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Sample records for damaged mammalian spinal

  1. Repair of radiation damage in mammalian cells

    SciTech Connect

    Setlow, R.B.

    1981-01-01

    The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis.

  2. Novel combination strategies to repair the injured mammalian spinal cord.

    PubMed

    Bunge, Mary Bartlett

    2008-01-01

    Due to the varied and numerous changes in spinal cord tissue following injury, successful treatment for repair may involve strategies combining neuroprotection (pharmacological prevention of some of the damaging intracellular cascades that lead to secondary tissue loss), axonal regeneration promotion (cell transplantation, genetic engineering to increase growth factors, neutralization of inhibitory factors, reduction in scar formation), and rehabilitation. Our goal has been to find effective combination strategies to improve outcome after injury to the adult rat thoracic spinal cord. Combination interventions tested have been implantation of Schwann cells (SCs) plus neuroprotective agents and growth factors administered in various ways, olfactory ensheathing cell (OEC) implantation, chondroitinase addition, or elevation of cyclic AMP. The most efficacious strategy in our hands for the acute complete transection/SC bridge model, including improvement in locomotion [Basso, Beattie, Bresnahan Scale (BBB)], is the combination of SCs, OECs, and chondroitinase administration (BBB 2.1 vs 6.6, 3 times more myelinated axons in the SC bridge, increased serotonergic axons in the bridge and beyond, and significant correlation between the number of bridge myelinated axons and functional improvement). We found the most successful combination strategy for a subacute spinal cord contusion injury (12.5-mm, 10-g weight, MASCIS impactor) to be SCs and elevation of cyclic AMP (BBB 10.4 vs 15, significant increases in white matter sparing, in myelinated axons in the implant, and in responding reticular formation and red and raphe nuclei, and a significant correlation between the number of serotonergic fibers and improvement in locomotion). Thus, in two injury paradigms, these combination strategies as well as others studied in our laboratory have been found to be more effective than SCs alone and suggest ways in which clinical application may be developed. PMID:18795474

  3. Photooxidative damage to mammalian cells and proteins by visible light

    SciTech Connect

    Packer, L.; Kellogg, E.W. III

    1980-01-01

    In the present article, studies carried out in our laboratory on the effects of visible irradiation and O/sub 2/ in a variety of target systems ranging from cultured mammalian cells to purified catalase are reviewed. We will relate these studies of photooxidative damage to a scheme for the propagation of intracellular damage which traces a number of the possible pro-oxidant and anti-oxidant pathways found in the cell.

  4. Mechanisms underlying spinal cord damage in decompression sickness.

    PubMed

    Hallenbeck, J M; Bove, A A; Elliott, D H

    1975-04-01

    Decompression sickness, which damaged the spinal cord, was produced in anesthetized dogs using a compression chamber. Cerebrospinal fluid pressure and several intravascular and intracardiac pressures were monitored during the course of the simulated dives. Manometric responses to forcible lung inflation and abdominal compression were measured both predive and postdive after signs of spinal cord damage were evident. Cinevenography of the epidural vertebral venous system was performed both predive and postdive. Histopathologic studies of the brains and cords of both predive and postdive. Histopathologic studies of the brains and cords of paretic animals were carried out. The results indicate that the epidural vertebral venous system becomes obstructed during spinal cord damaging decompression sickness and strongly suggests that spinal cord infarction in decompression sickness is caused by obstruction of cord venous drainage at the level of the epidural vertebral venous system. PMID:1168317

  5. The distribution and origin of VIP in the spinal cord of six mammalian species.

    PubMed

    Gibson, S J; Polak, J M; Anand, P; Blank, M A; Morrison, J F; Kelly, J S; Bloom, S R

    1984-01-01

    The distribution of VIP-immunoreactivity was studied in the spinal cord and dorsal root ganglia of 6 mammalian species. Immunoreactive fibres and cell bodies were most apparent in the dorsal horn, dorsolateral funiculus, intermediolateral cell columns and the area around the central canal. The distribution of VIP immunoreactivity was similar in all species studied, mouse, rat, guinea pig, cat, horse and the marmoset monkey. There were fewer VIP fibres in the dorsal horn of cervical and thoracic segments than in lumbosacral segments. Using radioimmunoassay this gradient increase was quantitatively most marked in the sacral spinal cord of the cat. In dorsal root ganglia few nerve cell bodies but numerous fibres were present. A dual origin for VIP in the spinal cord is suggested: (A) Extrinsic, from dorsal root afferent fibres since immunoreactivity was decreased in dorsally rhizotomized animals (cats and rats) and in capsaicin pretreated rats (microinjection of dorsal root ganglia). (B) From local cell bodies intrinsic to the spinal cord which became visible after colchicine pretreatment of rats.

  6. Bacillus thuringiensis membrane-damaging toxins acting on mammalian cells.

    PubMed

    Celandroni, Francesco; Salvetti, Sara; Senesi, Sonia; Ghelardi, Emilia

    2014-12-01

    Bacillus thuringiensis is widely used as a biopesticide in forestry and agriculture, being able to produce potent species-specific insecticidal toxins and considered nonpathogenic to other animals. More recently, however, repeated observations are documenting the association of this microorganism with various infectious diseases in humans, such as food-poisoning-associated diarrheas, periodontitis, bacteremia, as well as ocular, burn, and wound infections. Similar to B. cereus, B. thuringiensis produces an array of virulence factors acting against mammalian cells, such as phosphatidylcholine- and phosphatidylinositol-specific phospholipase C (PC-PLC and PI-PLC), hemolysins, in particular hemolysin BL (HBL), and various enterotoxins. The contribution of some of these toxins to B. thuringiensis pathogenicity has been studied in animal models of infection, following intravitreous, intranasal, or intratracheal inoculation. These studies lead to the speculation that the activities of PC-PLC, PI-PLC, and HBL are responsible for most of the pathogenic properties of B. thuringiensis in nongastrointestinal infections in mammals. This review summarizes data regarding the biological activity, the genetic basis, and the structural features of these membrane-damaging toxins.

  7. Axotomy of single fluorescent nerve fibers in developing mammalian spinal cord by photoconversion of diaminobenzidine.

    PubMed

    De-Miguel, Francisco F; Muller, Kenneth J; Adams, William B; Nicholls, John G

    2002-05-30

    A technique has been developed for cutting single nerve fibers in mammalian spinal cord. In the presence of diaminobenzidine (DAB), a laser microbeam was applied to carbocyanine (Dil) stained sensory fibers in cultured spinal cords of the newly born opossum Monodelphis domestica. Digital images of fluorescent fibers were acquired with an intensified video CCD-camera coupled to an image processor. Laser illumination of two spots on a fiber in the presence of 3 mg/ml DAB cut it, so that following DAB wash out, Dil fluorescence did not return after the intermediate segment was bleached. In contrast, when a similar procedure was carried out without DAB, fluorescence of the bleached segment was recovered within minutes in darkness, by dye diffusion from adjacent regions of the uncut fiber. After exposure to DAB, through-conduction of compound action potentials continued in undamaged fibers. The DAB reaction product remained as a dark precipitate, helping to localize the lesion sites. By illuminating a continuous series of spots it was possible to cut whole nerve roots. Fluorescent fibers extended across the cut segment 24 h later. With minor modifications, the procedure described here allows a precise lesioning of single fibers within an intact nervous system.

  8. In situ analysis of repair processes for oxidative DNA damage in mammalian cells

    NASA Astrophysics Data System (ADS)

    Lan, Li; Nakajima, Satoshi; Oohata, Yoshitsugu; Takao, Masashi; Okano, Satoshi; Masutani, Mitsuko; Wilson, Samuel H.; Yasui, Akira

    2004-09-01

    Oxidative DNA damage causes blocks and errors in transcription and replication, leading to cell death and genomic instability. Although repair mechanisms of the damage have been extensively analyzed in vitro, the actual in vivo repair processes remain largely unknown. Here, by irradiation with an UVA laser through a microscope lens, we have conditionally produced single-strand breaks and oxidative base damage at restricted nuclear regions of mammalian cells. We showed, in real time after irradiation by using antibodies and GFP-tagged proteins, rapid and ordered DNA repair processes of oxidative DNA damage in human cells. Furthermore, we characterized repair pathways by using repair-defective mammalian cells and found that DNA polymerase accumulated at single-strand breaks and oxidative base damage by means of its 31- and 8-kDa domains, respectively, and that XRCC1 is essential for both polymerase -dependent and proliferating cell nuclear antigen-dependent repair pathways of single-strand breaks. Thus, the repair of oxidative DNA damage is based on temporal and functional interactions among various proteins operating at the site of DNA damage in living cells.

  9. Quantitative PCR-based measurement of nuclear and mitochondrial DNA damage and repair in mammalian cells.

    PubMed

    Furda, Amy; Santos, Janine H; Meyer, Joel N; Van Houten, Bennett

    2014-01-01

    In this chapter, we describe a gene-specific quantitative PCR (QPCR)-based assay for the measurement of DNA damage, using amplification of long DNA targets. This assay has been used extensively to measure the integrity of both nuclear and mitochondrial genomes exposed to different genotoxins and has proven to be particularly valuable in identifying reactive oxygen species-mediated mitochondrial DNA damage. QPCR can be used to quantify both the formation of DNA damage as well as the kinetics of damage removal. One of the main strengths of the assay is that it permits monitoring the integrity of mtDNA directly from total cellular DNA without the need for isolating mitochondria or a separate step of mitochondrial DNA purification. Here we discuss advantages and limitations of using QPCR to assay DNA damage in mammalian cells. In addition, we give a detailed protocol of the QPCR assay that helps facilitate its successful deployment in any molecular biology laboratory.

  10. Reconstitution of the cellular response to DNA damage in vitro using damage-activated extracts from mammalian cells

    SciTech Connect

    Roper, Katherine; Coverley, Dawn

    2012-03-10

    In proliferating mammalian cells, DNA damage is detected by sensors that elicit a cellular response which arrests the cell cycle and repairs the damage. As part of the DNA damage response, DNA replication is inhibited and, within seconds, histone H2AX is phosphorylated. Here we describe a cell-free system that reconstitutes the cellular response to DNA double strand breaks using damage-activated cell extracts and naieve nuclei. Using this system the effect of damage signalling on nuclei that do not contain DNA lesions can be studied, thereby uncoupling signalling and repair. Soluble extracts from G1/S phase cells that were treated with etoposide before isolation, or pre-incubated with nuclei from etoposide-treated cells during an in vitro activation reaction, restrain both initiation and elongation of DNA replication in naieve nuclei. At the same time, H2AX is phosphorylated in naieve nuclei in a manner that is dependent upon the phosphatidylinositol 3-kinase-like protein kinases. Notably, phosphorylated H2AX is not focal in naieve nuclei, but is evident throughout the nucleus suggesting that in the absence of DNA lesions the signal is not amplified such that discrete foci can be detected. This system offers a novel screening approach for inhibitors of DNA damage response kinases, which we demonstrate using the inhibitors wortmannin and LY294002. -- Highlights: Black-Right-Pointing-Pointer A cell free system that reconstitutes the response to DNA damage in the absence of DNA lesions. Black-Right-Pointing-Pointer Damage-activated extracts impose the cellular response to DNA damage on naieve nuclei. Black-Right-Pointing-Pointer PIKK-dependent response impacts positively and negatively on two separate fluorescent outputs. Black-Right-Pointing-Pointer Can be used to screen for inhibitors that impact on the response to damage but not on DNA repair. Black-Right-Pointing-Pointer LY294002 and wortmannin demonstrate the system's potential as a pathway focused screening

  11. DNA damage response to different surface chemistry of silver nanoparticles in mammalian cells

    SciTech Connect

    Ahamed, Maqusood; Karns, Michael; Goodson, Michael; Rowe, John; Hussain, Saber M.; Schlager, John J.

    2008-12-15

    Silver nanoparticles (Ag NPs) have recently received much attention for their possible applications in biotechnology and life sciences. Ag NPs are of interest to defense and engineering programs for new material applications as well as for commercial purposes as an antimicrobial. However, little is known about the genotoxicity of Ag NPs following exposure to mammalian cells. This study was undertaken to examine the DNA damage response to polysaccharide surface functionalized (coated) and non-functionalized (uncoated) Ag NPs in two types of mammalian cells; mouse embryonic stem (mES) cells and mouse embryonic fibroblasts (MEF). Both types of Ag NPs up-regulated the cell cycle checkpoint protein p53 and DNA damage repair proteins Rad51 and phosphorylated-H2AX expression. Furthermore both of them induced cell death as measured by the annexin V protein expression and MTT assay. Our observations also suggested that the different surface chemistry of Ag NPs induce different DNA damage response: coated Ag NPs exhibited more severe damage than uncoated Ag NPs. The results suggest that polysaccharide coated particles are more individually distributed while agglomeration of the uncoated particles limits the surface area availability and access to membrane bound organelles.

  12. Dantrolene can reduce secondary damage after spinal cord injury

    PubMed Central

    Cemek, Mustafa; Buyukokuroglu, Mehmet Emin; Altunbas, Korhan; Bas, Orhan; Yurumez, Yusuf; Cosar, Murat

    2009-01-01

    The aim of this experimental study was to investigate the possible protective effects of dantrolene on traumatic spinal cord injury (SCI). Twenty-four New Zealand rabbits were divided into three groups: Sham (no drug or operation, n = 8), Control (SCI + 1 mL saline intraperitoneally (i.p.), n = 8), and DNT (SCI + 10 mg/kg dantrolene in 1 mL, i.p., n = 8). Laminectomy was performed at T10 and balloon catheter was applied extradurally. Four and 24 h after surgery, rabbits were evaluated according to the Tarlov scoring system. Blood, cerebrospinal fluid and tissue sample from spinal cord were taken for measurements of antioxidant status or detection of apoptosis. After 4 h SCI, all animals in control or DNT-treated groups became paraparesic. Significant improvement was observed in DNT-treated group, 24 h after SCI, with respect to control. Traumatic SCI led to an increase in the lipid peroxidation and a decrease in enzymic or non-enzymic endogenous antioxidative defense systems, and increase in apoptotic cell numbers. DNT treatment prevented lipid peroxidation and augmented endogenous enzymic or non-enzymic antioxidative defense systems. Again, DNT treatment significantly decreased the apoptotic cell number induced by SCI. In conclusion, experimental results observed in this study suggest that treatment with dantrolene possess potential benefits for traumatic SCI. PMID:19468761

  13. Resident neural stem cells restrict tissue damage and neuronal loss after spinal cord injury in mice.

    PubMed

    Sabelström, Hanna; Stenudd, Moa; Réu, Pedro; Dias, David O; Elfineh, Marta; Zdunek, Sofia; Damberg, Peter; Göritz, Christian; Frisén, Jonas

    2013-11-01

    Central nervous system injuries are accompanied by scar formation. It has been difficult to delineate the precise role of the scar, as it is made by several different cell types, which may limit the damage but also inhibit axonal regrowth. We show that scarring by neural stem cell-derived astrocytes is required to restrict secondary enlargement of the lesion and further axonal loss after spinal cord injury. Moreover, neural stem cell progeny exerts a neurotrophic effect required for survival of neurons adjacent to the lesion. One distinct component of the glial scar, deriving from resident neural stem cells, is required for maintaining the integrity of the injured spinal cord.

  14. Complex interactions between the DNA-damage response and mammalian telomeres

    PubMed Central

    Arnoult, Nausica; Karlseder, Jan

    2016-01-01

    Natural chromosome ends resemble double-stranded DNA breaks, but they do not activate a damage response in healthy cells. Telomeres therefore have evolved to solve the ‘end-protection problem’ by inhibiting multiple DNA damage–response pathways. During the past decade, the view of telomeres has progressed from simple caps that hide chromosome ends to complex machineries that have an active role in organizing the genome. Here we focus on mammalian telomeres and summarize and interpret recent discoveries in detail, focusing on how repair pathways are inhibited, how resection and replication are controlled and how these mechanisms govern cell fate during senescence, crisis and transformation. PMID:26581520

  15. Quantitation of heavy ion damage to the mammalian brain - Some preliminary findings

    NASA Technical Reports Server (NTRS)

    Cox, A. B.; Kraft, L. M.

    1984-01-01

    For several years, studies have been conducted regarding late effects of particulate radiations in mammalian tissues, taking into account the brains of rodents and lagomorphs. Recently, it has become feasible to quantify pathological damage and morpho-physiologic alterations accurately in large numbers of histological specimens. New investigative procedures make use of computer-assisted automated image analysis systems. Details regarding the employed methodology are discussed along with the results of the information. The radiations of high linear energy transfer (LET) cause apparently earlier and more dramatic shrinkage of olfactory glomeruli in exposed rabbit brains than comparable doses of Co-60 gamma photons.

  16. An Optogenetic Demonstration of Motor Modularity in the Mammalian Spinal Cord

    PubMed Central

    Caggiano, Vittorio; Cheung, Vincent C. K.; Bizzi, Emilio

    2016-01-01

    Motor modules are neural entities hypothesized to be building blocks of movement construction. How motor modules are underpinned by neural circuits has remained obscured. As a first step towards dissecting these circuits, we optogenetically evoked motor outputs from the lumbosacral spinal cord of two strains of transgenic mice – the Chat, with channelrhodopsin (ChR2) expressed in motoneurons, and the Thy1, expressed in putatively excitatory neurons. Motor output was represented as a spatial field of isometric ankle force. We found that Thy1 force fields were more complex and diverse in structure than Chat fields: the Thy1 fields comprised mostly non-parallel vectors while the Chat fields, mostly parallel vectors. In both, most fields elicited by co-stimulation of two laser beams were well explained by linear combination of the separately-evoked fields. We interpreted the Thy1 force fields as representations of spinal motor modules. Our comparison of the Chat and Thy1 fields allowed us to conclude, with reasonable certainty, that the structure of neuromotor modules originates from excitatory spinal interneurons. Our results not only demonstrate, for the first time using optogenetics, how the spinal modules follow linearity in their combinations, but also provide a reference against which future optogenetic studies of modularity can be compared. PMID:27734925

  17. An efficient device to experimentally model compression injury of mammalian spinal cord.

    PubMed

    Ropper, Alexander E; Zeng, Xiang; Anderson, Jamie E; Yu, Dou; Han, InBo; Haragopal, Hariprakash; Teng, Yang D

    2015-09-01

    We report an efficient and effective device to reproducibly model clinically relevant spinal cord injury (SCI) via controlled mechanical compression. In the present study, following skin incision, dorsal laminectomy was performed to expose T10 spinal cord of adult female Sprague-Dawley rats (230-250 g). The vertebral column was suspended and stabilized by Allis clamps at T8 and 12 spinous processes. A metal impounder was then gently loaded onto T10 dura (20, 35 or 50 g × 5 min; n=7/group), resulting in acute mild, moderate, or severe standing weight compression, respectively. Neurobehavioral outcomes were evaluated using the BBB locomotor scale and inclined plane test for coordinated hindlimb function, and a battery of spinal reflex tests for sensorimotor functions, at 1 day following SCI and weekly thereafter for 7 weeks. Quantitative histopathology was used to assess injury-triggered loss of white matter, gray matter and ventral horn motor neurons. Immunocytochemical levels of glial fibrillary acidic protein (GFAP) and β-amyloid precursor protein (APP) at the cervical and lumbar regions were measured to determine the distal segment impact of T10 compression. The data demonstrates that the standardized protocol generates weight-dependent hindlimb motosensory deficits and neurodegeneration primarily at and near the lesion epicenter. Importantly, there are significantly increased GFAP and APP expressions in spinal cord segments involved in eliciting post-SCI allodynia. Therefore, the described system reliably produces compression trauma in manners partially emulating clinical quasi-static insults to the spinal cord, providing a pragmatic model to investigate pathophysiological events and potential therapeutics for compression SCI. PMID:26210871

  18. Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.; Katz, Robert; Wilson, John W.; Townsend, Lawrence W.; Nealy, John E.; Shinn, Judy L.

    1991-01-01

    The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space.

  19. Neuroprotective role of hydralazine in rat spinal cord injury-attenuation of acrolein-mediated damage.

    PubMed

    Park, Jonghyuck; Zheng, Lingxing; Marquis, Andrew; Walls, Michael; Duerstock, Brad; Pond, Amber; Vega-Alvarez, Sasha; Wang, He; Ouyang, Zheng; Shi, Riyi

    2014-04-01

    Acrolein, an α,β-unsaturated aldehyde and a reactive product of lipid peroxidation, has been suggested as a key factor in neural post-traumatic secondary injury in spinal cord injury (SCI), mainly based on in vitro and ex vivo evidence. Here, we demonstrate an increase of acrolein up to 300%; the elevation lasted at least 2 weeks in a rat SCI model. More importantly, hydralazine, a known acrolein scavenger can provide neuroprotection when applied systemically. Besides effectively reducing acrolein, hydralazine treatment also resulted in significant amelioration of tissue damage, motor deficits, and neuropathic pain. This effect was further supported by demonstrating the ability of hydralazine to reach spinal cord tissue at a therapeutic level following intraperitoneal application. This suggests that hydralazine is an effective neuroprotective agent not only in vitro, but in a live animal model of SCI as well. Finally, the role of acrolein in SCI was further validated by the fact that acrolein injection into the spinal cord caused significant SCI-like tissue damage and motor deficits. Taken together, available evidence strongly suggests a critical causal role of acrolein in the pathogenesis of spinal cord trauma. Since acrolein has been linked to a variety of illness and conditions, we believe that acrolein-scavenging measures have the potential to be expanded significantly ensuring a broad impact on human health.

  20. Early history of glycine receptor biology in Mammalian spinal cord circuits.

    PubMed

    Callister, Robert John; Graham, Brett Anthony

    2010-01-01

    In this review we provide an overview of key in vivo experiments undertaken in the cat spinal cord in the 1950s and 1960s, and point out their contributions to our present understanding of glycine receptor (GlyR) function. Importantly, some of these discoveries were made well before an inhibitory receptor, or its agonist, was identified. These contributions include the universal acceptance of a chemical mode of synaptic transmission; that GlyRs are chloride channels; are involved in reciprocal and recurrent spinal inhibition; are selectively blocked by strychnine; and can be distinguished from the GABA(A) receptor by their insensitivity to bicuculline. The early in vivo work on inhibitory mechanisms in spinal neurons also contributed to several enduring principles on synaptic function, such as the time associated with synaptic delay, the extension of Dale's hypothesis (regarding the chemical unity of nerve cells and their terminals) to neurons within the central nervous system, and the importance of inhibition for synaptic integration in motor and sensory circuits. We hope the work presented here will encourage those interested in GlyR biology and inhibitory mechanisms to seek out and read some of the "classic" articles that document the above discoveries. PMID:20577630

  1. a Study of Biophysical Mechanisms of Damage by Ionizing Radiation to Mammalian Cells in Vitro.

    NASA Astrophysics Data System (ADS)

    Chen, Chun-Zhang

    Available from UMI in association with The British Library. An extensive survey made of published survival data of damage by ionizing radiation to mammalian cells in vitro has led to the new conclusion that the damage is determined by the specific ionization or the mean free path between ionizing events along the charged particle tracks. The optimum damage is observed when the mean free path is equivalent to the DNA double strand spacing of 1.8 nm. Therefore, the biological mechanism of ionizing radiation to mammalian cells in vitro is intra track dominant. A 100 keV electron accelerator has been constructed and commissioned to produce a broad beam irradiation field of greater than 1 cm diameter. The fluence rate may be adjusted from 10^8cm^ {-2}sec^{-1} downwards to enable further development as a chronic irradiation facility. Another new feature of the accelerator is that it incorporates a differential vacuum system which permits irradiation of the monolayer cell cultures to be carried out in normal pressure. Experiments of irradiation to Chinese hamster cells, by ^{241}Am alpha particles at low fluence rate, have supplied satisfactory data for testing a new DNA-rupture model which is under development. For V79 cells irradiated at a low fluence rate of 10^5cm^{ -2}min^{-1}, when survival data were fitted into the model, new biophysical parameters were extracted and a proposal was made that the repair phenomenon of cellular survival at very low doses is determined by three time factors: the irradiation time, the damage fixation time and the repair time. The values obtained were 3-4 hours for the mean repair time, and more than 10 hours for the damage to be considered permanent. Details of the monolayer cell culture technique developed and used in the present experiments are described. Consideration has been given to the significance of the results obtained from the study in radiation protection and in radiotherapy. In future studies it is recommended that more

  2. N-nitroso-N-ethylurea activates DNA damage surveillance pathways and induces transformation in mammalian cells

    PubMed Central

    2014-01-01

    treatment indicating NEU to have the potential to cause early transformation in the cells. Conclusion NEU causes damage in mammalian cells in the form of double strand and single strand breaks that temporally activate the major checkpoint signalling kinases without the occurrence of cross-talk between the pathways. NEU also appear to cause transformation in three-dimensional spheroid cultures. PMID:24758542

  3. Damage proneness induced by genomic DNA demethylation in mammalian cells cultivated in vitro.

    PubMed

    Perticone, P; Gensabella, G; Cozzi, R

    1997-07-01

    Variations in the genomic DNA methylation level have been shown to be an epigenetic inheritable modification affecting, among other targets, the sister chromatid exchange (SCE) rate in mammalian cells in vitro. The inheritable increase in SCE rate in affected cell populations appears as a puzzling phenomenon in view of the well established relation between SCE and both mutagenesis and carcinogenesis. In the present work we demonstrate that, in a treated cell population, demethylation could be responsible for the inheritable induction of damage proneness affecting both damage induction and repair. Normal and ethionine or azacytidine treated Chinese hamster ovary cells, subclone K1 (CHO-K1), were challenged with UV light (UV) or mitomycin-C (MMC) at different times from the demethylating treatment. The SCE rate was measured with two main objects in view: (i) the induction of synergism or additivity in combined treatments, where mutagen (UV or MMC) pulse is supplied from 0 to 48 h after the end of the demethylating treatment; and (ii) the pattern of damage extinction, for the duration of up to six cell cycles after the end of the combined (demethylating agent + mutagen) treatment. Results indicate both a synergism in SCE induction by mutagens in demethylated cells even if supplied up to four cell cycles after the end of the demethylation treatment and a delay in recovery of induced damage, compared with normally methylated cells. These data are discussed in the light of the supposed mechanism of SCE increase and of the possible biological significance in terms of mutagenesis and carcinogenesis.

  4. Damage proneness induced by genomic DNA demethylation in mammalian cells cultivated in vitro.

    PubMed

    Perticone, P; Gensabella, G; Cozzi, R

    1997-07-01

    Variations in the genomic DNA methylation level have been shown to be an epigenetic inheritable modification affecting, among other targets, the sister chromatid exchange (SCE) rate in mammalian cells in vitro. The inheritable increase in SCE rate in affected cell populations appears as a puzzling phenomenon in view of the well established relation between SCE and both mutagenesis and carcinogenesis. In the present work we demonstrate that, in a treated cell population, demethylation could be responsible for the inheritable induction of damage proneness affecting both damage induction and repair. Normal and ethionine or azacytidine treated Chinese hamster ovary cells, subclone K1 (CHO-K1), were challenged with UV light (UV) or mitomycin-C (MMC) at different times from the demethylating treatment. The SCE rate was measured with two main objects in view: (i) the induction of synergism or additivity in combined treatments, where mutagen (UV or MMC) pulse is supplied from 0 to 48 h after the end of the demethylating treatment; and (ii) the pattern of damage extinction, for the duration of up to six cell cycles after the end of the combined (demethylating agent + mutagen) treatment. Results indicate both a synergism in SCE induction by mutagens in demethylated cells even if supplied up to four cell cycles after the end of the demethylation treatment and a delay in recovery of induced damage, compared with normally methylated cells. These data are discussed in the light of the supposed mechanism of SCE increase and of the possible biological significance in terms of mutagenesis and carcinogenesis. PMID:9237771

  5. Cervicolumbar coordination in mammalian quadrupedal locomotion: role of spinal thoracic circuitry and limb sensory inputs.

    PubMed

    Juvin, Laurent; Le Gal, Jean-Patrick; Simmers, John; Morin, Didier

    2012-01-18

    Effective quadrupedal locomotion requires a close coordination between the spatially distant central pattern generators (CPGs) controlling forelimb and hindlimb movements. Using isolated preparations of the neonatal rat spinal cord, we explore the role of intervening thoracic circuitry in cervicolumbar CPG coordination and the contribution to this remote coupling of limb somatosensory inputs. In preparations activated with bath-applied N-methyl-D,L-aspartate, serotonin, and dopamine, the coordination between locomotor-related bursts recorded in cervical and lumbar ventral roots was substantially weakened, although not abolished, when the thoracic segments were selectively withheld from neurochemical stimulation or were exposed to a low Ca(2+) solution to block synaptic transmission. Moreover, cervicolumbar CPG coordination was reduced after a thoracic midsagittal section, suggesting that cross-cord projections participate in the anteroposterior coupling. In quiescent preparations, either cyclic or tonic electrical stimulation of low-threshold afferent pathways in C8 or L2 dorsal roots (DRs) could elicit coordinated ventral root bursting at both cervical and lumbar levels via an activation of the underlying CPG networks. When lumbar rhythmogenesis was prevented by local synaptic transmission blockade, L2 DR stimulation could still drive left-right alternating cervical bursting in preparations otherwise exposed to normal bathing medium. In contrast, when the cervical generators were selectively blocked, C8 DR stimulation was unable to activate the lumbar CPGs. Thus, in the newborn rat, anteroposterior limb coordination relies on active burst generation within midcord thoracic circuitry that additionally conveys ascending and weaker descending coupling influences of distant limb proprioceptive inputs to the cervical and lumbar generators, respectively. PMID:22262893

  6. Nutritional management of a patient with brain damage and spinal cord injury.

    PubMed

    Bildsten, C; Lamid, S

    1983-08-01

    Few reports on nutritional management of patients with both brain damage and spinal-cord-injury appear in the literature. We present a case of a 20-year-old male quadriplegic, C4 complete, who also sustained brain damage secondary to cerebral anoxia. When the patient was transferred to our rehabilitation unit, deterioration in nutritional status was noted, as evidenced by weight loss and depressed serum albumin and hemoglobin. Nutritional rehabilitation consisted of weaning from nasogastric tube feedings to an oral diet providing snacks and commercial supplements. This resulted in a positive nitrogen balance. Other factors, such as mobilization, exercises, and closure of a pressure sore, contributed favorably to improvement of nutritional status. PMID:6411046

  7. Nutritional management of a patient with brain damage and spinal cord injury.

    PubMed

    Bildsten, C; Lamid, S

    1983-08-01

    Few reports on nutritional management of patients with both brain damage and spinal-cord-injury appear in the literature. We present a case of a 20-year-old male quadriplegic, C4 complete, who also sustained brain damage secondary to cerebral anoxia. When the patient was transferred to our rehabilitation unit, deterioration in nutritional status was noted, as evidenced by weight loss and depressed serum albumin and hemoglobin. Nutritional rehabilitation consisted of weaning from nasogastric tube feedings to an oral diet providing snacks and commercial supplements. This resulted in a positive nitrogen balance. Other factors, such as mobilization, exercises, and closure of a pressure sore, contributed favorably to improvement of nutritional status.

  8. Genomic assay reveals tolerance of DNA damage by both translesion DNA synthesis and homology-dependent repair in mammalian cells.

    PubMed

    Izhar, Lior; Ziv, Omer; Cohen, Isadora S; Geacintov, Nicholas E; Livneh, Zvi

    2013-04-16

    DNA lesions can block replication forks and lead to the formation of single-stranded gaps. These replication complications are mitigated by DNA damage tolerance mechanisms, which prevent deleterious outcomes such as cell death, genomic instability, and carcinogenesis. The two main tolerance strategies are translesion DNA synthesis (TLS), in which low-fidelity DNA polymerases bypass the blocking lesion, and homology-dependent repair (HDR; postreplication repair), which is based on the homologous sister chromatid. Here we describe a unique high-resolution method for the simultaneous analysis of TLS and HDR across defined DNA lesions in mammalian genomes. The method is based on insertion of plasmids carrying defined site-specific DNA lesions into mammalian chromosomes, using phage integrase-mediated integration. Using this method we show that mammalian cells use HDR to tolerate DNA damage in their genome. Moreover, analysis of the tolerance of the UV light-induced 6-4 photoproduct, the tobacco smoke-induced benzo[a]pyrene-guanine adduct, and an artificial trimethylene insert shows that each of these three lesions is tolerated by both TLS and HDR. We also determined the specificity of nucleotide insertion opposite these lesions during TLS in human genomes. This unique method will be useful in elucidating the mechanism of DNA damage tolerance in mammalian chromosomes and their connection to pathological processes such as carcinogenesis. PMID:23530190

  9. Risk control and prevention of spinal cord damage due to surgery of thoracoabdominal aneurysms: medicolegal aspects.

    PubMed

    de Mol, B; Hamerlijnck, R; Vermeulen, F E; de Geest, R

    1991-01-01

    Surgery of thoracoabdominal aneurysms is accompanied by many complications of which spinal cord damage is the most serious. Such a complication tends to be the subject of litigation and medicolegal assessment. This report presents a risk control concept focussed on the reduction of spinal cord damage after surgery for a thoracoabdominal aneurysm. This concept may provide a basis for a risk management program in major surgery. Apart from sparing the patient a serious complication, improvement of the quality of care and anticipation of a medicolegal assessment were considered valuable benefits of such an effort. It is described how the threat of litigation--also in Europe--may affect clinical practice. A definition of surgical failure is described related to the five elements of risk homeostasis: complexity, linkage, cascade, human factor and safety margins. Limitations of risk control in the surgery of thoracoabdominal aneurysms are described. Finally the role of perception of risks by patient and doctor as well as the importance of informed consent and adequate disclosure are described in respect of medical quality improvement and litigation.

  10. Oxidative DNA damage contributes to the toxic activity of propylparaben in mammalian cells.

    PubMed

    Pérez Martín, José Manuel; Peropadre, Ana; Herrero, Oscar; Fernández Freire, Paloma; Labrador, Verónica; Hazen, María José

    2010-09-30

    Propyl p-hydroxybenzoate, commonly referred to as propylparaben, is the most frequently used preservative to inhibit microbial growth and extend shelf life of a range of consumer products. The objective of this study was to provide further insight into the toxicological profile of this compound, because of the current discrepancy in the literature with regard to the safety of parabens. The Vero cell line, derived from the kidney of the green monkey, was selected to evaluate the adverse effects of propylparaben by use of a set of mechanistically relevant endpoints for detecting cytotoxicity and genotoxic activities. Our results demonstrate that exposure to the compound for 24h causes changes in cell-proliferation rates rather than in cell viability. A significant and dose-dependent decline in the percentage of mitotic cells was observed at the lowest concentration tested, mainly due to cell-cycle arrest at the G0/G1 phase. Immunodetection techniques revealed that induction of DNA double-strand breaks and oxidative damage underlies the cytostatic effect observed in treated Vero cells. Additional studies are in progress to extend these findings, which define a novel mode of action of propylparaben in cultured mammalian cells.

  11. The organization of spinal motor neurons in a monotreme is consistent with a six-region schema of the mammalian spinal cord.

    PubMed

    Mitchelle, Amer; Watson, Charles

    2016-09-01

    The motor neurons in the spinal cord of an echidna (Tachyglossus aculeatus) have been mapped in Nissl-stained sections from spinal cord segments defined by spinal nerve anatomy. A medial motor column of motor neurons is found at all spinal cord levels, and a hypaxial column is found at most levels. The organization of the motor neuron clusters in the lateral motor column of the brachial (C5 to T3) and crural (L2 to S3) limb enlargements is very similar to the pattern previously revealed by retrograde tracing in placental mammals, and the motor neuron clusters have been tentatively identified according to the muscle groups they are likely to supply. The region separating the two limb enlargements (T4 to L1) contains preganglionic motor neurons that appear to represent the spinal sympathetic outflow. Immediately caudal to the crural limb enlargement is a short column of preganglionic motor neurons (S3 to S4), which it is believed represents the pelvic parasympathetic outflow. The rostral and caudal ends of the spinal cord contain neither a lateral motor column nor a preganglionic column. Branchial motor neurons (which are believed to supply the sternomastoid and trapezius muscles) are present at the lateral margin of the ventral horn in rostral cervical segments (C2-C4). These same segments contain the phrenic nucleus, which belongs to the hypaxial column. The presence or absence of the main spinal motor neuron columns in the different regions echidna spinal cord (and also in that of other amniote vertebrates) provides a basis for dividing the spinal cord into six main regions - prebrachial, brachial, postbrachial, crural, postcrural and caudal. The considerable biological and functional significance of this subdivision pattern is supported by recent studies on spinal cord hox gene expression in chicks and mice. On the other hand, the familiar 'segments' of the spinal cord are defined only by the anatomy of adjacent vertebrae, and are not demarcated by intrinsic gene

  12. The organization of spinal motor neurons in a monotreme is consistent with a six-region schema of the mammalian spinal cord.

    PubMed

    Mitchelle, Amer; Watson, Charles

    2016-09-01

    The motor neurons in the spinal cord of an echidna (Tachyglossus aculeatus) have been mapped in Nissl-stained sections from spinal cord segments defined by spinal nerve anatomy. A medial motor column of motor neurons is found at all spinal cord levels, and a hypaxial column is found at most levels. The organization of the motor neuron clusters in the lateral motor column of the brachial (C5 to T3) and crural (L2 to S3) limb enlargements is very similar to the pattern previously revealed by retrograde tracing in placental mammals, and the motor neuron clusters have been tentatively identified according to the muscle groups they are likely to supply. The region separating the two limb enlargements (T4 to L1) contains preganglionic motor neurons that appear to represent the spinal sympathetic outflow. Immediately caudal to the crural limb enlargement is a short column of preganglionic motor neurons (S3 to S4), which it is believed represents the pelvic parasympathetic outflow. The rostral and caudal ends of the spinal cord contain neither a lateral motor column nor a preganglionic column. Branchial motor neurons (which are believed to supply the sternomastoid and trapezius muscles) are present at the lateral margin of the ventral horn in rostral cervical segments (C2-C4). These same segments contain the phrenic nucleus, which belongs to the hypaxial column. The presence or absence of the main spinal motor neuron columns in the different regions echidna spinal cord (and also in that of other amniote vertebrates) provides a basis for dividing the spinal cord into six main regions - prebrachial, brachial, postbrachial, crural, postcrural and caudal. The considerable biological and functional significance of this subdivision pattern is supported by recent studies on spinal cord hox gene expression in chicks and mice. On the other hand, the familiar 'segments' of the spinal cord are defined only by the anatomy of adjacent vertebrae, and are not demarcated by intrinsic gene

  13. Neuroprotective effects of adipose-derived stem cells against ischemic neuronal damage in the rabbit spinal cord.

    PubMed

    Chung, Jin Young; Kim, Woosuk; Im, Wooseok; Yoo, Dae Young; Choi, Jung Hoon; Hwang, In Koo; Won, Moo-Ho; Chang, In Bok; Cho, Byung Moon; Hwang, Hyung Sik; Moon, Seung Myung

    2012-06-15

    Transplantation of adipose-derived stem cells (ASCs) is one of the possible therapeutic tools for ischemic damage. In this study, we observed the effects of ASCs against ischemic damage in the ventral horn of L(5-6) levels in the rabbit spinal cord. ASCs were isolated from rabbits, and cell type was confirmed by flow cytometry analysis, labeling with CM-DiI dye and differentiation into adipocytes in adipogenesis differentiation medium. ASCs were administered intrathecally into recipient rabbits (2 × 10⁵) immediately after reperfusion following a 15-min aortic artery occlusion in the subrenal region. Transplantation of ASCs significantly improved functions of the hindlimb and morphology of the ventral horn of spinal cord although CM-DiI-labeled ASCs were not observed in the spinal cord parenchyma. In addition, transplantation of ASCs significantly increased brain-derived neurotrophic factor (BDNF) levels at 72h after ischemia/reperfusion. These results suggest that transplantation of ASCs prevents motor neurons from spinal ischemic damage and reactive gliosis by increasing neurotrophic factors such as BDNF in the spinal cord.

  14. Implication of mammalian ribosomal protein S3 in the processing of DNA damage.

    PubMed

    Kim, J; Chubatsu, L S; Admon, A; Stahl, J; Fellous, R; Linn, S

    1995-06-01

    A human apurinic/apyrimidinic endonuclease activity, called AP endonuclease I, is missing from or altered specifically in cells cultured from Xeroderma pigmentosum group-D individuals (XP-D cells) (Kuhnlein, U., Lee, B., Penhoet, E. E., and Linn, S. (1978) Nucleic Acids Res. 5,951-960). We have now observed that another nuclease activity, UV endonuclease III, is similarly not detected in XP-D cells and is inseparable from the AP endonuclease I activity. This activity preferentially cleaves the phosphodiester backbone of heavily ultraviolet-irradiated DNA at unknown lesions as well as at one of the phosphodiester bonds within a cyclobutane pyrimidine dimer. The nuclease activities have been purified from mouse cells to yield a peptide of M(r) = 32,000, whose sequence indicates identity with ribosomal protein S3. The nuclease activities all cross-react with immunopurified antibody directed against authentic rat ribosomal protein S3, and, upon expression in Escherichia coli of a cloned rat cDNA for ribosomal protein S3, each of the activities was recovered and was indistinguishable from those of the mammalian UV endonuclease III. Moreover, the protein expressed in E. coli and its activities cross-react with the rat protein antibody. Ribosomal protein S3 contains a potential nuclear localization signal, and the protein isolated as a nuclease also has a glycosylation pattern consistent with a nuclear localization as determined by lectin binding. The unexpected role of a ribosomal protein in DNA damage processing and the unexplained inability to detect the nuclease activities in extracts from XP-D cells are discussed. PMID:7775413

  15. Growth inhibition and DNA damage induced by Cre recombinase in mammalian cells.

    PubMed

    Loonstra, A; Vooijs, M; Beverloo, H B; Allak, B A; van Drunen, E; Kanaar, R; Berns, A; Jonkers, J

    2001-07-31

    The use of Cre/loxP recombination in mammalian cells has expanded rapidly. We describe here that Cre expression in cultured mammalian cells may result in a markedly reduced proliferation and that this effect is dependent on the endonuclease activity of Cre. Chromosome analysis after Cre expression revealed numerous chromosomal aberrations and an increased number of sister chromatid exchanges. Titration experiments in mouse embryo fibroblasts with a ligand-regulatable Cre-ER(T) show that toxicity is dependent on the level of Cre activity. Prolonged, low levels of Cre activity permit recombination without concomitant toxicity. This urges for a careful titration of Cre activity in conditional gene modification in mammalian cells.

  16. Gene-Silencing Screen for Mammalian Axon Regeneration Identifies Inpp5f (Sac2) as an Endogenous Suppressor of Repair after Spinal Cord Injury

    PubMed Central

    Zou, Yixiao; Stagi, Massimiliano; Wang, Xingxing; Yigitkanli, Kazim; Siegel, Chad S.; Nakatsu, Fubito; Cafferty, William B. J.

    2015-01-01

    Axonal growth and neuronal rewiring facilitate functional recovery after spinal cord injury. Known interventions that promote neural repair remain limited in their functional efficacy. To understand genetic determinants of mammalian CNS axon regeneration, we completed an unbiased RNAi gene-silencing screen across most phosphatases in the genome. We identified one known and 17 previously unknown phosphatase suppressors of injury-induced CNS axon growth. Silencing Inpp5f (Sac2) leads to robust enhancement of axon regeneration and growth cone reformation. Results from cultured Inpp5f−/− neurons confirm lentiviral shRNA results from the screen. Consistent with the nonoverlapping substrate specificity between Inpp5f and PTEN, rapamycin does not block enhanced regeneration in Inpp5f−/− neurons, implicating mechanisms independent of the PI3K/AKT/mTOR pathway. Inpp5f−/− mice develop normally, but show enhanced anatomical and functional recovery after mid-thoracic dorsal hemisection injury. More serotonergic axons sprout and/or regenerate caudal to the lesion level, and greater numbers of corticospinal tract axons sprout rostral to the lesion. Functionally, Inpp5f-null mice exhibit enhanced recovery of motor functions in both open-field and rotarod tests. This study demonstrates the potential of an unbiased high-throughput functional screen to identify endogenous suppressors of CNS axon growth after injury, and reveals Inpp5f (Sac2) as a novel suppressor of CNS axon repair after spinal cord injury. SIGNIFICANCE STATEMENT The extent of axon regeneration is a critical determinant of neurological recovery from injury, and is extremely limited in the adult mammalian CNS. We describe an unbiased gene-silencing screen that uncovered novel molecules suppressing axonal regeneration. Inpp5f (Sac2) gene deletion promoted recovery from spinal cord injury with no side effects. The mechanism of action is distinct from another lipid phosphatase implicated in regeneration

  17. Co-visualization of DNA damage and ion traversals in live mammalian cells using a fluorescent nuclear track detector.

    PubMed

    Kodaira, Satoshi; Konishi, Teruaki; Kobayashi, Alisa; Maeda, Takeshi; Ahmad, Tengku Ahbrizal Farizal Tengku; Yang, Gen; Akselrod, Mark S; Furusawa, Yoshiya; Uchihori, Yukio

    2015-03-01

    The geometric locations of ion traversals in mammalian cells constitute important information in the study of heavy ion-induced biological effect. Single ion traversal through a cellular nucleus produces complex and massive DNA damage at a nanometer level, leading to cell inactivation, mutations and transformation. We present a novel approach that uses a fluorescent nuclear track detector (FNTD) for the simultaneous detection of the geometrical images of ion traversals and DNA damage in single cells using confocal microscopy. HT1080 or HT1080-53BP1-GFP cells were cultured on the surface of a FNTD and exposed to 5.1-MeV/n neon ions. The positions of the ion traversals were obtained as fluorescent images of a FNTD. Localized DNA damage in cells was identified as fluorescent spots of γ-H2AX or 53BP1-GFP. These track images and images of damaged DNA were obtained in a short time using a confocal laser scanning microscope. The geometrical distribution of DNA damage indicated by fluorescent γ-H2AX spots in fixed cells or fluorescent 53BP1-GFP spots in living cells was found to correlate well with the distribution of the ion traversals. This method will be useful for evaluating the number of ion hits on individual cells, not only for micro-beam but also for random-beam experiments.

  18. Co-visualization of DNA damage and ion traversals in live mammalian cells using a fluorescent nuclear track detector.

    PubMed

    Kodaira, Satoshi; Konishi, Teruaki; Kobayashi, Alisa; Maeda, Takeshi; Ahmad, Tengku Ahbrizal Farizal Tengku; Yang, Gen; Akselrod, Mark S; Furusawa, Yoshiya; Uchihori, Yukio

    2015-03-01

    The geometric locations of ion traversals in mammalian cells constitute important information in the study of heavy ion-induced biological effect. Single ion traversal through a cellular nucleus produces complex and massive DNA damage at a nanometer level, leading to cell inactivation, mutations and transformation. We present a novel approach that uses a fluorescent nuclear track detector (FNTD) for the simultaneous detection of the geometrical images of ion traversals and DNA damage in single cells using confocal microscopy. HT1080 or HT1080-53BP1-GFP cells were cultured on the surface of a FNTD and exposed to 5.1-MeV/n neon ions. The positions of the ion traversals were obtained as fluorescent images of a FNTD. Localized DNA damage in cells was identified as fluorescent spots of γ-H2AX or 53BP1-GFP. These track images and images of damaged DNA were obtained in a short time using a confocal laser scanning microscope. The geometrical distribution of DNA damage indicated by fluorescent γ-H2AX spots in fixed cells or fluorescent 53BP1-GFP spots in living cells was found to correlate well with the distribution of the ion traversals. This method will be useful for evaluating the number of ion hits on individual cells, not only for micro-beam but also for random-beam experiments. PMID:25324538

  19. Co-visualization of DNA damage and ion traversals in live mammalian cells using a fluorescent nuclear track detector

    PubMed Central

    Kodaira, Satoshi; Konishi, Teruaki; Kobayashi, Alisa; Maeda, Takeshi; Ahmad, Tengku Ahbrizal Farizal Tengku; Yang, Gen; Akselrod, Mark S.; Furusawa, Yoshiya; Uchihori, Yukio

    2015-01-01

    The geometric locations of ion traversals in mammalian cells constitute important information in the study of heavy ion-induced biological effect. Single ion traversal through a cellular nucleus produces complex and massive DNA damage at a nanometer level, leading to cell inactivation, mutations and transformation. We present a novel approach that uses a fluorescent nuclear track detector (FNTD) for the simultaneous detection of the geometrical images of ion traversals and DNA damage in single cells using confocal microscopy. HT1080 or HT1080–53BP1-GFP cells were cultured on the surface of a FNTD and exposed to 5.1-MeV/n neon ions. The positions of the ion traversals were obtained as fluorescent images of a FNTD. Localized DNA damage in cells was identified as fluorescent spots of γ-H2AX or 53BP1-GFP. These track images and images of damaged DNA were obtained in a short time using a confocal laser scanning microscope. The geometrical distribution of DNA damage indicated by fluorescent γ-H2AX spots in fixed cells or fluorescent 53BP1-GFP spots in living cells was found to correlate well with the distribution of the ion traversals. This method will be useful for evaluating the number of ion hits on individual cells, not only for micro-beam but also for random-beam experiments. PMID:25324538

  20. Interpreting sperm DNA damage in a diverse range of mammalian sperm by means of the two-tailed comet assay

    PubMed Central

    Cortés-Gutiérrez, Elva I.; López-Fernández, Carmen; Fernández, José Luis; Dávila-Rodríguez, Martha I.; Johnston, Stephen D.; Gosálvez, Jaime

    2014-01-01

    Key Concepts The two-dimensional Two-Tailed Comet assay (TT-comet) protocol is a valuable technique to differentiate between single-stranded (SSBs) and double-stranded DNA breaks (DSBs) on the same sperm cell.Protein lysis inherent with the TT-comet protocol accounts for differences in sperm protamine composition at a species-specific level to produce reliable visualization of sperm DNA damage.Alkaline treatment may break the sugar–phosphate backbone in abasic sites or at sites with deoxyribose damage, transforming these lesions into DNA breaks that are also converted into ssDNA. These lesions are known as Alkali Labile Sites “ALSs.”DBD–FISH permits the in situ visualization of DNA breaks, abasic sites or alkaline-sensitive DNA regions.The alkaline comet single assay reveals that all mammalian species display constitutive ALS related with the requirement of the sperm to undergo transient changes in DNA structure linked with chromatin packing.Sperm DNA damage is associated with fertilization failure, impaired pre-and post- embryo implantation and poor pregnancy outcome.The TT is a valuable tool for identifying SSBs or DSBs in sperm cells with DNA fragmentation and can be therefore used for the purposes of fertility assessment. Sperm DNA damage is associated with fertilization failure, impaired pre-and post- embryo implantation and poor pregnancy outcome. A series of methodologies to assess DNA damage in spermatozoa have been developed but most are unable to differentiate between single-stranded DNA breaks (SSBs) and double-stranded DNA breaks (DSBs) on the same sperm cell. The two-dimensional Two-Tailed Comet assay (TT-comet) protocol highlighted in this review overcomes this limitation and emphasizes the importance in accounting for the difference in sperm protamine composition at a species-specific level for the appropriate preparation of the assay. The TT-comet is a modification of the original comet assay that uses a two dimensional electrophoresis to

  1. Interpreting sperm DNA damage in a diverse range of mammalian sperm by means of the two-tailed comet assay.

    PubMed

    Cortés-Gutiérrez, Elva I; López-Fernández, Carmen; Fernández, José Luis; Dávila-Rodríguez, Martha I; Johnston, Stephen D; Gosálvez, Jaime

    2014-01-01

    Key ConceptsThe two-dimensional Two-Tailed Comet assay (TT-comet) protocol is a valuable technique to differentiate between single-stranded (SSBs) and double-stranded DNA breaks (DSBs) on the same sperm cell.Protein lysis inherent with the TT-comet protocol accounts for differences in sperm protamine composition at a species-specific level to produce reliable visualization of sperm DNA damage.Alkaline treatment may break the sugar-phosphate backbone in abasic sites or at sites with deoxyribose damage, transforming these lesions into DNA breaks that are also converted into ssDNA. These lesions are known as Alkali Labile Sites "ALSs."DBD-FISH permits the in situ visualization of DNA breaks, abasic sites or alkaline-sensitive DNA regions.The alkaline comet single assay reveals that all mammalian species display constitutive ALS related with the requirement of the sperm to undergo transient changes in DNA structure linked with chromatin packing.Sperm DNA damage is associated with fertilization failure, impaired pre-and post- embryo implantation and poor pregnancy outcome.The TT is a valuable tool for identifying SSBs or DSBs in sperm cells with DNA fragmentation and can be therefore used for the purposes of fertility assessment. Sperm DNA damage is associated with fertilization failure, impaired pre-and post- embryo implantation and poor pregnancy outcome. A series of methodologies to assess DNA damage in spermatozoa have been developed but most are unable to differentiate between single-stranded DNA breaks (SSBs) and double-stranded DNA breaks (DSBs) on the same sperm cell. The two-dimensional Two-Tailed Comet assay (TT-comet) protocol highlighted in this review overcomes this limitation and emphasizes the importance in accounting for the difference in sperm protamine composition at a species-specific level for the appropriate preparation of the assay. The TT-comet is a modification of the original comet assay that uses a two dimensional electrophoresis to allow for

  2. Potential of adult mammalian lumbosacral spinal cord to execute and acquire improved locomotion in the absence of supraspinal input

    NASA Technical Reports Server (NTRS)

    Edgerton, V. R.; Roy, R. R.; Hodgson, J. A.; Prober, R. J.; de Guzman, C. P.; de Leon, R.

    1992-01-01

    The neural circuitry of the lumbar spinal cord can generate alternating extension and flexion of the hindlimbs. The hindlimbs of adult cats with complete transection of the spinal cord at a low thoracic level (T12-T13) can perform full weight-supporting locomotion on a treadmill belt moving at a range of speeds. Some limitations in the locomotor capacity can be associated with a deficit in the recruitment level of the fast extensors during the stance phase and the flexors during the swing phase of a step cycle. The level of locomotor performance, however, can be enhanced by daily training on a treadmill while emphasizing full weight-support stepping and by providing appropriately timed sensory stimulation, loading, and/or pharmacologic stimulation of the hindlimb neuromuscular apparatus. Furthermore, there appears to be an interactive effect of these interventions. For example, the maximum treadmill speed that a spinal adult cat can attain and maintain is significantly improved with daily full weight-supporting treadmill training, but progressive recruitment of fast extensors becomes apparent only when the hindlimbs are loaded by gently pulling down on the tail during the stepping. Stimulation of the sural nerve at the initiation of the flexion phase of the step cycle can likewise markedly improve the locomotor capability. Administration of clonidine, in particular in combination with an elevated load, resulted in the most distinct and consistent alternating bursts of electromyographic activity during spinal stepping. These data indicate that the spinal cord has the ability to execute alternating activation of the extensor and flexor musculature of the hindlimbs (stepping) and that this ability can be improved by several interventions such as training, sensory stimulation, and use of some pharmacologic agents. Thus, it appears that the spinal cord, without supraspinal input, is highly plastic and has the potential to "learn," that is, to acquire and improve its

  3. Nanoscale imaging of untreated mammalian cells in a medium with low radiation damage using scanning electron-assisted dielectric microscopy

    NASA Astrophysics Data System (ADS)

    Okada, Tomoko; Ogura, Toshihiko

    2016-07-01

    Imaging of untreated living cells in a medium at a nanometre-scale resolution under physiological conditions is a significant challenge. Scanning electron microscopy (SEM) is widely used to observe cells in various atmospheric holders or special equipment. However, untreated biological specimens in aqueous solution generally incur heavy radiation damage from the direct electron beam (EB); and these images exhibit very poor contrast. Therefore, a new method for generating high-contrast images of living cells under physiological conditions without radiation damage has been strongly desired. Here, we demonstrate the first nanoscale observation of living cultured mammalian cells using our newly developed scanning-electron assisted dielectric microscopy (SE-ADM) method with a culture dish holder. Using the difference in relative permittivity between water and specimens, our SE-ADM system aids in the visualisation of untreated biological samples in aqueous solution. In addition, specimens incurred only a low level of radiation damage because the tungsten (W)-coated silicon nitride (SiN) film absorbs irradiated electrons. Untreated cells and organelles are clearly visible in high-contrast and high-resolution images without staining and fixation. Furthermore, our method enables the detection of changes in organelle structures within cells via time-lapse imaging with minimal radiation damage.

  4. Quantifying hyperoxia-mediated damage to mammalian respiratory cilia-driven fluid flow using particle tracking velocimetry optical coherence tomography

    PubMed Central

    Gamm, Ute A.; Huang, Brendan K.; Syed, Mansoor; Zhang, Xuchen; Bhandari, Vineet; Choma, Michael A.

    2015-01-01

    Abstract. Oxygen supplementation [hyperoxia, increased fraction of inspired oxygen (FiO2)] is an indispensable treatment in the intensive care unit for patients in respiratory failure. Like other treatments or drugs, hyperoxia has a risk-benefit profile that guides its clinical use. While hyperoxia is known to damage respiratory epithelium, it is unknown if damage can result in impaired capacity to generate cilia-driven fluid flow. Here, we demonstrate that quantifying cilia-driven fluid flow velocities in the sub-100 μm/s regime (sub-0.25 in./min regime) reveals hyperoxia-mediated damage to the capacity of ciliated respiratory mucosa to generate directional flow. Flow quantification was performed using particle tracking velocimetry optical coherence tomography (PTV-OCT) in ex vivo mouse trachea. The ability of PTV-OCT to detect biomedically relevant flow perturbations in the sub-100 μm/s regime was validated by quantifying temperature- and drug-mediated modulation of flow performance in ex vivo mouse trachea. Overall, PTV-OCT imaging of cilia-driven fluid flow in ex vivo mouse trachea is a powerful and straightforward approach for studying factors that modulate and damage mammalian respiratory ciliary physiology. PMID:26308164

  5. Nanoscale imaging of untreated mammalian cells in a medium with low radiation damage using scanning electron-assisted dielectric microscopy

    PubMed Central

    Okada, Tomoko; Ogura, Toshihiko

    2016-01-01

    Imaging of untreated living cells in a medium at a nanometre-scale resolution under physiological conditions is a significant challenge. Scanning electron microscopy (SEM) is widely used to observe cells in various atmospheric holders or special equipment. However, untreated biological specimens in aqueous solution generally incur heavy radiation damage from the direct electron beam (EB); and these images exhibit very poor contrast. Therefore, a new method for generating high-contrast images of living cells under physiological conditions without radiation damage has been strongly desired. Here, we demonstrate the first nanoscale observation of living cultured mammalian cells using our newly developed scanning-electron assisted dielectric microscopy (SE-ADM) method with a culture dish holder. Using the difference in relative permittivity between water and specimens, our SE-ADM system aids in the visualisation of untreated biological samples in aqueous solution. In addition, specimens incurred only a low level of radiation damage because the tungsten (W)-coated silicon nitride (SiN) film absorbs irradiated electrons. Untreated cells and organelles are clearly visible in high-contrast and high-resolution images without staining and fixation. Furthermore, our method enables the detection of changes in organelle structures within cells via time-lapse imaging with minimal radiation damage. PMID:27375121

  6. Quantifying hyperoxia-mediated damage to mammalian respiratory cilia-driven fluid flow using particle tracking velocimetry optical coherence tomography.

    PubMed

    Gamm, Ute A; Huang, Brendan K; Syed, Mansoor; Zhang, Xuchen; Bhandari, Vineet; Choma, Michael A

    2015-08-01

    Oxygen supplementation [hyperoxia, increased fraction of inspired oxygen (FiO 2 )] is an indispensable treatment in the intensive care unit for patients in respiratory failure. Like other treatments or drugs, hyperoxia has a risk-benefit profile that guides its clinical use. While hyperoxia is known to damage respiratory epithelium, it is unknown if damage can result in impaired capacity to generate cilia-driven fluid flow. Here, we demonstrate that quantifying cilia-driven fluid flow velocities in the sub-100 μm/s regime (sub-0.25 in./min regime) reveals hyperoxia-mediated damage to the capacity of ciliated respiratory mucosa to generate directional flow. Flow quantification was performed using particle tracking velocimetry optical coherence tomography (PTV-OCT) in ex vivo mouse trachea. The ability of PTV-OCT to detect biomedically relevant flow perturbations in the sub-100 μm/s regime was validated by quantifying temperature- and drug-mediated modulation of flow performance in ex vivo mouse trachea. Overall, PTV-OCT imaging of cilia-driven fluid flow in ex vivo mouse trachea is a powerful and straightforward approach for studying factors that modulate and damage mammalian respiratory ciliary physiology.

  7. Nanoscale imaging of untreated mammalian cells in a medium with low radiation damage using scanning electron-assisted dielectric microscopy.

    PubMed

    Okada, Tomoko; Ogura, Toshihiko

    2016-01-01

    Imaging of untreated living cells in a medium at a nanometre-scale resolution under physiological conditions is a significant challenge. Scanning electron microscopy (SEM) is widely used to observe cells in various atmospheric holders or special equipment. However, untreated biological specimens in aqueous solution generally incur heavy radiation damage from the direct electron beam (EB); and these images exhibit very poor contrast. Therefore, a new method for generating high-contrast images of living cells under physiological conditions without radiation damage has been strongly desired. Here, we demonstrate the first nanoscale observation of living cultured mammalian cells using our newly developed scanning-electron assisted dielectric microscopy (SE-ADM) method with a culture dish holder. Using the difference in relative permittivity between water and specimens, our SE-ADM system aids in the visualisation of untreated biological samples in aqueous solution. In addition, specimens incurred only a low level of radiation damage because the tungsten (W)-coated silicon nitride (SiN) film absorbs irradiated electrons. Untreated cells and organelles are clearly visible in high-contrast and high-resolution images without staining and fixation. Furthermore, our method enables the detection of changes in organelle structures within cells via time-lapse imaging with minimal radiation damage. PMID:27375121

  8. Meta-analysis of attitudes toward damage-causing mammalian wildlife.

    PubMed

    Kansky, Ruth; Kidd, Martin; Knight, Andrew T

    2014-08-01

    Many populations of threatened mammals persist outside formally protected areas, and their survival depends on the willingness of communities to coexist with them. An understanding of the attitudes, and specifically the tolerance, of individuals and communities and the factors that determine these is therefore fundamental to designing strategies to alleviate human-wildlife conflict. We conducted a meta-analysis to identify factors that affected attitudes toward 4 groups of terrestrial mammals. Elephants (65%) elicited the most positive attitudes, followed by primates (55%), ungulates (53%), and carnivores (44%). Urban residents presented the most positive attitudes (80%), followed by commercial farmers (51%) and communal farmers (26%). A tolerance to damage index showed that human tolerance of ungulates and primates was proportional to the probability of experiencing damage while elephants elicited tolerance levels higher than anticipated and carnivores elicited tolerance levels lower than anticipated. Contrary to conventional wisdom, experiencing damage was not always the dominant factor determining attitudes. Communal farmers had a lower probability of being positive toward carnivores irrespective of probability of experiencing damage, while commercial farmers and urban residents were more likely to be positive toward carnivores irrespective of damage. Urban residents were more likely to be positive toward ungulates, elephants, and primates when probability of damage was low, but not when it was high. Commercial and communal farmers had a higher probability of being positive toward ungulates, primates, and elephants irrespective of probability of experiencing damage. Taxonomic bias may therefore be important. Identifying the distinct factors explaining these attitudes and the specific contexts in which they operate, inclusive of the species causing damage, will be essential for prioritizing conservation investments.

  9. G-CSF promotes autophagy and reduces neural tissue damage after spinal cord injury in mice.

    PubMed

    Guo, Yuji; Liu, Shangming; Zhang, Xianghong; Wang, Liyan; Gao, Jiangang; Han, Aiqing; Hao, Aijun

    2015-12-01

    Granulocyte colony-stimulating factor (G-CSF) was investigated for its capacity to induce autophagy and related neuroprotective mechanisms in an acute spinal cord injury model. To accomplish this goal, we established a mouse spinal cord hemisection model to test the effects of recombinant human G-CSF. The results showed that autophagy was activated after spinal cord injury and G-CSF appears to induce a more rapid activation of autophagy within injured spinal cords as compared with that of non-treated animals. Apoptosis as induced in mechanically injured neurons with G-CSF treatment was enhanced after inhibiting autophagy by 3-methyladenine (3-MA), which partially blocked the neuroprotective effect of autophagy as induced by G-CSF. In addition, G-CSF inhibited the activity of the NF-κB signal pathway in neurons after mechanical injury. We conclude that G-CSF promotes autophagy by inhibiting the NF-κB signal pathway and protects neuronal structure after spinal cord injury. We therefore suggest that G-CSF, which rapidly induces autophagy after spinal cord injury to inhibit neuronal apoptosis, may thus provide an effective auxiliary therapeutic intervention for spinal cord injury.

  10. Tissue Damage Markers after a Spinal Manipulation in Healthy Subjects: A Preliminary Report of a Randomized Controlled Trial

    PubMed Central

    Achalandabaso, A.; Plaza-Manzano, G.; Lomas-Vega, R.; Martínez-Amat, A.; Camacho, M. V.; Gassó, M.; Hita-Contreras, F.; Molina, F.

    2014-01-01

    Spinal manipulation (SM) is a manual therapy technique frequently applied to treat musculoskeletal disorders because of its analgesic effects. It is defined by a manual procedure involving a directed impulse to move a joint past its physiologic range of movement (ROM). In this sense, to exceed the physiologic ROM of a joint could trigger tissue damage, which might represent an adverse effect associated with spinal manipulation. The present work tries to explore the presence of tissue damage associated with SM through the damage markers analysis. Thirty healthy subjects recruited at the University of Jaén were submitted to a placebo SM (control group; n = 10), a single lower cervical manipulation (cervical group; n = 10), and a thoracic manipulation (n = 10). Before the intervention, blood samples were extracted and centrifuged to obtain plasma and serum. The procedure was repeated right after the intervention and two hours after the intervention. Tissue damage markers creatine phosphokinase (CPK), lactate dehydrogenase (LDH), C-reactive protein (CRP), troponin-I, myoglobin, neuron-specific enolase (NSE), and aldolase were determined in samples. Statistical analysis was performed through a 3 × 3 mixed-model ANOVA. Neither cervical manipulation nor thoracic manipulation did produce significant changes in the CPK, LDH, CRP, troponin-I, myoglobin, NSE, or aldolase blood levels. Our data suggest that the mechanical strain produced by SM seems to be innocuous to the joints and surrounding tissues in healthy subjects. PMID:25609853

  11. Genetic ablation of V2a ipsilateral interneurons disrupts left-right locomotor coordination in mammalian spinal cord.

    PubMed

    Crone, Steven A; Quinlan, Katharina A; Zagoraiou, Laskaro; Droho, Steven; Restrepo, Carlos Ernesto; Lundfald, Line; Endo, Toshiaki; Setlak, Jennifer; Jessell, Thomas M; Kiehn, Ole; Sharma, Kamal

    2008-10-01

    The initiation and coordination of activity in limb muscles are the main functions of neural circuits that control locomotion. Commissural neurons connect locomotor circuits on the two sides of the spinal cord, and represent the known neural substrate for left-right coordination. Here we demonstrate that a group of ipsilateral interneurons, V2a interneurons, plays an essential role in the control of left-right alternation. In the absence of V2a interneurons, the spinal cord fails to exhibit consistent left-right alternation. Locomotor burst activity shows increased variability, but flexor-extensor coordination is unaffected. Anatomical tracing studies reveal a direct excitatory input of V2a interneurons onto commissural interneurons, including a set of molecularly defined V0 neurons that drive left-right alternation. Our findings imply that the neural substrate for left-right coordination consists of at least two components; commissural neurons and a class of ipsilateral interneurons that activate commissural pathways. PMID:18940589

  12. Anatomical and functional evidence for trace amines as unique modulators of locomotor function in the mammalian spinal cord.

    PubMed

    Gozal, Elizabeth A; O'Neill, Brannan E; Sawchuk, Michael A; Zhu, Hong; Halder, Mallika; Chou, Ching-Chieh; Hochman, Shawn

    2014-01-01

    The trace amines (TAs), tryptamine, tyramine, and β-phenylethylamine, are synthesized from precursor amino acids via aromatic-L-amino acid decarboxylase (AADC). We explored their role in the neuromodulation of neonatal rat spinal cord motor circuits. We first showed that the spinal cord contains the substrates for TA biosynthesis (AADC) and for receptor-mediated actions via trace amine-associated receptors (TAARs) 1 and 4. We next examined the actions of the TAs on motor activity using the in vitro isolated neonatal rat spinal cord. Tyramine and tryptamine most consistently increased motor activity with prominent direct actions on motoneurons. In the presence of N-methyl-D-aspartate, all applied TAs supported expression of a locomotor-like activity (LLA) that was indistinguishable from that ordinarily observed with serotonin, suggesting that the TAs act on common central pattern generating neurons. The TAs also generated distinctive complex rhythms characterized by episodic bouts of LLA. TA actions on locomotor circuits did not require interaction with descending monoaminergic projections since evoked LLA was maintained following block of all Na(+)-dependent monoamine transporters or the vesicular monoamine transporter. Instead, TA (tryptamine and tyramine) actions depended on intracellular uptake via pentamidine-sensitive Na(+)-independent membrane transporters. Requirement for intracellular transport is consistent with the TAs having much slower LLA onset than serotonin and for activation of intracellular TAARs. To test for endogenous actions following biosynthesis, we increased intracellular amino acid levels with cycloheximide. LLA emerged and included distinctive TA-like episodic bouts. In summary, we provided anatomical and functional evidence of the TAs as an intrinsic spinal monoaminergic modulatory system capable of promoting recruitment of locomotor circuits independent of the descending monoamines. These actions support their known sympathomimetic

  13. The reduction of radiation damage to the spinal cord by post-irradiation administration of vasoactive drugs

    SciTech Connect

    Hornsey, S.; Myers, R.; Jenkinson, T. )

    1990-06-01

    Radiation induced white matter necrosis in the rat spinal cord is preceded by changes in permeability of the blood brain-barrier, reduced blood flow, and infarction so that the necrosis is an ischemic necrosis. Attempts have been made to modify this developing pathology by the administration of drugs post-irradiation but just prior to the changes in vascular permeability. Verapamyl, a calcium channel blocker, had no effect on the development of ataxia. Dipyridamole, a drug which increases blood flow and reduces thrombosis, delayed and reduced the onset of ataxia. A low iron diet and desferrioxamine which reduces reperfusion injury also delayed and reduced ataxia. These results support the thesis that vascular changes are an important pathway in the development of radiation necrosis and that reperfusion injury is an important factor in the development and exacerbation of radiation damage to the spinal cord.

  14. Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

    SciTech Connect

    Feinendegen, L.E.; Bond, V.P.; Sondhaus, C.A.; Altman, K.I.

    1998-12-31

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.

  15. Enhanced replication of UV-damaged Simian virus 40 DNA in carcinogen-treated mammalian cells

    SciTech Connect

    Maga, J.A.

    1983-01-01

    The replication of UV-damaged Simian virus 40 (SV40) in carcinogen-treated monkey cells has been studied to elucidate the mechanism of carcinogen-enhanced reactivation. Carcinogen enhanced reactivation is the observed increase in UV-irradiated virus survival in host cells treated with low doses of carcinogen compared to UV-irradiated virus survival in untreated hosts. Carcinogen treatment of monkey kidney cells with either N-acetoxy-2-acetylaminofluorene (AAAF) or UV radiation leads to an enhanced capacity to replicate UV-damaged virus during the first round of infection. To further define the mechanism leading to enhanced replication, a detailed biochemical analysis of replication intermediates in carcinogen-treated cells was performed. Several conclusions can be drawn. First enhanced replication can be observed in the first four rounds of replication after UV irradiation of viral templates. The second major finding is that the relaxed circular intermediate model proposed for the replication of UV-damaged templates in untreated cells appears valid for replication of UV-damaged templates in carcinogen-treated cells. Possible mechanisms and the supporting evidence are discussed and future experiments outlined.

  16. Nerve cell damage in mammalian brain after exposure to microwaves from GSM mobile phones.

    PubMed

    Salford, Leif G; Brun, Arne E; Eberhardt, Jacob L; Malmgren, Lars; Persson, Bertil R R

    2003-06-01

    The possible risks of radio-frequency electromagnetic fields for the human body is a growing concern for our society. We have previously shown that weak pulsed microwaves give rise to a significant leakage of albumin through the blood-brain barrier. In this study we investigated whether a pathologic leakage across the blood-brain barrier might be combined with damage to the neurons. Three groups each of eight rats were exposed for 2 hr to Global System for Mobile Communications (GSM) mobile phone electromagnetic fields of different strengths. We found highly significant (p< 0.002) evidence for neuronal damage in the cortex, hippocampus, and basal ganglia in the brains of exposed rats.

  17. Meta-Analysis of Attitudes toward Damage-Causing Mammalian Wildlife

    PubMed Central

    KANSKY, RUTH; KIDD, MARTIN; KNIGHT, ANDREW T

    2014-01-01

    Many populations of threatened mammals persist outside formally protected areas, and their survival depends on the willingness of communities to coexist with them. An understanding of the attitudes, and specifically the tolerance, of individuals and communities and the factors that determine these is therefore fundamental to designing strategies to alleviate human-wildlife conflict. We conducted a meta-analysis to identify factors that affected attitudes toward 4 groups of terrestrial mammals. Elephants (65%) elicited the most positive attitudes, followed by primates (55%), ungulates (53%), and carnivores (44%). Urban residents presented the most positive attitudes (80%), followed by commercial farmers (51%) and communal farmers (26%). A tolerance to damage index showed that human tolerance of ungulates and primates was proportional to the probability of experiencing damage while elephants elicited tolerance levels higher than anticipated and carnivores elicited tolerance levels lower than anticipated. Contrary to conventional wisdom, experiencing damage was not always the dominant factor determining attitudes. Communal farmers had a lower probability of being positive toward carnivores irrespective of probability of experiencing damage, while commercial farmers and urban residents were more likely to be positive toward carnivores irrespective of damage. Urban residents were more likely to be positive toward ungulates, elephants, and primates when probability of damage was low, but not when it was high. Commercial and communal farmers had a higher probability of being positive toward ungulates, primates, and elephants irrespective of probability of experiencing damage. Taxonomic bias may therefore be important. Identifying the distinct factors explaining these attitudes and the specific contexts in which they operate, inclusive of the species causing damage, will be essential for prioritizing conservation investments. Meta-Análisis de las Posturas hacia la Mam

  18. Track structure model for damage to mammalian cell cultures during solar proton events

    NASA Technical Reports Server (NTRS)

    Cucinotta, F. A.; Wilson, J. W.; Townsend, L. W.; Shinn, J. L.; Katz, R.

    1992-01-01

    Solar proton events (SPEs) occur infrequently and unpredictably, thus representing a potential hazard to interplanetary space missions. Biological damage from SPEs will be produced principally through secondary electron production in tissue, including important contributions due to delta rays from nuclear reaction products. We review methods for estimating the biological effectiveness of SPEs using a high energy proton model and the parametric cellular track model. Results of the model are presented for several of the historically largest flares using typical levels and body shielding.

  19. Protection against UVA-induced photooxidative damage in mammalian cell lines expressing increased levels of metallothionein

    SciTech Connect

    Dudek, E.J. Illinois Inst. of Tech., Chicago, IL . Dept. of Biology); Peak, J.G.; Peak, M.J. ); Roth, R.M. . Dept. of Biology)

    1990-01-01

    Metallothionein (MT) is an endogenous low molecular weight protein that is inducible in a variety of eukaryotic cells and has the ability to selectivity bind heavy metal ions such as zinc and the cadmium. Although the exact physiological role of MT is still not understood, there is strong evidence that MT is involved in providing cellular resistance against the damaging effects of heavy metals and in the regulation of intracellular zinc and copper. Recently, it has been demonstrated that MT can scavenge radiation-induced reactive oxygen intermediates in vitro, specifically hydroxyl and superoxide radicals, and because of these observations it has been suggested that MT may provide protection against radiation-induced oxidative stress in vivo. Cell lines expressing increased levels of MT have demonstrated resistance to ionizing radiation, to ultraviolet radiation, and also to various DNA damaging agents including melphalan and cis-diaminedichloroplatinum. It is therefore important to gain some insight into the relationship between cellular MT content and cellular resistance to radiation and other DNA damaging agents. In this study we investigated the role of MT in providing protection against monochromatic 365-nm UVA radiation, which is known to generate intracellular reactive oxygen species that are involved in both DNA damage and cell killing. For this purpose, we used zinc acetate, a potent inducer of MT, to elevate MT levels in V79 Chinese hamster fibroblasts prior to UVA exposure and determined cell survival for uninduced and induced cultures. In order to eliminate any zinc effects other than MT induction, we also isolated and characterized cadmium chloride-resistant clones of V79 cells that have increased steady-state levels of both MT mRNA and protein, and we examined their survival characteristics against 365-nm radiation in the absence of zinc acetate. 14 refs., 3 figs.

  20. Single-hit potentially lethal damage: evidence of its repair in mammalian cells

    SciTech Connect

    Utsumi, H.; Hill, C.K.; Ben-Hur, E.; Elkind, M.M.

    1981-09-01

    Following mid to large doses of X rays, or of fission spectrum neutrons, the repair of potentially lethal damage in V79 Chinese hamster cells can be inhibited by anisotonic phosphate-buffered saline or by medium containing 90% D/sub 2/O. The foregoing post-treatments do not affect the viability of unirradiated cells. Using single synchronized cells irradiated in late S-phase, the most resistant phase of the cell cycle, repair of potentially lethal damage in late S-phase, the most resistant phase of the cell cycle, repair of potentially lethal damage in the single-hit, initially exponential, or small-dose part of the survival curve was examined. The use of synchronized cells avoids misinterpretations due to population heterogeneity. The slope of the small-dose, exponential region of the neutron survival curve is much steeper than that of the x-ray survival curve. Even so, it is demonstrated with post-treatments consisting of hypertonic phosphate-buffered saline, medium containing D/sub 2/O,adiation is connected with their proliferation but not with the migration out from lymphoid organs.

  1. Multi-walled carbon nanotubes (MWCNT): induction of DNA damage in plant and mammalian cells.

    PubMed

    Ghosh, Manosij; Chakraborty, Anirban; Bandyopadhyay, Maumita; Mukherjee, Anita

    2011-12-15

    Increasing use of multiwalled carbon nanotubes (MWCNT) necessitates an improved understanding of their potential impact on environment health. In the present study we evaluated the genotoxicity of MWCNT on plant and mammalian test systems. Genotoxic responses such as chromosomal aberrations and DNA strand breakages were studied in Allium cepa, human lymphocytes, mouse bone marrow cells and pBR322 plasmid DNA. Results showed that MWCNT could cause chromosomal aberrations, DNA fragmentation and apoptosis in Allium root cells that could be correlated with the internalization of MWCNT in the plant cells. In human lymphocytes significant genotoxic response was observed at the concentration 2 μg/ml. Higher concentrations led to a decrease in values of the tail DNA percent that may be due to the formation of crosslinks. Annexin V-FITC-PI staining indicated only a small percentage of cells were undergoing apoptosis. Genotoxic effects were shown by micronuclei (MN) frequencies in experiments on mouse bone marrow cells. In the cell free DNA system (plasmid pBR322), a strong correlation between DNA strand break and concentration was observed. Based on the findings of the present study MWCNT may have significant impact on genomic activities.

  2. Progesterone Reduces Secondary Damage, Preserves White Matter, and Improves Locomotor Outcome after Spinal Cord Contusion

    PubMed Central

    Garcia-Ovejero, Daniel; González, Susana; Paniagua-Torija, Beatriz; Lima, Analía; Molina-Holgado, Eduardo; De Nicola, Alejandro F.

    2014-01-01

    Abstract Progesterone is an anti-inflammatory and promyelinating agent after spinal cord injury, but its effectiveness on functional recovery is still controversial. In the current study, we tested the effects of chronic progesterone administration on tissue preservation and functional recovery in a clinically relevant model of spinal cord lesion (thoracic contusion). Using magnetic resonance imaging, we observed that progesterone reduced both volume and rostrocaudal extension of the lesion at 60 days post-injury. In addition, progesterone increased the number of total mature oligodendrocytes, myelin basic protein immunoreactivity, and the number of axonal profiles at the epicenter of the lesion. Further, progesterone treatment significantly improved motor outcome as assessed using the Basso-Bresnahan-Beattie scale for locomotion and CatWalk gait analysis. These data suggest that progesterone could be considered a promising therapeutical candidate for spinal cord injury. PMID:24460450

  3. Meta-Analysis of Attitudes toward Damage-Causing Mammalian Wildlife

    PubMed Central

    KANSKY, RUTH; KIDD, MARTIN; KNIGHT, ANDREW T

    2014-01-01

    Many populations of threatened mammals persist outside formally protected areas, and their survival depends on the willingness of communities to coexist with them. An understanding of the attitudes, and specifically the tolerance, of individuals and communities and the factors that determine these is therefore fundamental to designing strategies to alleviate human-wildlife conflict. We conducted a meta-analysis to identify factors that affected attitudes toward 4 groups of terrestrial mammals. Elephants (65%) elicited the most positive attitudes, followed by primates (55%), ungulates (53%), and carnivores (44%). Urban residents presented the most positive attitudes (80%), followed by commercial farmers (51%) and communal farmers (26%). A tolerance to damage index showed that human tolerance of ungulates and primates was proportional to the probability of experiencing damage while elephants elicited tolerance levels higher than anticipated and carnivores elicited tolerance levels lower than anticipated. Contrary to conventional wisdom, experiencing damage was not always the dominant factor determining attitudes. Communal farmers had a lower probability of being positive toward carnivores irrespective of probability of experiencing damage, while commercial farmers and urban residents were more likely to be positive toward carnivores irrespective of damage. Urban residents were more likely to be positive toward ungulates, elephants, and primates when probability of damage was low, but not when it was high. Commercial and communal farmers had a higher probability of being positive toward ungulates, primates, and elephants irrespective of probability of experiencing damage. Taxonomic bias may therefore be important. Identifying the distinct factors explaining these attitudes and the specific contexts in which they operate, inclusive of the species causing damage, will be essential for prioritizing conservation investments. Meta-Análisis de las Posturas hacia la Mam

  4. DNA Damage Response and DNA Repair in Skeletal Myocytes From a Mouse Model of Spinal Muscular Atrophy.

    PubMed

    Fayzullina, Saniya; Martin, Lee J

    2016-09-01

    We studied DNA damage response (DDR) and DNA repair capacities of skeletal muscle cells from a mouse model of infantile spinal muscular atrophy (SMA) caused by loss-of-function mutation of survival of motor neuron (Smn). Primary myocyte cultures derived from skeletal muscle satellite cells of neonatal control and mutant SMN mice had similar myotube length, myonuclei, satellite cell marker Pax7 and differentiated myotube marker myosin, and acetylcholine receptor clustering. DNA damage was induced in differentiated skeletal myotubes by γ-irradiation, etoposide, and methyl methanesulfonate (MMS). Unexposed control and SMA myotubes had stable genome integrity. After γ-irradiation and etoposide, myotubes repaired most DNA damage equally. Control and mutant myotubes exposed to MMS exhibited equivalent DNA damage without repair. Control and SMA myotube nuclei contained DDR proteins phospho-p53 and phospho-H2AX foci that, with DNA damage, dispersed and then re-formed similarly after recovery. We conclude that mouse primary satellite cell-derived myotubes effectively respond to and repair DNA strand-breaks, while DNA alkylation repair is underrepresented. Morphological differentiation, genome stability, genome sensor, and DNA strand-break repair potential are preserved in mouse SMA myocytes; thus, reduced SMN does not interfere with myocyte differentiation, genome integrity, and DNA repair, and faulty DNA repair is unlikely pathogenic in SMA. PMID:27452406

  5. Systematic analysis of axonal damage and inflammatory response in different white matter tracts of acutely injured rat spinal cord.

    PubMed

    Gomes-Leal, W; Corkill, D J; Picanço-Diniz, C W

    2005-12-20

    The mechanisms of white matter (WM) damage during secondary degeneration are a fundamental issue in the pathophysiology of central nervous system (CNS) diseases. Our main goal was to describe the pattern of an acute inflammatory response and secondary damage to axons in different WM tracts of acutely injured rat spinal cord. Adult rats were deeply anesthetized and injected with 20 nmol of NMDA into the spinal cord ventral horn on T7. Animals were perfused after survival times of 1 day, 3 days and 7 days. Ten micrometer sections were submitted to immunocytochemical analysis for activated macrophages/microglia, neutrophils and damaged axons. There were inflammatory response and progressive tissue destruction of ventral WM (VWM) with formation of microcysts in both VWM and lateral WM (LWM). In the VWM, the number of beta-amyloid precursor protein (beta-APP) end-bulbs increased from 1 day with a peak at 3 days, decreasing by 7 days following the injection. APP end-bulbs were present in the dorsal WM (DWM) at 3 days survival time but were not in the LWM. Electron microscopic analysis revealed different degrees of myelin disruption and axonal pathology in the vacuolated WM up to 14 mm along the rostrocaudal axis. Quantitative analysis revealed a significant loss of medium and large axons (P < 0.05), but not of small axons (P > 0.05). Our results suggest that bystander axonal damage and myelin vacuolation are important secondary component of the pathology of WM tracts following rat SCI. Further studies are needed to understand the mechanisms of these pathological events.

  6. Does dexmedetomidine reduce secondary damage after spinal cord injury? An experimental study

    PubMed Central

    Cemek, Mustafa; Eser, Olcay; Altunbaş, Korhan; Buyukokuroglu, Mehmet Emin; Cosar, Murat; Baş, Orhan; Ela, Yuksel; Fidan, Huseyin

    2009-01-01

    The aim of this experimental study was to investigate the possible protective effect of dexmedetomidine (DEX) on traumatic spinal cord injury (SCI). Twenty-two New Zealand rabbits were divided into three groups: sham (no drug or operation, n = 6), Control [SCI + single dose of 1 mL saline intraperitoneally (i.p), after trauma; n = 8] and DEX (SCI + 1 μg/kg dexmedetomidine in 1 mL, i.p, after trauma, n = 8). Laminectomy was performed at T10 and balloon angioplasty catheter was applied extradurally. Four and 24 h after surgery, rabbits were evaluated by an independent observer according to the Tarlov scoring system. Blood, cerebrospinal fluid (CSF), tissue samples from spinal cord were taken for biochemical and histopathological evaluations. After 4 h of SCI, all animals in control or DEX treated groups became paraparesic. On the other hand, 24 h after SCI, partial improvements were observed in both control and DEX treated groups. Traumatic SCI leads to increase in the lipid peroxidation and decreases enzymatic or nonenzymatic endogenous antioxidative defense systems. Again, SCI leads to apoptosis in spinal cord. DEX treatment slightly prevented lipid peroxidation and augmented endogenous antioxidative defense systems in CSF or spinal cord tissue, but failed to prevent apoptosis or neurodeficit after traumatic SCI. Therefore, it could be suggested that treatment with dexmedetomidine does not produce beneficial results in SCI. PMID:19130093

  7. Structural damage to meiotic chromosomes impairs DNA recombination and checkpoint control in mammalian oocytes.

    PubMed

    Wang, Hong; Höög, Christer

    2006-05-22

    Meiosis in human oocytes is a highly error-prone process with profound effects on germ cell and embryo development. The synaptonemal complex protein 3 (SYCP3) transiently supports the structural organization of the meiotic chromosome axis. Offspring derived from murine Sycp3(-)(/)(-) females die in utero as a result of aneuploidy. We studied the nature of the proximal chromosomal defects that give rise to aneuploidy in Sycp3(-)(/)(-) oocytes and how these errors evade meiotic quality control mechanisms. We show that DNA double-stranded breaks are inefficiently repaired in Sycp3(-)(/)(-) oocytes, thereby generating a temporal spectrum of recombination errors. This is indicated by a strong residual gammaH2AX labeling retained at late meiotic stages in mutant oocytes and an increased persistence of recombination-related proteins associated with meiotic chromosomes. Although a majority of the mutant oocytes are rapidly eliminated at early postnatal development, a subset with a small number of unfinished crossovers evades the DNA damage checkpoint, resulting in the formation of aneuploid gametes. PMID:16717125

  8. Mass spectrometer for quantification and characterization of DNA damage in mammalian and human systems. Final report

    SciTech Connect

    1997-12-31

    The instrument grant was used to purchase a Finnigan TSQ 7000 tandem quadruple mass spectrometer with electrospray and atmospheric-pressure chemical-ionization ion sources for the amount of the grant, $371,857. MIT contributed $50,000 in refurbishing costs for the laboratory in which the instrument is used. This mass spectrometer has been in operation since July, 1995 in professor Steven Tannenbaum`s Laboratory in the MIT Division of Toxicology, under the direct supervision of Dr. John S. Wishnok. Its current location is in MIT Building 56, room 747. It is in good operating condition, and is being actively used. Since the original purchase, the instrument has been upgraded by the addition of a (1) dedicated high-performance liquid chromatograph with an autosampler and (2) a nanoelectrospray ion source. The instrument has been used in a number of research projects including the identification of proteins and oligonucleotides, identification of PAH-DNA and PAH-protein adducts, quantitation of food-related carcinogens, and characterization of nitric oxide- and peroxynitrite-related DNA damage.

  9. Q-space and Conventional Diffusion Imaging of Axon and Myelin Damage in the Rat Spinal Cord after Axotomy

    PubMed Central

    Farrell, Jonathan A.D.; Zhang, Jiangyang; Jones, Melina V.; DeBoy, Cynthia A.; Hoffman, Paul N.; Landman, Bennett A.; Smith, Seth A.; Reich, Daniel S.; Calabresi, Peter A.; van Zijl, Peter C.M.

    2010-01-01

    Parallel and perpendicular diffusion properties of water in the rat spinal cord were investigated 3 and 30 days after dorsal root axotomy, a specific insult resulting in early axonal degeneration followed by later myelin damage in the dorsal column white matter (WM). Results from q-space analysis (i.e. the diffusion probability density function, PDF) obtained with strong diffusion weighting were compared to conventional anisotropy and diffusivity measurements at low b-values, as well as to histology for axon and myelin damage. Q-space contrasts included the height (PZERO), full width at half maximum (FWHM), root mean square displacement (RMSD), and kurtosis excess (KE) of the PDF, which quantifies the deviation from Gaussian diffusion. Following axotomy, a significant increase in perpendicular diffusion (with decreased KE) and decrease in parallel diffusion (with increased KE) were found in lesions relative to uninjured WM. Notably, a significant change in abnormal parallel diffusion was detected from 3 to 30 days with FWHM, but not with conventional diffusivity. Also, directional FWHM and RMSD measurements exhibited different sensitivities to WM damage. When compared to histology, the increase in perpendicular diffusion was not specific to demyelination, whereas combined reduced parallel diffusion and increased perpendicular diffusion was associated with axon damage. PMID:20432303

  10. Topoisomerase II Inhibitors Can Enhance Baculovirus-Mediated Gene Expression in Mammalian Cells through the DNA Damage Response

    PubMed Central

    Liu, Ming-Kun; Lin, Jhe-Jhih; Chen, Chung-Yung; Kuo, Szu-Cheng; Wang, Yu-Ming; Chan, Hong-Lin; Wu, Tzong Yuan

    2016-01-01

    BacMam is an insect-derived recombinant baculovirus that can deliver genes into mammalian cells. BacMam vectors carrying target genes are able to enter a variety of cell lines by endocytosis, but the level of expression of the transgene depends on the cell line and the state of the transduced cells. In this study, we demonstrated that the DNA damage response (DDR) could act as an alternative pathway to boost the transgene(s) expression by BacMam and be comparable to the inhibitors of histone deacetylase. Topoisomerase II (Top II) inhibitor-induced DDR can enhance the CMV-IE/enhancer mediated gene expression up to 12-fold in BacMam-transduced U-2OS cells. The combination of a Top II inhibitor, VM-26, can also augment the killing efficiency of a p53-expressing BacMam vector in U-2OS osteosarcoma cells. These results open a new avenue to facilitate the application of BacMam for gene delivery and therapy. PMID:27314325

  11. Prolonged Subdural Infusion of Kynurenic Acid Is Associated with Dose-Dependent Myelin Damage in the Rat Spinal Cord

    PubMed Central

    Dabrowski, Wojciech; Kwiecien, Jacek M.; Rola, Radoslaw; Klapec, Michal; Stanisz, Greg J.; Kotlinska-Hasiec, Edyta; Oakden, Wendy; Janik, Rafal; Coote, Margaret; Frey, Benicio N.; Turski, Waldemar A.

    2015-01-01

    Background Kynurenic acid (KYNA) is the end stage metabolite of tryptophan produced mainly by astrocytes in the central nervous system (CNS). It has neuroprotective activities but can be elevated in the neuropsychiatric disorders. Toxic effects of KYNA in the CNS are unknown. The aim of this study was to assess the effect of the subdural KYNA infusion on the spinal cord in adult rats. Methods A total of 42 healthy adult rats were randomly assigned into six groups and were infused for 7 days with PBS (control) or 0.0002 pmol/min, 0.01 nmol/min, 0.1 nmol/min, 1 nmol/min, and 10 nmol/min of KYNA per 7 days. The effect of KYNA on spinal cord was determined using histological and electron microscopy examination. Myelin oligodendrocyte glycoprotein (MOG) was measured in the blood serum to assess a degree of myelin damage. Result In all rats continuous long-lasting subdural KYNA infusion was associated with myelin damage and myelin loss that was increasingly widespread in a dose-depended fashion in peripheral, sub-pial areas. Damage to myelin sheaths was uniquely related to the separation of lamellae at the intraperiod line. The damaged myelin sheaths and areas with complete loss of myelin were associated with limited loss of scattered axons while vast majority of axons in affected areas were morphologically intact. The myelin loss-causing effect of KYNA occurred with no necrosis of oligodendrocytes, with locally severe astrogliosis and no cellular inflammatory response. Additionally, subdural KYNA infusion increased blood MOG concentration. Moreover, the rats infused with the highest doses of KYNA (1 and 10 nmol/min) demonstrated adverse neurological signs including weakness and quadriplegia. Conclusions We suggest, that subdural infusion of high dose of KYNA can be used as an experimental tool for the study of mechanisms of myelin damage and regeneration. On the other hand, the administration of low, physiologically relevant doses of KYNA may help to discover the role

  12. Intrathecal Injection of 3-Methyladenine Reduces Neuronal Damage and Promotes Functional Recovery via Autophagy Attenuation after Spinal Cord Ischemia/Reperfusion Injury in Rats.

    PubMed

    Wei, Xing; Zhou, Zhentao; Li, Lingyun; Gu, Jun; Wang, Chen; Xu, Fuqi; Dong, Qirong; Zhou, Xiaozhong

    2016-01-01

    The present study aimed to determine the occurrence of autophagy following ischemia/reperfusion (I/R) injury in the rat spinal cord and whether autophagy inhibition contributes to neural tissue damage and locomotor impairment. A spinal cord I/R model was induced via descending thoracic aorta occlusion for 10 min using systemic hypotension (40 mmHg) in adult male Sprague-Dawley rats. Then, 600 nmol 3-methyladenine (3-MA) or vehicle was intrathecally administered. Ultrastructural spinal cord changes were observed via transmission electron microscopy (TEM) and immunofluorescent double-labeling. Western blots were used to determine the protein expression of microtubule-associated protein light chain 3 (LC3) and Beclin 1. Autophagy was activated after spinal cord I/R injury as demonstrated by significantly increased LC3 and Beclin 1 expression at 3-48 h after injury. Furthermore, TEM images indicated the presence of autophagosomes and autolysosomes in the injured spinal cord. 3-MA significantly decreased LC3 and Beclin 1 expression and the number of LC3-positive cells in spinal cord of I/R versus vehicle groups. Moreover, the 3-MA-treated rats exhibited better neurobehavioral scores compared with control rats. These findings suggest activation of autophagy leading to neuronal cell death in the I/R injured spinal cord. These effects were significantly inhibited by intrathecal 3-MA administration. Thus intrathecal 3-MA administration may represent a novel treatment target following spinal cord I/R injury. PMID:27150140

  13. High-resolution genomic assays provide insight into the division of labor between TLS and HDR in mammalian replication of damaged DNA.

    PubMed

    Livneh, Zvi; Cohen, Isadora S; Paz-Elizur, Tamar; Davidovsky, Dana; Carmi, Dalit; Swain, Umakanta; Mirlas-Neisberg, Nataly

    2016-08-01

    The multitude of DNA lesions that continuously form in DNA cannot all be detected and removed prior to replication. Thus, encounters of the replication fork with DNA damage become inevitable. Such encounters inhibit fork progression, leading to replication fork arrest or to replication re-priming downstream of the damage site. Either of these events will result in the formation of gap-lesion structures, in which a damaged base is located in a single stranded stretch of DNA, that is vulnerable to subsequent nicking. The double strand break that would ensue if ssDNA becomes nicked constitutes escalation of the damage from nucleotide(s)-specific to chromosomal scale. Cells employ two universal DNA damage tolerance (DDT) strategies to resolve these situations, by converting the gap-lesion structures into dsDNA without repairing the damage. The first is translesion DNA synthesis (TLS), in which a specialized low-fidelity DNA polymerase inserts a nucleotide opposite the damaged one. TLS is inherently mutagenic, due to the miscoding nature of most damaged nucleotides. The second strategy is homology-dependent repair (HDR), which relies on the presence of an identical intact sister chromatid. The molecular mechanisms that regulate the division of labor between these pathways are poorly understood. This review focuses on the balance between TLS and HDR in mammalian cells, discussing recent findings that were made possible thanks to newly developed high resolution genomic assays, and highlighting the role of the DNA lesion's properties in DDT pathway choice.

  14. High-resolution genomic assays provide insight into the division of labor between TLS and HDR in mammalian replication of damaged DNA.

    PubMed

    Livneh, Zvi; Cohen, Isadora S; Paz-Elizur, Tamar; Davidovsky, Dana; Carmi, Dalit; Swain, Umakanta; Mirlas-Neisberg, Nataly

    2016-08-01

    The multitude of DNA lesions that continuously form in DNA cannot all be detected and removed prior to replication. Thus, encounters of the replication fork with DNA damage become inevitable. Such encounters inhibit fork progression, leading to replication fork arrest or to replication re-priming downstream of the damage site. Either of these events will result in the formation of gap-lesion structures, in which a damaged base is located in a single stranded stretch of DNA, that is vulnerable to subsequent nicking. The double strand break that would ensue if ssDNA becomes nicked constitutes escalation of the damage from nucleotide(s)-specific to chromosomal scale. Cells employ two universal DNA damage tolerance (DDT) strategies to resolve these situations, by converting the gap-lesion structures into dsDNA without repairing the damage. The first is translesion DNA synthesis (TLS), in which a specialized low-fidelity DNA polymerase inserts a nucleotide opposite the damaged one. TLS is inherently mutagenic, due to the miscoding nature of most damaged nucleotides. The second strategy is homology-dependent repair (HDR), which relies on the presence of an identical intact sister chromatid. The molecular mechanisms that regulate the division of labor between these pathways are poorly understood. This review focuses on the balance between TLS and HDR in mammalian cells, discussing recent findings that were made possible thanks to newly developed high resolution genomic assays, and highlighting the role of the DNA lesion's properties in DDT pathway choice. PMID:27262613

  15. Alterations in the expression of the apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/ref-1) and DNA damage in the caudal region of acute and chronic spinal cord injured rats treated by embryonic neural stem cells.

    PubMed

    DAGCI, T; ARMAGAN, G; KONYALIOGLU, S; YALCIN, A

    2009-01-01

    The oxidative mechanisms of injury-induced damage of neurons within the spinal cord are not very well understood. We used a model of T8-T9 spinal cord injury (SCI) in the rat to induce neuronal degeneration. In this spinal cord injury model, unilateral avulsion of the spinal cord causes oxidative stress of neurons. We tested the hypothesis that apurinic/apyrimidinic endonuclease (or redox effector factor-1, APE/Ref-1) regulates this neuronal oxidation mechanism in the spinal cord region caudal to the lesion, and that DNA damage is an early upstream signal. The embryonic neural stem cell therapy significantly decreased DNA-damage levels in both study groups - acutely (followed up to 7 days after SCI), and chronically (followed up to 28 days after SCI) injured animals. Meanwhile, mRNA levels of APE/Ref-1 significantly increased after embryonic neural stem cell therapy in acutely and chronically injured animals when compared to acute and chronic sham groups. Our data has demonstrated that an increase of APE/Ref-1 mRNA levels in the caudal region of spinal cord strongly correlated with DNA damage after traumatic spinal cord injury. We suggest that DNA damage can be observed both in lesional and caudal regions of the acutely and chronically injured groups, but DNA damage is reduced with embryonic neural stem cell therapy.

  16. Spinal Cord Diseases

    MedlinePlus

    ... damages the vertebrae or other parts of the spine, this can also injure the spinal cord. Other spinal cord problems include Tumors Infections such as meningitis and polio Inflammatory diseases Autoimmune diseases Degenerative diseases such as amyotrophic lateral sclerosis and spinal ...

  17. Not just the brain: methamphetamine disrupts blood-spinal cord barrier and induces acute glial activation and structural damage of spinal cord cells.

    PubMed

    Kiyatkin, Eugene A; Sharma, Hari S

    2015-01-01

    Acute methamphetamine (METH) intoxication induces metabolic brain activation as well as multiple physiological and behavioral responses that could result in life-threatening health complications. Previously, we showed that METH (9 mg/kg) used in freely moving rats induces robust leakage of blood-brain barrier, acute glial activation, vasogenic edema, and structural abnormalities of brain cells. These changes were tightly correlated with drug-induced brain hyperthermia and were greatly potentiated when METH was used at warm ambient temperatures (29°C), inducing more robust and prolonged hyperthermia. Extending this line of research, here we show that METH also strongly increases the permeability of the blood-spinal cord barrier as evidenced by entry of Evans blue and albumin immunoreactivity in T9-12 segments of the spinal cord. Similar to the blood-brain barrier, leakage of bloodspinal cord barrier was associated with acute glial activation, alterations of ionic homeostasis, water tissue accumulation (edema), and structural abnormalities of spinal cord cells. Similar to that in the brain, all neurochemical alterations correlated tightly with drug-induced elevations in brain temperature and they were enhanced when the drug was used at 29°C and brain hyperthermia reached pathological levels (>40°C). We discuss common features and differences in neural responses between the brain and spinal cord, two inseparable parts of the central nervous system affected by METH exposure. PMID:25687701

  18. Not just the brain: methamphetamine disrupts blood-spinal cord barrier and induces acute glial activation and structural damage of spinal cord cells.

    PubMed

    Kiyatkin, Eugene A; Sharma, Hari S

    2015-01-01

    Acute methamphetamine (METH) intoxication induces metabolic brain activation as well as multiple physiological and behavioral responses that could result in life-threatening health complications. Previously, we showed that METH (9 mg/kg) used in freely moving rats induces robust leakage of blood-brain barrier, acute glial activation, vasogenic edema, and structural abnormalities of brain cells. These changes were tightly correlated with drug-induced brain hyperthermia and were greatly potentiated when METH was used at warm ambient temperatures (29°C), inducing more robust and prolonged hyperthermia. Extending this line of research, here we show that METH also strongly increases the permeability of the blood-spinal cord barrier as evidenced by entry of Evans blue and albumin immunoreactivity in T9-12 segments of the spinal cord. Similar to the blood-brain barrier, leakage of bloodspinal cord barrier was associated with acute glial activation, alterations of ionic homeostasis, water tissue accumulation (edema), and structural abnormalities of spinal cord cells. Similar to that in the brain, all neurochemical alterations correlated tightly with drug-induced elevations in brain temperature and they were enhanced when the drug was used at 29°C and brain hyperthermia reached pathological levels (>40°C). We discuss common features and differences in neural responses between the brain and spinal cord, two inseparable parts of the central nervous system affected by METH exposure.

  19. Spinal tumor

    MedlinePlus

    Tumor - spinal cord ... spinal tumors occur in the nerves of the spinal cord itself. Most often these are ependymomas and other ... gene mutations. Spinal tumors can occur: Inside the spinal cord (intramedullary) In the membranes (meninges) covering the spinal ...

  20. Ochratoxin A: induction of (oxidative) DNA damage, cytotoxicity and apoptosis in mammalian cell lines and primary cells.

    PubMed

    Kamp, Hennicke G; Eisenbrand, Gerhard; Schlatter, Josef; Würth, Kirsten; Janzowski, Christine

    2005-01-31

    Ochratoxin A (OTA) is a nephrotoxic/-carcinogenic mycotoxin, produced by several Aspergillus- and Penicillium-strains. Humans are exposed to OTA via food contamination, a causal relationship of OTA to human endemic Balkan nephropathy is still under debate. Since DNA-adducts of OTA or its metabolites could not be identified unambiguously, its carcinogenic effectiveness might be related to secondary effects, such as oxidative cell damage or cell proliferation. In this study, OTA mediated induction of (oxidative) DNA damage, cytotoxicity (necrosis, growth inhibition, apoptosis) and modulation of glutathione were investigated in cell lines (V79, CV-1) and primary rat kidney cells. After 24 h incubation, viability of V79 cells was strongly decreased by OTA concentrations >2.5 micromol/L, whereas CV-1 cells were clearly less sensitive. Strong growth inhibition occurred in both cell lines (IC(50) approximately 2 micromol/L). Apoptosis, detected with an immunochemical test and with flow cytometry, was induced by >1 micromol/L OTA. Oxidative DNA damage, detected by comet assay after additional treatment with repair enzymes, was induced in all cell systems already at five-fold lower concentrations. Glutathione in CV-1 cells was depleted after 1 h incubation (>100 micromol/L). In contrast, an increase was measured after 24 h incubation (>0.5 micromol/L). In conclusion, OTA induces oxidative DNA damage at low, not yet cytotoxic concentrations. Oxidative DNA damage might initiate cell transformation eventually in connection with proliferative response following cytotoxic cell death. Both events might represent pivotal factors in the chain of cellular events leading into nephro-carcinogenicity of OTA.

  1. 4(α-l-rhamnosyloxy)-benzyl isothiocyanate, a bioactive phytochemical that attenuates secondary damage in an experimental model of spinal cord injury.

    PubMed

    Giacoppo, Sabrina; Galuppo, Maria; De Nicola, Gina Rosalinda; Iori, Renato; Bramanti, Placido; Mazzon, Emanuela

    2015-01-01

    4(α-l-Rhamnosyloxy)-benzyl isothiocyanate (glucomoringin isothiocyanate; GMG-ITC) is released from the precursor 4(α-l-rhamnosyloxy)-benzyl glucosinolate (glucomoringin; GMG) by myrosinase (β-thioglucoside glucohydrolase; E.C. 3.2.1.147) catalyzed hydrolysis. GMG is an uncommon member of the glucosinolate group as it presents a unique characteristic consisting in a second glycosidic residue within the side chain. It is a typical glucosinolate found in large amounts in the seeds of Moringa oleifera Lam., the most widely distributed plant of the Moringaceae family. GMG was purified from seed-cake of M. oleifera and was hydrolyzed by myrosinase at neutral pH in order to form the corresponding GMG-ITC. This bioactive phytochemical can play a key role in counteracting the inflammatory response connected to the oxidative-related mechanisms as well as in the control of the neuronal cell death process, preserving spinal cord tissues after injury in mice. Spinal cord trauma was induced in mice by the application of vascular clips (force of 24g) for 1 min., via four-level T5-T8 after laminectomy. In particular, the purpose of this study was to investigate the dynamic changes occurring in the spinal cord after ip treatment with bioactive GMG-ITC produced 15 min before use from myrosinase-catalyzed hydrolysis of GMG (10mg/kg body weight+5 μl Myr mouse/day). The following parameters, such as histological damage, distribution of reticular fibers in connective tissue, nuclear factor (NF)-κB translocation and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α) degradation, expression of inducible Nitric Oxide Synthases (iNOS), as well as apoptosis, were evaluated. In conclusion, our results show a protective effect of bioactive GMG-ITC on the secondary damage, following spinal cord injury, through an antioxidant mechanism of neuroprotection. Therefore, the bioactive phytochemical GMG-ITC freshly produced before use by myrosinase

  2. Caffeine stimulates locomotor activity in the mammalian spinal cord via adenosine A1 receptor-dopamine D1 receptor interaction and PKA-dependent mechanisms.

    PubMed

    Acevedo, JeanMarie; Santana-Almansa, Alexandra; Matos-Vergara, Nikol; Marrero-Cordero, Luis René; Cabezas-Bou, Ernesto; Díaz-Ríos, Manuel

    2016-02-01

    Caffeine is a potent psychostimulant that can have significant and widely variable effects on the activity of multiple neuronal pathways. The most pronounced caffeine-induced behavioral effect seen in rodents is to increase locomotor activity which has been linked to a dose-dependent inhibition of A1 and A(2A) receptors. The effects of caffeine at the level of the lumbar spinal central pattern generator (CPG) network for hindlimb locomotion are lacking. We assessed the effects of caffeine to the locomotor function of the spinal CPG network via extracellular ventral root recordings using the isolated neonatal mouse spinal cord preparation. Addition of caffeine and of an A1 receptor antagonist significantly decreased the cycle period accelerating the ongoing locomotor rhythm, while decreasing burst duration reversibly in most preparations suggesting the role of A1 receptors as the primary target of caffeine. Caffeine and an A1 receptor antagonist failed to stimulate ongoing locomotor activity in the absence of dopamine or in the presence of a D1 receptor antagonist supporting A1/D1 receptor-dependent mechanism of action. The use of caffeine or an A1 receptor blocker failed to stimulate an ongoing locomotor rhythm in the presence of a blocker of the cAMP-dependent protein kinase (PKA) supporting the need of this intracellular pathway for the modulatory effects of caffeine to occur. These results support a stimulant effect of caffeine on the lumbar spinal network controlling hindlimb locomotion through the inhibition of A1 receptors and subsequent activation of D1 receptors via a PKA-dependent intracellular mechanism.

  3. Yields of biologically significant damage produced in mammalian DNA by irradiation associated with radon decay. Final progress report

    SciTech Connect

    Ward, J.F.

    1994-03-01

    The objective of this project was to characterize the difference between damage to DNA caused by alpha particles and by low LET radiation. Estimation of the risk posed by exposure to high LET radiation (such as that from radon) relies at present on epidemiological data, and is therefore largely empirical. This empiricism is evident from the concepts of quality factor or RBE that find use for describing the biological effects of high LET radiation. The author argues that some effort should be made to address the mechanisms of DNA damage by high and low LET forms of radiation, and how these mechanisms might relate to the biological endpoints. This report summarizes the results of the author`s investigations and the current understanding of these mechanisms.

  4. Shape of dose-survival curves for mammalian cells and repair of potentially lethal damage analyzed by hypertonic treatment

    SciTech Connect

    Pohlit, W.; Heyder, I.R.

    1981-09-01

    During the usual procedure of testing cell survival by colony-forming ability, repair of potentially lethal damage (PLD) takes place. By incubating the cells in hypertonic suspension a certain part of this repair can be inhibited, leading to an exponential dose-survival curve as expected from the Poisson distribution of lethal events in the cells. If such a hypertonic treatment is performed after increasing intervals following irradiation with x rays, curves with increasing shoulder length are obtained. Quantitative analysis of the kinetics of this repair shows that PLD is repaired for about 1 h after irradiation by a saturated repair system which eliminates about one lesion per 15 min per cell independent of the applied absorbed dose. PLD not eliminated by this last system is repaired by an unsaturated system with a time constant of several hours. Repair of PLD after x irradiation proceeds quantitatively in this way in plateau-phase cells suspended in a conditioned medium, which seems optimal for such repair. If these cells are suspended after irradiation in normal nutrient medium a certain fraction of the PLD is transformed into irreparable damage. The final survival after repair in nutrient medium is then identical with that obtained by the usual measurement of colony-forming ability on nutrient agar. This indicates that the shoulder in dose-survival curves for plateau phase cells ispartly due to repair of PLD and partly due to manifestation of this damage during repair time.

  5. Spinal cord contusion models.

    PubMed

    Young, Wise

    2002-01-01

    Most human spinal cord injuries involve contusions of the spinal cord. Many investigators have long used weight-drop contusion animal models to study the pathophysiology and genetic responses of spinal cord injury. All spinal cord injury therapies tested to date in clinical trial were validated in such models. In recent years, the trend has been towards use of rats for spinal cord injury studies. The MASCIS Impactor is a well-standardized rat spinal cord contusion model that produces very consistent graded spinal cord damage that linearly predicts 24-h lesion volumes, 6-week white matter sparing, and locomotor recovery in rats. All aspects of the model, including anesthesia for male and female rats, age rather than body weight criteria, and arterial blood gases were empirically selected to enhance the consistency of injury. PMID:12440371

  6. Transplanted neural stem/precursor cells instruct phagocytes and reduce secondary tissue damage in the injured spinal cord.

    PubMed

    Cusimano, Melania; Biziato, Daniela; Brambilla, Elena; Donegà, Matteo; Alfaro-Cervello, Clara; Snider, Silvia; Salani, Giuliana; Pucci, Ferdinando; Comi, Giancarlo; Garcia-Verdugo, Jose Manuel; De Palma, Michele; Martino, Gianvito; Pluchino, Stefano

    2012-02-01

    Transplanted neural stem/precursor cells possess peculiar therapeutic plasticity and can simultaneously instruct several therapeutic mechanisms in addition to cell replacement. Here, we interrogated the therapeutic plasticity of neural stem/precursor cells after their focal implantation in the severely contused spinal cord. We injected syngeneic neural stem/precursor cells at the proximal and distal ends of the contused mouse spinal cord and analysed locomotor functions and relevant secondary pathological events in the mice, cell fate of transplanted neural stem/precursor cells, and gene expression and inflammatory cell infiltration at the injured site. We used two different doses of neural stem/precursor cells and two treatment schedules, either subacute (7 days) or early chronic (21 days) neural stem/precursor cell transplantation after the induction of experimental thoracic severe spinal cord injury. Only the subacute transplant of neural stem/precursor cells enhanced the recovery of locomotor functions of mice with spinal cord injury. Transplanted neural stem/precursor cells survived undifferentiated at the level of the peri-lesion environment and established contacts with endogenous phagocytes via cellular-junctional coupling. This was associated with significant modulation of the expression levels of important inflammatory cell transcripts in vivo. Transplanted neural stem/precursor cells skewed the inflammatory cell infiltrate at the injured site by reducing the proportion of 'classically-activated' (M1-like) macrophages, while promoting the healing of the injured cord. We here identify a precise window of opportunity for the treatment of complex spinal cord injuries with therapeutically plastic somatic stem cells, and suggest that neural stem/precursor cells have the ability to re-programme the local inflammatory cell microenvironment from a 'hostile' to an 'instructive' role, thus facilitating the healing or regeneration past the lesion.

  7. Surface modification of amorphous nanosilica particles suppresses nanosilica-induced cytotoxicity, ROS generation, and DNA damage in various mammalian cells

    SciTech Connect

    Yoshida, Tokuyuki; Yoshioka, Yasuo; Matsuyama, Keigo; Nakazato, Yasutaro; Tochigi, Saeko; Hirai, Toshiro; Kondoh, Sayuri; Nagano, Kazuya; Abe, Yasuhiro; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Tsutsumi, Yasuo

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer There is increasing concern regarding the potential health risks of nanomaterials. Black-Right-Pointing-Pointer We evaluated the effect of surface properties of nanomaterials on cellular responses. Black-Right-Pointing-Pointer We showed that the surface properties play an important in determining its safety. Black-Right-Pointing-Pointer These data provide useful information for producing safer nanomaterials. -- Abstract: Recently, nanomaterials have been utilized in various fields. In particular, amorphous nanosilica particles are increasingly being used in a range of applications, including cosmetics, food technology, and medical diagnostics. However, there is concern that the unique characteristics of nanomaterials might induce undesirable effects. The roles played by the physical characteristics of nanomaterials in cellular responses have not yet been elucidated precisely. Here, by using nanosilica particles (nSPs) with a diameter of 70 nm whose surface was either unmodified (nSP70) or modified with amine (nSP70-N) or carboxyl groups (nSP70-C), we examined the relationship between the surface properties of nSPs and cellular responses such as cytotoxicity, reactive oxygen species (ROS) generation, and DNA damage. To compare the cytotoxicity of nSP70, nSP70-N, or nSP70-C, we examined in vitro cell viability after nSP treatment. Although the susceptibility of each cell line to the nSPs was different, nSP70-C and nSP70-N showed lower cytotoxicity than nSP70 in all cell lines. Furthermore, the generation of ROS and induction of DNA damage in nSP70-C- and nSP70-N-treated cells were lower than those in nSP70-treated cells. These results suggest that the surface properties of nSP70 play an important role in determining its safety, and surface modification of nSP70 with amine or carboxyl groups may be useful for the development of safer nSPs. We hope that our results will contribute to the development of safer nanomaterials.

  8. Damage to cellular DNA from particulate radiations, the efficacy of its processing and the radiosensitivity of mammalian cells. Emphasis on DNA double strand breaks and chromatin breaks

    NASA Technical Reports Server (NTRS)

    Lett, J. T.

    1992-01-01

    For several years, it has been evident that cellular radiation biology is in a necessary period of consolidation and transition (Lett 1987, 1990; Lett et al. 1986, 1987). Both changes are moving apace, and have been stimulated by studies with heavy charged particles. From the standpoint of radiation chemistry, there is now a consensus of opinion that the DNA hydration shell must be distinguished from bulk water in the cell nucleus and treated as an integral part of DNA (chromatin) (Lett 1987). Concomitantly, sentiment is strengthening for the abandonment of the classical notions of "direct" and "indirect" action (Fielden and O'Neill 1991; O'Neill 1991; O'Neill et al. 1991; Schulte-Frohlinde and Bothe 1991 and references therein). A layer of water molecules outside, or in the outer edge of, the DNA (chromatin) hydration shell influences cellular radiosensitivity in ways not fully understood. Charge and energy transfer processes facilitated by, or involving, DNA hydration must be considered in rigorous theories of radiation action on cells. The induction and processing of double stand breaks (DSBs) in DNA (chromatin) seem to be the predominant determinants of the radiotoxicity of normally radioresistant mammalian cells, the survival curves of which reflect the patterns of damage induced and the damage present after processing ceases, and can be modelled in formal terms by the use of reaction (enzyme) kinetics. Incongruities such as sublethal damage are neither scientifically sound nor relevant to cellular radiation biology (Calkins 1991; Lett 1990; Lett et al. 1987a). Increases in linear energy transfer (LET infinity) up to 100-200 keV micron-1 cause increases in the extents of neighboring chemical and physical damage in DNA denoted by the general term DSB. Those changes are accompanied by decreasing abilities of cells normally radioresistant to sparsely ionizing radiations to process DSBs in DNA and chromatin and to recover from radiation exposure, so they make

  9. Neuroprotective effects of adipose-derived stem cells are maintained for 3 weeks against ischemic damage in the rabbit spinal cord.

    PubMed

    Moon, Seung Myung; Kim, Woosuk; Chung, Jin Young; Im, Wooseok; Yoo, Dae Young; Jung, Hyo Young; Won, Moo-Ho; Choi, Jung Hoon; Hwang, In Koo

    2014-01-01

    In the previous study, we demonstrated that adipose-derived stem cells (ASCs) have neuroprotective effects against ischemic damage in the ventral horn of L5-6 levels at 3 days after ischemia/reperfusion. In the present study, we expanded our observations for 3 weeks after ischemia/reperfusion to rule out the possibility of delayed neuronal death in several days after ischemia/reperfusion. Transient spinal cord ischemia was induced by a 15 min aortic artery occlusion in the subrenal region and rabbit ASCs were administered intrathecally into recipient rabbits (2 × 10(5)) immediately after reperfusion. Transplantation of ASCs improved the neurological motor functions of the hindlimb 3 weeks after ischemia/reperfusion. Similarly, the cresyl violet-positive neurons were significantly increased at 3 weeks after ischemia/reperfusion compared to that in the vehicle (artificial cerebrospinal fluid)-treated group. The transplantation of ASCs significantly reduced reactive microglia induced by ischemia at 3 weeks after ischemia/reperfusion. In addition, transplantation of ASCs maintained the brain-derived neurotrophic factor (BDNF) levels 3 weeks after ischemia/reperfusion. These results suggest that the neuroprotective effects of ASCs are maintained 3 weeks after ischemia/reperfusion by modulating microgliosis and BDNF levels in the spinal cord.

  10. Neuroprotective Effects of Adipose-Derived Stem Cells Are Maintained for 3 Weeks against Ischemic Damage in the Rabbit Spinal Cord

    PubMed Central

    Moon, Seung Myung; Kim, Woosuk; Chung, Jin Young; Im, Wooseok; Yoo, Dae Young; Jung, Hyo Young; Won, Moo-Ho

    2014-01-01

    In the previous study, we demonstrated that adipose-derived stem cells (ASCs) have neuroprotective effects against ischemic damage in the ventral horn of L5-6 levels at 3 days after ischemia/reperfusion. In the present study, we expanded our observations for 3 weeks after ischemia/reperfusion to rule out the possibility of delayed neuronal death in several days after ischemia/reperfusion. Transient spinal cord ischemia was induced by a 15 min aortic artery occlusion in the subrenal region and rabbit ASCs were administered intrathecally into recipient rabbits (2 × 105) immediately after reperfusion. Transplantation of ASCs improved the neurological motor functions of the hindlimb 3 weeks after ischemia/reperfusion. Similarly, the cresyl violet-positive neurons were significantly increased at 3 weeks after ischemia/reperfusion compared to that in the vehicle (artificial cerebrospinal fluid)-treated group. The transplantation of ASCs significantly reduced reactive microglia induced by ischemia at 3 weeks after ischemia/reperfusion. In addition, transplantation of ASCs maintained the brain-derived neurotrophic factor (BDNF) levels 3 weeks after ischemia/reperfusion. These results suggest that the neuroprotective effects of ASCs are maintained 3 weeks after ischemia/reperfusion by modulating microgliosis and BDNF levels in the spinal cord. PMID:24592394

  11. HDAC6 Regulates the Chaperone-Mediated Autophagy to Prevent Oxidative Damage in Injured Neurons after Experimental Spinal Cord Injury

    PubMed Central

    Su, Min; Guan, Huaqing; Zhang, Fan; Gao, Yarong; Teng, Xiaomei; Yang, Weixin

    2016-01-01

    Hypoxia-ischemia- (HI-) induced oxidative stress plays a role in secondary pathocellular processes of acute spinal cord injury (SCI) due to HI from many kinds of mechanical trauma. Increasing evidence suggests that the histone deacetylase-6 (HDAC6) plays an important role in cell homeostasis in both physiological and abnormal, stressful, pathological conditions. This paper found that inhibition of HDAC6 accelerated reactive oxygen species (ROS) generation and cell apoptosis in response to the HI. Deficiency of HDAC6 hindered the chaperone-mediated autophagy (CMA) activity to resistance of HI-induced oxidative stress. Furthermore, this study provided the experimental evidence for the potential role of HDAC6 in the regulation of CMA by affecting HSP90 acetylation. Therefore, HDAC6 plays an important role in the function of CMA pathway under the HI stress induced by SCI and it may be a potential therapeutic target in acute SCI model. PMID:26649145

  12. Methods for assisting recovery of damaged brain and spinal cord using arrays of X-ray microplanar beams

    DOEpatents

    Dilmanian, F. Avraham; McDonald, III, John W.

    2007-01-02

    A method of assisting recovery of an injury site of brain or spinal cord injury includes providing a therapeutic dose of X-ray radiation to the injury site through an array of parallel microplanar beams. The dose at least temporarily removes regeneration inhibitors from the irradiated regions. Substantially unirradiated cells surviving between the microplanar beams migrate to the in-beam irradiated portion and assist in recovery. The dose may be administered in dose fractions over several sessions, separated in time, using angle-variable intersecting microbeam arrays (AVIMA). Additional doses may be administered by varying the orientation of the microplanar beams. The method may be enhanced by injecting stem cells into the injury site.

  13. Methods for assisting recovery of damaged brain and spinal cord using arrays of X-Ray microplanar beams

    DOEpatents

    Dilmanian, F. Avraham; McDonald, III, John W.

    2007-12-04

    A method of assisting recovery of an injury site of brain or spinal cord injury includes providing a therapeutic dose of X-ray radiation to the injury site through an array of parallel microplanar beams. The dose at least temporarily removes regeneration inhibitors from the irradiated regions. Substantially unirradiated cells surviving between the microplanar beams migrate to the in-beam irradiated portion and assist in recovery. The dose may be administered in dose fractions over several sessions, separated in time, using angle-variable intersecting microbeam arrays (AVIMA). Additional doses may be administered by varying the orientation of the microplanar beams. The method may be enhanced by injecting stem cells into the injury site.

  14. Spinal fusion

    MedlinePlus

    ... Anterior spinal fusion; Spine surgery - spinal fusion; Low back pain - fusion; Herniated disk - fusion ... If you had chronic back pain before surgery, you will likely still have some pain afterward. Spinal fusion is unlikely to take away all your pain ...

  15. Spinal injury

    MedlinePlus

    ... head. Alternative Names Spinal cord injury; SCI Images Skeletal spine Vertebra, cervical (neck) Vertebra, lumbar (low back) Vertebra, thoracic (mid back) Vertebral column Central nervous system Spinal cord injury Spinal anatomy Two person roll - ...

  16. NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury

    PubMed Central

    Yang, Zhaoyang; Zhang, Aifeng; Duan, Hongmei; Zhang, Sa; Hao, Peng; Ye, Keqiang; Sun, Yi E.; Li, Xiaoguang

    2015-01-01

    Neural stem cells (NSCs) in the adult mammalian central nervous system (CNS) hold the key to neural regeneration through proper activation, differentiation, and maturation, to establish nascent neural networks, which can be integrated into damaged neural circuits to repair function. However, the CNS injury microenvironment is often inhibitory and inflammatory, limiting the ability of activated NSCs to differentiate into neurons and form nascent circuits. Here we report that neurotrophin-3 (NT3)-coupled chitosan biomaterial, when inserted into a 5-mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous NSCs in the injured spinal cord. Through slow release of NT3, the biomaterial attracted NSCs to migrate into the lesion area, differentiate into neurons, and form functional neural networks, which interconnected severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis could be a novel strategy for treatment of spinal cord injury. PMID:26460015

  17. NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury.

    PubMed

    Yang, Zhaoyang; Zhang, Aifeng; Duan, Hongmei; Zhang, Sa; Hao, Peng; Ye, Keqiang; Sun, Yi E; Li, Xiaoguang

    2015-10-27

    Neural stem cells (NSCs) in the adult mammalian central nervous system (CNS) hold the key to neural regeneration through proper activation, differentiation, and maturation, to establish nascent neural networks, which can be integrated into damaged neural circuits to repair function. However, the CNS injury microenvironment is often inhibitory and inflammatory, limiting the ability of activated NSCs to differentiate into neurons and form nascent circuits. Here we report that neurotrophin-3 (NT3)-coupled chitosan biomaterial, when inserted into a 5-mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous NSCs in the injured spinal cord. Through slow release of NT3, the biomaterial attracted NSCs to migrate into the lesion area, differentiate into neurons, and form functional neural networks, which interconnected severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis could be a novel strategy for treatment of spinal cord injury. PMID:26460015

  18. The Mammalian Brain in the Electromagnetic Fields Designed by Man with Special Reference to Blood-Brain Barrier Function, Neuronal Damage and Possible Physical Mechanisms

    NASA Astrophysics Data System (ADS)

    Salford, L. G.; Nittby, H.; Brun, A.; Grafström, G.; Malmgren, L.; Sommarin, M.; Eberhardt, J.; Widegren, B.; Persson, B. R.

    Life on earth was formed during billions of years, exposed to,and shaped by the original physical forces such as gravitation, cosmic irradiation, atmospheric electric fields and the terrestrial magnetism. The Schumann resonances at 7.4 Hz are an example of oscillations possibly important for life. The existing organisms are created to function in harmony with these forces. However, in the late 19th century mankind introduced the use of electricity, in the early 20th century long-wave radio and in the 1940-ies short-wave radio. High frequency RF was introduced in the 50-ies as FM and television and during the very last decades, microwaves of the modern communication society spread around the world. Today, however, one third of the world's population is owner of the microwave-producing mobile phones and an even larger number is exposed to the cordless RF emitting systems. To what extent are all living organisms affected by these, almost everywhere present radio freque ncy fields? And what will be the effects of many years of continuing exposure? Since 1988 our group has studied the effects upon the mammalian blood-brain barrier (BBB) in rats by non-thermal radio frequency electromagnetic fields (RF-EMF). These have been shown to cause significantly increased leakage of the rats' own blood albumin through the BBB of exposed rats, at energy levels of 1W/kg and below, as compared to non-exposed animals in a total series of about two thousand animals.-6)} One remarkable observation is the fact that the lowest energy levels, with whole-body average power densities below 10mW/kg, give rise to the most pronounced albumin leakage. If mobile communication, even at extremely low energy levels, causes the users' own albumin to leak out through the BBB, also other unwanted and toxic molecules in the blood, may leak into the brain tissue and concentrate in and damage the neurons and glial cells of the brain. In later studies we have shown that a 2-h exposure to GSM 915 MHz, at

  19. Spinal Injury Rehabilitation in Singapore.

    ERIC Educational Resources Information Center

    Yen, H. L.; Chua, K.; Chan, W.

    1998-01-01

    This study reviewed 231 cases of spinal cord injury treated in Singapore. Data on demographic characteristics, common causes (mostly falls and traffic accidents), types of spinal damage, and outcomes are reported. Following rehabilitation, 68 patients were able to ambulate independently and 45 patients achieved independence in activities of daily…

  20. Inhibition of EGFR/MAPK signaling reduces microglial inflammatory response and the associated secondary damage in rats after spinal cord injury

    PubMed Central

    2012-01-01

    Background Emerging evidence indicates that reactive microglia-initiated inflammatory responses are responsible for secondary damage after primary traumatic spinal cord injury (SCI); epidermal growth factor receptor (EGFR) signaling may be involved in cell activation. In this report, we investigate the influence of EGFR signaling inhibition on microglia activation, proinflammatory cytokine production, and the neuronal microenvironment after SCI. Methods Lipopolysaccharide-treated primary microglia/BV2 line cells and SCI rats were used as model systems. Both C225 and AG1478 were used to inhibit EGFR signaling activation. Cell activation and EGFR phosphorylation were observed after fluorescent staining and western blot. Production of interleukin-1beta (IL-1β) and tumor necrosis factor alpha (TNFα) was tested by reverse transcription PCR and ELISA. Western blot was performed to semi-quantify the expression of EGFR/phospho-EGFR, and phosphorylation of Erk, JNK and p38 mitogen-activated protein kinases (MAPK). Wet-dry weight was compared to show tissue edema. Finally, axonal tracing and functional scoring were performed to show recovery of rats. Results EGFR phosphorylation was found to parallel microglia activation, while EGFR blockade inhibited activation-associated cell morphological changes and production of IL-1β and TNFα. EGFR blockade significantly downregulated the elevated MAPK activation after cell activation; selective MAPK inhibitors depressed production of cytokines to a certain degree, suggesting that MAPK mediates the depression of microglia activation brought about by EGFR inhibitors. Subsequently, seven-day continual infusion of C225 or AG1478 in rats: reduced the expression of phospho-EGFR, phosphorylation of Erk and p38 MAPK, and production of IL-1β and TNFα; lessened neuroinflammation-associated secondary damage, like microglia/astrocyte activation, tissue edema and glial scar/cavity formation; and enhanced axonal outgrowth and functional

  1. Assessment of Crop Damage by Protected Wild Mammalian Herbivores on the Western Boundary of Tadoba-Andhari Tiger Reserve (TATR), Central India.

    PubMed

    Bayani, Abhijeet; Tiwade, Dilip; Dongre, Ashok; Dongre, Aravind P; Phatak, Rasika; Watve, Milind

    2016-01-01

    Crop raiding by wild herbivores close to an area of protected wildlife is a serious problem that can potentially undermine conservation efforts. Since there is orders of magnitude difference between farmers' perception of damage and the compensation given by the government, an objective and realistic estimate of damage was found essential. We employed four different approaches to estimate the extent of and patterns in crop damage by wild herbivores along the western boundary of Tadoba-Andhari Tiger Reserve in the state of Maharashtra, central India. These approaches highlight different aspects of the problem but converge on an estimated damage of over 50% for the fields adjacent to the forest, gradually reducing in intensity with distance. We found that the visual damage assessment method currently employed by the government for paying compensation to farmers was uncorrelated to and grossly underestimated actual damage. The findings necessitate a radical rethinking of policies to assess, mitigate as well as compensate for crop damage caused by protected wildlife species.

  2. Assessment of Crop Damage by Protected Wild Mammalian Herbivores on the Western Boundary of Tadoba-Andhari Tiger Reserve (TATR), Central India

    PubMed Central

    Bayani, Abhijeet; Tiwade, Dilip; Dongre, Ashok; Dongre, Aravind P.; Phatak, Rasika; Watve, Milind

    2016-01-01

    Crop raiding by wild herbivores close to an area of protected wildlife is a serious problem that can potentially undermine conservation efforts. Since there is orders of magnitude difference between farmers’ perception of damage and the compensation given by the government, an objective and realistic estimate of damage was found essential. We employed four different approaches to estimate the extent of and patterns in crop damage by wild herbivores along the western boundary of Tadoba-Andhari Tiger Reserve in the state of Maharashtra, central India. These approaches highlight different aspects of the problem but converge on an estimated damage of over 50% for the fields adjacent to the forest, gradually reducing in intensity with distance. We found that the visual damage assessment method currently employed by the government for paying compensation to farmers was uncorrelated to and grossly underestimated actual damage. The findings necessitate a radical rethinking of policies to assess, mitigate as well as compensate for crop damage caused by protected wildlife species. PMID:27093293

  3. Assessment of Crop Damage by Protected Wild Mammalian Herbivores on the Western Boundary of Tadoba-Andhari Tiger Reserve (TATR), Central India.

    PubMed

    Bayani, Abhijeet; Tiwade, Dilip; Dongre, Ashok; Dongre, Aravind P; Phatak, Rasika; Watve, Milind

    2016-01-01

    Crop raiding by wild herbivores close to an area of protected wildlife is a serious problem that can potentially undermine conservation efforts. Since there is orders of magnitude difference between farmers' perception of damage and the compensation given by the government, an objective and realistic estimate of damage was found essential. We employed four different approaches to estimate the extent of and patterns in crop damage by wild herbivores along the western boundary of Tadoba-Andhari Tiger Reserve in the state of Maharashtra, central India. These approaches highlight different aspects of the problem but converge on an estimated damage of over 50% for the fields adjacent to the forest, gradually reducing in intensity with distance. We found that the visual damage assessment method currently employed by the government for paying compensation to farmers was uncorrelated to and grossly underestimated actual damage. The findings necessitate a radical rethinking of policies to assess, mitigate as well as compensate for crop damage caused by protected wildlife species. PMID:27093293

  4. Mammalian Pheromones

    PubMed Central

    Liberles, Stephen D.

    2015-01-01

    Mammalian pheromones control a myriad of innate social behaviors and acutely regulate hormone levels. Responses to pheromones are highly robust, reproducible, and stereotyped and likely involve developmentally predetermined neural circuits. Here, I review several facets of pheromone transduction in mammals, including (a) chemosensory receptors and signaling components of the main olfactory epithelium and vomeronasal organ involved in pheromone detection; (b) pheromone-activated neural circuits subject to sex-specific and state-dependent modulation; and (c) the striking chemical diversity of mammalian pheromones, which range from small, volatile molecules and sulfated steroids to large families of proteins. Finally, I review (d ) molecular mechanisms underlying various behavioral and endocrine responses, including modulation of puberty and estrous; control of reproduction, aggression, suckling, and parental behaviors; individual recognition; and distinguishing of own species from predators, competitors, and prey. Deconstruction of pheromone transduction mechanisms provides a critical foundation for understanding how odor response pathways generate instinctive behaviors. PMID:23988175

  5. What Are the Treatments for Spinal Cord Injury (SCI)?

    MedlinePlus

    ... Resources and Publications What are the treatments for spinal cord injury (SCI)? Skip sharing on social media links ... no known ways to reverse damage to the spinal cord. However, researchers are continually working on new treatments, ...

  6. AtPolλ, a homolog of mammalian DNA polymerase λ in Arabidopsis thaliana, is involved in the repair of UV-B induced DNA damage through the dark repair pathway.

    PubMed

    Roy, Sujit; Choudhury, Swarup Roy; Singh, Sanjay Kumar; Das, Kali Pada

    2011-02-01

    Plants are constantly exposed to a wide range of environmental genotoxic stress factors including obligatory exposure to UV radiation in sunlight. Here, we report the functional characterization of a DNA repair protein, AtPolλ, a homolog of mammalian DNA polymerase λ in Arabidopsis, in relation to its role in repair of UV-B-induced DNA damage during early stages of seedling development. The abundance of the AtPolλ transcript and the protein levels were distinctly increased in response to UV-B irradiation in 6-day-old wild-type seedlings. Growth of atpolλ mutant seedlings, deficient in AtPolλ expression, was more sensitive to UV-B radiation compared with wild-type plants when seeds were exposed to UV-B radiation before germination. The atpolλ mutants showed accumulation of relatively higher amounts of DNA lesions than wild-type plants following UV-B exposure and were less proficient in repair of UV-induced DNA damage. Increased accumulation of AtPolλ protein in UV-B-irradiated 6-day-old wild-type seedlings during the dark recovery period has indicated a possible role for the protein in repair of UV-B-induced lesions in the dark. Overexpression of AtPolλ in the atpolλ mutant line partially complemented the repair proficiency of UV-B-induced DNA damage. In vitro repair synthesis assays using whole-cell extracts from the wild-type and atpolλ mutant line have further demonstrated the role of AtPolλ in repair synthesis of UV-B-damaged DNA in the dark through an excision repair mechanism. Overall, our results have indicated the possible involvement of AtPolλ in a plant's response for repair of UV-B-mediated DNA damage during seedling development.

  7. Spinal brucellosis.

    PubMed

    Tali, E Turgut; Koc, A Murat; Oner, A Yusuf

    2015-05-01

    Spinal involvement in human brucellosis is a common condition and a significant cause of morbidity and mortality, particularly in endemic areas, because it is often associated with therapeutic failure. Most chronic brucellosis cases are the result of inadequate treatment of the initial episode. Recognition of spinal brucellosis is challenging. Early diagnosis is important to ensure proper treatment and decrease morbidity and mortality. Radiologic evaluation has gained importance in diagnosis and treatment planning, including interventional procedures and monitoring of all spinal infections.

  8. DSB repair model for mammalian cells in early S and G1 phases of the cell cycle: application to damage induced by ionizing radiation of different quality.

    PubMed

    Taleei, Reza; Girard, Peter M; Nikjoo, Hooshang

    2015-02-01

    The purpose of this work is to test the hypothesis that kinetics of double strand breaks (DSB) repair is governed by complexity of DSB. To test the hypothesis we used our recent published mechanistic mathematical model of DSB repair for DSB induced by selected protons, deuterons, and helium ions of different energies representing radiations of different qualities. In light of recent advances in experimental and computational techniques, the most appropriate method to study cellular responses in radiation therapy, and exposures to low doses of ionizing radiations is using mechanistic approaches. To this end, we proposed a 'bottom-up' approach to study cellular response that starts with the DNA damage. Monte Carlo track structure method was employed to simulate initial damage induced in the genomic DNA by direct and indirect effects. Among the different types of DNA damage, DSB are known to be induced in simple and complex forms. The DSB repair model in G1 and early S phases of the cell cycle was employed to calculate the repair kinetics. The model considers the repair of simple and complex DSB, and the DSB produced in the heterochromatin. The inverse sampling method was used to calculate the repair kinetics for each individual DSB. The overall repair kinetics for 500 DSB induced by single tracks of the radiation under test were compared with experimental results. The results show that the model is capable of predicting the repair kinetics for the DSB induced by radiations of different qualities within an accepted range of uncertainty.

  9. Structural changes in mammalian cell DNA induced by low-dose x-ray damage and subsequent postirradiation incubation in the presence and absence of caffeine

    SciTech Connect

    Wun, K.L.W.; Shafer, R.H.

    1982-05-01

    DNA damage and postirradiation incubation effects from X-ray doses of 30-2000 rad delivered to rat 9L cells in vitro were detemined by viscoelastic analysis of neutral (pH 7) cell lysates. Damage studies showed first an increase in the principal viscoelastic retardation time, T, with increasing dose, followed by a decrease, with the maximum retardation time occurring at 1000 rad. Also, the variation of retardation time with increasing postirradiation incubation time at 37/sup 0/C was determined. At doses greater than 50 rad, this variation was quite complicated; e.g., following 100 rad, the retardation time showed a minimum followed by a maximum as a function of incubation time. All doses showed an initial return of T to close to control values at early times. Following 50 rad, control viscoelastic behavior was recovered in 1 hr. For doses of 100 rad and higher, 5 hr or more were required for complete return to control behavior has determined by both the value of T and the viscoelastic response to a probe dose of 200 rad immediately prior to lysis. These results are analyzed in terms of the dependence of the principal retardation time T on DNA molecular weight and conformation. Evidence is discussed indicating that the observed changes in T during postirradiation incubation reflect repair of DNA damage. Postirradiation incubation in the presence of 0.5 mM caffeine appeared to result in an inhibition of repair. In this case, both 30- and 50-rad doses required 5 hr for complete recovery of control behavior and showed the minimum and maximum in the T vs incubation time curve observed for incubation in the absence of caffeine following a dose of 100 rad.

  10. Iron oxide nanoparticles and magnetic field exposure promote functional recovery by attenuating free radical-induced damage in rats with spinal cord transection

    PubMed Central

    Pal, Ajay; Singh, Anand; Nag, Tapas C; Chattopadhyay, Parthaprasad; Mathur, Rashmi; Jain, Suman

    2013-01-01

    Background Iron oxide nanoparticles (IONPs) can attenuate oxidative stress in a neutral pH environment in vitro. In combination with an external electromagnetic field, they can also facilitate axon regeneration. The present study demonstrates the in vivo potential of IONPs to recover functional deficits in rats with complete spinal cord injury. Methods The spinal cord was completely transected at the T11 vertebra in male albino Wistar rats. Iron oxide nanoparticle solution (25 μg/mL) embedded in 3% agarose gel was implanted at the site of transection, which was subsequently exposed to an electromagnetic field (50 Hz, 17.96 μT for two hours daily for five weeks). Results Locomotor and sensorimotor assessment as well as histological analysis demonstrated significant functional recovery and a reduction in lesion volume in rats with IONP implantation and exposure to an electromagnetic field. No collagenous scar was observed and IONPs were localized intracellularly in the immediate vicinity of the lesion. Further, in vitro experiments to explore the cytotoxic effects of IONPs showed no effect on cell survival. However, a significant decrease in H2O2-mediated oxidative stress was evident in the medium containing IONPs, indicating their free radical scavenging properties. Conclusion These novel findings indicate a therapeutic role for IONPs in spinal cord injury and other neurodegenerative disorders mediated by reactive oxygen species. PMID:23818782

  11. Mammalian sleep

    NASA Astrophysics Data System (ADS)

    Staunton, Hugh

    2005-05-01

    This review examines the biological background to the development of ideas on rapid eye movement sleep (REM sleep), so-called paradoxical sleep (PS), and its relation to dreaming. Aspects of the phenomenon which are discussed include physiological changes and their anatomical location, the effects of total and selective sleep deprivation in the human and animal, and REM sleep behavior disorder, the latter with its clinical manifestations in the human. Although dreaming also occurs in other sleep phases (non-REM or NREM sleep), in the human, there is a contingent relation between REM sleep and dreaming. Thus, REM is taken as a marker for dreaming and as REM is distributed ubiquitously throughout the mammalian class, it is suggested that other mammals also dream. It is suggested that the overall function of REM sleep/dreaming is more important than the content of the individual dream; its function is to place the dreamer protagonist/observer on the topographical world. This has importance for the developing infant who needs to develop a sense of self and separateness from the world which it requires to navigate and from which it is separated for long periods in sleep. Dreaming may also serve to maintain a sense of ‘I’ness or “self” in the adult, in whom a fragility of this faculty is revealed in neurological disorders.

  12. Singular contributions of fish neuroendocrinology to mammalian regulatory peptide research.

    PubMed

    Conlon, J M

    2000-09-25

    During the past 20 years, several bioactive peptides have been identified in teleost fishes that subsequently have been shown to play important regulatory roles in mammalian physiology. The urophysis, corpuscles of Stannius and Brockmann body are anatomical structures particular to fish that have no obvious counterpart in mammals. Extracts and/or cDNA libraries prepared from these tissues have been used to identify for the first time urotensin II (U-II), urotensin-I (U-I), stanniocalcin and glucagon-like peptide-1 (GLP-1). Although U-II and U-I were originally regarded as exclusively the products of the teleost urophysis, the peptides have a wide phylogenetic distribution across the vertebrate lineage, including mammals. U-II is localized to motor neurones in the human spinal cord and is a potent vasoconstrictor that may be implicated in the pathogenesis of heart failure. The human ortholog of urotensin-I is urocortin which is synthesized in selected regions of the brain and is the endogenous ligand for the CRF type 2 receptor. Urocortin is believed to important in mediating the effects of stress on appetite. Stanniocalcin is involved in maintaining calcium and phosphate homeostasis in teleost fish. An ortholog of stanniocalcin has a widespread distribution in mammalian tissues and is postulated to regulate renal phosphate excretion and to protect neurons against damage during cerebral ischemia. The biological actions and therapeutic potential of GLP-1 in humans are now fully appreciated but the peptide was first identified as a domain in a preproglucagon cDNA prepared from anglerfish Brockmann bodies. In contrast to mammalian preproglucagons, GLP-1 is present in anglerfish preproglucagon as the bioactive, truncated sequence [corresponding to human GLP-1(7-37)] rather than the inactive, N-terminally extended form [corresponding to GLP-1(1-37)]. Failure to appreciate the significance of this fact retarded progress in the field for several years. PMID:11033047

  13. Spinal deformity.

    PubMed

    Bunnell, W P

    1986-12-01

    Spinal deformity is a relatively common disorder, particularly in teenage girls. Early detection is possible by a simple, quick visual inspection that should be a standard part of the routine examination of all preteen and teenage patients. Follow-up observation will reveal those curvatures that are progressive and permit orthotic treatment to prevent further increase in the deformity. Spinal fusion offers correction and stabilization of more severe degrees of scoliosis. PMID:3786010

  14. Zinc transporter 3 (ZnT3) gene deletion reduces spinal cord white matter damage and motor deficits in a murine MOG-induced multiple sclerosis model.

    PubMed

    Choi, Bo Young; Kim, In Yeol; Kim, Jin Hee; Kho, A Ra; Lee, Song Hee; Lee, Bo Eun; Sohn, Min; Koh, Jae-Young; Suh, Sang Won

    2016-10-01

    The present study aimed to evaluate the role of zinc transporter 3 (ZnT3) on multiple sclerosis (MS) pathogenesis. Experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis, was induced by immunization with myelin oligodendrocyte glycoprotein (MOG35-55) in female mice. Three weeks after the initial immunization, demyelination, immune cell infiltration and blood brain barrier (BBB) disruption in the spinal cord were analyzed. Clinical signs of EAE first appeared on day 11 and reached a peak level on day 19 after the initial immunization. ZnT3 gene deletion profoundly reduced the daily clinical score of EAE. The ZnT3 gene deletion-mediated inhibition of the clinical course of EAE was accompanied by suppression of inflammation and demyelination in the spinal cord. The motor deficit accompanying neuropathological changes associated with EAE were mild in ZnT3 gene deletion mice. This reduction in motor deficit was accompanied by coincident reductions in demyelination and infiltration of encephalitogenic immune cells including CD4+ T cells, CD8+ T cells, CD20+ B cells and F4/80+ microglia in the spinal cord. These results demonstrate that ZnT3 gene deletion inhibits the clinical features and neuropathological changes associated with EAE. ZnT3 gene deletion also remarkably inhibited formation of EAE-associated aberrant synaptic zinc patches, matrix metalloproteinases-9 (MMP-9) activation and BBB disruption. Therefore, amelioration of EAE-induced clinical and neuropathological changes by ZnT3 gene deletion suggests that vesicular zinc may be involved in several steps of MS pathogenesis.

  15. Characterization of a DNA damage-recognition protein mammalian cells that binds specifically to intrastrand d(GpG) and d(ApG) DNA adducts of the anticancer drug cisplatin

    SciTech Connect

    Donahue, B.A.; Augot, M.; Bellon, S.F.; Treiber, D.K.; Toney, J.H.; Lippard, S.J.; Essigmann, J.M. )

    1990-06-19

    A factor has been identified in extracts from human HeLa and hamster V79 cells that retards the electrophoretic mobility of several DNA restriction fragments modified with the antitumor drug cis-diamminedichloroplatinum(II) (cisplatin). Binding of the factor to cisplatin-modified DNA was sensitive to pretreatment with proteinase K, establishing that the factor is a protein. Gel mobility shifts were observed with probes containing as few as seven Pt atoms per kilobase of duplex DNA. By competition experiments the dissociation constant, K{sub d}, of the protein from cisplatin-modified DNA was estimated to be (1-20) {times} 10{sup {minus}10} M. Protein binding is selective for DNA modified with cisplatin, (Pt(en)Cl{sub 2}) (en, ethylenediamine), and (Pt(dach)Cl{sub 2}) (dach, 1,2-diaminocyclohexane) but not with chemotherapeutically inactive trans-diamminedichloroplatinum(II) or monofunctionally coordinating (Pt(dien)Cl)Cl (dien, diethylenetriamine) complexes. The protein binds specifically to 1,2-intrastrand d(GpG) and d(ApG) cross-links formed by cisplatin. The apparent molecular weight of the protein is 91,000, as determined by sucrose gradient centrifugation of a preparation partially purified by ammonium sulfate fractionation. Binding of the protein to platinum-modified DNA does not require cofactors but is sensitive to treatment with 5 mM MnCl{sub 2}, CdCl{sub 2}, CoCl{sub 2}, or ZnCl{sub 2} and with 1 mM HgCl{sub 2}. This protein, alone or in conjunction with other cellular constituents, could be of general importance in the initial stages of processing of mammalian DNA damaged by cisplatin or other genotoxic agents and may belong to a wider class of such cellular damage-recognition proteins (DRPs).

  16. Therapeutic approaches for spinal cord injury

    PubMed Central

    Cristante, Alexandre Fogaça; de Barros Filho, Tarcísio Eloy Pessoa; Marcon, Raphael Martus; Letaif, Olavo Biraghi; da Rocha, Ivan Dias

    2012-01-01

    This study reviews the literature concerning possible therapeutic approaches for spinal cord injury. Spinal cord injury is a disabling and irreversible condition that has high economic and social costs. There are both primary and secondary mechanisms of damage to the spinal cord. The primary lesion is the mechanical injury itself. The secondary lesion results from one or more biochemical and cellular processes that are triggered by the primary lesion. The frustration of health professionals in treating a severe spinal cord injury was described in 1700 BC in an Egyptian surgical papyrus that was translated by Edwin Smith; the papyrus reported spinal fractures as a “disease that should not be treated.” Over the last two decades, several studies have been performed to obtain more effective treatments for spinal cord injury. Most of these studies approach a patient with acute spinal cord injury in one of four manners: corrective surgery or a physical, biological or pharmacological treatment method. Science is unraveling the mechanisms of cell protection and neuroregeneration, but clinically, we only provide supportive care for patients with spinal cord injuries. By combining these treatments, researchers attempt to enhance the functional recovery of patients with spinal cord injuries. Advances in the last decade have allowed us to encourage the development of experimental studies in the field of spinal cord regeneration. The combination of several therapeutic strategies should, at minimum, allow for partial functional recoveries for these patients, which could improve their quality of life. PMID:23070351

  17. Damage and repair of irradiated mammalian brain

    SciTech Connect

    Frankel, K.; Lo, E.; Phillips, M.; Fabrikant, J.; Brennan, K.; Valk, P.; Poljak, A.; Delapaz, R.; Woodruff, K.; Stanford Univ., CA . Medical Center; Brookside Hospital, San Pablo, CA )

    1989-07-01

    We have demonstrated that focal charged particle irradiation of the rabbit brain can create well-defined lesions which are observable by nuclear magnetic resonance imaging (NMR) and positron emission tomography (PET) imaging techniques. These are similar, in terms of location and characteristic NMR and PET features, to those that occur in the brain of about 10% of clinical research human subjects, who have been treated for intracranial vascular malformations with stereotactic radiosurgery. These lesions have been described radiologically as vasogenic edema of the deep white matter,'' and the injury is of variable intensity and temporal duration, can recede or progress to serious neurologic sequelae, and persist for a considerable period of time, frequently 18 mon to 3 yr. 8 refs., 6 figs.

  18. Excitotoxic cell death induces delayed proliferation of endogenous neuroprogenitor cells in organotypic slice cultures of the rat spinal cord.

    PubMed

    Mazzone, G L; Mladinic, M; Nistri, A

    2013-10-31

    The aim of the present report was to investigate whether, in the mammalian spinal cord, cell death induced by transient excitotoxic stress could trigger activation and proliferation of endogenous neuroprogenitor cells as a potential source of a lesion repair process and the underlying time course. Because it is difficult to address these issues in vivo, we used a validated model of spinal injury based on rat organotypic slice cultures that retain the fundamental tissue cytoarchitecture and replicate the main characteristics of experimental damage to the whole spinal cord. Excitotoxicity evoked by 1 h kainate application produced delayed neuronal death (40%) peaking after 1 day without further losses or destruction of white matter cells for up to 2 weeks. After 10 days, cultures released a significantly larger concentration of endogenous glutamate, suggesting functional network plasticity. Indeed, after 1 week the total number of cells had returned to untreated control level, indicating substantial cell proliferation. Activation of progenitor cells started early as they spread outside the central area, and persisted for 2 weeks. Although expression of the neuronal progenitor phenotype was observed at day 3, peaked at 1 week and tapered off at 2 weeks, very few cells matured to neurons. Astroglia precursors started proliferating later and matured at 2 weeks. These data show insult-related proliferation of endogenous spinal neuroprogenitors over a relatively brief time course, and delineate a narrow temporal window for future experimental attempts to drive neuronal maturation and for identifying the factors regulating this process.

  19. Mechanisms of mammalian iron homeostasis.

    PubMed

    Pantopoulos, Kostas; Porwal, Suheel Kumar; Tartakoff, Alan; Devireddy, L

    2012-07-24

    Iron is vital for almost all organisms because of its ability to donate and accept electrons with relative ease. It serves as a cofactor for many proteins and enzymes necessary for oxygen and energy metabolism, as well as for several other essential processes. Mammalian cells utilize multiple mechanisms to acquire iron. Disruption of iron homeostasis is associated with various human diseases: iron deficiency resulting from defects in the acquisition or distribution of the metal causes anemia, whereas iron surfeit resulting from excessive iron absorption or defective utilization causes abnormal tissue iron deposition, leading to oxidative damage. Mammals utilize distinct mechanisms to regulate iron homeostasis at the systemic and cellular levels. These involve the hormone hepcidin and iron regulatory proteins, which collectively ensure iron balance. This review outlines recent advances in iron regulatory pathways as well as in mechanisms underlying intracellular iron trafficking, an important but less studied area of mammalian iron homeostasis.

  20. Spinal Osteosarcoma

    PubMed Central

    Katonis, P.; Datsis, G.; Karantanas, A.; Kampouroglou, A.; Lianoudakis, S.; Licoudis, S.; Papoutsopoulou, E.; Alpantaki, K.

    2013-01-01

    Although osteosarcoma represents the second most common primary bone tumor, spinal involvement is rare, accounting for 3%–5% of all osteosarcomas. The most frequent symptom of osteosarcoma is pain, which appears in almost all patients, whereas more than 70% exhibit neurologic deficit. At a molecular level, it is a tumor of great genetic complexity and several genetic disorders have been associated with its appearance. Early diagnosis and careful surgical staging are the most important factors in accomplishing sufficient management. Even though overall prognosis remains poor, en-block tumor removal combined with adjuvant radiotherapy and chemotherapy is currently the treatment of choice. This paper outlines histopathological classification, epidemiology, diagnostic procedures, and current concepts of management of spinal osteosarcoma. PMID:24179411

  1. Spinal Bracing

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Dr. Arthur Copes of the Copes Foundation, Baton Rouge, LA, says that 35 percent of the 50 technical reports he received from the NASA/Southern University Industrial Applications Center in Baton Rouge and the Central Industrial Applications Center, Durant, OK, were vital to the development of his Copes Scoliosis Braces, which are custom designed and feature a novel pneumatic bladder that exerts constant corrective pressure to the torso to slowly reduce or eliminate the spinal curve.

  2. Tethered Spinal Cord Syndrome

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Tethered Spinal Cord Syndrome Information Page Table of Contents (click to ... being done? Clinical Trials Organizations What is Tethered Spinal Cord Syndrome? Tethered spinal cord syndrome is a neurological ...

  3. Spinal Cord Infarction

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Spinal Cord Infarction Information Page Table of Contents (click to ... Organizations Related NINDS Publications and Information What is Spinal Cord Infarction? Spinal cord infarction is a stroke either ...

  4. Spinal injury - resources

    MedlinePlus

    Resources - spinal injury ... The following organizations are good resources for information on spinal injury : National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov The National Spinal Cord Injury ...

  5. Spinal Cord Injury Map

    MedlinePlus

    ... on the severity of the injury. Tap this spinal column to see how the level of injury affects loss of function and control. Learn more about spinal cord injuries. A spinal cord injury affects the ...

  6. Spinal dysraphism.

    PubMed

    Sgouros, Spyros

    2013-09-01

    In the last decade there have been significant improvements in all the fields of management of patients with spinal dysraphism, which have increased dramatically the quality of life of these children. Prevention of spina bifida with food fortification is becoming increasingly practiced worldwide. As result, in many parts of the world the frequency of myelomeningocele has decreased. Intrauterine closure of myelomeningocele has been attempted in many institutions with variable results. While it is still at the sphere of experimental therapy, it is reasonable to anticipate progress in this field in the next decade. Antenatal MR imaging is already providing very high level of detail even before the child is born. This creates new ethical dilemmas and requires additional care, but has improved significantly the overall management of patients and their families. Further improvements are anticipated in this field. Management of neuropathic bladder has improved significantly in the last decade and is anticipated to play an increasing role in the long term follow up. Surgery for spinal cord tethering in all its forms has improved in the last decade, with far more chances of complete untethering now in comparison to 10-15 years ago, with the use of micro-neurosurgical techniques and intraoperative monitoring. It is reasonable to expect that in the next decade, intraoperative neurophysiological monitoring during spinal cord surgery will become mandatory. In the 2013 Annual Special Issue we have assembled a team of authors distinguished in their fields, who bring us up to date with all the latest developments. PMID:24013314

  7. Spinal surgery -- cervical - series (image)

    MedlinePlus

    The cervical spinal column is made up of vertebral bodies which protect the spinal cord. ... spinal nerves, trauma, and narrowing (stenosis) of the spinal column around the spinal cord. Symptoms of cervical spine ...

  8. Hemoglobin potentiates central nervous system damage.

    PubMed Central

    Sadrzadeh, S M; Anderson, D K; Panter, S S; Hallaway, P E; Eaton, J W

    1987-01-01

    Iron and iron compounds--including mammalian hemoglobins--catalyze hydroxyl radical production and lipid peroxidation. To determine whether hemoglobin-mediated lipid peroxidation might be important in hemorrhagic injuries to the central nervous system (CNS), we studied the effects of purified hemoglobin on CNS homogenates and injected hemoglobin into the spinal cords of anesthetized cats. Hemoglobin markedly inhibits Na/K ATPase activity in CNS homogenates and spinal cords of living cats. Hemoglobin also catalyzes substantial peroxidation of CNS lipids. Importantly, the potent iron chelator, desferrioxamine, blocks these adverse effects of hemoglobin, both in vitro and in vivo. Because desferrioxamine is not known to interact with heme iron, these results indicate that free iron, derived from hemoglobin, is the proximate toxic species. Overall, our data suggest that hemoglobin, released from red cells after trauma, can promote tissue injury through iron-dependent mechanisms. Suppression of this damage by desferrioxamine suggests a rational therapeutic approach to management of trauma-induced CNS injury. Images PMID:3027133

  9. Nanomedicine for Treating Spinal Cord Injury

    PubMed Central

    Tyler, Jacqueline Y.; Xu, Xiao-Ming; Cheng, Ji-Xin

    2015-01-01

    Spinal cord injury results in significant mortality and morbidity, lifestyle changes, and difficult rehabilitation. Treatment of spinal cord injury is challenging because the spinal cord is both complex to treat acutely and difficult to regenerate. Nanomaterials can be used to provide effective treatments; their unique properties can facilitate drug delivery to the injury site, enact as neuroprotective agents, or provide platforms to stimulate regrowth of damaged tissues. We review recent uses of nanomaterials including nanowires, micelles, nanoparticles, liposomes, and carbon-based nanomaterials for neuroprotection in the acute phase. We also review the design and neural regenerative application of electrospun scaffolds, conduits, and self-assembling peptide scaffolds. PMID:23945984

  10. Nanomedicine for treating spinal cord injury

    NASA Astrophysics Data System (ADS)

    Tyler, Jacqueline Y.; Xu, Xiao-Ming; Cheng, Ji-Xin

    2013-09-01

    Spinal cord injury results in significant mortality and morbidity, lifestyle changes, and difficult rehabilitation. Treatment of spinal cord injury is challenging because the spinal cord is both complex to treat acutely and difficult to regenerate. Nanomaterials can be used to provide effective treatments; their unique properties can facilitate drug delivery to the injury site, enact as neuroprotective agents, or provide platforms to stimulate regrowth of damaged tissues. We review recent uses of nanomaterials including nanowires, micelles, nanoparticles, liposomes, and carbon-based nanomaterials for neuroprotection in the acute phase. We also review the design and neural regenerative application of electrospun scaffolds, conduits, and self-assembling peptide scaffolds.

  11. Arylsulfatase B Improves Locomotor Function after Mouse Spinal Cord Injury

    PubMed Central

    Yoo, Myungsik; Khaled, Muntasir; Gibbs, Kurt M.; Kim, Jonghun; Kowalewski, Björn; Dierks, Thomas; Schachner, Melitta

    2013-01-01

    Bacterial chondroitinase ABC (ChaseABC) has been used to remove the inhibitory chondroitin sulfate chains from chondroitin sulfate proteoglycans to improve regeneration after rodent spinal cord injury. We hypothesized that the mammalian enzyme arylsulfatase B (ARSB) would also enhance recovery after mouse spinal cord injury. Application of the mammalian enzyme would be an attractive alternative to ChaseABC because of its more robust chemical stability and reduced immunogenicity. A one-time injection of human ARSB into injured mouse spinal cord eliminated immunoreactivity for chondroitin sulfates within five days, and up to 9 weeks after injury. After a moderate spinal cord injury, we observed improvements of locomotor recovery assessed by the Basso Mouse Scale (BMS) in ARSB treated mice, compared to the buffer-treated control group, at 6 weeks after injection. After a severe spinal cord injury, mice injected with equivalent units of ARSB or ChaseABC improved similarly and both groups achieved significantly more locomotor recovery than the buffer-treated control mice. Serotonin and tyrosine hydroxylase immunoreactive axons were more extensively present in mouse spinal cords treated with ARSB and ChaseABC, and the immunoreactive axons penetrated further beyond the injury site in ARSB or ChaseABC treated mice than in control mice. These results indicate that mammalian ARSB improves functional recovery after CNS injury. The structural/molecular mechanisms underlying the observed functional improvement remain to be elucidated. PMID:23520469

  12. Therapeutic approaches for spinal cord injury.

    PubMed

    Cristante, Alexandre Fogaça; Barros Filho, Tarcísio Eloy Pessoa de; Marcon, Raphael Martus; Letaif, Olavo Biraghi; Rocha, Ivan Dias da

    2012-10-01

    This study reviews the literature concerning possible therapeutic approaches for spinal cord injury. Spinal cord injury is a disabling and irreversible condition that has high economic and social costs. There are both primary and secondary mechanisms of damage to the spinal cord. The primary lesion is the mechanical injury itself. The secondary lesion results from one or more biochemical and cellular processes that are triggered by the primary lesion. The frustration of health professionals in treating a severe spinal cord injury was described in 1700 BC in an Egyptian surgical papyrus that was translated by Edwin Smith; the papyrus reported spinal fractures as a "disease that should not be treated." Over the last biological or pharmacological treatment method. Science is unraveling the mechanisms of cell protection and neuroregeneration, but clinically, we only provide supportive care for patients with spinal cord injuries. By combining these treatments, researchers attempt to enhance the functional recovery of patients with spinal cord injuries. Advances in the last decade have allowed us to encourage the development of experimental studies in the field of spinal cord regeneration. The combination of several therapeutic strategies should, at minimum, allow for partial functional recoveries for these patients, which could improve their quality of life. PMID:23070351

  13. Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury

    PubMed Central

    Hou, Shaoping; Carson, David M.; Wu, Di; Klaw, Michelle C.; Houlé, John D.; Tom, Veronica J.

    2016-01-01

    Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH)+ neurons in the autonomic nuclei and superficial dorsal horn in L6–S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH)− and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH+ neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D2-like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH+ neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH+ cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH+ neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI. PMID:26655672

  14. Spinal instrumentation.

    PubMed

    Spivak, J M; Balderston, R A

    1994-03-01

    The past decade has seen a dramatic increase in the availability of spinal instrumentation devices, enabling surgeons to treat a variety of spinal disorders with improved results and lower morbidity. In each anatomic region new fixation systems exist. Improvement in fusion rates with supplemental plate fixation following anterior cervical diskectomies and reconstructions has been demonstrated; these devices can now be applied more safely than ever before. Posterior occipitocervical plating to the C-2 pedicle and C3-6 lateral masses can provide stable fixation despite incompetent posterior arch bony structures. Newer, more rigid anterior thoracolumbar instrumentation allows for correction of thoracolumbar and lumbar scoliosis along fewer levels and with better maintenance of lordosis and is also useful following anterior decompression for tumor and trauma. Segmental hook fixation of the posterior thoracolumbar spine has allowed for improved correction of deformity without increased morbidity or the need for postoperative bracing in many cases. Finally, the use of transpedicular screw fixation of the lumbosacral spine allows for excellent segmental fixation without intact posterior elements, including facet joints, and has significantly improved the fusion rate in lumbosacral fusions. PMID:8024965

  15. Spinal cord injury following an attempted thoracic epidural.

    PubMed

    Mayall, M F; Calder, I

    1999-10-01

    Unsuccessful attempts were made to insert a thoracic epidural in an anaesthetised patient. Signs of spinal cord damage were observed the following day. Magnetic resonance imaging demonstrated a haematoma anterior to the spinal cord. Surgical exploration revealed an intradural haematoma and a needle puncture of the cord. The patient suffered a permanent paraparesis.

  16. Degenerative spinal disease in large felids.

    PubMed

    Kolmstetter, C; Munson, L; Ramsay, E C

    2000-03-01

    Degenerative spinal disorders, including intervertebral disc disease and spondylosis, seldom occur in domestic cats. In contrast, a retrospective study of 13 lions (Panthera leo), 16 tigers (Panthera tigris), 4 leopards (Panthera pardis), 1 snow leopard (Panthera uncia), and 3 jaguars (Panthera onca) from the Knoxville Zoo that died or were euthanatized from 1976 to 1996 indicated that degenerative spinal disease is an important problem in large nondomestic felids. The medical record, radiographic data, and the necropsy report of each animal were examined for evidence of intervertebral disc disease or spondylosis. Eight (three lions, four tigers, and one leopard) animals were diagnosed with degenerative spinal disease. Clinical signs included progressively decreased activity, moderate to severe rear limb muscle atrophy, chronic intermittent rear limb paresis, and ataxia. The age at onset of clinical signs was 10-19 yr (median = 18 yr). Radiographic evaluation of the spinal column was useful in assessing the severity of spinal lesions, and results were correlated with necropsy findings. Lesions were frequently multifocal, included intervertebral disc mineralization or herniation with collapsed intervertebral disc spaces, and were most common in the lumbar area but also involved cervical and thoracic vertebrae. Marked spondylosis was present in the cats with intervertebral disc disease, presumably subsequent to vertebral instability. Six of the animals' spinal cords were examined histologically, and five had acute or chronic damage to the spinal cord secondary to disc protrusion. Spinal disease should be suspected in geriatric large felids with decreased appetite or activity. Radiographic evaluation of the spinal column is the most useful method to assess the type and severity of spinal lesions.

  17. Degenerative spinal disease in large felids.

    PubMed

    Kolmstetter, C; Munson, L; Ramsay, E C

    2000-03-01

    Degenerative spinal disorders, including intervertebral disc disease and spondylosis, seldom occur in domestic cats. In contrast, a retrospective study of 13 lions (Panthera leo), 16 tigers (Panthera tigris), 4 leopards (Panthera pardis), 1 snow leopard (Panthera uncia), and 3 jaguars (Panthera onca) from the Knoxville Zoo that died or were euthanatized from 1976 to 1996 indicated that degenerative spinal disease is an important problem in large nondomestic felids. The medical record, radiographic data, and the necropsy report of each animal were examined for evidence of intervertebral disc disease or spondylosis. Eight (three lions, four tigers, and one leopard) animals were diagnosed with degenerative spinal disease. Clinical signs included progressively decreased activity, moderate to severe rear limb muscle atrophy, chronic intermittent rear limb paresis, and ataxia. The age at onset of clinical signs was 10-19 yr (median = 18 yr). Radiographic evaluation of the spinal column was useful in assessing the severity of spinal lesions, and results were correlated with necropsy findings. Lesions were frequently multifocal, included intervertebral disc mineralization or herniation with collapsed intervertebral disc spaces, and were most common in the lumbar area but also involved cervical and thoracic vertebrae. Marked spondylosis was present in the cats with intervertebral disc disease, presumably subsequent to vertebral instability. Six of the animals' spinal cords were examined histologically, and five had acute or chronic damage to the spinal cord secondary to disc protrusion. Spinal disease should be suspected in geriatric large felids with decreased appetite or activity. Radiographic evaluation of the spinal column is the most useful method to assess the type and severity of spinal lesions. PMID:10884118

  18. Systemic Bisperoxovanadium Activates Akt/mTOR, Reduces Autophagy, and Enhances Recovery following Cervical Spinal Cord Injury

    PubMed Central

    Walker, Chandler L.; Walker, Melissa J.; Liu, Nai-Kui; Risberg, Emelie C.; Gao, Xiang; Chen, Jinhui; Xu, Xiao-Ming

    2012-01-01

    Secondary damage following primary spinal cord injury extends pathology beyond the site of initial trauma, and effective management is imperative for maximizing anatomical and functional recovery. Bisperoxovanadium compounds have proven neuroprotective effects in several central nervous system injury/disease models, however, no mechanism has been linked to such neuroprotection from bisperoxovanadium treatment following spinal trauma. The goal of this study was to assess acute bisperoxovanadium treatment effects on neuroprotection and functional recovery following cervical unilateral contusive spinal cord injury, and investigate a potential mechanism of the compound's action. Two experimental groups of rats were established to 1) assess twice-daily 7 day treatment of the compound, potassium bisperoxo (picolinato) vanadium, on long-term recovery of skilled forelimb activity using a novel food manipulation test, and neuroprotection 6 weeks following injury and 2) elucidate an acute mechanistic link for the action of the drug post-injury. Immunofluorescence and Western blotting were performed to assess cellular signaling 1 day following SCI, and histochemistry and forelimb functional analysis were utilized to assess neuroprotection and recovery 6 weeks after injury. Bisperoxovanadium promoted significant neuroprotection through reduced motorneuron death, increased tissue sparing, and minimized cavity formation in rats. Enhanced forelimb functional ability during a treat-eating assessment was also observed. Additionally, bisperoxovanadium significantly enhanced downstream Akt and mammalian target of rapamycin signaling and reduced autophagic activity, suggesting inhibition of the phosphatase and tensin homologue deleted on chromosome ten as a potential mechanism of bisperoxovanadium action following traumatic spinal cord injury. Overall, this study demonstrates the efficacy of a clinically applicable pharmacological therapy for rapid initiation of neuroprotection post-spinal

  19. Regenerative treatment in spinal cord injury.

    PubMed

    Ozdemir, Mevci; Attar, Ayhan; Kuzu, Isinsu

    2012-09-01

    Spinal cord injury is a devastating, traumatic event, and experienced mainly among young people. Until the modern era, spinal cord injury was so rapidly fatal that no seriously injured persons would survive long enough for regeneration to occur. Treatment of spinal cord injury can be summarized as follows: prevent further cord injury, maintain blood flow, relieve spinal cord compression, and provide secure vertebral stabilization so as to allow mobilization and rehabilitation, none of which achieves functional recovery. Previous studies have focused on analyzing the pathogenesis of secondary injury that extends from the injury epicenter to the periphery, as well as the tissue damage and neural cell death associated with secondary injury. Now, there are hundreds of current experimental and clinical regenerative treatment studies. One of the most popular treatment method is cell transplantation in injured spinal cord. For this purpose bone marrow stromal cells, mononuclear stem cells, mesenchymal stem cells, embryonic stem cells, neural stem cells, and olfactory ensheathing cells can be used. As a result, cell transplantation has become a promising therapeutic option for spinal cord injury patients. In this paper we discuss the effectiveness of stem cell therapy in spinal cord injury.

  20. Assessing small-volume spinal cord dose for repeat spinal stereotactic body radiotherapy treatments

    NASA Astrophysics Data System (ADS)

    Ma, Lijun; Kirby, Neil; Korol, Renee; Larson, David A.; Sahgal, Arjun

    2012-12-01

    Spinal cord biologically effective dose (BED) limits are critical to safe spine stereotactic body radiotherapy (SBRT) delivery. In particular, when repeating SBRT to the same site, the problem of adding non-uniform BED distributions within small volumes of spinal cord has yet to be solved. We report a probability-based generalized BED (gBED) model to guide repeat spine SBRT treatment planning. The gBED was formulated by considering the sequential damaging probabilities of repeat spine SBRT treatments. Parameters from the standard linear-quadratic model, such as α/β = 2 Gy for the spinal cord, were applied. We tested the model based on SBRT specific spinal cord tolerance using a simulated and ten clinical repeat SBRT cases. The gBED provides a consistent solution for superimposing non-uniform dose distributions from different fractionation schemes, analogous to the BED for uniform dose distributions. Based on ten clinical cases, the gBED was observed to eliminate discrepancies in the cumulative BED of approximately 5% to 20% within small volumes (e.g. 0.1-2.0 cc) of spinal cord, as compared to a conventional calculation method. When assessing spinal cord tolerance for repeat spinal SBRT treatments, caution should be exercised when applying conventional BED calculations for small volumes of spinal cord irradiated, and the gBED potentially provides more conservative and consistently derived dose surrogates to guide safe treatment planning and treatment outcome modeling.

  1. Percutaneous Radiofrequency Ablation of Painful Spinal Tumors Adjacent to the Spinal Cord with Real-Time Monitoring of Spinal Canal Temperature: A Prospective Study

    SciTech Connect

    Nakatsuka, Atsuhiro Yamakado, Koichiro; Takaki, Haruyuki; Uraki, Junji; Makita, Masashi; Oshima, Fumiyoshi; Takeda, Kan

    2009-01-15

    PurposeTo prospectively evaluate the feasibility, safety, and clinical utility of bone radiofrequency (RF) ablation with real-time monitoring of the spinal canal temperature for the treatment of spinal tumors adjacent to the spinal cord.Materials and MethodsOur Institutional Review Board approved this study. Patients gave informed consent. The inclusion criteria were (a) a painful spinal metastasis and (b) a distance of 1 cm or less between the metastasis and the spinal cord. The thermocouple was placed in the spinal canal under CT fluoroscopic guidance. When the spinal canal temperature reached 45{sup o}C, RF application was immediately stopped. RF ablation was considered technically successful when the procedure was performed without major complications. Clinical success was defined as a fall in the visual analogue scale score of at least 2 points.ResultsTen patients with spinal tumors measuring 3-8 cm (mean, 4.9 {+-} 1.5 cm) were enrolled. The distance between the tumor and the spinal cord was 1-6 mm (mean, 2.4 {+-} 1.6 mm). All procedures were judged technically successful (100%). The spinal canal temperature did not exceed 45{sup o}C in 9 of the 10 patients (90%). In the remaining patient, the temperature rose to 48{sup o}C, resulting in transient neural damage, although RF application was immediately stopped when the temperature reached 45{sup o}C. Clinical success was achieved within 1 week in all patients (100%).ConclusionBone RF ablation with real-time monitoring of the spinal canal temperature is feasible, safe, and clinically useful for the treatment of painful spinal metastases adjacent to the spinal cord.

  2. Spinal cord trauma

    MedlinePlus

    ... if the bones or disks have been weakened Fragments of bone (such as from broken vertebrae, which are the ... presses on the spinal cord (decompression laminectomy ) Remove bone fragments, disk fragments, or foreign objects Fuse broken spinal ...

  3. Clamping down on mammalian meiosis

    PubMed Central

    Lyndaker, Amy M; Vasileva, Ana; Wolgemuth, Debra J; Weiss, Robert S; Lieberman, Howard B

    2013-01-01

    The RAD9A-RAD1-HUS1 (9-1-1) complex is a PCNA-like heterotrimeric clamp that binds damaged DNA to promote cell cycle checkpoint signaling and DNA repair. While various 9-1-1 functions in mammalian somatic cells have been established, mounting evidence from lower eukaryotes predicts critical roles in meiotic germ cells as well. This was investigated in 2 recent studies in which the 9-1-1 complex was disrupted specifically in the mouse male germline through conditional deletion of Rad9a or Hus1. Loss of these clamp subunits led to severely impaired fertility and meiotic defects, including faulty DNA double-strand break repair. While 9-1-1 is critical for ATR kinase activation in somatic cells, these studies did not reveal major defects in ATR checkpoint pathway signaling in meiotic cells. Intriguingly, this new work identified separable roles for 9-1-1 subunits, namely RAD9A- and HUS1-independent roles for RAD1. Based on these studies and the high-level expression of the paralogous proteins RAD9B and HUS1B in testis, we propose a model in which multiple alternative 9-1-1 clamps function during mammalian meiosis to ensure genome maintenance in the germline. PMID:24013428

  4. Brain and Spinal Tumors

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Brain and Spinal Tumors Information Page Synonym(s): Spinal Cord ... en Español Additional resources from MedlinePlus What are Brain and Spinal Tumors? Tumors of the brain and ...

  5. Spinal Cord Injuries

    MedlinePlus

    ... your body and your brain. A spinal cord injury disrupts the signals. Spinal cord injuries usually begin with a blow that fractures or ... bone disks that make up your spine. Most injuries don't cut through your spinal cord. Instead, ...

  6. Management of Spinal Meningiomas.

    PubMed

    Ravindra, Vijay M; Schmidt, Meic H

    2016-04-01

    Spinal meningiomas are the most common spinal tumors encountered in adults, and account for 6.5% of all craniospinal tumors. The treatment for these lesions is primarily surgical, but emerging modalities may include chemotherapy and radiosurgery. In this article, the current management of spinal meningiomas and the body of literature surrounding conventional treatment is reviewed and discussed.

  7. Spinal pain.

    PubMed

    Izzo, R; Popolizio, T; D'Aprile, P; Muto, M

    2015-05-01

    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 pain, much more difficult to treat. The clinical assessment of pain source can be a challenge because of the complex anatomy and function of the spine; the advanced imaging methods are often not sufficient for a definitive diagnosis because similar findings could be present in either asymptomatic and symptomatic subjects: a clinical correlation is always mandatory and the therapy cannot rely uniquely upon any imaging abnormalities. Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally

  8. Mammalian airborne allergens.

    PubMed

    Aalberse, Rob C

    2014-01-01

    Historically, horse dandruff was a favorite allergen source material. Today, however, allergic symptoms due to airborne mammalian allergens are mostly a result of indoor exposure, be it at home, at work or even at school. The relevance of mammalian allergens in relation to the allergenic activity of house dust extract is briefly discussed in the historical context of two other proposed sources of house dust allergenic activity: mites and Maillard-type lysine-sugar conjugates. Mammalian proteins involved in allergic reactions to airborne dust are largely found in only 2 protein families: lipocalins and secretoglobins (Fel d 1-like proteins), with a relatively minor contribution of serum albumins, cystatins and latherins. Both the lipocalin and the secretoglobin family are very complex. In some instances this results in a blurred separation between important and less important allergenic family members. The past 50 years have provided us with much detailed information on the genomic organization and protein structure of many of these allergens. However, the complex family relations, combined with the wide range of post-translational enzymatic and non-enzymatic modifications, make a proper qualitative and quantitative description of the important mammalian indoor airborne allergens still a significant proteomic challenge. PMID:24925404

  9. Mammalian development in space

    NASA Technical Reports Server (NTRS)

    Ronca, April E.

    2003-01-01

    Life on Earth, and thus the reproductive and ontogenetic processes of all extant species and their ancestors, evolved under the constant influence of the Earth's l g gravitational field. These considerations raise important questions about the ability of mammals to reproduce and develop in space. In this chapter, I review the current state of our knowledge of spaceflight effects on developing mammals. Recent studies are revealing the first insights into how the space environment affects critical phases of mammalian reproduction and development, viz., those events surrounding fertilization, embryogenesis, pregnancy, birth, postnatal maturation and parental care. This review emphasizes fetal and early postnatal life, the developmental epochs for which the greatest amounts of mammalian spaceflight data have been amassed. The maternal-offspring system, the coordinated aggregate of mother and young comprising mammalian development, is of primary importance during these early, formative developmental phases. The existing research supports the view that biologically meaningful interactions between mothers and offspring are changed in the weightlessness of space. These changes may, in turn, cloud interpretations of spaceflight effects on developing offspring. Whereas studies of mid-pregnant rats in space have been extraordinarily successful, studies of young rat litters launched at 9 days of postnatal age or earlier, have been encumbered with problems related to the design of in-flight caging and compromised maternal-offspring interactions. Possibilities for mammalian birth in space, an event that has not yet transpired, are considered. In the aggregate, the results indicate a strong need for new studies of mammalian reproduction and development in space. Habitat development and systematic ground-based testing are important prerequisites to future research with young postnatal rodents in space. Together, the findings support the view that the environment within which young

  10. Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injury

    PubMed Central

    Aloe, Luigi; Bianchi, Patrizia; De Bellis, Alberto; Soligo, Marzia; Rocco, Maria Luisa

    2014-01-01

    The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an increased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deficits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells. PMID:25206755

  11. Spinal cord injury following operative shoulder intervention: A case report

    PubMed Central

    Cleveland, Christine; Walker, Heather

    2015-01-01

    Context Cervical myelopathy is a spinal cord dysfunction that results from extrinsic compression of the spinal cord, its blood supply, or both. It is the most common cause of spinal cord dysfunction in patients greater than 55 years of age. Findings: A 57-year-old male with right shoulder septic arthritis underwent surgical debridement of his right shoulder and sustained a spinal cord injury intraoperatively. The most likely etiology is damage to the cervical spinal cord during difficult intubation requiring multiple attempts in this patient with underlying asymptomatic severe cervical stenosis. Conclusion Although it is not feasible to perform imaging studies on all patients undergoing intubation for surgery, this patient's outcome would suggest consideration of inclusion of additional pre-surgical screening examination techniques, such as testing for a positive Hoffman's reflex, is appropriate to detect asymptomatic patients who may have underlying cervical stenosis. PMID:24679185

  12. Mammalian touch catches up

    PubMed Central

    Walsh, Carolyn M.; Bautista, Diana M.; Lumpkin, Ellen A.

    2015-01-01

    An assortment of touch receptors innervate the skin and encode different tactile features of the environment. Compared with invertebrate touch and other sensory systems, our understanding of the molecular and cellular underpinnings of mammalian touch lags behind. Two recent breakthroughs have accelerated progress. First, an arsenal of cell-type-specific molecular markers allowed the functional and anatomical properties of sensory neurons to be matched, thereby unraveling a cellular code for touch. Such markers have also revealed key roles of non-neuronal cell types, such as Merkel cells and keratinocytes, in touch reception. Second, the discovery of Piezo genes as a new family of mechanically activated channels has fueled the discovery of molecular mechanisms that mediate and mechanotransduction in mammalian touch receptors. PMID:26100741

  13. Molecular dosimetry of DNA damage caused by alkylation. II. The induction and repair of different classes of single-strand breaks in cultured mammalian cells treated with ethylating agents.

    PubMed

    Dogliotti, E; Lakhanisky, T; van der Schans, G P; Lohman, P H

    1984-01-01

    Cultured Chinese hamster ovary cells were treated with ethylating agents. DNA lesions giving rise to single-strand breaks (SSB) or alkali-labile sites were measured by elution through membrane filters at pH 12.0 and pH 12.6, and by centrifugation in alkaline sucrose gradients after 1 h and 21 h lysis in alkali. Two agents with different tendencies to ethylate preferentially either at N or O atoms were compared, namely N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) and diethyl sulphate (DES). The compounds differed greatly in their potency to induce lesions, but the ratios of SSB, measured with different methods after a treatment for 30 min, did not differ significantly. This suggested that the spectrum of lesions induced by the two compounds is very similar. However, when both agents were studied with alkaline elution at pH 12.0 after a short treatment time (5 min) only ENNG was found to induce rapidly-repairable SSB. Most of these were rejoined already within 5 min after treatment. These results suggest that rapidly-repairable lesions occurring in DNA after treatment of mammalian cells with ethylating agents are due mainly to alkylation at O-atoms. PMID:6472317

  14. Rheotaxis guides mammalian sperm

    PubMed Central

    Miki, Kiyoshi; Clapham, David E

    2013-01-01

    Background In sea urchins, spermatozoan motility is altered by chemotactic peptides, giving rise to the assumption that mammalian eggs also emit chemotactic agents that guide spermatozoa through the female reproductive tract to the mature oocyte. Mammalian spermatozoa indeed undergo complex adaptations within the female (the process of capacitation) that are initiated by agents ranging from pH to progesterone, but these factors are not necessarily taxic. Currently, chemotaxis, thermotaxis, and rheotaxis have not been definitively established in mammals. Results Here, we show that positive rheotaxis, the ability of organisms to orient and swim against the flow of surrounding fluid, is a major taxic factor for mouse and human sperm. This flow is generated within 4 hours of sexual stimulation and coitus in female mice; prolactin-triggered oviductal fluid secretion clears the oviduct of debris, lowers viscosity, and generates the stream that guides sperm migration in the oviduct. Rheotaxic movement is demonstrated in capacitated and uncapacitated spermatozoa in low and high viscosity medium. Finally, we show that a unique sperm motion we quantify using the sperm head's rolling rate reflects sperm rotation that generates essential force for positioning the sperm in the stream. Rotation requires CatSper channels, presumably by enabling Ca2+ influx. Conclusions We propose that rheotaxis is a major determinant of sperm guidance over long distances in the mammalian female reproductive tract. Coitus induces fluid flow to guide sperm in the oviduct. Sperm rheotaxis requires rotational motion during CatSper channel-dependent hyperactivated motility. PMID:23453951

  15. [Pre-hospital care management of acute spinal cord injury].

    PubMed

    Hess, Thorsten; Hirschfeld, Sven; Thietje, Roland; Lönnecker, Stefan; Kerner, Thoralf; Stuhr, Markus

    2016-04-01

    Acute injury to the spine and spinal cord can occur both in isolation as also in the context of multiple injuries. Whereas a few decades ago, the cause of paraplegia was almost exclusively traumatic, the ratio of traumatic to non-traumatic causes in Germany is currently almost equivalent. In acute treatment of spinal cord injury, restoration and maintenance of vital functions, selective control of circulation parameters, and avoidance of positioning or transport-related additional damage are in the foreground. This article provides information on the guideline for emergency treatment of patients with acute injury of the spine and spinal cord in the preclinical phase. PMID:27070515

  16. Damage and repair in mammalian cells after exposure to non-ionizing radiations. II. Photoreactivation and killing of rat kangaroo cells (Potorous tridactylus) and Herpes simplex virus-1 by exposure to fluorescent "white" light or sunlight.

    PubMed

    Harm, H

    1980-01-01

    Photoreactivation (PR) of ultraviolet (254 nm)-inactivated cornea cells of the potoroo (or rat kangaroo; Potorous tridacylus) has been studied at wavelengths greater than 375 nm from either fluorescent "white" light or sunlight. In both cases the PR kinetics curves pass through maxima, which most likely result from the superposition of concomitant inactivation by the photoreactivating light. The inactivating effect of light was directly demonstrated for non-UV-irradiated cells, permitting correction of the PR curves. Wavelengths greater than 475 nm, and even greater than 560 nm, which do not noticeably damage cells, still photoreactivate, though less effectively than shorter wavelengths. Light treatment of UV-inactivated Herpes simplex Virus-1 (HSV-1) after infection leads to PR effects resembling those observed for cells, while light treatment of unirradiated virus after infection likewise causes inactivation. The "fluence-reduction factor" of PR, which is greater than 3 for the virus, exceeds that for the cells, where it decreases with increasing UV fluence. In vitro tests have indicated that sunlight greater than 375 nm causes photorepairable DNA lesions which are virtually fully repaired by the same light. Thus cell inactivation resulting from these solar wavelengths must be due to non-photorepairable damage.

  17. Spinal subarachnoid haematoma after spinal anaesthesia: case report.

    PubMed

    Vidal, Marion; Strzelecki, Antoine; Houadec, Mireille; Krikken, Isabelle Ranz; Danielli, Antoine; Souza Neto, Edmundo Pereira de

    2016-01-01

    Subarachnoid haematoma after spinal anaesthesia is known to be very rare. In the majority of these cases, spinal anaesthesia was difficult to perform and/or unsuccessful; other risk factors included antiplatelet or anticoagulation therapy, and direct spinal cord trauma. We report a case of subarachnoid haematoma after spinal anaesthesia in a young patient without risk factors. PMID:27591468

  18. Autophagosome formation in mammalian cells.

    PubMed

    Burman, Chloe; Ktistakis, Nicholas T

    2010-12-01

    Autophagy is a fundamental intracellular trafficking pathway conserved from yeast to mammals. It is generally thought to play a pro-survival role, and it can be up regulated in response to both external and intracellular factors, including amino acid starvation, growth factor withdrawal, low cellular energy levels, endoplasmic reticulum (ER) stress, hypoxia, oxidative stress, pathogen infection, and organelle damage. During autophagy initiation a portion of the cytosol is surrounded by a flat membrane sheet known as the isolation membrane or phagophore. The isolation membrane then elongates and seals itself to form an autophagosome. The autophagosome fuses with normal endocytic traffic to mature into a late autophagosome, before fusing with lysosomes. The molecular machinery that enables formation of an autophagosome in response to the various autophagy stimuli is almost completely identified in yeast and-thanks to the observed conservation-is also being rapidly elucidated in higher eukaryotes including mammals. What are less clear and currently under intense investigation are the mechanism by which these various autophagy components co-ordinate in order to generate autophagosomes. In this review, we will discuss briefly the fundamental importance of autophagy in various pathophysiological states and we will then review in detail the various players in early autophagy. Our main thesis will be that a conserved group of heteromeric protein complexes and a relatively simple signalling lipid are responsible for the formation of autophagosomes in mammalian cells.

  19. Mammalian glycosylation in immunity

    PubMed Central

    Marth, Jamey D.; Grewal, Prabhjit K.

    2009-01-01

    Glycosylation produces a diverse and abundant repertoire of glycans, which are collectively known as the glycome. Glycans are one of the four fundamental macromolecular components of all cells, and are highly regulated in the immune system. Their diversity reflects their multiple biological functions that encompass ligands for proteinaceous of receptors known as lectins. Since the discovery that selectins and their glycan ligands are important for the regulation of leukocyte trafficking, it has been shown that additional features of the vertebrate immune system are also controlled by endogenous cellular glycosylation. This Review focuses on the emerging immunological roles of the mammalian glycome. PMID:18846099

  20. Epidemiology of spinal cord injury.

    PubMed

    Kurtzke, J F

    1977-01-01

    Accidents are the cause of some 50 deaths per 100 000 population each year in the US; some 3% of these are from traumatic spinal cord injury alone. Traumatic spinal cord injury in socioeconomically advanced countries, has a probably annual incidence rate of 3 per 100 000 population. Males are affected five times as often as females, and in the US, Negroes have twice the rates of whites. Half the cases are due to motor vehicle accidents, 1/4 to falls, and 1/10 to sports injuries. Maximal ages at risk are 15 to 34; only for cord damage due to falls do this risk differ, and here elderly are the more prone. Associated injuries are common in traumatic cord injury, and head injury and pulmonary dysfunction are frequent causes of the acute deaths in traumatic SCI which is why complete quadriplegia has a high early case-fatality ratio. Late deaths in SCI are principally the direct or indirect result of the neurogenic bladder. With treatment in comprehensive spinal cord injury centers, more than 4 of 5 traumatic SCI patients will survive ten years with an average of almost 18 years. Median survival may be almost 14 years for complete quadriplegia, 17 for complete paraplegia, 19 for incomplete quadriplegia, 20 for incomplete paraplegia and 28 for cauda equina lesions. Prevalence is likely to be some 50 per 100 000 population with about 20 per 100 000 completely paralyzed (3 quadriplegic and 19 paraplegic). Some 4 out of 5 survivors of traumatic SCI should be able to live at home and perform gainful work after such treatment. PMID:616527

  1. Mitochondria and mammalian reproduction.

    PubMed

    Ramalho-Santos, João; Amaral, Sandra

    2013-10-15

    Mitochondria are cellular organelles with crucial roles in ATP synthesis, metabolic integration, reactive oxygen species (ROS) synthesis and management, the regulation of apoptosis (namely via the intrinsic pathway), among many others. Additionally, mitochondria in different organs or cell types may have distinct properties that can decisively influence functional analysis. In terms of the importance of mitochondria in mammalian reproduction, and although there are species-specific differences, these aspects involve both energetic considerations for gametogenesis and fertilization, control of apoptosis to ensure the proper production of viable gametes, and ROS signaling, as well as other emerging aspects. Crucially, mitochondria are the starting point for steroid hormone biosynthesis, given that the conversion of cholesterol to pregnenolone (a common precursor for all steroid hormones) takes place via the activity of the cytochrome P450 side-chain cleavage enzyme (P450scc) on the inner mitochondrial membrane. Furthermore, mitochondrial activity in reproduction has to be considered in accordance with the very distinct strategies for gamete production in the male and female. These include distinct gonad morpho-physiologies, different types of steroids that are more prevalent (testosterone, estrogens, progesterone), and, importantly, the very particular timings of gametogenesis. While spermatogenesis is complete and continuous since puberty, producing a seemingly inexhaustible pool of gametes in a fixed environment; oogenesis involves the episodic production of very few gametes in an environment that changes cyclically. These aspects have always to be taken into account when considering the roles of any common element in mammalian reproduction.

  2. A 'tool box' for deciphering neuronal circuits in the developing chick spinal cord.

    PubMed

    Hadas, Yoav; Etlin, Alex; Falk, Haya; Avraham, Oshri; Kobiler, Oren; Panet, Amos; Lev-Tov, Aharon; Klar, Avihu

    2014-10-29

    The genetic dissection of spinal circuits is an essential new means for understanding the neural basis of mammalian behavior. Molecular targeting of specific neuronal populations, a key instrument in the genetic dissection of neuronal circuits in the mouse model, is a complex and time-demanding process. Here we present a circuit-deciphering 'tool box' for fast, reliable and cheap genetic targeting of neuronal circuits in the developing spinal cord of the chick. We demonstrate targeting of motoneurons and spinal interneurons, mapping of axonal trajectories and synaptic targeting in both single and populations of spinal interneurons, and viral vector-mediated labeling of pre-motoneurons. We also demonstrate fluorescent imaging of the activity pattern of defined spinal neurons during rhythmic motor behavior, and assess the role of channel rhodopsin-targeted population of interneurons in rhythmic behavior using specific photoactivation.

  3. Rehabilitation of spinal cord injuries

    PubMed Central

    Nas, Kemal; Yazmalar, Levent; Şah, Volkan; Aydın, Abdulkadir; Öneş, Kadriye

    2015-01-01

    Spinal cord injury (SCI) is the injury of the spinal cord from the foramen magnum to the cauda equina which occurs as a result of compulsion, incision or contusion. The most common causes of SCI in the world are traffic accidents, gunshot injuries, knife injuries, falls and sports injuries. There is a strong relationship between functional status and whether the injury is complete or not complete, as well as the level of the injury. The results of SCI bring not only damage to independence and physical function, but also include many complications from the injury. Neurogenic bladder and bowel, urinary tract infections, pressure ulcers, orthostatic hypotension, fractures, deep vein thrombosis, spasticity, autonomic dysreflexia, pulmonary and cardiovascular problems, and depressive disorders are frequent complications after SCI. SCI leads to serious disability in the patient resulting in the loss of work, which brings psychosocial and economic problems. The treatment and rehabilitation period is long, expensive and exhausting in SCI. Whether complete or incomplete, SCI rehabilitation is a long process that requires patience and motivation of the patient and relatives. Early rehabilitation is important to prevent joint contractures and the loss of muscle strength, conservation of bone density, and to ensure normal functioning of the respiratory and digestive system. An interdisciplinary approach is essential in rehabilitation in SCI, as in the other types of rehabilitation. The team is led by a physiatrist and consists of the patients’ family, physiotherapist, occupational therapist, dietician, psychologist, speech therapist, social worker and other consultant specialists as necessary. PMID:25621206

  4. Transplantation of Glial Cells Enhances Action Potential Conduction of Amyelinated Spinal Cord Axons in the Myelin-Deficient Rat

    NASA Astrophysics Data System (ADS)

    Utzschneider, David A.; Archer, David R.; Kocsis, Jeffery D.; Waxman, Stephen G.; Duncan, Ian D.

    1994-01-01

    A central issue in transplantation research is to determine how and when transplantation of neural tissue can influence the development and function of the mammalian central nervous system. Of particular interest is whether electrophysiological function in the traumatized or diseased mammalian central nervous system can be improved by the replacement of cellular elements that are missing or damaged. Although it is known that transplantation of neural tissue can lead to functional improvement in models of neurological disease characterized by neuronal loss, less is known about results of transplantation in disorders of myelin. We report here that transplantation of glial cells into the dorsal columns of neonatal myelin-deficient rat spinal cords leads to myelination and a 3-fold increase in conduction velocity. We also show that impulses can propagate into and out of the transplant region and that axons myelinated by transplanted cells do not have impaired frequency-response properties. These results demonstrate that myelination following central nervous system glial cell transplantation enhances action potential conduction in myelin-deficient axons, with conduction velocity approaching normal values.

  5. The mammalian blastocyst.

    PubMed

    Frankenberg, Stephen R; de Barros, Flavia R O; Rossant, Janet; Renfree, Marilyn B

    2016-01-01

    The blastocyst is a mammalian invention that carries the embryo from cleavage to gastrulation. For such a simple structure, it exhibits remarkable diversity in its mode of formation, morphology, longevity, and intimacy with the uterine endometrium. This review explores this diversity in the light of the evolution of viviparity, comparing the three main groups of mammals: monotremes, marsupials, and eutherians. The principal drivers in blastocyst evolution were loss of yolk coupled with evolution of the placenta. An important outcome of blastocyst development is differentiation of two extraembryonic lineages (trophoblast and hypoblast) that contribute to the placenta. While in many species trophoblast segregation is often coupled with blastocyst formation, in marsupials and at least some Afrotherians, these events do not coincide. Thus, many questions regarding the conservation of molecular mechanisms controlling these events are of great interest but currently unresolved. For further resources related to this article, please visit the WIREs website. PMID:26799266

  6. Depletion of endogenous spinal 5-HT attenuates the behavioural hypersensitivity to mechanical and cooling stimuli induced by spinal nerve ligation.

    PubMed

    Rahman, Wahida; Suzuki, Rie; Webber, Mark; Hunt, Stephen P; Dickenson, Anthony H

    2006-08-01

    There is compelling evidence for a strong facilitatory drive modulating spinal nociceptive transmission. This is in part via serotonergic pathways and originates from the rostroventral medulla. We previously demonstrated that neuropathic pain is associated with an enhanced descending facilitatory drive onto the mechanical evoked responses of dorsal horn neurones, mediated by 5-HT acting at spinal 5-HT3 receptors. Furthermore, depletion of spinal 5-HT has been shown to reduce the at-level mechanical allodynia that follows spinal cord injury. To further clarify the role and direction of effect of endogenous 5-HT, we investigated the effects of depleting spinal 5-HT, via intrathecal injection of 5,7di-hydroxytryptamine (5,7DHT), on pain behaviours after spinal nerve ligation (SNL). Depletion of spinal 5-HT in normal animals leads to reductions in mechanical and thermal evoked responses of deep dorsal horn neurones implying that spinal 5-HT has a predominant facilitatory function. After nerve injury, the frequency of paw withdrawals to low intensity mechanical and cooling stimulation of the ipsilateral hindpaw in the SNL-5,7DHT group was significantly attenuated when compared with the SNL-saline group from day seven post-nerve injury. Sham-5,7DHT and sham-saline animals showed very little response sensitivity on either hindpaw. This 5-HT-mediated difference in behaviour was independent of both the up-regulation of the NK1 receptor and spinal microglial activation produced by nerve injury. These data suggest that supraspinal serotonergic influences under these conditions are facilitatory and are implicated in the maintenance of spinal cord neuronal events leading to the behavioural hypersensitivity manifested after peripheral nerve damage. PMID:16644129

  7. Spinal and epidural anesthesia

    MedlinePlus

    Intraspinal anesthesia; Subarachnoid anesthesia; Epidural; Peridural anesthesia ... Spinal and epidural anesthesia have fewer side effects and risks than general anesthesia (asleep and pain-free). Patients usually recover their senses ...

  8. Spinal Muscular Atrophy

    MedlinePlus

    ... diseases that progressively destroy lower motor neurons—nerve cells in the brain stem and spinal cord that control essential voluntary muscle activity such as speaking, walking, breathing, and swallowing. ...

  9. Spinal Cord Injury 101

    MedlinePlus

    ... is "Braingate" research? What is the status of stem-cell research? How would stem-cell therapies work in the treatment of spinal cord injuries? What does stem-cell research on animals tell us? When can we expect ...

  10. Spinal Cord Injury

    MedlinePlus

    ... Dramatically Improves Function After Spinal Cord Injury in Rats May 2004 press release on an experimental treatment ... NINDS). Signaling Molecule Improves Nerve Cell Regeneration in Rats August 2002 news summary on a signaling molecule ...

  11. What Is Spinal Stenosis?

    MedlinePlus

    ... To order the Sports Injuries Handout on Health full-text version, please contact NIAMS using the contact information ... publication. To order the Spinal Stenosis Q&A full-text version, please contact NIAMS using the contact information ...

  12. Spinal cord abscess

    MedlinePlus

    ... irritation (inflammation) and the collection of infected material (pus) in or around the spinal cord. ... occurs as a complication of an epidural abscess . Pus forms as a collection of: Destroyed tissue cells ...

  13. [Meningitis after spinal anesthesia].

    PubMed

    Mouchrif, Issam; Berdaii, Adnane; Labib, Ismail; Harrandou, Moustapha

    2016-01-01

    Meningitis is a rare but serious complication of epidural and spinal anesthesia. Bacterial meningitis is mainly caused by Gram-positive cocci, implying an exogenous contamination which suggests a lack of asepsis. The evolution is usually favorable after treatment, but at the expense of increased health care costs and, sometimes, of significant neurological sequelae. We report a case of bacterial meningitis after spinal anesthesia for caesarean section. PMID:27642477

  14. Proprioceptive pathways of the spinal cord.

    PubMed Central

    Schneider, R J; Kulics, A T; Ducker, T B

    1977-01-01

    In the Macaque, surgical lesions were made in the dorsal funiculus, in the dorsolateral funiculus, and through half of the spinal cord. The somatosensory and motor capacity of the animal were examined neurologically and electrophysiologically. The exact lesion was then confirmed pathologically in detail. The results of these experiments indicate that limb position information from the distal limb and proximal limb are relayed to the brain in two different fashions. Distal limb position information, especially the cortical representation of the limbs' volar surface as it moves in space, is drastically impaired by dorsal funiculus or posterior white column lesions. Proximal limb position may or may not be impaired by similar lesions, for this information while initially in the dorsal or posterior white columns is sorted out (as it ascends in the spinal cord) to the dorsolateral funiculus or white columns. For example, in the lower thoracic spinal cord, both distal and proximal hind limb sensation are impaired by posterior white column damage; in the cervical cord, only distal sensation is impaired by the same lesion, and proximal information is spared. We refer to this neuroanatomic rearranging as "fibre sorting", and we believe that it is clinically significant in spinal cord disease. Images PMID:408463

  15. Complications after spinal anesthesia in adult tethered cord syndrome.

    PubMed

    Liu, Jing-Jie; Guan, Zheng; Gao, Zhen; Xiang, Li; Zhao, Feng; Huang, Sheng-Li

    2016-07-01

    Since little has been reported about complications of spinal anesthesia in adult tethered cord syndrome (TCS), we sought to delineate the characteristics of the condition.A total of 4 cases of adult TCS after spinal anesthesia were reviewed. The medical charts of the patients were obtained. Anesthesia, which was combined spinal and epidural anesthesia or spinal anesthesia was performed, and follow-up were carried out in all patients.The most common neurological symptom of adult TCS before surgery was occasional severe pain in back, perineal region, or legs. Frequent micturition, diminished knee and ankle reflexes, and difficulty in bending were exhibited in partial patients. Paraesthesia of perineal region or/and lower extremities existed 2 to 3 days after spinal anesthesia in all the cases. Weakness of lower extremities existed in 1 case. Lumbar magnetic resonance imaging showed the low location of conus medullaris. At follow-up, 3 cases recovered completely within 3 weeks, and 1 case underwent permanent disability.These cases suggest anesthesiologists and surgeons alert to the association of adult TCS and spinal anesthesia. Spinal anesthesia should be prohibited in patients with adult TCS to prevent neurological damages. PMID:27442670

  16. The Spinal Ependymal Layer in Health and Disease.

    PubMed

    Moore, S A

    2016-07-01

    Ependymal cells are epithelial support cells that line the central canal and ventricular cavities of the central nervous system, providing the interface between the cerebrospinal fluid and the parenchyma of the brain and spinal cord. The spinal ependymal layer (SEL) is composed of 3 main cell types: tanycytes, ependymocytes, and cerebrospinal fluid-contacting neurons. A fourth cell type, termed the supraependymal cell, is also occasionally described. Cells of the SEL show restricted proliferative capacity in health but display neural stem cell properties both in vitro and in vivo in various disease states. A growing body of literature is devoted to the regenerative roles of the SEL, particularly in the context of spinal cord injury, where mechanical damage to the spinal cord leads to a significant increase in SEL proliferation. SEL-derived cell progeny migrate to sites of injury within the injured spinal cord parenchyma and contribute primarily to glial scar formation. In additional to their role as endogenous neural stem cells, cells of the SEL may be an important source of cytokines and other cell signaling molecules, such as tumor necrosis factor, heat shock proteins, and various growth factors. The SEL has become of recent interest to neuroscience researchers because of its potential to participate in and respond to diseases affecting the spinal cord (eg, traumatic spinal cord injury) and neurodegenerative disease. The intimate association of the SEL with the cerebrospinal fluid makes intrathecal therapies a viable option, and recent studies highlight the potential promise of treatments that augment SEL responses to disease.

  17. Intermittent hypoxia induces functional recovery following cervical spinal injury

    PubMed Central

    Vinit, Stéphane; Lovett-Barr, Mary Rachael; Mitchell, Gordon S.

    2009-01-01

    Respiratory-related complications are the leading cause of death in spinal cord injury (SCI) patients. Few effective SCI treatments are available after therapeutic interventions are performed in the period shortly after injury (e.g. spine stabilization and prevention of further spinal damage). In this review we explore the capacity to harness endogenous spinal plasticity induced by intermittent hypoxia to optimize function of surviving (spared) neural pathways associated with breathing. Two primary questions are addressed: 1) does intermittent hypoxia induce plasticity in spinal synaptic pathways to respiratory motor neurons following experimental SCI? and 2) can this plasticity improve respiratory function? In normal rats, intermittent hypoxia induces serotonin-dependent plasticity in spinal pathways to respiratory motor neurons. Early experiments suggest that intermittent hypoxia also enhances respiratory motor output in experimental models of cervical SCI, (cervical hemisection) and that the capacity to induce functional recovery is greater with longer durations post-injury. Available evidence suggests that intermittent hypoxia-induced spinal plasticity has considerable therapeutic potential to treat respiratory insufficiency following chronic cervical spinal injury. PMID:19651247

  18. Modeling spinal cord biomechanics

    NASA Astrophysics Data System (ADS)

    Luna, Carlos; Shah, Sameer; Cohen, Avis; Aranda-Espinoza, Helim

    2012-02-01

    Regeneration after spinal cord injury is a serious health issue and there is no treatment for ailing patients. To understand regeneration of the spinal cord we used a system where regeneration occurs naturally, such as the lamprey. In this work, we analyzed the stress response of the spinal cord to tensile loading and obtained the mechanical properties of the cord both in vitro and in vivo. Physiological measurements showed that the spinal cord is pre-stressed to a strain of 10%, and during sinusoidal swimming, there is a local strain of 5% concentrated evenly at the mid-body and caudal sections. We found that the mechanical properties are homogeneous along the body and independent of the meninges. The mechanical behavior of the spinal cord can be characterized by a non-linear viscoelastic model, described by a modulus of 20 KPa for strains up to 15% and a modulus of 0.5 MPa for strains above 15%, in agreement with experimental data. However, this model does not offer a full understanding of the behavior of the spinal cord fibers. Using polymer physics we developed a model that relates the stress response as a function of the number of fibers.

  19. Spinal angiolipoma: case report and review of the literature.

    PubMed

    Samdani, A F; Garonzik, I M; Jallo, G; Eberhart, C G; Zahos, P

    2004-03-01

    Spinal angiolipomas are rare lesions usually found in the epidural space of the thoracic spine. This report presents a case of and reviews the literature on this rare entity. The etiology, clinical presentation, imaging, and treatment are discussed. In 92 reported cases of spinal angiolipoma 56 occurred in women (61%), and 36 in men (39%). Mean age of occurrence is 42.9 years (range 10 days-85 years) with most patients presenting with slowly progressive symptoms of spinal cord compression. Most cases occur in the extradural compartment, and are of the non-invasive subtype. This rare clinical entity must be considered in the differential diagnosis of spinal epidural lesions. In most cases complete removal is possible, however, prognosis is good even for infiltrating lesions. Thus, one must not risk neurological damage to attain complete resection.

  20. Role of endogenous neural stem cells in spinal cord injury and repair.

    PubMed

    Stenudd, Moa; Sabelström, Hanna; Frisén, Jonas

    2015-02-01

    Spinal cord injury is followed by glial scar formation, which has positive and negative effects on recovery from the lesion. More than half of the astrocytes in the glial scar are generated by ependymal cells, the neural stem cells in the spinal cord. We recently demonstrated that the neural stem cell-derived scar component has several beneficial functions, including restricting tissue damage and neural loss after spinal cord injury. This finding identifies endogenous neural stem cells as a potential therapeutic target for treatment of spinal cord injury.

  1. Spinal cord effects of antipyretic analgesics.

    PubMed

    Brune, K

    1994-01-01

    Tissue damage results in the release of inflammatory mediators, including prostaglandins, which sensitive fine nerve endings in the periphery to mechanical and thermal changes. Sensitisation of these nerve endings, or nociceptors, contributes to the phenomenon of hyperalgesia, which routinely accompanies tissue damage. It has been shown that the acidic antipyretic analgesics reduce or down-regulate the enhanced nociceptor sensitivity in damaged tissue, an effect probably attributable to inhibition of prostaglandin synthesis. Recent studies suggest that these drugs may have an additional mechanism of action in the spinal cord or higher centres. When enantiomers of flurbiprofen were used in the rat, it was shown that S- and R-flurbiprofen exert differential antinociceptive effects. The R-enantiomer, which is practically devoid of peripheral cyclo-oxygenase inhibitory activity in vitro, showed comparable analgesic potency to the S-enantiomer, which does inhibit cyclo-oxygenase activity, in experimental models of nociception. It is possible that the antinociceptive action of the R-enantiomer is related to a reduction in prostaglandin synthesis in the CNS rather than at the site of tissue damage, although other mechanisms may also contribute to its antinociceptive action. In contrast to earlier indications, it would appear that a significant part of the antinociceptive action of the antipyretic analgesics is exerted in the spinal cord. The observed accumulation of acidic antipyretic analgesics in inflamed tissue may account for the superior anti-inflammatory activity of these latter compounds.

  2. Mammalian Wax Biosynthesis

    PubMed Central

    Cheng, Jeffrey B.; Russell, David W.

    2009-01-01

    Wax monoesters are synthesized by the esterification of fatty alcohols and fatty acids. A mammalian enzyme that catalyzes this reaction has not been isolated. We used expression cloning to identify cDNAs encoding a wax synthase in the mouse preputial gland. The wax synthase gene is located on the X chromosome and encodes a member of the acyltransferase family of enzymes that synthesize neutral lipids. Expression of wax synthase in cultured cells led to the formation of wax monoesters from straight chain saturated, unsaturated, and polyunsaturated fatty alcohols and acids. Polyisoprenols also were incorporated into wax monoesters by the enzyme. The wax synthase had little or no ability to synthesize cholesteryl esters, diacylglycerols, or triacylglycerols, whereas other acyltransferases, including the acyl-CoA:monoacylglycerol acyltransferase 1 and 2 enzymes and the acyl-CoA:diacylglycerol acyltransferase 1 and 2 enzymes, exhibited modest wax monoester synthesis activities. Confocal light microscopy indicated that the wax synthase was localized in membranes of the endoplasmic reticulum. Wax synthase mRNA was abundant in tissues rich in sebaceous glands such as the preputial gland and eyelid and was present at lower levels in other tissues. Coexpression of cDNAs specifying fatty acyl-CoA reductase 1 and wax synthase led to the synthesis of wax monoesters. The data suggest that wax monoester synthesis in mammals involves a two step biosynthetic pathway catalyzed by fatty acyl-CoA reductase and wax synthase enzymes. PMID:15220349

  3. Mammalian Wax Biosynthesis

    PubMed Central

    Cheng, Jeffrey B.; Russell, David W.

    2009-01-01

    The conversion of fatty acids to fatty alcohols is required for the synthesis of wax monoesters and ether lipids. The mammalian enzymes that synthesize fatty alcohols have not been identified. Here, an in silico approach was used to discern two putative reductase enzymes designated FAR1 and FAR2. Expression studies in intact cells showed that FAR1 and FAR2 cDNAs encoded isozymes that reduced fatty acids to fatty alcohols. Fatty acyl-CoA esters were the substrate of FAR1, and the enzyme required NADPH as a cofactor. FAR1 preferred saturated and unsaturated fatty acids of 16 or 18 carbons as substrates, whereas FAR2 preferred saturated fatty acids of 16 or 18 carbons. Confocal light microscopy indicated that FAR1 and FAR2 were localized in the peroxisome. The FAR1 mRNA was detected in many mouse tissues with the highest level found in the preputial gland, a modified sebaceous gland. The FAR2 mRNA was more restricted in distribution and most abundant in the eyelid, which contains wax-laden meibomian glands. Both FAR mRNAs were present in the brain, a tissue rich in ether lipids. The data suggest that fatty alcohol synthesis in mammals is accomplished by two fatty acyl-CoA reductase isozymes that are expressed at high levels in tissues known to synthesize wax monoesters and ether lipids. PMID:15220348

  4. Mammalian Gut Immunity

    PubMed Central

    Chassaing, Benoit; Kumar, Manish; Baker, Mark T.; Singh, Vishal; Vijay-Kumar, Matam

    2016-01-01

    The mammalian intestinal tract is the largest immune organ in the body and comprises cells from non-hemopoietic (epithelia, Paneth cells, goblet cells) and hemopoietic (macrophages, dendritic cells, T-cells) origin, and is also a dwelling for trillions of microbes collectively known as the microbiota. The homeostasis of this large microbial biomass is prerequisite to maintain host health by maximizing beneficial symbiotic relationships and minimizing the risks of living in such close proximity. Both microbiota and host immune system communicate with each other to mutually maintain homeostasis in what could be called a “love–hate relationship.” Further, the host innate and adaptive immune arms of the immune system cooperate and compensate each other to maintain the equilibrium of a highly complex gut ecosystem in a stable and stringent fashion. Any imbalance due to innate or adaptive immune deficiency or aberrant immune response may lead to dysbiosis and low-grade to robust gut inflammation, finally resulting in metabolic diseases. PMID:25163502

  5. Effective repair of traumatically injured spinal cord by nanoscale block copolymer micelles

    NASA Astrophysics Data System (ADS)

    Shi, Yunzhou; Kim, Sungwon; Huff, Terry B.; Borgens, Richard B.; Park, Kinam; Shi, Riyi; Cheng, Ji-Xin

    2010-01-01

    Spinal cord injury results in immediate disruption of neuronal membranes, followed by extensive secondary neurodegenerative processes. A key approach for repairing injured spinal cord is to seal the damaged membranes at an early stage. Here, we show that axonal membranes injured by compression can be effectively repaired using self-assembled monomethoxy poly(ethylene glycol)-poly(D,L-lactic acid) di-block copolymer micelles. Injured spinal tissue incubated with micelles (60 nm diameter) showed rapid restoration of compound action potential and reduced calcium influx into axons for micelle concentrations much lower than the concentrations of polyethylene glycol, a known sealing agent for early-stage spinal cord injury. Intravenously injected micelles effectively recovered locomotor function and reduced the volume and inflammatory response of the lesion in injured rats, without any adverse effects. Our results show that copolymer micelles can interrupt the spread of primary spinal cord injury damage with minimal toxicity.

  6. Effective repair of traumatically injured spinal cord by nanoscale block copolymer micelles.

    PubMed

    Shi, Yunzhou; Kim, Sungwon; Huff, Terry B; Borgens, Richard B; Park, Kinam; Shi, Riyi; Cheng, Ji-Xin

    2010-01-01

    Spinal cord injury results in immediate disruption of neuronal membranes, followed by extensive secondary neurodegenerative processes. A key approach for repairing injured spinal cord is to seal the damaged membranes at an early stage. Here, we show that axonal membranes injured by compression can be effectively repaired using self-assembled monomethoxy poly(ethylene glycol)-poly(d,l-lactic acid) di-block copolymer micelles. Injured spinal tissue incubated with micelles (60 nm diameter) showed rapid restoration of compound action potential and reduced calcium influx into axons for micelle concentrations much lower than the concentrations of polyethylene glycol, a known sealing agent for early-stage spinal cord injury. Intravenously injected micelles effectively recovered locomotor function and reduced the volume and inflammatory response of the lesion in injured rats, without any adverse effects. Our results show that copolymer micelles can interrupt the spread of primary spinal cord injury damage with minimal toxicity.

  7. Stem Cells in Mammalian Gonads.

    PubMed

    Wu, Ji; Ding, Xinbao; Wang, Jian

    2016-01-01

    Stem cells have great value in clinical application because of their ability to self-renew and their potential to differentiate into many different cell types. Mammalian gonads, including testes for males and ovaries for females, are composed of germline and somatic cells. In male mammals, spermatogonial stem cells maintain spermatogenesis which occurs continuously in adult testis. Likewise, a growing body of evidence demonstrated that female germline stem cells could be found in mammalian ovaries. Meanwhile, prior studies have shown that somatic stem cells exist in both testes and ovaries. In this chapter, we focus on mammalian gonad stem cells and discuss their characteristics as well as differentiation potentials.

  8. Complete rat spinal cord transection as a faithful model of spinal cord injury for translational cell transplantation.

    PubMed

    Lukovic, Dunja; Moreno-Manzano, Victoria; Lopez-Mocholi, Eric; Rodriguez-Jiménez, Francisco Javier; Jendelova, Pavla; Sykova, Eva; Oria, Marc; Stojkovic, Miodrag; Erceg, Slaven

    2015-01-01

    Spinal cord injury (SCI) results in neural loss and consequently motor and sensory impairment below the injury. There are currently no effective therapies for the treatment of traumatic SCI in humans. Various animal models have been developed to mimic human SCI. Widely used animal models of SCI are complete or partial transection or experimental contusion and compression, with both bearing controversy as to which one more appropriately reproduces the human SCI functional consequences. Here we present in details the widely used procedure of complete spinal cord transection as a faithful animal model to investigate neural and functional repair of the damaged tissue by exogenous human transplanted cells. This injury model offers the advantage of complete damage to a spinal cord at a defined place and time, is relatively simple to standardize and is highly reproducible. PMID:25860664

  9. Complete rat spinal cord transection as a faithful model of spinal cord injury for translational cell transplantation.

    PubMed

    Lukovic, Dunja; Moreno-Manzano, Victoria; Lopez-Mocholi, Eric; Rodriguez-Jiménez, Francisco Javier; Jendelova, Pavla; Sykova, Eva; Oria, Marc; Stojkovic, Miodrag; Erceg, Slaven

    2015-04-10

    Spinal cord injury (SCI) results in neural loss and consequently motor and sensory impairment below the injury. There are currently no effective therapies for the treatment of traumatic SCI in humans. Various animal models have been developed to mimic human SCI. Widely used animal models of SCI are complete or partial transection or experimental contusion and compression, with both bearing controversy as to which one more appropriately reproduces the human SCI functional consequences. Here we present in details the widely used procedure of complete spinal cord transection as a faithful animal model to investigate neural and functional repair of the damaged tissue by exogenous human transplanted cells. This injury model offers the advantage of complete damage to a spinal cord at a defined place and time, is relatively simple to standardize and is highly reproducible.

  10. Pediatric spinal trauma.

    PubMed

    Huisman, Thierry A G M; Wagner, Matthias W; Bosemani, Thangamadhan; Tekes, Aylin; Poretti, Andrea

    2015-01-01

    Pediatric spinal trauma is unique. The developing pediatric spinal column and spinal cord deal with direct impact and indirect acceleration/deceleration or shear forces very different compared to adult patients. In addition children are exposed to different kind of traumas. Moreover, each age group has its unique patterns of injury. Familiarity with the normal developing spinal anatomy and kind of traumas is essential to correctly diagnose injury. Various imaging modalities can be used. Ultrasound is limited to the neonatal time period; plain radiography and computer tomography are typically used in the acute work-up and give highly detailed information about the osseous lesions. Magnetic resonance imaging is more sensitive for disco-ligamentous and spinal cord injuries. Depending on the clinical presentation and timing of trauma the various imaging modalities will be employed. In the current review article, a summary of the epidemiology and distribution of posttraumatic lesions is discussed in the context of the normal anatomical variations due to progressing development of the child. PMID:25512255

  11. Speed and spinal injuries.

    PubMed

    Healy, D G; Connolly, P; Stephens, M M; O'Byrne, J M; McManus, F; McCormack, D

    2004-09-01

    Road traffic accidents (RTA) are a significant cause of spinal trauma. On the 31st of October 2002 a new penalty system for speed related driving offences was introduced in Ireland. Our intention was to assess the effects of the introduction of this system on the activity of the National Spinal Injuries Centre (NSIC) with a retrospective review of all admissions from November 1998 until October 2003. The number of new acute admissions to the spinal injury unit during the study period was 831. In the first 6 months of the new system the number of RTA related admissions fell significantly to 17 compared to an average of 33 in the preceding 4 years. However, this effect was not maintained in the second 6 months. The fall in spinal injuries following RTA in the first 6 months of the new system parallels the pattern of road death reduction in this period. This suggests that driving behaviour can be modified with direct benefits in reducing spinal injuries. However, this effect has not persisted in the second 6 months of the new system suggesting that to maintain this change the perception and familiarity of a penalty are important factors in its impact.

  12. Learning Spinal Manipulation

    PubMed Central

    Harvey, Marie-Pierre; Wynd, Shari; Richardson, Lance; Dugas, Claude; Descarreaux, Martin

    2011-01-01

    Purpose: The goal of the present study was to quantify the high-velocity, low-amplitude spinal manipulation biomechanical parameters in two cohorts of students from different teaching institutions. The first cohort of students was taught chiropractic techniques in a patient–doctor positioning practice setting, while the second cohort of students was taught in a “complete practice” manipulation setting, thus performing spinal manipulation skills on fellow student colleagues. It was hypothesized that the students exposed to complete practice would perform the standardized spinal manipulation with better biomechanical parameters. Methods: Participants (n = 88) were students enrolled in two distinct chiropractic programs. Thoracic spine manipulation skills were assessed using an instrumented manikin, which allowed the measurement of applied force. Dependent variables included peak force, time to peak force, rate of force production, peak force variability, and global coordination. Results: The results revealed that students exposed to complete practice demonstrated lower time to peak force values, higher peak force, and a steeper rate of force production compared with students in the patient–doctor positioning scenario. A significant group by gender interaction was also noted for the time to peak force and rate of force production variables. Conclusion: The results of the present study confirm the importance of chiropractic technique curriculum and perhaps gender in spinal manipulation skill learning. It also stresses the importance of integrating spinal manipulation skills practice early in training to maximize the number and the quality of significant learner–instructor interactions. PMID:22069337

  13. Spinal Cord Anatomy and Clinical Syndromes.

    PubMed

    Diaz, Eric; Morales, Humberto

    2016-10-01

    We review the anatomy of the spinal cord, providing correlation with key functional and clinically relevant neural pathways, as well as magnetic resonance imaging. Peripherally, the main descending (corticospinal tract) and ascending (gracilis or cuneatus fasciculi and spinothalamic tracts) pathways compose the white matter. Centrally, the gray matter can be divided into multiple laminae. Laminae 1-5 carry sensitive neuron information in the posterior horn, and lamina 9 carries most lower motor neuron information in the anterior horn. Damage to the unilateral corticospinal tract (upper motor neuron information) or gracillis-cuneatus fasciculi (touch and vibration) correlates with ipsilateral clinical findings, whereas damage to unilateral spinothalamic tract (pain-temperature) correlates with contralateral clinical findings. Damage to commissural fibers correlates with a suspended bilateral "girdle" sensory level. Autonomic dysfunction is expected when there is bilateral cord involvement. PMID:27616310

  14. Neuroprotective role of neurophysiological monitoring during endovascular procedures in the spinal cord.

    PubMed

    Sala, F; Niimi, Y; Berenstein, A; Deletis, V

    2001-06-01

    The endovascular treatment of spinal vascular malformations places the spinal cord at risk for ischemia. When these procedures are performed using general anesthesia, the neurophysiological monitoring methods currently available provide the only means by which to assess the functional integrity of sensory and motor pathways. Neurophysiological monitoring allows a warning for the neuroradiologist of impending irreversible neurological damage so that action may be taken for the prompt restoration of adequate spinal cord perfusion. Muscle motor evoked potentials (mMEPs) better reflect spinal cord perfusion in the anterior spinal artery territory than do somatosensory evoked potentials (SEPs), although their use during spinal endovascular procedures remains anecdotal in the literature. In the study reported here we assessed: (1) the feasibility of intraoperative neurophysiological monitoring, (2) the role of provocative tests with Amytal and Xylocaine, and (3) the specific but complementary role played by SEPs and mMEPs, during endovascular embolization of spinal vascular malformations and tumors. The results suggest that: (1) neurophysiological monitoring is feasible during most endovascular procedures in the spine and spinal cord under general anesthesia, (2) provocative tests enhance the safety of the procedure, (3) mMEPs are more feasible than SEPs and more sensitive than SEPs to provocative tests. We strongly suggest the use of multimodal neurophysiological monitoring and provocative tests during the endovascular treatment of spinal and spinal cord vascular lesions.

  15. Effect of lycopene on the blood-spinal cord barrier after spinal cord injury in mice.

    PubMed

    Zhang, Qian; Wang, Jianbo; Gu, Zhengsong; Zhang, Qing; Zheng, Hong

    2016-09-01

    The current study aimed to investigate the effect of lycopene on the blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) in a mouse model. Lycopene inhibited lipid peroxidation and oxidative DNA damage as a highly efficient antioxidant and free radical scavenger. Lycopene (4 mg/kg/d) was administrated immediately following SCI. The permeability of the BSCB and water content in the spinal cord tissue were evaluated. Additionally, levels of expression of tight junction proteins and heme oxygenase-1 (HO-1) were determined with Western blotting. An enzyme-linked immunosorbent assay analysis of spinal cord tissue homogenates was performed 48 h after SCI to evaluate the expression of inflammation-related cytokines. In addition, recovery of motor function was assessed 1 d, 2 d, 5 d, 10 d, and 15 d after SCI using the Basso Mouse Scale to score locomotion. Compared to the group with an untreated SCI, mice with an SCI treated with lycopene had significantly reduced spinal cord tissue water content and BSCB permeability. Furthermore, motor function of mice with an SCI was also greatly improved by lycopene administration. The expression of the proinflammatory factors TNF-α and NF-kB increased markedly 48 h after SCI, and their upregulation was significantly attenuated by lycopene treatment. The expression of molecules that protect tight junctions, zonula occluden-1 and claudin-5, was upregulated by lycopene treatment after SCI. Taken together, these results clearly indicate that lycopene attenuated SCI by promoting repair of the damaged BSCB, so lycopene is a novel and promising treatment for SCI in humans. PMID:27357536

  16. Mammalian DNA Repair. Final Report

    SciTech Connect

    2003-01-24

    The Gordon Research Conference (GRC) on Mammalian DNA Repair was held at Harbortown Resort, Ventura Beach, CA. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  17. Polysome analysis of mammalian cells.

    PubMed

    He, Shan L; Green, Rachel

    2013-01-01

    To assess the global translational level of mammalian cells (see similar protocols for bacteria and yeast on Analysis of polysomes from bacteria, Polysome Profile Analysis - Yeast and Polysome analysis for determining mRNA and ribosome association in Saccharomyces cerevisiae).

  18. Maturation of the mammalian secretome

    PubMed Central

    Simpson, Jeremy C; Mateos, Alvaro; Pepperkok, Rainer

    2007-01-01

    A recent use of quantitative proteomics to determine the constituents of the endoplasmic reticulum and Golgi complex is discussed in the light of other available methodologies for cataloging the proteins associated with the mammalian secretory pathway. PMID:17472737

  19. [Lumbar spinal angiolipoma].

    PubMed

    Isla, Alberto; Ortega Martinez, Rodrigo; Pérez López, Carlos; Gómez de la Riva, Alvaro; Mansilla, Beatriz

    2016-01-01

    Spinal angiolipomas are fairly infrequent benign tumours that are usually located in the epidural space of the thoracic column and represent 0.14% to 1.3% of all spinal tumours. Lumbar angiolipomas are extremely rare, representing only 9.6% of all spinal extradural angiolipomas. We report the case of a woman who complained of a lumbar pain of several months duration with no neurological focality and that had intensified in the last three days without her having had any injury or made a physical effort. The MR revealed an extradural mass L1-L2, on the posterior face of the medulla, decreasing the anteroposterior diameter of the canal. The patient symptoms improved after surgery. Total extirpation of the lesion is possible in most cases, and the prognosis is excellent even if the lesion is infiltrative. For this reason, excessively aggressive surgery is not necessary to obtain complete resection. PMID:27263067

  20. Spinal injuries in children.

    PubMed

    Babcock, J L

    1975-05-01

    Spinal injuries with neurologic sequelae are a rare but catastrophic injury. Many of these injuries might be preventable through proper parent and child education, particularly in water sports and vehicles accidents. A significant number of neurologic injuries are incomplete at the time of injury and proper rescue and initial care may make the difference between life as a quadriplegic and life as a normal individual. Because of the complexity of the management of the child with spinal injuries and their relative rarity, the definitive care is best undertaken at hospitals which specialize in the care of spinal injuries. Progressive deformity of the spine, a problem unique to childhood and adolescent paralysis, is often preventable with prolonged immobilization and protection of the spine. Progressive deformities which interfere with function or result in neurologic deterioration require an aggressive surgical approach. PMID:1124228

  1. Spinal Subdural Haematoma

    PubMed Central

    Manish K, Kothari; Chandrakant, Shah Kunal; Abhay M, Nene

    2015-01-01

    Introduction: Spinal Subdural hematoma is a rare cause of radiculopathy and spinal cord compression syndromes. It’s early diagnosis is essential. Chronological appearance of these bleeds vary on MRI. Case Report: A 56 year old man presented with progressive left lower limb radiculopathy and paraesthesias with claudication of three days duration. MRI revealed a subdural space occupying lesion compressing the cauda equina at L5-S1 level producing a ‘Y’ shaped dural sac (Y sign), which was hyperintense on T1W imaging and hypointense to cord on T2W image. The STIR sequence showed hyperintensity to cord. There was no history of bleeding diathesis. The patient underwent decompressive durotomy and biopsy which confirmed the diagnosis. Conclusion: Spinal subdural hematoma may present with rapidly progressive neurological symptoms. MRI is the investigation of choice. The knowledge of MRI appearance with respect to the chronological stage of the bleed is essential to avoid diagnostic and hence surgical dilemma PMID:27299051

  2. [Spinal cord infarction].

    PubMed

    Naumann, N; Shariat, K; Ulmer, S; Stippich, C; Ahlhelm, F J

    2012-05-01

    Infarction of the spinal cord can cause a variety of symptoms and neurological deficits because of the complex vascular supply of the myelon. The most common leading symptom is distal paresis ranging from paraparesis to tetraplegia caused by arterial ischemia or infarction of the myelon. Venous infarction, however, cannot always be distinguished from arterial infarction based on the symptoms alone.Modern imaging techniques, such as computed tomography angiography (CTA) and magnetic resonance angiography (MRA) assist in preoperative planning of aortic operations to reliably identify not only the most important vascular structure supplying the spinal cord, the artery of Adamkiewicz, but also other pathologies such as tumors or infectious disorders. In contrast to CT, MRI can reliably depict infarction of the spinal cord.

  3. [Lumbar spinal angiolipoma].

    PubMed

    Isla, Alberto; Ortega Martinez, Rodrigo; Pérez López, Carlos; Gómez de la Riva, Alvaro; Mansilla, Beatriz

    2016-01-01

    Spinal angiolipomas are fairly infrequent benign tumours that are usually located in the epidural space of the thoracic column and represent 0.14% to 1.3% of all spinal tumours. Lumbar angiolipomas are extremely rare, representing only 9.6% of all spinal extradural angiolipomas. We report the case of a woman who complained of a lumbar pain of several months duration with no neurological focality and that had intensified in the last three days without her having had any injury or made a physical effort. The MR revealed an extradural mass L1-L2, on the posterior face of the medulla, decreasing the anteroposterior diameter of the canal. The patient symptoms improved after surgery. Total extirpation of the lesion is possible in most cases, and the prognosis is excellent even if the lesion is infiltrative. For this reason, excessively aggressive surgery is not necessary to obtain complete resection.

  4. Skiing and spinal trauma.

    PubMed

    Frymoyer, J W; Pope, M H; Kristiansen, T

    1982-07-01

    Spinal injury in skiers can either be acute or chronic. Acute spinal injury accounts for 3 to 3.6 per cent of all injuries occurring in Alpine skiing. Fewer acute injuries occur in cross-country skiing, and those that do usually are the result of a sudden, compressive force from a seated fall. The prevalence of chronic spinal trauma in skiing is unknown. Both cross-country and Alpine skiers appear to have greater complaints of mild to moderate low back pain as compared with their nonskiing counterparts. These differences may be the result of a complex interaction between recreational and occupational activities. Theoretical analyses suggest a risk for low-grade torsional injury to the Alpine skier's spine, whereas in cross-country skiing significant shear forces are applied to lumbar discs during the kick but not the double-poling phase.

  5. Changes in spinal alignment.

    PubMed

    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.

  6. Programmed cell senescence during mammalian embryonic development.

    PubMed

    Muñoz-Espín, Daniel; Cañamero, Marta; Maraver, Antonio; Gómez-López, Gonzalo; Contreras, Julio; Murillo-Cuesta, Silvia; Rodríguez-Baeza, Alfonso; Varela-Nieto, Isabel; Ruberte, Jesús; Collado, Manuel; Serrano, Manuel

    2013-11-21

    Cellular senescence disables proliferation in damaged cells, and it is relevant for cancer and aging. Here, we show that senescence occurs during mammalian embryonic development at multiple locations, including the mesonephros and the endolymphatic sac of the inner ear, which we have analyzed in detail. Mechanistically, senescence in both structures is strictly dependent on p21, but independent of DNA damage, p53, or other cell-cycle inhibitors, and it is regulated by the TGF-β/SMAD and PI3K/FOXO pathways. Developmentally programmed senescence is followed by macrophage infiltration, clearance of senescent cells, and tissue remodeling. Loss of senescence due to the absence of p21 is partially compensated by apoptosis but still results in detectable developmental abnormalities. Importantly, the mesonephros and endolymphatic sac of human embryos also show evidence of senescence. We conclude that the role of developmentally programmed senescence is to promote tissue remodeling and propose that this is the evolutionary origin of damage-induced senescence.

  7. Ischemic spinal cord infarction in children without vertebral fracture

    PubMed Central

    Nance, Jessica R.; Golomb, Meredith R.

    2007-01-01

    Spinal cord infarction in children is a rare condition which is becoming more widely recognized. There are few reports in the pediatric literature characterizing etiology, diagnosis, treament and prognosis. The risk factors for pediatric ischemic spinal cord infarction include obstruction of blood flow associated with cardiovascular compromise or malformation, iatrogenic or traumatic vascular inujury, cerebellar herniation, thrombotic or embolic disease, infection, and vasculitis. In many children the cause of spinal cord ischemia in the absence of vertebral fracture is unknown. Imaging diagnosis of spinal cord ischemia is often difficult due to the small transverse area of the cord, cerebrospinal fluid artifact and inadequate resolution of MRI. Physical therapy is the most important treatment option. The prognosis is dependent on the level of spinal cord damage, early identification and reversal of ischemia, and follow-up with intensive physical therapy and medical support. In addition to summarizing the literature regarding spinal cord infarction in children without vertebral fracture, this review article adds two cases to the literature which highlight the difficulties and controversies in the management of this condition. PMID:17437902

  8. Optimizing the management of patients with spinal myeloma disease.

    PubMed

    Molloy, Sean; Lai, Maggie; Pratt, Guy; Ramasamy, Karthik; Wilson, David; Quraishi, Nasir; Auger, Martin; Cumming, David; Punekar, Maqsood; Quinn, Michael; Ademonkun, Debo; Willis, Fenella; Tighe, Jane; Cook, Gordon; Stirling, Alistair; Bishop, Timothy; Williams, Cathy; Boszczyk, Bronek; Reynolds, Jeremy; Grainger, Mel; Craig, Niall; Hamilton, Alastair; Chalmers, Isobel; Ahmedzai, Sam; Selvadurai, Susanne; Low, Eric; Kyriakou, Charalampia

    2015-11-01

    Myeloma is one of the most common malignancies that results in osteolytic lesions of the spine. Complications, including pathological fractures of the vertebrae and spinal cord compression, may cause severe pain, deformity and neurological sequelae. They may also have significant consequences for quality of life and prognosis for patients. For patients with known or newly diagnosed myeloma presenting with persistent back or radicular pain/weakness, early diagnosis of spinal myeloma disease is therefore essential to treat and prevent further deterioration. Magnetic resonance imaging is the initial imaging modality of choice for the evaluation of spinal disease. Treatment of the underlying malignancy with systemic chemotherapy together with supportive bisphosphonate treatment reduces further vertebral damage. Additional interventions such as cement augmentation, radiotherapy, or surgery are often necessary to prevent, treat and control spinal complications. However, optimal management is dependent on the individual nature of the spinal involvement and requires careful assessment and appropriate intervention throughout. This article reviews the treatment and management options for spinal myeloma disease and highlights the value of defined pathways to enable the proper management of patients affected by it. PMID:26184699

  9. Rostro-Caudal Inhibition of Hindlimb Movements in the Spinal Cord of Mice

    PubMed Central

    Caggiano, Vittorio; Sur, Mirganka; Bizzi, Emilio

    2014-01-01

    Inhibitory neurons in the adult mammalian spinal cord are known to locally modulate afferent feedback - from muscle proprioceptors and from skin receptors - to pattern motor activity for locomotion and postural control. Here, using optogenetic tools, we explored how the same population of inhibitory interneurons globally affects hindlimb movements in the spinal cord of both anesthetized and freely moving mice. Activation of inhibitory interneurons up to the middle/lower spinal cord i.e. T8–T9, were able to completely and globally suppress all ipsilateral hindlimb movements. Furthermore, the same population of interneurons - which inhibited movements - did not significantly change the sensory and proprioceptive information from the affected limbs to the cortex. These results suggest a rostro-caudal organization of inhibition in the spinal cord motor output without modulation of ascending sensory pathways. PMID:24963653

  10. Structure of mammalian metallothionein.

    PubMed Central

    Kägi, J H; Vasák, M; Lerch, K; Gilg, D E; Hunziker, P; Bernhard, W R; Good, M

    1984-01-01

    All mammalian metallothioneins characterized contain a single polypeptide chain of 61 amino acid residues, among them 20 cysteines providing the ligands for seven metal-binding sites. Native metallothioneins are usually heterogeneous in metal composition, with Zn, Cd, and Cu occurring in varying proportions. However, forms containing only a single metal species, i.e., Zn, Cd, Ni, Co, Hg, Pb, Bi, have now been prepared by in vitro reconstitution from the metal-free apoprotein. By spectroscopic analysis of such derivatives it was established that all cysteine residues participate in metal binding, that each metal ion is bound to four thiolate ligands, and that the symmetry of each complex is close to that of a tetrahedron. To satisfy the requirements of the overall Me7(Cys-)20 stoichiometry, the complexes must be combined to form metal-thiolate cluster structures. Experimental proof for the occurrence of such clusters comes from the demonstration of metal-metal interactions by spectroscopic and magnetic means. Thus, in Co(II)7-metallothionein, the Co(II)-specific ESR signals are effectively suppressed by antiferromagnetic coupling of juxtaposed paramagnetic metal ions. By monitoring changes in ESR signal size occurring on stepwise incorporation of Co(II) into the protein, it is possible to follow the building up of the clusters. This process is biphasic. Up to binding of four equivalents of Co(II), the ESR amplitude increases in proportion to the metal content, indicating generation of magnetically noninteracting high-spin complexes. However, upon addition of the remaining three equivalents of Co(II), these features are progressively suppressed, signaling the formation of clusters. The same mode of cluster formation has also been documented for Cd and Hg. The actual spatial organization of the clusters and the polypeptide chain remains to be established. An attractive possibility is the arrangement of the tetrahedral metal-thiolates in adamantane-like structures

  11. Neurosurgical approaches to spinal infections.

    PubMed

    Hazer, Derya Burcu; Ayhan, Selim; Palaoglu, Selcuk

    2015-05-01

    Spinal infection is rare. Clinical suspicion is important in patients with nonmechanical neck and/or back pain to make the proper diagnosis in early disease. Before planning surgery, a thorough evaluation of the spinal stability, alignment, and deformity is necessary. Timing of surgery, side of approach, appropriate surgical technique, and spinal instruments used are crucial. Biomechanical preservation of the spinal column during and after the infection is a significant issue. Postoperative spine infection is another entity of which spinal surgeons should be aware of. Proper septic conditions with meticulous planning of surgery are essential for successful spine surgery and better outcome. PMID:25952179

  12. Redox regulation of mammalian sperm capacitation

    PubMed Central

    O’Flaherty, Cristian

    2015-01-01

    Capacitation is a series of morphological and metabolic changes necessary for the spermatozoon to achieve fertilizing ability. One of the earlier happenings during mammalian sperm capacitation is the production of reactive oxygen species (ROS) that will trigger and regulate a series of events including protein phosphorylation, in a time-dependent fashion. The identity of the sperm oxidase responsible for the production of ROS involved in capacitation is still elusive, and several candidates are discussed in this review. Interestingly, ROS-induced ROS formation has been described during human sperm capacitation. Redox signaling during capacitation is associated with changes in thiol groups of proteins located on the plasma membrane and subcellular compartments of the spermatozoon. Both, oxidation of thiols forming disulfide bridges and the increase on thiol content are necessary to regulate different sperm proteins associated with capacitation. Reducing equivalents such as NADH and NADPH are necessary to support capacitation in many species including humans. Lactate dehydrogenase, glucose-6-phospohate dehydrogenase, and isocitrate dehydrogenase are responsible in supplying NAD (P) H for sperm capacitation. Peroxiredoxins (PRDXs) are newly described enzymes with antioxidant properties that can protect mammalian spermatozoa; however, they are also candidates for assuring the regulation of redox signaling required for sperm capacitation. The dysregulation of PRDXs and of enzymes needed for their reactivation such as thioredoxin/thioredoxin reductase system and glutathione-S-transferases impairs sperm motility, capacitation, and promotes DNA damage in spermatozoa leading to male infertility. PMID:25926608

  13. Modification of radiosensitivity of mammalian cells by cyclic nucleotides. [Mice

    SciTech Connect

    Hess, D.; Prasad, K.N.

    1981-07-06

    Some in vitro and in vivo studies suggest that adenosine 3',5'-cyclic monophosphate (cyclic AMP) may be one of the important factors in determining the radiosensitivity of certain mammalian cells; however, the role of guanosine 3',5'-cyclic monophosphate (cyclic GMP) in radiosensitivity of mammalian cells is completely unknown. Recent data also suggest that the mechanism of radiation protection afforded by moderate hypoxia and SH-containing compounds may involve an alteration in the intracellular level of cyclic AMP. At least one in vivo study shows that cyclic AMP protects hair follicles and gut epithelial cells against radiation damage; however, it does not protect lymphosarcoma and breast carcinoma in mice. If a similar phenomenon is found in humans, an elevation of the intracellular level of cyclic AMP during radiation exposure may improve the effectiveness of radiation therapy in those cases where the radiation damage of normal tissue becomes the limiting factor for a continuation of the therapy program.

  14. Spinal Cord Injury

    MedlinePlus

    ... How much do you know about taking good care of yourself? Links to more information girlshealth glossary girlshealth.gov home http://www.girlshealth.gov/ Home Illness & disability Types of ... Spinal cord injury Read advice from Dr. Jeffrey Rabin , a pediatric rehabilitation specialist at the Children’s National Medical Center. ...

  15. Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury

    PubMed Central

    Ferguson, Adam R.; Huie, J. Russell; Crown, Eric D.; Baumbauer, Kyle M.; Hook, Michelle A.; Garraway, Sandra M.; Lee, Kuan H.; Hoy, Kevin C.; Grau, James W.

    2012-01-01

    Synaptic plasticity within the spinal cord has great potential to facilitate recovery of function after spinal cord injury (SCI). Spinal plasticity can be induced in an activity-dependent manner even without input from the brain after complete SCI. A mechanistic basis for these effects is provided by research demonstrating that spinal synapses have many of the same plasticity mechanisms that are known to underlie learning and memory in the brain. In addition, the lumbar spinal cord can sustain several forms of learning and memory, including limb-position training. However, not all spinal plasticity promotes recovery of function. Central sensitization of nociceptive (pain) pathways in the spinal cord may emerge in response to various noxious inputs, demonstrating that plasticity within the spinal cord may contribute to maladaptive pain states. In this review we discuss interactions between adaptive and maladaptive forms of activity-dependent plasticity in the spinal cord below the level of SCI. The literature demonstrates that activity-dependent plasticity within the spinal cord must be carefully tuned to promote adaptive spinal training. Prior work from our group has shown that stimulation that is delivered in a limb position-dependent manner or on a fixed interval can induce adaptive plasticity that promotes future spinal cord learning and reduces nociceptive hyper-reactivity. On the other hand, stimulation that is delivered in an unsynchronized fashion, such as randomized electrical stimulation or peripheral skin injuries, can generate maladaptive spinal plasticity that undermines future spinal cord learning, reduces recovery of locomotor function, and promotes nociceptive hyper-reactivity after SCI. We review these basic phenomena, how these findings relate to the broader spinal plasticity literature, discuss the cellular and molecular mechanisms, and finally discuss implications of these and other findings for improved rehabilitative therapies after SCI. PMID

  16. In Vivo Measurement of Cervical Spinal Cord Deformation During Traumatic Spinal Cord Injury in a Rodent Model.

    PubMed

    Bhatnagar, Tim; Liu, Jie; Yung, Andrew; Cripton, Peter A; Kozlowski, Piotr; Oxland, Thomas

    2016-04-01

    The spinal cord undergoes physical deformation during traumatic spinal cord injury (TSCI), which results in biological damage. This study demonstrates a novel approach, using magnetic resonance imaging and image registration techniques, to quantify the three-dimensional deformation of the cervical spinal cord in an in vivo rat model. Twenty-four male rats were subjected to one of two clinically relevant mechanisms of TSCI (i.e. contusion and dislocation) inside of a MR scanner using a novel apparatus, enabling imaging of the deformed spinal cords. The displacement fields demonstrated qualitative differences between injury mechanisms. Three-dimensional Lagrangian strain fields were calculated, and the results from the contusion injury mechanism were deemed most reliable. Strain field error was assessed using a Monte Carlo approach, which showed that simulated normal strain error experienced a bias, whereas shear strain error did not. In contusion injury, a large region of dorso-ventral compressive strain was observed under the impactor which extended into the ventral region of the spinal cord. High tensile lateral strains under the impactor and compressive lateral strains in the lateral white matter were also observed in contusion. The ability to directly observe and quantify in vivo spinal cord deformation informs our knowledge of the mechanics of TSCI.

  17. Quantifying the Nonlinear, Anisotropic Material Response of Spinal Ligaments

    NASA Astrophysics Data System (ADS)

    Robertson, Daniel J.

    Spinal ligaments may be a significant source of chronic back pain, yet they are often disregarded by the clinical community due to a lack of information with regards to their material response, and innervation characteristics. The purpose of this dissertation was to characterize the material response of spinal ligaments and to review their innervation characteristics. Review of relevant literature revealed that all of the major spinal ligaments are innervated. They cause painful sensations when irritated and provide reflexive control of the deep spinal musculature. As such, including the neurologic implications of iatrogenic ligament damage in the evaluation of surgical procedures aimed at relieving back pain will likely result in more effective long-term solutions. The material response of spinal ligaments has not previously been fully quantified due to limitations associated with standard soft tissue testing techniques. The present work presents and validates a novel testing methodology capable of overcoming these limitations. In particular, the anisotropic, inhomogeneous material constitutive properties of the human supraspinous ligament are quantified and methods for determining the response of the other spinal ligaments are presented. In addition, a method for determining the anisotropic, inhomogeneous pre-strain distribution of the spinal ligaments is presented. The multi-axial pre-strain distributions of the human anterior longitudinal ligament, ligamentum flavum and supraspinous ligament were determined using this methodology. Results from this work clearly demonstrate that spinal ligaments are not uniaxial structures, and that finite element models which account for pre-strain and incorporate ligament's complex material properties may provide increased fidelity to the in vivo condition.

  18. Penetrating spinal injuries and their management

    PubMed Central

    Kumar, A.; Pandey, P. N.; Ghani, A.; Jaiswal, G.

    2011-01-01

    Penetrating spinal trauma due to missile/gunshot injuries has been well reported in the literature and has remained the domain of military warfare more often. Civic society's recent upsurge in gunshot injuries has created a dilemma for the treating neurosurgeon in many ways as their management has always involved certain debatable and controversial issues. Both conservative and surgical management of penetrating spinal injuries (PSI) have been practiced widely. The chief neurosurgical concern in these types of firearm injuries is the degree of damage sustained during the bullet traversing through the neural tissue and the after-effects of the same in long term. We had an interesting case of a penetrating bullet injury to cervical spine at C2 vertebral level. He was operated and the bullets were removed from posterior midline approach. Usually, the management of such cases differs from region to region depending on the preference of the surgeon but still certain common principles are followed world over. Thus, we realized the need to review the literature regarding spinal injuries with special emphasis on PSI and to study the recent guidelines for their treatment in light of our case. PMID:23125489

  19. Rat models of spinal cord injury: from pathology to potential therapies

    PubMed Central

    2016-01-01

    ABSTRACT A long-standing goal of spinal cord injury research is to develop effective spinal cord repair strategies for the clinic. Rat models of spinal cord injury provide an important mammalian model in which to evaluate treatment strategies and to understand the pathological basis of spinal cord injuries. These models have facilitated the development of robust tests for assessing the recovery of locomotor and sensory functions. Rat models have also allowed us to understand how neuronal circuitry changes following spinal cord injury and how recovery could be promoted by enhancing spontaneous regenerative mechanisms and by counteracting intrinsic inhibitory factors. Rat studies have also revealed possible routes to rescuing circuitry and cells in the acute stage of injury. Spatiotemporal and functional studies in these models highlight the therapeutic potential of manipulating inflammation, scarring and myelination. In addition, potential replacement therapies for spinal cord injury, including grafts and bridges, stem primarily from rat studies. Here, we discuss advantages and disadvantages of rat experimental spinal cord injury models and summarize knowledge gained from these models. We also discuss how an emerging understanding of different forms of injury, their pathology and degree of recovery has inspired numerous treatment strategies, some of which have led to clinical trials. PMID:27736748

  20. Basic fibroblast growth factor attenuates the degeneration of injured spinal cord motor endplates

    PubMed Central

    Wang, Jianlong; Sun, Jianfeng; Tang, Yongxiang; Guo, Gangwen; Zhou, Xiaozhe; Chen, Yanliang; Shen, Minren

    2013-01-01

    The distal end of the spinal cord and neuromuscular junction may develop secondary degeneration and damage following spinal cord injury because of the loss of neural connections. In this study, a rat model of spinal cord injury, established using a modified Allen's method, was injected with basic fibroblast growth factor solution via subarachnoid catheter. After injection, rats with spinal cord injury displayed higher scores on the Basso, Beattie and Bresnahan locomotor scale. Motor function was also well recovered and hematoxylin-eosin staining showed that spinal glial scar hyperplasia was not apparent. Additionally, anterior tibial muscle fibers slowly, but progressively, atrophied. nohistochemical staining showed that the absorbance values of calcitonin gene related peptide and acetylcholinesterase in anterior tibial muscle and spinal cord were similar, and injection of basic broblast growth factor increased this absorbance. Results showed that after spinal cord injury, the distal motor neurons and motor endplate degenerated. Changes in calcitonin gene related peptide and acetylcholinesterase in the spinal cord anterior horn motor neurons and motor endplate then occurred that were consistent with this regeneration. Our findings indicate that basic fibroblast growth factor can protect the endplate through attenuating the decreased expression of calcitonin gene related peptide and acetylcholinesterase in anterior horn motor neurons of the injured spinal cord. PMID:25206531

  1. Electroporation into Cultured Mammalian Embryos

    NASA Astrophysics Data System (ADS)

    Nomura, Tadashi; Takahashi, Masanori; Osumi, Noriko

    Over the last century, mammalian embryos have been used extensively as a common animal model to investigate fundamental questions in the field of developmental biology. More recently, the establishment of transgenic and gene-targeting systems in laboratory mice has enabled researchers to unveil the genetic mechanisms under lying complex developmental processes (Mak, 2007). However, our understanding of cell—cell interactions and their molecular basis in the early stages of mammalian embryogenesis is still very fragmentary. One of the major problems is the difficulty of precise manipulation and limited accessibility to mammalian embryos via uterus wall. Unfortunately, existing tissue and organotypic culture systems per se do not fully recapitulate three-dimensional, dynamic processes of organogenesis observed in vivo. Although transgenic animal technology and virus-mediated gene delivery are useful to manipulate gene expression, these techniques take much time and financial costs, which limit their use.

  2. Combination of melatonin and Wnt-4 promotes neural cell differentiation in bovine amniotic epithelial cells and recovery from spinal cord injury.

    PubMed

    Gao, Yuhua; Bai, Chunyu; Zheng, Dong; Li, Changli; Zhang, Wenxiu; Li, Mei; Guan, Weijun; Ma, Yuehui

    2016-04-01

    Although melatonin has been shown to exhibit a wide variety of biological functions, its effects on promoting differentiation of neural cells remain unknown. Wnt signaling mediates major developmental processes during embryogenesis and regulates maintenance, self-renewal, and differentiation of adult mammalian stem cells. However, the role of the noncanonical Wnt pathway during neurogenesis remains poorly understood. In this study, the amniotic epithelial cells ( AECs) were isolated from bovine amnion and incubated with various melatonin concentrations (0.01, 0.1, 1, 10, or 100 μm) and 5 × 10(-5) m all-trans retinoic acid (RA) for screening optimum culture medium of neural differentiation, compared with each groups, 1 μm melatonin and 5 × 10(-5) m RA were selected to induce neural differentiation of AECs, and then siMT1, siMT2, oWnt-4, and siWnt-4 were expressed in AECs to research role of these genes in neural differentiation. Efficiency of neural differentiation was evaluated after expressed above genes using flow cytometry. Cell function of neural cells was demonstrated in vivo using spinal cord injury model after cell transplantation, and damage repair of spinal cord was assessed using cell tracking and Basso, Beattie, Bresnahan Locomotor Rating Scale scores. Results demonstrated that melatonin stimulated melatonin receptor 1, which subsequently increased bovine amniotic epithelial cell vitality and promoted differentiation into neural cells. This took place through cooperation with Wnt-4. Additionally, following cotreatment with melatonin and Wnt-4, neurogenesis gene expression was significantly altered. Furthermore, single inhibition of melatonin receptor 1 or Wnt-4 expression decreased expression of neurogenesis-related genes, and bovine amniotic epithelial cell-derived neural cells were successfully colonized into injured spinal cord, which suggested participation in tissue repair. PMID:26762966

  3. Combination of melatonin and Wnt-4 promotes neural cell differentiation in bovine amniotic epithelial cells and recovery from spinal cord injury.

    PubMed

    Gao, Yuhua; Bai, Chunyu; Zheng, Dong; Li, Changli; Zhang, Wenxiu; Li, Mei; Guan, Weijun; Ma, Yuehui

    2016-04-01

    Although melatonin has been shown to exhibit a wide variety of biological functions, its effects on promoting differentiation of neural cells remain unknown. Wnt signaling mediates major developmental processes during embryogenesis and regulates maintenance, self-renewal, and differentiation of adult mammalian stem cells. However, the role of the noncanonical Wnt pathway during neurogenesis remains poorly understood. In this study, the amniotic epithelial cells ( AECs) were isolated from bovine amnion and incubated with various melatonin concentrations (0.01, 0.1, 1, 10, or 100 μm) and 5 × 10(-5) m all-trans retinoic acid (RA) for screening optimum culture medium of neural differentiation, compared with each groups, 1 μm melatonin and 5 × 10(-5) m RA were selected to induce neural differentiation of AECs, and then siMT1, siMT2, oWnt-4, and siWnt-4 were expressed in AECs to research role of these genes in neural differentiation. Efficiency of neural differentiation was evaluated after expressed above genes using flow cytometry. Cell function of neural cells was demonstrated in vivo using spinal cord injury model after cell transplantation, and damage repair of spinal cord was assessed using cell tracking and Basso, Beattie, Bresnahan Locomotor Rating Scale scores. Results demonstrated that melatonin stimulated melatonin receptor 1, which subsequently increased bovine amniotic epithelial cell vitality and promoted differentiation into neural cells. This took place through cooperation with Wnt-4. Additionally, following cotreatment with melatonin and Wnt-4, neurogenesis gene expression was significantly altered. Furthermore, single inhibition of melatonin receptor 1 or Wnt-4 expression decreased expression of neurogenesis-related genes, and bovine amniotic epithelial cell-derived neural cells were successfully colonized into injured spinal cord, which suggested participation in tissue repair.

  4. Mammalian embryonic cerebrospinal fluid proteome has greater apolipoprotein and enzyme pattern complexity than the avian proteome.

    PubMed

    Parada, Carolina; Gato, Angel; Bueno, David

    2005-01-01

    During early stages of embryo development, the brain cavity is filled with Embryonic Cerebro-Spinal Fluid, which has an essential role in the survival, proliferation and neurogenesis of the neuroectodermal stem cells. We identified and analyzed the proteome of Embryonic Cerebro-Spinal Fluid from rat embryos (Rattus norvegicus), which includes proteins involved in the regulation of Central Nervous System development. The comparison between mammalian and avian Embryonic Cerebro-Spinal Fluid proteomes reveals great similarity, but also greater complexity in some protein groups. The pattern of apolipoproteins and enzymes in CSF is more complex in the mammals than in birds. This difference may underlie the greater neural complexity and synaptic plasticity found in mammals. Fourteen Embryonic Cerebro-Spinal Fluid gene products were previously identified in adult human Cerebro-Spinal Fluid proteome, and interestingly they are altered in patients with neurodegenerative diseases and/or neurological disorders. Understanding these molecules and the mechanisms they control during embryonic neurogenesis may contribute to our understanding of Central Nervous System development and evolution, and these human diseases. PMID:16335996

  5. Immunotherapy strategies for spinal cord injury.

    PubMed

    Wang, Yong-Tang; Lu, Xiu-Min; Chen, Kai-Ting; Shu, Ya-Hai; Qiu, Chun-Hong

    2015-01-01

    Regeneration in the central nervous system (CNS) of adult mammalian after traumatic injury is limited, which often causes permanent functional motor and sensory loss. After spinal cord injury (SCI), the lack of regeneration is mainly attributed to the presence of a hostile microenvironment, glial scarring, and cavitation. Besides, inflammation has also been proved to play a crucial role in secondary degeneration following SCI. The more prominent treatment strategies in experimental models focus mainly on drugs and cell therapies, however, only a few strategies applied in clinical studies and therapies still have only limited effects on the repair of SCI. Recently, the interests in immunotherapy strategies for CNS are increasing in number and breadth. Immunotherapy strategies have made good progresses in treating many CNS degenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), stroke, and multiple sclerosis (MS). However, the strategies begin to be considered to the treatment of SCI and other neurological disorders in recent years. Besides anti-inflamatory therapy, immunization with protein vaccines and DNA vaccines has emerged as a novel therapy strategy because of the simplicity of preparation and application. An inflammatory response followed by spinal cord injury, and is controled by specific signaling molecules, such as some cytokines playing a crucial role. As a result, appropriate immunoregulation, the expression of pro-inflammatory cytokines and anti-inflammatory cytokines may be an effective therapy strategy for earlier injury of spinal cord. In addition, myelinassociated inhibitors (MAIs) in the injured spinal cord, such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte- myelin glycoprotein (OMgp) are known to prevent axonal regeneration through their co-receptors, and to trigger demyelinating autoimmunity through T cell-mediated harmful autoimmune response. The antagonism of the MAIs through vaccinating with

  6. Aspergillus spinal epidural abscess

    SciTech Connect

    Byrd, B.F. III; Weiner, M.H.; McGee, Z.A.

    1982-12-17

    A spinal epidural abscess developed in a renal transplant recipient; results of a serum radioimmunoassay for Aspergillus antigen were positive. Laminectomy disclosed an abscess of the L4-5 interspace and L-5 vertebral body that contained hyphal forms and from which Aspergillus species was cultured. Serum Aspergillus antigen radioimmunoassay may be a valuable, specific early diagnostic test when systemic aspergillosis is a consideration in an immunosuppressed host.

  7. FAQs about Spinal Cord Injury (SCI)

    MedlinePlus

    ... Website Managing Bowel Function After Spinal Cord Injury Resilience, Depression and Bouncing Back after SCI Getting to ... a “complete” and “incomplete” spinal cord injury? What recovery is expected following spinal cord injury? Where is ...

  8. Chitosan produces potent neuroprotection and physiological recovery following traumatic spinal cord injury.

    PubMed

    Cho, Youngnam; Shi, Riyi; Borgens, Richard B

    2010-05-01

    Chitosan, a non-toxic biodegradable polycationic polymer with low immunogenicity, has been extensively investigated in various biomedical applications. In this work, chitosan has been demonstrated to seal compromised nerve cell membranes thus serving as a potent neuroprotector following acute spinal cord trauma. Topical application of chitosan after complete transection or compression of the guinea pig spinal cord facilitated sealing of neuronal membranes in ex vivo tests, and restored the conduction of nerve impulses through the length of spinal cords in vivo, using somatosensory evoked potential recordings. Moreover, chitosan preferentially targeted damaged tissues, served as a suppressor of reactive oxygen species (free radical) generation, and the resultant lipid peroxidation of membranes, as shown in ex vivo spinal cord samples. These findings suggest a novel medical approach to reduce the catastrophic loss of behavior after acute spinal cord and brain injury.

  9. Cerebral spinal fluid (CSF) collection

    MedlinePlus

    Spinal tap; Ventricular puncture; Lumbar puncture; Cisternal puncture; Cerebrospinal fluid culture ... brain stem. It is always done with fluoroscopy. Ventricular puncture may be recommended in people with possible ...

  10. Spinal angiolipoma--case report.

    PubMed

    Chotai, Silky; Hur, Jun Seok; Moon, Hong Joo; Kwon, Taek-Hyun; Park, Youn Kwan; Kim, Joo Han

    2011-01-01

    A 69-year-old male presented with a rare spinal angiolipoma manifesting as history of back pain, and numbness in both lower limbs, which progressed over a period of 5 years. Total T10-T12 laminectomy was performed and the tumor was removed en bloc. The symptoms gradually improved postoperatively. Spinal angiolipoma is an uncommon benign extradural tumor of spine, which accounts for 0.14-1.2% of all spinal tumors and is a rare cause of spinal cord compression. Recognition of this entity is crucial as a benign and curable cause of paraplegia and back pain.

  11. Potential associations between chronic whiplash and incomplete spinal cord injury

    PubMed Central

    Smith, Andrew C.; Parrish, Todd B.; Hoggarth, Mark A.; McPherson, Jacob G.; Tysseling, Vicki M.; Wasielewski, Marie; Kim, Hyosub E.; Hornby, T. George; Elliott, James M.

    2016-01-01

    Study Design This research utilized a cross-sectional design with control group inclusion. Objectives Preliminary evidence suggests that a portion of the patient population with chronic whiplash may have sustained spinal cord damage. Our hypothesis is that in some cases of chronic whiplash-associated disorders (WAD), observed muscle weakness in the legs will be associated with local signs of a partial spinal cord injury of the cervical spine. Setting University based laboratory in Chicago, IL, USA. Methods Five participants with chronic WAD were compared with five gender/age/height/weight/body mass index (BMI) control participants. For a secondary investigation, the chronic WAD group was compared with five unmatched participants with motor incomplete spinal cord injury (iSCI). Spinal cord motor tract integrity was assessed using magnetization transfer imaging. Muscle fat infiltration (MFI) was quantified using fat/water separation magnetic resonance imaging. Central volitional muscle activation of the plantarflexors was assessed using a burst superimposition technique. Results We found reduced spinal cord motor tract integrity, increased MFI of the neck and lower extremity muscles and significantly impaired voluntary plantarflexor muscle activation in five participants with chronic WAD. The lower extremity structural changes and volitional weakness in chronic WAD were comparable to participants with iSCI. Conclusion The results support the position that a subset of the chronic whiplash population may have sustained partial damage to the spinal cord. Sponsorship NIH R01HD079076-01A1, NIH T32 HD057845 and the Foundation for Physical Therapy Promotion of Doctoral Studies program.

  12. Potential associations between chronic whiplash and incomplete spinal cord injury

    PubMed Central

    Smith, Andrew C.; Parrish, Todd B.; Hoggarth, Mark A.; McPherson, Jacob G.; Tysseling, Vicki M.; Wasielewski, Marie; Kim, Hyosub E.; Hornby, T. George; Elliott, James M.

    2016-01-01

    Study Design This research utilized a cross-sectional design with control group inclusion. Objectives Preliminary evidence suggests that a portion of the patient population with chronic whiplash may have sustained spinal cord damage. Our hypothesis is that in some cases of chronic whiplash-associated disorders (WAD), observed muscle weakness in the legs will be associated with local signs of a partial spinal cord injury of the cervical spine. Setting University based laboratory in Chicago, IL, USA. Methods Five participants with chronic WAD were compared with five gender/age/height/weight/body mass index (BMI) control participants. For a secondary investigation, the chronic WAD group was compared with five unmatched participants with motor incomplete spinal cord injury (iSCI). Spinal cord motor tract integrity was assessed using magnetization transfer imaging. Muscle fat infiltration (MFI) was quantified using fat/water separation magnetic resonance imaging. Central volitional muscle activation of the plantarflexors was assessed using a burst superimposition technique. Results We found reduced spinal cord motor tract integrity, increased MFI of the neck and lower extremity muscles and significantly impaired voluntary plantarflexor muscle activation in five participants with chronic WAD. The lower extremity structural changes and volitional weakness in chronic WAD were comparable to participants with iSCI. Conclusion The results support the position that a subset of the chronic whiplash population may have sustained partial damage to the spinal cord. Sponsorship NIH R01HD079076-01A1, NIH T32 HD057845 and the Foundation for Physical Therapy Promotion of Doctoral Studies program. PMID:27630770

  13. Perfusion assessment in rat spinal cord tissue using photoplethysmography and laser Doppler flux measurements

    NASA Astrophysics Data System (ADS)

    Phillips, Justin P.; Cibert-Goton, Vincent; Langford, Richard M.; Shortland, Peter J.

    2013-03-01

    Animal models are widely used to investigate the pathological mechanisms of spinal cord injury (SCI), most commonly in rats. It is well known that compromised blood flow caused by mechanical disruption of the vasculature can produce irreversible damage and cell death in hypoperfused tissue regions and spinal cord tissue is particularly susceptible to such damage. A fiberoptic photoplethysmography (PPG) probe and instrumentation system were used to investigate the practical considerations of making measurements from rat spinal cord and to assess its suitability for use in SCI models. Experiments to assess the regional perfusion of exposed spinal cord in anesthetized adult rats using both PPG and laser Doppler flowmetry (LDF) were performed. It was found that signals could be obtained reliably from all subjects, although considerable intersite and intersubject variability was seen in the PPG signal amplitude compared to LDF. We present results from 30 measurements in five subjects, the two methods are compared, and practical application to SCI animal models is discussed.

  14. New strategies for repairing the injured spinal cord: the role of stem cells.

    PubMed

    Garbossa, D; Fontanella, M; Fronda, C; Benevello, C; Muraca, G; Ducati, A; Vercelli, A

    2006-07-01

    Thanks to advances in the stem cell biology of the central nervous system, the previously unconceivable regeneration of the damaged spinal cord is approaching reality. A number of potential strategies aim to optimize functional recovery after spinal cord injury. They include minimizing the progression of secondary injury, manipulating the inhibitory environment of the spinal cord, replacing lost tissue with transplanted cells or peripheral nerve grafts, remyelinating denuded axons and maximizing the intrinsic regenerative potential of endogenous progenitor cells. We review the application of stem cell transplantation to the spinal cord, emphasizing the use of embryonic stem cells for remyelinating damaged axons. Recent advancements in neural injury and repair, and the progress towards development of neuroprotective and regenerative interventions are discussed.

  15. Electrophysiological and Anatomical Correlates of Spinal Cord Optical Coherence Tomography.

    PubMed

    Giardini, Mario E; Zippo, Antonio G; Valente, Maurizio; Krstajic, Nikola; Biella, Gabriele E M

    2016-01-01

    Despite the continuous improvement in medical imaging technology, visualizing the spinal cord poses severe problems due to structural or incidental causes, such as small access space and motion artifacts. In addition, positional guidance on the spinal cord is not commonly available during surgery, with the exception of neuronavigation techniques based on static pre-surgical data and of radiation-based methods, such as fluoroscopy. A fast, bedside, intraoperative real-time imaging, particularly necessary during the positioning of endoscopic probes or tools, is an unsolved issue. The objective of our work, performed on experimental rats, is to demonstrate potential intraoperative spinal cord imaging and probe guidance by optical coherence tomography (OCT). Concurrently, we aimed to demonstrate that the electromagnetic OCT irradiation exerted no particular effect at the neuronal and synaptic levels. OCT is a user-friendly, low-cost and endoscopy-compatible photonics-based imaging technique. In particular, by using a Fourier-domain OCT imager, operating at 850 nm wavelength and scanning transversally with respect to the spinal cord, we have been able to: 1) accurately image tissue structures in an animal model (muscle, spine bone, cerebro-spinal fluid, dura mater and spinal cord), and 2) identify the position of a recording microelectrode approaching and inserting into the cord tissue 3) check that the infrared radiation has no actual effect on the electrophysiological activity of spinal neurons. The technique, potentially extendable to full three-dimensional image reconstruction, shows prospective further application not only in endoscopic intraoperative analyses and for probe insertion guidance, but also in emergency and adverse situations (e.g. after trauma) for damage recognition, diagnosis and fast image-guided intervention. PMID:27050096

  16. Electrophysiological and Anatomical Correlates of Spinal Cord Optical Coherence Tomography

    PubMed Central

    Valente, Maurizio; Krstajic, Nikola; Biella, Gabriele E. M.

    2016-01-01

    Despite the continuous improvement in medical imaging technology, visualizing the spinal cord poses severe problems due to structural or incidental causes, such as small access space and motion artifacts. In addition, positional guidance on the spinal cord is not commonly available during surgery, with the exception of neuronavigation techniques based on static pre-surgical data and of radiation-based methods, such as fluoroscopy. A fast, bedside, intraoperative real-time imaging, particularly necessary during the positioning of endoscopic probes or tools, is an unsolved issue. The objective of our work, performed on experimental rats, is to demonstrate potential intraoperative spinal cord imaging and probe guidance by optical coherence tomography (OCT). Concurrently, we aimed to demonstrate that the electromagnetic OCT irradiation exerted no particular effect at the neuronal and synaptic levels. OCT is a user-friendly, low-cost and endoscopy-compatible photonics-based imaging technique. In particular, by using a Fourier-domain OCT imager, operating at 850 nm wavelength and scanning transversally with respect to the spinal cord, we have been able to: 1) accurately image tissue structures in an animal model (muscle, spine bone, cerebro-spinal fluid, dura mater and spinal cord), and 2) identify the position of a recording microelectrode approaching and inserting into the cord tissue 3) check that the infrared radiation has no actual effect on the electrophysiological activity of spinal neurons. The technique, potentially extendable to full three-dimensional image reconstruction, shows prospective further application not only in endoscopic intraoperative analyses and for probe insertion guidance, but also in emergency and adverse situations (e.g. after trauma) for damage recognition, diagnosis and fast image-guided intervention. PMID:27050096

  17. Dynamic JUNQ inclusion bodies are asymmetrically inherited in mammalian cell lines through the asymmetric partitioning of vimentin.

    PubMed

    Ogrodnik, Mikołaj; Salmonowicz, Hanna; Brown, Rachel; Turkowska, Joanna; Średniawa, Władysław; Pattabiraman, Sundararaghavan; Amen, Triana; Abraham, Ayelet-chen; Eichler, Noam; Lyakhovetsky, Roman; Kaganovich, Daniel

    2014-06-01

    Aging is associated with the accumulation of several types of damage: in particular, damage to the proteome. Recent work points to a conserved replicative rejuvenation mechanism that works by preventing the inheritance of damaged and misfolded proteins by specific cells during division. Asymmetric inheritance of misfolded and aggregated proteins has been shown in bacteria and yeast, but relatively little evidence exists for a similar mechanism in mammalian cells. Here, we demonstrate, using long-term 4D imaging, that the vimentin intermediate filament establishes mitotic polarity in mammalian cell lines and mediates the asymmetric partitioning of damaged proteins. We show that mammalian JUNQ inclusion bodies containing soluble misfolded proteins are inherited asymmetrically, similarly to JUNQ quality-control inclusions observed in yeast. Mammalian IPOD-like inclusion bodies, meanwhile, are not always inherited by the same cell as the JUNQ. Our study suggests that the mammalian cytoskeleton and intermediate filaments provide the physical scaffold for asymmetric inheritance of dynamic quality-control JUNQ inclusions. Mammalian IPOD inclusions containing amyloidogenic proteins are not partitioned as effectively during mitosis as their counterparts in yeast. These findings provide a valuable mechanistic basis for studying the process of asymmetric inheritance in mammalian cells, including cells potentially undergoing polar divisions, such as differentiating stem cells and cancer cells.

  18. Spinal bone density following spinal fusion

    SciTech Connect

    Lipscomb, H.J.; Grubb, S.A.; Talmage, R.V.

    1989-04-01

    Spinal bone densities were assessed in 25 patients following lumbar fusion and bracing, in an attempt to study bone remodeling by noninvasive methods. Dual-photon densitometry was used to study specific areas of autologous bone grafts and adjacent vertebrae above the fusion mass. Measurements were made preoperatively and at 6-week intervals postoperatively. The data for the first 12 months postoperatively are reported here. In all patients there was at first a consistent loss in density in the vertebrae above the fusion mass, averaging 15.7%. This was followed by a gradual density increase such that by 1 year postoperatively, in 60% of the subjects, the density of these vertebrae was higher than the preoperative level. In the grafted areas, bone changes were cyclical, demonstrating a remodeling pattern consistent with that described in animal literature for graft healing and also consistent with modern bone remodeling theory. There was a general tendency toward a gradual increase in the density of the fusion mass.

  19. Neuromuscular interaction is required for neurotrophins-mediated locomotor recovery following treadmill training in rat spinal cord injury.

    PubMed

    Wu, Qinfeng; Cao, Yana; Dong, Chuanming; Wang, Hongxing; Wang, Qinghua; Tong, Weifeng; Li, Xiangzhe; Shan, Chunlei; Wang, Tong

    2016-01-01

    Recent results have shown that exercise training promotes the recovery of injured rat distal spinal cords, but are still unclear about the function of skeletal muscle in this process. Herein, rats with incomplete thoracic (T10) spinal cord injuries (SCI) with a dual spinal lesion model were subjected to four weeks of treadmill training and then were treated with complete spinal transection at T8. We found that treadmill training allowed the retention of hind limb motor function after incomplete SCI, even with a heavy load after complete spinal transection. Moreover, treadmill training alleviated the secondary injury in distal lumbar spinal motor neurons, and enhanced BDNF/TrkB expression in the lumbar spinal cord. To discover the influence of skeletal muscle contractile activity on motor function and gene expression, we adopted botulinum toxin A (BTX-A) to block the neuromuscular activity of the rat gastrocnemius muscle. BTX-A treatment inhibited the effects of treadmill training on motor function and BDNF/TrKB expression. These results indicated that treadmill training through the skeletal muscle-motor nerve-spinal cord retrograde pathway regulated neuralplasticity in the mammalian central nervous system, which induced the expression of related neurotrophins and promoted motor function recovery. PMID:27190721

  20. Neuromuscular interaction is required for neurotrophins-mediated locomotor recovery following treadmill training in rat spinal cord injury.

    PubMed

    Wu, Qinfeng; Cao, Yana; Dong, Chuanming; Wang, Hongxing; Wang, Qinghua; Tong, Weifeng; Li, Xiangzhe; Shan, Chunlei; Wang, Tong

    2016-01-01

    Recent results have shown that exercise training promotes the recovery of injured rat distal spinal cords, but are still unclear about the function of skeletal muscle in this process. Herein, rats with incomplete thoracic (T10) spinal cord injuries (SCI) with a dual spinal lesion model were subjected to four weeks of treadmill training and then were treated with complete spinal transection at T8. We found that treadmill training allowed the retention of hind limb motor function after incomplete SCI, even with a heavy load after complete spinal transection. Moreover, treadmill training alleviated the secondary injury in distal lumbar spinal motor neurons, and enhanced BDNF/TrkB expression in the lumbar spinal cord. To discover the influence of skeletal muscle contractile activity on motor function and gene expression, we adopted botulinum toxin A (BTX-A) to block the neuromuscular activity of the rat gastrocnemius muscle. BTX-A treatment inhibited the effects of treadmill training on motor function and BDNF/TrKB expression. These results indicated that treadmill training through the skeletal muscle-motor nerve-spinal cord retrograde pathway regulated neuralplasticity in the mammalian central nervous system, which induced the expression of related neurotrophins and promoted motor function recovery.

  1. Neuromuscular interaction is required for neurotrophins-mediated locomotor recovery following treadmill training in rat spinal cord injury

    PubMed Central

    Wu, Qinfeng; Cao, Yana; Dong, Chuanming; Wang, Hongxing; Wang, Qinghua; Tong, Weifeng; Li, Xiangzhe

    2016-01-01

    Recent results have shown that exercise training promotes the recovery of injured rat distal spinal cords, but are still unclear about the function of skeletal muscle in this process. Herein, rats with incomplete thoracic (T10) spinal cord injuries (SCI) with a dual spinal lesion model were subjected to four weeks of treadmill training and then were treated with complete spinal transection at T8. We found that treadmill training allowed the retention of hind limb motor function after incomplete SCI, even with a heavy load after complete spinal transection. Moreover, treadmill training alleviated the secondary injury in distal lumbar spinal motor neurons, and enhanced BDNF/TrkB expression in the lumbar spinal cord. To discover the influence of skeletal muscle contractile activity on motor function and gene expression, we adopted botulinum toxin A (BTX-A) to block the neuromuscular activity of the rat gastrocnemius muscle. BTX-A treatment inhibited the effects of treadmill training on motor function and BDNF/TrKB expression. These results indicated that treadmill training through the skeletal muscle-motor nerve-spinal cord retrograde pathway regulated neuralplasticity in the mammalian central nervous system, which induced the expression of related neurotrophins and promoted motor function recovery. PMID:27190721

  2. A simple field method for spinal cord removal demonstrated in the cheetah (Acinonyx jubatus).

    PubMed

    Walzer, Christian; Kübber-Heiss, Anna; Robert, Nadia

    2002-01-01

    Removal of the spinal cord is considered time consuming and difficult. A delay in the necropsy procedure, especially in the central nervous system, can result in significant tissue autolysis and subsequent diagnostic difficulties. In the field, where many necropsies are performed, suitable electric saws are mostly unavailable. A technically simple and rapid method for spinal cord removal, requiring only a straightforward tool, has been devised. No necropsy-induced structural damage has been noted on histopathologic examination.

  3. Transplantation of placenta-derived mesenchymal stem cell-induced neural stem cells to treat spinal cord injury.

    PubMed

    Li, Zhi; Zhao, Wei; Liu, Wei; Zhou, Ye; Jia, Jingqiao; Yang, Lifeng

    2014-12-15

    Because of their strong proliferative capacity and multi-potency, placenta-derived mesenchymal stem cells have gained interest as a cell source in the field of nerve damage repair. In the present study, human placenta-derived mesenchymal stem cells were induced to differentiate into neural stem cells, which were then transplanted into the spinal cord after local spinal cord injury in rats. The motor functional recovery and pathological changes in the injured spinal cord were observed for 3 successive weeks. The results showed that human placenta-derived mesenchymal stem cells can differentiate into neuron-like cells and that induced neural stem cells contribute to the restoration of injured spinal cord without causing transplant rejection. Thus, these cells promote the recovery of motor and sensory functions in a rat model of spinal cord injury. Therefore, human placenta-derived mesenchymal stem cells may be useful as seed cells during the repair of spinal cord injury.

  4. Three-dimensional imaging of microvasculature in the rat spinal cord following injury

    PubMed Central

    Cao, Yong; Wu, Tianding; yuan, Zhou; Li, Dongzhe; Ni, Shuangfei; Hu, Jianzhong; Lu, Hongbin

    2015-01-01

    Research studies on the three-dimensional (3D) morphological alterations of the spinal cord microvasculature after injury provide insight into the pathology of spinal cord injury (SCI). Knowledge in this field has been hampered in the past by imaging technologies that provided only two-dimensional (2D) information on the vascular reactions to trauma. The aim of our study is to investigate the 3D microstructural changes of the rat spinal cord microvasculature on day 1 post-injury using synchrotron radiation micro-tomography (SRμCT). This technology provides high-resolution 3D images of microvasculature in both normal and injured spinal cords, and the smallest vessel detected is approximately 7.4 μm. Moreover, we optimized the 3D vascular visualization with color coding and accurately calculated quantitative changes in vascular architecture after SCI. Compared to the control spinal cord, the damaged spinal cord vessel numbers decreased significantly following injury. Furthermore, the area of injury did not remain concentrated at the epicenter; rather, the signs of damage expanded rostrally and caudally along the spinal cord in 3D. The observed pathological changes were also confirmed by histological tests. These results demonstrate that SRμCT is an effective technology platform for imaging pathological changes in small arteries in neurovascular disease and for evaluating therapeutic interventions. PMID:26220842

  5. DNA repair and radiation sensitivity in mammalian cells

    SciTech Connect

    Chen, D.J.C.; Stackhouse, M.; Chen, D.S.

    1993-02-01

    Ionizing radiation induces various types of damage in mammalian cells including DNA single-strand breaks, DNA double-strand breaks (DSB), DNA-protein cross links, and altered DNA bases. Although human cells can repair many of these lesions there is little detailed knowledge of the nature of the genes and the encoded enzymes that control these repair processes. We report here on the cellular and genetic analyses of DNA double-strand break repair deficient mammalian cells. It has been well established that the DNA double-strand break is one of the major lesions induced by ionizing radiation. Utilizing rodent repair-deficient mutant, we have shown that the genes responsible for DNA double-strand break repair are also responsible for the cellular expression of radiation sensitivity. The molecular genetic analysis of DSB repair in rodent/human hybrid cells indicate that at least 6 different genes in mammalian cells are responsible for the repair of radiation-induced DNA double-strand breaks. Mapping and the prospect of cloning of human radiation repair genes are reviewed. Understanding the molecular and genetic basis of radiation sensitivity and DNA repair in man will provide a rational foundation to predict the individual risk associated with radiation exposure and to prevent radiation-induced genetic damage in the human population.

  6. DNA repair and radiation sensitivity in mammalian cells

    SciTech Connect

    Chen, D.J.C.; Stackhouse, M. ); Chen, D.S. . Dept. of Radiation Oncology)

    1993-01-01

    Ionizing radiation induces various types of damage in mammalian cells including DNA single-strand breaks, DNA double-strand breaks (DSB), DNA-protein cross links, and altered DNA bases. Although human cells can repair many of these lesions there is little detailed knowledge of the nature of the genes and the encoded enzymes that control these repair processes. We report here on the cellular and genetic analyses of DNA double-strand break repair deficient mammalian cells. It has been well established that the DNA double-strand break is one of the major lesions induced by ionizing radiation. Utilizing rodent repair-deficient mutant, we have shown that the genes responsible for DNA double-strand break repair are also responsible for the cellular expression of radiation sensitivity. The molecular genetic analysis of DSB repair in rodent/human hybrid cells indicate that at least 6 different genes in mammalian cells are responsible for the repair of radiation-induced DNA double-strand breaks. Mapping and the prospect of cloning of human radiation repair genes are reviewed. Understanding the molecular and genetic basis of radiation sensitivity and DNA repair in man will provide a rational foundation to predict the individual risk associated with radiation exposure and to prevent radiation-induced genetic damage in the human population.

  7. Adjustment to Spinal Cord Injury

    MedlinePlus

    ... of injury are alive and easily get educational information on the Internet. Web happy. sites such as the National Spinal Cord Injury Association (www.spinalcord.org) and SPINAL CORD Injury ♦ “Because of my injury, it is now impossible for me Information Network (www.spinalcord.uab.edu) have to ever ...

  8. Hemorrhagic onset of spinal angiolipoma.

    PubMed

    da Costa, Marcos Devanir Silva; Paz, Daniel de Araujo; Rodrigues, Thiago Pereira; Gandolfi, Ana Camila de Castro; Lamis, Fabricio Correa; Stavale, João Norberto; Suriano, Italo Capraro; Cetl, Luiz Daniel Marques Neves; Cavalheiro, Sergio

    2014-12-01

    Spinal angiolipomas are rare benign tumors that generally induce slow progressive cord compression. Here, the authors describe a case of sudden-onset palsy of the lower extremities caused by hemorrhagic spinal angiolipoma. An emergent laminectomy was performed to achieve total lesion removal. Follow-up examinations indicated neurological improvement and the absence of recurrence.

  9. Imaging modalities in spinal disorders

    SciTech Connect

    Kricun, M.E.

    1986-01-01

    This book provides an approach to the various imaging modalities used to view the spine. It discusses the indications, limitations and practical use of each in the diagnosis, work-up and staging of various spinal disorders, and compares each of them in various clinical settings. Topics covered include low back pain syndrome, disk disease, spinal cord lesions, congenital abnormalities, and trauma.

  10. The role of propriospinal interneurons in recovery from spinal cord injury.

    PubMed

    Flynn, Jamie R; Graham, Brett A; Galea, Mary P; Callister, Robert J

    2011-04-01

    Over one hundred years ago, Sir Charles Sherrington described a population of spinal cord interneurons (INs) that connect multiple spinal cord segments and participate in complex or 'long' motor reflexes. These neurons were subsequently termed propriospinal neurons (PNs) and are known to play a crucial role in motor control and sensory processing. Recent work has shown that PNs may also be an important substrate for recovery from spinal cord injury (SCI) as they contribute to plastic reorganisation of spinal circuits. The location, inter-segmental projection pattern and sheer number of PNs mean that after SCI, a significant number of them are capable of 'bridging' an incomplete spinal cord lesion. When these properties are combined with the capacity of PNs to activate and coordinate locomotor central pattern generators (CPGs), it is clear they are ideally placed to assist locomotor recovery. Here we summarise the anatomy, organisation and function of PNs in the uninjured spinal cord, briefly outline the pathophysiology of SCI, describe how PNs contribute to recovery of motor function, and finally, we discuss the mechanisms that underlie PN plasticity. We propose there are two major challenges for PN research. The first is to learn more about ways we can promote PN plasticity and manipulate the 'hostile' micro-environment that limits regeneration in the damaged spinal cord. The second is to study the cellular/intrinsic properties of PNs to better understand their function in both the normal and injured spinal cord. This article is part of a Special Issue entitled 'Synaptic Plasticity & Interneurons'.

  11. Critical ischemia time in a model of spinal cord section. A study performed on dogs

    PubMed Central

    Garcia Martinez, David; Rosales Corral, Sergio A.; Flores Soto, Mario E.; Velarde Silva, Gustavo; Portilla de Buen, Eliseo

    2006-01-01

    Vascular changes after acute spinal cord trauma are important factors that predispose quadriplegia, in most cases irreversible. Repair of the spinal blood flow helps the spinal cord recovery. The average time to arrive and perform surgery is 3 h in most cases. It is important to determine the critical ischemia time in order to offer better functional prognosis. A spinal cord section and vascular clamping of the spinal anterior artery at C5–C6 model was used to determine critical ischemia time. The objective was to establish a critical ischemia time in a model of acute spinal cord section. Four groups of dogs were used, anterior approach and vascular clamp of spinal anterior artery with 1, 2, 3, and 4 h of ischemia and posterior hemisection of spinal cord at C5–C6 was performed. Clinical evaluation was made during 12 weeks and morphological evaluation at the end of this period. We obtained a maximal neurological coordination at 23 days average. Two cases showed sequels of right upper limb paresis at 1 and 3 ischemia hours. There was nerve conduction delay of 56% at 3 h of ischemia. Morphological examination showed 25% of damaged area. The VIII and IX Rexed’s laminae were the most affected. The critical ischemia time was 3 h. Dogs with 4 h did not exhibit any recovery. PMID:17024402

  12. Spinal cord regeneration in Xenopus tadpoles proceeds through activation of Sox2-positive cells

    PubMed Central

    2012-01-01

    Background In contrast to mammals, amphibians, such as adult urodeles (for example, newts) and anuran larvae (for example, Xenopus) can regenerate their spinal cord after injury. However, the cellular and molecular mechanisms involved in this process are still poorly understood. Results Here, we report that tail amputation results in a global increase of Sox2 levels and proliferation of Sox2+ cells. Overexpression of a dominant negative form of Sox2 diminished proliferation of spinal cord resident cells affecting tail regeneration after amputation, suggesting that spinal cord regeneration is crucial for the whole process. After spinal cord transection, Sox2+ cells are found in the ablation gap forming aggregates. Furthermore, Sox2 levels correlated with regenerative capabilities during metamorphosis, observing a decrease in Sox2 levels at non-regenerative stages. Conclusions Sox2+ cells contribute to the regeneration of spinal cord after tail amputation and transection. Sox2 levels decreases during metamorphosis concomitantly with the lost of regenerative capabilities. Our results lead to a working hypothesis in which spinal cord damage activates proliferation and/or migration of Sox2+ cells, thus allowing regeneration of the spinal cord after tail amputation or reconstitution of the ependymal epithelium after spinal cord transection. PMID:22537391

  13. Assessment of spinal pain.

    PubMed

    Braun, J; Baraliakos, X; Regel, A; Kiltz, U

    2014-12-01

    Spinal pain or back pain is a very common symptom that can have many reasons. The most studied location is low back pain, and it is considered to be nonspecific in the majority of cases. Only a small proportion of patients have axial inflammation as the major cause of their back complaints with chronic inflammatory back pain (IBP) as the most prominent clinical feature of spondyloarthritis (SpA). The recognition of IBP and patients with axial spondyloarthritis (axSpA) is challenging in primary care, and it is important to further facilitate the early diagnosis of SpA. Proposals for improving the referral of patients with a possible diagnosis of axSpA include clinical parameters, human leukocyte antigen (HLA) B27, and imaging parameters. Imaging is crucial for the visualization, objective validation, and understanding of back pain. Numerous diseases such as degenerative disk disease, degenerative changes in the intervertebral (facet) joints and the associated ligaments, spinal instability, herniation of the intervertebral disk, and spinal stenosis have to be differentiated in interpreting imaging of the spine. The sacroiliac joints and the spine are of major importance for the diagnosis and classification of axSpA. Conventional radiographs and magnetic resonance imaging (MRI) are the most important imaging technologies for visualization of structural changes such as syndesmophytes and axial inflammation such as sacroiliitis and spondylitis. The pathogenesis of axSpA is largely genetically determined. HLA B27 has the strongest contribution to the total genetic burden, but other major contributors such as endoplasmic reticulum aminopeptidase (ERAP)-1 and interleukin (IL)-23R have also been identified. PMID:26096091

  14. The Gastrin-Releasing Peptide Receptor (GRPR) in the Spinal Cord as a Novel Pharmacological Target

    PubMed Central

    Takanami, Keiko; Sakamoto, Hirotaka

    2014-01-01

    Gastrin-releasing peptide (GRP) is a mammalian neuropeptide that acts through the G protein-coupled receptor, GRP receptor (GRPR). Increasing evidence indicates that GRPR-mediated signaling in the central nervous system plays an important role in many physiological processes in mammals. Additionally, we have recently reported that the GRP system within the lumbosacral spinal cord not only controls erection but also triggers ejaculation in male rats. This system of GRP neurons is sexually dimorphic, being prominent in male rats but vestigial or absent in females. It is suggested that the sexually dimorphic GRP/GRPR system in the lumbosacral spinal cord plays a critical role in the regulation of male sexual function. In parallel, it has been reported that the somatosensory GRP/GRPR system in the spinal cord contributes to the regulation of itch specific transmission independently of the pain transmission. Interestingly, these two distinct functions in the same spinal region are both regulated by the neuropeptide, GRP. In this report, we review findings on recently identified GRP/GRPR systems in the spinal cord. These GRP/GRPR systems in the spinal cord provide new insights into pharmacological treatments for psychogenic erectile dysfunction as well as for chronic pruritus. PMID:25426011

  15. Infiltrating spinal angiolipoma.

    PubMed

    Yen, Han-Lin; Tsai, Shih-Chung; Liu, Shian-Min

    2008-10-01

    Infiltrating angiolipomas are rarely encountered in the spine. We present a case involving a 71-year-old man with a dorsal epidural angiolipoma at the T5-T7 level. The tumor involved the T5-T6 vertebral bodies and left pedicle. The patient presented with acute paraparesis and MRI showed a homogeneously hyphointense lesion on T1-weighted images. The epidural component of the tumor was removed via laminectomy to achieve adequate cord decompression. The patient was symptom-free at a 2-year follow-up. This report emphasizes the unusual clinical presentation and MRI features of an infiltrating spinal angiolipoma and discusses therapeutic management options.

  16. Lumbar spinal epidural angiolipoma.

    PubMed

    Nanassis, Kimon; Tsitsopoulos, Parmenion; Marinopoulos, Dimitrios; Mintelis, Apostolos; Tsitsopoulos, Philippos

    2008-04-01

    Spinal angiolipomas are rare benign tumours most commonly found in the thoracic spine. A case of an extradural lumbar angiolipoma in a 47-year-old female is described. She had a recent history of lower back pain accompanied by sciatica. Lumbar MRI revealed a dorsal epidural mass at the L2-L3 level. The patient underwent a bilateral laminectomy, in which the tumour was totally excised. The pathological examination indicated haemangiolipoma. Post-operatively, the patient's neurological signs and symptoms improved remarkably quickly. MRI at 6 and 18 months after surgery revealed no evidence of tumour recurrence.

  17. Deoxyribophosphate lyase activity of mammalian endonuclease VIII-like proteins.

    PubMed

    Grin, Inga R; Khodyreva, Svetlana N; Nevinsky, Georgy A; Zharkov, Dmitry O

    2006-09-01

    Base excision repair (BER) protects cells from nucleobase DNA damage. In eukaryotic BER, DNA glycosylases generate abasic sites, which are then converted to deoxyribo-5'-phosphate (dRP) and excised by a dRP lyase (dRPase) activity of DNA polymerase beta (Polbeta). Here, we demonstrate that NEIL1 and NEIL2, mammalian homologs of bacterial endonuclease VIII, excise dRP by beta-elimination with the efficiency similar to Polbeta. DNA duplexes imitating BER intermediates after insertion of a single nucleotide were better substrates. NEIL1 and NEIL2 supplied dRPase activity in BER reconstituted with dRPase-null Polbeta. Our results suggest a role for NEILs as backup dRPases in mammalian cells.

  18. Regeneration of hair cells in the mammalian vestibular system.

    PubMed

    Li, Wenyan; You, Dan; Chen, Yan; Chai, Renjie; Li, Huawei

    2016-06-01

    Hair cells regenerate throughout the lifetime of non-mammalian vertebrates, allowing these animals to recover from hearing and balance deficits. Such regeneration does not occur efficiently in humans and other mammals. Thus, balance deficits become permanent and is a common sensory disorder all over the world. Since Forge and Warchol discovered the limited spontaneous regeneration of vestibular hair cells after gentamicininduced damage in mature mammals, significant efforts have been exerted to trace the origin of the limited vestibular regeneration in mammals after hair cell loss. Moreover, recently many strategies have been developed to promote the hair cell regeneration and subsequent functional recovery of the vestibular system, including manipulating the Wnt, Notch and Atoh1. This article provides an overview of the recent advances in hair cell regeneration in mammalian vestibular epithelia. Furthermore, this review highlights the current limitations of hair cell regeneration and provides the possible solutions to regenerate functional hair cells and to partially restore vestibular function.

  19. Olfactory sensitivity in mammalian species.

    PubMed

    Wackermannová, M; Pinc, L; Jebavý, L

    2016-07-18

    Olfaction enables most mammalian species to detect and discriminate vast numbers of chemical structures called odorants and pheromones. The perception of such chemical compounds is mediated via two major olfactory systems, the main olfactory system and the vomeronasal system, as well as minor systems, such as the septal organ and the Grueneberg ganglion. Distinct differences exist not only among species but also among individuals in terms of their olfactory sensitivity; however, little is known about the mechanisms that determine these differences. In research on the olfactory sensitivity of mammals, scientists thus depend in most cases on behavioral testing. In this article, we reviewed scientific studies performed on various mammalian species using different methodologies and target chemical substances. Human and non-human primates as well as rodents and dogs are the most frequently studied species. Olfactory threshold studies on other species do not exist with the exception of domestic pigs. Olfactory testing performed on seals, elephants, and bats focused more on discriminative abilities than on sensitivity. An overview of olfactory sensitivity studies as well as olfactory detection ability in most studied mammalian species is presented here, focusing on comparable olfactory detection thresholds. The basics of olfactory perception and olfactory sensitivity factors are also described. PMID:27070753

  20. Retraining the injured spinal cord

    NASA Technical Reports Server (NTRS)

    Edgerton, V. R.; Leon, R. D.; Harkema, S. J.; Hodgson, J. A.; London, N.; Reinkensmeyer, D. J.; Roy, R. R.; Talmadge, R. J.; Tillakaratne, N. J.; Timoszyk, W.; Tobin, A.

    2001-01-01

    The present review presents a series of concepts that may be useful in developing rehabilitative strategies to enhance recovery of posture and locomotion following spinal cord injury. First, the loss of supraspinal input results in a marked change in the functional efficacy of the remaining synapses and neurons of intraspinal and peripheral afferent (dorsal root ganglion) origin. Second, following a complete transection the lumbrosacral spinal cord can recover greater levels of motor performance if it has been exposed to the afferent and intraspinal activation patterns that are associated with standing and stepping. Third, the spinal cord can more readily reacquire the ability to stand and step following spinal cord transection with repetitive exposure to standing and stepping. Fourth, robotic assistive devices can be used to guide the kinematics of the limbs and thus expose the spinal cord to the new normal activity patterns associated with a particular motor task following spinal cord injury. In addition, such robotic assistive devices can provide immediate quantification of the limb kinematics. Fifth, the behavioural and physiological effects of spinal cord transection are reflected in adaptations in most, if not all, neurotransmitter systems in the lumbosacral spinal cord. Evidence is presented that both the GABAergic and glycinergic inhibitory systems are up-regulated following complete spinal cord transection and that step training results in some aspects of these transmitter systems being down-regulated towards control levels. These concepts and observations demonstrate that (a) the spinal cord can interpret complex afferent information and generate the appropriate motor task; and (b) motor ability can be defined to a large degree by training.

  1. Thermoelectric device for treatment of radiculitis and spinal massage

    NASA Astrophysics Data System (ADS)

    Anatychuk, L. I.; Kobylyansky, R. R.

    2012-06-01

    Results of development of a thermoelectric device that enables controlled cyclic temperature impact on the damaged area of human organism are presented. Unlike the existing medical devices employing direct supply current for thermoelectric module, the present device controls supply current according to time dependence of temperature change assigned by doctor. It is established that such a device is an efficient means of therapy at herniation of intervertebral disks with marked radiculitis and tunicary syndromes, at meningitis, other spinal diseases and back traumas.

  2. Attitudes Towards Individuals with Spinal Cord Injuries

    ERIC Educational Resources Information Center

    Conway, Cassandra Sligh D.; Gooden, Randy; Nowell, Jennifer; Wilson, Navodda

    2010-01-01

    This paper will shed light on the lives of persons with spinal cord injuries by revealing the literature on spinal cord injuries that focuses on research that can shed light on attitudes towards persons with spinal cord injuries. The background literature related to incidences, the definition of spinal cord injury, and vocational opportunities are…

  3. Spinal epidural angiolipoma: A rare cause of spinal cord compression.

    PubMed

    Ghanta, Rajesh K; Koti, Kalyan; Dandamudi, Srinivas

    2012-09-01

    Spinal epidural angiolipomas are rare, benign tumors composed of mature lipocytes admixed with abnormal blood vessels. Only 128 cases of spinal epidural angiolipomas have been reported in literature till now. Spinal angiolipomas are predominantly located in the mid-thoracic region. We report a case of dorsal epidural angiolipoma in a 56-year-old male who presented with paraparesis and was diagnosed to have D4-5 epidural angiolipoma. Total surgical excision of the epidural angiolipoma was done and his paraparesis gradually improved.

  4. Biodegradable biomatrices and bridging the injured spinal cord: the corticospinal tract as a proof of principle.

    PubMed

    Joosten, Elbert A J

    2012-07-01

    Important advances in the development of smart biodegradable implants for axonal regeneration after spinal cord injury have recently been reported. These advances are evaluated in this review with special emphasis on the regeneration of the corticospinal tract. The corticospinal tract is often considered the ultimate challenge in demonstrating whether a repair strategy has been successful in the regeneration of the injured mammalian spinal cord. The extensive know-how of factors and cells involved in the development of the corticospinal tract, and the advances made in material science and tissue engineering technology, have provided the foundations for the optimization of the biomatrices needed for repair. Based on the findings summarized in this review, the future development of smart biodegradable bridges for CST regrowth and regeneration in the injured spinal cord is discussed.

  5. Age-Related Uptake of Heavy Metals in Human Spinal Interneurons

    PubMed Central

    Kum Jew, Stephen

    2016-01-01

    Toxic heavy metals have been implicated in the loss of spinal motoneurons in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). Motoneuron loss in the spinal anterior horn is severe in ALS/MND at the time of death, making this tissue unsuitable for examination. We therefore examined spinal cords of people without muscle weakness to look for any presence of heavy metals that could make these neurons susceptible to damage. Spinal cord samples from 50 individuals aged 1–95 y who had no clinical or histopathological evidence of spinal motoneuron loss were studied. Seven μm formalin-fixed paraffin-embedded sections were stained for heavy metals with silver nitrate autometallography (AMGHM) which detects intracellular mercury, silver or bismuth. Neurons in the spinal cord were classified as interneurons or α-motoneurons based on their site and cell body diameter. Spinal interneurons containing heavy metals were present in 8 of 24 people (33%) aged 61–95 y, but not at younger ages. These AMGHM interneurons were most numerous in the lumbar spinal cord, with moderate numbers in the caudal cervical cord, few in the rostral cervical cord, and almost none in the thoracic cord. All people with AMGHM interneurons had occasional AMGHM staining in α-motoneurons as well. In one man AMGHM staining was present in addition in dorsomedial nucleus and sensory neurons. In conclusion, heavy metals are present in many spinal interneurons, and in a few α-motoneurons, in a large proportion of older people. Damage to inhibitory interneurons from toxic metals in later life could result in excitotoxic injury to motoneurons and may underlie motoneuron injury or loss in conditions such as ALS/MND, multiple sclerosis, sarcopenia and calf fasciculations. PMID:27611334

  6. Age-Related Uptake of Heavy Metals in Human Spinal Interneurons.

    PubMed

    Pamphlett, Roger; Kum Jew, Stephen

    2016-01-01

    Toxic heavy metals have been implicated in the loss of spinal motoneurons in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). Motoneuron loss in the spinal anterior horn is severe in ALS/MND at the time of death, making this tissue unsuitable for examination. We therefore examined spinal cords of people without muscle weakness to look for any presence of heavy metals that could make these neurons susceptible to damage. Spinal cord samples from 50 individuals aged 1-95 y who had no clinical or histopathological evidence of spinal motoneuron loss were studied. Seven μm formalin-fixed paraffin-embedded sections were stained for heavy metals with silver nitrate autometallography (AMGHM) which detects intracellular mercury, silver or bismuth. Neurons in the spinal cord were classified as interneurons or α-motoneurons based on their site and cell body diameter. Spinal interneurons containing heavy metals were present in 8 of 24 people (33%) aged 61-95 y, but not at younger ages. These AMGHM interneurons were most numerous in the lumbar spinal cord, with moderate numbers in the caudal cervical cord, few in the rostral cervical cord, and almost none in the thoracic cord. All people with AMGHM interneurons had occasional AMGHM staining in α-motoneurons as well. In one man AMGHM staining was present in addition in dorsomedial nucleus and sensory neurons. In conclusion, heavy metals are present in many spinal interneurons, and in a few α-motoneurons, in a large proportion of older people. Damage to inhibitory interneurons from toxic metals in later life could result in excitotoxic injury to motoneurons and may underlie motoneuron injury or loss in conditions such as ALS/MND, multiple sclerosis, sarcopenia and calf fasciculations. PMID:27611334

  7. Age-Related Uptake of Heavy Metals in Human Spinal Interneurons.

    PubMed

    Pamphlett, Roger; Kum Jew, Stephen

    2016-01-01

    Toxic heavy metals have been implicated in the loss of spinal motoneurons in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). Motoneuron loss in the spinal anterior horn is severe in ALS/MND at the time of death, making this tissue unsuitable for examination. We therefore examined spinal cords of people without muscle weakness to look for any presence of heavy metals that could make these neurons susceptible to damage. Spinal cord samples from 50 individuals aged 1-95 y who had no clinical or histopathological evidence of spinal motoneuron loss were studied. Seven μm formalin-fixed paraffin-embedded sections were stained for heavy metals with silver nitrate autometallography (AMGHM) which detects intracellular mercury, silver or bismuth. Neurons in the spinal cord were classified as interneurons or α-motoneurons based on their site and cell body diameter. Spinal interneurons containing heavy metals were present in 8 of 24 people (33%) aged 61-95 y, but not at younger ages. These AMGHM interneurons were most numerous in the lumbar spinal cord, with moderate numbers in the caudal cervical cord, few in the rostral cervical cord, and almost none in the thoracic cord. All people with AMGHM interneurons had occasional AMGHM staining in α-motoneurons as well. In one man AMGHM staining was present in addition in dorsomedial nucleus and sensory neurons. In conclusion, heavy metals are present in many spinal interneurons, and in a few α-motoneurons, in a large proportion of older people. Damage to inhibitory interneurons from toxic metals in later life could result in excitotoxic injury to motoneurons and may underlie motoneuron injury or loss in conditions such as ALS/MND, multiple sclerosis, sarcopenia and calf fasciculations.

  8. [Clinical use of spinal or epidural steroids].

    PubMed

    Marinangeli, F; Ciccozzi, A; Donatelli, F; Paladini, A; Varrassi, G

    2002-01-01

    Steroids, drugs with potent antiinflammatory properties on the damaged nervous roots, have been especially used as adjuvants of local anesthetics, by spinal route, in the treatments of low-back pain. Spinal route was chosen to obtain a higher local concentration of drug, with few systemic side effects and to improve drug's action mechanism. Steroids seem to interact with GABA receptors and thus control neural excitability through a stabilising effect on membranes, modification of nervous conduction and membrane hyperpolarization, in supraspinal and spinal site. Epidural steroids are especially used in the treatment of low back pain due to irritation of nervous roots. They have been administered alone or in association with local anesthetics and/or saline solution. Slow release formulations have been generally used (methylprednisolone acetate, and triamcinolone diacetate). Other indications of epidural steroids are: postoperative hemilaminectomy pain, prevention of post herpetic neuralgia, degenerative ostheoartrithis. Intra-thecal steroids have been frequently used in the treatment of lumbar radiculopathy due to discopathy, as an alternative treatment when epidural administration is ineffective. Positive results have been obtained with methylprednisolone acetate, alone or in association with local anesthetics. Complications related to intraspinal steroids injections are due to execution of the block and side effects of drugs. Complications associated with intrathecal steroids are more frequent and severe than epidural injections and include: adhesive arachnoiditis, aseptic meningitis, cauda equina syndrome. Steroidal toxicity seems to be related to the polyethylenic glycole vehicle. Anyway, slow release formulations contain less concentrated polyethylenic glycole. The epidural administration, a correct dilution of steroid with local anesthetics solution and/or saline solution, and a limited number of injections (no more than three) allows a significant reduction of

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

    PubMed Central

    Hui, Subhra Prakash; Nag, Tapas Chandra; Ghosh, Sukla

    2015-01-01

    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. PMID:26630262

  10. Engineering considerations for process development in mammalian cell cultivation.

    PubMed

    Zhang, Hu; Wang, Weixiang; Quan, Chunshan; Fan, Shengdi

    2010-01-01

    Mammalian cell cultivation plays a great role in producing protein therapeutics in the last decades. Many engineering parameters are considered for optimization during process development in mammalian cell cultivation, only shear and mixing are especially highlighted in this paper. It is believed that shear stress due to agitation has been over-estimated to damage cells, but shear may result in nonlethal physiological responses. There is no cell damage in the regions where bubbles form, break up and coalescence, but shear stress becomes significant in the wake of rising bubbles and causes great damage to cells in bubble burst regions. Mixing is not sufficient to provide homogeneous dissolved oxygen tension, pH, CO2 and nutrients in large-scale bioreactors, which can bring severe problems for cell growth, product formation and process control. Scale-down reactors have been developed to address mixing and shear problems for parallel operations. Engineering characterization in conventional and recently developed scale-down bioreactors has been briefly introduced. Process challenges for cultivation of industrial cell lines in high cell densities as well as cultivation of stem cells and other human cells for regenerative medicine, tissue engineering and gene therapy are prospected. Important techniques, such as micromanipulation and nanomanipulation (optical tweezers) for single cell analysis, computational fluid dynamics (CFD) for shear and mixing characterization, and miniaturized bioreactors, are being developed to address those challenges. PMID:19929819

  11. Spinal cord injury enables aromatic L-amino acid decarboxylase cells to synthesize monoamines.

    PubMed

    Wienecke, Jacob; Ren, Li-Qun; Hultborn, Hans; Chen, Meng; Møller, Morten; Zhang, Yifan; Zhang, Mengliang

    2014-09-01

    Serotonin (5-HT), an important modulator of both sensory and motor functions in the mammalian spinal cord, originates mainly in the raphe nuclei of the brainstem. However, following complete transection of the spinal cord, small amounts of 5-HT remain detectable below the lesion. It has been suggested, but not proven, that this residual 5-HT is produced by intraspinal 5-HT neurons. Here, we show by immunohistochemical techniques that cells containing the enzyme aromatic l-amino acid decarboxylase (AADC) occur not only near the central canal, as reported by others, but also in the intermediate zone and dorsal horn of the spinal gray matter. We show that, following complete transection of the rat spinal cord at S2 level, AADC cells distal to the lesion acquire the ability to produce 5-HT from its immediate precursor, 5-hydroxytryptophan. Our results indicate that this phenotypic change in spinal AADC cells is initiated by the loss of descending 5-HT projections due to spinal cord injury (SCI). By in vivo and in vitro electrophysiology, we show that 5-HT produced by AADC cells increases the excitability of spinal motoneurons. The phenotypic change in AADC cells appears to result from a loss of inhibition by descending 5-HT neurons and to be mediated by 5-HT1B receptors expressed by AADC cells. These findings indicate that AADC cells are a potential source of 5-HT at spinal levels below an SCI. The production of 5-HT by AADC cells, together with an upregulation of 5-HT2 receptors, offers a partial explanation of hyperreflexia below a chronic SCI. PMID:25186745

  12. Preferred locomotor phase of activity of lumbar interneurons during air-stepping in subchronic spinal cats.

    PubMed

    AuYong, Nicholas; Ollivier-Lanvin, Karen; Lemay, Michel A

    2011-03-01

    Spinal locomotor circuits are intrinsically capable of driving a variety of behaviors such as stepping, scratching, and swimming. Based on an observed rostrocaudal wave of activity in the motoneuronal firing during locomotor tasks, the traveling-wave hypothesis proposes that spinal interneuronal firing follows a similar rostrocaudal pattern of activation, suggesting the presence of spatially organized interneuronal modules within the spinal motor system. In this study, we examined if the spatial organization of the lumbar interneuronal activity patterns during locomotor activity in the adult mammalian spinal cord was consistent with a traveling-wave organizational scheme. The activity of spinal interneurons within the lumbar intermediate zone was examined during air-stepping in subchronic spinal cats. The preferred phase of interneuronal activity during a step cycle was determined using circular statistics. We found that the preferred phases of lumbar interneurons from both sides of the cord were evenly distributed over the entire step cycle with no indication of functional groupings. However, when units were subcategorized according to spinal hemicords, the preferred phases of units on each side largely fell around the period of extensor muscle activity on each side. In addition, there was no correlation between the preferred phases of units and their rostrocaudal locations along the spinal cord with preferred phases corresponding to both flexion and extension phases of the step cycle found at every rostrocaudal level of the cord. These results are consistent with the hypothesis that interneurons operate as part of a longitudinally distributed network rather than a rostrocaudally organized traveling-wave network.

  13. A Neonatal Mouse Spinal Cord Compression Injury Model.

    PubMed

    Züchner, Mark; Glover, Joel C; Boulland, Jean-Luc

    2016-01-01

    Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal cord. A major current area of research is focused on the mechanisms of adaptive plasticity that underlie spontaneous or induced functional recovery following SCI. Spontaneous functional recovery is reported to be greater early in life, raising interesting questions about how adaptive plasticity changes as the spinal cord develops. To facilitate investigation of this dynamic, we have developed a SCI model in the neonatal mouse. The model has relevance for pediatric SCI, which is too little studied. Because neural plasticity in the adult involves some of the same mechanisms as neural plasticity in early life(1), this model may potentially have some relevance also for adult SCI. Here we describe the entire procedure for generating a reproducible spinal cord compression (SCC) injury in the neonatal mouse as early as postnatal (P) day 1. SCC is achieved by performing a laminectomy at a given spinal level (here described at thoracic levels 9-11) and then using a modified Yasargil aneurysm mini-clip to rapidly compress and decompress the spinal cord. As previously described, the injured neonatal mice can be tested for behavioral deficits or sacrificed for ex vivo physiological analysis of synaptic connectivity using electrophysiological and high-throughput optical recording techniques(1). Earlier and ongoing studies using behavioral and physiological assessment have demonstrated a dramatic, acute impairment of hindlimb motility followed by a complete functional recovery within 2 weeks, and the first evidence of changes in functional circuitry at the level of identified descending synaptic connections(1). PMID:27078037

  14. A Neonatal Mouse Spinal Cord Compression Injury Model

    PubMed Central

    Züchner, Mark; Glover, Joel C.; Boulland, Jean-Luc

    2016-01-01

    Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal cord. A major current area of research is focused on the mechanisms of adaptive plasticity that underlie spontaneous or induced functional recovery following SCI. Spontaneous functional recovery is reported to be greater early in life, raising interesting questions about how adaptive plasticity changes as the spinal cord develops. To facilitate investigation of this dynamic, we have developed a SCI model in the neonatal mouse. The model has relevance for pediatric SCI, which is too little studied. Because neural plasticity in the adult involves some of the same mechanisms as neural plasticity in early life1, this model may potentially have some relevance also for adult SCI. Here we describe the entire procedure for generating a reproducible spinal cord compression (SCC) injury in the neonatal mouse as early as postnatal (P) day 1. SCC is achieved by performing a laminectomy at a given spinal level (here described at thoracic levels 9-11) and then using a modified Yasargil aneurysm mini-clip to rapidly compress and decompress the spinal cord. As previously described, the injured neonatal mice can be tested for behavioral deficits or sacrificed for ex vivo physiological analysis of synaptic connectivity using electrophysiological and high-throughput optical recording techniques1. Earlier and ongoing studies using behavioral and physiological assessment have demonstrated a dramatic, acute impairment of hindlimb motility followed by a complete functional recovery within 2 weeks, and the first evidence of changes in functional circuitry at the level of identified descending synaptic connections1. PMID:27078037

  15. From Immunity and Vaccines to Mammalian Regeneration

    PubMed Central

    Heber-Katz, Ellen

    2015-01-01

    Our current understanding of major histocompatibility complex (MHC)-mediated antigen presentation in self and nonself immune recognition was derived from immunological studies of autoimmunity and virus-host interactions, respectively. The trimolecular complex of the MHC molecule, antigen, and T-cell receptor accounts for the phenomena of immunodominance and MHC degeneracy in both types of responses and constrains vaccine development. Out of such considerations, we developed a simple peptide vaccine construct that obviates immunodominance, resulting in a broadly protective T-cell response in the absence of antibody. In the course of autoimmunity studies, we identified the MRL mouse strain as a mammalian model of amphibian-like regeneration. A significant level of DNA damage in the cells from this mouse pointed to the role of the cell cycle checkpoint gene CDKN1a, or p21cip1/waf1. The MRL mouse has highly reduced levels of this molecule, and a genetic knockout of this single gene in otherwise nonregenerating strains led to an MRL-type regenerative response, indicating that the ability to regenerate has not been lost during evolution. PMID:26116734

  16. From Immunity and Vaccines to Mammalian Regeneration.

    PubMed

    Heber-Katz, Ellen

    2015-07-15

    Our current understanding of major histocompatibility complex (MHC)-mediated antigen presentation in self and nonself immune recognition was derived from immunological studies of autoimmunity and virus-host interactions, respectively. The trimolecular complex of the MHC molecule, antigen, and T-cell receptor accounts for the phenomena of immunodominance and MHC degeneracy in both types of responses and constrains vaccine development. Out of such considerations, we developed a simple peptide vaccine construct that obviates immunodominance, resulting in a broadly protective T-cell response in the absence of antibody. In the course of autoimmunity studies, we identified the MRL mouse strain as a mammalian model of amphibian-like regeneration. A significant level of DNA damage in the cells from this mouse pointed to the role of the cell cycle checkpoint gene CDKN1a, or p21(cip1/waf1). The MRL mouse has highly reduced levels of this molecule, and a genetic knockout of this single gene in otherwise nonregenerating strains led to an MRL-type regenerative response, indicating that the ability to regenerate has not been lost during evolution. PMID:26116734

  17. Mammalian cells defective in DNA mismatch correction

    SciTech Connect

    Branch, P.; Aquilina, G.; Hess, P.

    1994-12-31

    Mammalian cells counteract the cytotoxicity of methylating agents, including some used in antitumor chemotherapy, by removing the methylated base, O{sup 6}-methylguanine (O{sup 6}-meG) from their DNA. This removal is normally effected by a specific DNA repair enzyme (O{sup 6}-meG-DNA methyltransferase) that is expressed constitutively. In addition, an alternative type of resistance to methylating agents can be acquired after exposure of cells to the drug. This acquired resistance is highly specific for O{sup 6}-meG and is unusual in that alkylation of DNA is normal and there is no increase in the rate of repair of O{sup 6}-meG or any other damaged base. Instead, the cell is able to tolerate the presence of the usually cytotoxic O{sup 6}-meG and to replicate its DNA normally. The ambiguity of base pairing by O{sup 6}-meG and the observation that tolerant cells are also cross-resistant to the structurally similar 6-thioguanine in DNA has led to the suggestion that the cytotoxicity of O{sup 6}-meG (and 6-thioguanine) arises from ineffective attempts at DNA mismatch correction. This model postulates that tolerance arises as a consequence of loss of this important pathway.

  18. Spinal Plasticity following Intermittent Hypoxia: Implications for Spinal Injury

    PubMed Central

    Dale-Nagle, Erica A.; Hoffman, Michael S.; MacFarlane, Peter M.; Satriotomo, Irawan; Lovett-Barr, Mary Rachael; Vinit, Stéphane; Mitchell, Gordon S.

    2011-01-01

    Plasticity is a fundamental property of the neural system controlling breathing. One frequently studied model of respiratory plasticity is long-term facilitation of phrenic motor output (pLTF) following acute intermittent hypoxia (AIH). pLTF arises from spinal plasticity, increasing respiratory motor output through a mechanism that requires new synthesis of brain derived neurotrophic factor (BDNF), activation of its high affinity receptor, tropomyosin-related kinase B (TrkB) and extracellular-related kinase (ERK) mitogen-activated protein (MAP) kinase signaling in or near phrenic motor neurons. Since intermittent hypoxia induces spinal plasticity, we are exploring the potential to harness repetitive AIH as a means of inducing functional recovery in conditions causing respiratory insufficiency, such as cervical spinal injury. Since repetitive AIH induces phenotypic plasticity in respiratory and motor neurons, it may restore respiratory motor function in patients with incomplete spinal injury. PMID:20536940

  19. An update on spinal cord injury research.

    PubMed

    Cao, He-Qi; Dong, Er-Dan

    2013-02-01

    Spinal cord injury (SCI) can have a range of debilitating effects and permanently alter the capabilities and quality of life of survivors. The first specialized centers of care for SCI were established in 1944 and since then an increasing amount of research has been carried out in this area. Despite this, the present treatment and care levels for SCI are not comparable to those in other areas of medicine. In the clinic, the aim of SCI treatment is primarily to limit secondary damage by reducing compression in trauma spots and stabilizing the spinal column. Currently, no effective strategy for functional recovery is offered. In this review, we focus on research progress on the molecular mechanisms underlying SCI, and assess the treatment outcomes of SCI in animal models, i.e., neurotrophins and stem cells are discussed as pre-clinical therapies in animal models. We also assess the resources available and national research projects carried out on SCI in China in recent years, as well as making recommendations for the future allocation of funds in this area.

  20. Relating Histopathology and Mechanical Strain in Experimental Contusion Spinal Cord Injury in a Rat Model

    PubMed Central

    Liu, Jie; Yung, Andrew; Cripton, Peter; Kozlowski, Piotr; Tetzlaff, Wolfram; Oxland, Thomas

    2016-01-01

    Abstract During traumatic spinal cord injury (SCI), the spinal cord is subject to external displacements that result in damage of neural tissues. These displacements produce complex internal deformations, or strains, of the spinal cord parenchyma. The aim of this study is to determine a relationship between these internal strains during SCI and primary damage to spinal cord gray matter (GM) in an in vivo rat contusion model. Using magnetic resonance imaging and novel image registration methods, we measured three-dimensional (3D) mechanical strain in in vivo rat cervical spinal cord (n = 12) during an imposed contusion injury. We then assessed expression of the neuronal transcription factor, neuronal nuclei (NeuN), in ventral horns of GM (at the epicenter of injury as well as at intervals cranially and caudally), immediately post-injury. We found that minimum principal strain was most strongly correlated with loss of NeuN stain across all animals (R2 = 0.19), but varied in strength between individual animals (R2 = 0.06–0.52). Craniocaudal distribution of anatomical damage was similar to measured strain distribution. A Monte Carlo simulation was used to assess strain field error, and minimum principal strain (which ranged from 8% to 36% in GM ventral horns) exhibited a standard deviation of 2.6% attributed to the simulated error. This study is the first to measure 3D deformation of the spinal cord and relate it to patterns of ensuing tissue damage in an in vivo model. It provides a platform on which to build future studies addressing the tolerance of spinal cord tissue to mechanical deformation. PMID:26729511

  1. Relating Histopathology and Mechanical Strain in Experimental Contusion Spinal Cord Injury in a Rat Model.

    PubMed

    Bhatnagar, Tim; Liu, Jie; Yung, Andrew; Cripton, Peter; Kozlowski, Piotr; Tetzlaff, Wolfram; Oxland, Thomas

    2016-09-15

    During traumatic spinal cord injury (SCI), the spinal cord is subject to external displacements that result in damage of neural tissues. These displacements produce complex internal deformations, or strains, of the spinal cord parenchyma. The aim of this study is to determine a relationship between these internal strains during SCI and primary damage to spinal cord gray matter (GM) in an in vivo rat contusion model. Using magnetic resonance imaging and novel image registration methods, we measured three-dimensional (3D) mechanical strain in in vivo rat cervical spinal cord (n = 12) during an imposed contusion injury. We then assessed expression of the neuronal transcription factor, neuronal nuclei (NeuN), in ventral horns of GM (at the epicenter of injury as well as at intervals cranially and caudally), immediately post-injury. We found that minimum principal strain was most strongly correlated with loss of NeuN stain across all animals (R(2) = 0.19), but varied in strength between individual animals (R(2) = 0.06-0.52). Craniocaudal distribution of anatomical damage was similar to measured strain distribution. A Monte Carlo simulation was used to assess strain field error, and minimum principal strain (which ranged from 8% to 36% in GM ventral horns) exhibited a standard deviation of 2.6% attributed to the simulated error. This study is the first to measure 3D deformation of the spinal cord and relate it to patterns of ensuing tissue damage in an in vivo model. It provides a platform on which to build future studies addressing the tolerance of spinal cord tissue to mechanical deformation.

  2. Contribution of bone marrow-derived endothelial progenitor cells to neovascularization and astrogliosis following spinal cord injury.

    PubMed

    Kamei, Naosuke; Kwon, Sang-Mo; Kawamoto, Atsuhiko; Ii, Masaaki; Ishikawa, Masakazu; Ochi, Mitsuo; Asahara, Takayuki

    2012-12-01

    Spinal cord injury causes initial mechanical damage, followed by ischemia-induced, secondary degeneration, worsening the tissue damage. Although endothelial progenitor cells (EPCs) have been reported to play an important role for pathophysiological neovascularization in various ischemic tissues, the EPC kinetics following spinal cord injury have never been elucidated. In this study, we therefore assessed the in vivo kinetics of bone marrow-derived EPCs by EPC colony-forming assay and bone marrow transplantation from Tie2/lacZ transgenic mice into wild-type mice with spinal cord injury. The number of circulating mononuclear cells and EPC colonies formed by the mononuclear cells peaked at day 3 postspinal cord injury. Bone marrow transplantation study revealed that bone marrow-derived EPCs recruited into the injured spinal cord markedly increased at day 7, when neovascularization and astrogliosis drastically occurred in parallel with axon growth in the damaged tissue. To elucidate further the contribution of EPCs to recovery after spinal cord injury, exogenous EPCs were systemically infused immediately after the injury. The administered EPCs were incorporated into the injured spinal cord and accelerated neovascularization and astrogliosis. These findings suggest that bone marrow-derived EPCs may contribute to the tissue repair by augmenting neovascularization and astrogliosis following spinal cord injury.

  3. Evolutionary paths to mammalian cochleae.

    PubMed

    Manley, Geoffrey A

    2012-12-01

    Evolution of the cochlea and high-frequency hearing (>20 kHz; ultrasonic to humans) in mammals has been a subject of research for many years. Recent advances in paleontological techniques, especially the use of micro-CT scans, now provide important new insights that are here reviewed. True mammals arose more than 200 million years (Ma) ago. Of these, three lineages survived into recent geological times. These animals uniquely developed three middle ear ossicles, but these ossicles were not initially freely suspended as in modern mammals. The earliest mammalian cochleae were only about 2 mm long and contained a lagena macula. In the multituberculate and monotreme mammalian lineages, the cochlea remained relatively short and did not coil, even in modern representatives. In the lineage leading to modern therians (placental and marsupial mammals), cochlear coiling did develop, but only after a period of at least 60 Ma. Even Late Jurassic mammals show only a 270 ° cochlear coil and a cochlear canal length of merely 3 mm. Comparisons of modern organisms, mammalian ancestors, and the state of the middle ear strongly suggest that high-frequency hearing (>20 kHz) was not realized until the early Cretaceous (~125 Ma). At that time, therian mammals arose and possessed a fully coiled cochlea. The evolution of modern features of the middle ear and cochlea in the many later lineages of therians was, however, a mosaic and different features arose at different times. In parallel with cochlear structural evolution, prestins in therian mammals evolved into effective components of a new motor system. Ultrasonic hearing developed quite late-the earliest bat cochleae (~60 Ma) did not show features characteristic of those of modern bats that are sensitive to high ultrasonic frequencies.

  4. Evolutionary paths to mammalian cochleae.

    PubMed

    Manley, Geoffrey A

    2012-12-01

    Evolution of the cochlea and high-frequency hearing (>20 kHz; ultrasonic to humans) in mammals has been a subject of research for many years. Recent advances in paleontological techniques, especially the use of micro-CT scans, now provide important new insights that are here reviewed. True mammals arose more than 200 million years (Ma) ago. Of these, three lineages survived into recent geological times. These animals uniquely developed three middle ear ossicles, but these ossicles were not initially freely suspended as in modern mammals. The earliest mammalian cochleae were only about 2 mm long and contained a lagena macula. In the multituberculate and monotreme mammalian lineages, the cochlea remained relatively short and did not coil, even in modern representatives. In the lineage leading to modern therians (placental and marsupial mammals), cochlear coiling did develop, but only after a period of at least 60 Ma. Even Late Jurassic mammals show only a 270 ° cochlear coil and a cochlear canal length of merely 3 mm. Comparisons of modern organisms, mammalian ancestors, and the state of the middle ear strongly suggest that high-frequency hearing (>20 kHz) was not realized until the early Cretaceous (~125 Ma). At that time, therian mammals arose and possessed a fully coiled cochlea. The evolution of modern features of the middle ear and cochlea in the many later lineages of therians was, however, a mosaic and different features arose at different times. In parallel with cochlear structural evolution, prestins in therian mammals evolved into effective components of a new motor system. Ultrasonic hearing developed quite late-the earliest bat cochleae (~60 Ma) did not show features characteristic of those of modern bats that are sensitive to high ultrasonic frequencies. PMID:22983571

  5. Patterning of the mammalian cochlea

    PubMed Central

    Cantos, Raquel; Cole, Laura K.; Acampora, Dario; Simeone, Antonio; Wu, Doris K.

    2000-01-01

    The mammalian cochlea is sophisticated in its function and highly organized in its structure. Although the anatomy of this sense organ has been well documented, the molecular mechanisms underlying its development have remained elusive. Information generated from mutant and knockout mice in recent years has increased our understanding of cochlear development and physiology. This article discusses factors important for the development of the inner ear and summarizes cochlear phenotypes of mutant and knockout mice, particularly Otx and Otx2. We also present data on gross development of the mouse cochlea. PMID:11050199

  6. Putrescine catabolism in mammalian brain

    PubMed Central

    Seiler, N.; Al-Therib, M. J.

    1974-01-01

    In contrast with putrescine (1,4-diaminobutane), which is a substrate of diamine oxidase, monoacetylputrescine is oxidatively deaminated both in vitro and in vivo by monoamine oxidase. The product of this reaction is N-acetyl-γ-aminobutyrate. The existence of a degradative pathway in mammalian brain for putrescine is shown, which comprises acetylation of putrescine, oxidative deamination of monoacetylputrescine to N-acetyl-γ-aminobutyrate, transformation of N-acetyl-γ-aminobutyrate to γ-aminobutyrate and degradation of γ-aminobutyrate to CO2 via the tricarboxylic acid cycle. PMID:4156831

  7. Markers of epidermal stem cell subpopulations in adult mammalian skin.

    PubMed

    Kretzschmar, Kai; Watt, Fiona M

    2014-10-01

    The epidermis is the outermost layer of mammalian skin and comprises a multilayered epithelium, the interfollicular epidermis, with associated hair follicles, sebaceous glands, and eccrine sweat glands. As in other epithelia, adult stem cells within the epidermis maintain tissue homeostasis and contribute to repair of tissue damage. The bulge of hair follicles, where DNA-label-retaining cells reside, was traditionally regarded as the sole epidermal stem cell compartment. However, in recent years multiple stem cell populations have been identified. In this review, we discuss the different stem cell compartments of adult murine and human epidermis, the markers that they express, and the assays that are used to characterize epidermal stem cell properties.

  8. Cytometry of deoxyribonuclei acid content and morphology of mammalian sperm

    SciTech Connect

    Gledhill, B.L.

    1983-01-01

    Because spermatogenesis is exquisitely sensitive to external influences, sperm can serve as a biological dosimeter. Advances in interpreting induced sperm abnormalities require a better understanding of sperm characteristics. This report reviews the application of several methods for automated, quantitative detection of shape changes, methods that are faster and more sensitive than conventional subjective technqiues. Variability of sperm deoxyribonucleic acid content as a bioassay of genetic damage is explored, and limitations of the bioassay are discussed. New flow cytometric techniques that could lead to sexing mammalian sperm are examined.

  9. Nestin-Positive Ependymal Cells Are Increased in the Human Spinal Cord after Traumatic Central Nervous System Injury

    PubMed Central

    Cawsey, Thomas; Duflou, Johan; Weickert, Cynthia Shannon

    2015-01-01

    Abstract Endogenous neural progenitor cell niches have been identified in adult mammalian brain and spinal cord. Few studies have examined human spinal cord tissue for a neural progenitor cell response in disease or after injury. Here, we have compared cervical spinal cord sections from 14 individuals who died as a result of nontraumatic causes (controls) with 27 who died from injury with evidence of trauma to the central nervous system. Nestin immunoreactivity was used as a marker of neural progenitor cell response. There were significant increases in the percentage of ependymal cells that were nestin positive between controls and trauma cases. When sections from lumbar and thoracic spinal cord were available, nestin positivity was seen at all three spinal levels, suggesting that nestin reactivity is not simply a localized reaction to injury. There was a positive correlation between the percentage of ependymal cells that were nestin positive and post-injury survival time but not for age, postmortem delay, or glial fibrillary acidic protein (GFAP) immunoreactivity. No double-labelled nestin and GFAP cells were identified in the ependymal, subependymal, or parenchymal regions of the spinal cord. We need to further characterize this subset of ependymal cells to determine their role after injury, whether they are a population of neural progenitor cells with the potential for proliferation, migration, and differentiation for spinal cord repair, or whether they have other roles more in line with hypothalamic tanycytes, which they closely resemble. PMID:25599268

  10. Spinal Chondrosarcoma: A Review

    PubMed Central

    Katonis, Pavlos; Alpantaki, Kalliopi; Michail, Konstantinos; Lianoudakis, Stratos; Christoforakis, Zaharias; Tzanakakis, George; Karantanas, Apostolos

    2011-01-01

    Chondrosarcoma is the third most common primary malignant bone tumor. Yet the spine represents the primary location in only 2% to 12% of these tumors. Almost all patients present with pain and a palpable mass. About 50% of patients present with neurologic symptoms. Chemotherapy and radiotherapy are generally unsuccessful while surgical resection is the treatment of choice. Early diagnosis and careful surgical staging are important to achieve adequate management. This paper provides an overview of the histopathological classification, clinical presentation, and diagnostic procedures regarding spinal chondrosarcoma. We highlight specific treatment modalities and discuss which is truly the most suitable approach for these tumors. Abstracts and original articles in English investigating these tumors were searched and analyzed with the use of the PubMed and Scopus databases with “chondrosarcoma and spine” as keywords. PMID:21437176

  11. Simulation in spinal diseases.

    PubMed

    Aso Escario, José; Martínez Quiñones, José Vicente; Aso Vizán, Alberto; Arregui Calvo, Ricardo; Bernal Lafuente, Marta; Alcázar Crevillén, Andrés

    2014-01-01

    Simulation is frequent in spinal disease, resulting in problems for specialists like Orthopedic Surgeons, Neurosurgeons, Reumathologists, etc. Simulation requires demonstration of the intentional production of false or exaggerated symptoms following an external incentive. The clinician has difficulties in demonstrating these criteria, resulting in misdiagnosis of simulation or misinterpretation of the normal patient as a simulator, with the possibility of iatrogenic distress and litigation. We review simulation-related problems in spine, proposing a terminological, as well as a diagnostic strategy including clinical and complementary diagnosis, as a way to avoid misinterpretation and minimize the iatrogenic distress and liability Based on the clinical-Forensic author's expertise, the literature is analyzed and the terminology readdressed to develop new terms (inconsistences, incongruences, discrepancies and contradictions). Clinical semiology and complementary test are adapted to the new scenario. Diagnostic strategy relies on anamnesis, clinical and complementary tests, adapting them to a uniform terminology with clear meaning of signs and symptoms.

  12. Simulation in spinal diseases.

    PubMed

    Aso Escario, José; Martínez Quiñones, José Vicente; Aso Vizán, Alberto; Arregui Calvo, Ricardo; Bernal Lafuente, Marta; Alcázar Crevillén, Andrés

    2014-01-01

    Simulation is frequent in spinal disease, resulting in problems for specialists like Orthopedic Surgeons, Neurosurgeons, Reumathologists, etc. Simulation requires demonstration of the intentional production of false or exaggerated symptoms following an external incentive. The clinician has difficulties in demonstrating these criteria, resulting in misdiagnosis of simulation or misinterpretation of the normal patient as a simulator, with the possibility of iatrogenic distress and litigation. We review simulation-related problems in spine, proposing a terminological, as well as a diagnostic strategy including clinical and complementary diagnosis, as a way to avoid misinterpretation and minimize the iatrogenic distress and liability Based on the clinical-Forensic author's expertise, the literature is analyzed and the terminology readdressed to develop new terms (inconsistences, incongruences, discrepancies and contradictions). Clinical semiology and complementary test are adapted to the new scenario. Diagnostic strategy relies on anamnesis, clinical and complementary tests, adapting them to a uniform terminology with clear meaning of signs and symptoms. PMID:24913963

  13. MAMMALIAN DNA IN PCR REAGENTS

    EPA Science Inventory

    Ancient DNA analysis is becoming widespread. These studies use polymerase chain reaction (PCR) to amplify minute quantities of heavily damaged template. Unusual steps are taken to achieve the sensitivity necessary to detect ancient DNA, including high- cycle PCR amplification t...

  14. Two-photon Imaging of Cellular Dynamics in the Mouse Spinal Cord

    PubMed Central

    Weinger, Jason G.; Greenberg, Milton L.; Matheu, Melanie P.; Parker, Ian; Walsh, Craig M.; Lane, Thomas E.; Cahalan, Michael D.

    2016-01-01

    Two-photon (2P) microscopy is utilized to reveal cellular dynamics and interactions deep within living, intact tissues. Here, we present a method for live-cell imaging in the murine spinal cord. This technique is uniquely suited to analyze neural precursor cell (NPC) dynamics following transplantation into spinal cords undergoing neuroinflammatory demyelinating disorders. NPCs migrate to sites of axonal damage, proliferate, differentiate into oligodendrocytes, and participate in direct remyelination. NPCs are thereby a promising therapeutic treatment to ameliorate chronic demyelinating diseases. Because transplanted NPCs migrate to the damaged areas on the ventral side of the spinal cord, traditional intravital 2P imaging is impossible, and only information on static interactions was previously available using histochemical staining approaches. Although this method was generated to image transplanted NPCs in the ventral spinal cord, it can be applied to numerous studies of transplanted and endogenous cells throughout the entire spinal cord. In this article, we demonstrate the preparation and imaging of a spinal cord with enhanced yellow fluorescent protein-expressing axons and enhanced green fluorescent protein-expressing transplanted NPCs. PMID:25742043

  15. Rebuilding motor function of the spinal cord based on functional electrical stimulation

    PubMed Central

    Shen, Xiao-yan; Du, Wei; Huang, Wei; Chen, Yi

    2016-01-01

    Rebuilding the damaged motor function caused by spinal cord injury is one of the most serious challenges in clinical neuroscience. The function of the neural pathway under the damaged sites can be rebuilt using functional electrical stimulation technology. In this study, the locations of motor function sites in the lumbosacral spinal cord were determined with functional electrical stimulation technology. A three-dimensional map of the lumbosacral spinal cord comprising the relationship between the motor function sites and the corresponding muscle was drawn. Based on the individual experimental parameters and normalized coordinates of the motor function sites, the motor function sites that control a certain muscle were calculated. Phasing pulse sequences were delivered to the determined motor function sites in the spinal cord and hip extension, hip flexion, ankle plantarflexion, and ankle dorsiflexion movements were successfully achieved. The results show that the map of the spinal cord motor function sites was valid. This map can provide guidance for the selection of electrical stimulation sites during the rebuilding of motor function after spinal cord injury.

  16. Two-photon imaging of cellular dynamics in the mouse spinal cord.

    PubMed

    Weinger, Jason G; Greenberg, Milton L; Matheu, Melanie P; Parker, Ian; Walsh, Craig M; Lane, Thomas E; Cahalan, Michael D

    2015-02-22

    Two-photon (2P) microscopy is utilized to reveal cellular dynamics and interactions deep within living, intact tissues. Here, we present a method for live-cell imaging in the murine spinal cord. This technique is uniquely suited to analyze neural precursor cell (NPC) dynamics following transplantation into spinal cords undergoing neuroinflammatory demyelinating disorders. NPCs migrate to sites of axonal damage, proliferate, differentiate into oligodendrocytes, and participate in direct remyelination. NPCs are thereby a promising therapeutic treatment to ameliorate chronic demyelinating diseases. Because transplanted NPCs migrate to the damaged areas on the ventral side of the spinal cord, traditional intravital 2P imaging is impossible, and only information on static interactions was previously available using histochemical staining approaches. Although this method was generated to image transplanted NPCs in the ventral spinal cord, it can be applied to numerous studies of transplanted and endogenous cells throughout the entire spinal cord. In this article, we demonstrate the preparation and imaging of a spinal cord with enhanced yellow fluorescent protein-expressing axons and enhanced green fluorescent protein-expressing transplanted NPCs.

  17. Rebuilding motor function of the spinal cord based on functional electrical stimulation.

    PubMed

    Shen, Xiao-Yan; Du, Wei; Huang, Wei; Chen, Yi

    2016-08-01

    Rebuilding the damaged motor function caused by spinal cord injury is one of the most serious challenges in clinical neuroscience. The function of the neural pathway under the damaged sites can be rebuilt using functional electrical stimulation technology. In this study, the locations of motor function sites in the lumbosacral spinal cord were determined with functional electrical stimulation technology. A three-dimensional map of the lumbosacral spinal cord comprising the relationship between the motor function sites and the corresponding muscle was drawn. Based on the individual experimental parameters and normalized coordinates of the motor function sites, the motor function sites that control a certain muscle were calculated. Phasing pulse sequences were delivered to the determined motor function sites in the spinal cord and hip extension, hip flexion, ankle plantarflexion, and ankle dorsiflexion movements were successfully achieved. The results show that the map of the spinal cord motor function sites was valid. This map can provide guidance for the selection of electrical stimulation sites during the rebuilding of motor function after spinal cord injury. PMID:27651782

  18. Rebuilding motor function of the spinal cord based on functional electrical stimulation.

    PubMed

    Shen, Xiao-Yan; Du, Wei; Huang, Wei; Chen, Yi

    2016-08-01

    Rebuilding the damaged motor function caused by spinal cord injury is one of the most serious challenges in clinical neuroscience. The function of the neural pathway under the damaged sites can be rebuilt using functional electrical stimulation technology. In this study, the locations of motor function sites in the lumbosacral spinal cord were determined with functional electrical stimulation technology. A three-dimensional map of the lumbosacral spinal cord comprising the relationship between the motor function sites and the corresponding muscle was drawn. Based on the individual experimental parameters and normalized coordinates of the motor function sites, the motor function sites that control a certain muscle were calculated. Phasing pulse sequences were delivered to the determined motor function sites in the spinal cord and hip extension, hip flexion, ankle plantarflexion, and ankle dorsiflexion movements were successfully achieved. The results show that the map of the spinal cord motor function sites was valid. This map can provide guidance for the selection of electrical stimulation sites during the rebuilding of motor function after spinal cord injury.

  19. Rebuilding motor function of the spinal cord based on functional electrical stimulation

    PubMed Central

    Shen, Xiao-yan; Du, Wei; Huang, Wei; Chen, Yi

    2016-01-01

    Rebuilding the damaged motor function caused by spinal cord injury is one of the most serious challenges in clinical neuroscience. The function of the neural pathway under the damaged sites can be rebuilt using functional electrical stimulation technology. In this study, the locations of motor function sites in the lumbosacral spinal cord were determined with functional electrical stimulation technology. A three-dimensional map of the lumbosacral spinal cord comprising the relationship between the motor function sites and the corresponding muscle was drawn. Based on the individual experimental parameters and normalized coordinates of the motor function sites, the motor function sites that control a certain muscle were calculated. Phasing pulse sequences were delivered to the determined motor function sites in the spinal cord and hip extension, hip flexion, ankle plantarflexion, and ankle dorsiflexion movements were successfully achieved. The results show that the map of the spinal cord motor function sites was valid. This map can provide guidance for the selection of electrical stimulation sites during the rebuilding of motor function after spinal cord injury. PMID:27651782

  20. Overview of Spinal Cord Disorders

    MedlinePlus

    ... temperature from the body to the spinal cord. Did You Know... Doctors can often tell where the ... on symptoms and results of a physical examination. Did You Know... Nerves from the lowest parts of ...

  1. What Is Spinal Cord Injury?

    MedlinePlus

    ... lowest point on the spinal cord below which sensory feeling and motor movement diminish or disappear. The ... injury is so severe that almost all feeling (sensory function) and all ability to control movement (motor ...

  2. Management of severe spinal cord injury following hyperbaric exposure.

    PubMed

    Mathew, Bruce; Laden, Gerard

    2015-09-01

    There is an increasing body of evidence that drainage of lumbar cerebrospinal fluid (CSF) improves functional neurological outcome after reperfusion injury to the spinal cord that occasionally follows aortic reconstructive surgery. This beneficial effect is considered owing to lowering of the CSF pressure thereby normalising spinal cord blood flow and reducing the 'secondary' cord injury caused by vascular congestion and cord swelling in the relatively confined spinal canal. Whilst lacking definitive proof, there are convincing randomised controlled trials (RCTs), cohort data and systematic reviews supporting this intervention. The therapeutic window for lumbar CSF drainage requires further elucidation; however, it appears to be days rather than hours post insult. We contend that the same benefit is likely to be achieved following other primary spinal cord injuries that cause cord swelling and elicit the 'secondary' injury. Traditionally the concept of CSF drainage has been considered more applicable to the brain as contained in a 'closed box' by lowering intracranial pressure (ICP) to improve cerebral perfusion pressure (CPP). The control of CPP is intended to limit 'secondary' brain injury and is a key concept of brain injury management. Using microdialysis in the spinal cords of trauma patients, it has been shown that intraspinal pressure (ISP) needs to be kept below 20 mmHg and spinal cord perfusion pressure (SCPP) above 70 mmHg to avoid biochemical evidence of secondary cord damage. Vasopressor have also been used in spinal cord injury to improve perfusion, however complications are common, typically cardiac in nature, and require very careful monitoring; the evidence supporting this approach is notably less convincing. Decompression illness (DCI) of the spinal cord is treated with recompression, hyperbaric oxygen, various medications designed to reduce the inflammatory response and fluid administration to normalise blood pressure and haematocrit. These

  3. An innovative spinal cord injury model for the study of locomotor networks.

    PubMed

    Nistri, A

    2012-03-01

    An acute lesion to the spinal cord triggers complex mechanisms responsible for amplification of the initial damage and its chronicity. In vitro preparations of the rodent spinal cord retain the intrinsic ability to produce locomotor-like discharges from lumbar ventral roots and, thus, offer the opportunity to study the still unclear process of lesion progression in relation to cell number and topography. In addition, these models enable a detailed approach to the molecular mechanisms of damage and to pharmacological tools to counteract them. Using the rat spinal cord in vitro, our laboratory has shown how to reliably produce discrete lesions by applying the glutamate agonist kainate that evokes delayed neuronal loss via a non-apoptotic cell death mechanism termed parthanatos. Parthanatos is believed to be due to mitochondrial damage and exhaustion of cell energy stores caused by hyperactivation of enzymatic systems initially set to repair DNA damage. Locomotor network activity is irreversibly destroyed by kainate in a virtually all-or-none manner, suggesting destruction of a highly-vulnerable cell population crucial for the expression of locomotion. Hypoxic challenge to the spinal cord together with toxic radicals primarily damages white matter cells with deficit (without full suppression) of locomotor network function, while neurons are less vulnerable. Pharmacological agents to inhibit different targets involved in the early pathophysiology of spinal injury provided limited success, indicating that novel approaches based on newly identified steps in the biochemical cascade leading to cell death should be investigated for their potential to improve the outcome of spinal cord injury.

  4. An innovative spinal cord injury model for the study of locomotor networks.

    PubMed

    Nistri, A

    2012-03-01

    An acute lesion to the spinal cord triggers complex mechanisms responsible for amplification of the initial damage and its chronicity. In vitro preparations of the rodent spinal cord retain the intrinsic ability to produce locomotor-like discharges from lumbar ventral roots and, thus, offer the opportunity to study the still unclear process of lesion progression in relation to cell number and topography. In addition, these models enable a detailed approach to the molecular mechanisms of damage and to pharmacological tools to counteract them. Using the rat spinal cord in vitro, our laboratory has shown how to reliably produce discrete lesions by applying the glutamate agonist kainate that evokes delayed neuronal loss via a non-apoptotic cell death mechanism termed parthanatos. Parthanatos is believed to be due to mitochondrial damage and exhaustion of cell energy stores caused by hyperactivation of enzymatic systems initially set to repair DNA damage. Locomotor network activity is irreversibly destroyed by kainate in a virtually all-or-none manner, suggesting destruction of a highly-vulnerable cell population crucial for the expression of locomotion. Hypoxic challenge to the spinal cord together with toxic radicals primarily damages white matter cells with deficit (without full suppression) of locomotor network function, while neurons are less vulnerable. Pharmacological agents to inhibit different targets involved in the early pathophysiology of spinal injury provided limited success, indicating that novel approaches based on newly identified steps in the biochemical cascade leading to cell death should be investigated for their potential to improve the outcome of spinal cord injury. PMID:22407008

  5. Reducing synuclein accumulation improves neuronal survival after spinal cord injury.

    PubMed

    Fogerson, Stephanie M; van Brummen, Alexandra J; Busch, David J; Allen, Scott R; Roychaudhuri, Robin; Banks, Susan M L; Klärner, Frank-Gerrit; Schrader, Thomas; Bitan, Gal; Morgan, Jennifer R

    2016-04-01

    Spinal cord injury causes neuronal death, limiting subsequent regeneration and recovery. Thus, there is a need to develop strategies for improving neuronal survival after injury. Relative to our understanding of axon regeneration, comparatively little is known about the mechanisms that promote the survival of damaged neurons. To address this, we took advantage of lamprey giant reticulospinal neurons whose large size permits detailed examination of post-injury molecular responses at the level of individual, identified cells. We report here that spinal cord injury caused a select subset of giant reticulospinal neurons to accumulate synuclein, a synaptic vesicle-associated protein best known for its atypical aggregation and causal role in neurodegeneration in Parkinson's and other diseases. Post-injury synuclein accumulation took the form of punctate aggregates throughout the somata and occurred selectively in dying neurons, but not in those that survived. In contrast, another synaptic vesicle protein, synaptotagmin, did not accumulate in response to injury. We further show that the post-injury synuclein accumulation was greatly attenuated after single dose application of either the "molecular tweezer" inhibitor, CLR01, or a translation-blocking synuclein morpholino. Consequently, reduction of synuclein accumulation not only improved neuronal survival, but also increased the number of axons in the spinal cord proximal and distal to the lesion. This study is the first to reveal that reducing synuclein accumulation is a novel strategy for improving neuronal survival after spinal cord injury.

  6. Nonlinear Viscoelastic Characterization of the Porcine Spinal Cord

    PubMed Central

    Shetye, Snehal; Troyer, Kevin; Streijger, Femke; Lee, Jae H. T.; Kwon, Brian K.; Cripton, Peter; Puttlitz, Christian M.

    2014-01-01

    Although quasi-static and quasi-linear viscoelastic properties of the spinal cord have been reported previously, there are no published studies that have investigated the fully (strain-dependent) nonlinear viscoelastic properties of the spinal cord. In this study, stress relaxation experiments and dynamic cycling were performed on six fresh porcine lumbar cord specimens to examine their viscoelastic mechanical properties. The stress relaxation data were fitted to a modified superposition formulation and a novel finite ramp time correction technique was applied. The parameters obtained from this fitting methodology were used to predict the average dynamic cyclic viscoelastic behavior of the porcine cord. The data indicate that the porcine spinal cord exhibited fully nonlinear viscoelastic behavior. The average weighted RMSE for a Heaviside ramp fit was 2.8kPa, which was significantly greater (p < 0.001) than that of the nonlinear (comprehensive viscoelastic characterization (CVC) method) fit (0.365kPa). Further, the nonlinear mechanical parameters obtained were able to accurately predict the dynamic behavior, thus exemplifying the reliability of the obtained nonlinear parameters. These parameters will be important for future studies investigating various damage mechanisms of the spinal cord and studies developing high resolution finite elements models of the spine. PMID:24211612

  7. [Subarachnoid hematoma and spinal anesthesia].

    PubMed

    Dupeyrat, A; Dequiré, P M; Mérouani, A; Moullier, P; Eid, G

    1990-01-01

    Two cases of spinal subarachnoid haematoma occurring after spinal anaesthesia are reported. In the first case, lumbar puncture was attempted three times in a 81-year-old man; spinal anaesthesia trial was than abandoned, and the patient given a general anaesthetic. He was given prophylactic calcium heparinate soon after surgery. On the fourth day, the patient became paraparetic. Radioculography revealed a blockage between T10 and L3. Laminectomy was performed to remove the haematoma, but the patient recovered motor activity only very partially. The second case was a 67-year-old man, in whom spinal anaesthesia was easily carried out. He was also given prophylactic calcium heparinate soon after surgery. On the fourth postoperative day, pulmonary embolism was suspected. Heparin treatment was then started. Twelve hours later, lumbar and bilateral buttock pain occurred, which later spread to the neck. On the eighth day, the patient had neck stiffness and two seizures. Emergency laminectomy was carried out, which revealed a subarachnoid haematoma spreading to a level higher than T6 and below L1, with no flow of cerebrospinal fluid, and a non pulsatile spinal cord. Surgery was stopped. The patient died on the following day. Both these cases are similar to those previously reported and point out the role played by anticoagulants. Because early diagnosis of spinal cord compression is difficult, the prognosis is poor, especially in case of paraplegia. PMID:2278424

  8. Neurotrophins and spinal circuit function

    PubMed Central

    Boyce, Vanessa S.; Mendell, Lorne M.

    2014-01-01

    Work early in the last century emphasized the stereotyped activity of spinal circuits based on studies of reflexes. However, the last several decades have focused on the plasticity of these spinal circuits. These considerations began with studies of the effects of monoamines on descending and reflex circuits. In recent years new classes of compounds called growth factors that are found in peripheral nerves and the spinal cord have been shown to affect circuit behavior in the spinal cord. In this review we will focus on the effects of neurotrophins, particularly nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), on spinal circuits. We also discuss evidence that these molecules can modify functions including nociceptive behavior, motor reflexes and stepping behavior. Since these substances and their receptors are normally present in the spinal cord, they could potentially be useful in improving function in disease states and after injury. Here we review recent findings relevant to these translational issues. PMID:24926235

  9. Space radiation effects on plant and mammalian cells

    NASA Astrophysics Data System (ADS)

    Arena, C.; De Micco, V.; Macaeva, E.; Quintens, R.

    2014-11-01

    The study of the effects of ionizing radiation on organisms is related to different research aims. The current review emphasizes the studies on the effects of different doses of sparsely and densely ionizing radiation on living organisms, with the final purpose of highlighting specific and common effects of space radiation in mammals and plants. This topic is extremely relevant in the context of radiation protection from space environment. The response of different organisms to ionizing radiation depends on the radiation quality/dose and/or the intrinsic characteristics of the living system. Macromolecules, in particular DNA, are the critical targets of radiation, even if there is a strong difference between damages encountered by plant and mammalian cells. The differences in structure and metabolism between the two cell types are responsible for the higher resistance of the plant cell compared with its animal counterpart. In this review, we report some recent findings from studies performed in Space or on Earth, simulating space-like levels of radiation with ground-based facilities, to understand the effect of ionizing radiation on mammalian and plant cells. In particular, our attention is focused on genetic alterations and repair mechanisms in mammalian cells and on structures and mechanisms conferring radioresistance to plant cells.

  10. DNA modifications in the mammalian brain

    PubMed Central

    Shin, Jaehoon; Ming, Guo-li; Song, Hongjun

    2014-01-01

    DNA methylation is a crucial epigenetic mark in mammalian development, genomic imprinting, X-inactivation, chromosomal stability and suppressing parasitic DNA elements. DNA methylation in neurons has also been suggested to play important roles for mammalian neuronal functions, and learning and memory. In this review, we first summarize recent discoveries and fundamental principles of DNA modifications in the general epigenetics field. We then describe the profiles of different DNA modifications in the mammalian brain genome. Finally, we discuss roles of DNA modifications in mammalian brain development and function. PMID:25135973

  11. The Mammalian Cervical Vertebrae Blueprint Depends on the T (brachyury) Gene

    PubMed Central

    Kromik, Andreas; Ulrich, Reiner; Kusenda, Marian; Tipold, Andrea; Stein, Veronika M.; Hellige, Maren; Dziallas, Peter; Hadlich, Frieder; Widmann, Philipp; Goldammer, Tom; Baumgärtner, Wolfgang; Rehage, Jürgen; Segelke, Dierck; Weikard, Rosemarie; Kühn, Christa

    2015-01-01

    A key common feature of all but three known mammalian genera is the strict seven cervical vertebrae blueprint, suggesting the involvement of strong conserving selection forces during mammalian radiation. This is further supported by reports indicating that children with cervical ribs die before they reach reproductive age. Hypotheses were put up, associating cervical ribs (homeotic transformations) to embryonal cancer (e.g., neuroblastoma) or ascribing the constraint in cervical vertebral count to the development of the mammalian diaphragm. Here, we describe a spontaneous mutation c.196A > G in the Bos taurus T gene (also known as brachyury) associated with a cervical vertebral homeotic transformation that violates the fundamental mammalian cervical blueprint, but does not preclude reproduction of the affected individual. Genome-wide mapping, haplotype tracking within a large pedigree, resequencing of target genome regions, and bioinformatic analyses unambiguously confirmed the mutant c.196G allele as causal for this previously unknown defect termed vertebral and spinal dysplasia (VSD) by providing evidence for the mutation event. The nonsynonymous VSD mutation is located within the highly conserved T box of the T gene, which plays a fundamental role in eumetazoan body organization and vertebral development. To our knowledge, VSD is the first unequivocally approved spontaneous mutation decreasing cervical vertebrae number in a large mammal. The spontaneous VSD mutation in the bovine T gene is the first in vivo evidence for the hypothesis that the T protein is directly involved in the maintenance of the mammalian seven-cervical vertebra blueprint. It therefore furthers our knowledge of the T-protein function and early mammalian notochord development. PMID:25614605

  12. Finding New Components of the Mammalian Immune System*

    PubMed Central

    Beutler, Bruce

    2016-01-01

    The use of forward genetics to analyze mammalian biology has been dramatically accelerated by methods that make it possible instantly to determine which mutation causes a phenotype. Now it is possible to discover gene function as rapidly as mutations can be created and screened: approximately 1,000 coding changes per week are interrogated in our laboratory. Moreover, it is possible to know approximately how much damage has been done to the genome over time. We estimate that we have damaged or destroyed about one-quarter of all protein encoding genes and tested the effects of variant alleles within these genes three times or more in a set of phenotypic assays that interest us. Only about two years were required to reach this level of saturation. PMID:27487306

  13. Functional Organization of Locomotor Interneurons in the Ventral Lumbar Spinal Cord of the Newborn Rat

    PubMed Central

    Antri, Myriam; Mellen, Nicholas; Cazalets, Jean-René

    2011-01-01

    Although the mammalian locomotor CPG has been localized to the lumbar spinal cord, the functional-anatomical organization of flexor and extensor interneurons has not been characterized. Here, we tested the hypothesis that flexor and extensor interneuronal networks for walking are physically segregated in the lumbar spinal cord. For this purpose, we performed optical recordings and lesion experiments from a horizontally sectioned lumbar spinal cord isolated from neonate rats. This ventral hemi spinal cord preparation produces well-organized fictive locomotion when superfused with 5-HT/NMDA. The dorsal surface of the preparation was visualized using the Ca2+ indicator fluo-4 AM, while simultaneously monitoring motor output at ventral roots L2 and L5. Using calcium imaging, we provided a general mapping view of the interneurons that maintained a stable phase relationship with motor output. We showed that the dorsal surface of L1 segment contains a higher density of locomotor rhythmic cells than the other segments. Moreover, L1 segment lesioning induced the most important changes in the locomotor activity in comparison with lesions at the T13 or L2 segments. However, no lesions led to selective disruption of either flexor or extensor output. In addition, this study found no evidence of functional parcellation of locomotor interneurons into flexor and extensor pools at the dorsal-ventral midline of the lumbar spinal cord of the rat. PMID:21698092

  14. Pathophysiology of primary spinal syringomyelia

    PubMed Central

    Heiss, John D.; Snyder, Kendall; Peterson, Matthew M.; Patronas, Nicholas J.; Butman, John A.; Smith, René K.; DeVroom, Hetty L.; Sansur, Charles A.; Eskioglu, Eric; Kammerer, William A.; Oldfield, Edward H.

    2013-01-01

    Object The pathogenesis of syringomyelia in patients with an associated spinal lesion is incompletely understood. The authors hypothesized that in primary spinal syringomyelia, a subarachnoid block effectively shortens the length of the spinal subarachnoid space (SAS), reducing compliance and the ability of the spinal theca to dampen the subarachnoid CSF pressure waves produced by brain expansion during cardiac systole. This creates exaggerated spinal subarachnoid pressure waves during every heartbeat that act on the spinal cord above the block to drive CSF into the spinal cord and create a syrinx. After a syrinx is formed, enlarged subarachnoid pressure waves compress the external surface of the spinal cord, propel the syrinx fluid, and promote syrinx progression. Methods To elucidate the pathophysiology, the authors prospectively studied 36 adult patients with spinal lesions obstructing the spinal SAS. Testing before surgery included clinical examination; evaluation of anatomy on T1-weighted MRI; measurement of lumbar and cervical subarachnoid mean and pulse pressures at rest, during Valsalva maneuver, during jugular compression, and after removal of CSF (CSF compliance measurement); and evaluation with CT myelography. During surgery, pressure measurements from the SAS above the level of the lesion and the lumbar intrathecal space below the lesion were obtained, and cardiac-gated ultrasonography was performed. One week after surgery, CT myelography was repeated. Three months after surgery, clinical examination, T1-weighted MRI, and CSF pressure recordings (cervical and lumbar) were repeated. Clinical examination and MRI studies were repeated annually thereafter. Findings in patients were compared with those obtained in a group of 18 healthy individuals who had already undergone T1-weighted MRI, cine MRI, and cervical and lumbar subarachnoid pressure testing. Results In syringomyelia patients compared with healthy volunteers, cervical subarachnoid pulse pressure

  15. Mammalian eusociality: a family affair.

    PubMed

    Jarvis, J U; O'Riain, M J; Bennett, N C; Sherman, P W

    1994-02-01

    Comparative studies of two species of mole-rat are helping to clarify the ecological correlates of mammalian eusociality. Both species live in social groups composed of close kin, within which breeding is restricted to one female and one to three males. They inhabit xeric areas with dispersed, patchy food and unpredictable rainfall. During droughts, they can neither expand their tunnel systems nor disperse. In brief periods after rain the animals must cooperate and dig furiously to locate rich food patches. By living in groups, arid-zone mole-rats can take full advantage of windows of opportunity when conditions are right for burrowing. Thus, ecological factors and kin selection have apparently interacted in the evolution of eusociality in these species. PMID:21236765

  16. Body Size in Mammalian Paleobiology

    NASA Astrophysics Data System (ADS)

    Damuth, John; MacFadden, Bruce J.

    1990-11-01

    This valuable collection of essays presents and evaluates techniques of body-mass estimation and reviews current and potential applications of body-size estimates in paleobiology. Papers discuss explicitly the errors and biases of various regression techniques and predictor variables, and the identification of functionally similar groups of species for improving the accuracy of estimates. At the same time other chapters review and discuss the physiological, ecological, and behavioral correlates of body size in extant mammals; the significance of body-mass distributions in mammalian faunas; and the ecology and evolution of body size in particular paleofaunas. Coverage is particularly detailed for carnivores, primates, and ungulates, but information is also presented on marsupials, rodents, and proboscideans.

  17. Producing Newborn Synchronous Mammalian Cells

    NASA Technical Reports Server (NTRS)

    Gonda, Steve R.; Helmstetter, Charles E.; Thornton, Maureen

    2008-01-01

    A method and bioreactor for the continuous production of synchronous (same age) population of mammalian cells have been invented. The invention involves the attachment and growth of cells on an adhesive-coated porous membrane immersed in a perfused liquid culture medium in a microgravity analog bioreactor. When cells attach to the surface divide, newborn cells are released into the flowing culture medium. The released cells, consisting of a uniform population of synchronous cells are then collected from the effluent culture medium. This invention could be of interest to researchers investigating the effects of the geneotoxic effects of the space environment (microgravity, radiation, chemicals, gases) and to pharmaceutical and biotechnology companies involved in research on aging and cancer, and in new drug development and testing.

  18. Determinants of Mammalian Nucleolar Architecture

    PubMed Central

    Farley, Katherine I.; Surovtseva, Yulia; Merkel, Janie; Baserga, Susan J.

    2015-01-01

    The nucleolus is responsible for the production of ribosomes, essential machines which synthesize all proteins needed by the cell. The structure of human nucleoli is highly dynamic and is directly related to its functions in ribosome biogenesis. Despite the importance of this organelle, the intricate relationship between nucleolar structure and function remains largely unexplored. How do cells control nucleolar formation and function? What are the minimal requirements for making a functional nucleolus? Here we review what is currently known regarding mammalian nucleolar formation at nucleolar organizer regions (NORs), which can be studied by observing the dissolution and reformation of the nucleolus during each cell division. Additionally, the nucleolus can be examined by analyzing how alterations in nucleolar function manifest in differences in nucleolar architecture. Furthermore, changes in nucleolar structure and function are correlated with cancer, highlighting the importance of studying the determinants of nucleolar formation. PMID:25670395

  19. Suspension culture of mammalian cells.

    PubMed

    Birch, J R; Arathoon, R

    1990-01-01

    Mammalian cell suspension culture systems are being used increasingly in the biotechnology industry. This is due to their many advantages including simplicity and homogeneity of culture. Suspension systems are very adaptable (e.g., for microcarrier, microencapsulation, or other methods of culture). Their engineering is thoroughly understood and standardized at large scale, and automation and cleaning procedures are well established. Suspension systems offer the possibility of quick implementation of production protocols due to their ability to be scaled easily once the basic culture parameters are understood. The only main disadvantage of the suspension culture systems to date is their inapplicability for the production of human vaccines from either primary cell lines or from normal human diploid cell lines (Hayflick et al., 1987 and references therein). One of the great advantages of suspension culture is the opportunity it provides to study interactions of metabolic and production phenomena in chemostat or turbidostat steady-state systems. Furthermore, in suspension culture systems from which cell number and cell mass measurements are easy to obtain, rigorous and quantitative estimations of the effects of growth conditions or perturbations of metabolic homeostasis can be made. Such studies can speed up the development of optimal processes. With our increasing understanding of factors influencing expression in mammalian cells (Cohen and Levinson, 1988; Santoro et al., 1988) and the direct application of new methods in suspension culture (Rhodes and Birch, 1988), its usefulness and importance is likely to increase in the future. In this chapter, we have described some of the potential uses of the various suspension culture systems and have covered most of the established technology and literature. Due to the rapid developments and needs in the biotechnology industry and the versatility of suspension culture systems, it is probable that many more variations on this

  20. Qualification of the Most Statistically "Sensitive" Diffusion Tensor Imaging Parameters for Detection of Spinal Cord Injury

    NASA Astrophysics Data System (ADS)

    Krzyżak, A. T.; Jasiński, A.; Adamek, D.

    2006-07-01

    Qualification of the most statistically "sensitive" diffusion parameters using Magnetic Resonance (MR) Diffusion Tensor Imaging (DTI) of the control and injured spinal cord of a rat in vivo and in vitro after the trauma is reported. Injury was induced in TH12/TH13 level by a controlled "weight-drop". In vitro experiments were performed in a home-built MR microscope, with a 6.4 T magnet, in vivo samples were measured in a 9.4 T/21 horizontal magnet The aim of this work was to find the most effective diffusion parameters which are useful in the statistically significant detection of spinal cord tissue damage. Apparent diffusion tensor (ADT) weighted data measured in vivo and in vitro on control and injured rat spinal cord (RSC) in the transverse planes and analysis of the diffusion anisotropy as a function of many parameters, which allows statisticall expose of the existence of the damage are reported.

  1. Plasma glutamine concentration in spinal cord injured patients.

    PubMed

    Rogeri, P S; Costa Rosa, L F B P

    2005-09-23

    Glutamine, a non-essential amino acid, is the most important source of energy for macrophages and lymphocytes. Reduction in its plasma concentration is related with loss of immune function, as leukocyte proliferation and cytokine production. It is well known that glutamine is largely produced by the skeletal muscle which is severely compromised as a consequence of the paralysis due to the damage of the spinal cord. In spinal cord injury (SCI) patients, infections, such as pneumonia and sepsis in general, are a major cause of morbidity and mortality. In comparison with the control group, a 54% decrease in plasma glutamine concentration was observed as well as a decrease in the production of TNF and IL-1 by peripheral blood mononuclear cells cultivated for 48 h in SCI patients. Therefore, we propose that a decrease in plasma glutamine concentration is an important contributor to the immunosuppression seen in SCI patients. PMID:16024049

  2. Radiation Dose-Volume Effects in the Spinal Cord

    SciTech Connect

    Kirkpatrick, John P.; Kogel, Albert J. van der; Schultheiss, Timothy E.

    2010-03-01

    Dose-volume data for myelopathy in humans treated with radiotherapy (RT) to the spine is reviewed, along with pertinent preclinical data. Using conventional fractionation of 1.8-2 Gy/fraction to the full-thickness cord, the estimated risk of myelopathy is <1% and <10% at 54 Gy and 61 Gy, respectively, with a calculated strong dependence on dose/fraction (alpha/beta = 0.87 Gy.) Reirradiation data in animals and humans suggest partial repair of RT-induced subclinical damage becoming evident about 6 months post-RT and increasing over the next 2 years. Reports of myelopathy from stereotactic radiosurgery to spinal lesions appear rare (<1%) when the maximum spinal cord dose is limited to the equivalent of 13 Gy in a single fraction or 20 Gy in three fractions. However, long-term data are insufficient to calculate a dose-volume relationship for myelopathy when the partial cord is treated with a hypofractionated regimen.

  3. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    PubMed Central

    Costa, Liliana; Faustino, Maria Amparo F.; Neves, Maria Graça P. M. S.; Cunha, Ângela; Almeida, Adelaide

    2012-01-01

    Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process. PMID:22852040

  4. Photodynamic inactivation of mammalian viruses and bacteriophages.

    PubMed

    Costa, Liliana; Faustino, Maria Amparo F; Neves, Maria Graça P M S; Cunha, Angela; Almeida, Adelaide

    2012-07-01

    Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

  5. Recent advances in mammalian protein production

    PubMed Central

    Bandaranayake, Ashok D.; Almo, Steven C.

    2014-01-01

    Mammalian protein production platforms have had a profound impact in many areas of basic and applied research, and an increasing number of blockbuster drugs are recombinant mammalian proteins. With global sales of these drugs exceeding US$120 billion per year, both industry and academic research groups continue to develop cost effective methods for producing mammalian proteins to support preclinical and clinical evaluations of potential therapeutics. While a wide range of platforms have been successfully exploited for laboratory use, the bulk of recent biologics have been produced in mammalian cell lines due to the requirement for post translational modification and the biosynthetic complexity of the target proteins. In this review we highlight the range of mammalian expression platforms available for recombinant protein production, as well as advances in technologies for the rapid and efficient selection of highly productive clones. PMID:24316512

  6. Distribution and morphology of sacral spinal cord neurons innervating pelvic structures in Xenopus laevis.

    PubMed

    Campbell, H L; Beattie, M S; Bresnahan, J C

    1994-09-22

    Relatively little is known about the organization of neural input to pelvic viscera in amphibia. In this study, sacral spinal efferent neurons were labeled in Xenopus laevis frogs by application of horseradish peroxidase (HRP) to the tenth spinal nerve, to pelvic musculature, or to the pelvic nerve. DiI was applied to the pelvic nerve with similar results. Labeled spinal neurons were located in the intermediate gray or in the ventral horn. Neurons in the tenth dorsal root ganglion, but not in the spinal cord, were labeled after application of HRP or DiI to the pudendal nerve. The labeled neurons in the spinal cord intermediate gray were in a position comparable to that of the mammalian sacral parasympathetic nucleus (SPN). Two apparent subdivisions included 1) a medial cluster of cells with mediolaterally oriented dendrites and 2) a lateral group with dorsoventrally oriented dendrites. An intermediate group, not clearly classed with the other two, was also identifiable. In some cases, labeled tenth nerve primary afferents were seen in contact with efferent neurons of the intermediate gray. Labeled neurons in the ventral horn medial to the lateral motor column were small, with dendrites oriented mediolaterally, in a position comparable to that of the mammalian Onuf's nucleus. The peripheral targets of DiI-labeled pelvic nerve axons were the compressor cloaca muscle, cloaca, and bladder. DiI-labeled pudendal nerve axons distributed peripherally to cloacal lip and medial thigh integument. These data suggest that the pudendal nerve in amphibians is purely sensory and that both somatic and autonomic motor axons traverse the pelvic nerve.

  7. Genetics Home Reference: spinal muscular atrophy

    MedlinePlus

    ... a loss of specialized nerve cells, called motor neurons , in the spinal cord and the part of ... spinal cord ( the brainstem ). The loss of motor neurons leads to weakness and wasting ( atrophy ) of muscles ...

  8. Rehabilitation in spinal infection diseases.

    PubMed

    Nas, Kemal; Karakoç, Mehmet; Aydın, Abdulkadir; Öneş, Kadriye

    2015-01-18

    Spinal cord infections were the diseases defined by Hypocrite yet the absence of modern medicine and there was not a real protocol in rehabilitation although there were many aspects in surgical treatment options. The patients whether surgically or conservatively treated had a lot of neurological, motor, and sensory disturbances. Our clinic has quite experience from our previous researchs. Unfortunately, serious spinal cord infections are still present in our region. In these patients the basic rehabilitation approaches during early, pre-operation, post-operation period and in the home environment will provide significant contributions to improve the patients' sensory and motor skills, develop the balance and proriocaption, increase the independence of patients in daily living activities and minimize the assistance of other people. There is limited information in the literature related with the nature of the rehabilitation programmes to be applied for patients with spinal infections. The aim of this review is to share our clinic experience and summarise the publications about spinal infection rehabilitation. There are very few studies about the rehabilitation of spinal infections. There are still not enough studies about planning and performing rehabilitation programs in these patients. Therefore, a comprehensive rehabilitation programme during the hospitalisation and home periods is emphasised in order to provide optimal management and prevent further disability.

  9. Rehabilitation in spinal infection diseases

    PubMed Central

    Nas, Kemal; Karakoç, Mehmet; Aydın, Abdulkadir; Öneş, Kadriye

    2015-01-01

    Spinal cord infections were the diseases defined by Hypocrite yet the absence of modern medicine and there was not a real protocol in rehabilitation although there were many aspects in surgical treatment options. The patients whether surgically or conservatively treated had a lot of neurological, motor, and sensory disturbances. Our clinic has quite experience from our previous researchs. Unfortunately, serious spinal cord infections are still present in our region. In these patients the basic rehabilitation approaches during early, pre-operation, post-operation period and in the home environment will provide significant contributions to improve the patients’ sensory and motor skills, develop the balance and proriocaption, increase the independence of patients in daily living activities and minimize the assistance of other people. There is limited information in the literature related with the nature of the rehabilitation programmes to be applied for patients with spinal infections. The aim of this review is to share our clinic experience and summarise the publications about spinal infection rehabilitation. There are very few studies about the rehabilitation of spinal infections. There are still not enough studies about planning and performing rehabilitation programs in these patients. Therefore, a comprehensive rehabilitation programme during the hospitalisation and home periods is emphasised in order to provide optimal management and prevent further disability. PMID:25621205

  10. Ruptured Isolated Spinal Artery Aneurysms

    PubMed Central

    Gutierrez Romero, Diego; Batista, Andre Lima; Gentric, Jean Christoph; Raymond, Jean; Roy, Daniel; Weill, Alain

    2014-01-01

    Summary Isolated spinal artery aneurysms are exceedingly rare vascular lesions thought to be related to dissection of the arterial wall. We describe two cases presenting with spinal subarachnoid haemorrhage that underwent conservative management. In the first patient the radiculomedullary branch involved was feeding the anterior spinal artery at the level of D3 and thus, neither endovascular nor surgical approach was employed. Control angiography was performed at seven days and at three months, demonstrating complete resolution of the lesion. In our second case, neither the anterior spinal artery or the artery of Adamkiewicz could be identified during angiography, thus endovascular management was deemed contraindicated. Magnetic resonance imaging showed a stable lesion in the second patient. No rebleeding or other complications were seen. In comparison to intracranial aneurysms, spinal artery aneurysms tend to display a fusiform appearance and lack a clear neck in relation to the likely dissecting nature of the lesions. Due to the small number of cases reported, the natural history of these lesions is not well known making it difficult to establish the optimal treatment approach. Various management strategies may be supported, including surgical and endovascular treatment, but It would seem that a wait and see approach is also viable, with control angiogram and treatment decisions based on the evolution of the lesion. PMID:25496690

  11. Shoulder Pain in Cases of Spinal Injury: Influence of the Position of the Wheelchair Seat

    ERIC Educational Resources Information Center

    Giner-Pascual, Manuel; Alcanyis-Alberola, Modesto; Millan Gonzalez, Luis; Aguilar-Rodriguez, Marta; Querol, Felipe

    2011-01-01

    The objective of this study was to determine the relationship between shoulder pain and the position of the seat of a wheelchair relative to the ground and to determine the relationship between shoulder pain and structural damage. A transversal study of a patient cohort of 140 patients with grade A and B spinal cord injuries below the T1 vertebra,…

  12. Recurrence of spinal schwannoma: Is it preventable?

    PubMed Central

    Senapati, Satya B.; Mishra, Sudhansu S.; Dhir, Manmath K.; Patnaik, Ashis; Panigrahi, Souvagya

    2016-01-01

    Spinal schwannomas account for about 25% of primary intradural spinal cord tumors in adult. The prognosis for spinal schwannomas is excellent in most cases. Complete resection is curative. However following subtotal removal, recurrence develops after several years. We describe a case of recurrent spinal schwannoma who had been operated twice before for same disease. The possible cause of recurrence and difficulties in reoperation are discussed.

  13. Recurrence of spinal schwannoma: Is it preventable?

    PubMed Central

    Senapati, Satya B.; Mishra, Sudhansu S.; Dhir, Manmath K.; Patnaik, Ashis; Panigrahi, Souvagya

    2016-01-01

    Spinal schwannomas account for about 25% of primary intradural spinal cord tumors in adult. The prognosis for spinal schwannomas is excellent in most cases. Complete resection is curative. However following subtotal removal, recurrence develops after several years. We describe a case of recurrent spinal schwannoma who had been operated twice before for same disease. The possible cause of recurrence and difficulties in reoperation are discussed. PMID:27695564

  14. Spinal angiolipoma with acute subarachnoid hemorrhage.

    PubMed

    Raghavendra, S; Krishnamoorthy, T; Ashalatha, R; Kesavadas, C

    2007-10-01

    Angiolipoma is a rare tumor of the spine commonly presenting with compressive myelopathy. We report a spinal angiolipoma in a 14-year-old patient with acute spinal subarachnoid hemorrhage (SAH). To our knowledge this is the first reported case of a spinal angiolipoma presenting with SAH, associated with post-subclavian coarctation with diffuse hypoplasia of the descending aorta. This association of coarctation of aorta, aortic hypoplasia and spinal angiolipoma has also not been reported previously.

  15. Adult spinal cord ependymal layer: a promising pool of quiescent stem cells to treat spinal cord injury.

    PubMed

    Panayiotou, Elena; Malas, Stavros

    2013-11-28

    Spinal cord injury (SCI) is a major health burden and currently there is no effective medical intervention. Research performed over the last decade revealed that cells surrounding the central canal of the adult spinal cord and forming the ependymal layer acquire stem cell properties either in vitro or in response to injury. Following SCI activated ependymal cells generate progeny cells which migrate to the injury site but fail to produce the appropriate type of cells in sufficient number to limit the damage, rendering this physiological response mainly ineffective. Research is now focusing on the manipulation of ependymal cells to produce cells of the oligodendrocyte lineage which are primarily lost in such a situation leading to secondary neuronal degeneration. Thus, there is a need for a more focused approach to understand the molecular properties of adult ependymal cells in greater detail and develop effective strategies for guiding their response during SCI.

  16. Restoration of upper limb movement via artificial corticospinal and musculospinal connections in a monkey with spinal cord injury.

    PubMed

    Nishimura, Yukio; Perlmutter, Steve I; Fetz, Eberhard E

    2013-01-01

    Functional loss of limb control in individuals with spinal cord injury or stroke can be caused by interruption of corticospinal pathways, although the neural circuits located above and below the lesion remain functional. An artificial neural connection that bridges the lost pathway and connects cortical to spinal circuits has potential to ameliorate the functional loss. We investigated the effects of introducing novel artificial neural connections in a paretic monkey that had a unilateral spinal cord lesion at the C2 level. The first application bridged the impaired spinal lesion. This allowed the monkey to drive the spinal stimulation through volitionally controlled power of high-gamma activity in either the premotor or motor cortex, and thereby to acquire a force-matching target. The second application created an artificial recurrent connection from a paretic agonist muscle to a spinal site, allowing muscle-controlled spinal stimulation to boost on-going activity in the muscle. These results suggest that artificial neural connections can compensate for interrupted descending pathways and promote volitional control of upper limb movement after damage of descending pathways such as spinal cord injury or stroke. PMID:23596396

  17. Evaluation of spinal cord injury animal models

    PubMed Central

    Zhang, Ning; Fang, Marong; Chen, Haohao; Gou, Fangming; Ding, Mingxing

    2014-01-01

    Because there is no curative treatment for spinal cord injury, establishing an ideal animal model is important to identify injury mechanisms and develop therapies for individuals suffering from spinal cord injuries. In this article, we systematically review and analyze various kinds of animal models of spinal cord injury and assess their advantages and disadvantages for further studies. PMID:25598784

  18. Four cases of spinal epidural angiolipoma.

    PubMed

    Sim, Kenneth; Tsui, Alpha; Paldor, Iddo; Kaye, Andrew H; Gaillard, Frank

    2016-03-01

    Spinal angiolipomas are uncommon benign tumours composed of mature fatty tissue and abnormal vascular elements, most commonly found within the posterior spinal epidural space. Most tumours are located within the mid-thoracic spine; in contrast thoracolumbar junction and purely lumbar angiolipomas are rare. We report a case series of four spinal angiolipomas, including a thoracolumbar junction and a purely lumbar tumour.

  19. Spinal reflexes in brain death.

    PubMed

    Beckmann, Yesim; Çiftçi, Yeliz; Incesu, Tülay Kurt; Seçil, Yaprak; Akhan, Galip

    2014-12-01

    Spontaneous and reflex movements have been described in brain death and these unusual movements might cause uncertainties in diagnosis. In this study we evaluated the presence of spinal reflexes in patients who fulfilled the criteria for brain death. Thirty-two (22 %) of 144 patients presented unexpected motor movements spontaneously or during examinations. These patients exhibited the following signs: undulating toe, increased deep tendon reflexes, plantar responses, Lazarus sign, flexion-withdrawal reflex, facial myokymia, neck-arm flexion, finger jerks and fasciculations. In comparison, there were no significant differences in age, sex, etiology of brain death and hemodynamic laboratory findings in patients with and without reflex motor movement. Spinal reflexes should be well recognized by physicians and it should be born in mind that brain death can be determined in the presence of spinal reflexes.

  20. Improved rat spinal cord injury model using spinal cord compression by percutaneous method

    PubMed Central

    Chung, Wook-Hun; Lee, Jae-Hoon; Chung, Dai-Jung; Yang, Wo-Jong; Lee, A-Jin; Choi, Chi-Bong; Chang, Hwa-Seok; Kim, Dae-Hyun; Chung, Hyo Jin; Suh, Hyun Jung; Hwang, Soo-Han; Han, Hoon; Do, Sun Hee

    2013-01-01

    Here, percutaneous spinal cord injury (SCI) methods using a balloon catheter in adult rats are described. A balloon catheter was inserted into the epidural space through the lumbosacral junction and then inflated between T9-T10 for 10min under fluoroscopic guidance. Animals were divided into three groups with respect to inflation volume: 20 µL (n = 18), 50 µL (n = 18) and control (Fogarty catheter inserted but not inflated; n = 10). Neurological assessments were then made based on BBB score, magnetic resonance imaging and histopathology. Both inflation volumes produced complete paralysis. Gradual recovery of motor function occurred when 20 µL was used, but not after 50 µL was applied. In the 50 µL group, all gray and white matter was lost from the center of the lesion. In addition, supramaximal damage was noted, which likely prevented spontaneous recovery. This percutaneous spinal cord compression injury model is simple, rapid with high reproducibility and the potential to serve as a useful tool for investigation of pathophysiology and possible protective treatments of SCI in vivo. PMID:23820159

  1. Spinal injuries in contact sports.

    PubMed

    Wilson, Joseph B; Zarzour, Robert; Moorman, Claude T

    2006-02-01

    Contact and collision sports such as American football expose the athlete to a wide array of potential injuries. Knee injuries garner much of the attention, but spinal injuries are potentially catastrophic and all levels of medical coverage of football must be knowledgeable and prepared to attend to an athlete with a neck injury. Of the other possible spinal conditions, some resolve on their own, others might require conservative therapy, and still others might require surgical intervention. The spectrum of potential injury is wide, yet the medical team must practice and prepare to treat the possible catastrophic neck injury.

  2. Selective opioid agonist and antagonist competition for [3H]-naloxone binding in amphibian spinal cord

    PubMed Central

    Newman, Leslie C.; Wallace, David R.; Stevens, Craig W.

    2011-01-01

    Opioids elicit antinociception in mammals through three distinct types of receptors designated as μ, κ and δ. However, it is not clear what type of opioid receptor mediates antinociception in non-mammalian vertebrates. Radioligand binding techniques were employed to characterize the site(s) of opioid action in the amphibian, Rana pipiens. Naloxone is a general opioid antagonist that has not been characterized in Rana pipiens. Using the non-selective opioid antagonist, [3H]-naloxone, opioid binding sites were characterized in amphibian spinal cord. Competitive binding assays were done using selective opioid agonists and highly-selective opioid antagonists. Naloxone bound to a single-site with an affinity of 11.3 nM and 18.7 nM for kinetic and saturation studies, respectively. A Bmax value of 2725 fmol/mg protein in spinal cord was observed. The competition constants (Ki) of unlabeled μ, κ and δ ranged from 2.58 nM to 84 μM. The highly-selective opioid antagonists yielded similar Ki values ranging from 5.37 to 31.1 nM. These studies are the first to examine opioid binding in amphibian spinal cord. In conjunction with previous behavioral data, these results suggest that non-mammalian vertebrates express a unique opioid receptor which mediates the action of selective μ, κ and δ opioid agonists. PMID:11082500

  3. Mammalian cell cultivation in space

    NASA Astrophysics Data System (ADS)

    Gmünder, Felix K.; Suter, Robert N.; Kiess, M.; Urfer, R.; Nordau, C.-G.; Cogoli, A.

    Equipment used in space for the cultivation of mammalian cells does not meet the usual standard of earth bound bioreactors. Thus, the development of a space worthy bioreactor is mandatory for two reasons: First, to investigate the effect on single cells of the space environment in general and microgravity conditions in particular, and second, to provide researchers on long term missions and the Space Station with cell material. However, expertise for this venture is not at hand. A small and simple device for animal cell culture experiments aboard Spacelab (Dynamic Cell Culture System; DCCS) was developed. It provides 2 cell culture chambers, one is operated as a batch system, the other one as a perfusion system. The cell chambers have a volume of 200 μl. Medium exchange is achieved with an automatic osmotic pump. The system is neither mechanically stirred nor equipped with sensors. Oxygen for cell growth is provided by a gas chamber that is adjacent to the cell chambers. The oxygen gradient produced by the growing cells serves to maintain the oxygen influx by diffusion. Hamster kidney cells growing on microcarriers were used to test the biological performance of the DCCS. On ground tests suggest that this system is feasible.

  4. Chapter 2--the spinal generation of phases and cycle duration.

    PubMed

    Gossard, Jean-Pierre; Sirois, Jennifer; Noué, Patrick; Côté, Marie-Pascale; Ménard, Ariane; Leblond, Hugues; Frigon, Alain

    2011-01-01

    during fictive locomotion but did not alter cycle period during scratching. These data indicate that cycle period, phase durations, and phase transitions are not regulated similarly during fictive locomotion and scratching, with or without sensory inputs, providing evidence for the existence of distinct interneuronal components of rhythm generation within the mammalian spinal cord.

  5. Inflammogenesis of Secondary Spinal Cord Injury

    PubMed Central

    Anwar, M. Akhtar; Al Shehabi, Tuqa S.; Eid, Ali H.

    2016-01-01

    Spinal cord injury (SCI) and spinal infarction lead to neurological complications and eventually to paraplegia or quadriplegia. These extremely debilitating conditions are major contributors to morbidity. Our understanding of SCI has certainly increased during the last decade, but remains far from clear. SCI consists of two defined phases: the initial impact causes primary injury, which is followed by a prolonged secondary injury consisting of evolving sub-phases that may last for years. The underlying pathophysiological mechanisms driving this condition are complex. Derangement of the vasculature is a notable feature of the pathology of SCI. In particular, an important component of SCI is the ischemia-reperfusion injury (IRI) that leads to endothelial dysfunction and changes in vascular permeability. Indeed, together with endothelial cell damage and failure in homeostasis, ischemia reperfusion injury triggers full-blown inflammatory cascades arising from activation of residential innate immune cells (microglia and astrocytes) and infiltrating leukocytes (neutrophils and macrophages). These inflammatory cells release neurotoxins (proinflammatory cytokines and chemokines, free radicals, excitotoxic amino acids, nitric oxide (NO)), all of which partake in axonal and neuronal deficit. Therefore, our review considers the recent advances in SCI mechanisms, whereby it becomes clear that SCI is a heterogeneous condition. Hence, this leads towards evidence of a restorative approach based on monotherapy with multiple targets or combinatorial treatment. Moreover, from evaluation of the existing literature, it appears that there is an urgent requirement for multi-centered, randomized trials for a large patient population. These clinical studies would offer an opportunity in stratifying SCI patients at high risk and selecting appropriate, optimal therapeutic regimens for personalized medicine. PMID:27147970

  6. A Contusive Model of Unilateral Cervical Spinal Cord Injury Using the Infinite Horizon Impactor

    PubMed Central

    Lee, Jae H.T.; Streijger, Femke; Tigchelaar, Seth; Maloon, Michael; Liu, Jie; Tetzlaff, Wolfram; Kwon, Brian K.

    2012-01-01

    While the majority of human spinal cord injuries occur in the cervical spinal cord, the vast majority of laboratory research employs animal models of spinal cord injury (SCI) in which the thoracic spinal cord is injured. Additionally, because most human cord injuries occur as the result of blunt, non-penetrating trauma (e.g. motor vehicle accident, sporting injury) where the spinal cord is violently struck by displaced bone or soft tissues, the majority of SCI researchers are of the opinion that the most clinically relevant injury models are those in which the spinal cord is rapidly contused.1 Therefore, an important step in the preclinical evaluation of novel treatments on their way to human translation is an assessment of their efficacy in a model of contusion SCI within the cervical spinal cord. Here, we describe the technical aspects and resultant anatomical and behavioral outcomes of an unilateral contusive model of cervical SCI that employs the Infinite Horizon spinal cord injury impactor. Sprague Dawley rats underwent a left-sided unilateral laminectomy at C5. To optimize the reproducibility of the biomechanical, functional, and histological outcomes of the injury model, we contused the spinal cords using an impact force of 150 kdyn, an impact trajectory of 22.5° (animals rotated at 22.5°), and an impact location off of midline of 1.4 mm. Functional recovery was assessed using the cylinder rearing test, horizontal ladder test, grooming test and modified Montoya's staircase test for up to 6 weeks, after which the spinal cords were evaluated histologically for white and grey matter sparing. The injury model presented here imparts consistent and reproducible biomechanical forces to the spinal cord, an important feature of any experimental SCI model. This results in discrete histological damage to the lateral half of the spinal cord which is largely contained to the ipsilateral side of injury. The injury is well tolerated by the animals, but does result in

  7. Ghrelin Receptors in Non-Mammalian Vertebrates

    PubMed Central

    Kaiya, Hiroyuki; Kangawa, Kenji; Miyazato, Mikiya

    2012-01-01

    The growth hormone secretagogue-receptor (GHS-R) was discovered in humans and pigs in 1996. The endogenous ligand, ghrelin, was discovered 3 years later, in 1999, and our understanding of the physiological significance of the ghrelin system in vertebrates has grown steadily since then. Although the ghrelin system in non-mammalian vertebrates is a subject of great interest, protein sequence data for the receptor in non-mammalian vertebrates has been limited until recently, and related biological information has not been well organized. In this review, we summarize current information related to the ghrelin receptor in non-mammalian vertebrates. PMID:23882259

  8. Cell elimination as a strategy for repair in acute spinal cord injury.

    PubMed

    Kalderon, Nurit

    2005-01-01

    Following injury, as part of the wound-healing process, cell proliferation occurs mostly to replace damaged cells and to reconstitute the tissue back to normal condition/function. In the spinal cord some of the dividing cells following injury interfere with the repair processes. This interference occurs at the later stages of wound healing (the third week after injury) triggering chronic inflammation and progressive tissue decay that is the characteristic pathology of spinal cord injury. Specific cell elimination within a critical time window after injury can lead to repair in the acutely injured spinal cord. Cell proliferation events can be manipulated/modified by x-irradiation. Clinically, numerous radiation protocols (i.e., radiation therapy) have been developed that specifically eliminate the rapidly dividing cells without causing any noticeable/significant damage to the tissue as a whole. Radiation therapy when applied within the critical time window after injury prevents the onset of chronic inflammation thus leading to repair of structure and function. Various aspects of the development of this cell-elimination strategy for repair in acute spinal cord injury by utilizing radiation therapy are being reviewed. Topics reviewed here: identifying the window of opportunity; and the beneficial repair effects of radiation therapy in a transection injury model and in a model relevant to human injury, the contusion injury model. The possible involvement of cellular components of the blood-spinal cord barrier as the trigger of chronic inflammation and/or target of the radiation therapy is discussed. PMID:15853680

  9. Management of Chronic Spinal Cord Dysfunction

    PubMed Central

    Abrams, Gary M.; Ganguly, Karunesh

    2015-01-01

    Purpose of Review: Both acute and chronic spinal cord disorders present multisystem management problems to the clinician. This article highlights key issues associated with chronic spinal cord dysfunction. Recent Findings: Advances in symptomatic management for chronic spinal cord dysfunction include use of botulinum toxin to manage detrusor hyperreflexia, pregabalin for management of neuropathic pain, and intensive locomotor training for improved walking ability in incomplete spinal cord injuries. Summary: The care of spinal cord dysfunction has advanced significantly over the past 2 decades. Management and treatment of neurologic and non-neurologic complications of chronic myelopathies ensure that each patient will be able to maximize their functional independence and quality of life. PMID:25651225

  10. Lipid Peroxidation-Derived Reactive Aldehydes Directly and Differentially Impair Spinal Cord and Brain Mitochondrial Function

    PubMed Central

    Vaishnav, Radhika A.; Singh, Indrapal N.; Miller, Darren M.

    2010-01-01

    Abstract Mitochondrial bioenergetic dysfunction in traumatic spinal cord and brain injury is associated with post-traumatic free radical–mediated oxidative damage to proteins and lipids. Lipid peroxidation by-products, such as 4-hydroxy-2-nonenal and acrolein, can form adducts with proteins and exacerbate the effects of direct free radical–induced protein oxidation. The aim of the present investigation was to determine and compare the direct contribution of 4-hydroxy-2-nonenal and acrolein to spinal cord and brain mitochondrial dysfunction. Ficoll gradient–isolated mitochondria from normal rat spinal cords and brains were treated with carefully selected doses of 4-hydroxy-2-nonenal or acrolein, followed by measurement of complex I– and complex II–driven respiratory rates. Both compounds were potent inhibitors of mitochondrial respiration in a dose-dependent manner. 4-Hydroxy-2-nonenal significantly compromised spinal cord mitochondrial respiration at a 0.1-μM concentration, whereas 10-fold greater concentrations produced a similar effect in brain. Acrolein was more potent than 4-hydroxy-2-nonenal, significantly decreasing spinal cord and brain mitochondrial respiration at 0.01 μM and 0.1 μM concentrations, respectively. The results of this study show that 4-hydroxy-2-nonenal and acrolein can directly and differentially impair spinal cord and brain mitochondrial function, and that the targets for the toxic effects of aldehydes appear to include pyruvate dehydrogenase and complex I–associated proteins. Furthermore, they suggest that protein modification by these lipid peroxidation products may directly contribute to post-traumatic mitochondrial damage, with spinal cord mitochondria showing a greater sensitivity than those in brain. PMID:20392143

  11. Treatment of Spinal Tuberculosis by Debridement, Interbody Fusion and Internal Fixation via Posterior Approach Only.

    PubMed

    Tang, Ming-xing; Zhang, Hong-qi; Wang, Yu-xiang; Guo, Chao-feng; Liu, Jin-yang

    2016-02-01

    Surgical treatment for spinal tuberculosis includes focal tuberculosis debridement, segmental stability reconstruction, neural decompression and kyphotic deformity correction. For the lesions mainly involved anterior and middle column of the spine, anterior operation of debridement and fusion with internal fixation has been becoming the most frequently used surgical technique for the spinal tuberculosis. However, high risk of structural damage might relate with anterior surgery, such as damage in lungs, heart, kidney, ureter and bowel, and the deformity correction is also limited. Due to the organs are in the front of spine, there are less complications in posterior approach. Spinal pedicle screw passes through the spinal three-column structure, which provides more powerful orthopedic forces compared with the vertebral body screw, and the kyphotic deformity correction effect is better in posterior approach. In this paper, we report a 68-year-old male patient with thoracic tuberculosis who underwent surgical treatment by debridement, interbody fusion and internal fixation via posterior approach only. The patient was placed in prone position under general anesthesia. Posterior midline incision was performed, and the posterior spinal construction was exposed. Then place pedicle screw, and fix one side rod temporarily. Make the side of more bone destruction and larger abscess as lesion debridement side. Resect the unilateral facet joint, and retain contralateral structure integrity. Protect the spinal cord, nerve root. Clear sequestrum, necrotic tissue, abscess of paravertebral and intervertebral space. Specially designed titanium mesh cages or bone blocks were implanted into interbody. Fix both side rods and compress both sides to make the mesh cages and bone blocks tight. Reconstruct posterior column structure with allogeneic bone and autologous bone. Using this technique, the procedures of debridement, spinal cord decompression, deformity correction, bone grafting

  12. Treatment of Spinal Tuberculosis by Debridement, Interbody Fusion and Internal Fixation via Posterior Approach Only.

    PubMed

    Tang, Ming-xing; Zhang, Hong-qi; Wang, Yu-xiang; Guo, Chao-feng; Liu, Jin-yang

    2016-02-01

    Surgical treatment for spinal tuberculosis includes focal tuberculosis debridement, segmental stability reconstruction, neural decompression and kyphotic deformity correction. For the lesions mainly involved anterior and middle column of the spine, anterior operation of debridement and fusion with internal fixation has been becoming the most frequently used surgical technique for the spinal tuberculosis. However, high risk of structural damage might relate with anterior surgery, such as damage in lungs, heart, kidney, ureter and bowel, and the deformity correction is also limited. Due to the organs are in the front of spine, there are less complications in posterior approach. Spinal pedicle screw passes through the spinal three-column structure, which provides more powerful orthopedic forces compared with the vertebral body screw, and the kyphotic deformity correction effect is better in posterior approach. In this paper, we report a 68-year-old male patient with thoracic tuberculosis who underwent surgical treatment by debridement, interbody fusion and internal fixation via posterior approach only. The patient was placed in prone position under general anesthesia. Posterior midline incision was performed, and the posterior spinal construction was exposed. Then place pedicle screw, and fix one side rod temporarily. Make the side of more bone destruction and larger abscess as lesion debridement side. Resect the unilateral facet joint, and retain contralateral structure integrity. Protect the spinal cord, nerve root. Clear sequestrum, necrotic tissue, abscess of paravertebral and intervertebral space. Specially designed titanium mesh cages or bone blocks were implanted into interbody. Fix both side rods and compress both sides to make the mesh cages and bone blocks tight. Reconstruct posterior column structure with allogeneic bone and autologous bone. Using this technique, the procedures of debridement, spinal cord decompression, deformity correction, bone grafting

  13. Treatment of Spinal Tuberculosis by Debridement, Interbody Fusion and Internal Fixation via Posterior Approach Only

    PubMed Central

    Tang, Ming‐xing; Wang, Yu‐xiang; Guo, Chao‐feng; Liu, Jin‐yang

    2016-01-01

    Surgical treatment for spinal tuberculosis includes focal tuberculosis debridement, segmental stability reconstruction, neural decompression and kyphotic deformity correction. For the lesions mainly involved anterior and middle column of the spine, anterior operation of debridement and fusion with internal fixation has been becoming the most frequently used surgical technique for the spinal tuberculosis. However, high risk of structural damage might relate with anterior surgery, such as damage in lungs, heart, kidney, ureter and bowel, and the deformity correction is also limited. Due to the organs are in the front of spine, there are less complications in posterior approach. Spinal pedicle screw passes through the spinal three‐column structure, which provides more powerful orthopedic forces compared with the vertebral body screw, and the kyphotic deformity correction effect is better in posterior approach. In this paper, we report a 68‐year‐old male patient with thoracic tuberculosis who underwent surgical treatment by debridement, interbody fusion and internal fixation via posterior approach only. The patient was placed in prone position under general anesthesia. Posterior midline incision was performed, and the posterior spinal construction was exposed. Then place pedicle screw, and fix one side rod temporarily. Make the side of more bone destruction and larger abscess as lesion debridement side. Resect the unilateral facet joint, and retain contralateral structure integrity. Protect the spinal cord, nerve root. Clear sequestrum, necrotic tissue, abscess of paravertebral and intervertebral space. Specially designed titanium mesh cages or bone blocks were implanted into interbody. Fix both side rods and compress both sides to make the mesh cages and bone blocks tight. Reconstruct posterior column structure with allogeneic bone and autologous bone. Using this technique, the procedures of debridement, spinal cord decompression, deformity correction, bone

  14. Protective effect of rosemary on acrylamide motor neurotoxicity in spinal cord of rat offspring: postnatal follow-up study

    PubMed Central

    Al-Gholam, Marwa A.; El-Mehi, Abeer E.; El-Barbary, Abd El-Moneum; Fokar, Ahmed Zo El

    2016-01-01

    The direct interactive effects of rosemary and acrylamide on the development of motor neurons in the spinal cord remains unknown. Our goal is to confirm the protective effects of rosemary against motor neuronal degeneration induced by acrylamide in the developing postnatal rat spinal cord using a postnatal rat model. We assigned the offspring of treated female rats into control, rosemary; acrylamide group; and recovery groups. This work depended on clinical, histopathological, morphometrically, immunohistochemical and genetic methods. In the acrylamide group, we observed oxidation, motor neuron degeneration, apoptosis, myelin degeneration, neurofilament reduction, reactive gliosis. Whoever, concomitant rosemary intake and withdrawal of acrylamide modulate these effects. These findings proof that dietary rosemary can directly protect motor neuron against acrylamide toxicity in the mammalian developing spinal cord. PMID:27051566

  15. Protective effect of rosemary on acrylamide motor neurotoxicity in spinal cord of rat offspring: postnatal follow-up study.

    PubMed

    Al-Gholam, Marwa A; Nooh, Hanaa Zakaria; El-Mehi, Abeer E; El-Barbary, Abd El-Moneum; Fokar, Ahmed Zo El

    2016-03-01

    The direct interactive effects of rosemary and acrylamide on the development of motor neurons in the spinal cord remains unknown. Our goal is to confirm the protective effects of rosemary against motor neuronal degeneration induced by acrylamide in the developing postnatal rat spinal cord using a postnatal rat model. We assigned the offspring of treated female rats into control, rosemary; acrylamide group; and recovery groups. This work depended on clinical, histopathological, morphometrically, immunohistochemical and genetic methods. In the acrylamide group, we observed oxidation, motor neuron degeneration, apoptosis, myelin degeneration, neurofilament reduction, reactive gliosis. Whoever, concomitant rosemary intake and withdrawal of acrylamide modulate these effects. These findings proof that dietary rosemary can directly protect motor neuron against acrylamide toxicity in the mammalian developing spinal cord. PMID:27051566

  16. Global developmental delay, progressive relapsing-remitting parkinsonism, and spinal syrinx in a child with SOX6 mutation.

    PubMed

    Scott, Ori; Pugh, Jeffrey; Kiddoo, Darcie; Sonnenberg, Lyn K; Bamforth, Steven; Goez, Helly R

    2014-11-01

    SOX6, a member of the SOX gene family, plays a key role in the development of several mammalian tissues and organs, including the central nervous system. Specifically, this gene modulates the differentiation and proliferation of interneurons in the medial ganglionic eminence, as well as oligodendrocytes in the spinal cord. We describe the case of a 4-year-old girl with global developmental delay and a spinal cord syrinx who presented with recurrent episodes of parkinsonian symptoms subsequent to febrile illnesses. The symptoms included gait instability, tremor, and dysarthria, with a progressive relapsing-remitting course over the span of 2 years. The patient was later found to have a large deletion-type mutation in the SOX6 gene. This case is the first report in humans implying a role for SOX6 in basal ganglia function, as well as spinal cord development.

  17. Protective effect of rosemary on acrylamide motor neurotoxicity in spinal cord of rat offspring: postnatal follow-up study.

    PubMed

    Al-Gholam, Marwa A; Nooh, Hanaa Zakaria; El-Mehi, Abeer E; El-Barbary, Abd El-Moneum; Fokar, Ahmed Zo El

    2016-03-01

    The direct interactive effects of rosemary and acrylamide on the development of motor neurons in the spinal cord remains unknown. Our goal is to confirm the protective effects of rosemary against motor neuronal degeneration induced by acrylamide in the developing postnatal rat spinal cord using a postnatal rat model. We assigned the offspring of treated female rats into control, rosemary; acrylamide group; and recovery groups. This work depended on clinical, histopathological, morphometrically, immunohistochemical and genetic methods. In the acrylamide group, we observed oxidation, motor neuron degeneration, apoptosis, myelin degeneration, neurofilament reduction, reactive gliosis. Whoever, concomitant rosemary intake and withdrawal of acrylamide modulate these effects. These findings proof that dietary rosemary can directly protect motor neuron against acrylamide toxicity in the mammalian developing spinal cord.

  18. Right Hemisphere Brain Damage

    MedlinePlus

    ... Language and Swallowing / Disorders and Diseases Right Hemisphere Brain Damage [ en Español ] What is right hemisphere brain ... right hemisphere brain damage ? What is right hemisphere brain damage? Right hemisphere brain damage (RHD) is damage ...

  19. Vestibulo-spinal reflex mechanisms

    NASA Technical Reports Server (NTRS)

    Reschke, M. F.

    1981-01-01

    The specific objectives of experiments designed to investigate postural reflex behavior during sustained weightlessness are discussed. The first is to investigate, during prolonged weightlessness with Hoffmann response (H-reflex) measurement procedures, vestibulo-spinal reflexes associated with vestibular (otolith) responses evoked during an applied linear acceleration. This objective includes not only an evaluation of otolith-induced changes in a major postural muscle but also an investigation with this technique of the adaptive process of the vestibular system and spinal reflex mechanisms to this unique environment. The second objective is to relate space motion sickness to the results of this investigation. Finally, a return to the vestibulo-spinal and postural reflexes to normal values following the flight will be examined. The flight experiment involves activation of nerve tissue (tibial N) with electrical shock and the recording of resulting muscle activity (soleus) with surface electrodes. Soleus/spinal H-reflex testing procedures will be used in conjuction with linear acceleration through the subject's X-axis.

  20. Chemosignals, Hormones and Mammalian Reproduction

    PubMed Central

    Petrulis, Aras

    2013-01-01

    Many mammalian species use chemosignals to coordinate reproduction by altering the physiology and behavior of both sexes. Chemosignals prime reproductive physiology so that individuals become sexually mature and active at times when mating is most probable and suppress it when it is not. Once in reproductive condition, odors produced and deposited by both males and females are used to find and select individuals for mating. The production, dissemination and appropriate responses to these cues are modulated heavily by organizational and activational effects of gonadal sex steroids and thereby intrinsically link chemical communication to the broader reproductive context. Many compounds have been identified as “pheromones” but very few have met the expectations of that term: a unitary, species-typical substance that is both necessary and sufficient for an experience-independent behavioral or physiological response. In contrast, most responses to chemosignals are dependent or heavily modulated by experience, either in adulthood or during development. Mechanistically, chemosignals are perceived by both main and accessory (vomeronasal) olfactory systems with the importance of each system tied strongly to the nature of the stimulus rather than to the response. In the central nervous system, the vast majority of responses to chemosignals are mediated by cortical and medial amygdala connections with hypothalamic and other forebrain structures. Despite the importance of chemosignals in mammals, many details of chemical communication differ even among closely related species and defy clear categorization. Although generating much research and public interest, strong evidence for the existence of a robust chemical communication among humans is lacking. PMID:23545474

  1. Baculovirus Stimulates Antiviral Effects in Mammalian Cells

    PubMed Central

    Gronowski, Ann M.; Hilbert, David M.; Sheehan, Kathleen C. F.; Garotta, Gianni; Schreiber, Robert D.

    1999-01-01

    Herein, we report that Autographa californica nucleopolyhedrovirus, a member of the Baculoviridae family, is capable of stimulating antiviral activity in mammalian cells. Baculoviruses are not pathogenic to mammalian cells. Nevertheless, live baculovirus is shown here to induce interferons (IFN) from murine and human cell lines and induces in vivo protection of mice from encephalomyocarditis virus infection. Monoclonal antibodies specific for the baculovirus envelope gp67 neutralize baculovirus-dependent IFN production. Moreover, UV treatment of baculovirus eliminates both infectivity and IFN-inducing activity. In contrast, the IFN-inducing activity of the baculovirus was unaffected by DNase or RNase treatment. These data demonstrate that IFN production can be induced in mammalian cells by baculovirus even though the cells fail to serve as a natural host for an active viral infection. Baculoviruses, therefore, provide a novel model in which to study at least one alternative mechanism for IFN induction in mammalian cells. PMID:10559307

  2. Mammalian synthetic biology: emerging medical applications

    PubMed Central

    Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M.; Krams, Rob

    2015-01-01

    In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON–OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. PMID:25808341

  3. Mammalian synthetic biology: emerging medical applications.

    PubMed

    Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M; Krams, Rob

    2015-05-01

    In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON-OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes.

  4. Bats and Rodents Shape Mammalian Retroviral Phylogeny

    PubMed Central

    Cui, Jie; Tachedjian, Gilda; Wang, Lin-Fa

    2015-01-01

    Endogenous retroviruses (ERVs) represent past retroviral infections and accordingly can provide an ideal framework to infer virus-host interaction over their evolutionary history. In this study, we target high quality Pol sequences from 7,994 Class I and 8,119 Class II ERVs from 69 mammalian genomes and surprisingly find that retroviruses harbored by bats and rodents combined occupy the major phylogenetic diversity of both classes. By analyzing transmission patterns of 30 well-defined ERV clades, we corroborate the previously published observation that rodents are more competent as originators of mammalian retroviruses and reveal that bats are more capable of receiving retroviruses from non-bat mammalian origins. The powerful retroviral hosting ability of bats is further supported by a detailed analysis revealing that the novel bat gammaretrovirus, Rhinolophus ferrumequinum retrovirus, likely originated from tree shrews. Taken together, this study advances our understanding of host-shaped mammalian retroviral evolution in general. PMID:26548564

  5. Pain and spinal cord imaging measures in children with demyelinating disease.

    PubMed

    Barakat, Nadia; Gorman, Mark P; Benson, Leslie; Becerra, Lino; Borsook, David

    2015-01-01

    Pain is a significant problem in diseases affecting the spinal cord, including demyelinating disease. To date, studies have examined the reliability of clinical measures for assessing and classifying the severity of spinal cord injury (SCI) and also to evaluate SCI-related pain. Most of this research has focused on adult populations and patients with traumatic injuries. Little research exists regarding pediatric spinal cord demyelinating disease. One reason for this is the lack of reliable and useful approaches to measuring spinal cord changes since currently used diagnostic imaging has limited specificity for quantitative measures of demyelination. No single imaging technique demonstrates sufficiently high sensitivity or specificity to myelin, and strong correlation with clinical measures. However, recent advances in diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) measures are considered promising in providing increasingly useful and specific information on spinal cord damage. Findings from these quantitative imaging modalities correlate with the extent of demyelination and remyelination. These techniques may be of potential use for defining the evolution of the disease state, how it may affect specific spinal cord pathways, and contribute to the management of pediatric demyelination syndromes. Since pain is a major presenting symptom in patients with transverse myelitis, the disease is an ideal model to evaluate imaging methods to define these regional changes within the spinal cord. In this review we summarize (1) pediatric demyelinating conditions affecting the spinal cord; (2) their distinguishing features; and (3) current diagnostic and classification methods with particular focus on pain pathways. We also focus on concepts that are essential in developing strategies for the detection, monitoring, treatment and repair of pediatric myelitis. PMID:26509120

  6. Periaqueductal Grey EP3 Receptors Facilitate Spinal Nociception in Arthritic Secondary Hypersensitivity

    PubMed Central

    Drake, R.A.R.; Leith, J.L.; Almahasneh, F.; Martindale, J.; Wilson, A.W.; Lumb, B.

    2016-01-01

    Descending controls on spinal nociceptive processing play a pivotal role in shaping the pain experience after tissue injury. Secondary hypersensitivity develops within undamaged tissue adjacent and distant to damaged sites. Spinal neuronal pools innervating regions of secondary hypersensitivity are dominated by descending facilitation that amplifies spinal inputs from unsensitized peripheral nociceptors. Cyclooxygenase–prostaglandin (PG) E2 signaling within the ventrolateral periaqueductal gray (vlPAG) is pronociceptive in naive and acutely inflamed animals, but its contributions in more prolonged inflammation and, importantly, secondary hypersensitivity remain unknown. In naive rats, PG EP3 receptor (EP3R) antagonism in vlPAG modulated noxious withdrawal reflex (EMG) thresholds to preferential C-nociceptor, but not A-nociceptor, activation and raised thermal withdrawal thresholds in awake animals. In rats with inflammatory arthritis, secondary mechanical and thermal hypersensitivity of the hindpaw developed and was associated with spinal sensitization to A-nociceptor inputs alone. In arthritic rats, blockade of vlPAG EP3R raised EMG thresholds to C-nociceptor activation in the area of secondary hypersensitivity to a degree equivalent to that evoked by the same manipulation in naive rats. Importantly, vlPAG EP3R blockade also affected responses to A-nociceptor activation, but only in arthritic animals. We conclude that vlPAG EP3R activity exerts an equivalent facilitation on the spinal processing of C-nociceptor inputs in naive and arthritic animals, but gains in effects on spinal A-nociceptor processing from a region of secondary hypersensitivity. Therefore, the spinal sensitization to A-nociceptor inputs associated with secondary hypersensitivity is likely to be at least partly dependent on descending prostanergic facilitation from the vlPAG. SIGNIFICANCE STATEMENT After tissue damage, sensitivity to painful stimulation develops in undamaged areas (secondary

  7. Hacking the genetic code of mammalian cells.

    PubMed

    Schwarzer, Dirk

    2009-07-01

    A genetic shuttle: The highlighted article, which was recently published by Schultz, Geierstanger and co-workers, describes a straightforward scheme for enlarging the genetic code of mammalian cells. An orthogonal tRNA/aminoacyl-tRNA synthetase pair specific for a new amino acid can be evolved in E. coli and subsequently transferred into mammalian cells. The feasibility of this approach was demonstrated by adding a photocaged lysine derivative to the genetic repertoire of a human cell line. PMID:19533721

  8. Hacking the genetic code of mammalian cells.

    PubMed

    Schwarzer, Dirk

    2009-07-01

    A genetic shuttle: The highlighted article, which was recently published by Schultz, Geierstanger and co-workers, describes a straightforward scheme for enlarging the genetic code of mammalian cells. An orthogonal tRNA/aminoacyl-tRNA synthetase pair specific for a new amino acid can be evolved in E. coli and subsequently transferred into mammalian cells. The feasibility of this approach was demonstrated by adding a photocaged lysine derivative to the genetic repertoire of a human cell line.

  9. Simplified Bioreactor For Growing Mammalian Cells

    NASA Technical Reports Server (NTRS)

    Spaulding, Glenn F.

    1995-01-01

    Improved bioreactor for growing mammalian cell cultures developed. Designed to support growth of dense volumes of mammalian cells by providing ample, well-distributed flows of nutrient solution with minimal turbulence. Cells relatively delicate and, unlike bacteria, cannot withstand shear forces present in turbulent flows. Bioreactor vessel readily made in larger sizes to accommodate greater cell production quantities. Molding equipment presently used makes cylinders up to 30 centimeters long. Alternative sintered plastic techniques used to vary pore size and quantity, as necessary.

  10. Biomechanics of Degenerative Spinal Disorders

    PubMed Central

    Iorio, Justin A.; Jakoi, Andre M.

    2016-01-01

    The spine has several important functions including load transmission, permission of limited motion, and protection of the spinal cord. The vertebrae form functional spinal units, which represent the smallest segment that has characteristics of the entire spinal column. Discs and paired facet joints within each functional unit form a three-joint complex between which loads are transmitted. Surrounding the spinal motion segment are ligaments, composed of elastin and collagen, and joint capsules which restrict motion to within normal limits. Ligaments have variable strengths and act via different lever arm lengths to contribute to spinal stability. As a consequence of the longer moment arm from the spinous process to the instantaneous axis of rotation, inherently weaker ligaments (interspinous and supraspinous) are able to provide resistance to excessive flexion. Degenerative processes of the spine are a normal result of aging and occur on a spectrum. During the second decade of life, the intervertebral disc demonstrates histologic evidence of nucleus pulposus degradation caused by reduced end plate blood supply. As disc height decreases, the functional unit is capable of an increased range of axial rotation which subjects the posterior facet capsules to greater mechanical loads. A concurrent change in load transmission across the end plates and translation of the instantaneous axis of rotation further increase the degenerative processes at adjacent structures. The behavior of the functional unit is impacted by these processes and is reflected by changes in the stress-strain relationship. Back pain and other clinical symptoms may occur as a result of the biomechanical alterations of degeneration. PMID:27114783

  11. Management of lumbar spinal stenosis.

    PubMed

    Lurie, Jon; Tomkins-Lane, Christy

    2016-01-01

    Lumbar spinal stenosis (LSS) affects more than 200,000 adults in the United States, resulting in substantial pain and disability. It is the most common reason for spinal surgery in patients over 65 years. Lumbar spinal stenosis is a clinical syndrome of pain in the buttocks or lower extremities, with or without back pain. It is associated with reduced space available for the neural and vascular elements of the lumbar spine. The condition is often exacerbated by standing, walking, or lumbar extension and relieved by forward flexion, sitting, or recumbency. Clinical care and research into lumbar spinal stenosis is complicated by the heterogeneity of the condition, the lack of standard criteria for diagnosis and inclusion in studies, and high rates of anatomic stenosis on imaging studies in older people who are completely asymptomatic. The options for non-surgical management include drugs, physiotherapy, spinal injections, lifestyle modification, and multidisciplinary rehabilitation. However, few high quality randomized trials have looked at conservative management. A systematic review concluded that there is insufficient evidence to recommend any specific type of non-surgical treatment. Several different surgical procedures are used to treat patients who do not improve with non-operative therapies. Given that rapid deterioration is rare and that symptoms often wax and wane or gradually improve, surgery is almost always elective and considered only if sufficiently bothersome symptoms persist despite trials of less invasive interventions. Outcomes (leg pain and disability) seem to be better for surgery than for non-operative treatment, but the evidence is heterogeneous and often of limited quality. PMID:26727925

  12. Mammalian phylogeny reveals recent diversification rate shifts.

    PubMed

    Stadler, Tanja

    2011-04-12

    Phylogenetic trees of present-day species allow investigation of the rate of evolution that led to the present-day diversity. A recent analysis of the mammalian phylogeny challenged the view of explosive mammalian evolution after the Cretaceous-Tertiary (K/T) boundary (65 Mya). However, due to lack of appropriate methods, the diversification (speciation minus extinction) rates in the more recent past of mammalian evolution could not be determined. In this paper, I provide a method that reveals that the tempo of mammalian evolution did not change until ∼ 33 Mya. This constant period was followed by a peak of diversification rates between 33 and 30 Mya. Thereafter, diversification rates remained high and constant until 8.55 Mya. Diversification rates declined significantly at 8.55 and 3.35 Mya. Investigation of mammalian subgroups (marsupials, placentals, and the six largest placental subgroups) reveals that the diversification rate peak at 33-30 Mya is mainly driven by rodents, cetartiodactyla, and marsupials. The recent diversification rate decrease is significant for all analyzed subgroups but eulipotyphla, cetartiodactyla, and primates. My likelihood approach is not limited to mammalian evolution. It provides a robust framework to infer diversification rate changes and mass extinction events in phylogenies, reconstructed from, e.g., present-day species or virus data. In particular, the method is very robust toward noise and uncertainty in the phylogeny and can account for incomplete taxon sampling. PMID:21444816

  13. Chondroitinase ABC plus bone marrow mesenchymal stem cells for repair of spinal cord injury.

    PubMed

    Zhang, Chun; He, Xijing; Li, Haopeng; Wang, Guoyu

    2013-04-15

    As chondroitinase ABC can improve the hostile microenvironment and cell transplantation is proven to be effective after spinal cord injury, we hypothesized that their combination would be a more effective treatment option. At 5 days after T8 spinal cord crush injury, rats were injected with bone marrow mesenchymal stem cell suspension or chondroitinase ABC 1 mm from the edge of spinal cord damage zone. Chondroitinase ABC was first injected, and bone marrow mesenchymal stem cell suspension was injected on the next day in the combination group. At 14 days, the mean Basso, Beattie and Bresnahan score of the rats in the combination group was higher than other groups. Hematoxylin-eosin staining showed that the necrotic area was significantly reduced in the combination group compared with other groups. Glial fibrillary acidic protein-chondroitin sulfate proteoglycan double staining showed that the damage zone of astrocytic scars was significantly reduced without the cavity in the combination group. Glial fibrillary acidic protein/growth associated protein-43 double immunostaining revealed that positive fibers traversed the damage zone in the combination group. These results suggest that the combination of chondroitinase ABC and bone marrow mesenchymal stem cell transplantation contributes to the repair of spinal cord injury.

  14. Connexin43 mimetic peptide is neuroprotective and improves function following spinal cord injury.

    PubMed

    O'Carroll, Simon J; Gorrie, Catherine A; Velamoor, Sailakshmi; Green, Colin R; Nicholson, Louise F B

    2013-03-01

    Connexin43 (Cx43) is a gap junction protein up-regulated after spinal cord injury and is involved in the on-going spread of secondary tissue damage. To test whether a connexin43 mimetic peptide (Peptide5) reduces inflammation and tissue damage and improves function in an in vivo model of spinal cord injury, rats were subjected to a 10g, 12.5mm weight drop injury at the vertebral level T10 using a MASCIS impactor. Vehicle or connexin43 mimetic peptide was delivered directly to the lesion via intrathecal catheter and osmotic mini-pump for up to 24h after injury. Treatment with Peptide5 led to significant improvements in hindlimb function as assessed using the Basso-Beattie-Bresnahan scale. Peptide5 caused a reduction in Cx43 protein, increased Cx43 phosphorylation and decreased levels of TNF-α and IL-1β as assessed by Western blotting. Immunohistochemistry of tissue sections 5 weeks after injury showed reductions in astrocytosis and activated microglia as well as an increase in motor neuron survival. These results show that administration of a connexin mimetic peptide reduces secondary tissue damage after spinal cord injury by reducing gliosis and cytokine release and indicate the clinical potential for mimetic peptides in the treatment of spinal cord patients. PMID:23403365

  15. Unilateral microinjection of acrolein into thoracic spinal cord produces acute and chronic injury and functional deficits.

    PubMed

    Gianaris, Alexander; Liu, Nai-Kui; Wang, Xiao-Fei; Oakes, Eddie; Brenia, John; Gianaris, Thomas; Ruan, Yiwen; Deng, Ling-Xiao; Goetz, Maria; Vega-Alvarez, Sasha; Lu, Qing-Bo; Shi, Riyi; Xu, Xiao-Ming

    2016-06-21

    Although lipid peroxidation has long been associated with spinal cord injury (SCI), the specific role of lipid peroxidation-derived byproducts such as acrolein in mediating damage remains to be fully understood. Acrolein, an α-β unsaturated aldehyde, is highly reactive with proteins, DNA, and phospholipids and is considered as a second toxic messenger that disseminates and augments initial free radical events. Previously, we showed that acrolein increased following traumatic SCI and injection of acrolein induced tissue damage. Here, we demonstrate that microinjection of acrolein into the thoracic spinal cord of adult rats resulted in dose-dependent tissue damage and functional deficits. At 24h (acute) after the microinjection, tissue damage, motoneuron loss, and spinal cord swelling were observed on sections stained with Cresyl Violet. Luxol fast blue staining further showed that acrolein injection resulted in dose-dependent demyelination. At 8weeks (chronic) after the microinjection, cord shrinkage, astrocyte activation, and macrophage infiltration were observed along with tissue damage, neuron loss, and demyelination. These pathological changes resulted in behavioral impairments as measured by both the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and grid walking analysis. Electron microscopy further demonstrated that acrolein induced axonal degeneration, demyelination, and macrophage infiltration. These results, combined with our previous reports, strongly suggest that acrolein may play a critical causal role in the pathogenesis of SCI and that targeting acrolein could be an attractive strategy for repair after SCI. PMID:27058147

  16. [Iatrogenic spinal epidermoid tumors. A late complication of spinal puncture].

    PubMed

    Reina, M A; López-García, A; Dittmann, M; de Andrés, J A; Blázquez, M G

    1996-04-01

    INTRODUCTION. Epidermoid tumors in the spinal canal are rare. Whether congenitally or iatrogenically caused, they form as the result of epidermal cells implanted within the spinal channel. Such implantation can occur during a variety of procedures and events such as bullet wounds, surgery, myelography or punctures for diagnosis, anesthesia or treatment. Although this complication is not discussed in books or journals on anesthesiology, we have found it mentioned in over 100 published cases reporting iatrogenically caused spinal epidermoid tumors. ETIOPATHOGENESIS. Iatrogenic epidermoid tumors of the spine derive from the implantation of epidermal tissue transported inside the spinal canal during lumbar punctures without guidance or with inadequate guidance. There is ample evidence that such tumors are iatrogenic. All cases occur in patients with a history of lumbar puncture. They are rarely associated with congenital anomalies. They are extramedullary. They tend to develop near sites of earlier lumbar puncture, usually near the conus medullaris and the cauda equina. Iatrogenic epidermoid tumors of the spine have been reproduced experimentally in two studies in which autologous skin fragments were implanted in the spinal canal. CLINICAL SIGNS. These tumors are well tolerated by patients for extended periods of time, ranging from 2 to 10 years. At the cauda equinus, tumors can grow slowly for long periods without signs of nerve compression. Symptoms are directly related to tumor size and site. All patients with tumors at the cauda equinus report severe pain radiating toward the roots of compressed nerves. Nuclear magnetic resonance makes it possible to detect the tumor without administration of intrathecal contrast. At present gadolinium-DTPA improves the image so that these tumors can be distinguished from other types. The prognosis for epidermoid tumors of the spine is good, as they are histologically benign. Treatment is always surgical. CONCLUSION. Although the

  17. Mammalian Target of Rapamycin Inhibitors and Nephrotoxicity: Fact or Fiction.

    PubMed

    Barbari, Antoine; Maawad, Maria; Kfoury Kassouf, Hala; Kamel, Gaby

    2015-10-01

    Mammalian target of rapamycin inhibitors, such as rapamycin and more recently everolimus, have substituted calcineurin inhibitors in many minimization strategies. Despite their acclaimed renal safety profile, several lines of evidence are emerging on their potential nephrotoxic effect. Predisposing conditions for nephrotoxicity involve a complex interplay between several environmental and genetic factors in the donor-recipient pair. Renal injury may be enhanced by pharmacodynamic interactions when combined with other drugs such as calcineurin inhibitors or nutrients that are predominantly related to an increase in local tissue exposure. These toxic interactions may occur within adequate doses and therapeutic blood levels. This explains the occurrence of nephrotoxicity in some but not all cases. Here, we postulated that activity of a low permeability glycoprotein efflux pump related to low protein expression and/or inhibition enhanced immunosuppressive drug entry in different cells. A rise in intracellular drug concentration increases bioactivity, leading to greater immunosuppression and more immune-related, nonrenal adverse events in the recipient and increased nephrotoxicity in the kidney graft. Under specific isolated or combined environmental and/or genetic conditions in both the recipient and donor affecting the glycoprotein efflux pump and/or the mammalian target of rapamycin pathway, these renal injuries may be aggravated by heightened drug tissue concentrations despite adherence to therapeutic drug and blood levels. Mammalian target of rapamycin inhibitors may induce predominantly a dose-dependent renal epithelial cell injury affecting either the glomerular or the renal tubular epithelial cells, leading to cell death and apoptosis. Epithelial mesenchymal transition mediated interstitial fibrosis and tubular atrophy observed with these drugs may be the result of a cumulative toxic renal tubular injury induced by the direct insult of the drug itself and

  18. Cellular Transplantation Strategies for Spinal Cord Injury and Translational Neurobiology

    PubMed Central

    Reier, Paul J.

    2004-01-01

    Summary: Basic science advances in spinal cord injury and regeneration research have led to a variety of novel experimental therapeutics designed to promote functionally effective axonal regrowth and sprouting. Among these interventions are cell-based approaches involving transplantation of neural and non-neural tissue elements that have potential for restoring damaged neural pathways or reconstructing intraspinal synaptic circuitries by either regeneration or neuronal/glial replacement. Notably, some of these strategies (e.g., grafts of peripheral nerve tissue, olfactory ensheathing glia, activated macrophages, marrow stromal cells, myelin-forming oligodendrocyte precursors or stem cells, and fetal spinal cord tissue) have already been translated to the clinical arena, whereas others have imminent likelihood of bench-to-bedside application. Although this progress has generated considerable enthusiasm about treating what once was thought to be a totally incurable condition, there are many issues to be considered relative to treatment safety and efficacy. The following review reflects on different experimental applications of intraspinal transplantation with consideration of the underlying pathological, pathophysiological, functional, and neuroplastic responses to spinal trauma that such treatments may target along with related issues of procedural and biological safety. The discussion then moves to an overview of ongoing and completed clinical trials to date. The pros and cons of these endeavors are considered, as well as what has been learned from them. Attention is primarily directed at preclinical animal modeling and the importance of patterning clinical trials, as much as possible, according to laboratory experiences. PMID:15717046

  19. Endogenous repair after spinal cord contusion injuries in the rat.

    PubMed

    Beattie, M S; Bresnahan, J C; Komon, J; Tovar, C A; Van Meter, M; Anderson, D K; Faden, A I; Hsu, C Y; Noble, L J; Salzman, S; Young, W

    1997-12-01

    Contusion injuries of the rat thoracic spinal cord were made using a standardized device developed for the Multicenter Animal Spinal Cord Injury Study (MASCIS). Lesions of different severity were studied for signs of endogenous repair at times up to 6 weeks following injury. Contusion injuries produced a typical picture of secondary damage resulting in the destruction of the cord center and the chronic sparing of a peripheral rim of fibers which varied in amount depending upon the injury magnitude. It was noted that the cavities often developed a dense cellular matrix that became partially filled with nerve fibers and associated Schwann cells. The amount of fiber and Schwann cell ingrowth was inversely related to the severity of injury and amount of peripheral fiber sparing. The source of the ingrowing fibers was not determined, but many of them clearly originated in the dorsal roots. In addition to signs of regeneration, we noted evidence for the proliferation of cells located in the ependymal zone surrounding the central canal at early times following contusion injuries. These cells may contribute to the development of cellular trabeculae that provide a scaffolding within the lesion cavity that provides the substrates for cellular infiltration and regeneration of axons. Together, these observations suggest that the endogenous reparative response to spinal contusion injury is substantial. Understanding the regulation and restrictions on the repair processes might lead to better ways in which to encourage spontaneous recovery after CNS injury. PMID:9417825

  20. Cellular transplantation strategies for spinal cord injury and translational neurobiology.

    PubMed

    Reier, Paul J

    2004-10-01

    Basic science advances in spinal cord injury and regeneration research have led to a variety of novel experimental therapeutics designed to promote functionally effective axonal regrowth and sprouting. Among these interventions are cell-based approaches involving transplantation of neural and non-neural tissue elements that have potential for restoring damaged neural pathways or reconstructing intraspinal synaptic circuitries by either regeneration or neuronal/glial replacement. Notably, some of these strategies (e.g., grafts of peripheral nerve tissue, olfactory ensheathing glia, activated macrophages, marrow stromal cells, myelin-forming oligodendrocyte precursors or stem cells, and fetal spinal cord tissue) have already been translated to the clinical arena, whereas others have imminent likelihood of bench-to-bedside application. Although this progress has generated considerable enthusiasm about treating what once was thought to be a totally incurable condition, there are many issues to be considered relative to treatment safety and efficacy. The following review reflects on different experimental applications of intraspinal transplantation with consideration of the underlying pathological, pathophysiological, functional, and neuroplastic responses to spinal trauma that such treatments may target along with related issues of procedural and biological safety. The discussion then moves to an overview of ongoing and completed clinical trials to date. The pros and cons of these endeavors are considered, as well as what has been learned from them. Attention is primarily directed at preclinical animal modeling and the importance of patterning clinical trials, as much as possible, according to laboratory experiences.

  1. Modification of N-glycosylation sites allows secretion of bacterial chondroitinase ABC from mammalian cells.

    PubMed

    Muir, Elizabeth M; Fyfe, Ian; Gardiner, Sonya; Li, Li; Warren, Philippa; Fawcett, James W; Keynes, Roger J; Rogers, John H

    2010-01-15

    Although many eukaryotic proteins have been secreted by transfected bacterial cells, little is known about how a bacterial protein is treated as it passes through the secretory pathway when expressed in a eukaryotic cell. The eukaryotic N-glycosylation system could interfere with folding and secretion of prokaryotic proteins whose sequence has not been adapted for glycosylation in structurally appropriate locations. Here we show that such interference does indeed occur for chondroitinase ABC from the bacterium Proteus vulgaris, and can be overcome by eliminating potential N-glycosylation sites. Chondroitinase ABC was heavily glycosylated when expressed in mammalian cells or in a mammalian translation system, and this process prevented secretion of functional enzyme. Directed mutagenesis of selected N-glycosylation sites allowed efficient secretion of active chondroitinase. As these proteoglycans are known to inhibit regeneration of axons in the mammalian central nervous system, the modified chondroitinase gene is a potential tool for gene therapy to promote neural regeneration, ultimately in human spinal cord injury.

  2. Modification of N-glycosylation sites allows secretion of bacterial chondroitinase ABC from mammalian cells

    PubMed Central

    Muir, Elizabeth M.; Fyfe, Ian; Gardiner, Sonya; Li, Li; Warren, Philippa; Fawcett, James W.; Keynes, Roger J.; Rogers, John H.

    2010-01-01

    Although many eukaryotic proteins have been secreted by transfected bacterial cells, little is known about how a bacterial protein is treated as it passes through the secretory pathway when expressed in a eukaryotic cell. The eukaryotic N-glycosylation system could interfere with folding and secretion of prokaryotic proteins whose sequence has not been adapted for glycosylation in structurally appropriate locations. Here we show that such interference does indeed occur for chondroitinase ABC from the bacterium Proteus vulgaris, and can be overcome by eliminating potential N-glycosylation sites. Chondroitinase ABC was heavily glycosylated when expressed in mammalian cells or in a mammalian translation system, and this process prevented secretion of functional enzyme. Directed mutagenesis of selected N-glycosylation sites allowed efficient secretion of active chondroitinase. As these proteoglycans are known to inhibit regeneration of axons in the mammalian central nervous system, the modified chondroitinase gene is a potential tool for gene therapy to promote neural regeneration, ultimately in human spinal cord injury. PMID:19900493

  3. Germline ablation of dermatan-4O-sulfotransferase1 reduces regeneration after mouse spinal cord injury.

    PubMed

    Rost, S; Akyüz, N; Martinovic, T; Huckhagel, T; Jakovcevski, I; Schachner, M

    2016-01-15

    Chondroitin/dermatan sulfate proteoglycans (CSPGs/DSPGs) are major components of the extracellular matrix. Their expression is generally upregulated after injuries to the adult mammalian central nervous system, which is known for its low ability to restore function after injury. Several studies support the view that CSPGs inhibit regeneration after injury, whereas the functions of DSPGs in injury paradigms are less certain. To characterize the functions of DSPGs in the presence of CSPGs, we studied young adult dermatan-4O-sulfotransferase1-deficient (Chst14(-/-)) mice, which express chondroitin sulfates (CSs), but not dermatan sulfates (DSs), to characterize the functional outcome after severe compression injury of the spinal cord. In comparison to their wild-type (Chst14(+/+)) littermates, regeneration was reduced in Chst14(-/-) mice. No differences between genotypes were seen in the size of spinal cords, numbers of microglia and astrocytes neither in intact nor injured spinal cords after injury. Monoaminergic innervation and re-innervation of the spinal cord caudal to the lesion site as well as expression levels of glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) were similar in both genotypes, independent of whether they were injured and examined 6weeks after injury or not injured. These results suggest that, in contrast to CSPGs, DSPGs, being the products of Chst14 enzymatic activity, promote regeneration after injury of the adult mouse central nervous system.

  4. Survey of intermediate filament proteins in optic nerve and spinal cord: evidence for differential expression.

    PubMed

    Quitschke, W; Jones, P S; Schechter, N

    1985-05-01

    The distribution of intermediate filament proteins in optic nerve and spinal cord from rat, hamster, goldfish, frog, and newt were analyzed by two-dimensional gel electrophoresis. General as well as specific monoclonal and polyclonal antibodies were reacted against putative intermediate filament proteins. In vitro incubations of excised optic nerve in the presence of [35S]methionine distinguished between neuronal and nonneuronal intermediate filament proteins. The proteins of the intermediate filament complex in the two tissues for rat and hamster were similar. The typical neurofilament triplet and glial fibrillary acidic protein (GFAP) were observed. Vimentin was more concentrated in the optic nerve than in the spinal cord. The goldfish, newt, and frog contained neurofilament proteins in the 145-150K range and in the 70-85K range. In addition, predominant neurofilament proteins in the 58-62K molecular-weight range were found in all three species. In contrast to mammalian species, the goldfish, newt, and frog displayed extensive heterogeneity between optic nerve and spinal cord in the expression of both neuronal and nonneuronal intermediate filament proteins. The distinctive presence of low-molecular-weight intermediate filament proteins and their high concentration in the optic nerve and spinal cord of these nonmammalian vertebrates is discussed in terms of neuronal development and regeneration.

  5. Mutagenicity of hydralazine in mammalian cells and bacteria.

    PubMed

    McQueen, C A; Way, B M; Queener, S M

    1993-01-01

    The genotoxicity of hydralazine (HDZ), an antihypertensive agent, was evaluated in mammalian cells and bacteria. The formation of mutants at the hypoxanthine guanine phosphoribosyl transferase locus in an adult rat liver cell line ARL 18 was determined. Bacterial mutagenicity was assessed in Salmonella typhimurium strains TA100 and TA102. The latter strain was chosen because it has A:T bases at the reversion site and HDZ has been reported to interact with thymidine. HDZ was mutagenic to ARL 18 cells with a concentration-dependent increase in mutants observed at 5 x 10(-6) to 5 x 10(-4) M. At 5 x 10(-4) M HDZ, there were 110 mutants/10(6) colony-forming cells compared to 129 for cells exposed to 10(-4) M benzo(a)pyrene, a known genotoxin. Bacterial mutants were observed with HDZ in both strains in the absence of an activating system. HDZ also induced mutants in the presence of S-9 from Aroclor-induced rat liver or uninduced rabbit liver. These results were consistent with previous reports of the mutagenicity of HDZ in TA100 and extend the observations to TA102, a strain designed to detect oxidative damage. This study also provides the first evidence of the mutagenicity of HDZ in mammalian cells. These data support the genotoxicity of HDZ in in vitro systems.

  6. Evolutionary history and metabolic insights of ancient mammalian uricases

    PubMed Central

    Kratzer, James T.; Lanaspa, Miguel A.; Murphy, Michael N.; Cicerchi, Christina; Graves, Christina L.; Tipton, Peter A.; Ortlund, Eric A.; Johnson, Richard J.; Gaucher, Eric A.

    2014-01-01

    Uricase is an enzyme involved in purine catabolism and is found in all three domains of life. Curiously, uricase is not functional in some organisms despite its role in converting highly insoluble uric acid into 5-hydroxyisourate. Of particular interest is the observation that apes, including humans, cannot oxidize uric acid, and it appears that multiple, independent evolutionary events led to the silencing or pseudogenization of the uricase gene in ancestral apes. Various arguments have been made to suggest why natural selection would allow the accumulation of uric acid despite the physiological consequences of crystallized monosodium urate acutely causing liver/kidney damage or chronically causing gout. We have applied evolutionary models to understand the history of primate uricases by resurrecting ancestral mammalian intermediates before the pseudogenization events of this gene family. Resurrected proteins reveal that ancestral uricases have steadily decreased in activity since the last common ancestor of mammals gave rise to descendent primate lineages. We were also able to determine the 3D distribution of amino acid replacements as they accumulated during evolutionary history by crystallizing a mammalian uricase protein. Further, ancient and modern uricases were stably transfected into HepG2 liver cells to test one hypothesis that uricase pseudogenization allowed ancient frugivorous apes to rapidly convert fructose into fat. Finally, pharmacokinetics of an ancient uricase injected in rodents suggest that our integrated approach provides the foundation for an evolutionarily-engineered enzyme capable of treating gout and preventing tumor lysis syndrome in human patients. PMID:24550457

  7. Toxic effects of Karenia mikimotoi extracts on mammalian cells

    NASA Astrophysics Data System (ADS)

    Chen, Yang; Yan, Tian; Yu, Rencheng; Zhou, Mingjiang

    2011-07-01

    Karenia is one of the most harmful and representative red tide genus in a temperate zone. Blooms caused by this genus have resulted in massive fish death in the South China Sea and the East China Sea. However, the potential effects of this dinoflagellate on human health through the transfer of toxins via marine food webs, and the mechanisms of toxicity, are still unknown. Therefore, we examined the toxic effects of a strain of K. mikimotoi (isolated from the South China Sea) on the proliferation and morphology of four mammalian cell lines (two normal cell lines and two cancer cell lines). In addition, we carried out a preliminary investigation on the mechanism of toxicity of the alga. The results show that the polar lipid-soluble component of K. mikimotoi significantly inhibited proliferation of the four cell lines, and resulted in the cells becoming spherical, swollen and damaged. The result of Annexin V and PI double-staining confirmed that cell membranes were disrupted. The malonaldehyde (MDA) contents in the medium of the four cell lines treated with the polar-lipid extracts all increased significantly, which indicates that the polar-lipid toxins produced by K. mikimotoi could adversely affect mammalian cells by inducing lipid peroxidation. We conclude that K. mikimotoi is a potential threat to human health, and the comprehensive effect of this dinoflagellate and its mechanisms should be investigated further.

  8. Garcinielliptone FC: antiparasitic activity without cytotoxicity to mammalian cells.

    PubMed

    Silva, Ana P; Silva, Marcos P; Oliveira, Cristiano G; Monteiro, Daniela C; Pinto, Pedro L; Mendonça, Ronaldo Z; Costa Júnior, Joaquim S; Freitas, Rivelilson M; de Moraes, Josué

    2015-06-01

    Garcinielliptone FC (GFC) is a natural prenylated benzophenone found in the seeds of Platonia insignis Mart. (Clusiaceae), a native Brazilian plant. It has been chemically characterized and it is known that GFC has several biological activities such as antioxidant and vasorelaxant properties. In this study, we report the in vitro effect of GFC against the blood fluke Schistosoma mansoni, the parasite responsible for schistosomiasis mansoni. The anti-S. mansoni activity and cytotoxicity toward mammalian cells were determined for the compound. GFC⩾6.25 μM showed antischistosomal activity and confocal laser scanning microscopy analysis demonstrated several morphological alterations on the tegument of worms, and a correlation between viability and tegumental damage was observed. In addition, at sub-lethal concentrations of GFC (⩽3.125 μM), the number of S. mansoni eggs was reduced. More importantly, GFC exhibited no activity toward mammalian cells and, therefore, there is an appreciable selectivity of this compound against the helminths. In conclusion, these findings indicate the potential of GFC as an antiparasitic agent. PMID:25553916

  9. Receptor-mediated mitophagy in yeast and mammalian systems

    PubMed Central

    Liu, Lei; Sakakibara, Kaori; Chen, Quan; Okamoto, Koji

    2014-01-01

    Mitophagy, or mitochondria autophagy, plays a critical role in selective removal of damaged or unwanted mitochondria. Several protein receptors, including Atg32 in yeast, NIX/BNIP3L, BNIP3 and FUNDC1 in mammalian systems, directly act in mitophagy. Atg32 interacts with Atg8 and Atg11 on the surface of mitochondria, promoting core Atg protein assembly for mitophagy. NIX/BNIP3L, BNIP3 and FUNDC1 also have a classic motif to directly bind LC3 (Atg8 homolog in mammals) for activation of mitophagy. Recent studies have shown that receptor-mediated mitophagy is regulated by reversible protein phosphorylation. Casein kinase 2 (CK2) phosphorylates Atg32 and activates mitophagy in yeast. In contrast, in mammalian cells Src kinase and CK2 phosphorylate FUNDC1 to prevent mitophagy. Notably, in response to hypoxia and FCCP treatment, the mitochondrial phosphatase PGAM5 dephosphorylates FUNDC1 to activate mitophagy. Here, we mainly focus on recent advances in our understanding of the molecular mechanisms underlying the activation of receptor-mediated mitophagy and the implications of this catabolic process in health and disease. PMID:24903109

  10. Axonal growth and connectivity from neural stem cell grafts in models of spinal cord injury.

    PubMed

    Lu, Paul; Kadoya, Ken; Tuszynski, Mark H

    2014-08-01

    Spinal cord injury (SCI) damages both gray matter and white matter, but white matter damage is responsible for the vast majority of the subsequent functional loss. Neural stem cells (NSCs) have been investigated as a means of improving outcomes after SCI, either through neuroprotective properties that limit secondary damage or by direct cell replacement. This review will focus on cell replacement strategies, and the ability of multipotent NSCs to form new functional synaptic relays across sites of even severe SCI. The ability of these early stage neurons to extend axons from the lesion site in large numbers and over long distances constitutes an important mechanism underlying their potential to promote neural repair.

  11. 4-hydroxynonenal, a lipid peroxidation product, rapidly accumulates following traumatic spinal cord injury and inhibits glutamate uptake.

    PubMed

    Springer, J E; Azbill, R D; Mark, R J; Begley, J G; Waeg, G; Mattson, M P

    1997-06-01

    Traumatic injury to the spinal cord initiates a host of pathophysiological events that are secondary to the initial insult. One such event is the accumulation of free radicals that damage lipids, proteins, and nucleic acids. A major reactive product formed following lipid peroxidation is the aldehyde, 4-hydroxynonenal (HNE), which cross-links to side chain amino acids and inhibits the function of several key metabolic enzymes. In the present study, we used immunocytochemical and immunoblotting techniques to examine the accumulation of protein-bound HNE, and synaptosomal preparations to study the effects of spinal cord injury and HNE formation on glutamate uptake. Protein-bound HNE increased in content in the damaged spinal cord at early times following injury (1-24 h) and was found to accumulate in myelinated fibers distant to the site of injury. Immunoblots revealed that protein-bound HNE levels increased dramatically over the same postinjury interval. Glutamate uptake in synaptosomal preparations from injured spinal cords was decreased by 65% at 24 h following injury. Treatment of control spinal cord synaptosomes with HNE was found to decrease significantly, in a dose-dependent fashion, glutamate uptake, an effect that was mimicked by inducers of lipid peroxidation. Taken together, these findings demonstrate that the lipid peroxidation product HNE rapidly accumulates in the spinal cord following injury and that a major consequence of HNE accumulation is a decrease in glutamate uptake, which may potentiate neuronal cell dysfunction and death through excitotoxic mechanisms. PMID:9166741

  12. Effect of intra-cisternal application of kainic acid on the spinal cord and locomotor activity in rats

    PubMed Central

    Mitra, Nilesh K; Goh, Tiffanie EW; Bala Krishnan, Thalisha; Nadarajah, Vishna D; Vasavaraj, Arun K; Soga, Tomoko

    2013-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease of idiopathic etiology. Glutamate excitotoxicity is one of the proposed hypotheses causing progressive death of motor neurons. We aimed to develop an experimental animal model of this disease to enhance the knowledge of pathophysiological mechanism of ALS. Male Wistar rats were infused with Kainic acid (KA) intra-cisternally for 5 days at the dosage of 50 fmol/day and 150 fmol/day. Locomotor activity, sensory function and histological changes in cervical and lumbar sections of spinal cord were evaluated. Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Protein (NFP) were used as immunohistochemical marker for reactive astrogliosis and neuronal damage respectively. Specific Superoxide Dismutase (SOD) activity of spinal cord was estimated. The locomotor activity in the parameter of observed mean action time remained reduced on 14th day after administration of KA. Spinal motor neurons under Nissl stain showed pyknosis of nucleus and vacuolation of neuropil. GFAP expression increased significantly in the lumbar section of the spinal cord with high dose of KA treatment (p<0.05). NFP was expressed in axonal fibres around the neurons in KA-treated rats. A significant increase in specific SOD activity in both cervical and lumbar sections of the spinal cord was found with low dose of KA treatment (p<0.05). This study concludes that spinal cord damage with some features similar to ALS can be produced by low dose intra-cisternal administration of KA. PMID:23923068

  13. Retinoic Acid Stimulates Regeneration of Mammalian Auditory Hair Cells

    NASA Astrophysics Data System (ADS)

    Lefebvre, Philippe P.; Malgrange, Brigitte; Staecker, Hinrich; Moonen, Gustave; van de Water, Thomas R.

    1993-04-01

    Sensorineural hearing loss resulting from the loss of auditory hair cells is thought to be irreversible in mammals. This study provides evidence that retinoic acid can stimulate the regeneration in vitro of mammalian auditory hair cells in ototoxic-poisoned organ of Corti explants in the rat. In contrast, treatment with retinoic acid does not stimulate the formation of extra hair cells in control cultures of Corti's organ. Retinoic acid-stimulated hair cell regeneration can be blocked by cytosine arabinoside, which suggests that a period of mitosis is required for the regeneration of auditory hair cells in this system. These results provide hope for a recovery of hearing function in mammals after auditory hair cell damage.

  14. Markers of Epidermal Stem Cell Subpopulations in Adult Mammalian Skin

    PubMed Central

    Kretzschmar, Kai; Watt, Fiona M.

    2014-01-01

    The epidermis is the outermost layer of mammalian skin and comprises a multilayered epithelium, the interfollicular epidermis, with associated hair follicles, sebaceous glands, and eccrine sweat glands. As in other epithelia, adult stem cells within the epidermis maintain tissue homeostasis and contribute to repair of tissue damage. The bulge of hair follicles, where DNA-label-retaining cells reside, was traditionally regarded as the sole epidermal stem cell compartment. However, in recent years multiple stem cell populations have been identified. In this review, we discuss the different stem cell compartments of adult murine and human epidermis, the markers that they express, and the assays that are used to characterize epidermal stem cell properties. PMID:24993676

  15. Isolation of Lysosomes from Mammalian Tissues and Cultured Cells.

    PubMed

    Aguado, Carmen; Pérez-Jiménez, Eva; Lahuerta, Marcos; Knecht, Erwin

    2016-01-01

    Lysosomes participate within the cells in the degradation of organelles, macromolecules, and a wide variety of substrates. In any study on specific roles of lysosomes, both under physiological and pathological conditions, it is advisable to include methods that allow their reproducible and reliable isolation. However, purification of lysosomes is a difficult task, particularly in the case of cultured cells. This is mainly because of the heterogeneity of these organelles, along with their low number and high fragility. Also, isolation methods, while disrupting plasma membranes, have to preserve the integrity of lysosomes, as the breakdown of their membranes releases enzymes that could damage all cell organelles, including themselves. The protocols described below have been routinely used in our laboratory for the specific isolation of lysosomes from rat liver, NIH/3T3, and other cultured cells, but can be adapted to other mammalian tissues or cell lines. PMID:27613045

  16. Serious complication of cement augmentation for damaged pilot hole.

    PubMed

    Jung, Moon Young; Shin, Dong Ah; Hahn, In Bo; Kim, Tae Gon; Huh, Ryoong; Chung, Sang Sup

    2010-05-01

    Polymethl methacrylate (PMMA) screw reinforcement is frequently used in osteoporotic bone as well as in damaged pilot holes. However, PMMA use can be dangerous, since the amount of applied cement is uncontrolled. A 47-year-old male with traumatic cervical spondylolisthesis at C6-7 underwent anterior cervical plate fixation. During repeated drilling and tapping for false trajectory correction, a pilot hole was damaged. Although it was an unconventional method, PMMA augmentation was tried. However, PMMA was accidentally injected to the cervical spinal cord owing to lack of fluoroscopic guidance. The PMMA was surgically removed after corpectomy and durotomy. The patient had left side hemiparesis (Grade 2/5) immediately post operation. The patient improved spontaneously (Grade 4/5) except for 4th and 5th digit extension. Here, we report a rare complication of PMMA extrusion in the spinal cord during a damaged pilot hole injection, which has not previously been described. PMID:20376906

  17. Whole Spontaneous Spinal Epidural Hematoma

    PubMed Central

    Yoon, Kyeong-Wook; Song, Jae Gyok; Ryu, Jae-Wook

    2014-01-01

    A 26-year-old male who had no underlying disease, including coagulopathy, underwent thoracotomy and bleeding control due to hemothorax. On the fifth postoperative day, paralysis of both lower limbs occurred. Urgent spine magnetic resonance imaging showed a massive anterior spinal epidural hematoma from C2 to L1 level with different signal intensities, which was suspected to be staged hemorrhage. Hematoma evacuation with decompressive laminectomy was performed. The patient's neurologic deterioration was recovered immediately, and he was discharged without neurological deficits. A drug history of naftazone, which could induce a drug-induced platelet dysfunction, was revealed retrospectively. To our knowledge, this is the first report of whole spontaneous spinal epidural hematoma in a young patient, with a history of hemorrhoid medication. PMID:24967052

  18. Spontaneous Spinal Epidural Hematoma Report.

    PubMed

    Kukreja, Sunil; Nanda, Anil

    2016-01-01

    We report a case of spontaneous spinal epidural hematoma in a 12-year-old female, who presented with significant upper and lower extremities weakness preceded by pain around the neck and shoulder girdle. Magnetic resonance imaging revealed epidural hematoma extending from C6-T2 with characteristic heterogeneously hyperintensity on T2 and homogenously isointensity on T1. Emergent spinal decompression was performed. However, the patient remained substantially weak in her lower extremities and was wheelchair bound at 3 months postoperatively. We have discussed clinical features, predisposing events, pathogenesis and treatment guidelines described in the literature. We also aim to reinforce the notion of keeping a high degree of clinical suspicion to identify and intervene at the earliest stage to prevent the physically and socially challenging consequences of SSEH. PMID:27598898

  19. [Spinal stenosis: diagnosis and treatment].

    PubMed

    Faundez, Antonio; Genevay, Stéphane

    2012-06-27

    Spondylotic cervical myelopathy (SCM) is a radiologic entity that can match a clinical syndrome of varying degree of severity, and results from spinal canal narrowing due to physiological degeneration of the cervical spine. Clinically, cervical spinal canal narrowing can produce minimal symptoms such as non-specific neck pain, foraminal entrapment of nerve roots, or more severe, chronic myelopathy. SCM initially manifests by signs of posterior medullary tract dysfunction with subsequent pallesthesia, resulting in gait and balance disturbance. Spasticity due to lower motoneurone impairment and incontinence may appear in later stages. Once the symptoms of myelopathy occur, functional deterioration will take place sooner or later. Surgery can then be recommended and scheduled according to the severity of functional impairment and imaging.

  20. Archetype, adaptation and the mammalian heart.

    PubMed

    Meijler, F L; Meijler, T D

    2011-03-01

    Forty years ago, we started our quest for 'The Holy Grail' of understanding ventricular rate control and rhythm in atrial fibrillation (AF). We therefore studied the morphology and function of a wide range of mammalian hearts. From mouse to whale, we found that all hearts show similar structural and functional characteristics. This suggests that the mammalian heart remained well conserved during evolution and in this aspect it differs from other organs and parts of the mammalian body. The archetype of the mammalian heart was apparently so successful that adaptation by natural selection (evolution) caused by varying habitat demands, as occurred in other organs and many other aspects of mammalian anatomy, bypassed the heart. The structure and function of the heart of placental mammals have thus been strikingly conserved throughout evolution. The changes in the mammalian heart that did take place were mostly adjustments (scaling), to compensate for variations in body size and shape. A remarkable scaling effect is, for instance, the difference in atrioventricular (AV) conduction time, which is vital for optimal cardiac function in all mammals, small and large. Scaling of AV conduction takes place in the AV node (AVN), but its substrate is unknown. This sheds new light on the vital role of the AVN in health and disease. The AVN is master and servant of the heart at the same time and is of salient importance for our understanding of supraventricular arrhythmias in humans, especially AF. In Information Technology a software infra-structure called 'enterprise service bus' (ESB) may provide understanding of the mammalian heart's conservation during evolution. The ESB is quite unspecific (and thus general) when compared with the specialised components it has to support. For instance, one of the functions of an ESB is the routing of messages between system nodes. This routing is independent and unaware of the content of the messages. The function of the heart is likewise

  1. Blood-Spinal Cord Barrier Alterations in Subacute and Chronic Stages of a Rat Model of Focal Cerebral Ischemia.

    PubMed

    Garbuzova-Davis, Svitlana; Haller, Edward; Tajiri, Naoki; Thomson, Avery; Barretta, Jennifer; Williams, Stephanie N; Haim, Eithan D; Qin, Hua; Frisina-Deyo, Aric; Abraham, Jerry V; Sanberg, Paul R; Van Loveren, Harry; Borlongan, Cesario V

    2016-07-01

    We previously demonstrated blood-brain barrier impairment in remote contralateral brain areas in rats at 7 and 30 days after transient middle cerebral artery occlusion (tMCAO), indicating ischemic diaschisis. Here, we focused on effects of subacute and chronic focal cerebral ischemia on the blood-spinal cord barrier (BSCB). We observed BSCB damage on both sides of the cervical spinal cord in rats at 7 and 30 days post-tMCAO. Major BSCB ultrastructural changes in spinal cord gray and white matter included vacuolated endothelial cells containing autophagosomes, pericyte degeneration with enlarged mitochondria, astrocyte end-feet degeneration and perivascular edema; damaged motor neurons, swollen axons with unraveled myelin in ascending and descending tracts and astrogliosis were also observed. Evans Blue dye extravasation was maximal at 7 days. There was immunofluorescence evidence of reduction of microvascular expression of tight junction occludin, upregulation of Beclin-1 and LC3B immunoreactivities at 7 days and a reduction of the latter at 30 days post-ischemia. These novel pathological alterations on the cervical spinal cord microvasculature in rats after tMCAO suggest pervasive and long-lasting BSCB damage after focal cerebral ischemia, and that spinal cord ischemic diaschisis should be considered in the pathophysiology and therapeutic approaches in patients with ischemic cerebral infarction. PMID:27283328

  2. Increased S-nitrosothiols are associated with spinal cord injury in multiple sclerosis.

    PubMed

    Fominykh, Vera; Onufriev, Mikhail V; Vorobyeva, Anna; Brylev, Lev; Yakovlev, Alexander A; Zakharova, Maria N; Gulyaeva, Natalia V

    2016-06-01

    Multiple sclerosis (MS) is an immune-mediated disorder associated with inflammation, demyelination and axonal damage. In search of potential biomarkers of spinal cord lesions in MS related to nitric oxide metabolites, we measured total nitrite and nitrate levels, and protein-bound nitrotyrosine and S-nitrosothiol concentrations in the serum of MS patients at different stages of the disease. Sixty-eight patients and 36 healthy volunteers were included in the study. Total nitrite and nitrate levels were augmented in relapsing-remitting MS, while increased S-nitrosothiol concentrations were found both in relapsing-remitting and secondary-progressive MS. Further analysis demonstrated that S-nitrosothiol levels were selectively increased in patients with spinal cord injury. The data suggest that high S-nitrosothiol concentration may be a potential serum biomarker for spinal cord injury in MS. PMID:26778356

  3. Oxidative stress in toxicology: established mammalian and emerging piscine model systems.

    PubMed Central

    Kelly, K A; Havrilla, C M; Brady, T C; Abramo, K H; Levin, E D

    1998-01-01

    Interest in the toxicological aspects of oxidative stress has grown in recent years, and research has become increasingly focused on the mechanistic aspects of oxidative damage and cellular responses in biological systems. Toxic consequences of oxidative stress at the subcellular level include lipid peroxidation and oxidative damage to DNA and proteins. These effects are often used as end points in the study of oxidative stress. Typically, mammalian species have been used as models to study oxidative stress and to elucidate the mechanisms underlying cellular damage and response, largely because of the interest in human health issues surrounding oxidative stress. However, it is becoming apparent that oxidative stress also affects aquatic organisms exposed to environmental pollutants. Research in fish has demonstrated that mammalian and piscine systems exhibit similar toxicological and adaptive responses to oxidative stress. This suggests that piscine models, in addition to traditional mammalian models, may be useful for further understanding the mechanisms underlying the oxidative stress response. Images Figure 1 Figure 2 Figure 3 PMID:9637794

  4. Ganglioglioma of the Spinal Cord

    PubMed Central

    Oppenheimer, Daniel C; Johnson, Mahlon D; Judkins, Alexander R

    2015-01-01

    Ganglioglioma is a rare tumor consisting of neoplastic glial and neuronal elements. It accounts for only 0.5% of all primary central nervous system (CNS) neoplasms. We report an unusual case of extensive intramedullary thoracic spinal cord ganglioglioma in a 14-month-old girl who underwent subtotal resection followed by adjuvant chemotherapy. The epidemiology, histopathologic features, imaging findings, treatment, and prognosis are subsequently reviewed. PMID:26605127

  5. Neuroprotective Effects of Perflurocarbon (Oxycyte) after Contusive Spinal Cord Injury

    PubMed Central

    Yacoub, Adly; Hajec, Marygrace C.; Stanger, Richard; Wan, Wen; Young, Harold

    2014-01-01

    Abstract Spinal cord injury (SCI) often results in irreversible and permanent neurological deficits and long-term disability. Vasospasm, hemorrhage, and loss of microvessels create an ischemic environment at the site of contusive or compressive SCI and initiate the secondary injury cascades leading to progressive tissue damage and severely decreased functional outcome. Although the initial mechanical destructive events cannot be reversed, secondary injury damage occurs over several hours to weeks, a time frame during which therapeutic intervention could be achieved. One essential component of secondary injury cascade is the reduction in spinal cord blood flow with resultant decrease in oxygen delivery. Our group has recently shown that administration of fluorocarbon (Oxycyte) significantly increased parenchymal tissue oxygen levels during the usual postinjury hypoxic phase, and fluorocarbon has been shown to be effective in stroke and head injury. In the current study, we assessed the beneficial effects of Oxycyte after a moderate-to-severe contusion SCI was simulated in adult Long-Evans hooded rats. Histopathology and immunohistochemical analysis showed that the administration of 5 mL/kg of Oxycyte perfluorocarbon (60% emulsion) after SCI dramatically reduced destruction of spinal cord anatomy and resulted in a marked decrease of lesion area, less cell death, and greater white matter sparing at 7 and 42 days postinjury. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining showed a significant reduced number of apoptotic cells in Oxycyte-treated animals, compared to the saline group. Collectively, these results demonstrate the potential neuroprotective effect of Oxycyte treatment after SCI, and its beneficial effects may be, in part, a result of reducing apoptotic cell death and tissue sparing. Further studies to determine the most efficacious Oxycyte dose and its mechanisms of protection are warranted. PMID:24025081

  6. How Are Brain and Spinal Cord Tumors in Children Diagnosed?

    MedlinePlus

    ... spinal cord tumors in children staged? How are brain and spinal cord tumors diagnosed in children? Brain ... resonance angiography (MRA) or computerized tomographic angiography (CTA). Brain or spinal cord tumor biopsy Imaging tests such ...

  7. Testosterone Plus Finasteride Treatment After Spinal Cord Injury

    ClinicalTrials.gov

    2016-07-07

    Spinal Cord Injury; Spinal Cord Injuries; Trauma, Nervous System; Wounds and Injuries; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Gonadal Disorders; Endocrine System Diseases; Hypogonadism; Genital Diseases, Male

  8. Advances in Spinal Interbody Cages.

    PubMed

    Jain, Sukrit; Eltorai, Adam E M; Ruttiman, Roy; Daniels, Alan H

    2016-08-01

    Since the late 1980s, spinal interbody cages (ICs) have been used to aid bone fusion in a variety of spinal disorders. Utilized to restore intervertebral height, enable bone graft containment for arthrodesis, and restore anterior column biomechanical stability, ICs have since evolved to become a highly successful means of achieving fusion, being associated with less postoperative pain, shorter hospital stay, fewer complications and higher rates of fusion when than bone graft only spinal fusion. IC design and materials have changed considerably over the past two decades. The threaded titanium-alloy cylindrical screw cages, typically filled with autologous bone graft, of the mid-1990s achieved greater fusion rates than bone grafts and non-threaded cages. Threaded screw cages, however, were soon found to be less stable in extension and flexion; additionally, they had a high incidence of cage subsidence. As of the early 2000s, non-threaded box-shaped titanium or polyether ether ketone IC designs have become increasingly more common. This modern design continues to achieve greater cage stability in flexion, axial rotation and bending. However, cage stability and subsidence, bone fusion rates and surgical complications still require optimization. Thus, this review provides an update of recent research findings relevant to ICs over the past 3 years, highlighting trends in optimization of cage design, materials, alternatives to bone grafts, and coatings that may enhance fusion. PMID:27627709

  9. Postoperative posterior spinal wound infections.

    PubMed

    Massie, J B; Heller, J G; Abitbol, J J; McPherson, D; Garfin, S R

    1992-11-01

    The incidence of postoperative spinal infections increases with the complexity of the procedure. Diskectomy is associated with less than a 1% risk of infection; spinal fusion without instrumentation is associated with a 1%-5% risk; and fusion with instrumentation may be associated with a risk of 6% or more. Twenty-two postoperative posterior spinal infections that occurred during a three-year period were reviewed for this report. Staphylococcus aureus was the most frequent organism cultured (more than 50% of the cases). Other recurring organisms were Staphylococcus epidermis, Peptococcus, Enterobacter cloacae, and Bacteroides. Many patients had multiple organisms. Risk factors appeared to include advanced age, prolonged hospital bed rest, obesity, diabetes, immunosuppression, and infection at remote sites. Operative factors included prolonged surgery (greater than five hours), high volume of personnel moving through the operating room, and instrumentation. Postoperative contamination may occur and may be related to prolonged postoperative bed rest, skin maceration (thoracolumbosacral orthoses), and drainage tubes exiting distally from lumbar wounds (toward the rectum). Effective treatment includes early diagnosis, surgical debridement and irrigation, and parenteral antibiotics. Superficial infections were treated successfully with wound closure over outflow tubes, and deep infections with inflow-outflow systems. Maintaining the instrumentation in place was possible in most cases. Parenteral antibiotics were maintained for six weeks in every case. PMID:1395319

  10. FGF-1 Triggers Pannexin-1 Hemichannel Opening in Spinal Astrocytes of Rodents and Promotes Inflammatory Responses in Acute Spinal Cord Slices

    PubMed Central

    Yang, Guang; Bukauskas, Feliksas F.

    2016-01-01

    receptors and Px1 HCs. This proinflammatory microenvironment may favor recruitment of leukocytes into the spinal cord and impacts negatively on neuronal structure and function in vivo. Any step in these processes provides a potential therapeutic target for treatment of secondary damage in various spinal cord pathologies. PMID:27122036

  11. Spinal cord compression due to ethmoid adenocarcinoma.

    PubMed

    Johns, D R; Sweriduk, S T

    1987-10-15

    Adenocarcinoma of the ethmoid sinus is a rare tumor which has been epidemiologically linked to woodworking in the furniture industry. It has a low propensity to metastasize and has not been previously reported to cause spinal cord compression. A symptomatic epidural spinal cord compression was confirmed on magnetic resonance imaging (MRI) scan in a former furniture worker with widely disseminated metastases. The clinical features of ethmoid sinus adenocarcinoma and neoplastic spinal cord compression, and the comparative value of MRI scanning in the neuroradiologic diagnosis of spinal cord compression are reviewed.

  12. Effect of Microgravity on Mammalian Lymphocytes

    NASA Technical Reports Server (NTRS)

    Banerjee, H.; Blackshear, M.; Mahaffey, K.; Knight, C.; Khan, A. A.; Delucas, L.

    2004-01-01

    The effect of microgravity on mammalian system is an important and interesting topic for scientific investigation, since NASA s objective is to send manned flights to planets like Mars and eventual human colonization.The Astronauts will be exposed to microgravity environment for a long duration of time during these flights.Our objective of research is to conduct in vitro studies for the effect of microgravity on mammalian immune system.We did our preliminary investigations by exposing mammalian lymphocytes to a microgravity simulator cell bioreactor designed by NASA and manufactured at Synthecon Inc (USA).Our initial results showed no significant change in cytokine expression in these cells for a time period of forty eight hours exposure.Our future experiments will involve exposure for a longer period of time.

  13. Effect of Microgravity on Mammalian Lymphocytes

    NASA Technical Reports Server (NTRS)

    Banerjee, H.; Blackshear, M.; Mahaffey, K.; Khan, A. A.; Delucas, L.

    2004-01-01

    The effect of microgravity on mammalian system is an important and interesting topic for scientific investigation, since NASA s objective is to send manned flights to planets like Mars and eventual human colonization. The Astronauts will be exposed to microgravity environment for a long duration of time during these flights. Our objective of research is to conduct in vitro studies for the effect of microgravity on mammalian immune system and nervous system. We did our preliminary investigations by exposing mammalian lymphocytes and astrocyte cells to a microgravity simulator cell bioreactor designed by NASA and manufactured at Synthecon, Inc. (USA).Our initial results showed no significant change in cytokine expression in these cells up to a time period of 120 hours exposure. Our future experiments will involve exposure for a longer period of time.

  14. Synthetic therapeutic gene circuits in mammalian cells.

    PubMed

    Ye, Haifeng; Fussenegger, Martin

    2014-08-01

    In the emerging field of synthetic biology, scientists are focusing on designing and creating functional devices, systems, and organisms with novel functions by engineering and assembling standardised biological building blocks. The progress of synthetic biology has significantly advanced the design of functional gene networks that can reprogram metabolic activities in mammalian cells and provide new therapeutic opportunities for future gene- and cell-based therapies. In this review, we describe the most recent advances in synthetic mammalian gene networks designed for biomedical applications, including how these synthetic therapeutic gene circuits can be assembled to control signalling networks and applied to treat metabolic disorders, cancer, and immune diseases. We conclude by discussing the various challenges and future prospects of using synthetic mammalian gene networks for disease therapy.

  15. Mammalian diversity: gametes, embryos and reproduction.

    PubMed

    Behringer, Richard R; Eakin, Guy S; Renfree, Marilyn B

    2006-01-01

    The class Mammalia is composed of approximately 4800 extant species. These mammalian species are divided into three subclasses that include the monotremes, marsupials and eutherians. Monotremes are remarkable because these mammals are born from eggs laid outside of the mother's body. Marsupial mammals have relatively short gestation periods and give birth to highly altricial young that continue a significant amount of 'fetal' development after birth, supported by a highly sophisticated lactation. Less than 10% of mammalian species are monotremes or marsupials, so the great majority of mammals are grouped into the subclass Eutheria, including mouse and human. Mammals exhibit great variety in morphology, physiology and reproduction. In the present article, we highlight some of this remarkable diversity relative to the mouse, one of the most widely used mammalian model organisms, and human. This diversity creates challenges and opportunities for gamete and embryo collection, culture and transfer technologies.

  16. Synthetic mammalian gene circuits for biomedical applications.

    PubMed

    Ye, Haifeng; Aubel, Dominique; Fussenegger, Martin

    2013-12-01

    Synthetic biology is the science of reassembling cataloged and standardized biological items in a systematic and rational manner to create and engineer functional biological designer devices, systems and organisms with novel and useful, preferably therapeutic functions. Synthetic biology has significantly advanced the design of complex genetic networks that can reprogram metabolic activities in mammalian cells and provide novel therapeutic strategies for future gene-based and cell-based therapies. Synthetic biology-inspired therapeutic strategies provide new opportunities for improving human health in the 21st century. This review covers the most recent synthetic mammalian circuits designed for therapy of diseases such as metabolic disorders, cancer, and immune disorders. We conclude by discussing current challenges and future perspectives for biomedical applications of synthetic mammalian gene networks.

  17. Involvement of opsins in mammalian sperm thermotaxis

    PubMed Central

    Pérez-Cerezales, Serafín; Boryshpolets, Sergii; Afanzar, Oshri; Brandis, Alexander; Nevo, Reinat; Kiss, Vladimir; Eisenbach, Michael

    2015-01-01

    A unique characteristic of mammalian sperm thermotaxis is extreme temperature sensitivity, manifested by the capacity of spermatozoa to respond to temperature changes of <0.0006 °C as they swim their body-length distance. The identity of the sensing system that confers this exceptional sensitivity on spermatozoa is not known. Here we show that the temperature-sensing system of mammalian spermatozoa involves opsins, known to be G-protein-coupled receptors that act as photosensors in vision. We demonstrate by molecular, immunological, and functional approaches that opsins are present in human and mouse spermatozoa at specific sites, which depend on the species and the opsin type, and that they are involved in sperm thermotaxis via two signalling pathways—the phospholipase C and the cyclic-nucleotide pathways. Our results suggest that, depending on the context and the tissue, mammalian opsins act not only as photosensors but also as thermosensors. PMID:26537127

  18. Sponge-mediated Lentivirus Delivery to Acute and Chronic Spinal Cord Injuries

    PubMed Central

    Thomas, Aline M.; Palma, Jaime L.; Shea, Lonnie D.

    2015-01-01

    The environment within the spinal cord after injury, which changes in the progression from the acute to chronic stages, limits the extent of regeneration. The delivery of inductive factors to promote regeneration following spinal cord injury has been promising, yet, few strategies are have are versatile to allow delivery during acute or chronic injury that would facilitate screening of candidate therapies. This report investigates the intrathecal delivery of lentiviruses for long-term expression of regenerative factors. Lentivirus-filled sponges were inserted into the intrathecal space surrounding the spinal cord, with transgene expression observed within multiple cell types that persists for 12 weeks for both intact and injured spinal cord, without any apparent damage to the spinal cord tissue. Sponges loaded with lentivirus encoding for Sonic hedgehog (Shh) were investigated for acute (delivered at 0 weeks) and chronic (at 4 weeks) injuries, and for multiple locations relative to the injury. In an acute model, sponges placed directly above the injury increased oligodendrocyte and decreased astrocyte presence. Sponges placed caudal to the injury had reduced impact on oligodendrocytes and astrocytes in the injury. In a chronic model, sponges increased oligodendrocyte and decreased astrocyte presence. Furthermore, the effect of Shh was shown to be mediated in part by reduction of Bmp signaling, monitored with an Msx2-sensitive reporter vector. The implantation of lentivirus-loaded biomaterials intrathecally provides the opportunity to induce the expression of a factor at a specified time without entering the spinal cord, and has the potential to promote gene delivery within the spinal cord, which can influence the extent of regeneration. PMID:25724274

  19. Syrinx fluid transport: modeling pressure-wave-induced flux across the spinal pial membrane.

    PubMed

    Elliott, N S J

    2012-03-01

    Syrinxes are fluid-filled cavities of the spinal cord that characterize syringomyelia, a disease involving neurological damage. Their formation and expansion is poorly understood, which has hindered successful treatment. Syrinx cavities are hydraulically connected with the spinal subarachnoid space (SSS) enveloping the spinal cord via the cord interstitium and the network of perivascular spaces (PVSs), which surround blood vessels penetrating the pial membrane that is adherent to the cord surface. Since the spinal canal supports pressure wave propagation, it has been hypothesized that wave-induced fluid exchange across the pial membrane may play a role in syrinx filling. To investigate this conjecture a pair of one-dimensional (1-d) analytical models were developed from classical elastic tube theory coupled with Darcy's law for either perivascular or interstitial flow. The results show that transpial flux serves as a mechanism for damping pressure waves by alleviating hoop stress in the pial membrane. The timescale ratio over which viscous and inertial forces compete was explicitly determined, which predicts that dilated PVS, SSS flow obstructions, and a stiffer and thicker pial membrane-all associated with syringomyelia-will increase transpial flux and retard wave travel. It was also revealed that the propagation of a pressure wave is aided by a less-permeable pial membrane and, in contrast, by a more-permeable spinal cord. This is the first modeling of the spinal canal to include both pressure-wave propagation along the spinal axis and a pathway for fluid to enter and leave the cord, which provides an analytical foundation from which to approach the full poroelastic problem.

  20. Syrinx fluid transport: modeling pressure-wave-induced flux across the spinal pial membrane.

    PubMed

    Elliott, N S J

    2012-03-01

    Syrinxes are fluid-filled cavities of the spinal cord that characterize syringomyelia, a disease involving neurological damage. Their formation and expansion is poorly understood, which has hindered successful treatment. Syrinx cavities are hydraulically connected with the spinal subarachnoid space (SSS) enveloping the spinal cord via the cord interstitium and the network of perivascular spaces (PVSs), which surround blood vessels penetrating the pial membrane that is adherent to the cord surface. Since the spinal canal supports pressure wave propagation, it has been hypothesized that wave-induced fluid exchange across the pial membrane may play a role in syrinx filling. To investigate this conjecture a pair of one-dimensional (1-d) analytical models were developed from classical elastic tube theory coupled with Darcy's law for either perivascular or interstitial flow. The results show that transpial flux serves as a mechanism for damping pressure waves by alleviating hoop stress in the pial membrane. The timescale ratio over which viscous and inertial forces compete was explicitly determined, which predicts that dilated PVS, SSS flow obstructions, and a stiffer and thicker pial membrane-all associated with syringomyelia-will increase transpial flux and retard wave travel. It was also revealed that the propagation of a pressure wave is aided by a less-permeable pial membrane and, in contrast, by a more-permeable spinal cord. This is the first modeling of the spinal canal to include both pressure-wave propagation along the spinal axis and a pathway for fluid to enter and leave the cord, which provides an analytical foundation from which to approach the full poroelastic problem. PMID:22482686

  1. Spatio-Temporal Expression Pattern of Frizzled Receptors after Contusive Spinal Cord Injury in Adult Rats

    PubMed Central

    Arenas, Ernest; Rodriguez, Francisco Javier

    2012-01-01

    Background Wnt proteins are a large family of molecules that are critically involved in multiple central nervous system (CNS) developmental processes. Experimental evidences suggest a role for this family of proteins in many CNS disorders, including spinal cord injury (SCI), which is a major neuropathology owing to its high prevalence and chronic sensorimotor functional sequelae. Interestingly, most Wnt proteins and their inhibitors are expressed in the uninjured spinal cord, and their temporal expression patterns are dramatically altered after injury. However, little is known regarding the expression of their better-known receptors, the Frizzled family, after SCI. Thus, the aim of the present study was to evaluate the expression of Frizzled receptors in the damaged spinal cord. Findings Based on the evidence that Wnts are expressed in the spinal cord and are transcriptionally regulated by SCI in adulthood, we analysed the spatio-temporal mRNA and protein expression patterns of Frizzled receptors after contusive SCI using quantitative RT-PCR and single and double immunohistochemistry, respectively. Our results show that almost all of the 10 known Frizzled receptors were expressed in specific spatial patterns in the uninjured spinal cords. Moreover, the Frizzled mRNAs and proteins were expressed after SCI, although their expression patterns were altered during the temporal progression of SCI. Finally, analysis of cellular Frizzled 5 expression pattern by double immunohistochemistry showed that, in the uninjured spinal cord, this receptor was expressed in neurons, oligodendrocytes, astrocytes, microglia and NG2+ glial precursors. After injury, Frizzled 5 was not only still expressed in oligodendrocytes, astrocytes and NG2+ glial precursors but also in axons at all evaluated time points. Moreover, Frizzled 5 was expressed in reactive microglia/macrophages from 3 to 14 days post-injury. Conclusions Our data suggest the involvement of Frizzled receptors in physiological

  2. Sponge-mediated lentivirus delivery to acute and chronic spinal cord injuries.

    PubMed

    Thomas, Aline M; Palma, Jaime L; Shea, Lonnie D

    2015-04-28

    The environment within the spinal cord after injury, which changes in the progression from the acute to chronic stages, limits the extent of regeneration. The delivery of inductive factors to promote regeneration following spinal cord injury has been promising, yet, few strategies are versatile to allow delivery during acute or chronic injury that would facilitate screening of candidate therapies. This report investigates the intrathecal delivery of lentiviruses for long-term expression of regenerative factors. Lentivirus-filled sponges were inserted into the intrathecal space surrounding the spinal cord, with transgene expression observed within multiple cell types that persists for 12 weeks for both intact and injured spinal cord, without any apparent damage to the spinal cord tissue. Sponges loaded with lentivirus encoding for Sonic hedgehog (Shh) were investigated for acute (delivered at 0 weeks) and chronic (at 4 weeks) injuries, and for multiple locations relative to the injury. In an acute model, sponges placed directly above the injury increased oligodendrocyte and decreased astrocyte presence. Sponges placed caudal to the injury had reduced impact on oligodendrocytes and astrocytes in the injury. In a chronic model, sponges increased oligodendrocyte and decreased astrocyte presence. Furthermore, the effect of Shh was shown to be mediated in part by reduction of Bmp signaling, monitored with an Msx2-sensitive reporter vector. The implantation of lentivirus-loaded biomaterials intrathecally provides the opportunity to induce the expression of a factor at a specified time without entering the spinal cord, and has the potential to promote gene delivery within the spinal cord, which can influence the extent of regeneration.

  3. Odor Coding by a Mammalian Receptor Repertoire

    PubMed Central

    Saito, Harumi; Chi, Qiuyi; Zhuang, Hanyi; Matsunami, Hiro; Mainland, Joel D.

    2009-01-01

    Deciphering olfactory encoding requires a thorough description of the ligands that activate each odorant receptor (OR). In mammalian systems, however, ligands are known for fewer than 50 of over 1400 human and mouse ORs, greatly limiting our understanding of olfactory coding. We performed high-throughput screening of 93 odorants against 464 ORs expressed in heterologous cells and identified agonists for 52 mouse and 10 human ORs. We used the resulting interaction profiles to develop a predictive model relating physicochemical odorant properties, OR sequences, and their interactions. Our results provide a basis for translating odorants into receptor neuron responses and unraveling mammalian odor coding. PMID:19261596

  4. Autofluorescence of viable cultured mammalian cells.

    PubMed

    Aubin, J E

    1979-01-01

    The autofluorescence other than intrinsic protein emission of viable cultured mammalian cells has been investigated. The fluorescence was found to originate in discrete cytoplasmic vesicle-like regions and to be absent from the nucleus. Excitation and emission spectra of viable cells revealed at least two distinct fluorescent species. Comparison of cell spectra with spectra of known cellular metabolites suggested that most, if not all, of the fluorescence arises from intracellular nicotinamide adenine dinucleotide (NADH) and riboflavin and flavin coenzymes. Various changes in culture conditions did not affect the observed autofluorescence intensity. A multiparameter flow system (MACCS) was used to compare the fluorescence intensities of numerous cultured mammalian cells.

  5. The mammalian blastema: regeneration at our fingertips

    PubMed Central

    Simkin, Jennifer; Sammarco, Mimi C.; Dawson, Lindsay A.; Schanes, Paula P.; Yu, Ling

    2015-01-01

    Abstract In the mouse, digit tip regeneration progresses through a series of discrete stages that include inflammation, histolysis, epidermal closure, blastema formation, and redifferentiation. Recent studies reveal how each regenerative stage influences subsequent stages to establish a blastema that directs the successful regeneration of a complex mammalian structure. The focus of this review is on early events of healing and how an amputation wound transitions into a functional blastema. The stepwise formation of a mammalian blastema is proposed to provide a model for how specific targeted treatments can enhance regenerative performance in humans. PMID:27499871

  6. Building mammalian signalling pathways with RNAi screens.

    PubMed

    Moffat, Jason; Sabatini, David M

    2006-03-01

    Technological advances in mammalian systems are providing new tools to identify the molecular components of signalling pathways. Foremost among these tools is the ability to knock down gene function through the use of RNA interference (RNAi). The fact that RNAi can be scaled up for use in high-throughput techniques has motivated the creation of genome-wide RNAi reagents. We are now at the brink of being able to harness the power of RNAi for large-scale functional discovery in mammalian cells.

  7. Human spinal locomotor control is based on flexibly organized burst generators.

    PubMed

    Danner, Simon M; Hofstoetter, Ursula S; Freundl, Brigitta; Binder, Heinrich; Mayr, Winfried; Rattay, Frank; Minassian, Karen

    2015-03-01

    samples of rhythmic patterns. The basic activation patterns can be interpreted as central drives implemented by spinal burst generators that impose specific spatiotemporally organized activation on the lumbosacral motor neuron pools. Our data thus imply that the human lumbar spinal cord circuits can form burst-generating elements that flexibly combine to obtain a wide range of locomotor outputs from a constant, repetitive input. It may be possible to use this flexibility to incorporate specific adaptations to gait and stance to improve locomotor control, even after severe central nervous system damage. PMID:25582580

  8. Spinal cord injury in rats treated using bone marrow mesenchymal stem-cell transplantation

    PubMed Central

    Chen, Yu-Bing; Jia, Quan-Zhang; Li, Dong-Jun; Sun, Jing-Hai; Xi, Shuang; Liu, Li-Ping; Gao, De-Xuan; Jiang, Da-Wei

    2015-01-01

    The aim of this study was to observe the effects of bone marrow mesenchymal stem-cell transplantation (BMSCs) in repairing acute spinal cord damage in rats and to examine the potential beneficial effects. 192 Wistar rats were randomized into 8 groups. Spinal cord injury was created. Behavior and limb functions were scored. Repairing effects of BMSCs transplantation was evaluated and compared. In vitro 4’,6-diamidino-2-phenylindole (DAPI)-tagged BMSCs were observed, and whether they migrated to the area of spinal cord injury after intravenous tail injection was investigated. The expression of neuron-specific protein (NSE) on BMSCs was examined. Fifteen days after transplantation, the BMSCs-treated groups scored significantly higher in limb function tests than the untreated group. Pathological sections of the bone marrow after operation showed significant recovery in treated groups in comparison to the control group. After transplantation, small amounts of fluorescent-tagged BMSCs can be found in the blood vessels in the area of spinal cord injury, and fluorescent-tagged BMSCs were diffused in extravascular tissues, whereas the DAPI-tagged BMSCs could not be detected,and BrdU/NSE double-labeled cells were found in the injured marrow. BMSCs improve behavioral responses and can repair spinal cord injuries by migrating to the injured area, where they can differentiate into neurons. PMID:26309595

  9. Site-specific gene transfer into the rat spinal cord by photomechanical waves

    NASA Astrophysics Data System (ADS)

    Ando, Takahiro; Sato, Shunichi; Toyooka, Terushige; Uozumi, Yoichi; Nawashiro, Hiroshi; Ashida, Hiroshi; Obara, Minoru

    2011-10-01

    Nonviral, site-specific gene delivery to deep tissue is required for gene therapy of a spinal cord injury. However, an efficient method satisfying these requirements has not been established. This study demonstrates efficient and targeted gene transfer into the spinal cord by using photomechanical waves (PMWs), which were generated by irradiating a black laser absorbing rubber with 532-nm nanosecond Nd:YAG laser pulses. After a solution of plasmid DNA coding for enhanced green fluorescent protein (EGFP) or luciferase was intraparenchymally injected into the spinal cord, PMWs were applied to the target site. In the PMW application group, we observed significant EGFP gene expression in the white matter and remarkably high luciferase activity only in the spinal cord segment exposed to the PMWs. We also assessed hind limb movements 24 h after the application of PMWs based on the Basso-Beattie-Bresnahan (BBB) score to evaluate the noninvasiveness of this method. Locomotor evaluation showed no significant decrease in BBB score under optimum laser irradiation conditions. These findings demonstrated that exogenous genes can be efficiently and site-selectively delivered into the spinal cord by applying PMWs without significant locomotive damage.

  10. Time representation of mitochondrial morphology and function after acute spinal cord injury.

    PubMed

    Jia, Zhi-Qiang; Li, Gang; Zhang, Zhen-Yu; Li, Hao-Tian; Wang, Ji-Quan; Fan, Zhong-Kai; Lv, Gang

    2016-01-01

    Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acute spinal cord injury. Results showed that mitochondria had an irregular shape, and increased in size. Mitochondrial cristae were disordered and mitochondrial membrane rupture was visible at 2-24 hours after injury. Fusion protein mitofusin 1 expression gradually increased, peaked at 8 hours after injury, and then decreased to its lowest level at 24 hours. Expression of dynamin-related protein 1, amitochondrial fission protein, showed the opposite kinetics. At 2-24 hours after acute spinal cord injury, malondialdehyde content, cytochrome c levels and caspase-3 expression were increased, but glutathione content, adenosine triphosphate content, Na(+)-K(+)-ATPase activity and mitochondrial membrane potential were gradually reduced. Furthermore, mitochondrial morphology altered during the acute stage of spinal cord injury. Fusion was important within the first 8 hours, but fission played a key role at 24 hours. Oxidative stress was inhibited, biological productivity was diminished, and mitochondrial membrane potential and permeability were reduced in the acute stage of injury. In summary, mitochondrial apoptosis is activated when the time of spinal cord injury is prolonged.

  11. Effects of Rolipram on Adult Rat Oligodendrocytes and Functional Recovery after Contusive Cervical Spinal Cord Injury

    PubMed Central

    Beaumont, Eric; Whitaker, Christopher M.; Burke, Darlene A.; Hetman, Michal; Onifer, Stephen M.

    2009-01-01

    Traumatic human spinal cord injury causes devastating and long-term hardships. These are due to the irreparable primary mechanical injury and secondary injury cascade. In particular, oligodendrocyte cell death, white matter axon damage, spared axon demyelination, and the ensuing dysfunction in action potential conduction lead to the initial deficits and impair functional recovery. For these reasons, and that oligodendrocyte and axon survival may be related, various neuroprotective strategies after SCI are being investigated. We previously demonstrated that oligodendrocytes in the adult rat epicenter ventrolateral funiculus express 3′-5′-cyclic adenosine monophosphate-dependent phosphodiesterase 4 subtypes and that their death was attenuated up to 3 days after contusive cervical spinal cord injury when rolipram, a specific inhibitor of phosphodiesterase 4, was administered. Here, we report that 1) there are more oligodendrocyte somata in the adult rat epicenter ventrolateral funiculus, 2) descending and ascending axonal conductivity in the ventrolateral funiculus improves, and that 3) there are fewer hindlimb footfall errors during grid-walking at 5 weeks after contusive cervical spinal cord injury when rolipram is delivered for 2 weeks. This is the first demonstration of improved descending and ascending long-tract axonal conductivity across a spinal cord injury with this pharmacological approach. Since descending long-tract axonal conductivity did not return to normal, further evaluations of the pharmacokinetics and therapeutic window of rolipram as well as optimal combinations are necessary before consideration for neuroprotection in humans with spinal cord injury. PMID:19635528

  12. Time representation of mitochondrial morphology and function after acute spinal cord injury

    PubMed Central

    Jia, Zhi-qiang; Li, Gang; Zhang, Zhen-yu; Li, Hao-tian; Wang, Ji-quan; Fan, Zhong-kai; Lv, Gang

    2016-01-01

    Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acute spinal cord injury. Results showed that mitochondria had an irregular shape, and increased in size. Mitochondrial cristae were disordered and mitochondrial membrane rupture was visible at 2–24 hours after injury. Fusion protein mitofusin 1 expression gradually increased, peaked at 8 hours after injury, and then decreased to its lowest level at 24 hours. Expression of dynamin-related protein 1, amitochondrial fission protein, showed the opposite kinetics. At 2–24 hours after acute spinal cord injury, malondialdehyde content, cytochrome c levels and caspase-3 expression were increased, but glutathione content, adenosine triphosphate content, Na+-K+-ATPase activity and mitochondrial membrane potential were gradually reduced. Furthermore, mitochondrial morphology altered during the acute stage of spinal cord injury. Fusion was important within the first 8 hours, but fission played a key role at 24 hours. Oxidative stress was inhibited, biological productivity was diminished, and mitochondrial membrane potential and permeability were reduced in the acute stage of injury. In summary, mitochondrial apoptosis is activated when the time of spinal cord injury is prolonged. PMID:26981103

  13. Spinal cord injury in rats treated using bone marrow mesenchymal stem-cell transplantation.

    PubMed

    Chen, Yu-Bing; Jia, Quan-Zhang; Li, Dong-Jun; Sun, Jing-Hai; Xi, Shuang; Liu, Li-Ping; Gao, De-Xuan; Jiang, Da-Wei

    2015-01-01

    The aim of this study was to observe the effects of bone marrow mesenchymal stem-cell transplantation (BMSCs) in repairing acute spinal cord damage in rats and to examine the potential beneficial effects. 192 Wistar rats were randomized into 8 groups. Spinal cord injury was created. Behavior and limb functions were scored. Repairing effects of BMSCs transplantation was evaluated and compared. In vitro 4',6-diamidino-2-phenylindole (DAPI)-tagged BMSCs were observed, and whether they migrated to the area of spinal cord injury after intravenous tail injection was investigated. The expression of neuron-specific protein (NSE) on BMSCs was examined. Fifteen days after transplantation, the BMSCs-treated groups scored significantly higher in limb function tests than the untreated group. Pathological sections of the bone marrow after operation showed significant recovery in treated groups in comparison to the control group. After transplantation, small amounts of fluorescent-tagged BMSCs can be found in the blood vessels in the area of spinal cord injury, and fluorescent-tagged BMSCs were diffused in extravascular tissues, whereas the DAPI-tagged BMSCs could not be detected,and BrdU/NSE double-labeled cells were found in the injured marrow. BMSCs improve behavioral responses and can repair spinal cord injuries by migrating to the injured area, where they can differentiate into neurons.

  14. Arachidonic acid-induced oxidative injury to cultured spinal cord neurons.

    PubMed

    Toborek, M; Malecki, A; Garrido, R; Mattson, M P; Hennig, B; Young, B

    1999-08-01

    Spinal cord trauma can cause a marked release of free fatty acids, in particular, arachidonic acid (AA), from cell membranes. Free fatty acids, and AA by itself, may lead to secondary damage to spinal cord neurons. To study this hypothesis, cultured spinal cord neurons were exposed to increasing concentrations of AA (0.01-10 microM). AA-induced injury to spinal cord neurons was assessed by measurements of cellular oxidative stress, intracellular calcium levels, activation of nuclear factor-KB (NF-kappaB), and cell viability. AA treatment increased intracellular calcium concentrations and decreased cell viability. Oxidative stress increased significantly in neurons exposed to 1 and 10 microM AA. In addition, AA treatment activated NF-kappaB and decreased levels of the inhibitory subunit, IKB. It is interesting that manganese superoxide dismutase protein levels and levels of intracellular total glutathione increased in neurons exposed to this fatty acid for 24 h, consistent with a compensatory response to increased oxidative stress. These results strongly support the hypothesis that free fatty acids contribute to the tissue injury observed following spinal cord trauma. PMID:10428065

  15. In vivo imaging of spinal cord in contusion injury model mice by multi-photon microscopy

    NASA Astrophysics Data System (ADS)

    Oshima, Y.; Horiuchi, H.; Ogata, T.; Hikita, A.; Miura, H.; Imamura, T.

    2014-03-01

    Fluorescent imaging technique is a promising method and has been developed for in vivo applications in cellular biology. In particular, nonlinear optical imaging technique, multi-photon microscopy has make it possible to analyze deep portion of tissues in living animals such as axons of spinal code. Traumatic spinal cord injuries (SCIs) are usually caused by contusion damages. Therefore, observation of spinal cord tissue after the contusion injury is necessary for understanding cellular dynamics in response to traumatic SCI and development of the treatment for traumatic SCI. Our goal is elucidation of mechanism for degeneration of axons after contusion injuries by establishing SCI model and chronic observation of injured axons in the living animals. Firstly we generated and observed acute SCI model by contusion injury. By using a multi-photon microscope, axons in dorsal cord were visualized approximately 140 micron in depth from the surface. Immediately after injury, minimal morphological change of spinal cord was observed. At 3 days after injury, spinal cord was swelling and the axons seem to be fragmented. At 7 days after injury, increased degradation of axons could be observed, although the image was blurred due to accumulation of the connective tissue. In the present study, we successfully observed axon degeneration after the contusion SCI in a living animal in vivo. Our final goal is to understand molecular mechanisms and cellular dynamics in response to traumatic SCIs in acute and chronic stage.

  16. Damaged Skylab

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The Saturn V vehicle, carrying the unmarned orbital workshop for the Skylab-1 mission, lifted off successfully and all systems performed normally. Sixty-three seconds into the flight, engineers in the operation support and control center saw an unexpected telemetry indication that signalled that damages occurred on one solar array and the micrometeoroid shield during the launch. The micrometeoroid shield, a thin protective cylinder surrounding the workshop protecting it from tiny space particles and the sun's scorching heat, ripped loose from its position around the workshop. This caused the loss of one solar wing and jammed the other. Still unoccupied, the Skylab was stricken with the loss of the heat shield and sunlight beat mercilessly on the lab's sensitive skin. Internal temperatures soared, rendering the station uninhabitable, threatening foods, medicines, films, and experiments. This image, taken during a fly-around inspection by the Skylab-2 crew, shows a crippled Skylab in orbit. The crew found their home in space to be in serious shape; the heat shield gone, one solar wing gone, and the other jammed. The Marshall Space Flight Center (MSFC) developed, tested, rehearsed, and approved three repair options. These options included a parasol sunshade and a twin-pole sunshade to restore the temperature inside the workshop, and a set of metal cutting tools to free the jammed solar panel.

  17. Fetal segmental spinal dysgenesis and unusual segmental agenesis of the anterior spinal artery.

    PubMed

    Valdez Quintana, Melissa; Michaud, Jean; El-Chaar, Darine; El Demellawy, Dina; Nikkel, Sarah M; Miller, Elka

    2016-08-01

    Segmental spinal dysgenesis (SSD) is a rare congenital spinal abnormality characterized by segmental dysgenesis or agenesis of the thoracolumbar or lumbar spine, congenital kyphosis, and abnormal configuration of the underlying spinal cord. A unique feature of SSD is that the vertebrae are present above and below the defect, and there is often a lower cord segment in the caudal spinal canal. We report a fetal MRI case of SSD with postmortem and neuropathological correlations. Our report confirms already published findings including the presence of a neurenteric cyst but is the first to document anterior spinal artery segmental agenesis in SSD. PMID:26969176

  18. Spinal deformity after multilevel osteoplastic laminotomy

    PubMed Central

    Juergen, Krauss; Gloger, Harald; Soerensen, Nils; Wild, Alexander

    2007-01-01

    Multilevel laminectomy in children has a significant rate of postoperative spinal deformity. To decrease the incidence of this complication, the use of osteoplastic laminotomy is advocated to minimise the risk of spinal deformity by preserving the normal architecture of the spine. In this retrospective study, a 10-year series of a paediatric population undergoing multilevel osteoplastic laminotomy is reviewed to determine the incidence, especially in contrast to laminectomies, and to identify factors that affect the occurrence of spinal column deformity. Seventy patients (mean age 4.2 years) underwent multilevel osteoplastic laminotomy for congenital anomalies or removal of spinal tumours. All patients had a clinical and radiographic examination preoperatively, 12 months postoperatively and at follow-up. Mean follow-up was 5.3 years (range 3–12.6 years). Nineteen patients (27%) had a new or progressive spinal deformity. There was an increased incidence in patients who had surgery for spinal tumours (P < 0.05), surgery of the cervical spine (P < 0.01), and who had more than five levels of the spine included (P < 0.05). A review of the literature on children with multilevel laminectomy (n = 330), the incidence of spinal deformity found a significantly higher (46%) compared to our study group. This study demonstrates that osteoplastic laminotomy was found to be very effective in decreasing the incidence of spinal deformities after spinal-canal surgery for spinal-cord tumours or congenital anomalies in children and adolescents. The choice of an anatomical reconstructive surgical technique such as osteoplastic laminotomy seems to be essential to minimise secondary problems due to the surgical technique itself. Nevertheless, growing patients should be followed up for several years after the initial operation for early detection and consequent management of any possible deformity of the spinal column. PMID:17323095

  19. High-efficiency electroporation of the spinal cord in larval axolotl.

    PubMed

    Rodrigo Albors, Aida; Tanaka, Elly M

    2015-01-01

    Axolotls are well known for their remarkable ability to regenerate complex body parts and structures throughout life, including the entire limb and tail. Particularly fascinating is their ability to regenerate a fully functional spinal cord after losing the tail. Electroporation of DNA plasmids or morpholinos is a valuable tool to gain mechanistic insight into the cellular and molecular basis of regeneration. It provides among other advantages a simple and fast method to test gene function in a temporally and spatially controlled manner. Some classic drawbacks of the method, such as low transfection efficiency and damage to the tissue, had hindered our understanding of the contribution of different signaling pathways to regeneration. Here, we describe a comprehensive protocol for electroporation of the axolotl spinal cord that overcomes this limitations using a combination of high-voltage and short-length pulses followed by lower-voltage and longer-length pulses. Our approach yields highly efficient transfection of spinal cord cells with minimal tissue damage, which now allows the molecular dissection of spinal cord regeneration.

  20. High-efficiency electroporation of the spinal cord in larval axolotl.

    PubMed

    Rodrigo Albors, Aida; Tanaka, Elly M

    2015-01-01

    Axolotls are well known for their remarkable ability to regenerate complex body parts and structures throughout life, including the entire limb and tail. Particularly fascinating is their ability to regenerate a fully functional spinal cord after losing the tail. Electroporation of DNA plasmids or morpholinos is a valuable tool to gain mechanistic insight into the cellular and molecular basis of regeneration. It provides among other advantages a simple and fast method to test gene function in a temporally and spatially controlled manner. Some classic drawbacks of the method, such as low transfection efficiency and damage to the tissue, had hindered our understanding of the contribution of different signaling pathways to regeneration. Here, we describe a comprehensive protocol for electroporation of the axolotl spinal cord that overcomes this limitations using a combination of high-voltage and short-length pulses followed by lower-voltage and longer-length pulses. Our approach yields highly efficient transfection of spinal cord cells with minimal tissue damage, which now allows the molecular dissection of spinal cord regeneration. PMID:25740481

  1. IL-6 induces regionally selective spinal cord injury in patients with the neuroinflammatory disorder transverse myelitis

    PubMed Central

    Kaplin, Adam I.; Deshpande, Deepa M.; Scott, Erick; Krishnan, Chitra; Carmen, Jessica S.; Shats, Irina; Martinez, Tara; Drummond, Jennifer; Dike, Sonny; Pletnikov, Mikhail; Keswani, Sanjay C.; Moran, Timothy H.; Pardo, Carlos A.; Calabresi, Peter A.; Kerr, Douglas A.

    2005-01-01

    Transverse myelitis (TM) is an immune-mediated spinal cord disorder associated with inflammation, demyelination, and axonal damage. We investigated the soluble immune derangements present in TM patients and found that IL-6 levels were selectively and dramatically elevated in the cerebrospinal fluid and directly correlated with markers of tissue injury and sustained clinical disability. IL-6 was necessary and sufficient to mediate cellular injury in spinal cord organotypic tissue culture sections through activation of the JAK/STAT pathway, resulting in increased activity of iNOS and poly(ADP-ribose) polymerase (PARP). Rats intrathecally infused with IL-6 developed progressive weakness and spinal cord inflammation, demyelination, and axonal damage, which were blocked by PARP inhibition. Addition of IL-6 to brain organotypic cultures or into the cerebral ventricles of adult rats did not activate the JAK/STAT pathway, which is potentially due to increased expression of soluble IL-6 receptor in the brain relative to the spinal cord that may antagonize IL-6 signaling in this context. The spatially distinct responses to IL-6 may underlie regional vulnerability of different parts of the CNS to inflammatory injury. The elucidation of this pathway identifies specific therapeutic targets in the management of CNS autoimmune conditions. PMID:16184194

  2. Behavioral and Histopathological Study of Changes in Spinal Cord Injured Rats Supplemented with Spirulina platensis

    PubMed Central

    Che Ramli, Muhammad Danial

    2014-01-01

    Spinal cord injury (SCI) is a devastating disease that leads to permanent disability and causes great suffering. The resulting neurological dysfunction and paralysis is proportional to the severity of the trauma itself. Spirulina is widely used as a nutritional supplement due to its high protein and antioxidant content. In the present study, the protective effect of the Spirulina treatment on locomotor function and morphological damage after SCI was investigated. Seventy Sprague-Dawley (SD) rats were divided into three groups: Sham (laminectomy alone), Control (laminectomy with SCI), and Experimental (laminectomy with SCI +180 mg/kg per day Spirulina platensis). A laminectomy was performed at T12 and an Inox No.2 modified forceps was used to perform a partial crush injury on the spinal cord. The rats were then perfused at 3, 7, 14, 21, and 28 days after injury for morphological investigations. The injured rat spinal cord indicated a presence of hemorrhage, cavity, and necrosis. Pretreatment with Spirulina significantly improved the locomotor function and showed a significant reduction on the histological changes. The experimental results observed in this study suggest that treatment with Spirulina platensis possesses potential benefits in improving hind limb locomotor function and reducing morphological damage to the spinal cord. PMID:25152764

  3. Spinal 5-HT7 receptors induce phrenic motor facilitation via EPAC-mTORC1 signaling.

    PubMed

    Fields, D P; Springborn, S R; Mitchell, G S

    2015-09-01

    Spinal serotonin type 7 (5-HT7) receptors elicit complex effects on motor activity. Whereas 5-HT7 receptor activation gives rise to long-lasting phrenic motor facilitation (pMF), it also constrains 5-HT2 receptor-induced pMF via "cross-talk inhibition." We hypothesized that divergent cAMP-dependent signaling pathways give rise to these distinct 5-HT7 receptor actions. Specifically, we hypothesized that protein kinase A (PKA) mediates cross-talk inhibition of 5-HT2 receptor-induced pMF whereas 5-HT7 receptor-induced pMF results from exchange protein activated by cAMP (EPAC) signaling. Anesthetized, paralyzed, and ventilated rats receiving intrathecal (C4) 5-HT7 receptor agonist (AS-19) injections expressed pMF for >90 min, an effect abolished by pretreatment with a selective EPAC inhibitor (ESI-05) but not a selective PKA inhibitor (KT-5720). Furthermore, intrathecal injections of a selective EPAC activator (8-pCPT-2'-Me-cAMP) were sufficient to elicit pMF. Finally, spinal mammalian target of rapamycin complex-1 (mTORC1) inhibition via intrathecal rapamycin abolished 5-HT7 receptor- and EPAC-induced pMF, demonstrating that spinal 5-HT7 receptors elicit pMF by an EPAC-mTORC1 signaling pathway. Thus 5-HT7 receptors elicit and constrain spinal phrenic motor plasticity via distinct signaling mechanisms that diverge at cAMP (EPAC vs. PKA). Selective manipulation of these molecules may enable refined regulation of serotonin-dependent spinal motor plasticity for therapeutic advantage. PMID:26269554

  4. Spinal 5-HT7 receptors induce phrenic motor facilitation via EPAC-mTORC1 signaling

    PubMed Central

    Fields, D. P.; Springborn, S. R.

    2015-01-01

    Spinal serotonin type 7 (5-HT7) receptors elicit complex effects on motor activity. Whereas 5-HT7 receptor activation gives rise to long-lasting phrenic motor facilitation (pMF), it also constrains 5-HT2 receptor-induced pMF via “cross-talk inhibition.” We hypothesized that divergent cAMP-dependent signaling pathways give rise to these distinct 5-HT7 receptor actions. Specifically, we hypothesized that protein kinase A (PKA) mediates cross-talk inhibition of 5-HT2 receptor-induced pMF whereas 5-HT7 receptor-induced pMF results from exchange protein activated by cAMP (EPAC) signaling. Anesthetized, paralyzed, and ventilated rats receiving intrathecal (C4) 5-HT7 receptor agonist (AS-19) injections expressed pMF for >90 min, an effect abolished by pretreatment with a selective EPAC inhibitor (ESI-05) but not a selective PKA inhibitor (KT-5720). Furthermore, intrathecal injections of a selective EPAC activator (8-pCPT-2′-Me-cAMP) were sufficient to elicit pMF. Finally, spinal mammalian target of rapamycin complex-1 (mTORC1) inhibition via intrathecal rapamycin abolished 5-HT7 receptor- and EPAC-induced pMF, demonstrating that spinal 5-HT7 receptors elicit pMF by an EPAC-mTORC1 signaling pathway. Thus 5-HT7 receptors elicit and constrain spinal phrenic motor plasticity via distinct signaling mechanisms that diverge at cAMP (EPAC vs. PKA). Selective manipulation of these molecules may enable refined regulation of serotonin-dependent spinal motor plasticity for therapeutic advantage. PMID:26269554

  5. Microelectrode arrays in combination with in vitro models of spinal cord injury as tools to investigate pathological changes in network activity: facts and promises

    PubMed Central

    Mladinic, Miranda; Nistri, Andrea

    2013-01-01

    Microelectrode arrays (MEAs) represent an important tool to study the basic characteristics of spinal networks that control locomotion in physiological conditions. Fundamental properties of this neuronal rhythmicity like burst origin, propagation, coordination, and resilience can, thus, be investigated at multiple sites within a certain spinal topography and neighboring circuits. A novel challenge will be to apply this technology to unveil the mechanisms underlying pathological processes evoked by spinal cord injury (SCI). To achieve this goal, it is necessary to fully identify spinal networks that make up the locomotor central pattern generator (CPG) and to understand their operational rules. In this review, the use of isolated spinal cord preparations from rodents, or organotypic spinal slice cultures is discussed to study rhythmic activity. In particular, this review surveys our recently developed in vitro models of SCI by evoking excitotoxic (or even hypoxic/dysmetabolic) damage to spinal networks and assessing the impact on rhythmic activity and cell survival. These pathological processes which evolve via different cell death mechanisms are discussed as a paradigm to apply MEA recording for detailed mapping of the functional damage and its time-dependent evolution. PMID:23459694

  6. Microelectrode arrays in combination with in vitro models of spinal cord injury as tools to investigate pathological changes in network activity: facts and promises.

    PubMed

    Mladinic, Miranda; Nistri, Andrea

    2013-01-01

    Microelectrode arrays (MEAs) represent an important tool to study the basic characteristics of spinal networks that control locomotion in physiological conditions. Fundamental properties of this neuronal rhythmicity like burst origin, propagation, coordination, and resilience can, thus, be investigated at multiple sites within a certain spinal topography and neighboring circuits. A novel challenge will be to apply this technology to unveil the mechanisms underlying pathological processes evoked by spinal cord injury (SCI). To achieve this goal, it is necessary to fully identify spinal networks that make up the locomotor central pattern generator (CPG) and to understand their operational rules. In this review, the use of isolated spinal cord preparations from rodents, or organotypic spinal slice cultures is discussed to study rhythmic activity. In particular, this review surveys our recently developed in vitro models of SCI by evoking excitotoxic (or even hypoxic/dysmetabolic) damage to spinal networks and assessing the impact on rhythmic activity and cell survival. These pathological processes which evolve via different cell death mechanisms are discussed as a paradigm to apply MEA recording for detailed mapping of the functional damage and its time-dependent evolution. PMID:23459694

  7. Z-DNA-forming sequences generate large-scale deletions in mammalian cells

    PubMed Central

    Wang, Guliang; Christensen, Laura A.; Vasquez, Karen M.

    2006-01-01

    Spontaneous chromosomal breakages frequently occur at genomic hot spots in the absence of DNA damage and can result in translocation-related human disease. Chromosomal breakpoints are often mapped near purine–pyrimidine Z-DNA-forming sequences in human tumors. However, it is not known whether Z-DNA plays a role in the generation of these chromosomal breakages. Here, we show that Z-DNA-forming sequences induce high levels of genetic instability in both bacterial and mammalian cells. In mammalian cells, the Z-DNA-forming sequences induce double-strand breaks nearby, resulting in large-scale deletions in 95% of the mutants. These Z-DNA-induced double-strand breaks in mammalian cells are not confined to a specific sequence but rather are dispersed over a 400-bp region, consistent with chromosomal breakpoints in human diseases. This observation is in contrast to the mutations generated in Escherichia coli that are predominantly small deletions within the repeats. We found that the frequency of small deletions is increased by replication in mammalian cell extracts. Surprisingly, the large-scale deletions generated in mammalian cells are, at least in part, replication-independent and are likely initiated by repair processing cleavages surrounding the Z-DNA-forming sequence. These results reveal that mammalian cells process Z-DNA-forming sequences in a strikingly different fashion from that used by bacteria. Our data suggest that Z-DNA-forming sequences may be causative factors for gene translocations found in leukemias and lymphomas and that certain cellular conditions such as active transcription may increase the risk of Z-DNA-related genetic instability. PMID:16473937

  8. Aberrant Synaptic Integration in Adult Lamina I Projection Neurons Following Neonatal Tissue Damage

    PubMed Central

    Li, Jie; Kritzer, Elizabeth; Craig, Paige E.

    2015-01-01

    Mounting evidence suggests that neonatal tissue damage evokes alterations in spinal pain reflexes which persist into adulthood. However, less is known about potential concomitant effects on the transmission of nociceptive information to the brain, as the degree to which early injury modulates synaptic integration and membrane excitability in mature spinal projection neurons remains unclear. Here we demonstrate that neonatal surgical injury leads to a significant shift in the balance between synaptic excitation and inhibition onto identified lamina I projection neurons of the adult mouse spinal cord. The strength of direct primary afferent input to mature spino-parabrachial neurons was enhanced following neonatal tissue damage, whereas the efficacy of both GABAergic and glycinergic inhibition onto the same population was compromised. This was accompanied by reorganization in the pattern of sensory input to adult projection neurons, which included a greater prevalence of monosynaptic input from low-threshold A-fibers when preceded by early tissue damage. In addition, neonatal incision resulted in greater primary afferent-evoked action potential discharge in mature projection neurons. Overall, these results demonstrate that tissue damage during early life causes a long-term increase in the gain of spinal nociceptive circuits, and suggest that the prolonged consequences of neonatal trauma may not be restricted to the spinal cord but rather include excessive ascending signaling to supraspinal pain centers. PMID:25673839

  9. Rugby union injuries to the cervical spine and spinal cord.

    PubMed

    Quarrie, Kenneth L; Cantu, Robert C; Chalmers, David J

    2002-01-01

    Injuries to the cervical spine are among the most serious injuries occurring as a result of participation in rugby. Outcomes of such injuries range from complete recovery to death, depending on the degree of spinal cord damage sustained. Much information has been gained regarding the mechanisms and frequency of such injuries, from case reports and case series studies. The most commonly reported mechanism of injury has been hyperflexion of the cervical spine, resulting in fracture dislocation of C4-C5 or C5-C6. Tracking both the trends of incidence of spinal injuries, and the effectiveness of injury prevention initiatives has proved difficult because of a lack of properly conducted epidemiological studies. Within the constraints of the research published to date, it appears that hookers and props have been at disproportionate risk of cervical spine injury, predominantly because of injuries sustained during scrummaging. While the scrum was the phase of play most commonly associated with spinal injuries throughout the 1980s in most rugby playing countries, there has been a trend through the 1990s of an increasing proportion of spinal injuries occurring in the tackle situation. The majority of injuries have occurred early in the season, when grounds tend to be harder, and players are lacking both practice and physical conditioning for the physical contact phases of the sport. A number of injury prevention measures have been launched, including changes to the laws of the game regarding scrummaging, and education programmes aimed at enforcing safe techniques and eliminating illegal play. Calls for case-registers and effective epidemiological studies have been made by researchers and physicians in most countries where rugby is widespread, but it appears to be only recently that definite steps have been made towards this goal. Well-designed epidemiological studies will be able to provide more accurate information about potential risk factors for injury such as age, grade

  10. Subclinical lumbar polyradiculopathy, polyneuritis and ganglionitis in aged wild and exotic mammalians.

    PubMed

    Anderson, W I; Cummings, J F; Steinberg, H; deLahunta, A; King, J M

    1993-07-01

    Subclinical lumbar polyradiculopathy was present in the intradural dorsal and ventral nerve rootlets of 19 aged individuals of the following wild and exotic mammalian species: woodrat, raccoon, mink, lynx, reindeer, red deer, musk ox, scimitar-horned oryx, Arabian oryx, hybrid waterbuck, Persian onager, Przewalski's wild horse, Malayan sun bear, Asian elephant, East African river hippopotamus, vervet monkey and rhesus monkey. It was characterized by mild to severe multifocal ballooning of myelin sheaths. Occasionally, ballooned myelin sheaths contained thin strands of myelin and macrophages surrounding distorted axons. Additionally, a mild incidental lymphocytic polyneuritis was present in intradural nerve rootlets of the Malayan sun bear, and a moderate lymphocytic spinal ganglionitis in the East African river hippopotamus. PMID:8408784

  11. Subclinical lumbar polyradiculopathy, polyneuritis and ganglionitis in aged wild and exotic mammalians.

    PubMed

    Anderson, W I; Cummings, J F; Steinberg, H; deLahunta, A; King, J M

    1993-07-01

    Subclinical lumbar polyradiculopathy was present in the intradural dorsal and ventral nerve rootlets of 19 aged individuals of the following wild and exotic mammalian species: woodrat, raccoon, mink, lynx, reindeer, red deer, musk ox, scimitar-horned oryx, Arabian oryx, hybrid waterbuck, Persian onager, Przewalski's wild horse, Malayan sun bear, Asian elephant, East African river hippopotamus, vervet monkey and rhesus monkey. It was characterized by mild to severe multifocal ballooning of myelin sheaths. Occasionally, ballooned myelin sheaths contained thin strands of myelin and macrophages surrounding distorted axons. Additionally, a mild incidental lymphocytic polyneuritis was present in intradural nerve rootlets of the Malayan sun bear, and a moderate lymphocytic spinal ganglionitis in the East African river hippopotamus.

  12. Medical and experimental mammalian genetics: A perspective

    SciTech Connect

    McKusick, V.A.; Roderick, T.H.; Mori, J.; Paul, N.W.

    1987-01-01

    This book contains 14 papers. Some of the titles are: Structure and Organization of Mammalian Chromosomes: Normal and Abnormal; Globin Gene Structure and the Nature of Mutation; Retroviral DNA Content of the Mouse Genome; Maternal Genes: Mitochondrial Diseases; Human Evolution; and Prospects for Gene Replacement Therapy.

  13. Ticks Take Cues from Mammalian Interferon.

    PubMed

    de Silva, Aravinda M

    2016-07-13

    Interferons are considered a first line of immune defense restricted to vertebrates. In this issue of Cell Host & Microbe, Smith et al. (2016) demonstrate that mammalian interferon γ activates an antimicrobial response within ticks feeding on blood. The study suggests that arthropods have a parallel interferon-like defense system. PMID:27414493

  14. Cultured normal mammalian tissue and process

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J. (Inventor); Prewett, Tacey L. (Inventor); Wolf, David A. (Inventor); Spaulding, Glenn F. (Inventor)

    1993-01-01

    Normal mammalian tissue and the culturing process has been developed for the three groups of organ, structural and blood tissue. The cells are grown in vitro under microgravity culture conditions and form three dimensional cell aggregates with normal cell function. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.

  15. Structure of mammalian respiratory complex I.

    PubMed

    Zhu, Jiapeng; Vinothkumar, Kutti R; Hirst, Judy

    2016-08-18

    Complex I (NADH:ubiquinone oxidoreductase), one of the largest membrane-bound enzymes in the cell, powers ATP synthesis in mammalian mitochondria by using the reducing potential of NADH to drive protons across the inner mitochondrial membrane. Mammalian complex I (ref. 1) contains 45 subunits, comprising 14 core subunits that house the catalytic machinery (and are conserved from bacteria to humans) and a mammalian-specific cohort of 31 supernumerary subunits. Knowledge of the structures and functions of the supernumerary subunits is fragmentary. Here we describe a 4.2-Å resolution single-particle electron cryomicroscopy structure of complex I from Bos taurus. We have located and modelled all 45 subunits, including the 31 supernumerary subunits, to provide the entire structure of the mammalian complex. Computational sorting of the particles identified different structural classes, related by subtle domain movements, which reveal conformationally dynamic regions and match biochemical descriptions of the 'active-to-de-active' enzyme transition that occurs during hypoxia. Our structures therefore provide a foundation for understanding complex I assembly and the effects of mutations that cause clinically relevant complex I dysfunctions, give insights into the structural and functional roles of the supernumerary subunits and reveal new information on the mechanism and regulation of catalysis. PMID:27509854

  16. Genomics in mammalian cell culture bioprocessing

    PubMed Central

    Wuest, Diane M.; Harcum, Sarah W.; Lee, Kelvin H.

    2013-01-01

    Explicitly identifying the genome of a host organism including sequencing, mapping, and annotating its genetic code has become a priority in the field of biotechnology with aims at improving the efficiency and understanding of cell culture bioprocessing. Recombinant protein therapeutics, primarily produced in mammalian cells, constitute a $108 billion global market. The most common mammalian cell line used in biologic production processes is the Chinese hamster ovary (CHO) cell line, and although great improvements have been made in titer production over the past 25 years, the underlying molecular and physiological factors are not well understood. Confident understanding of CHO bioprocessing elements (e.g. cell line selection, protein production, and reproducibility of process performance and product specifications) would significantly improve with a well understood genome. This review describes mammalian cell culture use in bioprocessing, the importance of obtaining CHO cell line genetic sequences, and the current status of sequencing efforts. Furthermore, transcriptomic techniques and gene expression tools are presented, and case studies exploring genomic techniques and applications aimed to improve mammalian bioprocess performance are reviewed. Finally, future implications of genomic advances are surmised. PMID:22079893

  17. [Placental developmental defects in cloned mammalian animals].

    PubMed

    Ao, Zheng; Liu, Dewu; Cai, Gengyuan; Wu, Zhenfang; Li, Zicong

    2016-05-01

    The cloning technique, also called somatic cell nuclear transfer (SCNT), has been successfully established and gradually applied to various mammalian species. However, the developmental rate of SCNT mammalian embryos is very low, usually at 1% to 5%, which limits the application of SCNT. Placental developmental defects are considered as the main cause of SCNT embryo development inhibition. Almost all of SCNT-derived mammalian placentas exhibit various abnormalities, such as placental hyperplasia, vascular defects and umbilical cord malformation. Mechanistically, these abnormalities result from failure of establishment of correct epigenetic modification in the trophectoderm genome, which leads to erroneous expression of important genes for placenta development-related, particularly imprinted genes. Consequently, aberrant imprinted gene expression gives rise to placental morphologic abnormalities and functional defects, therefore decreases developmental competence of cloned embryos. Currently, although numerous methods that can improve the developmental ability of SCNT-derived embryos have been reported, most of them are unable to substantially enhance the success rate of SCNT due to failure to eliminate the placental development defects. In this review, we summarize placental abnormalities and imprinted gene expression in mammalian cloning, and propose directions for the future research aiming to improve the cloning efficiency. PMID:27232488

  18. Erythropoietin binding protein from mammalian serum

    DOEpatents

    Clemons, G.K.

    1997-04-29

    Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described. 11 figs.

  19. A promoter-level mammalian expression atlas

    PubMed Central

    2015-01-01

    Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research. PMID:24670764

  20. Erythropoietin binding protein from mammalian serum

    DOEpatents

    Clemons, Gisela K.

    1997-01-01

    Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described.

  1. Evaluation of Injured Axons Using Two-Photon Excited Fluorescence Microscopy after Spinal Cord Contusion Injury in YFP-H Line Mice

    PubMed Central

    Horiuchi, Hideki; Oshima, Yusuke; Ogata, Tadanori; Morino, Tadao; Matsuda, Seiji; Miura, Hiromasa; Imamura, Takeshi

    2015-01-01

    Elucidation of the process of degeneration of injured axons is important for the development of therapeutic modules for the treatment of spinal cord injuries. The aim of this study was to establish a method for time-lapse observation of injured axons in living animals after spinal cord contusion injury. YFP (yellow fluorescent protein)-H transgenic mice, which we used in this study, express fluorescence in their nerve fibers. Contusion damage to the spinal cord at the 11th vertebra was performed by IH (Infinite Horizon) impactor, which applied a pressure of 50 kdyn. The damaged spinal cords were re-exposed during the observation period under anesthesia, and then observed by two-photon excited fluorescence microscopy, which can observe deep regions of tissues including spinal cord axons. No significant morphological change of injured axons was observed immediately after injury. Three days after injury, the number of axons decreased, and residual axons were fragmented. Seven days after injury, only fragments were present in the damaged tissue. No hind-limb movement was observed during the observation period after injury. Despite the immediate paresis of hind-limbs following the contusion injury, the morphological degeneration of injured axons was delayed. This method may help clarification of pathophysiology of axon degeneration and development of therapeutic modules for the treatment of spinal cord injury. PMID:26184175

  2. Evaluation of Injured Axons Using Two-Photon Excited Fluorescence Microscopy after Spinal Cord Contusion Injury in YFP-H Line Mice.

    PubMed

    Horiuchi, Hideki; Oshima, Yusuke; Ogata, Tadanori; Morino, Tadao; Matsuda, Seiji; Miura, Hiromasa; Imamura, Takeshi

    2015-07-13

    Elucidation of the process of degeneration of injured axons is important for the development of therapeutic modules for the treatment of spinal cord injuries. The aim of this study was to establish a method for time-lapse observation of injured axons in living animals after spinal cord contusion injury. YFP (yellow fluorescent protein)-H transgenic mice, which we used in this study, express fluorescence in their nerve fibers. Contusion damage to the spinal cord at the 11th vertebra was performed by IH (Infinite Horizon) impactor, which applied a pressure of 50 kdyn. The damaged spinal cords were re-exposed during the observation period under anesthesia, and then observed by two-photon excited fluorescence microscopy, which can observe deep regions of tissues including spinal cord axons. No significant morphological change of injured axons was observed immediately after injury. Three days after injury, the number of axons decreased, and residual axons were fragmented. Seven days after injury, only fragments were present in the damaged tissue. No hind-limb movement was observed during the observation period after injury. Despite the immediate paresis of hind-limbs following the contusion injury, the morphological degeneration of injured axons was delayed. This method may help clarification of pathophysiology of axon degeneration and development of therapeutic modules for the treatment of spinal cord injury.

  3. Cytotoxic responses to 405nm light exposure in mammalian and bacterial cells: Involvement of reactive oxygen species.

    PubMed

    Ramakrishnan, Praveen; Maclean, Michelle; MacGregor, Scott J; Anderson, John G; Grant, M Helen

    2016-06-01

    Light at wavelength 405 nm is an effective bactericide. Previous studies showed that exposing mammalian cells to 405 nm light at 36 J/cm(2) (a bactericidal dose) had no significant effect on normal cell function, although at higher doses (54 J/cm(2)), mammalian cell death became evident. This research demonstrates that mammalian and bacterial cell toxicity induced by 405 nm light exposure is accompanied by reactive oxygen species production, as detected by generation of fluorescence from 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate. As indicators of the resulting oxidative stress in mammalian cells, a decrease in intracellular reduced glutathione content and a corresponding increase in the efflux of oxidised glutathione were observed from 405 nm light treated cells. The mammalian cells were significantly protected from dying at 54 J/cm(2) in the presence of catalase, which detoxifies H2O2. Bacterial cells were significantly protected by sodium pyruvate (H2O2 scavenger) and by a combination of free radical scavengers (sodium pyruvate, dimethyl thiourea (OH scavenger) and catalase) at 162 and 324 J/cm(2). Results therefore suggested that the cytotoxic mechanism of 405 nm light in mammalian cells and bacteria could be oxidative stress involving predominantly H2O2 generation, with other ROS contributing to the damage.

  4. Effect of locomotor training in completely spinalized cats previously submitted to a spinal hemisection.

    PubMed

    Martinez, Marina; Delivet-Mongrain, Hugo; Leblond, Hugues; Rossignol, Serge

    2012-08-01

    After a spinal hemisection in cats, locomotor plasticity occurring at the spinal level can be revealed by performing, several weeks later, a complete spinalization below the first hemisection. Using this paradigm, we recently demonstrated that the hemisection induces durable changes in the symmetry of locomotor kinematics that persist after spinalization. Can this asymmetry be changed again in the spinal state by interventions such as treadmill locomotor training started within a few days after the spinalization? We performed, in 9 adult cats, a spinal hemisection at thoracic level 10 and then a complete spinalization at T13, 3 weeks later. Cats were not treadmill trained during the hemispinal period. After spinalization, 5 of 9 cats were not trained and served as control while 4 of 9 cats were trained on the treadmill for 20 min, 5 d a week for 3 weeks. Using detailed kinematic analyses, we showed that, without training, the asymmetrical state of locomotion induced by the hemisection was retained durably after the subsequent spinalization. By contrast, training cats after spinalization induced a reversal of the left/right asymmetries, suggesting that new plastic changes occurred within the spinal cord through locomotor training. Moreover, training was shown to improve the kinematic parameters and the performance of the hindlimb on the previously hemisected side. These results indicate that spinal locomotor circuits, previously modified by past experience such as required for adaptation to the hemisection, can remarkably respond to subsequent locomotor training and improve bilateral locomotor kinematics, clearly showing the benefits of locomotor training in the spinal state.

  5. Nutrition of People with Spinal Cord Injuries

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This conference proceeding summarizes current knowledge about the nutritional status and needs of the spinal cord injured patient. Topics covered include the aspects of spinal cord injury that influence nutrient intakes and status, and the nutrients most likely to be problematic in this diverse gro...

  6. Intraoperative neurophysiological monitoring in spinal surgery

    PubMed Central

    Park, Jong-Hwa; Hyun, Seung-Jae

    2015-01-01

    Recently, many surgeons have been using intraoperative neurophysiological monitoring (IOM) in spinal surgery to reduce the incidence of postoperative neurological complications, including level of the spinal cord, cauda equina and nerve root. Several established technologies are available and combined motor and somatosensory evoked potentials are considered mandatory for practical and successful IOM. Spinal cord evoked potentials are elicited compound potentials recorded over the spinal cord. Electrical stimulation is provoked on the dorsal spinal cord from an epidural electrode. Somatosensory evoked potentials assess the functional integrity of sensory pathways from the peripheral nerve through the dorsal column and to the sensory cortex. For identification of the physiological midline, the dorsal column mapping technique can be used. It is helpful for reducing the postoperative morbidity associated with dorsal column dysfunction when distortion of the normal spinal cord anatomy caused by an intramedullary cord lesion results in confusion in localizing the midline for the myelotomy. Motor evoked potentials (MEPs) consist of spinal, neurogenic and muscle MEPs. MEPs allow selective and specific assessment of the functional integrity of descending motor pathways, from the motor cortex to peripheral muscles. Spinal surgeons should understand the concept of the monitoring techniques and interpret monitoring records adequately to use IOM for the decision making during the surgery for safe surgery and a favorable surgical outcome. PMID:26380823

  7. Psychological Aspects of Spinal Cord Injury

    ERIC Educational Resources Information Center

    Cook, Daniel W.

    1976-01-01

    Reviewing literature on the psychological impact of spinal cord injury suggests: (a) depression may not be a precondition for injury adjustment; (b) many persons sustaining cord injury may have experienced psychological disruption prior to injury; and (c) indexes of rehabilitation success need to be developed for the spinal cord injured. (Author)

  8. Neuroprotective and Neurorestorative Processes after Spinal Cord Injury: The Case of the Bulbospinal Respiratory Neurons.

    PubMed

    Kastner, Anne; Matarazzo, Valéry

    2016-01-01

    High cervical spinal cord injuries interrupt the bulbospinal respiratory pathways projecting to the cervical phrenic motoneurons resulting in important respiratory defects. In the case of a lateralized injury that maintains the respiratory drive on the opposite side, a partial recovery of the ipsilateral respiratory function occurs spontaneously over time, as observed in animal models. The rodent respiratory system is therefore a relevant model to investigate the neuroplastic and neuroprotective mechanisms that will trigger such phrenic motoneurons reactivation by supraspinal pathways. Since part of this recovery is dependent on the damaged side of the spinal cord, the present review highlights our current understanding of the anatomical neuroplasticity processes that are developed by the surviving damaged bulbospinal neurons, notably axonal sprouting and rerouting. Such anatomical neuroplasticity relies also on coordinated molecular mechanisms at the level of the axotomized bulbospinal neurons that will promote both neuroprotection and axon growth. PMID:27563469

  9. Neuroprotective and Neurorestorative Processes after Spinal Cord Injury: The Case of the Bulbospinal Respiratory Neurons

    PubMed Central

    2016-01-01

    High cervical spinal cord injuries interrupt the bulbospinal respiratory pathways projecting to the cervical phrenic motoneurons resulting in important respiratory defects. In the case of a lateralized injury that maintains the respiratory drive on the opposite side, a partial recovery of the ipsilateral respiratory function occurs spontaneously over time, as observed in animal models. The rodent respiratory system is therefore a relevant model to investigate the neuroplastic and neuroprotective mechanisms that will trigger such phrenic motoneurons reactivation by supraspinal pathways. Since part of this recovery is dependent on the damaged side of the spinal cord, the present review highlights our current understanding of the anatomical neuroplasticity processes that are developed by the surviving damaged bulbospinal neurons, notably axonal sprouting and rerouting. Such anatomical neuroplasticity relies also on coordinated molecular mechanisms at the level of the axotomized bulbospinal neurons that will promote both neuroprotection and axon growth. PMID:27563469

  10. Fictive motor patterns in chronic spinal cats.

    PubMed

    Pearson, K G; Rossignol, S

    1991-12-01

    1. Fictive motor patterns were recorded in hind leg nerves of 10 adult chronic spinal cats (spinalized at T13). Four of these animals had been trained to step with their hind legs on a treadmill (late-spinal animals), whereas the remainder received no training and were examined a short time after spinalization (early-spinal animals). 2. A fictive pattern resembling the locomotor pattern for stepping was evoked in all animals in response to stimulation of the skin of the perineal region. (2-[2,6-Dichloroaniline]-2-imidazoline) hydrochloride (Clonidine) at doses ranging from 100 to 500 micrograms/kg iv facilitated the production of this pattern, particularly in early-spinal animals. 3. The fictive locomotor pattern in late-spinal animals was more complex than that occurring in early-spinal animals. In the latter the pattern consisted of an alternation of activity in flexor and extensor nerves, and changing leg position did not qualitatively alter the pattern, whereas in late-spinal animals the relative durations of the bursts in different flexors were usually not the same, and the pattern of flexor activity was dependent on leg position. 4. Moving the legs from extension to flexion progressively decreased the duration of flexor bursts, increased the cycle period, and decreased the ease with which the pattern could be evoked in both early- and late-spinal animals. 5. 1-beta-3,4-Dihydroxyphenylalanine (DOPA)/Isonocotinic acid 2-[(2-benzylcarbamoyl)ethyl]hydrazide (Nialamide) treatment following Clonidine in early-spinal animals increased the complexity of flexor burst activity. This, and other observations, indicates that DOPA and Clonidine do not have strictly identical actions on the locomotor pattern generator. 6. Stimulation of the paws in late-spinal animals produced two patterns of activity distinctly different from the locomotor pattern. of activity distinctly different from the locomotor pattern. One was a short sequence of high-frequency rhythmic activity (at

  11. Sphingolipids in spinal cord injury

    PubMed Central

    Jones, Zachary B; Ren, Yi

    2016-01-01

    Spinal cord injury (SCI) is a debilitating condition that affects millions of individuals worldwide. Despite progress over the last few decades, the molecular mechanisms of secondary SCI that continue to occur days and weeks after the original trauma remain poorly understood. As a result, current therapies for SCI are only marginally effective. Sphingolipids, a diverse class of bioactive lipids, have been shown to regulate SCI repair and key secondary injury processes such as apoptosis, ischemia and inflammation. This review will discuss the numerous roles of sphingolipids and highlight the potential of sphingolipid-targeted therapies for SCI. PMID:27570580

  12. Parasitic and rare spinal infections.

    PubMed

    do Amaral, Lázaro Luís Faria; Nunes, Renato Hoffmann; da Rocha, Antonio Jose

    2015-05-01

    The imaging features of spinal parasitic diseases and other rare infections are herein discussed. These diseases are distributed worldwide, with increased prevalence in areas with poor sanitary conditions and in developing countries. In nonendemic areas, sporadic cases may occur, consequent to increased international travel and immunocompromising conditions. Infectious diseases are usually treatable, and early detection is often crucial. A thorough comprehension of the imaging patterns associated with the clinical features, epidemiology, and laboratory results allows the radiologist to narrow down the options for differential diagnosis and facilitates the timely implementation of appropriate therapies. PMID:25952177

  13. Ambulation and spinal cord injury.

    PubMed

    Hardin, Elizabeth C; Kobetic, Rudi; Triolo, Ronald J

    2013-05-01

    Walking is possible for many patients with a spinal cord injury. Avenues enabling walking include braces, robotics and FES. Among the benefits are improved musculoskeletal and mental health, however unrealistic expectations may lead to negative changes in quality of life. Use rigorous assessment standards to gauge the improvement of walking during the rehabilitation process, but also yearly. Continued walking after discharge may be limited by challenges, such as lack of accessibility in and outside the home, and complications, such as shoulder pain or injuries from falls. It is critical to determine the risks and benefits of walking for each patient.

  14. Sphingolipids in spinal cord injury.

    PubMed

    Jones, Zachary B; Ren, Yi

    2016-01-01

    Spinal cord injury (SCI) is a debilitating condition that affects millions of individuals worldwide. Despite progress over the last few decades, the molecular mechanisms of secondary SCI that continue to occur days and weeks after the original trauma remain poorly understood. As a result, current therapies for SCI are only marginally effective. Sphingolipids, a diverse class of bioactive lipids, have been shown to regulate SCI repair and key secondary injury processes such as apoptosis, ischemia and inflammation. This review will discuss the numerous roles of sphingolipids and highlight the potential of sphingolipid-targeted therapies for SCI. PMID:27570580

  15. Neuroimaging of Spinal Canal Stenosis.

    PubMed

    Cowley, Peter

    2016-08-01

    Spinal stenosis is common and presents in a variety of forms. Symptomatic lumbar stenosis occurs in approximately 10% of the population and cervical stenosis in 9% over age 70. Imaging is central to the management decision process and first-choice MR imaging may be substituted with CT and CT myelography. A review of the literature is presented with particular emphasis on the clinical-radiologic correlation in both neurogenic intermittent claudication and cervical spondylotic myelopathy. Advanced techniques promise improvements, particularly with radicular compressive lesions, but remain underutilized in routine clinical practice.

  16. Spinal morphine anesthesia and urinary retention.

    PubMed

    Mahan, K T; Wang, J

    1993-11-01

    Spinal anesthetic is a common form of surgical anesthetic used in foot and ankle surgery. Spinal morphine anesthetic is less common, but has the advantage of providing postoperative analgesia for 12 to 24 hr. A number of complications can occur with spinal anesthesia, including urinary retention that may be a source of severe and often prolonged discomfort and pain for the patient. Management of this problem may require repeated bladder catheterization, which may lead to urinary tract infections or impairment of urethrovesicular function. This study reviews the incidence of urinary retention in 80 patients (40 after general anesthesia and 40 after spinal anesthesia) who underwent foot and ankle surgery at Saint Joseph's Hospital, Philadelphia, PA. Twenty-five percent of the patients who had spinal anesthesia experienced urinary retention, while only 7 1/2% of the group who had general anesthesia had this complication. Predisposing factors, treatment regimen, and recommendations for the prevention and management of urinary retention are presented.

  17. Ergonomics and biology of spinal rotation.

    PubMed

    Kumar, Shrawan

    2004-03-15

    Spinal rotation, though being a very common motion of the body, is poorly understood. Furthermore, this motion and the extent of its development is unique to the human. Beyond the extent of its need in common activities, spinal rotation is a destabilizating motion for an inherently unstable structure. Spinal rotation has been argued to be an essential feature for an efficient bipedal gait. Also, it provides leverage to the upper extremities in delivering a forceful impact. An artificial restriction/elimination of spinal rotation resulted in significantly shorter stride length, slower walking velocity, and higher energy consumption in walking (p < 0.05). Spinal rotation also decreases the amount of force the spinal muscles can generate (to 25% of spinal extension). However, its extensive employment in industrial activities has been associated with 60.4% of back injuries. It is further stated that the amount of scientific information currently available is inadequate to biomechanically model the spinal response in a working environment. For example, when the spine is pre-rotated, a further rotation in the direction of pre-rotation decreases the force production significantly (p < 0.01) and increases the EMG activity significantly (p < 0.01) but the pattern changes with effort in the opposite direction. This and other properties (described in the paper) render biomechanical models inadequate. Muscle activation pattern and neuromotor behaviour of spinal muscles in flexion/extension and rotation of the spine are significantly different from each other (p < 0.01). The localized fatigue in different spinal muscles in the same contraction is significantly different and has been called differential fatigue. Finally, the trunk rotation, being pivotal for bipedal locomotion has brought many back problems to the human race.

  18. Spinal cord deformation due to nozzle gas flow effects using optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Wong, Ronnie J.; Jivraj, Jamil; Vuong, Barry; Ramjist, Joel; Sun, Cuiru; Huang, Yize; Yang, Victor X. D.

    2015-03-01

    The use of gas assistance in laser machining hard materials is well established in manufacturing but not in the context of surgery. Laser cutting of osseous tissue in the context of neurosurgery can benefit from gas-assist but requires an understanding of flow and pressure effects to minimize neural tissue damage. In this study we acquire volumetric flow rates through a gas nozzle on the spinal cord, with dura and without dura.

  19. Sexing mammalian sperm - Where do we go from here?

    PubMed

    Seidel, George E

    2012-01-01

    The only commercially viable method of sexing mammalian sperm is to use a flow cytometer to measure sperm DNA content via fluorescence of the DNA-bound fluorophore Hoechst 33342, and then sort sperm into three populations, probably X, probably Y, and undetermined. Millions of insemination doses of sexed sperm are produced annually by this procedure. Although accuracy of sexing usually exceeds 90%, this procedure of sexing one sperm at a time has serious limitations, including cost, sort rates, and damage to sperm resulting in lowered fertility, but not abnormalities in offspring. Suggested areas for research include determining how sperm are damaged and where in the process of fertilization and embryonic development the infertility is manifest. Pre and post sorting procedures are done in approximately hourly batches, and these might be changed to continuous procedures. Numerous genetic, physical, and immunological procedures for sexing millions of sperm in parallel have been proposed, but none appears to be suitable for commercialization at this time due to issues of accuracy, repeatability, damage to sperm, and other problems. However, increasing numbers of reports are appearing concerning improvements in these procedures, and it appears inevitable that one or more of them eventually will prove to be efficacious. In developing such procedures, it is critical to monitor sexing accuracy regularly by rapid and inexpensive procedures such as fluorescence in situ hybridization, quantitative PCR, or sort reanalysis by flow cytometry. Furthermore, monitoring fertility of sexed sperm such as in vitro fertilization should be integral to the development process. Intellectual property issues could be substantive.

  20. Descending pathways to the spinal cord: a comparative study of 22 mammals.

    PubMed

    Nudo, R J; Masterton, R B

    1988-11-01

    In order to estimate the qualitative commonalities and range of variation among major descending spinal pathways relevant to mankind's ancestral lineage, the supraspinal cell groups originating fibers descending directly to the spinal cord were examined in 22 mammalian species. In a standardized retrograde tract-tracing procedure, flakes of raw HRP were applied directly to the freshly cut fibers of the spinal cord after it had been hemisected at the C1-C2 junction. After a 72-hour survival period, brain and spinal cord tissues were processed by conventional HRP-processing techniques. This procedure was performed on 94 individual animals. Of this total, 41 individual cases were eliminated by a rigorous culling procedure. The results are based on 53 individuals representing 15 species selected for their successive kinship with mankind and seven species in two other lineages selected for the convergence of their visual or sensorimotor systems with anthropoids. The 22 species represent 19 genera, 14 families, eight orders, and two subclasses of Mammalia. The results show that at least 27 supraspinal cell groups, each containing intensely labeled cells, can be readily identified in each of the species. Despite vast quantitative differences in cell number and cell size, this qualitative uniformity among the relatively large number of diverse taxa suggests that the same pathways were probably present in the extinct ancestors throughout mankind's mammalian lineage and are probably still present in extant viviparous mammals as well. If so, these pathways are as old in phylogenetic history as the last common ancestor of marsupial and placental mammals--dating from the late Jurassic to early Cretaceous, perhaps 145-120 million years ago. Further comparison of the results with similar experimental findings in members of other vertebrate classes supports the notion that several of these same pathways can be traced to even more remote ancestry, with some possibly as old as the

  1. Descending pathways to the spinal cord: a comparative study of 22 mammals.

    PubMed

    Nudo, R J; Masterton, R B

    1988-11-01

    In order to estimate the qualitative commonalities and range of variation among major descending spinal pathways relevant to mankind's ancestral lineage, the supraspinal cell groups originating fibers descending directly to the spinal cord were examined in 22 mammalian species. In a standardized retrograde tract-tracing procedure, flakes of raw HRP were applied directly to the freshly cut fibers of the spinal cord after it had been hemisected at the C1-C2 junction. After a 72-hour survival period, brain and spinal cord tissues were processed by conventional HRP-processing techniques. This procedure was performed on 94 individual animals. Of this total, 41 individual cases were eliminated by a rigorous culling procedure. The results are based on 53 individuals representing 15 species selected for their successive kinship with mankind and seven species in two other lineages selected for the convergence of their visual or sensorimotor systems with anthropoids. The 22 species represent 19 genera, 14 families, eight orders, and two subclasses of Mammalia. The results show that at least 27 supraspinal cell groups, each containing intensely labeled cells, can be readily identified in each of the species. Despite vast quantitative differences in cell number and cell size, this qualitative uniformity among the relatively large number of diverse taxa suggests that the same pathways were probably present in the extinct ancestors throughout mankind's mammalian lineage and are probably still present in extant viviparous mammals as well. If so, these pathways are as old in phylogenetic history as the last common ancestor of marsupial and placental mammals--dating from the late Jurassic to early Cretaceous, perhaps 145-120 million years ago. Further comparison of the results with similar experimental findings in members of other vertebrate classes supports the notion that several of these same pathways can be traced to even more remote ancestry, with some possibly as old as the

  2. Construct validity of clinical spinal mobility tests in ankylosing spondylitis: a systematic review and meta-analysis.

    PubMed

    Castro, Marcelo P; Stebbings, Simon M; Milosavljevic, Stephan; Bussey, Melanie D

    2016-07-01

    The study aimed to determine, using systematic review and meta-analysis, the level of evidence supporting the construct validity of spinal mobility tests for assessing patients with ankylosing spondylitis. Following the guidelines proposed in the Preferred Reporting Items for Systematic reviews and Meta-Analyses, three sets of keywords were used for data searching: (i) ankylosing spondylitis, spondyloarthritis, spondyloarthropathy, spondylarthritis; (ii) accuracy, association, construct, correlation, Outcome Measures in Rheumatoid Arthritis Clinical Trials, OMERACT, truth, validity; (iii) mobility, Bath Ankylosing Spondylitis Metrology Index-BASMI, radiography, spinal measures, cervical rotation, Schober (a further 19 keywords were used). Initially, 2558 records were identified, and from these, 21 studies were retained. Fourteen of these studies were considered high level of evidence. Compound indexes of spinal mobility showed mostly substantial to excellent levels of agreement with global structural damage. Individual mobility tests for the cervico-thoracic spine showed only moderate agreements with cervical structural damage, and considering structural damage at the lumbar spine, the original Schober was the only test that presented consistently substantial levels of agreement. Three studies assessed the construct validity of mobility measures for inflammation and low to fair levels of agreement were observed. Two meta-analyses were conducted, with assessment of agreement between BASMI and two radiological indexes of global structural damage. The spinal mobility indexes and the original Schober test show acceptable construct validity for inferring the extent of structural damage when assessing patients with ankylosing spondylitis. Spinal mobility measures do not reflect levels of inflammation at either the sacroiliac joints and/or the spine.

  3. Cytotoxicity and genotoxicity of urban particulate matter in mammalian cells.

    PubMed

    Dumax-Vorzet, Audrey F; Tate, M; Walmsley, Richard; Elder, Rhod H; Povey, Andrew C

    2015-09-01

    Ambient air particulate matter (PM)-associated reactive oxygen species (ROS) have been linked to a variety of altered cellular outcomes. In this study, three different PM samples from diesel exhaust particles (DEPs), urban dust standard reference material SRM1649a and air collected in Manchester have been tested for their ability to oxidise DNA in a cell-free assay, to increase intracellular ROS levels and to induce CYP1A1 gene expression in mammalian cells. In addition, the cytotoxicity and genotoxicity of PM were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and alkaline comet assay, respectively. All PM samples catalysed the Fenton reaction in a cell-free assay, but only DEP resulted in the generation of ROS as measured by dichlorodihydrofluorescein diacetate oxidation in mammalian cells. However, there was no evidence that increased ROS was a consequence of polycyclic aromatic hydrocarbon metabolism via CYP1A1 induction as urban dust, the Manchester dust samples but not DEP-induced CYP1A1 expression. Urban dust was more cytotoxic in murine embryonic fibroblasts (MEFs) than the other PM samples and also induced expression of GADD45a in the GreenScreen Human Cell assay without S9 activation suggesting the presence of a direct-acting genotoxicant. Urban dust and DEP produced comparable levels of DNA damage, as assessed by the alkaline comet assay, in MEFs at higher levels than those induced by Manchester PM. In conclusion, results from the cytotoxic and genotoxic assays are not consistent with ROS production being the sole determinant of PM-induced toxicity. This suggests that the organic component can contribute significantly to this toxicity and that further work is required to better characterise the extent to which ROS and organic components contribute to PM-induced toxicity.

  4. Cytotoxicity and genotoxicity of urban particulate matter in mammalian cells

    PubMed Central

    Dumax-Vorzet, Audrey F.; Tate, M.; Walmsley, Richard; Elder, Rhod H.; Povey, Andrew C.

    2015-01-01

    Ambient air particulate matter (PM)-associated reactive oxygen species (ROS) have been linked to a variety of altered cellular outcomes. In this study, three different PM samples from diesel exhaust particles (DEPs), urban dust standard reference material SRM1649a and air collected in Manchester have been tested for their ability to oxidise DNA in a cell-free assay, to increase intracellular ROS levels and to induce CYP1A1 gene expression in mammalian cells. In addition, the cytotoxicity and genotoxicity of PM were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and alkaline comet assay, respectively. All PM samples catalysed the Fenton reaction in a cell-free assay, but only DEP resulted in the generation of ROS as measured by dichlorodihydrofluorescein diacetate oxidation in mammalian cells. However, there was no evidence that increased ROS was a consequence of polycyclic aromatic hydrocarbon metabolism via CYP1A1 induction as urban dust, the Manchester dust samples but not DEP-induced CYP1A1 expression. Urban dust was more cytotoxic in murine embryonic fibroblasts (MEFs) than the other PM samples and also induced expression of GADD45a in the GreenScreen Human Cell assay without S9 activation suggesting the presence of a direct-acting genotoxicant. Urban dust and DEP produced comparable levels of DNA damage, as assessed by the alkaline comet assay, in MEFs at higher levels than those induced by Manchester PM. In conclusion, results from the cytotoxic and genotoxic assays are not consistent with ROS production being the sole determinant of PM-induced toxicity. This suggests that the organic component can contribute significantly to this toxicity and that further work is required to better characterise the extent to which ROS and organic components contribute to PM-induced toxicity. PMID:26113525

  5. Spinal Cord Stimulation and Augmentative Control Strategies for Leg Movement after Spinal Paralysis in Humans.

    PubMed

    Minassian, Karen; Hofstoetter, Ursula S

    2016-04-01

    Severe spinal cord injury is a devastating condition, tearing apart long white matter tracts and causing paralysis and disability of body functions below the lesion. But caudal to most injuries, the majority of neurons forming the distributed propriospinal system, the localized gray matter spinal interneuronal circuitry, and spinal motoneuron populations are spared. Epidural spinal cord stimulation can gain access to this neural circuitry. This review focuses on the capability of the human lumbar spinal cord to generate stereotyped motor output underlying standing and stepping, as well as full weight-bearing standing and rhythmic muscle activation during assisted treadmill stepping in paralyzed individuals in response to spinal cord stimulation. By enhancing the excitability state of the spinal circuitry, the stimulation can have an enabling effect upon otherwise "silent" translesional volitional motor control. Strategies for achieving functional movement in patients with severe injuries based on minimal translesional intentional control, task-specific proprioceptive feedback, and next-generation spinal cord stimulation systems will be reviewed. The role of spinal cord stimulation can go well beyond the immediate generation of motor output. With recently developed training paradigms, it can become a major rehabilitation approach in spinal cord injury for augmenting and steering trans- and sublesional plasticity for lasting therapeutic benefits.

  6. Spinal intradural extraosseous Ewing's sarcoma.

    PubMed

    Mateen, Farrah J; Nassar, Aziza; Bardia, Aditya; Jatoi, Aminah; Haddock, Michael G; Buckner, Jan C; Lachance, Daniel H

    2011-03-30

    Extraosseous Ewing's sarcoma (EES) involving the central nervous system is rare, but can be diagnosed and distinguished from other primitive neuroectodermal tumors (PNET) by identification of the chromosomal translocation (11;22)(q24;q12). We report EES arising from the spinal intradural extramedullary space, based on imaging, histopathological, and molecular data in two men, ages 50 and 60 years old and a review of the literature using PubMed (1970-2009). Reverse transcriptase polymerase chain reaction (RT-PCR) identified the fusion product FL1-EWS. Multimodal therapy, including radiation and alternating chemotherapy including vincristine, cyclophosphamide, doxorubicin and ifosfamide and etoposide led to local tumor control and an initial, favorable therapeutic response. No systemic involvement was seen from the time of diagnosis to the time of last follow-up (26 months) or death (4 years). This report confirms that EES is not confined to the earliest decades of life, and like its rare occurrence as an extra-axial meningeal based mass intracranially, can occasionally present as an intradural mass in the spinal canal without evidence of systemic tumor. Gross total resection followed by multimodal therapy may provide for extended progression free and overall survival.

  7. Intraoperative clinical use of low-power laser irradiation following surgical treatment of the tethered spinal cord

    NASA Astrophysics Data System (ADS)

    Rochkind, S.; Alon, M.; Ouaknine, G. E.; Weiss, S.; Avram, J.; Razon, Nisim; Lubart, Rachel; Friedmann, Harry

    1991-05-01

    Based on previous experimental investigations which indicated that low-power laser irradiation has a significant therapeutic effect and treatment potential on the injured nerve tissue, the authors began using this method in clinical practice. This data represents the first clinical results in the treatment of four patients with tethered spinal cord resulting from fibrous adhesions at the site of previous myelomeningocele and lypomyelomeningocele repair, thickened filum terminale and spinal lipoma. After surgical release of the tethered spinal cord, stable evoked responses were recorded and the conus medullaris was subjected to direct laser irradiation (CW He-Ne laser, 632.8nm, 7Jcm2). The findings show intraoperative laser treatment increases evoked responses from 15-52% (mean 26.7%). In a previous work, it was shown that direct laser irradiation promotes restoration of the electrophysiological activity of the severely injured peripheral nerve, prevents degenerative changes in neurons of the spinal cord and induces proliferation of astrocytes and oligodendrocytes. This suggested a higher metabolism in neurons and improved ability for myelin production under the influence of laser treatment. It is well known that tethering of the spinal cord causes mechanical damage to neuronal cell membranes leading to metabolic disturbances in the neurons. For this reason, the authors believe that using low-power laser irradiation may improve neuronal metabolism, prevent neuronal degeneration and promote improved spinal cord function and repair.

  8. DNA damage induces a meiotic arrest in mouse oocytes mediated by the spindle assembly checkpoint

    PubMed Central

    Collins, Josie K.; Lane, Simon I. R.; Merriman, Julie A.; Jones, Keith T.

    2015-01-01

    Extensive damage to maternal DNA during meiosis causes infertility, birth defects and abortions. However, it is unknown if fully grown oocytes have a mechanism to prevent the creation of DNA-damaged embryos. Here we show that DNA damage activates a pathway involving the spindle assembly checkpoint (SAC) in response to chemically induced double strand breaks, UVB and ionizing radiation. DNA damage can occur either before or after nuclear envelope breakdown, and provides an effective block to anaphase-promoting complex activity, and consequently the formation of mature eggs. This contrasts with somatic cells, where DNA damage fails to affect mitotic progression. However, it uncovers a second function for the meiotic SAC, which in the context of detecting microtubule–kinetochore errors has hitherto been labelled as weak or ineffectual in mammalian oocytes. We propose that its essential role in the detection of DNA damage sheds new light on its biological purpose in mammalian female meiosis. PMID:26522232

  9. Spinal Recurrence From Intracranial Germinoma: Risk Factors and Treatment Outcome for Spinal Recurrence

    SciTech Connect

    Ogawa, Kazuhiko Yoshii, Yoshihiko; Shikama, Naoto; Nakamura, Katsumasa; Uno, Takashi; Onishi, Hiroshi; Itami, Jun; Shioyama, Yoshiyuki; Iraha, Shiro; Hyodo, Akio; Toita, Takafumi; Kakinohana, Yasumasa; Tamaki, Wakana; Ito, Hisao; Murayama, Sadayuki

    2008-12-01

    Purpose: To analyze retrospectively the risk factors of spinal recurrence in patients with intracranial germinoma and clinical outcomes of patients who developed spinal recurrence. Methods and Materials: Between 1980 and 2007, 165 patients with no evidence of spinal metastases at diagnosis were treated with cranial radiotherapy without spinal irradiation. The median follow-up in all 165 patients was 61.2 months (range, 1.2-260.1 months). Results: After the initial treatment, 15 patients (9.1%) developed spinal recurrences. Multivariate analysis revealed that large intracranial disease ({>=}4 cm) and multifocal intracranial disease were independent risk factors for spinal recurrence. Radiation field, total radiation dose, and the use of chemotherapy did not affect the occurrence of spinal recurrences. Of the 15 patients who experienced spinal recurrence, the 3-year actuarial overall survival and disease-free survival (DFS) rates from the beginning of salvage treatments were 65% and 57%, respectively. In the analysis, presence of intracranial recurrence and salvage treatment modality (radiotherapy with chemotherapy vs. radiotherapy alone) had a statistically significant impact on DFS. The 3-year DFS rate in patients with no intracranial recurrence and treated with both spinal radiotherapy and chemotherapy was 100%, whereas only 17% in patients with intracranial recurrence or treated with radiotherapy alone (p = 0.001). Conclusion: Large intracranial disease and multifocal intracranial disease were risk factors for spinal recurrence in patients with intracranial germinoma with no evidence of spinal metastases at diagnosis. For patients who developed spinal recurrence alone, salvage treatment combined with spinal radiotherapy and chemotherapy was effective in controlling the recurrent disease.

  10. 21 CFR 880.2500 - Spinal fluid manometer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... column fluid space, to connect the spinal fluid to a graduated column so that the pressure can be... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Spinal fluid manometer. 880.2500 Section 880.2500... Devices § 880.2500 Spinal fluid manometer. (a) Identification. A spinal fluid manometer is a device...

  11. Clinical radiology of the spine and spinal cord

    SciTech Connect

    Banna, M.

    1985-01-01

    This book is a source of information about aspects of radiology of the spine and spinal column. It presents coverage of both normal and abnormal conditions. Contents: Spinal fractures and dislocations. Degenerative diseases of the spine. Gross anatomy of the spinal cord and meninges. Intraspinal mass lesions. Spinal dysraphism. Congenital anomalies. Tumors of the vertebral column, and more.

  12. 21 CFR 880.2500 - Spinal fluid manometer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... column fluid space, to connect the spinal fluid to a graduated column so that the pressure can be... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Spinal fluid manometer. 880.2500 Section 880.2500... Devices § 880.2500 Spinal fluid manometer. (a) Identification. A spinal fluid manometer is a device...

  13. 21 CFR 880.2500 - Spinal fluid manometer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... column fluid space, to connect the spinal fluid to a graduated column so that the pressure can be... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Spinal fluid manometer. 880.2500 Section 880.2500... Devices § 880.2500 Spinal fluid manometer. (a) Identification. A spinal fluid manometer is a device...

  14. 21 CFR 888.3070 - Pedicle screw spinal system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... immobilization and stabilization of spinal segments in skeletally mature patients as an adjunct to fusion in the...; spinal tumor; and failed previous fusion (pseudarthrosis). These pedicle screw spinal systems must comply... stabilization of spinal segments in the thoracic, lumbar, and sacral spine as an adjunct to fusion in...

  15. 21 CFR 888.3070 - Pedicle screw spinal system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... immobilization and stabilization of spinal segments in skeletally mature patients as an adjunct to fusion in the...; spinal tumor; and failed previous fusion (pseudarthrosis). These pedicle screw spinal systems must comply... stabilization of spinal segments in the thoracic, lumbar, and sacral spine as an adjunct to fusion in...

  16. 21 CFR 888.3070 - Pedicle screw spinal system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... immobilization and stabilization of spinal segments in skeletally mature patients as an adjunct to fusion in the...; spinal tumor; and failed previous fusion (pseudarthrosis). These pedicle screw spinal systems must comply... stabilization of spinal segments in the thoracic, lumbar, and sacral spine as an adjunct to fusion in...

  17. 21 CFR 888.3070 - Pedicle screw spinal system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... immobilization and stabilization of spinal segments in skeletally mature patients as an adjunct to fusion in the...; spinal tumor; and failed previous fusion (pseudarthrosis). These pedicle screw spinal systems must comply... stabilization of spinal segments in the thoracic, lumbar, and sacral spine as an adjunct to fusion in...

  18. 21 CFR 888.3070 - Pedicle screw spinal system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... immobilization and stabilization of spinal segments in skeletally mature patients as an adjunct to fusion in the...; spinal tumor; and failed previous fusion (pseudarthrosis). These pedicle screw spinal systems must comply... stabilization of spinal segments in the thoracic, lumbar, and sacral spine as an adjunct to fusion in...

  19. Axonal plasticity and functional recovery after spinal cord injury in mice deficient in both glial fibrillary acidic protein and vimentin genes

    NASA Astrophysics Data System (ADS)

    Menet, V.; Prieto, M.; Privat, A.; Giménez Y Ribotta, M.

    2003-07-01

    The lack of axonal regeneration in the injured adult mammalian spinal cord leads to permanent functional disabilities. The inability of neurons to regenerate their axon is appreciably due to an inhospitable environment made of an astrocytic scar. We generated mice knock-out for glial fibrillary acidic protein and vimentin, the major proteins of the astrocyte cytoskeleton, which are upregulated in reactive astrocytes. These animals, after a hemisection of the spinal cord, presented reduced astroglial reactivity associated with increased plastic sprouting of supraspinal axons, including the reconstruction of circuits leading to functional restoration. Therefore, improved anatomical and functional recovery in the absence of both proteins highlights the pivotal role of reactive astrocytes in axonal regenerative failure in adult CNS and could lead to new therapies of spinal cord lesions.

  20. Operant conditioning of spinal reflexes: from basic science to clinical therapy.

    PubMed

    Thompson, Aiko K; Wolpaw, Jonathan R

    2014-01-01

    New appreciation of the adaptive capabilities of the nervous system, recent recognition that most spinal cord injuries are incomplete, and progress in enabling regeneration are generating growing interest in novel rehabilitation therapies. Here we review the 35-year evolution of one promising new approach, operant conditioning of spinal reflexes. This work began in the late 1970's as basic science; its purpose was to develop and exploit a uniquely accessible model for studying the acquisition and maintenance of a simple behavior in the mammalian central nervous system (CNS). The model was developed first in monkeys and then in rats, mice, and humans. Studies with it showed that the ostensibly simple behavior (i.e., a larger or smaller reflex) rests on a complex hierarchy of brain and spinal cord plasticity; and current investigations are delineating this plasticity and its interactions with the plasticity that supports other behaviors. In the last decade, the possible therapeutic uses of reflex conditioning have come under study, first in rats and then in humans. The initial results are very exciting, and they are spurring further studies. At the same time, the original basic science purpose and the new clinical purpose are enabling and illuminating each other in unexpected ways. The long course and current state of this work illustrate the practical importance of basic research and the valuable synergy that can develop between basic science questions and clinical needs. PMID:24672441