures that met inclusion criteria, the rise of D-dimer was attenuated from 8.3 ± 5.0 μg/mL in the control cohort to 3.3 ± 3.2 μg/mL for the tranexamic acid cohort (p tranexamic acid cohort to 60.6 ± 35.1 mg/dL (p = 0.004). In patients undergoing spinal surgery, intravenous administration of tranexamic acid is effective at reducing intraoperative blood loss. Monitoring of D-dimer and fibrinogen during spinal surgery suggests that tranexamic acid

  3. Understanding Quality of Life in Adults with Spinal Cord Injury Via SCI-Related Needs and Secondary Complications.

    Science.gov (United States)

    Sweet, Shane N; Noreau, Luc; Leblond, Jean; Dumont, Frédéric S

    2014-01-01

    Understanding the factors that can predict greater quality of life (QoL) is important for adults with spinal cord injury (SCI), given that they report lower levels of QoL than the general population. To build a conceptual model linking SCI-related needs, secondary complications, and QoL in adults with SCI. Prior to testing the conceptual model, we aimed to develop and evaluate the factor structure for both SCI-related needs and secondary complications. Individuals with a traumatic SCI (N = 1,137) responded to an online survey measuring 13 SCI-related needs, 13 secondary complications, and the Life Satisfaction Questionnaire to assess QoL. The SCI-related needs and secondary complications were conceptualized into factors, tested with a confirmatory factor analysis, and subsequently evaluated in a structural equation model to predict QoL. The confirmatory factor analysis supported a 2-factor model for SCI related needs, χ(2)(61, N = 1,137) = 250.40, P SCI-related needs (β = -.22 and -.20, P SCI-related needs of individuals with SCI and preventing or managing secondary complications are essential to their QoL.

  4. Objective measures of motor dysfunction after compression spinal cord injury in adult rats: correlations with locomotor rating scores.

    Science.gov (United States)

    Semler, Joerg; Wellmann, Katharina; Wirth, Felicitas; Stein, Gregor; Angelova, Srebrina; Ashrafi, Mahak; Schempf, Greta; Ankerne, Janina; Ozsoy, Ozlem; Ozsoy, Umut; Schönau, Eckhard; Angelov, Doychin N; Irintchev, Andrey

    2011-07-01

    Precise assessment of motor deficits after traumatic spinal cord injury (SCI) in rodents is crucial for understanding the mechanisms of functional recovery and testing therapeutic approaches. Here we analyzed the applicability to a rat SCI model of an objective approach, the single-frame motion analysis, created and used for functional analysis in mice. Adult female Wistar rats were subjected to graded compression of the spinal cord. Recovery of locomotion was analyzed using video recordings of beam walking and inclined ladder climbing. Three out of four parameters used in mice appeared suitable: the foot-stepping angle (FSA) and the rump-height index (RHI), measured during beam walking, and for estimating paw placement and body weight support, respectively, and the number of correct ladder steps (CLS), assessing skilled limb movements. These parameters, similar to the Basso, Beattie, and Bresnahan (BBB) locomotor rating scores, correlated with lesion volume and showed significant differences between moderately and severely injured rats at 1-9 weeks after SCI. The beam parameters, but not CLS, correlated well with the BBB scores within ranges of poor and good locomotor abilities. FSA co-varied with RHI only in the severely impaired rats, while RHI and CLS were barely correlated. Our findings suggest that the numerical parameters estimate, as intended by design, predominantly different aspects of locomotion. The use of these objective measures combined with BBB rating provides a time- and cost-efficient opportunity for versatile and reliable functional evaluations in both severely and moderately impaired rats, combining clinical assessment with precise numerical measures.

  5. Advantages and Disadvantages of Adult Spinal Deformity Surgery and Its Impact on Health-Related Quality of Life.

    Science.gov (United States)

    Yoshida, Go; Boissiere, Louis; Larrieu, Daniel; Bourghli, Anouar; Vital, Jean Marc; Gille, Olivier; Pointillart, Vincent; Challier, Vincent; Mariey, Remi; Pellisé, Ferran; Vila-Casademunt, Alba; Perez-Grueso, Francisco Javier Sánchez; Alanay, Ahmet; Acaroglu, Emre; Kleinstück, Frank; Obeid, Ibrahim

    2017-03-15

    Prospective multicenter study of adult spinal deformity (ASD) surgery. To clarify the effect of ASD surgery on each health-related quality of life (HRQOL) subclass/domain. For patients with ASD, surgery offers superior radiological and HRQOL outcomes compared with nonoperative care. HRQOL may, however, be affected by surgical advantages related to corrective effects, yielding adequate spinopelvic alignment and stability or disadvantages because of long segment fusion. The study included 170 consecutive patients with ASD from a multicenter database with more than 2-year follow-up period. We analyzed each HRQOL domain/subclass (short form-36 items, Oswestry Disability Index, Scoliosis Research Society-22 [SRS-22] questionnaire), and radiographic parameters preoperatively and at 1 and 2 years postoperatively. We divided the patients into two groups each based on lowest instrumented vertebra (LIV; above L5 or S1 to ilium) or surgeon-determined preoperative pathology (idiopathic or degenerative). Improvement rate (%) was calculated as follows: 100 × |pre.-post.|/preoperative points (%) (+, advantages; -, disadvantages). The scores of all short form-36 items and SRS-22 subclasses improved at 1 and 2 years after surgery, regardless of LIV location and preoperative pathology. Personal care and lifting in Oswestry Disability Index were, however, not improved after 1 year. These disadvantages were correlated to sagittal modifiers of SRS-Schwab classification similar to other HRQOL. The degree of personal care disadvantage mainly depended on LIV location and preoperative pathology. Although personal care improved after 2 years postoperatively, no noticeable improvements in lifting were recorded. HRQOL subclass analysis indicated two disadvantages of ASD surgery, which were correlated to sagittal radiographic measures. Fusion to the sacrum or ilium greatly restricted the ability to stretch or bend, leading to limited daily activities for at least 1 year postoperatively

  6. Calculation of the Target Lumbar Lordosis Angle for Restoring an Optimal Pelvic Tilt in Elderly Patients With Adult Spinal Deformity.

    Science.gov (United States)

    Yamato, Yu; Hasegawa, Tomohiko; Kobayashi, Sho; Yasuda, Tatsuya; Togawa, Daisuke; Arima, Hideyuki; Oe, Shin; Iida, Takahiro; Matsumura, Akira; Hosogane, Naobumi; Matsumoto, Morio; Matsuyama, Yukihiro

    2016-02-01

    This investigation consisted of a cross-sectional study and a retrospective multicenter case series. This investigation sought to identify the ideal lumbar lordosis (LL) angle for restoring an optimal pelvic tilt (PT) in patients with adult spinal deformity (ASD). To achieve successful corrective fusion in ASD patients with sagittal imbalance, it is essential to correct the sagittal spinal alignment and obtain a suitable pelvic inclination. We determined the LL angle that would restore the optimal PT following ASD surgery. The cross-sectional study included 184 elderly volunteers (mean age 64 years) with an Oswestry Disability Index score less than 20%. The relationship between PT or LL and the pelvic incidence (PI) in normal individuals was investigated. The second study included 116 ASD patients (mean age 66 years) who underwent thoracolumbar corrective fusion at 1 of 4 spine centers. The postoperative PT values were calculated using the parameters measured. On the basis of these studies, an ideal LL angle was determined. In the cross-sectional study, the linear regression equation for the optimal PT as a function of PI was "optimal PT = 0.47 × PI - 7.5." In the second study, the postoperative PT was determined as a function of PI and corrected LL, using the equation "postoperative PT = 0.7 × PI - 0.5 × corrected LL + 8.1." The target LL angle was determined by mathematically equalizing the PTs of these 2 equations: "target LL = 0.45 × PI + 31.8." The ideal LL angle can be determined using the equation "LL = 0.45 × PI + 31.8," which can be used as a reference during surgical planning in ASD cases. 4.

  7. Deconstructing Chronic Low Back Pain in the Older Adult-Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment. Part VI: Lumbar Spinal Stenosis.

    Science.gov (United States)

    Fritz, Julie M; Rundell, Sean D; Dougherty, Paul; Gentili, Angela; Kochersberger, Gary; Morone, Natalia E; Naga Raja, Srinivasa; Rodriguez, Eric; Rossi, Michelle I; Shega, Joseph; Sowa, Gwendolyn; Weiner, Debra K

    2016-03-01

    . To present the sixth in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. This article focuses on the evaluation and management of lumbar spinal stenosis (LSS), the most common condition for which older adults undergo spinal surgery. . The evaluation and treatment algorithm, a table articulating the rationale for the individual algorithm components, and stepped-care drug recommendations were developed using a modified Delphi approach. The Principal Investigator, a five-member content expert panel and a nine-member primary care panel were involved in the iterative development of these materials. The illustrative clinical case was taken from the clinical practice of a contributor's colleague (SR). . We present an algorithm and supportive materials to help guide the care of older adults with LSS, a condition that occurs not uncommonly in those with CLBP. The case illustrates the importance of function-focused management and a rational approach to conservative care. . Lumbar spinal stenosis exists not uncommonly in older adults with CLBP and management often can be accomplished without surgery. Treatment should address all conditions in addition to LSS contributing to pain and disability. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Establishment of a tamoxifen-inducible Cre-driver mouse strain for widespread and temporal genetic modification in adult mice.

    Science.gov (United States)

    Ichise, Hirotake; Hori, Akiko; Shiozawa, Seiji; Kondo, Saki; Kanegae, Yumi; Saito, Izumu; Ichise, Taeko; Yoshida, Nobuaki

    2016-07-29

    Temporal genetic modification of mice using the ligand-inducible Cre/loxP system is an important technique that allows the bypass of embryonic lethal phenotypes and access to adult phenotypes. In this study, we generated a tamoxifen-inducible Cre-driver mouse strain for the purpose of widespread and temporal Cre recombination. The new line, named CM32, expresses the GFPneo-fusion gene in a wide variety of tissues before FLP recombination and tamoxifen-inducible Cre after FLP recombination. Using FLP-recombined CM32 mice (CM32Δ mice) and Cre reporter mouse lines, we evaluated the efficiency of Cre recombination with and without tamoxifen administration to adult mice, and found tamoxifen-dependent induction of Cre recombination in a variety of adult tissues. In addition, we demonstrated that conditional activation of an oncogene could be achieved in adults using CM32Δ mice. CM32Δ;T26 mice, which harbored a Cre recombination-driven, SV40 large T antigen-expressing transgene, were viable and fertile. No overt phenotype was found in the mice up to 3 months after birth. Although they displayed pineoblastomas (pinealoblastomas) and/or thymic enlargement due to background Cre recombination by 6 months after birth, they developed epidermal hyperplasia when administered tamoxifen. Collectively, our results suggest that the CM32Δ transgenic mouse line can be applied to the assessment of adult phenotypes in mice with loxP-flanked transgenes.

  9. Wnt3 and Gata4 regulate axon regeneration in adult mouse DRG neurons.

    Science.gov (United States)

    Duan, Run-Shan; Liu, Pei-Pei; Xi, Feng; Wang, Wei-Hua; Tang, Gang-Bin; Wang, Rui-Ying; Saijilafu; Liu, Chang-Mei

    2018-05-05

    Neurons in the adult central nervous system (CNS) have a poor intrinsic axon growth potential after injury, but the underlying mechanisms are largely unknown. Wingless-related mouse mammary tumor virus integration site (WNT) family members regulate neural stem cell proliferation, axon tract and forebrain development in the nervous system. Here we report that Wnt3 is an important modulator of axon regeneration. Downregulation or overexpression of Wnt3 in adult dorsal root ganglion (DRG) neurons enhances or inhibits their axon regeneration ability respectively in vitro and in vivo. Especially, we show that Wnt3 modulates axon regeneration by repressing mRNA translation of the important transcription factor Gata4 via binding to the three prime untranslated region (3'UTR). Downregulation of Gata4 could restore the phenotype exhibited by Wnt3 downregulation in DRG neurons. Taken together, these data indicate that Wnt3 is a key intrinsic regulator of axon growth ability of the nervous system. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Dynamic Remodeling of Pericytes In Vivo Maintains Capillary Coverage in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Andrée-Anne Berthiaume

    2018-01-01

    Full Text Available Summary: Direct contact and communication between pericytes and endothelial cells is critical for maintenance of cerebrovascular stability and blood-brain barrier function. Capillary pericytes have thin processes that reach hundreds of micrometers along the capillary bed. The processes of adjacent pericytes come in close proximity but do not overlap, yielding a cellular chain with discrete territories occupied by individual pericytes. Little is known about whether this pericyte chain is structurally dynamic in the adult brain. Using in vivo two-photon imaging in adult mouse cortex, we show that while pericyte somata were immobile, the tips of their processes underwent extensions and/or retractions over days. The selective ablation of single pericytes provoked exuberant extension of processes from neighboring pericytes to contact uncovered regions of the endothelium. Uncovered capillary regions had normal barrier function but were dilated until pericyte contact was regained. Pericyte structural plasticity may be critical for cerebrovascular health and warrants detailed investigation. : Pericyte-endothelial contact is important for many aspects of cerebrovascular health. Berthiaume et al. use longitudinal two-photon imaging to show that the processes of brain capillary pericytes are structurally plastic in vivo. Their processes can grow hundreds of micrometers to ensure contact with exposed endothelium following ablation of a single pericyte. Keywords: capillary, pericyte, endothelium, blood-brain barrier, blood flow, plasticity, two-photon imaging, Alzheimer’s disease, dementia, stroke

  11. Cell proliferation, movement and differentiation during maintenance of the adult mouse adrenal cortex.

    Directory of Open Access Journals (Sweden)

    Su-Ping Chang

    Full Text Available Appropriate maintenance and regeneration of adult endocrine organs is important in both normal physiology and disease. We investigated cell proliferation, movement and differentiation in the adult mouse adrenal cortex, using different 5-bromo-2'-deoxyuridine (BrdU labelling regimens and immunostaining for phenotypic steroidogenic cell markers. Pulse-labelling showed that cell division was largely confined to the outer cortex, with most cells moving inwards towards the medulla at around 13-20 µm per day, though a distinct labelled cell population remained in the outer 10% of the cortex. Pulse-chase-labelling coupled with phenotypic immunostaining showed that, unlike cells in the inner cortex, most BrdU-positive outer cortical cells did not express steroidogenic markers, while co-staining for BrdU and Ki67 revealed that some outer cortical BrdU-positive cells were induced to proliferate following acute adrenocorticotropic hormone (ACTH treatment. Extended pulse-chase-labelling identified cells in the outer cortex which retained BrdU label for up to 18-23 weeks. Together, these observations are consistent with the location of both slow-cycling stem/progenitor and transiently amplifying cell populations in the outer cortex. Understanding the relationships between these distinct adrenocortical cell populations will be crucial to clarify mechanisms underpinning adrenocortical maintenance and long-term adaptation to pathophysiological states.

  12. Expression of a truncated receptor protein tyrosine phosphatase kappa in the brain of an adult transgenic mouse

    DEFF Research Database (Denmark)

    Shen, P; Canoll, P D; Sap, J

    1999-01-01

    that goal, we have used this mouse model to map the distribution of the truncated RPTP-kappa/beta-geo fusion protein in the adult mouse brain using beta-galactosidase as a marker enzyme. Visualization of the beta-galactosidase activity revealed a non-random pattern of expression, and identified cells......-6596]. Nevertheless, since the transgene's expression is driven by the endogenous RPTP-kappa promoter, distribution of the truncated RPTP-kappa/beta-geo fusion protein should reflect the regional and cellular expression of wild-type RPTP-kappa, and thus may identify sites where RPTP-kappa is important. Towards...

  13. Rhythmic ganglion cell activity in bleached and blind adult mouse retinas.

    Science.gov (United States)

    Menzler, Jacob; Channappa, Lakshmi; Zeck, Guenther

    2014-01-01

    In retinitis pigmentosa--a degenerative disease which often leads to incurable blindness--the loss of photoreceptors deprives the retina from a continuous excitatory input, the so-called dark current. In rodent models of this disease this deprivation leads to oscillatory electrical activity in the remaining circuitry, which is reflected in the rhythmic spiking of retinal ganglion cells (RGCs). It remained unclear, however, if the rhythmic RGC activity is attributed to circuit alterations occurring during photoreceptor degeneration or if rhythmic activity is an intrinsic property of healthy retinal circuitry which is masked by the photoreceptor's dark current. Here we tested these hypotheses by inducing and analysing oscillatory activity in adult healthy (C57/Bl6) and blind mouse retinas (rd10 and rd1). Rhythmic RGC activity in healthy retinas was detected upon partial photoreceptor bleaching using an extracellular high-density multi-transistor-array. The mean fundamental spiking frequency in bleached retinas was 4.3 Hz; close to the RGC rhythm detected in blind rd10 mouse retinas (6.5 Hz). Crosscorrelation analysis of neighbouring wild-type and rd10 RGCs (separation distance rhythmic RGC spiking in these retinas is driven by a network of presynaptic neurons. The inhibition of glutamatergic ganglion cell input or the inhibition of gap junctional coupling abolished the rhythmic pattern. In rd10 and rd1 retinas the presynaptic network leads to local field potentials, whereas in bleached retinas additional pharmacological disinhibition is required to achieve detectable field potentials. Our results demonstrate that photoreceptor bleaching unmasks oscillatory activity in healthy retinas which shares many features with the functional phenotype detected in rd10 retinas. The quantitative physiological differences advance the understanding of the degeneration process and may guide future rescue strategies.

  14. Adult plasticity in the subcortical auditory pathway of the maternal mouse.

    Directory of Open Access Journals (Sweden)

    Jason A Miranda

    Full Text Available Subcortical auditory nuclei were traditionally viewed as non-plastic in adulthood so that acoustic information could be stably conveyed to higher auditory areas. Studies in a variety of species, including humans, now suggest that prolonged acoustic training can drive long-lasting brainstem plasticity. The neurobiological mechanisms for such changes are not well understood in natural behavioral contexts due to a relative dearth of in vivo animal models in which to study this. Here, we demonstrate in a mouse model that a natural life experience with increased demands on the auditory system - motherhood - is associated with improved temporal processing in the subcortical auditory pathway. We measured the auditory brainstem response to test whether mothers and pup-naïve virgin mice differed in temporal responses to both broadband and tone stimuli, including ultrasonic frequencies found in mouse pup vocalizations. Mothers had shorter latencies for early ABR peaks, indicating plasticity in the auditory nerve and the cochlear nucleus. Shorter interpeak latency between waves IV and V also suggest plasticity in the inferior colliculus. Hormone manipulations revealed that these cannot be explained solely by estrogen levels experienced during pregnancy and parturition in mothers. In contrast, we found that pup-care experience, independent of pregnancy and parturition, contributes to shortening auditory brainstem response latencies. These results suggest that acoustic experience in the maternal context imparts plasticity on early auditory processing that lasts beyond pup weaning. In addition to establishing an animal model for exploring adult auditory brainstem plasticity in a neuroethological context, our results have broader implications for models of perceptual, behavioral and neural changes that arise during maternity, where subcortical sensorineural plasticity has not previously been considered.

  15. Adult plasticity in the subcortical auditory pathway of the maternal mouse.

    Science.gov (United States)

    Miranda, Jason A; Shepard, Kathryn N; McClintock, Shannon K; Liu, Robert C

    2014-01-01

    Subcortical auditory nuclei were traditionally viewed as non-plastic in adulthood so that acoustic information could be stably conveyed to higher auditory areas. Studies in a variety of species, including humans, now suggest that prolonged acoustic training can drive long-lasting brainstem plasticity. The neurobiological mechanisms for such changes are not well understood in natural behavioral contexts due to a relative dearth of in vivo animal models in which to study this. Here, we demonstrate in a mouse model that a natural life experience with increased demands on the auditory system - motherhood - is associated with improved temporal processing in the subcortical auditory pathway. We measured the auditory brainstem response to test whether mothers and pup-naïve virgin mice differed in temporal responses to both broadband and tone stimuli, including ultrasonic frequencies found in mouse pup vocalizations. Mothers had shorter latencies for early ABR peaks, indicating plasticity in the auditory nerve and the cochlear nucleus. Shorter interpeak latency between waves IV and V also suggest plasticity in the inferior colliculus. Hormone manipulations revealed that these cannot be explained solely by estrogen levels experienced during pregnancy and parturition in mothers. In contrast, we found that pup-care experience, independent of pregnancy and parturition, contributes to shortening auditory brainstem response latencies. These results suggest that acoustic experience in the maternal context imparts plasticity on early auditory processing that lasts beyond pup weaning. In addition to establishing an animal model for exploring adult auditory brainstem plasticity in a neuroethological context, our results have broader implications for models of perceptual, behavioral and neural changes that arise during maternity, where subcortical sensorineural plasticity has not previously been considered.

  16. Transplantation of adult mouse iPS cell-derived photoreceptor precursors restores retinal structure and function in degenerative mice.

    Directory of Open Access Journals (Sweden)

    Budd A Tucker

    2011-04-01

    Full Text Available This study was designed to determine whether adult mouse induced pluripotent stem cells (iPSCs, could be used to produce retinal precursors and subsequently photoreceptor cells for retinal transplantation to restore retinal function in degenerative hosts. iPSCs were generated using adult dsRed mouse dermal fibroblasts via retroviral induction of the transcription factors Oct4, Sox2, KLF4 and c-Myc. As with normal mouse ES cells, adult dsRed iPSCs expressed the pluripotency genes SSEA1, Oct4, Sox2, KLF4, c-Myc and Nanog. Following transplantation into the eye of immune-compromised retinal degenerative mice these cells proceeded to form teratomas containing tissue comprising all three germ layers. At 33 days post-differentiation a large proportion of the cells expressed the retinal progenitor cell marker Pax6 and went on to express the photoreceptor markers, CRX, recoverin, and rhodopsin. When tested using calcium imaging these cells were shown to exhibit characteristics of normal retinal physiology, responding to delivery of neurotransmitters. Following subretinal transplantation into degenerative hosts differentiated iPSCs took up residence in the retinal outer nuclear layer and gave rise to increased electro retinal function as determined by ERG and functional anatomy. As such, adult fibroblast-derived iPSCs provide a viable source for the production of retinal precursors to be used for transplantation and treatment of retinal degenerative disease.

  17. Doublecortin (DCX is not essential for survival and differentiation of newborn neurons in the adult mouse dentate gyrus

    Directory of Open Access Journals (Sweden)

    Jagroop eDhaliwal

    2016-01-01

    Full Text Available In the adult brain, expression of the microtubule-associated protein Doublecortin (DCX is associated with neural progenitor cells (NPCs that give rise to new neurons in the dentate gyrus. Many studies quantify the number of DCX-expressing cells as a proxy for the level of adult neurogenesis, yet no study has determined the effect of removing DCX from adult hippocampal NPCs. Here, we use a retroviral and inducible mouse transgenic approach to either knockdown or knockout DCX from adult NPCs in the dentate gyrus and examine how this affects cell survival and neuronal maturation. Our results demonstrate that shRNA-mediated knockdown of DCX or Cre-mediated recombination in floxed DCX mice does not alter hippocampal neurogenesis and does not change the neuronal fate of the NPCs. Together these findings show that the survival and maturation of adult-generated hippocampal neurons does not require DCX.

  18. Expression of a truncated receptor protein tyrosine phosphatase kappa in the brain of an adult transgenic mouse

    DEFF Research Database (Denmark)

    Shen, P; Canoll, P D; Sap, J

    1999-01-01

    processes such as axonal growth and target recognition, as has been demonstrated for certain Drosophila RPTPs. The brain distribution of RPTP-kappa-expressing cells has not been determined, however. In a gene-trap mouse model with a beta-gal+neo (beta-geo) insertion in the endogenous RPTP-kappa gene......-6596]. Nevertheless, since the transgene's expression is driven by the endogenous RPTP-kappa promoter, distribution of the truncated RPTP-kappa/beta-geo fusion protein should reflect the regional and cellular expression of wild-type RPTP-kappa, and thus may identify sites where RPTP-kappa is important. Towards...... that goal, we have used this mouse model to map the distribution of the truncated RPTP-kappa/beta-geo fusion protein in the adult mouse brain using beta-galactosidase as a marker enzyme. Visualization of the beta-galactosidase activity revealed a non-random pattern of expression, and identified cells...

  19. Vitamin B(12) dependent changes in mouse spinal cord expression of vitamin B(12) related proteins and the epidermal growth factor system

    DEFF Research Database (Denmark)

    Mutti, Elena; Lildballe, Dorte L; Kristensen, Lise

    2013-01-01

    Chronic vitamin B(12) (cobalamin) deficiency in the mammalian central nervous system causes degenerative damage, especially in the spinal cord. Previous studies have shown that cobalamin status alters spinal cord expression of epidermal growth factor (EGF) and its receptor in rats. Employing...

  20. Analysis of factors affecting baseline SF-36 Mental Component Summary in Adult Spinal Deformity and its impact on surgical outcomes.

    Science.gov (United States)

    Mmopelwa, Tiro; Ayhan, Selim; Yuksel, Selcen; Nabiyev, Vugar; Niyazi, Asli; Pellise, Ferran; Alanay, Ahmet; Sanchez Perez Grueso, Francisco Javier; Kleinstuck, Frank; Obeid, Ibrahim; Acaroglu, Emre

    2018-03-01

    To identify the factors that affect SF-36 mental component summary (MCS) in patients with adult spinal deformity (ASD) at the time of presentation, and to analyse the effect of SF-36 MCS on clinical outcomes in surgically treated patients. Prospectively collected data from a multicentric ASD database was analysed for baseline parameters. Then, the same database for surgically treated patients with a minimum of 1-year follow-up was analysed to see the effect of baseline SF-36 MCS on treatment results. A clinically useful SF-36 MCS was determined by ROC Curve analysis. A total of 229 patients with the baseline parameters were analysed. A strong correlation between SF-36 MCS and SRS-22, ODI, gender, and diagnosis were found (p baseline SF-36 MCS (p baseline SF-36 MCS in an ASD population are other HRQOL parameters such as SRS-22 and ODI as well as the baseline thoracic kyphosis and gender. This study has also demonstrated that baseline SF-36 MCS does not necessarily have any effect on the treatment results by surgery as assessed by SRS-22 or ODI. Level III, prognostic study. Copyright © 2018 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

  1. Lifestyle Changes and Pressure Ulcer Prevention in Adults With Spinal Cord Injury in the Pressure Ulcer Prevention Study Lifestyle Intervention

    Science.gov (United States)

    Ghaisas, Samruddhi; Pyatak, Elizabeth A.; Blanche, Erna; Clark, Florence

    2015-01-01

    Pressure ulcers (PrUs) are a major burden to patients with spinal cord injury (SCI), affecting their psychological, physical, and social well-being. Lifestyle choices are thought to contribute to the risk of developing PrUs. This article focuses on the interaction between lifestyle choices and the development of PrUs in community settings among participants in the University of Southern California–Rancho Los Amigos National Rehabilitation Center Pressure Ulcer Prevention Study (PUPS II), a randomized controlled trial of a lifestyle intervention for adults with SCI. We conducted a secondary cross-case analysis of treatment notes of 47 PUPS II participants and identified four patterns relating PrU development to lifestyle changes: positive PrU changes (e.g., healing PrUs) with positive lifestyle changes, negative or no PrU changes with positive lifestyle changes, positive PrU changes with minor lifestyle changes, and negative or no PrU changes with no lifestyle changes. We present case studies exemplifying each pattern. PMID:25553751

  2. Mediating effects of social support and self-concept on depressive symptoms in adults with spinal cord injury.

    Science.gov (United States)

    Huang, C-Y; Chen, W-K; Lu, C-Y; Tsai, C-C; Lai, H-L; Lin, H-Y; Guo, S-E; Wu, L-M; Chen, C-I

    2015-05-01

    Cross-sectional, correlational design. To examine the effects of individual demographics, activities of daily living, social support, and self-concept on depressive symptoms in people with spinal cord injury (SCI). A convenience sample of 135 adults with SCI was recruited from medical and rehabilitation centres in Taiwan. Face-to-face, structured interviews were employed to collect information. Study questionnaires included a demographic sheet, the Barthel scale, the modified Social Support Inventory, the Huang self-concept scale and the Beck Depression Inventory. Data were analysed by structural equation modelling (SEM). The average age of the participants was 43.3 years (±11.98), the mean duration of injury was 114 months (±93.78), and most were males. Emotional support (r=-0.173, Pself-concept as significant predictors of depressive symptoms, with self-concept acting as a mediator in this relationship. Participants' characteristics and social support both contributed substantial indirect effects on depressive symptoms via self-concept. Self-concept also mediated the relationship between education, income, physical functioning and participants' depressive symptoms. For this sample, the more negative that individuals perceived themselves, the more likely they were to report worsening depressive symptoms. The more social support that individuals have, the more likely they were to report less depressive symptoms. Further longitudinal research will help clarify the direction of these relationships.

  3. Endogenous neural stem cells in central canal of adult rats acquired limited ability to differentiate into neurons following mild spinal cord injury

    Science.gov (United States)

    Liu, Yuan; Tan, Botao; Wang, Li; Long, Zaiyun; Li, Yingyu; Liao, Weihong; Wu, Yamin

    2015-01-01

    Endogenous neural stem cells in central canal of adult mammalian spinal cord exhibit stem cell properties following injury. In the present study, the endogenous neural stem cells were labeled with Dil to track the differentiation of cells after mild spinal cord injury (SCI). Compared with 1 and 14 days post mild injury, the number of endogenous neural stem cells significantly increased at the injured site of spinal cord on 3 and 7 days post-injury. Dil-labeled βIII-tublin and GFAP expressing cells could be detected on 7 days post-injury, which indicated that the endogenous neural stem cells in central canal of spinal cord differentiated into different type of neural cells, but there were more differentiated astrocytes than the neurons after injury. Furthermore, after injury the expression of inhibitory Notch1 and Hes1 mRNA began to increase at 6 hours and was evident at 12 and 24 hours, which maintained high levels up to 7 days post-injury. These results indicated that a mild SCI in rat is sufficient to induce endogenous neural stem cells proliferation and differentiation. However, the ability to differentiate into neurons is limited, which may be, at least in part, due to high expression of inhibitory Notch1 and Hes1 genes after injury. PMID:26097566

  4. Astrocytes from the contused spinal cord inhibit oligodendrocyte differentiation of adult oligodendrocyte precursor cells by increasing the expression of bone morphogenetic proteins.

    Science.gov (United States)

    Wang, Yaping; Cheng, Xiaoxin; He, Qian; Zheng, Yiyan; Kim, Dong H; Whittemore, Scott R; Cao, Qilin L

    2011-04-20

    Promotion of remyelination is an important therapeutic strategy to facilitate functional recovery after traumatic spinal cord injury (SCI). Transplantation of neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) has been used to enhance remyelination after SCI. However, the microenvironment in the injured spinal cord is inhibitory for oligodendrocyte (OL) differentiation of NSCs or OPCs. Identifying the signaling pathways that inhibit OL differentiation in the injured spinal cord could lead to new therapeutic strategies to enhance remyelination and functional recovery after SCI. In the present study, we show that reactive astrocytes from the injured rat spinal cord or their conditioned media inhibit OL differentiation of adult OPCs with concurrent promotion of astrocyte differentiation. The expression of bone morphogenetic proteins (BMP) is dramatically increased in the reactive astrocytes and their conditioned media. Importantly, blocking BMP activity by BMP receptor antagonist, noggin, reverse the effects of active astrocytes on OPC differentiation by increasing the differentiation of OL from OPCs while decreasing the generation of astrocytes. These data indicate that the upregulated bone morphogenetic proteins in the reactive astrocytes are major factors to inhibit OL differentiation of OPCs and to promote its astrocyte differentiation. These data suggest that manipulation of BMP signaling in the endogenous or grafted NSCs or OPCs may be a useful therapeutic strategy to increase their OL differentiation and remyelination and enhance functional recovery after SCI.

  5. Lifestyle intervention for adults with spinal cord injury: Results of the USC-RLANRC Pressure Ulcer Prevention Study.

    Science.gov (United States)

    Carlson, Mike; Vigen, Cheryl Lp; Rubayi, Salah; Blanche, Erna Imperatore; Blanchard, Jeanine; Atkins, Michal; Bates-Jensen, Barbara; Garber, Susan L; Pyatak, Elizabeth A; Diaz, Jesus; Florindez, Lucia I; Hay, Joel W; Mallinson, Trudy; Unger, Jennifer B; Azen, Stanley Paul; Scott, Michael; Cogan, Alison; Clark, Florence

    2017-04-17

    Medically serious pressure injuries (MSPrIs), a common complication of spinal cord injury (SCI), have devastating consequences on health and well-being and are extremely expensive to treat. We aimed to test the efficacy of a lifestyle-based intervention designed to reduce incidence of MSPrIs in adults with SCI. A randomized controlled trial (RCT), and a separate study wing involving a nonrandomized standard care control group. Rancho Los Amigos National Rehabilitation Center, a large facility serving ethnically diverse, low income residents of Los Angeles County. Adults with SCI, with history of one or more MSPrIs over the past 5 years: N=166 for RCT component, N=66 in nonrandomized control group. The Pressure Ulcer Prevention Program, a 12-month lifestyle-based treatment administered by healthcare professionals, largely via in-home visits and phone contacts. Blinded assessments of annualized MSPrI incidence rates at 12 and 24 months, based on: skin checks, quarterly phone interviews with participants, and review of medical charts and billing records. Secondary outcomes included number of surgeries and various quality-of-life measures. Annualized MSPrI rates did not differ significantly between study groups. At 12 months, rates were .56 for intervention recipients, .48 for randomized controls, and .65 for nonrandomized controls. At follow-up, rates were .44 and .39 respectively for randomized intervention and control participants. Evidence for intervention efficacy was inconclusive. The intractable nature of MSPrI threat in high-risk SCI populations, and lack of statistical power, may have contributed to this inability to detect an effect. ClinicalTrials.gov NCT01999816.

  6. Early Outcomes of Minimally Invasive Anterior Longitudinal Ligament Release for Correction of Sagittal Imbalance in Patients with Adult Spinal Deformity

    Directory of Open Access Journals (Sweden)

    Armen R. Deukmedjian

    2012-01-01

    Full Text Available The object of this study was to evaluate a novel surgical technique in the treatment of adult degenerative scoliosis and present our early experience with the minimally invasive lateral approach for anterior longitudinal ligament release to provide lumbar lordosis and examine its impact on sagittal balance. Methods. All patients with adult spinal deformity (ASD treated with the minimally invasive lateral retroperitoneal transpsoas interbody fusion (MIS LIF for release of the anterior longitudinal ligament were examined. Patient demographics, clinical data, spinopelvic parameters, and outcome measures were recorded. Results. Seven patients underwent release of the anterior longitudinal ligament (ALR to improve sagittal imbalance. All cases were split into anterior and posterior stages, with mean estimated blood loss of 125 cc and 530 cc, respectively. Average hospital stay was 8.3 days, and mean follow-up time was 9.1 months. Comparing pre- and postoperative 36′′ standing X-rays, the authors discovered a mean increase in global lumbar lordosis of 24 degrees, increase in segmental lumbar lordosis of 17 degrees per level of ALL released, decrease in pelvic tilt of 7 degrees, and decrease in sagittal vertical axis of 4.9 cm. At the last followup, there was a mean improvement in VAS and ODI scores of 26.2% and 18.3%. Conclusions. In the authors’ early experience, release of the anterior longitudinal ligament using the minimally invasive lateral retroperitoneal transpsoas approach may be a feasible alternative in correcting sagittal deformity.

  7. Understanding about diagnosis of acute small bowel retrograde intussusception in adults by means of 64-slice-spinal CT

    International Nuclear Information System (INIS)

    Jiang Ruizhou; Chen Jincheng

    2009-01-01

    Objective: To have a further study of the value of MSCT in diagnosing acute small bowel retrograde intussusception in adults by means of 64-slice-spinal CT. Methods: A 46-year-old female patient with the history of abdominal operation was found having acute mechanical small bowel obstruction through plain X-ray radiograph. 64-slice MSCT was performed afterwards (plain scan + 3 stage contrast scans). Hence, evidence is provided for operation. Results: Using the technique of MSCT for the patient can promptly approach the diagnosis of jejuno-jejunal intussusception with severe bowel obstruction; no small bowel tumor or other organic lesion found in this case. With the patient who has the history of abdominal operations, MSCT can predict the reason of adhesion causing bowel intussusception, and provide the evidence for operation; whereas MSCT with contrast media offers a further investigation of the blood supply to the bowels through SMA, and observation of blood circulation through the intussuscepting site, which represents venous congestion of intussusception. This case is a retrograde small bowel intussusception and confirmed with operation evidence. A greater amount of gas and fluid is accumulated between the dilated space of middle-distal portion of intussusceptum and intussuscipiens. Nevertheless, less gas at the proximal portion and that can be an important sign for retrograde intussusception. Conclusion: MSCT is a good choice of examination for diagnosis of adult's intussusception. As the literature mentioned the advantages of MSCT for observing the circulation of intussusceptum and whether the diagnosis is antegrade or retrograde intussusception is also essential. (authors)

  8. Rupture Following Biceps-to-Triceps Tendon Transfer in Adolescents and Young Adults With Spinal Cord Injury:

    Science.gov (United States)

    Merenda, Lisa A.; Rutter, Laure; Curran, Kimberly; Kozin, Scott H.

    2012-01-01

    Background: Tendon transfer surgery can restore elbow extension in approximately 70% of persons with tetraplegia and often results in antigravity elbow extension strength. However, we have noted an almost 15% rupture/attenuation rate. Objective: This investigation was conducted to analyze potential causes in adolescents/young adults with spinal cord injury (SCI) who experienced tendon rupture or attenuation after biceps-to-triceps transfer. Methods: Medical charts of young adults with SCI who underwent biceps-to-triceps transfer and experienced tendon rupture or attenuation were reviewed. Data collected by retrospective chart review included general demographics, surgical procedure(s), use and duration of antibiotic treatment, time from tendon transfer surgery to rupture/attenuation, and method of diagnosis. Results: Twelve subjects with tetraplegia (mean age, 19 years) who underwent biceps-to-triceps reconstruction with subsequent tendon rupture or attenuation were evaluated. Mean age at time of tendon transfer was 18 years (range, 14-21 years). A fluoroquinolone was prescribed for 42% (n=5) of subjects. Tendon rupture was noted in 67% (n=8), and attenuation was noted in 33% (n=4). Average length of time from surgery to tendon rupture/attenuation was 5.7 months (range, 3-10 months). Conclusion: Potential contributing causes of tendon rupture/attenuation after transfer include surgical technique, rehabilitation, co-contraction of the transfer, poor patient compliance, and medications. In this cohort, 5 subjects were prescribed fluoroquinolones that have a US Food and Drug Administration black box concerning tendon ruptures. Currently, all candidates for upper extremity tendon transfer reconstruction are counseled on the effects of fluoroquinolones and the potential risk for tendon rupture. PMID:23459326

  9. The impact of maternal separation on adult mouse behaviour and on the total neuron number in the mouse hippocampus

    DEFF Research Database (Denmark)

    Fabricius, K.; Wörtwein, Gitta; Pakkenberg, B.

    2008-01-01

    , the number of errors made by the MS24 mice compared to controls and in total distance moved. The mice were subsequently sacrificed and the total number of neurons estimated in the hippocampus using the optical fractionator. We found a significant loss of neurons in the dentate gyrus in MS mice compared...... to controls. Apparently a single maternal separation can impact the number of neurons in mouse hippocampus either by a decrease of neurogenesis or as an increase in neuron apoptosis. This study is the first to assess the result of maternal separation combining behaviour and stereology Udgivelsesdato: 2008/2...

  10. Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear.

    Science.gov (United States)

    Kilpatrick, L A; Li, Q; Yang, J; Goddard, J C; Fekete, D M; Lang, H

    2011-06-01

    Murine models are ideal for studying cochlear gene transfer, as many hearing loss-related mutations have been discovered and mapped within the mouse genome. However, because of the small size and delicate nature, the membranous labyrinth of the mouse is a challenging target for the delivery of viral vectors. To minimize injection trauma, we developed a procedure for the controlled release of adeno-associated viruses (AAVs) into the scala media of adult mice. This procedure poses minimal risk of injury to structures of the cochlea and middle ear, and allows for near-complete preservation of low and middle frequency hearing. In this study, transduction efficiency and cellular specificity of AAV vectors (serotypes 1, 2, 5, 6 and 8) were investigated in normal and drug-deafened ears. Using the cytomegalovirus promoter to drive gene expression, a variety of cell types were transduced successfully, including sensory hair cells and supporting cells, as well as cells in the auditory nerve and spiral ligament. Among all five serotypes, inner hair cells were the most effectively transduced cochlear cell type. All five serotypes of AAV vectors transduced cells of the auditory nerve, though serotype 8 was the most efficient vector for transduction. Our findings indicate that efficient AAV inoculation (via the scala media) can be performed in adult mouse ears, with hearing preservation a realistic goal. The procedure we describe may also have applications for intra-endolymphatic drug delivery in many mouse models of human deafness.

  11. Systematic reviews of physical and rehabilitation medicine Cochrane contents. Part 1. Disabilities due to spinal disorders and pain syndromes in adults.

    Science.gov (United States)

    Negrini, S; Imperio, G; Villafañe, J H; Negrini, F; Zaina, F

    2013-08-01

    This article is the first in a series presenting the strongest published evidence for physical and rehabilitation medicine (PRM) to date coming from the Cochrane Collaboration. The intent of the series is to stimulate ideas for reviews and research in neglected areas of PRM. To systematically review the rehabilitation contents of the Cochrane Collaboration on disabilities due to spinal disorders or pain syndromes in adults. The Cochrane Database of Systematic Reviews was searched at the end of June 2013 for articles relevant for PRM about disabilities resulting from spinal disorders or pain syndromes in adults. Retrieved papers were classified according to the PRM approach: active therapies, which require active participation by patients to achieve treatment goals, and passive treatments, which rely on the application of external forces. The quality of the reviews was checked against the AMSTAR checklist. Reviews on spinal disorders or pain syndromes were found in the Cochrane Back Group (CBG) and in the Pain, Palliative and Supportive Care Group (CPPSCG). Thirty-eight (42.8%) of 89 Cochrane reviews in the CBG and 7 (2.4%) of 293 Cochrane reviews in the CPPSCG were included. All were of high quality (range, 8-11 points out of 11 on the AMSTAR checklist). The contents of the reviews are given in detail. This review presents an overview of the current evidence for PRM in the treatment of disabilities due to spinal disorders or pain syndromes in adults. Within PRM there is ample space for research in the Cochrane Collaboration and for producing original studies (randomized controlled trials [RCTs]). To apply evidence-based clinical practice, clinicians must be familiar with the current best evidence.

  12. A Comprehensive Analysis of the SRS-Schwab Adult Spinal Deformity Classification and Confounding Variables: A Prospective, Non-US Cross-sectional Study in 292 Patients.

    Science.gov (United States)

    Hallager, Dennis Winge; Hansen, Lars Valentin; Dragsted, Casper Rokkjær; Peytz, Nina; Gehrchen, Martin; Dahl, Benny

    2016-05-01

    Cross-sectional analyses on a consecutive, prospective cohort. To evaluate the ability of the Scoliosis Research Society (SRS)-Schwab Adult Spinal Deformity Classification to group patients by widely used health-related quality-of-life (HRQOL) scores and examine possible confounding variables. The SRS-Schwab Adult Spinal Deformity Classification includes sagittal modifiers considered important for HRQOL and the clinical impact of the classification has been validated in patients from the International Spine Study Group database; however, equivocal results were reported for the Pelvic Tilt modifier and potential confounding variables were not evaluated. Between March 2013 and May 2014, all adult spinal deformity patients from our outpatient clinic with sufficient radiographs were prospectively enrolled. Analyses of HRQOL variance and post hoc analyses were performed for each SRS-Schwab modifier. Age, history of spine surgery, and aetiology of spinal deformity were considered potential confounders and their influence on the association between SRS-Schwab modifiers and aggregated Oswestry Disability Index (ODI) scores was evaluated with multivariate proportional odds regressions. P values were adjusted for multiple testing. Two hundred ninety-two of 460 eligible patients were included for analyses. The SRS-Schwab Classification significantly discriminated HRQOL scores between normal and abnormal sagittal modifier classifications. Individual grade comparisons showed equivocal results; however, Pelvic Tilt grade + versus +  + did not discriminate patients according to any HRQOL score. All modifiers showed significant proportional odds for worse aggregated ODI scores with increasing grade levels and the effects were robust to confounding. However, age group and aetiology had individual significant effects. The SRS-Schwab sagittal modifiers reliably grouped patients graded 0 versus + / +  + according to the most widely used HRQOL scores and the

  13. Quantitative expression profile of distinct functional regions in the adult mouse brain.

    Directory of Open Access Journals (Sweden)

    Takeya Kasukawa

    Full Text Available The adult mammalian brain is composed of distinct regions with specialized roles including regulation of circadian clocks, feeding, sleep/awake, and seasonal rhythms. To find quantitative differences of expression among such various brain regions, we conducted the BrainStars (B* project, in which we profiled the genome-wide expression of ∼50 small brain regions, including sensory centers, and centers for motion, time, memory, fear, and feeding. To avoid confounds from temporal differences in gene expression, we sampled each region every 4 hours for 24 hours, and pooled the samples for DNA-microarray assays. Therefore, we focused on spatial differences in gene expression. We used informatics to identify candidate genes with expression changes showing high or low expression in specific regions. We also identified candidate genes with stable expression across brain regions that can be used as new internal control genes, and ligand-receptor interactions of neurohormones and neurotransmitters. Through these analyses, we found 8,159 multi-state genes, 2,212 regional marker gene candidates for 44 small brain regions, 915 internal control gene candidates, and 23,864 inferred ligand-receptor interactions. We also found that these sets include well-known genes as well as novel candidate genes that might be related to specific functions in brain regions. We used our findings to develop an integrated database (http://brainstars.org/ for exploring genome-wide expression in the adult mouse brain, and have made this database openly accessible. These new resources will help accelerate the functional analysis of the mammalian brain and the elucidation of its regulatory network systems.

  14. Visualizing form and function in organotypic slices of the adult mouse parotid gland.

    Science.gov (United States)

    Warner, Jennifer D; Peters, Christian G; Saunders, Rudel; Won, Jong Hak; Betzenhauser, Matthew J; Gunning, William T; Yule, David I; Giovannucci, David R

    2008-09-01

    An organotypic slice preparation of the adult mouse parotid salivary gland amenable to a variety of optical assessments of fluid and protein secretion dynamics is described. The semi-intact preparation rendered without the use of enzymatic treatment permitted live-cell imaging and multiphoton analysis of cellular and supracellular signals. Toward this end we demonstrated that the parotid slice is a significant addition to the repertoire of tools available to investigators to probe exocrine structure and function since there is currently no cell culture system that fully recapitulates parotid acinar cell biology. Importantly, we show that a subpopulation of the acinar cells of parotid slices can be maintained in short-term culture and retain their morphology and function for up to 2 days. This in vitro model system is a significant step forward compared with enzymatically dispersed acini that rapidly lose their morphological and functional characteristics over several hours, and it was shown to be long enough for the expression and trafficking of exogenous protein following adenoviral infection. This system is compatible with a variety of genetic and physiological approaches used to study secretory function.

  15. Defining Spino-Pelvic Alignment Thresholds: Should Operative Goals in Adult Spinal Deformity Surgery Account for Age?

    Science.gov (United States)

    Lafage, Renaud; Schwab, Frank; Challier, Vincent; Henry, Jensen K; Gum, Jeffrey; Smith, Justin; Hostin, Richard; Shaffrey, Christopher; Kim, Han J; Ames, Christopher; Scheer, Justin; Klineberg, Eric; Bess, Shay; Burton, Douglas; Lafage, Virginie

    2016-01-01

    Retrospective review of prospective, multicenter database. The aim of the study was to determine age-specific spino-pelvic parameters, to extrapolate age-specific Oswestry Disability Index (ODI) values from published Short Form (SF)-36 Physical Component Score (PCS) data, and to propose age-specific realignment thresholds for adult spinal deformity (ASD). The Scoliosis Research Society-Schwab classification offers a framework for defining alignment in patients with ASD. Although age-specific changes in spinal alignment and patient-reported outcomes have been established in the literature, their relationship in the setting of ASD operative realignment has not been reported. ASD patients who received operative or nonoperative treatment were consecutively enrolled. Patients were stratified by age, consistent with published US-normative values (Norms) of the SF-36 PCS (75  y old). At baseline, relationships between between radiographic spino-pelvic parameters (lumbar-pelvic mismatch [PI-LL], pelvic tilt [PT], sagittal vertical axis [SVA], and T1 pelvic angle [TPA]), age, and PCS were established using linear regression analysis; normative PCS values were then used to establish age-specific targets. Correlation analysis with ODI and PCS was used to determine age-specific ideal alignment. Baseline analysis included 773 patients (53.7 y old, 54% operative, 83% female). There was a strong correlation between ODI and PCS (r = 0.814, P US-normative ODI by age group. Linear regression analysis (all with r > 0.510, P US-normative PCS values demonstrated that ideal spino-pelvic values increased with age, ranging from PT = 10.9 degrees, PI-LL = -10.5 degrees, and SVA = 4.1 mm for patients under 35 years to PT = 28.5 degrees, PI-LL = 16.7 degrees, and SVA = 78.1 mm for patients over 75 years. Clinically, older patients had greater compensation, more degenerative loss of lordosis, and were more pitched forward. This study demonstrated that

  16. Olfactory discrimination training up-regulates and reorganizes expression of microRNAs in adult mouse hippocampus

    OpenAIRE

    Smalheiser, Neil R; Lugli, Giovanni; Lenon, Angela L; Davis, John M; Torvik, Vetle I; Larson, John

    2010-01-01

    Adult male mice (strain C57Bl/6J) were trained to execute nose-poke responses for water reinforcement; then they were randomly assigned to either of two groups: olfactory discrimination training (exposed to two odours with reward contingent upon correctly responding to one odour) or pseudo-training (exposed to two odours with reward not contingent upon response). These were run in yoked fashion and killed when the discrimination-trained mouse reached a learning criterion of 70% correct respon...

  17. Repeated touch and needle-prick stimulation in the neonatal period increases the baseline mechanical sensitivity and postinjury hypersensitivity of adult spinal sensory neurons.

    Science.gov (United States)

    van den Hoogen, Nynke J; Patijn, Jacob; Tibboel, Dick; Joosten, Bert A; Fitzgerald, Maria; Kwok, Charlie H T

    2018-03-08

    Noxious stimulation at critical stages of development has long-term consequences on somatosensory processing in later life, but it is not known whether this developmental plasticity is restricted to nociceptive pathways. Here, we investigate the effect of repeated neonatal noxious or innocuous hind paw stimulation on adult spinal dorsal horn cutaneous mechanical sensitivity. Neonatal Sprague-Dawley rats of both sexes received 4 unilateral left hind paw needle pricks (NPs, n = 13) or 4 tactile (cotton swab touch) stimuli, per day (TC, n = 11) for the first 7 days of life. Control pups were left undisturbed (n = 17). When adult (6-8 weeks), lumbar wide-dynamic-range neuron activity in laminae III-V was recorded using in vivo extracellular single-unit electrophysiology. Spike activity evoked by cutaneous dynamic tactile (brush), pinch and punctate (von Frey hair) stimulation, and plantar receptive field areas were recorded, at baseline and 2 and 5 days after left plantar hind paw incision. Baseline brush receptive fields, von Frey hair, and pinch sensitivity were significantly enhanced in adult NP and TC animals compared with undisturbed controls, although effects were greatest in NP rats. After incision, injury sensitivity of adult wide-dynamic-range neurons to both noxious and dynamic tactile hypersensitivity was significantly greater in NP animals compared with TC and undisturbed controls. We conclude that both repeated touch and needle-prick stimulation in the neonatal period can alter adult spinal sensory neuron sensitivity to both innocuous and noxious mechanical stimulation. Thus, spinal sensory circuits underlying touch and pain processing are shaped by a range of early-life somatosensory experiences.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

  18. PAX6 MiniPromoters drive restricted expression from rAAV in the adult mouse retina

    Directory of Open Access Journals (Sweden)

    Jack W Hickmott

    2016-01-01

    Full Text Available Current gene therapies predominantly use small, strong, and readily available ubiquitous promoters. However, as the field matures, the availability of small, cell-specific promoters would be greatly beneficial. Here we design seven small promoters from the human paired box 6 (PAX6 gene and test them in the adult mouse retina using recombinant adeno-associated virus. We chose the retina due to previous successes in gene therapy for blindness, and the PAX6 gene since it is: well studied; known to be driven by discrete regulatory regions; expressed in therapeutically interesting retinal cell types; and mutated in the vision-loss disorder aniridia, which is in need of improved therapy. At the PAX6 locus, 31 regulatory regions were bioinformatically predicted, and nine regulatory regions were constructed into seven MiniPromoters. Driving Emerald GFP, these MiniPromoters were packaged into recombinant adeno-associated virus, and injected intravitreally into postnatal day 14 mice. Four MiniPromoters drove consistent retinal expression in the adult mouse, driving expression in combinations of cell-types that endogenously express Pax6: ganglion, amacrine, horizontal, and Müller glia. Two PAX6-MiniPromoters drive expression in three of the four cell types that express PAX6 in the adult mouse retina. Combined, they capture all four cell types, making them potential tools for research, and PAX6-gene therapy for aniridia.

  19. PAX6 MiniPromoters drive restricted expression from rAAV in the adult mouse retina.

    Science.gov (United States)

    Hickmott, Jack W; Chen, Chih-Yu; Arenillas, David J; Korecki, Andrea J; Lam, Siu Ling; Molday, Laurie L; Bonaguro, Russell J; Zhou, Michelle; Chou, Alice Y; Mathelier, Anthony; Boye, Sanford L; Hauswirth, William W; Molday, Robert S; Wasserman, Wyeth W; Simpson, Elizabeth M

    2016-01-01

    Current gene therapies predominantly use small, strong, and readily available ubiquitous promoters. However, as the field matures, the availability of small, cell-specific promoters would be greatly beneficial. Here we design seven small promoters from the human paired box 6 (PAX6) gene and test them in the adult mouse retina using recombinant adeno-associated virus. We chose the retina due to previous successes in gene therapy for blindness, and the PAX6 gene since it is: well studied; known to be driven by discrete regulatory regions; expressed in therapeutically interesting retinal cell types; and mutated in the vision-loss disorder aniridia, which is in need of improved therapy. At the PAX6 locus, 31 regulatory regions were bioinformatically predicted, and nine regulatory regions were constructed into seven MiniPromoters. Driving Emerald GFP, these MiniPromoters were packaged into recombinant adeno-associated virus, and injected intravitreally into postnatal day 14 mice. Four MiniPromoters drove consistent retinal expression in the adult mouse, driving expression in combinations of cell-types that endogenously express Pax6: ganglion, amacrine, horizontal, and Müller glia. Two PAX6-MiniPromoters drive expression in three of the four cell types that express PAX6 in the adult mouse retina. Combined, they capture all four cell types, making them potential tools for research, and PAX6-gene therapy for aniridia.

  20. MYC gene delivery to adult mouse utricles stimulates proliferation of postmitotic supporting cells in vitro.

    Science.gov (United States)

    Burns, Joseph C; Yoo, James J; Atala, Anthony; Jackson, John D

    2012-01-01

    The inner ears of adult humans and other mammals possess a limited capacity for regenerating sensory hair cells, which can lead to permanent auditory and vestibular deficits. During development and regeneration, undifferentiated supporting cells within inner ear sensory epithelia can self-renew and give rise to new hair cells; however, these otic progenitors become depleted postnatally. Therefore, reprogramming differentiated supporting cells into otic progenitors is a potential strategy for restoring regenerative potential to the ear. Transient expression of the induced pluripotency transcription factors, Oct3/4, Klf4, Sox2, and c-Myc reprograms fibroblasts into neural progenitors under neural-promoting culture conditions, so as a first step, we explored whether ectopic expression of these factors can reverse supporting cell quiescence in whole organ cultures of adult mouse utricles. Co-infection of utricles with adenoviral vectors separately encoding Oct3/4, Klf4, Sox2, and the degradation-resistant T58A mutant of c-Myc (c-MycT58A) triggered significant levels of supporting cell S-phase entry as assessed by continuous BrdU labeling. Of the four factors, c-MycT58A alone was both necessary and sufficient for the proliferative response. The number of BrdU-labeled cells plateaued between 5-7 days after infection, and then decreased ~60% by 3 weeks, as many cycling cells appeared to enter apoptosis. Switching to differentiation-promoting culture medium at 5 days after ectopic expression of c-MycT58A temporarily attenuated the loss of BrdU-labeled cells and accompanied a very modest but significant expansion of the sensory epithelium. A small number of the proliferating cells in these cultures labeled for the hair cell marker, myosin VIIA, suggesting they had begun differentiating towards a hair cell fate. The results indicate that ectopic expression of c-MycT58A in combination with methods for promoting cell survival and differentiation may restore regenerative

  1. MYC gene delivery to adult mouse utricles stimulates proliferation of postmitotic supporting cells in vitro.

    Directory of Open Access Journals (Sweden)

    Joseph C Burns

    Full Text Available The inner ears of adult humans and other mammals possess a limited capacity for regenerating sensory hair cells, which can lead to permanent auditory and vestibular deficits. During development and regeneration, undifferentiated supporting cells within inner ear sensory epithelia can self-renew and give rise to new hair cells; however, these otic progenitors become depleted postnatally. Therefore, reprogramming differentiated supporting cells into otic progenitors is a potential strategy for restoring regenerative potential to the ear. Transient expression of the induced pluripotency transcription factors, Oct3/4, Klf4, Sox2, and c-Myc reprograms fibroblasts into neural progenitors under neural-promoting culture conditions, so as a first step, we explored whether ectopic expression of these factors can reverse supporting cell quiescence in whole organ cultures of adult mouse utricles. Co-infection of utricles with adenoviral vectors separately encoding Oct3/4, Klf4, Sox2, and the degradation-resistant T58A mutant of c-Myc (c-MycT58A triggered significant levels of supporting cell S-phase entry as assessed by continuous BrdU labeling. Of the four factors, c-MycT58A alone was both necessary and sufficient for the proliferative response. The number of BrdU-labeled cells plateaued between 5-7 days after infection, and then decreased ~60% by 3 weeks, as many cycling cells appeared to enter apoptosis. Switching to differentiation-promoting culture medium at 5 days after ectopic expression of c-MycT58A temporarily attenuated the loss of BrdU-labeled cells and accompanied a very modest but significant expansion of the sensory epithelium. A small number of the proliferating cells in these cultures labeled for the hair cell marker, myosin VIIA, suggesting they had begun differentiating towards a hair cell fate. The results indicate that ectopic expression of c-MycT58A in combination with methods for promoting cell survival and differentiation may restore

  2. Activation of the Wnt/{beta}-catenin signaling pathway is associated with glial proliferation in the adult spinal cord of ALS transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yanchun [Department of Histology and Embryology, Weifang Medical University, Weifang, Shandong (China); Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong (China); Guan, Yingjun, E-mail: guanyj@wfmc.edu.cn [Department of Histology and Embryology, Weifang Medical University, Weifang, Shandong (China); Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong (China); Liu, Huancai [Department of Orthopedic, Affiliated Hospital, Weifang Medical University, Weifang, Shandong (China); Wu, Xin; Yu, Li; Wang, Shanshan; Zhao, Chunyan; Du, Hongmei [Department of Histology and Embryology, Weifang Medical University, Weifang, Shandong (China); Wang, Xin, E-mail: xwang@rics.bwh.harvard.edu [Department of Neurosurgery, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States)

    2012-04-06

    Highlights: Black-Right-Pointing-Pointer Wnt3a and Cyclin D1 were upregulated in the spinal cord of the ALS mice. Black-Right-Pointing-Pointer {beta}-catenin translocated from the cell membrane to the nucleus in the ALS mice. Black-Right-Pointing-Pointer Wnt3a, {beta}-catenin and Cyclin D1 co-localized for astrocytes were all increased. Black-Right-Pointing-Pointer BrdU/Cyclin D1 double-positive cells were increased in the spinal cord of ALS mice. Black-Right-Pointing-Pointer BrdU/Cyclin D1/GFAP triple-positive cells were detected in the ALS mice. -- Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive and fatal loss of motor neurons. In ALS, there is a significant cell proliferation in response to neurodegeneration; however, the exact molecular mechanisms of cell proliferation and differentiation are unclear. The Wnt signaling pathway has been shown to be involved in neurodegenerative processes. Wnt3a, {beta}-catenin, and Cyclin D1 are three key signaling molecules of the Wnt/{beta}-catenin signaling pathway. We determined the expression of Wnt3a, {beta}-catenin, and Cyclin D1 in the adult spinal cord of SOD1{sup G93A} ALS transgenic mice at different stages by RT-PCR, Western blot, and immunofluorescence labeling techniques. We found that the mRNA and protein of Wnt3a and Cyclin D1 in the spinal cord of the ALS mice were upregulated compared to those in wild-type mice. In addition, {beta}-catenin translocated from the cell membrane to the nucleus and subsequently activated transcription of the target gene, Cyclin D1. BrdU and Cyclin D1 double-positive cells were increased in the spinal cord of these mice. Moreover, Wnt3a, {beta}-catenin, and Cyclin D1 were also expressed in both neurons and astrocytes. The expression of Wnt3a, {beta}-catenin or Cyclin D1 in mature GFAP{sup +} astrocytes increased. Moreover, BrdU/Cyclin D1/GFAP triple-positive cells were detected in the ALS mice. Our findings suggest that

  3. Activation of the Wnt/β-catenin signaling pathway is associated with glial proliferation in the adult spinal cord of ALS transgenic mice

    International Nuclear Information System (INIS)

    Chen, Yanchun; Guan, Yingjun; Liu, Huancai; Wu, Xin; Yu, Li; Wang, Shanshan; Zhao, Chunyan; Du, Hongmei; Wang, Xin

    2012-01-01

    Highlights: ► Wnt3a and Cyclin D1 were upregulated in the spinal cord of the ALS mice. ► β-catenin translocated from the cell membrane to the nucleus in the ALS mice. ► Wnt3a, β-catenin and Cyclin D1 co-localized for astrocytes were all increased. ► BrdU/Cyclin D1 double-positive cells were increased in the spinal cord of ALS mice. ► BrdU/Cyclin D1/GFAP triple-positive cells were detected in the ALS mice. -- Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive and fatal loss of motor neurons. In ALS, there is a significant cell proliferation in response to neurodegeneration; however, the exact molecular mechanisms of cell proliferation and differentiation are unclear. The Wnt signaling pathway has been shown to be involved in neurodegenerative processes. Wnt3a, β-catenin, and Cyclin D1 are three key signaling molecules of the Wnt/β-catenin signaling pathway. We determined the expression of Wnt3a, β-catenin, and Cyclin D1 in the adult spinal cord of SOD1 G93A ALS transgenic mice at different stages by RT-PCR, Western blot, and immunofluorescence labeling techniques. We found that the mRNA and protein of Wnt3a and Cyclin D1 in the spinal cord of the ALS mice were upregulated compared to those in wild-type mice. In addition, β-catenin translocated from the cell membrane to the nucleus and subsequently activated transcription of the target gene, Cyclin D1. BrdU and Cyclin D1 double-positive cells were increased in the spinal cord of these mice. Moreover, Wnt3a, β-catenin, and Cyclin D1 were also expressed in both neurons and astrocytes. The expression of Wnt3a, β-catenin or Cyclin D1 in mature GFAP + astrocytes increased. Moreover, BrdU/Cyclin D1/GFAP triple-positive cells were detected in the ALS mice. Our findings suggest that neurodegeneration activates the Wnt/β-catenin signaling pathway, which is associated with glial proliferation in the adult spinal cord of ALS transgenic mice. This

  4. Comparison of functional recovery of manual dexterity after unilateral spinal cord lesion or motor cortex lesion in adult macaque monkeys

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    Florence eHoogewoud

    2013-07-01

    Full Text Available In relation to mechanisms involved in functional recovery of manual dexterity from cervical cord injury or from motor cortical injury, our goal was to determine whether the movements that characterize post-lesion functional recovery are comparable to original movement patterns or do monkeys adopt distinct strategies to compensate the deficits depending on the type of lesion? To this aim, data derived from earlier studies, using a skilled finger task (the modified Brinkman board from which pellets are retrieved from vertical or horizontal slots, in spinal cord and motor cortex injured monkeys were analyzed and compared. Twelve adult macaque monkeys were subjected to a hemi-section of the cervical cord (n=6 or to a unilateral excitotoxic lesion of the hand representation in the primary motor cortex (n=6. In addition, in each subgroup, one half of monkeys (n=3 were treated for 30 days with a function blocking antibody against the neurite growth inhibitory protein Nogo-A, while the other half (n=3 represented control animals. The motor deficits, and the extent and time course of functional recovery were assessed.For some of the parameters investigated (wrist angle for horizontal slots and movement types distribution for vertical slots after cervical injury; movement types distribution for horizontal slots after motor cortex lesion, post-lesion restoration of the original movement patterns (true recovery led to a quantitatively better functional recovery. In the motor cortex lesion groups, pharmacological reversible inactivation experiments showed that the peri-lesion territory of the primary motor cortex or re-arranged, spared domain of the lesion zone, played a major role in the functional recovery, together with the ipsilesional intact premotor cortex.

  5. Myelosuppressive conditioning using busulfan enables bone marrow cell accumulation in the spinal cord of a mouse model of amyotrophic lateral sclerosis.

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    Coral-Ann B Lewis

    Full Text Available Myeloablative preconditioning using irradiation is the most commonly used technique to generate rodents having chimeric bone marrow, employed for the study of bone marrow-derived cell accumulation in the healthy and diseased central nervous system. However, irradiation has been shown to alter the blood-brain barrier, potentially creating confounding artefacts. To better study the potential of bone marrow-derived cells to function as treatment vehicles for neurodegenerative diseases alternative preconditioning regimens must be developed. We treated transgenic mice that over-express human mutant superoxide dismutase 1, a model of amyotrophic lateral sclerosis, with busulfan to determine whether this commonly used chemotherapeutic leads to stable chimerism and promotes the entry of bone marrow-derived cells into spinal cord. Intraperitoneal treatment with busulfan at 60 mg/kg or 80 mg/kg followed by intravenous injection of green fluorescent protein-expressing bone marrow resulted in sustained levels of chimerism (~80%. Bone marrow-derived cells accumulated in the lumbar spinal cord of diseased mice at advanced stages of pathology at both doses, with limited numbers of bone marrow derived cells observed in the spinal cords of similarly treated, age-matched controls; the majority of bone marrow-derived cells in spinal cord immunolabelled for macrophage antigens. Comparatively, significantly greater numbers of bone marrow-derived cells were observed in lumbar spinal cord following irradiative myeloablation. These results demonstrate bone marrow-derived cell accumulation in diseased spinal cord is possible without irradiative preconditioning.

  6. Effect of cyanotoxins on the hypothalamic-pituitary-gonadal axis in male adult mouse.

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    Xiong, Xiaolu; Zhong, Anyuan; Xu, Huajun

    2014-01-01

    Microcystins LR (MC-LR) are hepatotoxic cyanotoxins that have been shown to induce reproductive toxicity, and Hypothalamic-Pituitary-Gonadal Axis (HPG) is responsible for the control of reproductive functions. However, few studies have been performed to evaluate the effects of MC-LR on HPG axis. This study aimed to investigate the MC-LR-induced toxicity in the reproductive system of mouse and focus on the HPG axis. Adult male C57BL/6 mice were exposed to various concentrations of MC-LR (0, 3.75, 7.50, 15.00 and 30.00 µg/kg body weight per day) for 1 to 14 days, and it was found that exposure to different concentrations of MC-LR significantly disturbed sperm production in the mice testes in a dose- and time-dependent manner. To elucidate the associated possible mechanisms, the serum levels of testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were assessed. Meanwhile, PCR assays were employed to detect alterations in a series of genes involved in HPG axis, such as FSH, LH, gonadotropin-releasing hormone (GnRH) and their complement receptors. Furthermore, the effect of MC-LR on the viability and testosterone production of Leydig cells were tested in vitro. MC-LR significantly impaired the spermatogenesis of mice possibly through the direct or indirect inhibition of GnRH synthesis at the hypothalamic level, which resulted in reduction of serum levels of LH that lead to suppression of testosterone production in the testis of mice. MC-LR may be a GnRH toxin that would disrupt the reproductive system of mice.

  7. Effect of cyanotoxins on the hypothalamic-pituitary-gonadal axis in male adult mouse.

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    Xiaolu Xiong

    Full Text Available Microcystins LR (MC-LR are hepatotoxic cyanotoxins that have been shown to induce reproductive toxicity, and Hypothalamic-Pituitary-Gonadal Axis (HPG is responsible for the control of reproductive functions. However, few studies have been performed to evaluate the effects of MC-LR on HPG axis. This study aimed to investigate the MC-LR-induced toxicity in the reproductive system of mouse and focus on the HPG axis.Adult male C57BL/6 mice were exposed to various concentrations of MC-LR (0, 3.75, 7.50, 15.00 and 30.00 µg/kg body weight per day for 1 to 14 days, and it was found that exposure to different concentrations of MC-LR significantly disturbed sperm production in the mice testes in a dose- and time-dependent manner. To elucidate the associated possible mechanisms, the serum levels of testosterone, follicle-stimulating hormone (FSH and luteinizing hormone (LH were assessed. Meanwhile, PCR assays were employed to detect alterations in a series of genes involved in HPG axis, such as FSH, LH, gonadotropin-releasing hormone (GnRH and their complement receptors. Furthermore, the effect of MC-LR on the viability and testosterone production of Leydig cells were tested in vitro.MC-LR significantly impaired the spermatogenesis of mice possibly through the direct or indirect inhibition of GnRH synthesis at the hypothalamic level, which resulted in reduction of serum levels of LH that lead to suppression of testosterone production in the testis of mice.MC-LR may be a GnRH toxin that would disrupt the reproductive system of mice.

  8. Uptake of ingested bovine lactoferrin and its accumulation in adult mouse tissues.

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    Fischer, Romy; Debbabi, Hajer; Blais, Anne; Dubarry, Michel; Rautureau, Michèle; Boyaka, Prosper N; Tome, Daniel

    2007-10-01

    Lactoferrin is a glycoprotein with antimicrobial and immunoregulatory properties, which is found in milk, other external secretions, and in the secondary granules of neutrophils. The present study examined the time course of uptake and the pattern of tissue accumulation of bovine lactoferrin (bLf) following intragastric intubation of a single dose to adult naïve mice or to mice daily fed bLf for 4 weeks. Following ingestion, bLf was transferred from the intestine into peripheral blood in a form with intact molecular weight (80 kDa) and localized within 10 to 20 min after oral administration in the liver, kidneys, gall bladder, spleen, and brain of both groups of mice. Immunoreactive bLf could also be detected in the luminal contents of the stomach, small intestine and colon 1 h after intragastric intubation. Interestingly, serum and tissue accumulation of bLf was approximately 50% lower in mice chronically fed this protein than in those given only the single oral dose. Furthermore, significant levels of bLf-specific IgA and IgG antibodies as well as bLf-containing IgA- and IgG immune complexes were detected in mice chronically fed bLf but not in those fed only once. Taken together, these results indicate that bLf resists major proteolytic degradation in the intestinal lumen and is readily absorbed in an antigenic form in blood and various mouse tissues. Chronic ingestion of lactoferrin reduces its uptake, probably through mechanisms such as immune exclusion, which minimize potential harmful reactions to food products.

  9. GLOBAL BALANCE IN ADULT SPINAL DEFORMITIES. A STUDY OF 60 CASES

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    Victor Misael Galicia Luna

    Full Text Available ABSTRACT Objectives: Determine the most prevalent type of curve in our population, to quantify the radiographic parameters such as PT, IP, SS and compare the physical function according to ODI and SRS-22r. Methods: Retrospective, observational, longitudinal, single-center study, carried out from January 2010 to May 2015 at the Centro Médico ISSEMYM Ecatepec, Spine Surgery Service. Results: A total of 60 patients were obtained, 60% female, with curvatures according to SRS-Schwab, type T (28%, TL (46.6%, D (15%, N (10%, with a mean preoperative VAS of 7 for all curves and post-surgical 2 after 6 months. The SRS-22r preoperative test was 2.1 and postoperatively was 3.75, with p<0.001. Conclusions: Deformities of the adult spine are a growing disease in our country. The surgical management of deformities requires proper clinical and radiographic planning. Patients undergoing surgical treatment in our study showed curvature type TL and demonstrated significant improvement in ODI and SRS-22r.

  10. BAG3 regulates contractility and Ca(2+) homeostasis in adult mouse ventricular myocytes.

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    Feldman, Arthur M; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Myers, Valerie D; Tilley, Douglas G; Gao, Erhe; Hoffman, Nicholas E; Tomar, Dhanendra; Madesh, Muniswamy; Rabinowitz, Joseph; Koch, Walter J; Su, Feifei; Khalili, Kamel; Cheung, Joseph Y

    2016-03-01

    Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations, including mutations leading to loss of protein, are associated with familial cardiomyopathy. Furthermore, BAG3 levels have been found to be reduced in end-stage non-familial failing myocardium. In contrast to neonatal myocytes in which BAG3 is found in the cytoplasm and involved in protein quality control and apoptosis, in adult mouse left ventricular (LV) myocytes BAG3 co-localized with Na(+)-K(+)-ATPase and L-type Ca(2+) channels in the sarcolemma and t-tubules. BAG3 co-immunoprecipitated with β1-adrenergic receptor, L-type Ca(2+) channels and phospholemman. To simulate decreased BAG3 protein levels observed in human heart failure, we targeted BAG3 by shRNA (shBAG3) in adult LV myocytes. Reducing BAG3 by 55% resulted in reduced contraction and [Ca(2+)]i transient amplitudes in LV myocytes stimulated with isoproterenol. L-type Ca(2+) current (ICa) and sarcoplasmic reticulum (SR) Ca(2+) content but not Na(+)/Ca(2+) exchange current (INaCa) or SR Ca(2+) uptake were reduced in isoproterenol-treated shBAG3 myocytes. Forskolin or dibutyryl cAMP restored ICa amplitude in shBAG3 myocytes to that observed in WT myocytes, consistent with BAG3 having effects upstream and at the level of the receptor. Resting membrane potential and action potential amplitude were unaffected but APD50 and APD90 were prolonged in shBAG3 myocytes. Protein levels of Ca(2+) entry molecules and other important excitation-contraction proteins were unchanged in myocytes with lower BAG3. Our findings that BAG3 is localized at the sarcolemma and t-tubules while modulating myocyte contraction and action potential duration through specific interaction with the β1-adrenergic receptor and L-type Ca(2+) channel provide novel insight into the role of BAG3 in cardiomyopathies and increased arrhythmia risks in heart failure. Copyright © 2016 Elsevier Ltd. All rights

  11. BAG3 regulates contractility and Ca2+ homeostasis in adult mouse ventricular myocytes

    Science.gov (United States)

    Feldman, Arthur M.; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Myers, Valerie D.; Tilley, Douglas G.; Gao, Erhe; Hoffman, Nicholas E.; Tomar, Dhanendra; Madesh, Muniswamy; Rabinowitz, Joseph; Koch, Walter J.; Su, Feifei; Khalili, Kamel; Cheung, Joseph Y.

    2016-01-01

    Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations, including mutations leading to loss of protein, are associated with familial cardiomyopathy. Furthermore, BAG3 levels have been found to be reduced in end-stage non-familial failing myocardium. In contrast to neonatal myocytes in which BAG3 is found in the cytoplasm and involved in protein quality control and apoptosis, in adult mouse left ventricular (LV) myocytes BAG3 co-localized with Na+-K+-ATPase and L-type Ca2+ channels in the sarcolemma and t-tubules. BAG3 co-immunoprecipitated with β1-adrenergic receptor, L-type Ca2+ channels and phospholemman. To simulate decreased BAG3 protein levels observed in human heart failure, we targeted BAG3 by shRNA (shBAG3) in adult LV myocytes. Reducing BAG3 by 55% resulted in reduced contraction and [Ca2+]i transient amplitudes in LV myocytes stimulated with isoproterenol. L-type Ca2+ current (ICa) and sarcoplasmic reticulum (SR) Ca2+ content but not Na+/Ca2+ exchange current (INaCa) or SR Ca2+ uptake were reduced in isoproterenol-treated shBAG3 myocytes. Forskolin or dibutyrl cAMP restored ICa amplitude in shBAG3 myocytes to that observed in WT myocytes, consistent with BAG3 having effects upstream and at the level of the receptor. Resting membrane potential and action potential amplitude were unaffected but APD50 and APD90 were prolonged in shBAG3 myocytes. Protein levels of Ca2+ entry molecules and other important excitation-contraction proteins were unchanged in myocytes with lower BAG3. Our findings that BAG3 is localized at the sarcolemma and t-tubules while modulating myocyte contraction and action potential duration through specific interaction with the β1-adrenergic receptor and L-type Ca2+ channel provide novel insight into the role of BAG3 in cardiomyopathies and increased arrhythmia risks in heart failure. PMID:26796036

  12. Trends in isolated lumbar spinal stenosis surgery among working US adults aged 40-64 years, 2010-2014.

    Science.gov (United States)

    Raad, Micheal; Donaldson, Callum J; El Dafrawy, Mostafa H; Sciubba, Daniel M; Riley, Lee H; Neuman, Brian J; Kebaish, Khaled M; Skolasky, Richard L

    2018-05-25

    OBJECTIVE Recommendations for the surgical treatment of isolated lumbar spinal stenosis (LSS) (i.e., in the absence of concomitant scoliosis or spondylolisthesis) are unclear. The aims of this study were to investigate trends in the surgical treatment of isolated LSS in US adults and determine implications for outcomes. METHODS The authors analyzed inpatient and outpatient claims from the Truven Health Analytics MarketScan Commercial Claims and Encounters Database for 20,279 patients aged 40-64 years who underwent surgery for LSS between 2010 and 2014. Only patients with continuous 12-month insurance coverage after surgery were included. The rates of decompression with arthrodesis versus decompression only and of simple (1- or 2-level, single-approach) versus complex (> 2-level or combined-approach) arthrodesis were analyzed by year and geographic region. These trends were further analyzed with respect to complications, length of hospital stay, payments made to the hospital, and patient discharge status. Statistical significance was set at p < 0.05. RESULTS The proportion of patients who underwent decompression with arthrodesis compared with decompression only increased significantly and linearly from 2010 to 2014 (OR 1.08; 95% CI 1.06-1.10). Arthrodesis was more likely to be complex rather than simple with each subsequent year (OR 1.4; 95% CI 1.33-1.49). This trend was accompanied by an increased likelihood of postoperative complications (OR 1.11; 95% CI 1.02-1.21), higher costs (payments increased by a mean of US$1633 per year; 95% CI 1327-1939), and greater likelihood of being discharged to a skilled nursing facility as opposed to home (OR 1.11; 95% CI 1.03-1.20). The South and Midwest regions of the US had the highest proportions of patients undergoing arthrodesis (48% and 42%, respectively). The mean length of hospital stay did not change significantly (p = 0.324). CONCLUSIONS From 2010 to 2014, the proportion of adults undergoing decompression with

  13. Oligodendrocyte- and Neuron-Specific Nogo-A Restrict Dendritic Branching and Spine Density in the Adult Mouse Motor Cortex.

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    Zemmar, Ajmal; Chen, Chia-Chien; Weinmann, Oliver; Kast, Brigitt; Vajda, Flora; Bozeman, James; Isaad, Noel; Zuo, Yi; Schwab, Martin E

    2018-06-01

    Nogo-A has been well described as a myelin-associated inhibitor of neurite outgrowth and functional neuroregeneration after central nervous system (CNS) injury. Recently, a new role of Nogo-A has been identified as a negative regulator of synaptic plasticity in the uninjured adult CNS. Nogo-A is present in neurons and oligodendrocytes. However, it is yet unclear which of these two pools regulate synaptic plasticity. To address this question we used newly generated mouse lines in which Nogo-A is specifically knocked out in (1) oligodendrocytes (oligoNogo-A KO) or (2) neurons (neuroNogo-A KO). We show that both oligodendrocyte- and neuron-specific Nogo-A KO mice have enhanced dendritic branching and spine densities in layer 2/3 cortical pyramidal neurons. These effects are compartmentalized: neuronal Nogo-A affects proximal dendrites whereas oligodendrocytic Nogo-A affects distal regions. Finally, we used two-photon laser scanning microscopy to measure the spine turnover rate of adult mouse motor cortex layer 5 cells and find that both Nogo-A KO mouse lines show enhanced spine remodeling after 4 days. Our results suggest relevant control functions of glial as well as neuronal Nogo-A for synaptic plasticity and open new possibilities for more selective and targeted plasticity enhancing strategies.

  14. A computed tomographic anatomical study of the upper sacrum. Application for a user guide of pelvic fixation with iliosacral screws in adult spinal deformity.

    Science.gov (United States)

    Dubory, Arnaud; Bouloussa, Houssam; Riouallon, Guillaume; Wolff, Stéphane

    2017-12-01

    Widely used in traumatic pelvic ring fractures, the iliosacral (IS) screw technique for spino-pelvic fixation remains anecdotal in adult spinal deformity. The objective of this study was to assess anatomical variability of the adult upper sacrum and to provide a user guide of spino-pelvic fixation with IS screws in adult spinal deformity. Anatomical variability of the upper sacrum according to age, gender, height and weight was sought on 30 consecutive pelvic CT-scans. Thus, a user guide of spino-pelvic fixation with IS screws was modeled and assessed on ten CT-scans as described below. Two invariable landmarks usable during the surgical procedure were defined: point A (corresponding to the connector binding the IS screw to the spinal rod), equidistant from the first posterior sacral hole and the base of the S1 articular facet and 10 mm-embedded into the sacrum; point B (corresponding to the tip of the IS screw) located at the junction of the anterior third and middle third of the sacral endplate in the sagittal plane and at the middle of the endplate in the coronal plane. Point C corresponded to the intersection between the A-B direction and the external facet of the iliac wing. Three-dimensional reconstructions modeling the IS screw optimal direction according to the A-B-C straight line were assessed. Age had no effect on the anatomy of the upper sacrum. The distance between the base of the S1 superior articular facet and the top of the first posterior sacral hole was correlated with weight (r = 0.6; 95% CI [0.6-0.9]); p guide of spinopelvic fixation with IS screws seems to be reliable and reproducible independently of age, gender and morphologic characteristics but needs clinical assessment. Level IV.

  15. Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult.

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    Vinicius S Carreira

    Full Text Available The Developmental Origins of Health and Disease (DOHaD Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR, either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr-/- and in utero TCDD-exposed Ahr+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease.

  16. Assessment of the Cross-Sectional Areas of the Psoas Major and Multifidus Muscles in Patients With Adult Spinal Deformity: A Case-Control Study.

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    Banno, Tomohiro; Yamato, Yu; Hasegawa, Tomohiko; Kobayashi, Sho; Togawa, Daisuke; Oe, Shin; Mihara, Yuki; Kurosu, Kenta; Yamamoto, Naoto; Matsuyama, Yukihiro

    2017-08-01

    This is a case-control study. The present study aimed to compare the cross-sectional areas of the psoas major and multifidus muscles between elderly patients with adult spinal deformity (ASD) and age-matched and body weight-matched controls, and to evaluate the associations between the cross-sectional areas of these muscles and the severity of spinal deformity. The study included 49 female kyphosis patients with mild scoliosis (Cobb angle muscles were calculated using preoperative L4/L5 axial computed tomography images. In group D, the following spinopelvic parameters were assessed: sagittal vertical axis, pelvic tilt, pelvic incidence, lumbar lordosis, and thoracic kyphosis. The relationships between the muscle cross-sectional areas and spinopelvic parameters were evaluated. The cross-sectional area of the multifidus muscle was lower in group D than in group C. However, the cross-sectional area of the psoas major muscle was not different between the 2 groups. In multiple regression analysis, the cross-sectional area of the multifidus muscle was significantly associated with all spinopelvic parameters. The cross-sectional area of the multifidus muscle might be lower in elderly patients with ASD than in controls. In the elderly population, the severity of sagittal spinal deformity might be correlated with the cross-sectional area of the multifidus muscle. Therefore, muscle imbalances between the flexors and extensors of the spine could participate in the pathology of ASD.

  17. First Case of Autonomic Dysreflexia Following Elective Lower Thoracic Spinal Cord Transection in a Spina Bifida Adult.

    Science.gov (United States)

    Garces, Juanita; Mathkour, Mansour; Scullen, Tyler; Kahn, Lora; Biro, Erin; Pham, Alex; Sulaiman, Olawale A R; Smith, Roger; Bui, Cuong J

    2017-12-01

    Spinal cord transection is a radical but effective treatment for highly selective cases of symptomatic spinal retethering in paraplegic spina bifida patients. Autonomic dysreflexia (AD) is a potentially life-threatening syndrome involving a dysregulated sympathetic discharge reflex commonly seen following cervical and high thoracic spinal cord injury, leading to a disconnect between autonomic pathways above and below the lesion that can lead to severe complications including uncontrolled hypertension, bradycardia, stroke, and potentially death. Herein we present a case in which a paraplegic spina bifida patient presenting with symptomatic spinal retethering experienced autonomic dysreflexia following an elective spinal cord transection. A 51-year-old male with a history of complex spina bifida presented with an active cerebrospinal fluid leak. Physical examination revealed a thin covering of abnormal epidermis over the large placode. Magnetic resonance imaging revealed a large myelomeningocele defect with posterior element defects spanning from L2 to the sacrum with evidence of tethering. The patient underwent an intradural transection of the spinal cord with a "blind-pouch" closure of the dura at the level of T12/L1. Postoperatively, the patient developed intermittent episodes of hypertension, bradycardia, headaches, altered mental status, severe perspiration, and red flushing of the upper torso, face, and arms. The diagnosis of AD was made clinically and managed with a positive response to a combination of beta- and alpha-blockade along with patient education on avoidance of common AD triggers. At 5-year follow-up the patient has continued to do well on medication. This case highlights a potential major side effect from elective transection of the spinal cord. If unrecognized and untreated, AD can cause significant distress and morbidity. We hope this first case report serves to supplement existing data and aid in future surgical and medical decision

  18. Thalamocortical Projection Neuron and Interneuron Numbers in the Visual Thalamic Nuclei of the Adult C57BL/6 Mouse.

    Science.gov (United States)

    Evangelio, Marian; García-Amado, María; Clascá, Francisco

    2018-01-01

    A key parameter to constrain predictive, bottom-up circuit models of a given brain domain is the number and position of the neuronal populations involved. These include not only the neurons whose bodies reside within the domain, but also the neurons in distant regions that innervate the domain. The mouse visual cortex receives its main subcortical input from the dorsal lateral geniculate nucleus (dLGN) and the lateral posterior (LP) complex of the thalamus. The latter consists of three different nuclei: lateral posterior lateral (LPL), lateral posterior medial rostral (LPMR), and lateral posterior medial caudal (LPMC), each exhibiting specific patterns of connections with the various visual cortical areas. Here, we have determined the number of thalamocortical projection neurons and interneurons in the LP complex and dLGN of the adult C57BL/6 male mouse. We combined Nissl staining and histochemical and immunolabeling methods for consistently delineating nuclei borders, and applied unbiased stereological cell counting methods. Thalamic interneurons were identified using GABA immunolabeling. The C57BL/6 dLGN contains ∼21,200 neurons, while LP complex contains ∼31,000 total neurons. The dLGN and LP are the only nuclei of the mouse dorsal thalamus containing substantial numbers GABA-immunoreactive interneurons. These interneurons, however, are scarcer than previously estimated; they are 5.6% of dLGN neurons and just 1.9% of the LP neurons. It can be thus inferred that the dLGN contains ∼20,000 and the LP complex ∼30,400 thalamocortical projection neurons (∼12,000 in LPL, 15,200 in LPMR, and 4,200 in LPMC). The present dataset is relevant for constraining models of mouse visual thalamocortical circuits, as well as for quantitative comparisons between genetically modified mouse strains, or across species.

  19. Spinal Cord Injury 101

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    Full Text Available ... Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal Cord Injury Rehabilitation Pediatric Spinal ... Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal Cord Injury Rehabilitation Pediatric Spinal ...

  20. Spinal Cord Injury 101

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    Full Text Available ... Animated Spinal Cord Injury Chart Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal ... Animated Spinal Cord Injury Chart Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal ...

  1. C/EBPalpha and C/EBPbeta are required for Sebocyte differentiation and stratified squamous differentiation in adult mouse skin.

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    John S House

    Full Text Available C/EBPalpha and C/EBPbeta are bZIP transcription factors that are highly expressed in the interfollicular epidermis and sebaceous glands of skin and yet germ line deletion of either family member alone has only mild or no effect on keratinocyte biology and their role in sebocyte biology has never been examined. To address possible functional redundancies and reveal functional roles of C/EBPalpha and C/EBPbeta in postnatal skin, mouse models were developed in which either family member could be acutely ablated alone or together in the epidermis and sebaceous glands of adult mice. Acute removal of either C/EBPalpha or C/EBPbeta alone in adult mouse skin revealed modest to no discernable changes in epidermis or sebaceous glands. In contrast, co-ablation of C/EBPalpha and C/EBPbeta in postnatal epidermis resulted in disruption of stratified squamous differentiation characterized by hyperproliferation of basal and suprabasal keratinocytes and a defective basal to spinous keratinocyte transition involving an expanded basal compartment and a diminished and delayed spinous compartment. Acute co-ablation of C/EBPalpha and C/EBPbeta in sebaceous glands resulted in severe morphological defects, and sebocyte differentiation was blocked as determined by lack of sebum production and reduced expression of stearoyl-CoA desaturase (SCD3 and melanocortin 5 receptor (MC5R, two markers of terminal sebocyte differentiation. Specialized sebocytes of Meibomian glands and preputial glands were also affected. Our results indicate that in adult mouse skin, C/EBPalpha and C/EBPbeta are critically involved in regulating sebocyte differentiation and epidermal homeostasis involving the basal to spinous keratinocyte transition and basal cell cycle withdrawal.

  2. Results of the 2015 Scoliosis Research Society Survey on Single Versus Dual Attending Surgeon Approach for Adult Spinal Deformity Surgery.

    Science.gov (United States)

    Scheer, Justin K; Sethi, Rajiv K; Hey, Lloyd A; LaGrone, Michael O; Keefe, Malla; Aryan, Henry E; Errico, Thomas J; Deviren, Vedat; Hart, Robert A; Lafage, Virginie; Schwab, Frank; Daubs, Michael D; Ames, Christopher P

    2017-06-15

    An electronic survey administered to Scoliosis Research Society (SRS) membership. To characterize surgeon practices and views regarding the use of two attending surgeons for adult spinal deformity (ASD) surgery. The use of two experienced attending surgeons can decrease the operative time, estimated blood loss, and perioperative complication rates. However, the current practice patterns for the use of two attending surgeons remains unknown. An electronic, 27-question survey regarding single/dual attending surgeons was administered to the SRS membership. Determinants included: surgeon/practice demographics, assistant type/level of training, and questions regarding use of two attending surgeons. Overall reporting and comparisons between groups were made: US versus international, academic versus private practice, and experience 15 years. A total of 199 surgeons responded from 27 different countries. Overall and between the groups, the respondents significantly reported believing that two attending spine surgeons improves safety, decreases complications, and improves outcomes (P < 0.01). Approximately, 67.3% reported using a second attending ≤25% of the time (33.2% do not), and 24.1% use one ≥51% of the time (similar between groups); 51.1% that have a second attending feel it's limited by reimbursement and access concerns and 71.9% have difficulty getting the second attending reimbursed. 72.3% use a second attending for ALL of the following reasons (no difference between groups): "it's safer/reduces complications," "it decreases operative time," "it decreases blood loss," "it results in improved outcomes," "it's less work and stress for me." If reimbursement was equal/assured for a second attending, 67.5% would use one "more often" or "always." The respondents feel that having a second attending surgeon improves patient care, however most do not use one often. Reasons include reimbursement/access concerns and the majority would use one if reimbursement was

  3. Overcorrection of lumbar lordosis for adult spinal deformity with sagittal imbalance: comparison of radiographic outcomes between overcorrection and undercorrection.

    Science.gov (United States)

    Lee, Jung-Hee; Kim, Ki-Tack; Lee, Sang-Hun; Kang, Kyung-Chung; Oh, Hyun-Seok; Kim, Young-Jun; Jung, Hyuk

    2016-08-01

    To determine the correlation of the difference between postoperative lumbar lordosis (LL) and ideal LL with the sagittal vertical axis (SVA) at the final follow-up in patients with adult spinal deformity (ASD). Fifty-one patients with degenerative lumbar kyphosis (DLK) (mean age 66.5 years) who underwent surgical correction with a minimum 2-year follow-up were evaluated. Based on the difference between postoperative LL and ideal LL using the Korean version of Legaye's formula, we divided the 51 patients into two groups: overcorrection (degree of postoperative LL > ideal LL) and undercorrection (degree of postoperative LL < ideal LL). Our clinical series of patients comprised 24 in the overcorrection and 27 in the undercorrection group. No significant differences were found in preoperative pelvic incidence (PI 52.6° vs. 57.3°), sacral slope (SS 23.3° vs. 18.3°), LL (-6.9° vs. -2.3°), thoracic kyphosis (TK 4.7° vs. 4.9°) and SVA (140 vs. 139 mm) except pelvic tilt (PT 29.4° vs. 39.0°), between the two groups. All the patients in the overcorrection group and 16 in the undercorrection group achieved postoperative optimal sagittal balance based on SVA ≤ 50 mm. In addition, significant differences in PT (10.5° vs. 26.7°), SS (42.1° vs. 30.6°), LL (-64.3° vs. -37.1°), TK (22.6° vs. 15.8°), and SVA (-1 vs. 41 mm) between the two groups were observed postoperatively. Furthermore, four patients (16.7 %) in the overcorrection group and eight (50 %) in the undercorrection group had sagittal decompensation at the final follow-up. Our results showed that the difference between postoperative LL and ideal LL had a significant correlation with postoperative and final follow-up SVA in our clinical series. Overcorrection of LL is an effective treatment modality to maintain optimal sagittal alignment in patients with DLK; this suggests that it should be considered in preoperative planning for patients with ASD with sagittal imbalance.

  4. Association between baseline cognitive impairment and postoperative delirium in elderly patients undergoing surgery for adult spinal deformity.

    Science.gov (United States)

    Adogwa, Owoicho; Elsamadicy, Aladine A; Vuong, Victoria D; Fialkoff, Jared; Cheng, Joseph; Karikari, Isaac O; Bagley, Carlos A

    2018-01-01

    OBJECTIVE Postoperative delirium is common in elderly patients undergoing spine surgery and is associated with a longer and more costly hospital course, functional decline, postoperative institutionalization, and higher likelihood of death within 6 months of discharge. Preoperative cognitive impairment may be a risk factor for the development of postoperative delirium. The aim of this study was to investigate the relationship between baseline cognitive impairment and postoperative delirium in geriatric patients undergoing surgery for degenerative scoliosis. METHODS Elderly patients 65 years and older undergoing a planned elective spinal surgery for correction of adult degenerative scoliosis were enrolled in this study. Preoperative cognition was assessed using the validated Saint Louis University Mental Status (SLUMS) examination. SLUMS comprises 11 questions, with a maximum score of 30 points. Mild cognitive impairment was defined as a SLUMS score between 21 and 26 points, while severe cognitive impairment was defined as a SLUMS score of ≤ 20 points. Normal cognition was defined as a SLUMS score of ≥ 27 points. Delirium was assessed daily using the Confusion Assessment Method (CAM) and rated as absent or present on the basis of CAM. The incidence of delirium was compared in patients with and without baseline cognitive impairment. RESULTS Twenty-two patients (18%) developed delirium postoperatively. Baseline demographics, including age, sex, comorbidities, and perioperative variables, were similar in patients with and without delirium. The length of in-hospital stay (mean 5.33 days vs 5.48 days) and 30-day hospital readmission rates (12.28% vs 12%) were similar between patients with and without delirium, respectively. Patients with preoperative cognitive impairment (i.e., a lower SLUMS score) had a higher incidence of postoperative delirium. One- and 2-year patient reported outcomes scores were similar in patients with and without delirium. CONCLUSIONS

  5. Development of an evidence-informed leisure time physical activity resource for adults with spinal cord injury: the SCI Get Fit Toolkit.

    Science.gov (United States)

    Arbour-Nicitopoulos, K P; Martin Ginis, K A; Latimer-Cheung, A E; Bourne, C; Campbell, D; Cappe, S; Ginis, S; Hicks, A L; Pomerleau, P; Smith, K

    2013-06-01

    To systematically develop an evidence-informed leisure time physical activity (LTPA) resource for adults with spinal cord injury (SCI). Canada. The Appraisal of Guidelines, Research and Evaluation (AGREE) II protocol was used to develop a toolkit to teach and encourage adults with SCI how to make smart and informed choices about being physically active. A multidisciplinary expert panel appraised the evidence and generated specific recommendations for the content of the toolkit. Pilot testing was conducted to refine the toolkit's presentation. Recommendations emanating from the consultation process were that the toolkit be a brief, evidence-based resource that contains images of adults with tetraplegia and paraplegia, and links to more detailed online information. The content of the toolkit should include the physical activity guidelines (PAGs) for adults with SCI, activities tailored to manual and power chair users, the benefits of LTPA, and strategies to overcome common LTPA barriers for adults with SCI. The inclusion of action plans and safety tips was also recommended. These recommendations have resulted in the development of an evidence-informed LTPA resource to assist adults with SCI in meeting the PAGs. This toolkit will have important implications for consumers, health care professionals and policy makers for encouraging LTPA in the SCI community.

  6. Expression of the low affinity neurotrophin receptor p75 in spinal motoneurons in a transgenic mouse model for amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Copray, JCVM; Jaarsma, D; Kust, BM; Bruggeman, RWG; Mantingh, [No Value; Brouwer, N; Boddeke, HWGM

    2003-01-01

    Amyotrophic lateral sclerosis is a lethal neurodegenerative disorder involving motoneuron loss in the cortex, brainstem and spinal cord, resulting in progressive paralysis. Aberrant neurotrophin signalling via the low affinity neurotrophin receptor p75 has been suggested to be involved in the

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Transplantation of oligodendrocyte precursors and sonic hedgehog results in improved function and white matter sparing in the spinal cords of adult rats after contusion.

    Science.gov (United States)

    Bambakidis, Nicholas C; Miller, Robert H

    2004-01-01

    A substantial cause of neurological disability in spinal cord injury is oligodendrocyte death leading to demyelination and axonal degeneration. Rescuing oligodendrocytes and preserving myelin is expected to result in significant improvement in functional outcome after spinal cord injury. Although previous investigators have used cellular transplantation of xenografted pluripotent embryonic stem cells and observed improved functional outcome, these transplants have required steroid administration and only a minority of these cells develop into oligodendrocytes. The objective of the present study was to determine whether allografts of oligodendrocyte precursors transplanted into an area of incomplete spinal cord contusion would improve behavioral and electrophysiological measures of spinal cord function. Additional treatment incorporated the use of the glycoprotein molecule Sonic hedgehog (Shh), which has been shown to play a critical role in oligodendroglial development and induce proliferation of endogenous neural precursors after spinal cord injury. Laboratory study. Moderate spinal cord contusion injury was produced in 39 adult rats at T9-T10. Ten animals died during the course of the study. Nine rats served as contusion controls (Group 1). Six rats were treated with oligodendrocyte precursor transplantation 5 days after injury (Group 2). The transplanted cells were isolated from newborn rat pups using immunopanning techniques. Another eight rats received an injection of recombinant Shh along with the oligodendrocyte precursors (Group 3), while six more rats were treated with Shh alone (Group 4). Eight additional rats received only T9 laminectomies to serve as noninjured controls (Group 0). Animals were followed for 28 days. After an initial complete hindlimb paralysis, rats of all groups receiving a contusive injury recovered substantial function within 1 week. By 28 days, rats in Groups 2 and 3 scored 4.7 and 5.8 points better on the Basso, Beattie, Bresnahan

  9. A Cystine-Rich Whey Supplement (Immunocal® Delays Disease Onset and Prevents Spinal Cord Glutathione Depletion in the hSOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Erika K. Ross

    2014-12-01

    Full Text Available Depletion of the endogenous antioxidant, glutathione (GSH, underlies progression of the devastating neurodegenerative disease, amyotrophic lateral sclerosis (ALS. Thus, strategies aimed at elevating GSH may yield new therapeutics for ALS. Here, we investigated the effects of a unique non-denatured whey protein supplement, Immunocal®, in the transgenic Gly position 93 to Ala (G93A mutant hSOD1 (hSOD1G93A mouse model of ALS. Immunocal® is rich in the GSH precursor, cystine, and is therefore capable of bolstering GSH content. Transgenic hSOD1G93A mice receiving Immunocal® displayed a significant delay in disease onset compared to untreated hSOD1G93A controls. Additionally, Immunocal® treatment significantly decreased the rate of decline in grip strength and prevented disease-associated reductions in whole blood and spinal cord tissue GSH levels in end-stage hSOD1G93A mice. However, Immunocal® did not extend survival, likely due to its inability to preserve the mitochondrial GSH pool in spinal cord. Combination treatment with Immunocal® and the anti-glutamatergic compound, riluzole, delayed disease onset and extended survival in hSOD1G93A mice. These findings demonstrate that sustaining tissue GSH with Immunocal® only modestly delays disease onset and slows the loss of skeletal muscle strength in hSOD1G93A mice. Moreover, the inability of Immunocal® to rescue mitochondrial GSH in spinal cord provides a possible mechanism for its lack of effect on survival and is a limiting factor in the potential utility of this supplement as a therapeutic for ALS.

  10. Cost-effectiveness of spinal manipulative therapy, supervised exercise, and home exercise for older adults with chronic neck pain.

    Science.gov (United States)

    Leininger, Brent; McDonough, Christine; Evans, Roni; Tosteson, Tor; Tosteson, Anna N A; Bronfort, Gert

    2016-11-01

    Chronic neck pain is a prevalent and disabling condition among older adults. Despite the large burden of neck pain, little is known regarding the cost-effectiveness of commonly used treatments. This study aimed to estimate the cost-effectiveness of home exercise and advice (HEA), spinal manipulative therapy (SMT) plus HEA, and supervised rehabilitative exercise (SRE) plus HEA. Cost-effectiveness analysis conducted alongside a randomized clinical trial (RCT) was performed. A total of 241 older adults (≥65 years) with chronic mechanical neck pain comprised the patient sample. The outcome measures were direct and indirect costs, neck pain, neck disability, SF-6D-derived quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) over a 1-year time horizon. This work was supported by grants from the National Center for Complementary and Integrative Health (#F32AT007507), National Institute of Arthritis and Musculoskeletal and Skin Diseases (#P60AR062799), and Health Resources and Services Administration (#R18HP01425). The RCT is registered at ClinicalTrials.gov (#NCT00269308). A societal perspective was adopted for the primary analysis. A healthcare perspective was adopted as a sensitivity analysis. Cost-effectivenesswas a secondary aim of the RCT which was not powered for differences in costs or QALYs. Differences in costs and clinical outcomes were estimated using generalized estimating equations and linear mixed models, respectively. Cost-effectiveness acceptability curves were calculated to assess the uncertainty surrounding cost-effectiveness estimates. Total costs for SMT+HEA were 5% lower than HEA (mean difference: -$111; 95% confidence interval [CI] -$1,354 to $899) and 47% lower than SRE+HEA (mean difference: -$1,932; 95% CI -$2,796 to -$1,097). SMT+HEA also resulted in a greater reduction of neck pain over the year relative to HEA (0.57; 95% CI 0.23 to 0.92) and SRE+HEA (0.41; 95% CI 0.05 to 0.76). Differences in disability and

  11. Axonal sprouting of a brainstem-spinal pathway after estrogen administration in the adult female rhesus monkey

    NARCIS (Netherlands)

    Vanderhorst, VGJM; Terasawa, E; Ralston, HJ

    2002-01-01

    The nucleus retroambiguus (NRA) is located in the caudal medulla oblongata and contains premotor neurons that project to motoneuronal cell groups in the brainstem and spinal cord. NRA projections to the lumbosacral cord are species specific and might be involved in mating behavior. In the female

  12. Diffusion tensor imaging of the cervical spinal cord in healthy adult population: normative values and measurement reproducibility at 3T MRI.

    Science.gov (United States)

    Brander, Antti; Koskinen, Eerika; Luoto, Teemu M; Hakulinen, Ullamari; Helminen, Mika; Savilahti, Sirpa; Ryymin, Pertti; Dastidar, Prasun; Ohman, Juha

    2014-05-01

    Compared to diffusion tensor imaging (DTI) of the brain, there is a paucity of reports addressing the applicability of DTI in the evaluation of the spinal cord. Most normative data of cervical spinal cord DTI consist of relatively small and arbitrarily collected populations. Comprehensive normative data are necessary for clinical decision-making. To establish normal values for cervical spinal cord DTI metrics with region of interest (ROI)- and fiber tractography (FT)-based measurements and to assess the reproducibility of both measurement methods. Forty healthy adults underwent cervical spinal cord 3T MRI. Sagittal and axial conventional T2 sequences and DTI in the axial plane were performed. Whole cord fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were determined at different cervical levels from C2 to C7 using the ROI method. DTI metrics (FA, axial, and radial diffusivities based on eigenvalues λ1, λ2, and λ3, and ADC) of the lateral and posterior funicles were measured at C3 level. FA and ADC of the whole cord and the lateral and posterior funicles were also measured using quantitative tractography. Intra- and inter-observer variation of the measurement methods were assessed. Whole cord FA values decreased and ADC values increased in the rostral to caudal direction from C2 to C7. Between the individual white matter funicles no statistically significant difference for FA or ADC values was found. Both axial diffusivity and radial diffusivity of both lateral funicles differed significantly from those of the posterior funicle. Neither gender nor age correlated with any of the DTI metrics. Intra-observer variation of the measurements for whole cord FA and ADC showed almost perfect agreement with both ROI and tractography-based measurements. There was more variation in measurements of individual columns. Inter-observer agreement varied from moderate to strong for whole cord FA and ADC. Both ROI- and FT-based measurements are applicable

  13. Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain.

    Science.gov (United States)

    Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

    2013-01-01

    An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain.

  14. PPARg mRNA in the adult mouse hypothalamus: distribution and regulation in response to dietary challenges

    Directory of Open Access Journals (Sweden)

    Yang eLiu

    2015-09-01

    Full Text Available Peroxisome proliferator-activated receptor gamma (PPARg is a ligand-activated transcription factor that was originally identified as a regulator of peroxisome proliferation and adipocyte differentiation. Emerging evidence suggests that functional PPARg signaling also occurs within the hypothalamus. However, the exact distribution and identities of PPARg-expressing hypothalamic cells remains under debate. The present study systematically mapped PPARg mRNA expression in the adult mouse brain using in situ hybridization histochemistry. PPARg mRNA was found to be expressed at high levels outside the hypothalamus including the neocortex, the olfactory bulb, the organ of the vasculosum of the lamina terminalis, and the subfornical organ. Within the hypothalamus, PPARg was present at moderate levels in the suprachiasmatic nucleus and the ependymal of the 3rd ventricle. In all examined feeding-related hypothalamic nuclei, PPARg was expressed at very low levels that were close to the limit of detection. Using qPCR techniques, we demonstrated that PPARg mRNA expression was upregulated in the suprachiasmatic nucleus in response to fasting. Double in situ hybridization further demonstrated that PPARg was primarily expressed in neurons. Collectively, our observations provide a comprehensive map of PPARg distribution and regulation in the intact adult mouse hypothalamus.

  15. A Novel Procedure for Rapid Imaging of Adult Mouse Brains with MicroCT Using Iodine-Based Contrast.

    Directory of Open Access Journals (Sweden)

    Ryan Anderson

    Full Text Available High-resolution Magnetic Resonance Imaging (MRI has been the primary modality for obtaining 3D cross-sectional anatomical information in animals for soft tissue, particularly brain. However, costs associated with MRI can be considerably high for large phenotypic screens for gross differences in the structure of the brain due to pathology and/or experimental manipulations. MicroCT (mCT, especially benchtop mCT, is becoming a common laboratory equipment with throughput rates equal or faster than any form of high-resolution MRI at lower costs. Here we explore adapting previously developed contrast based mCT to image adult mouse brains in-situ. We show that 2% weight per volume (w/v iodine-potassium iodide solution can be successfully used to image adult mouse brains within 48 hours post-mortem when a structural support matrix is used. We demonstrate that hydrogel can be effectively used as a perfusant which limits the tissue shrinkage due to iodine.

  16. Anthocyanins protect against LPS-induced oxidative stress-mediated neuroinflammation and neurodegeneration in the adult mouse cortex.

    Science.gov (United States)

    Khan, Muhammad Sohail; Ali, Tahir; Kim, Min Woo; Jo, Myeung Hoon; Jo, Min Gi; Badshah, Haroon; Kim, Myeong Ok

    2016-11-01

    Several studies provide evidence that reactive oxygen species (ROS) are key mediators of various neurological disorders. Anthocyanins are polyphenolic compounds and are well known for their anti-oxidant and neuroprotective effects. In this study, we investigated the neuroprotective effects of anthocyanins (extracted from black soybean) against lipopolysaccharide (LPS)-induced ROS-mediated neuroinflammation and neurodegeneration in the adult mouse cortex. Intraperitoneal injection of LPS (250 μg/kg) for 7 days triggers elevated ROS and oxidative stress, which induces neuroinflammation and neurodegeneration in the adult mouse cortex. Treatment with 24 mg/kg/day of anthocyanins for 14 days in LPS-injected mice (7 days before and 7 days co-treated with LPS) attenuated elevated ROS and oxidative stress compared to mice that received LPS-injection alone. The immunoblotting results showed that anthocyanins reduced the level of the oxidative stress kinase phospho-c-Jun N-terminal Kinase 1 (p-JNK). The immunoblotting and morphological results showed that anthocyanins treatment significantly reduced LPS-induced-ROS-mediated neuroinflammation through inhibition of various inflammatory mediators, such as IL-1β, TNF-α and the transcription factor NF- k B. Anthocyanins treatment also reduced activated astrocytes and microglia in the cortex of LPS-injected mice, as indicated by reductions in GFAP and Iba-1, respectively. Anthocyanins also prevent overexpression of various apoptotic markers, i.e., Bax, cytosolic cytochrome C, cleaved caspase-3 and PARP-1. Immunohistochemical fluoro-jade B (FJB) and Nissl staining indicated that anthocyanins prevent LPS-induced neurodegeneration in the mouse cortex. Our results suggest that dietary flavonoids, such as anthocyanins, have antioxidant and neuroprotective activities that could be beneficial to various neurological disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Pediatric spinal infections

    Directory of Open Access Journals (Sweden)

    Raj Kumar

    2014-01-01

    Full Text Available The infections of the spinal axis in children are rare when compared with adults. They encompass a large spectrum of diseases ranging from relatively benign diskitis to spinal osteomyleitis and to the rapidly progressive, rare, and potentially devastating spinal epidural, subdural, and intramedullary spinal cord infections. We present a comprehensive review of the literature pertaining to these uncommon entities, in light of our experience from northern India. The most prevalent pediatric spinal infection in Indian scenario is tuberculosis, where an extradural involvement is more common than intradural. The craniovertebral junction is not an uncommon site of involvement in children of our milieu. The majority of pyogenic infections of pediatric spine are associated with congenital neuro-ectodermal defects such as congenital dermal sinus. The clinico-radiological findings of various spinal infections commonly overlap. Hence the endemicity of certain pathogens should be given due consideration, while considering the differential diagnosis. However, early suspicion, rapid diagnosis, and prompt treatment are the key factors in avoiding neurological morbidity and deformity in a growing child.

  18. Maternal western diet primes non-alcoholic fatty liver disease in adult mouse offspring

    NARCIS (Netherlands)

    Pruis, M. G. M.; Lendvai, A.; Bloks, V. W.; Zwier, M. V.; Baller, J. F. W.; de Bruin, A.; Groen, A. K.; Plosch, T.

    AimMetabolic programming via components of the maternal diet during gestation may play a role in the development of different aspects of the metabolic syndrome. Using a mouse model, we aimed to characterize the role of maternal western-type diet in the development of non-alcoholic fatty liver

  19. The Satellite Cell in Male and Female, Developing and Adult Mouse Muscle: Distinct Stem Cells for Growth and Regeneration

    Science.gov (United States)

    Neal, Alice; Boldrin, Luisa; Morgan, Jennifer Elizabeth

    2012-01-01

    Satellite cells are myogenic cells found between the basal lamina and the sarcolemma of the muscle fibre. Satellite cells are the source of new myofibres; as such, satellite cell transplantation holds promise as a treatment for muscular dystrophies. We have investigated age and sex differences between mouse satellite cells in vitro and assessed the importance of these factors as mediators of donor cell engraftment in an in vivo model of satellite cell transplantation. We found that satellite cell numbers are increased in growing compared to adult and in male compared to female adult mice. We saw no difference in the expression of the myogenic regulatory factors between male and female mice, but distinct profiles were observed according to developmental stage. We show that, in contrast to adult mice, the majority of satellite cells from two week old mice are proliferating to facilitate myofibre growth; however a small proportion of these cells are quiescent and not contributing to this growth programme. Despite observed changes in satellite cell populations, there is no difference in engraftment efficiency either between satellite cells derived from adult or pre-weaned donor mice, male or female donor cells, or between male and female host muscle environments. We suggest there exist two distinct satellite cell populations: one for muscle growth and maintenance and one for muscle regeneration. PMID:22662253

  20. Neuroprotective effect of non-viral gene therapy treatment based on tetanus toxin C-fragment in a severe mouse model of Spinal Muscular Atrophy.

    Directory of Open Access Journals (Sweden)

    Sara Olivan Garcia

    2016-08-01

    Full Text Available Spinal muscular atrophy (SMA is a hereditary childhood disease that causes paralysis and progressive degeneration of skeletal muscles and spinal motor neurons. SMA is associated with reduced levels of full-length Survival of Motor Neuron (SMN protein, due to mutations in the Survival of Motor Neuron 1 gene. Nowadays there are no effective therapies available to treat patients with SMA, so our aim was to test whether the non-toxic carboxy-terminal fragment of tetanus toxin heavy chain (TTC, which exhibits neurotrophic properties, might have a therapeutic role or benefit in SMA. In this manuscript, we have demonstrated that TTC enhance the SMN expression in motor neurons in vitro and evaluated the effect of intramuscular injection of TTC-encoding plasmid in the spinal cord and the skeletal muscle of SMNdelta7 mice. For this purpose, we studied the weight and the survival time, as well as, the survival and cell death pathways and muscular atrophy. Our results showed that TTC treatment reduced the expression of autophagy markers (Becn1, Atg5, Lc3 and p62 and pro-apoptotic genes such as Bax and Casp3 in spinal cord. In skeletal muscle, TTC was able to downregulate the expression of the main marker of autophagy, Lc3, to wild type levels and the expression of the apoptosis effector protein, Casp3. Regarding the genes related to muscular atrophy (Ankrd1, Calm1, Col19a1, Fbox32, Mt2, Myod1, NogoA, Pax7, Rrad, and Sln, TTC suggest a compensatory effect for muscle damage response, diminished oxidative stress and modulated calcium homeostasis. These preliminary findings suggest the need for further experiments to depth study the effect of TTC in SMA disease.

  1. A combined electrophysiological and morphological study of neuropeptide Y?expressing inhibitory interneurons in the spinal dorsal horn of the mouse

    OpenAIRE

    Iwagaki, Noboru; Ganley, Robert P.; Dickie, Allen C.; Polg?r, Erika; Hughes, David I.; Del Rio, Patricia; Revina, Yulia; Watanabe, Masahiko; Todd, Andrew J.; Riddell, John S.

    2015-01-01

    Abstract The spinal dorsal horn contains numerous inhibitory interneurons that control transmission of somatosensory information. Although these cells have important roles in modulating pain, we still have limited information about how they are incorporated into neuronal circuits, and this is partly due to difficulty in assigning them to functional populations. Around 15% of inhibitory interneurons in laminae I-III express neuropeptide Y (NPY), but little is known about this population. We th...

  2. [The influence of metabolic disturbances present in diabetes mellitus type I on vestibulo-spinal reflexes in children and young adults].

    Science.gov (United States)

    Gawron, Wojciech; Pośpiech, Lucyna; Orendorz-Fraczkowska, Krystyna; Noczyńska, Anna

    2002-01-01

    Diabetic neuropathy encompasses various disturbances concerning somatic and autonomic nervous system and has significant impact on prognosis and course of diabetes mellitus. The aim of the work is an evaluation of vestibulo-spinal reflexes in children and young adults suffering from diabetes mellitus type 1. Material--95 children and young adults aged from 6 to 28 years with diabetes mellitus type 1 diagnosed. The control group consisted of 44 otoneurologically healthy subjects aged from 6 to 28 years. After detailed medical history collection and physical ENT examination stato-posturography was performed in each case. Posturographer PE 62 Model 04 was applied in the studies. Static posturography as well as dynamic one (one leg standing test) was performed in each case. 6 patients belonging to diabetic group complained about vertigo or dizziness. There were worse stabilograms parameters in diabetic group in comparison to control one, statistically significant in younger children. There were better stabilogram parameters in diabetic patients with longer history of the disease. The parameters analysed were significantly worse in the subgroup with not compensated diabetes. The parameters were slightly better in relation to the presence of hypoglycaemic incidents. No apparent differences in stabilograms parameters were present in relation to the presence of diabetic complications. Diabetes mellitus type 1 with slight or without complications does not have significant influence on vestibulo-spinal reflexes and posture stability of the patients. Balance organ disturbances in diabetes mellitus type 1 in children and young adults despite their presence have subclinical course. Perhaps one should consider monitoring of those disturbances in the course of the disease.

  3. Spinal Cord Injury 101

    Medline Plus

    Full Text Available menu Understanding Spinal Cord Injury What is a Spinal Cord Injury Levels of Injury and What They Mean Animated Spinal Cord Injury Chart Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal ...

  4. Potential use of "1"8F-FDG-PET/CT to visualize hypermetabolism associated with muscle pain in patients with adult spinal deformity: a case report

    International Nuclear Information System (INIS)

    Taniguchi, Yuki; Takahashi, Miwako; Momose, Toshimitsu; Matsudaira, Ko; Oka, Hiroyuki

    2016-01-01

    Patients with adult spinal deformity (ASD) are surgically treated for pain relief; however, visualization of the exact origin of the pain with imaging modalities is still challenging. We report the first case of a 60-year-old female patient who presented with painful degenerative kyphoscoliosis and was evaluated with flourine-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ("1"8F-FDG-PET/CT) preoperatively. Because her low back pain was resistant to conservative treatment, she was treated with posterior spinal correction and fusion surgery from Th2 to the ilium. One year after the surgery, her low back pain had disappeared completely. In accordance with her clinical course, "1"8F-FDG-PET imaging revealed the uptake of "1"8F-FDG in the paravertebral muscles preoperatively and showed the complete absence of uptake at 1 year after surgery. The uptake site coincided with the convex part of each curve of the lumbar spine and was thought to be the result of the increased activity of paravertebral muscles due to their chronic stretched state in the kyphotic posture. This case report suggests the possibility of using "1"8F-FDG-PET/CT to visualize increased activity in paravertebral muscles and the ensuing pain in ASD patients. (orig.)

  5. Potential use of {sup 18}F-FDG-PET/CT to visualize hypermetabolism associated with muscle pain in patients with adult spinal deformity: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Taniguchi, Yuki [The University of Tokyo Hospital, Department of Orthopedic Surgery, Bunkyo-ku, Tokyo (Japan); Takahashi, Miwako; Momose, Toshimitsu [The University of Tokyo, Division of Nuclear Medicine, Department of Radiology, Graduate School of Medicine, Tokyo (Japan); Matsudaira, Ko; Oka, Hiroyuki [The University of Tokyo, Department of Medical Research and Management for Musculoskeletal Pain, 22nd Century Medical and Research Center, Faculty of Medicine, Tokyo (Japan)

    2016-11-15

    Patients with adult spinal deformity (ASD) are surgically treated for pain relief; however, visualization of the exact origin of the pain with imaging modalities is still challenging. We report the first case of a 60-year-old female patient who presented with painful degenerative kyphoscoliosis and was evaluated with flourine-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ({sup 18}F-FDG-PET/CT) preoperatively. Because her low back pain was resistant to conservative treatment, she was treated with posterior spinal correction and fusion surgery from Th2 to the ilium. One year after the surgery, her low back pain had disappeared completely. In accordance with her clinical course, {sup 18}F-FDG-PET imaging revealed the uptake of {sup 18}F-FDG in the paravertebral muscles preoperatively and showed the complete absence of uptake at 1 year after surgery. The uptake site coincided with the convex part of each curve of the lumbar spine and was thought to be the result of the increased activity of paravertebral muscles due to their chronic stretched state in the kyphotic posture. This case report suggests the possibility of using {sup 18}F-FDG-PET/CT to visualize increased activity in paravertebral muscles and the ensuing pain in ASD patients. (orig.)

  6. Transient activation of Wnt/β-catenin signaling reporter in fibrotic scar formation after compression spinal cord injury in adult mice.

    Science.gov (United States)

    Yamagami, Takashi; Pleasure, David E; Lam, Kit S; Zhou, Chengji J

    2018-02-19

    After traumatic spinal cord injury (SCI), a scar may form with a fibrotic core (fibrotic scar) and surrounding reactive astrocytes (glial scar) at the lesion site. The scar tissue is considered a major obstacle preventing regeneration both as a physical barrier and as a source for secretion of inhibitors of axonal regeneration. Understanding the mechanism of scar formation and how to control it may lead to effective SCI therapies. Using a compression-SCI model on adult transgenic mice, we demonstrate that the canonical Wnt/β-catenin signaling reporter TOPgal (TCF/Lef1-lacZ) positive cells appeared at the lesion site by 5 days, peaked on 7 days, and diminished by 14 days post injury. Using various representative cell lineage markers, we demonstrate that, these transiently TOPgal positive cells are a group of Fibronectin(+);GFAP(-) fibroblast-like cells in the core scar region. Some of them are proliferative. These results indicate that Wnt/β-catenin signaling may play a key role in fibrotic scar formation after traumatic spinal cord injury. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Non-pineal supratentorial primitive neuro-ectodermal tumors (sPNET) in teenagers and young adults: Time to reconsider cisplatin based chemotherapy after cranio-spinal irradiation?

    Science.gov (United States)

    Biswas, Swethajit; Burke, Amos; Cherian, Sheen; Williams, Denise; Nicholson, James; Horan, Gail; Jefferies, Sarah; Williams, Michael; Earl, Helena M; Burnet, Neil G; Hatcher, Helen

    2009-07-01

    Supratentorial PNET (sPNET) are rare CNS tumors of embryonal origin arising in children and adults. The treatment of sPNET for all age groups at our cancer center has been based on the management of medulloblastoma (MB), involving neurosurgical debulking followed by cranio-spinal irradiation (CSI) and systemic chemotherapy. Medical records were reviewed to gather demographic and clinical data about all embryonal CNS tumors in children and adults from 2001 to 2007. Tumor pathology, clinical management and survival data were also assessed, particularly as regards those patients who received the Packer chemotherapy regimen for either sPNET or MB. Eleven patients (five children and six adults) were identified with non-pineal sPNET, three children with pineal sPNET, and 19 patients (18 children and 1 adult) with MB. There was no difference in overall survival (OS) rates between pediatric and adult sPNET. When all sPNET were compared to all MB, 5-year OS was 14% versus 73%, respectively, but was only 9% for non-pineal sPNET. When only considering those patients treated with the Packer chemotherapy regimen, the 5-year OS was 12% for sPNET versus 79% for MB. This retrospective study demonstrates that non-pineal sPNET are clinically distinct from MB and are resistant to the Packer chemotherapy regimen. We suggest that it is time to reconsider the use of this regimen in teenage and young adult non-pineal sPNET and to investigate the utility of alternative approaches. (c) 2009 Wiley-Liss, Inc.

  8. Gene expression of drug metabolizing enzymes in adult and aged mouse liver: A modulation by immobilization stress

    International Nuclear Information System (INIS)

    Mikhailova, O.N.; Gulyaeva, L.F.; Filipenko, M.L.

    2005-01-01

    The role of stress in the regulation of enzymatic systems involved in the biotransformation of xenobiotics, as well as endogenous substrates in the liver was investigated using single immobilization stress as a model. Adult (3 months of age) and aged (26 months) C3H/a male mice were used. Cytochrome P450 1A1 and 1A2 (CYP1A1 and CYP1A2), glutathione S-transferase M1 (GSTM1), aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT) and catechol-O-methyltransferase (COMT) mRNA levels in the mouse liver were measured by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. Excluding CYP1A1, experiments revealed significant differences in the expression of these genes between adult- and aged-control animals. The influence of stress on the expression of genes studied was shown to be higher in adult mice than in aged ones. Our results clearly demonstrate the lack of response or even the attenuation of gene expression in aged animals that may play an important role in age-related pathologies and diseases

  9. Human neural stem cells differentiate and promote locomotor recovery in an early chronic spinal cord injury NOD-scid mouse model.

    Directory of Open Access Journals (Sweden)

    Desirée L Salazar

    2010-08-01

    Full Text Available Traumatic spinal cord injury (SCI results in partial or complete paralysis and is characterized by a loss of neurons and oligodendrocytes, axonal injury, and demyelination/dysmyelination of spared axons. Approximately 1,250,000 individuals have chronic SCI in the U.S.; therefore treatment in the chronic stages is highly clinically relevant. Human neural stem cells (hCNS-SCns were prospectively isolated based on fluorescence-activated cell sorting for a CD133(+ and CD24(-/lo population from fetal brain, grown as neurospheres, and lineage restricted to generate neurons, oligodendrocytes and astrocytes. hCNS-SCns have recently been transplanted sub-acutely following spinal cord injury and found to promote improved locomotor recovery. We tested the ability of hCNS-SCns transplanted 30 days post SCI to survive, differentiate, migrate, and promote improved locomotor recovery.hCNS-SCns were transplanted into immunodeficient NOD-scid mice 30 days post spinal cord contusion injury. hCNS-SCns transplanted mice demonstrated significantly improved locomotor recovery compared to vehicle controls using open field locomotor testing and CatWalk gait analysis. Transplanted hCNS-SCns exhibited long-term engraftment, migration, limited proliferation, and differentiation predominantly to oligodendrocytes and neurons. Astrocytic differentiation was rare and mice did not exhibit mechanical allodynia. Furthermore, differentiated hCNS-SCns integrated with the host as demonstrated by co-localization of human cytoplasm with discrete staining for the paranodal marker contactin-associated protein.The results suggest that hCNS-SCns are capable of surviving, differentiating, and promoting improved locomotor recovery when transplanted into an early chronic injury microenvironment. These data suggest that hCNS-SCns transplantation has efficacy in an early chronic SCI setting and thus expands the "window of opportunity" for intervention.

  10. The Phospholipase D2 Knock Out Mouse Has Ectopic Purkinje Cells and Suffers from Early Adult-Onset Anosmia.

    Directory of Open Access Journals (Sweden)

    Matthieu M Vermeren

    Full Text Available Phospholipase D2 (PLD2 is an enzyme that produces phosphatidic acid (PA, a lipid messenger molecule involved in a number of cellular events including, through its membrane curvature properties, endocytosis. The PLD2 knock out (PLD2KO mouse has been previously reported to be protected from insult in a model of Alzheimer's disease. We have further analysed a PLD2KO mouse using mass spectrophotometry of its lipids and found significant differences in PA species throughout its brain. We have examined the expression pattern of PLD2 which allowed us to define which region of the brain to analyse for defect, notably PLD2 was not detected in glial-rich regions. The expression pattern lead us to specifically examine the mitral cells of olfactory bulbs, the Cornus Amonis (CA regions of the hippocampus and the Purkinje cells of the cerebellum. We find that the change to longer PA species correlates with subtle architectural defect in the cerebellum, exemplified by ectopic Purkinje cells and an adult-onset deficit of olfaction. These observations draw parallels to defects in the reelin heterozygote as well as the effect of high fat diet on olfaction.

  11. Taurine in drinking water recovers learning and memory in the adult APP/PS1 mouse model of Alzheimer's disease

    Science.gov (United States)

    Kim, Hye Yun; Kim, Hyunjin V.; Yoon, Jin H.; Kang, Bo Ram; Cho, Soo Min; Lee, Sejin; Kim, Ji Yoon; Kim, Joo Won; Cho, Yakdol; Woo, Jiwan; Kim, YoungSoo

    2014-01-01

    Alzheimer's disease (AD) is a lethal progressive neurological disorder affecting the memory. Recently, US Food and Drug Administration mitigated the standard for drug approval, allowing symptomatic drugs that only improve cognitive deficits to be allowed to accelerate on to clinical trials. Our study focuses on taurine, an endogenous amino acid found in high concentrations in humans. It has demonstrated neuroprotective properties against many forms of dementia. In this study, we assessed cognitively enhancing property of taurine in transgenic mouse model of AD. We orally administered taurine via drinking water to adult APP/PS1 transgenic mouse model for 6 weeks. Taurine treatment rescued cognitive deficits in APP/PS1 mice up to the age-matching wild-type mice in Y-maze and passive avoidance tests without modifying the behaviours of cognitively normal mice. In the cortex of APP/PS1 mice, taurine slightly decreased insoluble fraction of Aβ. While the exact mechanism of taurine in AD has not yet been ascertained, our results suggest that taurine can aid cognitive impairment and may inhibit Aβ-related damages. PMID:25502280

  12. Spinal stenosis

    Science.gov (United States)

    ... in the spine that was present from birth Narrow spinal canal that the person was born with Herniated or slipped disk, which ... when you sit down or lean forward. Most people with spinal stenosis cannot walk for a long ... During a physical exam, your health care provider will try to ...

  13. Spinal sagittal balance substantially influences locomotive syndrome and physical performance in community-living middle-aged and elderly women.

    Science.gov (United States)

    Muramoto, Akio; Imagama, Shiro; Ito, Zenya; Hirano, Kenichi; Ishiguro, Naoki; Hasegawa, Yukiharu

    2016-03-01

    Spinal sagittal imbalance has been well known risk factor of decreased quality of life in the field of adult spinal deformity. However, the impact of spinal sagittal balance on locomotive syndrome and physical performance in community-living elderly has not yet been clarified. The present study investigated the influence of spinal sagittal alignment on locomotive syndrome (LS) and physical performance in community-living middle-aged and elderly women. A total of 125 women between the age of 40-88 years (mean 66.2 ± 9.7 years) who completed the questionnaires, spinal mouse test, physical examination and physical performance tests in Yakumo study were enrolled in this study. Participants answered the 25-Question Geriatric Locomotive Function Scale (GLFS-25), the visual analog scale (VAS) for low back pain (LBP), knee pain. LS was defined as having a score of >16 points on the GLFS-25. Using spinal mouse, spinal inclination angle (SIA), thoracic kyphosis angle (TKA), lumbar lordosis angle (LLA), sacral slope angle (SSA), thoracic spinal range of motion (TSROM), lumbar spinal range of motion (LSROM) were measured. Timed-up-and-go test (TUG), one-leg standing time with eyes open (OLS), and maximum stride, back muscle strength were also measured. The relationship between spinal sagittal parameters and GLFS-25, VAS and physical performance tests were analyzed. 26 people were diagnosed as LS and 99 were diagnosed as non-LS. LBP and knee pain were greater, physical performance tests were poorer, SIA were greater, LLA were smaller in LS group compared to non-LS group even after adjustment by age. SIA significantly correlated with GLFS-25, TUG, OLS and maximum stride even after adjustment by age. The cutoff value of SIA for locomotive syndrome was 6°. People with a SIA of 6° or greater were grouped as "Inclined" and people with a SIA of less than 6° were grouped as "Non-inclined". 21 people were "Inclined" and 104 were "Non-inclined". Odds ratio to fall in LS of

  14. The morphological changes of adult mouse testes after 60Co Gamma-radiation

    International Nuclear Information System (INIS)

    Koruji, M.; Movahedin, M.; Gourabi, H.; Jabbary Arfaee, A.

    2008-01-01

    Cytotoxic therapy can lead to prolonged azoospermia or even sterility. In the present study, we investigated the morphological changes of mouse testes after γ-Radiation. Methods: After anesthetizing of NMRI mice, testes and their surrounding tissues were irradiated using a cobalt therapy machine. Four experimental groups were irradiated with fractionated doses of: 1.5+8, 1.5+12 and 1.5+16 Gy (with an interval of 24 h) and single dose of 14 Gy. Non-irradiated mice were considered as control group. Testes were removed 4, 6 and 8 weeks following irradiation, weighed and processed for light microscopic study. Diameters of seminiferous tubules and their lumens, epithelium thickness, percentage of different types of tubules and number of spermatogenic cell were measured. Moreover, sperm count motility and viability rates were evaluated in epididymis. Results: Number of normal tubules, epithelium thickness, tubules diameter and lumen diameter were significantly reduced with high dose irradiation in comparison with control testes. The recovery was observed after 8 weeks. Epididymal sperm count, motility and viability rates were significantly decreased in the irradiated mice comparing non-irradiated ones. These parameters were increased after 8 weeks. Conclusion: According to the results, irradiation can cause temporary azoospermia in mouse and this effect is reversible after 8 weeks

  15. Quiescent Oct4+ Neural Stem Cells (NSCs) Repopulate Ablated Glial Fibrillary Acidic Protein+ NSCs in the Adult Mouse Brain.

    Science.gov (United States)

    Reeve, Rachel L; Yammine, Samantha Z; Morshead, Cindi M; van der Kooy, Derek

    2017-09-01

    Adult primitive neural stem cells (pNSCs) are a rare population of glial fibrillary acidic protein (GFAP) - Oct4 + cells in the mouse forebrain subependymal zone bordering the lateral ventricles that give rise to clonal neurospheres in leukemia inhibitory factor in vitro. pNSC neurospheres can be passaged to self-renew or give rise to GFAP + NSCs that form neurospheres in epidermal growth factor and fibroblast growth factor 2, which we collectively refer to as definitive NSCs (dNSCs). Label retention experiments using doxycycline-inducible histone-2B (H2B)-green fluorescent protein (GFP) mice and several chase periods of up to 1 year quantified the adult pNSC cell cycle time as 3-5 months. We hypothesized that while pNSCs are not very proliferative at baseline, they may exist as a reserve pool of NSCs in case of injury. To test this function of pNSCs, we obtained conditional Oct4 knockout mice, Oct4 fl/fl ;Sox1 Cre (Oct4 CKO ), which do not yield adult pNSC-derived neurospheres. When we ablated the progeny of pNSCs, namely all GFAP + dNSCs, in these Oct4 CKO mice, we found that dNSCs did not recover as they do in wild-type mice, suggesting that pNSCs are necessary for dNSC repopulation. Returning to the H2B-GFP mice, we observed that the cytosine β-d-arabinofuranoside ablation of proliferating cells including dNSCs-induced quiescent pNSCs to proliferate and significantly dilute their H2B-GFP label. In conclusion, we demonstrate that pNSCs are the most quiescent stem cells in the adult brain reported to date and that their lineage position upstream of GFAP + dNSCs allows them to repopulate a depleted neural lineage. Stem Cells 2017;35:2071-2082. © 2017 AlphaMed Press.

  16. Spinal kinematics during smartphone texting - A comparison between young adults with and without chronic neck-shoulder pain.

    Science.gov (United States)

    Xie, Yan Fei; Szeto, Grace; Madeleine, Pascal; Tsang, Sharon

    2018-04-01

    To advance our understanding about the association between smartphone use and chronic neck-shoulder pain, the objective of this study was to compare spinal kinematics between different text-entry methods in smartphone users with and without chronic neck-shoulder pain. Symptomatic (n = 19) and healthy participants (n = 18) were recruited and they performed three tasks: texting on a smartphone with one hand, with two hands, and typing on a desktop computer. Three-dimensional kinematics were examined in the cervical, thoracic and lumbar regions for each task. This study suggests that altered kinematics may be associated with pain since significantly increased angles of cervical right side flexion during smartphone texting and greater postural changes in cervical rotation were found during all text-entry tasks in the symptomatic group. Two-handed texting was associated with increased cervical flexion while one-handed texting was correlated with an asymmetric neck posture, indicating both text-entry methods are not favorable in terms of spinal postures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Expression of tryptophan 2,3-dioxygenase in mature granule cells of the adult mouse dentate gyrus

    Directory of Open Access Journals (Sweden)

    Ohira, Koji

    2010-09-01

    Full Text Available Abstract New granule cells are continuously generated in the dentate gyrus of the adult hippocampus. During granule cell maturation, the mechanisms that differentiate new cells not only describe the degree of cell differentiation, but also crucially regulate the progression of cell differentiation. Here, we describe a gene, tryptophan 2,3-dioxygenase (TDO, whose expression distinguishes stem cells from more differentiated cells among the granule cells of the adult mouse dentate gyrus. The use of markers for proliferation, neural progenitors, and immature and mature granule cells indicated that TDO was expressed in mature cells and in some immature cells. In mice heterozygous for the alpha-isoform of calcium/calmodulin-dependent protein kinase II, in which dentate gyrus granule cells fail to mature normally, TDO immunoreactivity was substantially downregulated in the dentate gyrus granule cells. Moreover, a 5-bromo-2'-deoxyuridine labeling experiment revealed that new neurons began to express TDO between 2 and 4 wk after the neurons were generated, when the axons and dendrites of the granule cells developed and synaptogenesis occurred. These findings indicate that TDO might be required at a late-stage of granule cell development, such as during axonal and dendritic growth, synaptogenesis and its maturation.

  18. Expression of the Argonaute protein PiwiL2 and piRNAs in adult mouse mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Qiuling; Ma, Qi; Shehadeh, Lina A.; Wilson, Amber; Xia, Linghui; Yu, Hong [Department of Molecular and Cellular Pharmacology, Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Webster, Keith A., E-mail: kwebster@med.miami.edu [Department of Molecular and Cellular Pharmacology, Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, FL 33136 (United States)

    2010-06-11

    Piwi (P-element-induced wimpy testis) first discovered in Drosophila is a member of the Argonaute family of micro-RNA binding proteins with essential roles in germ-cell development. The murine homologue of PiwiL2, also known as Mili is selectively expressed in the testes, and mice bearing targeted mutations of the PiwiL2 gene are male-sterile. PiwiL2 proteins are thought to protect the germ line genome by suppressing retrotransposons, stabilizing heterochromatin structure, and regulating target genes during meiosis and mitosis. Here, we report that PiwiL2 and associated piRNAs (piRs) may play similar roles in adult mouse mesenchymal stem cells. We found that PiwiL2 is expressed in the cytoplasm of metaphase mesenchymal stem cells from the bone marrow of adult and aged mice. Knockdown of PiwiL2 with a specific siRNA enhanced cell proliferation, significantly increased the number of cells in G1/S and G2/M cell cycle phases and was associated with increased expression of cell cycle genes CCND1, CDK8, microtubule regulation genes, and decreased expression of tumor suppressors Cables 1, LATS, and Cxxc4. The results suggest broader roles for Piwi in genome surveillance beyond the germ line and a possible role in regulating the cell cycle of mesenchymal stem cells.

  19. Expression of the Argonaute protein PiwiL2 and piRNAs in adult mouse mesenchymal stem cells

    International Nuclear Information System (INIS)

    Wu, Qiuling; Ma, Qi; Shehadeh, Lina A.; Wilson, Amber; Xia, Linghui; Yu, Hong; Webster, Keith A.

    2010-01-01

    Piwi (P-element-induced wimpy testis) first discovered in Drosophila is a member of the Argonaute family of micro-RNA binding proteins with essential roles in germ-cell development. The murine homologue of PiwiL2, also known as Mili is selectively expressed in the testes, and mice bearing targeted mutations of the PiwiL2 gene are male-sterile. PiwiL2 proteins are thought to protect the germ line genome by suppressing retrotransposons, stabilizing heterochromatin structure, and regulating target genes during meiosis and mitosis. Here, we report that PiwiL2 and associated piRNAs (piRs) may play similar roles in adult mouse mesenchymal stem cells. We found that PiwiL2 is expressed in the cytoplasm of metaphase mesenchymal stem cells from the bone marrow of adult and aged mice. Knockdown of PiwiL2 with a specific siRNA enhanced cell proliferation, significantly increased the number of cells in G1/S and G2/M cell cycle phases and was associated with increased expression of cell cycle genes CCND1, CDK8, microtubule regulation genes, and decreased expression of tumor suppressors Cables 1, LATS, and Cxxc4. The results suggest broader roles for Piwi in genome surveillance beyond the germ line and a possible role in regulating the cell cycle of mesenchymal stem cells.

  20. Genistein exposure inhibits growth and alters steroidogenesis in adult mouse antral follicles

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Shreya, E-mail: Shreya.patel214@gmail.com [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Peretz, Jackye, E-mail: Jackye.peretz@gmail.com [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Pan, Yuan-Xiang, E-mail: yxpan@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois, 905 S. Goodwin, Urbana, IL 61801 (United States); Helferich, William G., E-mail: helferic@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois, 905 S. Goodwin, Urbana, IL 61801 (United States); Flaws, Jodi A., E-mail: jflaws@illinois.edu [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States)

    2016-02-15

    Genistein is a naturally occurring isoflavone phytoestrogen commonly found in plant products such as soybeans, lentils, and chickpeas. Genistein, like other phytoestrogens, has the potential to mimic, enhance, or impair the estradiol biosynthesis pathway, thereby potentially altering ovarian follicle growth. Previous studies have inconsistently indicated that genistein exposure may alter granulosa cell proliferation and hormone production, but no studies have examined the effects of genistein on intact antral follicles. Thus, this study was designed to test the hypothesis that genistein exposure inhibits follicle growth and steroidogenesis in intact antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice were cultured with vehicle (dimethyl sulfoxide; DMSO) or genistein (6.0 and 36 μM) for 18–96 h. Every 24 h, follicle diameters were measured to assess growth. At the end of each culture period, the media were pooled to measure hormone levels, and the cultured follicles were collected to measure expression of cell cycle regulators and steroidogenic enzymes. The results indicate that genistein (36 μM) inhibits growth of mouse antral follicles. Additionally, genistein (6.0 and 36 μM) increases progesterone, testosterone, and dehydroepiandrosterone (DHEA) levels, but decreases estrone and estradiol levels. The results also indicate that genistein alters the expression of steroidogenic enzymes at 24, 72 and 96 h, and the expression of cell cycle regulators at 18 h. These data indicate that genistein exposure inhibits antral follicle growth by inhibiting the cell cycle, alters sex steroid hormone levels, and dysregulates steroidogenic enzymes in cultured mouse antral follicles. - Highlights: • Genistein exposure inhibits antral follicle growth. • Genistein exposure alters expression of cell cycle regulators. • Genistein exposure alters sex steroid hormones. • Genistein exposure alters expression of steroidogenic enzymes.

  1. Genistein exposure inhibits growth and alters steroidogenesis in adult mouse antral follicles

    International Nuclear Information System (INIS)

    Patel, Shreya; Peretz, Jackye; Pan, Yuan-Xiang; Helferich, William G.; Flaws, Jodi A.

    2016-01-01

    Genistein is a naturally occurring isoflavone phytoestrogen commonly found in plant products such as soybeans, lentils, and chickpeas. Genistein, like other phytoestrogens, has the potential to mimic, enhance, or impair the estradiol biosynthesis pathway, thereby potentially altering ovarian follicle growth. Previous studies have inconsistently indicated that genistein exposure may alter granulosa cell proliferation and hormone production, but no studies have examined the effects of genistein on intact antral follicles. Thus, this study was designed to test the hypothesis that genistein exposure inhibits follicle growth and steroidogenesis in intact antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice were cultured with vehicle (dimethyl sulfoxide; DMSO) or genistein (6.0 and 36 μM) for 18–96 h. Every 24 h, follicle diameters were measured to assess growth. At the end of each culture period, the media were pooled to measure hormone levels, and the cultured follicles were collected to measure expression of cell cycle regulators and steroidogenic enzymes. The results indicate that genistein (36 μM) inhibits growth of mouse antral follicles. Additionally, genistein (6.0 and 36 μM) increases progesterone, testosterone, and dehydroepiandrosterone (DHEA) levels, but decreases estrone and estradiol levels. The results also indicate that genistein alters the expression of steroidogenic enzymes at 24, 72 and 96 h, and the expression of cell cycle regulators at 18 h. These data indicate that genistein exposure inhibits antral follicle growth by inhibiting the cell cycle, alters sex steroid hormone levels, and dysregulates steroidogenic enzymes in cultured mouse antral follicles. - Highlights: • Genistein exposure inhibits antral follicle growth. • Genistein exposure alters expression of cell cycle regulators. • Genistein exposure alters sex steroid hormones. • Genistein exposure alters expression of steroidogenic enzymes.

  2. Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons.

    Science.gov (United States)

    Lee, Young Il; Mikesh, Michelle; Smith, Ian; Rimer, Mendell; Thompson, Wesley

    2011-08-15

    A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precede the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any significant impairment in neuromuscular transmission, even when animals were maintained up to 5days longer via a supplementary diet. However, the muscles were clearly weaker, generating less than half their normal tension. Weakness in 3 muscles examined in the study appears due to a severe but uniform reduction in muscle fiber size. The size reduction results from a failure of muscle fibers to grow during early postnatal development and, in soleus, to a reduction in number of fibers generated. Neuromuscular development is severely delayed in these mutant animals: expression of myosin heavy chain isoforms, the elimination of polyneuronal innervation, the maturation in the shape of the AChR plaque, the arrival of SCs at the junctions and their coverage of the nerve terminal, the development of junctional folds. Thus, if SMA in this particular mouse is a disease of motor neurons, it can act in a manner that does not result in their death or disconnection from their targets but nonetheless alters many aspects of neuromuscular development. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Molecular properties of adult mouse gastric and intestinal epithelial progenitors in their niches

    DEFF Research Database (Denmark)

    Giannakis, Marios; Stappenbeck, Thaddeus S; Mills, Jason C

    2006-01-01

    pathways. Wnt/beta-catenin, phosphoinositide-3/Akt kinase, insulin-like growth factor-1, vascular endothelial growth factor, integrin, and gamma-aminobutyric acid receptor signaling cascades, plus glycerolipid, fatty acid, and amino acid metabolic pathways are among those prominently represented in adult...

  4. Myogenin regulates exercise capacity and skeletal muscle metabolism in the adult mouse.

    Directory of Open Access Journals (Sweden)

    Jesse M Flynn

    2010-10-01

    Full Text Available Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin's role in adult skeletal muscle is unclear. We sought to determine myogenin's function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were analyzed for exercise capacity by involuntary treadmill running. To assess oxidative and glycolytic metabolism, we performed indirect calorimetry, monitored blood glucose and lactate levels, and performed histochemical analyses on muscle fibers. Surprisingly, we found that Myog-deleted mice performed significantly better than controls in high- and low-intensity treadmill running. This enhanced exercise capacity was due to more efficient oxidative metabolism during low- and high-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise. Furthermore, Myog-deleted mice had an enhanced response to long-term voluntary exercise training on running wheels. We identified several candidate genes whose expression was altered in exercise-stressed muscle of mice lacking myogenin. The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle.

  5. Spinal trauma in children

    International Nuclear Information System (INIS)

    Roche, C.; Carty, H.

    2001-01-01

    Evaluation of the child with suspected spinal injury can be a difficult task for the radiologist. Added to the problems posed by lack of familiarity with the normal appearances of the paediatric spine is anxiety about missing a potentially significant injury resulting in neurological damage. Due to differences in anatomy and function, the pattern of injury in the paediatric spine is different from that in the adolescent or adult. Lack of appreciation of these differences may lead to over investigation and inappropriate treatment. This review attempts to clarify some of the problems frequently encountered. It is based on a review of the literature as well as personal experience. The normal appearances and variants of the spine in children, the mechanisms and patterns of injury are reviewed highlighting the differences between children and adults. Specific fractures, a practical scheme for the assessment of spinal radiographs in children, and the role of cross sectional imaging are discussed. (orig.)

  6. An e-learning program to prevent pressure ulcers in adults with spinal cord injury: a pre- and post- pilot test among rehabilitation patients following discharge to home.

    Science.gov (United States)

    Schubart, Jane

    2012-10-01

    Pressure ulcers (PrUs) are the most common medical complication following spinal cord injury (SCI), as well as costly and potentially life-threatening. Every individual with SCI is at life-long risk for developing PrUs, yet many lack access to readily available, understandable, and effective PrU prevention strategies and practices. To address barriers to adequate PrU prevention education, an interactive e-learning program to educate adults with SCI about PrU prevention and management was developed and previously pilot-tested among inpatients. This recent pilot study was conducted to evaluate the feasibility of using the learning portion of the program by adults with SCI following discharge to home among 15 outpatients with SCI. Fourteen patients (nine men, five women, median age 37 years) completed the program intervention and pre- and follow-up questionnaires. The median score for pre-program knowledge and skin care management practice was 96 (possible score: 0 to 120; range 70-100). Post-program use median score was 107 (range 97-114). The greatest improvement was in the responses to knowledge and practice questions about skin checks and preventing skin problems (P effect of this e-learning program on PrU incidence. Internet interventions that are proven effective hold tremendous potential for bringing prevention education to groups who would otherwise not receive it.

  7. The relationship of older age and perioperative outcomes following thoracolumbar three-column osteotomy for adult spinal deformity: an analysis of 300 consecutive cases.

    Science.gov (United States)

    Lau, Darryl; Osorio, Joseph A; Deviren, Vedat; Ames, Christopher P

    2018-04-06

    OBJECTIVE Three-column osteotomies are increasingly being used in the elderly population to correct rigid spinal deformities. There is hesitation, however, in performing the technique in older patients because of the high risk for blood loss, longer operative times, and complications. This study assesses whether age alone is an independent risk factor for complications and length of stay. METHODS All patients with thoracolumbar adult spinal deformity (ASD) who underwent 3-column osteotomy (vertebral column resection or pedicle subtraction osteotomy) performed by the senior author from 2006 to 2016 were identified. Demographics, clinical baseline, and surgical details were collected. Outcomes of interest included perioperative complication, ICU stay, and hospital stay. Bivariate and multivariate analyses were used to assess the association of age with outcomes of interest. RESULTS A total of 300 patients were included, and 38.3% were male. The mean age was 63.7 years: 10.3% of patients were younger than 50 years, 36.0% were 50-64 years, 45.7% were 65-79 years, and 8.0% were 80 years or older. The overall mean EBL was 1999 ml. The overall perioperative complication rate was 24.7%: 18.0% had a medical complication and 7.0% had a surgical complication. There were no perioperative or 30-day deaths. Age was associated with overall complications (p = 0.002) and medical-specific complications (p column osteotomy for ASD. Comorbidities and other unknown variables that come with age are likely what put these patients at higher risk for complications. Older age, however, is independently associated with longer ICU and hospital stays.

  8. Spinal injury

    Science.gov (United States)

    ... Dallas, TX: American Red Cross; 2016. Kaji AH, Newton EJ, Hockberger RS. Spinal injuries. In: Marx JA, ... member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www. ...

  9. Olfactory discrimination training up-regulates and reorganizes expression of microRNAs in adult mouse hippocampus.

    Science.gov (United States)

    Smalheiser, Neil R; Lugli, Giovanni; Lenon, Angela L; Davis, John M; Torvik, Vetle I; Larson, John

    2010-02-26

    Adult male mice (strain C57Bl/6J) were trained to execute nose-poke responses for water reinforcement; then they were randomly assigned to either of two groups: olfactory discrimination training (exposed to two odours with reward contingent upon correctly responding to one odour) or pseudo-training (exposed to two odours with reward not contingent upon response). These were run in yoked fashion and killed when the discrimination-trained mouse reached a learning criterion of 70% correct responses in 20 trials, occurring after three sessions (a total of approximately 40 min of training). The hippocampus was dissected bilaterally from each mouse (N = 7 in each group) and profiling of 585 miRNAs (microRNAs) was carried out using multiplex RT-PCR (reverse transcription-PCR) plates. A significant global up-regulation of miRNA expression was observed in the discrimination training versus pseudo-training comparison; when tested individually, 29 miRNAs achieved significance at P = 0.05. miR-10a showed a 2.7-fold increase with training, and is predicted to target several learning-related mRNAs including BDNF (brain-derived neurotrophic factor), CAMK2b (calcium/calmodulin-dependent protein kinase IIβ), CREB1 (cAMP-response-element-binding protein 1) and ELAVL2 [ELAV (embryonic lethal, abnormal vision, Drosophila)-like; Hu B]. Analysis of miRNA pairwise correlations revealed the existence of several miRNA co-expression modules that were specific to the training group. These in vivo results indicate that significant, dynamic and co-ordinated changes in miRNA expression accompany early stages of learning.

  10. Olfactory Discrimination Training Up-Regulates and Reorganizes Expression of MicroRNAs in Adult Mouse Hippocampus

    Directory of Open Access Journals (Sweden)

    Neil R Smalheiser

    2010-01-01

    Full Text Available Adult male mice (strain C57Bl/6J were trained to execute nose-poke responses for water reinforcement; then they were randomly assigned to either of two groups: Olfactory discrimination training (exposed to two odours with reward contingent upon correctly responding to one odour or pseudo-training (exposed to two odours with reward not contingent upon response. These were run in yoked fashion and killed when the discrimination-trained mouse reached a learning criterion of 70% correct responses in 20 trials, occurring after three sessions (a total of ~40 min of training. The hippocampus was dissected bilaterally from each mouse (N=7 in each group and profiling of 585 miRNAs (microRNAs was carried out using multiplex RT–PCR (reverse transcription–PCR plates. A significant global up-regulation of miRNA expression was observed in the discrimination training versus pseudo-training comparison; when tested individually, 29 miRNAs achieved significance at P=0.05. miR-10a showed a 2.7-fold increase with training, and is predicted to target several learning-related mRNAs including BDNF (brain-derived neurotrophic factor, CAMK2b (calcium/calmodulin-dependent protein kinase IIβ, CREB1 (cAMP-response-element-binding protein 1 and ELAVL2 [ELAV (embryonic lethal, abnormal vision, Drosophila-like; Hu B]. Analysis of miRNA pairwise correlations revealed the existence of several miRNA co-expression modules that were specific to the training group. These in vivo results indicate that significant, dynamic and co-ordinated changes in miRNA expression accompany early stages of learning.

  11. Spinal infections

    International Nuclear Information System (INIS)

    Tali, E. Turgut; Gueltekin, Serap

    2005-01-01

    Spinal infections have an increasing prevalence among the general population. Definitive diagnosis based solely on clinical grounds is usually not possible and radiological imaging is used in almost all patients. The primary aim of the authors is to present an overview of spinal infections located in epidural, intradural and intramedullary compartments and to provide diagnostic clues regarding different imaging modalities, particularly MRI, to the practicing physicians and radiologists. (orig.)

  12. Spinal cysticercosis

    International Nuclear Information System (INIS)

    Goedert, A.V.; Silva, S.H.F.

    1990-01-01

    Spinal cysticercosis is an extremely uncommon condition. We have examined four patients with complaints that resembled nervous root compression by disk herniation. Myelography was shown to be an efficient method to evaluate spinal involvement, that was characterized by findings of multiple filling defect images (cysts) plus signs of adhesive arachnoiditis. One cyst was found to be mobile. Because of the recent development of medical treatment, a quick and precise diagnosis is of high importance to determine the prognosis of this condition. (author)

  13. Transmitter release in the neuromuscular synapse of the protein kinase C theta-deficient adult mouse.

    Science.gov (United States)

    Besalduch, Núria; Santafé, Manel M; Garcia, Neus; Gonzalez, Carmen; Tomás, Marta; Tomás, Josep; Lanuza, Maria A

    2011-04-01

    We studied structural and functional features of the neuromuscular junction in adult mice (P30) genetically deficient in the protein kinase C (PKC) theta isoform. Confocal and electron microscopy shows that there are no differences in the general morphology of the endplates between PKC theta-deficient and wild-type (WT) mice. Specifically, there is no difference in the density of the synaptic vesicles. However, the myelin sheath is not as thick in the intramuscular nerve fibers of the PKC theta-deficient mice. We found a significant reduction in the size of evoked endplate potentials and in the frequency of spontaneous, asynchronous, miniature endplate potentials in the PKC theta-deficient neuromuscular preparations in comparison with the WT, but the mean amplitude of the spontaneous potentials is not different. These changes indicate that PKC theta has a presynaptic role in the function of adult neuromuscular synapses. Copyright © 2010 Wiley-Liss, Inc.

  14. Adult neurogenesis and specific replacement of interneuron subtypes in the mouse main olfactory bulb

    Directory of Open Access Journals (Sweden)

    LaRocca Greg

    2007-11-01

    Full Text Available Abstract Background New neurons are generated in the adult brain from stem cells found in the subventricular zone (SVZ. These cells proliferate in the SVZ, generating neuroblasts which then migrate to the main olfactory bulb (MOB, ending their migration in the glomerular layer (GLL and the granule cell layer (GCL of the MOB. Neuronal populations in these layers undergo turnover throughout life, but whether all neuronal subtypes found in these areas are replaced and when neurons begin to express subtype-specific markers is not known. Results Here we use BrdU injections and immunohistochemistry against (calretinin, calbindin, N-copein, tyrosine hydroxylase and GABA and show that adult-generated neurons express markers of all major subtypes of neurons in the GLL and GCL. Moreover, the fractions of new neurons that express subtype-specific markers at 40 and 75 days post BrdU injection are very similar to the fractions of all neurons expressing these markers. We also show that many neurons in the glomerular layer do not express NeuN, but are readily and specifically labeled by the fluorescent nissl stain Neurotrace. Conclusion The expression of neuronal subtype-specific markers by new neurons in the GLL and GCL changes rapidly during the period from 14–40 days after BrdU injection before reaching adult levels. This period may represent a critical window for cell fate specification similar to that observed for neuronal survival.

  15. Mitochondrial DNA deletion mutations in adult mouse cardiac side population cells

    International Nuclear Information System (INIS)

    Lushaj, Entela B.; Lozonschi, Lucian; Barnes, Maria; Anstadt, Emily; Kohmoto, Takushi

    2012-01-01

    We investigated the presence and potential role of mitochondrial DNA (mtDNA) deletion mutations in adult cardiac stem cells. Cardiac side population (SP) cells were isolated from 12-week-old mice. Standard polymerase chain reaction (PCR) was used to screen for the presence of mtDNA deletion mutations in (a) freshly isolated SP cells and (b) SP cells cultured to passage 10. When present, the abundance of mtDNA deletion mutation was analyzed in single cell colonies. The effect of different levels of deletion mutations on SP cell growth and differentiation was determined. MtDNA deletion mutations were found in both freshly isolated and cultured cells from 12-week-old mice. While there was no significant difference in the number of single cell colonies with mtDNA deletion mutations from any of the groups mentioned above, the abundance of mtDNA deletion mutations was significantly higher in the cultured cells, as determined by quantitative PCR. Within a single clonal cell population, the detectable mtDNA deletion mutations were the same in all cells and unique when compared to deletions of other colonies. We also found that cells harboring high levels of mtDNA deletion mutations (i.e. where deleted mtDNA comprised more than 60% of total mtDNA) had slower proliferation rates and decreased differentiation capacities. Screening cultured adult stem cells for mtDNA deletion mutations as a routine assessment will benefit the biomedical application of adult stem cells.

  16. Geminin Participates in Differentiation Decisions of Adult Neural Stem Cells Transplanted in the Hemiparkinsonian Mouse Brain.

    Science.gov (United States)

    Taouki, Ioanna; Tasiudi, Eve; Lalioti, Maria-Eleni; Kyrousi, Christina; Skavatsou, Eleni; Kaplani, Konstantina; Lygerou, Zoi; Kouvelas, Elias D; Mitsacos, Adamantia; Giompres, Panagiotis; Taraviras, Stavros

    2017-08-15

    Neural stem cells have been considered as a source of stem cells that can be used for cell replacement therapies in neurodegenerative diseases, as they can be isolated and expanded in vitro and can be used for autologous grafting. However, due to low percentages of survival and varying patterns of differentiation, strategies that will enhance the efficacy of transplantation are under scrutiny. In this article, we have examined whether alterations in Geminin's expression, a protein that coordinates the balance between self-renewal and differentiation, can improve the properties of stem cells transplanted in 6-OHDA hemiparkinsonian mouse model. Our results indicate that, in the absence of Geminin, grafted cells differentiating into dopaminergic neurons were decreased, while an increased number of oligodendrocytes were detected. The number of proliferating multipotent cells was not modified by the absence of Geminin. These findings encourage research related to the impact of Geminin on transplantations for neurodegenerative disorders, as an important molecule in influencing differentiation decisions of the cells composing the graft.

  17. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Cord Injury What is a Spinal Cord Injury Levels of Injury and What They Mean Animated Spinal ... Cord Injury What is a Spinal Cord Injury Levels of Injury and What They Mean Animated Spinal ...

  18. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Injury Chart Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal Cord Injury Rehabilitation ... Injury Chart Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal Cord Injury Rehabilitation ...

  19. Characterizing newly repopulated microglia in the adult mouse: impacts on animal behavior, cell morphology, and neuroinflammation.

    Directory of Open Access Journals (Sweden)

    Monica R P Elmore

    Full Text Available Microglia are the primary immune cell in the brain and are postulated to play important roles outside of immunity. Administration of the dual colony-stimulating factor 1 receptor (CSF1R/c-Kit kinase inhibitor, PLX3397, to adult mice results in the elimination of ~99% of microglia, which remain eliminated for as long as treatment continues. Upon removal of the inhibitor, microglia rapidly repopulate the entire adult brain, stemming from a central nervous system (CNS resident progenitor cell. Using this method of microglial elimination and repopulation, the role of microglia in both healthy and diseased states can be explored. Here, we examine the responsiveness of newly repopulated microglia to an inflammatory stimulus, as well as determine the impact of these cells on behavior, cognition, and neuroinflammation. Two month-old wild-type mice were placed on either control or PLX3397 diet for 21 d to eliminate microglia. PLX3397 diet was then removed in a subset of animals to allow microglia to repopulate and behavioral testing conducted beginning at 14 d repopulation. Finally, inflammatory profiling of the microglia-repopulated brain in response to lipopolysaccharide (LPS; 0.25 mg/kg or phosphate buffered saline (PBS was determined 21 d after inhibitor removal using quantitative real time polymerase chain reaction (RT-PCR, as well as detailed analyses of microglial morphologies. We find mice with repopulated microglia to perform similarly to controls by measures of behavior, cognition, and motor function. Compared to control/resident microglia, repopulated microglia had larger cell bodies and less complex branching in their processes, which resolved over time after inhibitor removal. Inflammatory profiling revealed that the mRNA gene expression of repopulated microglia was similar to normal resident microglia and that these new cells appear functional and responsive to LPS. Overall, these data demonstrate that newly repopulated microglia function

  20. Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta.

    Science.gov (United States)

    Oestreich, Arin K; Kamp, William M; McCray, Marcus G; Carleton, Stephanie M; Karasseva, Natalia; Lenz, Kristin L; Jeong, Youngjae; Daghlas, Salah A; Yao, Xiaomei; Wang, Yong; Pfeiffer, Ferris M; Ellersieck, Mark R; Schulz, Laura C; Phillips, Charlotte L

    2016-11-22

    During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstn tm1Sjl/+ ) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstn tm1Sjl/+ dams would also confer increased bone strength. In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial collagen content of newborn mice and conferred a lasting impact on bone geometry and biomechanical integrity of offspring at 4 mo of age, the age of peak bone mass. Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis imperfecta (Col1a2 oim ), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2 oim/+ offspring from natural mating of Mstn tm1Sjl/+ dams to Col1a2 oim/+ sires had a 15% increase in torsional ultimate strength, a 29% increase in tensile strength, and a 24% increase in energy to failure compared with age, sex, and genotype-matched offspring from natural mating of Col1a2 oim/+ dams to Col1a2 oim/+ sires. Finally, increased bone biomechanical strength of Col1a2 oim/+ offspring that had been transferred into Mstn tm1Sjl/+ dams as blastocysts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantation environment. Thus, targeting the gestational environment, and specifically prenatal myostatin pathways, provides a potential therapeutic window and an approach for treating osteogenesis imperfecta.

  1. Morphological analysis of activity-reduced adult-born neurons in the mouse olfactory bulb

    Directory of Open Access Journals (Sweden)

    Jeffrey E Dahlen

    2011-05-01

    Full Text Available Adult born neurons are added to the olfactory bulb (OB throughout life in rodents. While many factors have been identified as regulating the survival and integration of adult-born neurons (ABNs into existing circuitry, the understanding of how these factors affect ABN morphology and connectivity is limited. Here we compare how cell intrinsic (siRNA knock down of voltage gated sodium channels NaV1.1-1.3 and circuit level (naris occlusion reductions in activity affect ABN morphology during integration into the OB. We found that both manipulations reduce the number of dendritic spines (and thus likely the number of reciprocal synaptic connections formed with the surrounding circuitry and inhibited dendritic ramification of ABNs. Further, we identified regions of ABN apical dendrites where the largest and most significant decreases occur following siRNA knock down or naris occlusion. In siRNA knock down cells, reduction of spines is observed in proximal regions of the apical dendrite. This suggests that distal regions of the dendrite may remain active independent of NaV1.1-1.3 channel expression, perhaps facilitated by activation of T-type calcium channels and NMDA receptors. By contrast, circuit level reduction of activity by naris occlusion resulted in a global depression of spine number. Together, these results indicate that ABNs retain the ability to develop their typical overall morphological features regardless of experienced activity, and activity modulates the number and location of formed connections.

  2. Evidence of functional duplicity of Nestin expression in the adult mouse midbrain

    Directory of Open Access Journals (Sweden)

    Parisa Farzanehfar

    2017-03-01

    Full Text Available Whether or not neurogenesis occurs in the adult substantia nigra pars compacta (SNc is an important question relevant for developing better treatments for the motor symptoms of Parkinson's disease (PD. Although controversial, it is generally believed that dividing cells here remain undifferentiated or differentiate into glia, not neurons. However, there is a suggestion that Nestin-expressing neural precursor cells (NPCs in the adult SNc have a propensity to differentiate into neurons, which we sought to confirm in the present study. Adult (>8-weeks old transgenic NesCreERT2/GtROSA or NesCreERT2/R26eYFP mice were used to permanently label Nestin-expressing cells and their progeny with β-galactosidase (β-gal or enhanced yellow fluorescent protein (eYFP, respectively. Most β-gal+ or eYFP+ cells were found in the ependymal lining of the midbrain aqueduct (Aq and in the midline ventral to Aq. Smaller but significant numbers were in the periaqueductal gray (PAG, the ventral tegmental area (VTA, and in SNc. Low-level basal proliferation was evidenced by a modest increase in number of β-gal+ or eYFP+ cells over time, fewer β-gal+ or eYFP+ cells when mice were administered the anti-mitotic agent Cytarabine, and incorporation of the proliferation marker bromodeoxyuridine (BrdU in a very small number of β-gal+ cells. No evidence of migration was found, including no immunoreactivity against the migration markers doublecortin (DCX or polysialic acid neural cell adhesion molecule (PSA-NCAM, and no dispersal of β-gal+ or eYFP+ cells through the midbrain parenchyma over time. However, β-gal+ or eYFP+ cells did increase in size and express higher levels of mature neuronal genes over time, indicating growth and neuronal differentiation. In mice whose SNc dopamine neurons had been depleted with 6-hydroxy-dopamine, a model of PD, there were ~2-fold more β-gal+ cells in SNc specifically, although the proportion that were also NeuN+ was not affected

  3. Astrocytes from the Contused Spinal Cord Inhibit Oligodendrocyte Differentiation of Adult Oligodendrocyte Precursor Cells by Increasing the Expression of Bone Morphogenetic Proteins

    OpenAIRE

    Wang, Yaping; Cheng, Xiaoxin; He, Qian; Zheng, Yiyan; Kim, Dong H.; Whittemore, Scott R.; Cao, Qilin L.

    2011-01-01

    Promotion of remyelination is an important therapeutic strategy to facilitate functional recovery after traumatic spinal cord injury (SCI). Transplantation of neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) has been used to enhance remyelination after SCI. However, the microenvironment in the injured spinal cord is inhibitory for oligodendrocyte (OL) differentiation of NSCs or OPCs. Identifying the signaling pathways that inhibit OL differentiation in the injured spinal cor...

  4. Hericium erinaceus Extract Reduces Anxiety and Depressive Behaviors by Promoting Hippocampal Neurogenesis in the Adult Mouse Brain.

    Science.gov (United States)

    Ryu, Sun; Kim, Hyoun Geun; Kim, Joo Youn; Kim, Seong Yun; Cho, Kyung-Ok

    2018-02-01

    Versatile biological activities of Hericium erinaceus (HE) have been reported in many brain diseases. However, roles of HE in major psychiatric disorders such as depression and anxiety remain to be investigated. Therefore, we evaluated whether HE could reduce anxiety and depressive behaviors in the adult mouse and its underlying mechanisms. Male C57BL/6 mice were administered HE (20 or 60 mg/kg, p.o.) or saline once a day for 4 weeks. Open field and tail suspension tests were performed 30 min after the last administration of HE, followed by forced swim test 2 days later. We found that chronic administration of HE showed anxiolytic and antidepressant-like effects. To elucidate possible mechanisms, proliferative activity of the hippocampal progenitor cells was assessed by immunohistochemistry of proliferating cell nuclear antigen (PCNA) and Ki67. Moreover, to evaluate neuronal survival in the dentate gyrus, 5-bromo-2'-deoxyuridine (BrdU) (120 mg/kg, i.p.) was given at the first day of HE administration, followed by isolation of the brains 4 weeks later. HE (60 mg/kg) increased the number of PCNA- and Ki67-positive cells in the subgranular zone of the hippocampus, indicating increased proliferation of hippocampal progenitors. In addition, BrdU- and BrdU/NeuN-positive cells in the dentate gyrus were significantly increased when treated with HE (60 mg/kg) compared with the saline-treated group, demonstrating enhanced neurogenesis by HE treatment. Taken together, the results indicate that chronic HE administration can exert anxiolytic and antidepressant-like effects, possibly by enhancing adult hippocampal neurogenesis.

  5. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Kathrin Hemmer

    2014-09-01

    Full Text Available Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]. iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

  6. EMMPRIN (basigin/CD147) expression is not correlated with MMP activity during adult mouse mammary gland development.

    Science.gov (United States)

    Szymanowska, Malgorzata; Hendry, Kay A K; Robinson, Claire; Kolb, Andreas F

    2009-01-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN/basigin/CD147) is a cell surface protein, which has been associated with the induction of matrix metalloproteinase (MMP) genes during cancer metastasis. EMMPRIN plays a role in a variety of physiological processes as is evident by the diverse deficiencies detectable in EMMPRIN knockout mice. We have analysed the role of EMMPRIN in the induction of MMP genes during mammary gland differentiation and involution. Co-transfection studies showed that EMMPRIN has diverse effects on MMP promoter activity in different mammary and non-mammary cell lines. Expression of EMMPRIN mRNA is enhanced markedly by insulin in a mammary gland cell line but appears to have no direct effect on MMP gene expression in these cells. Microarray analysis and quantitative PCR show that EMMPRIN is expressed throughout mammary gland differentiation in the mouse. Its expression decreases during early pregnancy and briefly after induction of mammary gland involution by litter removal. Immunohistochemical analysis shows that EMMPRIN expression is limited to the stromal compartment during pregnancy, whereas it is strongly expressed in the epithelium during lactation. In summary the data argue against a causal role for EMMPRIN for the induction of MMP gene expression during adult mammary gland development. These data therefore support a physiological role for EMMPRIN other than MMP induction in mammary gland biology. 2008 Wiley-Liss, Inc.

  7. Induced neural stem cells achieve long-term survival and functional integration in the adult mouse brain.

    Science.gov (United States)

    Hemmer, Kathrin; Zhang, Mingyue; van Wüllen, Thea; Sakalem, Marna; Tapia, Natalia; Baumuratov, Aidos; Kaltschmidt, Christian; Kaltschmidt, Barbara; Schöler, Hans R; Zhang, Weiqi; Schwamborn, Jens C

    2014-09-09

    Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Spinal tumors

    International Nuclear Information System (INIS)

    Goethem, J.W.M. van; Hauwe, L. van den; Oezsarlak, Oe.; Schepper, A.M.A. de; Parizel, P.M.

    2004-01-01

    Spinal tumors are uncommon lesions but may cause significant morbidity in terms of limb dysfunction. In establishing the differential diagnosis for a spinal lesion, location is the most important feature, but the clinical presentation and the patient's age and gender are also important. Magnetic resonance (MR) imaging plays a central role in the imaging of spinal tumors, easily allowing tumors to be classified as extradural, intradural-extramedullary or intramedullary, which is very useful in tumor characterization. In the evaluation of lesions of the osseous spine both computed tomography (CT) and MR are important. We describe the most common spinal tumors in detail. In general, extradural lesions are the most common with metastasis being the most frequent. Intradural tumors are rare, and the majority is extramedullary, with meningiomas and nerve sheath tumors being the most frequent. Intramedullary tumors are uncommon spinal tumors. Astrocytomas and ependymomas comprise the majority of the intramedullary tumors. The most important tumors are documented with appropriate high quality CT or MR images and the characteristics of these tumors are also summarized in a comprehensive table. Finally we illustrate the use of the new World Health Organization (WHO) classification of neoplasms affecting the central nervous system

  9. Quantitative Evaluation of 3D Mouse Behaviors and Motor Function in the Open-Field after Spinal Cord Injury Using Markerless Motion Tracking

    Science.gov (United States)

    Sheets, Alison L.; Lai, Po-Lun; Fisher, Lesley C.; Basso, D. Michele

    2013-01-01

    Thousands of scientists strive to identify cellular mechanisms that could lead to breakthroughs in developing ameliorative treatments for debilitating neural and muscular conditions such as spinal cord injury (SCI). Most studies use rodent models to test hypotheses, and these are all limited by the methods available to evaluate animal motor function. This study’s goal was to develop a behavioral and locomotor assessment system in a murine model of SCI that enables quantitative kinematic measurements to be made automatically in the open-field by applying markerless motion tracking approaches. Three-dimensional movements of eight naïve, five mild, five moderate, and four severe SCI mice were recorded using 10 cameras (100 Hz). Background subtraction was used in each video frame to identify the animal’s silhouette, and the 3D shape at each time was reconstructed using shape-from-silhouette. The reconstructed volume was divided into front and back halves using k-means clustering. The animal’s front Center of Volume (CoV) height and whole-body CoV speed were calculated and used to automatically classify animal behaviors including directed locomotion, exploratory locomotion, meandering, standing, and rearing. More detailed analyses of CoV height, speed, and lateral deviation during directed locomotion revealed behavioral differences and functional impairments in animals with mild, moderate, and severe SCI when compared with naïve animals. Naïve animals displayed the widest variety of behaviors including rearing and crossing the center of the open-field, the fastest speeds, and tallest rear CoV heights. SCI reduced the range of behaviors, and decreased speed (r = .70 pstudies are conducted. By providing scientists with sensitive, quantitative measurement methods, subjectivity and human error is reduced, potentially providing insights leading to breakthroughs in treating human disease. PMID:24058586

  10. Neuroendocrine and Cardiac Metabolic Dysfunction and NLRP3 Inflammasome Activation in Adipose Tissue and Pancreas following Chronic Spinal Cord Injury in the Mouse

    Directory of Open Access Journals (Sweden)

    Gregory E. Bigford

    2013-08-01

    Full Text Available CVD (cardiovascular disease represents a leading cause of mortality in chronic SCI (spinal cord injury. Several component risk factors are observed in SCI; however, the underlying mechanisms that contribute to these risks have not been defined. Central and peripheral chronic inflammation is associated with metabolic dysfunction and CVD, including adipokine regulation of neuroendocrine and cardiac function and inflammatory processes initiated by the innate immune response. We use female C57 Bl/6 mice to examine neuroendocrine, cardiac, adipose and pancreatic signaling related to inflammation and metabolic dysfunction in response to experimentally induced chronic SCI. Using immunohistochemical, -precipitation, and -blotting analysis, we show decreased POMC (proopiomelanocortin and increased NPY (neuropeptide-Y expression in the hypothalamic ARC (arcuate nucleus and PVN (paraventricular nucleus, 1-month post-SCI. Long-form leptin receptor (Ob-Rb, JAK2 (Janus kinase/STAT3 (signal transducer and activator of transcription 3/p38 and RhoA/ROCK (Rho-associated kinase signaling is significantly increased in the heart tissue post-SCI, and we observe the formation and activation of the NLRP3 (NOD-like receptor family, pyrin domain containing 3 inflammasome in VAT (visceral adipose tissue and pancreas post-SCI. These data demonstrate neuroendocrine signaling peptide alterations, associated with central inflammation and metabolic dysfunction post-SCI, and provide evidence for the peripheral activation of signaling mechanisms involved in cardiac, VAT and pancreatic inflammation and metabolic dysfunction post-SCI. Further understanding of biological mechanisms contributing to SCI-related inflammatory processes and metabolic dysfunction associated with CVD pathology may help to direct therapeutic and rehabilitation countermeasures.

  11. Toward a Broader View of Ube3a in a Mouse Model of Angelman Syndrome: Expression in Brain, Spinal Cord, Sciatic Nerve and Glial Cells.

    Directory of Open Access Journals (Sweden)

    Mark D Grier

    Full Text Available Angelman Syndrome (AS is a devastating neurodevelopmental disorder characterized by developmental delay, speech impairment, movement disorder, sleep disorders and refractory epilepsy. AS is caused by loss of the Ube3a protein encoded for by the imprinted Ube3a gene. Ube3a is expressed nearly exclusively from the maternal chromosome in mature neurons. While imprinting in neurons of the brain has been well described, the imprinting and expression of Ube3a in other neural tissues remains relatively unexplored. Moreover, given the overwhelming deficits in brain function in AS patients, the possibility of disrupted Ube3a expression in the infratentorial nervous system and its consequent disability have been largely ignored. We evaluated the imprinting status of Ube3a in the spinal cord and sciatic nerve and show that it is also imprinted in these neural tissues. Furthermore, a growing body of clinical and radiological evidence has suggested that myelin dysfunction may contribute to morbidity in many neurodevelopmental syndromes. However, findings regarding Ube3a expression in non-neuronal cells of the brain have varied. Utilizing enriched primary cultures of oligodendrocytes and astrocytes, we show that Ube3a is expressed, but not imprinted in these cell types. Unlike many other neurodevelopmental disorders, AS symptoms do not become apparent until roughly 6 to 12 months of age. To determine the temporal expression pattern and silencing, we analyzed Ube3a expression in AS mice at several time points. We confirm relaxed imprinting of Ube3a in neurons of the postnatal developing cortex, but not in structures in which neurogenesis and migration are more complete. This furthers the hypothesis that the apparently normal window of development in AS patients is supported by an incompletely silenced paternal allele in developing neurons, resulting in a relative preservation of Ube3a expression during this crucial epoch of early development.

  12. Distribution of ELOVL4 in the Developing and Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    David M. Sherry

    2017-05-01

    Full Text Available ELOngation of Very Long chain fatty acids (ELOVL-4 is essential for the synthesis of very long chain-fatty acids (fatty acids with chain lengths ≥ 28 carbons. The functions of ELOVL4 and its very long-chain fatty acid products are poorly understood at present. However, mutations in ELOVL4 cause neurodevelopmental or neurodegenerative diseases that vary according to the mutation and inheritance pattern. Heterozygous inheritance of different ELOVL4 mutations causes Stargardt-like Macular Dystrophy or Spinocerebellar Ataxia type 34. Homozygous inheritance of ELOVL4 mutations causes more severe disease characterized by seizures, intellectual disability, ichthyosis, and premature death. To better understand ELOVL4 and very long chain fatty acid function in the brain, we examined ELOVL4 expression in the mouse brain between embryonic day 18 and postnatal day 60 by immunolabeling using ELOVL4 and other marker antibodies. ELOVL4 was widely expressed in a region- and cell type-specific manner, and was restricted to cell bodies, consistent with its known localization to endoplasmic reticulum. ELOVL4 labeling was most prominent in gray matter, although labeling also was present in some cells located in white matter. ELOVL4 was widely expressed in the developing brain by embryonic day 18 and was especially pronounced in regions underlying the lateral ventricles and other neurogenic regions. The basal ganglia in particular showed intense ELOVL4 labeling at this stage. In the postnatal brain, cerebral cortex, hippocampus, cerebellum, thalamus, hypothalamus, midbrain, pons, and medulla all showed prominent ELOVL4 labeling, although ELOVL4 distribution was not uniform across all cells or subnuclei within these regions. In contrast, the basal ganglia showed little ELOVL4 labeling in the postnatal brain. Double labeling studies showed that ELOVL4 was primarily expressed by neurons, although presumptive oligodendrocytes located in white matter tracts also showed

  13. Imaging of extradural spinal lesions

    International Nuclear Information System (INIS)

    Ahlhelm, F.; Schulte-Altedorneburg, G.; Naumann, N.; Reith, W.; Nabhan, A.

    2006-01-01

    There is a wide variety of spinal extradural tumors. In addition to real neoplasms, degenerative diseases, congenital abnormalities and inflammatory disorders can be causes of extradural masses. Due to the bony boundary of the spinal canal, both benign as well as malignant masses can cause progressive neurological deficits including paraplegia. Most of the spinal tumors are benign (hemangioma of the vertebral body, degenerative diseases). In younger patients congenital abnormalities and primary tumors of the spine have to be considered, whereas in adults the list of differential diagnoses should include secondary malignancies such as metastases and lymphomas as well as metabolic disorders such as osteoporotic vertebral compression fracture and Paget's disease. Cross-sectional imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) of the spine often help to make a specific diagnosis of extradural spinal lesions and represent important tools for tumor staging and preoperative evaluation. (orig.) [de

  14. PPARs Expression in Adult Mouse Neural Stem Cells: Modulation of PPARs during Astroglial Differentiaton of NSC

    Directory of Open Access Journals (Sweden)

    A. Cimini

    2007-01-01

    Full Text Available PPAR isotypes are involved in the regulation of cell proliferation, death, and differentiation, with different roles and mechanisms depending on the specific isotype and ligand and on the differentiated, undifferentiated, or transformed status of the cell. Differentiation stimuli are integrated by key transcription factors which regulate specific sets of specialized genes to allow proliferative cells to exit the cell cycle and acquire specialized functions. The main differentiation programs known to be controlled by PPARs both during development and in the adult are placental differentiation, adipogenesis, osteoblast differentiation, skin differentiation, and gut differentiation. PPARs may also be involved in the differentiation of macrophages, brain, and breast. However, their functions in this cell type and organs still awaits further elucidation. PPARs may be involved in cell proliferation and differentiation processes of neural stem cells (NSC. To this aim, in this work the expression of the three PPAR isotypes and RXRs in NSC has been investigated.

  15. Electrophysiological evidence of increased glycine receptor-mediated phasic and tonic inhibition by blockade of glycine transporters in spinal superficial dorsal horn neurons of adult mice

    Directory of Open Access Journals (Sweden)

    Misa Oyama

    2017-03-01

    Full Text Available To understand the synaptic and/or extrasynaptic mechanisms underlying pain relief by blockade of glycine transporter subtypes GlyT1 and GlyT2, whole-cell recordings were made from dorsal horn neurons in spinal slices from adult mice, and the effects of NFPS and ALX-1393, selective GlyT1 and GlyT2 inhibitors, respectively, on phasic evoked or miniature glycinergic inhibitory postsynaptic currents (eIPSCs or mIPSCs were examined. NFPS and ALX-1393 prolonged the decay phase of eIPSCs without affecting their amplitude. In the presence of tetrodotoxin to record mIPSCs, NFPS and ALX-1393 induced a tonic inward current that was reversed by strychnine. Although NFPS had no statistically significant influences on mIPSCs, ALX-1393 significantly increased their frequency. We then further explored the role of GlyTs in the maintenance of glycinergic IPSCs. To facilitate vesicular release of glycine, repetitive high-frequency stimulation (HFS was applied at 10 Hz for 3 min during continuous recordings of eIPSCs at 0.1 Hz. Prominent suppression of eIPSCs was evident after HFS in the presence of ALX-1393, but not NFPS. Thus, it appears that phasic and tonic inhibition may contribute to the analgesic effects of GlyT inhibitors. However, reduced glycinergic inhibition due to impaired vesicular refilling could hamper the analgesic efficacy of GlyT2 inhibitors.

  16. The validity of anthropometric leg muscle volume estimation across a wide spectrum: from able-bodied adults to individuals with a spinal cord injury.

    Science.gov (United States)

    Layec, Gwenael; Venturelli, Massimo; Jeong, Eun-Kee; Richardson, Russell S

    2014-05-01

    The assessment of muscle volume, and changes over time, have significant clinical and research-related implications. Methods to assess muscle volume vary from simple and inexpensive to complex and expensive. Therefore this study sought to examine the validity of muscle volume estimated simply by anthropometry compared with the more complex proton magnetic resonance imaging ((1)H-MRI) across a wide spectrum of individuals including those with a spinal cord injury (SCI), a group recognized to exhibit significant muscle atrophy. Accordingly, muscle volume of the thigh and lower leg of eight subjects with a SCI and eight able-bodied subjects (controls) was determined by anthropometry and (1)H-MRI. With either method, muscle volumes were significantly lower in the SCI compared with the controls (P muscle volume were strongly correlated to the values assessed by (1)H-MRI in both the thigh (r(2) = 0.89; P muscle volume compared with (1)H-MRI in both the thigh (mean bias = 2407cm(3)) and the lower (mean bias = 170 cm(3)) leg. Thus with an appropriate correction for this systemic overestimation, muscle volume estimated from anthropometric measurements is a valid approach and provides acceptable accuracy across a spectrum of adults with normal muscle mass to a SCI and severe muscle atrophy. In practical terms this study provides the formulas that add validity to the already simple and inexpensive anthropometric approach to assess muscle volume in clinical and research settings.

  17. Spinal tuberculosis.

    Science.gov (United States)

    Dunn, R N; Ben Husien, M

    2018-04-01

    Tuberculosis (TB) remains endemic in many parts of the developing world and is increasingly seen in the developed world due to migration. A total of 1.3 million people die annually from the disease. Spinal TB is the most common musculoskeletal manifestation, affecting about 1 to 2% of all cases of TB. The coexistence of HIV, which is endemic in some regions, adds to the burden and the complexity of management. This review discusses the epidemiology, clinical presentation, diagnosis, impact of HIV and both the medical and surgical options in the management of spinal TB. Cite this article: Bone Joint J 2018;100-B:425-31.

  18. Generation of hyaline cartilaginous tissue from mouse adult dermal fibroblast culture by defined factors

    Science.gov (United States)

    Hiramatsu, Kunihiko; Sasagawa, Satoru; Outani, Hidetatsu; Nakagawa, Kanako; Yoshikawa, Hideki; Tsumaki, Noriyuki

    2011-01-01

    Repair of cartilage injury with hyaline cartilage continues to be a challenging clinical problem. Because of the limited number of chondrocytes in vivo, coupled with in vitro de-differentiation of chondrocytes into fibrochondrocytes, which secrete type I collagen and have an altered matrix architecture and mechanical function, there is a need for a novel cell source that produces hyaline cartilage. The generation of induced pluripotent stem (iPS) cells has provided a tool for reprogramming dermal fibroblasts to an undifferentiated state by ectopic expression of reprogramming factors. Here, we show that retroviral expression of two reprogramming factors (c-Myc and Klf4) and one chondrogenic factor (SOX9) induces polygonal chondrogenic cells directly from adult dermal fibroblast cultures. Induced cells expressed marker genes for chondrocytes but not fibroblasts, i.e., the promoters of type I collagen genes were extensively methylated. Although some induced cell lines formed tumors when subcutaneously injected into nude mice, other induced cell lines generated stable homogenous hyaline cartilage–like tissue. Further, the doxycycline-inducible induction system demonstrated that induced cells are able to respond to chondrogenic medium by expressing endogenous Sox9 and maintain chondrogenic potential after substantial reduction of transgene expression. Thus, this approach could lead to the preparation of hyaline cartilage directly from skin, without generating iPS cells. PMID:21293062

  19. Potassium Bromate-induced Changes in the Adult Mouse Cerebellum Are Ameliorated by Vanillin.

    Science.gov (United States)

    Ben Saad, Hajer; Driss, Dorra; Jaballi, Imen; Ghozzi, Hanen; Boudawara, Ons; Droguet, Michael; Magné, Christian; Nasri, Monsef; Zeghal, Khaled Mounir; Hakim, Ahmed; Ben Amara, Ibtissem

    2018-02-01

    The current study aimed to elucidate the effect of vanillin on behavioral changes, oxidative stress, and histopathological changes induced by potassium bromate (KBrO3), an environmental pollutant, in the cerebellum of adult mice. The animals were divided into four groups: group 1 served as a control, group 2 received KBrO3, group 3 received KBrO3 and vanillin, and group 4 received only vanillin. We then measured behavioral changes, oxidative stress, and molecular and histological changes in the cerebellum. We observed significant behavioral changes in KBrO3-exposed mice. When investigating redox homeostasis in the cerebellum, we found that mice treated with KBrO3 had increased lipid peroxidation and protein oxidation in the cerebellum. These effects were accompanied by decreased Na+-K+ and Mg2+ ATPase activity and antioxidant enzyme gene expression when compared to the control group. Additionally, there was a significant increase in cytokine gene expression in KBrO3-treated mice. Microscopy revealed that KBrO3 intoxication resulted in numerous degenerative changes in the cerebellum that were substantially ameliorated by vanillin supplementation. Co-administration of vanillin blocked the biochemical and molecular anomalies induced by KBrO3. Our results demonstrate that vanillin is a potential therapeutic agent for oxidative stress associated with neurodegenerative diseases. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  20. The electrocorticograms of the aged mouse x-irradiated at juvenile or young adult

    International Nuclear Information System (INIS)

    Minamisawa, Takeru; Sasaki, Shunsaku.

    1984-01-01

    The electrocorticograms (ECoGs) of the (C57BL/6 x C3H)F 1 mice irradiated at juvenile or young adult were studied when they attained the age of 24-26 months. One group of mice was irradiated 35 days post partum (35-DPP) and another 105 days (105-DPP). All the animals were irradiated with 300 R of X-rays to whole body. The ECoGs were recorded from the freely moving animals with the permanently implanted electrodes fixed over the visual cortical surface. The resulted ECoGs were divided into 3 patterns: wakefulness (W), slow wave sleep (SWS), and paradoxical sleep (PS). Six parameters of the 3 patterns were compared among the 2 irradiated groups and the non-irradiated control group. The mean SWS- and PS-cycle times, and mean SWS length were significantly longer in the 35-DPP group than in the control group. Changes in the ECoGs were less profound in the 105-DPP group than those in the 35-DPP group: only a significant change due to irradiation at 105-DPP was a decrease in the ratio of the total PS time to the total sleep time (TST = total SWS time + total PS time). There was no difference in the body weight and brain weight among the 2 irradiated groups and the control group. (author)

  1. Mash1-expressing cells could differentiate to type III cells in adult mouse taste buds.

    Science.gov (United States)

    Takagi, Hiroki; Seta, Yuji; Kataoka, Shinji; Nakatomi, Mitsushiro; Toyono, Takashi; Kawamoto, Tatsuo

    2018-03-10

    The gustatory cells in taste buds have been identified as paraneuronal; they possess characteristics of both neuronal and epithelial cells. Like neurons, they form synapses, store and release transmitters, and are capable of generating an action potential. Like epithelial cells, taste cells have a limited life span and are regularly replaced throughout life. However, little is known about the molecular mechanisms that regulate taste cell genesis and differentiation. In the present study, to begin to understand these mechanisms, we investigated the role of Mash1-positive cells in regulating adult taste bud cell differentiation through the loss of Mash1-positive cells using the Cre-loxP system. We found that the cells expressing type III cell markers-aromatic L-amino acid decarboxylase (AADC), carbonic anhydrase 4 (CA4), glutamate decarboxylase 67 (GAD67), neural cell adhesion molecule (NCAM), and synaptosomal-associated protein 25 (SNAP25)-were significantly reduced in the circumvallate taste buds after the administration of tamoxifen. However, gustducin and phospholipase C beta2 (PLC beta2)-markers of type II taste bud cells-were not significantly changed in the circumvallate taste buds after the administration of tamoxifen. These results suggest that Mash1-positive cells could be differentiated to type III cells, not type II cells in the taste buds.

  2. Quantitative evaluation of 3D mouse behaviors and motor function in the open-field after spinal cord injury using markerless motion tracking.

    Science.gov (United States)

    Sheets, Alison L; Lai, Po-Lun; Fisher, Lesley C; Basso, D Michele

    2013-01-01

    Thousands of scientists strive to identify cellular mechanisms that could lead to breakthroughs in developing ameliorative treatments for debilitating neural and muscular conditions such as spinal cord injury (SCI). Most studies use rodent models to test hypotheses, and these are all limited by the methods available to evaluate animal motor function. This study's goal was to develop a behavioral and locomotor assessment system in a murine model of SCI that enables quantitative kinematic measurements to be made automatically in the open-field by applying markerless motion tracking approaches. Three-dimensional movements of eight naïve, five mild, five moderate, and four severe SCI mice were recorded using 10 cameras (100 Hz). Background subtraction was used in each video frame to identify the animal's silhouette, and the 3D shape at each time was reconstructed using shape-from-silhouette. The reconstructed volume was divided into front and back halves using k-means clustering. The animal's front Center of Volume (CoV) height and whole-body CoV speed were calculated and used to automatically classify animal behaviors including directed locomotion, exploratory locomotion, meandering, standing, and rearing. More detailed analyses of CoV height, speed, and lateral deviation during directed locomotion revealed behavioral differences and functional impairments in animals with mild, moderate, and severe SCI when compared with naïve animals. Naïve animals displayed the widest variety of behaviors including rearing and crossing the center of the open-field, the fastest speeds, and tallest rear CoV heights. SCI reduced the range of behaviors, and decreased speed (r = .70 p<.005) and rear CoV height (r = .65 p<.01) were significantly correlated with greater lesion size. This markerless tracking approach is a first step toward fundamentally changing how rodent movement studies are conducted. By providing scientists with sensitive, quantitative measurement methods

  3. Quantitative evaluation of 3D mouse behaviors and motor function in the open-field after spinal cord injury using markerless motion tracking.

    Directory of Open Access Journals (Sweden)

    Alison L Sheets

    Full Text Available Thousands of scientists strive to identify cellular mechanisms that could lead to breakthroughs in developing ameliorative treatments for debilitating neural and muscular conditions such as spinal cord injury (SCI. Most studies use rodent models to test hypotheses, and these are all limited by the methods available to evaluate animal motor function. This study's goal was to develop a behavioral and locomotor assessment system in a murine model of SCI that enables quantitative kinematic measurements to be made automatically in the open-field by applying markerless motion tracking approaches. Three-dimensional movements of eight naïve, five mild, five moderate, and four severe SCI mice were recorded using 10 cameras (100 Hz. Background subtraction was used in each video frame to identify the animal's silhouette, and the 3D shape at each time was reconstructed using shape-from-silhouette. The reconstructed volume was divided into front and back halves using k-means clustering. The animal's front Center of Volume (CoV height and whole-body CoV speed were calculated and used to automatically classify animal behaviors including directed locomotion, exploratory locomotion, meandering, standing, and rearing. More detailed analyses of CoV height, speed, and lateral deviation during directed locomotion revealed behavioral differences and functional impairments in animals with mild, moderate, and severe SCI when compared with naïve animals. Naïve animals displayed the widest variety of behaviors including rearing and crossing the center of the open-field, the fastest speeds, and tallest rear CoV heights. SCI reduced the range of behaviors, and decreased speed (r = .70 p<.005 and rear CoV height (r = .65 p<.01 were significantly correlated with greater lesion size. This markerless tracking approach is a first step toward fundamentally changing how rodent movement studies are conducted. By providing scientists with sensitive, quantitative

  4. The prevalence of undiagnosed pre-surgical cognitive impairment and its post-surgical clinical impact in elderly patients undergoing surgery for adult spinal deformity.

    Science.gov (United States)

    Adogwa, Owoicho; Elsamadicy, Aladine A; Lydon, Emily; Vuong, Victoria D; Cheng, Joseph; Karikari, Isaac O; Bagley, Carlos A

    2017-09-01

    Pre-existing cognitive impairment (CI) is emerging as a predictor of poor post-operative outcomes in elderly patients. Little is known about impaired preoperative cognition and outcomes after elective spine surgery in this patient population. The purpose of this study was to assess the prevalence of neuro CI in elderly patients undergoing deformity surgery and its impact on postoperative outcomes. Elderly subjects undergoing elective spinal surgery for correction of adult degenerative scoliosis were enrolled in this study. Pre-operative baseline cognition was assessed using the Saint Louis Mental Status (SLUMS) test. SLUMS consists of 11 questions, which can give a maximum of 30 points. Mild CI was defined as a SLUMS score between 21-26 points, while severe CI was defined as a SLUMS score of ≤20 points. Normal cognition was defined as a SLUMS score of ≥27 points. Complication rates, duration of hospital stay, and 30-day readmission rates were compared between patients with and without baseline CI. Eighty-two subjects were included in this study, with mean age of 73.26±6.08 years. Fifty-seven patients (70%) had impaired cognition at baseline. The impaired cognition group had the following outcomes: increased incidence of one or more postoperative complications (39% vs. 20%), higher incidence of delirium (20% vs. 8%), and higher rate of discharge institutionalization at skilled nursing or acute rehab facilities (54% vs. 30%). The length of hospital stay and 30-day hospital readmission rates were similar between both cohorts (5.33 vs. 5.48 days and 12.28% vs. 12%, respectively). CI is highly prevalent in elderly patients undergoing surgery for adult degenerative scoliosis. Impaired cognition before surgery was associated with higher rates of post-operative delirium, complications, and discharge institutionalization. CI assessments should be considered in the pre-operative evaluations of elderly patients prior to surgery.

  5. Adeno-associated viral vector-mediated neurotrophin gene transfer in the injured adult rat spinal cord improves hind-limb function

    NARCIS (Netherlands)

    Blits, B; Oudega, M.; Boer, G J; Bartlett Bunge, M; Verhaagen, J

    2003-01-01

    To foster axonal growth from a Schwann cell bridge into the caudal spinal cord, spinal cells caudal to the implant were transduced with adeno-associated viral (AAV) vectors encoding for brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (AAV-NT-3). Control rats received AAV vectors encoding

  6. Changes in spinal alignment.

    Science.gov (United States)

    Veintemillas Aráiz, M T; Beltrán Salazar, V P; Rivera Valladares, L; Marín Aznar, A; Melloni Ribas, P; Valls Pascual, R

    2016-04-01

    Spinal misalignments are a common reason for consultation at primary care centers and specialized departments. Misalignment has diverse causes and is influenced by multiple factors: in adolescence, the most frequent misalignment is scoliosis, which is idiopathic in 80% of cases and normally asymptomatic. In adults, the most common cause is degenerative. It is important to know the natural history and to detect factors that might predict progression. The correct diagnosis of spinal deformities requires specific imaging studies. The degree of deformity determines the type of treatment. The aim is to prevent progression of the deformity and to recover the flexibility and balance of the body. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  7. Patient profiling can identify patients with adult spinal deformity (ASD) at risk for conversion from nonoperative to surgical treatment: initial steps to reduce ineffective ASD management.

    Science.gov (United States)

    Passias, Peter G; Jalai, Cyrus M; Line, Breton G; Poorman, Gregory W; Scheer, Justin K; Smith, Justin S; Shaffrey, Christopher I; Burton, Douglas C; Fu, Kai-Ming G; Klineberg, Eric O; Hart, Robert A; Schwab, Frank; Lafage, Virginie; Bess, Shay

    2018-02-01

    Non-operative management is a common initial treatment for patients with adult spinal deformity (ASD) despite reported superiority of surgery with regard to outcomes. Ineffective medical care is a large source of resource drain on the health system. Characterization of patients with ASD likely to elect for operative treatment from non-operative management may allow for more efficient patient counseling and cost savings. This study aimed to identify deformity and disability characteristics of patients with ASD who ultimately convert to operative treatment compared with those who remain non-operative and those who initially choose surgery. A retrospective review was carried out. A total of 510 patients with ASD (189 non-operative, 321 operative) with minimum 2-year follow-up comprised the patient sample. Oswestry Disability Index (ODI), Short-Form 36 Health Assessment (SF-36), Scoliosis Research Society questionnaire (SRS-22r), and spinopelvic radiographic alignment were the outcome measures. Demographic, radiographic, and patient-reported outcome measures (PROMs) from a cohort of patients with ASD prospectively enrolled into a multicenter database were evaluated. Patients were divided into three treatment cohorts: Non-operative (NON=initial non-operative treatment and remained non-operative), Operative (OP=initial operative treatment), and Crossover (CROSS=initial non-operative treatment with subsequent conversion to operative treatment). NON and OP groups were propensity score-matched (PSM) to CROSS for baseline demographics (age, body mass index, Charlson Comorbidity Index). Time to crossover was divided into early (1 year). Outcome measures were compared across and within treatment groups at four time points (baseline, 6 weeks, 1 year, and 2 years). Following PSM, 118 patients were included (NON=39, OP=38, CROSS=41). Crossover rate was 21.7% (41/189). Mean time to crossover was 394 days. All groups had similar baseline sagittal alignment, but CROSS had larger

  8. Preprotachykinin A is expressed by a distinct population of excitatory neurons in the mouse superficial spinal dorsal horn including cells that respond to noxious and pruritic stimuli.

    Science.gov (United States)

    Gutierrez-Mecinas, Maria; Bell, Andrew M; Marin, Alina; Taylor, Rebecca; Boyle, Kieran A; Furuta, Takahiro; Watanabe, Masahiko; Polgár, Erika; Todd, Andrew J

    2017-03-01

    The superficial dorsal horn, which is the main target for nociceptive and pruritoceptive primary afferents, contains a high density of excitatory interneurons. Our understanding of their roles in somatosensory processing has been restricted by the difficulty of distinguishing functional populations among these cells. We recently defined 3 nonoverlapping populations among the excitatory neurons, based on the expression of neurotensin, neurokinin B, and gastrin-releasing peptide. Here we identify and characterise another population: neurons that express the tachykinin peptide substance P. We show with immunocytochemistry that its precursor protein (preprotachykinin A, PPTA) can be detected in ∼14% of lamina I-II neurons, and these are concentrated in the outer part of lamina II. Over 80% of the PPTA-positive cells lack the transcription factor Pax2 (which determines an inhibitory phenotype), and these account for ∼15% of the excitatory neurons in this region. They are different from the neurotensin, neurokinin B, or gastrin-releasing peptide neurons, although many of them contain somatostatin, which is widely expressed among superficial dorsal horn excitatory interneurons. We show that many of these cells respond to noxious thermal and mechanical stimuli and to intradermal injection of pruritogens. Finally, we demonstrate that these cells can also be identified in a knock-in Cre mouse line (Tac1), although our findings suggest that there is an additional population of neurons that transiently express PPTA. This population of substance P-expressing excitatory neurons is likely to play an important role in the transmission of signals that are perceived as pain and itch.

  9. Analysis of Adult Female Mouse (Mus musculus) Group Behavior on the International Space Station (ISS)

    Science.gov (United States)

    Solomides, P.; Moyer, E. L.; Talyansky, Y.; Choi, S.; Gong, C.; Globus, R. K.; Ronca, A. E.

    2016-01-01

    As interest in long duration effects of space habitation increases, understanding the behavior of model organisms living within the habitats engineered to fly them is vital for designing, validating, and interpreting future spaceflight studies. A handful of papers have previously reported behavior of mice and rats in the weightless environment of space. The Rodent Research Hardware and Operations Validation (Rodent Research-1; RR1) utilized the Rodent Habitat (RH) developed at NASA Ames Research Center to fly mice on the ISS (International Space Station). Ten adult (16-week-old) female C57BL/6 mice were launched on September 21st, 2014 in an unmanned Dragon Capsule, and spent 37 days in microgravity. Here we report group behavioral phenotypes of the RR1 Flight (FLT) and environment-matched Ground Control (GC) mice in the Rodent Habitat (RH) during this long-duration flight. Video was recorded for 33 days on the ISS, permitting daily assessments of overall health and well-being of the mice, and providing a valuable repository for detailed behavioral analysis. We previously reported that, as compared to GC mice, RR1 FLT mice exhibited the same range of behaviors, including eating, drinking, exploration, self- and allo-grooming, and social interactions at similar or greater levels of occurrence. Overall activity was greater in FLT as compared to GC mice, with spontaneous ambulatory behavior, including organized 'circling' or 'race-tracking' behavior that emerged within the first few days of flight following a common developmental sequence, and comprised the primary dark cycle activity persisting throughout the remainder of the experiment. Participation by individual mice increased dramatically over the course of the flight. Here we present a detailed analysis of 'race-tracking' behavior in which we quantified: (1) Complete lap rotations by individual mice; (2) Numbers of collisions between circling mice; (3) Lap directionality; and (4) Recruitment of mice into a group

  10. Transplantation of adult monkey neural stem cells into a contusion spinal cord injury model in rhesus macaque monkeys

    DEFF Research Database (Denmark)

    Nemati, Shiva Nemati; Jabbari, Reza; Hajinasrollah, Mostafa

    2014-01-01

    , therefore, to explore the efficacy of adult monkey NSC (mNSC) in a primate SCI model. MATERIALS AND METHODS: In this experimental study, isolated mNSCs were analyzed by flow cytometry, immunocytochemistry, and RT-PCR. Next, BrdU-labeled cells were transplanted into a SCI model. The SCI animal model...... on Tarlov's scale and our established behavioral tests for monkeys. CONCLUSION: Our findings have indicated that mNSCs can facilitate recovery in contusion SCI models in rhesus macaque monkeys. Additional studies are necessary to determine the im- provement mechanisms after cell transplantation....

  11. Expression of extracellular matrix components is disrupted in the immature and adult estrogen receptor β-null mouse ovary.

    Directory of Open Access Journals (Sweden)

    Alexandra Zalewski

    Full Text Available Within the ovary, Estrogen Receptor β (ERβ is localized to the granulosa cells of growing follicles. 17β-estradiol (E2 acting via ERβ augments the actions of follicle stimulating hormone in granulosa cells, leading to granulosa cell differentiation and formation of a preovulatory follicle. Adult ERβ-null females are subfertile and possess ovaries with reduced numbers of growing follicles and corpora lutea. Because the majority of E2 production by granulosa cells occurs once puberty is reached, a role for ERβ in the ovary prior to puberty has not been well examined. We now provide evidence that lack of ERβ disrupts gene expression as early as post-natal day (PND 13, and in particular, we identify a number of genes of the extracellular matrix (ECM that are significantly higher in ERβ-null follicles than in wildtype (WT follicles. Considerable changes occur to the ECM occur during normal folliculogenesis to allow for the dramatic growth, cellular differentiation, and reorganization of the follicle from the primary to preovulatory stage. Using quantitative PCR and immunofluorescence, we now show that several ECM genes are aberrantly overexpressed in ERβ-null follicles. We find that Collagen11a1, a protein highly expressed in cartilage, is significantly higher in ERβ-null follicles than WT follicles as early as PND 13, and this heightened expression continues through PND 23-29 into adulthood. Similarly, Nidogen 2, a highly conserved basement membrane glycoprotein, is elevated in ERβ-null follicles at PND 13 into adulthood, and is elevated specifically in the ERβ-null focimatrix, a basal lamina-like matrix located between granulosa cells. Focimatrix laminin and Collagen IV expression were also higher in ERβ-null ovaries than in WT ovaries at various ages. Our findings suggest two novel observations: a that ERβ regulates granulosa cell gene expression ovary prior to puberty, and b that ERβ regulates expression of ECM components in the

  12. Deep-brain magnetic stimulation promotes adult hippocampal neurogenesis and alleviates stress-related behaviors in mouse models for neuropsychiatric disorders

    Science.gov (United States)

    2014-01-01

    Background Repetitive Transcranial Magnetic Stimulation (rTMS)/ Deep-brain Magnetic Stimulation (DMS) is an effective therapy for various neuropsychiatric disorders including major depression disorder. The molecular and cellular mechanisms underlying the impacts of rTMS/DMS on the brain are not yet fully understood. Results Here we studied the effects of deep-brain magnetic stimulation to brain on the molecular and cellular level. We examined the adult hippocampal neurogenesis and hippocampal synaptic plasticity of rodent under stress conditions with deep-brain magnetic stimulation treatment. We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons. Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats. Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically. Conclusions Deep-brain magnetic stimulation greatly facilitates adult hippocampal neurogenesis and maturation, also alleviates depression and stress-related responses in animal models. PMID:24512669

  13. Bone Marrow-Derived Cell Accumulation in the Spinal Cord Is Independent of Peripheral Mobilization in a Mouse Model of Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Peake, Kyle; Manning, John; Lewis, Coral-Ann; Tran, Kevin; Rossi, Fabio; Krieger, Charles

    2017-01-01

    Bone marrow-derived cells (BMDCs) are capable of migrating across the blood–brain barrier (BBB) and accumulating in the central nervous system (CNS) when transplanted into recipients conditioned with whole-body irradiation or chemotherapy. We used the chemotherapeutic agents busulfan and treosulfan to condition recipient mice for transplantation with bone marrow (BM) cells isolated from donor mice ubiquitously expressing green fluorescent protein. We attempted to increase the accumulation of BMDCs in the CNS by mobilization of BMDCs using either, or both, granulocyte colony-stimulating factor (GCSF) or plerixafor (AMD3100). We also used several concentrations of busulfan. We hypothesized that higher concentrations of busulfan and BMDC mobilization would increase numbers of GFP+ cells in the CNS. The doses of busulfan employed (60–125 mg/kg) all resulted in high levels of sustained chimerism (>85% 1 year post-transplant) in both the blood and BM of wild-type (WT) mice and an amyotrophic lateral sclerosis (ALS) mouse model. Moreover, cells accumulated within the CNS in a dose-, time-, and disease-dependent manner. Conditioning with the hydrophilic busulfan analog treosulfan, which is unable to cross the BBB efficiently, also resulted in a high degree of BM chimerism. However, few GFP+ BMDCs were found within the CNS of WT or ALS mice of treosulfan-conditioned mice. Mobilization of BMDCs into the circulation using GCSF and/or AMD3100 did not lead to increased accumulation of GFP+ BMDCs within the CNS of WT or ALS mice. Weekly analysis of BMDC accumulation revealed that BMDCs accumulated more rapidly and to a greater extent in the CNS of ALS mice conditioned with a high dose (125 mg/kg) of busulfan compared to a lower dose (80 mg/kg). The number of GFP+ BMDCs in the CNS labeling with the proliferation marker Ki67 increased in parallel with BMDC accumulation within the CNS. Our results indicate that establishment of high levels of blood and BM chimerism

  14. The Free-Hand Technique for S2-Alar-Iliac Screw Placement: A Safe and Effective Method for Sacropelvic Fixation in Adult Spinal Deformity.

    Science.gov (United States)

    Shillingford, Jamal N; Laratta, Joseph L; Tan, Lee A; Sarpong, Nana O; Lin, James D; Fischer, Charla R; Lehman, Ronald A; Kim, Yongjung J; Lenke, Lawrence G

    2018-02-21

    Spinopelvic fixation is an integral part of achieving solid fusion across the lumbosacral junction, especially in deformity procedures requiring substantial correction or long-segment constructs. Traditional S2-alar-iliac (S2AI) screw-placement techniques utilize fluoroscopy, increasing operative time and radiation exposure to the patient and surgeon. We describe a novel free-hand technique for S2AI screw placement in patients with adult spinal deformity. We reviewed the records of 45 consecutive patients who underwent spinopelvic fixation performed with use of S2AI screws by the senior surgeon and various fellows or residents over a 12-month period (2015 to 2016). In each case, the S2AI screws were placed utilizing a free-hand technique without fluoroscopic or image guidance. Screw position and accuracy were assessed by intraoperative O-arm imaging and analyzed using 3-dimensional interactive manipulation of computed tomography images. A total of 100 screws were placed, 51 by the senior surgeon and 49 by trainees. The mean patient age was 57.4 ± 12.7 years at the time of surgery; 37 (82.2%) of the patients were female. Preoperative diagnoses included adult idiopathic scoliosis (n = 19), adult degenerative scoliosis (n = 15), flatback syndrome (n = 2), fixed sagittal imbalance (n = 6), and distal junctional kyphosis (n = 3). Five (5%) of the screws were placed with moderate to severe cortical breaches, all of which perforated the pelvis posteriorly, with no clinically notable neurovascular or visceral complications. The breach rate did not differ significantly between the senior surgeon and trainees. The free-hand technique for S2AI screw placement, when performed in a standardized manner, was demonstrated to be safe and reliable in constructs requiring spinopelvic fixation. The accuracy of screw placement relies on visible and palpable anatomic landmarks that obviate the need for intraoperative fluoroscopy or image guidance, potentially reducing operative time

  15. Purification of oogonial stem cells from adult mouse and human ovaries: an assessment of the literature and a view toward the future.

    Science.gov (United States)

    Woods, Dori C; White, Yvonne A R; Tilly, Jonathan L

    2013-01-01

    Contemporary claims that mitotically active female germ line or oogonial stem cells (OSCs) exist and support oogenesis during postnatal life in mammals have been debated in the field of reproductive biology since March 2004, when a mouse study posed the first serious challenge to the dogma of a fixed pool of oocytes being endowed at birth in more than 50 years. Other studies have since been put forth that further question the validity of this dogma, including the isolation of OSCs from neonatal and adult mouse ovaries by 4 independent groups using multiple strategies. Two of these groups also reported that isolated mouse OSCs, once transplanted back into ovaries of adult female mice, differentiate into fully functional eggs that ovulate, fertilize, and produce healthy embryos and offspring. Arguably, one of the most significant advances in this emerging field was provided by a new research study published this year, which reported the successful isolation and functional characterization of OSCs from ovaries of reproductive age women. Two commentaries on this latest work, one cautiously supportive and one highly skeptical, were published soon afterward. This article evaluates the current literature regarding postnatal oogenesis in mammals and discusses important next steps for future work on OSC biology and function.

  16. Mouse adenovirus type 1 infection of macrophages

    NARCIS (Netherlands)

    Ashley, S.L.; Welton, A.R.; Harwood, K.M.; Rooijen, van N.; Spindler, K.R.

    2009-01-01

    Mouse adenovirus type 1 (MAV-1) causes acute and persistent infections in mice, with high levels of virus found in the brain, spinal cord and spleen in acute infections. MAV-1 infects endothelial cells throughout the mouse, and monocytes/macrophages have also been implicated as targets of the virus.

  17. Langerhans′ cell histiocytosis involving posterior elements of the dorsal spine: An unusual cause of extradural spinal mass in an adult

    Directory of Open Access Journals (Sweden)

    Devendra K Tyagi

    2011-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is a clonal proliferation of Langerhans cells occurring as an isolated lesion or as part of a systemic proliferation. It is commoner in children younger than 10 years of age with sparing of the posterior elements in more than 95% of cases. We describe a case of LCH in an adult female presenting with paraplegia. MRI revealed a well-defined extradural contrast enhancing mass at D2-D4 vertebral level involving the posterior elements of spine. D2-5 laminectomy with excision of lesion was performed which lead to marked improvement of patients neurological status. Histopathology was suggestive of eosinophilic granuloma. We describe the case, discuss its uniqueness and review the literature on this rare tumor presentation.

  18. Measuring outcomes in adult spinal deformity surgery: a systematic review to identify current strengths, weaknesses and gaps in patient-reported outcome measures.

    Science.gov (United States)

    Faraj, Sayf S A; van Hooff, Miranda L; Holewijn, Roderick M; Polly, David W; Haanstra, Tsjitske M; de Kleuver, Marinus

    2017-08-01

    Adult spinal deformity (ASD) causes severe disability, reduces overall quality of life, and results in a substantial societal burden of disease. As healthcare is becoming more value based, and to facilitate global benchmarking, it is critical to identify and standardize patient-reported outcome measures (PROMs). This study aims to identify the current strengths, weaknesses, and gaps in PROMs used for ASD. Studies were included following a systematic search in multiple bibliographic databases between 2000 and 2015. PROMs were extracted and linked to the outcome domains of WHO's International Classification of Functioning and Health (ICF) framework. Subsequently, the clinimetric quality of identified PROMs was evaluated. The literature search identified 144 papers that met the inclusion criteria, and nine frequently used PROMs were identified. These covered 29 ICF outcome domains, which could be grouped into three of the four main ICF chapters: body function (n = 7), activity and participation (n = 19), environmental factors (n = 3), and body structure (n = 0). A low quantity (n = 3) of papers was identified that studied the clinimetric quality of PROMs. The Scoliosis Research Society (SRS)-22 has the highest level of clinimetric quality for ASD. Outcome domains related to mobility and pain were well represented. We identified a gap in current outcome measures regarding neurological and pulmonary function. In addition, no outcome domains were measured in the ICF chapter body structure. These results will serve as a foundation for the process of seeking international consensus on a standard set of outcome domains, accompanied PROMs and contributing factors to be used in future clinical trials and spine registries.

  19. Impact of case type, length of stay, institution type, and comorbidities on Medicare diagnosis-related group reimbursement for adult spinal deformity surgery.

    Science.gov (United States)

    Nunley, Pierce D; Mundis, Gregory M; Fessler, Richard G; Park, Paul; Zavatsky, Joseph M; Uribe, Juan S; Eastlack, Robert K; Chou, Dean; Wang, Michael Y; Anand, Neel; Frank, Kelly A; Stone, Marcus B; Kanter, Adam S; Shaffrey, Christopher I; Mummaneni, Praveen V

    2017-12-01

    OBJECTIVE The aim of this study was to educate medical professionals about potential financial impacts of improper diagnosis-related group (DRG) coding in adult spinal deformity (ASD) surgery. METHODS Medicare's Inpatient Prospective Payment System PC Pricer database was used to collect 2015 reimbursement data for ASD procedures from 12 hospitals. Case type, hospital type/location, number of operative levels, proper coding, length of stay, and complications/comorbidities (CCs) were analyzed for effects on reimbursement. DRGs were used to categorize cases into 3 types: 1) anterior or posterior only fusion, 2) anterior fusion with posterior percutaneous fixation with no dorsal fusion, and 3) combined anterior and posterior fixation and fusion. RESULTS Pooling institutions, cases were reimbursed the same for single-level and multilevel ASD surgery. Longer stay, from 3 to 8 days, resulted in an additional $1400 per stay. Posterior fusion was an additional $6588, while CCs increased reimbursement by approximately $13,000. Academic institutions received higher reimbursement than private institutions, i.e., approximately $14,000 (Case Types 1 and 2) and approximately $16,000 (Case Type 3). Urban institutions received higher reimbursement than suburban institutions, i.e., approximately $3000 (Case Types 1 and 2) and approximately $3500 (Case Type 3). Longer stay, from 3 to 8 days, increased reimbursement between $208 and $494 for private institutions and between $1397 and $1879 for academic institutions per stay. CONCLUSIONS Reimbursement is based on many factors not controlled by surgeons or hospitals, but proper DRG coding can significantly impact the financial health of hospitals and availability of quality patient care.

  20. External Validation of the Adult Spinal Deformity (ASD) Frailty Index (ASD-FI) in the Scoli-RISK-1 Patient Database.

    Science.gov (United States)

    Miller, Emily K; Lenke, Lawrence G; Neuman, Brian J; Sciubba, Daniel M; Kebaish, Khaled M; Smith, Justin S; Qiu, Yong; Dahl, Benny T; Pellisé, Ferran; Matsuyama, Yukihiro; Carreon, Leah Y; Fehlings, Michael G; Cheung, Kenneth M; Lewis, Stephen; Dekutoski, Mark B; Schwab, Frank J; Boachie-Adjei, Oheneba; Mehdian, Hossein; Bess, Shay; Shaffrey, Christopher I; Ames, Christopher P

    2018-05-14

    Analysis of a prospective multicenter database. To assess the ability of the recently created Adult Spinal Deformity (ASD) Frailty Index (ASD-FI) to predict odds of major complications and length of hospital stay for patients who had more severe preoperative deformity and underwent more invasive ASD surgery compared with patients in the database used to create the index. Accurate preoperative estimates of risk are necessary given the high complication rates currently associated with ASD surgery. Patients were enrolled by participating institutions in Europe, Asia, and North America from 2009 to 2011. ASD-FI scores were used to classify 267 patients as not frail (NF) (0.5). Multivariable logistic regression, adjusted for preoperative and surgical covariates such as operative time and blood loss, was performed to determine the relationship between ASD-FI category and incidence of major complications, overall incidence of complications, and length of hospital stay. The mean ASD-FI score was 0.3 (range, 0-0.7). We categorized 105 patients as NF, 103 as frail, and 59 as SF. The adjusted odds of developing a major complication were higher for SF patients (odds ratio = 4.4; 95% CI 2.0, 9.9) compared with NF patients. After adjusting for covariates, length of hospital stay for SF patients increased by 19% (95% CI 1.4%, 39%) compared with NF patients. The odds of developing a major complication or having increased length of stay were similar between frail and NF patients. Greater patient frailty, as measured by the ASD-FI, is associated with a longer hospital stay and greater risk of major complications among patients who have severe preoperative deformity and undergo invasive surgical procedures. 2.

  1. Spinal Cord Injury 101

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    Full Text Available ... spinal cord injury? play_arrow What kind of surgery is common after a spinal cord injury? play_ ... How soon after a spinal cord injury should surgery be performed? play_arrow Is it common to ...

  2. Spinal Cord Injury 101

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    Full Text Available ... L Sarah Harrison, OT Anne Bryden, OT The Role of the Social Worker after Spinal Cord Injury ... a spinal cord injury important? play_arrow What role does “compression” play in a spinal cord injury? ...

  3. Spinal Cord Injury 101

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    Full Text Available ... Cord Injury Diane M. Rowles, MS, NP How Family Life Changes After Spinal Cord Injury Nancy Rosenberg, ... Children with Spinal Cord Injury Patricia Mucia, RN Family Life After Pediatric Spinal Injury Dawn Sheaffer, MSW ...

  4. Spinal Cord Injury 101

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    Full Text Available ... Counseling Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury ... Jennifer Piatt, PhD David Chen, MD Read Bio Medical Director, Spinal Cord Injury Rehabilitation Program, Rehabilitation Institute ...

  5. Spinal Cord Injury 101

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    Full Text Available ... Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury 101 ... arrow What is the “Spinal Cord Injury Model Systems” program? play_arrow What are the most promising ...

  6. Spinal Cord Diseases

    Science.gov (United States)

    Your spinal cord is a bundle of nerves that runs down the middle of your back. It carries signals back ... of the spine, this can also injure the spinal cord. Other spinal cord problems include Tumors Infections such ...

  7. Spinal Cord Injury 101

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    Full Text Available ... Spinal Cord Injury 101 Lawrence Vogel, MD The Basics of Pediatric SCI Rehabilitation Sara Klaas, MSW Transitions for Children with Spinal Cord Injury Patricia Mucia, RN Family Life After Pediatric Spinal Injury Dawn Sheaffer, MSW Rehabilitation ...

  8. Spinal cord injury reveals multilineage differentiation of ependymal cells.

    Directory of Open Access Journals (Sweden)

    Konstantinos Meletis

    2008-07-01

    Full Text Available Spinal cord injury often results in permanent functional impairment. Neural stem cells present in the adult spinal cord can be expanded in vitro and improve recovery when transplanted to the injured spinal cord, demonstrating the presence of cells that can promote regeneration but that normally fail to do so efficiently. Using genetic fate mapping, we show that close to all in vitro neural stem cell potential in the adult spinal cord resides within the population of ependymal cells lining the central canal. These cells are recruited by spinal cord injury and produce not only scar-forming glial cells, but also, to a lesser degree, oligodendrocytes. Modulating the fate of ependymal progeny after spinal cord injury may offer an alternative to cell transplantation for cell replacement therapies in spinal cord injury.

  9. Serotonin receptor and dendritic plasticity in the spinal cord mediated by chronic serotonergic pharmacotherapy combined with exercise following complete SCI in the adult rat.

    Science.gov (United States)

    Ganzer, Patrick D; Beringer, Carl R; Shumsky, Jed S; Nwaobasi, Chiemela; Moxon, Karen A

    2018-06-01

    Severe spinal cord injury (SCI) damages descending motor and serotonin (5-HT) fiber projections leading to paralysis and serotonin depletion. 5-HT receptors (5-HTRs) subsequently upregulate following 5-HT fiber degeneration, and dendritic density decreases indicative of atrophy. 5-HT pharmacotherapy or exercise can improve locomotor behavior after SCI. One might expect that 5-HT pharmacotherapy acts on upregulated spinal 5-HTRs to enhance function, and that exercise alone can influence dendritic atrophy. In the current study, we assessed locomotor recovery and spinal proteins influenced by SCI and therapy. 5-HT, 5-HT 2A R, 5-HT 1A R, and dendritic densities were quantified both early (1 week) and late (9 weeks) after SCI, and also following therapeutic interventions (5-HT pharmacotherapy, bike therapy, or a combination). Interestingly, chronic 5-HT pharmacotherapy largely normalized spinal 5-HTR upregulation following injury. Improvement in locomotor behavior was not correlated to 5-HTR density. These results support the hypothesis that chronic 5-HT pharmacotherapy can mediate recovery following SCI, despite acting on largely normal spinal 5-HTR levels. We next assessed spinal dendritic plasticity and its potential role in locomotor recovery. Single therapies did not normalize the loss of dendritic density after SCI. Groups displaying significantly atrophied dendritic processes were rarely able to achieve weight supported open-field locomotion. Only a combination of 5-HT pharmacotherapy and bike therapy enabled significant open-field weigh-supported stepping, mediated in part by restoring spinal dendritic density. These results support the use of combined therapies to synergistically impact multiple markers of spinal plasticity and improve motor recovery. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Spinal cord contusion.

    Science.gov (United States)

    Ju, Gong; Wang, Jian; Wang, Yazhou; Zhao, Xianghui

    2014-04-15

    Spinal cord injury is a major cause of disability with devastating neurological outcomes and limited therapeutic opportunities, even though there are thousands of publications on spinal cord injury annually. There are two major types of spinal cord injury, transaction of the spinal cord and spinal cord contusion. Both can theoretically be treated, but there is no well documented treatment in human being. As for spinal cord contusion, we have developed an operation with fabulous result.

  11. Assessing the use of immersive virtual reality, mouse and touchscreen in pointing and dragging-and-dropping tasks among young, middle-aged and older adults.

    Science.gov (United States)

    Chen, Jiayin; Or, Calvin

    2017-11-01

    This study assessed the use of an immersive virtual reality (VR), a mouse and a touchscreen for one-directional pointing, multi-directional pointing, and dragging-and-dropping tasks involving targets of smaller and larger widths by young (n = 18; 18-30 years), middle-aged (n = 18; 40-55 years) and older adults (n = 18; 65-75 years). A three-way, mixed-factorial design was used for data collection. The dependent variables were the movement time required and the error rate. Our main findings were that the participants took more time and made more errors in using the VR input interface than in using the mouse or the touchscreen. This pattern applied in all three age groups in all tasks, except for multi-directional pointing with a larger target width among the older group. Overall, older adults took longer to complete the tasks and made more errors than young or middle-aged adults. Larger target widths yielded shorter movement times and lower error rates in pointing tasks, but larger targets yielded higher rates of error in dragging-and-dropping tasks. Our study indicated that any other virtual environments that are similar to those we tested may be more suitable for displaying scenes than for manipulating objects that are small and require fine control. Although interacting with VR is relatively difficult, especially for older adults, there is still potential for older adults to adapt to that interface. Furthermore, adjusting the width of objects according to the type of manipulation required might be an effective way to promote performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Expression of C4.4A, a structural uPAR homolog, reflects squamous epithelial differentiation in the adult mouse and during embryogenesis

    DEFF Research Database (Denmark)

    Kriegbaum, Mette Camilla; Jacobsen, Benedikte; Hald, Andreas

    2011-01-01

    by a comprehensive immunohistochemical mapping. This task was accomplished by staining paraffin-embedded tissues with a specific rabbit polyclonal anti-C4.4A antibody. In the adult mouse, C4.4A was predominantly expressed in the suprabasal layers of the squamous epithelia of the oral cavity, esophagus, non...... expression first appears in the developing squamous epithelium at embryonic day 13.5. This anatomical location of C4.4A is thus concordant with a possible functional role in early differentiation of stratified squamous epithelia....

  13. Differential Structural Development of Adult-Born Septal Hippocampal Granule Cells in the Thy1-GFP Mouse, Nuclear Size as a New Index of Maturation.

    Directory of Open Access Journals (Sweden)

    Tijana Radic

    Full Text Available Adult neurogenesis is frequently studied in the mouse hippocampus. We examined the morphological development of adult-born, immature granule cells in the suprapyramidal blade of the septal dentate gyrus over the period of 7-77 days after mitosis with BrdU-labeling in 6-weeks-old male Thy1-GFP mice. As Thy1-GFP expression was restricted to maturated granule cells, it was combined with doublecortin-immunolabeling of immature granule cells. We developed a novel classification system that is easily applicable and enables objective and direct categorization of newborn granule cells based on the degree of dendritic development in relation to the layer specificity of the dentate gyrus. The structural development of adult-generated granule cells was correlated with age, albeit with notable differences in the time course of development between individual cells. In addition, the size of the nucleus, immunolabeled with the granule cell specific marker Prospero-related homeobox 1 gene, was a stable indicator of the degree of a cell's structural maturation and could be used as a straightforward parameter of granule cell development. Therefore, further studies could employ our doublecortin-staging system and nuclear size measurement to perform investigations of morphological development in combination with functional studies of adult-born granule cells. Furthermore, the Thy1-GFP transgenic mouse model can be used as an additional investigation tool because the reporter gene labels granule cells that are 4 weeks or older, while very young cells could be visualized through the immature marker doublecortin. This will enable comparison studies regarding the structure and function between young immature and older matured granule cells.

  14. Identification of the sexually dimorphic gastrin-releasing peptide system in the lumbosacral spinal cord that controls male reproductive function in the mouse and Asian house musk shrew (Suncus murinus).

    Science.gov (United States)

    Tamura, Kei; Kobayashi, Yasuhisa; Hirooka, Asuka; Takanami, Keiko; Oti, Takumi; Jogahara, Takamichi; Oda, Sen-Ichi; Sakamoto, Tatsuya; Sakamoto, Hirotaka

    2017-05-01

    Several regions of the brain and spinal cord control male reproductive function. We previously demonstrated that the gastrin-releasing peptide (GRP) system, located in the lumbosacral spinal cord of rats, controls spinal centers to promote penile reflexes during male copulatory behavior. However, little information exists on the male-specific spinal GRP system in animals other than rats. The objective of this study was to examine the functional generality of the spinal GRP system in mammals using the Asian house musk shrew (Suncus murinus; suncus named as the laboratory strain), a specialized placental mammal model. Mice are also used for a representative model of small laboratory animals. We first isolated complementary DNA encoding GRP in suncus. Phylogenetic analysis revealed that suncus preproGRP was clustered to an independent branch. Reverse transcription-PCR showed that GRP and its receptor mRNAs were both expressed in the lumbar spinal cord of suncus and mice. Immunohistochemistry for GRP demonstrated that the sexually dimorphic GRP system and male-specific expression/distribution patterns of GRP in the lumbosacral spinal cord in suncus are similar to those of mice. In suncus, we further found that most GRP-expressing neurons in males also express androgen receptors, suggesting that this male-dominant system in suncus is also androgen-dependent. Taken together, these results indicate that the sexually dimorphic spinal GRP system exists not only in mice but also in suncus, suggesting that this system is a conserved property in mammals. J. Comp. Neurol. 525:1586-1598, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Reliability of the revised Scoliosis Research Society-22 and Oswestry Disability Index (ODI) questionnaires in adult spinal deformity when administered by telephone.

    Science.gov (United States)

    Bokshan, Steven L; Godzik, Jakub; Dalton, Jonathan; Jaffe, Jennifer; Lenke, Lawrence G; Kelly, Michael P

    2016-09-01

    The non-response rates are as high as 20% to 50% after 5 years of follow-up in adult spinal deformity (ASD) surgery. Minimizing loss to follow-up is essential to protect the quality of data in long-term studies. Phone and internet administration of outcomes instruments has grown in popularity and has been found to not only provide a convenient way of collecting data, but also show improved response rates. The study aimed to examine the reliability of the revised Scoliosis Research Society-22 (SRS-22r) and the Oswestry Disability Index (ODI) questionnaires in ASD patients when administered by telephone. This is a single-center, randomized crossover phone validation of ASD patients. The study included ASD patients presenting to a tertiary spine care center. The outcome measures were ODI and SRS-22r. Forty-nine patients (mean age: 55.7 years) with ASD were randomized in a 1:1 ratio to either phone completion of the SRS-22r and ODI followed by in-office completion, or to in-office completion followed by phone completion. An interval of 2 to 4 weeks was placed between administrations of each version. A paired t test was used to assess the difference between the written and phone versions, and intraclass correlation coefficients were used to assess homogeneity. Finally, goodness-of-fit testing was used to assess version preference. There was no significant difference between the phone and in-office versions of the SRS-22r (p=.174) or the ODI (p=.320). The intraclass correlation coefficients of the SRS-22r and ODI were 0.91 and 0.86, respectively. Completion over the phone was the most popular option (57% preferred phone, 29% preferred in-office, and 14% had no preference). Phone administration of the SRS-22r and ODI to ASD patients provides a convenient and reliable tool for reducing loss of follow-up data. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Spinal Cord Injury 101

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    Full Text Available ... Abuse and Spinal Cord Injury Allen Heinemann, PhD How Peer Counseling Works Julie Gassaway, MS, RN Pediatric Injuries Pediatric Spinal ... What is a spinal cord injury? play_arrow How does the spinal cord work? play_arrow Why is the level of a ...

  17. H3 and H4 Lysine Acetylation Correlates with Developmental and Experimentally Induced Adult Experience-Dependent Plasticity in the Mouse Visual Cortex

    Directory of Open Access Journals (Sweden)

    Gabriela Vierci

    2016-01-01

    Full Text Available Histone posttranslational modifications play a fundamental role in orchestrating gene expression. In this work, we analyzed the acetylation of H3 and H4 histones (AcH3-AcH4 and its modulation by visual experience in the mouse visual cortex (VC during normal development and in two experimental conditions that restore juvenile-like plasticity levels in adults (fluoxetine treatment and enriched environment. We found that AcH3-AcH4 declines with age and is upregulated by treatments restoring plasticity in the adult. We also found that visual experience modulates AcH3-AcH4 in young and adult plasticity-restored mice but not in untreated ones. Finally, we showed that the transporter vGAT is downregulated in adult plasticity-restored models. In summary, we identified a dynamic regulation of AcH3-AcH4, which is associated with high plasticity levels and enhanced by visual experience. These data, along with recent ones, indicate H3-H4 acetylation as a central hub in the control of experience-dependent plasticity in the VC.

  18. Spinal pain

    International Nuclear Information System (INIS)

    Izzo, R.; Popolizio, T.; D’Aprile, P.; Muto, M.

    2015-01-01

    Highlights: • Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional spinal pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally invasive interventional techniques. • Special attention will be given to the discogenic pain, actually considered as the most frequent cause of chronic low back pain. • The correct distinction between referred pain and radicular pain contributes to give a more correct approach to spinal pain. • The pathogenesis of chronic pain renders this pain a true pathology requiring a specific management. - Abstract: The spinal pain, and expecially the low back pain (LBP), represents the second cause for a medical consultation in primary care setting and a leading cause of disability worldwide [1]. LBP is more often idiopathic. It has as most frequent cause the internal disc disruption (IDD) and is referred to as discogenic pain. IDD refers to annular fissures, disc collapse and mechanical failure, with no significant modification of external disc shape, with or without endplates changes. IDD is described as a separate clinical entity in respect to disc herniation, segmental instability and degenerative disc desease (DDD). The radicular pain has as most frequent causes a disc herniation and a canal stenosis. Both discogenic and radicular pain also have either a mechanical and an inflammatory genesis. For to be richly innervated, facet joints can be a direct source of pain, while for their degenerative changes cause compression of nerve roots in lateral recesses and in the neural foramina. Degenerative instability is a common and often misdiagnosed cause of axial and radicular pain, being also a frequent indication for surgery. Acute pain tends to extinguish along with its cause, but the setting of complex processes of peripheral and central sensitization may influence its evolution in chronic

  19. Spinal pain

    Energy Technology Data Exchange (ETDEWEB)

    Izzo, R., E-mail: roberto1766@interfree.it [Neuroradiology Department, A. Cardarelli Hospital, Naples (Italy); Popolizio, T., E-mail: t.popolizio1@gmail.com [Radiology Department, Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo (Fg) (Italy); D’Aprile, P., E-mail: paoladaprile@yahoo.it [Neuroradiology Department, San Paolo Hospital, Bari (Italy); Muto, M., E-mail: mutomar@tiscali.it [Neuroradiology Department, A. Cardarelli Hospital, Napoli (Italy)

    2015-05-15

    Highlights: • Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional spinal pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally invasive interventional techniques. • Special attention will be given to the discogenic pain, actually considered as the most frequent cause of chronic low back pain. • The correct distinction between referred pain and radicular pain contributes to give a more correct approach to spinal pain. • The pathogenesis of chronic pain renders this pain a true pathology requiring a specific management. - Abstract: The spinal pain, and expecially the low back pain (LBP), represents the second cause for a medical consultation in primary care setting and a leading cause of disability worldwide [1]. LBP is more often idiopathic. It has as most frequent cause the internal disc disruption (IDD) and is referred to as discogenic pain. IDD refers to annular fissures, disc collapse and mechanical failure, with no significant modification of external disc shape, with or without endplates changes. IDD is described as a separate clinical entity in respect to disc herniation, segmental instability and degenerative disc desease (DDD). The radicular pain has as most frequent causes a disc herniation and a canal stenosis. Both discogenic and radicular pain also have either a mechanical and an inflammatory genesis. For to be richly innervated, facet joints can be a direct source of pain, while for their degenerative changes cause compression of nerve roots in lateral recesses and in the neural foramina. Degenerative instability is a common and often misdiagnosed cause of axial and radicular pain, being also a frequent indication for surgery. Acute pain tends to extinguish along with its cause, but the setting of complex processes of peripheral and central sensitization may influence its evolution in chronic

  20. Spinal stenosis

    International Nuclear Information System (INIS)

    Beale, S.; Pathria, M.N.; Ross, J.S.; Masaryk, T.J.; Modic, M.T.

    1988-01-01

    The authors studied 50 patients who had spinal stenosis by means of MR imaging. All patients had undergone myelography and CT. Thirty patients underwent surgery. MR imaging included T1-weighted spin echo sequences with repetition time = 600 msec, echo time = 20 (600/20) sagittal and axial sections 4 mm thick with 2 mm gap. T2-weighted 2,000/60 axial images were obtained on 14 patients. Examinations were retrospectively evaluated for central stenosis, lateral recess narrowing, and foraminal encroachment. Measurements of sagittal, interpedicular, interfacet, and recess dimensions were made at L3-5. On MR images, 20 patients had single-level and 30 had multiple-level stenosis. There was excellent agreement between modalities with central canal stenosis, but a discrepancy in six patients with bony foraminal stenosis. MR imaging was an accurate method for assessment of lumbar stenosis, but CT appears marginally better for detection of bony foraminal stenosis in certain cases

  1. Reduce, reuse, recycle - Developmental signals in spinal cord regeneration.

    Science.gov (United States)

    Cardozo, Marcos Julian; Mysiak, Karolina S; Becker, Thomas; Becker, Catherina G

    2017-12-01

    Anamniotes, fishes and amphibians, have the capacity to regenerate spinal cord tissue after injury, generating new neurons that mature and integrate into the spinal circuitry. Elucidating the molecular signals that promote this regeneration is a fundamental question in regeneration research. Model systems, such as salamanders and larval and adult zebrafish are used to analyse successful regeneration. This shows that many developmental signals, such as Notch, Hedgehog (Hh), Bone Morphogenetic Protein (BMP), Wnt, Fibroblast Growth Factor (FGF), Retinoic Acid (RA) and neurotransmitters are redeployed during regeneration and activate resident spinal progenitor cells. Here we compare the roles of these signals in spinal cord development and regeneration of the much larger and fully patterned adult spinal cord. Understanding how developmental signalling systems are reactivated in successfully regenerating species may ultimately lead to ways to reactivate similar systems in mammalian progenitor cells, which do not show neurogenesis after spinal injury. Copyright © 2017. Published by Elsevier Inc.

  2. Dynamics of intrinsic electrophysiological properties in spinal cord neurones

    DEFF Research Database (Denmark)

    Russo, R E; Hounsgaard, J

    1999-01-01

    The spinal cord is engaged in a wide variety of functions including generation of motor acts, coding of sensory information and autonomic control. The intrinsic electrophysiological properties of spinal neurones represent a fundamental building block of the spinal circuits executing these tasks. ....... Specialised, cell specific electrophysiological phenotypes gradually differentiate during development and are continuously adjusted in the adult animal by metabotropic synaptic interactions and activity-dependent plasticity to meet a broad range of functional demands....

  3. Protease-activated receptor-1 negatively regulates proliferation of neural stem/progenitor cells derived from the hippocampal dentate gyrus of the adult mouse

    Directory of Open Access Journals (Sweden)

    Masayuki Tanaka

    2016-07-01

    Full Text Available Thrombin-activated protease-activated receptor (PAR-1 regulates the proliferation of neural cells following brain injury. To elucidate the involvement of PAR-1 in the neurogenesis that occurs in the adult hippocampus, we examined whether PAR-1 regulated the proliferation of neural stem/progenitor cells (NPCs derived from the murine hippocampal dentate gyrus. NPC cultures expressed PAR-1 protein and mRNA encoding all subtypes of PAR. Direct exposure of the cells to thrombin dramatically attenuated the cell proliferation without causing cell damage. This thrombin-induced attenuation was almost completely abolished by the PAR antagonist RWJ 56110, as well as by dabigatran and 4-(2-aminoethylbenzenesulfonyl fluoride (AEBSF, which are selective and non-selective thrombin inhibitors, respectively. Expectedly, the PAR-1 agonist peptide (AP SFLLR-NH2 also attenuated the cell proliferation. The cell proliferation was not affected by the PAR-1 negative control peptide RLLFT-NH2, which is an inactive peptide for PAR-1. Independently, we determined the effect of in vivo treatment with AEBSF or AP on hippocampal neurogenesis in the adult mouse. The administration of AEBSF, but not that of AP, significantly increased the number of newly-generated cells in the hippocampal subgranular zone. These data suggest that PAR-1 negatively regulated adult neurogenesis in the hippocampus by inhibiting the proliferative activity of the NPCs.

  4. Maternal high-protein diet during pregnancy, but not during suckling, induced altered expression of an increasing number of hepatic genes in adult mouse offspring.

    Science.gov (United States)

    Vanselow, Jens; Kucia, Marzena; Langhammer, Martina; Koczan, Dirk; Metges, Cornelia C

    2016-04-01

    Indirect effects of a high-protein maternal diet are not well understood. In this study, we analyzed short-term and sustainable effects of a prenatal versus early postnatal maternal high-protein diet on growth and hepatic gene expression in mouse offspring. Dams were exposed to an isoenergetic high-protein (HP, 40 % w/w) diet during pregnancy or lactation. Growth and hepatic expression profiles of male offspring were evaluated directly after weaning and 150 days after birth. Offspring from two dietary groups, high-protein diet during pregnancy and control diet during lactation (HPC), and control diet during pregnancy and high-protein diet during lactation (CHP), were compared with offspring (CC) from control-fed dams. Maternal CHP treatment was associated with sustained offspring growth retardation, but decreased numbers of affected hepatic genes in adults compared to weanlings. In contrast, offspring of the HPC group did not show persistent effects on growth parameters, but the number of affected hepatic genes was even increased at adult age. In both dietary groups, however, only a small subset of genes was affected in weanlings as well as in adults. We conclude that (1) prenatal and early postnatal maternal HP diet caused persistent, but (2) different effects and partially complementary trends on growth characteristics and on the hepatic transcriptome and associated pathways and that (3) only a small number of genes and associated upstream regulators might be involved in passing early diet-induced imprints to adulthood.

  5. Effects of long-term theophylline exposure on recovery of respiratory function and expression of adenosine A1 mRNA in cervical spinal cord hemisected adult rats.

    Science.gov (United States)

    Nantwi, Kwaku D; Basura, Gregory J; Goshgarian, Harry G

    2003-07-01

    Our lab has previously shown that when administered acutely, the methylxanthine theophylline can activate a latent respiratory motor pathway to restore function to the hemidiaphragm paralyzed by an ipsilateral C2 spinal cord hemisection. The recovery is mediated by the antagonism of CNS adenosine A1 receptors. The objective of the present study was to assess quantitatively recovery after chronic theophylline administration, the effects of weaning from the drug, and the effects of the drug on adenosine A1 receptor mRNA expression in adult rats subjected to a C2 hemisection. Rats subjected to a left C2 hemisection received theophylline orally for 3, 7, 12, or 30 days and were classified as 3D, 7D, 12D, or 30D respectively. Separate groups of 3D animals were weaned from drug administration for 7, 12, and 30 days before assessment of respiratory recovery. Additional groups of 7D and 12D animals were also weaned from drug administration for 7 and 12 days prior to assessment. Sham-operated controls received theophylline vehicle for similar periods. Quantitative assessment of recovered respiratory activity was conducted under standardized electrophysiologic recording conditions approximately 18 h after each drug application period. Serum theophylline analysis was conducted at the end of electrophysiologic recordings. Adenosine A1 receptor mRNA expression in the phrenic nucleus was assessed with in situ hybridization and immunohistochemistry. Chronic theophylline induced a dose-dependent effect on respiratory recovery over a serum theophylline range of 1.2-1.9 microg/ml. Recovery was characterized as respiratory-related activity in the left phrenic nerve and expressed as a percentage of activity in the homolateral nerve in noninjured animals under similar recording conditions. Recovered activity was 34.13 +/- 2.07, 55.89 +/- 2.96, 74.78 +/- 1.93, and 79.12 +/- 1.75% respectively in the 3D, 7D, 12D, and 30D groups. Theophylline-induced recovered activity persisted for as

  6. Adult mouse motor units develop almost all of their force in the subprimary range: a new all-or-none strategy for force recruitment?

    Science.gov (United States)

    Manuel, Marin; Heckman, C J

    2011-10-19

    Classical studies of the mammalian neuromuscular system have shown an impressive adaptation match between the intrinsic properties of motoneurons and the contractile properties of their motor units. In these studies, the rate at which motoneurons start to fire repetitively corresponds to the rate at which individual twitches start to sum, and the firing rate increases linearly with the amount of excitation ("primary range") up to the point where the motor unit develops its maximal force. This allows for the gradation of the force produced by a motor unit by rate modulation. In adult mouse motoneurons, however, we recently described a regime of firing ("subprimary range") that appears at lower excitation than what is required for the primary range, a finding that might challenge the classical conception. To investigate the force production of mouse motor units, we simultaneously recorded, for the first time, the motoneuron discharge elicited by intracellular ramps of current and the force developed by its motor unit. We showed that the motor unit developed nearly its maximal force during the subprimary range. This was found to be the case regardless of the input resistance of the motoneuron, the contraction speed, or the tetanic force of the motor unit. Our work suggests that force modulation in small mammals mainly relies on the number of motor units that are recruited rather than on rate modulation of individual motor units.

  7. Alteration of Gene Expression, DNA Methylation, and Histone Methylation in Free Radical Scavenging Networks in Adult Mouse Hippocampus following Fetal Alcohol Exposure.

    Directory of Open Access Journals (Sweden)

    Eric J Chater-Diehl

    Full Text Available The molecular basis of Fetal Alcohol Spectrum Disorders (FASD is poorly understood; however, epigenetic and gene expression changes have been implicated. We have developed a mouse model of FASD characterized by learning and memory impairment and persistent gene expression changes. Epigenetic marks may maintain expression changes over a mouse's lifetime, an area few have explored. Here, mice were injected with saline or ethanol on postnatal days four and seven. At 70 days of age gene expression microarray, methylated DNA immunoprecipitation microarray, H3K4me3 and H3K27me3 chromatin immunoprecipitation microarray were performed. Following extensive pathway analysis of the affected genes, we identified the top affected gene expression pathway as "Free radical scavenging". We confirmed six of these changes by droplet digital PCR including the caspase Casp3 and Wnt transcription factor Tcf7l2. The top pathway for all methylation-affected genes was "Peroxisome biogenesis"; we confirmed differential DNA methylation in the Acca1 thiolase promoter. Altered methylation and gene expression in oxidative stress pathways in the adult hippocampus suggests a novel interface between epigenetic and oxidative stress mechanisms in FASD.

  8. Alteration of Gene Expression, DNA Methylation, and Histone Methylation in Free Radical Scavenging Networks in Adult Mouse Hippocampus following Fetal Alcohol Exposure.

    Science.gov (United States)

    Chater-Diehl, Eric J; Laufer, Benjamin I; Castellani, Christina A; Alberry, Bonnie L; Singh, Shiva M

    2016-01-01

    The molecular basis of Fetal Alcohol Spectrum Disorders (FASD) is poorly understood; however, epigenetic and gene expression changes have been implicated. We have developed a mouse model of FASD characterized by learning and memory impairment and persistent gene expression changes. Epigenetic marks may maintain expression changes over a mouse's lifetime, an area few have explored. Here, mice were injected with saline or ethanol on postnatal days four and seven. At 70 days of age gene expression microarray, methylated DNA immunoprecipitation microarray, H3K4me3 and H3K27me3 chromatin immunoprecipitation microarray were performed. Following extensive pathway analysis of the affected genes, we identified the top affected gene expression pathway as "Free radical scavenging". We confirmed six of these changes by droplet digital PCR including the caspase Casp3 and Wnt transcription factor Tcf7l2. The top pathway for all methylation-affected genes was "Peroxisome biogenesis"; we confirmed differential DNA methylation in the Acca1 thiolase promoter. Altered methylation and gene expression in oxidative stress pathways in the adult hippocampus suggests a novel interface between epigenetic and oxidative stress mechanisms in FASD.

  9. Cytosolic Phospholipase A2 Protein as a Novel Therapeutic Target for Spinal Cord Injury

    Science.gov (United States)

    Liu, Nai-Kui; Deng, Ling-Xiao; Zhang, Yi Ping; Lu, Qing-Bo; Wang, Xiao-Fei; Hu, Jian-Guo; Oakes, Eddie; Bonventre, Joseph V; Shields, Christopher B; Xu, Xiao-Ming

    2014-01-01

    Objective The objective of this study was to investigate whether cytosolic phospholipase A2 (cPLA2), an important isoform of PLA2 that mediates the release of arachidonic acid, plays a role in the pathogenesis of spinal cord injury (SCI). Methods A combination of molecular, histological, immunohistochemical, and behavioral assessments were used to test whether blocking cPLA2 activation pharmacologically or genetically reduced cell death, protected spinal cord tissue, and improved behavioral recovery after a contusive SCI performed at the 10th thoracic level in adult mice. Results SCI significantly increased cPLA2 expression and activation. Activated cPLA2 was localized mainly in neurons and oligodendrocytes. Notably, the SCI-induced cPLA2 activation was mediated by the extracellular signal-regulated kinase signaling pathway. In vitro, activation of cPLA2 by ceramide-1-phosphate or A23187 induced spinal neuronal death, which was substantially reversed by arachidonyl trifluoromethyl ketone, a cPLA2 inhibitor. Remarkably, blocking cPLA2 pharmacologically at 30 minutes postinjury or genetically deleting cPLA2 in mice ameliorated motor deficits, and reduced cell loss and tissue damage after SCI. Interpretation cPLA2 may play a key role in the pathogenesis of SCI, at least in the C57BL/6 mouse, and as such could be an attractive therapeutic target for ameliorating secondary tissue damage and promoting recovery of function after SCI. PMID:24623140

  10. Notch Signaling Pathway Is Activated in Motoneurons of Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Gabriel Olmos

    2013-05-01

    Full Text Available Spinal muscular atrophy (SMA is a neurodegenerative disease produced by low levels of Survival Motor Neuron (SMN protein that affects alpha motoneurons in the spinal cord. Notch signaling is a cell-cell communication system well known as a master regulator of neural development, but also with important roles in the adult central nervous system. Aberrant Notch function is associated with several developmental neurological disorders; however, the potential implication of the Notch pathway in SMA pathogenesis has not been studied yet. We report here that SMN deficiency, induced in the astroglioma cell line U87MG after lentiviral transduction with a shSMN construct, was associated with an increase in the expression of the main components of Notch signaling pathway, namely its ligands, Jagged1 and Delta1, the Notch receptor and its active intracellular form (NICD. In the SMNΔ7 mouse model of SMA we also found increased astrocyte processes positive for Jagged1 and Delta1 in intimate contact with lumbar spinal cord motoneurons. In these motoneurons an increased Notch signaling was found, as denoted by increased NICD levels and reduced expression of the proneural gene neurogenin 3, whose transcription is negatively regulated by Notch. Together, these findings may be relevant to understand some pathologic attributes of SMA motoneurons.

  11. Regional localization of activin-βA, activin-βC, follistatin, proliferation, and apoptosis in adult and developing mouse prostate ducts.

    Science.gov (United States)

    Gold, Elspeth; Zellhuber-McMillan, Sylvia; Risbridger, Gail; Marino, Francesco Elia

    2017-01-01

    Activins and inhibins, members of the TGF-β superfamily, are growth and differentiation factors involved in the regulation of several biological processes, including reproduction, development, and fertility. Previous studies have shown that the activin-β A subunit plays a pivotal role in prostate development. Activin-A inhibits branching morphogenesis in the developing prostate, and its expression is associated with increased apoptosis in the adult prostate. Follistatin, a structurally unrelated protein to activins, is an antagonist of activin-A. A balance between endogenous activin-A and follistatin is required to maintain prostatic branching morphogenesis. Deregulation of this balance leads to branching inhibition or excessive branching and increased maturation of the stroma surrounding the differentiating epithelial ducts. Recent work identified another member of the TGF-β superfamily, the activin-β C subunit, as a novel antagonist of activin-A. Over-expression of activin-C (β C -β C ) alters prostate homeostasis, by interfering with the activin-A signaling. The current study characterized the spatiotemporal localization of activin-A, activin-C and follistatin in the adult and developing mouse prostate using immunohistochemical analysis. Results showed activin-C and follistatin are differentially expressed during prostate development and suggested that the antagonistic property of follistatin is secondary to the action of activin-C. In conclusion, the present study provides evidence to support a role of activin-C in prostate development and provides new insights in the spatiotemporal localization of activins and their antagonists during mouse prostate development. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Development and regulation of response properties in spinal cord motoneurons

    DEFF Research Database (Denmark)

    Perrier, J F; Hounsgaard, J

    2000-01-01

    vertebrates in terms of both phylogeny and ontogeny. Spinal motoneurons in adults are remarkably similar in many respects ranging from the resting membrane potential to pacemaker properties. Apart from the axolotls, spinal motoneurons from all species investigated have latent intrinsic response properties...

  13. Adult Brtl/+ mouse model of osteogenesis imperfecta demonstrates anabolic response to sclerostin antibody treatment with increased bone mass and strength.

    Science.gov (United States)

    Sinder, B P; White, L E; Salemi, J D; Ominsky, M S; Caird, M S; Marini, J C; Kozloff, K M

    2014-08-01

    Treatments to reduce fracture rates in adults with osteogenesis imperfecta are limited. Sclerostin antibody, developed for treating osteoporosis, has not been explored in adults with OI. This study demonstrates that treatment of adult OI mice respond favorably to sclerostin antibody therapy despite retention of the OI-causing defect. Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk. Although OI fracture risk is greatest before puberty, adults with OI remain at risk of fracture. Antiresorptive bisphosphonates are commonly used to treat adult OI, but have shown mixed efficacy. New treatments which consistently improve bone mass throughout the skeleton may improve patient outcomes. Neutralizing antibodies to sclerostin (Scl-Ab) are a novel anabolic therapy that have shown efficacy in preclinical studies by stimulating bone formation via the canonical wnt signaling pathway. The purpose of this study was to evaluate Scl-Ab in an adult 6 month old Brtl/+ model of OI that harbors a typical heterozygous OI-causing Gly > Cys substitution on Col1a1. Six-month-old WT and Brtl/+ mice were treated with Scl-Ab (25 mg/kg, 2×/week) or Veh for 5 weeks. OCN and TRACP5b serum assays, dynamic histomorphometry, microCT and mechanical testing were performed. Adult Brtl/+ mice demonstrated a strong anabolic response to Scl-Ab with increased serum osteocalcin and bone formation rate. This anabolic response led to improved trabecular and cortical bone mass in the femur. Mechanical testing revealed Scl-Ab increased Brtl/+ femoral stiffness and strength. Scl-Ab was successfully anabolic in an adult Brtl/+ model of OI.

  14. Spinal Cord Injury 101

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    Full Text Available ... About Media Donate Spinal Cord Injury Medical Expert Videos ... Home Kim Eberhardt Muir, MS Coping with a New Injury Robin Dorman, PsyD Sex and Fertility After Spinal Cord Injury Diane M. ...

  15. Spinal Cord Injury 101

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    Full Text Available ... of Spinal Cord Injury Rehabilitation Kristine Cichowski, MS Occupational Therapy after Spinal Cord Injury Katie Powell, OT ... does not provide medical advice, recommend or endorse health care products or services, or control the information ...

  16. Spinal Cord Dysfunction (SCD)

    Data.gov (United States)

    Department of Veterans Affairs — The Spinal Cord Dysfunction (SCD) module supports the maintenance of local and national registries for the tracking of patients with spinal cord injury and disease...

  17. Spinal Cord Injury 101

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    Full Text Available ... OT Anne Bryden, OT The Role of the Social Worker after Spinal Cord Injury Patti Rogers, SW Marguerite ... play_arrow What are the latest developments in the use of electrical stimulation for spinal ...

  18. Spinal Cord Injury 101

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    Full Text Available ... with SCI Personal Experiences by Topic Resources Peer Counseling Blog About Media Donate close search Understanding Spinal ... with SCI Personal Experiences by Topic Resources Peer Counseling Blog About Media Donate Spinal Cord Injury Medical ...

  19. Spinal Cord Injury 101

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    Full Text Available ... Injury Facts and Figures Care and Treatment After SCI Spinal Cord Injury Rehabilitation Pediatric Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal Experiences ...

  20. Spinal Cord Injury 101

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    Full Text Available ... Cord Injury Rehabilitation Pediatric Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal ... Cord Injury Rehabilitation Pediatric Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal ...

  1. Spinal Cord Injury 101

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    Full Text Available ... of spinal cord injuries? play_arrow What does stem-cell research on animals tell us? play_arrow When can we expect stem-cell treatments to become available for spinal cord injuries? ...

  2. Spinal Cord Injury 101

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    Full Text Available ... spinal cord injuries? play_arrow What does stem-cell research on animals tell us? play_arrow When can we expect stem-cell treatments to become available for spinal cord injuries? ...

  3. Spinal Cord Injury 101

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    Full Text Available ... Resources Peer Counseling Blog About Media Donate close search Understanding Spinal Cord Injury What is a Spinal ... health care products or services, or control the information found on external websites. The Hill Foundation is ...

  4. Spinal Cord Injury 101

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    Full Text Available ... Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal Experiences by Topic Resources ... Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal Experiences by Topic Resources ...

  5. Spinal Cord Injury 101

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    Full Text Available ... play_arrow What are the chances of regaining feeling and mobility after a spinal cord injury? play_arrow How long does it usually take for feeling and movement to return after a spinal cord ...

  6. Spinal Cord Injury 101

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    Full Text Available ... RN Pediatric Injuries Pediatric Spinal Cord Injury 101 Lawrence Vogel, MD The Basics of Pediatric SCI Rehabilitation ... Rogers, PT Recreational Therapy after Spinal Cord Injury Jennifer Piatt, PhD David Chen, MD Read Bio Medical ...

  7. Spinal Cord Injury 101

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    Full Text Available ... Disabilities Photography by Rona Talcott Website by Mobile Marketing LLC Understanding Spinal Cord Injury About Us Expert Videos Contact Us Personal Experience Videos Blog Videos By Topic Media Resources Donate to support families facing spinal cord ...

  8. Spinal cord stimulation

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007560.htm Spinal cord stimulation To use the sharing features on this page, please enable JavaScript. Spinal cord stimulation is a treatment for pain that uses ...

  9. Spinal Cord Injury 101

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    Full Text Available ... Spinal Cord Injury 101 David Chen, MD Preventing Pressure Sores Mary Zeigler, MS Transition from Hospital to ... a spinal cord injury? play_arrow Why are high-dose steroids often used right after an injury? ...

  10. Tet2 Rescues Age-Related Regenerative Decline and Enhances Cognitive Function in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Geraldine Gontier

    2018-02-01

    Full Text Available Restoring adult stem cell function provides an exciting approach for rejuvenating the aging brain. However, molecular mechanisms mediating neurogenic rejuvenation remain elusive. Here we report that the enzyme ten eleven translocation methylcytosine dioxygenase 2 (Tet2, which catalyzes the production of 5-hydroxymethylcytosine (5hmC, rescues age-related decline in adult neurogenesis and enhances cognition in mice. We detected a decrease in Tet2 expression and 5hmC levels in the aged hippocampus associated with adult neurogenesis. Mimicking an aged condition in young adults by abrogating Tet2 expression within the hippocampal neurogenic niche, or adult neural stem cells, decreased neurogenesis and impaired learning and memory. In a heterochronic parabiosis rejuvenation model, hippocampal Tet2 expression was restored. Overexpressing Tet2 in the hippocampal neurogenic niche of mature adults increased 5hmC associated with neurogenic processes, offset the precipitous age-related decline in neurogenesis, and enhanced learning and memory. Our data identify Tet2 as a key molecular mediator of neurogenic rejuvenation.

  11. Spinal segmental dysgenesis

    Directory of Open Access Journals (Sweden)

    N Mahomed

    2009-06-01

    Full Text Available Spinal segmental dysgenesis is a rare congenital spinal abnormality , seen in neonates and infants in which a segment of the spine and spinal cord fails to develop normally . The condition is segmental with normal vertebrae above and below the malformation. This condition is commonly associated with various abnormalities that affect the heart, genitourinary, gastrointestinal tract and skeletal system. We report two cases of spinal segmental dysgenesis and the associated abnormalities.

  12. Spinal Cord Injury 101

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    Full Text Available ... the spinal cord work? play_arrow Why is the level of a spinal cord injury important? play_arrow What role does “compression” play in a spinal cord injury? play_arrow Why are high-dose steroids often used right after an injury? play_arrow What is meant ...

  13. Spinal Cord Injury 101

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    Full Text Available ... arrow What is the “Spinal Cord Injury Model Systems” program? play_arrow What are the most promising new treatments for spinal cord injuries? play_arrow What are the latest developments in the use of electrical stimulation for spinal cord injuries? play_arrow ...

  14. Spinal Cord Injuries

    Science.gov (United States)

    ... forth between your body and your brain. A spinal cord injury disrupts the signals. Spinal cord injuries usually begin with a blow that fractures or ... down on the nerve parts that carry signals. Spinal cord injuries can be complete or incomplete. With a complete ...

  15. Spinal Cord Injury 101

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    Full Text Available ... injury? play_arrow How does the spinal cord work? play_arrow Why is the level of a spinal cord injury important? play_arrow What role does “compression” play in a spinal cord injury? play_arrow Why are high-dose steroids often used right after an injury? play_arrow What is meant ...

  16. Tissue distribution and developmental expression of type XVI collagen in the mouse.

    Science.gov (United States)

    Lai, C H; Chu, M L

    1996-04-01

    The expression of a recently identified collagen, alpha 1 (XVI), in adult mouse tissue and developing mouse embryo was examined by immunohistochemistry and in situ hybridization. A polyclonal antiserum was raised against a recombinant fusion protein, which contained a segment of 161 amino acids in the N-terminal noncollagenous domain of the human alpha 1 (XVI) collagen. Immunoprecipitation of metabolically labelled human or mouse fibroblast cell lysates with this antibody revealed a major, bacterial collagenase sensitive polypeptide of approximately 210 kDa. The size agrees with the prediction from the full-length cDNA. Immunofluorescence examination of adult mouse tissues using the affinity purified antibody revealed a rather broad distribution of the protein. The heart, kidney, intestine, ovary, testis, eye, arterial walls and smooth muscles all exhibited significant levels of expression, while the skeletal muscle, lung and brain showed very restricted and low signals. During development, no significant expression of the mRNA or protein was observed in embryo of day 8 of gestation, but strong signals was detected in placental trophoblasts. Expression in embryos was detectable first after day 11 of gestation with weak positive signals appearing in the heart. In later stages of development, stronger RNA hybridizations were observed in a variety of tissues, particularly in atrial and ventricular walls of the developing heart, spinal root neural fibers and skin. These data demonstrate that type XVI collagen represents another collagenous component widely distributed in the extracellular matrix and may contribute to the structural integrity of various tissues.

  17. GABA, not glycine, mediates inhibition of latent respiratory motor pathways after spinal cord injury

    OpenAIRE

    Zimmer, M. Beth; Goshgarian, Harry G.

    2006-01-01

    Previous work has shown that latent respiratory motor pathways known as crossed phrenic pathways are inhibited via a spinal inhibitory process; however, the underlying mechanisms remain unknown. The present study investigated whether spinal GABA-A and/or glycine receptors are involved in the inhibition of the crossed phrenic pathways after a C2 spinal cord hemisection injury. Under ketamine/xylazine anesthesia, adult, female, Sprague Dawley rats were hemisected at the C2 spinal cord level. Fo...

  18. POSTNATAL PHENOTYPE AND LOCALIZATION OF SPINAL CORD V1 DERIVED INTERNEURONS

    Science.gov (United States)

    Alvarez, Francisco J.; Jonas, Philip C.; Sapir, Tamar; Hartley, Robert; Berrocal, Maria C.; Geiman, Eric J.; Todd, Andrew J.; Goulding, Martyn

    2010-01-01

    Developmental studies identified four classes (V0, V1, V2, V3) of embryonic interneurons in the ventral spinal cord. Very little however is known about their adult phenotypes. In order to further characterize interneuron cell types in the adult, the location, neurotransmitter phenotype, calcium-buffering protein expression and axon distributions of V1-derived neurons in the mouse spinal cord was determined. In the mature (P20 and older) spinal cord, most V1-derived neurons are located in lateral LVII and in LIX, few in medial LVII and none in LVIII. Approximately 40% express calbindin and/or parvalbumin, while few express calretinin. Of seven groups of ventral interneurons identified according to calcium-buffering protein expression, two groups (1 and 4) correspond with V1-derived neurons. Group 1 are Renshaw cells and intensely express calbindin and coexpress parvalbumin and calretinin. They represent 9% of the V1 population. Group 4 express only parvalbumin and represent 27% of V1-derived neurons. V1-derived group 4 neurons receive contacts from primary sensory afferents and are therefore proprioceptive interneurons and the most ventral neurons in this group receive convergent calbindin-IR Renshaw cell inputs. This subgroup resembles Ia inhibitory interneurons (IaINs) and represents 13% of V1-derived neurons. Adult V1-interneuron axons target LIX and LVII and some enter the deep dorsal horn. V1-axons do not cross the midline. V1 derived axonal varicosities were mostly (>80%) glycinergic and a third were GABAergic. None were glutamatergic or cholinergic. In summary, V1 interneurons develop into ipsilaterally projecting, inhibitory interneurons that include Renshaw cells, Ia inhibitory interneurons and other unidentified proprioceptive interneurons. PMID:16255029

  19. Adult-Onset Fluoxetine Treatment Does Not Improve Behavioral Impairments and May Have Adverse Effects on the Ts65Dn Mouse Model of Down Syndrome

    Directory of Open Access Journals (Sweden)

    Markus Heinen

    2012-01-01

    Full Text Available Down syndrome is caused by triplication of chromosome 21 and is associated with neurocognitive phenotypes ranging from severe intellectual disability to various patterns of more selective neuropsychological deficits, including memory impairments. In the Ts65Dn mouse model of Down syndrome, excessive GABAergic neurotransmission results in local over-inhibition of hippocampal circuits, which dampens hippocampal synaptic plasticity and contributes to cognitive impairments. Treatments with several GABAA receptor antagonists result in increased plasticity and improved memory deficits in Ts65Dn mice. These GABAA receptor antagonists are, however, not suitable for clinical applications. The selective serotonin reuptake inhibitor fluoxetine, in contrast, is a widely prescribed antidepressant that can also enhance plasticity in the adult rodent brain by lowering GABAergic inhibition. For these reasons, we wondered if an adult-onset 4-week oral fluoxetine treatment restores spatial learning and memory impairments in Ts65Dn mice. Fluoxetine did not measurably improve behavioral impairments of Ts65Dn mice. On the contrary, we observed seizures and mortality in fluoxetine-treated Ts65Dn mice, raising the possibility of a drug × genotype interaction with respect to these adverse treatment outcomes. Future studies should re-address this in larger animal cohorts and determine if fluoxetine treatment is associated with adverse treatment effects in individuals with Down syndrome.

  20. Selective Deletion of Sodium Salt Taste during Development Leads to Expanded Terminal Fields of Gustatory Nerves in the Adult Mouse Nucleus of the Solitary Tract.

    Science.gov (United States)

    Sun, Chengsan; Hummler, Edith; Hill, David L

    2017-01-18

    Neuronal activity plays a key role in the development of sensory circuits in the mammalian brain. In the gustatory system, experimental manipulations now exist, through genetic manipulations of specific taste transduction processes, to examine how specific taste qualities (i.e., basic tastes) impact the functional and structural development of gustatory circuits. Here, we used a mouse knock-out model in which the transduction component used to discriminate sodium salts from other taste stimuli was deleted in taste bud cells throughout development. We used this model to test the hypothesis that the lack of activity elicited by sodium salt taste impacts the terminal field organization of nerves that carry taste information from taste buds to the nucleus of the solitary tract (NST) in the medulla. The glossopharyngeal, chorda tympani, and greater superficial petrosal nerves were labeled to examine their terminal fields in adult control mice and in adult mice in which the α-subunit of the epithelial sodium channel was conditionally deleted in taste buds (αENaC knockout). The terminal fields of all three nerves in the NST were up to 2.7 times greater in αENaC knock-out mice compared with the respective field volumes in control mice. The shapes of the fields were similar between the two groups; however, the density and spread of labels were greater in αENaC knock-out mice. Overall, our results show that disruption of the afferent taste signal to sodium salts disrupts the normal age-dependent "pruning" of all terminal fields, which could lead to alterations in sensory coding and taste-related behaviors. Neural activity plays a major role in the development of sensory circuits in the mammalian brain. To date, there has been no direct test of whether taste-elicited neural activity has a role in shaping central gustatory circuits. However, recently developed genetic tools now allow an assessment of how specific taste stimuli, in this case sodium salt taste, play a role

  1. The role of long-term label-retaining cells in the regeneration of adult mouse kidney after ischemia/reperfusion injury.

    Science.gov (United States)

    Liu, Xiangchun; Liu, Haiying; Sun, Lina; Chen, Zhixin; Nie, Huibin; Sun, Aili; Liu, Gang; Guan, Guangju

    2016-04-30

    Label-retaining cells (LRCs) have been recognized as rare stem and progenitor-like cells, but their complex biological features in renal repair at the cellular level have never been reported. This study was conducted to evaluate whether LRCs in kidney are indeed renal stem/progenitor cells and to delineate their potential role in kidney regeneration. We utilized a long-term pulse chase of 5-bromo-2'-deoxyuridine (BrdU)-labeled cells in C57BL/6J mice to identify renal LRCs. We tracked the precise morphological characteristics and locations of BrdU(+)LRCs by both immunohistochemistry and immunofluorescence. To examine whether these BrdU(+)LRCs contribute to the repair of acute kidney injury, we analyzed biological characteristics of BrdU(+)LRCs in mice after ischemia/reperfusion (I/R) injury. The findings revealed that the nuclei of BrdU(+) LRCs exhibited different morphological characteristics in normal adult kidneys, including nuclei in pairs or scattered, fragmented or intact, strongly or weakly positive. Only 24.3 ± 1.5 % of BrdU(+) LRCs co-expressed with Ki67 and 9.1 ± 1.4 % of BrdU(+) LRCs were positive for TUNEL following renal I/R injury. Interestingly, we found that newly regenerated cells formed a niche-like structure and LRCs in pairs tended to locate in this structure, but the number of those LRCs was very low. We found a few scattered LRCs co-expressed Lotus tetragonolobus agglutinin (LTA) in the early phase of injury, suggesting differentiation of those LRCs in mouse kidney. Our findings suggest that LRCs are not a simple type of slow-cycling cells in adult kidneys, indicating a limited role of these cells in the regeneration of I/R injured kidney. Thus, LRCs cannot reliably be considered stem/progenitor cells in the regeneration of adult mouse kidney. When researchers use this technique to study the cellular basis of renal repair, these complex features of renal LRCs and the purity of real stem cells among renal LRCs should be considered.

  2. Moderate activation of IKK2-NF-kB in unstressed adult mouse liver induces cytoprotective genes and lipogenesis without apparent signs of inflammation or fibrosis.

    Science.gov (United States)

    Lu, Hong; Lei, Xiaohong; Zhang, Qinghao

    2015-07-30

    The NF-kB signaling, regulated by IKK1-p52/RelB and IKK2-p65, is activated by various stresses to protect or damage the liver, in context-specific manners. Two previous studies of liver-specific expression of constitutive active IKK2 (IKK2ca) showed that strong activation of IKK2-NF-kB in mouse livers caused inflammation, insulin resistance, and/or fibrosis. The purpose of this study was to understand how moderate activation of IKK2-NF-kB in adult mouse livers alters hepatic gene expression and pathophysiology. We generated mice with adult hepatocyte-specific activation of Ikk2 (Liv-Ikk2ca) using Alb-cre mice and Ikk2ca Rosa26 knockin mice in which a moderate expression of Ikk2ca transgene was driven by the endogenous Rosa26 promoter. Surprisingly, compared to wild-type mice, adult male Liv-Ikk2ca mice had higher hepatic mRNA expression of Ikk2 and classical NF-kB targets (e.g. Lcn2 and A20), as well as IKK1, NIK, and RelB, but no changes in markers of inflammation or fibrosis. Blood levels of IL-6 and MCP-1 remained unchanged, and histology analysis showed a lack of injury or infiltration of inflammatory cells in livers of Liv-Ikk2ca mice. Moreover, Liv-Ikk2ca mice had lower mRNA expression of prooxidative enzymes Cyp2e1 and Cyp4a14, higher expression of antioxidative enzymes Sod2, Gpx1, and Nqo1, without changes in key enzymes for fatty acid oxidation, glucose utilization, or gluconeogenesis. In parallel, Liv-Ikk2ca mice and wild-type mice had similar levels of hepatic reduced glutathione, endogenous reactive oxygen species, and lipid peroxidation. Additionally, Liv-Ikk2ca mice had higher Cyp3a11 without down-regulation of most drug processing genes. Regarding nuclear proteins of NF-kB subunits, Liv-Ikk2ca mice had moderately higher p65 and p50 but much higher RelB. Results of ChIP-qPCR showed that the binding of p50 to multiple NF-kB-target genes was markedly increased in Liv-Ikk2ca mice. Additionally, Liv-Ikk2ca mice had moderate increase in triglycerides in

  3. Are there endogenous stem cells in the spinal cord?

    Science.gov (United States)

    Ferrucci, Michela; Ryskalin, Larisa; Busceti, Carla L; Gaglione, Anderson; Biagioni, Francesca; Fornai, Francesco

    2017-12-01

    Neural progenitor cells (NPC) represent the stem-like niche of the central nervous system that maintains a regenerative potential also in the adult life. Despite NPC in the brain are well documented, the presence of NPC in the spinal cord has been controversial for a long time. This is due to a scarce activity of NPC within spinal cord, which also makes difficult their identification. The present review recapitulates the main experimental studies, which provided evidence for the occurrence of NPC within spinal cord, with a special emphasis on spinal cord injury and amyotrophic lateral sclerosis. By using experimental models, here we analyse the site-specificity, the phenotype and the main triggers of spinal cord NPC. Moreover, data are reported on the effect of specific neurogenic stimuli on these spinal cord NPC in an effort to comprehend the endogenous neurogenic potential of this stem cell niche.

  4. Spinal osteomyelitis caused by Proteus mirabilis in a child

    NARCIS (Netherlands)

    deWeerd, W; Kimpen, JLL; Miedema, CJ

    Osteomyelitis due to Proteus mirabilis is rare. Spinal osteomyelitis caused by this organism has only been described in adults. This is the first paediatric case of P. mirabilis vertebral osteomyelitis.

  5. Trauma: Spinal Cord Injury.

    Science.gov (United States)

    Eckert, Matthew J; Martin, Matthew J

    2017-10-01

    Injuries to the spinal column and spinal cord frequently occur after high-energy mechanisms of injury, or with lower-energy mechanisms, in select patient populations like the elderly. A focused yet complete neurologic examination during the initial evaluation will guide subsequent diagnostic procedures and early supportive measures to help prevent further injury. For patients with injury to bone and/or ligaments, the initial focus should be spinal immobilization and prevention of inducing injury to the spinal cord. Spinal cord injury is associated with numerous life-threatening complications during the acute and long-term phases of care that all acute care surgeons must recognize. Published by Elsevier Inc.

  6. Human spinal motor control

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo

    2016-01-01

    Human studies in the past three decades have provided us with an emerging understanding of how cortical and spinal networks collaborate to ensure the vast repertoire of human behaviors. We differ from other animals in having direct cortical connections to spinal motoneurons, which bypass spinal...... the central motor command by opening or closing sensory feedback pathways. In the future, human studies of spinal motor control, in close collaboration with animal studies on the molecular biology of the spinal cord, will continue to document the neural basis for human behavior. Expected final online...

  7. Amplification of R-spondin1 signaling induces granulosa cell fate defects and cancers in mouse adult ovary

    NARCIS (Netherlands)

    De Cian, M-C; Pauper, E.; Bandiera, R.; Vidal, V. P. I.; Sacco, S.; Gregoire, E. P.; Chassot, A-A; Panzolini, C.; WILHELM, D; Pailhoux, E.; Youssef, Sameh A.; de Bruin, A.; Teerds, K.; Schedl, A.; Gillot, I.; Chaboissier, M-C

    2017-01-01

    R-spondin1 is a secreted regulator of WNT signaling, involved in both embryonic development and homeostasis of adult organs. It can have a dual role, acting either as a mitogen or as a tumor suppressor. During ovarian development, Rspo1 is a key factor required for sex determination and

  8. International Spinal Cord Injury

    DEFF Research Database (Denmark)

    Dvorak, M F; Itshayek, E; Fehlings, M G

    2015-01-01

    STUDY DESIGN: Survey of expert opinion, feedback and final consensus. OBJECTIVE: To describe the development and the variables included in the International Spinal Cord Injury (SCI) Spinal Interventions and Surgical Procedures Basic Data set. SETTING: International working group. METHODS......: A committee of experts was established to select and define data elements. The data set was then disseminated to the appropriate committees and organizations for comments. All suggested revisions were considered and both the International Spinal Cord Society and the American Spinal Injury Association endorsed...... spinal intervention and procedure is coded (variables 1 through 7) and the spinal segment level is described (variables 8 and 9). Sample clinical cases were developed to illustrate how to complete it. CONCLUSION: The International SCI Spinal Interventions and Surgical Procedures Basic Data Set...

  9. Dose of Phenobarbital and Age of Treatment at Early Life are Two Key Factors for the Persistent Induction of Cytochrome P450 Enzymes in Adult Mouse Liver.

    Science.gov (United States)

    Tien, Yun-Chen; Liu, Ke; Pope, Chad; Wang, Pengcheng; Ma, Xiaochao; Zhong, Xiao-bo

    2015-12-01

    Drug treatment of neonates and infants and its long-term consequences on drug responses have emerged in recent years as a major challenge for health care professionals. In the current study, we use phenobarbital as a model drug and mouse as an in vivo model to demonstrate that the dose of phenobarbital and age of treatment are two key factors for the persistent induction of gene expression and consequential increases of enzyme activities of Cyp2b, Cyp2c, and Cyp3a in adult livers. We show that phenobarbital treatment at early life of day 5 after birth with a low dose (phenobarbital treatment with a high dose (>200 mg/kg) significantly increases expression and enzyme activities of these P450s in adult liver. We also demonstrate that phenobarbital treatment before day 10 after birth, but not at later ages, significantly increases mRNAs, proteins, and enzyme activities of the tested P450s. Such persistent induction of P450 gene expression and enzyme activities in adult livers by phenobarbital treatment only occurs within a sensitive age window early in life. The persistent induction in gene expression and enzyme activities is higher in female mice than in male mice for Cyp2b10 but not for Cyp2c29 and Cyp3a11. These results will stimulate studies to evaluate the long-term impacts of drug treatment with different doses at neonatal and infant ages on drug metabolism, therapeutic efficacy, and drug-induced toxicity throughout the rest of life. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  10. Lead induces similar gene expression changes in brains of gestationally exposed adult mice and in neurons differentiated from mouse embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Francisco Javier Sánchez-Martín

    Full Text Available Exposure to environmental toxicants during embryonic life causes changes in the expression of developmental genes that may last for a lifetime and adversely affect the exposed individual. Developmental exposure to lead (Pb, an ubiquitous environmental contaminant, causes deficits in cognitive functions and IQ, behavioral effects, and attention deficit hyperactivity disorder (ADHD. Long-term effects observed after early life exposure to Pb include reduction of gray matter, alteration of myelin structure, and increment of criminal behavior in adults. Despite growing research interest, the molecular mechanisms responsible for the effects of lead in the central nervous system are still largely unknown. To study the molecular changes due to Pb exposure during neurodevelopment, we exposed mice to Pb in utero and examined the expression of neural markers, neurotrophins, transcription factors and glutamate-related genes in hippocampus, cortex, and thalamus at postnatal day 60. We found that hippocampus was the area where gene expression changes due to Pb exposure were more pronounced. To recapitulate gestational Pb exposure in vitro, we differentiated mouse embryonic stem cells (ESC into neurons and treated ESC-derived neurons with Pb for the length of the differentiation process. These neurons expressed the characteristic neuronal markers Tubb3, Syp, Gap43, Hud, Ngn1, Vglut1 (a marker of glutamatergic neurons, and all the glutamate receptor subunits, but not the glial marker Gafp. Importantly, several of the changes observed in Pb-exposed mouse brains in vivo were also observed in Pb-treated ESC-derived neurons, including those affecting expression of Ngn1, Bdnf exon IV, Grin1, Grin2D, Grik5, Gria4, and Grm6. We conclude that our ESC-derived model of toxicant exposure during neural differentiation promises to be a useful model to analyze mechanisms of neurotoxicity induced by Pb and other environmental agents.

  11. Characterization of Aromatase Expression in the Adult Male and Female Mouse Brain. I. Coexistence with Oestrogen Receptors α and β, and Androgen Receptors

    Science.gov (United States)

    Stanić, Davor; Dubois, Sydney; Chua, Hui Kheng; Tonge, Bruce; Rinehart, Nicole; Horne, Malcolm K.; Boon, Wah Chin

    2014-01-01

    Aromatase catalyses the last step of oestrogen synthesis. There is growing evidence that local oestrogens influence many brain regions to modulate brain development and behaviour. We examined, by immunohistochemistry, the expression of aromatase in the adult male and female mouse brain, using mice in which enhanced green fluorescent protein (EGFP) is transcribed following the physiological activation of the Cyp19A1 gene. EGFP-immunoreactive processes were distributed in many brain regions, including the bed nucleus of the stria terminalis, olfactory tubercle, medial amygdaloid nucleus and medial preoptic area, with the densest distributions of EGFP-positive cell bodies in the bed nucleus and medial amygdala. Differences between male and female mice were apparent, with the density of EGFP-positive cell bodies and fibres being lower in some brain regions of female mice, including the bed nucleus and medial amygdala. EGFP-positive cell bodies in the bed nucleus, lateral septum, medial amygdala and hypothalamus co-expressed oestrogen receptor (ER) α and β, or the androgen receptor (AR), although single-labelled EGFP-positive cells were also identified. Additionally, single-labelled ERα−, ERβ- or AR-positive cell bodies often appeared to be surrounded by EGFP-immunoreactive nerve fibres/terminals. The widespread distribution of EGFP-positive cell bodies and fibres suggests that aromatase signalling is common in the mouse brain, and that locally synthesised brain oestrogens could mediate biological effects by activating pre- and post-synaptic oestrogen α and β receptors, and androgen receptors. The higher number of EGFP-positive cells in male mice may indicate that the autocrine and paracrine effects of oestrogens are more prominent in males than females. PMID:24646567

  12. Sex-comparative study of mouse cerebellum physiology under adult-onset hypothyroidism: The significance of GC-MS metabolomic data normalization in meta-analysis.

    Science.gov (United States)

    Maga-Nteve, Christoniki; Vasilopoulou, Catherine G; Constantinou, Caterina; Margarity, Marigoula; Klapa, Maria I

    2017-01-15

    A systematic data quality validation and normalization strategy is an important component of the omic profile meta-analysis, ensuring comparability of the profiles and exclusion of experimental biases from the derived biological conclusions. In this study, we present the normalization methodology applied on the sets of cerebellum gas chromatography-mass spectrometry metabolic profiles of 124days old male and female animals in an adult-onset-hypothyroidism (AOH) mouse model before combining them into a sex-comparative analysis. The employed AOH model concerns the monitoring of the brain physiology of Balb/cJ mice after eight-week administration of 1%w/v KClO 4 in the drinking water, initiated on the 60th day of their life. While originating from the same animal study, the tissues of the two sexes were processed and their profiles acquired and analyzed at different time periods. Hence, the previously published profile set of male mice was first re-annotated based on the presently available resources. Then, after being validated as acquired under the same analytical conditions, both profiles sets were corrected for derivatization biases and filtered for low-confidence measurements based on the same criteria. The final normalized 73-metabolite profiles contribute to the currently few available omic datasets of the AOH effect on brain molecular physiology, especially with respect to sex differentiation. Multivariate statistical analysis indicated one (unknown) and three (succinate, benzoate, myristate) metabolites with significantly higher and lower, respectively, cerebellum concentration in the hypothyroid compared to the euthyroid female mice. The respective numbers for the males were two and 24. Comparison of the euthyroid cerebellum metabolic profiles between the two sexes indicated 36 metabolites, including glucose, myo- and scyllo-inositol, with significantly lower concentration in the females versus the males. This implies that the female mouse cerebellum has

  13. OCAM regulates embryonic spinal cord stem cell proliferation by modulating ErbB2 receptor.

    Directory of Open Access Journals (Sweden)

    Loïc Deleyrolle

    Full Text Available The proliferation and differentiation of neural stem cells are tightly controlled by intrinsic and extrinsic cues. Cell adhesion molecules are increasingly recognized as regulators of these processes. Here we report the expression of the olfactory cell adhesion molecule (OCAM/NCAM2/RNCAM during mouse spinal cord development and in neural stem cells cultured as neurospheres. OCAM is also weakly expressed in the dormant adult stem cell niche around the central canal and is overexpressed after spinal cord injury. Both transmembrane (TM and glycosylphosphatidylinositol (GPI-linked isoforms are present in neurospheres. Electron microscopy and internalisation experiments revealed a dynamic trafficking of OCAM between the membrane and intracellular compartments. After differentiation, OCAM remains in neurons and oligodendrocytes whereas no expression is detected in astrocytes. Using OCAM knockout (KO mice, we found that mutant spinal cord stem cells showed an increased proliferation and self-renewal rates although no effect on differentiation was observed. This effect was reversed by lentivirus-mediated re-introduction of OCAM. Mechanistically, we identified the ErbB2/Neu/HER2 protein as being implicated in the enhanced proliferation of mutant cells. ErbB2 protein expression and phosphorylation level were significantly increased in KO cells whereas no difference was observed at the mRNA level. Overexpression of ErbB2 in wild-type and mutant cells also increased their growth while reintroduction of OCAM in mutant cells reduced the level of phosphorylated ErbB2. These results indicate that OCAM exerts a posttranscriptional control on the ErbB2 signalling in spinal cord stem cells. This study adds further support for considering cell adhesion molecules as regulators of the ErbB signalling.

  14. SPINAL CORD- A CADAVERIC STUDY

    Directory of Open Access Journals (Sweden)

    Vijayamma K. N

    2018-01-01

    Full Text Available BACKGROUND Spinal cord is situated within the vertebral canal extending from the lower end of the medulla oblongata at the upper border of first cervical vertebra. In early foetal life, it extends throughout the length of the vertebral canal, and at the time of birth, it reaches the level of third lumbar vertebra. In adult, it ends at the lower border of first lumbar vertebra and thereafter continued as filum terminale, which gets attached to tip of coccyx. Spinal cord is covered by three protective membranes called spinal meninges, diameter, arachnoid and pia mater. The diameter and arachnoid mater extent up to second sacral vertebra and the pia mater forms filum terminale and extend at the tip of coccyx. MATERIALS AND METHODS Forty spinal cord cadaveric specimen were studied by dissection method after exposing the vertebral canal. The roots of spinal nerve were sectioned on both sides and the cord is released along with its coverings. The dura and arachnoid mater were incised longitudinally and the subarachnoid space, blood vessels, nerve roots, ligament denticulata, cervical and lumbar enlargements were observed. The blood vessels including radicular arteries were also studied photographed. RESULTS The spinal cord is a highly vascular structure situated within the vertebral canal, covered by diameter, arachnoid mater and pia mater. Spinal dura is thicker anteriorly than posteriorly. The pia mater forms linea splendens, which extend along the whole length of the cord in front of the anterior median fissure. The average length of the cord is 38 cm. The length and breadth of cervical enlargement was more compared to lumbar enlargement. The number of rootlets in both dorsal and ventral roots accounts more in cervical compared to other regions of the cord. The ligament denticulata is a thin transparent bands of pia mater attached on either sides of the cord between the dorsal and ventral roots of spinal nerves. The tooth like extensions are well

  15. Adult Mouse DRG Explant and Dissociated Cell Models to Investigate Neuroplasticity and Responses to Environmental Insults Including Viral Infection.

    Science.gov (United States)

    Fornaro, Michele; Sharthiya, Harsh; Tiwari, Vaibhav

    2018-03-09

    This protocol describes an ex vivo model of mouse-derived dorsal root ganglia (DRG) explant and in vitro DRG-derived co-culture of dissociated sensory neurons and glial satellite cells. These are useful and versatile models to investigate a variety of biological responses associated with physiological and pathological conditions of the peripheral nervous system (PNS) ranging from neuron-glial interaction, neuroplasticity, neuroinflammation, and viral infection. The usage of DRG explant is scientifically advantageous compared to simplistic single cells models for multiple reasons. For instance, as an organotypic culture, the DRG explant allows ex vivo transfer of an entire neuronal network including the extracellular microenvironment that play a significant role in all the neuronal and glial functions. Further, DRG explants can also be maintained ex vivo for several days and the culture conditions can be perturbed as desired. In addition, the harvested DRG can be further dissociated into an in vitro co-culture of primary sensory neurons and satellite glial cells to investigate neuronal-glial interaction, neuritogenesis, axonal cone interaction with the extracellular microenvironment, and more general, any aspect associated with the neuronal metabolism. Therefore, the DRG-explant system offers a great deal of flexibility to study a wide array of events related to biological, physiological, and pathological conditions in a cost-effective manner.

  16. Electrophysiological and gene expression characterization of the ontogeny of nestin-expressing cells in the adult mouse midbrain

    Directory of Open Access Journals (Sweden)

    Anupama Dey

    2017-08-01

    Full Text Available The birth of new neurons, or neurogenesis, in the adult midbrain is important for progressing dopamine cell-replacement therapies for Parkinson's disease. Most studies suggest newborn cells remain undifferentiated or differentiate into glia within the adult midbrain. However, some studies suggest nestin + neural precursor cells (NPCs have a propensity to generate new neurons here. We sought to confirm this by administering tamoxifen to adult NesCreERT2/R26eYFP transgenic mice, which permanently labelled adult nestin-expressing cells and their progeny with enhanced yellow fluorescent protein (eYFP. eYFP+ midbrain cells were then characterized 1–32 weeks later in acutely prepared brain slices using whole-cell patch clamp electrophysiology combined with single-cell RT-qPCR. Most eYFP+ cells exhibited a mature neuronal phenotype with large amplitude fast action potentials (APs, spontaneous post-synaptic currents (sPSCs, and expression of ‘mature’ neuronal genes (NeuN, Gad1, Gad2 and/or VGLUT2. This was the case even at the earliest time-point following tamoxifen (i.e. 1 week. In comparison to neighboring eYFP− (control cells, eYFP+ cells discharged more APs per unit current injection, and had faster AP time-to-peak, hyperpolarized resting membrane potential, smaller membrane capacitance and shorter duration sPSCs. eYFP+ cells were also differentiated from eYFP− cells by increased expression of ‘immature’ pro-neuronal genes (Pax6, Ngn2 and/or Msx1. However, further analyses failed to reveal evidence of a place of birth, neuronal differentiation, maturation and integration indicative of classical neurogenesis. Thus our findings do not support the notion that nestin + NPCs in the adult SNc and midbrain generate new neurons via classical neurogenesis. Rather, they raise the possibility that mature neurons express nestin under unknown circumstances, and that this is associated with altered physiology and gene expression.

  17. Radiation effects in brain and spinal cord

    International Nuclear Information System (INIS)

    Franke, H.D.; Lierse, W.

    1978-01-01

    Radiation sensitivity of both the brain and spinal cord in prenatal and postnatal stages, in infancy and adult age is represented also in consideration of a combined treatment with methotrexate. In adults, application of important doses of high-energy radiation increases the risk of injurious effects to the central nervous system. If the spinal cord is involved, more than 60% of the radiolesions have a progredient course ending with death. The pathogenesis and disposing factors are referred to, and the incidence of radiation necrosis with regard to age and sex, the degrees of injury and their frequence within different ranges of dosage are analyzed on the basis of data from universal literature. An examination of 'tolerance doses' for the spinal cord is made by means of Strandquist-diagrams and of the Ellis-formula. The slopes of regression lines are reported for various 'degrees of response' in skin, brain and spinal cord following radiation therapy. In the Strandquist-diagram, slopes of regression lines are dependent on the 'degree of response', flattening if skin and spinal cord are affected by radiation in the same degree, necroses having the same slope for both the organs. (orig./MG) [de

  18. Late gestational hypoxia and a postnatal high salt diet programs endothelial dysfunction and arterial stiffness in adult mouse offspring.

    Science.gov (United States)

    Walton, Sarah L; Singh, Reetu R; Tan, Tiffany; Paravicini, Tamara M; Moritz, Karen M

    2016-03-01

    Gestational hypoxia and high dietary salt intake have both been associated with impaired vascular function in adulthood. Using a mouse model of prenatal hypoxia, we examined whether a chronic high salt diet had an additive effect in promoting vascular dysfunction in offspring. Pregnant CD1 dams were placed in a hypoxic chamber (12% O2) or housed under normal conditions (21% O2) from embryonic day 14.5 until birth. Gestational hypoxia resulted in a reduced body weight for both male and female offspring at birth. This restriction in body weight persisted until weaning, after which the animals underwent catch-up growth. At 10 weeks of age, a subset of offspring was placed on a high salt diet (5% NaCl). Pressurized myography of mesenteric resistance arteries at 12 months of age showed that both male and female offspring exposed to maternal hypoxia had significantly impaired endothelial function, as demonstrated by impaired vasodilatation to ACh but not sodium nitroprusside. Endothelial dysfunction caused by prenatal hypoxia was not exacerbated by postnatal consumption of a high salt diet. Prenatal hypoxia increased microvascular stiffness in male offspring. The combination of prenatal hypoxia and a postnatal high salt diet caused a leftward shift in the stress-strain relationship in both sexes. Histopathological analysis of aortic sections revealed a loss of elastin integrity and increased collagen, consistent with increased vascular stiffness. These results demonstrate that prenatal hypoxia programs endothelial dysfunction in both sexes. A chronic high salt diet in postnatal life had an additive deleterious effect on vascular mechanics and structural characteristics in both sexes. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  19. Activation of Akt/FKHR in the medulla oblongata contributes to spontaneous respiratory recovery after incomplete spinal cord injury in adult rats.

    Science.gov (United States)

    Felix, M S; Bauer, S; Darlot, F; Muscatelli, F; Kastner, A; Gauthier, P; Matarazzo, V

    2014-09-01

    After incomplete spinal cord injury (SCI), patients and animals may exhibit some spontaneous functional recovery which can be partly attributed to remodeling of injured neural circuitry. This post-lesion plasticity implies spinal remodeling but increasing evidences suggest that supraspinal structures contribute also to the functional recovery. Here we tested the hypothesis that partial SCI may activate cell-signaling pathway(s) at the supraspinal level and that this molecular response may contribute to spontaneous recovery. With this aim, we used a rat model of partial cervical hemisection which injures the bulbospinal respiratory tract originating from the medulla oblongata of the brainstem but leads to a time-dependent spontaneous functional recovery of the paralyzed hemidiaphragm. We first demonstrate that after SCI the PI3K/Akt signaling pathway is activated in the medulla oblongata of the brainstem, resulting in an inactivation of its pro-apoptotic downstream target, forkhead transcription factor (FKHR/FOXO1A). Retrograde labeling of medullary premotoneurons including respiratory ones which project to phrenic motoneurons reveals an increased FKHR phosphorylation in their cell bodies together with an unchanged cell number. Medulla infusion of the PI3K inhibitor, LY294002, prevents the SCI-induced Akt and FKHR phosphorylations and activates one of its death-promoting downstream targets, Fas ligand. Quantitative EMG analyses of diaphragmatic contractility demonstrate that the inhibition of medulla PI3K/Akt signaling prevents spontaneous respiratory recovery normally observed after partial cervical SCI. Such inhibition does not however affect either baseline contractile frequency or the ventilatory reactivity under acute respiratory challenge. Together, these findings provide novel evidence of supraspinal cellular contribution to the spontaneous respiratory recovery after partial SCI. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring.

    Science.gov (United States)

    Azuma, Kagaku; Ogura, Minori; Kondo, Hiroko; Suzuki, Ayumi; Hayashi, Sakurako; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

    2017-01-01

    Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring.

  1. Effects of perinatal daidzein exposure on subsequent behavior and central estrogen receptor α expression in the adult male mouse.

    Science.gov (United States)

    Yu, Chengjun; Tai, Fadao; Zeng, Shuangyan; Zhang, Xia

    2013-06-03

    Daidzein is one of the most important isoflavones present in soy and it is unique as it can be further metabolized to equol, a compound with greater estrogenic activity than other isoflavones. The potential role of daidzein in the prevention of some chronic diseases has drawn public attention and increased its consumption in human, including in pregnant women and adolescent. It is unclear whether perinatal exposure to daidzein through maternal diets affects subsequent behavior and central estrogen receptor α (ERα) expression in male adults. Following developmental exposure to daidzein through maternal diets during perinatal period, subsequent anxiety-like behavior, social behavior, spatial learning and memory of male mice at adulthood were assessed using a series of tests. The levels of central ER α expression were also examined using immunocytochemistry. Compared with the controls, adult male mice exposed to daidzein during the perinatal period showed significantly less exploration, higher levels of anxiety and aggression. They also displayed more social investigation for females and a tendency to improve spatial learning and memory. The mice with this early daidzein treatment demonstrated significantly higher levels of ERα expression in several brain regions such as the bed nucleus of the stria terminalis, medial preoptic, arcuate hypothalamic nucleus and central amygdaloid mucleus, but decreased it in the lateral septum. Our results indicated that perinatal exposure to daidzein enhanced masculinization on male behaviors which is assocciated with alterations in ERα expression levels led by perinatal daidzein exposure. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Pituitary adenylate cyclase activating polypeptide reduces A-type K+ currents and caspase activity in cultured adult mouse olfactory neurons.

    Science.gov (United States)

    Han, P; Lucero, M T

    2005-01-01

    Pituitary adenylate cyclase activating polypeptide has been shown to reduce apoptosis in neonatal cerebellar and olfactory receptor neurons, however the underlying mechanisms have not been elucidated. In addition, the neuroprotective effects of pituitary adenylate cyclase activating polypeptide have not been examined in adult tissues. To study the effects of pituitary adenylate cyclase activating polypeptide on neurons in apoptosis, we measured caspase activation in adult olfactory receptor neurons in vitro. Interestingly, we found that the protective effects of pituitary adenylate cyclase activating polypeptide were related to the absence of a 4-aminopyridine (IC50=144 microM) sensitive rapidly inactivating potassium current often referred to as A-type current. In the presence of 40 nM pituitary adenylate cyclase activating polypeptide 38, both A-type current and activated caspases were significantly reduced. A-type current reduction by pituitary adenylate cyclase activating polypeptide was blocked by inhibiting the phospholipase C pathway, but not the adenylyl cyclase pathway. Our observation that 5 mM 4-aminopyridine mimicked the caspase inhibiting effects of pituitary adenylate cyclase activating polypeptide indicates that A-type current is involved in apoptosis. This work contributes to our growing understanding that potassium currents are involved with the activation of caspases to affect the balance between cell life and death.

  3. Long-chain n-3 PUFAs from fish oil enhance resting state brain glucose utilization and reduce anxiety in an adult nonhuman primate, the grey mouse lemur.

    Science.gov (United States)

    Pifferi, Fabien; Dorieux, Olène; Castellano, Christian-Alexandre; Croteau, Etienne; Masson, Marie; Guillermier, Martine; Van Camp, Nadja; Guesnet, Philippe; Alessandri, Jean-Marc; Cunnane, Stephen; Dhenain, Marc; Aujard, Fabienne

    2015-08-01

    Decreased brain content of DHA, the most abundant long-chain n-3 polyunsaturated fatty acid (n-3 LCPUFA) in the brain, is accompanied by severe neurosensorial impairments linked to impaired neurotransmission and impaired brain glucose utilization. In the present study, we hypothesized that increasing n-3 LCPUFA intake at an early age may help to prevent or correct the glucose hypometabolism observed during aging and age-related cognitive decline. The effects of 12 months' supplementation with n-3 LCPUFA on brain glucose utilization assessed by positron emission tomography was tested in young adult mouse lemurs (Microcebus murinus). Cognitive function was tested in parallel in the same animals. Lemurs supplemented with n-3 LCPUFA had higher brain glucose uptake and cerebral metabolic rate of glucose compared with controls in all brain regions. The n-3 LCPUFA-supplemented animals also had higher exploratory activity in an open-field task and lower evidence of anxiety in the Barnes maze. Our results demonstrate for the first time in a nonhuman primate that n-3 LCPUFA supplementation increases brain glucose uptake and metabolism and concomitantly reduces anxiety. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  4. Variations in DNA synthesis and mitotic indices in hepatocytes and sinusoid litoral cells of adult intact male mouse along a circadian time span.

    Science.gov (United States)

    Surur, J M; Moreno, F R; Badrán, A F; Llanos, J M

    1985-01-01

    Variations of DNA synthesis (DNAS) and mitotic indices along a circadian time span are described in the hepatocyte and sinusoid litoral cell populations of adult intact male mouse liver. Standardized (light from 0600 to 1800) mice were killed in groups of six to nine animals, every 2-4 hr along a circadian time span. Hepatocytes show significant peaks in the synthesis of DNA and the mitotic activity at 0200 and 1400, respectively. These results correspond to those previously described by us in young immature liver, regenerating liver and hepatomas. The phase differences between these peaks and the differences between their absolute values are discussed. Also considered are the practical consequences of our findings for experimental design. The curve of DNA synthesis of sinusoid litoral cells show a peak at 0200. The mitotic index show a bimodal waveform with peaks at 0800 and 2000. The existence of four different cell populations composing the so called sinusoid litoral cells and also the migration into and out of the liver of some macrophages considered as litoral (Kupffer) cells in our counts, makes interpretation of the curves somewhat complicated and deserves further analysis.

  5. The lncRNA Malat1 Is Dispensable for Mouse Development but Its Transcription Plays a cis-Regulatory Role in the Adult

    Directory of Open Access Journals (Sweden)

    Bin Zhang

    2012-07-01

    Full Text Available Genome-wide studies have identified thousands of long noncoding RNAs (lncRNAs lacking protein-coding capacity. However, most lncRNAs are expressed at a very low level, and in most cases there is no genetic evidence to support their in vivo function. Malat1 (metastasis associated lung adenocarcinoma transcript 1 is among the most abundant and highly conserved lncRNAs, and it exhibits an uncommon 3′-end processing mechanism. In addition, its specific nuclear localization, developmental regulation, and dysregulation in cancer are suggestive of it having a critical biological function. We have characterized a Malat1 loss-of-function genetic model that indicates that Malat1 is not essential for mouse pre- and postnatal development. Furthermore, depletion of Malat1 does not affect global gene expression, splicing factor level and phosphorylation status, or alternative pre-mRNA splicing. However, among a small number of genes that were dysregulated in adult Malat1 knockout mice, many were Malat1 neighboring genes, thus indicating a potential cis-regulatory role of Malat1 gene transcription.

  6. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Disabilities Photography by Rona Talcott Website by Mobile Marketing LLC Understanding Spinal Cord Injury About ... Your email address * This iframe contains the logic required to ...

  7. Spinal injury in sport

    Energy Technology Data Exchange (ETDEWEB)

    Barile, Antonio [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy)]. E-mail: antonio.barile@cc.univaq.it; Limbucci, Nicola [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy); Splendiani, Alessandra [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy); Gallucci, Massimo [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy); Masciocchi, Carlo [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy)

    2007-04-15

    Spinal injuries are very common among professional or amateur athletes. Spinal sport lesions can be classified in overuse and acute injuries. Overuse injuries can be found after years of repetitive spinal load during sport activity; however specific overuse injuries can also be found in adolescents. Acute traumas are common in contact sports. Most of the acute injuries are minor and self-healing, but severe and catastrophic events are possible. The aim of this article is to review the wide spectrum of spinal injuries related to sport activity, with special regard to imaging finding.

  8. Spinal CT scan, 1

    International Nuclear Information System (INIS)

    Nakagawa, Hiroshi

    1982-01-01

    Methods of CT of the cervical and thoracic spines were explained, and normal CT pictures of them were described. Spinal CT was evaluated in comparison with other methods in various spinal diseases. Plain CT revealed stenosis due to spondylosis or ossification of posterior longitudinal ligament and hernia of intervertebral disc. CT took an important role in the diagnosis of spinal cord tumors with calcification and destruction of the bone. CT scan in combination with other methods was also useful for the diagnosis of spinal injuries, congenital anomalies and infections. (Ueda, J.)

  9. MULTIPLE SPINAL CANAL MENINGIOMAS

    Directory of Open Access Journals (Sweden)

    Nandigama Pratap Kumar

    2016-10-01

    Full Text Available BACKGROUND Meningiomas of the spinal canal are common tumours with the incidence of 25 percent of all spinal cord tumours. But multiple spinal canal meningiomas are rare in compare to solitary lesions and account for 2 to 3.5% of all spinal meningiomas. Most of the reported cases are both intra cranial and spinal. Exclusive involvement of the spinal canal by multiple meningiomas are very rare. We could find only sixteen cases in the literature to the best of our knowledge. Exclusive multiple spinal canal meningiomas occurring in the first two decades of life are seldom reported in the literature. We are presenting a case of multiple spinal canal meningiomas in a young patient of 17 years, who was earlier operated for single lesion. We analysed the literature, with illustration of our case. MATERIALS AND METHODS In September 2016, we performed a literature search for multiple spinal canal meningiomas involving exclusively the spinal canal with no limitation for language and publication date. The search was conducted through http://pubmed.com, a wellknown worldwide internet medical address. To the best of our knowledge, we could find only sixteen cases of multiple meningiomas exclusively confined to the spinal canal. Exclusive multiple spinal canal meningiomas occurring in the first two decades of life are seldom reported in the literature. We are presenting a case of multiple spinal canal meningiomas in a young patient of 17 years, who was earlier operated for solitary intradural extra medullary spinal canal meningioma at D4-D6 level, again presented with spastic quadriparesis of two years duration and MRI whole spine demonstrated multiple intradural extra medullary lesions, which were excised completely and the histopathological diagnosis was transitional meningioma. RESULTS Patient recovered from his weakness and sensory symptoms gradually and bladder and bowel symptoms improved gradually over a period of two to three weeks. CONCLUSION Multiple

  10. Spinal injury in sport

    International Nuclear Information System (INIS)

    Barile, Antonio; Limbucci, Nicola; Splendiani, Alessandra; Gallucci, Massimo; Masciocchi, Carlo

    2007-01-01

    Spinal injuries are very common among professional or amateur athletes. Spinal sport lesions can be classified in overuse and acute injuries. Overuse injuries can be found after years of repetitive spinal load during sport activity; however specific overuse injuries can also be found in adolescents. Acute traumas are common in contact sports. Most of the acute injuries are minor and self-healing, but severe and catastrophic events are possible. The aim of this article is to review the wide spectrum of spinal injuries related to sport activity, with special regard to imaging finding

  11. Effects of Chronic Sleep Restriction during Early Adolescence on the Adult Pattern of Connectivity of Mouse Secondary Motor Cortex123

    Science.gov (United States)

    Billeh, Yazan N.; Bernard, Amy; de Vivo, Luisa; Honjoh, Sakiko; Mihalas, Stefan; Ng, Lydia; Koch, Christof

    2016-01-01

    Abstract Cortical circuits mature in stages, from early synaptogenesis and synaptic pruning to late synaptic refinement, resulting in the adult anatomical connection matrix. Because the mature matrix is largely fixed, genetic or environmental factors interfering with its establishment can have irreversible effects. Sleep disruption is rarely considered among those factors, and previous studies have focused on very young animals and the acute effects of sleep deprivation on neuronal morphology and cortical plasticity. Adolescence is a sensitive time for brain remodeling, yet whether chronic sleep restriction (CSR) during adolescence has long-term effects on brain connectivity remains unclear. We used viral-mediated axonal labeling and serial two-photon tomography to measure brain-wide projections from secondary motor cortex (MOs), a high-order area with diffuse projections. For each MOs target, we calculated the projection fraction, a combined measure of passing fibers and axonal terminals normalized for the size of each target. We found no homogeneous differences in MOs projection fraction between mice subjected to 5 days of CSR during early adolescence (P25–P30, ≥50% decrease in daily sleep, n=14) and siblings that slept undisturbed (n=14). Machine learning algorithms, however, classified animals at significantly above chance levels, indicating that differences between the two groups exist, but are subtle and heterogeneous. Thus, sleep disruption in early adolescence may affect adult brain connectivity. However, because our method relies on a global measure of projection density and was not previously used to measure connectivity changes due to behavioral manipulations, definitive conclusions on the long-term structural effects of early CSR require additional experiments. PMID:27351022

  12. Paired immunoglobulin-like receptor B knockout does not enhance axonal regeneration or locomotor recovery after spinal cord injury.

    Science.gov (United States)

    Nakamura, Yuka; Fujita, Yuki; Ueno, Masaki; Takai, Toshiyuki; Yamashita, Toshihide

    2011-01-21

    Myelin components that inhibit axonal regeneration are believed to contribute significantly to the lack of axonal regeneration noted in the adult central nervous system. Three proteins found in myelin, Nogo, myelin-associated glycoprotein, and oligodendrocyte-myelin glycoprotein, inhibit neurite outgrowth in vitro. All of these proteins interact with the same receptors, namely, the Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PIR-B). As per previous reports, corticospinal tract (CST) regeneration is not enhanced in NgR-knock-out mice after spinal cord injury. Therefore, we assessed CST regeneration in PIR-B-knock-out mice. We found that hindlimb motor function, as assessed using the Basso mouse scale, footprint test, inclined plane test, and beam walking test, did not differ between the PIR-B-knock-out and wild-type mice after dorsal hemisection of the spinal cord. Further, tracing of the CST fibers after injury did not reveal enhanced axonal regeneration or sprouting in the CST of the PIR-B-knock-out mice. Systemic administration of NEP1-40, a NgR antagonist, to PIR-B knock-out mice did not enhance the regenerative response. These results indicate that PIR-B knock-out is not sufficient to induce extensive axonal regeneration after spinal cord injury.

  13. Adenosine Receptors in Developing and Adult Mouse Neuromuscular Junctions and Functional Links With Other Metabotropic Receptor Pathways.

    Science.gov (United States)

    Tomàs, Josep; Garcia, Neus; Lanuza, Maria A; Santafé, Manel M; Tomàs, Marta; Nadal, Laura; Hurtado, Erica; Simó-Ollé, Anna; Cilleros-Mañé, Víctor; Just-Borràs, Laia

    2018-01-01

    In the last few years, we have studied the presence and involvement in synaptogenesis and mature transmitter release of the adenosine autoreceptors (AR) in the mammalian neuromuscular junction (NMJ). Here, we review and bring together the previously published data to emphasize the relevance of these receptors for developmental axonal competition, synaptic loss and mature NMJ functional modulation. However, in addition to AR, activity-dependent mediators originating from any of the three cells that make the synapse (nerve, muscle, and glial cells) cross the extracellular cleft to generate signals in target metabotropic receptors. Thus, the integrated interpretation of the complementary function of all these receptors is needed. We previously studied, in the NMJ, the links of AR with mAChR and the neurotrophin receptor TrkB in the control of synapse elimination and transmitter release. We conclude that AR cooperate with these receptors through synergistic and antagonistic effects in the developmental synapse elimination process. In the adult NMJ, this cooperation is manifested so as that the functional integrity of a given receptor group depends on the other receptors operating normally (i.e., the functional integrity of mAChR depends on AR operating normally). These observations underlie the relevance of AR in the NMJ function.

  14. Adenosine Receptors in Developing and Adult Mouse Neuromuscular Junctions and Functional Links With Other Metabotropic Receptor Pathways

    Directory of Open Access Journals (Sweden)

    Josep Tomàs

    2018-04-01

    Full Text Available In the last few years, we have studied the presence and involvement in synaptogenesis and mature transmitter release of the adenosine autoreceptors (AR in the mammalian neuromuscular junction (NMJ. Here, we review and bring together the previously published data to emphasize the relevance of these receptors for developmental axonal competition, synaptic loss and mature NMJ functional modulation. However, in addition to AR, activity-dependent mediators originating from any of the three cells that make the synapse (nerve, muscle, and glial cells cross the extracellular cleft to generate signals in target metabotropic receptors. Thus, the integrated interpretation of the complementary function of all these receptors is needed. We previously studied, in the NMJ, the links of AR with mAChR and the neurotrophin receptor TrkB in the control of synapse elimination and transmitter release. We conclude that AR cooperate with these receptors through synergistic and antagonistic effects in the developmental synapse elimination process. In the adult NMJ, this cooperation is manifested so as that the functional integrity of a given receptor group depends on the other receptors operating normally (i.e., the functional integrity of mAChR depends on AR operating normally. These observations underlie the relevance of AR in the NMJ function.

  15. Single cell electroporation for longitudinal imaging of synaptic structure and function in the adult mouse neocortex in vivo

    Directory of Open Access Journals (Sweden)

    Stephane ePages

    2015-04-01

    Full Text Available Longitudinal imaging studies of neuronal structures in vivo have revealed rich dynamics in dendritic spines and axonal boutons. Spines and boutons are considered to be proxies for synapses. This implies that synapses display similar dynamics. However, spines and boutons do not always bear synapses, some may contain more than one, and dendritic shaft synapses have no clear structural proxies. In addition, synaptic strength is not always accurately revealed by just the size of these structures. Structural and functional dynamics of synapses could be studied more reliably using fluorescent synaptic proteins as markers for size and function. These proteins are often large and possibly interfere with circuit development, which renders them less suitable for conventional transfection or transgenesis methods such as viral vectors, in utero electroporation and germline transgenesis. Single cell electroporation has been shown to be a potential alternative for transfection of recombinant fluorescent proteins in adult cortical neurons. Here we provide proof of principle for the use of single cell electroporation to express and subsequently image fluorescently tagged synaptic proteins over days to weeks in vivo.

  16. Transcriptional profiling reveals gland-specific differential expression in the three major salivary glands of the adult mouse.

    Science.gov (United States)

    Gao, Xin; Oei, Maria S; Ovitt, Catherine E; Sincan, Murat; Melvin, James E

    2018-04-01

    RNA-Seq was used to better understand the molecular nature of the biological differences among the three major exocrine salivary glands in mammals. Transcriptional profiling found that the adult murine parotid, submandibular, and sublingual salivary glands express greater than 14,300 protein-coding genes, and nearly 2,000 of these genes were differentially expressed. Principle component analysis of the differentially expressed genes revealed three distinct clusters according to gland type. The three salivary gland transcriptomes were dominated by a relatively few number of highly expressed genes (6.3%) that accounted for more than 90% of transcriptional output. Of the 912 transcription factors expressed in the major salivary glands, greater than 90% of them were detected in all three glands, while expression for ~2% of them was enriched in an individual gland. Expression of these unique transcription factors correlated with sublingual and parotid specific subsets of both highly expressed and differentially expressed genes. Gene ontology analyses revealed that the highly expressed genes common to all glands were associated with global functions, while many of the genes expressed in a single gland play a major role in the function of that gland. In summary, transcriptional profiling of the three murine major salivary glands identified a limited number of highly expressed genes, differentially expressed genes, and unique transcription factors that represent the transcriptional signatures underlying gland-specific biological properties.

  17. Kinematic analysis of the gait of adult sheep during treadmill locomotion: Parameter values, allowable total error, and potential for use in evaluating spinal cord injury.

    Science.gov (United States)

    Safayi, Sina; Jeffery, Nick D; Shivapour, Sara K; Zamanighomi, Mahdi; Zylstra, Tyler J; Bratsch-Prince, Joshua; Wilson, Saul; Reddy, Chandan G; Fredericks, Douglas C; Gillies, George T; Howard, Matthew A

    2015-11-15

    We are developing a novel intradural spinal cord (SC) stimulator designed to improve the treatment of intractable pain and the sequelae of SC injury. In-vivo ovine models of neuropathic pain and moderate SC injury are being implemented for pre-clinical evaluations of this device, to be carried out via gait analysis before and after induction of the relevant condition. We extend previous studies on other quadrupeds to extract the three-dimensional kinematics of the limbs over